Antimicrobials

Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S147 - 56
Restricting the selection of antibiotic-resistant mutants: a general strategy derived from fluoroquinolone studies; Zhao X et al.; Studies with fluoroquinolones have led to a general method for restricting the selection of antibiotic-resistant mutants . The strategy is based on the use of antibiotic concentrations that require cells to obtain 2 concurrent resistance mutations for growth . That concentration has been called the "mutant prevention concentration" (MPC) because no resistant colony is recovered even when >10(10) cells are plated . Resistant mutants are selected exclusively within a concentration range (mutant selection window) that extends from the point where growth inhibition begins, approximated by the minimal inhibitory concentration, up to the MPC . The dimensions of the mutant selection window can be reduced in a variety of ways, including adjustment of antibiotic structure and dosage regimens . The window can be closed to prevent mutant selection through combination therapy with > or =2 antimicrobial agents if their normalized pharmacokinetic profiles superimpose at concentrations that inhibit growth . Application of these principles could drastically restrict the selection of drug-resistant pathogens.

Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S133 - 7
Consequences of inaction: importance of infection control practices; Boyce JM; The increasing prevalence of antimicrobial-resistant pathogens in health care facilities is due in large part to overuse of antibiotics and poor compliance with recommended infection control practices . To control the spread of such pathogens, health care facilities must reduce overuse and abuse of antibiotics, and they must implement new multidisciplinary programs to improve hand hygiene practices among health care workers and improve compliance with recommended barrier precautions.

Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S118 - 23
Using internet discussion of antimicrobial susceptibility databases for continuous quality improvement of the testing and management of antimicrobial resistance; O'Brien TF et al.; Accurate results from the world's microbiology laboratories are essential for care of patients, control of hospital and community infections, and global epidemiology . Yet those laboratories differ greatly in their access to supplies, published literature and standards, training courses, peer interaction, and mandated quality control . Because much of what is needed is information, new information technology should help . In particular, measurements of susceptibility to antimicrobial agents, now increasingly filed in electronic databases, exhibit many kinds of variances due both to test performance and to the diversity of bacteria and of their mechanisms of resistance . In industry, workers' ongoing evaluation of variances in measurements of performance has been the basis of management programs of continuous quality improvement . Examples suggest how collegial evaluation of variances in shared susceptibility test data might similarly improve quality not only of testing but also of other aspects of the management of antimicrobial resistance . Internet access is now making such ongoing evaluation and discussion increasingly possible in most parts of the world.

Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S116 - 7
Globalization of antimicrobial resistance: epidemiological challenges; Williams RJ; Globalization of antimicrobial resistance is a reality, but before the relative impact of global versus local spread of resistant microorganisms can be quantified, surveillance capacity and information transfer must be greatly enhanced.

Clin Microbiol Infect, 2001, 7 Suppl 3, 30 - 8
Community-acquired pneumonia: the evolving challenge; Finch R; Community-acquired pneumonia (CAP) is a common disorder that has been the focus of a major international research effort to define its epidemiology, etiology and management . The microbial etiology of CAP is complex and severity assessment is important in identifying at-risk populations as well as defining therapeutic strategies . Laboratory investigations rarely influence initial therapy, which remains empirical . Guidelines have been developed in many countries in response to the need to optimize management and outcomes . However, many of these guidelines have been based on expert opinion rather than robust evidence . New evidence-based guidelines have been developed that take into account disease severity, the local distribution of pathogens and their likely susceptibility to antimicrobials, and that include newer treatment options . Macrolide and fluoroquinolone antimicrobials feature heavily in these new treatment recommendations . Promising new therapies continue to emerge that may offer advantages over fluoroquinolones and macrolides, in particular with regard to the problem of resistance . Of these, the ketolides are of special interest . Telithromycin, the first ketolide antibacterial, has been evaluated in the treatment of > 700 patients with CAP . A once-daily oral dose of telithromycin 800 mg for 7-10 days produces clinical and bacteriological success rates > 90% and equivalent to standard comparator agents, whilst maintaining efficacy against resistant pathogens.

Clin Microbiol Infect, 2001, 7 Suppl 3, 24 - 9
Pharmacodynamic and pharmacokinetic considerations in antimicrobial selection: focus on telithromycin; Drusano G; The effectiveness of empirical treatment for respiratory tract infections (RTIs) with commonly available antimicrobials is threatened by the development of microbial resistance and cross-resistance between treatments . Pharmacokinetic and pharmacodynamic profiling of antimicrobial agents is increasingly being used to select the most appropriate treatment and dosage schedules for RTIs . In addition to enhancing management strategies with existing treatments, these profiles have played a key part in identifying dosage schedules for a new family of semisynthetic antimicrobials, the ketolides . The first member of this family, telithromycin, has potent activity against both common and atypical pathogens involved in RTIs and does not induce resistance to the macrolide-lincosamide-streptogramin B (MLS(B)) antimicrobials in vitro . Its pharmacokinetic profile reveals that telithromycin can be administered once daily without regard for meals, requires no dose reduction in elderly patients or those with hepatic impairment, and penetrates rapidly into respiratory tissues and fluids, a feature probably related to its ability to concentrate inside white blood cells . Pharmacodynamic studies indicate that the area under the concentration-time curve (AUC):minimum inhibitory concentration (MIC) and the peak plasma concentration (Cmax):MIC ratios are important determinants of bacteriological outcome with telithromycin . Telithromycin has a high AUC:MIC ratio compared with macrolide antimicrobials, which is expected to result in enhanced antimicrobial activity . These properties of telithromycin, combined with its good tolerability and low propensity for drug interactions, provide the basis for potent and reliable treatment of RTIs with a convenient, once-daily regimen.

Clin Microbiol Infect, 2001, 7 Suppl 3, 18 - 23
Safeguarding future antimicrobial options: strategies to minimize resistance; Leclercq R; Current antimicrobial therapy for community-acquired respiratory tract infections (RTIs) is empirical and is influenced by local differences in etiology and bacterial susceptibility . As the rates of resistance and cross-resistance to currently available classes of antimicrobial agents increase, their effectiveness becomes compromised . These issues demand improved strategies for antimicrobial usage, and the development of new agents that do not select resistance are essential to safeguard future antimicrobial efficacy . Strategies to minimize antimicrobial resistance among common RTIs include reducing antimicrobial consumption and controlling the development and spread of resistance through appropriate prescribing and the use of short-duration, once-daily treatments to improve patient compliance . Importantly, the ketolides, which are a new family of antimicrobials, have been recently developed specifically for the treatment of community-acquired RTIs . The first member of this new family, telithromycin, has been shown to have potent activity against common and atypical respiratory pathogens, including beta-lactam- and macrolide-resistant strains, and has a low potential to select for or induce cross-resistance . These properties, combined with its good tolerability across patient groups, make telithromycin an attractive option for the first-line empiric treatment of RTIs with the potential to limit the future development of resistance.

Nippon Ronen Igakkai Zasshi, 2001 Jul, 38(4), 440 - 3
{Defensins as a mechanism of host defense and innate immunity}; Tomita T et al.; Antimicrobial peptides, including beta-defensins, are thought to be effective agents against opportunistic infections . In humans, three beta-defensins have been identified . The first human beta-defensin, hBD-1, is predominantly expressed in epithelia of the urogenital tract and has been reported to be constitutive . The second and third human beta-defensins, hBD-2 and hBD-3, were isolated from psoriatic skin and found to be predominantly expressed in skin and respiratory tract . Of note, the hBD-2 gene expression is inducible by various proinflammatory agents such as TNF-alpha, IL-1 beta, IL-8, LPS, bacteria, and yeasts . It has been shown that LPS-induced expression of hBD-2 in human tracheobronchial epithelial cells requires CD14, which may complex with Toll-like receptors (TLRs) to ultimately activate NF-kappa B . In addition, beta-defensins have been recently reported to promote immune responses by recruiting dendritic and T cells . Defensins may play a key role in the mechanism of host defense and innate immunity . These defensins, including hBD-2, might provide a new therapeutic approach to infectious diseases.

Drug Discov Today, 2001 Sep 1, 6(17), 887 - 892
Finding drug targets in microbial genomes; Read TD et al.; In this era of genomic science, knowledge about biological function is integrated increasingly with DNA sequence data . One area that has been significantly impacted by this accumulation of information is the discovery of drugs to treat microbial infections . Genome sequencing and bioinformatics is driving the discovery and development of novel classes of broad-spectrum antimicrobial compounds, and could enable medical science to keep pace with the increasing resistance of bacteria, fungi and parasites to current antimicrobials . This review discusses the use of genomic information in the rapid identification of target genes for antimicrobial drug discovery.

FEBS Lett, 2001 Aug 24, 504(1-2), 5 - 10
Calcitermin, a novel antimicrobial peptide isolated from human airway secretions; Cole AM et al.; The human airways are protected from pathogenic colonization by a blanket of fluid impregnated with innate antimicrobial effector molecules . Among several previously uncharacterized components, we isolated a peptide that had activity primarily targeting Gram-negative bacteria . We named the peptide 'calcitermin' since its amino acid sequence and mass were equivalent to the 15 C-terminal residues of the S100 protein, calgranulin C . The antimicrobial activity of calcitermin was enhanced in acidic buffers (pH 5.4) and in the presence of micromolar concentrations of ZnCl(2) . Analysis revealed a putative zinc-binding consensus sequence as well as an alpha-helical conformation in structure-promoting solvents.

Semin Respir Infect, 2001 Jun, 16(2), 91 - 101
Pathogenesis of Histoplasma capsulatum; Woods JP et al.; Histoplasma capsulatum is well adapted to be infectious and pathogenic for humans . As a soil fungus with no known requirement for interacting with a mammalian host as part of an obligate lifecycle, its plethora of strategies for successful pathogenesis is particularly remarkable . These features include the dimorphic mold-yeast transition, entry into host macrophages, subcellular localization, intracellular survival and proliferation during active infection, and persistence during clinically inapparent infection with the capacity for reactivation . To thrive within the harsh environment of a professionally phagocytic and antimicrobial host cell, H . capsulatum displays mechanisms for modulating its microenvironmental pH level, resisting host reactive oxygen and nitrogen intermediates and degradative enzymes, and withstanding nutrient starvation conditions, including acquisition of iron and calcium and biosynthesis of nucleic acid precursors . Attention has been focused on identifying virulence-associated phenotypic traits and genes that are differentially expressed under relevant conditions, such as yeast morphotype-specific genes and genes that are up-regulated during infection . These studies, together with the increasing ability to perform molecular genetic manipulations in this fungus, may yield novel antifungal drug or vaccine targets as well as elucidating pathogenic mechanisms .

Can Respir J, 2001 Jul-Aug, 8(4), 255 - 60
The use of guidelines for the empirical treatment of hospital-acquired pneumonia; Miletin MS et al.; BACKGROUND: Several practice guidelines for the empirical antimicrobial treatment of hospital-acquired pneumonia (HAP) have been developed, but the acceptance and use of such guidelines are unknown . OBJECTIVE: To assess physicians' use of empirical HAP guidelines published by the American Thoracic Society (ATS) and by The University Health Network, Toronto, Ontario . DESIGN: A retrospective assembly and chart review . SETTING: A university teaching hospital . PATIENTS: One hundred fifteen consecutive patients who had been diagnosed with pneumonia more than 48 h after admission to hospital over a 10-month period . RESULTS: The charts of 115 patients were reviewed . Seventy-five patients (65%) were treated empirically . Forty patients (35%) were treated based on microbiological data that were available before the initiation of antibiotics . Patients who received nonempirical treatment for HAP had a significantly greater acuity of illness than the empirically treated group . Thirty-seven patients (49%) who received empirical therapy were treated according to either ATS or hospital guidelines for HAP . The use of guideline-concordant antimicrobial therapy had no measurable effect on in-hospital mortality (eight of 37 patients {21.6%} versus seven of 38 patients {18.4%}, P=0.96) or median length of stay (19 days versus 21 days, P=0.30) . Patients whose treatment did not follow guideline recommendations tended to receive appropriate antimicrobial coverage more often than did those patients whose treatment was guideline concordant (15 of 18 patients {83%} versus six of 11 patients {55%}, P=0.49) . CONCLUSIONS: Institutional and ATS guidelines for the empirical treatment of HAP are less widely used than would be predicted by chance at The University Health Network . The clinical utility of these guidelines remains to be proven.

J Endotoxin Res, 2000, 6(6), 459 - 62
LPS-induced immune response in Drosophila; Imler JL et al.; The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity . In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity . We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection . We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors . However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes . These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila.

J Nat Prod, 2001 Aug, 64(8), 1095 - 7
Samioside, a new phenylethanoid glycoside with free-radical scavenging and antimicrobial activities from Phlomis samia; Kyriakopoulou I et al.; A new phenylethanoid glycoside, samioside, was isolated from the aerial parts of Phlomis samia and identified as 1-O-3,4-(dihydroxyphenyl)ethyl beta-D-apiofuranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)-4-O-caffeoyl-beta-D-glucopyranoside (1) . In addition, one known phenylethanoid glycoside and three known flavonoids were identified as acteoside (2), apigenin, chrysoeriol, and ermanin, respectively . The structure of 1 was elucidated on the basis of its spectroscopic data . Samioside (1) demonstrated scavenging properties toward the DPPH radical and antimicrobial activity against Gram-positive and -negative bacteria.

Biochem Biophys Res Commun, 2001 Aug 31, 286(4), 820 - 5
IsCT, a novel cytotoxic linear peptide from scorpion Opisthacanthus madagascariensis; Dai L et al.; A novel cytotoxic linear peptide, IsCT, was characterized from scorpion Opisthacanthus madagascariensis . It is a linear peptide with a molecular weight of 1501.9 Da composed of 13 amino acid residues without cysteines . MS/MS analysis showed that its C-terminal is amidated . The identity of IsCT is re-confirmed by comparing the chemical synthesized peptide with the natural one . IsCT demonstrated antimicrobial activity against both gram-positive and gram-negative bacteria and hemolytic activity to sheep red blood cells . Also, it can release histamine from rat peritoneal mast cells . The CD absorption suggested that IsCT had an alpha-helix configuration in aqueous TFE . IsCT is one of the shortest natural cytotoxic peptides described, and it will be a suitable model for studying peptide-lipid interactions .

Infect Control Hosp Epidemiol, 2001 Jun, 22(6), 379 - 82
Differences in antimicrobial susceptibility among hospitals in an integrated health system; Lubowski TJ et al.; We evaluated the differences in antimicrobial susceptibility among hospitals in three different integrated healthcare systems . Each system provided antibiogram-susceptibility reports from representative hospitals . Reports were analyzed for statistically significant differences between hospitals in a given system for nine important organisms . We found numerous significant interhospital differences in antimicrobial-susceptibility patterns within health systems . For this reason, the practice of combining antibiotic-susceptibility data into a systemwide antibiogram should be discouraged.

Yonsei Med J, 2001 Aug, 42(4), 457 - 70
Helicobacter pylori infection in Korea; Park IS et al.; Helicobacter pylori is a gram-negative bacterium that was first isolated in 1982 . Since then, H . pylori infection in humans has been shown to be associated with gastritis, peptic ulcer disease, gastric carcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma as well . The epidemiology, transmission, and pathogenicity of H . pylori has been a subject of intensive study . Successful treatment improves the cure rate of peptic ulcerations and treatment with antimicrobials also decreases the recurrence rate of these diseases . Better regimens having less toxicity and a good eradication rate have also been developed . A better understanding of the pathophysiologic mechanisms relating to H . pylori induced mucosal damages would result in more options for the prevention of peptic ulcers and carcinogenesis . Korea has a relatively high incidence of H . pylori infection and gastric cancer . Growing interest has developed in view of its importance in being associated with various gastroduodenal diseases . Furthermore, along with a high incidence of H . pylori-related disease in Korea, because the interaction between H . pylori, host factors and environmental factors is important in disease pathogenesis, we need to have precise data on the characteristics of H . pylori-related diseases that occur in Korea . In the present report we review the epidemiology, transmission route, diagnosis, pathogenesis, treatment methods and relationship with gastroduodenal diseases with in special references to basic and clinical data that have been published.

J Mol Biol, 2001 Aug 24, 311(4), 789 - 801
Crystal structures of cystathionine gamma-synthase inhibitor complexes rationalize the increased affinity of a novel inhibitor; Steegborn C et al.; Cystathionine gamma-synthase catalyzes the committed step of methionine biosynthesis . This pathway is unique to microorganisms and plants, rendering the enzyme an attractive target for the development of antimicrobials and herbicides . We solved the crystal structures of complexes of cystathionine gamma-synthase (CGS) from Nicotiana tabacum with inhibitors of different compound classes . The complex with the substrate analog dl-E-2-amino-5-phosphono-3-pentenoic acid verifies the carboxylate-binding function of Arg423 and identifies the phosphate-binding pocket of the active site . The structure shows the function of Lys165 in specificity determination and suggests a role for the flexible side-chain of Tyr163 in catalysis . The importance of hydrophobic interactions for binding to the active-site center is highlighted by the complex with 3-(phosphonomethyl)pyridine-2-carboxylic acid . The low affinity of this compound is due to the non-optimal arrangement of the functional groups binding to the phosphate and carboxylate-recognition site, respectively . The newly identified inhibitor 5-carboxymethylthio-3-(3'-chlorophenyl)-1,2,4-oxadiazol, in contrast, shows the highest affinity to CGS reported so far . This affinity is due to binding to an additional active-site pocket not used by the physiological substrates . The inhibitor binds to the carboxylate-recognition site, and its tightly bent conformation enables it to occupy the novel binding pocket between Arg423 and Ser388 . The described structures suggest improvements for known inhibitors and give guidelines for the development of new lead compounds .

Int J Food Microbiol, 2001 Aug 5, 67(3), 227 - 39
Modelling the effects of (green) antifungals, droplet size distribution and temperature on mould outgrowth in water-in-oil emulsions; ter Steeg PF et al.; Prevention of fungal spoilage is a key microbiological issue for the shelf life of fat spreads . Our aim was to assess and model the scope of (natural) antimicrobials for extending shelf life of spreads (water-in-oil emulsions) . Production conditions were established to make 60% model fat spreads with reproducible droplet size distributions . The mould vulnerabilities ranged from 1 to 20 weeks . The system allowed feasibility testing of lytic enzymes (Novozym 234) and LMW compounds against Penicillium roqueforti, a key-spoilage mould . The action of Novozym 234, carvacrol, undecanol and dihydrocarveol was benchmarked against sorbate and preservative-free controls under ambient and chilled conditions . Novozym 234 was ineffective to prevent outgrowth of P . roqueforti . Carvacrol, undecanol and dihydrocarveol had limited effects on shelf-life extension compared to sorbate . Fungal growth boundaries of (un-)preserved spreads were modelled . The emulsion droplet size distribution (DSD) was first captured in a mechanistic parameter DSD-I (I = Influence) . DSD-I was a move away from the mean droplet diameter D3,3 as sole quantitative droplet-size distribution parameter for mould susceptibility of emulsions . DSD-I is a combination of available water droplets and surface area to initiate and sustain fungal outgrowth . Followup experiments showed that modelling D3,3 and distribution width (e(sigma)) instead of DSD-I gave better results for emulsions with high e(sigma) . Empirical predictive models were subsequently developed for the effects of D3,3, e(sigma) and undissociated sorbic acid (HSO) on the shelf life of emulsions.

J Air Waste Manag Assoc, 2001 Aug, 51(8), 1219 - 26
Investigation of the potential antimicrobial efficacy of sealants used in HVAC systems; Foarde KK et al.; Recent experiments confirm field experience that duct cleaning alone may not provide adequate protection from regrowth of fungal contamination on fiberglass duct liner (FGDL) . Current recommendations for remediation of fungally contaminated fiberglass duct materials specify complete removal of the materials . But removal of contaminated materials can be extremely expensive . Therefore, a common practice in the duct-cleaning industry is the postcleaning use of antimicrobial surface coatings with the implication that they may contain or limit regrowth . Little information is available on the efficacy of these treatments . This paper describes a study to evaluate whether three commercially available antimicrobial coatings, placed on a cleaned surface that 1 year previously had been actively growing microorganisms, would be able to prevent regrowth . The three coatings contained different active antimicrobial compounds . All three of the coatings were designed for use on heating, ventilation, and air conditioning (HVAC) system components or interior surfaces of lined and unlined duct systems . Coating I was a polyacrylate copolymer containing zinc oxide and borates . Coating II was an acrylic coating containing decabromodiphenyl oxide and antimony trioxide . Coating III was an acrylic primer containing a phosphated quaternary amine complex . The study included field and laboratory assessments . The three treatments were evaluated in an uncontrolled field setting in an actual duct system . The laboratory study broadened the field study to include a range of humidities under controlled conditions . Both static and dynamic chamber laboratory experiments were performed . The results showed that two of the three antimicrobial coatings limited the regrowth of fungal contamination, at least in the short term (the 3-month time span of the study); the third did not . Before use in the field, testing of the efficacy of antimicrobial coatings under realistic use conditions is recommended because antimicrobials have different baseline activities and interact differently with the substrate that contains them and their local environment.

J Pharm Pharmacol, 2001 Aug, 53(8), 1047 - 67
Chitosan: some pharmaceutical and biological aspects--an update; Singla AK et al.; Chitosan, a natural polysaccharide, is being widely used as a pharmaceutical excipient . It is obtained by the partial deacetylation of chitin, the second most abundant natural polymer . Chitosan comprises a series of polymers varying in their degree of deacetylation, molecular weight, viscosity, pKa etc . The presence of a number of amino groups permit chitosan to chemically react with anionic systems, thereby resulting in alteration of physicochemical characteristics of such combinations . Chitosan has found wide applicability in conventional pharmaceutical devices as a potential formulation excipient, some of which include binding, disintegrating and tablet coating properties . The polymer has also been investigated as a potential adjuvant for swellable controlled drug delivery systems . Use of chitosan in novel drug delivery as mucoadhesive, gene and peptide drug administration via the oral route as well as its absorption enhancing effects have been explored by a number of researchers . Chitosan exhibits myriad biological actions, namely hypocholesterolemic, antimicrobial and wound healing properties . Low toxicity coupled with wide applicability makes it a promising candidate not only for the purpose of drug delivery for a host of drug moieties (antiinflammatories, peptides etc.) but also as a biologically active agent . It is the endeavour of the present review to provide an insight into the biological and pharmaceutical profile of chitosan . Various investigations carried out recently are reported, although references to research performed on chitosan prior to the recent reviews have also been included, where appropriate.

Vestn Ross Akad Med Nauk, 2001, (6), 45 - 52
{Free radical oxidation as a link of early and prolonged adaptation to environmental factors}; Velichkovskii BT; Analyzing his own findings and the data available in the literature, the author has found that free radicals are a connecting link in the development of early and prolonged adaptation . With rapid adaptation, they make a weighty contribution to the body's bactericidal protection and antimicrobial constitutional immunity . This role is mainly played by the oxygen-dependent phagocytic bactericidal system that generates active oxygen forms and by the inducible arginine-dependent connective tissue cell system that synthesizes nitrogen oxide . While performing, the above enzymatic systems spend their cell energy resources on two concurrent processes: the formation of free radical products and the work of ionic pumps that restore an intracellular ionic and osmotic balance . This causes the accelerated expenditure of the body's energy "currency" ATP and the development of energy deficiency in the cells and tissues . Energy shortage serves as a signal for triggering the cellular genetic apparatus to primarily induce the increased development of the cell energy system, namely that of mitochondria, and the activation of the key systems responsible for steady-state long-term individual adaptation of the immune system, antioxidative protection, etc . It has been now ascertained that there is a common pathogenetic link (excessive production of free radicals) in the mechanism responsible for the influence of not only infections on the body, but other environmental factors (fibrogenic dust, ionizing or ultraviolet radiation, cooling, toxic agents oxidized on cytochrome P-450, hypoxia, hyperoxia, etc.) and vital functions (physical overstrain, emotional stress, informational overload, etc.) . The above factors all cause the same metabolic change in different ways: the production of higher quantities of active oxygen forms, nitrogen oxide, and other radical products . So the generation of free radicals is an universal connecting link of early and prolonged adaptation . The fact that there is a common link (the excessive production of radicals) in the mechanism of influence of environmental factors and vital activities makes the most important biological reserve (cross adaptation that lies in higher resistance to the whole complex of active influences at adaptation to one of them) serve as a preventive means . The most rapid increase in the production of free radicals and the development of energy-rich products are achieved by hypoxia . So the adaptive and preventive effect of dosage hypoxia are the most pronounced.

J Immunol Methods, 2001 Oct 1, 256(1-2), 65 - 76
Detection of beta-defensins secreted by human oral epithelial cells; Diamond DL et al.; Human beta-defensins are antimicrobial peptides that may be critical in the innate immune response to infection . hBD1 and hBD2 are expressed in oral epithelial cells and are detected near the surface of oral tissue, consistent with a role in the epithelial protective barrier function . In this report, we examine secretion of beta-defensins in vitro and in biological fluid using ProteinChip(R) Array, surface enhanced laser desorption/ionization (SELDI) technology combined with time-of-flight mass spectrometry . We show that the 47-amino acid form of hBD1 and the 41-amino acid form of hBD2 are the major secreted forms . These forms are both expressed and secreted under conditions anticipated from previous analysis of beta-defensin mRNAs; specifically, hBD1 is detected in culture supernatant from both unstimulated and stimulated cells, and hBD2 is detected only in stimulated cells . Identity of hBD1 and hBD2 was confirmed by immunocapture on the ProteinChip surface . Both peptides are also present in gingival crevicular fluid that accumulates between the tissue and tooth surface, although hBD1 is also found in several smaller forms suggesting extracellular proteolysis . This methodology offers several technical advantages for detection of defensins in biological fluids, including ease and speed of screening, no need for HPLC preliminary processing, and small sample size.

J Chromatogr Sci, 2001 Aug, 39(8), 339 - 44
A simplex-optimized chromatographic separation of fourteen cosmetic preservatives: analysis of commercial products; Marengo E et al.; An ion-interaction high-performance liquid chromatography (HPLC)-diode-array detection method is developed and optimized for the separation of typical antimicrobial agents used in cosmetics and hygiene products . The most used preservatives contain different molecular structures, different functionalities, and are characterized by different chemical properties . Organic acids, alkyl esters of benzoic acids, alkyl p-hydroxy benzoic acids (parabens), phenol derivatives, and carbanilides represent the most used preservatives, and are often present in multicomponent mixtures . In order to develop a multicomponent method to be used in quality control analysis, the ion-interaction reagent reversed-phase HPLC technique seems to be particularly suitable, because it allows for the simultaneous separation of acidic, basic, and neutral species . The experimental conditions of the method are developed by OVAT (one variable at a time) treatment and further optimized by a multivariate approach based on a Simplex algorithm that works on a desirability function targeted to maximize the resolution in a multicomponent mixture . The new method proposed that is able to simultaneously separate fourteen preservatives is applied in the analysis of commercial products.

Immunol Rev, 2001 Jun, 181, 158 - 69
Ligands for natural killer cell receptors: redundancy or specificity; Cerwenka A et al.; Several inhibitory and activating receptors involved in natural killer cell activation have been characterized . The increasing knowledge about their ligands, including classical MHC class I molecules, non-classical MHC class I molecules and MHC class I-related molecules, is shedding new light on the targets of innate immune recognition . While classical MHC class I molecules are constitutively expressed, some MHC class I-related (MIC) molecules, however, are stress-induced by ill-defined stimuli . Two families of ligands for the human activating NKG2D receptor have been identified . These are the MIC proteins encoded by two highly polymorphic genes within the MHC class I and the retinoic acid-inducible early gene-1-like (also designated UL16-binding) proteins encoded by genes outside the MHC . For the mouse NKG2D receptor, one family, containing at least five distinct ligands, has been described . A better understanding about how targets signal their distress, which renders them susceptible to natural killer (NK)-cell attack, will help to define the role of NK cells in antimicrobial and antitumor immunity and transplantation.

Obstet Gynecol Clin North Am, 2001 Sep, 28(3), 553 - 69
Pneumonia in pregnancy; Ramsey PS et al.; Although the advent of broad-spectrum antibiotics has markedly improved the maternal outcomes of pneumonia complicating pregnancy, pneumonia remains a significant condition that may complicate pregnancy . This article has reviewed the inherent physiologic respiratory changes that accompany pregnancy and the common causes of pneumonia in the pregnant woman . The clinical course of bacterial pneumonia seems to be minimally altered by pregnancy, whereas viral pneumonia carries a significantly worse prognosis when encountered during gestation . Prompt diagnosis, the initiation of respiratory support, and appropriate antimicrobial/antiviral therapy are key components of therapy for women in whom pregnancy is complicated by pneumonia . Because preterm labor frequently accompanies pneumonia, women should be monitored closely for the occult onset of preterm labor and appropriate interventions initiated if indicated . Perhaps even more important than interventions to treat acute pneumonia are efforts directed at active immunization or prophylactic therapy to prevent the development of pneumonia in select patient populations . The combination of these efforts is essential to optimize medical care for pregnant women.

Clin Infect Dis, 2001 Sep 15, 33(6), 817 - 28 Epub 2001 Aug 06.
Infectious diseases journals on the World Wide Web: attractions and limitations; Abbas UL et al.; Online infectious diseases (ID) journals are an increasingly common Web phenomenon . We performed a study of practices in this evolving area that make these sites more usable and useful from the perspective of ID physicians . The Web sites of 18 journals pertaining to general ID and infection control and hospital epidemiology were evaluated for a set of 24 Web interface characteristics and online features . Journals hosted by the High Wire Press (Antimicrobial Agents and Chemotherapy, Infection and Immunity, and the Journal of Antimicrobial Chemotherapy) and the University of Chicago Press (The Journal of Infectious Diseases and Clinical Infectious Diseases) best fulfilled our criteria . Electronic reference linking, archives, e-mail alerts, and links to external resources are some of the features of electronic journals that users in the ID specialty may find especially useful.

Crit Care, 2001 Aug, 5(4), 189 - 95 Epub 2001 Jun 28.
Optimizing antibiotic therapy in the intensive care unit setting; Kollef MH; Antibiotics are one of the most common therapies administered in the intensive care unit setting . In addition to treating infections, antibiotic use contributes to the emergence of resistance among pathogenic microorganisms . Therefore, avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will help to improve patient outcomes while minimizing further pressures for resistance . This review will present several strategies aimed at achieving optimal use of antimicrobial agents . It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilization and its effectiveness . Only in this way can the impact of interventions aimed at improving antibiotic use (e.g . antibiotic rotation, de-escalation therapy) be evaluated at the local level.

Adv Perit Dial, 2001, 17, 180 - 90
The case for oral treatment of peritonitis in continuous ambulatory peritoneal dialysis; Passadakis P et al.; Among several regimes used in the oral treatment of continuous ambulatory peritoneal dialysis (CAPD)--related peritonitis, ciprofloxacin and ofloxacin showed the higher treatment efficacy, with an overall cure rate of 80% over a treatment duration of 10-16 days . The antimicrobial activity of these agents against gram-positive episodes was equal to or even higher than that against other peritonitis episodes, and the effectiveness of oral ciprofloxacin can be further increased either by an additional intraperitoneal dose for the first 1-5 days, or by a simultaneous intraperitoneal dose of vancomycin in the first 24 hours . Clinical resistance to the new quinolones has been uncommon . The possibly increasing resistance to ciprofloxacin is a consequence of suboptimal dosing, with the resulting low local concentrations of the antibiotic . Oral treatment with quinolones provides a good therapeutic alternative to more widely used antibiotics for initial treatment of peritonitis episodes . However, more extensive data from comparative randomized studies with agents administered orally and intraperitoneally would be able to clearly elucidate the overall safety and success of oral treatment of PD-related peritonitis with quinolones or any new agent.

Rev Med Chil, 2001 Jun, 129(6), 643 - 6
{In vitro antimicrobial susceptibility of Helicobacter pylori strains: isolation of strains resistant to clarithromycin}; Gonzalez C et al.; BACKGROUND: Our laboratory has carried out an epidemiological surveillance of Helicobacter pylori antimicrobial susceptibility since 1997 . AIM: To report the antimicrobial susceptibility of H pylori strains, isolated in Chile from August 1997 to August 2000 . MATERIAL AND METHODS: Ninety one H pylori strains, obtained from antral gastric biopsies during upper gastrointestinal endoscopies were studied . Susceptibility towards clarithromycin, amoxicillin, bismuth subcitrate and metronidazole was studied by an agar diffusion technique . RESULTS: All strains were susceptible to amoxicillin and two strains were resistant to clarithromycin . Forty two percent of strains were resistant to metronidazole and 13% were resistant to bismuth subcitrate . CONCLUSIONS: These results underscore the need to maintain an epidemiological surveillance of H pylori antimicrobial susceptibility, to modify its eradication therapy accordingly.

Planta Med, 2001 Aug, 67(6), 580 - 4
Essential oil composition and antimicrobial activity of three Zingiberaceae from S.Tomé e Príncipe; Martins AP et al.; The essential oil composition of three Zingiberaceae widely used as medicinal aromatic plants from S . Tome and Principe: Aframomum danielli (Hook . f.) K . Schum., Curcuma longa L . and Zingiber officinale Rosc . was studied . Two samples of the essential oils from fruit of A . danielli and from rhizomes of the other two species, were obtained by hydrodistillation and analyzed by GC, GC-MS, and (13)C-NMR . The essential oil from fruits of A . danielli has been studied for the first time and was characterised by its high content of monoterpenes, with 1,8-cineole (25.5 - 34.4 %) the major constituent, followed by beta-pinene (14.1 - 15.2 %) and alpha-terpineol (9.9 - 12.1 %) . Essential oils from the rhizomes of C . longa contained a lower content of ar-turmerone (4.0 - 12.8 %) than those reported in the literature for C . longa from other origins (24.7 - 31.4 %), whereas the results for Z . officinale essential oils were in accordance with the literature data . The essential oils of A . danielli and Z . officinale showed antimicrobial activity against all Gram-positive and Gram-negative bacteria tested, as well as against yeasts and filamentous fungi, using the agar diffusion method.

J Immunol, 2001 Sep 1, 167(5), 2861 - 8
Human IgA activates the complement system via the mannan-binding lectin pathway; Roos A et al.; The recently identified lectin pathway of the complement system, initiated by binding of mannan-binding lectin (MBL) to its ligands, is a key component of innate immunity . MBL-deficient individuals show an increased susceptibility for infections, especially of the mucosal system . We examined whether IgA, an important mediator of mucosal immunity, activates the complement system via the lectin pathway . Our results indicate a dose-dependent binding of MBL to polymeric, but not monomeric IgA coated in microtiter plates . This interaction involves the carbohydrate recognition domain of MBL, because it was calcium dependent and inhibited by mannose and by mAb against this domain of MBL . Binding of MBL to IgA induces complement activation, as demonstrated by a dose-dependent deposition of C4 and C3 upon addition of a complement source . The MBL concentrations required for IgA-induced C4 and C3 activation are well below the normal MBL plasma concentrations . In line with these experiments, serum from individuals having mutations in the MBL gene showed significantly less activation of C4 by IgA and mannan than serum from wild-type individuals . We conclude that MBL binding to IgA results in complement activation, which is proposed to lead to a synergistic action of MBL and IgA in antimicrobial defense . Furthermore, our results may explain glomerular complement deposition in IgA nephropathy.

Phytother Res, 2001 Aug, 15(5), 437 - 40
Antimicrobial activity of seed extracts and bondenolide from Caesalpinia bonduc (L.) Roxb; Simin K et al.; The antibacterial and antifungal activities, along with a phytotoxicity test of the newly isolated diterpene bondenolide (1), of a methanol extract, ethylacetate fraction and water soluble part of the methanol extract of Caesalpinia bonduc (L.) Roxb . were assayed .

Eur J Gastroenterol Hepatol, 2001 Aug, 13(8), 967 - 9
Metallic cough and pyogenic liver abscess; Ala A et al.; The curious symptom of a metallic cough in association with a pyogenic hepatic abscess should heighten awareness of a fistula . We describe a 78-year-old female with severe diverticular disease, on long-term steroid treatment for polymyalgia rheumatica . She developed a pyogenic liver abscess, treated initially by antimicrobial therapy, and subsequently drained by ultrasound and computed tomography-guided percutaneous transhepatic pigtail catheterization . This was complicated by a fistulous communication between the abscess cavity and the bronchus, confirmed by radiology . After repeated attempts at drainage and antimicrobial therapy the abscess cavity, including the hepatobronchial fistula, resolved.

Braz J Infect Dis, 2001 Jun, 5(3), 124 - 9 Epub 2003 Feb 19.
Treatment of nosocomial pneumonia: an experience with meropenem; Santos SS et al.; This study aimed at evaluating the efficacy and safety of meropenem as first choice treatment for nosocomial pneumonia (NP) in intensive care units (ICU) in Hospital das Clinicas (HC) - University of Sao Paulo; a hospital with high incidence of antimicrobial resistance . Prospective, open, and non-comparative trial with meropenem were done in patients with ventilator-associated or aspiration NP in 2 ICUs at HC - University of Sao Paulo . Etiologic investigation was done through bronchoalveolar lavage and blood cultures prior to study entry . Twenty-five (25) critically ill patients with NP were enrolled (mean age 40 years) . Ventilator-acquired pneumonia was responsible for 76% of cases and aspiration NP for 24% . Specific etiologic agents were identified and considered to be clinically and temporally responsible for NP in 11 (44%) patients . A . baumanii was responsible for 6 cases (55%), P . aeruginosa for 3 (27%), and S . aureus for 2 (18%) . At completion of treatment, 19 patients (76%) showed either cure (48%) or improvement (28%) after use of meropenem therapy . Mortality was 12% at the end of therapy (8% after excluding 1 non-evaluable patient) . After 4 to 6 weeks of follow-up, 12 (48%) patients had improved or been totally cured, and overall mortality was 24% . Clinical complications were observed in 11 patients (44%), with none of them definitely related to the study drug . Meropenem as monotherapy was effective and well-tolerated in most NP patients in our ICU . The low mortality rate in this study might have been due to first choice use of this drug . Controlled, drug comparative clinical trials are needed to support this preliminary observation.

Am J Reprod Immunol, 2001 Aug, 46(2), 169 - 79
Comparative T-cell responses during pregnancy in large animals and humans; Meeusen EN et al.; PROBLEM: Placentation in different large animal species shows a remarkable diversity in the level of trophoblast invasion into the maternal endometrial tissues . We wish to determine the influence of implantation on T-cell responses during pregnancy . METHOD OF STUDY: Review of the literature and current data . RESULTS: alphabeta-TCR+ T cells are only prominent during early pregnancy in species with relatively non-invasive placentation (pig and horse) but are rapidly downregulated in species with more invasive placentae . gammadelta-TCR+ T cells are prominent in species with moderate trophoblast invasion (ruminants) where they increase dramatically during mid and late pregnancy . gammadelta-TCR+ T cells remain prominent during late gestation in species with highly invasive placentation (humans) and, in addition, a distinct gammadelta T-cell population is present in first trimester decidua where it may play a regulatory role in controlling natural killer cell activity . The gammadelta-TCR+ population present in both ruminants and humans shows large granular morphology and contains antimicrobial proteins, suggesting their function may be to protect the uterine environment from infection during pregnancy and parturition . CONCLUSION: The comparative analysis of T-cell responses during pregnancy in different large animal species supports an increasing role for cells of the innate immune response (NK and gammadelta T cells) and a downregulation of the adaptive immune response with increasingly invasive placentation.

Arch Ital Urol Androl, 2001 Mar, 73(1), 15 - 25
{Antioxidant therapeutic efficiency after the use of carnitine in infertile patients with bacterial or non bacterial prostato-vesiculo-epididymitis}; Vicari E et al.; OBJECTIVE: In the male genital tract, reactive oxygen species (ROS) overproduction generated by infiltrating WBC or spermatozoa is one of the major causes of defective sperm function . Recently, we demonstrated that prostato-vesiculo-epididymitis (PVE) is the male accessory gland infection more crucial for the establishment of this cellular (sperm and/or WBC oxidative) response . This biochemical stress is due to an imbalance of pro and antioxidants factors and persists even after treatment with antimicrobials . Thus, the antioxidative properties of Carnitines (in terms of combined "Carnitine-Acetil-Carnitine" system) have currently found more attention as part of antimicrobial therapies . In this study, we compared which antioxidative strategy was more beneficial for the treatment of PVE . MATERIALS AND METHODS: We selected two groups of infertile patients . One group consisted of 55 abacterial PVE patients (mean age 34 yrs, range 27-40) (group A); the other included other 35 bacterial PVE patients (mean age 35 yrs, range 28-38) (group B) . Each group was randomly subdivided into the following treatment subsets: 1) A1 (n = 14) and B1 (n = 23) subsets received respectively a combined antibiotic and/or antiphlogistic regimen (x 14 days/ monthly x 3 months) (first step) followed by L-Carnitine 1 g x 2 day + acetyl-Carnitine 0.5 g x 2/day x other 3 months (second step) and finally no drug x other 3 months (third step) . 2) A2 (n = 8) and B2 (n = 16) subsets received, for a 3 month period, in the meantime the combined antibiotic and/or antiphlogistic regimen (x 14 days/monthly) and L-Carnitine 1 g x 2/day + acetyl-Carnitine 0.5 g x 2/day (first step) and finally no drug x other 3 months (second step) . 3) A3 (n = 8) and B3 (n = 12) subsets received for a 3-month period L-Carnitine 1 g x 2/day + acetyl-Carnitine 0.5 g x 2 day (first step) and finally no drug x other 3 months (second step) . Before and after each step of the therapeutical design, all patients underwent semen and quantitative bacteriological analyses and 60/90 semen specimens were also investigated about ROS production analysis by chemiluminescence in their 45% and 90% Percoll-generated fractions . RESULTS: The antioxidative response either in terms of significant decrease in the ROS production and increase in some semen parameters (sperm motility and viability) were highest in the patients of A1/B1 subsets, followed by A2/B2 subsets and lowest in the A3/B3 subsets . CONCLUSION: These results indicate that in PVE patients antimicrobials and/or antiphlogistic drugs get a full positive antimicrobial response but a partial antioxidative response, which seems to be potentiated by the addition of antioxidative agents (Carnitines) . Furthermore, it is important to underline that the antioxidative treatment with Carnitines administered in the meantime with antiinfectious agents is less effective, and finally this treatment is unsuccessful without the eradication of the pro-oxidant (germs and WBC) agents.

Arzneimittelforschung, 2001, 51(7), 588 - 95
Efficacy of cetylpyridinium chloride used as oropharyngeal antiseptic; Pitten FA et al.; Cetylpyridinium chloride, (CPC, CAS 123-03-5) as active ingredient of antiseptic oral mouthrinses has a broad antimicrobial spectrum with a rapid bactericidal effect on gram-positive pathogens and a fungicide effect on yeasts in particular . There are gaps in its effectiveness against gram-negative pathogens and mycobacteria . Application of CPC at a concentration of 0.05% as a mouthrinse results in an immediate reduction in bacterial counts of 2.0 to 2.5 log steps (which is adequate to > 99%) . This reverts to about 1 log step (= 90%) 1 h after application . The ability of CPC to inhibit plaque and thereby reduce gingivitis is assured . In comparison to chlorhexidine, CPC has a lower residual effect, and as a result a lesser effect against plaque and gingivitis . The efficacy of CPC against oropharyngeal candidiasis is assured . CPC mouthrinses can significantly reduce infectious aerosols in dental practice, thereby protecting both staff and the patient . The balance of intra-oral bacterial flora is not disturbed even in the case of relatively long-term use of CPC (up to six weeks) . Taking these properties into consideration, CPC may be considered as an alternative active ingredient in the case of chlorhexidine intolerance in the treatment and prevention of bacterial or fungal disorders of the oropharyngeal cavity . It is also of interest as an element for combination in the development of new types of oropharyngeal antiseptics.

Rev Belge Med Dent, 2000, 55(4), 345 - 51
{The use of glass ionomer cements in endodontics}; De Moor R et al.; Glass ionomer cements are currently used in endodontic therapy for sealing root canals (orthogradely and retrogradely), for sealing and restoring the pulp chamber, for repairing perforations and root resorption defects, and, rarely, for treating vertically fractured teeth . The successful use of these cements is the result of their particular characteristics: a chemical bond to dentin, which enhances the seal of the root canal and the reinforcement of the tooth; a good biocompatibility in the periradicular area and a fluoride release without loss of strength of the material . The fluoride release imparts an antimicrobial effect to combat root canal infection and attributes to bone mineralization after surgery . The present paper reviews the literature regarding the various applications of glass ionomer cements in present-day endodontics.

Am J Physiol Lung Cell Mol Physiol, 2001 Sep, 281(3), L517 - 23
Lung surfactant and reactive oxygen-nitrogen species: antimicrobial activity and host-pathogen interactions; Hickman-Davis JM et al.; Surfactant protein (SP) A and SP-D are members of the collectin superfamily . They are widely distributed within the lung, are capable of antigen recognition, and can discern self versus nonself . SPs recognize bacteria, fungi, and viruses by binding mannose and N-acetylglucosamine residues on microbial cell walls . SP-A has been shown to stimulate the respiratory burst as well as nitric oxide synthase expression by alveolar macrophages . Although nitric oxide (NO.) is a well-recognized microbicidal product of macrophages, the mechanism(s) by which NO . contributes to host defense remains undefined . The purpose of this symposium was to present current research pertaining to the specific role of SPs and reactive oxygen-nitrogen species in innate immunity . The symposium focused on the mechanisms of NO*-mediated toxicity for bacterial, human, and animal models of SP-A- and NO.-mediated pathogen killing, microbial defense mechanisms against reactive oxygen-nitrogen species, specific examples and signaling pathways involved in the SP-A-mediated killing of pulmonary pathogens, the structure and binding of SP-A and SP-D to bacterial targets, and the immunoregulatory functions of SP-A.

Bioorg Med Chem, 2001 Aug, 9(8), 2015 - 24
The synthesis and screening of 1,4,5,8-naphthalenetetracarboxylic diimide-peptide conjugates with antibacterial activity; Miller CT et al.; We have employed an initial combinatorial approach followed by systematic lead optimization to investigate a series of novel molecules that exhibit antimicrobial activity against Gram-negative and Gram-positive bacteria . The new molecules contain various sequences of amino acids, generally L-lysine and glycine, attached to the 1,4,5,8-naphthalenetetracarboxylic diimide aromatic unit . Systematic structure-activity studies found that increasing positive charge enhanced activity and molecules containing one naphthalenetetracarboxylic diimide unit as well as at least seven lysine residues were optimum for antimicrobial activity . The naphthalenetetracarboxylic diimide derivatives were found to be inactive against mammalian cell lines, making them excellent antimicrobial candidates . Our results indicate that combining positive charge with aromatic and/or hydrophobic elements may be an interesting new approach to antimicrobial agents and adds an important new dimension to the field of cationic peptides.

Drug Resist Updat, 1999 Apr, 2(2), 116 - 126
Antimicrobial peptides from platelets; Yeaman MR et al.; The fact that platelets play a key role in host defense against infection has been demonstrated by the following observations(1): (a) platelets rapidly respond to sites of endovascular trauma and chemotactic stimuli associated with microbial colonization, and they are the earliest and predominant cells at sites of microbial colonization of vascular endothelium; (b) platelets have surface receptors and cytoplasmic granules comparable in structure and function to those of neutrophils, monocytes, or macrophages; (c) platelets adhere directly to, and may internalize, microbial pathogens, thereby enhancing their clearance from the bloodstream and limiting their potential for hematogenous dissemination; (d) bacterial, fungal, and protozoal pathogens are damaged or killed by activated platelets in vitro; (e) platelets are capable of initiating or amplifying complement fixation in the presence of microorganisms; (f) platelets generate oxygen metabolites which likely contribute to their antimicrobial activity; (g) platelets and leukocytes interact synergistically to exert enhanced antimicrobial functions in vitro; (h) thrombocytopenia increases susceptibility to and severity of certain infections . Importantly, rabbit and human platelets are now known to contain and release microbicidal proteins (termed platelet microbicidal proteins {PMPs} or thrombin-induced PMPs {tPMPs}) when stimulated with microorganisms or platelet agonists associated with infection in vitro . It is hypothesized that these microbicidal peptides accumulate locally at sites of endovascular damage or infection . Recent investigations have confirmed that tPMP-susceptible pathogens are less capable of proliferation or hematogenous dissemination in vivo as compared with their isogenic counterpart strains that are resistant to PMPs . Collectively, the above observations strongly suggest that platelets play key and multi-faceted roles in antimicrobial host defense which appear to be significantly mediated by PMPs and tPMPs .

Mol Biotechnol, 2001 Jul, 18(3), 193 - 8
A simple method for the purification of an antimicrobial peptide in recombinant Escherichia coli; Hwang SW et al.; A magainin derivative, designated MSI-344, was produced in Escherichia coli as fusion protein, by utilizing a truncated amidophsphoribosyltransferase of E . coli as a fusion partner . Bacterial cells transformed with the gene encoding the fusion protein were grown to a high cell density and induced with isopropyl-1-thio-b-D-galatoside (IPTG) to initiate product expression . The fusion protein was accumulated into cytoplasmic inclusion body and recombinant MSI-344 was released from the fusion partner by hydroxylamine treatment . Following cleavage of the fusion protein with hydroxylamine, the released MSI-344 was purified to homogeneity by cationic exchange chromatography . The final purity was at least 95% by reversed-phase high performance liquid chromatography (RP-HPLC) . Purified recombinant MSI-344 was found to be indistinguishable from the synthetic peptide determined by amino acid sequences and antimicrobial activity assay.

Antimicrob Agents Chemother, 2001 Sep, 45(9), 2604 - 8
Susceptibilities of Mycoplasma hominis, M . pneumoniae, and Ureaplasma urealyticum to GAR-936, dalfopristin, dirithromycin, evernimicin, gatifloxacin, linezolid, moxifloxacin, quinupristin-dalfopristin, and telithromycin compared to their susceptibilities to reference macrolides, tetracyclines, and quinolones; Kenny GE et al.; The susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to eight new antimicrobial agents were determined by agar dilution . M . pneumoniae was susceptible to the new glycylcycline GAR-936 at 0.12 microg/ml and evernimicin at 4 microg/ml, but it was resistant to linezolid . It was most susceptible to dirithromycin, quinupristin-dalfopristin, telithromycin, reference macrolides, and josamycin . M . hominis was susceptible to linezolid, evernimicin, and GAR-936 . It was resistant to macrolides and the ketolide telithromycin but susceptible to quinupristin-dalfopristin and josamycin . U . urealyticum was susceptible to evernimicin (8 to 16 microg/ml) and resistant to linezolid . It was less susceptible to GAR-936 (4.0 microg/ml) than to tetracycline (0.5 microg/ml) . Telithromycin and quinupristin-dalfopristin were the most active agents against ureaplasmas (0.06 microg/ml) . The new quinolone gatifloxacin was active against M . pneumoniae and M . hominis at 0.12 to 0.25 microg/ml and active against ureaplasmas at 1.0 microg/ml . The MICs of macrolides were markedly affected by pH, with an 8- to 32-fold increase in the susceptibility of M . pneumoniae as the pH increased from 6.9 to 7.8 . A similar increase in susceptibility with increasing pH was also observed with ureaplasmas . Tetracyclines showed a fourfold increase of activity as the pH decreased 1 U, whereas GAR-936 showed a fourfold decrease in activity with a decrease in pH.

Pharmacotherapy, 2001 Aug, 21(8 Pt 2), 133S - 148S
Antifungal pharmacodynamics: concentration-effect relationships in vitro and in vivo; Groll AH et al.; The pharmacodynamics of antifungal compounds involve relationships among drug concentrations, time, and antimicrobial effects in vitro and in vivo . Beyond better understanding of a drug's mode of action, characterization of these relationships has important implications for setting susceptibility breakpoints, establishing rational dosing regimens, and facilitating drug development . Important advances have been made in the experimental investigation of pharmacokinetics and pharmacodynamics of antifungal drugs; however, much remains to be learned about specific pathogens and specific sites of infection . Increased incorporation of pharmacokinetic and pharmacodynamic principles in experimental and clinical studies with antifungal agents is an important objective that will benefit the treatment and prophylaxis of life-threatening invasive fungal infections in immunocompromised patients.

Anticancer Res, 2001 May-Jun, 21(3C), 2171 - 4
Human alpha-and beta-defensin immunoreactivity in oral mucoepidermoid carcinomas; Mizukawa N et al.; The purpose of this study was to demonstrate the immunohistochemical localization and distribution of human alpha- and beta-defensins, peptides with antimicrobial activity, in oral mucoepidermoid carcinoma tissue . Tissue samples were embedded in paraffin and alpha- and beta-defensins were immunostained by the streptavidin-biotin coupled peroxidase method . Cancer cells that constituted the ducts, as well as neutrophils, were positively immunostained with the anti-alpha-defensin antibody (HNPs) . On the other hand, epidermoid cells and intermediate cells were intensely stained with the anti-beta-defensin-2 (HBD-2) antibody . Mucous-secreting cells were clearly not immunostained with the anti-HBD-2 antibody . The epithelial hyperplasia region adjacent to the tumor tissues was also positively immunostained with the anti-HBD-2 antibody.

Am J Respir Crit Care Med, 2001 Aug 1, 164(3), 382 - 8
Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study; Bergmans DC et al.; Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated . Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis . In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis {control group A} and 61 patients were studied in an intensive care unit where no topical prophylaxis was used {control group B}) . Baseline characteristics were comparable in all three groups . Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A {p < 0.00001} and 9% in control group B patients {p < 0.00001}) and in trachea (52% versus 22% in A {p = 0.03} and 7% in B {p = 0.004}) . Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A {p < 0.00001} and 63% in B {p < 0.00001}) . Colonization rates in stomach and intestine were not affected . Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively) . This was not associated with shorter durations of ventilation or ICU stay or better survival . Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention . Keywords: cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects

Pharmacoepidemiol Drug Saf, 2001 Mar-Apr, 10(2), 143 - 8
Minimized analysis of costs applied to antimicrobial consumption in a rural area; Sanchez CC et al.; PURPOSE: Antimicrobial agents constitute one of the most utilized groups of drugs in daily clinical practice and, therefore they involve a significant expense . The aim of this study was to evaluate the economic cost of the antimicrobials prescribed in a rural area as well as to search for some cheaper alternatives . METHODS: Retrospective study . The economic cost of antimicrobial agents prescribed at a health centre over 18 months was studied . To do this, clinical histories of 800 people were reviewed . Afterwards, a minimized analysis of costs was carried out . RESULTS: The total cost of antimicrobial consumption came to 2,080.752 pts . The average expenditure per patient came to 6,433.85 +/- 14 269.29 pts . Significant differences between the sexes were not found; however, the expenditure in patients of 65 years of age or over was significantly higher than the rest . After applying the ABC analysis it was noticed that macrolides, cephalosporins, antimicrobial combinations and quinolones were the most important groups from an economic point of view . The use of monodose containers would allow us to save up to 7.83% of the total expenditure . In addition, by prescribing the cheapest marketed pharmaceutical product we could save a further 6.54%, and, finally, by combining these two measures the total possible saving would reach 299,052 pts, a 14.37% of the total expenditure . CONCLUSION: We consider important the elaboration of pharmacoeconomic guides as well as the introduction of monodose containers not only at hospitals but also at community pharmacists.

J Dent Res, 2001 Jun, 80(6), 1545 - 9
The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats; Sulkala M et al.; Previous studies suggest that salivary and pulp-derived host enzymes, matrix metalloproteinases (MMPs), may be involved in dentin caries pathogenesis . To study the inhibition of acid-activated human salivary MMPs by non-antimicrobial chemically modified tetracyclines (CMTs), we used a functional activity assay with 125I-labeled gelatin as a substrate . To address the role of MMPs in the progression of fissure caries in vivo, we administered the MMP inhibitors CMT-3 and zoledronate to young rats per os for 7 weeks, 5 days a week . Caries lesions were visualized by Schiff reagent in sagittally sectioned mandibular molars . Marked reduction in gelatinolytic activity of human salivary MMPs was observed with CMT-3 . CMT-3 and zoledronate, both alone and in combination, also reduced dentin caries progression in the rats . These results suggest that MMPs have an important role in dentin caries pathogenesis, and that MMP inhibitors may prove to be useful in the prevention of caries progression.

Drug Resist Updat, 2000 Oct, 3(5), 265 - 269
Infectious disease 2000: drug resistance and new drugs; Georgopapadakou NH; 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) was held in Toronto on 17-20 September 2000 . It attracted thousands of delegates from industry and academia and covered, in over 2300 oral and poster presentations, topics ranging from microbial pathogenesis to infection control, vaccines, antibiotic resistance and new antimicrobial agents . Summarized here are highlights on microbial resistance and agents in clinical and preclinical development .

Mol Plant Microbe Interact, 2001 Aug, 14(8), 947 - 54
Maize rhm1 resistance to Bipolaris maydis is associated with few differences in pathogenesis-related proteins and global mRNA profiles; Simmons CR et al.; The maize rhm1 mutant resists Bipolaris maydis, the causal agent of Southern corn leaf blight, by producing small necrotic lesions surrounded by chlorotic haloes . The rhm1 and wild-type lesions contain viable fungus in equal frequency, but fungal sporulation was markedly inhibited on rhm1 . The levels of the pathogenesis-related (PR) proteins chitinase, PR1, and peroxidase differ little between rhm1 and wild type, with or without B . maydis inoculation . The global mRNA profiles surveyed revealed hundreds of cDNA fragments that were twofold or more induced or suppressed in rhm1 and wild-type plants following B . maydis inoculation . Nonetheless, between rhm1 and wild type, only 0.4 to 0.7% of the cDNA fragments were expressed differentially by twofold or more . Among the up-regulated genes in rhm1 was beta-glucosidase glu1, which prompted a test of whether rhm1 resistance depends upon the antimicrobial compound 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one or other hydroxamic acids whose glucosyl conjugates are preferred substrates for the Glu1 enzyme . Double mutants of rhm1 and bx1, a hydroxamic acid-deficient mutant, indicate that rhm1 resistance is hydroxamic acid independent . The rhm1 resistance presently appears to operate via a mechanism unlike those of previously described resistance genes.

Support Care Cancer, 2001 Jul, 9(5), 372 - 9
Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients; Fleischhack G et al.; The beta-lactam/beta-lactamase inhibitor combinations are a good choice for empirical antimicrobial therapy in febrile neutropenic patients, because their antibacterial spectra include both gram-negative and gram-positive pathogens . This trial was initiated to assess the efficacy and safety of piperacillin with the beta-lactam inhibitors sulbactam (PSG group) or tazobactam (PTG group) and gentamicin as initial therapy in febrile neutropenia of pediatric patients . In a prospective study, 239 episodes of fever and neutropenia were analyzed for the clinical and microbiological response dependent on infection etiology and treatment group: 66.5% of episodes were classified as fever of unknown origin (FUO) and 33.5%, as microbiologically or clinically documented infections; 19.2% of all episodes were due to bacteremia, predominantly caused by gram-positive organisms (69.6%) . The response to the initial therapy was 55.2% overall and 65.4% in episodes of FUO with a significant higher success rate in the PSG group than in the PTG group (70.1% vs . 52.4%, P=0.039), and 35.0% in documented infections . In episodes with documented infection longer duration of fever and antimicrobial therapy was recorded than for FUO episodes . Four patients died of causes related to infection . Fever relapse occurred in 26 episodes (11.1%), predominantly in patients who were still neutropenic . Toxic side effects were minimal . The initial therapy of piperacillin with sulbactam or tazobactam in combination with gentamicin is well tolerated, and its efficacy is comparable to that of other combination therapies or of monotherapy with beta-lactam antibiotics in pediatric neutropenic cancer patients.

Cell Mol Life Sci, 2001 Jun, 58(7), 978 - 89
The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity; Yang D et al.; Since we live in a dirty environment, we have developed many host defenses to contend with microorganisms . The epithelial lining of our skin, gastrointestinal tract and bronchial tree produces a number of antibacterial peptides, and our phagocytic neutrophils rapidly ingest and enzymatically degrade invading organisms, as well as produce peptides and enzymes with antimicrobial activities . Some of these antimicrobial moieties also appear to alert host cells involved in both innate host defense and adaptive immune responses . The epithelial cells are a source of constitutively produced beta defensin (HBD1) and proinflammatory cytokine-inducible beta defensins (HBD2 and -3) and cathelicidin (LL37) . The neutrophils-derived antimicrobial peptides are released on demand from their cytoplasmic granules . They include the enzymes cathepsin G and chymase, azurocidin, a defensins and cathelicidin . In contrast, C5a and C3b are produced by activation of the serum complement cascade . The antimicrobial moieties direct the migration and activate target cells by interacting with selected G-protein-coupled seven-transmembrane receptors (GPCRs) on cell surfaces . The beta defensins interact with the CCR6 chemokine GPCRs, whereas cathelicidins interact with the low-affinity FPRL-1 receptors . The neutrophil-derived cathepsin G acts on the high-affinity FMLP receptor (GPCR) known as FPR, while the receptors for chymase and azurocidin have not been identified as yet . The serum-derived C5a uses a GPCR known as C5aR to mediate its chemotactic and cell-activating effects . Consequently, all these ligand-receptor interactions in addition to mediating chemotaxis also activate receptor-expressing cells to produce other mediators of inflammation.

J Am Vet Med Assoc, 2001 Aug 1, 219(3), 341 - 5
Osteomyelitis of the sustentaculum tali in horses: 10 cases (1992-1998); Hand DR et al.; OBJECTIVE: To determine outcome of horses with osteomyelitis of the sustentaculum tali (ST), with or without associated tarsal sheath tenosynovitis, following surgical debridement and lavage . DESIGN: Retrospective study . ANIMALS: 10 horses in which a diagnosis of osteomyelitis of the ST had been made on the basis of history, physical examination findings, and results of radiography . PROCEDURE: Information on results of diagnostic testing, surgical findings, postoperative treatment, and short-term outcome was obtained from the medical records . Long-term follow-up information was obtained through reevaluation of horses at the teaching hospital and telephone conversations with referring veterinarians, owners, and trainers . RESULTS: Treatment consisted of surgical debridement, intra- and postoperative lavage, and long-term antimicrobial and anti-inflammatory treatment . Eight horses had evidence of involvement of the tarsal sheath . One horse was euthanatized after surgery because of a lack of response to treatment; the other 9 were discharged from the hospital . Severity of lameness had improved, but all still had grade-1 or -2 lameness at the time of discharge . One horse was euthanatized after discharge because of contralateral hind limb laminitis, and another horse was lost to follow-up . Of the remaining 7 horses, 6 returned to their previous use, and 1 was sound but retired for breeding for unrelated reasons . CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that horses with osteomyelitis of the ST, with or without concomitant tarsal sheath tenosynovitis, can have an excellent to good outcome and may return to their previous use after surgical debridement of affected tissues and lavage of the tarsal sheath.

J Am Vet Med Assoc, 2001 Aug 1, 219(3), 334 - 7
Owner survey of headshaking in horses; Madigan JE et al.; OBJECTIVE: To determine signalment, history, clinical signs, duration, seasonality, and response to various treatments reported by owners for headshaking in horses . DESIGN: Owner survey . ANIMALS: 109 horses with headshaking . PROCEDURE: Owners of affected horses completed a survey questionnaire . RESULTS: 78 affected horses were geldings, 29 were mares, and 2 were stallions . Mean age of onset was 9 years . Headshaking in 64 horses had a seasonal component, and for most horses, headshaking began in spring and ceased in late summer or fall . The most common clinical signs were shaking the head in a vertical plane, acting like an insect was flying up the nostril, snorting excessively, rubbing the muzzle on objects, having an anxious expression while headshaking, worsening of clinical signs with exposure to sunlight, and improvement of clinical signs at night . Treatment with antihistamines, nonsteroidal anti-inflammatory drugs, corticosteroids, antimicrobials, fly control, chiropractic, and acupuncture had limited success . Sixty-one horses had been treated with cyproheptadine; 43 had moderate to substantial improvement . CONCLUSIONS AND CLINICAL RELEVANCE: Headshaking may have many causes . A large subset of horses have similar clinical signs including shaking the head in a vertical plane, acting as if an insect were flying up the nostrils, and rubbing the muzzle on objects . Seasonality and worsening of clinical signs with exposure to light are also common features of this syndrome . Geldings and Thoroughbreds appear to be overrepresented . Cyproheptadine treatment was beneficial in more than two thirds of treated horses.

Pharm Res, 2001 Jul, 18(7), 937 - 42
The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs; Adriaens E et al.; PURPOSE: The objective of this study was to evaluate the mucosal toxicity of different benzalkonium chloride (BAC) analogues using slugs as the alternative test organism . METHODS: The effect of different BAC analogues on the mucosal tissue of slugs was determined from the protein, lactate dehydrogenase, and alkaline phosphatase released from the foot mucosa after treatment . Additionally, mucus production and reduction in body weight of the slugs were measured . The eye irritation potency of the molecules was evaluated with the Bovine Corneal Opacity and Permeability (BCOP) assay . The antimicrobial activity of the different BAC analogues was also assessed . RESULTS: All BAC analogues induced severe damage to the mucosal epithelium of the slugs, and the irritation increased with decreasing alkyl chain length: BAC-C16 < BAC-C14 < BAC-C12 approximately BAC-mix . A similar ranking was obtained with the BCOP assay for eye irritation . The relative order of activities among the three BAC analogues was the same, i.e., BAC-C14 > or = BAC-C16 > BAC-C12 . The BAC-C14 exhibited higher activity than the BAC-mix . CONCLUSIONS: The toxicity and activity of BAC analogues depend on the alkyl chain length . The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAC-mix should be considered.

Vestn Khir Im I I Grek, 2001, 160(2), 39 - 45
{Local application of low-energy aerial and argon plasma in the treatment of suppurative wounds and trophic ulcers}; Khrupkin VI et al.; The authors describe experimental and clinical (113 patients) data demonstrating the antimicrobial, hemostatic and stimulating the regenerating processes property of the low energy plasma in local treatment of purulent and long-standing wounds and trophic ulcers.

Am J Health Syst Pharm, 2001 Aug 1, 58(15), 1406 - 12
Potential risks and prevention, Part 4: Reports of significant adverse drug events; Kelly WN; A summary analysis of three descriptive studies of significant adverse drug events (ADEs) was conducted . Case reports of ADEs published in Clin-Alert during 1976-97 were the source of information on ADEs, including drug-induced deaths, disabilities, and threats to life . The results of the three studies were compared, and recommendations were made . During the 21-year period, 1520 significant ADEs were reported (29% resulting in death, 15% in permanent disability, and 56% in life threats) . Event types were distributed as adverse drug reactions (52%), allergic drug reactions (25%), medication errors (15%), and drug interactions (8%) . Only 12% of the drug interactions were classified as having highest significance by one drug information reference, while 32% of the drug interactions were unclassified . Typically, patients were 40-69 years old and relatively healthy or only moderately ill and had received usual dosages . However, 29% of the patients with a drug-induced permanent disability were less than 10 years old . Only 17% of the drugs that could have been monitored by blood level tests were so monitored . The drug categories most commonly involved in ADEs were central-nervous-system agents, antimicrobials, antineoplastics, and cardiovascular agents . The nervous, hematopoietic, cardiovascular, and respiratory systems were affected the most . Faulty prescribing was the most common reason for medication error, and wrong dosage was the most common type of error . A lawsuit was reported in 13% of the cases . Overall, 52% of the cases were judged to have been preventable; of these, 50% could have been prevented by a pharmacist . Litigation was reported for 13% of the cases; settlements and judgments averaged $3.1 million . A summary analysis of more than 1500 published case reports of ADEs for 1976-97 yielded information on possible risk factors for drug-related deaths, disabilities, and life threats and on which events may have been preventable.

Am J Health Syst Pharm, 2001 Aug 1, 58(15), 1399 - 405
Potential risks and prevention, Part 3: Drug-induced threats to life; Marcellino K et al.; Potential risk factors for and the preventability of drug-induced threats to life were studied . Case reports of adverse drug events (ADEs) published in Clin-Alert during 1977-97 were the source of information on drug-induced life threats . Patient, drug, and event variables were identified, and the causality, predictability, and preventability of each case were assessed . Data were entered into a relational database for analysis . The data indicated 846 drug-induced life threats . Seventy-four percent of the cases were assessed as definite or probable . Patients received usual or below-usual dosages in 89% of the cases . Patients tended to be middle-aged and only moderately ill . The drug categories most frequently associated with life threats were antimicrobials and central-nervous-system agents . Plasma drug level monitoring should have been performed in 127 cases but occurred only in 31 cases (24%) . Event types were distributed as adverse drug reactions (50%), allergic reactions (35%), drug interactions (11%), and medication errors (4%) . A commercial reference classified almost half of the drug interactions associated with a life threat as posing minimal or no potential risk to the patient . Half of the life-threatening events were judged to have been preventable; about half of these could have been prevented by a pharmacist . Litigation was reported for only 1% of the cases of drug-induced threats to life; judgments and settlements averaged $1.2 million . A review of published case reports of ADEs for 1977-97 yielded information on possible risk factors for drug-induced life threats and on which events may have been preventable.

Rev Argent Microbiol, 2001 Apr-Jun, 33(2), 113 - 7
{Determination of the antibacterial and antiviral activity of the essential oil from Minthostachys verticillata (Griseb.) Epling}; Primo V et al.; The in vitro antiviral activity of the essential oil from Minthostachys verticillata was investigated against herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PrV) . The viral inhibition was assayed employing viral plaque reduction assay . The antiviral activity of the essential oil specifically affects PrV and HSV-1 multiplication, since it was found that non toxic effects on cells were observed at the concentrations assayed . The therapeutic index values were 10.0 and 9.5 for HSV-1 and PrV, respectively . The antibacterial activity was studied using a diffusion assay and the broth tube dilution method . Gram-positive bacteria were more sensitive to inhibition by plant essential oil than the gram-negative bacteria . The essential oil of M . verticillata was analyzed by gas chromatography (GC) technique . Of the six components identified in the volatile oil, pulegone (44.56%) and menthone (39.51%) were the major constituents . The antimicrobial activity can be explained to some extent by the presence of pulegone . Results suggest that further investigations concerning the isolation of the substance responsible for the antimicrobial activity and an effort to define the mechanisms of action are warranted.

J Clin Periodontol, 2001 Sep, 28(9), 833 - 9
Systemic and local antimicrobial use in periodontal therapy in England and Wales; Choudhury M et al.; BACKGROUND/AIMS: The aim of this study was to investigate antimicrobial use during periodontal therapy in dental practice in England & Wales . METHOD: This was a postal questionnaire survey of 800 dentists, 400 general dental practitioners (GDP) in National Health Service practice and 400 members of the British Society of Periodontology (Periodontal Society) primarily in dental practice . We designed and piloted a questionnaire to evaluate both systemic and local antibiotic use with periodontal therapy as well as factors affecting their prescription . In addition, we also investigated the potential use of antibiotic sensitivity testing, since this has been recommended prior to prescribing antibiotics . Two follow-up mailings were used to encourage non-responders . RESULTS: The useable return rate for the questionnaires was 587/800 (73%) . Systemic antibiotics were used by 7.4% Periodontal Society members and 18.4% GDP for untreated adult periodontitis patients (p<0.001) . Antimicrobials were prescribed more frequently by Periodontal Society members in early onset (52.7%) and refractory periodontitis patients (49.6%), and this was highly statistically significantly greater usage than GDP (p<0.001) . Regarding local antimicrobials, usage for untreated adult periodontitis was Periodontal Society 8.9% and GDP 5.4% . Higher usage of local antimicrobials was found both for the treatment of recurrent pocketing in adult periodontitis (Periodontal Society 26.3%, GDP 14.8%, p<0.014) and refractory periodontitis (Periodontal Society 30.8%, GDP 15.2%, p<0.001) . As reasons for using local antimicrobials, more than 80% of all respondents stated superiority over root debridement alone . Barriers to use included cost, no perceived need and lack of supporting research data . The percentage of responders considering diagnostic microbiology either theoretically or at a cost of pound 60 were by group, Periodontal Society 83% & 70.4% and GDP 76% & 51.2% . 33% of Periodontal Society members and 3.8% of GDP spent at least 45 min per quadrant on root planing and Periodontal Society members had a greater exposure to lectures on both systemic and local drug therapy compared with GDP (p<0.001) . CONCLUSIONS: Systemic antimicrobial use was infrequent for adult periodontitis and generally in line with current recommendations for other disease types . Whilst local antimicrobial therapy for periodontitis was not widespread, a substantial minority of dentists use this form of therapy and most believe that it is more effective than root debridement alone.

Aust Vet J, 2001 Jun, 79(6), 398 - 402
Thoracic actinomycosis (arcanobacteriosis) or nocardiosis causing thoracic pyogranuloma formation in three dogs; Sivacolundhu RK et al.; OBJECTIVE: To describe three cases of canine thoracic actinomycosis (arcanobacteriosis) or nocardiosis in which the primary pathological lesion was a pyogranulomatous abscess in the mediastinum . Clinical signs, difficulties in diagnosis, treatment and prognosis are examined . Comparisons are made between human and veterinary literature to assist in formulating a rational treatment plan . DESIGN: Retrospective clinical study . PROCEDURE: Review of case records from 1984 to 1998 . RESULTS: Three dogs presented with large intrathoracic pyogranulomas producing variable clinical signs, not necessarily associated with the respiratory tract . Ages ranged from 2 to 5 years old . Two dogs responded to surgical opening and passive drainage of the abscess, or surgical excision of the granuloma with associated structures, and medical therapy . One dog died intra-operatively . CONCLUSION: A combination of surgical and antimicrobial therapy may carry a fair-to-good prognosis for thoracic granuloma caused by actinomycosis (arcanobacteriosis) or nocardiosis . The extent of surgery should be based on assessment of individual cases and must include surgical biopsy for histology and culture to enable a specific diagnosis to be made . Complete surgical excision is not necessarily required . Prolonged antimicrobial therapy is indicated.

Gerontology, 2001 Sep-Oct, 47(5), 246 - 53
Salivary concentration of secretory leukocyte protease inhibitor, an antimicrobial protein, is decreased with advanced age; Shugars DC et al.; BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) exhibits antimicrobial activities that, in addition to other well-characterized proteins such as lysozyme and lactoferrin, is thought to play a critical role in mucosal defenses . Although elderly individuals are particularly susceptible to mucosal infections, salivary production of SLPI has not been assessed in an aged cohort . OBJECTIVES: Hypothesizing that oral SLPI concentrations are reduced with advanced age, this cross-sectional study compared SLPI concentrations to concentrations of lysozyme, lactoferrin and total protein in unstimulated salivary secretions of healthy, community-dwelling 79+-year-old and younger adults . METHODS: Study participants were 45 non-hospitalized dentate adults aged 79-89 (23 elderly) or 21-51 years (22 non-elderly) . Home-based interviews and clinical examinations determined dentate status and confirmed the absence of dentures, oral mucosal disease, anti-infective medication use, irradiation therapy for head and neck cancer and self-perceived xerostomia . Whole unstimulated saliva was collected from all subjects and analyzed for antimicrobial protein concentration by enzyme-linked immunosorbent assay and for total protein content by the bicinchoninic acid method . Bivariate and multivariate (generalized linear modeling) analyses evaluated the relationships between age, gender and salivary protein concentrations . RESULTS: Mean salivary levels of SLPI and lysozyme were lower in elderly compared with non-elderly subjects (p < 0.001), unlike lactoferrin and total protein levels . Similar results were obtained when concentrations of the individual proteins were normalized to the total protein concentration, suggesting that glandular production of SLPI and lysozyme preferentially decreases with aging . Gender differences were detected only for SLPI concentrations; males had lower SLPI levels than females regardless of age (p < 0.01) . Generalized linear models confirmed that age (p < 0.001) and gender (p < 0.05) were each associated with the SLPI concentration and together accounted for 50% of the variation in SLPI concentration in this population . CONCLUSION: These findings indicate that SLPI production is diminished among healthy community-dwelling older adults, particularly elderly males . Further investigation should determine the impact of decreased local SLPI production on the increased risk of oral mucosal disease with advanced age .

Eur J Biochem, 2001 Aug, 268(15), 4278 - 84
Crumpled structure of the custom hydrophobic lytic peptide cecropin B3; Srisailam S et al.; The solution structure of a custom lytic peptide, cecropin B3 (CB3), having two identical hydrophobic segments on both the N- and C-termini, was investigated by two-dimensional NMR spectroscopy . The need to determine the structure of this peptide is rooted in its specific ability to lyse lipid layers that have a high content of anionic lipid . The lytic activities of CB3 on cell membranes including cancer cells and bacteria is found to be less than cecropin B1 . The results show that CB3 has four discrete segments forming alpha helical structures . The crumpled structure of CB3 provides evidence for the lysis of the lipid layer being via a pathway that differs from pore formation . The results in this study provide strong clues towards a rational design for a potent antimicrobial and antitumor peptide.

Arch Biochem Biophys, 2001 Aug 15, 392(2), 180 - 91
Potential involvement of several nitroreductases in metronidazole resistance in Helicobacter pylori; Jorgensen MA et al.; Susceptibility of Helicobacter pylori to the antibiotic metronidazole has been attributed to the activity of an oxygen-insensitive NADPH-dependent nitroreductase (RdxA), with resistance to this antimicrobial arising from null mutations in rdxA . To obtain a better understanding of the factors involved in resistance, nitroreductase and metronidazole reduction activities were investigated in matched pairs of clinical and laboratory-derived sensitive and resistant H . pylori strains . Significant differences in enzyme activities were observed between sensitive and resistant strains, suggesting that metronidazole susceptibility in H . pylori was associated with more than one enzyme activity . To establish the mutations occurring in rdxA, the genes from seventeen bacterial strains, including matched pairs were sequenced . To assess whether metronidazole was responsible for inducing random mutations in this gene, the complete nucleotide sequence of gene hp0630, encoding an NAD(P)H-quinone reductase which also has NADPH-dependent nitroreductase activity, was determined in the same strains . All resistant strains showed nonsense, missense, or frameshift mutations randomly throughout rdxA . In contrast, no mutations were observed in hp0630 . The results confirmed the presence of rdxA null mutations in resistant strains and suggested that other factors involved in the metabolism of metronidazole contributed to the resistant phenotype .

Ear Nose Throat J, 2001 Jun, 80(6 Suppl), 4 - 7
Post-tympanostomy tube otorrhea; Myer CM 3rd; Post-tympanostomy tube otorrhea is a common problem that is treated by both primary care physicians and otolaryngologists . Physicians should take a logical approach to managing this condition in order to prevent the development of antimicrobial resistance and to minimize healthcare expenditures . Once the diagnosis has been made, first-line therapy with fluoroquinolone drops, with or without suctioning, is preferred . If the condition does not resolve after a few days, suctioning is recommended and oral antimicrobial therapy can be initiated, depending on the clinical situation . Parenteral therapy is sometimes necessary for those very few patients who do not improve with oral and topical antimicrobial therapy and aggressive local care . The use of prophylactic drug therapy is controversial.

Boll Chim Farm, 2001 May-Jun, 140(3), 149 - 54
Synthesis of some pyridone derivatives; Dawood NT et al.; Chlorination of 6-aryl-3-cyano-2-pyridone-4-carboxylic acid (1) afforded the corresponding acid chloride (2) and the 2-chloro derivative (3) . Esterification of (2) gave the corresponding esters (4a; b) . Hydrazinolysis of (4a) afforded the respective pyridazinone derivative (5) . Treatment of 6-aryl-2-chloro-3-cyano-4-pyridine carboxylic acid (3) with acetyl hydrazine, gave the triazinopyridine derivative (6), while treatment of 3 with sodium azide in DMF afforded the tetrazinopyridine derivative (7) . Treatment of the N-acetyl derivative (1b) with thiosemicarbazide and/or hydroxylamine hydrochloride, yielded the correspoding semicarbazone and oxine derivatives (8) and (10), respectively . The reaction of 6-aryl-3-cyano-1,2-dihydro-2-thioxo-4-pyridinecarboxylic acid (1c) with ethylchloro acetate and/or thiourea yielded the mercapto ester derivative (11) and the corresponding pyrido {2,3-d} pyrimidine thione derivative (12) . Condensation reaction of (1d) with anthranilic acid, afforded the quinazolone derivative (11) . The reactivity of 11 towards hydrazine hydrate was investigated . The structural assignment of the new derivatives were based on IR, 1H NMR and mass data . Some of the new compounds were screened, in vitro, for antimicrobial activity and the results were encouraging.

Boll Chim Farm, 2001 May-Jun, 140(3), 129 - 39
Simple synthesis of condensed pyran containing compounds and their antimicrobial properties; Mishriky N et al.; Reaction of various fused pyran compounds with formic acid was studied . Thus, refluxing 6-aminopyrano{2,3-c}pyrazole-5-carbonitriles 3 with formic acid afforded the corresponding 3-aryl-3-(5-hydroxy-3-methyl-1H-pyrazole-4-yl)propanoic acids 4 . Whereas, reaction of formic acid with 2-amino-4H-1-benzopyran-3-carbonitriles 6 gave the corresponding quinoline-2,5(1H,6H)-diones 7 . The study was also extended towards many spiro compounds possessing pyran residue . The antimicrobial properties of the prepared compounds was screened.

Clin Infect Dis, 2001 Sep 1, 33 Suppl 2, S94 - 106
New developments in diagnosis and treatment of infection in orthopedic implants; Widmer AF; Orthopedic implants have revolutionized treatment of bone fractures and noninfectious joint arthritis . Today, the risk for orthopedic device-related infection (ODRI) is <1%-2% . However, the absolute number of patients with infection continuously increases as the number of patients requiring such implants grows . Treatment of ODRIs most frequently includes long-term antimicrobial treatment and removal of the implant . Recent evidence from observational trials and 1 randomized clinical trial indicate that a subset of patients can be successfully treated with retention of the implant . Patients eligible for such a treatment must meet the following criteria: acute infection defined as signs and symptoms lasting <14-28 days, an unambiguous diagnosis based on histopathology and microbiology, a stable implant, and susceptibility of the microorganism to an effective orally available antimicrobial agent.

Clin Infect Dis, 2001 Sep 1, 33 Suppl 2, S78 - 83
Maximizing appropriate antibiotic prophylaxis for surgical patients: an update from LDS Hospital, Salt Lake City; Burke JP; Errors in antimicrobial prophylaxis for surgical patients remain one of the most frequent types of medication errors in hospitals . Failure to administer the first dose of antimicrobial prophylaxis within the 2-h window of time before incision is associated with 2- to 6-fold increases in rates of surgical site infection . Optimal use of antimicrobial prophylaxis includes proper case selection; use of appropriate agents; proper dosing, route of administration, timing, and duration; and intraoperative dosing when appropriate . Effective use of antimicrobial prophylaxis also requires monitoring of and feedback on patterns of use . Programs to improve antimicrobial prophylaxis should be multidisciplinary and should aim to improve use of medications, not simply to change physician practice patterns . The LDS Hospital experience demonstrates the clinical and financial benefits of such a program and also shows the pitfalls of and great difficulties associated with changing systems of care.

Am J Infect Control, 2001 Aug, 29(4), 275 - 80
Descriptive study of nosocomial infections in a short-term inpatient behavioral health setting; Shandera TJ; BACKGROUND: Surveillance methods for nosocomial infections, with the use of a sound epidemiologic foundation, have not been published for behavioral healthcare settings . METHODS: Nosocomial infection rates in a behavioral health care setting were quantified by integrating the following: (1) rounds/review of selected charts, (2) microbiology reports, and (3) records of antimicrobials dispensed . Incidence density rates were calculated with 1000 patient-days as the denominator . RESULTS: The incidence of nosocomial infections of all types among all patients was 3.9 infections per 1000 patient-days . Rates among specific groups of behavioral patients ranged from children (6.4 infections per 1000 patient-days) to adults (3.9 infections per 1000 patient-days) to adolescents (3.2 infections per 1000 patient-days) . Adult substance-abuse patients had a rate of 1.9 infections per 1000 patient-days . The most frequently diagnosed nosocomial infection among adult substance-abuse and behavioral patients was bronchitis at 0.5 and 0.6 infections per 1000 patient-days, respectively . The most frequently diagnosed nosocomial infection among adolescents and children was cellulitis at 0.6 and 1.3 infections per 1000 patient-days, respectively . Female patients experienced significantly more nosocomial infections than male patients, except among adult substance-abuse patients . Nosocomial infections usually occurred in patients who were hospitalized longer than the average length of stay, except among children . CONCLUSION: Nosocomial infections occur in behavioral health settings . Surveillance methods, with a sound epidemiologic foundation, must be developed.

J Biol Chem, 2001 Oct 19, 276(42), 39021 - 6 Epub 2001 Aug 02.
The structure of human beta-defensin-1: new insights into structural properties of beta-defensins; Hoover DM et al.; Defensins are a class of small cationic peptides found in higher organisms that serve as both antimicrobial and cell signaling molecules . The exact mechanism of the antimicrobial activity of defensins is not known, but two models have been postulated, one involving pore formation and the other involving nonspecific electrostatic interaction with the bacterial membrane . Here we report the high resolution structures of human beta-defensin-1 (hBD1) in two crystallographic space groups . The structure of a single molecule is very similar to that of human beta-defensin-2 (hBD2), confirming the presence of an N-terminal alpha-helix . However, while the packing of hBD1 is conserved across both space groups, there is no evidence for any larger quaternary structure similar to octameric hBD2 . Furthermore, the topology of hBD1 dimers that are formed between monomers in the asymmetric unit is distinct from both hBD2 and other mammalian alpha-defensins . The structures of hBD1 and hBD2 provide a first step toward understanding the structural basis of antimicrobial and chemotactic properties of human beta-defensins.

Genes Dev, 2001 Aug 1, 15(15), 1900 - 12
Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel/NF-kappaB-dependent innate immune responses; Vidal S et al.; In mammals, TAK1, a MAPKKK kinase, is implicated in multiple signaling processes, including the regulation of NF-kappaB activity via the IL1-R/TLR pathways . TAK1 function has largely been studied in cultured cells, and its in vivo function is not fully understood . We have isolated null mutations in the Drosophila dTAK1 gene that encodes dTAK1, a homolog of TAK1 . dTAK1 mutant flies are viable and fertile, but they do not produce antibacterial peptides and are highly susceptible to Gram-negative bacterial infection . This phenotype is similar to the phenotypes generated by mutations in components of the Drosophila Imd pathway . Our genetic studies also indicate that dTAK1 functions downstream of the Imd protein and upstream of the IKK complex in the Imd pathway that controls the Rel/NF-kappaB like transactivator Relish . In addition, our epistatic analysis places the caspase, Dredd, downstream of the IKK complex, which supports the idea that Relish is processed and activated by a caspase activity . Our genetic demonstration of dTAK1's role in the regulation of Drosophila antimicrobial peptide gene expression suggests an evolutionary conserved role for TAK1 in the activation of Rel/NF-kappaB-mediated host defense reactions.

Hum Gene Ther, 2001 Jul 20, 12(11), 1395 - 406
Regulation of adenovirus-mediated elafin transgene expression by bacterial lipopolysaccharide; Simpson AJ et al.; Lipopolysaccharide (LPS) is a mediator of inflammatory lung injury . Selective augmentation of host defense molecules such as elafin (an elastase inhibitor with antimicrobial activity) at the onset of pulmonary inflammation is an attractive potential therapeutic strategy . The aim of this study was to determine whether elafin expression could be induced by LPS administered after transfection with adenovirus (Ad) encoding human elafin downstream of the murine cytomegalovirus (CMV) promoter (known to be potentially responsive to LPS) . In addition, we aimed to determine the effect of local elafin augmentation on neutrophil migration to the lung . LPS significantly up-regulated elafin expression from pulmonary epithelial cells transfected with Ad-elafin in vitro . In murine airways expression of human elafin was achieved using doses low enough (3 x 10(7) plaque forming units) to circumvent overt vector-induced inflammation . LPS significantly up-regulated human elafin secretion in murine airways treated with Ad-elafin {117 ng/ml in bronchoalveolar lavage fluid (BALF) after LPS administration, 5.9 ng/ml after PBS, p < 0.01)} . Over-expression of elafin significantly augmented LPS-mediated neutrophil migration into the airways in vivo (1.30 x 10(6) neutrophils in BALF after Ad-elafin/LPS treatment, 0.54 x 10(6) after Ad-lacZ/LPS (p < 0.05), 0.63 x 10(6) after PBS/LPS (p < 0.05)) and significantly enhanced human neutrophil migration in vitro . These data suggest novel functions for elafin in neutrophil migration, and that judicious selection of promoters may allow single, low-dose adenoviral administration to effect inflammation-specific expression of potentially therapeutic transgenes.

AIDS Res Hum Retroviruses, 2001 Jul 20, 17(11), 1041 - 5
Differential pattern in circulating nitrogen derivatives, lactoferrin, and anti-lactoferrin antibodies in HIV type 1 and HIV type 2 infections; Dapsanse V et al.; HIV-1 infection is associated with a dramatic reduction in antioxidative molecules both at the cellular level and in the circulation . This is particularly so for lactoferrin, an iron-binding protein involved in natural defenses (antimicrobial and antiviral activities, etc.) and found in whole secretions, including milk and mucus . In addition to its ability to chelate iron ions, lactoferrin inhibits hydroxy radical formation and interacts with nitric oxide (NO) . Levels of plasma lactoferrin decreased in HIV-1-infected patients in correlation with progression of the disease, and highly specific anti-lactoferrin autoantibodies increased . This profile was specific to HIV-1 infection; it was not found in HIV-2-infected patients . In parallel with the drop in lactoferrin, a marked increase in circulating nitrogen derivatives was observed in HIV-1-infected patients, whereas low levels were found in normal donors and in HIV-2-infected patients . These data suggested hyperstimulation of the NO pathway throughout HIV-1 but not HIV-2 infection . This overproduction of NO could play an important role in the development of AIDS symptoms and signs.

Pharm Dev Technol, 2001 Aug, 6(3), 431 - 40
Sorption of parabens by flexible tubings; Bahal SM et al.; Flexible tubings are extensively used in pharmaceuticals, food industry, and in hospitals . This study was undertaken to compare various flexible tubings to determine their sorption characteristics, using methyl and propyl parabens . After 24 h, some tubings showed 100% sorption of propylparaben and over 40% for methylparaben . Significant losses were observed within a few hours using several tubings . For methylparaben, the losses were in the following decreasing order of sorption: Tygon, Clearflo, silicone, Nylotube, and Newtex . For propylparaben, the losses were in the following order: Tygon, Clearflo, silicone, Newtex, and Nylotube . Teflon, Zelite, and Vitube showed little to no losses of methyl and propylparaben over 120 h of study . The silicone tubing, refilled after 120 h with fresh methylparaben or propylparaben solutions, again showed significant losses within a few hours . The tubings show slow desorption when filled with the buffer vehicle . For Silastic tubing, increase in temperature from 25 to 40 degrees C, increase in pH from 3.5 to 6.5, tubing lot to lot variation, or curing with peroxide or platinum had little or no effect on paraben sorption . As expected, the sorption of parabens increased with increasing surface area of Silastic tubing . Results provided can be used to select the best tubings and to minimize paraben losses during production and filling of liquid pharmaceuticals andfood products containing these antimicrobial preservatives.

J Biol Chem, 2001 Oct 5, 276(40), 37199 - 205 Epub 2001 Aug 01.
Oxazolidinones mechanism of action: inhibition of the first peptide bond formation; Patel U et al.; Oxazolidinones are potent inhibitors of bacterial protein biosynthesis . Previous studies have demonstrated that this new class of antimicrobial agent blocks translation by inhibiting initiation complex formation, while post-initiation translation by polysomes and poly(U)-dependent translation is not a target for these compounds . We found that oxazolidinones inhibit translation of natural mRNA templates but have no significant effect on poly(A)-dependent translation . Here we show that various oxazolidinones inhibit ribosomal peptidyltransferase activity in the simple reaction of 70 S ribosomes using initiator-tRNA or N-protected CCA-Phe as a P-site substrate and puromycin as an A-site substrate . Steady-state kinetic analysis shows that oxazolidinones display a competitive inhibition pattern with respect to both the P-site and A-site substrates . This is consistent with a rapid equilibrium, ordered mechanism of the peptidyltransferase reaction, wherein binding of the A-site substrate can occur only after complex formation between peptidyltransferase and the P-site substrate . We propose that oxazolidinones inhibit bacterial protein biosynthesis by interfering with the binding of initiator fMet-tRNA(i)(Met) to the ribosomal peptidyltransferase P-site, which is vacant only prior to the formation of the first peptide bond.

J Ethnopharmacol, 2001 Sep, 77(1), 37 - 40
Antimicrobial activity of Argentine plants used in the treatment of infectious diseases . Isolation of active compounds from Sebastiania brasiliensis; Penna C et al.; Different extracts of Sebastiania brasiliensis, Sebastiania klotszchiana, Polygonum punctatum, Lithraea molleoides and Myrcianthes cisplatensis, all plants growing in Entre Rios Province and traditionally used as antiseptics, were tested against a set of Gram positive and Gram negative bacteria and fungi . All the species, with the exception of M . cisplatensis, presented activity against some of the microorganisms tested . A 50% hydroalcoholic extract of S . brasiliensis was selected for bioguided fractionation . Two antimicrobial compounds identified as methylgallate (MIC 128 microg/ml) and protocatechuic acid (MIC 128 microg/ml) were isolated apart from quercetin, kaempferol, quercitrin and gallic acid.

Vaccine, 2001 Aug 14, 19(31), 4496 - 504
Plasmodium falciparum acid basic repeat antigen (ABRA) peptides: erythrocyte binding and biological activity; Curtidor H et al.; Non overlapping 20-mer peptides, covering the complete sequence of acid basic repeat antigen (ABRA) of Plasmodium falciparum, were synthesised and tested in binding assays to erythrocytes . Five peptides localised in the N-terminal region coded 2148 (121LQSHKKLIKALKKNIESYQN(140)), 2149 (141KKHLIYKNKSYNPLLLSCVK(160)), 2150 (161KMNMLKENVDYIQKNQNLFK(180)), 2152 (201YKSQGHKKETSQNQNENNDN(220)) and 2153 (221QKYQEVNDEDDVNDEEDTND(240)) specifically bind to erythrocytes . These peptides bind independently of the peptide and erythrocyte charge, with high affinity (Kd between 70 and 180 nM) and the hydrophobic interaction is important for this binding ( approximately 30% hydrophobic critical residues) . These results allow us define a specific erythrocyte binding region (residues 121-240), which may bound to at least three different binding sites on erythrocytes . Peptide 2153 shares the underlined sequence 221QKYQEVNDEDDVNDEEDTND(240) with an earlier 18-mer peptide recognised by human exposed sera . Peptides number 2148 and 2149 in vitro inhibit erythrocyte invasion by merozoites . We found that 2149 peptide and some of its glycine analogues show specific haemolytic and/or antimicrobial activity . We discuss a possible role of ABRA or its regions in the merozoite invasion of erythrocyte.

Farmaco, 2001 May-Jul, 56(5-7), 345 - 8
Antimicrobial activity of Epilobium spp . extracts; Battinelli L et al.; The antimicrobial activity of the Epilobium angustifolium, E . hirsutum, E . palustre, E . tetragonum and E . rosmarinifolium ethanolic extracts was studied in vitro on Gram-positive and Gram-negative bacteria, yeasts and fungi . The cytotoxicity of the extracts was also evaluated using the Artemia salina test . All the extracts showed antimicrobial activity in a range of concentrations between 10 and 650 microgml of dry extract . E . angustifolium and E . rosmarinifolium had the most broad spectrum of action inhibiting bacteria, yeasts and fungi . The extracts were devoid of toxicity on Artemia salina within the range of antimicrobial concentrations, suggesting that the action is selective on microorganisms.

J Burn Care Rehabil, 2001 Jul-Aug, 22(4), 282 - 7
Does the addition of nystatin to 5% mafenide acetate and genitourinary irrigant solutions interfere with their antimicrobial activity? Assessment by two topical antimicrobial test assay systems; Holder IA et al.; Results previously reported using the Wet Disc Topical Antimicrobial Assay (WDA) suggested that adding nystatin (NY) to a 0.5% mafenide acetate (MA) suspension or genitourinary irrigant (double antibiotic {DAB}) to expand their antimicrobial activity to include Candida sp . antagonized the antibacterial effect of MA but not DAB . We use DAB solution as described by the authors of the previous study, also, but we use a 5% commercially available mafenide acetate solution instead of the in-house prepared 0.5% mafenide acetate suspension that they used . Further, we use both the WDA and the Agar Well Diffusion Topical Antimicrobial Assay (AWDA) to test topical antimicrobials at this institution . In light of the previously reported results, this study 1) examined whether adding nystatin to DAB or the 5% mafenide acetate solution used at this institution caused any interference in the ability of these substances to migrate through the agar matrices and cause zones of growth inhibition in the two test assay systems and 2) compared the assessment of microbial susceptibility (by very precise definition) between the two systems . The addition of nystatin did not interfere with the ability of either DAB or mafenide acetate to migrate through the agar matrices and cause clear zones . However, on the assessment of susceptibility a significantly larger number of organisms were judged susceptible using the AWDA than the WDA . We believe that the disparity is caused by a large difference in agar diffusion kinetics between the two assays . Therefore, we recommend the AWDA rather than the WDA for susceptibility studies.

Arch Toxicol, 2001 Jun, 75(4), 227 - 33
Differential response of mast cells separated from various organs and basophils of dogs to the fluoroquinolone antimicrobial levofloxacin; Mori K et al.; Histamine releases induced by the fluoroquinolone antimicrobial levofloxacin (LVFX) were investigated using mast cells separated from various organs and peripheral basophils of dogs, being the most susceptible species to quinolone derivatives, in both in vivo and in vitro systems . An intravenous infusion of LVFX at 30 mg/kg over a 30-min period produced endogenous histamine release from 5 min, and a maximum at 30 min, in which the plasma LVFX concentration was approximately 50 microM . A close correlation (r = 0.87, n = 20) between histamine and LVFX concentrations in plasma during the infusion was observed . In the in vitro study, LVFX at 30 microM or more caused histamine release from mast cells separated from the liver and skin, but not from the gastric mucosa, lung, and peripheral basophils . More exactly, the liver mast cells were most susceptible to LVFX among the organs tested . On the other hand, compound 48/80, a prototype histamine liberator, elicited the histamine release from the liver or skin mast cells at 10 microg/ml, and the calcium ionophore A23187 at 1 microM exhibited the histamine release from the mast cells derived from all organs examined . Histochemical analysis revealed that the liver and skin mast cells had positive reaction for both alcian blue and safranin staining, but the gastric mucosa and lung mast cells were only positive for alcian blue staining, indicating that LVFX preferably activated the connective tissue-type mast cells rather than the mucosal-type mast cells . The degranulation of the liver and skin mast cells brought about by either LVFX or compound 48/80, unlike the calcium ionophore A23187, was blocked by pretreatment with pertussis toxin, suggesting the involvement of pertussis toxin-sensitive G proteins . The results obtained from the canine experiments strongly suggest that LVFX induces histamine release from the connective tissue-type mast cells distributed mainly in the liver, somewhat in the cutaneous tissue, through the activation of pertussis toxin-sensitive G proteins.

J Am Chem Soc, 2001 Aug 8, 123(31), 7553 - 9
De novo design, synthesis, and characterization of antimicrobial beta-peptides; Liu D et al.; beta-Peptides are a class of polyamides that have been demonstrated to adopt a variety of helical conformations . Recently, a series of amphiphilic L(+2) helical beta-peptides were designed, which were intended to mimic the overall physicochemical properties of a class of membrane-active antimicrobial peptides, including magainin and cecropin . Although these peptides showed potent antimicrobial activity, they also showed significant activity against human erythrocytes . Operating under the assumption that their lack of specificity arose from excessive hydrophobicity, two additional beta-peptides H-(beta(3)-HAla-beta(3)-HLys-beta(3)-HVal)(n)-NH(2) (n = 4, 5) were designed and synthesized . Both have high antimicrobial activities, but very low hemolytic potencies . The peptides bind in an L(+2) conformation to phospholipid vesicles, inducing leakage of entrapped small molecules . The peptides have a low affinity for membranes consisting of neutral phosphatidylcholine lipids, but bind avidly to vesicles containing 10 mol % of acidic phosphatidylserine lipids . Differences in vesicle leakage kinetics for the two peptides suggest that chain length could affect their mechanisms of disrupting cell membranes . Thus, insights gained from the study of variants of natural alpha-peptides have provided a useful guide for the design of nonnatural antimicrobial beta-peptides.

Indian J Physiol Pharmacol, 2001 Apr, 45(2), 249 - 52
Antimicrobial effect of protein(s) isolated from a marine mollusc Telescopium telescopium; Pakrashi A et al.; Ammonium sulfate precipitated protein (SF-50) isolated from the spermatheca gland of Telescopium telescopium, an invertebrate marine snail, showed antimicrobial effect on Escherichia coli . The antimicrobial effect varied with the concentration of "SF-50" used and the effect was found to be comparable to antibiotics like amikacin, contrimoxazole and gentamycin in disc diffusion test . The "SF-50" was devoid of erythrocyte haemolysis property.

Jt Comm J Qual Improv, 2001 Aug, 27(8), 387 - 402
Improving inpatient antibiotic prescribing: insights from participation in a national collaborative; Schiff GD et al.; BACKGROUND: Increasing rates of antimicrobial resistance and the role antibiotic overuse plays in contributing to this problem have been widely documented and have prompted appeals to change prescribing practices . How to actually achieve such changes represents a major challenge . As part of the Institute for Healthcare Improvement (IHI) Breakthrough Series project Improving Prescribing Practices (IPP), in 1997-1998, Cook County Hospital (Chicago) worked with other institutions that chose antibiotics as their focus in this national collaborative . PRACTICAL SUGGESTIONS: Practical suggestions are offered within six categories--adopting a general approach to improving antibiotic prescribing (marshalling credible evidence, addressing physician concerns and skepticism, and removing barriers to make it easier for prescribers to change); rethinking guidelines (providing syndrome-based guidance, revising national guidelines for local use, defining scenarios in which drug(s) can be safely withheld, offering alternatives, prospectively resolving conflicts over drug of choice and empiric regimens, and defining situations in which immediate treatment is and is not critical); getting the message out and changes implemented (using antibiotic order forms, computer order entry, and infectious disease specialist consultation); building viable linkages to leverage change (bridging disciplines); improving measurement; and promoting nondrug strategies and patients' roles in treating and preventing infection . CONCLUSION: Antimicrobials are unique, being the only class of drug therapy that affects not only the patient to whom it is prescribed but other current and future patients as well . Institutions therefore have a special responsibility to ensure their efficient and judicious use . It is often easier to prescribe antibiotics than to exercise restraint.

J Pediatr Surg, 2001 Aug, 36(8), 1118 - 21
The use of a bioactive skin substitute decreases length of stay for pediatric burn patients; Lukish JR et al.; BACKGROUND: To optimize burn care for children, the authors introduced a protocol incorporating the use of a bioactive skin substitute, TransCyte (Advanced Tissue Sciences, La Jolla, CA) . This study was designed to determine whether this management plan was safe, efficacious, and decreased hospital inpatient length of stay (LOS) compared with conventional burn management in children . METHODS: All pediatric burns greater than 7% total body surface area (TBSA) that occurred after October 1999 underwent wound closure with TransCyte (n = 20) . These cases were compared with the previous 20 consecutive burn cases greater than 7% TBSA that received standard therapy . Standard therapy consisted of application of antimicrobial ointments and hydrodebridement . The following information was obtained: burn mechanism, age, size of burn, requirement of autograft, and LOS . Data were analyzed using the student's t test . RESULTS: Data for age, percent TBSA burn and LOS are reported as means +/- SEM . The children who received standard therapy were 2.99 +/- 0.7 years compared with those receiving TransCyte were 3.1 +/- 0.8 years . There was no difference between the treatment groups with regard to percent TBSA burn: standard therapy, 14.3 +/- 1.4% TBSA versus TransCyte, 12.7 +/- 1.3% TBSA . There was no difference in the type of burns in each group, the majority were liquid scald type, 70% in the standard therapy group versus 90% in the TransCyte group . Only 1 child in the TransCyte group required autografting (5%) compared with 7 children in the standard therapy group (35%) . Children treated with TransCyte had a statistically 6 significant decreaed LOS compared with those receiving standard therapy, 5.9 +/- 0.9 days versus 13.8 +/- 2.2 days, respectively (P =.002) . CONCLUSIONS: This is the first study using TransCyte in children . The authors found that this protocol of burn care was safe, effective, and significantly reduced the LOS . This new approach to pediatric burn care is effective and improves the quality of care for children with burns .

J Gen Physiol, 2001 Aug, 118(2), 223 - 36
The relative roles of passive surface forces and active ion transport in the modulation of airway surface liquid volume and composition; Tarran R et al.; Two hypotheses have been proposed recently that offer different views on the role of airway surface liquid (ASL) in lung defense . The "compositional" hypothesis predicts that ASL {NaCl} is kept low (<50 mM) by passive forces to permit antimicrobial factors to act as a chemical defense . The "volume" hypothesis predicts that ASL volume (height) is regulated isotonically by active ion transport to maintain efficient mechanical mucus clearance as the primary form of lung defense . To compare these hypotheses, we searched for roles for: (1) passive forces (surface tension, ciliary tip capillarity, Donnan, and nonionic osmolytes) in the regulation of ASL composition; and (2) active ion transport in ASL volume regulation . In primary human tracheobronchial cultures, we found no evidence that a low {NaCl} ASL could be produced by passive forces, or that nonionic osmolytes contributed substantially to ASL osmolality . Instead, we found that active ion transport regulated ASL volume (height), and that feedback existed between the ASL and airway epithelia to govern the rate of ion transport and volume absorption . The mucus layer acted as a "reservoir" to buffer periciliary liquid layer height (7 microm) at a level optimal for mucus transport by donating or accepting liquid to or from the periciliary liquid layer, respectively . These data favor the active ion transport/volume model hypothesis to describe ASL physiology.

Ann Med Interne (Paris), 2001 Jun, 152(4), 279 - 82
{Septic arthritis of a lumbar facet joint . A case report}; Derouet N et al.; Septic arthritis of the posterior lumbar joints is extremely rare in comparison with spondylodiscitis which is much more common . We report a case of an 86-year-old women with septic arthritis of the left L4-L5 lumbar facet joint associated with endocarditis . Arthritis diagnosis was made on CT scan and MRI, infection by Staphyloccocus aureus was proved by blood cultures . Heart growth was seen by echocardiography . Twenty-three cases were reported in the literature . Clinical and biological data failed to discriminate between facet joint septic arthritis and spondylodicitis . Diagnosis is established on imaging findings, computed tomography and magnetic resonance imaging, completed by blood cultures and, if they are negative, by aspiration-biopsy . Appropriate antimicrobial therapy is usually successful . Some back pain generally persists . In conclusion, lumbar pain with fever without spondylodiscitis is suggestive of septic arthritis of a lumbar facet joint . Epiduritis associated in 60% patients requires rapid treatment.

Eur J Gastroenterol Hepatol, 2001 Jul, 13(7), 771 - 6
Defensins -- innate immunity at the epithelial frontier; Fellermann K et al.; Physical barrier function was formerly believed to play the major role in mucosal protection against luminal bacteria . This view has now been challenged by the discovery of specialized molecules that possess antimicrobial activity . More than 100 peptides have been identified so far, and the number is still growing . These peptides are distributed widely and conserved throughout phylogeny . The epithelial expression of antimicrobial peptides is of particular interest as many pathogens adhere to epithelial surfaces and may eventually invade the host . This rapidly acting defence system of innate immunity is already engaged before adoptive immune interactions take place . These antimicrobial peptides consist of constitutive and inducible forms, potentiating this barrier function in terms of an inflammatory response.One important subgroup of antimicrobial peptides is the family of defensins, which are classified as alpha (alpha-) and beta (beta-) defensins . Eight different peptides with varying antimicrobial properties have been identified . They are distributed widely in humans, and organ-specific expression patterns have been observed . Homologous peptides have been found in other mammals, vertebrates, invertebrates, insects and plants . The identification of alpha-defensins and their murine counterparts, cryptdins, in the small intestine prompted intensive research into epithelial antimicrobial defence.

Cytogenet Cell Genet, 2001, 93(1-2), 100 - 4
Organization and chromosomal localization of the human and mouse genes coding for LanC-like protein 1 (LANCL1); Mayer H et al.; We have determined the organization and chromosome location of the human LANCL1 and mouse Lancl1 genes encoding LANCL1, the lanthionine synthetase component C (LanC)-like protein 1 . LANCL1 is related to the bacterial LanC family which is involved in the biosynthesis of antimicrobial peptides . The human and mouse genes span 45 kb and 38 kb, respectively, each comprising ten exons . Within the potential promoter regions, several consensus sequences for ubiquitous and tissue-specific transcription factors are present, reflecting the expression data . The nucleotide sequence of the previously unknown mouse full-length transcript is also reported here . Fluorescence in situ hybridization analyses assigned the LANCL1 gene to human chromosome 2q34 and the Lancl1 gene to mouse chromosome 1, region C2-C5, in accordance with the known homology .

Mol Med, 2001 Jan, 7(1), 1 - 10
Essential components of antimicrobial gastrointestinal epithelial barrier: specific interaction of mucin with an integral apical membrane protein of gastric mucosa; Slomiany A et al.; BACKGROUND: The gastric mucosal protective barrier consists of two essential elements: mucus glycoprotein, mucin, secreted by gastric mucosal cells, and the mucin binding protein (MBP), an integral component of the apical epithelial membrane . The studies described here provide evidence on the structure of MBP, its interaction with mucin, and the susceptibility to phospholipase C (PLC) and Helicobacter pylori protease . MATERIAL AND METHODS: The rat gastric mucosa was used to isolate mucin and the apical epithelial membranes . A buffered saline extract of the mucosal cells was used for the isolation of mucin and the 1% Triton X-100-insoluble gastric apical membranes for the preparation of MBP . RESULTS: The studies on MBP, the mucosal mucin receptor revealed that the protein is anchored in apical membrane through glycosylphosphatidylinositol (GPI) . The deamination of MBP with nitrous acid afforded phosphatidylinositols (PIs) and a water soluble, 97 kDa glycosylated protein . The in situ studies with untreated rat gastric mucosa and the mucosa depleted of mucin showed that MBP without mucin was susceptible to the proteolytic degradation with pepsin and H . pylori proteases, but was not released from the apical membrane by the treatment with bacterial PLC . CONCLUSION: The study of carbohydrate ligands for MBP revealed binding of octa- and decasaccharides of gastric mucin . The severe impairment in mucin adhesion to MBP, induced by the diet containing ethanol, supports the conclusion that specific carbohydrate determinants participate in mucin attachment to MBP and epigenetic control of the processes that coordinates its interaction with apical mucosal epithelium in the formation of innate protective barrier.

J Clin Microbiol, 2001 Aug, 39(8), 2829 - 34
Clinical isolates of non-O157 Shiga toxin-producing Escherichia coli: serotypes, virulence characteristics, and molecular profiles of strains of the same serotype; Eklund M et al.; All human Shiga toxin-producing Escherichia coli (STEC) non-O157 strains (n = 56) isolated in Finland from 1990 to August 2000 were characterized for the O:H serotype, stx(1) and stx(2) genes, production of enterohemolysin, and sensitivity to 12 antimicrobial agents . Strains of the same serotype were genotyped by pulsed-field gel electrophoresis (PFGE) after XbaI restriction of total DNA . The 56 non-O157 isolates belonged to 29 serotypes . Two of the serotypes (O102:H7 and OX181:H49) have not previously been described as being associated with STEC infections in humans or isolated from animals . Thirty-four strains (61%) within seven serotypes (O103:H2 {14 isolates}, O26:H11 {6 isolates}, O145:H28 {4 isolates}, O145:HNM {3 isolates}, O15:HNM {3 isolates}, OX174:H21 {2 isolates}, and O Rough:HNM {2 isolates}) were represented by more than one isolate . Of these strains, O103:H2 isolates were divided into seven, O26:H11 isolates were divided into four, and the rest within a serotype were divided into two genotypes in PFGE . In PCR, 31 (55%) of the 56 strains were positive for the stx(2) gene only and 24 strains (43%) were positive for stx(1) only . One strain (O43:H2) carried both stx(1) and stx(2) . Forty-two strains (75%) produced enterohemolysin, and 39 strains (70%) possessed the eae gene . Of the latter 39 strains, 36 (92%) were enterohemolytic, whereas only 6 (35%) of the 17 isolates lacking the eae gene were enterohemolytic (P < 0.001) . The majority of the strains (44 strains, 79%) were sensitive to all 12 antimicrobials tested . Of the 56 strains, 20 (36%) were associated with small family outbreaks in nine families and 14 (25%) were associated with recent travel abroad.

J Clin Microbiol, 2001 Aug, 39(8), 2823 - 8
Improved antimicrobial interventions have benefits; Barenfanger J et al.; Studies have shown benefits to patients from improved interventions involving antimicrobial therapy . The purpose of the present study was to evaluate prospectively the impact of improved interventions by (i) the use of TheraTrac 2, a computer software program which electronically links susceptibility testing results immediately to the pharmacy and alerts pharmacists of potential interventions, and (ii) the education of pharmacists involving microbiologic topics . The study group had the new intervention program . The control group had interventions performed the way that they had previously been done by manually reviewing hard copies of susceptibility testing data . In a 5-month period, all inpatients whose last names began with A to K were the study group; inpatients whose last names began with L to Z were controls . Three analyses were done; one analysis (analysis A) involved only patients with interventions, one analysis (analysis B) involved all patients for whom antimicrobial testing was done and who were matched for diagnosis-related groups (DRGs), regardless of whether an intervention occurred, and one analysis (analysis C) involved these DRG-matched patients by using severity-adjusted data . In analysis A, the study group had a 4.8% decreased rate of mortality, an average of a 16.5-day decreased length of stay per patient, and $20,886 decreased variable direct costs per patient . None of these differences was statistically significant . In analysis B, the study patients had a 1.2% higher mortality rate (P = 0.741), an average of a 2.7-day decreased length of stay per patient (P = 0.035), and $2,626 decreased variable direct costs per patient (P = 0.008) . In analysis C, the study patients had a 1.4% lower mortality rate, a 1.2-day decreased length of stay per patient, and $1,466 decreased variable direct costs per patient . In conclusion, the institution of this program caused substantial cost savings.

J Biol Chem, 2001 Sep 21, 276(38), 35714 - 22 Epub 2001 Jul 25.
Interaction of cationic antimicrobial peptides with model membranes; Zhang L et al.; A series of natural and synthetic cationic antimicrobial peptides from various structural classes, including alpha-helical, beta-sheet, extended, and cyclic, were examined for their ability to interact with model membranes, assessing penetration of phospholipid monolayers and induction of lipid flip-flop, membrane leakiness, and peptide translocation across the bilayer of large unilamellar liposomes, at a range of peptide/lipid ratios . All peptides were able to penetrate into monolayers made with negatively charged phospholipids, but only two interacted weakly with neutral lipids . Peptide-mediated lipid flip-flop generally occurred at peptide concentrations that were 3- to 5-fold lower than those causing leakage of calcein across the membrane, regardless of peptide structure . With the exception of two alpha-helical peptides V681(n) and V25(p,) the extent of peptide-induced calcein release from large unilamellar liposomes was generally low at peptide/lipid molar ratios below 1:50 . Peptide translocation across bilayers was found to be higher for the beta-sheet peptide polyphemusin, intermediate for alpha-helical peptides, and low for extended peptides . Overall, whereas all studied cationic antimicrobial peptides interacted with membranes, they were quite heterogeneous in their impact on these membranes.

Am J Respir Cell Mol Biol, 2001 Jul, 25(1), 21 - 5
Salt-independent abnormality of antimicrobial activity in cystic fibrosis airway surface fluid; Bals R et al.; The link between the genetic defect in cystic fibrosis (CF) and the recently described breach in pulmonary host defense has focused on the role of salt and water metabolism in the airways . Using a human bronchial xenograft model we demonstrate a salt-independent abnormality in bacterial killing in CF airway surface fluid (ASF) . Biochemical characterization implicates the absence or dysfunction of a molecule critical to the constitution of normal bacterial killing . Our study suggests that CF transmembrane conductance regulator (CFTR) deficiency causes a primary abnormality in the composition of ASF that leads to a salt-independent defect in host defense . Importantly, this defect is corrected by adenovirus-mediated gene transfer of CFTR.

Appl Environ Microbiol, 2001 Aug, 67(8), 3732 - 4
Horizontal transfer of a multi-drug resistance plasmid between coliform bacteria of human and bovine origin in a farm environment; Oppegaard H et al.; Multi-drug-resistant coliform bacteria were isolated from feces of cattle exposed to antimicrobial agents and humans associated with the animals . Isolates from both cattle and humans harbored an R plasmid of 65 kb (pTMS1) that may have been transferred between them due to selective antibiotic pressure in the farm environment.

Appl Environ Microbiol, 2001 Aug, 67(8), 3542 - 8
Fate of the biological control agent Pseudomonas aureofaciens TX-1 after application to turfgrass; Sigler WV et al.; The fate and impact of Pseudomonas aureofaciens TX-1 following application as a biocontrol agent for fungi in turfgrass were studied . The organism was applied with a modified irrigation system by using a preparation containing 1 x 10(6) P . aureofaciens TX-1 CFU ml(-1) about 100 times between May and August . We examined the impact of this repeated introduction of P . aureofaciens TX-1 (which is known to produce the antimicrobial compound phenazine-1-carboxylic acid) on the indigenous microbial community of the turfgrass system and on establishment of introduced bacteria in the soil system . A PCR primer-DNA hybridization probe combination was developed to accurately monitor the fate of P . aureofaciens TX-1 following application in irrigation water . To assess the impact of frequent P . aureofaciens TX-1 applications on the indigenous bacterial community, turfgrass canopy, thatch, and rhizosphere samples were obtained during the growing season from control and treated plots and subjected to DNA extraction procedures and denaturing gradient gel electrophoresis (DGGE) . PCR amplification and hybridization of extracted DNA with the P . aureofaciens TX-1-specific primer-probe combination revealed that P . aureofaciens TX-1 not only became established in the rhizosphere and thatch but also was capable of overwintering . Separation of PCR-amplified partial 16S rRNA genes by DGGE showed that the repeated application of P . aureofaciens TX-1 in irrigation water resulted in transient displacement of a leaf surface bacterial community member . There was no obvious alteration of any dominant members of the thatch and rhizosphere microbial communities.

Dev Comp Immunol, 2001 Sep, 25(7), 565 - 77
Immune gene discovery by expressed sequence tag analysis of hemocytes and hepatopancreas in the Pacific White Shrimp, Litopenaeus vannamei, and the Atlantic White Shrimp, L . setiferus; Gross PS et al.; A pilot program was undertaken in immune gene discovery in two sister species of litopenaeid shrimp, the Pacific white shrimp, Litopenaeus vannamei and the Atlantic white shrimp, L . setiferus . RNA from the hemocytes and hepatopancreas of single individuals from each species was recovered, 4 cDNA libraries (one from each tissue/species) were made by a PCR-based method and a total of approximately 2045 randomly selected clones were sequenced . A total of 268 expressed sequence tags (ESTs) were found that corresponded to 44 immune function genes . The most common immune-function ESTs (172) were antimicrobial peptides, which were restricted to the hemocyte libraries . Lectins were the largest group of immune-function ESTs found in the hepatopancreas . Analysis of these libraries indicates that EST approaches are effective for immune gene discovery in shrimp and that the diversity of these PCR-generated libraries would support full-scale EST collection.

Aliment Pharmacol Ther, 2001 Aug, 15(8), 1187 - 91
Efficacy of ecabet sodium for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole-based regimen; Adachi K et al.; BACKGROUND: The cytoprotective agent, ecabet sodium, inhibits urease activity and growth of Helicobacter pylori . AIM: To evaluate the efficacy and safety of ecabet sodium-based eradication of H . pylori infection, compared with a lansoprazole-based regimen, in a randomized multicentre study . SUBJECTS AND METHODS: A total of 120 H . pylori-positive patients were assigned to one of two treatment regimens for 2 weeks: ecabet sodium 1 g b.d., amoxicillin 500 mg t.d.s . and clarithromycin 400 mg b.d . (EAC: 60 patients); or lansoprazole 30 mg (o.m.) with the same antimicrobial agents (LAC: 60 patients) . Cure of infection was assessed by a 13C-urea breath test 1 month after completion of treatment . RESULTS: One patient in the EAC group and two in the LAC group did not complete therapy because of an adverse event, and three did not undergo the 13C-urea breath test . Cure rates for the intention-to-treat, all-patients-treated and per protocol analysis in the EAC group were 85%, 86% and 88%, respectively, whereas those in the LAC group were 85%, 88% and 91% . There were no significant differences in cure rate or adverse events between the two regimens . CONCLUSIONS: Ecabet sodium in combination with amoxicillin and clarithromycin is as effective as lansoprazole-based eradication therapy for H . pylori.

J Int Med Res, 2001 May-Jun, 29(3), 147 - 53
A randomized comparison of triple therapy Helicobacter pylori eradication regimens in children with peptic ulcers; Shcherbakov PL et al.; An open, randomized trial was performed to compare the efficacy of three Helicobacter pylori eradication regimens in children with peptic ulcer disease . A total of 106 children (5 - 15 years) were treated for 1 week with metronidazole, 30 - 40 mg/kg per day depending on age, amoxycillin, 750 mg/day, and one of three anti-secretory agents: proprietary omeprazole, 20 - 40 mg/day depending on age; generic omeprazole, 20 - 40 mg/day; or ranitidine, 150 mg twice daily . The H . pylori eradication rate was significantly higher in patients receiving proprietary omeprazole (88.9%) than in those receiving generic omeprazole (80.0%) or ranitidine (74.3%), and this was associated with a trend towards faster ulcer healing . It is concluded that triple therapy consisting of an anti-secretory agent and two antimicrobials produces effective eradication of H . pylori and ulcer healing in children with peptic ulcer disease, and that proprietary omeprazole is more effective than both ranitidine and the generic formulation used in this study.

Microbiol Immunol, 2001, 45(5), 333 - 40
Menadione-catalyzed O2- production by Escherichia coli cells: application of rapid chemiluminescent assay to antimicrobial susceptibility testing; Yamashoji S et al.; This study proposes a novel chemiluminescent assay of bacterial activity . Luminol chemiluminescence (LC) was amplified on addition of menadione to Escherichia coli suspension, and it was effectively inhibited by addition of superoxide dismutase rather than catalase . This fact suggests that H2O2 produced from O2 by superoxide dismutase is decomposed by catalase of E . coli . NAD(P)H:menadione reductase activities in periplasm and cytosol corresponded to the amplification of menadione-catalyzed LC, and outer and cytoplasmic membranes were only slightly involved in the LC . The total activity and Vmax of NAD(P)H:menadione reductase in the cytoplasm were greater than those in the periplasm . A transient increase in menadione-catalyzed LC was observed in the exponential phase and the LC decreased in the stationary phase during growth of E . coli . Menadione-catalyzed LC was sensitive to antibiotic action . A decrease in menadione-catalyzed LC by the impairment of membrane functions and by the inhibition of protein synthesis was observed at 5 min and 3 hr, respectively . These findings suggest the possibility that menadione-catalyzed luminol chemiluminescent assay is applicable to rapid antimicrobial assay because LC is sensitive to the change in growth and cytotoxic events caused by antimicrobial agents.

Am J Health Syst Pharm, 2001 Jul 15, 58(14), 1325 - 9
Potential risks and prevention, Part 2: Drug-induced permanent disabilities; Kelly WN; Potential risk factors for and the preventability of drug-induced permanent disabilities were studied . Case reports of adverse drug events (ADEs) published in Clin-Alert during 1978-97 were the source of information on drug-induced permanent disabilities . Patient, drug, and event variables were identified, and the causality, predictability, and preventability of each case were assessed . Data were entered into a relational database for analysis . The data indicated 227 cases of drug-induced permanent disabilities . Twenty-three percent of the cases were assessed as definite, 47% as probable, and 30% as possible . Twenty-nine percent of the patients were less than 10 years old, and 36% were considered healthy . The drug categories most commonly associated with a drug-induced permanent disability were antimicrobials, vaccines, central-nervous-system agents, and antineoplastics . About half of the patients received more than the usual dosage . The most common permanent disabilities were brain damage, blindness, tardive dyskinesia, deafness, quadriplegia, and hearing loss . Event types were distributed as medication errors (55%), adverse drug reactions (43%), and drug interactions (2%) . Eighty-four percent of the drug-induced permanent disabilities were judged to have been preventable; of these, a pharmacist could have prevented 40% . Litigation was reported for 56% of the cases of drug-induced permanent disability; judgments and settlements averaged $4.3 million . A review of published case reports of ADEs for 1978-97 yielded information on possible risk factors for drug-induced permanent disabilities and on which events may have been preventable.

Am J Health Syst Pharm, 2001 Jul 15, 58(14), 1317 - 24
Potential risks and prevention, Part 1: Fatal adverse drug events; Kelly WN; Potential risk factors for and the preventability of fatal adverse drug events (ADEs) were studied . Case reports of ADEs published in Clin-Alert during 1976-95 were the source of information on fatal ADEs, Patient, drug, and event variables were identified, and the causality, predictability, and preventability of each case were assessed . Data were entered into a relational database for analysis . The data indicated 447 cases involving a fatal ADE . Ten percent of the fatal ADEs were assessed as definite, 46% as probable, and 44% as possible . Fatal-ADE frequency increased with age . Forty-five percent of the patients were 40-69 years of age, and 40% were healthy . Central-nervous-system agents, antineoplastics, antimicrobials, and cardiovascular agents accounted for 69% of the deaths . Only 33% of patients received more than the usual dosage . Many of the suspected drugs could have been monitored with blood level tests but were not, and baseline testing of critical blood count and liver and renal function was often not performed . The most common causes of death were hepatitis, hepatic failure, cardiopulmonary arrest, overdose, and agranulocytosis . ADE types were distributed as adverse drug reactions (58%), allergic reactions (19%), medication errors (17%), and drug interactions (6%) . Sixty-eight percent of the fatal ADEs were judged to have been preventable; of these, a pharmacist could have prevented 57% . Litigation was reported for 14% of the fatal-ADE cases; judgments and settlements averaged $1.1 million . A review of published case reports of ADEs for 1976-95 yielded information on possible risk factors for fatal ADEs and on which events may have been preventable.

FEBS Lett, 2001 Jul 20, 501(2-3), 146 - 50
Optimization of the antimicrobial activity of magainin peptides by modification of charge; Dathe M et al.; Investigation of magainin II amide analogs with cationic charges ranging between +3 and +7 showed that enhancement of the peptide charge up to a threshold value of +5 and conservation of appropriate hydrophobic properties optimized the antimicrobial activity and selectivity . High selectivity was the result of both enhanced antimicrobial and reduced hemolytic activity . Charge increase beyond +5 with retention of other structural motifs led to a dramatic increase of hemolytic activity and loss of antimicrobial selectivity . Selectivity could be restored by reduction of the hydrophobicity of the hydrophobic helix surface (H(hd)), a structural parameter not previously considered to modulate activity . Dye release experiments with lipid vesicles revealed that the potential of peptide charge to modulate membrane activity is limited: on highly negatively charged 1-palmitoyl-2-oleoylphosphatidyl-DL-glycerol bilayers, reinforcement of electrostatic interactions had an activity-reducing effect . On neutral 1-palmitoyl-2-oleoylphosphatidylcholine bilayers, the high activity was determined by H(hd) . H(hd) values above a certain threshold led to effective permeabilization of all lipid systems and even compensated for the activity-reducing effect of charge increase on highly negatively charged membranes.

Curr Infect Dis Rep, 2001 Aug, 3(4), 360 - 364
Timing of Administration of Antimicrobial Therapy in Bacterial Meningitis; Short WR et al.; Bacterial meningitis is an important cause of morbidity and mortality in the United States and throughout the world . The diagnosis of bacterial meningitis is often delayed in patients as a result of numerous factors such as length of illness, use of radiologic imaging studies, and/or prior use of antimicrobial agents . Many textbooks emphasize the need for prompt initiation of antimicrobial therapy in a patient with suspected acute bacterial meningitis to prevent many of the long-term sequelae associated with this disorder . We have reviewed the literature to determine if there is a standard of care for timing of administration of antimicrobial therapy in patients with a diagnosis of acute bacterial meningitis . Although the clinical data are inconclusive, it makes intuitive sense to initiate antimicrobial therapy as soon as possible in any patient with suspected or proven bacterial meningitis before the patient's illness advances to a high level of clinical severity, beyond which antimicrobial therapy is less likely to be of benefit . However, clinical experiences suggest that patient outcome in bacterial meningitis is a result of multiple factors, since some patients treated within a few hours of symptoms develop an adverse outcome whereas others who are symptomatic for days prior to presentation suffer no adverse sequelae.

Curr Infect Dis Rep, 2001 Aug, 3(4), 319 - 327
Outpatient Management of Infective Endocarditis; Monteiro CA et al.; Because of unique host defense characteristics of the endocardium, successful therapy for infective endocarditis (IE) has necessitated bactericidal antimicrobial agents, generally administered in high doses for prolonged periods of time . This has required therapy in the hospital setting . However, in recent years, it has become apparent that outpatient therapy is feasible if appropriate agents can be administered at home, for example, using either home parenteral therapy or oral preparations . Over the past few decades, there has been a trend toward reducing inpatient reimbursement for various conditions, including serious infections . The decision to treat IE on an outpatient basis is made more easily if based on previous published experience . Published reports have concluded that outpatient therapy is more appropriate for "uncomplicated" IE caused by relatively susceptible microorganisms . The purpose of this paper is to review data describing the results of management of IE in the outpatient setting.

Curr Gastroenterol Rep, 2001 Aug, 3(4), 315 - 21
New developments in the understanding of cholera; Butler T; Recent advances in prevention and treatment of cholera have occurred in the areas of vaccine testing, modifications of oral-rehydration solutions (ORS), and antimicrobial treatment . Oral vaccines consisting of killed whole bacterial cells (WC) with and without the B-subunit of cholera toxin (BS) were shown to be effective in large trials in Bangladesh, Peru, and Vietnam . However, the trials did not resolve whether two or three doses of vaccine are required and whether BS adds significantly to the immune protection of WC . Live, attenuated bacterial vaccines that are immunogenic and have been shown protective in human volunteer studies are candidates for future field trials . Rehydration of patients is a life- saving effort . The best ORS contains rice powder in place of glucose, and solutions with reduced osmolarity (245 mOsm/L, sodium 75 mEq/L) are as effective as standard ORS . Ciprofloxacin in a single dose is effective in adults, and erythromycin or ampicillin in multiple doses is effective in children.

Arch Biochem Biophys, 2001 Aug 1, 392(1), 3 - 7
Antimicrobial peptide buforin I inhibits tissue factor-initiated coagulation; Chu AJ et al.; The enhanced extrinsic blood coagulation following septic shock often manifests cardiovascular complications . The upregulated monocytic tissue factor (mTF) was shown to be a primary contributor to the extrinsic hypercoagulation following acute bacterial endotoxin (LPS) infection . A single-stage clotting assay monitors TF-initiated coagulation . We herein demonstrate a novel anticoagulant activity of antimicrobial peptide Buforin I (BF I) in offsetting LPS-induced mTF hypercoagulation in THP-1 cells, which was confirmed in a cell-free in vitro model, showing that BF I effectively blocked rabbit brain thromboplastin (rbTF) procoagulant activity . Upon inclusion of 25 microM BF I into human plasma, the prolonged prothrombin time (PT) was consistent with the depressed TF-initiated coagulation . In a two-stage chromogenic assay monitoring S-2288 hydrolysis, BF I significantly inhibited not only mTF- but also rbTF-catalyzed FVII activation accompanied by the diminished FVIIa formation . The inhibition by BF I of FVII activation accounted for its novel anticoagulant activity in offsetting mTF-initiated hypercoagulation .

J Endod, 2000 Nov, 26(11), 649 - 51
Influence of mixing vehicle on dissociation of calcium hydroxide in solution; Safavi K et al.; The antimicrobial effects of aqueous preparations of calcium hydroxide have been demonstrated in the past . Calcium hydroxide, when dissolved in water, dissociates into hydroxide and calcium ions . The presence of hydroxide ions in a solution makes it antimicrobial . Recently it was shown that the use of glycerin as a mixing vehicle facilitates placement of calcium hydroxide in the root canals . The influence of nonaqueous mixing vehicles on the dissociation of calcium hydroxide is not clearly understood . In this study the conductivity of aqueous and nonaqueous solutions of calcium hydroxide was measured . The conductivity values for saturated solutions of calcium hydroxide in water was 7.3+/-3 mS/cm . The conductivity of calcium hydroxide in pure glycerin or propylene glycol was essentially zero . It was concluded that use of nonaqueous mixing vehicles may impede the effectiveness of calcium hydroxide as a root canal dressing.

Rev Esp Enferm Dig, 2000 Dec, 92(12), 793 - 8
Resistance of Helicobacter pylori to antimicrobial treatment in a Seville hospital catchment area; Rojas Feria M et al.; AIM: To determine the sensitivity to metronidazol, clarithromycin, amoxicillin and tetracycline of strains of Helicobacter pylori isolated in a prospective series of patients referred to a university hospital in Seville for endoscopic examination . METHODS: During the period from March 1998 to July 1999 we studied 117 patients with ulcer . The diagnosis of bacterial infection was based on the rapid urease test, histological study, Gram staining or culture of gastric biopsy material (from the antrum and corpus) obtained during gastroscopy . Susceptibility studies were done with the diffusion method using E-test strips . RESULTS: Helicobacter pylori infection was found in 64 patients . A total of 58 strains were grown, 40 of which were from patients who had received no previous treatment to eradicate the infection (69%), and 18 of which were from patients who had failed one or more eradication therapies (31%) . In the first group, metronidazol resistance was found in 42%, clarithromycin resistance in 13%, and resistance to both in 10% of the patients . In the second group these rates were 39%, 44% and 17% respectively, and one strain was found which was also resistant to tetracyclines (2%) . No strains resistant to amoxicillin were found . CONCLUSIONS: We found high rates of resistance, especially to clarithromycin, and especially in patients who had received previous eradication therapy . Empirical treatments should use effective antimicrobials and avoid regimens based on a single antibiotic . Culture of gastric biopsy samples provides information on the resistance to antimicrobials in a given setting, and this information can be used to develop the most rational treatment for the infection.

Fundam Clin Pharmacol, 2001 Apr, 15(2), 85 - 93
Inflammation, infection and antimicrobial therapy in coronary heart disease--where do we currently stand?
Ngeh J, Gupta S.
Traditional atherosclerotic risk factors such as hypertension, smoking, hyperlipidaemia and diabetes mellitus, account for only about 50% of the clinical occurrence of coronary heart disease (CHD) . The infectious hypothesis proposes that various microorganisms, in particular, Chlamydia pneumoniae, may serve as potential etiological factors, linking inflammation and atherosclerosis (or its clinical manifestations) . Evidence from seroepidemiology, pathology, animal models, molecular biology and immunology, and human antibiotic intervention studies, collectively have suggested a largely positive association between C . pneumoniae infection and CHD . As CHD is a multifactorial disease, it is possible that C . pneumoniae may interact with conventional cardiovascular risk factors and predispose certain genetically susceptible people to atherosclerotic disease . However, the precise nature of a causal or coincidental link between C . pneumoniae and CHD remains to be determined . The results of ongoing antibiotic intervention studies may help to further clarify the role of infection and inflammation in CHD, but until such a role is proven beyond reasonable doubt, antimicrobial therapy cannot yet be justified in the treatment or prevention of CHD . A current perspective is presented in this review.

Biochem Biophys Res Commun, 2001 Jul 27, 285(4), 1046 - 51
Structure-activity analysis of SMAP-29, a sheep leukocytes-derived antimicrobial peptide; Shin SY et al.; SAMP-29 is a cathelecidin-derived antimicrobial peptide deduced from sheep myeloid mRNA . To elucidate the structural-activity relationship of SMAP-29, several analogues were synthesized and their antibiotic activity was investigated . Compared to parental SMAP-29, SMAP-29(1-17) and {K(22,25,27)}-SMAP-29 retained relatively effective antimicrobial activity (MIC: 1.0-8.0 microM), but resulted in a complete loss of hemolytic activity . Pro-19 --> Ala substitution ({A19}-SMAP-29) in SMAP-29 induced a significant reduction in antibacterial activity . These results suggested that the N-terminal amphipathic alpha-helical region and the C-terminal hydrophobic region of SMAP-29 are responsible for antimicrobial activity and hemolytic activity, respectively, and the central Pro-19 in SMAP-29 plays a critical role in showing improved antibacterial activity . In particular, {K(2,7,13)}-SMAP-29(1-17) showed potent antimicrobial activity under high salt conditions without hemolytic activity . Thus, this short peptide could serve as an attractive candidate for the development of therapeutic antimicrobial drugs . Structural analysis by circular dichroism suggested that SMAP-29 seems to adopt a helix-bend/turn-extended random conformation .

Parasitology, 2001 Jul, 123(Pt 1), 57 - 65
Histone-like proteins from fish are lethal to the parasitic dinoflagellate Amyloodinium ocellatum; Noga EJ et al.; Antimicrobial proteins were purified from acid extracts of rainbow trout (Oncorhynchus mykiss) and sunshine bass (Morone saxatilis male x M . chrysops female) skin, gill and spleen by reverse-phase HPLC . Mass spectrometry and amino acid sequence data suggest that these proteins are closely related to histone H2B and histone H1 and thus they were designated histone-like proteins (HLPs) . These proteins were lethal to Amyloodinium ocellatum, which is one of the most important parasitic agents affecting fish . Antibiotic concentrations as low as 12.5 microg/ml were inhibitory . Activity was directed against the trophont (feeding) stage of the parasite, while the disseminative (dinospore) stage was unaffected . Thus, HLPs act unlike typical drugs used to treat amyloodiniosis, which usually target the dinospore . Both the ability of the parasite to infect host cells, as well as the ability to grow and differentiate after infection were severely inhibited . This is in contrast to magainin 2, which was similarly toxic to both the dinospore and trophont stages . These findings provide further evidence that histone-like proteins may be important defensive molecules in fish.

Diabetes Technol Ther, 2000 Spring, 2(1), 61 - 6
Stability of U-10 and U-50 dilutions of insulin lispro; Stickelmeyer MP et al.; BACKGROUND: Insulin lispro, a rapid acting analog of human insulin, has been shown to be useful in the treatment of children with diabetes . However, lower concentrations of this insulin may be needed to facilitate optimal clinical use . Therefore, the stability of insulin lispro when diluted with an appropriate diluent was evaluated . METHODS: Insulin lispro (U-100, 100 U/mL) was diluted with sterile Neutral Protamine Hagedorn (NPH) diluent to U-10 and U-50 . After storage for 7, 14, 21, 28, and 32 days at 5 degrees C and 30 degrees C, the diluted insulins were analyzed by high-performance liquid chromatography (HPLC) to determine potency, purity, polymer, and preservative (metacresol or phenol) content in addition to physical appearance and pH determinations . Microbiological testing for preservative effectiveness was performed on the U-10 and U-50 solutions after 32 days at both temperatures . RESULTS: U-10 and U-50 dilutions of insulin lispro stored at 5 degrees C and 30 degrees C maintained potency and purity throughout the 32-day testing period . Additionally, both control and diluted vials maintained antimicrobial effectiveness . CONCLUSION: Insulin lispro when diluted with the appropriate diluent demonstrates acceptable stability when stored at 5 degrees C and 30 degrees C for a period of 32 days.

Pediatr Infect Dis J, 2001 Jul, 20(7), 679 - 84
Physician control of pediatric antimicrobial use in Beijing, China, and its rural environs; O'Connor S et al.; BACKGROUND: Antibiotic resistance is recognized as an increasing problem in China . It is widely believed that because antibiotics are available without a prescription, changing physician prescribing behaviors will not decrease inappropriate usage . This study identified the sources of antibiotics and the important influence that physicians have on antibiotic use by children in one region of China . METHODS: Trained medical professionals surveyed parents of children attending several kindergartens in urban Beijing and rural Gu'An, Hebei County . Parents completed a questionnaire concerning the children's recent illnesses, care-seeking patterns and antibiotic use . The team also observed hospital- and non-hospital-based pharmacy purchases of antibiotics for children, assessed the proportion accompanied by a prescription and then interviewed parents about factors influencing those purchases . RESULTS: Of 241 urban and 143 rural kindergarten parents, 76 to 82% usually obtained children's antibiotics from a hospital pharmacy (with a prescription) . For 84% the first source of care was usually a physician (primarily western medicine, sometimes traditional Chinese medicine) . Only 5% of antibiotics were obtained from independent vendors without prior physician consultation . Among 229 observed antibiotic purchases 72% occurred at hospital-based facilities, even after longer observation times at nonhospital pharmacies . Prescriptions accompanied all hospital-based antibiotic purchases, contrasting with 18% of nonhospital transactions (P < 0.001) . Together 86% of parents self-reported that the observed purchase stemmed from a doctor's recommendation . CONCLUSIONS: Doctors directly and indirectly controlled the majority of antibiotic usage for childhood illnesses in Beijing and Gu'An (Hebei County) . Physician education and implementation of treatment guidelines might substantially reduce inappropriate antimicrobial usage and help prevent antimicrobial resistance in this region.

Pediatr Infect Dis J, 2001 Jul, 20(7), 662 - 6
Prevalence and rapid identification of clarithromycin-resistant Helicobacter pylori isolates in children; Yang YJ et al.; BACKGROUND: Little is known about the prevalence of antibiotic-resistant Helicobacter pylori infection in children . Culture and antimicrobial susceptibility testing are generally time-consuming and not a routine in many hospitals . OBJECTIVE: To investigate the prevalence of clarithromycin-resistant H . pylori strains in children, to identify those isolates via rapid methodology and to examine the severity of gastritis caused by the antibiotic-resistant H . pylori isolates . METHODS: Enrolled were 245 children investigated for H . pylori infection by endoscopic examination . The gastric antral specimens were subjected to DNA extraction and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with primers specific to the H . pylori 23S rRNA gene . Conventional bacterial cultures were performed simultaneously as the diagnostic standard . Minimal inhibitory concentrations of clarithromycin and metronidazole were determined by E test . This was used as a standard to determine the sensitivity and specificity of the above PCR-RFLP assay . The specimens were processed for histologic examination and evaluated by the updated Sydney system . RESULTS: H . pylori was isolated in 67 of the 245 children; 12 (18%) of them were clarithromycin-resistant and 6 (9%) were metronidazole-resistant . No difference in histologic examinations was noted between the antibiotic-resistant and -susceptible strains . We performed PCR-RFLP with all 12 clarithromycin-resistant isolates: 10 had a 23S ribosomal RNA A2144G point mutation; 1 had a mixture of an A2143G point mutant and susceptible strains; and 1 had neither of the 2 mutations . CONCLUSIONS: The prevalence of clarithromycin-resistant H . pylori isolates in Taiwanese children is 18% . PCR-RFLP had a high sensitivity (92%) and specificity (100%) for the clarithromycin resistance gene mutation determination . The dominant mutation is A2144G . PCR-RFLP provides a rapid and accurate approach to detect clarithromycin-resistant strains within 24 h.

Pharm Res, 2001 May, 18(5), 615 - 21
CYP2C19 genotype related effect of omeprazole on intragastric pH and antimicrobial stability; Kita T et al.; PURPOSE: A combination of proton pump inhibitors and antimicrobials has been applied as an anti-Helicobacter pylori (H . pylori) therapy . Omeprazole, one of the proton pump inhibitors, is metabolized by CYP2C19 . which exhibits genetic polymorphism . It was reported previously that the overall anti-H . pylori efficacy can be related to the CYP2C19 genotype . The main aim of the present study was to obtain a rational explanation for the relationship between the overall anti-H . pylori efficacy and the CYP2C19 genotype . METHODS: Six healthy volunteers were classified as extensive metabolizers and poor metabolizers, according to their CYP2C19 genotypes . Plasma concentrations and intragastric pH were monitored prior to and until 24 h after the administration of 20 mg omeprazole . The stability of amoxicillin, clarithromycin, and metronidazole was examined using buffer solutions with monitored intragastric pH, and their remaining percentage in the intragastric space was simulated . RESULTS: The poor metabolizers, classified by the CYP2C19 genotypes, showed the higher effectiveness in anti-H . pylori therapy, via the higher plasma concentration of omeprazole and the higher intragastric pH, and possibly the higher stability of antimicrobials in the higher intragastric pH . CONCLUSIONS: CYP2C19 genotyping is a very useful method to determine the effective and safe dosage regimen including the selection of the dual and triple therapy in anti-H . pylori therapy.

Curr Drug Targets, 2000 Nov, 1(3), 237 - 45
Antitumor potential and possible targets of phenothiazine-related compounds; Motohashi N et al.; Phenothiazines and its related compounds have shown diverse biological activities including psychotropic, anticancer and other pharmacological activities . Recent studies have suggested the possible interactions between phenothiazines and their physiological targets or potential receptors . New types of phenothiazine, such as "half-mustard type" phenothiazines and benzo{a}phenothiazines, have been synthesized . These compounds stimulated T-cell blast formation, natural killer cell activity (possibly via activation of monocytes and macrophages) and antibody-dependent cellular cytotoxicity of human peripheral blood mononuclear cells, and showed cytotoxicity against several human cancer cell lines . Benzo{a}phenothiazines induced monocytic differentiation and apoptotic cell death (characterized by internucleosomal DNA fragmentation) in human myelogenous leukemic cell lines, but not in other cancer cell lines . These compounds also induced antimicrobial activity in vivo, possibly by host-mediated immunopotentiation . On the other hand, phenothiazines did not induce such immunopotentiation activity, but showed direct antibacterial activity in vitro . There was positive relation between their radical intensity and biological activities . These compounds did not show any apparent mutagenic activity, but rather be antimutagenic . These data suggest their possible applicability of "half-mustard type" phenothiazines and benzo{a}phenothiazines for cancer chemotherapy.

Med Pediatr Oncol, 2001 Jan, 36(1), 177 - 80
Reversal of multidrug resistance-associated protein-mediated drug resistance in cultured human neuroblastoma cells by the quinolone antibiotic difloxacin; Norris MD et al.; BACKGROUND: We have recently shown that high-level expression of the multidrug resistance-associated protein (MRP) gene is a powerful independent predictor of poor outcome in neuroblastoma . The clinical implication of these findings is that MRP modulators may prove therapeutically useful . PROCEDURE: We therefore investigated the ability of difloxacin, a quinolone antimicrobial antibiotic, to increase drug cytotoxicity in unselected cultured human neuroblastoma cells . Drug cytotoxicity was determined using a microtiter assay in neuroblastoma cells expressing low (SH-EP), intermediate (NBL-S), or high {BE(2)-C} levels of MRP . RESULTS: Difloxacin (50 microg/ml) increased sensitivity to the MRP substrates, vincristine, doxorubicin, daunorubicin, and potassium antimony tartrate to an extent directly proportional to their level of MRP expression . No change in the response to cisplatin, which is not a substrate for MRP, was observed in any of the cell lines . CONCLUSIONS: The data demonstrate that difloxacin can reverse drug resistance in unselected human neuroblastoma cells and is therefore a potential candidate for future clinical trials.

Int J Antimicrob Agents, 2001 Jul, 18(1), 49 - 54
Comparative in vitro bacteriostatic and bactericidal activity of trovafloxacin, levofloxacin and moxifloxacin against clinical and environmental isolates of Legionella spp; Gomez-Lus R et al.; The susceptibility of 140 Legionella spp isolates (106 clinical and 34 environmental isolates) to trovafloxacin (TRFX), levofloxacin (LEVX), moxifloxacin (MOFX), ciprofloxacin (CIPX), ofloxacin (OFLX), erythromycin (ERY), azithromycin (AZI) and rifampicin (RIF) was studied using a standard microdilution method and buffered yeast extract broth (BYE) supplemented with 0.1% alpha-ketoglutarate . The post-antibiotic effects (PAEs) of the study drugs against 10 clinical isolates of Legionella pneumophila sg.1 were compared . The MIC inhibiting 90% of strains tested on BYEalpha broth were 0.008, 0.016, 0.016, 0.06, 0.125, 0.5, 0.5, and 0.004 mg/l for TRFX, LEVX, MOXX, CIP, OFLX, ERY, AZI, and RIF, respectively . The MBC/MIC ratios ranged from one to eight depending on the antibiotic tested: TRFX {1x-2 x MIC}, LEVX, MOFX, CIPX and OFLX {1x-4 x MIC}, RIF {2x-4 x MIC}, ERY and AZI {2x-8 x MIC} . TRFX, RIF, LEVX, MOFX, CIPX, OFLX, ERY and AZI showed similar activity against Legionella species other than L . pneumophila . One-hour exposures to the study antimicrobial agents at a concentration of 4 x MIC resulted in PAEs as follows (average in hours): TRFX: 2.68 h; RIF: 2.63 h; CIPX: 2.62 h; MOFX: 2.56 h; LEVX: 2.41 h; OFLX: 2.25 h; AZI: 1.65 h; and ERY: 1.54 h . In conclusion, our in vitro data confirm that trovafloxacin, levofloxacin, moxifloxacin and rifampicin have excellent bacteriostatic and bactericidal activity against Legionella spp and show significant post-antibiotic effect.

Clin Infect Dis, 2001 Aug 15, 33(4), 542 - 7 Epub 2001 Jul 11.
Better control of antibiotic resistance; Guillemot D et al.; This text summarizes the conclusions of the French Working Party to Promote Research to Control Bacterial Resistance, initiated by the French Institute for Public Health Surveillance . The goal was to identify and prioritize the research areas most pertinent to the evolution of antibiotic resistance . The working group was part of a nationwide consultation of experts in the field of bacterial resistance and was coordinated with 2 other groups addressing (1) the use and surveillance of resistance to antibiotics and (2) the control and prevention of resistance to antibiotics . The proposals were discussed at a meeting held on 13 January 1999 by a large group of French microbiologists and clinicians who specialize in infectious diseases . The expert panel stressed that the determinants of evolution of antimicrobial resistance and the possibility of reversing this evolution are not completely known or understood . It emphasized the need for efforts to anticipate emergence of new resistances, to analyze the consequences of bacterial resistance, to develop rapid tests for determination of susceptibility to antibiotics, and to develop new antibiotics.

J Hosp Infect, 2001 Aug, 48(4), 249 - 57
Sequential antibiotic therapy for cost containment in the hospital setting: why not?
Lelekis M, Gould IM.
Antibiotic cost represents a significant part of hospital budgets all over the world . Restriction policies, however and other similar programmes intervening in antimicrobial prescribing have not always been successful in lowering antibiotic expenditure . Timely switch or sequential therapy from initial intravenous to subsequent equivalent oral treatment has been implemented in many institutions for the same purpose . Using strict criteria for optimum patient selection, switch therapy has been proven both effective as antimicrobial treatment and cost saving . As healthcare resources remain lower than needed, cost-saving policies become very desirable . Thus, switch therapy is expected to be more widely used, since it is a cost containing policy which does not compromise treatment outcome .

J Clin Dent, 2000, 11(4), 89 - 93
A rapid method for evaluating microbicidal activity of dentifrice formulations against salivary bacteria ex vivo; Harper DS et al.; A new rapid ex vivo method was developed for evaluating the short-term bactericidal activity of dentifrices against salivary microorganisms . Dentifrice aliquots of 0.25 or 1.0 g were rapidly dispersed into 3.5 mL of freshly pooled human saliva, and 1.0 mL aliquots of the dentifrice-saliva suspension were collected after 30 or 60 seconds of exposure, diluted in neutralizing broth and plated on non-selective agar media for enumeration of surviving total cultivable microflora . Eight experimental dentifrices containing increasing amounts (0 to 2.6%) of a fixed ratio of essential oils (thymol, menthol, methyl salicylate and eucalyptol) were dispersed in saliva at a 0.25:3.5 (w/v) dentifrice:saliva ratio . Recoverable CFUs/mL at 30 sec . were reduced in a dose-responsive manner from > 10(6) to < 10(4) . Additional tests using both 0.25 and 1.0 g amounts of dentifrice prototypes containing 2.1% of the essential oil mixture showed that the experimental dentifrices exhibited highly significant (approximately 2.5 log) reductions in viable recoverable microorganisms relative to essential oil-free placebos after both 30- and 60-second exposures . When compared to in vitro models previously used to evaluate the antimicrobial activity of dentifrices, this method provides a rapid, reproducible, more biologically representative means of screening dentifrice formulations for microbicidal activity using dilutions and exposure times approximating those achieved during toothbrushing . However, since other factors may influence microbicidal activity of dentifrice formulations in vivo, conclusions drawn using this model require clinical confirmation.

J Clin Dent, 2000, 11(4), 107 - 13
Plaque regrowth effects of a triclosan/pyrophosphate dentifrice in a 4-day non-brushing model; McClanahan SF et al.; Triclosan is a lipophilic antimicrobial agent which, when present in an aqueous dentifrice vehicle, is complexed by or in close contact with polymers and surface-active molecules, emulsifying agents, flavoring oils and other hydrophobic ingredients . Because of this, dentifrice products containing triclosan may not have triclosan in a bioavailable state and, hence, the products themselves can not be assumed to possess antimicrobial activity . In order to determine the antimicrobial effects on dental plaque of a triclosan/pyrophosphate dentifrice relative to a negative control (without triclosan or pyrophosphate), a crossover 4-day non-brushing study was conducted . Thirty-four subjects were enrolled in this randomized two-period, double-blind crossover investigation with thirty-three subjects completing all aspects . Following a baseline plaque examination and complete plaque removal at the start of the first 4-day treatment period, subjects initiated a twice-daily supervised dosing regimen, during which they rinsed with their first assigned dentifrice in slurry form while refraining from tooth-brushing and all other oral hygiene procedures . Evaluations to quantify test product effects on plaque were conducted on Day 5 . After a week-long interim washout period, subjects repeated the twice daily rinsing regimen over Days 1-4 of Treatment Period 2 with their second assigned product, again with examinations on Day 5 . Analysis of data demonstrated subjects had significantly (p = 0.0296) less plaque when rinsing with the triclosan/pyrophosphate dentifrice slurry as compared to the negative control dentifrice slurry; the relative treatment difference as determined by the primary examiner was 12.7% . A trainee examiner observed a 16.0% reduction on a subset of subjects (p = 0.0139) . This efficacy result compares favorably with results from other studies of triclosan-containing products . The examinations for oral safety demonstrated no meaningful clinical differences between the triclosan/pyrophosphate dentifrice and control dentifrice.

Bioorg Med Chem Lett, 2001 Jul 23, 11(14), 1829 - 32
Novel piperidinyloxy oxazolidinone antimicrobial agents; Weidner-Wells MA et al.; Oxazolidinone antibacterial agents, where the N-substituted piperazinyl group of eperezolid was replaced with a N-substituted piperidinyloxy moiety, were synthesized and shown to be active against a variety of resistant and susceptible Gram-positive organisms . The effect of ring size, positional isomerism, and fluorine substitution on antibacterial activity was examined.

Planta Med, 2001 Jun, 67(4), 335 - 9
New antioxidant and antimicrobial ellagic acid derivatives from Pteleopsis hylodendron; Atta-Ur-Rahman et al.; Bioassay-guided isolation of two new compounds, 3,4-methylenedioxy-3'-O-methyl-4'-O-glucoside ellagic acid (1) and the pteleoellagic acid derivative (2), from the stem bark of Pteleopsis hylodendron is reported along with 3,4-methylenedioxy-3'-O-methyl ellagic acid (3), 3,3'-di-O-methyl ellagic acid (4) and 3,3',4'-tri-O-methyl ellagic acid (5), which were obtained for the first time from this plant . The structures of these compounds were elucidated with the help of spectroscopic studies . Compounds 1 and 4 were found to have significant antioxidant activity, while compounds 1-4 showed antibacterial activity against different pathogenic bacteria.

Chem Phys Lipids, 2001 Jun, 111(2), 177 - 92
Packing characteristics of a model system mimicking cytoplasmic bacterial membranes; Lohner K et al.; The phase diagram of fully hydrated mixtures of dipalmitoylphosphatidylethanolamine and -phosphatidylglycerol was constructed and the coexistence lines of the solidus and liquidus curve calculated based on regular solution theory using two nonideality parameters for each of the phase to account for nonideal and nonsymmetric mixing . Both lipids show nonideal miscibility in the liquid-crystalline phase, while a region of immiscibility exists in the lamellar-gel phase between the mole fraction x(DPPE)=0.05-0.4 . Two lines of three-phase coexistence around 35 and 40 degrees C reflects the presence of lipid domains predominantly composed of phosphatidylglycerol as well as of the mixed lipid system . This is reflected in the positive nonideality parameters of the gel phase obtained from the simulation of the phase diagram . Moreover, segregation of pure phosphatidylethanolamine domains was detected in mixtures x(DPPE)>0.9, which formed multilamellar liposomes, while unilamellarity was observed for the mixed lipid systems owing to the presence of the negatively charged phosphatidylglycerol . The packing constraints of these phospholipids, major components of cytoplasmic bacterial membranes, may be of importance in the interaction with various solutes like antimicrobial peptides, and were explained based on the nature of the headgroups and the molecular geometry of the phospholipids.

J Am Chem Soc, 2001 Feb 7, 123(5), 870 - 4
Stereochemical elucidation and total synthesis of dihydropacidamycin D, a semisynthetic pacidamycin; Boojamra CG et al.; Hydrogenation of the C(4') exocyclic olefin of the pacidamycins has been shown to produce a series of semisynthetic compounds, the dihydropacidamycins, with antimicrobial activity similar to that of the natural products . Elucidation of stereochemistry in the pacidamycins has been completed through a campaign of natural product degradation experiments in combination with the total synthesis of the lowest-molecular weight dihydropacidamycin, dihydropacidamycin D . The stereochemical identities of the tryptophan and two alanine residues contained in pacidamycin D have been shown to be of the natural (S) configuration, and the unique 3-methylamino-2-aminobutyric acid contained in this series of antibiotics has been shown to be of the (2S,3S) configuration . Finally, the stereochemistry obtained by hydrogenation of the C(4')-C(5') exocyclic olefin has been shown to be (R) at the C(4') nucleoside site.

Pharmacoeconomics, 2001, 19(6), 623 - 42
An economic overview of chronic obstructive pulmonary disease; Ruchlin HS et al.; Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity . Relatively few pharmacoeconomic studies have been conducted on this disease . This article reviews available information about the utilisation of healthcare resources and cost of care, and the cost or cost effectiveness of therapeutic interventions reported for this disease . Burden-of-illness data indicate that hospital care, medications and oxygen therapy were the major cost drivers in these studies . Mean annual Medicare expenditures in the US were $US11,841 (2000 values) for patients with COPD compared with $US4,901 for all covered patients . Utilisation was skewed; the most expensive 10% of the Medicare beneficiaries accounted for nearly 50% of total expenditures for this disease . Costs are associated with health status, age, physician specialty, geographic location and type of insurance coverage . Six types of interventions were assessed in the literature--pharmacotherapy, oxygen therapy, home care, surgery, exercise and rehabilitation and health education . The studies used different analytic strategies (e.g . cost-minimisation and cost-effectiveness analyses) and even within the realm of cost-effectiveness analyses, no uniformity existed as to how outcome was measured . Patient severity was not always delineated, and the length of the follow-up period, while quite short, varied . Only 11 of the 34 evaluations were based on randomised controlled trials . Cost-minimisation studies generally found no significant difference in the cost of antimicrobial treatment for first-line, second-line and third-line agents . Studies of bronchodilators indicated that ipratropium bromide alone or in combination with salbutamol (albuterol) was the preferred medication . The major area for achieving cost savings is by reducing hospital utilisation . As the annual rate of hospitalisation is relatively low, large patient samples will be required to demonstrate an economic advantage for a new therapy . The major challenges will be financing such a study, and selecting an outcome measure that satisfies both clinical and economic conventions.

Chem Pharm Bull (Tokyo), 2001 Jul, 49(7), 814 - 7
New hemisynthetic manoyl oxide derivatives with antimicrobial activity; Kalpoutzakis E et al.; The synthesis and antimicrobial activity of ten labdane-type diterpenes derived from ent-3-beta-hydroxy-13-epi-manoyl oxide (ribenol) is reported . The chloroethyl carbamidic ester 9 showed the strongest antimicrobial activity against all the tested gram (+), gram (-) bacteria and pathogenic fungi . Moreover, the glycoside 11 exhibited an interesting activity against the three tested fungi.

J Infect Chemother, 2001 Jun, 7(2), 121 - 3
Comparison of in-vitro activities of SCH27899 and other antibiotics against Mycoplasma pneumoniae; Ikejima H et al.; We examined the in-vitro activities of various antibiotics against 25 strains of Mycoplasma pneumoniae (22 clinical isolates and 3 standard strains) . In the 22 clinical isolates, the 90% minimum inhibitory concentrations (MIC 90) of SCH27899, ofloxacin, levofloxacin, ciprofloxacin, erythromycin, clarithromycin, roxithromycin, clindamycin, and minocycline were 16, 2, 2, 4, 0.0039, 0.0039, 0.016, 2, and 4 microg/ml, respectively . The minimum bactericidal concentrations (MBC 90) of SCH27899, ofloxacin, levofloxacin, ciprofloxacin, erythromycin, clarithromycin, roxithromycin, clindamycin, and minocycline were 64, 4, 2, 8, 0.0625, 0.0625, 0.125, 8, and 64 microg/ml, respectively . The low sensitivity of M . pneumoniae to SCH27899 may be a result of the impermeability of the bacteria to this molecule . The results of this study suggest that SCH27899 would not be a suitable antimicrobial agent to use in the alternative chemotherapy of M . pneumoniae infection.

J Infect Chemother, 2001 Jun, 7(2), 102 - 9
A study of quality assessment in clinical microbiology performance of independent laboratories in Tokyo: 18-year participation in the Tokyo Metropolitan Government External Quality Assessment Program; Kumasaka K et al.; We evaluated the performance of independent microbiology laboratories in Tokyo over an 18-year period of participation in the external quality assessment (EQA) program, and we estimated the impact of the EQA program . The study design was a longitudinal retrospective analysis of performance, including isolation, identification, and antimicrobial susceptibility testing of bacteria from simulated patients' samples, in "open" surveys compared with "blind" surveys . Independent microbiology laboratories, licensed by the Tokyo Metropolitan Government, have been subject to mandatory evaluation by the EQA program since 1982 . Survey reports, correspondence, annual guidance meetings, and inspections are used as quality improvement strategies . The performance for identification in "blind" surveys was significantly worse than that in "open" surveys (P < 0.001) . Poorly performing laboratories had common features, including inadequate supervision by physicians and lack of familiarity with the impact of variations on the use of the standards . However, there were improvements in the performance of identification of some pathogens . The performance of susceptibility testing has not yet reached the relatively high level seen for identification . Some of the smaller laboratories have been gradually acquired by commercial chains operating outside Tokyo . The EQA program has established a role both in regard to laboratory improvement and as an educational tool . However, the program lags behind these of other developed countries in regard to the practical sciences . The main problems in regard to laboratory improvements are a shortage of human resources in clinical microbiology, lack of standardization of laboratory methods, and the pressures of financial constraints in the Japanese medical insurance system.

J Hepatobiliary Pancreat Surg, 2001, 8(3), 211 - 5
Prophylaxis for septic complications in acute necrotizing pancreatitis; Bassi C et al.; Because the mortality of severe pancreatitis is higher when infected necrosis supervenes, prevention of infections has become a relevant endpoint for management . The "ideal" drug should be characterized by specific activity against the bacteria known to be responsible for infection and should be able to penetrate the gland in a sufficient concentration . To date there have been eight prospective trials with antibiotics, one on selective digestive decontamination, and others with enteral nutrition . A meta-analysis regarding experiences with antimicrobial drugs reports a significant reduction in the incidence of infected necrosis and pancreatic abscesses during severe pancreatitis . In conclusion, among the several options aimed at reducing infections during necrotizing pancreatitis, the prophylactic use of antibacterial drugs is the only one to have been tested to date in several randomized studies . Strong consideration should be given to treating patients with severe pancreatitis with broadspectrum antibiotics, selective digestive decontamination, and enteral nutrition.

Am J Bot, 2001 Jul, 88(7), 1199 - 1208
New observations on the secondary chemistry of world Ephedra (Ephedraceae); Caveney S et al.; For several millennia, stem extracts of Ephedra (Ephedraceae, Gnetales) have been used as folk medicines in both the Old and New World . Some species were used in treatments of questionable efficacy for venereal disease in North America during the last century . Many Eurasian species produce phenylethylamine alkaloids, mostly ephedrine and pseudoephedrine, that interact with adrenergic receptors in the mammalian sympathetic nervous system . Asian Ephedra have been used recently in the clandestine manufacture of a street drug, methamphetamine . Although ephedrine alkaloids are not detectable in New World species of Ephedra, together with Asian species they contain other nitrogen-containing secondary metabolites with known neuropharmacological activity . Many mesic and particularly xeric species worldwide accumulate substantial amounts of quinoline-2-carboxylic acids, or kynurenates, in their aerial parts . Many species of Ephedra accumulate cyclopropyl amino acid analogues of glutamate and proline in their stems and roots, and particularly in the seed endosperm . Mesic species synthesize substantial amounts of three L-2-(carboxycyclopropyl)glycine stereomers rarely seen in nature . A cyclopropyl analogue of proline with known antimicrobial activity, cis-3,4-methanoproline, is found in large amounts in the stems and seeds of many Ephedra species . The ability to synthesize cyclopropyl amino acids may be an ancestral feature in the taxon . The natural function in the taxon of these three groups of secondary compounds remains to be established.

J Pept Res, 2001 Jul, 58(1), 45 - 55
Molecular dynamics simulation of the antimicrobial salivary peptide histatin-5 in water and in trifluoroethanol: a microscopic description of the water destructuring effect; Iovino M et al.; The results of 520 ps molecular dynamics simulation of histatin-5, a small peptide present in human saliva and possessing antimicrobial activity, dissolved in water and in 2,2,2-trifluoroethanol, are reported . The simulations indicate that histatin-5 is destabilized in water and begins to unfold after 250 ps, while in organic solvent it maintains a regular secondary structure throughout the trajectory . Analysis of the peptide-solvent hydrogen bonds indicates that 2,2,2-trifluoroethanol is a poorer proton acceptor than water . The fluorine atom of the alcohol is almost never engaged in a hydrogen bond and the organic solvent interacts mainly with the peptide through its hydroxyl group . For some residues analysis of the solvent residence time indicated longer values for 2,2,2-trifluoroethanol than for water . The most striking difference is related to the number of times the solvent enters and leaves the first coordination shell of the peptide . This value was more than one order of magnitude higher for water than for the alcohol, suggesting that this may be the main cause of alpha-helix destabilization perpetrated by water.

Br J Dermatol, 2001 Jul, 145(1), 19 - 27
Lipid analysis of follicular casts from cyanoacrylate strips as a new method for studying therapeutic effects of antiacne agents; Thielitz A et al.; BACKGROUND: The cyanoacrylate follicular biopsy is an established method for the examination of the horny layer and quantitative assessment of microcomedones . We have optimized the method by separating follicular casts mechanically from the cyanoacrylate strips . OBJECTIVES: To use this method to analyse topical therapy-induced changes of the lipid composition in the sebaceous follicular infundibulum . METHODS: Both the follicular casts and the residual skin surface strip, the last representing a mixture of stratum corneum and surface lipids, were extracted twice with n-hexane-ethanol under ultrasonication, evaporated, redissolved in chloroform-methanol and separated by high-performance thin layer chromatography, using cholesterol sulphate, cerebroside, ceramide types 3 and 4, cholesterol, oleic acid, triolein, cholesterol oleate and squalene as standards . Identification was performed by computer-assisted densitometric analysis . Six patient groups receiving adapalene 0.1%, tretinoin 0.025%, clindamycin 1%, clindamycin 1% + tretinoin 0.025%, benzoyl peroxide 5% or benzoyl peroxide 5% + erythromycin 2% were investigated before and 12 weeks after application . RESULTS: A significant decrease in free fatty acid proportions combined with an increase in triglycerides was observed in the groups receiving antimicrobial therapy, supporting the hypothesis of lipolysis due to microbial colonization . The groups treated with topical retinoids showed an additional significant increase in ceramide subfractions, most probably reflecting their influence on epidermal keratinization . CONCLUSIONS: Our method proved suitable for the detection of quantitative and qualitative changes in lipid profiles of both infundibulum cast content and surface lipids . It enabled simple, non-invasive and objective assessment of the most relevant lipid classes in the sebaceous infundibulum, and efficient monitoring of drug effects on the follicular infundibulum.

J Agric Food Chem, 2001 Jul, 49(7), 3316 - 20
Identification of benzethonium chloride in commercial grapefruit seed extracts; Takeoka G et al.; Commercial grapefruit seed extracts (GSE) were extracted with chloroform . The solvent was evaporated, and the resulting solid was subsequently analyzed by high-performance liquid chromatography, electrospray ionization mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis (by proton-induced X-ray emission {PIXE} analysis) . The main constituent was identified as benzethonium chloride, a synthetic antimicrobial agent commonly used in cosmetics and other topical applications . This compound comprised 8.03% (n = 2) of the liquid GSE sample . Higher amounts of benzethonium chloride were found in powder GSE samples.

Am J Rhinol, 2001 May-Jun, 15(3), 175 - 9
Production of beta-defensin antimicrobial peptides by maxillary sinus mucosa; Carothers DG et al.; beta-Defensins are endogenous cationic peptides with broad-spectrum antimicrobial activity that are thought to play a role in the innate immune response . Two human beta-defensins, beta-defensin-1 (HBD-1) and beta-defensin-2 (HBD-2), have been identified . These peptides have recently been characterized in several human tissues . The presence of these peptides in the paranasal sinuses has not been investigated . We examined maxillaary sinus secretions from six patients with sinusitis and 10 patients without signs, symptoms, or radiologic evidence of sinus disease for the presence of beta-defensins . Cationic peptides were extracted from antral lavage specimens and examined for the presence of HBD-1 and HBD-2 by Western blot . Normal maxillary sinus epithelium was obtained from two patients and analyzed by RT-PCR for the presence of HBD-1 and HBD-2 mRNA . Tissue immunostaining for the two peptides was also used . Western blot analysis identified HBD-1 in two of 10 patients in the control group and in three of six patients in the sinusitis group . HBD-2 was identified in one of 10 patients in the control group and in four of six patients in the sinusitis group . RT-PCR revealed HBD-1 mRNA in one of two normal controls tested . Immunostaining localized HBD-1 and HBD-2 to the epithelial cell cytoplasm . This is the first demonstration of HBD-1 and HBD-2 production in the paranasal sinuses . In the present study, HBD-1 and HBD-2 were detected more frequently in the maxillary sinus fluid of patients with inflamed sinuses than in normal controls.

J Periodontol, 2001 Jun, 72(6), 774 - 8
The effect of antimicrobial periodontal treatment on circulating tumor necrosis factor-alpha and glycated hemoglobin level in patients with type 2 diabetes; Iwamoto Y et al.; BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) may play an important role in insulin resistance . In this study, we hypothesized that TNF-alpha produced due to periodontal inflammation synergistically affects insulin resistance as well as TNF-alpha produced from adipose tissues in insulin-resistant type 2 diabetes patients . Therefore, to understand the effects of antimicrobial periodontal therapy on serum TNF-alpha concentration and subsequent metabolic control of diabetes, we examined the periodontal and diabetic status on 13 type-2 diabetes patients . METHODS: These patients were treated with local minocycline administration in every periodontal pocket around all existing teeth once a week for a month . Before and after treatment, the number of total bacteria in the periodontal pockets and circulating TNF-alpha concentration were measured and the HbA1c value was assessed . RESULTS: Antimicrobial therapy significantly reduced the number of microorganisms in periodontal pockets (P <0.01) . After treatment, the circulating TNF-alpha level was significantly reduced (P <0.015) . The HbA1c value was also reduced significantly (P <0.007) . In addition, the 6 patients who were not receiving insulin therapy demonstrated decreased fasting insulin levels (P <0.03), and HOMA-R (P <0.03) indices . The average reductions in circulating TNF-alpha concentration and HbA1c value were 0.49 pg/ml and 0.8%, respectively . CONCLUSION: The results indicate that anti-infectious treatment is effective in improving metabolic control in diabetics, possibly through reduced serum TNF-alpha and improved insulin resistance.

J Periodontal Res, 2001 Jun, 36(3), 187 - 93
Phase 1 evaluation of a local delivery device releasing silver ions in periodontal pockets: safety, pharmacokinetics and bioavailability; Straub AM et al.; A new local delivery device (LDD) capable of releasing silver in periodontal pockets has been developed and tested pre-clinically . Silver has potent antimicrobial effects on Gram-negative periodontal pathogens with a mean in vitro minimum bactericidal concentration (MBC) < or =0.5 microg/ml . This phase 1 study assessed the safety, pharmacokinetics and bioavailability of silver ions delivered intracrevicularly with a resorbable LDD (PocketGuard) in a group of 9 volunteers affected with periodontitis . In each subject, a PLGA/PEG LDD loaded with 12% silver nitrate (w/w) was inserted in each of 4 selected pockets > or =5 mm . Serum, gingival fluid and subgingival plaque samples were evaluated before and at various time points after LDD placement for 21 days . At each time point, the concentration of silver in gingival crevicular fluid (GCF) was quantified with an Inductively Coupled Plasma-Mass Spectrometer . Subgingival plaque samples were processed for evaluation of total anaerobic and aerobic counts (CFU/ml) . The maximum mean silver concentration in GCF was 1,493 +/- 709 microg/ml (range 589-2,245) . It decayed exponentially with a half-life of 7.1 +/- 6.1 days (2.7-20.4) . Average silver concentrations in excess of 10 microg/ml were detected in each patient for 14 days after LDD placement with the average concentration for all patients in excess of 25 microg/mL at day 21 . Total anaerobic counts decreased an average of 1.7 +/- 1.9 x 10(6) CFU/ml (p= 0.0078) from baseline to day 7, indicating that the silver was biologically active . A mild increase in cervical root discoloration was observed at day 21:0.25 +/- 0.31 stain index units . Discoloration that did not resolve spontaneously could be removed at the end of the study with polishing . No systemic effects were observed . It is concluded that local silver concentrations above the MBC in serum were maintained for at least 21 days . A specific microbiologic effect was also observed.

Chest, 2001 Jul, 120(1 Suppl), 36S - 41S
Matrilysin in epithelial repair and defense; Parks WC et al.; Repair involves an orderly progression of events to reestablish the integrity of the injured tissue . During each stage in this process, secreted proteinases are needed to remodel extracellular matrix, facilitate cell migration, and process latent proteins, among other functions . In lung epithelium, several of these processes are mediated by matrilysin, a matrix metalloproteinase (MMP) . Unlike most MMPs, matrilysin is produced by intact, noninjured airway and peribronchial epithelial cells . In other intact epithelial tissues, namely the small intestine, matrilysin functions in host defense by activating the latent form of defensins, a family of antimicrobial peptides . This metalloproteinase may serve a similar function in the lung . Furthermore, in models of airway injury, matrilysin expression is upregulated in migrating epithelial cells, and the activity of this proteinase is required for repair of airway wounds . These observations indicate that matrilysin serves key functions in both epithelial defense and repair.

Antimicrob Agents Chemother, 2001 Aug, 45(8), 2204 - 9
In vitro activity of gemifloxacin (SB-265805, LB20304a) against Legionella pneumophila and its pharmacokinetics in guinea pigs with L . pneumophila pneumonia; Edelstein PH et al.; The activity of gemifloxacin against intracellular Legionella pneumophila and for the treatment of guinea pigs with L . pneumophila pneumonia was studied . Gemifloxacin, azithromycin, and levofloxacin (1 microg/ml) reduced bacterial counts of two L . pneumophila strains grown in guinea pig alveolar macrophages by 2 to 3 log(10) units . Gemifloxacin and levofloxacin had roughly equivalent intracellular activities . In contrast, erythromycin had static activity only . Therapy studies of gemifloxacin, azithromycin, and levofloxacin were performed in guinea pigs with L . pneumophila pneumonia . When gemifloxacin (10 mg/kg) was given by the intraperitoneal (i.p.) route to infected guinea pigs, mean peak levels in plasma were 1.3 microg/ml at 0.5 h and 1.2 microg/ml at 1 h postinjection . The terminal half-life phase of elimination from plasma was 1.3 h, and the area under the concentration-time curve from 0 to 24 h (AUC(0--24)) was 2.1 microg . h/ml . For the same drug dose, mean levels in lungs were 3.4 microg/g at both 0.5 and 1 h, with a half-life of 1.5 h and an AUC(0--24) of 6.0 microg . h/ml . All 15 L . pneumophila-infected guinea pigs treated with gemifloxacin (10 mg/kg/dose given i.p . once daily) for 2 days survived for 9 days after antimicrobial therapy, as did 13 of 14 guinea pigs treated with the same dose of gemifloxacin given for 5 days . All 12 azithromycin-treated animals (15 mg/kg/dose given i.p . once daily for 2 days) survived, as did 11 of 12 animals treated with levofloxacin (10 mg/kg/dose given i.p . once daily for 5 days) . None of 12 animals treated with saline survived . Gemifloxacin is effective against L . pneumophila in infected macrophages and in a guinea pig model of Legionnaires' disease, even with an abbreviated course of therapy . These data support studies of the clinical effectiveness of gemifloxacin for the treatment of Legionnaires' disease.

Burns, 2001 Aug, 27(5), 465 - 9
Topical use of Sucralfate Cream in second and third degree burns; Banati A et al.; This clinical study was undertaken to test the efficacy of topical Sucralfate Cream in second and third degree burns . Topical Sucralfate Cream has been used on a wide variety of lesions from radiation proctitis and dermatitis to keratoconjunctivitis with remarkable results . The study was carried out in two phases . The first phase comprised 60 patients, 30 of whom were treated with Sucralfate Cream while the other 30 were treated with other topical antimicrobial agents . Twenty-one of the patients in the study group had second-degree burns and nine patients' third degree burns . In the second phase, a double blind study was carried out on 25 patients where one area of burns was treated with Sucralfate Cream while another control area of the same patient was treated with a placebo ointment, containing the excipients used during preparation of the Sucralfate Cream, without Sucralfate . In the first phase, it was seen that the period of epithelialisation of second degree burns in the study group treated with Sucralfate Cream was 18.8 days compared with 24.6 days with other topical agents . This difference is statistically significant with a P value of <0.00001 . In the double blind study, also healing in the areas treated with Sucralfate was more rapid than those treated with bland placebo ointment . The difference in the two rates of healing was statistically significant with a P value of 0.00067 . Histopathological studies were also carried out in 10 patients of phase I of the trial . Sucralfate Cream promotes rapid epithelialisation of second degree burns with minimal said effects and offers another topical agent in the burn care specialist's armamentarium.

Eur J Med Chem, 2001 May, 36(5), 421 - 33
Synthesis of some 1-(2-naphthyl)-2-(imidazole-1-yl)ethanone oxime and oxime ether derivatives and their anticonvulsant and antimicrobial activities; Karakurt A et al.; In this study, oxime and oxime ether derivatives of anticonvulsant nafimidone {1-(2-naphthyl)-2-(imidozole-1-yl)ethanone} were prepared as potential anticonvulsant compounds . Nafimidone oxime was synthesized by the reaction of nafimidone and hydroxylamine hydrochloride . O-Alkylation of the oxime by various alkyl halides gave the oxime ether derivatives . Anticonvulsant activity of the compounds was determined by maximal electroshock (MES) and subcutaneous metrazole (scMet) tests in mice and rats according to procedures of the Antiepileptic Drug Development (ADD) program of the National Institutes of Health (NIH) . In addition to anticonvulsant evaluation, compounds were also screened for possible antibacterial and antifungal activities because of the structural resemblance to the azole antifungals, especially to oxiconazole . All compounds were evaluated against three human pathogenic fungi and four bacteria using the microdilution method . Most of the compounds exhibited both anticonvulsant and antimicrobial activities; the O-alkyl substituted compounds (2, 3, 4 and 5) were found to be more active than the O-arylalkyl substituted compounds in both screening paradigms.

FEMS Microbiol Ecol, 2001 Jul, 36(2-3), 105 - 112
Growth of a bacterial consortium on triclosan; Hay AG et al.; Triclosan is a polychlorinated hydroxy diphenylether that has been widely used as an antimicrobial compound . An enrichment using triclosan as a sole source of carbon and energy yielded a consortium of bacteria capable of growing on this compound . The dichloro ring was partially mineralized, resulting in the conversion of approximately 35% of the {(14)C}triclosan to {(14)C}CO(2) . Use of molecular fingerprinting techniques and 16S rDNA cloning and sequencing aided in the identification and eventual isolation of an auxotrophic Sphingomonas-like organism, strain Rd1, which was able to partially mineralize triclosan when grown on complex media.

N Engl J Med, 2001 Jul 12, 345(2), 79 - 84
Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite; Nadelman RB et al.; BACKGROUND: It is unclear whether antimicrobial treatment after an Ixodes scapularis tick bite will prevent Lyme disease . METHODS: In an area of New York where Lyme disease is hyperendemic we conducted a randomized, double-blind, placebo-controlled trial of treatment with a single 200-mg dose of doxycycline in 482 subjects who had removed attached I . scapularis ticks from their bodies within the previous 72 hours . At base line, three weeks, and six weeks, subjects were interviewed and examined, and serum antibody tests were performed, along with blood cultures for Borrelia burgdorferi . Entomologists confirmed the species of the ticks and classified them according to sex, stage, and degree of engorgement . RESULTS: Erythema migrans developed at the site of the tick bite in a significantly smaller proportion of the subjects in the doxycycline group than of those in the placebo group (1 of 235 subjects {0.4 percent} vs . 8 of 247 subjects {3.2 percent}, P<0.04) . The efficacy of treatment was 87 percent (95 percent confidence interval, 25 to 98 percent) . Objective extracutaneous signs of Lyme disease did not develop in any subject, and there were no asymptomatic seroconversions . Treatment with doxycycline was associated with more frequent adverse effects (in 30.1 percent of subjects, as compared with 11.1 percent of those assigned to placebo; P<0.001), primarily nausea (15.4 percent vs . 2.6 percent) and vomiting (5.8 percent vs . 1.3 percent) . Erythema migrans developed more frequently after untreated bites from nymphal ticks than after bites from adult female ticks (8 of 142 bites {5.6 percent} vs . 0 of 97 bites {0 percent}, P=0.02) and particularly after bites from nymphal ticks that were at least partially engorged with blood (8 of 81 bites {9.9 percent}, as compared with 0 of 59 bites from unfed, or flat, nymphal ticks {0 percent}; P=0.02) . CONCLUSIONS: A single 200-mg dose of doxycycline given within 72 hours after an I . scapularis tick bite can prevent the development of Lyme disease.

Am J Health Syst Pharm, 2001 Jul 1, 58(13), 1224 - 8
National supply-chain survey of drug manufacturer back orders; Wellman GS; The impact of manufacturer back orders on the supply chain for pharmaceuticals in the institutional setting was studied . A questionnaire was distributed during May and June 2000 to 600 institutional pharmacies affiliated with a major national drug and supply group purchasing organization . The instrument included questions on basic institutional demographics, perceptions about the frequency of manufacturer back orders for pharmaceuticals, the quality of communication with manufacturers and wholesalers about back orders, the two most significant back orders that had occurred in the 12 months preceding the survey, and the reasons for and impact of back orders . A total of 170 usable surveys were returned (net response rate, 28.3%) . Reported manufacturer back orders included an array of drug classes, including blood products, antimicrobials, antiarrhythmics, benzodiazepine antagonists, thrombolytics, corticosteroids, and antihypertensives . Respondents perceived significant back orders as increasing in frequency . Communication by manufacturers and wholesalers about back orders was reported to be relatively poor . A raw-material shortage was the most common reason given by manufacturers for back orders (36.5%), followed by a regulatory issue (23.2%) . In most cases (92%), medical staff members had to be contacted, indicating an interruption in the normal drug distribution process . In over a third of instances, respondents stated that the back order resulted in less optimal therapy . A survey found that manufacturer back orders for pharmaceuticals were increasing in frequency and that information flow within the supply chain was insufficient to meet the needs of end users.

Am J Health Syst Pharm, 2001 Jun 15, 58(12), 1146 - 9
Implementing a program for switching from i.v . to oral antimicrobial therapy; Wong-Beringer A et al.; Management Case Studies describe approaches to real-life management problems in health systems . Each installment is a brief description of a problem and how it was dealt with . The cases are intended to help readers deal with similar experiences in their own work sites . Problem solving, not hypothesis testing, is emphasized . Successful resolution of the management issue is not a criterion for publication--important lessons can be learned from failures, too.

Fitoterapia, 2000 Feb, 71(1), 75 - 6
Antimicrobial activity of Bridelia ferruginea fruit; Akinpelu DA et al.; Bridelia ferruginea fruit 60% methanolic extract exhibited antimicrobial activity against seven out of eight bacterial isolates at a concentration of 20 mg/ml.

Fitoterapia, 2000 Feb, 71(1), 72 - 4
Antimicrobial activity of Evodia elleryana; Khan MR et al.; The methanol extracts of Evodia elleryana, leaves, stem wood, stem bark, root wood and root bark were partitioned (petrol, dichloromethane, ethyl acetate) . All obtained fractions showed a broad spectrum of antibacterial activity, while none were active against tested moulds.

Prev Vet Med, 2001 Jul 19, 50(1-2), 53 - 70
The effect of discontinuing the use of antimicrobial growth promoters on the productivity in the Danish broiler production; Emborg H et al.; On 15 February 1998, the Danish poultry industry voluntarily decided to discontinue the use of all antimicrobial growth promoters (AGPs) . To investigate how the removal of AGPs influenced the broiler productivity in Denmark, data from 6815 flocks collected from November 1995 to July 1999 by the Danish Poultry Council were analysed . The three flock parameters were: kilogram broilers produced per square meter (per rotation), feed-conversion ratio (total kilogram feed used per rotation/total kilogram live weight per rotation) and total percent dead broilers ((number of dead broilers during the rotation/number of broilers put in the house per rotation)x100) . Data were analysed using a mixed model, allowing the correlation structures in the data to be taken into account . The analyses showed that kilogram broilers produced per square meter and percent dead broilers in total were not affected by the discontinued use of AGPs . However, the feed-conversion ratio increased marginally 0.016 kg/kg and has remained at this level throughout the rest of the study period.

Ned Tijdschr Geneeskd, 2001 Jun 23, 145(25), 1192 - 3
{Antibiotic resistance: recommendations from the Advisory Council for Health Research}; Hoogkamp-Korstanje JA; The Advisory Council for Health Research (RGO) advised the Dutch Minister of Health on research into the epidemiology, prevention and research of antibiotic resistance in the Netherlands . Good antimicrobial practice, insight into antibiotic use, implementation of measures to prevent development of resistance and fundamental research on resistance should be promoted . It was concluded that there is very little extramural surveillance and that only a few existing intramural surveillance programmes appear useful for long-term monitoring, inclusion into international databases and comparison purposes . The initiatives taken by the Working Party on Antibiotic Policy (SWAB) and the National Institute of Public Health and the Environment (RIVM), including the development of a standard for susceptibility testing and the coordination of surveillance studies according to international standards, should be supported and continued . The RGO committee is impressed by central and integrated national surveillance programmes such as those in Denmark or Finland . This approach however seems not necessary for good medical practice and not currently feasible . Priority should now be given to specific projects which focus on specific resistance problems among well-defined patient groups, and on indicator-organisms and indicator-antibiotics.

Infect Dis Clin North Am, 2001 Jun, 15(2), 521 - 49
Infectious complications of solid organ transplantations; Simon DM et al.; The rate of infectious complications in SOT recipients has declined dramatically . As improvements in immunosuppressive therapy, surgical techniques, and diagnostics and antimicrobial treatment continue, further declines in infectious complications are expected . Refinements to preemptive therapy for high-risk patients are likely to contribute further to this decrease . Further investigation is required to define what role various infectious agents play in chronic allograft injury and rejection.

Infect Dis Clin North Am, 2001 Jun, 15(2), 457 - 82
Infectious complications of febrile leukopenia; Giamarellou H et al.; It can be foreseen that in the years to come major improvements in neutropenic host infections will be achieved regarding the exact identification of risk factors, allowing better patient stratification; the application of molecular techniques to recognize pathogens; the development of effective new oral antimicrobials allowing home therapy or abbreviated hospitalization; the development of new antifungals; and the development of new effective immunomodulators and cytokines to ameliorate chemotherapy-induced neutropenia . In the years to come the threat of nosocomial infections unfortunately will not be eliminated, while the development of major new parenteral antibiotics cannot be foreseen . It is therefore the caregiver/physician himself who, by applying rational antibiotic policies and strict handwashing rules, will probably escape, for his neutropenic patient's sake, the imminent threat of multiresistant pathogens.

Infect Immun, 2001 Aug, 69(8), 4980 - 7
Cu,Zn superoxide dismutase of Mycobacterium tuberculosis contributes to survival in activated macrophages that are generating an oxidative burst; Piddington DL et al.; Macrophages produce reactive oxygen species and reactive nitrogen species that have potent antimicrobial activity . Resistance to killing by macrophages is critical to the virulence of Mycobacterium tuberculosis . M . tuberculosis has two genes encoding superoxide dismutase proteins, sodA and sodC . SodC is a Cu,Zn superoxide dismutase responsible for only a minor portion of the superoxide dismutase activity of M . tuberculosis . However, SodC has a lipoprotein binding motif, which suggests that it may be anchored in the membrane to protect M . tuberculosis from reactive oxygen intermediates at the bacterial surface . To examine the role of the Cu,Zn superoxide dismutase in protecting M . tuberculosis from the toxic effects of exogenously generated reactive oxygen species, we constructed a null mutation in the sodC gene . In this report, we show that the M . tuberculosis sodC mutant is readily killed by superoxide generated externally, while the isogenic parental M . tuberculosis is unaffected under these conditions . Furthermore, the sodC mutant has enhanced susceptibility to killing by gamma interferon (IFN-gamma)-activated murine peritoneal macrophages producing oxidative burst products but is unaffected by macrophages not activated by IFN-gamma or by macrophages from respiratory burst-deficient mice . These observations establish that the Cu,Zn superoxide dismutase contributes to the resistance of M . tuberculosis against oxidative burst products generated by activated macrophages.

Pharmacotherapy, 2001 Jul, 21(7 Pt 2), 95S - 99S
New directions in antiinfective therapy for community-acquired pneumonia in the emergency department; Moran GJ; The emergency department is becoming an increasingly important setting for the management of community-acquired pneumonia (CAP) . This trend reflects the shortened hospital stays and decreased mortality among elderly hospitalized patients resulting from rapid administration of antimicrobials . In addition, decisions about the site of care (inpatient vs outpatient) and antimicrobial therapy frequently are made in the emergency department . Recent research and subsequent clinical guidelines may help with these decisions . For example, recently issued guidelines, such as those of the Infectious Diseases Society of America and the American Thoracic Society, suggest that selection of antimicrobials for CAP (which is typically empiric) should be based on the potential pathogens and likelihood of antimicrobial resistance . Macrolides and tetracyclines are recommended in younger patients with mild-to-moderate disease . Patients with more severe disease and those at risk for drug-resistant pathogens should be treated with broad-spectrum therapy, such as a newer fluoroquinolone or a cephalosporin plus a macrolide . When hospitalization is required, early switch from intravenous to oral therapy, followed by early discharge, can be a highly successful strategy . Antimicrobials that are available in both intravenous and oral formulations, such as the newer fluoroquinolones (e.g., levofloxacin and gatifloxacin), can simplify switch therapy For outpatients, an initial long-acting parenteral dose of azithromycin, ceftriaxone, or levofloxacin followed by oral therapy is an effective protocol . In addition, use of a prediction rule to identify low-risk patients with CAP may help guide decisions about the need for hospital admission.

Res Microbiol, 2001 Jun, 152(5), 421 - 30
Antibiotic resistance with particular reference to soil microorganisms; Nwosu VC; Evidence of increasing resistance to antibiotics in soil and other natural isolates highlights the importance of horizontal transfer of resistance genes in facilitating gene flux in bacteria . Horizontal gene transfer in bacteria is favored by the presence of mobile genetic elements and by the organization of bacterial genomes into operons allowing for the cooperative transfer of genes with related functions . The selective pressure for the spread of resistance genes correlates strongly with the clinical and agricultural overuse of antibiotics . The future of antimicrobial chemotherapy may lie in developing new antimicrobials using information from comparative functional microbial genomics to find genetic targets for antimicrobials and also to understand gene expression enabling selective targeting of genes with expression that correlates with the infectious process.

Crit Care Med, 2001 Jul, 29(7), 1318 - 24
Efficacy of a high-carbohydrate diet in catabolic illness; Hart DW et al.; OBJECTIVE: To determine within the setting of isocaloric, isonitrogenous enteral diets whether a diet that supplies most of its calories from fat or carbohydrate would be most beneficial at limiting muscle protein wasting in catabolic illness . DESIGN: Prospective, randomized, crossover trial . SETTING: Academic pediatric burn unit in tertiary medical center . PATIENTS: Fourteen severely burned (>40% total body surface area) children underwent systemic metabolic and cross-leg muscle protein kinetic studies . INTERVENTIONS: All were treated clinically in a similar manner, including early excision and grafting, antimicrobial therapy, and isocaloric, isonitrogenous enteral nutritional support . Subjects randomly received either a high-carbohydrate enteral diet (3% fat, 82% carbohydrate, 15% protein), or a high-fat enteral diet (44% fat, 42% carbohydrates, 14% protein) for 1 week and then crossed over to the other diet for a second week . MEASUREMENTS AND MAIN RESULTS: On day 5 of each diet, muscle protein kinetics were determined from femoral arterial and venous blood samples during a primed-constant d5-phenylalanine infusion . Indirect calorimetry was used to determine systemic resting energy expenditure and respiratory quotient . The seven boys and seven girls were 7.1 +/- 1.1 (mean +/- sem) years old and suffered burns over 65 +/- 4% of their bodies, with 52 +/- 6% being third-degree burns . Muscle protein degradation markedly decreased (p <.01) with administration of the high-carbohydrate diet . Protein synthesis was unaltered . Endogenous insulin concentrations increased during the high-carbohydrate feeding period . No differences in energy expenditure were seen between study diets . CONCLUSIONS: In severely burned pediatric patients, enteral nutrition supplied predominantly as carbohydrate rather than fat improves the net balance of skeletal muscle protein across the leg . This is attributable to decreased protein breakdown, suggesting a protein-sparing effect of high-carbohydrate feedings.

Scand J Gastroenterol, 2001 Jul, 36(7), 690 - 700
Pooled analysis on the efficacy of the second-line treatment regimens for Helicobacter pylori infection; Hojo M et al.; BACKGROUND: Although many of the currently available Helicobacter pylori eradication regimens fail to cure 5%-12% of patients, an optimal re-treatment therapy for eradication-failure patients has still not been established . The aim of this study was to examine all reports concerning the efficacy of re-eradication regimens for H . pylori infection, and to establish optimal re-eradication regimens . METHODS: Studies concerning re-eradication regimens were retrieved from the MEDLINE database, reference lists and major congress abstract lists up through December 1999 . Data from all selected reports were pooled into several groups depending on second-line or initial therapies . Pooled eradication rates of re-treatment regimens were compared using Fisher's exact test (P < 0.05) . RESULTS: Sixteen articles and 24 abstracts with 75 total treatment arms were included in this study . Pooled re-eradication rates by proton-pump inhibitor (PPI)-based dual therapy, PPI-based triple therapy, ranitidine bismuth-based triple therapy and quadruple therapy were 45.8%, 69.8%, 80.2% and 75.8%, respectively . Eradication rates from studies with two new antimicobials added were higher than rates from studies with only one new antimicrobial added (P = 0.0064) . CONCLUSION: Ranitidine bismuth-based triple therapies, as well as quadruple therapies, seem to be the most effective re-treatment therapies in all currently undertaken therapies . The strategy of adding two new antimicrobials to previous regimens was also effective in re-eradication therapy.

Mayo Clin Proc, 2001 Jul, 76(7), 713 - 24
Prevention of Lyme disease: a review of the evidence; Poland GA; The Healthy People 2010 public health goals targeted a 44% decrease in the incidence of Lyme disease, the most commonly reported tick-borne illness in the United States . To review Lyme disease prevention, clinical trials, epidemiological and experimental studies, and predictive models were evaluated . Geographic distribution of ixodid vectors and local landscape predict Lyme disease risk . Density of infected ticks correlates with incidence and prevalence of Lyme disease, but risk quantitation is made uncertain by tick aggregation and inability to predict tick-human interactions . Outdoor activities are inconsistently or weakly associated with risk, and most infections likely occur in residential areas during routine activities . Tick control (burning or removing vegetation, acaricide use, and deer elimination) reduces Ixodes scapularis populations by up to 94%, and acaricide application to wildlife decreases nymphal I scapularis populations by up to 83% . The effect of these strategies on incidence of Lyme disease in humans is unknown . Studies show that only 40% to 50% of adults take precautions against tick bites even when they are aware of Lyme disease . Effective protection afforded by personal precautions (wearing protective clothing, avoiding ticks, and using insect repellant) has not been shown prospectively . Antimicrobial prophylaxis of tick bites is not warranted . Clinical trials showed vaccines containing recombinant OspA of Borrelia burgdorferi to be efficacious and well tolerated . Currently, vaccination is the only empirically demonstrated method to prevent Lyme disease . The best evidence supports prevention efforts focused on practices that encourage immunization, Lyme disease awareness, and possibly treatment of deer.

Immunol Res, 2001, 23(2-3), 111 - 20
The role of surfactant-associated protein A in pulmonary host defense; Shepherd VL et al.; Resident alveolar macrophages play a key role in the initial defense against inhaled pathogens . Surface molecules bind opsonized as well as nonopsonized microbes and mediate their internalization by the macrophage . The recent discovery that specific C-type lectins can bind to the surface of a wide range of pathogens has led to the hypothesis that these lectins are involved in the initial phases of microbe recognition by the macrophage . Studies in our laboratory focus on the role of the lung-specific lectin surfactant associated protein A (SP-A) in host defense against pulmonary pathogens . SP-A contains a carbohdyrate recognition domain that appears to bind specifically to exposed carbohydrate residues on the surface of microorganisms . This lectin-microorganism interaction leads to entry of specific pathogens into macrophages and activation of intracellular pathways, resulting in the production of antimicrobial mediators such as nitric oxide . Many studies, including those involving SP-A-deficient mice, underscore the importance of this protein in pulmonary innate immunity . However, the intramacrophage mechanisms underlying the effects of SP-A are still unclear . This article describes our current knowledge of SP-A and its interactions with immune cells and pathogens with a focus on recent findings from our laboratory regarding SP-A interactions with mycobacteria.

Clin Chest Med, 2001 Jun, 22(2), 263 - 79, viii
Flexible bronchoscopy in nosocomial pneumonia; Ewig S et al.; In this article, an overview on the diagnostic performances of bronchoscopic techniques for the diagnosis of nosocomial pneumonia is given with special emphasis on the inherent problems of the methodology of validation applied to different studies . The current evidence about the importance of bronchoscopic techniques for the outcome is reviewed . It is outlined that future prospects of bronchoscopic investigations mainly include the evaluation of its role in the reassessment of the patient with pneumonia not responding to the initial antimicrobial treatment.

Oral Microbiol Immunol, 2001 Aug, 16(4), 253 - 6
Antimicrobial effect of acidified nitrite on periodontal bacteria; Allaker RP et al.; The antimicrobial agent nitric oxide (NO) is formed in the mouth and its concentration is directly related to salivary nitrite, which in turn is related to dietary nitrate intake . The aim of this study was to determine whether nitrite under acidic conditions will have an inhibitory effect, possibly occurring through NO production, on the periodontal disease pathogens Fusobacterium nucleatum, Eikenella corrodens and Porphyromonas gingivalis . Whereas the growth of these organisms was inhibited by a more acid pH, the addition of nitrite caused a marked, further dose-dependent reduction in bacterial numbers after exposure . The ability of these bacteria to recover from nitrite exposure was also affected by pH and nitrite concentration . At acidity levels below pH 5.0, low concentrations of nitrite (0.2 mM) caused effective complete killing of the periodontal bacteria . Addition of sodium thiocyanate did not increase the bacteriostatic or bacteriocidal activity of acidified nitrite against any of the 3 bacteria . These results demonstrate the possibility that nitrite in saliva, under appropriate conditions, may have an effect on the growth and survival of the bacteria implicated in periodontal disease.

Lett Appl Microbiol, 2001 Jul, 33(1), 50 - 5
Effect of trans-2-hexenal on the growth of Aspergillus flavus in relation to its concentration, temperature and water activity; Gardini F et al.; AIMS: The antifungal activity of trans-2-hexenal on Aspergillus flavus in a model system in relation to its concentration, incubation temperature and aw was assessed . METHODS AND RESULTS: A model describing the antifungal activity of the aldehyde in relation to these variables was obtained . CONCLUSION: According to this model, the inhibition of A . flavus was weakly dependent on the incubation temperature (at least within the range of values considered) and strongly affected by the trans-2-hexenal concentration and aw, which showed a remarkable synergistic effect . SIGNIFICANCE AND IMPACT OF THE STUDY: Trans-2-hexenal proved to be a molecule with remarkable antimicrobial properties, even when added in closed systems at low concentration.

J Invest Dermatol, 2001 Jul, 117(1), 44 - 51
Generation of free fatty acids from phospholipids regulates stratum corneum acidification and integrity; Fluhr JW et al.; There is evidence that the "acid mantle" of the stratum corneum is important for both permeability barrier formation and cutaneous antimicrobial defense . The origin of the acidic pH of the stratum corneum remains conjectural, however . Both passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g., proton pumps) mechanisms have been proposed . We assessed here whether the free fatty acid pool, which is derived from phospholipase-mediated hydrolysis of phospholipids during cornification, contributes to stratum corneum acidification and function . Topical applications of two chemically unrelated secretory phospholipase sPLA2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the pH of murine skin surface that was paralleled not only by a permeability barrier abnormality but also altered stratum corneum integrity (number of strippings required to break the barrier) and decreased stratum corneum cohesion (protein weight removed per stripping) . Not only stratum corneum pH but also all of the functional abnormalities normalized when either palmitic, stearic, or linoleic acids were coapplied with the inhibitors . Moreover, exposure of intact murine stratum corneum to a neutral pH for as little as 3 h produced comparable abnormalities in stratum corneum integrity and cohesion, and further amplified the inhibitor-induced functional alterations . Furthermore, short-term applications of an acidic pH buffer to inhibitor-treated skin also reversed the abnormalities in stratum corneum integrity and cohesion, despite the ongoing decrease in free fatty acid levels . Finally, the secretory-phospholipase-inhibitor-induced alterations in integrity/cohesion were in accordance with premature dissolution of desmosomes, demonstrated both by electron microscopy and by reduced desmoglein 1 levels in the stratum corneum (shown by immunofluorescence staining and visualized by confocal microscopy) . Together, these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid processing for normal stratum corneum acidification; and (ii) the potentially important role of this pathway not only for barrier homeostasis but also for the dual functions of stratum corneum integrity and cohesion.

J Appl Microbiol, 2001 Jul, 91(1), 118 - 30
An integrated method for the enrichment and selective isolation of Actinokineospora spp . in soil and plant litter; Otoguro M et al.; AIMS: To devise and evaluate a method for isolating the rare, zoosporic actinomycetes, Actinokineospora spp . in soil and plant litter . METHODS AND RESULTS: The newly developed method consists of two enrichment stages followed by plating on a selective medium . The source material is initially incubated with calcium carbonate to multiply the population of Actinokineospora spp., and is then air-dried . The second stage consists of rehydration-centrifugation, in which the amended substrate is immersed in phosphate buffer-soil extract to liberate actinomycete zoospores, and nonmotile microbial associates are then eliminated by centrifugation . Portions of the supernatant enriched with zoospores are plated on humic-acid vitamin agar supplemented with fradiomycin, kanamycin, nalidixic acid and trimethoprim . We examined 39 soil and plant-litter samples taken from fields, forests and stream banks . The proposed method consistently enriched and selectively isolated Actinokineospora spp . in 17 samples . Evidence for antimicrobial activity was found in most of the isolates . CONCLUSION: A combination of enrichment and a medium containing selective antibiotics can be used successfully for efficient isolation of certain rare actinomycete taxa . SIGNIFICANCE AND IMPACT OF THE STUDY: The development of new methodologies with which to isolate rare actinomycetes is of great importance to extend our understanding of their ecology, taxonomy and bioactivity.

Clin Microbiol Infect, 2001 Jun, 7(6), 316 - 25
Surveillance of antimicrobial resistance--what, how and whither?
Bax R, Bywater R, Cornaglia G, Goossens H, Hunter P, Isham V, Jarlier V, Jones R, Phillips I, Sahm D, Senn S, Struelens M, Taylor D, White A.
OBJECTIVE: To express the views of a working party held to consider antibiotic resistance surveillance systems, their strengths and weaknesses, and their current and future applications . METHODS: The participants, all of whom were experienced in this field, discussed the development of surveillance systems in relation to the increasing prevalence of resistance to antibacterial agents and the current interest in surveillance systems shown by many official bodies, in both the human and veterinary fields . The problems inherent in surveillance systems were considered together with the applications of different systems . RESULTS: The properties of good antibiotic resistance surveillance systems were defined . Surveillance systems vary widely from those with a narrow base, focusing on few organisms in one disease area, to those covering many diseases, many organisms (including normal flora) and many compounds . Whatever their design, they should be able to detect significant differences and shifts in susceptibility to various antibacterial agents, and the information derived from them should reach as many interested parties as possible in a timely manner . In using this information to decide strategies, criteria for action need to be determined by pragmatic consensus . Funding remains a major problem, with few large studies being supported by official bodies in spite of their professed enthusiasm for surveillance . In consequence, many current systems are funded by the pharmaceutical industry and are of necessity restricted in their focus . CONCLUSIONS: Antibiotic resistance surveillance studies should and can be well planned and well executed . Many current systems suffer from well-recognized but uncorrected biases . Consortium funding will be necessary for large schemes to be successful . There is no "ideal" surveillance system.

Microb Drug Resist, 2001 Summer, 7(2), 183 - 90
The Swedish experience of the 1986 year ban of antimicrobial growth promoters, with special reference to animal health, disease prevention, productivity, and usage of antimicrobials; Wierup M; In Sweden the use of antimicrobial growth promoters (AMGP) was banned in 1986 . The experiences gained from that ban are presented . In production of slaughter pigs, specialized beef, and turkeys, no negative clinical effects were reported as a consequence of the ban . In broiler chicken production, expected problems with necrotic enteritis were prevented by a continuous use of antibiotics, largely to the same extent during the first 2 years after the ban . Following the implementation of results from experimental activities during that period, the general usage of antimicrobials could be stopped and expected problems with outbreaks of necrotic enteritis was prevented . In piglet production, significant clinical problems emerged that created a demand for antibiotic-medicated feed at therapeutic dosages . During the subsequent 4-year period, the use of antibiotics increased, involving up to 75% of the pigs . Thereafter, the use of antibiotics decreased because of improved management, and could be halved in 1993 followed by a gradual further decrease supported by the addition of zinc oxide to the feed . In 1998, compared to 1994, the total use of zinc decreased by 90% . In 1998/1999, only 5% of weaning piglet producing herds used antibiotic medicated feed and 17% used zinc . The AMGP ban has shown that under good production conditions it is possible to reach good and competitive production results for the rearing of poultry, calves, and pigs without the continuous use of AMGP . As a result of the ban and a focus on disease prevention and correct use of antimicrobials, the total use of antibacterial drugs to animals in Sweden decreased by approximately 55% during the last 13-year period, and a relatively low prevalence of antimicrobial resistance has been maintained.

Indian J Dent Res, 2001 Jan-Mar, 12(1), 51 - 6
Study of drug utilization pattern in dental OPD at tertiary care teaching hospital; Rehan HS et al.; Irrational prescribing is a global phenomenon . The objective of the study was to find out the prescribing practices of dental prescribers in a tertiary care teaching hospital with special emphasis on the utilization of antimicrobial agents . A prospective study was conducted in the month of March 2000 . A total of 491 prescriptions were collected randomly . Prescribing pattern was analyzed using WHO basic drug indicators . The average number of drugs for prescription was 2.4 . 78.8% of all prescriptions contained antimicrobial agents . It was most commonly prescribed (40.37%) group of drugs followed by anti-inflammatory and analgesics (33.8%) . Fixed dose combination of ampicillin and cloxacillin was most commonly prescribed antimicrobial agents . Prophylactic use of AMA (78%) was more than therapeutic purpose (21.9%) . Prophylactic use of antimicrobial agents was irrational in all the cases as duration for the use of antimicrobial agents was 5.1 +/- 0.5 days . Fixed dose combinations (45%), drugs by brand name (98.5%) were frequently used . Drug prescribed from Essential Drug List was maximum when one drug was prescribed . Results indicate that there is a scope for improving prescribing habits and minimizing the use of antimicrobial agents . This could be facilitated by periodic education to the prescribers.

J Immunol, 2001 Jul 15, 167(2), 893 - 901
Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi; Gantt KR et al.; Leishmania chagasi, the cause of South American visceral leishmaniasis, must survive antimicrobial responses of host macrophages to establish infection . Macrophage oxidative responses have been shown to diminish in the presence of intracellular leishmania . However, using electron spin resonance we demonstrated that murine and human macrophages produce O2-during phagocytosis of opsonized promastigotes . Addition of the O2- scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl to cultures resulted in increased infection, suggesting that O2- enhances macrophage leishmanicidal activity . The importance of NO . produced by inducible NO synthase (iNOS) in controlling murine leishmaniasis is established, but its role in human macrophages has been debated . We detected NO . in supernatants from murine, but not human, macrophages infected with L . chagasi . Nonetheless, the iNOS inhibitor N(G)-monomethyl-L-arginine inhibited IFN-gamma-mediated intracellular killing by both murine and human macrophages . According to RNase protection assay and immunohistochemistry, iNOS mRNA and protein were expressed at higher levels in bone marrow of patients with visceral leishmaniasis than in controls . The iNOS protein also increased upon infection of human macrophages with L . chagasi promastigotes in vitro in the presence of IFN-gamma . These data suggest that O2- and NO . each contribute to intracellular killing of L . chagasi in human and murine macrophages.

Infection, 2001 May-Jun, 29(3), 127 - 37
Antimicrobial expenditures and usage at four university hospitals . Baden-Württemberg Interuniversity Study Group; Kern WV et al.; BACKGROUND: The increasing use of antimicrobiaL drugs is resulting in enormous hospital expenditures . Careful assessment of inappropriate prescribing and a search for more cost-effective treatment strategies are urgently required . Comparisons between hospitals should help identify areas of inappropriate prescribing as well as effective drug use programs, but such analyses may be severely biased if the impact of different case-mixes is not recognized . PATIENTS AND METHODS: We studied antimicrobial usage and expenditures at four state university hospitals in southwestern Germany and assessed the significance of differences between hospital services after adjustment for patient variables . A prevalence survey was done with review of 2,254 charts of patients admitted to the surgical, medical and pediatric services to obtain information on antimicrobial drug prescription and expenditures in the week preceding the survey . RESULTS: According to pharmacy data for the year 1994, maximal differences between these hospitals in the antibiotic costs per patient-day were 1.9-fold (surgical services), 1.5-fold (medical services), and 1.6-fold (pediatric services) . In a multivariate analysis, adjusted antibiotic prescription prevalence rates did not differ for medical and pediatric service patients, but did differ for surgical service patients (p = 0.03) . Similarly, adjusted expenditures per patient-week differed significantly between hospitals for surgical service patients (p = 0.001), but only marginally for medical (p = 0.14) and pediatric (p = 0.05) service patients . The adjusted difference in expenditures between surgical departments was as large as 2.8-fold (95% CI 1.8 to 4.3) and was primarily related to preferential use of expensive iv antimicrobial drugs . CONCLUSION: In two hospitals, lowest expenditures in either surgery or medicine were associated with active antimicrobial drug use programs suggesting an impact of these programs on drug use and expenditures limited to these services . The identification of such large patient-mix unrelated differences in antimicrobial usage and expenditures offers opportunities for quality improvements and cost reduction.

Plant J, 2001 May, 26(4), 435 - 46
Isolation and characterization of signal transduction mutants of Arabidopsis thaliana that constitutively activate the octadecanoid pathway and form necrotic microlesions; Hilpert B et al.; Thionins are a group of antimicrobial polypeptides that form part of the plant's defense mechanism against pathogens . The Thi 2.1 thionin gene of Arabidopsis thaliana has been shown to be inducible by jasmonic acid (JA), an oxylipin-like hormone derived from oxygenated linolenic acid and synthesized via the octadecanoid pathway . The JA-dependent regulation of the Thi 2.1 gene has been exploited for setting up a genetic screen for the isolation of signal transduction mutants that constitutively express the Thi 2.1 gene . Ten cet-mutants have been isolated which showed a constitutive expression of the thionin gene . Allelism tests revealed that they represent at least five different loci . Some mutants are dominant, others recessive, but all cet mutations behaved as monogenic traits when backcrossed with Thi 2.1-GUS plants . Some of the mutants overproduce JA and its bioactive precursor 12-oxophytodienoic acid (OPDA) up to 40-fold while others have the same low levels as the control wildtype plants . Two of the mutants showed a strong induction of both the salicylic acid (SA)- and the JA-dependent signaling pathways, while the majority seems to be affected only in the octadecanoid pathway . The Thi 2.1 thionin gene and the Pdf 1.2 defensin gene are activated independently, though both are regulated by JA . The cet-mutants, except for one, also show a spontaneous leaf cell necrosis, a reaction often associated with the systemic acquired resistance (SAR) pathway.

Clin Infect Dis, 2001 Aug 1, 33(3), 289 - 95 Epub 2001 Jul 05.
Impact of a hospital-based antimicrobial management program on clinical and economic outcomes; Gross R et al.; Inappropriate use of antimicrobial agents results in unnecessary exposure to medication, persistent or progressive infection, emergence of resistance, and increased costs . We implemented a program to control use of restricted agents while improving care . This study compared 2 major mechanisms for improving use of antimicrobial agents: (1) recommendations made by the Antimicrobial Management Team (AMT), which included a clinical pharmacist backed up by a physician from the Division of Infectious Diseases (ID), and (2) recommendations made by ID fellows . Outcome measures included appropriateness of recommendations, cure rate, number of treatment failures, and cost of care, which were assessed for 180 patients . The AMT outperformed the ID fellows in all outcomes examined by the study (including appropriateness {87% vs . 47%; P<.001}, cure rate {64% vs . 42%; P=.007}, and treatment failures {15% vs . 28%; P=.03}), although the differences in economic outcomes between cases managed by the AMT and those managed by the ID fellows were not statistically significant . In an academic setting with a restricted formulary, the AMT demonstrated better antimicrobial prescribing than ID fellows.

J Microbiol Methods, 2001 Sep, 46(3), 261 - 7
Potential problems with fluorescein diacetate assays of cell viability when testing natural products for antimicrobial activity; Clarke JM et al.; There are two potential problems in the use of fluorescein diacetate (FDA) as a measure of cell viability . The first is the hydrolysis of FDA to fluorescein in the absence of live cells and the second is the quenching of fluorescence by assay solutions . We show that common media components such as tryptone, peptone and yeast extract all promote hydrolysis of FDA in the absence of live cells, as do Tris-HCl and sodium phosphate buffers . As a consequence, various microbiological media promote hydrolysis of FDA in the absence of live cells . Different media were also shown to reduce the amount of visible fluorescence of fluorescein . Diluting the medium decreases the background hydrolysis of FDA as well as increases the amount of visible fluorescence . Both problems should be considered when using FDA as an indicator of cell viability when testing natural products for antimicrobial activity.

BioDrugs, 2001, 15(3), 199 - 206
An infectious basis for multiple sclerosis: perspectives on the role of Chlamydia pneumoniae and other agents; Moses H Jr et al.; The aetiology of multiple sclerosis (MS) remains unknown . Epidemiological, clinical and pathological data support the theory that MS is a complex disease/syndrome with many factors affecting its development and progression . It may be appropriate to regard MS as a syndrome with differing clinical and pathological features occurring along a spectrum . Patients with MS are more likely to have an affected relative than are individuals without MS, which suggests that there is a genetic component to this illness . Despite this genetic susceptibility, 85% of MS patients do not have an affected relative and only 1 in 3 monozygotic (identical) twins develops MS if the other twin already has it . These data strongly suggest that environmental factors influence the development of MS . Many putative infectious agents have been proposed to be involved in the aetiology of MS . Although research into identifying MS-causative agents dates back for more than 5 decades, no agent has yet emerged with any consensus as the cause of MS . This controversy is due to a number of factors, including lack of specificity of an agent to MS, lack of reproducibility in other laboratories, inappropriate controls, laboratory contamination and lack of a standard and easily reproducible assay system . Chlamydia pneumoniae is a recently described pathogen that may have a role in the pathogenesis of MS . C . pneumoniae is an intracellular bacterial organism that is infectious to humans . It has recently been detected in the cerebrospinal fluid (CSF) of MS patients but not in that of patients with other neurological diseases . There is also a case report of a patient with CNS C . pneumoniae infection and rapidly progressive MS responding to antimicrobial therapy directed against this pathogen . An association between C . pneumoniae in the CSF and MS is now apparent, but its role in the development of MS remains unknown . Further work exploring the role of C . pneumoniae in inflammatory demyelination is required . This may be accomplished either by developing an animal model or in a therapeutic trial in patients with MS.

Mol Plant Microbe Interact, 2001 Jul, 14(7), 925 - 8
Effect of fragarin on the cytoplasmic membrane of the phytopathogen Clavibacter michiganensis; Filippone MP et al.; Fragarin, an antibiotic that was isolated and purified from a soluble fraction of strawberry leaves, may be a new type of preformed antimicrobial compound (phytoanticipin) . Here, we report that the growth and oxygen consumption of the phytopathogenic bacterium Clavibacter michiganensis were rapidly inhibited after the addition of fragarin to cultures . Also, dissipation of the membrane potential and an increase of cell membrane permeability were observed in the presence of fragarin . The ability of fragarin to dissipate the membrane potential was confirmed with the use of small unilamellar liposomes made with lipids extracted from C . michiganensis . Our results suggest that fragarin is able to act at the membrane level, and that this action is correlated with a decrease in cell viability.

SADJ, 2001 Apr, 56(4), 178 - 81
Anti-plaque efficacy of a chalk-based antimicrobial dentifrice; Lewis RD et al.; A chalk-based antimicrobial dentifrice was developed and has undergone in vitro testing to determine antimicrobial efficacy by kill-time studies, and in vivo clinical studies to determine anti-plaque build-up properties . The antimicrobial efficacy of the formulation is attributable to the following components; sodium lauryl sulphate, sodium monofluorophosphate, flavouring oils, triclosan, and low water activity . In vitro kill-time testing showed the dentifrice to have good activity against organisms associated with plaque, showing at least 99% reductions in the numbers of each organism . In vivo clinical results showed the dentifrice to protect against the build-up of plaque when compared to water alone . These results demonstrate that this dentifrice is effective in controlling plaque, and can thus be expected to promote good oral hygiene.

Transplantation, 2001 Jun 15, 71(11), 1678 - 80
Human monocytic ehrlichiosis: an emerging pathogen in transplantation; Tan HP et al.; BACKGROUND: The spectrum of disease caused by Ehrlichia spp . ranges from asymptomatic to fatal . Awareness and early diagnosis of the infection is paramount because appropriate therapy leads to rapid defervescence and cure . If left untreated, particularly in immunosuppressed patients, ehrlichioses may result in multi-system organ failure and death . METHODS: We report the second case of human monocytic ehrlichiosis (HME) in a liver transplant recipient, and review the literature . RESULTS: The patient presented with fever and headache, had negative cultures, and despite broad-spectrum antimicrobial coverage appeared progressively septic . After eliciting a history of tick exposure we treated the patient empirically with doxycycline . The diagnosis of HME was confirmed by 1) polymerase chain reaction (PCR) for Ehrlichia chaffeensis, 2) acute and convalescent serum titers, and 3) in vitro cultivation of E chaffeensis from peripheral blood . CONCLUSION: Although human ehrlichioses are relatively uncommon, they are emerging as clinically significant arthropod-borne infections . Although epidemiological exposure is responsible for infection, immunosuppression makes patients more likely to succumb to disease . A high index of suspicion and early treatment results in a favorable outcome.

QJM, 2001 Jul, 94(7), 373 - 8
Antimicrobial management of acute exacerbation of chronic airflow limitation; Davies L et al.; Antibiotics are frequently administered for exacerbations of chronic obstructive pulmonary disease and asthma, yet their role remains unclear . We prospectively audited the antimicrobial management of 167 patients aged >50 years hospitalized for exacerbations of chronic airflow limitation . Antibiotics were commenced on admission for 151 (90%) patients (oral 52%, intravenous 38%), including 17/23 (74%) with no evidence of fever, purulent sputum, leucocytosis or inflammatory chest X-ray changes . The mean number of different antibiotics prescribed was 1.8 (range 0-6); a wide range of antibiotics and antibiotic combinations were used . Sputum samples were sent for microbiological examination in 101 (61%) patients . Sputum culture was positive in 34, but only 11 (7% of the total) had amoxycillin-resistant organisms in their sputum . Seventeen patients (10%) developed diarrhoea while in hospital . Under logistic regression analysis, total number of antibiotics prescribed (p<0.0001) and age (p=0.0062) were the two factors associated with hospital-acquired diarrhoea . Only 34% of patients had received an influenza vaccination in the winter of the study, and 10% a pneumococcal vaccination within the last 5 years . In routine clinical practice, aggressive antibiotic therapy was frequently administered to patients admitted with chronic airflow limitation, despite limited clinical, radiological and microbial indications . Excessive use of antibiotics has important implications, including morbidity (antibiotic-associated diarrhoea), cost and the potential for increased microbial antibiotic resistance . A minority of patients with chronic airflow limitation are being vaccinated against influenza and Pneumococcus.

J Biol Chem, 2001 Sep 7, 276(36), 33547 - 53 Epub 2001 Jul 02.
Barley lipid transfer protein, LTP1, contains a new type of lipid-like post-translational modification; Lindorff-Larsen K et al.; In plants a group of proteins termed nonspecific lipid transfer proteins are found . These proteins bind and catalyze transfer of lipids in vitro, but their in vivo function is unknown . They have been suggested to be involved in different aspects of plant physiology and cell biology, including the formation of cutin and involvement in stress and pathogen responses, but there is yet no direct demonstration of an in vivo function . We have found and characterized a novel post-translational modification of the barley nonspecific lipid transfer protein, LTP1 . The protein-modification bond is of a new type in which an aspartic acid in LTP1 is bound to the modification through what most likely is an ester bond . The chemical structure of the modification has been characterized by means of two-dimensional homo- and heteronuclear nuclear magnetic resonance spectroscopy as well as mass spectrometry and is found to be lipid-like in nature . The modification does not resemble any standard lipid post-translational modification but is similar to a compound with known antimicrobial activity.

Biochem Pharmacol, 2001 Aug 1, 62(3), 363 - 7
Inhibitory effect of quinolone antimicrobial and nonsteroidal anti-inflammatory drugs on a medium chain acyl-CoA synthetase; Kasuya F et al.; The inhibitory effects of quinolone antimicrobial agents and nonsteroidal anti-inflammatory drugs on purified mouse liver mitochondrial medium chain acyl-CoA synthetase catalyzing the first reaction of glycine conjugation were examined, using hexanoic acid as a substrate . Enoxacin, ofloxacin, nalidixic acid, diflunisal, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid, which do not act as substrates, were potent inhibitors . Diflunisal, nalidixic acid, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid inhibited competitively this medium chain acyl-CoA synthetase with K(i) values of 0.6, 12.4, 19.6, 13.4, and 15.0 microM, respectively . Enoxacin and ofloxacin inhibited this medium chain acyl-CoA synthetase in a mixed-type manner with K(i) values of 23.7 and 38.2 microM, respectively . Felbinac, which is a substrate, inhibited the activity of this medium chain acyl-CoA synthetase for hexanoic acid (IC50 = 25 microM) . The concomitant presence of enoxacin and felbinac strongly inhibited this medium chain acyl-CoA synthetase . These findings indicate that medium chain acyl-CoA synthetases may be influenced by quinolone antimicrobial and nonsteroidal anti-inflammatory drugs.

J Chemother, 2001 Apr, 13 Suppl 1, 40 - 4
Antibiotic resistance in developing countries; Shibl AM et al.; During the past decade there have been major changes in the susceptibility of bacteria that cause various infections . Resistance to anti-infective agents, including antibiotics, is worldwide, both in developed and developing countries . Almost all bacterial species can develop resistance to anti-infective agents and resistance can readily be transferred among bacteria by transmissible elements (plasmids) . Measures to prevent the emergence of resistance must be implemented urgently . A multiplicity of factors drive antibiotic resistance and solutions require the collaboration of governmental agencies, pharmaceutical companies, healthcare providers and consumers . Knowledge of resistance patterns and of the ways by which resistance is overcome is vital to the future of antimicrobial chemotherapy.

Yakugaku Zasshi, 2001 Jun, 121(6), 433 - 9
{Pharmaceutical investigation of vancomycin hydrochloride eye drops and their topical application to MRSA eye infection}; Itoh M et al.; Two formulations of 0.5% vancomycin hydrochloride (VM) eye drops (VM-B and VM-C eye drops) were prepared by dissolving commercial VM powder for injection with preserved water B (PWB) containing phosphate buffer and preserved water C (PWC) containing only antimicrobial preservative, respectively . The VM-B eye drops have neutral pH (about 6.3), and the VM-C eye drops acidic pH of about 3.5 . The pharmaceutical examination of these eye drops was performed regarding its clinical application to MRSA eye infection . In an irritability test using a rabbit's eye, the average number of winks after instillation of one drop of VM-B eye drops was 0.8 times/min and significantly smaller than that of VM-C eye drops (2.0 times/min) . In dark storage at 4 degrees C, no change of VM concentration in both eye drops was observed for 25 weeks after preparation and the mean residual concentrations as determined by the HPLC-UV (240 nm) method were constant over 90% for 8 weeks, of the initial concentration . However, the residual VM concentration of VM-B eye drops under a room condition declined to 58% after 4 weeks and 20% after 8 weeks, and VM in light storage at 40 degrees C was not detectable after 8 weeks . The drug concentration of VM-C eye drops declined to 83% after 4 weeks and 74% after 8 weeks under a room condition, and to 46% after 4 weeks and 20% after 8 weeks under light storage at 40 degrees C . Under these storage conditions, the precipitation of VM related crystals was observed in both the eye drops when the residual percentage of VM was lower than 80% . Judging from HPLC chromatograms of a solution of the precipitated crystals, it was suggested that this crystal was degradation products of VM . The VM-B eye drops was applied to a patient with MRSA eye infection, because other medication was not effective . After continuous instillation of a drop per times every hour to both eyes, MRSA in corneal culture turned out negative after one week, and the clinical condition was remarkably improved . On the basis of the result of eye-irritability, VM-B eye drops with neutral pH was suggested to be superior to acidic VM-C eye drops from a safety point of view . It was also indicated that VM-B eye drops can be effectively used for 8 weeks under dark storage at 4 degrees C for MRSA eye infection, which is a useful piece information for the proper usage of the VM eye drops.

Pediatrics . 2001 Jul;108(1):E12.
Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis; Nupponen I et al.; OBJECTIVE: To assess neutrophil CD11b and circulating interleukin 8 (IL-8) as markers of early-onset infection in neonates . METHODS: The study comprised 39 neonates, with a gestational age of 29 to 41 weeks, suspected of infection within 48 hours of life . Neutrophil surface expression of CD11b was quantified with flow cytometry and plasma IL-8 with an enzyme-linked immunosorbent assay . Both data were available from 35 of 39 neonates . Serum C-reactive protein was determined at initial evaluation and, later, on the basis of the clinical picture . Neonates were allocated retrospectively into 2 groups . In the sepsis group (N = 22), 4 had culture-proven sepsis, and 14 had an antenatal risk factor for infection . In the possible-infection group (N = 13), each neonate had a noninfective disorder, but co-occurring infection remained a possibility . Twelve healthy term infants served as controls . RESULTS: CD11b expression and IL-8 levels both increased in order of sepsis > possible infection > healthy . Sensitivity and specificity by the CD11b test for sepsis were equal, at 1.00, and those by the IL-8 test 0.91 and 1.00, respectively; 6 (17.1%) of the 35 neonates had CD11b and IL-8 below cutoff levels . CONCLUSIONS: Measuring neutrophil CD11b expression and circulating IL-8 provides a means to identify early-onset neonatal sepsis . The findings may be helpful in planning strategies to safely reduce the use of antimicrobials in neonates.

Pediatrics, 2001 Jul, 108(1), 1 - 7
Reducing antibiotic use in children: a randomized trial in 12 practices; Finkelstein JA et al.; OBJECTIVE: To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old . Setting . Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State . Patients . All enrolled children younger than 6 years old . METHODS: Practices stratified by MCO and size were randomized to intervention or control groups . The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided . Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms . Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996-1997) and intervention (1997-1998) years . The primary analysis (for children 3 to <36 months and 36 to <72 months) assessed the impact of the intervention among children during the intervention year, controlling for covariates including patient age and baseline prescription rate . Confirmatory analyses at the practice level were also performed . RESULTS: The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years . Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis . Antibiotic dispensing for children 3 to <36 months old decreased 0.41 antibiotics per person-year (18.6%) in intervention compared with 0.33 (11.5%) in control practices . Among children 36 to <72 months old, the rate decreased by 0.21 antibiotics per person-year (15%) in intervention and 0.17 (9.8%) in control practices . Multivariate analysis showed an adjusted intervention effect of 16% in the younger and 12% in the older age groups . The direction and approximate magnitude of effect were confirmed in practice-level analyses . CONCLUSIONS: A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing . Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse.

J Chemother, 2000 Sep, 12 Suppl 3, 23 - 8
Short-Term prophylaxis with ceftriaxone plus metronidazole in esophageal cancer surgery; Ruol A et al.; An open prospective study was carried out in 82 consecutive patients undergoing resective surgery for esophageal cancer from January 1995 to July 1996 . Antimicrobial prophylaxis was done using a single dose of ceftriaxone (2 g i.v.) given at the induction of anesthesia in combination with metronidazole (0.5 g i.v.) . Two further doses of metronidazole were administered 8 and 16 hours postoperatively . Fourteen patients (17%) experienced postoperative infections . This study, even though open and non-comparative, confirms that ceftriaxone given as a single-dose plus metronidazole provides adequate prophylaxis and significant cost-savings in comparison with multiple-dose prophylactic regimens in patients undergoing major surgery for esophageal cancer . Furthermore, the single-dose regimen reduces the workload for the nursing staff, the risk of side effects, and the possibility of selecting resistant strains.

J Chemother, 2000 Sep, 12 Suppl 3, 10 - 6
Antimicrobial prophylaxis with ceftriaxone for prevention of early postoperative infections after 49 liver transplantations; Grazi GL et al.; Infection remains a major problem for individuals who undergo solid organ transplantation and liver transplant recipients are particularly susceptible to infectious complications with a high morbidity and mortality rate . The risk of these infections is determined by previous or future environmental exposures as well as the patient's immune status . We report here the results of an open prospective study involving 49 consecutive liver transplantations, undertaken to evaluate the efficacy of ceftriaxone in the prevention of early postoperative infectious complications . Antimicrobial prophylaxis was done using a single dose of ceftriaxone (2 g i.v.) given at the induction of anesthesia and then 2 further once-daily doses were administered 2 days postoperatively . Early postoperative bacterial infection rate was 43.5% (20/46); this result is comparable or even lower than those documented in other studies . This study, even though open and non-comparative, showed that a once-daily regimen containing ceftriaxone provides adequate antimicrobial prophylaxis and significant cost-savings in comparison with multiple-dose prophylactic regimens in patients undergoing liver transplantation.

Vet Res, 2001 May-Aug, 32(3-4), 381 - 92
New trends in regulatory rules and surveillance of antimicrobial resistance in bacteria of animal origin; Martel JL et al.; Since the introduction in the 1940s of antibiotics as drugs against bacterial infections in human and then veterinary medicine, two major events have caused a shift in the antibiotherapy era: (1) the emergence of resistant bacteria and (2) the awareness of the limits of new drug development . It rapidly became urgent to set up measures in order to evaluate the importance of resistant bacteria and their origin as well as to limit the dissemination of resistant vectors (bacteria and bacterial genes) . This led to the establishment of guidelines and regulatory rules necessary for risk assessment and clearly dependent upon monitoring and research organisations . At a veterinary level, the possible dissemination of multiresistant bacteria from animals to humans, through feeding, urged various national European and international institutions to give general recommendations to monitor and contain the emergence and diffusion of resistant strains . This paper gives an overview of the evolution of regulatory rules and monitoring systems dealing with multiresistant bacteria.

Vet Res, 2001 May-Aug, 32(3-4), 275 - 84
Quinolone resistance in Escherichia coli; Webber M et al.; Escherichia coli is an important pathogen of animals and humans that causes great financial cost in food production by causing disease in food animals . The quinolones are a class of synthetic antimicrobial agents with excellent activity against Escherichia coli and other Gram-negative bacteria used in human and veterinary medicine . Different quinolones are used to treat various conditions in animals in different parts of the world . All members of this class of drug have the same mode of action: inhibition of topoisomerase enzymes, DNA Gyrase and Topoisomerase IV . Escherichia coli can become resistant to quinolones by altering the target enzymes, reducing permeability of the cell to inhibit their entry, or by actively pumping the drug out of the cell . All these resistance mechanisms can play a role in high-level fluoroquinolone resistance, however target site mutations appear to be most important . As all quinolones act in the same way resistance to one member of the class will also confer decreased susceptibility to all members of the family . Quinolone resistant Escherichia coli in animals have increased in numbers after quinolone introduction in a number of different case studies . The resistance mechanisms in these isolates are the same as those in resistant strains found in humans . Care needs to be taken to ensure that quinolones are used sparingly and appropriately as highly resistant strains of Escherichia coli can be selected and may pass into the food chain . As these drugs are of major therapeutic importance in human medicine, this is a public health concern . More information as to the numbers of quinolone resistant Escherichia coli and the relationship between resistance and quinolone use is needed to allow us to make better informed decisions about when and when not to use quinolones in the treatment of animals.

Vet Res, 2001 May-Aug, 32(3-4), 201 - 25
Use of antimicrobials in veterinary medicine and mechanisms of resistance; Schwarz S et al.; This review deals with the application of antimicrobial agents in veterinary medicine and food animal production and the possible consequences arising from the widespread and multipurpose use of antimicrobials . The various mechanisms that bacteria have developed to escape the inhibitory effects of the antimicrobials most frequently used in the veterinary field are reported in detail . Resistance of bacteria to tetracyclines, macrolide-lincosamide-streptogramin antibiotics, beta-lactam antibiotics, aminoglycosides, sulfonamides, trimethoprim, fluoroquinolones and chloramphenicol/florfenicol is described with regard to enzymatic inactivation, decreased intracellular drug accumulation and modification/protection/replacement of the target sites . In addition, basic information is given about mobile genetic elements which carry the respective resistance genes, such as plasmids, transposons, and gene cassettes/integrons, and their ways of spreading via conjugation, mobilisation, transduction, and transformation.

Drug Ther Bull, 2001 Jun, 39(6), 43 - 6
Antimicrobial prophylaxis for orthopaedic surgery; Lactoferrin and cyclic lactoferricin inhibit the entry of human cytomegalovirus into human fibroblasts; Department of Microbiology, University Hospital of Tromso, N 9038 Tromso, Norway . mlabjeh@rito.no

Lactoferrin is mainly produced by polymorphonuclear leukocytes and has been demonstrated in mammalian milk and external secretions . Lactoferrin is an iron-binding, multifunctional protein and may play an important role in immune regulation and in defense mechanisms against bacteria, fungi and viruses . Lactoferricin is a potent antimicrobial peptide generated from the N-terminal part of lactoferrin by pepsin cleavage . We demonstrate that lactoferrins from different species and its N-terminal peptide lactoferricin (particularly the cyclic form) inhibit expression of early and late antigens, as well as production of infectious viral progeny during human cytomegalovirus (HCMV) infection in vitro . Iron-saturated lactoferrin did not affect HCMV antigen expression . Heparin had the same effects as iron-depleted lactoferrin . Yet, mixtures of lactoferrin and heparin did not inhibit HCMV multiplication i.e . lactoferrin and heparin seemed to mutually block each other's antiviral activities . HCMV-infected cells exposed to lactoferrin and cyclic lactoferricin contained less intracellular virus than unexposed cells . The antiviral activity of cyclic lactoferricin was more than seven-fold weaker than that of the maternal molecule . Lactoferrin and cyclic lactoferricin prevented HCMV entrance into the host cell.

Obstet Gynecol Clin North Am, 2001 Jun, 28(2), 283 - 304
Diagnosis and management of respiratory tract infections for the primary care physician; Wei SC et al.; Respiratory tract infections cause nearly half of deaths owing to infectious disease in the United States . This article has discussed the management of several common respiratory tract infections, with an emphasis on appropriate diagnosis and use of antimicrobial agents . Understanding the cause of various respiratory tract infections enables primary care physicians to avoid unnecessary antibiotic use, decreasing adverse effects owing to medications and preventing the rise in antimicrobial resistance.

J Nat Prod, 2001 Feb, 64(2), 164 - 70
Sequences and antimycoplasmic properties of longibrachins LGB II and LGB III, two novel 20-residue peptaibols from Trichoderma longibrachiatum; Leclerc G et al.; Longibrachins are members of the class of natural Aib-containing peptides designated as peptaibols . Six longibrachins, LGA I-IV and LGB II and III, were purified from a Trichoderma longibrachiatum strain by a procedure employing several chromatography steps including reversed-phase HPLC . The amino acid sequence determination was based on a combination of liquid secondary ion mass spectrometry (LSIMS) and two-dimensional 1H and 13C NMR spectroscopy . Longibrachins are 20-residue peptaibols with a C-terminal phenylalaninol and either neutral (LGA; Gln18) or acidic (LGB; Glu18) character . Longibrachins LGB II and III have novel sequences . Both longibrachins LGA and LGB show significant bactericidal activity against mycoplasmas (Acholeplasma, Mycoplasma, and Spiroplasma), with minimal inhibitory concentrations in the range 1.56-12.5 microM (3-25 micrograms/mL), and also perturb the permeability of membrane bilayers . Longibrachin LGA IV is the most potent of the presently known 18-20-residue peptaibols . The antimicrobial and membrane-perturbing properties of longibrachins, which are described here for the first time, were shown to be correlated.

Curr Opin Oncol, 2001 Jul, 13(4), 229 - 35
Pneumonia in febrile neutropenic patients: radiologic diagnosis; Maschmeyer G; Pneumonia in febrile neutropenic cancer patients should be diagnosed as early as possible, because prompt institution of targeted therapeutic measures might be essential for their prognosis . Conventional chest radiographs frequently fail to detect lung infiltrates at an early stage, meaning that a normal chest radiograph finding must be interpreted with caution . Thoracic computed tomograph scans provide a much higher yield and are therefore recommended in patients at risk for a complicated pulmonary infection . Lung infiltrates documented by computed tomograph scans (eg, nodular infiltrates with or without a halo, ground-glass opacities, or cavitations with or without air crescent signs) open up a wide range of differential diagnoses, such as invasive pulmonary aspergillosis, other types of pneumonia, hemorrhage, infiltration by the underlying malignancy, drug toxicity, alveolar proteinosis, or acute respiratory distress syndrome . High-resolution techniques or magnetic resonance imaging may provide further details to help distinguish inflammatory processes from processes that may not require an antimicrobial intervention . Sequential nonculture-based monitoring for invasive fungal infections, using Aspergillus antigen sandwich enzyme-linked immunosorbent assay, and panfungal or Aspergillus-specific polymerase chain reaction, may add important tools in the early identification of patients who may benefit from systemic antifungal treatment.

Fitoterapia, 2001 Jun, 72(5), 579 - 82
Antimicrobial activity of Rhynchosia beddomei; Bakshu LM et al.; The petroleum ether and ethyl acetate extracts of Rhynchosia beddomei leaves showed inhibiting activity against some bacterial and fungal species at different concentrations.

Fitoterapia, 2001 Jun, 72(5), 575 - 8
Antimicrobial activity of Clematis papuasica and Nauclea obversifolia; Khan MR et al.; The methanol extracts of Clematis papuasica leaves and stem bark and of Nauclea obversifolia leaves, stem and root barks showed awide spectrum of antibacterial activity which was increased on fractionation (petrol, dichloromethane, ethyl acetate), the ethyl acetate fractions being in all cases the most effective . None of the extractives was active against tested moulds.

Fitoterapia, 2001 Jun, 72(5), 561 - 4
Antimicrobial activity of Cassia alata; Khan MR et al.; The methanol extracts of leaves, flowers, stem and root barks of Cassia alata showed a broad spectrum of antibacterial activity . The activity was increased on fractionation (petrol, dichloromethane, ethyl acetate), the dichloromethane fraction of the flower extract being the most effective . No activity was shown against tested moulds.

Fitoterapia, 2001 Jun, 72(5), 471 - 80
Fraxinus ornus L; Kostova I; The literature on the chemical constituents and the biological activity of Fraxinus ornus bark, leaves and flowers has been reviewed . Chemical studies show the presence of many compounds belonging mainly to the groups of hydroxycoumarins, secoiridoid glucosides, phenylethanoids and flavonoids . Biological studies reveal significant antimicrobial, antioxidative, photodynamic damage prevention, wound healing, anti-inflammatory, immunomodulatory and antiviral activities, and support the use of the bark in the folk medicine.

Transpl Infect Dis, 1999 Sep, 1(3), 153 - 6
Neutrophil respiratory burst following liver transplantation: in vitro effects of granulocyte colony-stimulating factor; Jaeger K et al.; Early postoperative infections and septic complications are predominant causes of morbidity and mortality in patients following orthotopic liver transplantation (OLTx) . Prophylactic granulocyte colony-stimulating factor (G-CSF) administration after OLTx was found to decrease the number of sepsis episodes and sepsis-related mortality . Since polymorphonuclear neutrophils (PMNs) are one of the major determinants of antimicrobial defense, alteration of their functions may influence the development of sepsis in these patients . Therefore, we investigated in vitro whether or not priming with G-CSF affects the neutrophils' respiratory burst (RB) in immunosuppressed liver-transplanted patients . Venous blood was drawn from liver allograft recipients (n=12) between the 5th and 15th day postoperatively . Patients without clinical signs of infection or rejection were included in this study . Leukocytes were obtained as supernatant following sedimentation and incubated with 1000 IE ml-1 G-CSF . The RB was measured by the intracellular oxidation of non-fluorescent dihydrorhodamine to the fluorescent rhodamine by flow cytometry . The results were expressed as a percentage of increasing stimulation compared to the control responses, which are made up of the percentage of cells with RB reaction after stimulation with phorbol ester (PMA), bacteria (E . coli), or the combination of a cytokine (TNF-alpha) and a bacterial peptide (FMLP) in the absence of G-CSF . In vitro priming with G-CSF resulted in significantly increased activity of the RB after PMA (from 71.7% to 85.6%) and TNF-alpha/FMLP (from 58.4% to 72.7%) stimulation . These data demonstrate that G-CSF in vitro augments the RB of PMNs, thereby suggesting a possible therapeutic role for G-CSF as immunomodulating agent during bacterial and fungal infections following OLTx.

Transpl Infect Dis, 1999 Mar, 1(1), 29 - 39
The therapeutic prescription for the organ transplant recipient: the linkage of immunosuppression and antimicrobial strategies; Rubin RH et al.; Infection and rejection, the two major barriers to successful organ transplantation, are closely linked, with immunosuppressive therapy being central to the pathogenesis of both . After almost two decades when azathioprine and prednisone, supplemented by antilymphocyte antibody therapy, were the cornerstones of post-transplant immunosuppressive programs, there has been a major increase in the therapeutic armamentarium available to treat rejection: cyclosporine, tacrolimus, mycophenolate mofetil, rapamycin, and antibodies directed against the interleukin-2 receptor . These agents are potent inhibitors of microbial specific T cell function, thus potentiating opportunistic infection with herpes group viruses, fungal and mycobacterial species, Strongyloides stercoralis, and a variety of intracellular pathogens . The mechanisms by which each of these drugs exerts its effects are an important determinant of the antimicrobial strategies that will be necessary to combat infection . Indeed, strategies to limit these infections are being linked to the nature of the immunosuppressive therapy required in a particular patient . Thus, the therapeutic prescription for the transplant patient is said to have two components: an immunosuppressive component to prevent and treat rejection, and an antimicrobial one to make it safe . In addition to using antimicrobial agents therapeutically, in the transplant patient prevention is stressed in which antibiotics are deployed prophylactically or preemptively.

Transpl Infect Dis, 1999 Mar, 1(1), 3 - 20
Opportunistic infections after blood and marrow transplantation; Wingard JR; Opportunistic infections are major causes of morbidity and mortality following bone marrow transplantation . Technological advances in stem cell procurement, the introduction of hematologic growth factors to speed engraftment, the development of new immunosuppressive regimens to control graft-versus-host disease (GVHD), the development of technology to perform graft engineering with removal of T lymphocytes in toto or subpopulations of T lymphocytes, the use of molecular techniques to optimize donor and recipient matching, advances in blood banking, and development of international donor registries, are among the various factors that have led to tremendous changes in transplant practices . Because of such changes in transplant practices, along with the advent of new antimicrobial agents, and development of infection control measures affecting pathogen exposure, alterations in the interplay between host and potential pathogens have occurred . Shifts in the incidence and types of opportunistic pathogens are taking place . Several historically important infectious syndromes are today well controlled; others have diminished in importance early after transplant but are more problematic at a later time; new emerging pathogens are being recognized due to selection pressures from antimicrobial usage and new hosts, such as recipients of alternate donor allogeneic transplant procedures, with even more profound and prolonged immune suppression . Such shifts and new syndromes pose continuing new challenges to the transplant clinician.

J Hosp Infect, 2001 Jun, 48(2), 83 - 5
The organization of infection control in Italy; Bassetti M et al.; This paper describes the organization of infection control in Italy with respect to regulatory requirements, the tasks and training of the infection control physician and nurse, and the function and responsibilities of the infection control committee . Moreover, the paper reports on incidence and prevalence of hospital-acquired infections (HAI), antibiotic usage and antimicrobial resistance in Italy.

J Microencapsul, 2001 Jul-Aug, 18(4), 457 - 65
Microencapsulation of gentamicin in biodegradable PLA and/or PLA/PEG copolymer; Huang YY et al.; Biodegradable carriers containing gentamicin for local treatment of bone infection were developed . This paper describes the preparation and in vitro evaluation of these biodegradable implants . Poly-L-lactic acid (PLA) and poly-L-lactic acid:polyethylene glycol (PLA/PEG) disk implants containing gentamicin sulphate were obtained by compression of microspheres prepared by a double emulsion process . The mean particle size distribution of the microspheres, based on volume, ranged from 95-270 microm . The gentamicin sulphate loading of the microspheres, after a methylene chloride-water extraction procedure, exceeded 90% of the theoretical value . In vitro dissolution studies on the microspheres and implants with drug loadings 10-40% w/w indicated that the rate of drug release from both PLA and PLA/PEG implants increased, with an increase in drug loading . The release of gentamicin from microspheres was dependent on the properties of PLA and/or PLA/PEG . The PLA/PEG copolymer was more hydrophilic than the PLA homopolymer, and with a smaller pH change in the microenvironment with polymer being degraded . In comparison, the PLA/PEG implant released antibiotic faster and had a larger inhibitory zone based on the Bauer-Kirby experiments used to test the inhibitory activity of antimicrobial devices . Experimental results showed that the biodegradable PLA/PEG gentamicin delivery system had a potential for prophylaxis of post-operative infection.

J Chemother, 2000 Jul, 12 Suppl 2, 28 - 38
{Antibiotic prophylaxis of postoperative infection in orthopedics . Results of an epidemiologic survey in Italy conducted by the Journal of Chemotherapy}; Periti P et al.; An epidemiological survey of the use of antimicrobial prophylaxis in Italian hospitals was carried out under the auspices of the Journal of Chemotherapy . Out of 500 Italian orthopedic centers requested, 225 have participated in this study . A total of 136,321 surgical procedures were reported in the 166 centers reporting complete answers on type of surgery . They comprised hip and knee prosthesis (13.9%), spine surgery (4%), hip endoprosthesis (5.2%), osteosynthesis (26.9%), arthroscopy (24.4%), and others (25.5%) . Perioperative antimicrobial prophylaxis was used in 75% of operations (ranging from 57.1% to 99.4% in arthroscopy and joint prosthesis, respectively) . Short term (< 24 h) antimicrobial prophylaxis was performed in 38.4% of the 206 Centers answering this question correctly . 61.1% of Centers employed single agent prophylaxis . 70.8% of these prescriptions were betalactam antibiotics . Bacteriological analysis of the wound in 86 Centers (total number of isolates 2013) revealed the presence of Gram-positive isolates in 73.7% of cases . Methicillin resistance was expressed in 45% of 915 tested strains . Out of 4221 patients with high risk of infectious complications (joint prosthesis surgery) given antimicrobial prophylaxis in 46 Centers, the percentage of surgical wound infections was overall 2.1%, while that of non-surgical wound infections was 3.6% . A decrease in the total infection rate by about half was associated with long-term (> 24 h) as compared to short-term (< 24 h) antibiotic treatment (3.7 vs 7.6%, respectively), and with the use of antibiotic drug combinations vs single antibiotic drugs (3.9 vs 6.6%, respectively) . The incidence of surgical-site infection is not decreased by extending the chemoprophylaxis for more than the first 24 h after surgery, while it is reduced from 2.5 to 1.4% by use of combination antibiotic therapy.

Ann Pharm Fr, 2001 May, 59(3), 147 - 75
{The worldwide challenges of "new" or reemerging communicable diseases at the dawn of the 21st century}; Werner GH; In spite of the very significant advances made during the 20 th century in the prevention and the treatment of communicable diseases, infections are still today, even in developed countries, a major cause of morbidity and mortality . New infectious diseases have emerged (AIDS, legionellosis, exterotoxigenic E . coli, Ebola fever), others have significantly reemerged (tuberculosis, diphtheria, Bartonella infections) or have seen their geographic distribution widen considerably (dengue, Hantavirus, West Nile Virus, Lyme disease) . New and widespread hepatotropic viruses (mainly hepatitis C) have been identified, while the bacterial cause (Helicobacter pylori) of gastric ulcer was demonstrated . The second part of this review will deal with other examples of emerging or reemerging infections and with the problem of the increasing resistance of pathogens to antimicrobial agents . It will analyse the multiple causes of these various phenomena and describe the diverse strategies which should become available for the prevention and/or treatment of these numerous infectious diseases.

J Clin Microbiol, 2001 Jul, 39(7), 2677 - 80
Increasing multidrug resistance in Helicobacter pylori strains isolated from children and adults in Mexico; Torres J et al.; The susceptibilities to three antimicrobials of 195 Helicobacter pylori strains isolated from Mexican patients is reported; 80% of the strains were resistant to metronidazole, 24% were resistant to clarithromycin, and 18% presented a transient resistance to amoxicillin . Resistance to two or more antimicrobials increased significantly from 1995 to 1997.

J Clin Microbiol, 2001 Jul, 39(7), 2648 - 51
Clarithromycin-susceptible and -resistant Helicobacter pylori isolates with identical randomly amplified polymorphic DNA-PCR genotypes cultured from single gastric biopsy specimens prior to antibiotic therapy; van der Ende A et al.; Of the Helicobacter pylori populations from 976 patients, six contained clarithromycin-resistant as well as -susceptible colonies . In each heterogeneous H . pylori population, resistant H . pylori colonies harbored identical 23S ribosomal DNA (rDNA) mutations associated with clarithromycin resistance, while the susceptible H . pylori colonies all had wild-type 23S rDNA . The resistant and susceptible colonies of each of the heterogeneous H . pylori populations had identical randomly amplified polymorphic DNA-PCR genotypes . In conclusion, evaluation of antimicrobial susceptibility can be misinterpreted if only a single colony from the primary H . pylori population is used to test for clarithromycin susceptibility.

J Clin Microbiol, 2001 Jul, 39(7), 2646 - 7
Antimicrobial susceptibilities of Helicobacter pylori isolates under microaerophilic atmospheres established by two different methods; Kobayashi I et al.; The MICs of clarithromycin, amoxicillin, and metronidazole for 150 Helicobacter pylori isolates were determined using the AnaeroPack system and were compared with those determined using a microaerophilic incubator . The MICs of clarithromycin, amoxicillin, and metronidazole determined under both microaerophilic atmospheres were mostly within one twofold dilution for 146 (97.3%), 150 (100%), and 149 (99.3%) of the isolates, respectively.

Res Exp Med (Berl), 2001 Mar, 200(3), 169 - 74
Risk of endotoxemia during the initial phase of gut decontamination with antimicrobial agents; Schulze C et al.; Decontamination of the digestive tract with antimicrobial agents has been used for prevention and therapy of bacterial translocation . With regard to the well-described endotoxin-releasing properties of these agents, the question arises as to whether their enteral administration might result in an increased amount of intestinal endotoxins entering the circulation . Immunocompromised Wistar rats were intraduodenally challenged with live E . coli . Control animals received saline solution, decontaminated rats were treated with either tobramycin plus polymyxin B or ciprofloxacin alone through the duodenal tube . Plasma endotoxin activity and blood bacteria count were measured hourly over an observation period of 5 h . The intestinal bacterial count was determined at the end of the experiment . Gut decontamination in both groups receiving antimicrobial agents resulted in elevated plasma endotoxin levels compared with nondecontaminated controls . Maximum endotoxin levels were found to be 5-6 times higher in the ciprofloxacin group than in the control group and 2 times higher than in the tobramycin/polymyxin group . No positive blood cultures were detected . Intestinal bacterial count was similar in both treatment groups . Enterally applied antimicrobial agents bear an elevated risk of endotoxemia during the initial phase of gut decontamination . The amount of endotoxin translocating from the digestive tract to the circulation varies with the agents used . Polymyxin only partially reduced the observed endotoxin leakage from the gut.

Oncogene, 2000 Dec 27, 19(56), 6680 - 6
The rapamycin-sensitive signal transduction pathway as a target for cancer therapy; Hidalgo M et al.; The high frequency of mutations in cancer cells which result in altered cell cycle regulation and growth signal transduction, conferring a proliferative advantage, indicates that many of these aberrant mechanisms may be strategic targets for cancer therapy . The macrolide fungicide rapamycin, a natural product with potent antimicrobial, immunosuppressant, and anti-tumor properties, inhibits the translation of key mRNAs of proteins required for cell cycle progression from G1 to S phase . Rapamycin binds intracellularly to the immunophilin FK506 binding protein 12 (FKBP12), and the resultant complex inhibits the protein kinase activity of a protein kinase termed mammalian target of rapamycin (mTOR) . The inhibition of mTOR, in turn, blocks signals to two separate downstream pathways which control the translation of specific mRNAs required for cell cycle traverse from G1 to S phase . Blocking mTOR affects the activity of the 40S ribosomal protein S6 kinase (p70s6k) and the function of the eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), leading to growth arrest in the the G1 phase of the cell cycle . In addition to its actions on p70s6k and 4E-BP1, rapamycin prevents cyclin-dependent kinase activation, inhibits retinoblastoma protein (pRb) phosphorylation, and accelerates the turnover of cyclin D1 that leads to a deficiency of active cdk4/cyclin D1 complexes, all of which can inhibit cell cycle traverse at the G1/S phase transition . Both rapamycin and CCI-779, an ester analog of rapamycin with improved pharmaceutical properties and aqueous solubility, have demonstrated impressive activity against a broad range of human cancers growing in tissue culture and in human tumor xenograft models, which has supported the development of compounds targeting rapamycin-sensitive signal-transduction pathways . CCI-779 has completed several phase I clinical evaluations and is currently undergoing broad disease-directed efficacy studies . The agent appears to be well tolerated at doses that have resulted in impressive anti-tumor activity in several types of refractory neoplasms . Important challenges during clinical development include the definition of a recommended dose range associated with optimal biological activity and maximal therapeutic indices, as well as the ability to predict which tumors will be sensitive or resistant to CCI-779.

Hum Reprod, 2001 Jul, 16(7), 1457 - 63
Embryotoxicity of magainin-2-amide and its enhancement by cyclodextrin, albumin, hydrogen peroxide and acidification; Mystkowska ET et al.; BACKGROUND: The channel-forming antimicrobial peptide, magainin-2-amide, interacts preferentially with negatively charged, non cholesterol-containing membranes, including those of sperm, oocytes and cells of pre-implantation embryos . Cyclodextrin and albumin remove membrane cholesterol and together with hydrogen peroxide (H2O2) are potential enhancers of embryotoxicity . METHODS: Two-cell murine embryos were cultured in vitro with magainin-2-amide at a high effective concentration (250 microg/ml) and at subthreshold concentrations (166 and 200 microg/ml) . Embryos treated with sub-threshold concentrations of magainin were additionally treated with cyclodextrin, bovine serum albumin or H2O2 or were cultured under acidified conditions . Cell viability was verified with propidium iodide and fluorescein diacetate . RESULTS: The embryotoxic effect of magainin and H2O2 was dose- and time-dependent . Cyclodextrin, H2O2, acidification of the medium, and to a lesser extent albumin, enhanced the embryotoxicity of magainin at sub-threshold concentrations . CONCLUSION: Magainin on its own is highly embryotoxic . Its embryotoxicity is enhanced by cyclodextrin, albumin, H2O2 and acidification . Thus, magainin which has antibacterial, antifungal and antiprotozoal activity may also have a potential role as a contraceptive agent . The harmful effects of various concentrations of the exogenous H2O2 on 2-cell stage mouse embryos are reported here, to the best of our knowledge, for the first time.

Appl Environ Microbiol, 2001 Jul, 67(7), 2973 - 81
Detoxification of corn antimicrobial compounds as the basis for isolating Fusarium verticillioides and some other Fusarium species from corn; Glenn AE et al.; The preformed antimicrobial compounds produced by maize, 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one and its desmethoxy derivative 2,4-dihydroxy-2H-1,4-benzoxazin-3-one, are highly reactive benzoxazinoids that quickly degrade to the antimicrobials 6-methoxy-2-benzoxazolinone (MBOA) and 2-benzoxazolinone (BOA), respectively . Fusarium verticillioides (= F . moniliforme) is highly tolerant to MBOA and BOA and can actively transform these compounds to nontoxic metabolites . Eleven of 29 Fusarium species had some level of tolerance to MBOA and BOA; the most tolerant, in decreasing order, were F . verticillioides, F . subglutinans, F . cerealis (= F . crookwellense), and F . graminearum . The difference in tolerance among species was due to their ability to detoxify the antimicrobials . The limited number of species having tolerance suggested the potential utility of these compounds as biologically active agents for inclusion within a semiselective isolation medium . By replacing the pentachloronitrobenzene in Nash-Snyder medium with 1.0 mg of BOA per ml, we developed a medium that resulted in superior frequencies of isolation of F . verticillioides from corn while effectively suppressing competing fungi . Since the BOA medium provided consistent, quantitative results with reduced in vitro and taxonomic efforts, it should prove useful for surveys of F . verticillioides infection in field samples.

Acta Otolaryngol, 2001 Apr, 121(3), 414 - 8
Expression of human beta-defensin 1 mRNA in human palatine tonsil; Chae SW et al.; Defensins are a newly delineated family of effector molecules whose contribution to host defense, inflammation and cytotoxicity may be considerable for humans . Beta-defensins are cationic peptides with broad-spectrum antimicrobial activity that are produced by epithelia at the mucosal surface . Tonsillar epithelium, which is constantly exposed to microorganisms, may express these natural antibiotic peptides as part of its protective function . In this study we searched for the expression of hBD-1 mRNA in palatine tonsillar epithelium without signs of infection, using reverse transcriptase-polymerase chain reaction and in situ hybridization . Total RNA was isolated from non-infected tonsil and hBD-1 mRNA was identified in these tissues . From in situ hybridization, the expression of hBD-1 mRNA was seen to be localized in the surface epithelia of palatine tonsil . These data suggest that hBD-1 of the palatine tonsil may also play an important role in innate defense against microorganisms.

J Gastroenterol Hepatol, 2001 Jun, 16(6), 613 - 8
Strategy for retreatment of therapeutic failure of eradication of Helicobacter pylori infection; Nagahara A et al.; BACKGROUND AND AIM: A proton pump inhibitor (PPI)-based triple therapy consisting of a PPI, amoxicillin (A) and clarithromycin (C) or metronidazole (M) provides an eradication rate ranging from 80 to 90% . However, there have been few controlled studies with regard to the most effective regimen to re-treat patients after failure of the first-line therapy . Accordingly, we retrospectively reviewed our experiences and compared regimens with different combinations of antimicrobials to determine the optimal retreatment regimen . METHODS: Out of 133 patients who had received second-line therapy after failure of first-line PPI/AC therapy, we selected, for review, patients who took the prescribed drugs for first-line therapy equal to, or more than 80% . As a result, data on 114 patients (83 males and 31 females; mean age 49.1 +/- 13.0 years; peptic ulcer n = 89; non-ulcer dyspepsia, n = 25) were eligible for evaluation . They had either repeated the PPI/AC regimen (n = 34; 5-14 days), or had been administered the PPI/AM regimen (n = 80; 10 days) . The cure rates of the two regimens were compared . RESULTS: The eradication rates for second-line therapy with the PPI/AC regimen versus the PPI/AM regimen were 52.9% (95% CI, 35-70) versus 81.3% (95% CI, 71-89) by intention-to-treat analysis (P < 0.01), and 62.1% (95% CI, 42-79) versus 91.4% (95% CI, 81-97) by per-protocol analysis (P < 0.01) . CONCLUSION: The eradication rate for the PPI/AM retreatment regimen was significantly higher than for the repeated PPI/AC regimen, suggesting that a 10-day PPI/AM regimen can be recommended as a retreatment regimen for patients who had first-line eradication therapy by PPI/AC regimens.

Helicobacter, 2001 Jun, 6(2), 84 - 92
Helicobacter pylori and early duodenal ulcer status post-treatment: a review; Meyer JM et al.; BACKGROUND: Data submitted to the FDA were reviewed to analyze the relationship between Helicobacter pylori infection and the incidence of early duodenal ulcers, within 6 weeks, following treatment . MATERIALS AND METHODS: Retrospective analyzes were performed on data from three H . pylori development programs submitted to the FDA: ranitidine-bismuth-citrate (RBC), lansoprazole (L) and omeprazole (O) . Efficacy assessments for the RBC, L and O programs were made at end of a 4-week treatment period, 4-6 weeks following the end of a 14-day treatment period, and 4 weeks following the end of a 4-week treatment period, respectively . RESULTS: Overall, there was a 15%, 21% and 23% decrease in the number of patients in the RBC, L and O programs, respectively, with ulcers among H . pylori cleared/eradicated patients post-treatment compared with patients with persistent infection . Among patients who did not have cleared/eradicated H . pylori in the RBC and O programs, where antisecretory agents were continued beyond the antimicrobial treatment period, the number of ulcers was lower in the antisecretory plus antimicrobial subgroups compared with the antimicrobial alone subgroups (37% vs . 46% for RBC and 33% vs . 42% for O) . Among patients with cleared/eradicated H . pylori, the number of patients with ulcers in the antimicrobial alone subgroups and antisecretory plus antimicrobial subgroups were similar within each program . Antimicrobials alone had significantly lower rates of ulcers among patients with cleared/eradicated H . pylori as compared with patients without clearance/eradication . CONCLUSIONS: The early incidence of duodenal ulcers is significantly decreased in patients with H . pylori clearance/eradication.

Helicobacter, 2001 Jun, 6(2), 81 - 3
In search of the Holy Grail of Heliocobacter pylori remedies; Hopkins RJ; In this issue, Gisbert et al . (pp . 157-62) present the results of a noncomparative study evaluating a twice daily, 5-day regimen of ranitidine bismuth citrate, amoxicillin, clarithromycin and metronidazole twice daily for Helicobacter pylori cure . This study is one of a few stuides that evaluate a 5-day triple antimicrobial regimen in combination with a antisecretory agent . Although the study design precludes making any definite conclusion, it does encourage additional investigation of these types of regimens . Randomized controlled trials (RCTs) using regimens containing multiple agents should consider both standard-of-care comparator regimens and comparator regimens that will provide a better understanding of why regimens are more effective or better tolerated . The goal of treatment should be to maintain a lower bound 95% confidence interval (CI) of the point estimate of greater than 80% and a 'delta' (lower bound 95% CI of the difference in rates) of less than 10% . All RCTs should conduct susceptibility testing to evaluate the impact of resistance on efficacy and explain eradication failures . Finally, consideration should be given to the inclusion of patients with functional dyspepsia in H . pylori studies evaluating H . pylori cure since patients with peptic ulcer disease are becoming harder to find.

Clin Exp Dermatol, 2001 May, 26(3), 251 - 5
Neonatal eosinophilic pustular folliculitis; Buckley DA et al.; Eosinophilic pustular folliculitis (EPF) of infancy is a rare disorder which may begin in the neonatal period and cause considerable parental anxiety . It must be distinguished from other causes of a pustular eruption in neonates, including infection and erythema toxicum neonatorum, and rare disorders such as transient neonatal pustular melanosis, infantile acropustulosis and Langerhans' cell histiocytosis . Skin smears and occasionally skin biopsy may be necessary to reach a diagnosis . We report a case of a Caucasian child with an unusually early onset of EPF in the first day of life . We wish to emphasize the importance of recognizing this self-limiting condition in order to prevent inappropriate antimicrobial treatment.

J Nat Prod, 2001 Jun, 64(6), 816 - 8
Two new antimicrobial lysoplasmanylinositols from the marine sponge Theonella swinhoei; Matsunaga S et al.; Two new antimicrobial lysoplasmanylinositols have been isolated from the marine sponge Theonella swinhoei . Their structures were elucidated on the basis of spectroscopic and chemical analysis.

Z Naturforsch {C}, 2001 May-Jun, 56(5-6), 444 - 54
Tannins and related compounds: killing of amastigotes of Leishmania donovani and release of nitric oxide and tumour necrosis factor alpha in macrophages in vitro; Kiderlen AF et al.; The antileishmanial and immunomodulatory potencies of a series of 28 polyphenols were evaluated in terms of extra- and intracellular leishmanicidal activity and macrophage activation for release of nitric oxide (NO), tumour necrosis factor (TNF) and interferon (IFN)-like properties . For this, several functional bioassays were employed including an in vitro model for leishmaniasis in which murine bone marrow-derived macrophages (BMMphi) were infected with the obligate intracellular parasite Leishmania donovani, an extracellular Leishmania proliferation assay, a fibroblast-lysis assay (TNF-activity), and a biochemical assay for NO . Except for gallic acid, its methyl ester, shikimic acid and catechin (EC50 25.8-67.9 nM) all polyphenols tested significantly inhibited the intracellular survival of L . donovani amastigotes (EC50 0.4-13.9 nM) when compared with the clinically used agent, sodium stibogluconate (EC50 10.6 nM) . In contrast, none of the samples proved to be directly toxic for the extracellular promastigote form of the parasite . Noteworthy, the phenolic samples showed only moderate or no cytotoxicity against the murine host cells (EC50 10 to >144 nM) . Although NO is an important effector molecule in macrophage microbicidal activity, the inducing potential of the test compounds for its release was found to be very moderate ranging from 7-54 microM (IFN-gamma/LPS 119 microM) . On the other hand, inhibition of NO production had no apparent effect on intracellular leishmanicidal activity of polyphenols . Their in vitro TNF-inducing potential producing 50% lysis in murine L929 cells increased in the order of simple phenols and flavanols (34-48 U/ml) < A-type proanthocyanidins (53-80 U/ml) < B-type proanthocyanidins (64-200 U/ml) < hydrolyzable tannins (287-350 U/ml) at the host cell subtoxic concentration of 50 microg/ml . Furthermore, gallic acid and some hydrolyzable tannins showed appreciable IFN-like activities (14-23 U/ml) as reflected by inhibition of the cytopathic effect of encephalomyocarditis virus on fibroblast L 929 cells . The results provide a rational basis for the recorded anti-infectious efficacy of traditionally used herbal medicines containing tannins in vivo, in the light of both only moderate direct antimicrobial activities of distinct polyphenols in vitro and the limited knowledge on their uptake in humans.

Farmaco, 2001 Apr, 56(4), 277 - 83
Some reactions with ketene dithioacetals part I: synthesis of antimicrobial pyrazol; Zaharan MA et al.; Pyrazolo{1,5-a}pyrimidines were synthesized via the reaction of ketene dithioacetals and 5-aminopyrazoles . The antibacterial and antifungal activities of some selected compounds are also reported.

Mol Hum Reprod, 2001 Jul, 7(7), 625 - 32
Cloning and sequencing of SOB3, a human gene coding for a sperm protein homologous to an antimicrobial protein and potentially involved in zona pellucida binding; Hammami-Hamza S et al.; We have previously characterized an 18-19 kDa cationic protein, SOB3, that was detected in the epididymis and localized within the acrosome and on the neck region of human spermatozoa . We suggested that it is involved in secondary sperm binding to the zona pellucida . The present study describes its purification to homogeneity by preparative electrophoresis and non-equilibrium pH gradient electrophoresis . Degenerate primers deduced from microsequencing were used to amplify a specific fragment from human epididymal RNA by reverse transcription-polymerase chain reaction (RT-PCR) . This 164 bp fragment was extended by 5' and 3'-RACE to obtain the 548 bp full length cDNA . The open reading frame encodes a 170 amino acid protein . SOB3 is a single copy gene . It is 98% identical to prepro-FALL39 and 100% identical to CAP18, two human genes which were initially identified by screening a human bone marrow (lambda)gt11 library, and which encode an antimicrobial protein . Northern blots of human tissues revealed a 1 kb transcript in corpus and cauda epididymis only, while RT-PCR showed presence of the mRNA in the three epididymal regions and also in round spermatids . The above results suggest that SOB3 has two roles in sperm protection and fertilization, depending on its dual origin and final sperm localization.

J Am Podiatr Med Assoc, 2001 Jun, 91(6), 288 - 93
Effectiveness of a nonrinse, alcohol-free antiseptic hand wash; Moadab A et al.; This study evaluated the efficacy of a novel surfactant, allantoin, and benzalkonium chloride hand sanitizer using the US Food and Drug Administration's method for testing antiseptic hand washes that podiatric physicians and other health-care personnel use . The alcohol-free product, HandClens, was compared with an alcohol-based product, Purell . Independent researchers from the California College of Podiatric Medicine conducted the study using 40 volunteer students from the class of 2001 . The results show that HandClens outperformed Purell and met the regulatory requirements for a hand sanitizer . Purell failed as an antimicrobial hand wash and was less effective than a control soap used in the study.

J Antimicrob Chemother, 2001 Jul, 48 Suppl 1, 71 - 6
Quality assurance of antimicrobial susceptibility testing by disc diffusion; King A et al.; Quality assurance is essential to ensure the quality of antimicrobial susceptibility tests by diffusion methods . Routine internal quality control testing with a range of control strains is a major part of the quality assurance process, as it facilitates monitoring of the performance of the test . Most standardized methods include tables of acceptable zone size ranges for control strains and, in addition to checking that control zone diameters are within the published ranges, rules or statistical approaches may be applied to indicate deviations from acceptable performance . If control tests indicate unacceptable performance, the source(s) of the error should be investigated and may include problems with media, antimicrobial discs, inoculum and plate reading . Participation in external quality assessment schemes provides an independent assessment of performance although the number of strains distributed in such schemes is limited . Internal quality assessment in which routine tests are repeated with the identity of the organisms blinded is a useful complementary approach to external quality assessment and may detect problem areas not highlighted by other control methods . Education is an important part of the quality assurance process . Knowledge of atypical results for different organism-agent combinations may provide warning of possibly erroneous results, and an understanding of the limitations and sources of error in disc diffusion methods contributes significantly to the recognition, resolution and avoidance of errors.

J Antimicrob Chemother, 2001 Jul, 48 Suppl 1, 17 - 28
Establishing MIC breakpoints and the interpretation of in vitro susceptibility tests; MacGowan AP et al.; The purpose of undertaking susceptibility testing, by whatever method, is to attempt to integrate the susceptibility of a population of potential pathogens with the pharmacokinetics of the antimicrobial and, whenever possible, to review this relationship in the light of clinical experience following therapy in clinical trials . Breakpoints are discriminatory antimicrobial concentrations used in the interpretation of results of susceptibility testing to define isolates as susceptible, intermediate or resistant . Clinical, pharmacological and microbiological considerations are important in setting breakpoints, and the ideal mix of these factors is unknown . Different countries have different approaches to this problem but, by and large, these approaches have much in common . This paper attempts to summarize the philosophy of the British Society for Antimicrobial Chemotherapy (BSAC) Working Party in its approach to setting breakpoints and to update the activities of the Working Party since it initially published breakpoints, approximately 10 years ago . The formula outlined by the BSAC Working Party in 1991 has been used to set the breakpoints presented here . The Working Party accepts that in the light of new knowledge, there is a need to reassess how breakpoints are defined, and this paper also summarizes the future activities of the Working Party.

J Antimicrob Chemother, 2001 Jul, 48 Suppl 1, 5 - 16
Determination of minimum inhibitory concentrations; Andrews JM; Minimum inhibitory concentrations (MICs) are defined as the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation, and minimum bactericidal concentrations (MBCs) as the lowest concentration of antimicrobial that will prevent the growth of an organism after subculture on to antibiotic-free media . MICs are used by diagnostic laboratories mainly to confirm resistance, but most often as a research tool to determine the in vitro activity of new antimicrobials, and data from such studies have been used to determine MIC breakpoints . MBC determinations are undertaken less frequently and their major use has been reserved for isolates from the blood of patients with endocarditis . Standardized methods for determining MICs and MBCs are described in this paper . Like all standardized procedures, the method must be adhered to and may not be adapted by the user . The method gives information on the storage of standard antibiotic powder, preparation of stock antibiotic solutions, media, preparation of inocula, incubation conditions, and reading and interpretation of results . Tables giving expected MIC ranges for control NCTC and ATCC strains are also supplied.

J Antimicrob Chemother, 2001 Jul, 48 Suppl 1, 1 - 4
History and development of antimicrobial susceptibility testing methodology; Wheat PF; Antimicrobial susceptibility testing (AST) is performed daily on bacterial isolates in clinical laboratories . The techniques employed are often taken for granted . This paper traces the history and development of some methods still in common use for routine AST, e.g . disc diffusion and agar dilution . It was quickly recognized by early investigators that there were many variables affecting the results of these tests . Consequently, there was recognition (as early as the late 1950s) that standardization of these techniques was required . This need has led to many organizations producing standardized AST methodologies . Although some disc diffusion techniques that generated results within 4-6 h were described, most relied on 18-24 h incubation before a result was available . The clinical and economic pressures for rapid methods with low labour input led to the development of semi-automated and automated AST methodologies in the 1970s . Until 10 years ago, AST techniques relied on phenotypically testing the bacteria isolated . However, to increase the speed and reliability of resistance testing, the use of a genotypic approach has been advocated . The limitations and benefits of this new approach are discussed.

J Theor Biol, 2001 Jul 21, 211(2), 101 - 13
The antimicrobial properties of melanocytes, melanosomes and melanin and the evolution of black skin; Mackintosh JA; A biological issue that has not been satisfactorily resolved is the role of melanin in skin and other animal tissues . A hypothesis is outlined here to account for the evolution of black skin and the ubiquity of melanin in vertebrate tissues . Evidence is presented that melanization of skin and other tissues forms an important component of the innate immune defense system . A major function of melanocytes, melanosomes and melanin in skin is to inhibit the proliferation of bacterial, fungal and other parasitic infections of the dermis and epidermis . This function can potentially explain (a) the latitudinal gradient in melanization of human skin; (b) the fact that melanocyte and melanization patterns among different parts of the vertebrate body do not reflect exposure to radiation; (c) provide a theoretical framework for recent empirical findings concerning the antimicrobial activity of melanocytes and melanosomes and their regulation by known mediators of inflammatory responses .

J Mol Biol, 2001 Jun 29, 310(1), 195 - 204
Crystal structure of thiamin pyrophosphokinase; Timm DE et al.; Thiamin pyrophosphate (TPP) is a coenzyme derived from vitamin B1 (thiamin) . TPP synthesis in eukaryotes requires thiamin pyrophosphokinase (TPK), which catalyzes the transfer of a pyrophosphate group from ATP to thiamin . TPP is essential for central metabolic processes, including the formation of acetyl CoA from glucose and the Krebs cycle . Deficiencies in human thiamin metabolism result in beriberi and Wernicke encephalopathy . The crystal structure of mouse TPK was determined by multiwavelength anomalous diffraction at 2.4 A resolution, and the structure of TPK complexed with thiamin has been refined at 1.9 A resolution . The TPK polypeptide folds as an alpha/beta-domain and a beta-sandwich domain, which share a central ten-stranded mixed beta-sheet . TPK subunits associate as a dimer, and thiamin is bound in the dimer interface . Despite lacking apparent sequence homology with other proteins, the alpha/beta-domain resembles the Rossman fold and is similar to other kinase structures, including another pyrophosphokinase and a thiamin biosynthetic enzyme . Comparison of mouse and yeast TPK structures reveals differences that could be exploited in developing species-specific inhibitors of potential use as antimicrobial agents .

Pediatr Infect Dis J, 2001 Jun, 20(6), 623 - 7
Successful treatment of Acanthamoeba meningitis with combination oral antimicrobials; Singhal T et al.; Acanthamoeba was implicated as the causative agent of chronic meningitis in three apparently immunocompetent children . Diagnosis was established by cerebrospinal fluid wet mount examination and culture . Two children improved rapidly with combination oral therapy composed of trimethoprim-sulfamethoxazole, rifampin and ketoconazole.

Clin Infect Dis, 2001 Jul 15, 33(2), 171 - 6 Epub 2001 Jun 15.
Treating cardiovascular disease with antimicrobial agents: a survey of knowledge, attitudes, and practices among physicians in the United States; Gimenez-Sanchez F et al.; To assess physicians' knowledge, attitudes, and prescribing behaviors with regard to the association between Chlamydia pneumoniae and cardiovascular disease, we surveyed 750 physicians in Alaska, 1172 in West Virginia, and 569 infectious disease (ID) specialists in a nationwide network during February-May 1999 . Eighty-five percent knew of the association between C . pneumoniae and atherosclerosis, but this awareness was more common among ID specialists and cardiologists than among generalists (96% vs . 77%; P<.001) . Knowledge scores were significantly higher among ID specialists and cardiologists (P<.001) and among physicians who saw relatively more patients who had myocardial infarction and/or were at risk of atherosclerotic disease . Four percent of physicians had treated or recommended treating cardiovascular diseases with antimicrobial agents; this percentage was significantly higher among cardiologists, physicians who empirically treat patients with peptic ulcers with antimicrobial agents, and physicians with a relatively high knowledge score.

J Immunol, 2001 Jul 1, 167(1), 392 - 8
IFN-gamma-independent autocrine cytokine regulatory mechanism in reprogramming of macrophage responses to bacterial lipopolysaccharide; Brewington R et al.; Macrophages are now well recognized to have a critical role in both innate and acquired immunity . The sentinel macrophage function is highly regulated and serves to allow for intrinsic plasticity of the innate immune responses to potential environmental signals . However, the mechanisms underlying the dynamic properties of the cellular arm of innate immunity are poorly understood . Therefore, we have conducted a series of in vitro studies to evaluate the contribution of immunoregulatory cytokines, such as IFN-gamma, IL-10, and IL-12, in modulation of macrophage responses . We found that macrophages from IFN-gamma knockout (IFN-gamma(-/-)) mice exhibit only marginal LPS-induced TNF-alpha, IL-12, and NO responses, all of which can be fully restored in the presence of rIFN-gamma . Pretreatment with substimulatory LPS concentrations led to reprogramming of IFN-gamma(-/-) macrophage responses in a dose-dependent manner that manifested by an increased TNF-alpha and IL-12, but not NO, production upon the subsequent LPS challenge . These reprogramming effects were substantially attenuated and profoundly enhanced in macrophages from IL-12(-/-) and IL-10(-/-) mice, respectively, as compared with those modulated in macrophages from the congenic wild-type mice . LPS-dependent reprogramming was also fully reproduced in macrophages isolated from SCID mice after immunodepletion of NK cells . Our data strongly imply that cytokine (TNF-alpha and IL-12), but not NO, responses in macrophages may, at least in part, be governed by an autocrine IFN-gamma-independent regulatory mechanism reciprocally controlled by IL-10 and IL-12 . This mechanism may serve as an alternative/coherent pathway to the canonical IFN-gamma-dependent induction of antimicrobial and tumoricidal activity in macrophages.

J Immunol, 2001 Jul 1, 167(1), 350 - 6
A distinct pathway of cell-mediated apoptosis initiated by granulysin; Kaspar AA et al.; Granulysin is an antimicrobial and tumoricidal molecule expressed in granules of CTL and NK cells . In this study, we show that granulysin damages cell membranes based upon negative charge, disrupts the transmembrane potential (Deltapsi) in mitochondria, and causes release of cytochrome c . Granulysin-induced apoptosis is blocked in cells overexpressing Bcl-2 . Despite the release of cytochrome c, procaspase 9 is not processed . Nevertheless, activation of caspase 3 is observed in granulysin-treated cells, suggesting that granulysin activates a novel pathway of CTL- and NK cell-mediated death distinct from granzyme- and death receptor-induced apoptosis.

Avian Dis, 2001 Apr-Jun, 45(2), 456 - 60
In vitro susceptibility of avian mycoplasmas to enrofloxacin, sarafloxacin, tylosin, and oxytetracycline; Wang C et al.; In vitro susceptibility of avian Mycoplasma gallisepticum (MG) and Mycoplasma synoviae (MS) to enrofloxacin, sarafloxacin, tylosin, and oxytetracycline was determined by a serial broth dilution method . The minimum inhibitory concentration (MIC) was recognized by a conversion of the pH indicator phenol red in culture media to a yellow color . Each isolate or type strain of mycoplasma was tested in two replicates . The MICs of tylosin, enrofloxacin, sarafloxacin, and oxytetracycline against five isolates and two reference strains of MG (approximately 10(5) colony-forming units {CFU}/ml) were 0.05, 0.14, 0.37, and 1.30 microg/ml, respectively . The MICs of the four antimicrobial agents against six isolates and one reference strain of MS (approximate 10(5) CFU/ml) were 0.13, 1.82, 1.76, and 0.91 microg/ml, respectively . There were no differences (P > 0.05) between tylosin, enrofloxacin, and sarafloxacin against MG, but these three antibiotics were different (P < 0.05) from oxytetracycline . The MIC value of tylosin against MS was different (P < 0.05) from those of sarafloxacin and enrofloxacin, but it was not different (P > 0.05) from that of oxytetracycline.

Am J Med Sci, 2001 Jun, 321(6), 367 - 71
Effect of bone biopsy in guiding antimicrobial therapy for osteomyelitis complicating open wounds; Khatri G et al.; BACKGROUND: Osteomyelitis associated with infected overlying wounds represents a difficult diagnostic and therapeutic problem; bone biopsies can be done during debridement of the overlying wounds, but it is unclear how often the results of these bone cultures actually affect subsequent antibiotic decisions . The present study was undertaken to evaluate the usefulness of bone biopsies in guiding antibiotic therapy for this type of osteomyelitis . METHODS: Culture results of 44 bone biopsies taken during surgical debridement in 41 patients over the period from June 1994 to August 1998 were compared with those from the overlying wounds to determine whether the data affected the subsequent choice of antibiotics . The study design was that of a retrospective chart review in which the standard operative and microbiological procedures in place at the Milwaukee Veterans Affairs Medical Center were used . RESULTS: Sixty-one wound and 55 bone isolates were obtained during this study . Thirty-one isolates were found in bone, but not the overlying wound; diphtheroids were the most common organism obtained in this fashion . Correlation between wound and bone isolates was generally poor . Antibiotics were subsequently changed in 20 of the 44 cases after results of the bone biopsy became known, with the bone isolates already being covered in 10 cases and the bone biopsy results ignored in 14 cases . CONCLUSION: Because bone biopsy results seem to aid in tailoring antibiotic therapy in almost half the cases when bone is sampled during wound debridement surgery, this technique may be very helpful in certain cases and should be regularly undertaken when these procedures are carried out.

Eur J Clin Pharmacol, 2001 May, 57(2), 177 - 80
The therapeutic course as a measure complementary to defined daily doses when studying exposure to antibacterial agents; Resi D et al.; OBJECTIVE: The defined daily dose (DDD) method may not provide accurate information about exposure to antibacterial agents, owing to their short-term use and the consequently high turnover of subjects . This study was addressed to evaluate whether the number of "therapeutic courses" could offer additional information . METHODS: Prescription data of antibacterial agents (ATC J01) in Ravenna, Italy (350,000 inhabitants), were studied in 1998 . All the prescriptions issued within 10 days were considered as belonging to one therapeutic course (TC) . The following measures were compared: DDD/1000 inhabitants/year, number of exposed subjects/1000 inhabitants/year and number of TC/1000 inhabitants/year . In order to compare the number of 10-day TCs with the number of DDDs, the latter was divided by 10 (DDD10) . The intensity of drug treatment was also evaluated as the average number of DDDs per TC (therapeutic intensity) . RESULTS: Sixty-one percent of the subjects received only one prescription in 1998 . Among the second prescriptions, 69% were issued after a time interval greater than 21 days . The overall prevalence of use was 329 per 1000 inhabitants, the TCs were 525 per 1000 inhabitants and DDD10/1000 inhabitants/year were 470 . The therapeutic intensity varied with the age classes (being lowest in the elderly) and with the individual antibiotics used . Two or more antibacterials were used within the same TC in 7% of the cases . CONCLUSION: The measures considered in this study provided different estimates of exposure to antimicrobial agents . The combined analysis of DDDs and TCs may offer a more reliable information about exposure to antimicrobial agents.

J Biomed Mater Res, 2001 Oct, 57(1), 1 - 7
Effect of plasma and matrix proteins on defensin-induced impairment of phagocytic killing by adherent neutrophils; Kaplan SS et al.; Infection is too often associated with prosthetic devices . Increased susceptibility to infection at these surgical sites appears to be associated with defective local phagocytic killing . The mechanisms for neutrophil down-regulation, however, continue to be obscure . We have recently demonstrated that cytotoxic substances are released from granulocytes associated with materials . One group of releasants, the cationic human neutrophil peptide(s) (also called defensins) not only impairs the antimicrobial capacity of the granulocyte that releases it but also impairs bystander phagocytes . Because plasma or matrix proteins soon become associated with implants, we investigated the interactive effect of adding these proteins, singly and in combination, on the microbicidal effect of bystander cells . Some plasma/matrix proteins (whole plasma, albumin, fibrinogen, and fibronectin) strongly interfered with the anti-microbicidal effects generated by neutrophil-polystyrene interaction . Other proteins (vitronectin and laminin) were without effect . These results suggest that protein composition at the prosthetic implant site could have a significant effect on infectivity, depending on whether neutrophils releasants were attenuated . In the absence of attenuation, the local environment would be hostile to host defenses, permitting bacterial survival and proliferation.

AIDS, 2001 Jun 15, 15(9), 1143 - 8
Initiating co-trimoxazole prophylaxis in HIV-infected patients in Africa: an evaluation of the provisional WHO/UNAIDS recommendations; Badri M et al.; OBJECTIVE: To evaluate the proposed WHO/UNAIDS criteria for initiating co-trimoxazole prophylaxis in adult HIV-infected patients in Africa {WHO clinical stages 2--4 or CD4 count < 500 x 10(6) /l or total lymphocyte count (TLC) equivalent} . DESIGN: Observational cohort study of 5-year follow-up . SETTING: Adult HIV clinics, University of Cape Town, South Africa . METHODS: Effect of prophylactic low dose co-trimoxazole (480 mg per day or 960 mg three times per week) on survival and morbidity was assessed in patients stratified by WHO clinical stage, CD4 T-lymphocyte count or TLC . Patients receiving antiretroviral therapy were excluded . RESULTS: Co-trimoxazole reduced mortality {adjusted hazard ratio (AHR), 0.56; 95% confidence interval (CI), 0.33--0.85; P > 0.001} and the incidence of severe HIV-related illnesses (AHR, 0.52; 95% CI, 0.38--0.68; P < 0.001) in patients with evidence of advanced immune suppression on clinical (WHO stages 3 and 4) or laboratory assessment (TLC < 1250 x 10(6)/l or CD4 count < 200 x 10(6)/l) . No significant evidence of efficacy was found in patients with WHO stage 2 or CD4 count 200--500 x 10(6)/l/TLC 1250--2000 x 10(6)/l . If we had applied the WHO/UNAIDS recommendations 88.3% of our patients would have received co-trimoxazole prophylaxis at their initial clinic visit . CONCLUSION: Co-trimoxazole in HIV-infected adults from an area in which Pneumocystis carinii pneumonia is uncommon demonstrated a survival benefit consistent with previous randomized trials . Further studies are needed to assess the optimal time of commencement of prophylaxis, as widespread co-trimoxazole use will lead to increasing antimicrobial resistance to other major pathogens in Africa.

Proc Natl Acad Sci U S A, 2001 Jul 3, 98(14), 8139 - 44 Epub 2001 Jun 19.
Hydroperoxide lyase depletion in transgenic potato plants leads to an increase in aphid performance; Vancanneyt G et al.; Hydroperoxide lyases (HPLs) catalyze the cleavage of fatty acid hydroperoxides to aldehydes and oxoacids . These volatile aldehydes play a major role in forming the aroma of many plant fruits and flowers . In addition, they have antimicrobial activity in vitro and thus are thought to be involved in the plant defense response against pest and pathogen attack . An HPL activity present in potato leaves has been characterized and shown to cleave specifically 13-hydroperoxides of both linoleic and linolenic acids to yield hexanal and 3-hexenal, respectively, and 12-oxo-dodecenoic acid . A cDNA encoding this HPL has been isolated and used to monitor gene expression in healthy and mechanically damaged potato plants . HPL gene expression is subject to developmental control, being high in young leaves and attenuated in older ones, and it is induced weakly by wounding . HPL enzymatic activity, nevertheless, remains constant in leaves of different ages and also after wounding, suggesting that posttranscriptional mechanisms may regulate its activity levels . Antisense-mediated HPL depletion in transgenic potato plants has identified this enzyme as a major route of 13-fatty acid hydroperoxide degradation in the leaves . Although these transgenic plants have highly reduced levels of both hexanal and 3-hexenal, they show no phenotypic differences compared with wild-type ones, particularly in regard to the expression of wound-induced genes . However, aphids feeding on the HPL-depleted plants display approximately a two-fold increase in fecundity above those feeding on nontransformed plants, consistent with the hypothesis that HPL-derived products have a negative impact on aphid performance . Thus, HPL-catalyzed production of C6 aldehydes may be a key step of a built-in resistance mechanism of plants against some sucking insect pests.

Int J Tuberc Lung Dis, 2001 Jun, 5(6), 539 - 45
The relationship between the in vitro drug susceptibility of opportunist mycobacteria and their in vivo response to treatment; Heginbothom ML; SETTING: It is generally accepted that qualitative drug susceptibility tests established and validated for Mycobacterium tuberculosis are not applicable to opportunist (non-tuberculous) mycobacteria . Previous studies have shown that in vitro antimicrobial susceptibilities for opportunist mycobacteria, performed by the method of modal resistance (MR), correlate poorly with clinical response . Minimum inhibitory concentration (MIC) determination may provide better correlation with predicted clinical response than the conventional MR results . OBJECTIVE: To determine the relationship between quantitative in vitro sensitivity results for opportunist mycobacteria and their in vivo response to treatment . DESIGN: MICs were performed radiometrically with the Bactec TB-460 system; 35 M . avium complex isolates, 29 isolates of M . malmoense and 16 isolates of M . xenopi were tested . RESULTS: Susceptibility results were analysed in comparison with therapeutic outcome by Fisher's exact probability test . Only one significant association was found; in vitro resistance to ethambutol correlated with treatment failure for M . malmoense infections (P = 0.027) . There were no other significant correlations between in vitro results and treatment outcome . CONCLUSION: Prediction of treatment outcome from in vitro susceptibility tests continues to be a problem in infections with opportunist mycobacteria.

J Rheumatol, 2001 Jun, 28(6), 1405 - 6
Malignant hyperthermia susceptibility revealed by myalgia and rhabdomyolysis during fluoroquinolone treatment; Guis S et al.; Fluoroquinolones cause myalgia, but this complication is not clearly documented . We describe a patient who developed myalgia and rhabdomyolysis during fluoroquinolone treatment . The patient was a 33-year-old man treated with norfloxacin for common cystitis . He complained of general muscular fatigue, tendon disorders, and articular pain during treatment . When the antimicrobial agent was stopped, symptoms decreased, with persistence of slight myalgia for 10 days . Rhabdomyolysis was detected . Six months later, investigation by 31P magnetic resonance spectroscopy revealed an oxidative disorder and an abnormal abundance of phosphomonoesters . In vitro contracture tests led to a diagnosis of malignant hyperthermia susceptibility . Our case shows that for any subject presenting myalgia with rhabdomyolysis triggered by fluoroquinolone treatment, the presence of a latent myopathy should be investigated.

Ann Pharmacother, 2001 Jun, 35(6), 745 - 54
Role of therapeutic drug monitoring for protease inhibitors; John L et al.; OBJECTIVE: To review the role of therapeutic drug monitoring (TDM) for protease inhibitors in the treatment of HIV infection . DATA SOURCES: Primary articles were identified using MEDLINE (1966-October 2000), EMBASE (1987-October 2000), AIDSLINE (1980-October 2000), Current Contents, PubMed, and Medscape . Further articles were identified from bibliographic review of primary articles and review papers . Abstracts presented at the World AIDS Conference, Interscience Conference on Antimicrobial Agents and Chemotherapy, and Conference on Retroviruses and Opportunistic Infections were also identified from 1997 to 2000 . STUDY SELECTION AND DATA EXTRACTION: All English-language, prospective clinical trials, as well as selected retrospective studies and case series, pertaining to therapeutic drug monitoring of protease inhibitors were included . DATA SYNTHESIS: A number of clinical studies have found a good relationship between concentration and pharmacologic response and/or toxicity as well as wide interpatient variability in the pharmacokinetics of protease inhibitors . There also is some preliminary evidence of the usefulness of plasma drug concentrations to guide dosage adjustments of protease inhibitors in patients with liver dysfunction . Furthermore, there is preliminary evidence of a relationship between drug concentrations and resistance . CONCLUSIONS: A number of clinical studies support the usefulness of TDM of protease inhibitors . However, before TDM can be of the most value, further evaluation requires simplified and standardized assays to be performed routinely by clinical laboratories; determination of the appropriate target concentration and therapeutic range, as well as the best predictor of pharmacologic response; and refined interpretation of plasma drug concentrations . Randomized, controlled clinical trials of patient outcomes are needed to assess the clinical utility of TDM for protease inhibitors.

Cornea, 2001 Jul, 20(5), 534 - 5
Aspergillus fumigatus keratitis with wreath pattern infiltrates; Sridhar MS et al.; PURPOSE: To report a case of Aspergillus fumigatus keratitis with clinical features simulating Nocardia keratitis and to highlight the utility of microbiologic investigation in the successful management of infectious keratitis . METHOD: Case report . RESULTS: A 62-year-old man presented with complaints of pain, redness, and watering of 10 days' duration in his right eye . Direct microscopic observation of smears of corneal scrapings revealed a fungal etiology . The patient was treated with 5% natamycin eye drops and 1% atropine sulphate eye drops and was advised to visit the hospital for observation . During his visit to the hospital on day 10 after medication, the eye demonstrated a wreath pattern corneal infiltrate that simulated Nocardia keratitis . The fungus grown from culture of corneal scraping was identified as A . fumigatus . CONCLUSION: This report highlights the significance of subjecting corneal scrapings from suspected cases of infectious keratitis to microbiologic evaluation and emphasizes the fact that a complete microbiologic work-up helps in establishing a definitive etiologic diagnosis and initiating specific antimicrobial therapy.

J Microbiol Methods, 2001 Aug, 46(2), 131 - 9
Detection of Escherichia coli O157:H7 by multiplex PCR and their characterization by plasmid profiling, antimicrobial resistance, RAPD and PFGE analyses; Radu S et al.; Twenty-five and three strains of Escherichia coli O157:H7 were identified from 25 tenderloin beef and three chicken meat burger samples, respectively . The bacteria were recovered using the immunomagnetic separation procedure followed by selective plating on sorbitol MacConkey agar and were identified as E . coli serotype O157:H7 with three primer pairs that amplified fragments of the SLT-I, SLT-II and H7 genes in PCR assays . Susceptibility testing to 14 antibiotics showed that all were resistant to two or more antibiotics tested . Although all 28 strains contained plasmid, there was very little variation in the plasmid sizes observed . The most common plasmid of 60 MDa was detected in all strains . We used DNA fingerprinting by randomly amplified polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) to compare the 28 E . coli O157:H7 strains . At a similarity level of 90%, the results of PFGE after restriction with XbaI separated the E . coli O157:H7 strains into 28 single isolates, whereas RAPD using a single 10-mer oligonucleotides separated the E . coli O157:H7 strains into two clusters and 22 single isolates . These typing methods should aid in the epidemiological clarification of the E . coli O157:H7 in the study area.

Indian J Pediatr, 2001 Apr, 68 Suppl 2, S39 - 49
Management of community acquired respiratory infections; Gupta BD et al.; Respiratory tract infections (RTIs) are the most common diagnosis in children visiting outpatient departments in both developing and developed countries . The impact of these infections is enormous in terms of total morbidity and mortality . Management of these infections requires a meticulous evaluation and a comprehensive but rational use of supportive, symptomatic and specific therapy . Antibiotics are widely prescribed for the treatment of community acquired respiratory infections to compensate uncertainties of diagnosis and prognosis; unnecessary anti-microbial drug therapy is expensive and resistance by respiratory pathogens is increasing at an exponential rate at a time when new anti-viral as well as anti-bacterial agents are being introduced into the therapeutic armamentarium . Major dilemmas persist regarding symptomatic therapy and the indications of antimicrobial agents . A comprehensive but brief review along with latest protocols and advancements is the management of community acquired respiratory infections in children in cited.

Eur J Med Res, 2001 May 29, 6(5), 215 - 8
Human natriuretic peptides exhibit antimicrobial activity; Krause A et al.; Here we describe a novel function for members of the well-characterized human natriuretic peptide family . Human "brain-type natriuretic peptide" (hBNP-32) as well as other members of this peptide class are antimicrobially active against Gram-positive and Gram-negative bacteria and yeast in a dose-dependent manner . This activity of natriuretic peptides is comparable to that of known antimicrobial peptides such as casocidins or magainins.

Chem Biol, 2001 Jun, 8(6), 569 - 81
Biosynthesis of the orthosomycin antibiotic avilamycin A: deductions from the molecular analysis of the avi biosynthetic gene cluster of Streptomyces viridochromogenes Tü57 and production of new antibiotics; Weitnauer G et al.; Background: Streptomyces viridochromogenes Tu57 is the producer of avilamycin A . The antibiotic consists of a heptasaccharide side chain and a polyketide-derived dichloroisoeverninic acid as aglycone . Molecular cloning and characterization of the genes governing the avilamycin A biosynthesis is of major interest as this information might set the direction for the development of new antimicrobial agents.Results: A 60-kb section of the S . viridochromogenes Tu57 chromosome containing genes involved in avilamycin biosynthesis was sequenced . Analysis of the DNA sequence revealed 54 open reading frames . Based on the putative function of the gene products a model for avilamycin biosynthesis is proposed . Inactivation of aviG4 and aviH, encoding a methyltransferase and a halogenase, respectively, prevented the mutant strains from producing the complete dichloroisoeverninic acid moiety resulting in the accumulation of new antibiotics named gavibamycins.Conclusions: The avilamycin A biosynthetic gene cluster represents an interesting system to study the formation and attachment of unusual deoxysugars . Several enzymes putatively responsible for specific steps of this pathway could be assigned . Two genes encoding enzymes involved in post-PKS tailoring reactions were deleted allowing the production of new analogues of avilamycin A.

Chem Biol, 2001 Jun, 8(6), 547 - 55
Construction of desosamine containing polyketide libraries using a glycosyltransferase with broad substrate specificity; Tang L et al.; BACKGROUND: Combinatorial biosynthesis techniques using polyketide synthases (PKSs) in heterologous host organisms have enabled the production of macrolide aglycone libraries in which many positions of the macrolactone ring have been manipulated . However, the deoxysugar moieties of macrolides, absent in previous libraries, play a critical role in contributing to the antimicrobial properties exhibited by compounds such as erythromycin . Since the glycosidic components of polyketides dramatically alter their molecular binding properties, it would be useful to develop general expression hosts and vectors for synthesis and attachment of deoxysugars to expand the nature and size of such polyketide libraries . RESULTS: A set of nine deoxysugar biosynthetic and auxiliary genes from the picromycin/methymycin (pik) cluster was integrated in the chromosome of Streptomyces lividans to create a host which synthesizes TDP-D-desosamine . The pik desosaminyl transferase was also included so that when the strain was transformed with a previously constructed library of expression plasmids encoding genetically modified PKSs that produce different macrolactones, the resulting strains produced desosaminylated derivatives . Although conversion of the macrolactones was generally low, bioassays revealed that, unlike their aglycone precursors, these novel macrolides possessed antibiotic activity . CONCLUSIONS: Based on the structural differences among the compounds that were glycosylated it appears that the desosaminyl transferase from the pik gene cluster is quite tolerant of changes in the macrolactone substrate . Since others have demonstrated tolerance towards modifications in the sugar substituent, one can imagine employing this approach to alter both polyketide and deoxysugar pathways to produce 'unnatural' natural product libraries.

Cochrane Database Syst Rev . 2001;(2):CD001815.
Erythromycin for feeding intolerance in preterm infants; Ng E et al.; BACKGROUND: Functional immaturity of gastrointestinal motility predisposes preterm infants to feeding intolerance . Motilin, a gastrointestinal peptide, stimulates propagative contractile activity during phase III of the migratory motor complex in the interdigestive state . Erythromycin (EM) is a motilin agonist with prokinetic effect at low doses (1-3mg/kg) . OBJECTIVES: To evaluate the effectiveness of EM in promoting gastrointestinal motility in preterm infants with feeding intolerance and assess clinically significant adverse effects associated with its use . SEARCH STRATEGY: Systematic literature search in accordance with the Cochrane Neonatal Collaborative Review Group search strategy . Randomized and quasi-randomized controlled trials of EM use, at any dose, in preterm infants to promote gastrointestinal motility were identified by searching MEDLINE, EMBASE, CINAHL, the Cochrane Library, reference lists of published studies, personal files, and abstracts published in Pediatric Research . SELECTION CRITERIA: Randomized controlled trials of oral or intravenous EM use at dose range of 3 to 12 mg/kg/day in preterm infants less than or equal to 36 weeks gestational age with feeding tolerance were included in this review . DATA COLLECTION AND ANALYSIS: Data regarding the primary clinical outcome of days to achieve full enteral feeding were compared among studies . Data on secondary outcomes including adverse effects associated with the use of EM (diarrhea, nosocomial infections, cardiac arrhythmias, or theophylline toxicity), duration of parenteral nutrition, weight gain, incidence of necrotizing enterocolitis (NEC), hypertrophic pyloric stenosis, and length of hospital stay were assessed . MAIN RESULTS: Two randomized controlled studies of EM use in preterm infants for improving gastrointestinal motility were identified . Since both studies involved preterm infants treated with EM at dose >12mg/kg/day at commencement of feeding, they did not meet inclusion criteria defined a priori for this review . There was no statistically significant difference in the incidence of NEC (RR 0.59, 95%CI 0.11, 3.01; RD -0.021, 95%CI -0.087, 0.045) . No statistically significant difference was noted in days to achieve full enteral feeds, length of hospital stay, and adverse events between groups . REVIEWER'S CONCLUSIONS: EM at antimicrobial doses may not be effective in preterm infants with feeding intolerance . Further studies are needed to determine whether EM in lower doses is effective as a prokinetic agent in such infants.

Cochrane Database Syst Rev . 2001;(2):CD001439.
Antibiotics versus placebo for prevention of postoperative infection after appendicectomy; Andersen BR et al.; BACKGROUND: Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention . The cause of appendicitis is unclear and the mechanism of pathogenesis continues to be debated . Despite improved asepsis and surgical techniques, postoperative complications, such as wound infection and intraabdominal abscess, still account for a significant morbidity . Several studies implicate that postoperative infections are reduced by administration of antimicrobial regimes . OBJECTIVES: The objective of this review is to compare the use of antibiotics with placebo or no treatment in patients undergoing appendectomy . Will these patients benefit from antimicrobial prophylaxis? The outcomes are described according to the nature of the appendix, as either simple appendicitis (including the non-infectious stage) and complicated appendicitis . This review do not attempt to compare the effect of different regimens, a clinical question that is addressed in another review undertaken by this Group (CCCG) . SEARCH STRATEGY: We searched The Cochrane Controlled Trials Register (Cochrane Library 2000 issue 4), Medline (January 1966 to September 2000), Embase and the Cochrane Colorectal Cancer Group specialised register (September 2000) . In addition we manually searched the reference lists of the primary identified trials . SELECTION CRITERIA: Randomised Controlled Trials (RCT) and Controlled Clinical Trials (CCT) in which any antibiotic regime were compared to placebo in patients suspected of having appendicitis undergoing appendectomy were evaluated . Both studies on children and adults were reviewed . The outcome measures of the studies were either wound infection, intraabdominal abscess, length of stay in hospital or mortality . DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed, recorded and cross-checked by to reviewers . MAIN RESULTS: Forty-four studies including 9298 patients were included in this review . The overall result is that use of antibiotics is superior to placebo for the outcome wound infection and intraabdominal abscess, with no apparent difference in the nature of the removed appendix . Studies exclusively on children and studies examining topical application reported results in favour to the above although the results were not significant . REVIEWER'S CONCLUSIONS: Antibiotic prophylaxis is effective in the prevention of postoperative complications in appendectomised patients, whether the administration are given pre-, per- and post-operatively and could be considered for routine in emergency appendectomies.

Org Lett, 2001 Jun 14, 3(12), 1845 - 8
A novel {60}fullerene amino acid for use in solid-phase peptide synthesis; Pellarini F et al.; {see structure} . A fullerene derivative containing a free amino group has been condensed with N-Fmoc-L-glutamic acid alpha-tert-butyl ester to give a C60-functionalized amino acid . The carboxylic end of this amino acid has been deprotected in acidic conditions, and the resulting acid has been used for solid-phase peptide synthesis . The final peptide, cleaved from the resin, was very soluble in water solutions and showed antimicrobial activity against two representative bacteria.

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