Chest, 1999 Mar, 115(3 Suppl), 24S - 27S New intervention strategies for reducing antibiotic resistance; Yates RR; Rising antibiotic resistance rates among bacterial pathogens have resulted in increased morbidity and mortality from nosocomial infections . Widespread use of certain antibiotics, particularly third-generation cephalosporins, has been shown to foster development of generalized beta-lactam resistance in previously susceptible bacterial populations . Reduction in the use of these agents (as well as imipenem and vancomycin) and concomitant increases in the use of extended-spectrum penicillins and combination therapy with aminoglycosides have been shown to restore bacterial susceptibility . Studies have shown that education-based methods, as opposed to coercive measures, are effective in changing the prescribing habits of physicians . Cooperative interaction among infectious-disease physicians, clinical pharmacists, microbiology-laboratory personnel, and infection-control specialists is essential to provide useful suggestions regarding antibiotic choice and dosing to the prescribing physician in real time . Several hospitals have implemented antimicrobial resistance management programs based on these findings . The results of these programs validate the use of a multidisciplinary, education-based, antibiotic-resistance management approach. Chest, 1999 Mar, 115(3 Suppl), 19S - 23S Pharmacodynamic principles of antimicrobial therapy in the prevention of resistance; Burgess DS; Pharmacodynamic properties can be used to divide antibiotics into two major classes based on their mechanism of bactericidal action: (1) concentration-dependent drugs, such as aminoglycosides and fluoroquinolones, and (2) concentration-independent drugs, including the beta-lactams . Antibiotics also differ in the postantibiotic effect (PAE) that they exert . In general, concentration-dependent drugs have a more prolonged PAE than concentration-independent drugs, particularly against Gram-negative pathogens . Pharmacodynamic classifications have important implications for the planning of drug regimens . For concentration-dependent drugs, peak concentration to minimal inhibitory concentration (MIC) ratios of approximately 10 are associated with clinical success . Therefore, high drug levels should be the goal of therapy . This is best achieved by high doses taken once daily . This approach, however, is not feasible for the fluoroquinolones owing to dose-limiting CNS toxicity . Concentration-independent agents are most effective when the duration of serum concentrations is higher than the pathogen's MIC (time >MIC) for a significant proportion of the dosing interval . Frequent dosing or continuous infusions can increase the time >MIC . Concentrations of antibiotics that are sublethal can permit the emergence of resistant pathogens . Optimization of antibiotic regimens on the basis of pharmacodynamic principles could thus significantly diminish the emergence of antibiotic resistance. Tijdschr Diergeneeskd, 1999 Mar 1, 124(5), 142 - 4 {Health council report: "Antimicrobial growth promoters"}; Goettsch W et al.; The Health Council of the Netherlands has issued a report on the risk of development of resistance among bacteria as result of the use of antibiotics as growth promotors in livestock farming . The committee appointed by the Health Council conclude that the use of antimicrobial growth promotors contributes to the problem of resistance among human pathogens . The conclusions are based on evidence regarding the development of resistance in livestock as the result of the use of antimicrobial growth promotors, the possibility of colonisation/infection of humans with resistant bacteria from the intestinal flora of productive livestock, and the transfer of resistance genes from livestock bacteria to human pathogenic microorganisms . Effective measures for the limitation of the public health risk should focus on termination of the use of antimicrobial growth promotors that confer resistance to (related) antibiotics currently used (or which will be available) to treat patients suffering from bacterial infections . In addition, the committee advised ending the use of antimicrobial growth promotors in 3 years. Biochim Biophys Acta, 1999 Mar 19, 1430(2), 262 - 8 A new antifungal peptide from the seeds of Phytolacca americana: characterization, amino acid sequence and cDNA cloning; Shao F et al.; An antifungal peptide from seeds of Phytolacca americana, designated PAFP-s, has been isolated . The peptide is highly basic and consists of 38 residues with three disulfide bridges . Its molecular mass of 3929.0 was determined by mass spectrometry . The complete amino acid sequence was obtained from automated Edman degradation, and cDNA cloning was successfully performed by 3'-RACE . The deduced amino acid sequence of a partial cDNA corresponded to the amino acid sequence from chemical sequencing . PAFP-s exhibited a broad spectrum of antifungal activity, and its activities differed among various fungi . PAFP-s displayed no inhibitory activity towards Escherichia coli . PAFP-s shows significant sequence similarities and the same cysteine motif with Mj-AMPs, antimicrobial peptides from seeds of Mirabilis jalapa belonging to the knottin-type antimicrobial peptide. Biochim Biophys Acta, 1999 Mar 4, 1417(2), 211 - 23 Differential scanning calorimetric study of the effect of the antimicrobial peptide gramicidin S on the thermotropic phase behavior of phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol lipid bilayer membranes; Prenner EJ et al.; We have studied the effects of the antimicrobial peptide gramicidin S (GS) on the thermotropic phase behavior of large multilamellar vesicles of dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylethanolamine (DMPE) and dimyristoyl phosphatidylglycerol (DMPG) by high-sensitivity differential scanning calorimetry . We find that the effect of GS on the lamellar gel to liquid-crystalline phase transition of these phospholipids varies markedly with the structure and charge of their polar headgroups . Specifically, the presence of even large quantities of GS has essentially no effect on the main phase transition of zwitterionic DMPE vesicles, even after repeating cycling through the phase transition, unless these vesicles are exposed to high temperatures, after which a small reduction in the temperature, enthalpy and cooperativity of the gel to liquid-crystalline phase transitions is observed . Similarly, even large amounts of GS produce similar modest decreases in the temperature, enthalpy and cooperativity of the main phase transition of DMPC vesicles, although the pretransition is abolished at low peptide concentrations . However, exposure to high temperatures is not required for these effects of GS on DMPC bilayers to be manifested . In contrast, GS has a much greater effect on the thermotropic phase behavior of anionic DMPG vesicles, substantially reducing the temperature, enthalpy and cooperativity of the main phase transition at higher peptide concentrations, and abolishing the pretransition at lower peptide concentrations as compared to DMPC . Moreover, the relatively larger effects of GS on the thermotropic phase behavior of DMPG vesicles are also manifest without cycling through the phase transition or exposure to high temperatures . Furthermore, the addition of GS to DMPG vesicles protects the phospholipid molecules from the chemical hydrolysis induced by their repeated exposure to high temperatures . These results indicate that GS interacts more strongly with anionic than with zwitterionic phospholipid bilayers, probably because of the more favorable net attractive electrostatic interactions between the positively charged peptide and the negatively charged polar headgroup in such systems . Moreover, at comparable reduced temperatures, GS appears to interact more strongly with zwitterionic DMPC than with zwitterionic DMPE bilayers, probably because of the more fluid character of the former system . In addition, the general effects of GS on the thermotropic phase behavior of zwitterionic and anionic phospholipids suggest that it is located at the polar/apolar interface of liquid-crystalline bilayers, where it interacts primarily with the polar headgroup and glycerol-backbone regions of the phospholipid molecules and only secondarily with the lipid hydrocarbon chains . Finally, the considerable lipid specificity of GS interactions with phospholipid bilayers may prove useful in the design of peptide analogs with stronger interactions with microbial as opposed to eucaryotic membrane lipids. Emerg Infect Dis, 1999 Jan-Feb, 5(1), 18 - 27 Socioeconomic and behavioral factors leading to acquired bacterial resistance to antibiotics in developing countries; Okeke IN et al.; In developing countries, acquired bacterial resistance to antimicrobial agents is common in isolates from healthy persons and from persons with community-acquired infections . Complex socioeconomic and behavioral factors associated with antibiotic resistance, particularly regarding diarrheal and respiratory pathogens, in developing tropical countries, include misuse of antibiotics by health professionals, unskilled practitioners, and laypersons; poor drug quality; unhygienic conditions accounting for spread of resistant bacteria; and inadequate surveillance. J Infect Dis, 1999 Mar, 179 Suppl 2, S360 - 5 Endocarditis at the millennium; Hoesley CJ et al.; The members of the Interplanetary Society (Pus Club) have made significant contributions to the understanding of the pathogenesis of infective endocarditis (IE) . Although the incidence of IE has essentially remained unchanged, the spectrum and characteristics of patients potentially affected by this disorder are expanding . Moreover, in addition to the typical microorganisms implicated in IE, there are increasing reports of new or atypical pathogens causing IE, including those that are resistant to standard antibiotic therapy . The infectious diseases community is challenged to continue to provide effective antimicrobial regimens for IE and to further develop diagnostic and surgical strategies to identify and treat patients with this disorder . New information is available regarding the demographics, diagnostic methods, and therapeutic options for the management of IE. J Infect Dis, 1999 Mar, 179 Suppl 2, S342 - 52 Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients; Root RK et al.; Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhance the antimicrobial functions of mature neutrophils . G-CSF differs from GM-CSF in its specificity of action on developing and mature neutrophils, its effects on neutrophil kinetics, and its toxicity profile . The toxicity profile of recombinant (r) GM-CSF is consistent with priming of macrophages for increased formation and release of inflammatory cytokines, whereas rG-CSF induces production of antiinflammatory factors, such as interleukin-1 receptor antagonist and soluble tumor necrosis factor receptors, and is protective against endotoxin- and sepsis-induced organ injury . The low toxicity of rG-CSF, results of animal models of infection, and extensive experience with neutropenic subjects have promoted clinical studies in nonneutropenic subjects, which indicate that rG-CSF may be beneficial as adjunctive therapy for treatment of serious bacterial and opportunistic fungal infections in nonneutropenic patients, including those with alterations in neutrophil function. J Infect Dis, 1999 Mar, 179 Suppl 2, S309 - 17 Activation of the neutrophil respiratory burst oxidase; Clark RA; The neutrophil respiratory burst oxidase is a multicomponent activatable enzyme comprising one of the major phagocyte antimicrobial systems . In the genetic disorder chronic granulomatous disease, absent oxidase function is associated with recurrent, severe, and often life-threatening infections . The components of the oxidase system include both membrane-bound and soluble cytosolic proteins . A primary feature of stimulus-dependent activation is the translocation of a complex of cytosolic factors to the membrane, where they associate with a flavocytochrome enzyme . Interactions among the various oxidase components occur through a number of specific regions, including SH3 domains and proline-rich motifs . The fully assembled complex functions as an electron transport system, moving electrons from cytosolic NADPH to molecular oxygen to form superoxide, which, along with subsequent reactive products, exerts microbicidal and cytotoxic activities. CMAJ, 1999 Feb 23, 160(4), 493 - 9 Candidemia at selected Canadian sites: results from the Fungal Disease Registry, 1992-1994 . Fungal Disease Registry of the Canadian Infectious Disease Society; Yamamura DL et al.; BACKGROUND: Candida species are important bloodstream pathogens that are being isolated with increasing frequency . Despite the availability of effective antifungal therapy, the mortality rate associated with Candida infection remains high . With the objective of describing the epidemiology of candidemia, the Canadian Infectious Disease Society conducted a study of candidemia in Canada . METHODS: Fourteen medical centres across Canada identified all patients with candidemia from March 1992 to February 1994 through blood culture surveillance for Candida spp . Patient-related data for invasive fungal infection were compiled retrospectively by chart review using a standardized data-recording form developed for the Fungal Disease Registry of the Canadian Infectious Disease Society . Cases of Candidemia were studied in relation to underlying medical conditions, predisposing factors, concurrent infection, antimicrobial agents, antifungal treatment and deaths . RESULTS: In total, 415 cases of candidemia were identified, 48 (11.6%) in children and 367 (88.4%) in adults . The causative pathogens were C . albicans in 286 cases (68.9%), C . parapsilosis in 43 (10.4%), C . glabrata in 34 (8.2%), C . tropicalis in 27 (6.5%) and other Candida species in 18 (4.3%); polymicrobial candidemia occurred in 7 cases (1.7%) . The overall mortality rate was 46%, and the rate of deaths clinically related to candidemia was 19% . However, only 13 (27%) of the children died . A univariate analysis indicated that significant risk factors for death were age greater than 60 years, therapy for concomitant bacterial infection, stay in an intensive care unit, concurrent malignant disease, cytotoxic chemotherapy and granulocytopenia, although only age and stay in an intensive care unit emerged as significant risk factors in the multivariate analysis . After adjustment for other predictors of death, only infection with C . parapsilosis was associated with a lower mortality rate than infection with C . albicans . Treatment was given in 352 (84.8%) of cases . Amphotericin B was the preferred agent in 244 cases (69.3% of those treated); fluconazole was used in 101 cases (28.7%) and ketoconazole in 5 cases (1.4%) . INTERPRETATION: Candidemia in Canada is caused predominantly by C . albicans . The mortality rate associated with candidemia is high, but it varies with the species of Candida and is lower in children than in adults . Age greater than 60 years and stay in an intensive care unit were the most significant risk factors for overall mortality. Chest Surg Clin N Am, 1999 Feb, 9(1), 39 - 61, vii-viii New directions in antimicrobial therapy; Greene JN et al.; The virulent microorganisms that we try to contain with new antimicrobial agents quickly find the gap in our defenses and exploit it . Resistance to all available antibiotics at the same time, however, rarely occurs . The authors report the most current antimicrobials used as monotherapy or in combination to successfully treat the more resistant pathogens . The higher mortality and subsequent cost to treat these infections are reviewed. FEMS Microbiol Lett, 1999 Mar 1, 172(1), 41 - 5 Effect on cell surface hydrophobicity and susceptibility of Helicobacter pylori to medicinal plant extracts; Annuk H et al.; Effects on aqueous extracts of medicinal plants on ten Helicobacter pylori strains were studied by the salt aggregation test to determine the possibility to modulate their cell surface hydrophobicity and by an agar diffusion assay for detection of antimicrobial activity . It was established that aqueous extracts of bearberry and cowberry leaves enhance cell aggregation of all H . pylori strains tested by the salt aggregation test, and the extract of bearberry possessed a remarkable bacteriostatic activity . Pure tannic acid showed a result similar to that of bearberry and cowberry extracts which contained a large amount of tannins . In contrast, extracts of wild camomile and pineapple-weed, which blocked aggregation of H . pylori, contained small amounts of tannins and did not reveal any antimicrobial activity . Tannic acid seems to be the component of bearberry and cowberry aqueous extracts with the highest activity to decrease cell surface hydrophobicity as well as in antibacterial activity against H . pylori. J Chemother, 1999 Feb, 11(1), 11 - 27 Clarithromycin: pharmacokinetic and pharmacodynamic interrelationships and dosage regimen; Periti P et al.; In the last decade three important pharmacodynamic parameters: T>MIC, Cmax/MIC and AUC/MIC, have been shown to correlate well with in-vitro antimicrobial efficacy and that found in animal models, differentiating among groups of antibiotics with diverse mechanisms of action such as exposure time or concentration-dependent effect . The macrolide antimicrobial agents display variable concentration-dependent killing, indicating the increasing importance of the Cmax parameter . Clarithromycin, whose T>MIC and AUC influence its clinical efficacy, is in an intermediate position between its progenitor, erythromycin, and the azalides . This paper reviews pharmacokinetic and pharmacodynamic characteristics of clarithromycin, examining the potential impact of these properties on the dose and the optimal interval between administrations. FEMS Microbiol Rev, 1999 Jan, 23(1), 69 - 91 Strategies for isolation of in vivo expressed genes from bacteria; Handfield M et al.; The discovery and characterization of genes specifically induced in vivo upon infection and/or at a specific stage of the infection will be the next phase in studying bacterial virulence at the molecular level . Genes isolated are most likely to encode virulence-associated factors or products essential for survival, bacterial cell division and multiplication in situ . Identification of these genes is expected to provide new means to prevent infection, new targets for, antimicrobial therapy, as well as new insights into the infection process . Analysis of genes and their sequences initially discovered as in vivo induced may now be revealed by functional and comparative genomics . The new field of virulence genomics and their clustering as pathogenicity islands makes feasible their in-depth analysis . Application of new technologies such as in vivo expression technologies, signature-tagged mutagenesis, differential fluorescence induction, differential display using polymerase chain reaction coupled to bacterial genomics is expected to provide a strong basis for studying in vivo induced genes, and a better understanding of bacterial pathogenicity in vivo . This review presents technologies for characterization of genes expressed in vivo. Biochim Biophys Acta, 1999 Feb 2, 1426(3), 439 - 48 Isolation and identification of three bactericidal domains in the bovine alpha-lactalbumin molecule; Pellegrini A et al.; Proteolytic digestion of alpha-lactalbumin by pepsin, trypsin and chymotrypsin yielded three polypeptide fragments with bactericidal properties . Two fragments were obtained from the tryptic digestion . One was a pentapeptide with the sequence EQLTK (residues 1-5) and the other, GYGGVSLPEWVCTTF ALCSEK (residues (17-31)S-S(109-114)), was composed of two polypeptide chains held together by a disulfide bridge . Fragmentation of alpha-lactalbumin by chymotrypsin yielded CKDDQNPH ISCDKF (residues (61-68)S-S(75-80)), also a polypeptide composed of two polypeptide chains held together by a disulfide bridge . The three polypeptides were synthesized and found to exert antimicrobial activities . The polypeptides were mostly active against Gram-positive bacteria . Gram-negative bacteria were only poorly susceptible to the bactericidal action of the polypeptides . GYGGVSLPEWVCTTF ALCSEK was most, EQLTK least bactericidal . Replacement of leucine (23) with isoleucine, having a similar chemical structure but higher hydrophobicity, in the sequence GYGGVSLPEWVCTTF ALCSEK significantly reduced the bactericidal capacity of the polypeptide . Digestion of alpha-lactalbumin by pepsin yielded several polypeptide fragments without antibacterial activity . alpha-Lactalbumin in contrast to its polypeptide fragments was not bactericidal against all the bacterial strains tested . Our results suggest a possible antimicrobial function of alpha-lactalbumin after its partial digestion by endopeptidases. J Clin Microbiol, 1999 Apr, 37(4), 1144 - 9 Rapid film-based determination of antibiotic susceptibilities of Mycobacterium tuberculosis strains by using a luciferase reporter phage and the Bronx Box; Riska PF et al.; Detecting antibiotic resistance in Mycobacterium tuberculosis is becoming increasingly important with the global recognition of drug-resistant strains and their adverse impact on clinical outcomes . Current methods of susceptibility testing are either time-consuming or costly; rapid, reliable, simple, and inexpensive methods would be highly desirable, especially in the developing world where most tuberculosis is found . The luciferase reporter phage is a unique reagent well-suited for this purpose: upon infection with viable mycobacteria, it produces quantifiable light which is not observed in mycobacterial cells treated with active antimicrobials . In this report, we describe a modification of our original assay, which allows detection of the emitted light with a Polaroid film box designated the Bronx Box . The technique has been applied to 25 M . tuberculosis reference and clinical strains, and criteria are presented which allow rapid and simple discrimination among strains susceptible or resistant to isoniazid and rifampin, the major antituberculosis agents. Planta Med, 1998 Dec, 64(8), 769 - 71 A new bioactive norquinone-methide triterpene from Maytenus scutioides; Gonzalez AG et al.; By antimicrobial and cytotoxic-guided fractionation, a bioactive norquinone-methide triterpene, 15 alpha-hydroxypristimerin, was isolated from a South American medicinal plant, Maytenus scutioides . Its structure was determined on the basis of spectroscopic evidence . Successful chemical transformation of pristimerin to netzahualcoyene indicates that the 15-hydroxy compounds seems to be a possible percursor of 14(15)-ene-quinone-methide-triterpenoids in the biogenetic pathway. Arch Oral Biol, 1999 Jan, 44(1), 67 - 79 Enhanced expression of activation-associated molecules on macrophages of heterogeneous populations in expanding periapical lesions in rat molars; Suzuki N et al.; Exudative macrophages are the most prevalent inflammatory cells during the entire pathogenetic process in experimentally induced rat periapical lesions . To clarify the significance of macrophages in the pathogenesis of periapical lesions, the way in which the phenotype of ED1 (a general marker for mononuclear phagocytes)-positive cells is modulated in actively expanding lesions was investigated, by immunoperoxidase staining with a panel of antibodies that recognize several activation-associated molecules on macrophages . Periapical lesions were induced experimentally by exposing the pulp in the lower first molars of Wistar rats . Active lesion expansion with morphological diversification of ED1-positive cells occurred between 14 and 28 days after the injury . Double immunoperoxidase staining revealed that ED1-positive cells coexpressing class II molecules of the major histocompatibility complex (MHC) molecules, inducible nitric oxide synthase (iNOS) and/or CD11a increased during the period of active lesion expansion . Increases of endothelial cells expressing intracellular adhesion molecule-1 and CD25 (interleukin-2 receptor)-expressing lymphocytes were also seen during the same period . Moreover, there existed two particular subpopulations of ED1 + cells in the established lesion at 28 days: (1) ED1++/class II MHC - /iNOS+ cells, located around the periapical abscess, and (2) ED1+/class II MHC+/ iNOS- cells with slender or dendritic morphology, distributed predominantly in the outer portion of the lesion where T lymphocytes were abundant . The first cell type could be a macrophage with potent phagocytic and antimicrobial actions, and the second might possess sufficient antigen-presenting capacity to cause the activation of T lymphocytes . It was concluded that macrophages, when activated, may participate in triggering lesion expansion . Functionally distinct subpopulations of macrophages may occupy different sites within the lesion where they can most effectively exert their specific functions. J Ethnopharmacol, 1999 Jan, 64(1), 69 - 77 Wide spectrum antibacterial and antifungal activities in the seeds of some coprophilous plants of north Indian plains; Bagchi GD et al.; In a survey at Lucknow, India, the seedlings of plant species which are prescribed in the Indian traditional system of medicine for a variety of infectious diseases were found to predominate on fresh or decomposing cattle dung, a harsh medium for plant growth due to high microbial load and other abiotic factors . Plants of most of the common species did not occur on the cattle dung heaps . It was hypothesized that plant species which are able to grow on cattle dung may have antimicrobial compounds in their seeds to protect them from microbial attack . In confirmation, the seeds of 15 of the coprophilous (kopros--dung, philein--to love) plant species, identified as occurring most frequently on fresh/decomposing cattle dung were directly tested against eight bacterial and three fungal strains . Interestingly, seeds of all the examined species exhibited antimicrobial activity . The seeds of the species found more frequently on the cattle dung heaps possessed higher levels of antimicrobial activities. Biophys Chem, 1999 Feb 22, 76(3), 161 - 83 Interactions of alpha-helices with lipid bilayers: a review of simulation studies; Biggin PC et al.; Membrane proteins, of which the majority seem to contain one or more alpha-helix, constitute approx . 30% of most genomes . A complete understanding of the nature of helix/bilayer interactions is necessary for an understanding of the structural principles underlying membrane proteins . This review describes computer simulation studies of helix/bilayer interactions . Key experimental studies of the interactions of alpha-helices and lipid bilayers are briefly reviewed . Surface associated helices are found in some membrane-bound enzymes (e.g . prostaglandin synthase), and as stages in the mechanisms of antimicrobial peptides and of pore-forming bacterial toxins . Transmembrane alpha-helices are found in most integral membrane proteins, and also in channels formed by amphipathic peptides or by bacterial toxins . Mean field simulations, in which the lipid bilayer is approximated as a hydrophobic continuum, have been used in studies of membrane-active peptides (e.g . alamethicin, melittin, magainin and dermaseptin) and of simple membrane proteins (e.g . phage Pf1 coat protein) . All atom molecular dynamics simulations of fully solvated bilayers with transmembrane helices have been applied to: the constituent helices of bacteriorhodopsin; peptide-16 (a simple model TM helix); and a number of pore-lining helices from ion channels . Surface associated helices (e.g . melittin and dermaseptin) have been simulated, as have alpha-helical bundles such as bacteriorhodopsin and alamethicin . From comparison of the results from the two classes of simulation, it emerges that a major theoretical challenge is to exploit the results of all atom simulations in order to improve the mean field approach. Br J Clin Pharmacol, 1999 Jan, 47(1), 23 - 30 The therapeutic monitoring of antimicrobial agents; Begg EJ et al.; AIMS: To review the basis and optimal use of therapeutic drug monitoring of antimicrobial agents . METHODS: Antimicrobial agents for which a reasonable case exists for therapeutic drug monitoring were reviewed under the following headings: pharmacokinetics, why monitor, therapeutic range, individualisation of therapy, sampling times, methods of analysis, interpretative problems and cost-effectiveness of monitoring . RESULTS: There is a strong historical case for monitoring aminoglycosides . The recent move to once-daily dosing means that criteria for therapeutic drug monitoring need to be redefined . Vancomycin has been monitored routinely but many questions remain about the most appropriate approach to this . A case can be made for monitoring teicoplanin, flucytosine and itraconazole in certain circumstances . CONCLUSIONS: The approach to monitoring aminoglycosides needs to be redefined in the light of once-daily dosing . It is premature to suggest that less stringent monitoring is necessary as toxicity remains a problem with these drugs . The ideal method of monitoring vancomycin remains to be defined although a reasonable case exists for measuring trough concentrations, mainly to ensure efficacy . Teicoplanin is monitored occasionally to ensure efficacy while flucytosine is monitored occasionally to avoid high concentrations associated with toxicity . Itraconazole has various pharmacokinetic problems and monitoring has been suggested to ensure that adequate concentrations are achieved. Drug Dev Ind Pharm, 1999 Mar, 25(3), 391 - 5 Studies of erythromycin maltobionate, a new derivative of erythromycin; Manna PK et al.; Erythromycin maltobionate, a new water-soluble derivative of erythromycin, was prepared, and its physiochemical and biological properties were evaluated . The derivative has considerable solubility in organic solvents . Its partition coefficient data in different organic solvent-water systems indicate it is possibly well distributed in various tissues in vivo . Antimicrobial potency in vitro of the derivative is 589 micrograms/mg, and its antimicrobial spectrum is comparable to that of the parent antibiotic . The LD50 value of the new derivative in mice intraperitoneally is 244.7 mg/kg . Results of this and the previous investigation of pharmacokinetics and protein binding indicate that the new derivative erythromycin maltobionate has a potential for possible clinical application. Drug Dev Ind Pharm, 1999 Mar, 25(3), 289 - 95 Development and in vitro evaluation of buccoadhesive tablets using a new model substrate for bioadhesion measures: the eggshell membrane; Parodi B et al.; For oral delivery of antimicrobial and anti-inflammatory drug, mucoadhesive tablets based on gelatin/hydroxypropylcellulose (HPC), gelatin/hydroxypropylmethyl-cellulose (HPMC), and gelatin/sodium carboxymethylcellulose (NaCMC) at different ratios were prepared by direct compression of the mixed powders . Metronidazole and benzydamine were used as model drugs . The in vitro bioadhesive properties, evaluated by a commercial tensile tester, were significantly affected by the model substrate employed, that is, a polypropylene (PP) membrane or a biological membrane (eggshell membrane) . The use of the biological substrate seemed to supply more reliable data . All studied formulations showed an erosion-diffusion mechanism of release, anomalous or non-Fickian release, in agreement with the behavior of the swellable systems. J Infect Dis, 1999 Apr, 179(4), 954 - 66 Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis; Wyrick PB et al.; An in vitro coculture model system was used to explore conditions that trigger neutrophil chemotaxis to Chlamydia trachomatis infected human epithelial cells (HEC-1B) . Polarized HEC-1B monolayers growing on extracellular matrix (ECM) were infected with C . trachomatis serovar E . By 36 h, coincident with the secretion of chlamydial lipopolysaccharide and major outer membrane protein to the surfaces of infected cells, human polymorphonuclear neutrophils (PMNL) loaded with azithromycin migrated through the ECM and infiltrated the HEC-1B monolayer . Bioreactive azithromycin was delivered by the chemotactic PMNL to infected epithelial cells in concentrations sufficient to kill intracellular chlamydiae . However, residual chlamydial envelopes persisted for 4 weeks, and PMNL chemotaxis was triggered to epithelial cells containing residual envelopes . Infected endometrial cells demonstrated up-regulation of ENA-78 and GCP-2 chemokine mRNA . Thus, despite appropriate antimicrobial therapy, residual chlamydial envelope antigens may persist in infected tissues of culture-negative women and provide one source for sustained inflammation. Mayo Clin Proc, 1999 Feb, 74(2), 187 - 95 The cephalosporins; Marshall WF et al.; The cephalosporins are a large group of related beta-lactam antimicrobial agents . Favorable attributes of the cephalosporins include low rates of toxicity, relatively broad spectrum of activity, and ease of administration . Various cephalosporins are effective for treatment of many conditions, including pneumonia, skin and soft tissue infections, bacteremia, and meningitis . Differences among the numerous cephalosporin antimicrobial agents are sometimes subtle; however, an understanding of these differences is essential for optimal use of these agents . As a result of widespread use of cephalosporins, bacterial resistance to these drugs is increasingly common . New, fourth-generation agents (such as cefepime) offer an alternative for the treatment of infections caused by some drug-resistant microorganisms. Clin Cancer Res, 1997 Dec, 3(12 Pt 2), 2660 - 5 The evolution of antibiotic therapy for neutropenic patients; Bodey GP; Considerable progress has been made in the treatment of infections in neutropenic patients during the past three decades . A major contribution to this progress has been the discovery of effective new therapies and their prompt administration . Unfortunately, successful therapy of each important pathogen has resulted in the emergence of new pathogens, usually with unique patterns of antibiotic susceptibility . Unfortunately, antibiotic resistance has become an increasing threat in recent years, raising the possibility of infections that will be difficult to eradicate . Fortunately, there are new classes of antimicrobials that hold promise for therapeutic success in the future. Kekkaku, 1999 Jan, 74(1), 63 - 70 {In vitro antimicrobial activities of quinolones, rifamycins and macrolides against Mycobacterium tuberculosis and M.avium complex: attempt to establish new assay methods which accurately reflect therapeutic effects of test agents in vivo}; Sato K et al.; Profiles of expression of the antimicrobial activities of LVFX, KRM-1648 (KRM), and CAM against M . tuberculosis (MTB) and M . avium complex (MAC) residing in MONO-MAC-6 human macrophage like cells (MM6-M phi s) and A-549 human type II alveolar pneumocyte cells (A-549 cells) were determined . First, the antimicrobial activities of LVFX, KRM, and CAM against intracellular organisms of MTB Kurono and MAC N-444 strains were examined under conditions in which infected MM6-M phi s and A-549 cells were cultured for up to 7 days or longer in medium containing the antimicrobials at their Cmaxs in the blood, achievable after oral administration of clinical dosages of these drugs . The antimicrobial effects of LVFX and KRM against respectively MTB and MAC within A-549 cells were significantly less than the activities they displayed against the same organisms residing in MM6-M phi s . Notably, it was also found that KRM had a markedly larger MIC (0.25 microgram/ml) for MAC N-444 within A-549 cells than its MIC (0.008 microgram/ml) for the same strain residing in MM6-M phi s . Thus, the profiles of LVFX- and KRM-mediated killing or inhibition of intracellular MTB or MAC organisms in A-549 cells were markedly different from those observed for the organisms residing in MM6-M phi s . Second, invasive and multiplicative phenotypes of MTB and MAC organisms, which had been adapted to either an extracellular or intracellular environment (designated as E- and I-type organisms, respectively), were studied . In the case of MTB, I-type organisms (retrieved from infected MM6-M phi s after bacterial growth within the M phi s during 5-day cultivation) were less efficient than E-type organisms (prepared by cultivating the organisms in 7H9 medium) in entering MM6-M phi s, whereas I-type organisms were more efficient than E-type organisms in invading A-549 cells . On the other hand, in the case of MAC, infectivity of I-type organisms not only in MM6-M phi s but also in A-549 cells was larger than that of E-type organisms . Next, while I-type organisms of MTB and MAC displayed more vigorous replication within MM6-M phi s than E-type organisms, the growth rate of E-type organisms within A-549 cells was more rapid than that of I-type organisms residing in A-549 cells . These findings indicate that there are significant differences between E- and I-type organisms of MTB or MAC in ability to invade and multiply within M phi s (professional phagocytes) and alveolar epithelial cells (nonprofessional phagocytic cells). Scand J Infect Dis, 1998, 30(5), 519 - 20 Cervicofacial and pulmonary actinomycosis associated with non-Hodgkin's lymphoma; Dentale N et al.; A case of cervicofacial and pulmonary actinomycosis associated with non-Hodgkin's lymphoma (NHL) is reported . The patient underwent antimicrobial treatment and surgical debridement of a palatine lesion . Complete clinical recovery was achieved . The presence of actinomycosis may obscure and delay the diagnosis of NHL. Scand J Infect Dis, 1998, 30(5), 513 - 7 Lactoferricin of bovine origin is more active than lactoferricins of human, murine and caprine origin; Vorland LH et al.; The antimicrobial peptide lactoferricin is generated by gastric pepsin cleavage of lactoferrin . We have examined the antimicrobial activity of lactoferricins derived from lactoferrin of human, murine, caprine and bovine origin with minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against E . coli ATCC 25922 and S . aureus ATCC 25923 . We found that lactoferricin of bovine origin (Lf-cin B) was the most efficacious of the lactoferricins tested . By comparing the linear and cyclic Lf-cin B we found the cyclic peptide to be the most active . Lactoferricin B was moderately active against E . coli ATCC 25922 and S . aureus ATCC 25923, but had no activity against P . mirabilis or Y . enterocolitica . Lf-cin B showed good activity against C . albicans, C . tropicalis and C . neoformans. J Zoo Wildl Med, 1998 Dec, 29(4), 479 - 83 Systemic candidiasis in a cheetah (Acinonyx jubatus); La Perle KM et al.; Systemic candidiasis, with involvement of the spleen, liver, kidneys, and lymph nodes, was diagnosed in a geriatric captive cheetah (Acinonyx jubatus) . The animal had a long clinical history of intermittent chronic gastritis associated with Helicobacter acinonyx and chronic renal failure, both of which were repeatedly treated with broad-spectrum antimicrobial therapy . Following euthanasia, a postmortem examination showed numerous microabscesses and granulomas composed of degenerate eosinophils and containing asteroids or Splendore-Hoeppli material throughout the body . Yeast, pseudohyphae, and infrequently branching septate hyphae, demonstrated with special stains, were identified as a Candida sp . by fluorescent antibody testing . Low genetic variation in cheetahs may increase their susceptibility to infectious agents . Additional factors contributing to the overgrowth and dissemination of Candida sp . in this case may have included changes in the bacterial flora of the alimentary tract as a result of repeated antimicrobial therapy and alterations in the topography of the alimentary mucosa caused by chronic gastritis. Ned Tijdschr Geneeskd, 1998 Dec 12, 142(50), 2746 - 50 {Imported skin diseases}; Cairo I et al.; In two Dutch subjects who had been on holiday in the tropics, a woman aged 32 and a man of Surinam descent aged 52 years, and in two men aged 21 and 38 years who had arrived from the tropics in the Netherlands, one recently and one 15 years previously, import skin diseases were diagnosed: larva migrans cutanea, cutaneous leishmaniasis, mycetoma and lobomycosis . The diagnosis was based on the anamnesis, the clinical picture and histopathological findings . The patients were cured by administration of antimicrobial agents and (or) excision . When travellers or immigrants from the tropics present with skin lesions, an imported skin disease should be considered. East Afr Med J, 1998 Dec, 75(12), 703 - 7 Antimicrobial prophylactic practice in surgical patients; al Harbi M; OBJECTIVE: To evaluate the prescribing patterns of surgeons for pre-operative antimicrobial prophylaxis . DESIGN: A retrospective study based on data obtained from case records of surgical patients admitted into the Department of Surgery . SETTING: Department of Surgery, Royal Commission Medical Center, Madinat Yambu Al-Sinayah . SUBJECTS: The study population comprised of 888 surgical patients who received antibiotic therapy either for prophylaxis or treatment during the period 1st November 1992 and 28th February 1995 . RESULTS: A total of 888 surgical patients received antibiotics during the study period, 191 (21.5%) for prophylaxis while 697 (78.5%) were given antibiotics for therapy before and after surgery . Ceftriaxone was the most commonly used antibiotic for prophylaxis, followed by augmentin and cefotaxime, and these were frequently given in multiple doses, extending beyond 24 hours . CONCLUSION: There was unwarranted and over use of prophylactic agents in at least 70% of the patients, with increased costs to the Hospital . Effective prophylaxis can be accomplished with a single dose of a cephalosporin, such as ceftriaxone, cefuroxime or cefazolin, for the common surgical procedures . It is recommended that better compliance with principles of surgical antimicrobial prophylaxis be implemented Prophylactic antibiotic audit measures should be carried out by the control committee . The development of guidelines and standing orders for antimicrobial prophylaxis should help to improve compliance. East Afr Med J, 1998 Dec, 75(12), 699 - 702 Toxin production and antimicrobial resistance of Escherichia coli river water isolates; Simiyu KW et al.; OBJECTIVES: To establish the types of E . coli isolates that are found in river water around Nairobi and to assess the potential risk of use of this water to human health . DESIGN: Multiple stratified sampling was carried out . Surface sampling was used in the entire study . SETTING: The study was carried out on river waters surrounding Nairobi, Kenya . SUBJECTS: Forty Escherichia coli strains isolated from river water . MAIN OUTCOME MEASURES: Serotyping, toxin gene tests and susceptibility to tetracyclines, ampicillin, chloramphenicol and kanamycin were analysed . RESULTS: None of the isolates could be specifically serotyped using the available antisera . Toxin gene production tests using the colony hybridisation technique revealed that nine (22.5%) of the strains were positive for heat stable (ST) toxin, seven (17.5%) to the heat labile (LT) toxin and two (5%) to both . Using the Agar Disk Diffusion technique, eighty per cent of the strains were susceptible to all four antibiotics, while twenty per cent of the strains showed multiple resistance . None of the strains was resistant to all four antibiotics while no strain showed resistance to kanamycin . CONCLUSION: None of the E . coli isolates was serotypable and it was therefore not possible to determine whether serologically identical strains of ETEC were haboured by man or animals . Toxin gene tests results showed that there is some risk of infection by diarrhoea causing ETEC to man and animals . Toxin gene tests results showed that there is some risk of infection by diarrhoea causing ETEC to man and animals if they consume this water untreated and there is evidence to show resistance of bacteria to antibiotics, hence appropriate health measures should be adhered to. Histopathology, 1999 Feb, 34(2), 124 - 33 Interobserver agreement in the assessment of gastritis reversibility after Helicobacter pylori eradication; Tepes B et al.; AIM: Our aim was to determine interobserver agreement in the application of the Sydney system to assess reversibility of gastritis after Helicobacter pylori eradication . METHODS AND RESULTS: Forty-three patients with a Helicobacter pylori-positive duodenal ulcer disease were included in the study . All patients included had successful H . pylori eradication after different antimicrobial drug combinations . Biopsy samples were collected from antrum and body, according to the Sydney recommendations, before antimicrobial therapy, 2 months after and at yearly intervals during 2-4 years of follow up . Three pathologists, who were blind to clinical data, evaluated histological changes in 221 antral and 219 body specimens stained with haematoxylin and eosin and with Warthin Starry . The percentage of pairwise agreement, kappa and weighted kappa statistic were used . Agreement in recognizing the presence of H . pylori colonization of the gastric mucosa, activity of inflammation and intestinal metaplasia was over 90% . Agreement in recognizing chronic inflammation in the body and atrophy in the antrum was between 78 and 89% respectively . The kappa values were excellent (more than 0.75) for the grade of H . pylori in the body, good (between 0.50 and 0.75) for the grade of H . pylori in the antrum, grade of inflammatory activity and intestinal metaplasia in the antrum and moderate to good (0.38-0.53) for the grade of chronic inflammation . Kappa values were poor to good (from 0.17 to 0.57) only in evaluation of the grade of atrophy . CONCLUSION: Interobserver agreement in the application of the Sydney system to reversibility of gastritis after H . pylori was good . More strict criteria should be used for atrophy and to differentiate normal and mild chronic inflammation. Biophys Chem, 1999 Feb 1, 76(2), 145 - 59 Peptide-bilayer interactions: simulations of dermaseptin B, an antimicrobial peptide; La Rocca P et al.; Dermaseptins, a family of antimicrobial peptides, are believed to act by forming amphipathic alpha-helices which associate with the cell membrane, leading to its permeabilisation and disruption . A simple mean field method is described for simulation of the interactions of peptides with lipid bilayers which includes an approximate representation of the electrostatic effects of the head-group region of the bilayer . Starting from an atomistic model of a PC phospholipid bilayer we calculate an average electrostatic potential along the bilayer normal . By combining the interaction of the peptide with this electrostatic potential and with the hydrophobic core of the membrane we arrive at a more complete description of peptide-bilayer energetics than would be obtained using sidechain hydrophobicities alone . Using this interaction potential in MD simulations of the frog skin peptide dermaseptin B reveals that the lipid bilayer stabilises the alpha-helical conformation of the peptide . This is in agreement with FTIR data . A surface associated orientation thus appears to be the most stable arrangement of the peptide, at least at zero ionic strength and without taking account of possible peptide-peptide interactions. Vet Microbiol, 1999 Feb 12, 64(4), 299 - 305 Susceptibility testing of Actinobacillus pleuropneumoniae in Denmark . Evaluation of three different media of MIC-determinations and tablet diffusion tests; Aarestrup FM et al.; This study was conducted to compare the applicability of three different media in sensitivity testing of Actinobacillus pleuropneumoniae by means of MIC and tablet diffusion tests . The media used were: modified PPLO agar, chocolatized Mueller-Hinton-II and Columbia agar supplemented with NAD . Seven antimicrobial agents were tested: ceftiofur, enrofloxacin, penicillin, spectinomycin, tiamulin, trimethoprim + sulfadiazine and tylosin, against 40 randomly selected A . pleuropneumoniae isolates . In general, good agreement was found between results obtained with all combinations of media, most antimicrobials tested and the two-test systems . Some variations between media were observed for spectinomycin, tiamulin and tylosin . For ceftiofur and trimethoprim + sulfadiazine some isolates with low MIC-values were classified as resistant using tablet diffusion, indicating that the break points of resistance for these antimicrobials using the tablet diffusion tests need adjustment . Using current break points for resistance with MIC-determinations, all isolates tested susceptible to ceftiofur, enrofloxacin, penicillin, tiamulin and trimethoprim + sulfadiazine . A larger number of isolates tested resistant to spectinomycin and tylosin on all three media using both MIC determinations and tablet diffusion. J Periodontol, 1999 Jan, 70(1), 1 - 7 A six-month comparison of three periodontal local antimicrobial therapies in persistent periodontal pockets; Kinane DF et al.; BACKGROUND: Currently, several local antimicrobial delivery systems are available to periodontists . The aim of this 6-month follow-up parallel study was to evaluate the efficacy of three commercially available local delivery systems as adjuncts to scaling and root planing in the treatment of sites with persistent periodontal lesions . METHODS: Seventy-nine patients with 4 pockets > or = 5 mm and bleeding on probing and/or suppuration were randomized into 4 treatment groups which included: scaling and root planing alone (S) (20 patients), or in conjunction with the application of 25% tetracycline fibers (S+Tet) (19 patients), or 2% minocycline gel (S+Min) (21 patients), or 25% metronidazole gel (S+Met) (19 patients) . Clinical measurements were taken at baseline, 6 weeks, 3 months, and 6 months after antimicrobial application . Treatments were applied using the distributors' recommended protocols . RESULTS: All 4 therapies resulted in significant improvements from baseline in probing depth, attachment level, bleeding on probing, and the Modified Gingival Index (MGI) scores . The improvements in clinical parameters were greater in all 3 adjunctive treatment groups than scaling and root planing alone . The mean probing depth reductions at 6 months were: scaling + tetracycline = 1.38 mm; scaling + metronidazole = 0.93 mm; scaling + minocycline = 1.10 mm; and scaling alone = 0.71 mm . The probing depth reduction at all time points was significantly greater in the scaling plus tetracycline fiber group than the scaling and root planing alone group (P<0.01) . There was also a significant improvement for scaling plus tetracycline fiber application over scaling and metronidazole at both 6 weeks and 3 months, although this did not remain significant at the 6-month visit . While the frequency of sites with suppuration was markedly reduced following all antimicrobial treatments, the most effective reductions were seen in the scaling plus tetracycline fiber group, followed by the minocycline group . CONCLUSIONS: Although all 3 locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone, a treatment regimen of scaling and root planing plus tetracycline fiber placement gave the greatest reduction in probing depth over the 6 months after treatment. Can Vet J, 1998 Feb, 39(2), 87 - 96 Antimicrobial drug use and related management practices among Ontario swine producers; Dunlop RH et al.; A mail survey of swine producers in Ontario was undertaken during 1991 to describe the types, frequency, and motives for antimicrobial use . Two hundred operations that marketed fewer than 350 hogs per year, and 800 that marketed more than 350 per year were sent questionnaires, 63% of which were completed and returned . Most operations (86%) added antimicrobials to starter (weanling pig) rations, while fewer (29%) added these drugs to finisher pig rations . The most commonly used antimicrobials were tylosin, carbadox, and furazolidone in weanling pigs, and tylosin, lincomycin, and tetracycline in finishers . Water medication of grower-finisher pigs was practised on 25% of farms; 80% of farms had injected at least some grower-finisher pigs with antimicrobials in the 12 mo preceding the survey . Approximately 20% of operations that added antimicrobials to finisher rations did so for growth promotion purposes only, while others used them for disease treatment, prevention, control, or a combination of reasons . Among those not using antimicrobials in finisher rations, 83% did not believe they were necessary and 37% were concerned about the potential for residues in marketed hogs. Protein Expr Purif, 1999 Mar, 15(2), 171 - 7 Purification and characterization of a plant antimicrobial peptide expressed in Escherichia coli; Harrison SJ et al.; MiAMP1 is a low-molecular-weight, cysteine-rich, antimicrobial peptide isolated from the nut kernel of Macadamia integrifolia . A DNA sequence encoding MiAMP1 with an additional ATG start codon was cloned into a modified pET vector under the control of the T7 RNA polymerase promoter . The pET vector was cotransformed together with the vector pSB161, which expresses a rare arginine tRNA . The peptide was readily isolated in high yield from the insoluble fraction of the Escherichia coli extract . The purified peptide was shown to have an identical molecular weight to the native peptide by mass spectroscopy indicating that the N-terminal methionine had been cleaved . Analysis by NMR spectroscopy indicated that the refolded recombinant peptide had a similar overall three-dimensional structure to that of the native peptide . The peptide inhibited the growth of phytopathogenic fungi in vitro in a similar manner to the native peptide . To our knowledge, MiAMP1 is the first antimicrobial peptide from plants to be functionally expressed in E . coli . This will permit a detailed structure-function analysis of the peptide and studies of its mode of action on phytopathogens . Eur J Pediatr, 1999 Feb, 158(2), 144 - 6 The effectiveness of single and multiple applications of triple dye on umbilical cord separation time; Hsu CF et al.; The effectiveness of single and multiple applications of triple dye for umbilical cord care in the umbilical cord separation time (UCST) was evaluated in 180 neonates . Seven neonates were excluded, three where the cord stump separation time was uncertain and four to whom contact was lost . The participating neonates were randomly assigned to two groups . Group 1, 101 neonates, were treated with a regimen of a single application of triple dye . Group 2, 79 neonates, were treated with multiple applications of triple dye . Complete information was obtained from 97 neonates (96.2%) in group 1 and 76 (96%) in group 2 . The UCST was 12.6 +/- 0.45 (mean +/- SE) days in group 1 and 16.68 +/- 0.65 days in group 2 (P < 0.0001) and showed no significant association with infants' gender, mode of delivery, gravidity, gestational age, birth weight, or hospital stay . CONCLUSION: A single application of triple dye may be a more favourable regimen with a similarly antimicrobial effect, a shorter UCST and may be more cost effective than multiple applications of triple dye in umbilical cord care. Toxicol Lett, 1999 Jan 11, 104(1-2), 43 - 8 Chromosomal aberrations in human lymphocytes exposed in vitro to enrofloxacin and ciprofloxacin; Gorla N et al.; Chromosomal aberrations were evaluated in cultures of human peripheral lymphocytes from eight healthy donors, exposed to the antimicrobial enrofloxacin (EFX) or to its major metabolite ciprofloxacin (CFX) . In both treatments cultures revealed an increase in the chromosomal aberration level, detected as chromatid and chromosome breaks and gaps . Control cultures analysis revealed 3.6 +/- 0.6 chromosomal aberrations per 100 cells while treated cultures exhibited 8.3 +/- 0.8 and 9.6 +/- 1.2 aberrations at 5 and 50 microg/ml of EFX respectively . In CFX treated cultures it was found 5.6 +/- 1.3 and 7.7 +/- 3.5 aberrations/100 cells at 5 and 25 microg/ml antimicrobial concentration . These results suggested a genotoxic effect of EFX and CFX in the system used (P < 0.001) . A reduction in the mitotic index and fuzzy metaphases were observed at 50 microg/ml of CFX, indicating a cytotoxic effect produced by this antimicrobial. Contact Dermatitis, 1999 Feb, 40(2), 104 - 8 Increase in occupational skin diseases of dental personnel; Kanerva L et al.; Occupational diseases of dentists and dental nurses were compiled from the Finnish Register of Occupational Diseases . The cases were recorded during 3 3-year observation periods, namely 1982-1984, 1986-1988, and 1992-1994 (i.e., 9 observation years) . The relative risk of developing occupational allergic contact dermatitis in different occupations was calculated from the statistics of the years 1986-1991, and was expressed as the age-standardized rate ratio (SRR) . During the 9 observation years, the majority of registered occupational diseases of dentists and dental nurses were skin diseases (221/312; 70.8%), followed by occupational repetitive strain injuries (61/312; 19.6%) and occupational respiratory diseases (20/312; 6.4%) . The incidence rate (IR) for allergic contact dermatoses/10,000 workers (contact urticaria included) increased from 26 (95% confidence interval (CI) 16-40) in 1982-1984 to 79 (95%, CI 64-97) in 1992-1994 . The IR/10,000 of allergic contact dermatoses increased especially for dentists, from 5.4 (95% CI 0.7-19) in 1982 to 67 (95% CI 45-95) in 1992-1994 . The increase of the IR/10,000 dental nurses was smaller: from 43 (95%, CI 26-66) in 1982-1984 to 87 (95% CI 67-111) in 1992-1994 . There was no increase in the IR/10,000 cases of irritant dermatoses . The most common causes of allergic contact dermatitis were plastics, disinfectants and antimicrobials, rubber chemicals, and mercury/mercury salts . The most common causes of irritant contact dermatitis were detergents, wet and dirty work, plastic chemicals and antimicrobials . Currently, Finnish dentists have the highest risk and dental nurses have the 4th highest risk of any occupation for developing occupational allergic contact dermatitis: the risk was 6.4-fold (SRR 6.4) in dentists and 6.1-fold in dental nurses, as compared to the general working population . It is evident that safer acrylics and protective gloves, better product declarations and material safety data sheets, as well as more information about protective measures, including non-touch working techniques, are needed. J Antibiot (Tokyo), 1998 Dec, 51(12), 1075 - 80 Apicularens A and B, new cytostatic macrolides from Chondromyces species (myxobacteria): production, physico-chemical and biological properties; Kunze B et al.; A novel macrolide, apicularen A, was produced by several species of the genus Chondromyces . Initially it was discovered by bioassay-guided RP-HPLC-fractionation of culture extracts of Chondromyces robustus, strain Cm a13 . Apicularen A showed no antimicrobial activity, but was highly cytotoxic for cultivated human and animal cells, with IC50 values ranging between 0.1 and 3 ng/ml . A cometabolite of apicularen A, the N-acetylglucosamine glycoside apicularen B, was distinctly less cytotoxic with IC50 values between 0.2 and 1.2 microg/ml, and showed weak activity against a few Gram-positive bacteria . Apicularen A is chemically closely related to the salicylihalamides A and B from the marine sponge Haliclona sp. Wien Med Wochenschr, 1998, 148(21), 481 - 7 {Therapy of febrile neutropenia episodes in systemic hematologic illnesses with new once daily ceftriaxone administration}; Karthaus M et al.; In this open label prospective multicenter trial, 420 patients with neutropenia < 1000/microliter, fever > 38.5 degrees C and hematological malignancies were treated with ceftriaxone . Acute leukemia (n = 238) and high-grade lymphoma patients (n = 182) from 35 centers were enrolled . Between February 1992 and January 1996, patients were treated with 2 g ceftriaxone i.v . per day either as monotherapy (n = 135), or in combination with aminoglycosides (n = 235), glycopeptides (n = 37), or other antimicrobial agents (n = 13) . Patients' median age was 54 years (range 15 to 97) with a median Karnofsky-performance-score of 6.0 . The median neutrophil counts were 400/microliter . Fever was of unknown origin (FUO) in 268 (63.8%) of patients . Clinically defined infections (CDI) were diagnosed in 152 (36.2%) cases, including 74 (17.8%) episodes with pneumonia . Response to the initial approach with ceftriaxone was observed in 56.2% of febrile episodes, including 93 (68.8%) treatment courses with ceftriaxone alone . Concerning defervescence of fever ceftriaxone monotherapy was successful as compared to ceftriaxone in combination . Analysis revealed a low risk characterized by higher neutrophil counts (> or = 500/microliter; p < 0.0001), better Karnofsky-performance-score (> or = 7; p = 0.01), duration of neutropenia (< or = 5 days; p = 0.008) from start of antimicrobial treatment and duration of neutropenia per cycle (< or = 10 days; p = 0.0016) . At the end of the observation, an overall response was obtained in 88.3% of the patients (n = 371) without statistical difference between patients treated with ceftriaxone alone or in combination . Once daily ceftriaxone either alone or in combination was effective in patients with hematological malignancies . Monotherapy was effective in a low risk group characterized by neutrophil counts (> or = 500/microliter), a Karnofsky-performance-score (> or = 7) and a duration of neutropenia (< or = 5 days) at the commencement of treatment. Curr Opin Microbiol, 1999 Feb, 2(1), 99 - 105 Cytokine responses during mucosal infections: role in disease pathogenesis and host defence; Svanborg C et al.; Mucosal pathogens use diverse and highly specific molecular mechanisms to activate mucosal inflammation . It may even be argued that their virulence depends on the inflammatory response that they induce . Some bacteria target epithelial cells and trigger them to produce inflammatory mediators but others cross the mucosa and activate macrophages or dendritic cells . Although systemic release of inflammatory mediators causes many symptoms and signs of infection, local chemokine production leads to the recruitment of inflammatory cells and lymphocytes that participate directly in the clearance of bacteria from mucosal sites . In this way, mucosal inflammation is a two-edged sword responsible for disease associated tissue destruction and crucial for the antimicrobial defence . Understanding of these pathways should create tools to enhance the defence and interfere with disease. Curr Opin Immunol, 1999 Feb, 11(1), 23 - 7 Antimicrobial peptides in mammalian and insect host defence; Lehrer RI et al.; During the past year, additional insights into systems that regulate antimicrobial peptide production in Drosophila were reported . Granulysin, a peptide stored in the cytoplasmic granules of human natural killer cells and cytolytic T cells, was shown to kill Mycobacterium tuberculosis . More data implicating antimicrobial peptides in the pathogenesis of bronchopulmonary infections in cystic fibrosis appeared . Studies that examined the potential contributions of antimicrobial peptides to regional innate immunity gained in prominence . Efforts to design peptide analogues to prevent or treat infections continued. Nippon Rinsho, 1999 Jan, 57(1), 157 - 61 {Long-term endoscopic follow-up for peptic ulcer patients after eradication of H . pylori; comparison with the maintainance therapy by H2-blocker}; Shirai T et al.; This study was aimed to clarify the endoscopic findings and the decline of serum IgG titer after successful eradication of H . pylori in long-term (from 2 to 7 years) . Forty-six H . pylori-positive peptic ulcer (22 GU and 26 DU) cases were eradicated with antimicrobial therapy . Sixty-nine non-eradicated DU cases who received maintainance therapy with H2-blocker were control group . Biopsy urease test (BUT) and culturing was performed to diagnose the H . pylori infection . Anti-H . pylori IgG titer (EIA) were also measured in some cases, pre and 6, 12, 24 months after the eradication . In 3 cases, H . pylori were recrudescent and only in a case, DU recurred during 5 years after eradication . Meanwhile, in 55% of control cases, DU were recurred during same periods . In 62% of eradicated cases, serum IgG-antibody to H . pylori declined below the cut-off level during 2 years after eradication . It was certified that eradication therapy against H . pylori prevents ulcer recurrence for long time, and re-rise of serum IgG titer to H . pylori might predict a recrudescence of infection. Nippon Rinsho, 1999 Jan, 57(1), 121 - 6 {The treatment strategy of H . pylori infection and the new triple therapy}; Hoshiya S et al.; The strategies against H . pylori infection have been developed very fast . Since the efficacy of mono-therapy (one antimicrobial drug) and dual-therapy (proton-pump inhibitor (PPI) + one antimicrobial drug) were not good, and the safety of classical triple therapy (bismuth + two antimicrobial drugs) was bad, new triple-therapy consisted with PPI + two antimicrobial drugs is considered as a standard regimen of the treatment of H . pylori infection . However there are several questions about this new strategy which we have to answer . The first question is how can we diagnose the cure of H . pylori infection and when we should do it? The second one is which statistical method should we choose for evaluating the success rate? The third one is which drug should we use and how long should the patient continuing to have the drug? A lot of scientific research are need to clarify these questions. Nippon Rinsho, 1999 Jan, 57(1), 107 - 10 {PCR-monitoring of gastric juice obtained with the capsuled string for the evaluation of H . pylori eradication}; Yoshida H et al.; We have developed a highly sensitive semi-nested PCR assay, URA-PCR, for the detection of H . pylori ureA gene in gastric juice . The primers were designed according to nucleotide sequence analyses of clinical isolates . The PCR assay has higher sensitivity than conventional methods such as culture . Characteristics of culture-negative but PCR-positive patients were similar to those of culture-positive ones . The PCR assay, using gastric juice samples obtained with capsuled strings, detected 97% cases of relapsed infection within eight weeks after antimicrobial therapy. Nippon Rinsho, 1999 Jan, 57(1), 76 - 80 {Antimicrobial resistance testing of H . pylori epsilometer test and disk diffusion test}; Fukazawa K et al.; The resistance of Helicobacter pylori to antibiotics leaves great influence on treatment outcome . Routine antimicrobial susceptibility testing of H . pylori should be a simple, inexpensive and standardized method to be adopted . Agar and broth dilution techniques are difficult to perform and not practical . E-test and disk diffusion methods have the advantage of allowing the visualization of resistant subpopulations of bacteria within zones of inhibitions . We studied the susceptibility results of 246 H . pylori isolates against metronidazole and clarithromycin using E-test and disk diffusion test . The results of disk diffusion test were well correlated with these of E-test . Our results showed that disk method is cost effective and simple for the screening for antimicrobial resistance of H . pylori. Nippon Rinsho, 1999 Jan, 57(1), 61 - 6 {In a view of international consensus conference for the treatment of H . pylori infection}; Watanabe K et al.; The first guideline of the treatment of H . pylori infection was reported by the working party of the World Congresses of Gastroenterology in 1990 . Subsequently, many international consensus statements for the indication and the methods of eradication therapy for H . pylori infection were reported . And, now the standard regimens have been developed in European countries and U.S.A . The other hand, in Japan, the Ministry of Welfare has never been to approve the both of testing and treatment of H . pylori . One of the reasons is that there is a few scientific evidence for the benefit of the treatment of H . pylori infection in Japan . Since the resistant strains of H . pylori against antimicrobial agents are increasing in our country, we have to develop a strong and safety therapeutic regimen in Japan. Nippon Rinsho, 1999 Jan, 57(1), 53 - 60 {The role and significance of acid suppressive drugs in the eradication of H . pylori}; Yakabi K et al.; Recently a new triple therapy with PPI and two antimicrobials is widely accepted instead of classical triple therapy . PPI has direct and indirect effects on H . pylori . Practically a single use of PPI is almost noneffective for eradication of H . pylori . In the combination therapy PPI is supposed to contribute to successful eradication through the inhibition of acid secretion . Because a raise of pH in stomach protects antimicrobials from the degradation by acidic environment . The decrease in the volume of gastric juice also contributes to concentrate antibiotics . Recently interaction between PPI and clarithromycin on metabolic enzyme in liver was reported that explains the synergistic effects of these drugs . The heterogeneity of genotype of metabolic enzyme was also elucidated which might be responsible for the difference in the effect of PPI between the patients . To accomplish successful eradication, full inhibition of acid secretion has to be done . To consider the interactions between PPI and antimicrobials and the heterogeneity of genotype of metabolic enzyme may improve eradication therapy of H . pylori. J Am Dent Assoc, 1999 Feb, 130(2), 236 - 51 Adverse drug interactions in dental practice: interactions involving antibiotics . Part II of a series; Hersh EV; BACKGROUND: The prudent use of antibiotics is an integral part of dental practice . While these agents generally are considered safe in the dental setting, their use can result in interactions that can lead to serious morbidity in dental patients . METHODS: The faculty of a symposium entitled "Adverse Drug Interactions in Dentistry: Separating the Myths From the Facts" did an extensive literature review on drug interactions . Through this, they were able to establish a significance rating of alleged adverse drug interactions as they relate to dentistry, based on their scientific documentation and severity of effect . The author of this article focused on antibiotics . RESULTS: Most of the reported drug interactions discussed in this article are well-documented by clinical studies . It is particularly important that dentists be aware of the potentially serious and life-threatening interactions of the antibiotics erythromycin, clarithromycin and metronidazole, and of the antifungal agents ketoconazole and itraconazole, with a host of other drugs whose metabolism is impaired by these antimicrobial agents . In contrast, the alleged ability of commonly employed antibiotics to reduce the effectiveness of oral contraceptive agents is not adequately supported by clinical research . It still is recommended, however, that clinicians discuss this possible interaction with their patients, as it might represent a relatively rare event that cannot be discerned in clinical trials . CONCLUSIONS: Potentially serious adverse drug interactions can occur between antimicrobial agents used in dental practice and other drugs patients are taking for a variety of medical conditions . CLINICAL IMPLICATIONS: It is important that dentists stay abreast of potential drug interactions involving antibiotics to avoid serious morbidity among their patients. Adv Nurse Pract, 1999 Jan, 7(1), 34 - 9 Repairing lacerations in children . Suture, staple or secure? Behr J. The challenges of pediatric laceration repair include the probability of an uncooperative participant, tense or frantic parents and a busy setting . Linear lacerations of the scalp, trunk and extremities are excellent sites for staples . Stapling may be less traumatic because it is generally quicker than suturing . Suture repair is necessary for lacerations of the face, over joints, on the hands and feet, and other areas that impede the use of a stapling device . The most common methods of anesthesia for laceration repair include topical agents, direct infiltration and blocks . All wounds that are deep, dirty or may contain a foreign body should be locally cleansed with antimicrobial agents and irrigated vigorously. J Ethnopharmacol, 1998 Dec, 63(3), 253 - 63 Antimicrobial properties of Honduran medicinal plants; Lentz DL et al.; Ninety-two plants used in the traditional pharmacopoeia of the Pech and neighboring Mestizo peoples of central Honduras are reported . The results of in vitro antimicrobial screens showed that 19 of the extracts from medicinal plants revealed signs of antifungal activity while 22 demonstrated a measurable inhibitory effect on one or more bacterial cultures . Bioassay-guided fractionation of extracts from Mikania micrantha, Neurolaena lobata and Piper aduncum produced weak to moderately active isolates . The broad spectrum of activity of the extracts helps to explain the widespread use of these plants for wound healing and other applications. Am J Health Syst Pharm, 1999 Jan 15, 56(2), 142 - 57 ASHP national survey of pharmacy practice in acute care settings: prescribing and transcribing--1998 . American Society of Health-System Pharmacists; Ringold DJ et al.; Results of the 1998 ASHP national survey of pharmacy practice in acute care settings that pertain to prescribing and transcribing practices are presented . Pharmacy directors at 1058 general and children's medical-surgical hospitals in the United States were surveyed by mail . Data on hospital characteristics were supplied by SMG Marketing Group, Inc.; the survey sample was drawn from SMG's hospital database . The response rate was 51.8% . Respondents reported that at least 90% of hospital and health-system pharmacy and therapeutics (P&T) committees are responsible for formulary development and management, drug policy development, medication-use evaluation, adverse-drug-reaction reporting, and medication error monitoring . More than 90% of the facilities use pharmacoeconomic, clinical and therapeutic, and cost information in formulary development; 83% have a medication-use-evaluation program designed to improve prescribing; more than 95% have P&T committees, infection control committees, and quality control committees; and more than 80% provide pharmacist consultations on drug information, dosage adjustments for patients with renal impairment, antimicrobials, and pharmacokinetics . A majority of respondents reported that accurate transcription of medication orders is ensured by use of standardized physician order forms, clarification of illegible orders, reconciliation of medication administration records (MARs) and pharmacy profiles at least daily, and use of computer-generated MARs . The 1998 ASHP survey results suggest that pharmacists in acute care settings have positioned themselves well to improve the prescribing and transcription components of the medication-use process. J Calif Dent Assoc, 1998 Nov, 26(11), 842 - 5 Effect of doxycycline on the apical seal of retrograde filling materials; Barkhordar RA et al.; In this study, we examined the effect of doxycycline hydrochloride (DH) on the apical seal . Results indicated that teeth that were retrofilled with IRM or amalgam following doxycycline irrigation had significantly less dye penetration (p < 0.05) . Due to its antimicrobial activity, smear layer removal ability, and improvement of apical seal, doxycycline solution may be used as an irrigant. Mol Diagn, 1998 Jun, 3(2), 81 - 91 Comparative Evaluation of Cleavase Fragment Length Polymorphism With PCR-SSCP and PCR-RFLP to Detect Antimicrobial Agent Resistance in Mycobacterium tuberculosis; Sreevatsan S et al.; Background: Several molecular methods potentially useful in the detection of Mycobacterium tuberculosis mutations, specifically in rpoB and katG, were compared . Methods and Results: DNA from 24 M . tuberculosis clinical isolates, with mutations associated with resistance to rifampin and/or isoniazid, was analyzed . A 128 bp amplicon, spanning the 81 bp rpoB region containing most mutations leading to rifampin resistance, was analyzed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and a recently introduced mutation scanning method, cleavase fragment length polymorphism (CFLP) analysis . Also, a 350 bp amplicon encompassing that region was analyzed by the CFLP method . CFLP analysis of the 350 bp amplicon (23 isolates) identified 14 of 17 mutants; however, CFLP analysis of the 128 bp amplicon accurately identified all mutants as did PCR-SSCP with interpretative difficulty for two codon 513 mutations . CFLP and PCR-restriction fragment length polymorphism (RFLP) analyses of a 623 bp amplicon encompassing katG codons 315 and 463 showed that the CFLP method identified single and dinucleotide codon 315 substitutions with or without codon 463 (CGG-->CTG) changes, whereas PCR-RFLP (MspI) missed one codon 315 polymorphism (AGC-->ACA) in three isolates . Conclusion: Both PCR-SSCP and CFLP analyses were sensitive in identifying all mutations on short sequences in the rpoB mutants . CFLP appears to be more efficient than SSCP and RFLP for the detection of mutations in large amplicons . J Dent Res, 1999 Feb, 78(2), 690 - 8 Construction and characterization of human salivary histatin-5 multimers; Situ H et al.; Human salivary histatin-5 (Hsn-5), a 24-amino acid polypeptide, is a potent candidacidal molecule . In this study, we have explored the following two hypotheses: More potent Hsn molecules may be achieved by duplication of the functional domain of Hsn-5 (C16, residues 9-24 of Hsn-5), and Hsn may act like other cationic peptides which aggregate and form channels across the target membrane . A PCR-based gene splicing by overlap extension (SOE) method was used to construct the DNA fragments encoding the following fusion molecules: Hsn-5--Hsn-5, Hsn-5--C16, and C16--C16 . These constructs were expressed in E . coli, the proteins produced were purified, and their anticandidal activities as well as secondary structures were determined . Contrary to our hypotheses, results showed that none of the multimers possessed increased candidacidal activity . Specifically, C16--C16 and Hsn-5--C16 displayed candidacidal activity comparable with that of Hsn-5, while Hsn-5--Hsn-5 possessed significantly decreased candidacidal activity, yet all molecules retained an alpha-helical structure in a hydrophobic environment . Additionally, the circular dichroism data showed that Hsn-5 in an alpha-helical conformation does not aggregate in a hydrophobic environment, not even at 14- to 18-fold its physiological concentration . Our results suggest that the development of enhanced Hsn-5 molecules may not be achieved by duplication of its functional domain, and that Hsns may not act like other antimicrobial cationic peptides which aggregate and form channels across the target membrane. Eur J Surg Suppl, 1998, (582), 90 - 8 Medical therapy of inflammatory bowel disease for the 21st century; Robinson M; Inflammatory bowel disease therapy can be considered in several subcategories, and this review is designed to provide selective updates for some of the most important therapeutic entities currently marketed or soon to be available for the medical management of IBD . Although conventional corticosteroids have been a major component of acute inflammatory bowel disease management, steroids have many serious disadvantages; and toxicity is heightened with chronic steroid therapy . Newer corticosteroids, particularly budesonide, may be less toxic than older agents such as prednisone . Budesonide may be used as an enema in active distal ulcerative colitis (UC) or as delayed release tablets in Crohn's disease (CD) . However, budesonide is not completely free from steroid side effects, and may share in some of the toxicity of older corticosteroids, particularly when high dose budesonide is administered . Topical and oral aminosalicylates are widely utilized for the treatment of mild to moderate active UC and mild active CD, and they also are efficacious for maintenance of IBD remission . Recent data continue to support the concept that higher doses and prolonged use of mesalamine-based drugs are therapeutically superior to lower doses and short term treatment . In addition, the combination of oral and rectal aminosalicylate formulations often succeeds in patients refractory to either used alone . The immunomodulatory drugs azathioprine and 6-mercaptopurine are particularly effective in treating both CD and UC, and methotrexate has also shown some promise in CD therapy . Immunosuppressive therapy for inflammatory bowel disease initially met with strong physician resistance . However, views have shifted in response to positive data on the utility of immunosuppressive agents in many cases of IBD . Although cyclosporine may be used as a 'rescue' medication in some severe IBD cases, it has been associated with severe toxic reactions . Possible candidates for cyclosporine treatment should be offered such therapy only in academic centers highly experienced with the nuances of this modality . Clinical trials of the newer entities IL-10, IL-11, tacrolimus, and anti-TNFalpha, have demonstrated variable efficacy in refractory IBD patients . Anti-TNFalpha has been very impressive, particularly in the presence of fistulizing Crohn's disease . Many physicians have utilized various antibiotics empirically as part of their 'general' management of IBD . Only metronidazole has been adequately studied in controlled CD trials, but other antibiotic studies are pending . Further exploration of antimicrobial treatment for IBD is clearly warranted . Many other investigational agents in disparate pharmaceutical categories have been employed in IBD therapy; and some of these also show varying degrees of promise, including the aloe vera derivative acemannan, several formulations of heparin, and both transdermal and intra-rectal nicotine . Despite the growing list of medications and formulations promoted for the treatment of IBD, no single drug or recognized combination has yet been confirmed as dependably clinically effective . Many additional investigations of IBD medical therapy are needed, including permutations of conventional medications, along with newer agents that may be more precisely targeted to specific aspects of IBD pathophysiology . All physicians who care for UC and CD patients enthusiastically await more optimal regimens for these challenging disorders. Eur J Surg Suppl, 1998, (582), 16 - 26 Antimicrobial treatment of H . pylori infection--a pooled efficacy analysis of eradication therapies; Unge P; OBJECTIVE: To evaluate the clinical efficacy of available therapies directed towards Helicobacter pylori eradication . DESIGN: Pooled overall analyses of a limited number of drug combinations regardless of dosage, duration, formulation etc . SUBJECTS: Helicobacter pylori infected patients with or without complications . INTERVENTIONS: Efficacy data from all studies included in the analysis are transformed to or retained as intention to treat data . MAIN OUTCOME: Efficacy is presented as proportion of patients cured from the infection . Confidence intervals are enlarged by 1.5 due to the inferior strength of a pooled analysis . RESULTS: Dual therapies are ineffective . Triple therapies cure 70-90% of the patients . Well documented high efficacy is shown for a proton pump inhibitor plus two antimicrobials . Less studied but effective alternatives are ranitidine-bismuth plus two antimicrobials . CONCLUSION: A proton pump inhibitor plus two antimicrobials is the best validated highly effective type of eradication therapy. J AOAC Int, 1999 Jan-Feb, 82(1), 79 - 84 Validation of the LacTek test applied to spiked extracts of tissue samples: determination of performance characteristics; Mitchell JM et al.; LacTek tests are competitive enzyme-linked immunosorbent assays intended for rapid detection of antimicrobial residues in bovine milk . In this study, the LacTek test protocol was modified for use with extracts of bovine tissue to detect beta-lactam, tetracycline, and sulfamethazine residues . Test performance characteristics--precision, accuracy, ruggedness, practicability, and analytical specificity and sensitivity--were investigated . Results suggest that LacTek tests can be easily adapted to detect antimicrobial residues in extracts of lean ground beef . However, positive samples may not contain residues at violative concentrations (i.e., Canadian maximum residue limits), and therefore, additional analysis would be required for final confirmation and quantitation (e.g., chromatography). Jpn J Antibiot, 1998 Nov, 51(11), 625 - 81 {Thirteen-week intravenous repeated dose toxicity study of T-3762, a novel parenteral quinolone antimicrobial agent, and four-week recovery test in cynomolgus monkeys}; Nagai A et al.; A thirteen-week intravenous repeated dose toxicity study of T-3762, parenteral quinolone antimicrobial agent, and four-week recovery test was carried out in male and female cynomolgus monkeys at dosages of 26, 52 and 104 mg/kg . The following results were obtained . 1) There was no death of animals during administration period at any dose levels . In general signs, there was no abnormality at any dose levels . 2) In appetite, body weights and ophthalmological examination, there was no abnormality attributable to the treatment . 3) In urinalysis, hematological examination and biochemical examination, there was no abnormality attributable to the treatment . 4) In organ weights, macroscopic findings and histopathological findings, there was no abnormality attributable to the treatment . 5) From these results in this study, no-toxic dose level of T-3762 for cynomolgus monkeys is considered over 104 mg/kg. Ned Tijdschr Geneeskd, 1998 Nov 14, 142(46), 2512 - 5 {Optimizing of antibiotics policy in the Netherlands . III . SWAB guidelines for antimicrobial therapy in adults hospitalized with bronchitis . Foundation Antibiotics Policy Work Group}; van Kasteren ME et al.; The Stichting Werkgroep Antibioticabeleid (SWAB, Foundation Antibiotics Policy Team) has issued guidelines for empirical antimicrobial therapy of adult patients with bronchitis in hospital . Acute bronchitis is rarely caused by bacteria: therefore antibiotic treatment is not indicated in most cases . In an exacerbation of asthma or chronic obstructive pulmonary disease (COPD), the primary treatment aims at combating the inflammatory reaction and the bronchospasm . In case of increasing dyspnoea, (increase of) sputum production and (increase of) purulence of the sputum, antibiotic treatment may lead to shortening of the symptoms and sickness duration . Doxycycline is to be preferred because of its spectrum, easy dosage and favourable price . If the patient has not had antibiotics earlier, amoxicillin also is a good choice . Macrolide antibiotics are no preparations of first choice because large-scale use readily leads to resistance. Chest, 1999 Feb, 115(2), 462 - 74 Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients; Kollef MH et al.; STUDY OBJECTIVE: To evaluate the relationship between inadequate antimicrobial treatment of infections (both community-acquired and nosocomial infections) and hospital mortality for patients requiring ICU admission . DESIGN: Prospective cohort study . SETTING: Barnes-Jewish Hospital, a university-affiliated urban teaching hospital . PATIENTS: Two thousand consecutive patients requiring admission to the medical or surgical ICU . INTERVENTIONS: Prospective patient surveillance and data collection . MEASUREMENTS AND RESULTS: One hundred sixty-nine (8.5%) infected patients received inadequate antimicrobial treatment of their infections . This represented 25.8% of the 655 patients assessed to have either community-acquired or nosocomial infections . The occurrence of inadequate antimicrobial treatment of infection was most common among patients with nosocomial infections, which developed after treatment of a community-acquired infection (45.2%), followed by patients with nosocomial infections alone (34.3%) and patients with community-acquired infections alone (17.1%) (p < 0.001) . Multiple logistic regression analysis, using only the cohort of infected patients (n = 655), demonstrated that the prior administration of antibiotics (adjusted odds ratio {OR}, 3.39; 95% confidence interval {CI}, 2.88 to 4.23; p < 0.001), presence of a bloodstream infection (adjusted OR, 1.88; 95% CI, 1.52 to 2.32; p = 0.003), increasing acute physiology and chronic health evaluation (APACHE) II scores (adjusted OR, 1.04; 95% CI, 1.03 to 1.05; p = 0.002), and decreasing patient age (adjusted OR, 1.01; 95% CI, 1.01 to 1.02; p = 0.012) were independently associated with the administration of inadequate antimicrobial treatment . The hospital mortality rate of infected patients receiving inadequate antimicrobial treatment (52.1%) was statistically greater than the hospital mortality rate of the remaining patients in the cohort (n = 1,831) without this risk factor (12.2%) (relative risk {RR}, 4.26; 95% CI, 3.52 to 5.15; p < 0.001) . Similarly, the infection-related mortality rate for infected patients receiving inadequate antimicrobial treatment (42.0%) was significantly greater than the infection-related mortality rate of infected patients receiving adequate antimicrobial treatment (17.7%) (RR, 2.37; 95% CI, 1.83 to 3.08; p < 0.001) . Using a logistic regression model, inadequate antimicrobial treatment of infection was found to be the most important independent determinant of hospital mortality for the entire patient cohort (adjusted OR, 4.27; 95% CI, 3.35 to 5.44; p < 0.001) . The other identified independent determinants of hospital mortality included the number of acquired organ system derangements, use of vasopressor agents, the presence of an underlying malignancy, increasing APACHE II scores, increasing age, and having a nonsurgical diagnosis at the time of ICU admission . CONCLUSIONS: Inadequate treatment of infections among patients requiring ICU admission appears to be an important determinant of hospital mortality . These data suggest that clinical efforts aimed at reducing the occurrence of inadequate antimicrobial treatment could improve the outcomes of critically ill patients . Additionally, prior antimicrobial therapy should be recognized as an important risk factor for the administration of inadequate antimicrobial treatment among ICU patients with clinically suspected infections. Infection, 1999 Jan-Feb, 27(1), 42 - 3 Hemophilus influenzae biotype III cellulitis in an adult; Lev EI et al.; The case of a patient with systemic lupus erythematosus presenting with severe leg cellulitis caused by Hemophilus influenzae non-B biotype III is reported . Skin infections caused by H . influenzae in general, and of the extremities in particular, seem to be rare in adults . This is the first reported case of cellulitis caused by H . influenzae biotype III . The infection was treated successfully with antibiotics . This case highlights the importance of blood cultures and prompt antimicrobial treatment in febrile adults with cellulitis, especially immunocompromised patients. Infect Immun, 1999 Mar, 67(3), 1386 - 92 Role of iron in Nramp1-mediated inhibition of mycobacterial growth; Zwilling BS et al.; Innate resistance to mycobacterial growth is mediated by a gene, Nramp1 . We have previously reported that Nramp1 mRNA from macrophages of Mycobacterium bovis BCG-resistant (Bcgr) mice is more stable than Nramp1 mRNA from macrophages of BCG-susceptible (Bcgs) mice . Based on these observations and on reports that show that the closely related Nramp2 gene is a metal ion transporter, we evaluated the effect of iron on the growth of Mycobacterium avium within macrophages as well as on the stability of Nramp1 mRNA . The addition of iron to macrophages from Bcgs mice resulted in a stimulation of mycobacterial growth . In contrast, iron increased the capacity of macrophages from Bcgr mice to control the growth of M . avium . When we treated recombinant gamma interferon (IFN-gamma)-activated macrophages with iron, we found that iron abrogated the growth inhibitory effect of IFN-gamma-activated macrophages from Bcgs mice but that it did not affect the capacity of macrophages from Bcgr mice to control microbial growth . A more detailed examination of the effect of iron on microbial growth showed that the addition of small quantities of iron to resident macrophages from Bcgr mice stimulated antimicrobial activity within a very narrow dose range . The effect of iron on the growth inhibitory activity of macrophages from Bcgr mice was abrogated by the addition of catalase or mannitol to the culture medium . These results are consistent with an Fe(II)-mediated stimulation of the Fenton/Haber-Weiss reaction and hydroxyl radical-mediated inhibition of mycobacterial growth. Infect Immun, 1999 Mar, 67(3), 1251 - 60 Dysregulated production of interleukin-8 in individuals infected with human immunodeficiency virus type 1 and Mycobacterium tuberculosis; Meddows-Taylor S et al.; Interleukin-8 (IL-8) production in vivo was monitored in four study groups: normal blood donors, patients with pulmonary tuberculosis (TB), patients with human immunodeficiency virus type 1 (HIV-1) infection, and dually infected (HIV/TB) patients . We show that whereas there was evidence of detectable levels of cell-associated IL-8 (mRNA and protein) in peripheral cells of healthy individuals, this was largely lost in the disease states studied . Coupled with this finding was significantly increased circulating levels of IL-8 in HIV-1-infected individuals with or without concomitant pulmonary TB (P < 0.001) . On the other hand, the capacity of peripheral mononuclear cells to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patients (P < 0.05) and many of the HIV/TB group, but their corresponding capacities to respond to various stimuli, in particular phytohemagglutinin, were significantly diminished compared to those of normal donors (P < 0.05) . Circulating levels of IL-8 in a group of HIV/TB patients were significantly positively correlated with the percentage of polymorphonuclear leukocytes (PMN) in the peripheral circulation (r = 0.65; P = 0.01), the proportions of IL-8 receptor A (IL-8RA)-expressing (r = 0.86; P < 0.01) and IL-8RB-expressing (r = 0.77; P < 0.01) PMN, and the capacity of PMN to migrate in response to IL-8 as chemoattractant (r = 0.68; P < 0 . 01) . IL-8RB fluorescence intensity, however, was negatively correlated with plasma IL-8 levels (r = -0.73; P < 0.01) . Our results suggest that altered regulation of IL-8 in HIV-1 may have important implications for antimicrobial defenses and for normal immune processes. Immunity, 1999 Jan, 10(1), 21 - 8 An antiviral mechanism of nitric oxide: inhibition of a viral protease; Saura M et al.; Although nitric oxide (NO) kills or inhibits the replication of a variety of intracellular pathogens, the antimicrobial mechanisms of NO are unknown . Here, we identify a viral protease as a target of NO . The life cycle of many viruses depends upon viral proteases that cleave viral polyproteins into individual polypeptides . NO inactivates the Coxsackievirus protease 3C, an enzyme necessary for the replication of Coxsackievirus . NO S-nitrosylates the cysteine residue in the active site of protease 3C, inhibiting protease activity and interrupting the viral life cycle . Substituting a serine residue for the active site cysteine renders protease 3C resistant to NO inhibition . Since cysteine proteases are critical for virulence or replication of many viruses, bacteria, and parasites, S-nitrosylation of pathogen cysteine proteases may be a general mechanism of antimicrobial host defenses. J Am Vet Med Assoc, 1999 Feb 1, 214(3), 382 - 90 Characteristics and risk factors for failure of horses with acute diarrhea to survive: 122 cases (1990-1996); Cohen ND et al.; OBJECTIVE: To characterize horses with acute diarrhea and determine risk factors for failure to survive . DESIGN: Retrospective study . ANIMALS: 122 adult horses admitted for acute diarrhea at the teaching hospital between Jan 1, 1990 and Dec 31, 1996 . PROCEDURE: Medical records of horses with acute diarrhea were reviewed to abstract information regarding signalment, history, physical examination, clinicopathologic testing, treatment, and outcome . RESULTS: 91 of 122 (74.6%) horses lived and were discharged from the hospital . Horses with history of administration of antimicrobials for a problem preceding diarrhea were approximately 4.5 times less likely to survive . The following variables that had been determined at the time of admission were significantly associated with failure to survive: administration of antimicrobial drugs for another illness, serum creatinine concentration > 2.0 mg/dl, PCV > 45%, tachycardia (heart rate > 60 beats/min), and low serum total protein concentration . Prevalence of laminitis was 11.5% . CLINICAL IMPLICATIONS: Diarrheic horses that are azotemic and have clinicopathologic findings consistent with hemoconcentration and hypoproteinemia have a poor prognosis for survival . Antimicrobial administration may induce diarrhea, and antimicrobial-associated diarrhea may have a worse prognosis than other types of acute diarrhea. Sex Transm Infect, 1998 Jun, 74 Suppl 1, S34 - 7 Specificity of dysuria and discharge complaints and presence of urethritis in male patients attending an STD clinic in Malawi; Dallabetta G et al.; OBJECTIVE: This study evaluated the specificity of discharge and dysuria for laboratory confirmed urethritis in symptomatic men presenting to an urban STD clinic in Malawi for treatment and returning for follow up evaluation . METHODS: Clinical treatment trial where consecutive consenting men with urethritis were enrolled and administered a questionnaire, examined, tested, and given one of five urethritis treatments with an efficacy range of 33-95% . Men returning for follow up were questioned, examined, and tested . RESULTS: The presence of both discharge and dysuria were highly specific for laboratory confirmed urethritis (over 90%) . Compared with men who had complaints of both discharge and dysuria, men with complaints of dysuria alone were more likely to have reported prior treatment, 72% v 48% (p = 0.003), and less likely to have had gonorrhoea, 64% v 83% (p = 0.04) . Men with complaints of discharge or dysuria without evidence of discharge were rare but half of them had documented urethritis . Among men who returned for follow up, 72% had no symptoms of either discharge or dysuria . However, among the 238 men with no symptoms at follow up, laboratory documented gonorrhoea occurred in 9% and non-gonococcal urethritis in 21% . DISCUSSION: In this population of men discharge or dysuria were specific symptoms for urethritis . The symptom of dysuria should be added as an entry criterion for evaluation for urethritis in the World Health Organisation's treatment recommendations . The high prevalence of asymptomatic infection at follow up in a population of men who received suboptimal antimicrobial therapy suggests that the most effective therapy available should be given at the first visit. Medicine (Baltimore), 1999 Jan, 78(1), 38 - 63 Lymphocutaneous syndrome . A review of non-sporothrix causes; Smego RA Jr et al.; The lymphocutaneous syndrome can be caused by a number of diverse microorganisms requiring very different antimicrobial therapy for resolution . The epidemiology and geographic occurrence of the infection often can provide important first clues to the microbiologic etiology . Accurate diagnosis can be accomplished usually by punch or wedge biopsy of a primary lesion or proximal subcutaneous nodule submitted for histopathologic examination and culture . The microbiology laboratory staff should be alerted to the diagnostic possibilities so that appropriate cultural and incubation techniques, procedures, and precautions can be initiated . Provision of a correct microbiologic diagnosis and institution of appropriate antimicrobial therapy will result in a complete cure in almost all instances . Adjunctive surgical debridement may be required for certain organisms such as Nocardia or Mycobacterium chelonae. Arch Histol Cytol, 1998 Dec, 61(5), 427 - 32 Immunohistochemical localization of secretory immunoglobulins in the main excretory duct of the human submandibular gland; Perra MT et al.; The localization of IgA, IgG, and IgM was investigated immunohistochemically in the mucosal surface of the main excretory duct of the human submandibular gland in order to verify the possible antimicrobial properties of this duct . Only secretory IgA-immunoreactivity was recognized in the epithelial cells of the duct . An intense immunoreactivity was observed in the cytoplasm of some cells and at the luminal surface of most of the cells . Clusters of IgA-positive immuno-competent cells were also recognizable in the subepithelial layers . No reactivity for IgG and IgM was noticed . The results suggest that the ductal epithelium may actively be involved in the release of secretory IgA, which could play a prominent role in the local defense mechanism of the duct. J Cell Physiol, 1999 Mar, 178(3), 379 - 86 SP-A as a cytokine: surfactant protein-A-regulated transcription of surfactant proteins and other genes; Korutla L et al.; Pulmonary surfactant is a mixture of phospholipids and surfactant-associated proteins made by alveolar type II cells that is necessary for normal lung function . Surfactant secretion and reuptake by type II cells are regulated in part by interaction of surfactant protein-A (SP-A) with a specific receptor (SPAR) on type 11 cells . Several chemicals and hormones affect both surfactant secretion and also surfactant gene expression, but consequences of SP-A-SPAR interaction beyond regulating surfactant secretion and reuptake are unknown . Accordingly, we studied the effects of SP-A on surfactant protein gene transcription, mRNA levels, and transcript stability . SP-A elicited new transcription of surfactant proteins SP-A, SP-B, and SP-C and SPAR and c-Jun but had no effect on beta-actin or c-fos transcription . Antibody against SP-A receptor blocked SP-A-induced transcription, confirming that these actions of SP-A were receptor-mediated . SP-A effects on overall transcript levels were more complex . However, SP-A, SP-B, and SP-C mRNA levels doubled in SP-A-treated cells compared to controls . SP-A is known to stabilize surfactant, control its secretion and reuptake by type II cells, and augment host antimicrobial defenses . These data indicate that SP-A also acts as an autocrine cytokine: it binds its receptor and specifically regulates transcription of surfactant proteins and other genes. Brain Pathol, 1999 Jan, 9(1), 57 - 67 Oxidative stress in bacterial meningitis; Koedel U et al.; Fifty years after the advent of antibiotics for clinical use, the rates of morbidity and mortality associated with bacterial meningitis remain high . The unfavourable clinical outcome is often due to intracranial complications including cerebrovascular insults, raised intracranial pressure, hydrocephalus, and brain edema . Reactive oxygen species (ROS) are known effector molecules in the antimicrobial armature of polymorphonuclear and mononuclear phagocytes . However, over the last decade, there has been a substantial body of work implicating a central role of ROS in the development of intracranial complications and brain damage in bacterial meningitis . Recently, it also became evident that reactive nitrogen species (RNS), especially nitric oxide, are important mediators of meningitis-associated pathophysiological changes, at least during the early phase of the disease . There is now substantial evidence that much of the oxidative injury associated by simultaneous production of superoxide and nitric oxide is mediated by the strong oxidant peroxynitrite . ROS and peroxynitrite can be cytotoxic via a number of independent mechanisms . Their cytotoxic effects include initiation of lipid peroxidation and induction of DNA single strand breakage . Damaged DNA activates poly(ADP-ribose) polymerase (PARP) . Recent experimental data propose a role of lipid peroxidation and PARP activation in the development of meningitis-associated intracranial complications and brain injury . Agents which interfere with the production of ROS and peroxynitrite, as well as with PARP activation and lipid peroxidation may represent novel, therapeutic strategies to limit meningitis-associated brain damage, and, thus, to improve the outcome of this serious disease. Zentralbl Bakteriol, 1998 Dec, 288(4), 441 - 9 Characterization of the periodontal microflora by the fatty acid profile of the broth-grown microbial population; Muller KD et al.; The applicability of fatty acid analysis to the characterization of periodontal microflora was investigated using gas-liquid chromatography (GLC) and the software of the Sherlock Microbial Identification System (MIS) from MIDI Inc . Sulcus fluid was collected with paper points and anaerobically cultured in broth at 35 degrees C for four days . The broth-grown microbial population was extracted and the fatty acid methyl esters (FAME) were separated by GLC . The investigation of 67 specimens from asymptomatic sulci and of 32 specimens from inflamed sulci showed that the patterns of FAME profiles, the clustering of FAME profiles by computerized 2-D plot procedure, and the determination of the peak area index (PAI) of the FAME profiles differentiate between normal and pathological sulcus flora . Comparison of the clinical sulcus rating and the FAME data indicated that a pathological FAME profile may precede manifest periodontitis, and the normalization of the FAME profile may precede healing . It is concluded that the FAME analysis of sulcus fluid is a diagnostic aid for periodontological surveillance, for the initiation of preventive treatment of periodontitis, and for controlling the antimicrobial efficiency of therapeutic measures. Med Mycol, 1998, 36 Suppl 1, 129 - 36 Selected animal models: vaginal candidosis, Pneumocystis pneumonia, dermatophytosis and trichosporosis; Sobel JD et al.; A clear understanding of the pathogenesis of fungal disease remains elusive . While technological advances in molecular biology and microbial genetics have provided scientists with major new insights into both microbial virulence factors as well as host susceptibility to infection, there is currently no substitute for animal models in elucidating microbe-host interactions . Animal models are also essential for the evaluation of new antimicrobial agents, including studies of efficacy, adverse reactions and pharmacokinetics . The single most important advance in animal models in the last decade, has been the availability of genetically unique strains of animals as alternative to animals treated with immunosuppressive drugs for use in studies on microbial virulence and host defence mechanisms . These unique strains of test animals also enhance our understanding of the modes of action of antifungal drugs and their metabolism . Some of these advances will be discussed in this symposium. Med Mycol, 1998, 36 Suppl 1, 26 - 37 Nocardia, nocardiosis and mycetoma; Boiron P et al.; The recent emergence of invasive infections due to Nocardia spp., including nosocomial outbreak, is now evident . Newer molecular diagnostic and typing methods are developed . Although sulfonamide-based therapy is generally effective, optimal treatment may be guided by antimicrobial susceptibility testing of isolates . The improved classification of nocardiae and other related genera such as actinomadurae, using the 16S ribosomal RNA sequencing, provide a sound basis for improved diagnostic methods for the identification of members of clinically significant species . The commonest cause of eumycetoma in Sudan is Madurella mycetomatis, and Streptomyces somaliensis and Actinomadura madurae for actinomycetoma . The humoral immunity response in actinomycetoma patients and in experimental mice was measured and significant titre of anti-P24 antibody was demonstrated. Compr Ther, 1999 Jan, 25(1), 20 - 9 Antimicrobial resistance in community-acquired respiratory tract pathogens; Lark RL et al.; Antimicrobial resistance among common respiratory pathogens has become a significant problem . However, there remain multiple treatment options, including the newer macrolides, third-generation cephalosporins, beta-lactam/beta-lactamase inhibitor antibiotics, and the newer fluoroquinolones. J Immunol, 1999 Feb 1, 162(3), 1851 - 8 CD1 expression by dendritic cells in human leprosy lesions: correlation with effective host immunity; Sieling PA et al.; A potential role for the CD1 family of lipid Ag-presenting molecules in antimicrobial immunity in vivo was investigated in human leprosy skin lesions . Strong induction of three CD1 proteins (CD1a, -b, and -c) was observed in dermal granulomas in biopsy samples of involved skin from patients with the tuberculoid form of leprosy or with reversal reactions, which represent clinical patterns of disease associated with active cellular immunity to Mycobacterium leprae . In contrast, lesions from patients with the le