Bactericidal

Nippon Rinsho, 2001 Apr, 59(4), 750 - 5
{Clinical characteristics of emerging multiple-drug-resistant gram-negative rods producing extended-spectrum beta-lactamases (ESBLs)}; Yamaguchi T et al.; The prevalence of organisms producing extended-spectrum beta-lactamases(ESBLs) has been increasing all over the world . ESBLs confer resistance to cefotaxime, ceftazidime, aztreonam, extended-spectrum penicillins, and structurally related beta-lactams in clinical isolates of K . pneumoniae and E . coli . Under the influence of antimicrobial agents, bacteria that primarily produce TEM-type or SHV-type beta-lactamases developed point mutations in structural genes which served to extend the substrate specificity of the enzymes . Infections caused by ESBLs producing isolates are difficult to detect with current susceptibility tests, and are difficult to treat . This article provides an historical overview of the emergence of ESBLs carrying gram-negative rods and consider how to treat their infections.

Nippon Rinsho, 2001 Apr, 59(4), 660 - 5
{Molecular biology of the mechanism of acquisition of antimicrobial-resistance}; Hashimoto H; There are two ways for a bacterium to acquire antimicrobial-resistance: 1) Horizontal transfer of resistance gene(s) from outside, 2) Mutation of its own chromosome . The former case includes conjugation, transduction and transformation . Resistance genes usually locate on transposon or integron and have inverted or direct repeats on both sides, or link to a special sequence at one side . A target of an antibiotic is an essential enzyme for the bacterium to survive, and the corresponding gene is located on the chromosome . The mutation of the essential gene may cause resistance to antimicrobials by decreasing the affinity of enzyme to the drug . The mutation of genes for drug influx or efflux also causes antimicrobial resistance.

Nippon Rinsho, 2001 Apr, 59(4), 645 - 51
{Present situation of drug resistance and future prospects}; Inoue M et al.; Antibiotic resistance has evolved over 60 years from a merely microbiological curiosity to a serious medical problem in hospitals . Resistance has been reported in almost all species of bacteria to various classes of antimicrobial agents including recently evaluated ones . Bacteria regulated resistance by different mechanisms . Inappropriate use of an antimicrobial agent selects resistant strains much more frequently . Since it is not expected that some epoch-making new antimicrobial agents will be developed in the near future, proper use of existing antimicrobial agents which is based on the mechanisms of action of antimicrobial agents and of resistance of bacteria, and of control of nosocomial infection are very important to reduce the further spread of resistant bacteria . With the search for natural sources of new antimicrobial substances now appearing frustrated, the genomic approach in the 21st century may be the only fruitful way to develop truly novel chemotherapeutic agents against bacterial diseases.

Arzneimittelforschung, 2001, 51(3), 264 - 7
Antimicrobial activity of thiamphenicol-glycinate-acetylcysteinate and other drugs against Chlamydia pneumoniae; Lombardi A et al.; Chlamydia pneumoniae is responsible for respiratory tract infections of both upper and lower respiratory tract . Although this bacterium is one of the most wide-spread pathogens of man, there are limited data on the antibiotic treatment of C . pneumoniae infections . The aim of this study has been to evaluate the in vitro activity of thiamphenicol glycinate acetylcysteinate (TGA, CAS 20192-91-0) in comparison with molecules with established activity against C . pneumoniae, as well as macrolides and quinolones . The results have shown that TGA and clarithromycin (CAS 81103-11-9) are the most active drugs tested, but it is important to underline that the minimal inhibitory concentration (MIC) ranges of TGA are very much lower than the breakpoint of thlamphenicol for the respiratory pathogens . In conclusion, the good antimicrobial in vitro activity of TGA against C . pneumoniae together with its in vivo characteristics, in particular the high concentration reached in lung and the combination with the mucolytic agent N-acetylcysteine (NAC, CAS 616-91-1), can make a valid choice in the treatment of respiratory tract infections caused by C . pneumoniae . These findings need further evaluation by clinical studies.

Am J Ther, 2000 Nov, 7(6), 393 - 8
Osteoarticular tuberculosis: current diagnosis and treatment; Sequeira W et al.; Tuberculous synovitis frequently presents as a monoarthritis of weight-bearing joints such as the hip, knee, or ankle . Owing to its low incidence in developed countries, the diagnosis is often delayed for months to years . Early diagnosis with a synovial biopsy permits prompt antituberculous therapy and substantially improves the prospect of preservation of joint structure and function . Initial treatment typically includes combination therapy with four drugs (isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol) because of the frequency of isoniazid resistance . Antimicrobial therapy should be of at least 9 months' duration, longer in immunocompromised hosts . Partial synovectomy and other surgical procedures should be restricted to joints with severe cartilage destruction, large abscesses, joint deformity, multiple drug resistance, or atypical mycobacteria.

Pediatr Infect Dis J, 2001 Mar, 20(3), 362 - 9
Comparative study of cefepime versus ceftazidime in the empiric treatment of pediatric cancer patients with fever and neutropenia; Mustafa MM et al.; BACKGROUND: In view of the recent trend toward monotherapy in the treatment of bacterial infection, we evaluate the clinical efficacy and safety of cefepime vs . ceftazidime for the empiric treatment of febrile episodes in neutropenic pediatric cancer patients . METHODS: In a single site, open label study, 104 neutropenic pediatric cancer patients {96% with absolute neutrophil count (ANC) of <500 neutrophils/mm3} with a median age of 6 years were randomized (1:1) to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose every 8 h; < or = 6 g/day) for empiric treatment of fever (temperature >38.0 degrees C occurring at least twice in 24 h, or single >38.5 degrees C) . Febrile episodes were classified as either microbiologically or clinically documented infection or fever of unknown origin . Therapy continued until the ANC was > or = 1,000 neutrophils/mm3 or there was an increasing ANC in low risk patients (maximum duration of treatment, 8 weeks) . The primary efficacy endpoints assessed were clinical and microbiologic response to assigned drug therapy . Secondary outcome measures were rate of early discontinuation of study drug and use of concomitant antibiotic therapy to modify initial study drug regimen . RESULTS: Of 68 patients who could be evaluated for efficacy, 74% (26 of 35) of cefepime-treated patients and 70% (23 of 33) of ceftazidime-treated patients responded to treatment . The small number of study patients precluded statistical analysis of results . In a modified intent-to-treat analysis, 59% of the patients treated with cefepime and 47% of ceftazidime-treated patients responded to therapy . Cefepime patients developed fewer new infections than ceftazidime patients (9% vs . 21%, respectively) and early discontinuation of study drug therapy occurred slightly more often in the ceftazidime group . Further, the use of concomitant systemic antimicrobial therapy (mostly vancomycin) occurred less often in the cefepime-treated patients, as compared with the ceftazidime group {35% {17 of 49} vs . 44% (24 of 55), respectively} . No deaths or serious adverse events were considered to be related to study therapy . The most frequent adverse event was rash that was moderate in severity, and it occurred equally in both groups . CONCLUSION: Cefepime appears to be safe and effective compared with ceftazidime for initial empiric therapy of febrile episodes in neutropenic pediatric cancer patients.

Scand J Infect Dis, 2001, 33(3), 219 - 21
Influence of an infectious disease consulting service on quality and costs of antibiotic prescriptions in a university hospital; Lemmen SW et al.; An infectious disease consulting service was set up at a large tertiary university hospital in 1996 to evaluate and to improve antibiotic prescription patterns . Treatment guidelines for the most common bacterial infections were implemented . On daily ward rounds antibiotic therapies without evidence of an infectious disease were stopped and inappropriate regimens were changed by an infectious disease specialist . During a 6-month prospective intervention period, 3,528 patients were studied on 13 wards of the department of internal medicine; 513 of these patients (14.5%) received antibiotic therapy . These treatment courses were evaluated as adequate in 394 cases (76.8%) and incorrect in 119 cases (23.2%) . Inadequate antibiotic substances were chosen in 72 out of 119 cases (60.5%) and there was no indication for treatment in 38 out of 119 cases (32%) . Pathogen-specific therapies were inadequate significantly more often than empirical antimicrobial therapies (p < 0.001) . In addition, the duration of the perioperative prophylaxis could be limited to 1 d . Comparing the intervention period with a 3-month control interval without an infectious disease consulting service, a total of 31,510 Euro (including the costs for the infectious disease specialist) could be saved . No increase in infection-related mortality or length of stay was observed . These data show that an infectious disease consulting service optimizes antibiotic usage, and is cost-effective as a result of a significant cost reduction in hospitals, while not interfering with the quality of medical care.

Scand J Infect Dis, 2001, 33(3), 211 - 4
Pulmonary imaging and function in the common cold; Puhakka T et al.; The common cold is generally considered to be an upper respiratory tract infection . We studied the lower respiratory tract in 76 otherwise healthy young adults with the common cold . Viral infection was diagnosed in 56 (74%) of the 76 subjects . Rhinovirus was detected in 42 (55%) subjects . Chest radiography (CR) and high-resolution computerized tomography (HRCT) were carried out in 40 subjects on day 7, and pulmonary function testing with bronchodilator challenge was carried out in 36 patients on days 7 and 21 of the study . Clinical examinations were carried out on days 1, 7 and 21 . The subjects recorded their symptoms on a diary card for 20 d . The mean duration of cough was 8.4 (SD 6.5) d and that of sputum production 5.9 (SD 6.4) d . No abnormal findings were detected in the lungs on auscultation . CR and HRCT showed no pulmonary changes associated with the common cold . No clinically remarkable increases were seen in peak expiratory flow, forced expiration volume in 1 s or forced vital capacity after bronchodilator challenge on either days 7 or 21 . All patients made a clinical recovery without antimicrobial therapy within 21 d . We conclude that the common cold in young otherwise healthy adults is an upper respiratory tract infection and that clinically important abnormalities in the lower respiratory tract are rare.

Scand J Infect Dis, 2001, 33(3), 200 - 5
Limited diagnostic usefulness of antibodies to cytoplasmic proteins of Brucella in early-treated human brucellosis; Baldi PC et al.; Antibodies to cytoplasmic proteins (CP) of Brucella have been shown to be useful for the diagnosis of human brucellosis; however, some early-diagnosed patients lack such an antibody response while having high titers of antibodies to lipopolysaccharide (LPS) . To address which factors determine this serological discrepancy in the early stages of brucellosis we examined the antibody response to CP and LPS of 21 patients involved in an outbreak of B . melitensis infection who had a short duration of clinical illness at diagnosis (3-40 d) . At diagnosis, antibodies to LPS (IgM and/or IgG) were found in all patients, while anti-CP antibodies were detected in 16 subjects (76%) . At 6 weeks post-diagnosis IgG to CP (with or without IgM) had been detected in 13 patients and IgM alone had been found in 4; however, 4 other patients (19%) had no response to CP . No significant differences were found between these 3 groups in terms of age, gender, antimicrobial agents or factors that could hamper the immune response . Notably, however, the 4 non-responders and 3 of the 4 patients having only IgM to CP had started antibiotic therapy within 14 d post-symptoms, while treatment was started later in 9 of 13 patients who developed anti-CP IgG . In addition, maximum titers of IgG to CP tended to be lower in early-treated patients . These results suggest that very early antibiotic therapy hampers the antibody response to Brucella CP but has little impact on the anti-LPS response . Given the higher specificity of the former and the higher sensitivity of the latter, both reactivities should be measured in order to diagnose human brucellosis.

Clin Infect Dis, 2001 May 1, 32(9), 1281 - 9 Epub 2001 Apr 10.
Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired lower respiratory tract infections; Principi N et al.; In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs) . The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999 . Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M . pneumoniae and C . pneumoniae antibodies . Nasopharyngeal aspirates for the detection of M . pneumoniae and C . pneumoniae were obtained on admission . Acute M . pneumoniae infections in 210 patients (34.3%) and acute C . pneumoniae infections in 87 (14.1%) were diagnosed . Fifteen of the 18 children with M . pneumoniae and/or C . pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides . Our study confirms that M . pneumoniae and/or C . pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.

Antimicrob Agents Chemother, 2001 May, 45(5), 1581 - 4
Antimicrobial susceptibilities of unique Stenotrophomonas maltophilia clinical strains; Valdezate S et al.; Susceptibility to 41 antimicrobials was studied with 99 Stenotrophomonas maltophilia strains, and different pulsed-field gel electrophoresis profiles were identified among 130 prospectively collected isolates . Moxalactam, doxycycline, minocycline, and clinafloxacin displayed the highest activity (> or = 98% susceptibility) . Ticarcillin resistance (75%) was reverted by clavulanate in 25% of strains . Trimethoprim-sulfamethoxazole resistance was 26.2% (> or = 4 {trimethoprim}/76 {sulfamethoxazole} microg/ml) and dropped to 11.1% when an 8/152-microg/ml breakpoint was applied based on its bimodal MIC distribution . Resistance was lower when unique strains were considered, because clonal organisms contribute to resistance.

Antimicrob Agents Chemother, 2001 May, 45(5), 1558 - 60
Synergistic interactions between mammalian antimicrobial defense peptides; Yan H et al.; A single animal can express several cationic antimicrobial peptides with different sequences and structures . We demonstrate that mammalian peptides from different structural classes frequently show synergy with each other and selectively show synergy with human lysozyme.

Antimicrob Agents Chemother, 2001 May, 45(5), 1450 - 5
Inhibition of intramacrophage growth of Penicillium marneffei by 4-aminoquinolines; Taramelli D et al.; The antimicrobial activities of chloroquine (CQ) and several 4-aminoquinoline drugs were tested against Penicillium marneffei, an opportunistic fungus that invades and grows inside macrophages and causes disseminated infection in AIDS patients . Human THP1 and mouse J774 macrophages were infected in vitro with P . marneffei conidia and treated with different doses of drugs for 24 to 48 h followed by cell lysis and the counting of P . marneffei CFU . CQ and amodiaquine exerted a dose-dependent inhibition of fungal growth, whereas quinine and artemisinin were fungistatic and not fungicidal . The antifungal activity of CQ was not due to an impairment of fungal iron acquisition in that it was not reversed by the addition of iron nitrilotriacetate, FeCl3, or iron ammonium citrate . Perl's staining indicated that CQ did not alter the ability of J774 cells to acquire iron from the medium . Most likely, CQ's antifungal activity is due to an increase in the intravacuolar pH and a disruption of pH-dependent metabolic processes . Indeed, we demonstrate that (i) bafilomycin A1 and ammonium chloride, two agents known to alkalinize intracellular vesicles by different mechanisms, were inhibitory as well and (ii) a newly synthesized 4-amino-7-chloroquinoline molecule (compound 9), lacking the terminal amino side chain of CQ that assists in drug accumulation, did not inhibit P . marneffei growth . These results suggest that CQ has a potential for use in prophylaxis of P . marneffei infections in human immunodeficiency virus-infected patients in countries where P . marneffei is endemic.

Biochem Biophys Res Commun, 2001 Apr 20, 282(5), 1224 - 8
Purification and characterization of three antifungal proteins from cheeseweed (Malva parviflora); Wang X et al.; Three potent antimicrobial proteins were purified from cheeseweed (Malva parviflora) seeds . These antimicrobial proteins, named CW-3, CW-4, and CW-5, showed different antimicrobial spectrum and potency compared to the two heterologous antimicrobial proteins (CW-1 and CW-2) purified previously . CW-3 and CW-4 possess antimicrobial activities against Phytophthora infestans (Pi), but not Fusarium graminearum (Fg) . A database search indicated that CW-3 shares high homology to cotton vicilin, an abundant seed storage protein . CW-4 shares homology to 2S albumin, another seed storage protein from cotton . CW-5 has antimicrobial activity against Fg, but no activity against Pi was observed at protein concentration up to 50 ppm . Under low salt condition, CW-5 showed potent antimicrobial activity against Fg, but under high salt condition, the antimicrobial activity was drastically diminished . Database search indicated that CW-5 has high homology to a lipid transfer protein from grape . The IC(50) values of the three purified antimicrobial proteins under both low and high salt conditions were determined . The isolation of five antimicrobial proteins for the first time from a single plant source provides further understanding of the plant innate defense system and insight on how plants evolve their complex and complementary antimicrobial system that is important in the early stage of development .

Ann Pharmacother, 2001 Apr, 35(4), 480 - 8
Pneumococcal resistance: the treatment challenge; Amsden GW et al.; OBJECTIVE: To review in vitro and in vivo information dealing with pneumococcal antibiotic resistance and provide a review of the incidence, mechanisms, and controversies surrounding this growing problem . The review is also intended to provide clinicians with relevant recommendations on treatment and prevention of this organism . DATA SOURCES AND SELECTION: Primary and review articles were identified by MEDLINE search (1966-August 2000) and through secondary resources such as conference proceedings . All of the articles identified from the data sources were evaluated, and all information deemed relevant was included in this review . DATA SYNTHESIS: The growing incidence and reporting of pneumococcal isolates that are resistant to one or more classes of antibiotics have become a troubling trend that has resulted in significant shifts in treatment . Although clinicians have shifted to a new generation or class of antibiotics when faced with a resistance trend, data with resistant pneumococci show that this may not be necessary . By incorporating the pharmacokinetic and pharmacodynamic data of antimicrobials into the decision-making process, many of the drugs that we have become hesitant to use due to this resistance may still be appropriate if used correctly . CONCLUSIONS: Appropriate dosing of antimicrobials, combined with optimal use of pneumococcal vaccines, will not only prolong the longevity of some agents, but also hopefully slow resistance development.

Z Naturforsch {C}, 2001 Jan-Feb, 56(1-2), 49 - 52
New semisynthetic antimicrobial labdane-type diterpenoids derived from the resin "ladano" of Cistus creticus; Kalpoutzakis E et al.; The antimicrobial activity of fifteen semisynthetic labdane-type diterpenes derived from the two major natural compounds 3 and 4 of the resin "ladano" of Cistus creticus is reported . The chloroethyl carbamidic esters 15 and 20 showed the strongest antimicrobial activity against Gram(+), Gram(-) bacteria and pathogenic fungi.

Z Naturforsch {C}, 2001 Jan-Feb, 56(1-2), 106 - 10
Mariannaepyrone--a new inhibitor of thromboxane A2 induced platelet aggregation; Fabian K et al.; Mariannaeapyrone ((E)-2-(1,3,5,7-tetramethyl-5-nonenyl)-3,5-dimethyl-6-hydroxy-4H-pyran-4-one) is a new fungal metabolite isolated from fermentations of the common mycophilic deuteromycete Mariannaea elegans . The chemical structure of the 4-pyrone was determined by spectroscopic techniques . Mariannaeapyrone is a selective inhibitor of the thromboxane A2 induced aggregation of human platelets, whereas only weak cytotoxic and antimicrobial effects could be observed.

Biochemistry, 2001 Apr 3, 40(13), 3810 - 6
The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment; Sawai MV et al.; Human beta-defensin-2 (HBD-2) is a member of the defensin family of antimicrobial peptides . HBD-2 was first isolated from inflamed skin where it is posited to participate in the killing of invasive bacteria and in the recruitment of cells of the adaptive immune response . Static light scattering and two-dimensional proton nuclear magnetic resonance spectroscopy have been used to assess the physical state and structure of HBD-2 in solution . At concentrations of < or = 2.4 mM, HBD-2 is monomeric . The structure is amphiphilic with a nonuniform surface distribution of positive charge and contains several key structural elements, including a triple-stranded, antiparallel beta-sheet with strands 2 and 3 in a beta-hairpin conformation . A beta-bulge in the second strand occurs at Gly28, a position conserved in the entire defensin family . In solution, HBD-2 exhibits an alpha-helical segment near the N-terminus that has not been previously ascribed to solution structures of alpha-defensins or to the beta-defensin BNBD-12 . This novel structural element may be a factor contributing to the specific microbicidal or chemokine-like properties of HBD-2.

Anticancer Res, 2001 Jan-Feb, 21(1A), 275 - 80
In vitro biological activity of prenylflavanones; Shirataki Y et al.; The biological activity of ten prenylflavanones purified from Sophora tomentosa L., and Sophora moorcroftiana Benth . ex Baker (Leguminosae) was investigated . The flavanones with prenyl-, lavandulyl- or geranyl groups on A ring, and two bioactive flavonostilbenes on ring B and stilbene (resveratrol) showed tumor-specific cytotoxic activity, antimicrobial activity, and anti-HIV activity, radical generation, and O2- scavenging activity . There was a positive relationship between radical generation and O2- scavenging activity in these prenylflavanones . These data suggest the medicinal significance of prenylflavanones.

J Pept Res, 2001 Mar, 57(3), 240 - 9
A novel bovine lactoferrin peptide, FKCRRWQWRM, suppresses Candida cell growth and activates neutrophils; Ueta E et al.; To identify potent new antifungal agents, the Candida cell growth inhibitory activities of six lactoferrin (Lf) peptides consisting of 6-25 amino acid residues (peptide 1, FKCRRWQWRMKKLGAPSITCVRRAF lactoferricin B; peptide 2, FKCRRWQWRM; peptide 2', FKARRWQWRM; peptide 3, GAPSITCVRRAF; peptide 4, RRWQWR; and peptide 5, RWQWRM) were examined . Of these, peptide 2 strongly suppressed the multiplication of Candida cells, but other peptides showed only weak activities . In two strains of C . albicans, the minimum inhibitory concentration 100 of peptide 2 (17.3+/-2.2 microM and 17.5+/-2.4 microM) was close to that of miconazole (13.0+/-1.7 microM and 13.1+/-1.6 microM) but markedly different from that of amphotericin B (0.52+/-0.09 microM and 0.56+/-0.11 microM) . The suppression of Candida cell growth was additively increased by a combination of peptide 2 with amphotericin B and miconazole . Peptides 1, 3, 4 and 5 and Lf suppressed iron uptake by Candida cells, inversely correlated with their Candida cell growth inhibition activities . However, iron uptake was not inhibited by peptide 2 . In addition, peptide 2 upregulated Candida cell killing activity of polymorphonuclear leukocytes (PMN) increasing their superoxide generation, protein kinase C activity, p38 MAPK activity and the expression of p47phox . These results indicated that the main antimicrobial activity of the Lf peptides is dependent on the N-terminal half of Lf and that the PMN upregulatory activity of peptide 2 and additive function of peptide 2 with antifungal drugs are useful for prophylaxis and control of candidiasis.

J Pept Res, 2001 Mar, 57(3), 175 - 87
Synthesis and characterization of the colistin peptide polymyxin E1 and related antimicrobial peptides; Kline T et al.; Two strategies were developed to synthesize the acylated cyclic peptides know as polymyxins . Synthesis of polymyxin E1 and several analogs enabled us to evaluate the minimum inhibitory concentration of individual compounds against Gram-negative bacteria . In this study we also report the first identification of two component peptides in the complex polymyxin fermentation product colistin, a Thr2Ser isoform and an acyl group isomer . Both of these peptides, as well as a known component peptide, Leu7Ile, were similar to polymyxin E1 in potency, suggesting that conservative mutations in the colistin family are functionally inconsequential . In contrast, the acyclic analogs of all of these peptides were inactive, indicating that the characteristic lariat structure of the polymyxins is necessary for antimicrobial activity.

Cell Microbiol, 2001 Apr, 3(4), 247 - 54
Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry; Chitale S et al.; The ability to gain entry and resist the antimicrobial intracellular environment of mammalian cells is an essential virulence property of Mycobacterium tuberculosis . A purified recombinant protein expressed by a 1362 bp locus (mce1) in the M . tuberculosis genome promoted uptake into HeLa cells of polystyrene latex microspheres coated with the protein . N-terminus deletion constructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity . Mce1 contained hydrophobic stretches at the N-terminus predictive of a signal sequence, and colloidal gold immunoelectron microscopy indicated that the corresponding native protein is expressed on the surface of the M . tuberculosis organism . The complete M . tuberculosis genome sequence revealed that it contained four homologues of mce (mce1, mce2, mce3, mce4) and that they were all located within operons composed of genes arranged similarly at different locations in the chromosome . Recombinant Mce2, which had the highest level of identity (67%) to Mce1, was unable to promote the association of microspheres with HeLa cells . Although the exact function of Mce1 is still unknown, it appears to serve as an effector molecule expressed on the surface of M . tuberculosis that is capable of eliciting plasma membrane perturbations in non-phagocytic mammalian cells.

Br J Dermatol, 2001 Apr, 144(4), 769 - 74
Mixed immunobullous disease of childhood: a good response to antimicrobials; Powell J et al.; BACKGROUND: Immunobullous diseases are uncommon in childhood . In contrast to adults, the most commonly seen is IgA-mediated chronic bullous disease of childhood (CBDC), while IgG-mediated bullous pemphigoid (BP), cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA) are rare . We have demonstrated both IgG and IgA autoantibodies to basement membrane zone target antigens in eight children with 'mixed immunobullous disease of childhood' . OBJECTIVES: To elucidate whether a dual antibody response makes these patients distinct regarding their presentation, immunopathology, course and prognosis . METHODS: We compared the eight children showing the double antibody response with 62 children with CBDC, BP, CP and EBA in whom only one antibody isotype was demonstrated . Clinical information at presentation, clinical course and response to treatment were recorded, and immunoblotting and direct and indirect immunofluorescence (IF) were performed . RESULTS: Six of the eight patients presented with clinical features of CBDC . In two others, it was uncertain whether they had CBDC or BP . Seven of the eight demonstrated a dual antibody response on indirect IF and three on direct IF . Immunoblotting revealed a variety of epidermal and dermal target antigens (BP230, BP180, 97-kDa protein and laminin 5) . Five of the eight responded well to dapsone, two to sulphonamides, and one to systemic erythromycin alone . The clinical course was not protracted . Five are in remission 1-4 years following treatment, and three still have active disease suppressed by treatment after 6 months-2 years . CONCLUSIONS: Although we do not know why these children have 'mixed immunobullous disease' (the dual antibody response), our results indicate that the presence of IgA is associated with a good response to treatment with antimicrobials (dapsone, sulphonamides, erythromycin), and the clinical course is no more protracted than that found in children with a single antibody response.

Am J Med Genet, 2001 Apr 22, 100(2), 145 - 51
Deficiency of the specific granule proteins, R-binder/transcobalamin I and lactoferrin, in plasma and saliva: a new disorder; Lin JC et al.; The mechanisms of hereditary deficiency of R binder, which originates in neutrophils and exocrine gland epithelium, are unknown and may be multiple . This led us to examine if defective R binder synthesis also involves proteins that colocalize with it in neutrophil-specific granules and exocrine epithelial cells and may be under common regulatory control . Stored plasma and saliva samples from five unrelated R binder-deficient patients and control subjects were assayed for R binder, lactoferrin, cationic antimicrobial protein-18, neutrophil gelatinase-associated lipocalin, gelatinase, lysozyme, and myeloperoxidase . One patient, patient A, had lactoferrin levels below the limits of detection in both plasma and saliva in addition to his R binder deficiency . Although his deficiency involved lactoferrin as well, he had no history of predisposition to infection . PCR amplification of his R binder gene promoter region and the beginning of the first exon revealed no DNA abnormalities . His son and the son of his equally deficient brother, both presumptive heterozygotes, had mild deficiency of both R binder and lactoferrin . The results show that R binder deficiency exists in at least two forms . One, presumably the less common of the two forms, is the new hereditary entity described here, which is characterized by deficiency of more than one specific granule protein in both plasma and saliva . Despite this more widely distributed absence of the proteins than is found in congenital specific granule deficiency, infection posed no clinical problem in the affected patient .

Eur J Immunol, 2001 Apr, 31(4), 1066 - 75
Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells; Niyonsaba F et al.; Antimicrobial peptides, human beta-defensins (hBD-1/-2), and LL-37 (a peptide of human cathelicidin CAP18) are predominately expressed at epithelial tissues, where they participate in the innate host defense by killing invading microorganisms . In this study, to investigate the interactions between epithelial cell-derived antimicrobial peptides and mast cells, we evaluated the effects of hBD-1/-2 and LL-37 on mast cell functions using rat peritoneal mast cells . hBD-2 and LL-37 but not hBD-1 induced histamine release and intracellular Ca(2+) mobilization, and hBD-2 was more potent than LL-37 . Interestingly, histamine release and intracellular Ca(2+) mobilization elicited by hBD-2 and LL-37 were markedly suppressed by BAPTA-AM (an intracellular Ca(2+) chelating agent), pertussis toxin and U-73122 (a phospholipase C inhibitor) . In addition, among the peptides examined, only hBD-2 significantly induced PGD(2) production, which was abolished by indomethacin (cyclooxygenase-1/-2 inhibitor) but not NS-398 (cyclooxygenase-2 inhibitor), suggesting that hBD-2-induced PGD(2) production is mediated by cyclooxygenase-1 . Likewise, the PGD(2) production was suppressed by pertussis toxin and U-73122 . These observations suggest that hBD-2 and LL-37 stimulate mast cells to mobilize intracellular Ca(2+) and release histamine or generate PGD(2) in a G protein-phospholipase C-dependent manner . Thus, hBD-2 and LL-37 may have modulatory effects on inflammatory reactions.

Allergy, 2001, 56 Suppl 67, 43 - 4
Plant food allergens homologous to pathogenesis-related proteins; Ebner C et al.; In general, pathogenesis-related (PR) proteins are expressed by plants in response to stress conditions like infection, exposure to certain chemicals, wounding and environmental conditions . In some plant tissues, however, PR proteins are constitutively expressed, e.g . in pollens or fruits, tissues that are more likely to be attacked (by insects or fungi) or exposed to atmospheric conditions (e.g . UV irradiation) . PR proteins display multiple effects within the plant and possess antimicrobial activity, and can thus be regarded as a part of the plant's defense system . Analyzing known amino acid sequences and functions of characterized (cloned) food allergens, it is remarkable that many of these molecules can be classified as PR proteins . Many PR proteins are stable at low pH, and display considerable resistance to proteases, requirements to act as food allergens . According to sequence characteristics and their enzymatic or biologic activity, PR proteins can be divided into 14 groups . Seven of these 14 groups contain proteins with allergenic properties, six groups contain food allergens.

J Rheumatol, 2001 Mar, 28(3), 601 - 3
Comparison of viral antibodies in 2 groups of patients with fibromyalgia; Wittrup IH et al.; OBJECTIVE: The etiologies of fibromyalgia (FM) are unknown . In some cases an acute onset following a flu-like episode is described; in other cases patients report slowly developing disease . We previously found increased prevalence of enterovirus IgM antibodies in patients with acute onset of FM compared to healthy controls . We looked for differences in antimicrobial IgM antibodies in acute versus nonacute onset FM . METHODS: Two well defined, comparable groups of patients with FM (acute 19, nonacute 20) were studied for antibodies in serum to an array of viruses including IgM antibodies . RESULTS: In most viruses no IgM antibodies were found . However, about 50% of the patients with acute FM onset had IgM antibodies against enterovirus compared to only 15% of the slow onset patients . CONCLUSION: The higher prevalence of IgM antibodies against enterovirus in patients with acute onset of FM may indicate a difference in the etiology or the immune response in these patients.

Nihon Kokyuki Gakkai Zasshi, 2001 Jan, 39(1), 12 - 6
{Beta-defensins in plasma and bronchoalveolar lavage fluid in patients with non-tuberculous mycobacterium infection}; Ashitani J et al.; We measured the levels of beta-defensin 1 and 2 (HBD-1, 2), novel antimicrobial peptides in plasma and in bronchoalveolar lavage fluid (BALF) from patients with with non-tuberculous mycobacterium infection (NTM) . Plasma HBD-2 levels in NTM patients before treatment were higher than those in the controls, while the HBD-1 levels were similar to the control levels . High levels of HBD-2, but not of HBD-1, in BALF were also observed in NTM patients . In NTM, a positive correlation was found between HBD-2 levels in BALF and plasma, and also between HBD-2 and IL-1 beta levels in BALF . NTM patients with cavities or ectasia on chest radiography had higher HBD-2 levels in BALF than those without . Plasma HBD-2 levels in NTM patients were markedly decreased after successful treatment, while those of patients with an intractable mycobacterium infection maintained the same high plasma HBD-2 levels as those before treatment . These findings suggest that HBD-2 may participate in the host defense and plasma HBD-2 levels may reflect disease activity in pulmonary NTM.

Chest, 2001 Apr, 119(4), 1131 - 7
Plasma and BAL fluid concentrations of antimicrobial peptides in patients with Mycobacterium avium-intracellulare infection; Ashitani J et al.; STUDY OBJECTIVES: To investigate the roles of human alpha-defensin (HAD), human beta-defensin (HBD)-1, and HBD-2, novel antimicrobial peptides, in patients with Mycobacterium avium-intracellulare infection (MAI) . PATIENTS: The study included 25 patients (10 men) with MAI who visited our hospital between June 1998 and August 1999 . MEASUREMENTS AND RESULTS: In patients with pulmonary MAI, we measured HAD and HBD-1, and HBD-2 levels in plasma and in BAL fluid (BALF) by radioimmunoassay . Plasma concentrations of HAD and HBD-2 in those patients were higher than those in control subjects, whereas HBD-1 levels were similar to those in the control subjects . High levels of HAD and HBD-2, but not HBD-1, also were observed in the BALF of MAI patients . There was a positive correlation between HAD and interleukin (IL)-8 concentrations in the BALF of patients with MAI . BALF HBD-2 concentrations also correlated positively with those of plasma HBD-2 and BALF IL-1 beta in MAI patients . Patients with cavity formation on the chest roentgenogram had higher HAD and HBD-2 levels in their BALF than those of patients without cavity formation . Treatment with clarithromycin combined with two or three other antibiotics, including ethambutol, rifampicin, ofloxacin, or ciprofloxacin, for at least 6 months resulted in a significant fall in plasma HBD-2 concentrations in responders, but not in nonresponders . CONCLUSION: Our findings suggest that HAD and HBD-2 may participate in host defense and local remodeling of the respiratory tract in patients with MAI and that plasma HBD-2 levels may be a useful marker of disease activity in patients with pulmonary MAI.

Fitoterapia, 2001 Mar, 72(3), 298 - 300
Antimicrobial activity of Harpullia ramiflora; Khan MR et al.; The methanol extracts of Harpullia ramiflora, leaves, flowers, stem and root barks were partitioned (petrol, dichloromethane, ethyl acetate) . In respect to crude extracts, all fractions demonstrated broader spectrum and higher levels of antibacterial activity . The ethyl acetate fraction of the flowers exhibited the highest activity . No activity was shown against the tested moulds.

Fitoterapia, 2001 Mar, 72(3), 286 - 7
Antimicrobial activity of Anacardium occidentale bark; Akinpelu DA; Anacardium occidentale bark 60% methanolic extract exhibited antimicrobial activity against 13 out of 15 bacterial isolates at a concentration of 20 mg/ml.

Fitoterapia, 2001 Mar, 72(3), 281 - 3
Antimicrobial activity of Omalanthus nervosus; Khan MR et al.; The ethanol extracts of Omalanthus nervosus leaves, stem and root barks, were partitioned (petrol, dichloromethane, ethyl acetate) . In respect to crude extracts, all fractions demonstrated broader spectrum and higher levels of antibacterial activity, ethyl acetate fractions being in all cases the more active . No fraction was active against tested moulds.

J Control Release, 2001 Apr 28, 71(3), 251 - 9
Novel periodontal drug delivery system for treatment of periodontitis; Bromberg LE et al.; A conceptually novel periodontal drug delivery system (DDS) is described that is intended for treatment of microbial infections associated with periodontitis . The DDS is a composite wafer with surface layers possessing adhesive properties, while the bulk layer consists of antimicrobial agents, biodegradable polymers, and matrix polymers . The wafers contain poly(lactic-co-glycolic acid) as the main bioerodible component used in the bulk layer and ethyl cellulose applied as a matrix polymer enabling diffusion-controlled release . Starch and other polymers in combination with AgNO(3) serve as coatings adhesive to the teeth . In vitro experiments demonstrate that the wafers are capable of zero-order release of antimicrobial agents such as silver nitrate, benzylpenicillin, and tetracycline, for over 4 weeks.

Emerg Infect Dis, 2001 Mar-Apr, 7(2), 348 - 53
New disinfection and sterilization methods; Rutala WA et al.; New disinfection methods include a persistent antimicrobial coating that can be applied to inanimate and animate objects (Surfacine), a high-level disinfectant with reduced exposure time (ortho-phthalaldehyde), and an antimicrobial agent that can be applied to animate and inanimate objects (superoxidized water) . New sterilization methods include a chemical sterilization process for endoscopes that integrates cleaning (Endoclens), a rapid (4-hour) readout biological indicator for ethylene oxide sterilization (Attest), and a hydrogen peroxide plasma sterilizer that has a shorter cycle time and improved efficacy (Sterrad 50).

Emerg Infect Dis, 2001 Mar-Apr, 7(2), 319 - 22
Building communication networks: international network for the study and prevention of emerging antimicrobial resistance; Richet HM et al.; The global nature of antimicrobial resistance and the failure to control the emergence of resistant organisms demand the implementation of a global surveillance program involving both developed and developing countries . Because of the urgent need for infection control interventions and for rapid distribution of information about emerging organisms, we initiated the International Network for the Study and Prevention of Emerging Antimicrobial Resistance (INSPEAR) . Its main objectives are to serve as an early warning system for emerging antimicrobial-drug resistant pathogens, to facilitate rapid distribution of information about emerging multidrug-resistant pathogens to hospitals and public health authorities worldwide, and to serve as a model for the development and implementation of infection control interventions.

Emerg Infect Dis, 2001 Mar-Apr, 7(2), 286 - 92
Economic impact of antimicrobial resistance; McGowan JE Jr; One reason antimicrobial-drug resistance is of concern is its economic impact on physicians, patients, health-care administrators, pharmaceutical producers, and the public . Measurement of cost and economic impact of programs to minimize antimicrobial-drug resistance is imprecise and incomplete . Studies to describe and evaluate the problem will have to employ new methods and be of large scale to produce information that is broadly applicable.

Emerg Infect Dis, 2001 Mar-Apr, 7(2), 231 - 3
Antiseptic technology: access, affordability, and acceptance; Boyce JM; Factors other than antimicrobial activity of soaps and antiseptic agents used for hand hygiene by health personnel play a role in compliance with recommendations . Hand hygiene products differ considerably in acceptance by hospital personnel . If switching from a nonmedicated soap to an antiseptic agent or increased use of an existing antiseptic agent for hand hygiene prevented a few more infections per year, additional expenditures for antiseptic agents would be offset by cost savings.

Emerg Infect Dis, 2001 Mar-Apr, 7(2), 205 - 7
Preventing infections in non-hospital settings: long-term care; Nicolle LE; Infection concerns in long-term care facilities include endemic infections, outbreaks, and colonization and infection with antimicrobial-drug resistant microorganisms . Infection control programs are now used in most long-term care facilities, but their impact on infections has not been rigorously evaluated . Preventive strategies need to address the changing complexity of care in these facilities, e.g., the increased use of invasive devices . The anticipated increase in the elderly population in the next several decades makes prevention of infection in long-term care facilities a priority.

Emerg Infect Dis, 2001 Mar-Apr, 7(2), 200 - 4
Ventilator-associated pneumonia or not? Contemporary diagnosis; Mayhall CG; Ventilator-associated pneumonia (VAP) is pneumonia in patients who have been on mechanical ventilation for > or =48 hours . VAP is most accurately diagnosed by quantitative culture and microscopy examination of lower respiratory tract secretions, which are best obtained by bronchoscopically directed techniques such as the protected specimen brush and bronchoalveolar lavage . These techniques have acceptable repeatability, and interpretation of results is unaffected by antibiotics administered concurrently for infection at extrapulmonary sites as long as antimicrobial therapy has not been changed for <72 hours before bronchoscopy.

Emerg Infect Dis, 2001 Mar-Apr, 7(2), 188 - 92
Controlling antimicrobial resistance in hospitals: infection control and use of antibiotics; Weinstein RA; Antimicrobial-drug resistance in hospitals is driven by failures of hospital hygiene, selective pressures created by overuse of antibiotics, and mobile genetic elements that can encode bacterial resistance mechanisms . Attention to hand hygiene is constrained by the time it takes to wash hands and by the adverse effects of repeated handwashing on the skin . Alcohol-based hand rubs can overcome the time problem and actually improve skin condition . Universal glove use could close gaps left by incomplete adherence to hand hygiene . Various interventions have been described to improve antibiotic use . The most effective have been programs restricting use of antibiotics and computer-based order forms for health providers.

Biochemistry, 2001 Apr 17, 40(15), 4531 - 8
Determination of the disulfide structure of sillucin, a highly knotted, cysteine-rich peptide, by cyanylation/cleavage mass mapping; Qi J et al.; The disulfide structure of sillucin, a highly knotted, cysteine-rich, antimicrobial peptide, isolated from Rhizomucor pusillus, has been determined to be Cys2--Cys7, Cys12--Cys24, Cys13--Cys30, and Cys14--Cys21 by disulfide mass mapping based on partial reduction and CN-induced cleavage enabled by cyanylation . The denatured 30-residue peptide was subjected to partial reduction by tris(2-carboxyethyl)phosphine hydrochloride at pH 3 to produce a mixture of partially reduced sillucin species; the nascent sulfhydryl groups were immediately cyanylated by 1-cyano-4-(dimethylamino)pyridinium tetrafluoroborate . The cyanylated species, separated and collected during reversed phase high-performance liquid chromatography, were treated with aqueous ammonia, which cleaved the peptide chain on the N-terminal side of cyanylated cysteine residues . The CN-induced cleavage mixture was analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry before and after complete reduction of residual disulfide bonds in partially reduced and cyanylated species to mass map the truncated peptides to the sequence . Because the masses of the CN-induced cleavage fragments of both singly and doubly reduced and cyanylated sillucin are related to the linkages of the disulfide bonds in the original molecule, the presence of certain truncated peptide(s) can be used to positively identify the linkage of a specific disulfide bond or exclude the presence of other possible linkages.

Bioorg Med Chem Lett, 2001 Apr 9, 11(7), 887 - 90
Synthesis of tetrocarcin derivatives with specific inhibitory activity towards Bcl-2 functions; Kaneko M et al.; Tetrocarcin A was recently identified as an inhibitor of the anti-apoptotic function of Bcl-2 . We synthesized novel tetrocarcin derivatives in order to increase their selective inhibitory activity against Bcl-2 . It was found that 21-acetoxy-9-glycosyloxy derivatives had potent Bcl-2 inhibitory activity without significant antimicrobial activity.

Ned Tijdschr Geneeskd, 2001 Mar 24, 145(12), 557 - 63
{Periodontitis: a hidden chronic infection}; van Winkelhoff AJ et al.; Periodontitis is a chronic inflammatory disease of the tooth supporting tissues which has a prevalence of 35% in the adult population . Risk factors are dental plaque, calculus, smoking, diabetes mellitus, stress and genetic traits . In parallel with chronic intestinal inflammatory diseases and stomach cancer, gene polymorphisms in the interleukin-I gene family are associated with severity of periodontitis . Periodontitis is usually painless . Symptoms of the disease are bleeding, redness and swelling of the gums, suppuration and migration of teeth . Halitosis may be present . Treatment of periodontitis involves supra- and subgingival mechanical debridement, oral hygiene instruction and surgical elimination of residual deepened and bleeding pockets on indication . Microbiological testing can be used to select patients who may benefit from additional systemic antimicrobial therapy . Periodontal lesions may act as a portal of entry for dissemination of periodontal bacteria into the blood stream, which may result in extraoral infections . For this reason it is recommended to include diagnosis of periodontitis in focal examination . Associations have been documented between periodontitis and cardiovascular diseases, arthritis and premature low birth weight infants.

Rev Clin Esp, 2001 Jan, 201(1), 21 - 4
{Guidelines for antibiotic prophylaxis of bacterial endocarditis in patients undergoing dental therapy}; Carmona IT et al.; The objective of the present work was to know the guidelines of antibiotic prophylaxis in bacterial endocarditis used in different spanish health centers . A general dental practitioner asked orally in 50 Cardiology and/or Internal Medicine departments throughout Spain which prophylaxis should be administered to a patient with a mitral valve prosthesis before a dental extraction . The results obtained showed that only 36 (72%) departments used the latest prophylactic guidelines recommended by the American Heart Association or the British Society for Antimicrobial Chemotherapy . Among penicillin allergic patients the antibiotic of choice was erythromycin (60%) followed by clindamycin (28%), although administered at very different dosages (11 and 3, respectively) . Only in 44% of the surveyed departments did the guidelines for allergic and non allergic patients correspond to the recommended protocol by the same study group . The controversy generated regarding the prophylactic indications for bacterial endocarditis might partially account for the results obtained in this study.

Crit Care Med, 2001 Apr, 29(4 Suppl), N135 - 42
Is there a role for antibiotic cycling in the intensive care unit?
Kollef MH.
Antibiotic resistance of bacterial pathogens has emerged as one of the most important issues facing critical care practitioners . Resistance of many commonly encountered bacterial species is increasing and has been associated with greater administration of inadequate antimicrobial therapy to patients within intensive care units . This has resulted in greater patient morbidity, higher mortality rates, and increased healthcare costs . Methods to reduce antimicrobial resistance have focused on increasing adherence to infection control practices and improving antibiotic utilization . Antibiotic cycling is a strategy to reduce antimicrobial resistance by withdrawing an antibiotic or antibiotic class from use and subsequently reintroducing it at a later point in time . The main goal of cycling is to allow resistance rates for specific antibiotics to decrease, or at least remain stable, when their use is periodically eliminated from the intensive care unit.

Crit Care Med, 2001 Apr, 29(4 Suppl), N121 - 7
Antimicrobial management measures to limit resistance: A process-based conceptual framework; DeLisle S et al.; To curb the trend toward increasingly resistant microorganisms, we must at least ensure that antibiotics are used in accordance with the best available scientific evidence . Here we review the control and streamlining measures aimed at optimizing the use of antibiotics, placing an emphasis on their demonstrated effectiveness in the intensive care unit environment . Because of their wide variety, the measures have been organized along the process of choosing, dosing, delivering, and then adjusting the initial antibiotics according to the culture results . By clarifying the range of options available, this process-based conceptual framework assists in best adapting a creative mixture of control measures to a particular healthcare system . The framework also facilitates the overview of a proposed multidisciplinary antibiotic management program, thereby helping to secure the administrative and local provider support necessary for its implementation and continued improvement.

Crit Care Med, 2001 Apr, 29(4 Suppl), N108 - 13
Intensive care unit antimicrobial resistance and the role of the pharmacist; Ibrahim KH et al.; Over the past 20 yrs, pharmacists have successfully integrated their services and expertise to gain acceptance as full members of pediatric, surgical, medical, and intensive care unit (ICU) patient care teams . The pharmacists' training in pharmacology, pharmacokinetics, pharmacodynamics, and pharmacoeconomics complements the expertise of other members of the patient care team . Generally, a strong background in infectious diseases and critical care also provides a focal point for clinical pharmacy service intervention . Although practitioners often focus on issues exclusively related to their specific hospital or ICU, the issues surrounding antibiotic resistance are more global and societal in nature . Medical, surgical, and pharmaceutical practices inside the hospital and ICU extend their influence into the community . Customs and practices of daily living in our society coupled with use of agents capable of altering microbial flora impact our hospital and ICU when patients from the community are admitted . The misuse of antibiotics and the lack of effective infection control programs are often identified as key components in the perpetuation of these phenomena . The focus for the pharmacist and the ICU team must be on the optimization of antibiotic use and infection control guidelines . This review will address the many issues that surround the appropriate use of antibiotics and what role the pharmacist can play in ensuring the optimal use of infection control measures in the ICU and hospital.

Crit Care Med, 2001 Apr, 29(4 Suppl), N87 - 91
Using information systems technology to improve antibiotic prescribing; Bailey TC et al.; The selection of antimicrobial agents in the hospital setting is still a largely manual task and, therefore, fraught with the potential for error . This includes the choice of agents, dosage regimens, and monitoring for response and toxicity . The authors describe current and future strategies to use information technology to improve the process of antimicrobial selection and to avoid dosing errors and contraindicated drug combinations . The possible role of decision support in preventing the emergence of resistance is also discussed.

Crit Care Med, 2001 Apr, 29(4 Suppl), N64 - 8
Increasing prevalence of antimicrobial resistance in intensive care units; Fridkin SK; The unique nature of the intensive care unit (ICU) environment makes this part of the hospital a focus for the emergence and spread of many antimicrobial-resistant pathogens . There are ample opportunities for the cross-transmission of resistant bacteria from patient to patient, and patients are commonly exposed to broad-spectrum antimicrobial agents . Rates of resistance have increased for most pathogens associated with hospital-acquired infections among ICU patients, and rates are almost universally higher among ICU patients than non-ICU patients . Likewise, ICU patients hospitalized longer (i.e., >7 days) are two- to three-fold more likely to be infected with a pathogen possessing an antimicrobial-resistant phenotype of concern . However, there are many opportunities to prevent the emergence and spread of these resistant pathogens through improved use of established infection control measures (patient isolation, handwashing, glove use, and appropriate gown use) and implementation of a systematic review of antimicrobial use . (Crit Care Med 2001; 29{Suppl.}: N64-N68)

J Biol Chem, 2001 Jun 22, 276(25), 22875 - 82 Epub 2001 Apr 05.
Circular proteins in plants: solution structure of a novel macrocyclic trypsin inhibitor from Momordica cochinchinensis; Felizmenio-Quimio ME et al.; Much interest has been generated by recent reports on the discovery of circular (i.e . head-to-tail cyclized) proteins in plants . Here we report the three-dimensional structure of one of the newest such circular proteins, MCoTI-II, a novel trypsin inhibitor from Momordica cochinchinensis, a member of the Cucurbitaceae plant family . The structure consists of a small beta-sheet, several turns, and a cystine knot arrangement of the three disulfide bonds . Interestingly, the molecular topology is similar to that of the plant cyclotides (Craik, D . J., Daly, N . L., Bond, T., and Waine, C . (1999) J . Mol . Biol . 294, 1327-1336), which derive from the Rubiaceae and Violaceae plant families, have antimicrobial activities, and exemplify the cyclic cystine knot structural motif as part of their circular backbone . The sequence, biological activity, and plant family of MCoTI-II are all different from known cyclotides . However, given the structural similarity, cyclic backbone, and plant origin of MCoTI-II, we propose that MCoTI-II can be classified as a new member of the cyclotide class of proteins . The expansion of the cyclotides to include trypsin inhibitory activity and a new plant family highlights the importance and functional variability of circular proteins and the fact that they are more common than has previously been believed . Insights into the possible roles of backbone cyclization have been gained by a comparison of the structure of MCoTI-II with the homologous acyclic trypsin inhibitors CMTI-I and EETI-II from the Cucurbitaceae plant family.

Infect Immun, 2001 May, 69(5), 3248 - 54
Calprotectin expression by gingival epithelial cells; Ross KF et al.; Calprotectin, a heterodimer of MRP8 and MRP14 with antimicrobial properties, is found in the cytosol of neutrophils, monocytes, and human gingival keratinocytes . During inflammation of the oral mucosa, the expression of immunoreactive calprotectin appears upregulated . Given the possible cell sources, we sought to learn if epithelial cells upregulate calprotectin in response to proinflammmatory agents . First, human gingival keratinocytes were maintained in primary culture until senescence . At each passage, cells were harvested and analyzed for quantitative expression of MRP8 and MRP14 subunit mRNA by RNase protection assays and calprotectin complex by enzyme-linked immunosorbent assay . Calprotectin expression was constitutive in the primary gingival keratinocytes, but calprotectin-specific mRNA and protein tended to increase as the cells neared senescence . To test whether calprotectin expression was inducible, immortalized gingival keratinocyte cultures were treated for 2 to 4 h with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta) . As a positive control for inducible expression, immortalized keratinocytes were incubated with phorbol myristate acetate (PMA) (50 ng/ml) for 24 h . Incubation with PMA stimulated increased expression of MRP8 and MRP14 mRNA within 2 h, peaking within 5 h . MRP8- and MRP14-specific mRNA expression by immortalized keratinocytes appeared to be unaffected by LPS or IL-1 beta . In contrast, LPS, IL-1 beta, and PMA each upregulated IL-8 . These data show that calprotectin mRNA is expressed constitutively in cultured keratinocytes, while expression by immortalized cells appears to be independent of the exogenous proinflammatory agents LPS and IL-1 beta.

J Pharm Pharmacol, 2001 Mar, 53(3), 283 - 94
Overcoming antimicrobial resistance by targeting resistance mechanisms; Poole K; Three mechanisms of antimicrobial resistance predominate in bacteria: antibiotic inactivation, target site modification, and altered uptake by way of restricted entry and/or enhanced efflux . Many of these involve enzymes or transport proteins whose activity can be targeted directly in an attemptto compromise resistance and, thus, potentiate antimicrobial activity . Alternatively, novel agents unaffected by these resistance mechanisms can be developed . Given the ongoing challenge posed by antimicrobial resistance in bacteria, targeting resistance in this way may be our best hope at prolonging the antibiotic era.

Eur J Cancer, 2001 Mar, 37(5), 597 - 604
Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma; Twelves C et al.; Standard therapy for advanced or metastatic colorectal cancer consists of 5-fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.) . Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and is a recently developed alternative to i.v . 5-FU/LV . The choice of oral rather than intravenous treatment may affect medical resource use because the two regimens do not require the same intensity of medical intervention for drug administration, and have different toxicity profiles . Here we examine medical resource use in the first-line treatment of colorectal cancer patients with capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV . In a prospective, randomised phase III clinical trial, 602 patients with advanced or metastatic colorectal cancer recruited from 59 centres worldwide were randomised to treatment with either capecitabine or the Mayo regimen of 5-FU/LV . In addition to clinical efficacy and safety endpoints, data were collected on hospital visits required for drug administration, hospital admissions, and drugs and unscheduled consultations with physicians required for the treatment of adverse events . Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved safety including less stomatitis and myelosuppression . Capecitabine patients required substantially fewer hospital visits for drug administration than 5-FU/LV patients . Medical resource use analysis showed that patients treated with capecitabine spent fewer days in hospital for the management of treatment related adverse events than did patients treated with 5-FU/LV . In addition, capecitabine reduced the requirement for expensive drugs, in particular antimicrobials fluconazole and 5-HT3-antagonists to manage adverse events . As anticipated with an oral home-based therapy patients receiving capecitabine needed more frequent unscheduled home, day care, office and telephone consultations with physicians . In the light of clinical results from the phase III trial demonstrating increased efficacy in terms of response rate, equivalent time to progression (TTP) and survival (OS), and a superior safety profile, the results from this medical resource assessment indicate that capecitabine treatment of colorectal cancer patients results in a substantial resource use saving relative to the Mayo Clinic regimen of 5-FU/LV . This benefit is derived principally from the avoidance of hospital visits for i.v . drug administration, less expensive drug therapy for the treatment of toxic side-effects, and fewer treatment-related hospitalisations required during the course of therapy for adverse drug reactions in comparison to patients treated with 5-FU/LV.

Braz J Infect Dis, 2001 Feb, 5(1), 13 - 20 Epub 2001 Aug 03.
Community acquired pneumonia among pediatric outpatients in Salvador, Northeast Brazil, with emphasis on the role of pneumococcus; Nascimento-Carvalho CM et al.; Pneumonia is one of the leading causes of hospitalization and death among children in developing countries, and mortality due to pneumonia has been associated with S . pneumoniae infection . This investigation was designed to describe the antimicrobial susceptibility and serotype patterns of pneumococcal strains recovered from the blood of children with community-acquired pneumonia (CAP) and to assess the clinical findings of pneumococcal bacteremic patients with pneumonia . In a 26 month prospective study, blood cultures were obtained as often as possible from children (<16 years of age) diagnosed with CAP in two emergency rooms . Antimicrobial drug susceptibility tests and serotyping were performed when pneumococcus was identified . We studied 3,431 cases and cultured blood samples from 65.5% of those . Pneumococcus was recovered from 0.8% of the blood samples . The differences in age, somnolence, wheezing and hospitalization among children with and without pneumococcal bacteremia were statistically significant . Pneumococcal bacteremia was age-related (mean 1.63 +/- 1.55; median 0.92) and associated with somnolence and hospitalization among children with CAP . One strain was recovered from pleural fluid . Penicillin resistance was detected in 21.0% (4/19) of the strains at an intermediate level, whereas 63.0% of the strains were resistant to trimethoprim-sulfamethoxazole . The most common serotypes were 14 and 6B, and these serotypes included the resistant strains . Eight of our 18 isolates from blood were of types included in the heptavalent conjugate pneumococcal vaccine, recently licensed in the USA.

Cancer Res, 2001 Mar 15, 61(6), 2434 - 8
RGD-Tachyplesin inhibits tumor growth; Chen Y et al.; Tachyplesin is an antimicrobial peptide present in leukocytes of the horseshoe crab (Tachypleus tridentatus) . In this study, a synthetic tachyplesin conjugated to the integrin homing domain RGD was tested for antitumor activity . The in vitro results showed that RGD-tachyplesin inhibited the proliferation of both cultured tumor and endothelial cells and reduced the colony formation of TSU prostate cancer cells . Staining with fluorescent probes of FITC-annexin V, JC-1, YO-PRO-1, and FITC-dextran indicated that RGD-tachyplesin could induce apoptosis in both tumor and endothelial cells . Western blotting showed that treatment of cells with RGD-tachyplesin could activate caspase 9, caspase 8, and caspase 3 and increase the expression of the Fas ligand, Fas-associated death domain, caspase 7, and caspase 6, suggesting that apoptotic molecules related to both mitochondrial and Fas-dependent pathways are involved in the induction of apoptosis . The in vivo studies indicated that the RGD-tachyplesin could inhibit the growth of tumors on the chorioallantoic membranes of chicken embryos and in syngenic mice.

J Periodontol, 2001 Feb, 72(2), 265 - 73
Management of soft tissue ridge deformities with acellular dermal matrix . Clinical approach and outcome after 6 months of treatment; Batista EL Jr et al.; BACKGROUND: Soft tissue ridge defects often hamper ideally shaped artificial crowns and are basically treated using autogenous soft tissue grafts or alloplastic materials . These approaches present disadvantages such as the necessity of creating additional surgical fields to harvest the graft and the requirement of primary closure, which may reduce ridge height . This investigation evaluated the use of acellular dermal matrix (ADM) in the treatment of soft tissue ridge defects . METHODS: Eight patients, non-smokers with non-contributory medical history, provided 18 sites corresponding to missing teeth in the anterior maxillary arch . The ideal horizontal gain (desired gain) was waxed up in study casts, which served as templates for construction of modified acrylic stents with orthodontic wires . These stents served as references for ideal horizontal gain and also as fixed reference points for further evaluation . The distance from the orthodontic wire to the buccal plate of the defect also represented its baseline horizontal component . Vertical variations were evaluated with another stent and, in this case, no desired gain was considered . After raising partial-thickness flaps, the ADM material was rehydrated and folded to fill the defect and reproduce the desired gain . Flaps were sutured with no tension, and part of the material was intentionally left exposed to avoid pressure on the incision line and prevent height loss . Patients used local and systemic antimicrobials, and the sutures were removed at 7 days . RESULTS: Evaluations were carried out at 30 days, and 3 and 6 months, and all sites healed uneventfully . Neither infection nor significant pain was reported by the patients, and the material was covered by tissue at about 21 days . Mean horizontal gain of 1.72 +/- 0.59 mm (58.5%) at 6 months and mean shrinkage of 1.22 +/- 0.46 mm (41.4%) were observed . There was a mean improvement in vertical gain of only 0.61 +/- 0 . 77 mm, although 66 . 7% of the treated sites showed a 1 to 2 mm gain . Clinically, the total gain in the subjects was very effective and matched the receptor tissues nicely . CONCLUSIONS: ADM may be a suitable material for the treatment of soft tissue ridge deformities due to its biocompatibility, color matching, and horizontal gain . Additional controlled, comparative trials are necessary to establish its advantages and potential compared to autogenous soft tissue techniques.

Am J Infect Control, 2001 Apr, 29(2), 124 - 5
Antibacterial efficacy of triclosan-incorporated polymers; Kalyon BD et al.; Triclosan (2, 4, 4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum antimicrobial agent, routinely used in various personal care products.(1) It is also incorporated into polymers through melt-mixing, with the aim of providing persistent antibacterial action on the surface of the polymer.(2,3) Such triclosan-incorporated polymers can be promoted for hospital use as fabric seat covers, tables, chairs, and clothing . We assessed the antibacterial efficacy of triclosan-incorporated polymer disks against 2 bacteria cultured in liquids in contact with the polymer . In spite of the relatively high concentrations of triclosan in the polymer, only some initial slowing of the bacterial growth rates was observed, followed by the absence of an antibacterial effect over extended periods . The triclosan at the surface of the disks dissolves into the liquids, and the rest of the triclosan, immobilized in the disks, does not contribute to the antibacterial effectiveness of triclosan-incorporated polymer . In light of recent studies, which have shown that triclosan acts on a specific target within the bacterial lipid synthesis pathway, triclosan-incorporated polymers may provide the ideal setting for resistant strains of bacteria to grow and thus should be used selectively in hospital environments.

Br J Oral Maxillofac Surg, 2001 Apr, 39(2), 134 - 7
Role of antimicrobials in third molar surgery: prospective, double blind,randomized, placebo-controlled clinical study; Sekhar CH et al.; AIM: To test the efficacy of two dosing regimens of antimicrobial prophylaxis during the removal of impacted lower third molars . DESIGN: Double blind, prospective, placebo-controlled trial . SETTING: Teaching hospital, India . SUBJECTS: 151 patients aged 19-36 having impacted lower third molars removed . METHODS: Random allocation into three groups: placebo (n= 34), metronidazole 1g orally, 1 hour preoperatively (n= 44), or metronidazole 400mg orally eight hourly for 5 days postoperatively (n= 47) . Patients were recalled on the sixth postoperative day for assessment of pain scores on the second and sixth days, swelling, differences in mouth opening between preoperative and the sixth postoperative day, and the state of the wound . RESULTS: There were no significant differences in the outcome between the three groups (P= 0.09) . CONCLUSION: Antimicrobial prophylaxis does not seem to reduce morbidity after removal of lower third molars .

Br J Oral Maxillofac Surg, 2001 Apr, 39(2), 122 - 6
Necrotizing fasciitis of odontogenic origin in Ibadan, Nigeria; Obiechina AE et al.; We reviewed eight patients with necrotizing fasciitis of odontogenic origin . There were three women and five men, mean age 58 (range 46-72), and none had any associated medical condition such as diabetes . All cases had symptoms of toothache for a mean duration of 34 days (range 26-42) before they sought treatment . Infection originated in the molar teeth region, and initially presented as an odontogenic or periodontal abscess . The clinical features of necrotizing fasciitis became apparent only after the superficial fascia had been invaded . The transient unusually reddish hue for a dark skin might be explained by the fact the deep fascia and muscles were affected before the superficial fascia and skin . Necrosis of the skin began in the submandibular region and progressed downwards . The necrotic area was less than the extent of infection . Antimicrobial treatment, debridement, and fasciotomy improved healing . Delay before appropriate treatment had an adverse affect on outcome, and one patient died .

Clin Pharmacokinet, 2001, 40(2), 125 - 34
A retrospective analysis of pharmacokinetic-pharmacodynamic parameters as indicators of the clinical efficacy of ceftizoxime; Sanchez-Navarro A et al.; OBJECTIVE: To analyse the relationship between a series of estimated pharmacokinetic-pharmacodynamic parameters and the reported efficacy of ceftizoxime . DESIGN: Retrospective literature search and analysis using different correlation models . METHODS: The following parameters were calculated for each group of patients included in the study from the simulated plasma concentration curves corresponding to the dosage regimen administered: (i) peak concentration at steady state divided by the minimum inhibitory concentration (CmaxSS/MIC); (ii) the time that the plasma drug concentration exceeded the MIC scaled to 24 hours at steady state {(tSS)24h > MIC}; (iii) the total area under the concentration-time curve over 24 hours at steady state divided by the MIC {(AUC(SS))24h/MIC}; and (iv) the AUC at steady state for the period of time that the concentration is above the MIC over a period of 24 hours divided by the MIC {(AUIC(SS))24h} . A univariate correlation analysis was performed considering efficacy {rate (%) of clinical cure or bacterial eradication} as the dependent variable and the pharmacokinetic-pharmacodynamic parameter as the independent variable, using linear and nonlinear models . RESULTS: (tSS)24h > MIC was the only parameter that was statistically correlated with efficacy, the linear model being the best choice among the 4 relationship approaches tested . A biased frequency distribution of reported efficacy data constricts the correlation analysis to a narrow range of efficacy and hinders interpretation of the results . CONCLUSIONS: The reporting of cases with low efficacy rates as well as those with high efficacy rates, including information on patient idiosyncrasies and the infecting organisms, would be of great help in performing retrospective analyses of the use of antimicrobial agents, leading to the optimisation of therapy with this type of drug in clinical practice.

World Health Organ Tech Rep Ser, 2000, 895, 1 - 61
The use of essential drugs; WHO Expert Committee; This report presents the recommendations of a WHO Expert Committee responsible for updating and revising the Model List of Essential Drugs . The first part describes the criteria for the selection of essential drugs and pharmaceutical dosage forms, and includes discussion of quality assurance, pharmacovigilance, drug utilization studies, drug information and educational activities, and future developments of the model list . In the light of increasing resistance to antimicrobials, particular attention is drawn to the need for and use of reserve antimicrobials . The second part presents the eleventh revised model list, together with details of the changes that have been made, a glossary of terms and an alphabetical index of all the drugs included.

Int J Infect Dis, 2001, 5(1), 3 - 8
Successful shortening from seven to four days of parenteral beta-lactam treatment for common childhood infections: a prospective and randomized study; Peltola H et al.; OBJECTIVES: To explore whether 4-day parenteral beta-lactam therapy is as effective as 7-day therapy for children hospitalized for parenteral antimicrobials . METHODS: A series of patients aged 3 months to 15 years who fulfilled strict criteria for bacterial pneumonia, other respiratory infections, sepsis-like infections, and other acute infections were prospectively randomized to receive parenteral penicillin or cefuroxime randomly for 4 or 7 days . Besides blood and throat cultures, the etiology was searched by serology for 23 different agents . RESULTS: Of 154 children analyzed, a probable etiology was established in 96 . Of those, a bacterial infection, with or without concomitant viral infection, was disclosed in 80% and 94% in the 4-day and 7-day treatment groups, respectively; pneumococcus being the commonest agent . There was one possible treatment failure in the 4-day group, but with a questionable relation to the short course . Three patients in the 4-day and two in the 7-day group underwent treatment changes, or were rehospitalized within 30 days . All children recovered entirely . CONCLUSIONS: Shortening parenteral beta-lactam treatment to 4 days in infections for which most parenteral antimicrobials are instituted, is not only safe, but reduces costs, is ecologically sound, and minimizes the risks of nosocomial infections and other adverse effects of treatment.

Aliment Pharmacol Ther, 2001 Apr, 15(4), 487 - 92
Comparative efficacy of new investigational agents against Helicobacter pylori; Osato MS et al.; BACKGROUND: Emergence of antibiotic resistant Helicobacter pylori has necessitated the identification of alternate therapies for the treatment of this infection . AIM: To assess the in vitro efficacy of two investigational agents: DMG-MINO CL 344 (a N,N-dimethylglycylamido derivative of minocycline), and davercin, a cyclic carbonate of erythromycin A as compared to older antibiotics (clarithromcyin, azithromycin, minocycline, tetracycline, ofloxacin, ciprofloxacin, cefixime) against clinical isolates of H . pylori . METHODS: Testing was performed using the agar dilution method approved by the NCCLS subcommittee on antimicrobial susceptibility testing, Helicobacter pylori working group . Under these guidelines, Mueller-Hinton agar containing 5% aged sheep blood was used . All incubations were done under CampyPak Plus conditions for 72 h at 37 degrees C . The drug concentrations in the agar ranged from 0.016 to 16 microg/mL . Twenty-one clarithromycin-resistant and 16 clarithromycin-susceptible clinical isolates of H . pylori obtained from patients with duodenal ulcer were used . H . pylori ATCC 43504 was used as the control in all determinations . RESULTS: Against clarithromycin susceptible isolates, all antimicrobial agents except the fluoroquinolones were highly effective . Against clarithromycin-resistant H . pylori, the MIC50/MIC90 values showed that the tetracyclines and cefixime were the most efficacious agents . The fluoroquinolones and macrolides were ineffective . Macrolide cross-resistance was detected . CONCLUSION: Macrolide cross-resistance prevents the use of this entire class of antimicrobials when clarithromycin resistance is present . Tetracyclines and cefixime are possible alternative agents for the treatment of H . pylori infection in these patients.

Biochemistry, 2001 Apr 10, 40(14), 4211 - 21
Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from Rhesus macaque leukocytes; Trabi M et al.; Most mammalian defensins are cationic peptides of 29-42 amino acids long, stabilized by three disulfide bonds . However, recently Tang et al . (1999, Science 286, 498-502) reported the isolation of a new defensin type found in the leukocytes of rhesus macaques . In contrast to all the other defensins found so far, rhesus theta defensin-1 (RTD-1) is composed of just 18 amino acids with the backbone cyclized through peptide bonds . Antibacterial activities of both the native cyclic peptide and a linear form were examined, showing that the cyclic form was 3-fold more active than the open chain analogue {Tang et al . (1999) Science 286, 498-502} . To elucidate the three-dimensional structure of RTD-1 and its open chain analogue, both peptides were synthesized using solid-phase peptide synthesis and tert-butyloxycarbonyl chemistry . The structures of both peptides in aqueous solution were determined from two-dimensional (1)H NMR data recorded at 500 and 750 MHz . Structural constraints consisting of interproton distances and dihedral angles were used as input for simulated-annealing calculations and water refinement with the program CNS . RTD-1 and its open chain analogue oRTD-1 adopt very similar structures in water . Both comprise an extended beta-hairpin structure with turns at one or both ends . The turns are well defined within themselves and seem to be flexible with respect to the extended regions of the molecules . Although the two strands of the beta-sheet are connected by three disulfide bonds, this region displays a degree of flexibility . The structural similarity of RTD-1 and its open chain analogue oRTD-1, as well as their comparable degree of flexibility, support the theory that the additional charges at the termini of the open chain analogue rather than overall differences in structure or flexibility are the cause for oRTD-1's lower antimicrobial activity . In contrast to numerous other antimicrobial peptides, RTD-1 does not display any amphiphilic character, even though surface models of RTD-1 exhibit a certain clustering of positive charges . Some amide protons of RTD-1 that should be solvent-exposed in monomeric beta-sheet structures show low-temperature coefficients, suggesting the possible presence of weak intermolecular hydrogen bonds.

Cas Lek Cesk, 2001 Mar 1, 140(4), 104 - 7
{Hyperbaric oxygen therapy in non-healing wounds and defects} }; Dolezal V; Our study presents effects of the hyperbaric inhalation oxygenotherapy in the treatment of ischaemic diseases of lower extremities and chronic refractory problem wounds . Hyperbaric oxygenotherapy (HO) has antioedemic effect, it stimulates collagen synthesis, formation of granular tissue, and antimicrobial capacity of leukocytes . It also stimulates formation of new blood vessels, which is important namely in tissue hypoxia accompanying microangiopathy of the diabetic foot . HO should be administered as soon as possible after the diagnosis is fixed . Treatment should be done in co-operation with various specialists: surgeons, diabetologists, angiologists, orthopaedic surgeons and specialist on the hyperbaric medicine . First evaluation of HO effects should be done after 15 expositions to HO . If effects are negative, treatment should continue till 25 expositions . If effects are still negative, the treatment should terminate . As a part of complex treatment, HO can prevent high amputations, decrease the duration of hospitalisation and thus economise the whole therapy . Similar results were described in several clinical studies from different developed industrial countries.

Clin Infect Dis, 2001 Apr 15, 32(8), 1172 - 7 Epub 2001 Apr 02.
Brucellosis in pregnant women; Khan MY et al.; Brucella species occasionally cause spontaneous human abortion, but theories regarding whether they do so more frequently than do other infectious pathogens remain controversial . We reviewed 92 pregnant women who presented with acute brucellosis at a Saudi Arabian hospital . From 1983 through 1995, the cumulative incidence of pregnancy and brucellosis was 1.3 cases per 1000 delivered obstetrical discharges . The incidence of spontaneous abortion in the first and second trimesters was 43%, and the incidence of intrauterine fetal death in the third trimester was 2% . Antepartum antimicrobial therapy with cotrimoxazole or cotrimoxazole/rifampin was protective against spontaneous abortion (relative risk, 0.14; 95% confidence interval, 0.06--0.37; P<.0001) . The beneficial effect of treatment occurred in women with febrile illness; vaginal bleeding at presentation usually led to spontaneous abortion . This study demonstrated that the incidence of spontaneous abortion among pregnant women with brucellosis is high and that these women should receive prompt therapy with antimicrobial agents when they present for medical care.

J Clin Microbiol, 2001 Apr, 39(4), 1654 - 6
Susceptibility of Arcobacter butzleri, Arcobacter cryaerophilus, and Arcobacter skirrowii to antimicrobial agents used in selective media; Houf K et al.; Several antimicrobial agents used in selective media for the isolation of Arcobacter were found to be inhibitory to strains belonging to this genus . All three species tested were susceptible to colistin and rifampin at concentrations used in selective media . Arcobacter skirrowii was the most susceptible species . 5-Fluorouracil, novobiocin, trimethoprim, and teicoplanin or vancomycin were found to be without any inhibitory effect on the strains tested at concentrations described for the isolation of Arcobacter species.

J Clin Microbiol, 2001 Apr, 39(4), 1368 - 77
Chlamydial serology: comparative diagnostic value of immunoblotting, microimmunofluorescence test, and immunoassays using different recombinant proteins as antigens; Bas S et al.; To improve the reliability of the serodiagnosis of Chlamydia trachomatis infections, an immunoblot analysis, a microimmunofluorescence titration, and different immunoassays using synthetic peptides derived from species-specific epitopes in variable domain IV of the major outer membrane protein or recombinant antigens (heat shock protein 70 {hsp70}, hsp60, hsp10, polypeptide encoded by open reading frame 3 of the plasmid {pgp3}, macrophage infectivity potentiator, and a fragment of the total lipopolysaccharide) were evaluated . Because cross-reactions between chlamydial species have been reported, the microimmunofluorescence tests were also performed with Chlamydia pneumoniae and Chlamydia psittaci used as antigens, and C . pneumoniae-specific antibodies were also determined by immunoassays . Since the presence of antimicrobial antibodies must be interpreted in light of their prevalence in the general population, responses obtained with serum samples from patients with well-defined infection (i.e., with positive urethral or endocervical C . trachomatis DNA amplification) were compared to those obtained with samples from healthy blood donors . The best sensitivity (86%) with a specificity of 81% was obtained for immunoblotting results, when the number of individuals with > or =10 immunoglobulin G (IgG) and/or > or =2 IgM responses to the different C . trachomatis antigens was considered . A 13-kDa antigen was recognized by most of the samples (86% for IgG) from patients with acute urogenital infection but rarely (3%) by those from healthy blood donors (P < 0.0001) . The sensitivity and specificity results obtained for serum antibodies to peptides or recombinant antigens were slightly lower than those results obtained for the number of responses to whole C . trachomatis antigens, which were 76 and 77%, respectively, when IgG responses to both recombinant hsp60 and pgp3 were considered.

Appl Environ Microbiol, 2001 Apr, 67(4), 1940 - 4
Genotypic analysis of Escherichia coli strains from poultry carcasses and their susceptibilities to antimicrobial agents; Geornaras I et al.; Plasmid profiling and amplified fragment length polymorphism (AFLP) analysis were used to genotype 50 Escherichia coli strains from poultry carcasses . Thirty different plasmid profiles were evident, and clustering of the AFLP data showed that they were a distinctly heterogeneous group of strains . Susceptibility testing against five antimicrobial agents used in the South African poultry industry showed all strains to be susceptible to danofloxacin and colistin, while the majority (96%) were resistant to two tetracyclines.

Int J Antimicrob Agents, 2001 Mar, 17(3), 237 - 40
An in vitro study of the efficacy of rifampicin and minocycline coated umbilical venous catheters; Norton RE et al.; The use of antibiotic coated catheters has been proposed as a means of reducing catheter related sepsis . In this study, an in vitro comparison of bacterial colonisation rates was made between uncoated umbilical venous catheters and catheters coated with rifampicin and minocycline . The following parameters were determined; the direct antimicrobial effect of coated and uncoated catheter segments against a range of organisms associated with line sepsis, the assessment of the decline in antimicrobial activity in coated catheters immersed in plasma and the inhibitory efficacy of the catheters to colonisation over a 28-day period . Minocycline and rifampicin coated umbilical catheters showed a superior inhibitory effect and prevented colonisation with the commoner line-related organisms, when compared with uncoated catheters . The inhibitory effect declined after 14 days in the human plasma . Resistance to colonisation in vitro may not extend beyond 21 days.

Int J Antimicrob Agents, 2001 Mar, 17(3), 233 - 6
Evolution of metronidazole and tetracycline susceptibility pattern in Helicobacter pylori at a hospital in Saudi Arabia; Al-Qurashi AR et al.; The association of Helicobacter pylori with chronic gastritis and peptic ulcer disease led to new therapeutic approaches including the use of antibiotics . Recently, resistance of H . pylori to antibiotics has emerged as the major cause of treatment failure . This retrospective analysis was aimed at investigating the development of antimicrobial susceptibility patterns amongst H . pylori strains isolated at King Fahd Hospital of the University, Al-Khobar . Susceptibility patterns obtained using isolates from a pilot study (1987-1988) were compared with those subsequently isolated (1990-1996) . Metronidazole resistance was estimated to be 35.2% in the first period but more than doubled (78.5%) during the second period . Isolates from females showed a higher resistance rate to metronidazole than those from males . Only one strain was tetracycline resistant . The extremely high resistance rate to metronidazole indicates that it may not be very effective for eradication of H . pylori . Tetracycline should prove a useful component of treatment regimens in this geographical region.

J Org Chem, 2001 Apr 6, 66(7), 2251 - 64
C(5)-C(5a)-modified bicyclomycins: synthesis, structure, and biochemical and biological properties; Vincent F et al.; Bicyclomycin (1) is a novel antibiotic that targets rho transcription termination factor in Escherichia coli . We have demonstrated that retention of the C(5)-C(5a) exomethylene unit in 1 is not essential for inhibition . In a recent paper we proposed a working model for 1 and rho function and suggested that 1 binds in a cleft with the C(5)-C(5a) exomethylene unit directed toward the dimeric interface of two rho monomers . This report examines the bicyclomycin C(5)-C(5a) structural constraints necessary for retention of rho inhibitory activity . Three classes of C(5)-C(5a)-modified bicyclomycins have been prepared and their inhibitory activities evaluated in the poly C-dependent ATPase and filter disk antimicrobial assays . The first series consisted of 12 analogues (8-19) that contained a C(5a)-unsaturated substituent and possessed C(5E)-geometry . The second set were a pair of C(5a)-substituted C(5E)- and C(5Z)-geometrical isomers (21 and 23) . The final group of compounds consisted of six C(5)-C(5a)-dihydrobicyclomycins (24-28, 34) where the terminal substituent was systematically varied . We find that extending the C(5)-C(5a) double bond with unsaturated substituents provides bicyclomycin derivatives with excellent inhibitory activities in the biochemical assay, and that enhanced inhibitory activity is observed for the C(5E) geometrical isomer compared with its C(5Z) counterpart . Finally, C(5a)-substituted dihydrobicyclomycin inhibitory activity appears to be tightly regulated by the nature and spatial placement of the C(5a)-terminal substituent with respect to the {4.2.2}-bicyclic ring system . The observed biochemical activities for the C(5a)-extended conjugated bicyclomycin derivatives and the (5E) and (5Z) isomers were correlated with a structural model for the 1-rho complex.

Protein Expr Purif, 2001 Apr, 21(3), 424 - 31
Production of recombinant bovine lactoferrin N-lobe in insect cells and its antimicrobial activity; Nakamura I et al.; Lactoferrin is a multifunctional, iron-binding glycoprotein found in physiological fluids of mammals . In the present study, a gene encoding the N-terminal half (N-lobe) of bovine lactoferrin was cloned and expressed in cultured insect cells using a baculovirus expression system . One mutation was found in the lactoferrin N-lobe gene, but it resulted in no amino acid substitution . The recombinant lactoferrin N-lobe was secreted into the culture medium and partially purified by means of an immobilized heparin column . The recombinant lactoferrin N-lobe secreted was not glycosylated, but it possessed antimicrobial activity toward Escherichia coli O111 . The recombinant product synthesized and accumulated in the host cells exhibited greater electrophoretic mobility on SDS-PAGE than the secreted product and showed no potency to inhibit the growth of bacteria . It is thought that the product accumulated intracellularly lacks antimicrobial ability due to its degradation in the host cells or due to disruption of the active conformation .

J Cutan Med Surg, 2001 Jan-Feb, 5(1), 37 - 42
The efficacy and safety of a combination benzoyl peroxide/clindamycin topical gel compared with benzoyl peroxide alone and a benzoyl peroxide/erythromycin combination product; Leyden JJ et al.; BACKGROUND: Topical clindamycin and benzoyl peroxide have each demonstrated clinical efficacy in the treatment of acne vulgaris . When used in tandem, they promise greater efficacy than either individual agent through their antibacterial and anti-inflammatory effects . OBJECTIVE: To determine the efficacy and safety of combination benzoyl peroxide/ clindamycin compared with benzoyl peroxide or benzoyl peroxide/erythromycin in the treatment of acne . METHODS: In this randomized, 10-week, multicenter, single-blind trial, 492 patients with moderate to moderately severe acne were treated twice daily with 5% benzoyl peroxide/1% clindamycin, 5% benzoyl peroxide, or 5% benzoyl peroxide/3% erythromycin and assessed every 2 weeks . RESULTS: Compared with benzoyl peroxide, benzoyl peroxide/clindamycin demonstrated significantly greater reductions in inflammatory lesions (p = 0.04) and significantly greater overall improvement as assessed by physicians (p < or = 0.04) and patients (p < 0.001) . Benzoyl peroxide/clindamycin demonstrated a nonsignificant trend for greater efficacy compared to benzoyl peroxide/erythromycin . Dry skin was the most frequent (< or = 7.3%) adverse event with all three therapies . CONCLUSION: Benzoyl peroxide/clindamycin demonstrated improved efficacy and similar tolerability; to benzoyl peroxide used alone and was similar to benzoyl peroxide/ erythromycin, making this combination product an effective alternative antimicrobial therapy for acne.

Phytochemistry, 2001 Mar, 56(6), 569 - 76
Phytoecdysteroids in the genus Asparagus (Asparagaceae); Dinan L et al.; Phytoecdysteroids, plant steroids which are analogues of invertebrate steroid hormones, probably contribute to the deterrence of phytophagous invertebrate predators . They also seem to possess antimicrobial activity and several pharmaceutical and medicinal benefits have been ascribed to them . Here . we present a survey of seeds of 16 species of the genus Asparagus (Asparagaceae), including the crop species A . officinalis, for ecdysteroid agonists (including phytoecdysteroids) and antagonists . Seven species were found to contain ecdysteroids with levels ranging from just detectable (A . racemosus and A . sarmentosus) to relatively high (A . laricinus) . RP-HPLC/RIA/bioassay has been used to separate positive extracts of four species (A . falcatus, A . laricinus, A . ramosissimus and A . scandens) and analyse the ecdysteroid profiles . The identities of the major ecdysteroids were confirmed by NP-HPLC . Seeds of A . officinalis do not contain detectable levels of ecdysteroids, but leaves, stems and roots contain low levels (detectable by RIA) . This indicates that A . officinalis retains the genetic capacity to synthesise ecdysteroids and that future strategies could be developed for enhanced protection of asparagus spears through elevated ecdysteroid levels.

Can Fam Physician, 2001 Mar, 47, 521 - 7
Prescribing practices and attitudes toward giving children antibiotics; Paluck E et al.; OBJECTIVE: To investigate whether overprescribing is common in treatment of pediatric upper respiratory infections and to examine factors that influence prescribing antibiotics for children . DESIGN: A random, stratified sample of practising family physicians was surveyed with a mailed questionnaire . Initial nonresponders were mailed a second questionnaire . SETTING: British Columbia . PARTICIPANTS: A total of 608 general and family physicians . Response rate was 64%; 392/612 surveys were completed . MAIN OUTCOME MEASURES: Physicians' self-reported prescribing practices and knowledge of and attitudes toward using antibiotics for children's upper respiratory tract infections . RESULTS: Relative to treatment guidelines developed for the study, most physicians responded appropriately to the cough (94%) and lobar pneumonia (99.1%) vignettes . More than half the physicians (56.5%) reported they would immediately prescribe antibiotics for tympanic membrane dysfunction, and 79.4% indicated they would prescribe antibiotics for pharyngitis without obtaining a laboratory culture . Approximately 25% of physicians in the study did not believe that prior antibiotic use increased personal risk for acquiring drug-resistant infection, and 23.1% did not believe that antibiotic use was an important factor in promoting resistance in their communities . CONCLUSION: Education in current treatment of pediatric upper respiratory tract illnesses and antimicrobial drug resistance is required . The high response to the questionnaire (64%) and the many requests from physicians to receive the project's educational materials (45%) indicate a high level of interest in this subject.

Am J Hematol, 2001 May, 67(1), 1 - 5
Clinical and pathologic findings in 52 consecutively autopsied cases with multiple myeloma; Oshima K et al.; We studied clinical features and pathologic findings in 52 consecutively autopsied patients with multiple myeloma in our center between 1979 and 1998 . Distant extraosseous involvement was found in 33 patients (63.5%) . Thirty-one patients (59.6%) were proven to have infection at autopsy, among which pneumonia was most common site of infection . Amyloidosis was shown in 8 patients . Second malignancies were observed in 4 cases . The three major causes of death were hemorrhage, infection, and renal failure, which accounted for death in approximately 70% of the patients . Advances in the anticancer and antimicrobial chemotherapies might have decreased deaths due to myeloma itself or infection .

Vet Pathol, 2001 Mar, 38(2), 230 - 2
Septicemia and peritonitis due to Actinobacillus equuli infection in an adult horse; Patterson-Kane JC et al.; Actinobacillus equuli is a rare cause of peritonitis in adult horses . Septicemia and peritonitis due to A . equuli were diagnosed at necropsy in an 8-year-old Saddlebred mare . The origin of the infection was not known; however, small necrotic colonic mucosal lesions presumed to have been caused by phenylbutazone treatment may have allowed bacterial invasion . A good response to antimicrobial treatment has been documented in the small numbers of previously reported acute cases of peritonitis . Because it is potentially treatable, it is important for pathologists and clinicians to identify horses with A . equuli peritonitis.

Commun Dis Public Health, 2000 Dec, 3(4), 305 - 6
Effects of infection control measures on skin of health care workers; Wilkinson SM; A review of patients presenting to a contact dermatitis investigation clinic in 1999 showed that almost half (60/124) of those with occupational hand dermatitis were health care workers . The use of fragrance-free products would be a simple intervention to reduce the prevalence of allergic contact dermatitis without affecting antimicrobial efficacy; other measures are discussed.

Commun Dis Public Health, 2000 Dec, 3(4), 234 - 9
PHLS works towards effective interaction with primary care; McNulty CA et al.; The PHLS primary care initiative was set up to develop and maintain links with primary care professionals, including researchers, GP research networks, and primary care groups in order to prioritize research and laboratory service developments . Such collaboration has spawned the development of antibiotic guidance, which has been posted on the Internet, and participation of the PHLS in other infectious disease guidance (for example, Prodigy) . The implementation of the NHS information strategy will further facilitate the development of and access to local and national primary care guidance, laboratory reporting, and participation in surveillance . Primary care professionals identified several main research priorities in an exercise that facilitated collaboration in the development of research projects and grant applications . These priorities are the natural history of infections presenting to GPs, antibiotic resistance, the role of clinical scores and the laboratory in the diagnosis of infection, the importance of patient and professional attitudes in modifying antimicrobial prescribing, and the role of health professionals in community infection control . Current rapid changes in primary care in the new NHS--such as NHS Direct and the establishment of walk-in centres--may affect the surveillance of communicable disease by offering opportunities for improved data collection but also by posing threats to current systems of surveillance.

J Biol Chem, 2001 May 25, 276(21), 17823 - 9 Epub 2001 Feb 22.
Ponericins, new antibacterial and insecticidal peptides from the venom of the ant Pachycondyla goeldii; Orivel J et al.; The antimicrobial, insecticidal, and hemolytic properties of peptides isolated from the venom of the predatory ant Pachycondyla goeldii, a member of the subfamily Ponerinae, were investigated . Fifteen novel peptides, named ponericins, exhibiting antibacterial and insecticidal properties were purified, and their amino acid sequences were characterized . According to their primary structure similarities, they can be classified into three families: ponericin G, W, and L . Ponericins share high sequence similarities with known peptides: ponericins G with cecropin-like peptides, ponericins W with gaegurins and melittin, and ponericins L with dermaseptins . Ten peptides were synthesized for further analysis . Their antimicrobial activities against Gram-positive and Gram-negative bacteria strains were analyzed together with their insecticidal activities against cricket larvae and their hemolytic activities . Interestingly, within each of the three families, several peptides present differences in their biological activities . The comparison of the structural features of ponericins with those of well-studied peptides suggests that the ponericins may adopt an amphipathic alpha-helical structure in polar environments, such as cell membranes . In the venom, the estimated peptide concentrations appear to be compatible with an antibacterial activity in vivo . This suggests that in the ant colony, the peptides exhibit a defensive role against microbial pathogens arising from prey introduction and/or ingestion.

Eur J Med Chem, 1999 Jul-Aug, 34(7-8), 639 - 43
In vitro antimicrobial activity of aromatic diamidines and diimidazolines related to pentamidine; Donkor IO et al.; Geometric isomers of pentamidine analogues were screened for antimicrobial activity in vitro . cis isomers demonstrated good antibacterial activity compared to their trans counterparts . Both isomers were moderately active against opportunistic pathogens that afflict AIDS patients with minimum inhibitory concentrations in the range of 3.12-12.5 microg/mL.

Eur J Med Chem, 1999 Jul-Aug, 34(7-8), 575 - 83
Synthesis and anti-Pneumocystis carinii pneumonia activity of novel dicationic dibenzothiophenes and orally active prodrugs; Patrick DA et al.; Dicationic carbazoles have been found to be highly active against a rat model of Pneumocystis carinii pneumonia (PCP) . Unfortunately, amidoxime derivatives, designed as prodrugs, were inactive against PCP even though the corresponding amidines were highly active . In the present work, a series of 2,8- and 3,7-bis cationic dibenzothiophenes was synthesized and assayed for anti-PCP activity . Three of the compounds proved to be more potent and less toxic than a standard anti-PCP drug (pentamidine) when given intravenously . Unlike the carbazoles, a dibenzothiophene amidoxime prodrug given orally reduced the parasite load by more than 99% . While no quantitative correlation was seen between anti-PCP activity and DNA binding, a strong level of DNA binding was found to be necessary for antimicrobial activity.

Eur J Biochem, 2001 Apr, 268(7), 2124 - 33
Solution structure of microcin J25, the single macrocyclic antimicrobial peptide from Escherichia coli; Blond A et al.; The three-dimensional solution structure of microcin J25, the single cyclic representative of the microcin antimicrobial peptide class produced by enteric bacteria, was determined using two-dimensional 1H NMR spectroscopy and molecular modeling . This hydrophobic 21-residue peptide exhibits potent activity directed to Gram-negative bacteria . Its primary structure, cyclo(-V1GIGTPISFY10GGGAGHVPEY20F-), has been determined previously {Blond, A., Peduzzi, J., Goulard, C., Chiuchiolo, M . J., Barthelemy, M., Prigent, Y., Salomon, R.A., Farias, R.N., Moreno, F . & Rebuffat, S . (1999) Eur . J . Biochem., 259, 747-755} . Conformational parameters (3JNHCalphaH coupling constants, quantitative nuclear Overhauser enhancement data, chemical shift deviations, temperature coefficients of amide protons, NH-ND exchange rates) were obtained in methanol solution . Structural restraints consisting of 190 interproton distances inferred from NOE data, 11 phi backbone dihedral angle and 9 chi1 angle restraints derived from the coupling constants and three hydrogen bonds in agreement with the amide exchange rates were used as input for simulated annealing calculations and energy minimization in the program XPLOR . Microcin J25 adopts a well-defined compact structure consisting of a distorted antiparallel beta sheet, which is twisted and folded back on itself, thus resulting in three loops . Residues 7-10 and 17-20 form the more regular part of the beta sheet . The region encompassing residues Gly11-His16 consists of a distorted beta hairpin, which divides into two small loops and is stabilized by an inverse gamma turn and a type I' beta turn . The reversal of the chain leading to the Phe21-Pro6 loop results from a mixed beta/gamma turn . A cavity, in which the hydrophilic Ser8 side-chain is confined, is delimited by two crab pincer-like regions that comprise residues 6-8 and 18-1.

J Nat Prod, 2001 Mar, 64(3), 341 - 4
Cortamidine oxide, a novel disulfide metabolite from the New Zealand basidiomycete (mushroom) Cortinarius species; Nicholas GM et al.; Three disulfide metabolites were isolated from the fruiting bodies of the basidiomycete (mushroom) Cortinarius sp., collected in the Catlins, New Zealand . The structures of these compounds were determined as the unsymmetrical disulfide cortamidine oxide (1), 2,2'-dithiobis(pyridine N-oxide) (2), and the symmetrical disulfide 3 . Both 1 and 2 showed significant antimicrobial activity and cytotoxicity . 2,2'-Dithiobis(pyridine N-oxide) (2) and the symmetrical disulfide 3 are assumed to be artifacts of the isolation procedure.

Am Fam Physician, 2001 Mar 15, 63(6), 1087 - 98
Antimicrobial resistance: a plan of action for community practice; Hooton TM et al.; Antibiotic resistance was once confined primarily to hospitals but is becoming increasingly prevalent in family practice settings, making daily therapeutic decisions more challenging . Recent reports of pediatric deaths and illnesses in communities in the United States have raised concerns about the implications and future of antibiotic resistance . Because 20 percent to 50 percent of antibiotic prescriptions in community settings are believed to be unnecessary, primary care physicians must adjust their prescribing behaviors to ensure that the crisis does not worsen . Clinicians should not accommodate patient demands for unnecessary antibiotics and should take steps to educate patients about the prudent use of these drugs . Prescriptions for targeted-spectrum antibiotics, when appropriate, can help preserve the normal susceptible flora . Antimicrobials intended for the treatment of bacterial infections should not be used to manage viral illnesses . Local resistance trends may be used to guide prescribing decisions.

Adv Dent Res, 1999 Jun, 13, 67 - 72
In vitro models of biological responses to implant microbiological models; Mombelli A; To study the etiology and explore possibilities for the therapy of implant-associated infections, investigators have developed and utilized various in vitro models . Major contributions have come from the non-oral medical field, where device-related infections can create life-threatening situations . Microbiological models may include (i) models to study the reaction of micro-organisms to the presence of implants, (ii) models to study the reaction of implant-associated micro-organisms to antimicrobial agents, and (iii) models to study the reaction of the host tissues to the presence of implants contaminated with micro-organisms . In evaluating the potential usefulness of these models for research in oral implantology, one must consider common features as well as important differences between implanted medical devices and oral implants . Although infections associated with implantable medical devices and oral peri-implant infections share a remarkable number of common features, there are also important differences that need attention when findings from in vitro experiments are extrapolated to clinical relevance.

J Ethnopharmacol, 2001 Mar 3, 74(3), 275 - 80
Bioactive chemical constituents from Alchornea laxiflora (benth) pax and hoffman; Ogundipe OO et al.; Quercetin-7,4'-disulphate (1) quercetin (2) quercetin-3',4'-disulphate (3) quercetin-3,4'-diacetate (4) rutin (5) and quercetrin (6) were isolated from the ethyl acetate soluble fraction (ESM) of the crude methanolic leaf extract of Alchornea laxiflora . Purification of these compounds was carried out by column chromatography utilising sephadex LH 20 and various mixtures of water, methanol, ethanol and toluene as eluents . Structural elucidation was by UV, IR, (1)HNMR and (13)CNMR spectroscopy as well as by FAB-MS . Antimicrobial activity of isolated compounds was detected in Gram-positive, Gram-negative and fungal organisms.

J Ethnopharmacol, 2001 Mar 3, 74(3), 217 - 20
Antimicrobial activity of certain Indian medicinal plants used in folkloric medicine; Srinivasan D et al.; Fifty medicinal plants belonging to 26 families were studied for their antimicrobial activity . Among 50 plants tested, 72% showed antimicrobial activity . About 22 plant extracts from 15 families exhibited activity against both Gram-positive and Gram-negative bacteria . Fourteen plants belonging to 11 families did not show activity against any of the bacteria tested . Only nine plant extracts showed antifungal activity . The bulb extracts of A . cepa and A . sativum exhibited activity against both filamentous and non-filamentous fungus . Eight plant extracts belonging to seven families exhibited both antibacterial and antifungal activity.

Biochem Syst Ecol, 2001 May, 29(5), 459 - 467
Exudation of low molecular weight compounds (thiobismethane, methyl isocyanide, and methyl isothiocyanate) as a possible chemical defense mechanism in the marine sponge Ircinia felix; Duque C et al.; The volatile constituents of the marine sponge Ircinia felix were obtained by dynamic headspace extraction and analyzed by HRGC, HRGC-MS and HRGC-Odor at sniffing port . Fifty-nine volatiles were identified for the first time in the odor of this sponge . Hydrocarbons (32.9%), alcohols (17.8%) and carbonyl compounds (16.0%) predominated in the sponge volatile profile, followed by esters (11.6%), halogen compounds (8.6%), ethers (7.7%), nitrogen and/or sulfur compounds (4.6%) and carboxylic acids (0.8%) . Among the identified volatiles, thiobismethane (commonly known as dimethylsulfide), methyl isocyanide and methyl isothiocyanate were found to be responsible for the nauseating and toxic smell emitted by the sponge and for the antimicrobial activity detected in the volatile extract . Exudation experiments in aquarium and in situ conditions revealed that thiobismethane, methyl isocyanide and methyl isothiocyanate are continuously released by the sponge . Upon injury, the concentration of these volatiles increased strongly . Hence, these substances form a chemical protective barrier which may help these sponges avoid fouling, compete for space, prevent infection in the short term, and/or signal generalist predators regarding the existence of other toxic substances in the internal tissues.

Proc Natl Acad Sci U S A, 2001 Mar 27, 98(7), 3884 - 8 Epub 2001 Mar 06.
The GATA factor Serpent is required for the onset of the humoral immune response in Drosophila embryos; Tingvall TO et al.; Innate immunity in Drosophila is characterized by the inducible expression of antimicrobial peptides . We have investigated the development and regulation of immune responsiveness in Drosophila embryos after infection . Immune competence, as monitored by the induction of Cecropin A1-lacZ constructs, was observed first in the embryonic yolk . This observation suggests that the yolk plays an important role in the humoral immune response of the developing embryo by synthesizing antimicrobial peptides . Around midembryogenesis, the response in the yolk was diminished . Simultaneously, Cecropin expression became inducible in a large number of cells in the epidermis, demonstrating that late-stage embryos can synthesize their own antibiotics in the epidermis . This production likely serves to provide the hatching larva with an active antimicrobial barrier and protection against systemic infections . Cecropin expression in the yolk required the presence of a GATA site in the promoter as well as the involvement of the GATA-binding transcription factor Serpent (dGATAb) . In contrast, neither the GATA site nor Serpent were necessary for Cecropin expression in the epidermis . Thus, the inducible immune responses in the yolk and in the epidermis can be uncoupled and call for distinct sets of transcription factors . Our data suggest that Serpent is involved in the distinction between a systemic response in the yolk/fat body and a local immune response in epithelial cells . In addition, the present study shows that signal transduction pathways controlling innate and epithelial defense reactions can be dissected genetically in Drosophila embryos.

J Pharm Pharmacol, 2001 Feb, 53(2), 187 - 91
Antimicrobial activity of tannin components from Vaccinium vitis-idaea L; Ho KY et al.; Reactive oxygen species have been implicated as important pathological mediators in many clinical disorders, including periodontal disease . As a possible alternative for the treatment of periodontal disease, the antimicrobial activity of six tannins isolated from Vaccinium vitis-idaea L., with confirmed antioxidant activity, were assayed by the agar dilution method against selected periodontal pathogens, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia . The results showed that epicatechin-(4beta-->8)-epicatechin-(4beta-->8, 2beta-->O-->7)-catechin had strong antimicrobial activity against P . gingivalis and P . intermedia, but not A . actinomycetemcomitans . The other tannins tested did not show antimicrobial activity . We conclude that tannins isolated from V . vitis-idaea L . with antimicrobial activity could potentially be used for the treatment of periodontal disease.

Br J Neurosurg, 2000 Dec, 14(6), 525 - 30
The rational use of antibiotics in the treatment of brain abscess; Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy; The Working Party was instituted to investigate the rationale of therapeutic antibiotic usage in patients with brain abscess and to make recommendations for current practice . A systematic review of English language publications on brain abscess over the last 25 years was carried out using electronic databases and secondary sources, and data were evaluated . Few publications were identified where the microbiological procedures were adequately described and many authors continue to report sterile pus in a proportion of cases . The vast majority of reports were retrospective neurosurgical assessments in which details of laboratory procedures and antibiotic regimens were missing . There are no published reports of controlled clinical trials or comparative therapeutic studies . The recommendations made by the Working Party are based on relevant published information and the expertise of Working Party members . Recommendations vary according to the location of the abscess which reflects the likely source of the infection and therefore the bacterial types most likely to be present in aspirated pus . Bacteria with multiple resistance to antimicrobial agents do not feature significantly in cases of brain abscess.

Food Addit Contam, 2000 Dec, 17(12), 1047 - 53
Properties of polyethylene films with incorporated benzoic anhydride and/or ethyl and propyl esters of 4-hydroxybenzoic acid and their suitability for food packaging; Dobias J et al.; Benzoic anhydride and ethyl and propyl esters of 4-hydroxybenzoic acid (ETP and PRP, respectively, also termed parabens) incorporated into low density polyethylene (LDPE) film were studied with regard to migration into food and food simulants at 6 degrees C and 25 degrees C, and changes in selected properties of the film were investigated . Antimicrobials were incorporated into polymer film in concentrations of 5 g/kg and 10 g/kg . The addition of parabens into the polymer was more difficult than benzoic anhydride due to their volatility . For benzoic anhydride, 30-40% and 10-20% of the added amount was found to leach from the film into aqueous and olive oil food simulants, respectively . The migration into both water and olive oil followed a very similar course in the case of parabens . Migration levels over 90% and in the range of 70% to 80%, relative to the amount of agent in the film, were determined for ETP and PRP respectively . The incorporation of antimicrobials into the film significantly changed the functional characteristics of the packaging material, i.e . permeability of oxygen, carbon dioxide and water vapour, tensile strength, coefficient of friction, sealing strength and transparency . Shelf life tests with packaged cheese and toasted bread demonstrated the efficiency of the film containing 10 g/kg of BA against mould growth on the food surface during storage at 6 degrees C.

J Am Diet Assoc, 2001 Feb, 101(2), 229 - 38; quiz 239-41
Prophylactic and therapeutic uses of probiotics: a review; Kopp-Hoolihan L; Probiotics, live microbial food supplements that beneficially affect the host by improving its intestinal microbial balance, are quickly gaining interest as functional foods in the current era of self-care and complementary medicine . Microbes have been used for years in food and alcoholic fermentations and relatively recently have undergone scientific scrutiny to examine their purported health benefits . Some of the claims for which research supports a beneficial effect of probiotic consumption include: improving intestinal tract health, enhancing the immune system, synthesizing and enhancing the bioavailability of nutrients, reducing symptoms of lactose intolerance, decreasing the prevalence of allergy in susceptible individuals, and reducing risk of certain cancers . The mechanisms by which probiotics exert their effects are largely unknown, but may involve modifying gut pH, antagonizing pathogens through production of antimicrobial and antibacterial compounds, competing for pathogen binding and receptor sites as well as for available nutrients and growth factors, stimulating immunomodulatory cells, and producing lactase . Selection criteria, efficacy, food and supplement sources and safety issues around probiotics are reviewed . Nutrition professionals can provide a tremendous service by helping clients overcome negative perceptions of all bacteria and, when appropriate, by developing individualized dietary plans to take advantage of the benefits probiotics may confer.

J Oral Pathol Med, 2001 Mar, 30(3), 154 - 8
Expression profile of human defensins and antimicrobial proteins in oral tissues; Dunsche A et al.; Antimicrobial peptides and proteins are an important part of the innate host defense . In the present study, the expression profile of three human alpha-defensins, of two human beta-defensins (hBD) and of phospholipase A-2 (PLA-2) and lysozyme was determined by reverse transcription-polymerase chain reaction (RT-PCR) in 56 non-inflamed and 18 inflamed oral tissue samples and primary oral keratinocytes and fibroblasts . The transcripts for hBD-1 and -2 as well as for PLA-2 and lysozyme were found to be widely expressed . In the group of the alpha-defensins, the message for the human neutrophil peptide-1 (HNP-1) was frequently detected, whereas an expression of human Paneth's cell defensin-5 (HD-5) was identified in only a minority of samples . Transcripts for HD-6 were not detectable in any sample . Oral keratinocytes but not fibroblasts contained transcripts for the beta-defensins, suggesting that these defensins are produced in the epithelial compartment . In contrast, mRNA expression of neutrophil-derived HNP-1 and PLA-2 was not observed in any of these cells . These results suggest an important role for hBD-1 and hBD-2 in the innate oral epithelial host defense.

Clin Excell Nurse Pract, 2000 May, 4(3), 151 - 7
Rational use of antibiotics for upper respiratory infections: an evidence-based approach; Ware J; Despite the lack of evidence of efficacy of antibiotic agents for treating upper respiratory tract infection (URI) symptoms (i.e., acute cough, sore throat, purulent nasal discharge, bronchitis, and the common cold), primary care providers frequently prescribe antibiotic agents for patients presenting with such symptoms . Far from being a harmless practice, prescribing antibiotics for conditions for which there is no proven benefit of such therapy contributes to a number of adverse consequences, including the development of antimicrobial resistance and an unnecessary expense to patients and the healthcare system as a whole . An evidence-based approach to practice can guide nurse practitioners in making the best clinical management decisions for patients presenting with URI symptoms.

J Chromatogr B Biomed Sci Appl, 2001 Mar 10, 752(2), 369 - 77
Purification of novel peptide antibiotics from human milk; Liepke C et al.; A strategy was established for the identification of novel antimicrobial peptides from human milk . For the generation of bioactive peptides human milk was acidified and proteolyzed with pepsin simulating the digest in infants stomachs . Separation of proteins and resulting fragments was performed by means of reversed-phase chromatography detecting the antimicrobial activity of each fraction using a sensitive radial diffusion assay . In order to avoid the purification of the known abundant antimicrobial milk protein lysozyme, it was identified in HPLC fractions by its enzymatic activity and by matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) . On condition that lysozyme was not detectable and antibacterial activity of HPLC fractions was caused by a peptide, which was confirmed by proteolytic cleavage leading to a loss of activity, further purification was performed by consecutive chromatographic steps guided by the antibacterial assay . Using this strategy, an as yet unknown casein fragment exhibiting antimicrobial activity was purified in addition to antimicrobial lactoferrin fragments . The new antimicrobial peptide resembles a proteolytic fragment of human casein-K (residues 63-117) and inhibits the growth of gram-positive, gram-negative bacteria, and yeasts . Our results confirm that antimicrobially-active peptides are liberated from human milk proteins during proteolytic hydrolysis and may play an important role in the host defense system of the newborn.

Planta Med, 2001 Feb, 67(1), 84 - 6
Composition and antimicrobial activity of the essential oil of Baccharis notosergila; Cobos MI et al.; The essential oil of the aerial parts of Baccharis notosergila was examined by GC and GC-MS . Thirty-one constituents were identified representing 96.4% and alpha-pinene, limonene, beta-caryophyllene, and spathulenol were found to be the major components . Furthermore, the oil was tested against eight gram-positive and -negative bacteria and it was found that they exhibited moderate antibacterial activity.

Planta Med, 2001 Feb, 67(1), 81 - 3
Composition and antimicrobial activity of the essential oil of Salvia ringens; Tzakou O et al.; The essential oils of Salvia ringens (samples A and B), were analyzed by means of GC and GC/MS . From the seventy-five identified constituents representing 99.82 and 99.86% of the oils, 1,8-cineole and alpha-pinene were the major components . Furthermore, sample B exhibited a very interesting antimicrobial profile after it was tested against six gram (+/-) bacteria and three pathogenic fungi.

Cancer Detect Prev, 2001, 25(1), 93 - 101
Assessment of the cytotoxic and clastogenic activities of the sesquiterpene lactone lynchnopholide in mammalian cells in vitro and in vivo; Canalle R et al.; Lychnopholide (LNP), a sesquiterpene lactone with antitumor, trypanocidal, and antimicrobial activities, was isolated from Vanillosmopsis erythropappa . The present study was carried out to assess the cytotoxic and clastogenic potential of this new agent in human cultured lymphocytes and Swiss bone marrow cells before the agent was used in medicine . The mitotic index, chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and proliferation index were investigated . There was no alteration in the number of CAs and SCEs in the continuous in vitro treatment . However, the highest concentration (0.2 microg/ml) of LNP was cytotoxic . LNP (0.1, 0.2, and 0.4 microg/ml) induced a significant increase in CA frequency at the G2 phase in all treated cultures . Only the highest concentration (26.67 mg/kg) caused a significant increase in the total number of CAs in the in vivo investigation . On the basis of these results, LNP had a clastogenic effect on both test systems and a cytotoxic effect in vitro.

Acta Otorrinolaringol Esp, 2000 Nov-Dec, 51(8), 737 - 9
{Peritonsillar abscess with parotid and peripharyngeal extension . Report of a case}; Barroso Braojos G et al.; Peritonsillar abscess is the most frequent complication of a tonsillar infection . The purulent material can spread from peritonsillar space to the fascial neck spaces . These deep neck infections may be a life threatening complication . The correct treatment of these infections is an appropriate antimicrobial therapy and abscess drainage, most of the times by surgery . We present a clinical case of a large perypharyngeal, and parotid abscess originated from a peritonsillar abscess . It was necessary surgical treatment to drain it.

Nat Immunol, 2001 Feb, 2(2), 116 - 22
Viral exploitation and subversion of the immune system through chemokine mimicry; Murphy PM; The chemokine superfamily of leukocyte chemoattractants coordinates development and deployment of the immune system by signaling through a family of G protein-coupled receptors . The importance of this system to antimicrobial host defense has been supported by the discovery of numerous herpesviruses and poxviruses that encode chemokine mimics able to block chemokine action . However, specific herpesviruses and lentiviruses can also exploit the immune system through chemokine mimicry, for example, to facilitate viral dissemination or, as in the case of HIV-1, to directly infect leukocyte target cells . The study of viral mimicry of chemokines and chemokine receptors is providing important new concepts in viral immunopathogenesis, new anti-inflammatory drug leads and new targets and concepts for antiviral drug and vaccine development.

EMBO Rep, 2000 Oct, 1(4), 353 - 8
The Drosophila caspase Dredd is required to resist gram-negative bacterial infection; Leulier F et al.; The Drosophila innate immune system discriminates between pathogens and responds by inducing the expression of specific antimicrobial peptide-encoding genes through distinct signaling cascades . Fungal infection activates NF-kappaB-like transcription factors via the Toll pathway, which also regulates innate immune responses in mammals . The pathways that mediate antibacterial defenses, however, are less defined . We have isolated loss-of-function mutations in the caspase encoding gene dredd, which block the expression of all genes that code for peptides with antibacterial activity . These mutations also render flies highly susceptible to infection by gram-negative bacteria . Our results demonstrate that Dredd regulates antibacterial peptide gene expression, and we propose that Dredd, Immune Deficiency and the P105-like rel protein Relish define a pathway that is required to resist gram-negative bacterial infections.

EMBO Rep, 2000 Oct, 1(4), 347 - 52
Activation of the Drosophila NF-kappaB factor Relish by rapid endoproteolytic cleavage; Stoven S et al.; The Rel/NF-kappaB transcription factor Relish plays a key role in the humoral immune response in Drosophila . We now find that activation of this innate immune response is preceded by rapid proteolytic cleavage of Relish into two parts . An N-terminal fragment, containing the DNA-binding Rel homology domain, translocates to the nucleus where it binds to the promoter of the Cecropin A1 gene and probably to the promoters of other antimicrobial peptide genes . The C-terminal IkappaB-like fragment remains in the cytoplasm . This endoproteolytic cleavage does not involve the proteasome, requires the DREDD caspase, and is different from previously described mechanisms for Rel factor activation.

J Med Liban, 2000 May-Jun, 48(3), 143 - 6
Bacterial etiology of otitis media with effusion in a group of Lebanese children; Hadi U et al.; Identification of the main bacteria causing otitis media with effusion (OME) in a given population is essential . It indicates the degree of involvement of a given bacterium in a particular disease of that population . Knowledge of the most prevalent bacteria would initiate the search for the mode of acquisition of such bacteria and may aid in establishing appropriate control and prevention programs, which may decrease the incidence of OME . The rapid response of most OME to a variety of broad-spectrum antimicrobials deprives the clinician from knowing the particular bacteriologic agent prevailing in a community . With the emergence of resistant strains and the change over time of the relative distribution of bacteriologic agents known to cause OME, the identification of the bacterial etiology of OME in Lebanese children was initiated.

Ann N Y Acad Sci, 2000, 917, 258 - 67
Control of salivary secretion by nitric oxide and its role in neuroimmunomodulation; Rettori V et al.; In many in vivo systems exposure to endotoxins (LPS) leads to the co-induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which is important to the regulation of the function of different systems during infection . In submandibular glands (SMG) neural (n)NOS is localized in neural terminals and in striated, granular convoluted and excretory ducts, endothelial (e)NOS in vascular endothelium and ducts, and iNOS in macrophages and in tubules and ducts . In normal adult male rats, injection of an inhibitor of NOS decreased the stimulated salivary secretion and a donor of NO potentiated it, indicating that NO exerts a stimulatory role . A single high dose of LPS (5 mg/kg, i.p.) induced an increase in NOS activity measured by the 14C-citrulline method, increased PGE content almost 100% as measured by RIA, and blocked stimulated salivary secretion . The administration of a specific iNOS inhibitor, aminoguanidine (AG), with LPS not only decreased NOS activity but significantly decreased PGE content, indicating that NO triggered the activation of COX-2 . LPS increased conversion of labeled arachidonate to prostaglandins (PGs) showing that COX was induced . Since a PGE1 analogue blocked stimulated salivation, the LPS-induced inhibition of salivation is probably due to release of PGs . Therefore, the use of inhibitors of iNOS and COX-2 could be very useful to increase salivation during infection since saliva has antimicrobial actions.

Ann N Y Acad Sci, 2000, 917, 19 - 28
Bidirectional heterologous desensitization of opioid and chemokine receptors; Rogers TJ et al.; Opioids are known to suppress a number of elements of the immune response, including antimicrobial resistance, antibody production, and delayed-type hypersensitivity . Phagocytic cells may be particularly susceptible to opioid administration, since reduced production of the cytokines IL-1, IL-6 and TNF-alpha, monocyte-mediated phagocytosis, and both neutrophil and monocyte chemotaxis have all been well established . Earlier studies have shown that both mu- and delta-opioid agonists induce a chemotactic response in monocytes and neutrophils . In addition, mu- and delta-opioid administration inhibited the chemotactic response of these cell populations to a number of chemokines through a process of heterologous desensitization . We report here that mu-, delta-, and kappa-opioid agonists also induce a chemotactic response in T lymphocytes . Using the human T-cell line Jurkat, we have confirmed previous observations that pre-incubation with met-enkephalin (MetEnk), an endogenous opioid agonist, prevents the subsequent chemotactic response to the chemokine RANTES . On the other hand, treatment with MetEnk does not alter the response to the chemokine SDF-1 alpha . Moreover, we found that pre-treatment with RANTES prevented a subsequent response of monocytes to the mu-opioid agonist DAMGO . These results suggest that activation of members of the opioid and chemokine receptor families leads to downregulation of each other's leukocyte migratory activities.

EMBO Rep, 2001 Mar, 2(3), 239 - 43
The imd gene is required for local Cecropin expression in Drosophila barrier epithelia; Onfelt Tingvall T et al.; Surfaces of higher eukaryotes are normally covered with microorganisms but are usually not infected by them . Innate immunity and the expression of gene-encoded antimicrobial peptides play important roles in the first line of defence in higher animals . The immune response in Drosophila promotes systemic expression of antimicrobial peptides in response to microbial infection . We now demonstrate that the epidermal cells underlying the cuticle of larvae respond to infected wounds by local expression of the genes for the antimicrobial peptide cecropin A . Thus, the Drosophila epidermis plays an active role in the innate defence against microorganisms . The immune deficiency (imd) gene was found to be a crucial component of the signal-induced epidermal expression in both embryos and larvae . In contrast, melanization, which is part of the wound healing process, is not dependent on the imd gene, indicating that the signalling pathways promoting melanization and antimicrobial peptide gene expression can be uncoupled.

Pharmazie, 2001 Mar, 56(3), 195 - 204
Role of uncondensed 1,2,4-triazine derivatives as biocidal plant protection agents--a review; Abdel-Rahman RM; The role of uncondensed 1,2,4-triazine derivatives and the related compounds as biocidal plant protection agents such as herbicides, bactericidal, fungicidal, antimicrobial, protozacides, anticoccidal, parasiticides, insecticides, acaricdes and pesticides, is reviewed.

Postgrad Med, 2001 Mar, 109(3), 87 - 91; quiz 28
What do the new antimicrobials offer? Weighing the advantages and disadvantages compared with traditional agents; Gleckman R; The newest antimicrobial drugs have broader spectrums of activity than their predecessors . But are they better than traditional antimicrobial agents? Several drugs recently approved by the US Food and Drug Administration (FDA) may be more effective against uncommon and antimicrobial-resistant pathogens, but their superior efficacy in treating common infections has yet to be proved . Dr Gleckman discusses the advantages and disadvantages of these new drugs and how they can best be used to avoid fostering the emergence of drug-resistant pathogens.

Can J Cardiol, 2001 Mar, 17(3), 297 - 303
Prosthetic valve fungal endocarditis due to histoplasmosis; Isotalo PA et al.; Fungal endocarditis is associated with severe patient morbidity and mortality . Unfortunately, fungal endocarditis is difficult to diagnose because fungal pathogens are uncommonly isolated from routine blood cultures . Histopathological examination of surgically excised cardiac valves, peripheral emboli and systemic ulcers may be useful in identifying pathogens as etiological agents of culture-negative endocarditis . The authors describe a 63-year-old man who had culture-negative endocarditis . Multiple echocardiograms showed progression of the vegetations with valve stenosis despite treatment with multiple antimicrobials . He had multiple peripheral emboli before surgery . Disseminated histoplasmosis was diagnosed by bone marrow culture . Yeast organisms consistent with histoplasma were shown in the vegetations of his excised mitral valve prosthesis . The patient was treated with amphotericin and has been doing well in the two years since his surgery . The diagnosis and management of fungal endocarditis are emphasized.

Science, 2001 Mar 23, 291(5512), 2413 - 7 Epub 2001 Mar 01.
Preferential localization of effector memory cells in nonlymphoid tissue; Masopust D et al.; Many intracellular pathogens infect a broad range of host tissues, but the importance of T cells for immunity in these sites is unclear because most of our understanding of antimicrobial T cell responses comes from analyses of lymphoid tissue . Here, we show that in response to viral or bacterial infection, antigen-specific CD8 T cells migrated to nonlymphoid tissues and were present as long-lived memory cells . Strikingly, CD8 memory T cells isolated from nonlymphoid tissues exhibited effector levels of lytic activity directly ex vivo, in contrast to their splenic counterparts . These results point to the existence of a population of extralymphoid effector memory T cells poised for immediate response to infection.

Clin Infect Dis, 2001 Apr 1, 32(7), 1085 - 9 Epub 2001 Mar 21.
New beta-lactamases in gram-negative bacteria: diversity and impact on the selection of antimicrobial therapy; Bush K; Of the 340 discrete beta-lactamases that have been identified, the most important groups of enzymes that are continuing to proliferate include the plasmid-encoded cephalosporinases, the metallo-beta-lactamases, and the extended-spectrum beta-lactamases . Resistance to specific beta-lactam-containing antimicrobial agents frequently can be traced to a single beta-lactamase, but this task is becoming more difficult for the clinical microbiology laboratory . Other factors, such as multiple beta-lactamase production, transferable multidrug-resistance genes, alterations in outer-membrane porins, and possible antibiotic efflux, all may contribute to a resistance phenotype . Appreciation of these factors may help the physician make a more informed decision when choosing therapy to try to avoid selection of even more pathogenic strains.

Ophthalmologe, 2001 Feb, 98(2), 143 - 6
{Antimicrobial decontamination of corneal donor material: infection prevention and quality assurance}; Wilhelm F et al.; BACKGROUND: Microbiological examinations in eye banks have found an increased contamination rate in preservation media . We studied the effect of prolonged submersion time for decontaminating donor globes . MATERIALS AND METHODS: We retrospectively analyzed the primary contamination of conjunctival smears in 76 cornea donors . The submersion time of donor eyes in PVP iodine solution before preparation was prolonged from 1 min to 5 min, and the contamination rate of storage vessels was compared . RESULTS: In 13 of the 76 conjunctival smears we found no contamination . Before prolonging submersion time, the preservation medium was contaminated in 15 cases, but after 5 min no contamination was observed . CONCLUSION: Prolonging the submersion time of donor globes from 1 to 5 min was effective . The model presented here provides guidelines for existing eye banks as well as for those yet to be established.

J Health Popul Nutr, 2000 Dec, 18(3), 139 - 44
Treatment of childhood diarrhoea in Nigeria: need for adaptation of health policy and programmes to cultural norms; Omotade OO et al.; A community survey of treatment regimens for acute diarrhoea in children was carried out in 10 villages in the Ona Ara Local Government Area of Oyo State, Nigeria, using a combination of qualitative (focus-group discussions) and quantitative (weekly surveillance of diarrhoea) methods . Focus-group discussions were conducted with parents of children aged less than 5 years, while a surveillance of diarrhoea among 550 children of same age was carried out during a 6-month period . The findings of the study showed that not all types of diarrhoea were recognized as illnesses, and only those considered to be illnesses were treated . Treatment often involved an adhoc group which comprised adults who were present at the time the illness occurred (including parents, neighbours, relatives, and elders) . Certain beliefs and practices, such as associating types of diarrhoea with occupation or ethnic groups, categorizing the severity on perceived causes, and withholding certain foods during episodes of diarrhoea, were common factors in decision-making for seeking treatment . Antimicrobial agents were used in the case of 46.8% of 205 diarrhoeal episodes, and 28.5% were not at all treated . The usual practice of focusing on a target group, such as mothers, during educational interventions may need to be modified in communities where nearly every adult has a role in decision-making in relation to health . The need to adapt health policy and programmes to cultural norms should be addressed to improve the impact of programmes.

Rev Med Virol, 2001 Mar-Apr, 11(2), 87 - 101
Role of free radicals in viral pathogenesis and mutation; Akaike T; Oxygen radicals and nitric oxide (NO) are generated in excess in a diverse array of microbial infections . Emerging concepts in free radical biology are now shedding light on the pathogenesis of various diseases . Free-radical induced pathogenicity in virus infections is of great importance, because evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases . Although oxygen radicals and NO have an antimicrobial effect on bacteria and protozoa, they have opposing effects in virus infections such as influenza virus pneumonia and several other neurotropic virus infections . A high output of NO from inducible NO synthase, occurring in a variety of virus infections, produces highly reactive nitrogen oxide species, such as peroxynitrite, via interaction with oxygen radicals and reactive oxygen intermediates . The production of these various reactive species confers the diverse biological functions of NO . The reactive nitrogen species cause oxidative tissue injury and mutagenesis through oxidation and nitration of various biomolecules . The unique biological properties of free radicals are further illustrated by recent evidence showing accelerated viral mutation by NO-induced oxidative stress . NO appears to affect a host's immune response, with immunopathological consequences . For example, NO is reported to suppress type 1 helper T cell-dependent immune responses during infections, leading to type 2 helper T cell-biased immunological host responses . NO-induced immunosuppression may thus contribute to the pathogenesis of virus infections and help expansion of quasispecies population of viral pathogens . This review describes the pathophysiological roles of free radicals in the pathogenesis of viral disease and in viral mutation as related to both nonspecific inflammatory responses and immunological host reactions modulated by NO .

J Agric Food Chem, 2001 Feb, 49(2), 811 - 5
Composition and antimicrobial activity of the essential oils of five taxa of Sideritis from Greece; Aligiannis N et al.; The chemical compositions of the essential oils obtained from the aerial parts of five taxa of Sideritis were analyzed using various GC-MS techniques . A total of 99 different compounds was identified, and significant differences (qualitative and quantitative) were observed between the samples . The in vitro antimicrobial activity of the essential oils against six bacteria and three fungi is also reported.

Infection, 2001 Jan-Feb, 29(1), 27 - 31
Collagen patches impregnated with antimicrobial agents have high local antimicrobial efficacy and achieve effective tissue gluing; Baar S et al.; BACKGROUND: Local antimicrobial systems have gained importance, as illustrated by current research on drug delivery systems (DDS) . We aimed to develop materials that combine hemostatic and antimicrobial efficacy as well as adhesiveness for use in surgical tissue management . MATERIALS AND METHODS: Materials were evaluated by in vitro studies employing microbiological and technological methods . RESULTS: Antimicrobial impregnation of a collagen fleece, which is a pre-coated fibrinogen-based adhesive and therefore ready-to-use (TachoComb), is significantly more efficient--both in terms of the antimicrobial efficacy (p < 0.001) as well as the adhesive strength (p = 0.03) -than coating an antibiotic-containing collagen fleece "on-site" with fibrin glue . CONCLUSION: Due to ease of practical handling and favorable pharmacoeconomics, this DDS is recommended for both open and minimally invasive surgery.

Biol Reprod, 2001 Apr, 64(4), 1072 - 9
Organization of the human gene encoding the epididymis-specific EP2 protein variants and its relationship to defensin genes; Frohlich O et al.; The EP2 gene codes for at least nine message variants that are all specifically expressed in the epididymis . These variants putatively encode small secretory proteins that differ in their N- and C-termini, resulting in proteins that can have little or no sequence similarity to each other . We have isolated and sequenced the human EP2 gene to determine the molecular origin of these variants . The EP2 gene has two promoters, eight exons, and seven introns . Exons 3 and 6 encode protein sequences homologous to beta-defensins, a family of antimicrobial peptides . This sequence homology and the arrangement of promoters and defensin-encoding exons suggest that the EP2 gene originated from two ancestral beta-defensin genes arranged in tandem, each contributing a promoter and two exons encoding a leader sequence and a defensin peptide . The proposed evolutionary relationship between the EP2 gene and defensin genes is supported by the observation that the EP2 gene is located on chromosome 8p23 near the defensin gene cluster and is separated by 100 kilobases or less from DEFB2, the gene for beta-defensin-2 . While the EP2 gene transcribes beta-defensin-like message variants, most of the known message variants code for nondefensin proteins or proteins containing only a partial defensin peptide sequence . We suggest that, during its evolution, the EP2 gene has acquired new functions that may be important for sperm maturation and/or storage in the epididymis.

Water Res, 2001 Jan, 35(1), 244 - 54
Chlorination of pure bacterial cultures in aqueous solution; Shang C et al.; The fate and distribution of chlorine in aqueous solutions containing four pure bacterial cultures was studied . Solutions were subjected to chlorination at different initial free chlorine concentrations . Resulting concentrations of residual chlorine were determined by both DPD/FAS titration and membrane introduction mass spectrometry (MIMS) . In all cases, false-positive breakpoint chlorination curves, probably attributable to the formation of chloroorganic-N compounds, were observed by DPD/FAS titration, while little or no inorganic residual chloramine was found by MIMS . Free chlorine was observed in similar quantities by both methods after chlorine demand by bacterial cellular materials in solution was satisfied . These results indicated the residual chloramines existed in the form of organic chloramines; these compounds are generally recognized as being poor antimicrobial agents . Further investigation confirmed that the bacterial cells were the source of organic-N compounds . The kinetics of chlorination of pure bacterial suspensions was also studied . The pattern of residual chlorine decay following chlorination of the bacterial suspensions indicated rapid initial free chlorine consumption, followed by slow free chlorine consumption, with trace quantities of inorganic chloramine being formed.

Antimicrob Agents Chemother, 2001 Apr, 45(4), 1295 - 7
In vitro activities of linezolid against multiple Nocardia species; Brown-Elliott BA et al.; Linezolid was tested by broth microdilution against 140 clinical Nocardia isolates belonging to seven species . The MIC at which 50% of the strains are inhibited (MIC50) and MIC90 for all species other than Nocardia farcinica were 2 and 4 microg/ml . Linezolid is the first antimicrobial agent demonstrated to be active against all Nocardia species.

Antimicrob Agents Chemother, 2001 Apr, 45(4), 1126 - 36
Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes; Sulavik MC et al.; The contribution of seven known and nine predicted genes or operons associated with multidrug resistance to the susceptibility of Escherichia coli W3110 was assessed for 20 different classes of antimicrobial compounds that include antibiotics, antiseptics, detergents, and dyes . Strains were constructed with deletions for genes in the major facilitator superfamily, the resistance nodulation-cell division family, the small multidrug resistance family, the ATP-binding cassette family, and outer membrane factors . The agar dilution MICs of 35 compounds were determined for strains with deletions for multidrug resistance (MDR) pumps . Deletions in acrAB or tolC resulted in increased susceptibilities to the majority of compounds tested . The remaining MDR pump gene deletions resulted in increased susceptibilities to far fewer compounds . The results identify which MDR pumps contribute to intrinsic resistance under the conditions tested and supply practical information useful for designing sensitive assay strains for cell-based screening of antibacterial compounds.

Antimicrob Agents Chemother, 2001 Apr, 45(4), 1094 - 8
Randomized prospective controlled trial of recombinant granulocyte colony-stimulating factor as adjunctive therapy for limb-threatening diabetic foot infection; de Lalla F et al.; Adult diabetic patients admitted to our Diabetes Center from September 1996 to January 1998 for severe, limb-threatening foot infection were consecutively enrolled in a prospective, randomized, controlled clinical study aimed at assessing the safety and efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) (lenograstim) as an adjunctive therapy for the standard treatment of diabetic foot infection . Forty patients, all of whom displayed evidence of osteomyelitis and long-standing ulcer infection, were randomized 1:1 to receive either conventional treatment (i.e., antimicrobial therapy plus local treatment) or conventional therapy plus 263 microg of G-CSF subcutaneously daily for 21 days . The empiric antibiotic treatment (a combination of ciprofloxacin plus clindamycin) was further adjusted, when necessary, according to the results of cultures and sensitivity testing . Microbiologic assessment of foot ulcers was performed by both deep-tissue biopsy and swab cultures, performed at enrollment and on days 7 and 21 thereafter . Patients were monitored for 6 months; the major endpoints (i.e., cure, improvement, failure, and amputation) were blindly assessed at weeks 3 and 9 . At enrollment, both patient groups were comparable in terms of both demographic and clinical data . None of the G-CSF-treated patients experienced either local or systemic adverse effects . At the 3- and 9-week assessments, no significant differences between the two groups could be observed concerning the number of patients either cured or improved, the number of patients displaying therapeutic failure, or the species and number of microorganisms previously yielded from cultures at day 7 and day 21 . Conversely, among this small series of patients the cumulative number of amputations observed after 9 weeks of treatment appeared to be lower in the G-CSF arm; in fact, only three patients (15%) in this group had required amputation, whereas nine patients (45%) in the other group had required amputation (P = 0.038) . In conclusion, the administration of G-CSF for 3 weeks as an adjunctive therapy for limb-threatening diabetic foot infection was associated with a lower rate of amputation within 9 weeks after the commencement of standard treatment . Further clinical studies aimed at precisely defining the role of this approach to this serious complication of diabetes mellitus appear to be justified.

Rev Immunogenet, 2000, 2(3), 387 - 415
NADPH oxidase, Nramp1 and nitric oxide synthase 2 in the host antimicrobial response; Karupiah G et al.; Using highly conserved, complex enzyme systems, leukocytes utilize the toxic nature of free radical intermediates, derived from oxygen and nitrogen, to control microbial pathogens as part of the innate immune response . Upon activation, NADPH oxidase generates superoxide anion radicals, which in turn give rise to further reactive oxygen intermediates . Similarly, activated nitric oxide synthase 2 catalyses the production of nitric oxide radicals, which leads to the formation of reactive nitrogen intermediates . Nitrogen- and oxygen-centered reactive intermediates can interact to form further reactive species . In addition, presence of the cationic transporter, Nrampl, may exacerbate the effects of these toxic compounds on invading microbes . While each of these antimicrobial systems can operate independently, the combination of their activities is synergistic in the successful containment of almost all invading pathogens . These systems are activated and modulated by microbial products and a series of temporally expressed cytokines . They also feed directly into the initiation of the adaptive immune response, which culminates in lasting specific immunity . The effector molecules, generated in the early innate immune response, are not specific to the invading pathogen and may also cause damage to the host . It is the critical balance of these processes in the initial stages of infection that determines the outcome of infectious disease.

Rev Immunogenet, 2000, 2(3), 359 - 73
Cytokines in innate and adaptive immunity; Banyer JL et al.; Cytokines and chemokines are hormone-like messengers which act to regulate the development and expression of the broad array of immune responses that are mounted against a variety of pathogens . As such, they are critical determinants of the types of cells which will regulate and participate in innate and adaptive immune responses, they may act both in highly localised environments but also in a systemic manner, and they may, themselves, directly mediate antimicrobial effector activities . In this article, we will outline current concepts of the activities of cytokines and chemokines in the immune response and discuss the various cell types, including dendritic cells and other antigen-presenting cells, T cells and B cells, which both produce and respond to these potent regulatory molecules.

Pharmacogenomics, 2000 May, 1(2), 169 - 78
DNA microarray technology and antimicrobial drug discovery; Ivanov I et al.; The genomics era is providing us with vast amounts of information derived from whole-genome sequencing . This will doubtlessly revolutionise biology and the way novel medicines will be discovered . To leverage this information efficiently, however, technologies in addition to high-throughput sequencing are required . DNA microarray technology is one technology that has already shown great potential for both basic research and drug discovery . With particular emphasis on antibacterial research we will summarise in this review the key technological aspects and most important applications of DNA microarrays demonstrated so far.

Minerva Ginecol, 2000 Nov, 52(11), 471 - 84
{Quaternary ammonium salts in gynecology and obstetrics}; Battaglia F et al.; We have summarized chemical, physical, and microbiological characteristics of Quaternary Ammonium Salts: particularly, benzalchromium chloride and didecyl-dimethyl-ammonium chloride characteristics were analyzed . These compounds may act as antimicrobial agents in different way: 1) they are surface-active agents and will denature protein or cause dissociation of an enzyme from its prosthetic group; 2) they may alter the cell permeability of bacteria and yeasts; 3) they may stimulate the glycolysis reaction and 4) may inhibit oxidation of lactate . These latest activities may play a role in maintenance of physiologic microbial ecology of vagina or in the re-establishment of the vaginal ecosystem after vaginitis or vaginosis . We have also summarized the physiologic variation of vaginal ecosystem during the different phases of women's life and the microbiology of vagina during vaginitis and vaginosis . The results of more recent studies about the therapeutic role of quaternary ammonium compounds in vulvo-vaginal infections an in vaginosis are synthetically reported . We concluded that quarternary ammonium compounds are efficacious, handy and safe, in obstetrics and gynecology . A very good compliance and low costs of these compounds suggest that they may be used alone as well in association with specific antimicrobial agents in the treatment of most of gynecological infections, and particularly in bacterial vaginosis.

Ann Intern Med, 2001 Mar 20, 134(6), 521 - 9
Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background; Gonzales R et al.; The following principles of appropriate antibiotic use for adults with acute bronchitis apply to immunocompetent adults without complicating comorbid conditions, such as chronic lung or heart disease.1 . The evaluation of adults with an acute cough illness or a presumptive diagnosis of uncomplicated acute bronchitis should focus on ruling out serious illness, particularly pneumonia . In healthy, nonelderly adults, pneumonia is uncommon in the absence of vital sign abnormalities or asymmetrical lung sounds, and chest radiography is usually not indicated . In patients with cough lasting 3 weeks or longer, chest radiography may be warranted in the absence of other known causes.2 . Routine antibiotic treatment of uncomplicated acute bronchitis is not recommended, regardless of duration of cough . If pertussis infection is suspected (an unusual circumstance), a diagnostic test should be performed and antimicrobial therapy initiated.3 . Patient satisfaction with care for acute bronchitis depends most on physician-patient communication rather than on antibiotic treatment.

J Biomed Mater Res, 2001 Jun 5, 55(3), 424 - 32
Chemical and biological evaluation of endotoxin contamination on natural rubber latex products; Haishima Y et al.; Relationship between pyrogenicity and bacterial endotoxin contamination on latex products was demonstrated by chemical analysis and biological assays . In commercially available latex products' surveillance, water extracts prepared from one surgical glove and two silicone elastomer-coated Foley catheters sterilized by gamma-irradiation were obviously pyrogenic in rabbits . The induced fever was monophasic at low dose of the pyrogenic extracts and biphasic at high dose . These extracts exhibited limulus amebocyte lysate gelation activity, and induced inflammatory cytokine (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) production from MM6-CA8 human monocytoid cells . These biological properties, including pyrogenicity, completely disappeared by treating the pyrogenic extracts with endotoxin-adsorbent affinity column . Limulus amebocyte lysate activity and cytokine production from MM6-CA8 cells induced by the extracts were significantly decreased by endotoxin inhibitors, an active fragment peptide of an 18-kDa cationic antimicrobial protein and a synthetic lipid A B464 analogue . Furthermore, very small amounts of 2-keto-3-deoxyoctonate and 3-hydroxy fatty acid, which are common constituents of bacterial endotoxins, were detected by gas chromatography-mass spectrometry analysis of the pyrogenic extracts . These findings clearly showed that the pyrogenicity found in these latex products originated from endotoxins contaminating the products .

Curr Pharm Des, 2001 Mar, 7(5), 355 - 92
Helicobacter pylori: current chemotherapy and new targets for drug design; Williamson JS; Helicobacter pylori infection is a major cause of many diseases of the gastrointestinal tract, including gastritis, non-ulcer dyspepsia, peptic ulcer disease, and gastric cancers . It is estimated that more than half of the human race is affected by this organism . Although effective treatments are available which will eliminate the organism in about 90 percent; of cases in developed countries, the pandemic occurrence of Helicobacter pylori infection coupled with its ability to develop resistance to our current arsenal of antimicrobial regimens and subsequently reinfect patients makes the pathogenic potential of this microorganism a major global health concern . Provided is a review of the current and evolving therapeutic regimens used in the eradication of Helicobacter pylori, the difficulties associated with in vitro drug screening, as well as potentially new therapeutic targets . In addition, the discovery, the unique physiology, biochemistry, and pathogenicity of this remarkable microorganism is examined.

Infect Immun, 2001 Apr, 69(4), 2692 - 9
Antimycobacterial agent based on mRNA encoding human beta-defensin 2 enables primary macrophages to restrict growth of Mycobacterium tuberculosis; Kisich KO et al.; Human macrophages are hosts for Mycobacterium tuberculosis, the causative agent of tuberculosis, which killed approximately 1.87 million people in 1997 . Human alveolar macrophages do not express alpha- or beta-defensins, broad-spectrum antimicrobial peptides which are expressed in macrophages from other species more resistant to infection with M . tuberculosis . It has been previously reported that M . tuberculosis is susceptible to killing by defensins, which may explain the difference in resistance . Defensin peptides have been suggested as a possible therapeutic strategy for a variety of infectious diseases, but development has been hampered by difficulties in their large-scale production . Here we report the cellular synthesis of human beta-defensin 2 via highly efficient mRNA transfection of human macrophages . This enabled mycobactericidal and mycobacteristatic activity by the macrophages . Although human macrophages are difficult to transfect with plasmid vectors, these studies illustrate that primary macrophages are permissive for mRNA transfection, which enabled expression of a potentially therapeutic protein.

Pharmacotherapy, 2001 Mar, 21(3), 301 - 19
Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes; Owens RC Jr; Over the past several years a multitude of new pharmaceutical agents have been released to the market . Several of them were withdrawn altogether or their use severely restricted to certain indications due to unexpected adverse events, including fatalities . Progress in developing new compounds clearly has surpassed our technology, in some cases, to measure and predict certain toxicities . Prolongation of the QT interval, which may lead to potentially life-threatening ventricular arrhythmias such as torsades de pointes, is one example . Regulatory agencies such as the Food and Drug Administration are increasing standards by which drugs are evaluated for cardiac toxicity related to QT interval prolongation . It is imperative that clinicians be knowledgeable of the risk factors for QT prolongation and avoid the use of culpable agents in patients at risk for QT prolongation.

Zentralbl Chir, 2001 Feb, 126(2), 84 - 92
{Prevention of postoperative wound infections . Evidence-based recommendations}; Geffers C et al.; Among all hospitalized patients, surgical site infections (SSI) are the third most frequently hospital-acquired-infection . SSIs remain a substantial cause of morbidity and mortality among surgical patients . This may be partially explained by the emergence of antimicrobial-resistant pathogens and the increased numbers of patients who are elderly and/or have a wide variety of chronic, debilitating, or immunocompromising underlying diseases . This is why it is essential to implement SSI prevention measures . In April 1999 the Centers for Disease Control and Prevention (CDC) presented the "Guideline for Prevention of Surgical Site Infection" . The recommendations represent the consensus of the Hospital Infection Control Practices Advisory Committee (HICPAC) regarding strategies for the prevention of SSIs . Whenever possible, the recommendations are based on data from well-designed scientific studies . This guideline is a major step forward and is also essential to optimize the management of surgical patients in Germany.

Rev Med Brux, 2001 Feb, 22(1), 15 - 25
{For rational use of antibiotics in the hospital}; Legrand JC et al.; Being faced with the risks of emergence and spread of antibiotic multiresistant bacterial strains in the hospital, it is a joint responsibility of all medical specialities and hospital management to promote the protection of the microbial ecology . Strategies to optimize antimicrobial use and practical approaches are discussed here . The need of mobilization of the entire hospital community and implementation of infectious diseases consultants is emphasized, as recommended by the "Groupement pour le Depistage, l'Etude et la Prevention des Infections Hospitalieres" (GDEPIH).

Biotechniques, 2001 Mar, 30(3), 594 - 8, 600-1
Microfluorometer assay to measure the expression of beta-galactosidase and green fluorescent protein reporter genes in single Drosophila flies; Jung AC et al.; beta-galactosidase and green fluorescent protein (GFP) are among the most commonly used reporter genes to monitor gene expression in various organisms including Drosophila melanogaster . Their expression is usually detected in a qualitative way by direct microscopic observations of cells, tissues, or whole animals . To measure in vivo the inducibility of two antimicrobial peptide genes expressed during the Drosophila innate immune response, we have adapted two reporter gene systems based on the beta-galactosidase enzymatic activity and GFP . We have designed a 96-well microplate fluorometric assay sensitive enough to quantify the expression of both reporter genes in single flies . The assay has enabled us to process efficiently and rapidly a large number of individual mutant flies generated during an ethylmethane sulfonate saturation mutagenesis of the Drosophila genome . This method may be used in any screen that requires the quantification of reporter gene activity in individual insects.

Scand J Gastroenterol, 2001 Feb, 36(2), 144 - 8
Histochemical tracing of bismuth in Helicobacter pylori after in vitro exposure to bismuth citrate; Stoltenberg M et al.; BACKGROUND: Bismuth-containing drugs are widely used in the treatment of Helicobacter pylori associated peptic ulcer . The mechanism of action of bismuth salts is, however, not fully understood, and at present no histochemical techniques for the demonstration of bismuth in H . pylori are available . The aims were to present a histochemical method for the detection of bismuth in H . pylori and to demonstrate bismuth uptake in H . pylori after in vitro exposure to bismuth citrate . METHODS: H . pylori cultures (the strain used in this study was CCUG 17874), were exposed to bismuth citrate at different concentrations (0, 4.6, 80, 200 microM) and for different lengths of time (0 min, 15 min, 1 h, 24 h, 48 h) . The samples were fixed in glutaraldehyde, centrifuged, and exposed to autometallographic (AMG) development in order to detect bismuth histochemically . RESULTS: A detailed protocol on the AMG bismuth technique on H . pylori exposed to bismuth in vitro is given . This method results in easily detectable AMG grains of silver enhanced bismuth particles at the electron microscopical level, and shows that bismuth accumulates in H . pylori, predominantly near the wall of the bacteria . Bismuth uptake is followed by bacterial degeneration . CONCLUSION: The present technique with its ability to trace bismuth constitutes a valuable tool in the efforts of clarifying the mechanism of action of bismuth on H . pylori, and supports the notion that bismuth has an antimicrobial activity in itself.

J Clin Oncol, 2001 Mar 15, 19(6), 1658 - 63
Recommendations for cancer prevention trials using potentially ototoxic test agents; Shotland LI et al.; PURPOSE: Preventive oncology applies pharmacologic agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy, a process that may require administration of agents over long periods of time . Although ototoxicity may be a tolerable side effect of anticancer or antimicrobial therapy, even modest ototoxicity may not be acceptable in agents developed for preventive oncology that are routinely administered to subjects who neither are, nor necessarily will become, clinically ill . MATERIALS AND METHODS: Age-related shifts in hearing may occur over the course of longterm or open-ended therapy; consequently, age-adjusted norms enable researchers to better distinguish hearing loss caused by drugs from that caused by aging . Norms for hearing sensitivity are derived from the Baltimore Longitudinal Study of Aging and are the basis for the proposed audiologic monitoring recommendations . RESULTS: Audiologic monitoring recommendations are presented that standardize patient selection, adverse event reporting, posttreatment follow-up, and audiologic testing for potentially ototoxic investigational agents . CONCLUSION: These recommendations are applicable to trials of investigational agents as well as various classes of drugs used in routine clinical care.

Clin Infect Dis, 2001 Mar 15, 32 Suppl 1, S72 - 9
Antimicrobial safety and tolerability: differences and dilemmas; Mandell LA et al.; The adverse drug reactions associated with antimicrobials have become a topic of major importance and concern in the last few years . Antimicrobial toxicity may take many forms, varying from mild, transient phenomena to dramatic, life-threatening events such as seizures or cardiac arrhythmias . We review the toxicity of antimicrobials in general and of the fluoroquinolones in particular and attempt to explain the adverse events by use of structure-adverse event relationships where possible . There are currently 5 main mechanisms that can be invoked to explain antimicrobial toxicity: direct effects, hypersensitivity, changes in microbial flora, drug interactions, and microbial lysis . The adverse drug reactions seen with fluoroquinolones are explained on the basis of these 5 mechanisms . The various organ systems affected by the fluoroquinolones are considered; then individual members of the fluoroquinolone class are reviewed . The unexpected and dramatic problems encountered with temafloxacin and trovafloxacin are discussed as well.

Clin Infect Dis, 2001 Mar 15, 32 Suppl 1, S9 - S15
Mechanisms of action of antimicrobials: focus on fluoroquinolones; Hooper DC; Five bacterial targets have been exploited in the development of antimicrobial drugs: cell wall synthesis, protein synthesis, ribonucleic acid synthesis, deoxyribonucleic acid (DNA) synthesis, and intermediary metabolism . Because resistance to drugs that interact with these targets is widespread, new antimicrobials and an understanding of their mechanisms of action are vital . The fluoroquinolones are the only direct inhibitors of DNA synthesis; by binding to the enzyme-DNA complex, they stabilize DNA strand breaks created by DNA gyrase and topoisomerase IV . Ternary complexes of drug, enzyme, and DNA block progress of the replication fork . Cytotoxicity of fluoroquinolones is likely a 2-step process involving (1) conversion of the topoisomerase-quinolone-DNA complex to an irreversible form and (2) generation of a double-strand break by denaturation of the topoisomerase . The molecular factors necessary for the transition from step 1 to step 2 remain unclear, but downstream pathways for cell death may overlap with those used by other bactericidal antimicrobials . Studies of fluoroquinolone-resistant mutants and purified topoisomerases indicate that many quinolones have differing activities against the two targets . Drugs with similar activities against both targets may prove less likely to select de novo resistance.

Curr Opin Mol Ther, 1999 Oct, 1(5), 558 - 64
Viral vectors for gene transfer into antigen presenting cells; Monahan SJ et al.; Crucial insights for vaccine development have come from examining how the immune system responds to antimicrobial vaccines, as well as to viral vectors employed for gene therapy . The effectiveness of a vaccine depends upon both the method of antigen delivery and the presentation of antigen to lymphocytes . Much focus has turned to delivering antigens to dendritic cells, to promote clinically beneficial T- and B-cell responses . Recombinant viral vectors represent a powerful vehicle to deliver genes encoding microbial- or tumor-derived antigens to generate clinically beneficial immunity . Dendritic cell-based and viral vector-based vaccines are currently being evaluated in clinical trials as a means of inducing antitumor immunity.

Expert Opin Pharmacother, 2000 Mar, 1(3), 507 - 14
Clarithromycin for Helicobacter pylori infection; Leung WK et al.; Helicobacter pylori, a Gram-negative organism that survives in the deep mucus layer and attaches to the gastric surface cells, is estimated to be present in up to one-half of the US population . Chronic H . pylori infection causes chronic gastritis, peptic ulcer diseases and even gastric cancer . Cure of the infection leads to healing of gastric inflammation, prevention of development of peptic ulcer, as well as accelerated healing of peptic ulcers, and prevention of ulcer recurrence . Treatment of H . pylori has undergone substantial evolution over the past decade . Despite the in vitro susceptibility, results from single or even dual drug therapy is typically unsatisfactory and the best therapy is yet to be defined . The best current therapies for H . pylori infection consist of a proton pump inhibitor (PPI) or ranitidine bismuth citrate and two antibiotics (triple therapies), or bismuth, tetracycline, metronidazole and a PPI (quadruple therapy) . Clarithromycin is one of the most useful antimicrobials against H . pylori . It is an acid-stable macrolide with a broad spectrum of antibacterial activity, well absorbed with a wide tissue distribution and with mild side effects . Clarithromycin has a low minimum inhibitory concentration (MIC50) for H . pylori and its effect is potentiated by acid inhibition . When combined with a PPI or ranitidine bismuth citrate and amoxicillin or metronidazole, eradication rates of more than 95% can be achieved with susceptible organisms . However, the prevalence of primary and acquired clarithromycin resistance, which is due to mutations within a conserved loop of 23S rRNA of H . pylori, is increasing . In practice, the presence of clarithromycin resistance usually implies reduced success when clarithromycin-containing regimes are used . There is a need for improved therapies for H . pylori where antibiotic resistance is less of a problem.

Expert Opin Pharmacother, 2000 Sep, 1(6), 1203 - 17
Current treatment of sepsis and endotoxaemia; Periti P; This article reviews the new criteria for selecting the proper antimicrobial agent and dosage regimen for standard treatment of severe sepsis, with the intention of preventing septic shock . After introducing new concepts on the pathogenesis of sepsis and septic shock, the authors analyse the parameters of beta-lactam antibacterial activity, the antibiotic-induced release of bacterial endotoxin and the interrelationships between pharmacokinetics and pharmacodynamics of antibiotics in the search for an optimum dosage regimen of antimicrobial mono- or polytherapy for severely ill septic patients admitted to the intensive care unit . The mortality rate resulting from severe bacterial sepsis, particularly that associated with shock, still approaches 50% in spite of appropriate antimicrobial therapy and optimum supportive care . Bacterial endotoxins that are part of the cell wall are one of the cofactors in the pathogenesis of sepsis and septic shock and are often induced by antimicrobial chemotherapy, even if administered rationally . Not all antimicrobial agents are equally capable of inducing septic shock; this is dependent on their mechanism of action rather than on the causative pathogen species . The quantity of endotoxin released depends on the drug dose and whether filaments or spheroplast formation predominate . Some antibiotics, such as carbapenems, ceftriaxone, cefepime, glycopeptides, aminoglycosides and quinolones, do not have the propensity to provoke septic shock because their rapid bacterial activity induces mainly spheroplast or fragile spheroplast-like bacterial forms.

Bioorg Med Chem, 2001 Feb, 9(2), 347 - 56
Synthesis of variously oxidized abietane diterpenes and their antibacterial activities against MRSA and VRE; Yang Z et al.; Variously oxidized 12 natural abietanes, 6,7-dehydroferruginol methyl ether (3), ferruginol (5), 11-hydroxy-12-oxo-7,9(11),13-abietatriene (7), royleanone (9), demethyl cryptojaponol (12), salvinolone (14), sugiol methyl ether (16), sugiol (17), 5,6-dehydrosugiol methyl ether (19), 5,6-dehydrosugiol (20), 6beta-hydroxyferruginol (23), and taxodione (25) were synthesized . Antimicrobial activities of synthesized phenolic diterpenes and their related compounds against MRSA and VRE were evaluated . Phenols (12-hydroxyabieta-8,11,13-trien-6-one 22 and 23), catechols (12 and 14) and taxodione 25 showed potent activity with 4-10 microg/mL of MIC against MRSA and 4-16 microg/mL of MIC against VRE . (-)-Ferruginol showed more potent activity than natural type (+)-ferruginol . Quinone methide 7 showed the most potent activity with 0.5-1 microg/mL of MIC against both MRSA and VRE.

Bioorg Med Chem, 2001 Feb, 9(2), 217 - 20
Microwave assisted solid support synthesis of novel 1,2,4-triazolo{3,4-b}-1,3,4-thiadiazepines as potent antimicrobial agents; Kidwai M et al.; An environmentally benign and economic synthesis of 1,2,4-triazolo{3,4-b}-1,3,4-thiadiazepines is described from readily accessible substituted 2-mercapto-1-amino triazoles and substituted chalcones on basic alumina that are accelerated by exposure to microwaves . The reaction time has been brought down from hours to seconds with improved yield as compared to conventional heating . The method reported herein is devoid of the hazards of solution phase reactions . All the synthesised compounds were tested for their in vitro antibacterial and antifungal activity . Some compounds showed significant antimicrobial properties . The best activity was observed with compounds 3a, 3c, 4a and 4d.

Diagn Microbiol Infect Dis, 2001 Feb, 39(2), 133 - 5
Activity and spectrum of BMS 284756, a new des-F (6) quinolone, tested against strains of ciprofloxacin-resistant Gram-positive cocci; Jones RN et al.; BMS 284756, a novel des-fluoroquinolone with an expanded potency versus Gram-positive pathogens, demonstrated potent activity against a wide range of 3,541 ciprofloxacin-resistant (MIC, > or = 2 microg/ml) Gram-positive cocci . These strains were selected from more than 24,000 isolates gathered as part of the 1999 SENTRY Antimicrobial Surveillance Program . Further clinical development appears warranted.

Leuk Res, 2001 Apr, 25(4), 339 - 46
Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by water-soluble chitosan oligomer; Pae HO et al.; Water-soluble chitosan oligomer (WSCO) has been reported to have anticancer activity, immuno-enhancing effect and antimicrobial activity . However, other biological activities are unknown . Herein, we have shown that WSCO is able to inhibit proliferation of human leukemia HL-60 cells and induce these cells to differentiate . Treatment with WSCO for 4 days resulted in a concentration-dependent reduction in HL-60 cell growth as measured by cell counting and MTT assay . This effect was accompanied by a marked increase in the proportion of G(0)/G(1) cells as measured by flow cytometry . WSCO also induced differentiation of the cells as measured by phorbol ester-dependent reduction of NBT, morphological changes as examined by Wright-Giemsa staining and expression of CD11b but not of CD14 as analysed by flow cytometry, indicating differentiation of HL-60 cells toward granulocyte-like cells . A combination of low dose of WSCO with all-trans retinoic acid, a differentiating agent toward granulocyte-like cells, exhibited a synergistic effect on the differentiation . In addition, treatment of HL-60 cells with WSCO for 6 or 8 days resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis and quantitatively by Annexin V technique using flow cytometry . Collectively, there is a potential for WSCO in the treatment of myeloid leukemia.

FEBS Lett, 2001 Mar 9, 492(1-2), 62 - 5
Lactoferricin B causes depolarization of the cytoplasmic membrane of Escherichia coli ATCC 25922 and fusion of negatively charged liposomes; Ulvatne H et al.; Antimicrobial peptides have been extensively studied in order to elucidate their mode of action . Most of these peptides have been shown to exert a bactericidal effect on the cytoplasmic membrane of bacteria . Lactoferricin is an antimicrobial peptide with a net positive charge and an amphipatic structure . In this study we examine the effect of bovine lactoferricin (lactoferricin B; Lfcin B) on bacterial membranes . We show that Lfcin B neither lyses bacteria, nor causes a major leakage from liposomes . Lfcin B depolarizes the membrane of susceptible bacteria, and induces fusion of negatively charged liposomes . Hence, Lfcin B may have additional targets responsible for the antibacterial effect.

Biochim Biophys Acta, 2001 Mar 9, 1511(1), 28 - 41
Effect of magainin, class L, and class A amphipathic peptides on fatty acid spin labels in lipid bilayers; Boggs JM et al.; Magainins and other antimicrobial peptides increase ion flux across the membrane . They may do this by forming some type of pore or by perturbing lipid organization due to peptide lying on the bilayer surface . In order to determine if magainins perturb the lipid sufficiently to permeabilize the bilayer, their effect on the motion of fatty acid and lipid spin labels in phosphatidylcholine/phosphatidylglycerol (PC/PG) lipid vesicles was determined . Their effect was compared to two synthetic peptides, 18L and Ac-18A-NH(2), designed to mimic the naturally occurring classes of lytic (class L) and apolipoprotein (class A) amphipathic helices, respectively . We show that although magainins and 18L both had significant effects on lipid chain order, much greater than Ac-18A-NH(2), there was no correlation between these effects and the relative ability of these three peptide classes to permeabilize PC/PG vesicles in the order magainins=Ac-18A-NH(2) >> 18L . This suggests that the perturbing effects of magainins on lipid chain order at permeabilizing concentrations are not directly responsible for the increased leakage of vesicle contents . The greater ability of the magainins to permeabilize PC/PG vesicles relative to 18L is thus more likely due to formation of some type of pore by magainins . The greater ability of Ac-18A-NH(2) relative to 18L to permeabilize PC/PG vesicles despite its lack of disordering effect must be due to its ability to cause membrane fragmentation . Effects of these peptides on other lipids indicated that the mechanism by which they permeabilize lipid bilayers depends both on the peptide and on the lipid composition of the vesicles.

J Hosp Infect, 2001 Mar, 47(3), 239 - 42
Candida colonization in mechanically ventilated patients; Palabiyikoglu I et al.; The diagnosis of pulmonary candidosis is controversial . We undertook a prospective study on 50 mechanically ventilated (>48 h) patients who were hospitalized (>72 h) in the intensive care unit (ICU) with the aim of assessing the incidence of the isolation of Candida species from endotracheal aspirates (EA) . Patients were categorized as individuals already colonized with Candida spp . on admission, individuals becoming colonized during hospitalization, or patients with no colonization . Patients in the ICU were hospitalized for a mean of 23 days . The percentage of patients already colonized with Candida was low (six of 50; 12%), the incidence of Candida isolation from EA in critically ill, mechanically ventilated patients in ICU was also low (six of 50; 12%) . Age, duration of hospitalization, pre-treatment with antimicrobials or immunosuppressive agents and occurrence of underlying disease were not risk factors in our study . Both antifungal usage and neutropenia were more common in already colonized patients . No risk factors were determined for patients colonized during hospitalization . As all the isolates identified were C . albicans . It appears that at present, colonization and/or infection by more resistant Candida species is not a problem in our unit .

Vestn Ross Akad Med Nauk, 2000, (10), 3 - 6
{Problems of disinfection and decontamination in the biological protection and prevention of contagious diseases}; Nikol'skaia VP et al.; The problems of biological protection of the general population and military staff against biological hazard sources, primarily against biological terrorism and military threat underlie works on the design of new disinfectants having a universal spectrum of antimicrobial action and less ecological hazard than currently available ones . Elimination of biological hazard require effective chemical disinfectants that can completely inactivate microbes of unknown etiology as rapidly as possible and that cause the minimum damage to environmental objects . The disinfectant PFK of various modifications is evaluated in terms of the requirements of that ecological and chemical concept aimed at testing chemicals entering the environment.

Epidemiology, 2001 Mar, 12(2), 209 - 14
Alcohol as a gastric disinfectant? The complex relationship between alcohol consumption and current Helicobacter pylori infection; Brenner H et al.; Alcoholic beverages have antimicrobial effects against Helicobacter pylori in vitro . To elucidate the relation between alcohol consumption and current infection with H . pylori in vivo, we carried out a pooled analysis of three recent studies from Southern Germany, comprising 1410 adults age 15 to 69 . Detailed information on consumption of various alcoholic beverages was collected through standardized questionnaires . Helicobacter pylori infection was measured by 15C-urea breath test . Overall, prevalence of current H . pylori infection was lower among subjects who consumed alcohol (34.9%) than among nondrinkers (38.0%) . The adjusted odds ratio was 0.79, with a 95% confidence interval of 0.58-1.08 . Furthermore, alcohol consumption showed a strong inverse relation to the result of the 13C-urea breath test, a semiquantitative measure of the bacterial load, among infected subjects . The inverse association between alcohol consumption and H . pylori infection was not monotonic, however . Odds of infection were lowest at moderate levels of alcohol consumption and increased at higher levels of alcohol consumption, regardless of the type of alcoholic beverages consumed . These results support the hypothesis that moderate alcohol consumption may favor suppression and eventual elimination of H . pylori infection . At higher levels of alcohol consumption, the antimicrobial effects of alcoholic beverages may be opposed by adverse systemic effects of drinking, such as adverse effects on the immune defense.

Crit Care Med, 2001 Feb, 29(2), 385 - 91
Impaired target site penetration of beta-lactams may account for therapeutic failure in patients with septic shock; Joukhadar C et al.; OBJECTIVE: Current guidelines for adjusting antimicrobial therapy regimens commonly are based on drug concentrations measured in plasma . In septic patients, however, the interstitial space of soft tissues in addition to the central compartment represents the target site of infection . We thus hypothesized that one explanation for therapeutic failure during antibiotic treatment might be the inability to achieve effective antimicrobial concentrations in the interstitial space fluid of soft tissues . This is corroborated by the fact that piperacillin, a frequently administered beta-lactam antibiotic, often fails to be effective despite documented susceptibility of the causative pathogen in vitro . DESIGN: Prospective comparative study of two groups . SETTING: The intensive care unit and research ward of an university hospital . SUBJECTS: Six patients with septic shock and a control group of six gender- and age-matched healthy volunteers . INTERVENTIONS: To measure piperacillin penetration into the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue, we employed microdialysis after a single intravenous administration of 4.0 g of piperacillin to patients and healthy volunteers . Piperacillin concentrations were assayed by using reversed-phase high-pressure liquid chromatography . MEASUREMENTS AND MAIN RESULTS: In septic shock patients, interstitial piperacillin concentrations in skeletal muscle and subcutaneous adipose tissue were five- to ten-fold lower than corresponding free plasma concentrations (p <.03) . Mean piperacillin concentrations in subcutaneous adipose tissue never exceeded 11 microg/mL, which is below the minimal inhibitory concentration for a range of relevant pathogens in patients with septic shock . CONCLUSION: The results of the present study demonstrate that in septic shock patients, piperacillin concentrations in the interstitial space may be subinhibitory, even though effective concentrations are attained in plasma . The lack of success of antimicrobial therapy in these patients thus might be attributable to inadequate target site penetration of antibiotics.

Crit Care Med, 2001 Feb, 29(2), 272 - 6
N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients; Heller AR et al.; OBJECTIVE: The antioxidant N-acetylcysteine (NAC) has been shown to attenuate septic tissue injury . To evaluate whether NAC affects host defense mechanisms in critically ill patients, thus predisposing to increased risk of infection, the current study focuses on neutrophil phagocytotic and burst activity after treatment with NAC . DESIGN: Prospective, randomized, clinical trial . SETTING: Twelve-bed operative intensive care unit in a university hospital . PATIENTS: Thirty patients diagnosed with sepsis/systemic inflammatory response syndrome, or multiple trauma . INTERVENTIONS: Patients were randomly assigned to receive either NAC (n = 15) for 4 days in increasing dosages (day 1: 6 g; day 2: 12 g; days 3 and 4: 18 g) or a mucolytic basis dosage of NAC (3 x 300 mg/day {control}; n = 15), respectively . MEASUREMENTS AND MAIN RESULTS: Blood samples were taken before NAC high-dose infusion (day 1), after increasing doses of NAC (days 3 and 5) and 4 days after the last high-dose treatment (day 8) . Neutrophil oxidative burst activity after stimulation with Escherichia coli and polymorphonuclear phagocytosis were determined in a flow cytometric assay . Baseline values of polymorphonuclear functions were comparable in both groups . NAC high-dose treatment resulted in a significantly improved phagocytosis activity compared with control patients . In contrast to this, polymorphonuclear burst activity was significantly reduced in the NAC high-dose treated group on day 3 . CONCLUSION: These findings suggest that infusion of NAC in high doses affects granulocyte functions in critically ill patients . Antimicrobial host defense requires the effective sequence of cell adhesion, phagocytosis, and bactericidal respiratory burst . The enhanced phagocytotic activity might be a compensatory mechanism in states of impaired respiratory burst to maintain tissue sterility . For certain mechanisms of disease, the effects observed might be favorable (e.g., ischemia/reperfusion, endothelial cell activation), for others (infection) this might be detrimental.

Am J Physiol Cell Physiol, 2001 Apr, 280(4), C796 - 806
K+ channels and the microglial respiratory burst; Khanna R et al.; Microglial activation following central nervous system damage or disease often culminates in a respiratory burst that is necessary for antimicrobial function, but, paradoxically, can damage bystander cells . We show that several K+ channels are expressed and play a role in the respiratory burst of cultured rat microglia . Three pharmacologically separable K+ currents had properties of Kv1.3 and the Ca2+/calmodulin-gated channels, SK2, SK3, and SK4 . mRNA was detected for Kv1.3, Kv1.5, SK2, and/or SK3, and SK4 . Protein was detected for Kv1.3, Kv1.5, and SK3 (selective SK2 and SK4 antibodies not available) . No Kv1.5-like current was detected, and confocal immunofluorescence showed the protein to be subcellular, in contrast to the robust membrane localization of Kv1.3 . To determine whether any of these channels play a role in microglial activation, a respiratory burst was stimulated with phorbol 12-myristate 13-acetate and measured using a single cell, fluorescence-based dihydrorhodamine 123 assay . The respiratory burst was markedly inhibited by blockers of SK2 (apamin) and SK4 channels (clotrimazole and charybdotoxin), and to a lesser extent, by the potent Kv1.3 blocker agitoxin-2.

J Biomol Struct Dyn, 2001 Feb, 18(4), 595 - 606
Interactions between mastoparan B and the membrane studied by 1H NMR spectroscopy; Yu K et al.; Mastoparan B (MP-B) is an antimicrobial cationic tetradecapeptide amide isolated from the venom of the hornet Vespa basalis . NMR spectroscopy was used to study the membrane associated structures of MP-B in various model membrane systems such as 120 mM DPC micelles, 200 mM SDS micelles, and 3%(w/v) DMPC/DHPC (1:2) bicelles . In all systems, MP-B has an amphiphilic alpha-helical structure from Lys2 to Leu14 . NOESY experiments performed on MP-B in nondeuterated SDS micelles show that protons in the indole ring of Trp9 are in close contact with methylene protons of SDS micelles . T1 relaxation data and NOE data revealed that the bound form of MP-B may be dominant in SDS micelles . The interactions between MP-B and zwitterionic DPC micelles were much weaker than those between MP-B and anionic SDS micelles . By substitution of Trp9 with Ala9, the pore-forming activity of MP-B was decreased dramatically . All of these results imply that strong electrostatic interactions between the positively charged Lys residues in MP-B and the anionic phospholipid head groups must be the primary factor for MP-B binding to the cell membrane . Then, insertion of the indole ring of Trp9 into the membrane, as well as the amphiphilic alpha-helical structures of MP-B may allow MP-B to span the lipid bilayer through the C-terminal portion . These structural features are crucial for the potent antibiotic activities of MP-B.

J Interferon Cytokine Res, 2001 Feb, 21(2), 65 - 73
Russian experience in screening, analysis, and clinical application of novel interferon inducers; Tazulakhova EB et al.; This review describes a long-standing experience of screening for interferon (IFN) inducers in Russia . IFN inducers represent a special group of potential antiviral compounds . The main requirements for them are (1) high IFN-inducing activity, (2) absence of side effects, (3) wide spectrum of antimicrobial activity, (4) broad therapeutic security and, (5) good solubility in water and biologic liquids . IFN inducers stimulate IFN production in different cells and organs, and that determines the strategy for their application . Amixin (OOO "Lancepharm," Moscow, Russia) induces IFN-alpha/beta production mostly in T cells . Cycloferon (NTFF "Polysan," St . Petersburg, Russia) stimulates B cells and macrophages to produce almost pure IFN-alpha . Double-stranded RNA (dsRNA) and polyphenols of natural origin stimulate IFN production in different populations of immunocytes . Only polymers, such as Larifan (Riga, Latvia), Kagocel ("NIARnedicplus," Moscow, Russia), and Ragosin (N.F . Gamaleya Institute, Moscow, Russia), induce IFN synthesis in muscles, so they may be effective against rabies . Cycloferon, Larifan, and Kagocel, which induce IFN formation in lungs, may be effective against influenza and rhinoviral infections . Cycloferon and Larifan stimulate IFN production in liver and spleen and may be effective against hepatitis B . Oral compounds (Amixin, Kagocel) that stimulate IFN production in intestines may be effective against hepatitis A and enteroviral infections . Low molecular weight inducers (Amixin, Cycloferon, Kagocel) that penetrate the blood-brain barrier may be active against viral encephalitis . At present, clinical trials of IFN inducers are limited, but in the near future, IFN inducers may be used against very different infections and conditions.

Am J Contact Dermat, 2001 Mar, 12(1), 35 - 7
Allergic contact dermatitis from a pyridine derivative in polyvinyl chloride leather; Huh WK et al.; Antimicrobial coating of household products has gained wide acceptance in Japan in the past several years . Pyridine derivatives, used as antifungal or antibacterial agents in many common products, are known to cause contact dermatitis . We present a case of severe contact dermatitis caused by a pyridine derivative used as an antifungal agent in the polyvinyl chloride (PVC) leather of a chair . An open patch test was performed with each ingredient of the PVC leather . Other products were previously eliminated from consideration based on a series of negative patch tests . The PVC leather obtained from the patient's chair gave a ++ reaction with evident blistering, according to the International Contact Dermatitis Research Group standard . Fifteen ingredients of the PVC leather were open patch tested; a positive reaction was found with 2,3,5,6-tetrachloro-4 (methylsulphonyl) pyridine (1% in petrolatum) . Clinicians should be aware that antifungal or antibacterial agents may be increasingly incorporated into common household products and should be suspected in cases of contact dermatitis .

Chest, 2001 Mar, 119(3), 844 - 51
Prognostic markers of short-term mortality in AIDS-associated Pneumocystis carinii pneumonia; Benfield TL et al.; BACKGROUND: Since 1990, corticosteroids have been recommended as adjunctive therapy for patients with AIDS-associated Pneumocystis carinii pneumonia (PCP) and respiratory failure . We hypothesized that the natural course of AIDS-associated PCP has changed in the era of adjunctive corticosteroid therapy . OBJECTIVE: To study variables obtained on hospital admission for possible prognostic value of short-term (3-month) outcome of PCP . DESIGN AND PATIENTS: Prospective observational study of 176 consecutive HIV-1-infected individuals with PCP between 1990 and 1999 . METHOD: Cox proportional-hazards regression models . RESULTS: Univariate analysis showed that age, one or more prior episodes of PCP, use of antimicrobial therapy other than trimethoprim-sulfamethoxazole (TMP-SMZ), use of PCP prophylaxis at diagnosis, and culture of cytomegalovirus (CMV) in BAL predicted progression to death within 3 months . After adjustment, age (relative risk {RR}, 4.1; 95% confidence interval {CI}, 1.8 to 9.3), initial antimicrobial therapy other than TMP-SMZ (RR, 3.1; 95% CI, 1.2 to 8.5), use of PCP prophylaxis (RR, 5.6; 95% CI, 2.2 to 14.4), and culture of CMV in BAL fluid (RR, 2.7; 95% CI, 1.3 to 5.6) remained independent predictors of a poor outcome . In contrast, neither PO(2) nor serum lactate dehydrogenase, which in earlier studies were identified as prognostic markers, were predictors of mortality . CONCLUSION: Age, initial anti-PCP therapy, use of PCP prophylaxis, and BAL CMV status may be useful predictors of outcome of PCP in patients treated in the era of adjunctive corticosteroid therapy.

Acta Derm Venereol, 2000 Nov-Dec, 80(6), 425 - 6
Is Helicobacter pylori infection associated with chronic urticaria?
Hook-Nikanne J, Varjonen E, Harvima RJ, Kosunen TU.
There have been controversial reports of an elevated prevalence rate of Helicobacter pylori infection in chronic urticaria patients . Furthermore, in some studies remission of chronic urticaria has been reported after eradication of H . pylori . The aim of this investigation was to evaluate the prevalence of H . pylori infection among chronic urticaria patients and to study the effect of eradication therapy on urticaria symptoms . Chronic urticaria patients (n=235) were enrolled and H . pylori status was determined serologically . Thirty-five patients received antimicrobial triple therapy . 25% of the patients were positive for H . pylori . The prevalence of H . pylori infection was not significantly higher among urticaria patients compared with the normal Finnish population in any of the age groups studied . Of the successfully treated patients, 27% showed remission of urticaria . Our data suggest that the prevalence of H . pylori infection is not elevated among chronic urticaria patients and that H . pylori eradication does not appear to influence the course of chronic urticaria.

Indian J Public Health, 1999 Apr-Jun, 43(2), 64 - 6
Paediatric inpatient morbidity patterns and drug usage in a teaching hospital serving an underdeveloped area; Dharnidharka VR et al.; Morbidity patterns and drug usage in hospitalized children in a developing area were prospectively studied . The study group consisted of 347 children (age 0-12 yrs) representing all admissions to a paediatric unit over a six month period . Respiratory tract diseases (30.5%) and infectious diseases (26.1%) were the most common reasons for hospitalization . Tuberculosis was the most common infectious disease seen among the hospitalized children . Antimicrobials (60.8%), iron preparations (45.5%), vitamins (43.2%) and antipyretics (29.9%) were the most frequently prescribed groups of drugs . Ampicillin was the most commonly used antimicrobial . Adverse drug reactions were seen in 1.7% of the children . The overall mortality was 9.2% . The mean length of stay was 7.9 days and the mean number of drugs used was 3.4 per patient . More than 4 drugs were prescribed in 54.4% of children . Approximately two thirds received parenteral therapy.

Tidsskr Nor Laegeforen, 2001 Jan 30, 121(3), 351 - 4
{Gene therapy in primary immunologic failure}; Froland SS; BACKGROUND: Primary immunodeficiency diseases (PID) represent a group of rare, usually congenital diseases . In most cases they are caused by mutations in genes essential for normal function of the immune system, leading to severe deficiency in antimicrobial defences, in many cases associated with other clinical manifestations . During the last decade the genetic defect and the function of the normal gene in the immune system has been delineated for a number of PID . The diseases are usually serious, and curative therapy is not available unless allogeneic bone marrow transplantation is possible . PID is therefore considered an attractive goal for gene therapy . MATERIAL AND METHODS: A systematic survey was made of protocols for gene therapy available in major databases, as well as of published reports on trials with gene therapy in man . RESULTS: Clinical trials with gene therapy are ongoing in several types of PID . While no case of PID has been documented to be definitely cured with gene therapy up to now, a landmark finding was recently made, reporting the use of gene therapy to successfully treat two infants with a type of severe combined immunodeficiency (SCID) . INTERPRETATION: Gene therapy holds considerable promise for treatment of several types of PID in the future . Important obstacles, which must be overcome, are partly associated with general problems in human gene therapy, partly with special difficulties associated with the complexity of the human immune system.

Br J Nutr, 2000 Nov, 84 Suppl 1, S127 - 34
In vivo antimicrobial and antiviral activity of components in bovine milk and colostrum involved in non-specific defence; van Hooijdonk AC et al.; The in vivo evidence of the antimicrobial and antiviral activity of bovine milk and colostrum derived components are reviewed with special emphasis on lactoferrin and lactoperoxidase . Their mode of action and the rationale for their application in efficacy trials with rodents, farm animals, fish and humans, to give protection against infectious agents, are described . A distinction is made between efficacy obtained by oral and non-oral administration of these non-specific defence factors which can be commercially applied in large quantities due to major achievements in dairy technology . From the in vivo studies one can infer that lactoferrin and lactoperoxidase are very promising, naturally occurring antimicrobials for use in fish farming, husbandry, oral hygiene and functional foods . Other promising milk-derived compounds include lipids, from which anti-infective degradation products are generated during digestion, and antimicrobial peptides hidden in the casein molecules.

Br J Nutr, 2000 Nov, 84 Suppl 1, S75 - 80
Milk immunoglobulins and complement factors; Korhonen H et al.; The importance of colostrum for the growth and health of newborn offspring is well known . In bovine colostrum, the antibody (immunoglobulin) complement system provides a major antimicrobial effect against a wide range of microbes and confers passive immunity until the calf's own immune system has matured . Bovine serum and lacteal secretions contain three major classes of immunoglobulins: IgG, IgM and IgA . The immunoglobulins are selectively transported from the serum into the mammary gland, as a result of which the first colostrum contains very high concentrations of immunoglobulins (40-200 mg/ml) . IgG1 accounts for over 75 % of the immunoglobulins in colostral whey, followed by IgM, IgA and IgG2 . All these immunoglobulins decrease within a few days to a total immunoglobulin concentration of 0.7-1.0 mg/ml, with IgG1 representing the major Ig class in milk throughout the lactation period . Together with the antibodies absorbed from colostrum after birth, the complement system plays a crucial role in the passive immunisation of the newborn calf . The occurrence of haemolytic or bactericidal complement activity in bovine colostrum and milk has been demonstrated in several studies . This review deals with the characteristics of bovine Igs and the complement system to be exploited as potential ingredients for health-promoting functional foods.

Br J Nutr, 2000 Nov, 84 Suppl 1, S19 - 25
Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications; Kussendrager KD et al.; Lactoperoxidase (LP) is one of the most prominent enzymes in bovine milk and catalyses the inactivation of a wide range of micro-organisms in the lactoperoxidase system (LP-s) . LP-systems are also identified as natural antimicrobial systems in human secretions such as saliva, tear-fluid and milk and are found to be harmless to mammalian cells . The detailed molecular structure of LP is identified and the major products generated by the LP-s and their antimicrobial action have been elucidated for the greater part . In this paper several aspects of bovine LP and LP-s are discussed, including physico-chemical properties, occurrence in milk and colostrum and mechanisms of action . Since the introduction of industrial processes for the isolation of LP from milk and whey the interest in this enzyme has increased considerably and attention will be paid to potential and actual applications of LP-systems as biopreservatives in food and other products.

Int J Biochem Cell Biol, 2001 Feb, 33(2), 143 - 53
Oxidases and reductases are involved in metronidazole sensitivity in Helicobacter pylori; Trend MA et al.; Helicobacter pylori is a contributing factor to the development of gastric and duodenal ulcers and some gastric cancers . Some therapeutic regimes comprise of a number of components, one of which is the antimicrobial metronidazole . A problem with these therapies is the increasing prevalence of metronidazole-resistant (MtrR) H . pylori strains . Several resistance mechanisms have been proposed, and this study addresses the 'scavenging of oxygen' hypothesis . Spectrophotometric assays of cytosolic fractions indicated that metronidazole-sensitive (MtrS) H . pylori isolates had 2.6-fold greater nicotinamide adenine dinucleotide (NADH) oxidase activity, 34-fold greater NADH nitroreductase activity, and eightfold greater nicotinamide adenine dinucleotide phosphate (NADPH) nitroreductase activity than cytosolic fractions from matched MtrR strains . Electrophoresis of cytosolic fractions in non-denaturing gels showed up to 10 protein bands when stained with Coomassie blue . Activity staining of non-denaturing, non-reducing polyacrylamide gels detected NAD(P)H oxidase, disulphide reductase, tetrazolium reductase and nitroreductase activities in the protein bands . Oxidase and reductase activities observed in a band from MtrS strains were absent in the corresponding band from MtrR strains . This band comprised at least 13 proteins, and the major constituent was identified as an alkyl hydroperoxide reductase AhpC subunit . The absence of oxidase and reductase activities in the band from MtrR strains indicated a correlation between the activity of the proteins in this band and the metronidazole-sensitive phenotype.

Trends Plant Sci, 2001 Mar, 6(3), 89 - 91
Quest for antimicrobial genes to engineer disease-resistant crops; van der Biezen EA; Antimicrobial peptides are ancient mediators of the innate defenses of all species of life . These small lytic peptides are being exploited to genetically engineer disease-resistant crop plants . It is anticipated that certain (combinations of) potent antimicrobial peptides will provide agronomically relevant levels of disease control and should contribute to more sustainable agricultural practices.

J Immunol, 2001 Mar 15, 166(6), 4231 - 6
A milk protein lactoferrin enhances human T cell leukemia virus type I and suppresses HIV-1 infection; Moriuchi M et al.; Human T cell leukemia virus type I (HTLV-I) and HIV-1, causative agents of adult T cell leukemia/lymphoma and AIDS, respectively, are transmitted vertically via breast milk . Here we demonstrate that lactoferrin, a milk protein that has a variety of antimicrobial and immunomodulatory activities, facilitates replication of HTLV-I in lymphocytes derived from asymptomatic HTLV-I carriers and transmission to cord blood lymphocytes in vitro . Transient expression assays revealed that lactoferrin can transactivate HTLV-I long terminal repeat promoter . In contrast, lactoferrin inhibits HIV-1 replication, at least in part, at the level of viral fusion/entry . These results suggest that lactoferrin may have different effects on vertical transmission of the two milk-borne retroviruses.

Clin Diagn Lab Immunol, 2001 Mar, 8(2), 370 - 5
Rhesus monkey (Macaca mulatta) mucosal antimicrobial peptides are close homologues of human molecules; Bals R et al.; One component of host defense at mucosal surfaces appears to be epithelium-derived antimicrobial peptides . Molecules of the defensin and cathelicidin families have been studied in several species, including human and mouse . We describe in this report the identification and characterization of rhesus monkey homologues of human mucosal antimicrobial peptides . Using reverse transcriptase PCR methodology, we cloned the cDNAs of rhesus monkey beta-defensin 1 and 2 (rhBD-1 and rhBD-2) and rhesus monkey LL-37/CAP-18 (rhLL-37/rhCAP-18) . The predicted amino acid sequences showed a high degree of homology to the human molecules . The expression of the monkey antimicrobial peptides was analyzed using immunohistochemistry with three polyclonal antibodies to the human molecules . As in humans, rhesus monkey antimicrobial peptides are expressed in epithelia of various organs . The present study demonstrates that beta-defensins and cathelicidins of rhesus monkeys are close homologues to the human molecules and indicate that nonhuman primates represent valid model organisms to study innate immune functions.

Leukemia, 2001 Feb, 15(2), 203 - 7
Clinical efficacy of granulocyte transfusion therapy in patients with neutropenia-related infections; Lee JJ et al.; Granulocyte transfusions have been advocated by some for the treatment of severe, progressive infections in neutropenic patients who fail to respond to antimicrobial agents and recombinant hematopoietic growth factors . We conducted the current study to determine an appropriate method of granulocyte mobilization in healthy donors, and to evaluate the safety and efficacy of granulocyte transfusion therapy in patients with neutropenia-related infections . To mobilize granulocytes (n=55), healthy normal donors were stimulated in one of the following ways: (1) dexamethasone, 3 mg/m2 intravenously 15 min prior to leukapheresis (n = 5); (2) granulocyte colony-stimulating factor (G-CSF), 5 microg/kg subcutaneously 12 to 14 h prior to collection (n=37); or (3) G-CSF and dexamethasone (n= 13) . The mean granulocyte yield from stimulation with G-CSF plus dexamethasone was significantly higher than from stimulation with dexamethasone or G-CSF alone . Twenty-five patients with severe neutropenia-related infections unresponsive to appropriate antimicrobial agents received a total of 55 granulocyte transfusions . The patients from whom fungi or Gram-negative organisms were isolated showed a more favorable response than those infected with Gram-positive organisms . However, the responses to the granulocyte transfusion therapy could not be correlated with the transfused dose, mobilization agents, or the 1 h or 24 h post-transfusion absolute neutrophil counts . We conclude that granulocyte transfusion therapy may be clinically useful for neutropenia-related infections by fungi or Gram-negative organisms.

Pediatr Clin North Am, 2001 Feb, 48(1), 207 - 19
The use of human milk for premature infants; Schanler RJ; Various methods have been reported and used clinically to augment the nutrient supply for human milk-fed premature infants . These methods include specialized maltinutrient powdered mixtures (fortifiers), complete liquid formulas designed to be mixed with human milk, complete powdered formulas to be mixed with human milk, and alternate feeding of human milk and preterm formula . Although the optimum nutrition of premature infants is unknown, data are accumulating to suggest that human milk, fortified with additional nutrients, is appropriate for tube-fed infants . The use of fortified human milk typically provides premature infants adequate growth, nutrient retention, and biochemical indices of nutritional status when fed at approximately 180 mL/kg/d compared with unfortified human milk . Data are needed to determine the precise quantity of nutrients to be added as supplements . Nutrient interactions have not been explored in detail . Although large quantities of calcium seem to be needed, the exogenous calcium may affect fat absorption adversely . Manipulation of milk may affect the intrinsic host-defense properties of the milk . Compared with preterm formula, the feeding of fortified human milk may provide significant protection from infection and NEC . Lastly, the potential stimulation of an enteromammary pathway through skin-to-skin contact provides species-specific antimicrobial protection for premature infants . Several of these areas require additional exploration . Thus, for premature infants, neonatal centers should encourage the feeding of fortified human milk, together with skin-to-skin contact, as reasonable methods to enhance milk production while potentially facilitating the development of an enteromammary response.

Zh Mikrobiol Epidemiol Immunobiol, 2001 Jan-Feb, (1), 74 - 5
{Antimicrobial activity of hyaluronic acid}; Radaeva IF et al.; In this work the biological activity of hyaluronic acid (HA), isolated from fowl crests, is evaluated . The data on the physico-chemical analysis of HA are presented . The preparation obtained is characterized by a high content of the main substance and high relative viscosity . Sterilization conditions for HA, depending on the degree of microbial contamination of the preparation, were carried out . As revealed in this study, irradiation with a dose of 1.0 Mrad is sufficient for obtaining a sterile preparation . HA has been found to possess inhibiting activity with respect to Pseudomonas.

Zh Mikrobiol Epidemiol Immunobiol, 2001 Jan-Feb, (1), 36 - 9
{Status of local reproductive tract immunity in men with inflammatory diseases of the reproductive system}; Ziganshin OR; The clinico-immunological study of 80 patients with chronic prostatitis of different etiology was carried out . As controls, 20 healthy adult males were used . Mucous membranes of the reproductive tract were found to have different mechanisms of antimicrobial protection whose disturbances led to the inflammatory process . The clinico-immunological analysis carried out in the course of this study made it possible to state that, in contrast to healthy adults, pronounced changes in the characteristics of the local immunity status of the reproductive system occur in chronic prostatitis patients.

Cutis, 2001 Feb, 67(2 Suppl), 13 - 20
Therapeutic studies with a new combination benzoyl peroxide/clindamycin topical gel in acne vulgaris; Ellis CN et al.; Three independent clinical studies were conducted in more than 1250 patients with moderate to moderately severe acne vulgaris to evaluate the efficacy and safety of a new combination gel that stably combines 5% benzoyl peroxide and 1% clindamycin . The results indicated that the benzoyl peroxide/clindamycin combination product was an effective treatment for reducing the inflammatory and noninflammatory lesions of acne vulgaris . In overall improvement as rated by the physicians and patients, the combination gel was superior to clindamycin alone, and in 2 of the 3 studies, to benzoyl peroxide alone . The antimicrobial activity of the combination gel was significantly (each P < .01) superior to that seen with topical application of its individual constituents, 5% benzoyl peroxide or 1% clindamycin, and was numerically better than that found with topical application of a 5% benzoyl peroxide/3% erythromycin combination product . As with benzoyl peroxide, dry skin was the most frequent side effect with use of the combination gel, with isolated incidences of other localized irritation . No other safety or tolerability concerns were identified.

Arch Pharm Res, 2001 Feb, 24(1), 27 - 34
Synthesis and preliminary antimicrobial screening of new benzimidazole heterocycles; Fahmy HH et al.; A series of 2-methylbenzimidazole incorporated to different heterocycles through ethyl or carbamoylethyl groups at position 1 of benzimidazole were synthesized . Also 3-(2-methylbenzimidazol-1-yl)propanoic acid hydrazide incorporated with semicarbazides and thiosemicarbazides were prepared . Moreover, the triazole 5e underwent Michael addition and alkylation reaction . Some of the newly synthesized compounds showed considerable antimicrobial activity against gram positive, negative bacteria and yeast.

J Chemother, 2001 Feb, 13(1), 82 - 7
The role of lomefloxacin in the treatment of chronic prostatitis; Scelzi S et al.; The choice of antimicrobial agents for treatment of prostatitis should be based on two factors: in vitro sensitivity of isolated pathogens and potential intraprostatic penetration of the molecule . Unfortunately, only a few antibiotic agents penetrate prostatic fluid which is the primary site of infection . Lomefloxacin, a once-daily difluoroquinolone, could play a central role in the therapy of prostatitis because it has sufficient liposolubility, low ionization (pKa), low protein binding, small molecular size, long serum elimination half-life and it can pass from interstital fluid across prostatic cells into the lumen . This study was carried out on 12 patients (mean age 65 years) with normal hepatic and renal function, divided into two groups of 6 subjects each . Lomefloxacin was administered for perioperative antisepsis at the dose of 400 mg orally once a day for 4 days . Serum and tissue were sampled in the two groups of patients 4 h (Group A) and 8 h (Group B) respectively after the last drug administration . Tissue penetration was higher than serum, with a T/S >2 in the prostatic capsule and seminal blister, and a T/S >1.6 in the adenomatous tissue, in both groups of patients . In addition, the prostatic tissue concentrations exceeded the MIC for the main pathogens usually involved in urogenital infections . Therefore, because of its pharmacokineitic and pharmacodynamic characteristics, lomefloxacin is proposed as an efficacious therapeutic option, even for the treatment of chronic prostatitis.

Scand J Gastroenterol Suppl, 2000, (232), 4 - 9
Topics in Helicobacter pylori infection: focus on a 'search-and-treat' strategy for ulcer disease; de Boer WA; Several new and interesting issues regarding Helicobacter infection are discussed . Test-and-treat strategies in young dyspeptics will do little to reduce the burden of ulcer disease . The prevalence of Helicobacter infection in young people is low and still declining; the incidence of ulcer disease is therefore low . Ulcer disease has a high prevalence and most cases occur in older people . There is a large pool of people who have suffered from a documented peptic ulcer in the past and most are still intermittently symptomatic . If we are to decrease the prevalence of ulcer disease we ought to promote case finding . Only 'search-and-treat' strategies will help to eliminate ulcer disease . These can focus on patients with an ulcer history or on populations that regularly use acid suppressants . Such strategies, of which several examples are discussed, are cost-effective and lead to improved health in the target population . We also discuss the use of serology as a follow-up instrument after anti-Helicobacter therapy and discuss issues regarding Helicobacter therapy in relation to antimicrobial resistance in The Netherlands.

Clin Liver Dis, 2000 Aug, 4(3), 657 - 73, ix
The current management of infectious diseases in the liver transplant recipient; Singh N; The spectrum of major infections after transplantation has undergone a striking evolution . The epidemiologic trends in infectious diseases through the last decade have been most notable for a dramatic decrease in the incidence of several opportunistic infections, largely because of advances in prophylaxis against these pathogens . Paralleling these trends has been an exponential rise in the proportion of infections caused by antimicrobial-resistant bacteria . These multiresistant organisms have now emerged as leading pathogens at many transplant centers, and their management is a daunting challenge.

Orv Hetil, 2001 Jan 28, 142(4), 169 - 71
{Antimicrobial peptides: a new way to treat bacterial infections}; Igaz P; The therapy of bacterial infections is currently a difficult problem of the contemporary medicine, mainly due to the increasing spread of resistance to conventional antibiotics and to the appearance of multi-resistant bacterial strains . Although the gene-encoded antimicrobial peptides were described for a while their intensive research and study of their possible clinical applications has started only in the recent years . These antimicrobial peptides appear to form part of the most ancient defense mechanisms of the phylogenesis by exerting cytotoxic (mainly membrane damaging) effects against many bacteria . In this review the author attempts to make a brief synopsis--from a medical point of view--of the most important antimicrobial peptides and their possible clinical applications.

Vet Microbiol, 2001 Mar 20, 79(2), 143 - 53
Serogroups and antimicrobial susceptibility among Escherichia coli isolated from farmed mink (Mustela vison Schreiber) in Denmark; Vulfson L et al.; Escherichia coli is commonly found in outbreaks of diarrhoea in mink during the production season although its role as a primary causal organism remains unclear . The present study was undertaken to determine the serogroups and antimicrobial susceptibility of E . coli isolates from healthy and diarrhoeic mink . Rectal swabs were taken from healthy and diseased animals, on six different farms, once at the onset of disease and again approximately 2 weeks later . The swabs were subjected to bacteriological investigation; a total of 210 E . coli were isolated, 98 from healthy animals and 112 from diseased . All isolates were serotyped and MICs were determined for nine antimicrobial compounds . Non-haemolytic isolates numbered 147, whereas 63 were haemolytic . Both haemolytic and non-haemolytic isolates were isolated from both healthy and diseased animals.A wide range of serogroups was detected, the most frequent being O2 (11.0%), O78 (11.0%), O153 (7.1%), O25 (5.7%), O6 (4.8%), and O15 (4.8%), but diarrhoea was not associated with specific serogroups . All isolates were sensitive to enrofloxacin, neomycin, gentamicin and colistin . In contrast, considerable variations in susceptibility were found among the six mink farms, for tetracycline (0-46.4%, average 21.9), ampicillin (2.9-50.0%, average 23.3), spectinomycin (8.0-35.7%, average 21.9), sulfamethoxazole (8.6-57.7%, average 30.0) and trimethoprim (0-35.7%, average 9.5) . Resistance to tetracycline was statistically more prevalent among haemolytic than among non-haemolytic strains.In conclusion, serogrouping and haemolysin testing failed to identify any association with diarrhoeal disease and antimicrobial resistance was highly variable between different mink farms.

Science, 2001 Mar 2, 291(5509), 1783 - 5
An antimicrobial peptide gene found in the male reproductive system of rats; Li P et al.; Little is known about the innate defense mechanisms of the male reproductive tract . We cloned a 385-base pair complementary DNA and its genomic DNA named Bin1b that is exclusively expressed in the caput region of the rat epididymis and that is responsible for sperm maturation, storage, and protection . Bin1b exhibits structural characteristics and antimicrobial activity similar to that of cationic antimicrobial peptides, beta-defensins . Bin1b is maximally expressed when the rats are sexually mature and can be up-regulated by inflammation . Bin1b appears to be a natural epididymis-specific antimicrobial peptide that plays a role in reproductive tract host defense and male fertility.

J Clin Microbiol, 2001 Mar, 39(3), 930 - 5
Clinical significance and taxonomy of Actinobacillus hominis; Friis-Moller A et al.; Clinical findings in 36 immunosuppressed patients with lower respiratory tract infection or bacteremia with Actinobacillus hominis are described . Animal contact was only recorded for three patients; nine patients died despite appropriate antimicrobial treatment . Although infections with this microorganism seem to be rare, the fact that 37 of 46 strains characterized in this study have been found in Copenhagen indicates that under-reporting may occur . A . hominis is phenotypically relatively homogeneous but can be difficult to differentiate from other Actinobacillus species unless extensive biochemical testing is performed . Mannose-positive strains of A . hominis are especially difficult to differentiate from A . equuli . Attempts to identify A . hominis by automatic identification systems may lead to misidentifications . Ribotyping and DNA-DNA hybridization data show that A . hominis is a homogeneous species clearly separated from other species within the genus Actinobacillus.

J Am Vet Med Assoc, 2001 Feb 15, 218(4), 541 - 2, 526
Intraosseous approach to the nasolacrimal duct for removal of a foreign body in a dog; Pope ER et al.; A Labrador retriever was evaluated because of chronic mucopurulent discharge from the left eye . A foreign body was identified in the nasolacrimal duct by use of dacryocystorhinography . Attempts to alleviate the inflammation by use of flushing and administration of antimicrobials were unsuccessful . At surgery, the infraorbital foramen was used as a landmark for a skin incision, because the nasolacrimal duct courses dorsal and parallel to the infraorbital canal . An air drill was used to remove the portion of the maxillary bone overlying the nasolacrimal duct, which exposed the intraosseous portion of the duct and allowed removal of a plant-material foreign body . The incision in the duct was allowed to heal by second intention, and the dog recovered without complications.

Veterinary Clin North Am Exot Anim Pract, 2000 Jan, 3(1), 333 - 58, viii
A formulary for lizards, snakes, and crocodilians; Funk RS; A formulary of drug dosages for use in lizards, snakes, and crocodilians based primarily on a survey of the existing literature is provided . The formulary is presented as a series of four tables: antimicrobial drugs; parasiticide drugs; anesthetic and analgesic drugs; and miscellaneous drugs . An extensive bibliography is included.

JAMA, 2001 Feb 28, 285(8), 1039 - 43
Culture and immunological detection of Tropheryma whippelii from the duodenum of a patient with Whipple disease; Raoult D et al.; CONTEXT: Culture of Tropheryma whippelii has been established only once, in human fibroblast cell lines from a heart valve inoculum . Molecular-based diagnostic techniques, although highly sensitive, may be less specific . New diagnostic tools involving isolation of bacteria from contaminated intestinal biopsies and immunohistological detection need to be developed . OBJECTIVE: To describe a novel method for detection and culture of T whippelii strains . DESIGN, SETTING, AND SUBJECTS: Laboratory analysis of duodenal biopsy specimens from a patient with typical relapsing Whipple disease with intestinal involvement, performed Marseille, France, in March 2000 . Biopsy specimens were decontaminated with antimicrobial agents and inoculated onto cell cultures . Mouse anti-T whippelii polyclonal antibodies were used to detect T whippelii in fixed specimens taken from the patient before and after relapse, compared with specimens from 10 controls . The genotype of the isolate was determined by amplification and sequencing of 2 DNA fragments (ITS and 23S rRNA) . MAIN OUTCOME MEASURE: Isolation and genotyping of a new strain(s) of T whippelii from the case patient's biopsy specimens . RESULTS: A strain was grown from the case patient's intestinal specimen that has a genotype different from the first strain isolated . During 2 episodes of Whipple disease, T whippelii bacteria were detected by immunochemistry in the patient's duodenal biopsy specimens, but not in controls . CONCLUSIONS: A second strain of T whippelii has been isolated and a protocol for isolation from the intestine has been proven to be efficient . Immunodetection of T whippelii in intestinal biopsy specimens may provide a useful tool for the diagnosis and follow-up of patients with Whipple disease . Both techniques need further evaluation and confirmation.

Am J Kidney Dis . 2001 Mar;37(3):E22.
Hemolytic uremic syndrome in an adolescent with Fusobacterium necrophorum bacteremia; Chand DH et al.; Microorganisms may produce substances that disrupt the interaction between platelets and vascular endothelium, which has been associated with atypical hemolytic uremic syndrome (HUS) . We present the first reported case of Fusobacterium necrophorum bacteremia that presented initially with atypical HUS . Antimicrobial therapy eradicated the patient's bacteremia, and plasmapheresis restored platelet-endothelial homeostasis . Understanding the pathophysiologic mechanisms involved in atypical HUS would guide the development of more precise therapies.

Acta Paediatr, 2001 Jan, 90(1), 96 - 8
Early sepsis, obstructive jaundice and right-sided diaphragmatic hernia in the newborn; Garcia-Munoz F et al.; A male newborn was admitted to our Unit because of early sepsis and shock . He required antimicrobial therapy and mechanical ventilation and initially did well, although he exhibited jaundice and cholestasis . During the second week he deteriorated, with radiological opacification of the right hemithorax and pleural effusion, and did poorly in spite of antibiotical therapy and drainage of the effusion . In the third week, the X-ray suggested some bowel loops in the right hemithorax . A right-sided diaphragmatic hernia was confirmed by a CT-scan, and surgery was performed with good outcome . The association of delayed-onset right-sided CDH following early sepsis and obstructive jaundice has not been published before, and illustrates a scarcely known form of presentation of this condition.

Rev Med Chil, 2000 Dec, 128(12), 1319 - 26
{In vitro comparative activity of moxifloxacin and other antimicrobials against respiratory pathogens}; Prado V et al.; BACKGROUND: Respiratory pathogens are becoming increasingly resistant to antimicrobials . A new group of drugs, called respiratory quinolones have been synthesized to overcome this problem . AIM: To study the in vitro susceptibility of respiratory pathogens to old and new antimicrobials . MATERIALS AND METHODS: Forty five strains of S pneumoniae, 44 strains of H influenzae, 21 strains of M catarrhalis, 10 strains of methicillin susceptible S aureus and 20 strains of methicillin resistant S aureus were studied . All were isolated from community acquired respiratory infections during 1999 . Minimal inhibitory concentrations of moxifloxacin, amoxicillin, amoxicillin/clavulanic acid, clarithromycin, azithromycin, ciprofloxacin and levofloxacin were determined using the Etest method . Beta-lactamase production by H influenzae and M catarrhalis was also studied . RESULTS: S pneumoniae strains were 100% susceptible to quinolones and cotrimoxazole, 2% were resistant to macrolides, 11% were resistant to amoxicillin/clavulanic acid and 47% were resistant to cefuroxime . H influenzae was 100% susceptible to quinolones, azithromycin and amoxicillin/clavulanic acid . There was a 53% resistance to cotrimoxazole, 21% to amoxicillin, 9% to clarithromycin and 7% to cefuroxime . M catarrahalis was 100% susceptible to quinolones and 100% resistant to amoxicillin, 5% resistant to macrolides, 14% resistant to amoxicillin/clavulanic acid, 20% to cefuroxime and 30% to cotrimoxazole . Methicillin susceptible S aureus was susceptible to all antimicrobials and methicillin resistant S aureus was resistant to all . CONCLUSIONS: Maxifloxacin and the new respiratory quinolones can be useful in the treatment of respiratory infections.

Burns, 2001 Mar, 27(2), 167 - 73
A newly developed hydrofibre dressing, in the treatment of partial-thickness burns; Vloemans AF et al.; A newly developed, carboxymethylcellulose based hydrofibre dressing, Aquacel, was tested for the treatment of partial thickness burns . In this study 84 patients with mainly partial thickness burns were included, 76 patients received 1 or 2 days pre-treatment with a topical antimicrobial agent . Clinical behaviour showed a strong resemblance with cadaver skin treatment with respect to adherence to the wound . Adverse reactions, incidence of clinical wound infection, healing time and the need for wound excision and grafting were analysed, as was the final outcome using the 'Vancouver Scar Scale' . The mean size of the wounds treated with the hydrofibre dressing was 6.0% body surface area (min: 1%, max: 18%) . Two patients clinically showed signs of a wound infection during treatment, but in general wound cultures were low or negative . In 42 patients (50%) the wounds healed completely within 10 days, in six patients (7%) small defects remained that healed by further treatment with a topical antimicrobial cream . In 36 patients (43%) excision and grafting of the remaining deeper parts of the wounds was performed as this is the standard therapy in the centre for all burned areas that have not healed within 2-3 weeks post-injury . The extent of the surgical procedures was limited since 66.1% of the wound area had healed already at the end of the hydrofibre treatment . In 54 patients the outcome of the treatment after 2-3 months was analysed by means of the Vancouver Scar Scale, which showed favourable results in general, and especially for patients who did not require surgery . Compared to earlier experience with allograft skin it was concluded that hydrofibre dressing is a safe, suitable and easy to use material for treatment of partial thickness burns.

Urologe A, 2001 Jan, 40(1), 24 - 8
{Therapy of prostatitis syndrome}; Wagenlehner FM et al.; The chronic prostatitis syndrome is a multifactorial disease of mainly unknown etiology . Quite different therapeutic options are therefore recommended . According to the new NIH classification only in acute and chronic bacterial prostatitis pathogens can be cultured . A long-term antimicrobial therapy, mainly with fluoroquinolones, is therefore recommended . Most of the patients, however, suffer from a chronic pelvic pain syndrome (CPPS) which can be subdivided into an inflammatory and a non-inflammatory CPPS . Whether the inflammatory CPPS is an infectious disease, remains uncertain . An antibiotic therapy therefore is not the first choice . Several patients, however, have been improved by such a therapy, especially in combination with alpha-receptor blockers . In case of proven or suspected functional obstruction of the bladder neck long-term treatment with relatively high dosages of alpha-receptor blockers is recommended . In case of failure other treatment modalities, including psychosomatics, may be applied, of which usually only results of sporadic reports but not of controlled studies are available . It is important, however, to keep the patient fully informed about the diagnostic and therapeutic problems not to interfere with a trustful therapist-patient relationship.

Urologe A, 2001 Jan, 40(1), 18 - 23
{Prostatitis syndrome . Changes in the ejaculate and effects on fertility}; Ludwig M et al.; Inflammation and infections of the male reproductive tract represent an important factor in male infertility that is potentially responsive to successful therapy . A standardized diagnostic procedure is a prerequisite for the exact evaluation of alterations of ejaculate specimens, especially in cases of the different forms of the prostatitis syndrome . Several alterations in ejaculate due to inflammation and infection have been identified that have a negative impact on the quality of sperm . Besides the influence of leuko- and bacteriospermia, the effect of inflammatory mediators, such as cytokines and reactive oxygen species (ROS), are being discussed as relevant pathomechanisms . These parameters just recently were incorporated into the conventional range of diagnostic criteria . Clinical studies that investigate the quality of ejaculate in the different forms of the prostatitis syndrome yielded contradictory results . Only antimicrobial therapy has been sufficiently described as a therapeutic option . In the future, it will be decisive to include novel functional and molecular parameters to define an interaction of urogenital infection and male infertility.

Am J Health Syst Pharm, 2001 Feb 15, 58(4), 307 - 16; quiz 317-9
Treatment of Crohn's disease with infliximab; Garnett WR et al.; The role of infliximab in managing Crohn's disease (CD) is described . CD is characterized by chronic transmural inflammation at various sites of the gastrointestinal tract, particularly the ileum and colon . The major symptoms are diarrhea, abdominal pain, enterocutaneous and perianal fistulas, and weight loss . Management goals include alleviating symptoms, inducing remission, promoting healing of the intestinal mucosa and fistulas, and modifying the disease process . Drugs traditionally used to manage CD are aminosalicylates, antimicrobials, immunomodulatory agents, and corticosteroids . Infliximab is a chimeric (human-mouse) monoclonal antibody targeted at human tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine important in the pathogenesis of CD . Infliximab antagonizes the biological activity of TNF-alpha by binding to it on macrophage and T-cell surfaces . Clinical trials have shown infliximab to be effective in producing and maintaining a clinical response in patients with refractory, moderate to severe CD . Treatment helps promote healing of intestinal mucosa and closure of fistulas . Infliximab may act more rapidly than most traditional agents and produces less severe adverse effects . The most frequent adverse effects are headache, nausea, and upper-respiratory-tract infections . The recommended dosage is 5 mg/kg i.v . infused over a two-hour period . Infliximab may be given at eight-week intervals for maintenance or management of flare-ups . Infliximab appears useful in the treatment of CD and may improve patients' quality of life.

WMJ, 2000 Dec, 99(9), 39 - 42
Preventing animal bites in children; Whalen B; Domesticated animals have become an increasingly important part of our human experience . Children today are likely to experience daily interactions with animals within their neighborhoods and homes . These animals can provide children with companionship, the opportunity to learn responsibility and respect for life . Yet they can also present children with the potential for injury under certain conditions . Almost half of all children will suffer an animal bite at some time during their childhood, and over 15% of these bites will require medical care . This article will discuss the circumstances leading to most domesticated animal bites, provide advice to the practitioner in helping families choose kid-friendly pets and provide guidance in promoting safe interactions with animals . A future article will review the management of animal bites, including wound care, antimicrobial prophylaxis and the treatment of infected bite wounds . Doctor Corden's article in this issue (p . 43) addresses the role for rabies prevention in animal bites.

Voen Med Zh, 2001 Jan, 322(1), 57 - 67, 92
{Treatment of pseudotuberculosis in military personnel (scientific basis and practical recommendations)}; Lobzin IuV et al.; The efficiency of 22 schemes of etiotropic therapy including treatment courses of different duration and new methods was studied basing on the results of examination of 1376 patients and retrospective analysis of 2008 cases of pseudotuberculosis in servicemen . Critical review of literature dealing with this problem was conducted . The causes of contradictory literary data have been revealed . Specificity of military service and pseudotuberculosis pathogenesis influencing on disease course and efficiency of its treatment has been shown . Taking into account our own investigations and analysis of literature there was developed the scheme of differentiated etiopathogenetic therapy of pseudotuberculosis with the use of original approaches including the method of two-stage intermittent antimicrobial therapy, stepped (parenteral-oral) etiotropic therapy, antihypoxants, gg-ABA-ergic and nootropic agents, adaptogenes, dose increase of physical load, new physiotherapeutic methods, endolymphatic administration of antibiotics.

Pediatr Infect Dis J, 2001 Feb, 20(2), 214 - 5
Misuse of antimicrobials in children with asthma and bronchiolitis: a review; Henderson M et al.; Of 200 children hospitalized because of asthma or bronchiolitis, 100 received antibiotics inappropriately.

Pediatr Infect Dis J, 2001 Feb, 20(2), 140 - 4
National differences in incidence of acute mastoiditis: relationship to prescribing patterns of antibiotics for acute otitis media?
Van Zuijlen DA, Schilder AG, Van Balen FA, Hoes AW.
BACKGROUND: Operating on the principle that most acute otitis media (AOM) episodes resolve without antibiotics, doctors in the Netherlands usually manage AOM in children with initial observation . Prescription of antibiotics is limited to children with a complicated course of AOM and those categorized as high risk . Consequently only 31% of patients with AOM receives antibiotics, compared with >90% in most other countries . OBJECTIVE: To substantiate the suggestion that this restrictive use of antibiotics leads to a higher incidence of acute mastoiditis . METHODS: A comparative study across several European countries, Canada, Australia and the United States was performed in the period 1991 to 1998 . The incidence rate of acute mastoiditis was defined as the total number of patients age 14 years and younger discharged from all hospitals with the primary diagnosis of acute mastoiditis, during a specified period (usually 5 years), divided by the number of person years (py) in that same age range and period . The latter was calculated by totaling the midyear population estimate of children age 14 years and younger of each year . The 95% confidence intervals and incidence rate ratios were calculated to compare the observed rates . RESULTS: The incidence rate of acute mastoiditis in the Netherlands, with a low antibiotic prescription rate for AOM, was 3.8/100,000 py; in Norway and Denmark, with high prescription rates, the incidence rate was comparable at 3.5/100,000 py and 4.2/100,000 py, respectively . In all other countries with very high prescription rates, incidence rates were considerably lower, ranging from 1.2 to 2.0/100,000 py . The incidence rate in the Netherlands was about twice that in the United States (rate ratio, 0.5) . CONCLUSION: The incidence rate of acute mastoiditis in the Netherlands is higher than in many countries with higher antibiotic prescription rates . Although the potential benefits of restricted use of antibiotics (i.e . cost reduction, fewer side effects from antibiotics and less antimicrobial resistance) are beyond dispute, such strategy may be associated with a somewhat higher incidence of acute mastoiditis.

Ann Surg, 2001 Mar, 233(3), 400 - 8
Use of porcine acellular dermal matrix as a dermal substitute in rats; Srivastava A et al.; OBJECTIVE: To examine porcine acellular dermal matrix (ADM) as a xenogenic dermal substitute in a rat model . SUMMARY BACKGROUND DATA: Acellular dermal matrix has been used in the treatment of full-thickness skin injuries as an allogenic dermal substitute providing a stable wound base in human and animal studies . METHODS: Xenogenic and allogenic ADMs were produced by treating porcine or rat skin with Dispase and Triton X-100 . Full-thickness skin defects (225 mm2) were created on the dorsum of rats (n = 29), porcine or rat ADMs were implanted in them, and these were overlain with ultrathin split-thickness skin grafts (STSGs) . In two adjacent wounds, 0.005- or 0.017-inch-thick autografts were implanted . In other experiments, the antimicrobial agent used during ADM processing (azide or a mixture of antibiotics) and the orientation of the implanted ADM (papillary or reticular side of ADM facing the STSG) were studied . Grafts were evaluated grossly and histologically for 30 days after surgery . RESULTS: Significant wound contraction was seen at 14, 20, and 30 days after surgery in wounds receiving xenogenic ADM, allogenic ADM, and thin STSGs . Contraction of wounds containing xenogenic ADM was significantly greater than that of wounds containing allogenic ADM at 30 days after surgery . Graft take was poor in wounds containing xenogenic ADM and moderately good in those containing allogenic ADM . Wound healing was not significantly affected by the antimicrobial agent used during ADM preparation or by the ADM orientation . CONCLUSION: Dispase-Triton-treated allogenic ADM was useful as a dermal substitute in full-thickness skin defects, but healing with xenogenic ADM was poor.

Gene, 2001 Jan 24, 263(1-2), 211 - 8
Discovery of new human beta-defensins using a genomics-based approach; Jia HP et al.; Epithelial beta-defensins are broad-spectrum cationic antimicrobial peptides that also act as chemokines for adaptive immune cells . In the human genome, all known defensin genes cluster to a <1 Mb region of chromosome 8p22-p23 . To identify new defensin genes, the DNA sequence from a contig of large-insert genomic clones from the region containing human beta-defensin-2 (HBD-2) was analyzed for the presence of defensin genes . This sequence survey identified a novel beta-defensin, termed HBD-3 . The HBD-3 gene contains two exons, is located 13 kb upstream from the HBD-2 gene, and it is transcribed in the same direction . A partial HBD-3 cDNA clone was amplified from cDNA derived from IL-1beta induced fetal lung tissue . The cDNA sequence encodes for a 67 amino acid peptide that is approximately 43% identical to HBD-2 and shares the beta-defensin six cysteine motif . By PCR analysis of two commercial cDNA panels, HBD-3 expression was detected in adult heart, skeletal muscle, placenta and in fetal thymus . From RT-PCR experiments, HBD-3 expression was observed in skin, esophagus, gingival keratinocytes, placenta and trachea . Furthermore, in fetal lung explants and gingival keratinocytes, HBD-3 mRNA expression was induced by IL-1beta . Additional sequence analysis identified the HE2 (human epididymis secretory protein) gene 17 kb upstream from the HBD-3 gene . One splice variant of this gene (HE2beta1) encodes a beta-defensin consensus cysteine motif, suggesting it represents a defensin gene product . HE2beta1 mRNA expression was detected in gingival keratinocytes and bronchial epithelia using RT-PCR analysis . The discovery of these novel beta-defensin genes may allow further understanding of the role of defensins in host immunity at mucosal surfaces.

Fitoterapia, 2001 Feb, 72(2), 174 - 6
Antimicrobial activity of Castanopsis acuminatissima; Khan MR et al.; The methanol extracts of Castanopsis acuminatissima leaves, stem and root barks were partitioned (petrol, dichloromethane, ethyl acetate) . Though all of the crude methanolic extracts and obtained fractions from them, showed a broad spectrum of antibacterial activity, in most cases the activity was decreased on fractionation . None was active against tested moulds.

J Bacteriol, 2001 Mar, 183(6), 2137 - 40
Construction and characterization of mutations at codon 751 of the Escherichia coli gyrB gene that confer resistance to the antimicrobial peptide microcin B17 and alter the activity of DNA gyrase; del Castillo FJ et al.; Microcin B17 is a peptide antibiotic that inhibits DNA replication in Escherichia coli by targeting DNA gyrase . Previously, two independently isolated microcin B17-resistant mutants were shown to harbor the same gyrB point mutation that results in the replacement of tryptophan 751 by arginine in the GyrB polypeptide . We used site-directed mutagenesis to construct mutants in which tryptophan 751 was deleted or replaced by other amino acids . These mutants exhibit altered DNA gyrase activity and different levels of resistance to microcin B17.

Vet Clin North Am Equine Pract, 2000 Dec, 16(3), 515 - 36, ix-x
Antimicrobic and anthelmintic resistance; Dargatz DA et al.; Antimicrobial and anthelmintic resistance are growing issues for the equine practitioner . The development of antimicrobial or anthelmintic resistance is a source of significant concern because of increased frequency of treatment failures and increased treatment costs . In addition, antimicrobial resistance may have important consequences for public health . Only through judicious use can the efficacy of antimicrobials and anthelmintics be prolonged . This article discusses the development of resistance and suggestions for control.

Int J Clin Pract Suppl . 2000 Dec;(115):26.
International outpatient parenteral antimicrobial therapy; Tice AD; On an international basis, outpatient parenteral antimicrobial therapy (OPAT) varies greatly . There are cultural as well as economic issues which make it different in every country . In general, the duration of hospital stay varies with the outpatient resources available and the economic base for them . In some countries, there may not be money available for any intravenous antibiotics, even in the hospital . In addition, there are great differences in outpatient intravenous therapy, with infusion clinics proliferating in China, yet these are scarce in the UK . There is also considerable variation in the use of intramuscular compared with intravenous therapies . In Italy, intramuscular ceftriaxone is used more often than intravenous therapy . While ceftriaxone use is high in the US, its use is surpassed on a per capita basis by Italy, and it is most interesting that the rate of antimicrobial resistance is lower in Italy than in most other European countries . Whether this relates to outpatient use, parenteral use or other unknown factors is unclear . Obviously, further studies are necessary.

Int J Clin Pract Suppl, 2000 Dec, (115), 14 - 7
Risk stratification for patients with community-acquired pneumonia; Fine MJ; Community-acquired pneumonia (CAP) is a common medical illness with a prognosis that ranges from rapid complete recovery to severe medical complications and death . Approximately 4 million adults are diagnosed with CAP in the US each year; with more than 600,000 (15%) hospitalised . An estimated $4 billion is expended annually on patients with CAP, with inpatient therapy costing as much as 20 times that of outpatient antimicrobial therapy . Determining severity of illness and using this information to risk-stratify patients with CAP is important from several perspectives . Clinically, understanding prognosis can assist physicians in the initial site of treatment decision (home versus hospital) and can be used to communicate expected outcomes to patients . From a research perspective, risk stratification can be used to select appropriate patient subgroups for clinical trials and to provide severity-adjusted outcomes comparisons . From a policy perspective, severity-adjusted outcomes can be used as a proxy for quality of medical care.

World Health Organ Tech Rep Ser, 2000, 893, i - viii, 1-102
Evaluation of certain veterinary drug residues in food; Joint FAO/WHO Expert Committee on Food Additives; This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs and to recommend maximum levels for such residues . The first part of the report considers an approach to assessing the safety of antimicrobial drug residues and their effects on the human intestinal microflora and general issues relating to the recommendation of Maximum Residue Levels (MRLs) for veterinary drug residues in food . A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: one beta-adrenoceptor-blocking agent (carazolol), one anthelminthic agent (doramectin), four antimicrobial agents (dihydrostreptomycin, streptomycin, neomycin and thiamphenicol), two insecticides (deltamethrin and phoxim), four production aids (estradiol-17 beta, progesterone, testosterone and porcine somatotropins) and one tranquillizing agent (azaperone) . Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and MRLs, and other information required.

Nippon Rinsho, 2001 Feb, 59(2), 291 - 5
{Antimicrobial resistant test of H . pylori}; Inoue K et al.; The resistance of Helicobacter pylori (H . pylori) to antibiotics leaves great influence on treatment outcome . Agar and broth dilution techniques are difficult to perform and not practical . E-test has the advantage of allowing visualization of resistant subpopulations of bacteria within zones of inhibitions . We studied point mutation of 23s-rRNA gene for H . pylori strains . (74 clarithromycin (CAM)-resistant, 6 CAM-susceptible) The results of these assays were well correlated with these of E-test . The cure rate of triple therapy with metoronidazole (MTZ) for CAM-resistant H . pylori is 100%(11/11), and that with CAM for MTZ-resistant H . pylori is 94.4% (17/18) . It is very difficult to eradicate CAM and MTZ-resistant H . pylori.

Kansenshogaku Zasshi, 2001 Jan, 75(1), 1 - 6
{Susceptibility testing of clinical strains of Legionella spp . isolated in Japan}; Murakami H et al.; We determined antimicrobial susceptibilities of 23 strains of Legionella spp . clinically isolated in Japan, between September 1994 through November 1999 by using Etest . The MICs of all isolates against macrorides, fluoroquinolones and rifampicin showed 1 microgram/ml or less . Especially rifampicin showed the most potent activity, of which the MICs of all isolates showed 0.064 microgram/ml or less . Although we could not find resistant strains against any antibiotics tested in this study, we think it is important to follow up the susceptibilities of clinical isolates of Legionella.

Scand J Gastroenterol, 2001 Jan, 36(1), 92 - 6
Small intestinal bacterial overgrowth versus antimicrobial capacity in patients with spontaneous bacterial peritonitis; Chang CS et al.; BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious infection in cirrhotic patients with ascites . Both defects in the host defense mechanisms and the enhancement of the offensive factor (small intestinal bacterial overgrowth (SIBO)) may contribute to the development of SBP . Therefore, the aim of this study was to evaluate the role of SIBO versus various antimicrobial capacities in the pathogenesis of SBP in cirrhotic patients . METHODS: Forty-five cirrhotic patients were enrolled in this study . Bacterial overgrowth was evaluated by breath hydrogen test (BH2T) . The hepatic reticuloendothelial system phagocytic index (HRESPI) was measured by intravenously injected colloid suspensions . RESULTS: The Child-Pugh scores in the SBP group were higher than in the non-SBP group (10.5 +/- 2.0 versus 8.0 +/- 1.8, P < 0.01) . The ascitic protein concentration was significantly lower in the SBP group than in the non-SBP group (897 +/- 425 mg/l versus 1,325 +/- 453 mg/l, P < 0.01) . Furthermore, the serum C3 concentration was lower in the SBP group than in the non-SBP group (43.1 +/- 13.6 ng/dl versus 73.2 +/- 26.4 ng/dl, P < 0.01) . The serum C4 concentration was also lower in the SBP group than in the non-SBP group (12.4 +/- 4.0 ng/dl versus 16.9 +/- 6.6 ng/dl, P < 0.05) . The incidence of SIBO was higher in the SBP group than in the non-SBP group (68.2% versus 17.4%, P < 0.01) . HRESPI values were significantly higher in the two groups of cirrhotic patients than in the normal reference . However, there were no statistical differences in HRESPI between the two groups (8.4 +/- 2.8 min in the SBP group versus 7.9 +/- 2.8 min in the non-SBP group) . CONCLUSIONS: The results of this study showed that the hepatic reticuloendothelial function is impaired in cirrhotic patients, but the degree of impairment does not differ between patients with and without previous history of SBP . Lower ascitic total protein, lower serum C3 and C4 concentrations, and presence of SIBO are all risk factors for SBP . Based on the results of our study, defects in the host defense mechanisms and the enhancement of the offensive factor (SIBO) may act in concert for the development of SBP.

Epidemiol Infect, 2000 Dec, 125(3), 561 - 72
Serotypes/groups distribution and antimicrobial resistance of invasive pneumococcal isolates: implications for vaccine strategies; Kyaw MH et al.; Based on the invasive pneumococcal isolates referred to reference laboratories in Scotland in 1988-99, we identified the distribution of serotypes/groups and their antimicrobial resistance patterns in order to evaluate the coverage of polysaccharide and the new pneumococcal conjugate vaccines . A total of 5659 invasive isolates were included . Of these, 5124 (90.5%) were blood isolates, 308 (5.5%) were CSF isolates, 143 (2.5%) were blood and CSF and 84 (1.5%) were other normally sterile isolates . The most prevalent 11 serotypes/groups were 14, 9, 19, 6, 23, 1, 3, 4, 7, 8 and 18, in numerical order . These accounted for 84% of total serotypes/groups . The serotypes/groups included in the 23 and 14-valent polysaccharide vaccines accounted for 96% and 88% of all isolates . Both vaccines accounted for 98% of penicillin non-susceptible and 100% of erythromycin non-susceptible isolates . The 7, 9, and 11-valent conjugate vaccines covered 61, 68 and 80% of invasive isolates respectively . The coverage of these vaccines was substantially higher in youngest age group with 84, 86 and 93% of invasive isolates in children < 2 years included in the 7, 9 and 11-valent conjugate vaccines compared with 58, 64 and 77% in adults > or = 65 years of age . The serotype/group distribution of invasive isolates in Scotland varied from year to year over the period 1993-9 . The coverage of the 23-valent vaccine remained above 95% in each year but the coverage of the 7, 9 and 11-valent conjugate vaccines showed more marked fluctuation with coverage as low as 53, 60 and 75% in some years . Continued surveillance of invasive pneumococcal isolates is required to inform the development of appropriate vaccine strategies to prevent pneumococcal disease in Scotland.

J Chromatogr A, 2001 Jan 12, 907(1-2), 173 - 9
Reversed-phase high-performance liquid chromatography versus spectrophotometric assay for thimerosal in Cuban recombinant hepatitis B vaccine; Costa L et al.; A reversed-phase liquid chromatographic method was applied to study the stability of thimerosal in Cuban recombinant hepatitis B vaccine samples stored under different temperature conditions . Salicylic acid was used as internal standard, it allowed one to determine the thimerosal in the presence of its degradation products . Good stability of the preservative was demonstrated in vaccine samples for as long as 6 years . The same results were obtained when the vaccine samples were incubated at 37 and 45 degrees C during 30 days . The results were in compliance with the microbiological test for determining the effectiveness of antimicrobial preservative in these samples.

Ann Plast Surg, 2001 Feb, 46(2), 174 - 7
Calcific myonecrosis: case report and review; Jassal DS et al.; Although a rare diagnosis, with few reports in the literature, calcific myonecrosis is a diagnosis that must be entertained in individuals presenting with expanding masses in the muscle compartments occurring years after an initial injury . The authors report a previously healthy 66-year-old man with an expanding right lower extremity mass felt initially to be an abscess . Despite presumably appropriate antimicrobial therapy, the lesion continued to expand, causing pain and loss of function . The patient subsequently underwent extensive debridement and free muscle flap transfer with an excellent outcome . This patient serves to remind us that, although calcific myonecrosis is an uncommonly encountered condition, it must be maintained in the differential diagnosis of an expanding muscle compartment mass.

Arzneimittelforschung, 2001 Jan, 51(1), 67 - 71
Antimicrobial activity of new coumarin derivatives; Kawase M et al.; A preliminary exploration of coumarin analogs as novel antimicrobial agents was carried out to determine the basic features of the structure responsible for the observed biological activity . The substituents ester or carboxylic acid on the coumarin ring were needed to have potent inhibitory activity against both Gram-positive and Gram-negative bacteria . The presence of phenolic hydroxyl group and/or carboxylic acid was necessary to possess higher activity against Helicobacter pylori.

Rinsho Byori, 2000 Oct, 48(10), 926 - 30
{What should a laboratory physician expect from a microbiology laboratory?}; Kumasaka K; Remarkable changes are affecting the discipline of Clinical Pathology/Laboratory Medicine in Japan . Laboratories are changing from revenue centers to cost centers that have many serious problems(ex . closure of the clinical laboratories in the hospitals and outsourcing of laboratory tests due to restructuring in response to economic aspect, limited numbers of certified laboratory physicians, and other factors) . And many clinicians in university hospitals do not know what they should expect correctly from the microbiology laboratory . Therefore, we, laboratory physicians and medical technologists must modify our behavior effectively and establish a good collaborative partnership with physicians, nurses and other health care professionals . The microbiology laboratory should provide information that will affect clinical management guidelines for obtaining specimens, microbial identification, antimicrobial susceptibilities, reporting of data and educational updating . Leadership and management skills must be increasingly critical to the success of laboratory physicians in and outside of academic centers.

Med Pregl, 2000 Jul-Aug, 53(7-8), 363 - 8
{The modern approach to wound treatment}; Komarcevic A; INTRODUCTION: Wound healing is a complex process involving interactions among a variety of different cell types . The normal wound repair process consists of three phases--inflammation, proliferation, and remodeling that occur in a predictable series of cellular and biochemical events . Wounds are classified according to various criteria: etiology, lasting, morphological characteristics, communications with solid or hollow organs, the degree of contamination . In the last few years many authors use the Color Code Concept, which classifies wounds as red, yellow and black wounds . This paper presents conventional methods of local wound treatment (mechanical cleansing, disinfection with antiseptic solutions, wound debridement--surgical, biological and autolytic; wound closure, topical antibiotic treatment, dressing), as well as general measures (sedation, antitetanous and antibiotic protection, preoperative evaluation and correction of malnutrition, vasoconstriction, hyperglycemia and steroid use, appropriate surgical technique, and postoperative prevention of vasoconstriction through pain relief, warming and adequate volume resuscitation) . THE ROLE OF PHYSIOLOGICAL FACTORS AND ANTIMICROBIAL AGENTS IN WOUND HEALING: Growth factors play a role in cell division, migration, differentiation, protein expression, enzyme production and have a potential ability to heal wounds by stimulating angiogenesis and cellular proliferation, affecting the production and the degradation of the extracellular matrix, and by being chemotactic for inflammatory cells and fibroblasts . There are seven major families of growth factors: epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), interleukins (ILs), and colony-stimulating factor (CSF) . Acute wounds contain many growth factors that play a crucial role in the initial phases of wound healing . The events of early wound healing reflect a finely balanced environment leading to uncomplicated and rapid wound healing . Chronic wounds, for many reasons, have lost this fine balance . Multiple studies have evaluated the effect that exogenously applied growth factors have on the healing of chronic wounds . In the study conducted by Knighton and colleagues, topical application of mixture of various growth factors (PDGF, TGF-beta, PDAF, PF4, PDEGF) demonstrated increased wound healing over controls . Brown and associates demonstrated a decrease in skin graft donor site healing time of 1 day using topically applied EGF . Herndon and ass . used systemic growth hormone in burned children and reduction in healing time made a significant clinical difference by allowing earlier wound coverage and decreasing the duration of hospitalization . The TGF family of growth factors is believed to be primarily responsible for excessive scar formation, especially the beta 1 and beta 2 isoforms . TGF-beta 3 isoform has recently been described and may have an inhibitory function on scar formation by being a natural antagonist to the TGF-beta 1 and TGF-beta 2 isoforms . Cytokines, especially interferon-alpha (INF-alpha), INF-alpha, and INF-alpha 2b, may also reduce scar formation . These cytokines decrease the proliferation rate of fibroblasts and reduce the rate of collagen and fibronectin synthesis by reducing the production of mRNA . Expression of nitric oxide synthase (NOS) and heat shock proteins (HSP) have an important role in wound healing, as well as trace elements (zinc, copper, manganese) . Applications of some drugs (antioxidants--asiaticoside, vitamin E and ascorbic acid; calcium D-pantothenate, exogenous fibronectin; antileprosy drugs--oil of hydnocarpus; alcoholic extract of yeast) accelerate wound healing . Thymic peptide thymosin beta 4 (T beta 4R) topically applicated, increases collagen deposition and angiogenesis and stimulates keratinocyte migration . Thymosin alpha 1 (T alpha 1R), peptide isolated from the thymus, is a potent chemoattractant which accelerates angiogenesis and wound healing . On the contrary, steroid drugs, hemorrhage and denervation of wounds have negative effect on the healing process.

J Med Liban, 2000 Jul-Aug, 48(4), 270 - 7
Infectious diarrhea: pathogens and treatment; Carroll KC et al.; Infectious diarrhea is the most common infectious disease syndrome worldwide resulting in more than five million deaths annually . The greatest morbidity and mortality is seen among children younger than two years of age . A variety of bacterial, viral and parasitic pathogens are responsible for the various syndromes . A combination of host susceptibility and organism virulence factors is responsible for disease . Most episodes of gastroenteritis are self-limited . The hallmark of patient management is strict attention to fluid and electrolyte disturbances . Antimotility agents should be used with caution if at all in children, but may be helpful in adults with travelers' diarrhea . Antimicrobial therapy may shorten the duration of diarrhea in some illnesses, but use is restricted due to emergence of resistance or due to lack of availability in some countries . Newer strategies for prevention include vaccine development.

J Med Liban, 2000 Jul-Aug, 48(4), 255 - 63
Treatment of human brucellosis; Solera J; Human brucellosis is a multisystem disease that may present with a broad spectrum of clinical manifestations . The primary goals of therapy for brucellosis are to improve the symptoms, reduce complications and prevent relapses . The choice of a regimen and duration of antimicrobial therapy should be based on the location of the disease and the underlying conditions . The regimen of choice is a combination therapy with doxycycline for 45 days and streptomycin for 14 days . A second-choice consists of a combination of doxycycline and rifampin for 45 days . Children under 8 years old and pregnant women should not be treated with tetracyclines . In children under 8 years old, the preferred regimen is rifampin with cotrimoxazole or gentamicin . Rifampin (900 mg once daily for 6 weeks) is considered the drug of choice for treating brucellosis in pregnant women . Surgery should be considered for patients with endocarditis, cerebral, epidural or splenic abscess or other abscesses, which are resistant to antibiotics.

J Med Liban, 2000 Jul-Aug, 48(4), 241 - 7
Antibiotic prophylaxis; Kanj SS; The use of antibiotic prophylaxis has long been established to prevent the development of invasive infections . In many settings, it is currently considered to be the standard of care to administer antibiotics prior to surgical procedures . The aim is to decrease the load of organisms at the site of manipulation and therefore minimize the appearance of local as well as distant infection . With the increasing number of antimicrobial agents available on the market, physicians are often faced with a dilemma when trying to decide which agent to use . This review addresses the current recommendations of antimicrobial prophylaxis in surgical procedures, in the prevention of infective endocarditis, as well as the prophylaxis required following exposure to highly infective bacteria.

J Med Liban, 2000 Jul-Aug, 48(4), 221 - 6
Current status and changing trends of antimicrobial resistance in Lebanon; Araj GF et al.; Antimicrobial resistance among microorganisms has been on the rise worldwide including Lebanon . Several surveillance programs have been initiated to monitor the patterns of resistance due to the deleterious consequences on patients management . Thus, knowledge about the local antimicrobial resistance patterns is essential for epidemiologic aspects as well as clinical practice . In this context, the current status and changing trends of antimicrobial resistance in Lebanon are addressed covering the most relevant bacterial, mycobacterial and fungal pathogens.

J Med Liban, 2000 Jul-Aug, 48(4), 215 - 20
The impact of antimicrobial resistance on empiric antibiotic selection and antimicrobial use in clinical practice; Sexton DJ; The prevalence of antimicrobial resistance may vary dramatically between countries and regions and even among different patient populations and between hospitals in the same community . In light of these variations, physicians in practice must make a clinical judgment about the likely pathogen(s) involved in the infectious process . They should have access to up-to-date data on the antimicrobial resistance pattern of commonly encountered pathogens . Such data should be subdivided and analyzed for isolates from community as opposed to hospitalized patients . The data on intensive care units patients and from special groups of patients, such as those undergoing dialysis, organ transplant recipients, or cancer patients receiving chemotherapy, should also be made available to practicing physicians . When antimicrobial resistance is considered to be probable or highly likely, or if empirical therapy has failed, a concerted effort should be made to make a microbiologic diagnosis which will ultimately reduce the cost, simplify therapy and improve the outcome over treatment that is solely empirically based.

J Med Liban, 2000 Jul-Aug, 48(4), 199 - 202
Available laboratory tests to guide antimicrobial therapy; Araj GF; Physicians are encountering more difficulties in treating and managing patients with infectious diseases due to the continued emergence of single and multi-drug resistant organisms . This emphasizes the need of laboratory tests that are of help in predicting or monitoring response to therapy . Several conventional, special, automated and molecular antimicrobial susceptibility tests are available including the disk diffusion test, determination of the minimal inhibitory concentration, the E test, serum bactericidal titers, and determination of antimicrobial levels in blood . This article addresses these and other antimicrobial tests to update and enlighten the physicians in selecting the most relevant test(s) that will help guiding the therapy of infections caused by different bacterial etiologic agents.

J Med Liban, 2000 Jul-Aug, 48(4), 186 - 98
Mechanisms of bacterial resistance to antimicrobial agents; Stratton CW; The 20th century has been considered the antimicrobial era--whereas the 21st century may well represent the post-antimicrobial era . The reason for this dramatic change, should it come to pass, is the development of bacterial resistance to antimicrobial agents . This emerging resistance is now challenging the clinical utility of many antimicrobial agents such that the chemotherapy of hospitalized patients with serious infections has been compromised . If the problem with resistance is to be successfully dealt with by clinicians, the mechanisms of such resistance must be known and understood . This paper thus reviews the most important mechanisms of resistance as well as some of the most important pathogens having these mechanisms . An understanding of these important microbial resistance mechanisms will help the clinician identify circumstances in which resistance may be a problem as well as evaluating the potential usefulness of an alternate antimicrobial agent against resistant microbes.

J Med Liban, 2000 Jul-Aug, 48(4), 182 - 5
Optimizing clinical outcomes by the use of pharmokinetic and pharmacodynamic principles; Quintiliani R; Since the advent of antimicrobial chemotherapy, considerable controversy has existed as to the most appropriate method to administer antibiotics to maximize the killing of microorganisms, while minimizing toxicity to the patient . Over the past decade, data gained from animal models of infection, in vitro pharmacodynamic studies, volunteer studies and human clinical trials have enabled us to establish the best mode of drug administration to achieve these goals . The clinician should be aware that appropriate antibiotic selection and dosing depends on pharmacodynamic concepts where there is an integration of the drug's microbiological activity, pharmacokinetic properties and mode of bacterial killing.

Cell Mol Life Sci, 1999 Oct 1, 56(1-2), 94 - 103
Evolutionary diversification of the mammalian defensins; Hughes AL; Defensins are cysteine-rich cationic peptides that function in antimicrobial defense in both invertebrates and vertebrates . Three main groups of animal defensins are known: insect defensins; mammalian alpha-defensins and vertebrate beta-defensins . It has been difficult to determine whether these molecules are homologous or have independently evolved similar features, but overall the evidence favors a distant relationship . The best evidence of this relationship is structural, particularly from their overall three-dimensional structure and from the spacing of half-cystine residues involved in intra-chain disulfide bonds . Some evidence favors a closer relationship between vertebrate beta-defensins and insect defensins than between the two groups of vertebrate defensins . Examination of nucleotide substitutions between recently duplicated mammalian defensin genes shows that the rate of nonsynonymous (amino-acid-altering) substitution exceeds that of synonymous substitution in the region of the gene encoding the mature defensin . This highly unusual pattern of nucleotide substitution is evidence that natural selection has acted to diversify defensins at the amino acid level . The resulting rapid evolution explains why it is difficult to reconstruct the evolutionary history of these molecules.

Cell Mol Life Sci, 1999 Oct 1, 56(1-2), 32 - 46
Epithelial antimicrobial peptides: innate local host response elements; Schroder JM; Multicellular organisms have to survive in an environment laden with numerous microorganisms, which represent a potential hazard to life . Different strategies have been developed to ward off infections by preventing microorganisms from entering surfaces and by preventing the attack of microorganisms that have already entered the epithelia . Therefore, it is not surprising that epithelia are equipped with various antimicrobial substances that act rapidly to kill a broad range of microorganisms . This review summarizes our present knowledge about epithelial peptide antibiotics produced in plants, invertebrates, and vertebrates including humans . There is now strong evidence that in addition to constitutively secreted peptide antibiotics, others are induced upon contact with microorganisms or by proinflammatory cytokines . beta-Defensins represent one family of vertebrate antimicrobial peptides, members of which are inducible and have recently been identified in humans . The defensin-characteristic local expression pattern may indicate that specialized surfaces express a characteristic surface antimicrobial peptide pattern that might define the characteristic microflora as well as the density of microorganisms present on the surface.

Cell Mol Life Sci, 1999 Oct 15, 56(3-4), 280 - 5
Oxazolidinones: a novel class of antibiotics; Muller M et al.; Oxazolidinones are a novel class of synthetic antimicrobial agents which have now entered phase III clinical trials . The most promising feature of these compounds is their oral activity against multidrug-resistant Gram-positive bacteria which have created tremendous therapeutic problems in recent years . In addition, development of resistance in vitro has so far remained below detectable levels . Different from many antibacterial agents used in the treatment of human infections, oxazolidinones do not block bacterial protein synthesis at the level of polypeptide chain elongation but rather seem to interfere with initiation of translation . Both binding of formylmethionine-transfer RNA to initiation complexes as well as release of formylmethioninepuromycin from initiation complexes have been reported to be targets for oxazolidinones . The major binding sites of oxazolidinones are the large (50S) ribosomal subunits.

Bioorg Med Chem Lett, 2001 Feb 12, 11(3), 403 - 6
Anti-Helicobacter pylori agents endowed with H2-antagonist properties; Sorba G et al.; New anti-Helicobacter pylori (H . pylori) agents endowed with H2-antagonists properties were obtained by combining the lamtidine derived pharmacophoric group with the antibiotic calvatic acid . All the compounds were tested for their irreversible H2-antagonist properties and for their ability to inhibit 20 H . pylori strains, two of them metronidazole resistant . The most active derivative (compound 4) displayed antimicrobial activity similar to metronidazole.

APMIS, 2000 Nov, 108(11), 761 - 3
Prevalence of EHEC O157:H7 in patients with diarrhoea in Lagos, Nigeria; Olorunshola ID et al.; The prevalence of sorbitol-nonfermenting Escherichia coli O157:H7 (EHEC) was assessed in 100 patients with diarrhoea by stool culture on sorbitol MacConkey agar . The cytotoxicity of the EHEC strains was analysed by Vero cell assay and the antimicrobial susceptibility pattern of the isolates was determined . Detection rate of EHEC O157:H7 was 6% . Five of the six patients were males . Three of the isolates were from children and one was from a teenager . All strains induced cytotoxic effects in the Vero cell assay . All isolates were susceptible to most of the antimicrobials tested . The results showed that diarrhoea caused by EHEC O157:H7, a potentially life-threatening pathogen, has remained common particularly among the child population of Lagos during the past 10 years (5) . There must therefore be adequate meat and food inspection to improve the general hygiene of local fast food restaurants, so-called 'bukkas', which are regarded as likely sources of infection.

Aging (Milano), 2000 Dec, 12(6), 445 - 8
Age-related modifications in human unstimulated whole saliva: a biochemical study; Salvolini E et al.; Human whole saliva contains a number of antimicrobial agents, and lysozyme, lactoferrin, secretory IgA and peroxidase are among the best known . Peroxidase catalyzes a reaction involved in the inhibition of bacterial growth and metabolism, and the prevention of hydrogen peroxide accumulation, thus protecting proteins from the action of oxygen and reactive oxygen species (ROS) . To better understand the role played by the oxidative stress in the aging process, we studied the relationship between total protein content, peroxidase activity, malondialdehyde (MDA) and nitric oxide (NO) content of human unstimulated whole saliva in 169 healthy subjects subdivided into groups according to age . Our results show a significant decrease in peroxidase activity with age . Moreover, the increase in saliva lipid peroxide levels indicates an enhanced free radical production that may contribute to tissue damage . On the other hand, findings concerning human unstimulated whole saliva NO content showed a significant increase in elderly subjects, suggesting that an enhanced NO production might depend on a stimulation of leukocyte-inducible NO synthase (i-NOS) activity . Our results suggest that during aging the oral tissues may become more susceptible to environmental factors due to a modification in the balance between different antimicrobial agents.

J Med Microbiol, 2001 Feb, 50(2), 135 - 42
Verocytotoxin-producing Escherichia coli (VTEC) O157 and other VTEC from human infections in England and Wales: 1995-1998; Willshaw GA et al.; A total of 3429 isolations of verocytotoxin-producing Escherichia coli O157 (VTEC O157) was confirmed from human sources in England and Wales during the period 1995-1998 . The largest annual total was 1087 in 1997 . Most infections occurred in the third quarter of each year . The overall rate of infection ranged from 1.28 to 2.10/100,000 population and showed regional variation . The highest incidence was in children aged 1-4 years . Annually, between 5% and 11% of strains were from patients who had travelled abroad . There were 67 general outbreaks of infection represented by 407 (11.9%) VTEC O157 isolates . Outbreaks involved transmission by contaminated food or water, person-to-person spread and direct or indirect animal contact, and five were associated with foreign travel . The majority (76%) of strains carried verocytotoxin (VT) 2 genes and 23.3% were VT1+VT2 . Most strains had the flagellar antigen H7, but c . 14% were non-motile . Approximately 20% of isolates were resistant to antimicrobial agents, predominantly streptomycin, sulphonamides and tetracycline . In addition to VTEC O157, strains of serogroup O157 that did not possess VT genes were identified . These were either derivatives of VTEC O157 that had lost VT genes or were strains with H antigens other than H7 that have never been associated with VT production . Strains of VTEC other than O157 were characterised . Most were associated with diarrhoea, bloody diarrhoea or haemolytic uraemic syndrome and had virulence markers in addition to VT.

Laryngoscope, 2001 Feb, 111(2), 329 - 35
The role of topical antibiotic prophylaxis in patients undergoing contaminated head and neck surgery with flap reconstruction; Simons JP et al.; OBJECTIVES/HYPOTHESIS: Patients undergoing contaminated head and neck surgery with flap reconstruction have wound infection rates of 20% to 25% with parenteral antibiotic prophylaxis . Studies suggest that perioperative antimicrobial mouthwash reduces oropharyngeal flora and may prevent wound infections . We hypothesized that the addition of topical antibiotics to a parenteral prophylactic regimen would reduce the incidence of wound infection in these high-risk patients . STUDY DESIGN: We performed a randomized, prospective clinical trial . METHODS: Patients received either 1) parenteral piperacillin/tazobactam (3.375 g every 6 hours for 48 h) or 2) parenteral piperacillin/tazobactam plus topical piperacillin/tazobactam administered as a mouthwash immediately before surgery and once a day for 2 days postoperatively, with piperacillin/tazobactam added to the intraoperative irrigation solution . The wounds of all patients were evaluated daily using predefined objective criteria . RESULTS: Sixty-two patients met inclusion criteria and were enrolled in the study . The overall wound infection rate was 8.1% (95% confidence interval {CI}, 2.7%-17.8%) . Two of 31 patients (6.4%) who received parenteral antibiotics alone developed a wound infection compared with 3 of 31 patients (9.7%) randomly assigned to receive topical plus parenteral antibiotics . This difference was not statistically significant (P = >.05) . Infection rate was not associated with flap type (rotational vs . free tissue transfer), mandibular reconstruction, age, gender, tumor site, stage, surgical duration, or blood loss . CONCLUSIONS: These results suggest that piperacillin/tazobactam is a highly effective antibiotic for prevention of wound infection in patients undergoing flap reconstruction following contaminated head and neck surgery . However, the addition of topical piperacillin/tazobactam does not appear to enhance the prophylactic benefit of parenteral antibiotics alone.

Pharmazie, 2001 Jan, 56(1), 28 - 32
Polysubstituted pyrazoles, Part 4: Synthesis, antimicrobial and antiinflammatory activity of some pyrazoles; Farghaly AM et al.; As a continuation of an earlier interest in polysubstituted pyrazoles, the synthesis of some derivatives of 1H-pyrazol-4-yl-2-oxo-but-3-enoic acid and ethyl 4-hydroxy-1H-pyrazole-3-carboxylates of potential antimicrobial and antiinflammatory activity is described . One compound showed in vitro antibacterial activity and two compounds displayed in vivo antiinflammatory potency in rats.

J Periodontol, 2001 Jan, 72(1), 96 - 106
A multidisciplinary approach to the diagnosis and treatment of early-onset periodontitis: a case report; Worch KP et al.; BACKGROUND: The diagnosis and treatment of early-onset forms of periodontitis (EOP) represent a major challenge to periodontists . In this case report, we describe a multidisciplinary approach for the treatment of a patient with severe generalized juvenile periodontitis (GJP) . Our approach incorporates clinical laboratory evaluation with conventional concepts of periodontal pathogenesis and therapeutics to diagnose and effectively treat EOP . METHODS: The 17-year-old female patient presented with clinical and radiographic evidence of severe attachment loss . Microbiological testing showed the presence of known periodontal pathogens including Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Porphyromonas gingivalis . Routine immunological tests did not reveal any of the functional defects thought to play a role in the pathogenesis of EOP After initiation of therapy, which consisted of scaling and root planing, supplemented with administration of systemic antibiotics, a reduction in probing depth and gain in clinical attachment could be demonstrated . Microbiological testing was used to monitor the composition of the periodontal microbiota and to adjust antimicrobial therapy accordingly . RESULTS: Using a non-surgical approach to treatment, except for 2 root amputations performed without flap reflection, we have been able to stabilize this patient's periodontal condition over the course of a 2-year follow-up period . CONCLUSIONS: This treatment strategy provides an efficacious alternative to more aggressive forms of therapy and should therefore be considered for the treatment of patients with severe EOP.

J Chromatogr A, 2001 Jan 5, 905(1-2), 359 - 66
Characterisation of sorbate geometrical isomers; Cigic IK et al.; trans,trans Isomers of sorbic acid, its potassium salt and ethyl sorbate isomerise under UV irradiation . All four geometrical isomers of the acid, salt and ester were separated using high-performance liquid chromatography on a nonpolar reversed-phase column (C18) and the ester also by gas chromatography on a VOCOL capillary column . The limit of detection and the interval of linearity were determined for all chromatographic methods . Individual isomers were identified with NMR analysis . Resolved chemical shifts of protons adjacent to the double bonds enabled qualitative and quantitative determination of isomers in the mixture . Antimicrobial activity of potassium sorbate isomers was tested on yeast Saccharomyces cerevisiae . Results show that the pure trans,trans isomer has a higher antimicrobial activity than the mixture of isomers.

Afr J Med Med Sci, 1999 Sep-Dec, 28(3-4), 167 - 9
Antimicrobial screening of Bridelia, micrantha, Alchormea cordifolia and Boerhavia diffusa; Abo KA et al.; This report is on the antimicrobial potential of Bridelia micrantha, Alchornea cordifolia and Boerhavia diffusa sourced from traditional healers through an ethnobotanical survey of antiinfective plants in Egbado South in Ogun State, Nigeria . Extracts of B . micrantha and A . cordifolia exhibited significant inhibitory activity against the pathogenic organisms . In some cases, the antibacterial activity was comparable to those of ampicillin and gentamycin . However, only the leaf of A . cordifolia showed reasonable antifungal activity when compared with Trosyd . The study shows that there is justification for the use of these medicinal plants in traditional medicine.

Eur J Clin Microbiol Infect Dis, 2000 Dec, 19(12), 956 - 9
Screening for antimicrobial resistance in normal bacterial flora of the skin using the replica plating method; Paavilainen T et al.; The replica plating method was evaluated for detection of the antimicrobial resistance of normal bacterial flora of the skin and was compared with the results of a ten-colony method . If > or = 10% of the colonies from the master plate grew on a plate containing an antibiotic, the sensitivity of replica plating was comparable to that of a ten-colony method for samples containing resistant bacteria . However, this method classified significantly more samples as resistant to all eight antibiotics tested if the detection breakpoint was lowered to > or = 1% of the original colonies . Replica plating is an effective and practical tool for screening skin flora for resistance, also in samples with a low proportion of resistant strains.

Anticancer Res, 2000 Nov-Dec, 20(6B), 4323 - 9
Biological activity of feijoa peel extracts; Motohashi N et al.; Fractionated extracts of Feijoa peels were studied for cytotoxic activity, anti-human immunodeficiency virus (HIV) activity and antibacterial activity . Two most cytotoxic fractions A3 of acetone extract and M2 of methanol extract had potent inhibitory activity against Gram-positive and Gram-negative bacteria as well as fungi tested . Fraction A4 of acetone extract showed multidrug resistance (MDR)-reversal activity comparable with that of verapamil (positive control) . These results indicate the therapeutic value of Feijoa peel extracts as potential antimicrobial and MDR-modulating agents.

J S Afr Vet Assoc, 2000 Sep, 71(3), 201 - 8
Bovine mastitis therapy and why it fails; du Preez JH; Treatment of bovine mastitis depends on the cause, the clinical manifestation and the antibiotic susceptibility of the agent . Mastitis therapy is commonly unsuccessful owing to pathological changes that occur in the udder parenchyma as a result of the inflammatory reaction to mastitogenic bacteria, pharmacokinetic properties of antimicrobial mastitis drugs, mastitogenic bacterial and related factors, and poor animal husbandry and veterinary interventions.

Farmaco, 2000 Nov-Dec, 55(11-12), 719 - 24
Synthesis, anti-inflammatory and antimicrobial activities of new 1,2,4-oxadiazoles peptidomimetics; Leite AC et al.; A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy . The prepared compounds were tested for anti-inflammatory and antimicrobial activities . The anti-inflammatory activities were determined in the rat paw oedema induced by carrageenin . Compounds 6a, c, f and g (i.v.) significantly inhibited the rat paw oedema induced by carrageenin depending upon the dose employed . The compounds were also evaluated for their in vitro antimicrobial activity . Some compounds were found to have significant activity against Gram positive and Gram negative microorganisms.

Farmaco, 2000 Nov-Dec, 55(11-12), 708 - 14
4-Hydroxycoumarin in heterocyclic synthesis . Part III . Synthesis of some new pyrano{2,3-d}pyrimidine, 2-substitute; Bedair AH et al.; The synthesis of new {1}benzopyrano{3',4':5,6}pyrano{2,3-d}pyrimidines and related heterocycles has been reported . The key intermediate 2-amino-3-cyano-4-methyl-4H,5H-pyrano{3,2-c}{1}benzopyran-5-one (3) was obtained in one pot synthesis from the reaction of 4-hydroxycoumarin and acetaldehyde-malononitrile (2) . The antimicrobial screening was performed for some of the synthesized compounds.

Farmaco, 2000 Nov-Dec, 55(11-12), 669 - 79
3H-{1,2}Dithiolo{3,4-b}pyridine-3-thione and its derivatives synthesis and antimicrobial activity; Pregnolato M et al.; A series of 2-substituted isothiazolo{5,4-b}pyridine-3(2H)-thiones, isothiazolo{5,4-b}pyridin-3(2H)-ones, N-substituted 2-sulfanylnicotinamides and the corresponding carbothioamide derivatives were synthesized and evaluated for their antimicrobial activity against several strains of Gram+ and Gram- bacteria and fungi . Chemical syntheses were resumed into a comprehensive cyclic route that enables the reversible conversion for each derivative of the series considered . Among the tested compounds the N-(aralkyl)-2-sulfanylnicotinamides show the highest fungitoxicity (MIC = 1.25-5 microg/ml) . The best activity towards Gram-positive bacteria was in the range of 2.5-5 microg/ml . Activity against Gram-negative bacteria was generally very poor for all compounds.

Pathol Biol (Paris), 2000 Dec, 48(10), 940 - 4
{Veterinary use of antibiotics and resistance in man: what relation?}; Laval A; Early in the 1950's antibiotic therapy was introduced in humans, as well as in animals . In 1997 48% of the total European antibiotic sales were intended to veterinary use . However, there are significant differences between antibiotic classes regarding either administered quantities or intent for use, e.g . growth factor or therapeutic use . Furthermore, food chain or direct contact may be responsible for antimicrobial resistance through animal-to-human transmission . Although various preventive measures were implemented during the past years, evidence of public health risks has been demonstrated . This should lead to better use of antibiotic therapy not only in animal husbandry but also in medical practice.

Mol Plant Microbe Interact, 2001 Feb, 14(2), 111 - 5
Production of antimicrobial defensin in Nicotiana benthamiana with a potato virus X vector; Saitoh H et al.; A recombinant plasmid, pTXS.TH, was constructed to express the gene-encoding wasabi (Wasabia japonica) defensin with the potato virus X (PVX) vector . pTXS.TH allows the expression of defensin in the host Nicotiana benthamiana, and the defensin protein WT1 can be purified from virus-infected leaves by heat treatment and affinity chromatography . WT1 exhibits strong antifungal activity toward the phytopathogenic fungi Magnaporthe grisea (50% inhibitory concentration {IC50} = 5 microg/ml) and Botrytis cinerea (IC50 = 20 microg/ml) but is weakly active against the phytopathogenic bacterium Pseudomonas cichorii . This virus-mediated expression system is a rapid and efficient method to produce and characterize antimicrobial proteins in plants . It is particularly useful for the study of proteins that are difficult to produce with other expression systems.

Antonie Van Leeuwenhoek, 2000 Aug, 78(2), 129 - 39
Screening of basidiomycetes for antimicrobial activities; Suay I et al.; As a part of a screening programme developed to evaluate the antimicrobial activity of basidiomycetes, 317 isolates representing 204 species collected in Spain were screened against a range of human clinical pathogens and laboratory controls . Extracts from 45% of the isolates, representing 109 species, showed antimicrobial activity . Antibacterial activity was more pronounced than antifungal activity . The proportion of extracts from basidiomycetes showing antimicrobial activity was similar to or above that obtained for representative orders of Ascomycetes, such as Pezizales and Xylariales, but lower than that produced by members of the orders Diaporthales, Eurotiales, Hypocreales, Leotiales and Sordariales . Suprageneric taxa (orders and families) did not show pronounced differences in their antimicrobial activities though such differences were observed at the genus level, suggesting that the ability to produce these bioactive compounds is not homogenously distributed amongst the basidiomycetes . Isolates from some species showed large differences in their ability to produce metabolites with antimicrobial activity, possibly reflecting genetic differences at the infraspecific level.

Farmaco, 2000 Jun-Jul, 55(6-7), 499 - 501
4,5-Dihydroisoxazoles: testing of antimicrobial activity; Zadrozna I et al.; In the 1,3-dipolar cycloaddition of aliphatic nitrile to selected olefins, a series of 4,5-dihydroisoxazoles substituted with various functional groups, ester, carbonyl and ethereal, was obtained . These compounds were investigated for antimicrobial activity on chosen strains.

Expert Opin Investig Drugs, 2000 Jul, 9(7), 1665 - 72
SMI's 2nd Annual Superbugs and Superdrugs Conference: innovations in anti-infectives; Barrett JF; The emergence of the 'Superbugs', resistant bacterial pathogens, is being aggressively met by the anti-infective community, both academia and industry, with an assortment of classical and novel approaches to control these resistant pathogens . The launch of improved quinolones (gatifloxacin and moxifloxacin), the launch of a new class of protein synthesis inhibitors (oxazolidinones; linezolid) and the ushering-in of the applied genomics age, all offer hope for the future control of resistant bacteria . The seemingly imminent development and completion of the first lipopeptide, daptomycin, offers great hope for the control of Gram-positive resistant pathogens . The first cationic peptide, IB-367, designed to combat the niche medical need of mucositis and the development of a specific antistaphylococcal glycopeptide . BI-397, all will precede the first wave of genomic-targets-based drug candidates, as the antimicrobial genomics effort remains in the target identification and validation stages of early discovery.

Am Fam Physician, 2001 Jan 15, 63(2), 326 - 32
Sporotrichoid lymphocutaneous infections: etiology, diagnosis and therapy; Tobin EH et al.; Sporotrichoid lymphocutaneous infection is an uncommon syndrome that is often misdiagnosed and improperly treated . Of the several hundred cases seen each year in the United States, the majority are caused by Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum or Leishmania brasiliensis . The "sporotrichoid" disease begins at a site of distal inoculation and leads to the development of nodular lymphangitis . Systemic symptoms are characteristically absent . By recognizing the distinct pattern of nodular lymphangitis and focusing on the diverse but limited etiologies, the physician can obtain the appropriate histologic and microbiologic studies and start targeted antimicrobial therapy . Therapy is generally continued for two to three months after the resolution of cutaneous disease.

Arch Histol Cytol, 2000, 63(5), 431 - 9
The presence of a local immune system in the upper blind and lower part of the human nasolacrimal duct; Sirigu P et al.; The nasolacrimal duct is exposed to exogenous agents, including potentially harmful microorganisms, coming from the eye surface by the lacrimal sac, and from the nasal cavity by the inferior meatus of the nose . The upper blind and lower part of the human nasolacrimal duct were examined immunohistochemically to ascertain the presence and localization of immunoglobulin-producing cells and the epithelial expression of IgA, IgM, and IgG in order to verify the possible antimicrobial properties of this duct . IgA-, IgM-, and IgG-positive immunocompetent cells were recognizable in the lamina propria of the upper blind and lower part of the human nasolacrimal duct, while an evident immunoreactivity for sIgA, IgM, and IgG was demonstrated in the cytoplasm of the apical epithelial cells . The results suggest that all the effector components of the mucosal immune system are present in that area of the human nasal mucosa next to the opening of the nasolacrimal duct as well as in the human lacrimal sac.

J Endod, 2000 May, 26(5), 274 - 7
Antimicrobial activity and flow rate of newer and established root canal sealers; Siqueira Junior JF et al.; Endodontic sealers that possess both optimum flow ability and antimicrobial properties may theoretically assist in the elimination of microorganisms located in confined areas of the root canal system . The antimicrobial effects and the flow rate of the following sealers were investigated and compared: Kerr Pulp Canal Sealer EWT, Grossman's Sealer, ThermaSeal, Sealer 26, AH Plus, and Sealer Plus . The agar diffusion test was used to assess the antimicrobial activity of the sealers . In the flow assay, the sealers were placed between two glass slabs and a weight of 500 g was placed on the top of the glass . The diameters of the formed discs were recorded . All root canal sealers tested showed some antimicrobial activity against most of the microorganisms . There were no significant differences between the materials tested (p > 0.05) . All root canal sealers also flowed under the conditions of this study . Statistical analysis of the results revealed that AH Plus and Kerr Pulp Canal Sealer EWT had flow values significantly superior to the other sealers tested (p > 0.05) . Taken together, these findings suggest that these sealers have the potential to help in the microbial control in the root canal system.

Compend Contin Educ Dent, 2000 Jan, 21(1), 59 - 62, 64, 66 passim; quiz 78
Antiseptics and antibiotics as chemotherapeutic agents for periodontitis management; Ciancio SG; Antiseptics and antibiotics have both been used to treat periodontal infections . Although antiseptics and antibiotics have antibacterial properties, they represent two distinct and separate categories for agents . Sustained-release delivery systems have made it possible to use these agents to augment the beneficial effects of mechanical periodontal therapy . This article provides an overview of antiseptics and antibiotics, and compares and makes recommendations for the use of these agents in periodontics . The objective of this article is to provide an understanding of the distinct properties of each of these categories of antimicrobial agentsPublication Types:

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