Clin Infect Dis, 2002 Jun 15, 34(12), 1621 - 6 Epub 2002 May 23. Decision-making on the use of antimicrobial prophylaxis for dental procedures: a survey of infectious disease consultants and review; Lockhart PB et al.; There is debate concerning use of antibiotic prophylaxis before invasive dental procedures for patients at risk of acquiring distant site infection (DSI) . We determined the opinions and practices of infectious disease consultants (IDCs) regarding antimicrobial prophylaxis to prevent DSIs that result from invasive dental procedures by conducting a survey of the 797 members of the Infectious Diseases Society of America Emerging Infections Network (477 members {60%} responded) . Ninety percent of respondents closely follow the American Heart Association guidelines for antibiotic prophylaxis for patients with valvular heart disease who undergo invasive dental procedures . In contrast, few IDCs recommend prophylaxis for patients with lupus erythematosus, poorly controlled diabetes mellitus, dialysis catheters or shunts, cardiac pacemakers, or ventriculoperitoneal shunts . Twenty-five percent to forty percent of respondents recommended prophylaxis for prosthetic vascular grafts, orthopedic implants, or chemotherapy-induced neutropenia . We conclude that IDCs differ considerably in their assessment of the need for prophylaxis for patients who have noncardiac risk factors for DSI . These differences underscore the need for definitive studies to delineate appropriate candidates for antimicrobial prophylaxis in dental practice. Microb Ecol, 2001 Feb, 41(2), 90 - 96 Competition-Mediated Antibiotic Induction in the Marine Bacterium Streptomyces tenjimariensis; Slattery M et al.; Microbial competition for limiting natural resources within a community is thought to be the selective force that promotes biosynthesis of antimicrobial compounds . The marine bacterium Streptomyces tenjimariensis produces the antibiotics istamycin A and B under select laboratory culture conditions; presumably these compounds serve an ecological role under natural conditions . Here we report results of a novel marine microbial competition experiment that examined the impact of co-culture of marine bacteria on istamycin production by S . tenjimariensis . Twelve of the 53 bacterial species tested (i.e., 22.6%) induced Istamycin production; this antibiotic also inhibited growth of the competitor colonies . These results suggest that marine bacterial metabolites serve an ecological role in countering competitive species. J Lab Clin Med, 2002 May, 139(5), 295 - 302 Doxycycline and tissue repair in rats; Lamparter S et al.; Iterations in collagen turnover are integral to tissue repair . Repair gone awry, as a result of excess collagen accumulation or degradation, can contribute to pathologic ventricular remodeling . Pharmacologic interventions that would attenuate either aspect of faulty repair have therefore attracted interest . Tetracyclines, which inhibit both collagen synthesis and degradation, as well as angiogenesis, may hold promise, unrelated to their antimicrobial properties, in this regard . Assessment of their potential in rodent hearts with experimental injury can be problematic, given the often microscopic nature of tissue repair and brief involvement of matrix metalloproteinases (MMPs) . We therefore selected a subcutaneous model in which granulation and fibrous tissues form over several weeks in response to croton oil and where fibrous tissue is subsequently resorbed because of high levels of collagenolytic activity . Untreated rats were compared with those given daily oral doxycycline (40 mg/kg) . We harvested pouch tissue and exudate weekly for 5 weeks to assess hydroxyproline concentration and MMP activity (gelatin substrate zymography) of pouch wall and mononuclear cell count of pouch exudate . At week 2, neovascularization in pouch wall was measured by means of intravenous infusion of carmine-red dye in gelatin . The resultant "vascular cast" was solubilized and dye content quantitated with the use of spectrophotometry . Serum was assayed weekly for type I collagen carboxyterminal telopeptide (ICTP), a marker of collagen degradation . During weeks 1 and 2 and compared with untreated controls, doxycycline-treated rats had attenuated pouch tissue weight, collagen concentration, MMP2 lytic activity and vascularity, and reduced exudate volume and mononuclear cells . In vitro, doxycycline inhibited tissue gelatinolytic activity in a dose-dependent manner . At weeks 4 and 5, pouches were larger and collagen concentration was higher in doxycycline-treated rats, and serum ICTP levels were reduced at weeks 3 and 4 . During the initial phase of pouch development, doxycycline exerts an inhibitory effect on tissue formation, likely mediated through its attenuation of angiogenesis and modulations of collagen turnover . As repair proceeds in subsequent weeks, doxycycline retards collagen degradation and pouch resorption by inhibiting MMPs . Doxycycline offers a multifaceted pharmacologic profile with which to modify various aspects of tissue repair in the rat. Proc Natl Acad Sci U S A, 2002 May 28, 99(11), 7610 - 5 Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo{a}pyrene-induced stomach tumors; Fahey JW et al.; Gastric infection with Helicobacter pylori is a cosmopolitan problem, and is especially common in developing regions where there is also a high prevalence of gastric cancer . These infections are known to cause gastritis and peptic ulcers, and dramatically enhance the risk of gastric cancer . Eradication of this organism is an important medical goal that is complicated by the development of resistance to conventional antimicrobial agents and by the persistence of a low level reservoir of H . pylori within gastric epithelial cells . Moreover, economic and practical problems preclude widespread and intensive use of antibiotics in most developing regions . We have found that sulforaphane {(-)-1-isothiocyanato-(4R)-(methylsulfinyl)butane}, an isothiocyanate abundant as its glucosinolate precursor in certain varieties of broccoli and broccoli sprouts, is a potent bacteriostatic agent against 3 reference strains and 45 clinical isolates of H . pylori {minimal inhibitory concentration (MIC) for 90% of the strains is <or=4 microg/ml}, irrespective of their resistance to conventional antibiotics . Further, brief exposure to sulforaphane was bactericidal, and eliminated intracellular H . pylori from a human epithelial cell line (HEp-2) . In complementary experiments, sulforaphane blocked benzo{a}pyrene-evoked forestomach tumors in ICR mice . This protection resulted from induction of phase 2 detoxication and antioxidant enzymes, and was abrogated in mice lacking the nrf2 gene, which regulates phase 2 enzymes . Thus, the dual actions of sulforaphane in inhibiting Helicobacter infections and blocking gastric tumor formation offer hope that these mechanisms might function synergistically to provide diet-based protection against gastric cancer in humans. Mol Biol Evol, 2002 Jun, 19(6), 858 - 64 Roles of diversifying selection and coordinated evolution in the evolution of amphibian antimicrobial peptides; Duda TF Jr et al.; Antimicrobial peptides are expressed in the skin of amphibians and are used to prevent infection by microorganisms . Frog species store distinct collections of antimicrobial peptides that show variation in size, charge, conformation, and bactericidal activity, and so the evolution of antimicrobial peptide gene families may reflect the adaptive diversification of these loci . We examined the molecular evolution of antimicrobial peptide transcripts from hylid and ranid frog species . Our results show that after the gene family arose in the common ancestor of the Hylidae and Ranidae, before the divergence of these families in the Mesozoic, it subsequently diversified within these groups with numerous duplication events and divergence of loci . Moreover, we provide evidence that suggests that members of the antimicrobial peptide gene family have been subject to diversifying selection within both propiece and mature domains of hylids and solely within the mature domain of ranids . Finally, our results suggest that coordinated and compensatory amino acid replacements have occurred within the acidic propiece and cationic mature domain of hylid antimicrobial peptide precursors, as has been observed for mammalian defensin genes, but not among those of ranid precursors. EMBO J, 2002 Jun 3, 21(11), 2568 - 79 The Toll and Imd pathways are the major regulators of the immune response in Drosophila; De Gregorio E et al.; Microarray studies have shown recently that microbial infection leads to extensive changes in the Drosophila gene expression programme . However, little is known about the control of most of the fly immune-responsive genes, except for the antimicrobial peptide (AMP)-encoding genes, which are regulated by the Toll and Imd pathways . Here, we used oligonucleotide microarrays to monitor the effect of mutations affecting the Toll and Imd pathways on the expression programme induced by septic injury in Drosophila adults . We found that the Toll and Imd cascades control the majority of the genes regulated by microbial infection in addition to AMP genes and are involved in nearly all known Drosophila innate immune reactions . However, we identified some genes controlled by septic injury that are not affected in double mutant flies where both Toll and Imd pathways are defective, suggesting that other unidentified signalling cascades are activated by infection . Interestingly, we observed that some Drosophila immune-responsive genes are located in gene clusters, which often are transcriptionally co-regulated. Phytochemistry, 2002 Jun, 60(3), 205 - 11 Genistein; Dixon RA et al.; Genistein (4',5,7-trihydroxyisoflavone) is a common precursor in the biosynthesis of antimicrobial phytoalexins and phytoanticipins in legumes, and an important nutraceutical molecule found in soybean seeds . Genistein is a phytoestrogen with a wide variety of pharmacological effects in animal cells, including tyrosine kinase inhibition, and dietary genistein ingestion has been linked, through epidemiological and animal model studies, with a range of potential health beneficial effects . These include chemoprevention of breast and prostate cancers, cardiovascular disease and post-menopausal ailments . In spite of an extensive literature on the effects of dietary genistein, questions still exist as to its potential overall benefits as a component of the human diet . Genistein can be synthesized chemically via the deoxybenzoin or chalcone route . Genistein is synthesized in plants from the flavanone naringenin by a novel ring migration reaction catalyzed by the cytochrome P450 enzyme isoflavone synthase (IFS) . IFS genes have recently been cloned from a number of plant species, and production of genistein can be now achieved in non-legumes by recombinant DNA approaches. Phytochemistry, 2002 Jun, 60(4), 431 - 5 Hericenols A-D and a chromanone from submerged cultures of a Stereum species; Omolo JO et al.; Extracts of submerged cultures of a Stereum species afforded four new pentasubstituted phenolic compounds, named hericenols A, B, C, and D (1-4), 6-hydroxymethyl-2,2-dimethylchroman-4-one (5) and the known erinapyrone C . Hericenol A (1) showed weak antimicrobial activity while hericenol C (3) was weakly cytotoxic . The structures of the metabolites were determined by spectroscopic techniques. Dev Comp Immunol, 2002 Jul, 26(6), 505 - 15 Immunolocalization of clavanins in Styela clava hemocytes; Menzel LP et al.; Antimicrobial peptides play an important role in innate host defenses against infection . Clavanins are histidine-rich, amidated, 23-residue alpha-helical antimicrobial peptides that were isolated from a mixed population of Styela clava hemocytes . To learn which types of hemocytes contained clavanins, we raised a polyclonal antibody that recognized five different clavanins, and used it to localize these peptides by light and electron microscopy . Clavanins were present in the cytoplasmic granules and/or cytoplasm of five different types of granulocytes and they also occurred throughout the cytoplasm of macrophages . The orange G component of Mallory's trichrome stain had a high affinity for clavanins, and for the cytoplasmic granules of S . clava's hemocytes . Semiquantitative analysis of acid urea-PAGE gels suggested that clavanins and styelins comprised between 10 and 20% of the total cellular protein of eosinophilic granulocytes . Orange G and the century-old trichrome stain may provide simple screening tools for identifying cells that contain large amounts of antimicrobial peptides in mixed hemocyte populations. Aliment Pharmacol Ther, 2002 Jun, 16(6), 1083 - 90 Sequential intravenous/oral antibiotic vs . continuous intravenous antibiotic in the treatment of pyogenic liver abscess; Ng FH et al.; AIM: Pyogenic liver abscesses result in substantial morbidity and mortality . Antimicrobial regimens using sequential intravenous/oral therapy may reduce the length of hospital stay . In this retrospective analysis, the efficacy of continuous intravenous antibiotic therapy (group I) vs . sequential intravenous/oral antibiotic therapy (group II) was studied in patients with pyogenic liver abscess . METHODS: One hundred and twelve consecutive patients (55 in group I and 57 in group II) with pyogenic liver abscess were analysed . Clinical response, length of hospital stay and relapse rates were examined . RESULTS: Group II had a significantly shorter duration of intravenous antibiotic treatment (3.2 weeks vs . 5.9 weeks, P < 0.01) and a shorter length of hospital stay (28 days vs . 42 days, P < 0.01) when compared to group I . Oral antibiotics were prescribed for a median duration of 2.9 weeks in group II after discharge . No relapse occurred within 6 weeks after the completion of treatment in both groups . The cost of therapy was significantly lower in group II than in group I by 33% . CONCLUSIONS: A sequential intravenous/oral antibiotic regime is a safe and effective treatment for pyogenic liver abscess . This reduces the cost of therapy and the length of hospital stay. J Food Prot, 2002 May, 65(5), 834 - 9 In vitro antifungal activity of several antimicrobial compounds against Penicillium expansum; Venturini ME et al.; Fungicides used in the prevention and control of mold rots in stored apples are subjected to legal, social, and biological limitations . The aim of this study was to find an alternative to postharvest fungicides currently used in the prevention and control of blue mold rot caused by Penicillium expansum in apples . For this purpose, the antimicrobial activity and MIC of several substances against P . expansum were evaluated in vitro using different end point methods: agar diffusion assay, volatility method, and agar dilution and broth dilution MIC assays . Most of the substances tested are common food ingredients and have a recognized antimicrobial activity . Essential oils, such as thymol, eugenol, citral and cineole, vanillin, sodium hypochlorite, acetic acid, potassium sorbate, and hydrogen peroxide, were the substances evaluated . Thymol and citral were the essential oil components that showed the greatest inhibitory effects . The effectiveness of 5 and 10% hydrogen peroxide in growth inhibition of P . expansum in the agar diffusion assay was total, and its MIC as determined by the agar and broth dilution assays was less than 0.025% . These results indicate that the application of small quantities of hydrogen peroxide to the apple skin might be an alternative to fungicides in the elimination of P . expansum. Kansenshogaku Zasshi, 2002 Apr, 76(4), 285 - 90 {Drug resistance of enterohemorrhagic Escherichia coli O157 and a possible relation of plasmids to the drug-resistance}; Miwa Y et al.; Antimicrobial susceptibility was examined using 89 enterohemorrhagic Escherichia coli O157 isolates obtained from diarrhea patients in Aichi Prefecture, Japan between June 1996 and June 1997 . Among the 89 isolates, 15 (16.9%) were found to be resistant to 6 of 9 antibiotics examined . These 6 antibiotics were ampicillin (ABPC), cefaloridine (CER), chloramphenicol (CP), kanamycin (KM), streptomycin (SM), and tetracycline (TC) . Among the 15 drug-resistant isolates, 7 were resistant to 4 drugs (ABPC, CER, SM, TC), 3 were resistant to 3 (ABPC and 2 of CER, SM, TC), 2 were resistant to 2 (SM, TC), one each to KM or SM . Another isolate showed resistance to 5 drugs (ABPC, CP, KM, SM, TC) . Selected 13 drug-sensitive and selected 12 multi-drug resistant isolates were tested for the presence of plasmids . All of the drug-sensitive isolates had 54 MDa plasmid and the majority (8/13) had 2.0 MDa plasmids, whereas; all of the drug-resistant isolates except one (1/12) had 54 MDa plasmid and the majority had 8.0 MDa (9/12) and 4.2 MDa (11/12) plasmids . The first transformation test revealed that plasmids of 8.0 MDa (3/4) and 46 MDa (1/4) were transferred to a donor cell with ABPC resistance . 54 MDa plasmid was transferred to a donor cell with both of ABPC and TC resistance . In the second transformation test, only the 8.0 MDa plasmid was confirmed to be transferred to a donor cell with ABPC resistance . Accordingly, it was indicated that the ABPC resistant gene was carried on 8.0 MDa plasmid, and it was suggested that resistant genes for ABPC and TC, and ABPC were carried on 54 MDa, and on 46 MDa plasmids, respectively. Science, 2002 Jul 5, 297(5578), 105 - 7 Epub 2002 May 23. An alternative flavin-dependent mechanism for thymidylate synthesis; Myllykallio H et al.; Although deoxythymidylate cannot be provided directly by ribonucleotide reductase, the gene encoding thymidylate synthase ThyA is absent from the genomes of a large number of nonsymbiotic microbes . We show that ThyX (Thy1) proteins of previously unknown function form a large and distinct class of thymidylate synthases . ThyX has a wide but sporadic phylogenetic distribution, almost exclusively limited to microbial genomes lacking thyA . ThyX and ThyA use different reductive mechanisms, because ThyX activity is dependent on reduced flavin nucleotides . Our findings reveal complexity in the evolution of thymidine in present-day DNA . Because ThyX proteins are found in many pathogenic microbes, they present a previously uncharacterized target for antimicrobial compounds. J Nat Prod, 2002 May, 65(5), 728 - 9 New labdene iterpenes from Eupatorium glutinosum; El-Seedi HR et al.; The new diterpene glucoside 3,15-dihydroxy-ent-labd-7-en-17-oic acid 3-O-beta-D-glucoside (1) and its aglycone (2) have been isolated from Eupatorium glutinosum . The structures were determined by IR, one- and two-dimensional NMR, high-resolution mass spectrometry, chemical transformations, and comparison of spectroscopic data with closely related diterpenes . Crude extracts showed antimicrobial and cytotoxic activities, but compounds 1 and 2 showed only antimicrobial activity . These results support the vernacular medicinal use of the plant as an antimicrobial. Joint Bone Spine, 2002 Mar, 69(2), 133 - 40 Whipple's disease; Puechal X; Whipple's disease is a chronic systemic bacterial infection that predominantly affects middle-aged men . Antimicrobial therapy is curative . The causative agent has been identified as Tropheryma whippelii . A PCR-based diagnostic test is now available and is particularly useful in patients with early-stage or atypical disease . The test can detect bacterial nucleic acids in tissues and body fluids, including joint fluid . Studies using this test found no evidence that T . whippelii may be a common cause of unexplained seronegative oligoarthritis or polyarthritis . Further work is needed to identify the patient subsets most likely to benefit from T . whippelii PCR testing in joint specimens . Isolation of the organism has been achieved recently . This will probably allow development of a serological test, which may facilitate the diagnosis . Weight loss and diarrhea are the most common symptoms of Whipple's disease . Joint manifestations antedate the intestinal complaints in three-fourths of patients, the mean interval being 6 years . In most patients, duodenal and jejunal biopsy specimens contain macrophages filled with PAS-stained granules corresponding to bacteria . Nevertheless, some patients have no intestinal symptoms, and a few have normal intestinal histological findings . Before the onset of intestinal symptoms, several clinical patterns should suggest Whipple's disease . Unexplained, chronic, seronegative oligoarthritis or polyarthritis affecting the large limb joints is the most common presentation . A characteristic feature is the intermittent occurrence of the joint manifestations, at least early in the disease . Other patterns are destructive polyarthritis and spondyloarthropathy . The major advances made recently in techniques for detecting and isolating the causative agent may show that Whipple's disease is more common and has a broader clinical spectrum than was previously thought . Another hope is that the diagnosis will be made earlier, before the development of potentially fatal systemic complications. Gen Dent, 2001 Nov-Dec, 49(6), 653 - 6 The antimicrobial properties of a urea-based handwash lotion with triclosan; Tung FF et al.; The purpose of this study was to determine and compare the antimicrobial action of a urea-based handwash lotion with triclosan with a lipid-depleting detergent-based handwash product with 4% chlorhexidine gluconate . The zones of inhibition produced by the two handwash lotions and the one produced by the positive control were similar against all strains of bacteria tested, indicating that a urea-based handwash lotion with triclosan is as effective as a lipid-depleting handwash lotion in inhibiting bacterial activity. Gen Dent, 2001 Nov-Dec, 49(6), 648 - 52 Reduction of bacteria-containing spray produced during ultrasonic scaling; Klyn SL et al.; Bacteria-containing spray (including both aerosols and splatter) has been shown to be a potential source of contagion in the dental environment . Bacterial air contamination increases during dental treatment; this is especially true during ultrasonic scaling procedures . This in vivo investigation evaluated the amount of bacteria-containing spray produced during ultrasonic scaling of 15 patients when using a suction-type aerosol reduction device (ARD) and/or a preoperative 0.12% chlorhexidine gluconate (CHX) antimicrobial rinse . When the study protocol was followed, the use of either an ARD or a CHX rinse produced significant bacterial reductions during ultrasonic scaling compared to the control . The use of an ARD produced the greatest bacterial reductions . Combining the ARD and the CHX rinse was no more effective than the use of an ARD alone. Pediatr Nurs, 1999 Nov-Dec, 25(6), 607 - 16 Antimicrobial resistance in pediatric upper respiratory infection: a prescription for change; Lang MM; The advent of antimicrobial usage in the 1930s provided effective weaponry to combat morbidity and mortality associated with infectious disease . Today, due primarily to inappropriate antibiotic prescribing, these antimicrobial weapons are being seriously threatened by the emerging danger of antimicrobial resistance . Despite guidelines formulated by the Centers for Disease Control and Prevention (CDC) to address judicious antibiotic use in managing pediatric upper respiratory infection, much unnecessary prescribing continues . Many factors contribute to these erroneous practices, including misconceptions held by both the medical community and the public sector . Additionally, patient expectations have an impact on treatment decisions despite advice to the contrary . A review of the literature provides support for the adoption of the CDC standards of care and underlines the need to further investigate practice patterns . Measures to encourage appropriate antibiotic usage and to reverse the trend toward antimicrobial resistance are needed. Minerva Anestesiol, 2002 Apr, 68(4), 258 - 60 Optimizing therapeutic approaches in ventilator-associated pneumonia; Brun-Buisson C; The world-wide increasing of antimicrobial resistance, face the clinician with the dilemma of treating patients in excess or under-treat patients who need therapy . Early empirical therapy, based on local epidemiological and surveillance data, clinical presentation, timing of onset of pneumonia relative to hospital admission, and administration of prior antibiotics, is often necessary . The first-line therapy in patients with early-onset pneumonia, no risk factor and no prior antibiotics, will be direct to community type organisms, while in patients with late-onset (>5 to 7 days mechanical ventilation) pneumonia, and after prior administration of antibiotics, will be direct to multi-resistant and difficult-to-treat organisms . Risk for development of self-resistance appears higher with imipenem and fluoroquinolones . Obtaining reliable samples to adapt therapy does not improve outcome, but may allow withdrawing of therapy when pneumonia is not confirmed, therefore reducing the overall selective pressure in the ICU environment. Transplantation, 2002 May 15, 73(9), 1522 - 6 Neutrophil defense in patients undergoing bone marrow transplantation: bactericidal/permeability-increasing protein (BPI) and defensins in graft-derived neutrophils; Levy O et al.; BACKGROUND: Even after neutrophil counts return to near normal levels, patients undergoing myeloablative chemotherapy and bone marrow transplantation (BMT) are at risk for invasive bacterial infections, raising the possibility that their neutrophil function might be impaired . To assess potential qualitative defects in neutrophil function in patients undergoing BMT, we measured neutrophil content of the antimicrobial (poly)peptides BPI and defensins . METHODS: Neutrophil extracts were analyzed for content of BPI by Western blotting and ELISA and for defensin peptides by acid-urea polyacrylamide gel electrophoresis (PAGE) . Antibacterial activity of neutrophil extracts was measured against Escherichia coli K1/r, a clinical isolate sensitive to synergistic killing by BPI and defensins . RESULTS: Neutrophil extract BPI content on post-BMT days +20, +30, and +100 (169+/-35, 232+/-57, and 160+/-55 ng per 106 neutrophils, respectively) was similar to the neutrophil BPI content of normal controls (163+/-35 ng per 106 neutrophils) . Neutrophil defensin content also did not vary during this time-span . Activity of neutrophil extracts against E . coli K1/r did not differ between BMT patients and controls . CONCLUSION: At post-BMT days +20 to +100, neutrophils derived from engrafted marrow contain normal quantities of BPI and defensins . Any deficiencies of neutrophil function during this phase are not due to inadequate expression of these antimicrobial (poly)peptides but could reflect abnormalities in other aspects of neutrophil function. FEBS Lett, 2002 May 22, 519(1-3), 141 - 6 Production of a recombinant antimicrobial peptide in transgenic plants using a modified VMA intein expression system; Morassutti C et al.; Tobacco plants were engineered to express SMAP-29, a mammalian antimicrobial peptide of innate immunity, as fusion protein with modified vacuolar membrane ATPase intein . The peptide was purified taking advantage of the intein-mediated self-cleaving mechanism . SMAP-29 was immunologically detected in the chromatographic eluate and appeared tightly bound to copurified plant proteins . Electrophoretic separation under disaggregating conditions indicated that the recombinant peptide was cleaved off by intein at the expected site and an overlay gel assay demonstrated that the peptide retained antimicrobial activity . These results indicate that a modified intein expression system can be used to produce pharmaceutical peptides in transgenic plants. Ann Pharmacother, 2002 Jun, 36(6), 975 - 80 Clinical outcomes of ambulatory acute exacerbations of chronic bronchitis with older versus newer antimicrobials; Madaras-Kelly KJ et al.; OBJECTIVE: To determine whether the cure rate was similar between traditional and newer antibiotics in the treatment of acute exacerbations of chronic bronchitis (AECB), to determine whether antibiotic selection during the first AECB of the season influences the frequency of subsequent AECB, and to identify variables associated with poor short- and long-term treatment outcome . METHODS: A retrospective analysis of subjects seen for management of their first seasonal AECB was conducted . Subjects were stratified into traditional therapies (n = 95) or newer therapies (n = 101) by antibiotic prescription . RESULTS: There was no difference in initial cure rates between older versus newer antibiotics (93% vs . 95%; p = 0.48) . There was no difference in the number of subjects that remained AECB-free for 6 months after initial treatment with older versus newer antibiotic regimens (34% vs . 28%; p = 0.37) . Oxygen initiation or increased dose (OR 10.9; 95% CI 1.4 to 84.2; p = 0.02) was the only variable independently associated with lack of AECB resolution . Nonsmoking status trended toward an association with remaining AECB-free at 180 days (OR 0.39; 95% CI 0.15 to 1.01; p = 0.053) . CONCLUSIONS: The use of older versus newer antibiotics did not independently predict short-term outcome or future AECB. J Am Anim Hosp Assoc, 2002 May-Jun, 38(3), 217 - 20 Rapidly growing members of the genus Mycobacterium affecting dogs and cats; Jang SS et al.; Rapidly growing members of the genus Mycobacterium were most often associated with chronic (2 to 72 months), nonhealing skin lesions of dogs and cats . Mycobacterium fortuitum (M . fortuitum) was the most commonly isolated mycobacterium obtained from these lesions, although M . chelonae-abscessus and M . flavescens were occasionally encountered . Isolates were tested in vitro to various antimicrobial agents and found to be susceptible to amikacin (100% of the isolates), cefoxitin (93.8%), ciprofloxacin (75%), clarithromycin (71.4%), doxycycline (28.6%), erythromycin (6.2%), gentamicin (68.8%), kanamycin (75%), minocycline (81.3%), streptomycin (14.3%), tobramycin (43.8%), trimethoprim/sulfonamides (57.1%), and vancomycin (15.4%). Curr Pharm Biotechnol, 2002 Jun, 3(2), 99 - 115 Pore-forming proteins and their application in biotechnology; Panchal RG et al.; Proteins and peptides that form membrane-spanning pores and channels comprise a diverse class of molecules ranging from short peptides that are unregulated and create non-selective pathways to large ion channel proteins that are highly regulated and exhibit exquisite selectivity for particular ions . The diversity of regulation and selectivity, together with recent advances in protein "re-engineering" technology, provide a strong framework on which to build custom molecules with wide-ranging biotechnological application . Here we review a selection of pore-forming peptides and proteins from a number of different species to highlight their structural and functional diversity . The current and potential uses of native and re-engineered molecules are discussed together with a novel strategy to re-engineer alpha-hemolysin to create targeted and regulable cell-killing agents termed proimmunolysins . Numerous pore-forming peptides are currently in development as antimicrobial agents with potential application as anti-tumorigenic agents . In addition to their roles as biotherapeutic agents, pore-forming proteins are also being developed as biosensors for a range of different analytes . Recent examples of this technology include the use of alpha-hemolysin with an adapter molecule to create sensors for organic molecules and gramicidin as a general-purpose sensor for a range of analytes . These approaches promise to deliver a configurable binding site for analytes encoded in a readily measured electrical signal . The number of applications for pore-forming molecules is sure to grow in both quantity and diversity with increased knowledge of the fundamental structure and function of pores. Curr Pharm Biotechnol, 2002 Jun, 3(2), 77 - 98 Outer membranes and efflux: the path to multidrug resistance in Gram-negative bacteria; Poole K; Intrinsic and acquired multidrug resistance in Gram-negative bacteria owes much to the synergy between limited outer membrane permeability and energy-dependent multidrug efflux . The importance of the outer membrane vis-a-vis resistance is aptly demonstrated by the impact of mutational changes in outer membrane constituents on drug susceptibility . Changes in lipopolysaccharide (LPS) that correlate with increased drug susceptibility confirm, for example, the significance of this macromolecule in the intrinsic antimicrobial resistance of Gram-negative bacteria . Alterations in LPS and porins correlating with increased resistance to a variety of antimicrobials are also known and highlight the significance of the outer membrane vis-a-vis acquired antimicrobial resistance . Efflux systems accommodating a range of structurally distinct antimicrobials, including antibiotics, detergents, dyes, biocides and aromatic hydrocarbons have been identified in a number of Gram-negative organisms . Mutational studies have confirmed the importance of these systems to intrinsic and acquired antimicrobial resistance in important disease-causing organisms . As such, strategies aimed at thwarting efflux and or the outer membrane barrier are effective at reversing antimicrobial resistance in these organisms. Antimicrob Agents Chemother, 2002 Jun, 46(6), 1996 - 9 Impact of N-chlorotaurine on viability and production of secreted aspartyl proteinases of Candida spp; Nagl M et al.; N-Chlorotaurine, an endogenous long-lived oxidant, demonstrated fungicidal activity against Candida spp . and a postantifungal effect . Secreted aspartyl proteinases, important fungal virulence factors, proved to be a first target of impact . These results provide support for the topical application of N-chlorotaurine as an antimicrobial agent in yeast infections. Antimicrob Agents Chemother, 2002 Jun, 46(6), 1870 - 4 Double-blind, randomized, placebo-controlled study of topical 5% acyclovir-1% hydrocortisone cream (ME-609) for treatment of UV radiation-induced herpes labialis; Evans TG et al.; Immunopathology is recognized as an important component of infectious disease manifestations, and corticosteroids have been used as an adjunct to antimicrobial therapy for a variety of conditions . Antiviral therapy of herpes labialis has been shown to result in only a small reduction in the time to healing and the duration of pain . To determine if topical application of a combination product containing 5% acyclovir and 1% hydrocortisone (ME-609) could provide benefit to herpes labialis patients, 380 immunocompetent adults with a history of herpes labialis were exposed to experimental UV radiation (UVR) to induce a recurrence . On day 2, just before the appearance of the majority of lesions ("delayed" lesions), subjects were randomized to receive active medication or vehicle control six times per day for 5 days . Overall, 120 of 380 patients developed delayed classical lesions, of whom 50 of 190 (26%) had been treated with ME-609 and 70 of 190 (37%) had received placebo (a reduction of 29% {P = 0.02}) . Healing time, measured as the time to normal skin, was reduced by treatment with ME-609 (9.0 days for treated patients versus 10.1 days for the controls {P = 0.04}) . There was a trend toward a reduction in the maximum lesion size in the ME-609 recipients compared to that in the controls (43 versus 60 mm(2), respectively {P = 0.07}) . The treatment had no effect on lesion pain, but ME-609 treatment reduced the number of patients with moderate or severe tenderness . Compared to treatment with a placebo, treatment with the combination antiviral-immunomodulatory cream provided benefit to patients with experimental UVR-induced herpes labialis, reducing classical lesion incidence, healing time, lesion size, and lesion tenderness . ME-609 is a novel product that merits further evaluation as a treatment for cold sores. Anal Biochem, 2002 Jun 1, 305(1), 97 - 105 A nonradioactive, high throughput assay for chitin synthase activity; Lucero HA et al.; Wheat germ agglutinin (WGA) binds with high affinity and specificity to several sites on chitin polymers . Based on these properties we have modified and adapted a previously patented (U.S . patent 5,888,757) nonradioactive, high throughput screening assay for antimicrobial agents, making it suitable as a quantitative enzymatic assay for the activity of individual chitin synthase isozymes in yeast . The procedure involves binding of synthesized chitin to a WGA-coated surface followed by detection of the polymer with a horseradish peroxidase-WGA conjugate . Horseradish peroxidase activity is then determined as an increment in absorbance at 600 nm . Absorbance values are converted to amounts of chitin using acid-solubilized chitin as a standard . The high sensitivity (lower limit of detection about 50 ng chitin), low dispersion (lower than 10%), and high throughput (96-well microtiter plate format) make this assay an excellent substitute for the conventional radioactive chitin synthase assay in cell-free extracts . We have applied this method to the differential assay of chitin synthase activities (Chs1, Chs2, and Chs3) in cell-free extracts of Saccharomyces cerevisiae . Analysis of Chs3 activity in chitosomal and plasma membrane fractions revealed that Chs3 in the plasma membrane fraction is about sixfold more active than in the chitosome . (c) 2002 Elsevier Science (USA). Am J Med Sci, 2002 May, 323(5), 269 - 72 Fulminant Stenotrophomonas maltophilia soft tissue infection in immunocompromised patients: an outbreak transmitted via tap water; Sakhnini E et al.; Soft tissue infection caused by Stenotrophomonas maltophilia is uncommon, but nosocomial infections had been reported . We describe herein 2 young female patients, with severe neutropenia, on broad spectrum antimicrobial agents for neutropenic fever, with Hickman-type central venous catheter, who developed mucocutaneous and soft tissue infections with rapidly progressive and devastating course . Cultures from the skin of both patients and from blood of one of them grew S . maltophilia . Both patients died and post mortem examination of the patient with S . maltophilia bacteremia revealed extensive soft tissue necrosis and a vegetation on the mitral valve that grew S . maltophilia . The infection occurred in both patients at the same time and in the same ward . Epidemiological study was done, and surveillance cultures grew the organism from the faucets from the room of 1 patient and also from some of the neighboring rooms in our ward but not from any other ward nor in the water reservoir of the building. Clin Ther, 2002 Apr, 24(4), 639 - 52 A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes; Wilson R et al.; BACKGROUND: Gemifloxacin is an enhanced-affinity quinolone with potent activity against lower respiratory tract pathogens . OBJECTIVE: The efficacy and safety of a 5-day course of gemifloxacin were compared with those of a standard 7-day regimen of clarithromycin in patients with an acute exacerbation of chronic bronchitis (AECB) . The impact of treatment on the long-term (26 weeks) clinical outcome was also assessed . METHODS: The acute phase of this randomized, double-blind study was performed in 93 centers in 7 countries . Adult patients (age >40 years) with a history of chronic bronchitis and an Anthonisen type 1 acute exacerbation (increased dyspnea, cough, and sputum purulence) were eligible . Patients receiving systemic steroids at a dose of >10 mg prednisone or the equivalent were excluded . Patients were randomized to receive gemifloxacin 320 mg once daily for 5 days or clarithromycin 500 mg twice daily for 7 days . Clinical and bacteriologic response rates were assessed at the end-of-therapy visit (days 8-12), the week 2-3 follow-up visit (days 13-24), and the week 4-5 follow-up visit (days 25-38) . The long-term phase (26 weeks), which included US and Canadian participants only, evaluated the proportion of patients who remained free of a recurrence of AECB requiring additional antimicrobial therapy after resolution of the initial episode . RESULTS: Seven hundred twelve patients were randomized to treatment, 351 to gemifloxacin and 361 to clarithromycin . The long-term study included 438 patients, 214 receiving gemifloxacin and 224 receiving clarithromycin . Clinical success rates at the 2-3 week follow-up visit were 85.4% for gemifloxacin and 84.6% for clarithromycin . Bacteriologic success rates were 86.7% for gemifloxacin and 73.1% for clarithromycin . Significantly more patients receiving gemifloxacin than clarithromycin remained free of AECB recurrences (71.0% vs 58.5%, respectively; P = 0.016) . Both treatments were well tolerated . CONCLUSIONS: In the acute treatment of Anthonisen type 1 AECB, a 5-day course of gemifloxacin was at least as effective as a 7-day regimen of clarithromycin . In this population, significantly more patients receiving gemifloxacin remained free of AECB recurrence after 26 weeks compared with those receiving clarithromycin. J Chemother, 2002 Apr, 14(2), 181 - 4 Physicians' antibiotic prescribing habits for upper respiratory tract infections in Turkey; Leblebicioglu H et al.; The aim of this study was to evaluate the antibiotic prescription rates for upper respiratory tract infections (uRTIs) by primary care physicians in Samsun, Turkey . Data were obtained from the records of 2,083 visits to 8 primary care areas . Trained research students were stationed on site at each of the 8 primary care areas during the study period . Clinical features of patients were documented on a standardized form . Patients who had acute pharyngitis, acute sinusitis, acute otitis media (AOM) and common cold were included in the study . This survey was conducted between June 1, 1999 and July 1, 1999 . A total of 2,083 office visits were recorded and 502 (24.1%) of the patients had uRTIs . Physicians approached these conditions empirically, with only 2.9% of patients having a diagnostic test at initial examination . Antibiotics were prescribed for 461 patients (91.8%) with uRTIs (common cold: 41.9%, acute pharyngitis: 94.7%, acute sinusitis: 94.1% and AOM: 100%) . 11.5% of the antibiotic prescriptions were inconsistent with current recommendations derived from the literature . Inadequate antibiotic prescribing was documented in 29.7% of antibiotic prescriptions . Errors were frequent in relation to dosage, dosage interval and duration of therapy . Overuse of antibiotics is widespread in our geographic area . Both administrative and educational intervention should be implemented to improve antibotic prescribing habits at the primary health care level to reduce the unnecessary use of antimicrobial agents. Ann Clin Lab Sci, 2002 Spring, 32(2), 142 - 7 Antimicrobial susceptibility testing of Mycobacterium tuberculosis to first-line drugs: comparisons of the MGIT 960 and BACTEC 460 systems; Huang TS et al.; The reliability of the Mycobacteria Growth Indicator Tube (MGIT) 960 system for rapid antimicrobial susceptibility testing (AST) of Mycobacterium tuberculosis was evaluated . Forty-seven isolates, including 10 fully susceptible and 37 resistant strains, were tested for susceptibility to the critical concentrations of streptomycin (STR), isoniazid (INH), rifampin (RMP), and ethambutol (EMB), as recommended by the manufacturer . Strains resistant to the critical concentrations were tested with higher concentrations . The results were compared to those obtained by a radiometric method (BACTEC 460TB) and by a conventional agar dilution method, which served as the reference method . Based on these data, we suggest that the following antibiotic concentrations give satisfactory results with the MGIT 960 system: STR, 4.0 microg/ml; INH, 0.1 microg/ml; RMP, 1.0 microg/ml; and EMB, 5.0 microg/ml . The time required to obtain susceptibility results averaged 6.9 days by the MGIT 960 system and 5.4 days by the BACTEC 460TB system; these intervals were not significantly different . This study shows that the MGIT 960 system is a reliable, rapid, automated method for testing the susceptibility of M . tuberculosis isolates to first-line drugs. Semin Liver Dis, 2002, 22(2), 157 - 67 Hepatotoxicity of antimicrobial agents; Brown SJ et al.; Antimicrobial agents are a common and important cause of hepatotoxicity . As a class, the antimicrobials contain many and varied structures, leading to a wide clinical spectrum of hepatotoxicity . Minor liver injury, manifest only as liver enzyme elevations, is common with some antimicrobials . Clinically significant injury is unusual but can adopt almost any form . Classical acute hepatocellular, cholestatic, or mixed reactions are most often seen . Other forms of hepatotoxicity including granulomatous reactions, steatosis, chronic hepatitis, and cirrhosis have also been described . Generally, antimicrobial-associated hepatotoxicity is mild and self-limited; most cases resolve after withdrawal of the offending medication . Occasionally, however, liver injury presents as a fulminant life-threatening condition or may develop into a chronic illness with significant morbidity . This article presents a summary of reported hepatotoxicity associated with the major classes of antimicrobials and, where possible, identifies potential risk factors and management strategies to assist clinical practice. Appl Microbiol Biotechnol, 2002 May, 58(6), 790 - 6 Epub 2002 Mar 07. Enhanced expression of tandem multimers of the antimicrobial peptide buforin II in Escherichia coli by the DEAD-box protein and trxB mutant; Lee JH et al.; The tandem multimeric expression of various peptides has been explored by many researchers . However, expression levels have usually not been proportional to the degree of multimerization . To increase the expression level in Escherichia coli of tandem multimers of a cationic antimicrobial peptide, buforin II, fused to an anionic peptide, we studied the effect of the DEAD-box protein and the trxB mutant on the expression of tandem multimers . An expression vector with a tac promoter was more effective in directing multimeric expression than one with a T7 promoter . The expression level of large multimers was substantially increased with the tac promoter, possibly through stabilization of long transcripts by synchronization of transcription and translation . Coexpression of the DEAD-box protein, an RNA-binding protein, with the T7 expression system increased the expression level of multimers, especially large multimers, due to protection of the long RNA transcripts . In addition, the use of the trxB mutant also enhanced the expression level of tandem multimers, which contain two cysteine residues at both ends of the monomeric unit . It seems that disulfide bonds formed in the multimers in the trxB mutant might help efficient charge neutralization for inclusion body formation of the multimers, resulting in enhancement of expression . Our results show that the expression of multimers can be improved through the stabilization of the long transcripts by the DEAD-box protein or the expression, under an oxidizing environment, of the trxB mutant in which covalent cross-links through disulfide bonds facilitate inclusion body formation of the multimeric fusion peptide. Appl Microbiol Biotechnol, 2002 May, 58(6), 695 - 703 Epub 2002 Mar 07. Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics; Heath RJ et al.; Fatty acid biosynthesis is an emerging target for the development of novel antibacterial chemotherapeutics . The dissociated bacterial system is substantially different from the large, multifunctional protein of mammals, and many possibilities exist for type-selective drugs . Several compounds, both synthetic and natural, target bacterial fatty acid synthesis . Three compounds target the FabI enoyl-ACP reductase step; isoniazid, a clinically used antituberculosis drug, triclosan, a widely used consumer antimicrobial, and diazaborines . In addition, cerulenin and thiolactomycin, two fungal products, inhibit the FabH, FabB and FabF condensation enzymes . Finally, the synthetic reaction intermediates BP1 and decynoyl- N-acetyl cysteamine inhibit the acetyl-CoA carboxylase and dehydratase isomerase steps, respectively . The mechanisms of action of these compounds, as well as the potential development of new drugs targeted against this pathway, are discussed. Nat Immunol, 2002 Jun, 3(6), 583 - 90 Epub 2002 May 20. Paneth cell trypsin is the processing enzyme for human defensin-5; Ghosh D et al.; The antimicrobial peptide human alpha-defensin 5 (HD5) is expressed in Paneth cells, secretory epithelial cells in the small intestine . Unlike other characterized defensins, HD5 is stored in secretory vesicles as a propeptide . The storage quantities of HD5 are approximately 90 450 microg per cm2 of mucosal surface area, which is sufficient to generate microbicidal concentrations in the intestinal lumen . HD5 peptides isolated from the intestinal lumen are proteolytically processed forms--HD5(56-94) and HD5(63-94)--that are cleaved at the Arg55-Ala56 and Arg62-Thr63 sites, respectively . We show here that a specific pattern of trypsin isozymes is expressed in Paneth cells, that trypsin colocalizes with HD5 and that this protease can efficiently cleave HD5 propeptide to forms identical to those isolated in vivo . By acting as a prodefensin convertase in human Paneth cells, trypsin is involved in the regulation of innate immunity in the small intestine. Nephron, 2002 May, 91(1), 156 - 8 Brucella peritonitis in a patient on continuous ambulatory peritoneal dialysis with acute brucellosis; Taskapan H et al.; Peritonitis is an uncommon complication of brucellosis . Brucella peritonitis in chronic ambulatory peritoneal dialysis (CAPD) patients has not been reported before . A male patient is presented with peritonitis caused by Brucella melitensis who was on CAPD . The source of infection was thought to be unpasteurized, unsalted cheese eaten a month before the onset of symptoms . At the beginning, antibiotic therapy with doxycyline and rifampicin led to a rapid clinical improvement, with disappearance of the organism in the peritoneal fluid . However, peritonitis relapsed after discontinuation of antimicrobial therapy . Successful management required a combination of medical therapy and removal of the Tenckhoff catheter . J Ethnopharmacol, 2002 Jun, 81(1), 101 - 4 Volatiles with antimicrobial activity from the roots of Greek Paeonia taxa; Papandreou V et al.; The traditional uses of the roots of Paeonia taxa are described . The volatile constituents, obtained by steam distillation of the roots of Paeonia clusii Stern subsp . clusii, Paeonia mascula L . subsp . hellenica and Paeonia parnassica, were studied by GC/MS . Salicylaldehyde, paeonol, methyl salicylate and benzoic acid were found to be the major components among the twelve constituents identified . The evaluation of the in vitro antimicrobial activity of the volatile compounds against six bacteria and three fungi is also reported. J Ethnopharmacol, 2002 Jun, 81(1), 43 - 7 Evaluation of the antinflammatory and analgesic activity of Sideritis canariensis var . pannosa in mice; Hernandez-Perez M et al.; A previous chemical study of Sideritis canariensis var . pannosa demonstrated the presence of some important classes of related organic compounds with anti-inflammatory activities . In the present study, the crude ethanol extract and the chloroformic and aqueous fractions of S . canariensis have been examined for their antimicrobial actions through the disk-diffusion method and for their anti-inflammatory and analgesic effects in several animal models . No relevant antimicrobial activity against the tested microorganisms was found . The chloroformic fraction was the most interesting, exhibiting a good analgesic and anti-inflammatory activity. Curr Opin Investig Drugs, 2002 Feb, 3(2), 225 - 8 Iseganan (IntraBiotics pharmaceuticals); Toney JH; Iseganan (IB-367) is a protegrin under development by IntraBiotics, as part of a larger protegrin program, for the potential treatment of oral mucositis, a frequent side effect of anticancer therapies . The company is developing three formulations of the drug: A rinse for the potential treatment of mucositis, an aerosolized liquid for the potential treatment of respiratory infection and a gel formulation for the potential treatment of pneumonia {376325} . Iseganan kills a broad-spectrum of bacteria and fungi, including those resistant to conventional antimicrobial drugs, by attaching to and destroying the integrity of the lipid cell membrane {241594} . Until August 1999, Pharmacia & Upjohn was a codeveloper of iseganan . IntraBiotics re-acquired the global rights to iseganan in December 1999, and both companies agreed to terminate the collaboration {335766} . In May 2000, analysts at SG Cowen predicted the drug's potential market at US $100 to US $200 million {376325}. Pol J Pharmacol, 2002 Jan-Feb, 54(1), 55 - 9 Synthesis, antibacterial, antifungal and genotoxic activity of bis-1,3,4-oxadiazole derivatives; Maslat AO et al.; In the present investigation, four 1,3,4-bis-oxadiazole derivatives were synthesized as potential antimicrobial agents . The compounds are: 5,5'-dimercapto-bis-{1,3,4-oxadiazol-2-yl}propane (2a), 5,5'-dimercapto-bis-{1,3,4-oxadiazol-2-yl}butane (2b), 5,5'-dimercapto-bis-{1,3,4-oxadiazol-2-yl}octane (2c) and 5,5'-dibenzylthio-bis-{1,3,4-oxadiazol-2-yl}butane (3) . The above newly synthesized compounds were investigated for their antibacterial, antifungal and mutagenic activities . The results of the biological activities revealed that the compounds 2a-c exhibited both antibacterial and antifungal activities against S . aureuss and B . subtilis . Compound 2a also showed activity against P . aeureoginosa . All the above compounds and compound 3 exhibited activity against C . albicans . Genotoxic studies showed that compound 2a had a weak base pair substitution mutagenicity but none of them exhibited a frameshift mutagenic action using Ames test. New Microbiol, 2002 Apr, 25(2), 213 - 22 Antimicrobial activity of two novel coumarin derivatives: 3-cyanonaphtho{1,2-(e)} pyran-2-one and 3-cyanocoumarin; Zaha AA et al.; The antimicrobial activity of the two novel coumarin derivatives, 3-cyanonaphthol{1,2-(e)}pyran-2-one and 3-cyanocoumarin was determined . The two novel coumarin derivatives showed specific activity against most gram-positive organisms and yeast with lower activity against most gram-negative bacteria . The MIC values of compounds showed that they are largely active against E . coli to a lesser extent against S . aureus and C . albicans. New Microbiol, 2002 Apr, 25(2), 157 - 64 Correlation study of two routine bacteriology systems with previously characterised strains; Giordano A et al.; The objective of this study was to evaluate the performance of the VITEK 2 and Advanced Expert System (bioMerieux) for antimicrobial testing of previously characterised Gram-positive and Gram-negative bacterial strains . These strains obtained from bioMerieux, Mrcy Le Toille, France, were well characterized with regard to the existing resistance mechanisms and the Minimal Inhibitory Concentration (MIC) values were determined by agar dilution . VITEK 2 was also compared with the Sceptor system (Becton Dickinson) routinely used in our laboratory . The results obtained were equally good for VITEK 2 and Sceptor with a rate of agreement between the two systems of 91.4% and 88.2% respectively . When the results were evaluated in relation to the different antibiotic concentrations, the agreement was 94% for VITEK 2 and 62% for Sceptor . The resistance mechanisms associated with each resistance pattern were determined by the Advanced Expert System (AES) in 79.6% of strains . The VITEK 2 provided, in 3-4 hours, an acceptable level of accuracy in testing antimicrobial sensitivity in Gram-positive and Gram-negative strains with diverse mechanisms of resistance found in clinical situations. Clin Infect Dis, 2002 Jun 1, 34(11), 1431 - 9 Epub 2002 Apr 30. Reappraisal of community-acquired bacteremia: a proposal of a new classification for the spectrum of acquisition of bacteremia; Siegman-Igra Y et al.; In recent years, dramatic changes in health care systems have shifted much of the care of sick individuals from hospitals to the community . Consequently, infections traditionally classified as community-acquired or hospital-acquired infections cannot now be readily classified into either category . We thus propose a new classification based on a wider spectrum of acquisition . A total of 1028 episodes of bloodstream infection (BSI) were divided into 5 categories: true community-acquired infections (370 episodes {36%}), infections in recently discharged patients (110 {11%}), infections associated with invasive procedures performed just before or at the time of admission (56 {5%}), infections in patients admitted from nursing homes (68 {7%}), and hospital-acquired infections (424 {41%}) . Thus, 234 (39%) of the 604 bloodstream infections traditionally defined as community acquired were reclassified into 3 newly defined groups, each of which has distinct epidemiologic, clinical, and bacteriologic characteristics, as well as distinct antimicrobial susceptibility profiles . There is a conceptual and practical need for such a new classification. Curr Opin Infect Dis, 2002 Jun, 15(3), 295 - 300 Mycoplasma pneumoniae and Chlamydia pneumoniae cause lower respiratory tract disease in paediatric patients; Principi N et al.; New studies suggest that Mycoplasma pneumoniae and Chlamydia pneumoniae play a more significant role as causes of lower respiratory tract infections in childhood than was previously thought . In particular, the incidence of infections caused by these pathogens is high in children aged less than 5 years, the infections themselves seem to be a possible cause of wheezing, and may present a more complicated course when not treated with adequate antimicrobial agents . However, despite the increasing pathogenic significance of M . pneumoniae and C . pneumoniae, progress in fighting them is hampered by the lack of rapid and standardized diagnostic methods . This not only makes it practically impossible for practitioners to make a specific microbiological diagnosis, but has also had an adverse effect on treatment trials and has generated some questionable results . Carefully randomized and controlled trials are clearly needed to examine the effectiveness of different antibiotics against M . pneumoniae or C . pneumoniae and the optimal duration of therapy in various patient populations. J Hosp Infect, 2002 Apr, 50(4), 293 - 7 Experience with a bone bank operation and allograft bone infection in recipients at a medical centre in southern Taiwan; Liu JW et al.; To assess the contamination rate of allograft bones at retrieval and the infection rate of the implanted allograft bone, we audited a bone bank retrospectively and reviewed the medical charts of allograft bone recipients between June 1999 and June 2000 at a medical centre in southern Taiwan . The bone bank did its utmost to minimize allograft contamination with hospital-acquired pathogens by adopting purposefully designed criteria for selection of donors . This protocol included sterilization with soaking of the retrieved allograft in a solution of a first-generation cephalosporin before storage and prophylaxis in recipients with first-generation cephalosporin . The contamination rates at allograft retrieval from living and cadaveric donors were 2.7% and 12.4%, respectively (P<0.001) . Culture of 262 specimens taken at allograft implant revealed 12 (4.6%) positive for culture . Of the 12 patients implanted with allograft bones positive for culture, nine (75.0%) had allograft bone infection, while three (25.0%) did not . Among the 250 recipients with sterile allograft bones, four (1.6%) were found to have allograft infection . None of the cases of infection required removal of the allograft bones, and all cases were successfully treated with tailored antimicrobial therapy based on susceptibility tests on isolated bacteria . The overall infection rate was 5.0%, which compared favourably with those in other series . A prospective cohort study is needed to determine which of the varied sterilization methodologies gives the best and/or most cost-effective outcome . Int J Clin Pract Suppl, 2002 Mar, (125), 29 - 36; discussion 37-9 Rational approaches to combating resistance; Burke JP; Traditional treatment paradigms based on national guidelines and administrative policies, such as restricted formularies, that are intended to guide antibiotic selection for empirical therapy of community- and hospital-acquired infections have been largely unsuccessful in curbing the spread of antimicrobial resistance . Evidence suggests that restricting antibiotic availability may lead to potential misuse of unrestricted agents as well as to increased adverse drug reactions, costs and, potentially, increased antibiotic resistance . New treatment paradigms, such as that embodied in the LDS Hospital computer-based "automated antibiotic assistant", that address antibiotic use from a process-of-care approach, using local clinician-derived solutions implemented at the patient's bedside, may offer strategic advantages over traditional approaches based on restricting antibiotic use . By using patient- and institution-specific data to tailor therapy to individual patient circumstances, such systems can help reduce the dosage, duration, frequency of adverse events and cost of antibiotic therapy as well as improving clinical outcomes and potentially avoiding drug resistance. Int J Clin Pract Suppl, 2002 Mar, (125), 10 - 17; discussion 37-9 Community-acquired lower respiratory tract infections: clinical experience with beta-lactam/beta-lactamase inhibitors; Lode H; Once universally susceptible to aminopenicillins and cephalosporins, an increasing percentage of the common respiratory pathogens that cause community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) are now resistant to these agents and exhibit cross-resistance to other commonly used antibiotics . In an era of multidrug resistance, guidelines for the management of both CAP and AECB can help to guide appropriate antibiotic prescribing, encourage the rational use of antibiotics, which will help to limit the emergence of resistance, and conserve the use of new antimicrobial agents for more serious infections . Central to all current management guidelines is risk assessment, which includes an appreciation of local antibiotic resistance patterns . beta-Lactam antibiotics are still considered among the drugs of choice for the treatment of CAP and AECB, although their use can be compromised by high rates of resistance . The beta-lactam/beta-lactamase inhibitor combinations, such as ampicillin/sulbactam, provide a means of overcoming such resistance and represent a suitable alternative. Anticancer Res, 2002 Mar-Apr, 22(2A), 879 - 81 Lysozyme-rich muciphages surrounding colorectal adenomas; Rubio CA; Muciphages are mucin-rich phagocytes believed to evolve as a result of the disruption of colorectal crypts . In a previous work we found, in rectal biopsies from patients with chronic ulcerative colitis, muciphages having not only mucin but also lysozyme, an enzyme with a potent antimicrobial activity . Recently we detected lysozyme-rich muciphages in the normal mucosa of the stalk of colonic adenomas . Filed hematoxylin and eosin (H&E)-stained sections from 30 consecutive colorectal adenomas with a stalk (lined by normal colorectal mucosa) were stained with PAS (for mucopolysaccharides), with CD68 (to label macrophages) and with lysozyme (Muramidase) . Of the 30 adenomas, 16 (40%) showed muciphages in the mucosa of the stalk . Those muciphages were PAS- CD68- and lysozyme-positive . Although the significance of these findings remains elusive, it is conceivable that lysozyme-rich muciphages mirror increased cell destruction in colorectal adenomas with a high cell turnover . The possibility that lysozyme-rich muciphages surrounding adenomas are instrumental in a novel molecular mechanism of host defense, effective at the early stages of colorectal carcinogenesis, was also entertained . Such a mechanism would prevent the lateral expansion of the dysplastic epithelium of the adenoma into the surrounding normal mucosa of the stalk. J Antibiot (Tokyo), 2002 Mar, 55(3), 308 - 14 New amidino-benzimidazolyl derivatives of tylosin and desmycosin; Hranjec M et al.; New amidino-benzimidazolyl derivatives of antibiotics tylosin and desmycosin are prepared in the reaction of corresponding amidino-substituted o-phenylendiamine with tylosin respectively desmyicosin on the 20-C aldehyde group . The reaction was carried out in absolute ethanol in the presence ofp-benzoquinone . On this way are prepared: 20-{5-(N-isopropylamidino)-2-benzimidazolyl}tylosin hydrochloride 9, 20-{5-(2-imidazolinyl)-2-benzimidazolyl}tylosin hydrochloride 10, 20-{5-(N-morpholinylamidino)-2-benzimidazolyl}tylosin hydrochloride 11, 20-{5-(N-isopropylamidino)-2-benzimidazolyl}desmycosin hydrochloride 12, 20-{5-(2-imidazolinyl)-2-benzimidazolyl}desmycosin hydrochloride 13, 20-{5-(N-morpholinylamidino)-2-benzimidazolyl}desmycosin hydrochloride 14 . Their antimicrobial activity was tested on a series of microorganisms. MMW Fortschr Med, 2002 Apr 4, 144(14), 28 - 34 {Diagnosis and therapy of infectious endocarditis . What measures are required?}; Koster R et al.; Infectious endocarditis remains a potentially life-threatening disease, the outcome of which can be substantially influenced by rapid diagnosis and initiation of suitable treatment . Leading clinical features are fever, a new sound suggestive of valvular insufficiency and, when the course is subacute, anemia . The main diagnostic procedures are transthoracic and transesophageal echocardiography that reliably identify vegetation, valvular insufficiency and abscess . Of decisive importance for treatment and prognosis is the rapid identification of the pathogen by means of blood culture and, if necessary, serologic and molecular-biologic measures . Antimicrobial treatment is applied in accordance with the recommendations of the American Heart Association . Surgical treatment is indicated in the event of refractory infection, severe valvular insufficiency with heart failure, valve avulsion, recurrent emboli or large floating vegetation with an elevated risk of embolism. Korean J Intern Med, 2002 Mar, 17(1), 38 - 44 Selective bowel decontamination for the prevention of infection in acute myelogenous leukemia: a prospective randomized trial; Lee DG et al.; BACKGROUND: Infection is still a frequent cause of morbidity and mortality in acute myelogenous leukemia (AML) patients receiving chemotherapy . Recently the main cause of infection has changed from gram-negative to gram-positive bacteria and the resistance to antibiotics has increased . This study aimed to access the effectiveness of antimicrobial prophylaxis (AP) with orally absorbable antibiotics . METHODS: Ninety-five AML patients receiving chemotherapy at Catholic Hemopoietic Stem Cell Transplantation Center from March 1999 to July 1999 were randomly divided into the AP group (250 mg ciprofloxacin twice a day, 150 mg roxithromycin twice a day, 50 mg fluconazole once a day) and the control group for a prospective analysis . RESULTS: The incidence of fever was 82.6% in the AP group and 91.6% in the control group (p = 0.15) . Though classification and sites of infections showed no difference between the two groups, the catheter associated infection occurred more frequently in the AP group in significance . The time interval between initiation of chemotherapy and onset of fever, white blood cell (WBC) count at the onset of fever, duration of leukopenia (WBC < 1,000/mm3), duration of systemic antibiotic therapy, mortality due to infection and hospitalization period from the data starting chemotherapy showed no differences between the two groups . Infections due to gram negative bacteria decreased to 33.3% in the AP group (vs . 92% in the control group), but infections due to gram positive bacteria increased to 66.7% (vs . 8% in the control group) . Gram negative bacteria showed 100% resistance to ciprofloxacin in the AP group and gram-positive bacteria showed 90-100% resistance to erythromycin, regardless of the presence of AP . CONCLUSION: The AP could not reduce the occurrence of infection or infection associated death in AML patients receiving chemotherapy . On considering increased gram-positive infection and resistance to fluoroquinolone and macrolide, routine prescription of AP should be reconsidered . Further studies that assess the effectiveness of AP in other malignancies, aplastic anemia and bone marrow transplantation are required. Arch Esp Urol, 2002 Mar, 55(2), 131 - 44 {Implementation of a clinical pathway for transurethral resection in benign prostatic hyperplasia}; Sanchez Merino JM et al.; OBJECTIVE: Clinical pathways constitute a powerful tool for reducing the variability that occurs in clinical practice . The results obtained with the use of a clinical pathway for patients undergoing transurethral resection for benign hyperplasia of the prostate (BPH) are presented . METHODS: A prospective study was carried out on a cohort of 80 consecutive patients that had undergone transurethral resection for BPH after the application of a clinical pathway (5 days hospitalization) and compared with the results of a historical cohort of 80 consecutive patients that had been treated before the application of the clinical pathway . The exclusion criteria were diabetes mellitus, anticoagulation therapy with dicoumarin and other pathologies that changed the length of the preoperative stay established in the clinical pathway . For the evaluation of the degree of satisfaction, patients were asked to fill out a questionnaire included in the pathway documents . RESULTS: 73 patients met the inclusion criteria of the clinical pathway . 67 of the 80 patients that underwent surgery before the application of the clinical pathway were valid for comparative analysis . No statistically significant differences were found between both groups for age, prostate volume measured by DRE and US, previous treatment for prostatism, anesthetic risk and weight of the resected specimen . With the application of the pathway, the mean duration of hospital stay was reduced from 6 (SD 1.7; range 4-15) to 4.9 (SD 1.4; range 3-13) days (p < 0.0001) and the duration of urethral catheterization from 4.5 (SD 1.4; range 3-13) to 3.8 (SD 1.3; range 2-11) days (p < 0.01) . Statistically significant differences were found before and after the application of the clinical pathway for degree of compliance of the preestablished antimicrobial prophylaxis guidelines during hospitalisation and after discharge, and thromboembolic prophylaxis . The relative risk of complications after discharge was less after the application of the clinical pathway (RR = 0.66), although it was not statistically significant (CI: 0.41-1.05) . 63 of the 73 patients included in the clinical pathway submitted the questionnaire without identifying themselves . Duration of hospitalization was considered adequate by 89%, and coincided with the programmed and actual duration according to 82.5% . CONCLUSIONS: The application of a clinical pathway for patients undergoing transurethral resection for BPH has reduced costs by reducing the length of hospital stay and adverse effects . Furthermore, reducing the variability of medical care has improved its quality. Dent Clin North Am, 2002 Apr, 46(2), 385 - 404, vii-viii Treating root-surface caries; Burgess JO et al.; This article summarizes the effectiveness of restorative materials used to restore root surfaces, the mechanisms by which these materials reduce caries, and placement techniques for restoring root-surface lesions . Patients may be classified into low, medium, and high caries risk groups for root caries, and specific dental restorative material recommendations are made for each category . Effective plaque control, xylitol-containing chewing gums, antimicrobial agents, fluoride-releasing restorative materials, topically applied fluoride, and fluoride-containing toothpastes provide maximum protection for the high caries risk patient. Dent Clin North Am, 2002 Apr, 46(2), 171 - 84, v Conservative cavity preparations; Summitt JB; When a caries lesion is detected, non-surgical means of treatment (fluorides, antimicrobials, and patient education) should be used unless it is a frank caries lesion . In that case, the lesion should be treated restoratively, but the patient should also be educated and treated to reduce caries risk . When the frank caries lesion is relatively small, the restorative treatment should simply involve removal of carious dentin and overlying unsupported enamel and placement of the restorative material . Of course, for weakened areas of the tooth, more extensive restorations may be indicated. Rinsho Byori, 2002 Apr, 50(4), 381 - 91 {Multicenter evaluation of a newly developed microdilution test, brothMIC NTM to determine minimum inhibitory concentrations of antimicrobial agents for nontuberculous mycobacteria}; Yamane N et al.; We developed a new broth microdilution susceptibility test for nontuberculous mycobacteria to determine minimum inhibitory concentrations(MICs) . The test method utilized air-dried microplates containing serially diluted antimicrobial agents and the modified Middlebrook 7H9 broth . The nine agents tested were rifampicin, isoniazid, ethambutol, streptomycin, kanamycin, levofloxacin, clarithromycin, ethionamide and amikacin . The test plates were reconstituted by inoculation of 0.1 ml of cell suspensions prepared in distilled water by a 1:100 dilution of the 0.5 McFarland suspension . After inoculation, the isolates resulted in incubation at 36 degrees C with clarithromycin at pH 7.4, and with the remaining agents at pH 6.6 . The growth endpoints were visually read after 7-day and 10-day incubations for slowly growing nontuberculous mycobacteria, and after 3-day and 5-day incubations for rapidly growing mycobacteria, respectively . The reproducibility was evaluated with the five ATCC reference strains of nontuberculous mycobacteria . Of the 1,287 repeated tests of the four ATCC slowly growing strains(M . avium, M . intracellulare, M . kansasii and M . gordonae), 1,200(93.2%) of the MICs read after 7-day incubation fell within 3 log 2 dilutions . Also, a strain of rapidly growing mycobacteria, M . fortuitum, was repeatedly tested, and the reproducibility was estimated to be 93.3% after 3-day incubation . A total of 728 clinical isolates of nontuberculous mycobacteria comprising 14 species were tested against nine agents . The MICs against nontuberculous mycobacteria distributed in a wide range, and the activities of rifampicin, levofloxacin, clarithromycin were more potent . These results demonstrate this newly developed test method to be a practical, rapid, quantitative means to determine MICs for nontuberculous mycobacteria in clinical laboratories. Am J Vet Res, 2002 May, 63(5), 660 - 8 Antimicrobial-induced endotoxin and cytokine activity in an in vitro model of septicemia in foals; Bentley AP et al.; OBJECTIVE: To determine which antimicrobials that are used to treat neonatal foals with septicemia attributable to Escherichia coli will minimize endotoxin release from bacteria and subsequent activity of inflammatory mediators while maintaining bactericidal efficacy . SAMPLE POPULATION: Blood samples from 10 healthy foals . PROCEDURE: Escherichia coli isolates A and B were isolated from 2 septicemic foals, and minimal inhibitory concentrations (MIC) were determined for 9 antimicrobials . Five of these antimicrobials were tested in vitro at 2 and 20 times their respective MIC . Whole blood or mononuclear cells grown in tissue-culture media were incubated with 105 colony-forming units of E . coli and each antimicrobial or saline (0.9% NaCl) solution . After 6 hours, number of viable bacteria remaining was determined, and supernatant was tested for endotoxin and tumor necrosis activity . RESULTS: Testing in whole blood was compromised by bactericidal effects of the blood itself . In mononuclear cell suspensions, each antimicrobial significantly reduced the number of viable bacteria to low or undetectable amounts . Antimicrobials did not differ significantly in efficacy of bacterial killing . Amikacin used alone or in combination with ampicillin resulted in significantly less endotoxin activity than did ampicillin, imipenem, or ceftiofur alone . There was a correlation between TNF-alpha and endotoxin activity . CONCLUSIONS AND CLINICAL RELEVANCE: Aminoglycosides appear less likely to induce endotoxemia and TNF-alpha synthesis during bactericidal treatment of E . coli septicemia, compared with beta-lactam antimicrobials . Use of ampicillin, imipenem, or ceftiofur in the treatment of septicemic neonatal foals should be accompanied by appropriate treatment for endotoxemia. Periodontol 2000, 2002, 28, 56 - 71 Antimicrobial effects of mechanical debridement; Petersilka GJ et al.; Self-performed plaque removal using manual or powered toothbrushes and interdental cleaning devices is improved in subjects that have received oral hygiene instructions . Personal oral hygiene coupled with regular professional supragingival debridement may further improve the level of plaque control but still fails to achieve a completely plaque-free dentition . Both patient-performed and professional supragingival plaque removal has an effect on subgingival microbiota that is limited to the marginal 3 mm of the periodontal pocket . At sites with 4 mm or more of probing depth, only subgingival scaling leads to a significant reduction of the bacterial load . The subgingival microflora can be further reduced by pocket elimination surgery . Due to the sequence of bacterial recolonization that occurs following mechanical debridement, the level of periodontal pathogens such as B . forsythus, P . gingivalis and T . denticola may be reduced for several months . Mechanical debridement also influences the patient's immune system response, resulting in antibody titers and avidity against periodontal pathogens . As a basis for the restoration and maintenance of periodontal health, repeated subgingival debridement, as performed in supportive periodontal therapy, can reduce the number and proportions of periodontopathogenic bacteria in subgingival plaque . However, intensive subgingival scaling and root planing should be avoided in sites that probe less than 3 mm, as this is likely to traumatize the periodontium and cause attachment loss. Periodontol 2000, 2002, 28, 298 - 312 Effective, safe, practical and affordable periodontal antimicrobial therapy: where are we going, and are we there yet? Slots J, Jorgensen MG. Several important trends are noticeable in the management of periodontal disease . Searching for specific risk factors for periodontal disease permits therapy planning with the intention of doing less for low-risk patients and increasing the preventive and therapeutic modalities for high-risk patients . Also, significant progress in the area of chemotherapeutic development enables dentists to increase the number of periodontitis patients receiving nondisruptive antimicrobial therapy and decreases the need for surgical treatment . Use of anti-infective chemotherapeutic and antibiotic agents has become a specialized and increasingly effective means of preventing and treating destructive periodontal disease . Local care, including subgingival application of some type of antiseptics, is widely accepted . The use of systemic antibiotics is not routine and should be reserved for aggressive and refractory periodontal infections . In general, it is better to be thoroughly familiar with a limited number of drugs and treatment methods and use them properly than to try to master a plethora of antimicrobial therapies . Combating periodontal infections is best accomplished by combined mechanical and chemotherapeutic efforts of the dental professional and the patient . The trend during recent years has been to treat periodontal infections aggressively, employing short-course antimicrobial therapy using a battery of safe and affordable antimicrobial agents, each exhibiting high activity against various periodontal pathogens and administered in ways to concurrently affect pathogens residing in different oral ecological niches, followed by regular maintenance visits having a strong anti-infective emphasis . At the beginning of therapy, patients should be assigned self-help tasks having maximal antimicrobial effectiveness, with a focus on control of the subgingival periodontopathic microbiota . When patients see positive clinical results from their daily oral hygiene efforts, they are motivated to remain active participants in managing their periodontal condition . This article emphasizes anti-infective periodontal therapies that are effective and, when properly administered, are essentially nontoxic; are widely available around the world to dentists as well as to patients; and are acceptable to most patients in terms of methods of application, supporting oral hygiene efforts and financial costs . We believe that, with improved knowledge of the periodontopathic microbiota, with the availability of microbiological tests to identify periodontal pathogens and optimal therapy, with various safe and affordable yet effective antimicrobial agents and therapies and, eventually, with the development of one or more effective vaccines, the future looks very bright for patients at risk for or suffering from destructive periodontal disease. Braz J Med Biol Res, 2002 May, 35(5), 613 - 6 Low-dose doxycycline prevents inflammatory bone resorption in rats; Bezerra MM et al.; Matrix metalloproteinases (MMP) are considered to be key initiators of collagen degradation, thus contributing to bone resorption in inflammatory diseases . We determined whether subantimicrobial doses of doxycycline (DX) (< or =10 mg kg-1 day-1), a known MMP inhibitor, could inhibit bone resorption in an experimental periodontitis model . Thirty male Wistar rats (180-200 g) were subjected to placement of a nylon thread ligature around the maxillary molars and sacrificed after 7 days . Alveolar bone loss (ABL) was measured macroscopically in one hemiarcade and the contralateral hemiarcade was processed for histopathologic analysis . Groups of six animals each were treated with DX (2.5, 5 or 10 mg kg-1 day-1, sc, 7 days) and compared to nontreated (NT) rats . NT rats displayed significant ABL, severe mononuclear cell influx and increase in osteoclast numbers, which were significantly reduced by 5 or 10 mg kg-1 day-1 DX . These data show that DX inhibits inflammatory bone resorption in a manner that is independent of its antimicrobial properties. Chemotherapy, 2002 May, 48(2), 64 - 70 Comparison of the BBL-mycobacteria growth indicator tube method with culture in the diagnosis of tuberculosis and evaluation of the resistance patterns of isolated strains to four major drugs; Kocazeybek BS; The BBL-mycobacteria growth indicator tube system (MGIT) is used for a rapid detection of the presence of mycobacteria . Our study aimed to compare MGIT with the Lowenstein-Jensen (LJ) reference method in clinical samples with suspected pulmonary and extrapulmonary tuberculosis, and to evaluate the primary and secondary resistance patterns by determining the resistances of the isolated strains to four major antimycobacterial drugs . 648 clinical samples from different clinics, with suspected pulmonary or extrapulmonary tuberculosis based on clinical, radiological, histopathological and immunological findings, were included in the investigation . The samples were first stained with Ziehl-Neelsen (ZN) and then cultured in LJ medium according to the standard bacteriological procedure and in the MGIT as recommended by the manufacturer . Conventional biochemical tests and p-nitro-alpha-acethylamino-beta-hydroxypropiophene of the Bactec system were used to identify the isolated mycobacterial strains . The susceptibilities to streptomycin, isoniazid, rifampicin, ethambutol were tested by the BBL-MGIT antibiotic susceptibility test and the resistances of the strains found to be resistant to any of the drugs were confirmed by the agar proportion method . Mycobacterium spp . were isolated in 61 (9.4%) out of 648 samples . Eventually, 58 out of 61 strains were classified as Mycobacterium tuberculosis and the other 3 as Mycobacterium tuberculosis complex . 32 of these were ZN positive . The growth time was determined as 12.2 days by the MGIT method and 24.1 days by the LJ method (p < 0.001) . 29 strains were ZN negative . Their growth time was 23 days by the MGIT method and 37 days by the LJ method (p < 0.001) . Drug resistance was detected in 23 (37.7%) of 61 cases (of whom 39 were new and 22 were former patients); of these resistances, 8 (20.51%) were primary and 15 (68.18%) were secondary . In double drug resistance, secondary resistance was found only to isoniazid + rifampin (4 cases) whereas both primary and secondary resistances were found to one drug . The highest cumulative drug resistance - both primary and secondary - was found to isoniazid . In conclusion, the MGIT was found to be advantageous because it enables rapid bacterial identification of tuberculosis and detection of antimicrobial resistance due to its high sensitivity and specificity . It is quicker than the LJ method . Its antibiotic susceptibility can be tested and it is easy to perform . We recommend to include it in routine laboratory work . In addition, our study suggests that the high ratio of secondary resistance in the public might be related to inappropriate and insufficient treatment of tuberculosis, and noncompliance, which appear to cause an important increase in primary tuberculosis as a result of new contaminations . Dermatology, 2002, 204 Suppl 1, 70 - 4 The beneficial toxicity paradox of antimicrobials in leg ulcer healing impaired by a polymicrobial flora: a proof-of-concept study; Fumal I et al.; BACKGROUND: Some of the views contrasting the beneficial and toxic effects of antimicrobials upon wound healing remain controversial . OBJECTIVE: To assess the clinical relevance of histological findings following antimicrobial applications on chronic leg ulcers . METHOD: The present study was performed in three parallel groups of 17 patients suffering from at least 2 similar chronic leg ulcers . Clinical planimetric assessments were performed before and after 3 and 6 weeks of treatment using hydrocolloid dressings . In addition, 1 ulcer in each patient received applications of povidone-iodine (PVP-I), silver sulfadiazine or chlorhexidine digluconate . Histological examinations were made at inclusion and after the 6-week therapy . Time to healing was also recorded . RESULTS: At entry in the study, fibroblasts, macrophages, neutrophils and vessels were abundant in the ulcers . In addition, focal necrotizing vasculitis was related to the microbiological load . Compared to the control lesions, both the healing rate and time to healing of the leg ulcers showed a modest improvement at the sites receiving silver sulfadiazine (2-7%) or chlorhexidine digluconate (-1 to 5%) . By contrast, PVP-I increased significantly the healing rate (4-18%, p < 0.01), and time to healing was reduced by 2-9 weeks (p < 0.01) . The 3 antimicrobials decreased the bacterial density, and the vascular margination and migration of inflammatory cells, thus abating the vasculitic changes . PVP-I applications did not alter the microvessels and did not significantly reduce the density in dendrocytes and fibroblasts . By contrast, both silver sulfadiazine and chorhexidine digluconate appeared to alter the superficial microsvasculature including the dendrocyte population . CONCLUSION: Although topical antimicrobials may apparently achieve almost similar activity on the bacterial load inside chronic leg ulcers, the toxicity upon host cells was different among these agents . PVP-I appeared to be an efficient compound in these respects exhibiting a positive and relevant clinical effect . J Clin Periodontol, 2002 May, 29 Suppl 2, 22 - 9 The clinical significance of local chemotherapies; Killoy WJ; This paper discusses differences between statistical and clinical significance . It suggests nine factors to consider when assessing clinical significance of periodontal therapy . The article reviews the multicentre randomized clinical trials on the four antimicrobial local delivery systems commercially available in the USA (tetracycline fibre, chlorhexidine chip, doxycycline gel and minocycline microspheres) and assesses their data in relation to the nine factors for clinical significance . Data from longitudinal studies comparing periodontal surgery to non-surgery were evaluated in a similar fashion to provide a frame of reference . It was concluded that the local delivery of an antimicrobial offers the clinician a statistically and clinically significant option in the treatment of chronic periodontitis . It is not an 'either/or' situation in selecting therapeutic methods . It is a choice of which treatment method works best for that patient by that clinician. J Pept Res, 2002 Jun, 59(6), 241 - 8 Chemical synthesis of beta-defensins and LEAP-1/hepcidin; Kluver E et al.; A large and steadily growing subfamily of antimicrobially active peptides of animals and plants is formed by the defensins, which are highly disulfide-bonded, cationic peptides with a molecular mass of about 4 kDa . The synthesis of the human beta-defensins 1 and 2 (hBD-1, hBD-2) as well as of the novel murine beta-defensins 7 and 8 (mBD-7 and mBD-8) is reported . The peptides were synthesized by solid-phase peptide synthesis using fluorenylmethoxycarbonyl chemistry . The linear products were oxidized in the presence of the cysteine/cystine redox system to the biologically active molecules . The correct disulfide connectivity of the resulting cyclic products was partly verified by mass spectrometry and sequence analysis of the fragments obtained after tryptic cleavage . In addition, the recently discovered antimicrobially active human peptide LEAP-1/hepcidin, which contains four disulfide bonds, was successfully synthesized and subsequently oxidized . For Liver-expressed anti microbial peptide (LEAP)-1/hepcidin and hBD-1, the identity of native and synthetic peptides was demonstrated by high-pressure liquid chromatography and capillary electrophoretic analysis . The general synthetic procedure is suitable to rapidly perform the total chemical synthesis of novel fully bioactive defensins, which are expected to be identified soon, as well as of structurally modified analogs. Clin Microbiol Infect, 2002 Mar, 8(3), 183 - 6 Vero cytotoxin-producing Escherichia coli in a study of infectious intestinal disease in England; Evans J et al.; An investigation of infectious intestinal disease in England included examination of feces for Vero cytotoxin-producing Escherichia coli (VTEC) . Using DNA probe hybridization 27 VTEC strains were identified, 12 were from cases, and of these three belonged to serogroup O157 . The remaining 15 strains were isolated from controls . The strains were confirmed biochemically as E . coli, they were serotyped and characterized according to their toxin production, the presence of sequences encoding intimin (eae) and enterohemolysin was determined and resistance to antimicrobial agents was determined . Six of the nine cases with non-O157 VTEC were less than 16 years old, only two of the 15 controls were under 16 . Infection with more than one micro-organism was also considered. J Hosp Infect, 2002 May, 51(1), 1 - 6 The organization of hospital infection control in Turkey; Leblebicioglu H et al.; This article describes the current organization of infection control in Turkey in regard to regulations, functions and responsibilities of infection control committees and the national NosoLINE project . Also, incidence and prevalence of hospital infections and antimicrobial resistance in Turkey are reported . Anal Biochem, 2002 May 15, 304(2), 174 - 9 Homogenous assays for Escherichia coli DnaB-stimulated DnaG primase and DnaB helicase and their use in screening for chemical inhibitors; Zhang Y et al.; Escherichia coli DnaG primase is a single-stranded DNA-dependent RNA polymerase . Primase catalyzes the synthesis of a short RNA primer to initiate DNA replication at the origin and to initiate Okazaki fragment synthesis for synthesis of the lagging strand . Primase activity is greatly stimulated through its interaction with DnaB helicase . Here we report a 96-well homogeneous scintillation proximity assay (SPA) for the study of DnaB-stimulated E . coli primase activity and the identification of E . coli primase inhibitors . The assay uses an adaptation of the general priming reaction by employing DnaG primase, DnaB helicase, and ribonucleotidetriphosphates (incorporation of {(3)H}CTP) for in vitro primer synthesis on single-stranded oligonucleotide and M13mp18 DNA templates . The primase product is captured by polyvinyl toluene-polyethyleneimine-coated SPA beads and quantified by counting by beta-scintography . In the absence of helicase as a cofactor, primer synthesis is reduced by 85% . The primase assay was used for screening libraries of compounds previously identified as possessing antimicrobial activities . Primase inhibitory compounds were then classified as direct primase inhibitors or mixed primase/helicase inhibitors by further evaluation in a specific assay for DnaB helicase activity . By this approach, specific primase inhibitors could be identified . (c) 2002 Elsevier Science (USA) Phytochemistry, 2002 May, 60(2), 109 - 16 Gene expression of 5-epi-aristolochene synthase and formation of capsidiol in roots of Nicotiana attenuata and N . sylvestris; Bohlmann J et al.; Three new copies of a sesquiterpenoid synthase gene encoding 5-epi-aristolochene synthase (EAS) were cloned as cDNAs from Nicotiana attenuata and functionally characterized after expression of the recombinant enzymes in E . coli . Differential patterns of EAS gene expression and formation of the antimicrobial sesquiterpenoid capsidiol were found in roots and shoots of two species of Nicotiana . EAS is expressed constitutively in roots of N . attenuata and N . sylvestris corresponding with constitutive capsidiol formation in roots . Constitutive expression of EAS and capsidiol accumulation were not detectable in shoots of rosette plants of N . attenuata, but accumulation of terpene synthase transcripts could be induced in shoots by feeding of the tobacco hornworm, Manduca sexta . Constitutive expression of EAS has not been previously reported from N . tabacum, where capsidiol is known as an elicitor- and pathogen-inducible phytoalexin . It is conceivable that capsidiol contributes not only to an inducible defense against pathogens, but also to a constitutive defense in an organ-specific manner in some species of Nicotiana. J Inorg Biochem, 2002 May 21, 90(1-2), 22 - 37 Synthesis and characterization of cobalt and nickel chelates of 5-dimethylaminomethyl-2-thiouracil and their evaluation as antimicrobial and anticancer agents; Kamalakannan P et al.; A new antimetabolite of adenine, viz . 5-dimethylaminomethyl-2-thiouracil, was synthesized using the Mannich reaction . Owing to the biological importance of metalloelements in many biological processes, especially metabolic processes, cobalt(II) and nickel(II) complexes were also synthesized and examined for their antimicrobial and anticancer activities . These new compounds were characterized structurally by various techniques ranging from micro-elemental analyses to spectral analyses . Cobalt(II) complexes were found to be four coordinate, among which the bromo, iodo, and nitrato complexes were polymeric . The nickel(II) isothiocyanato complex exhibited four-coordinate geometry and the remaining nickel(II) complexes were six coordinate . Thermodynamic and kinetic parameters evaluated based on TG/DSC suggested that the initial stage of thermal decomposition follows a diffusion-controlled mechanism and the final stage a chemically controlled mechanism . Antibacterial, antifungal, and antitumor studies undertaken for the above compounds indicated structure-activity relationships . These metalloderivatives were more active than the parent compound . The order of activity was influenced by the chelate geometry and thermal stability . Activity increased with a decrease in coordination number and increase in thermal lability. J Pharm Biomed Anal, 2002 May 15, 28(3-4), 645 - 51 Single-step extraction of fluconazole from plasma by ultra-filtration for the measurement of its free concentration by high performance liquid chromatography; Majcherczyk PA et al.; High performance liquid chromatography (HPLC) is the reference method for measuring concentrations of antimicrobials in blood . This technique requires careful sample preparation . Protocols using organic solvents and/or solid extraction phases are time consuming and entail several manipulations, which can lead to partial loss of the determined compound and increased analytical variability . Moreover, to obtain sufficient material for analysis, at least 1 ml of plasma is required . This constraint makes it difficult to determine drug levels when blood sample volumes are limited . However, drugs with low plasma-protein binding can be reliably extracted from plasma by ultra-filtration with a minimal loss due to the protein-bound fraction . This study validated a single-step ultra-filtration method for extracting fluconazole (FLC), a first-line antifungal agent with a weak plasma-protein binding, from plasma to determine its concentration by HPLC . Spiked FLC standards and unknowns were prepared in human and rat plasma . Samples (240 microl) were transferred into disposable microtube filtration units containing cellulose or polysulfone filters with a 5 kDa cut-off . After centrifugation for 60 min at 15000g, FLC concentrations were measured by direct injection of the filtrate into the HPLC . Using cellulose filters, low molecular weight proteins were eluted early in the chromatogram and well separated from FLC that eluted at 8.40 min as a sharp single peak . In contrast, with polysulfone filters several additional peaks interfering with the FLC peak were observed . Moreover, the FLC recovery using cellulose filters compared to polysulfone filters was higher and had a better reproducibility . Cellulose filters were therefore used for the subsequent validation procedure . The quantification limit was 0.195 mgl(-1) . Standard curves with a quadratic regression coefficient > or = 0.9999 were obtained in the concentration range of 0.195-100 mgl(-1) . The inter and intra-run accuracies and precisions over the clinically relevant concentration range, 1.875-60 mgl(-1), fell well within the +/-15% variation recommended by the current guidelines for the validation of analytical methods . Furthermore, no analytical interference was observed with commonly used antibiotics, antifungals, antivirals and immunosuppressive agents . Ultra-filtration of plasma with cellulose filters permits the extraction of FLC from small volumes (240 microl) . The determination of FLC concentrations by HPLC after this single-step procedure is selective, precise and accurate. Arch Pharm (Weinheim), 2002 May, 335(2), 94 - 98 Synthesis and Antimicrobial Activity of Hydroxyalkyl- and Hydroxyacyl-phenols and Their Benzyl Ethers; Krauss J et al.; New phenolic compounds with hydrophilic side chains were prepared from 4-benzyloxybenzaldehyde and alkenyl magnesium bromides, followed by Sharpless dihydroxylation and hydrogenolytic removal of the benzyl group . The resulting compounds were tested in an agar diffusion assay against gram positive bacteria, gram negative bacteria, and against the fungi Candida glabrata and Aspergillus niger. Crit Care Med, 2002 May, 30(5), 969 - 73 Association between a genomic polymorphism within the CD14 locus and septic shock susceptibility and mortality rate; Gibot S et al.; OBJECTIVE: Genetic differences in immune responses may affect susceptibility to and outcome of septic shock . CD14 seems to be an important part of the innate immune system, initiating antimicrobial response . We evaluated the frequency of a recently discovered CD14 promoter gene polymorphism (C to T transition at base pair -159) among patients with septic shock compared with those in a control group . DESIGN: Multiple-center study . SETTING: Hospital research department . PATIENTS: Ninety consecutive white patients with septic shock were included . The control group consisted of 122 age- and gender-matched white subjects . INTERVENTIONS: In both groups, the C-159T CD14 promoter genetic polymorphism was determined by using polymerase chain reaction and subsequent Hae III restriction enzyme digestion of the polymerase chain reaction products . MEASUREMENTS AND MAIN RESULTS: The C-159T polymorphism and the TT genotype were significantly overrepresented among septic shock patients compared with controls . Within the septic shock group, the mortality of patients with TT genotype (71%) was significantly higher than in patients with other genotypes (48%; Pearson chi-square, p =.008) . In a multiple logistic regression model, the TT genotype was independently associated with an increased relative risk of death (odds ratio, 5.30; 95% confidence interval, 1.20-22.50, p =.02) . CONCLUSIONS: The C-159T polymorphism affects susceptibility to septic shock and seems to be a new genetic risk factor for death. J Biomol Screen, 2002 Apr, 7(2), 119 - 25 An Escherichia coli biosensor strain for amplified and high throughput detection of antimicrobial agents; Anko ML et al.; We report here the construction of a bacterial reporter system for high-throughput screening of antimicrobial agents . The test organism is the Escherichia coli K-12 strain carrying luciferase genes luxC, luxD, luxA, luxB, and luxE from the bioluminescent bacterium Photorhabdus luminescens in a runaway replication plasmid . The replication of the plasmid can be induced, resulting in a change of the plasmid copy number from 1-2/cell to several hundreds per cell within tens of minutes . This increase in plasmid copies is independent of the replication of the host cells . The system will therefore amplify the effects of antibiotics inhibiting bacterial replication machinery, such as fluoroquinolones, and the inhibitory effects can be measured in real time by luminometry . The biosensor was compared with a strain engineered to emit light constitutively, and it was shown to be much more sensitive to various antibiotics than conventional overnight cultivation methods . The approach shows great potential for high-throughput screening of new compounds. J Pept Res, 2001 Dec, 58(6), 445 - 56 Clavaspirin, an antibacterial and haemolytic peptide from Styela clava; Lee IH et al.; We cloned the precursor of a novel peptide from a cDNA library prepared from pharyngeal tissues of the tunicate, Styela clava . Its sequence predicted a histidine-rich, amidated 23-residue peptide (FLRF(IG)SVIHGIGHLVHHIGVAL-NH2) that we named clavaspirin . A synthetic clavaspirin was prepared and it was found that it killed Gram-positive and Gram-negative bacteria, permeabilized the outer and inner membranes of Escherichia coli, lysed phosphatidylglycerol (POPG) liposomes, and was potently haemolytic towards human and bovine erythrocytes . Each of these activities was performed more effectively at an acidic pH . Circular dichroism measurements of synthetic clavaspirin revealed a largely alpha-helical structure and polarized and residue-specific FTIR spectrometry showed that its association with phospholipid membranes was influenced by pH . Peptides such as clavaspirin may equip tunicate haemocytes to mediate cytotoxicity and participate in antimicrobial defence. J Calif Dent Assoc, 2002 Apr, 30(4), 297 - 305 The ins and outs of periodontal antimicrobial therapy; Jorgensen MG et al.; A multifaceted antimicrobial approach is necessary for the successful management of destructive periodontal disease . Effective antimicrobial periodontal therapy aims to overwhelm periodontal pathogens with aggressive initial therapy and prevent previously suppressed pathogens from rising up anew through daily oral hygiene measures and frequent professional cleaning . Current antimicrobial periodontal therapy employs mechanical debridement performed with and without surgery, antibiotics, and antiseptics . Subgingival irrigation with povidone-iodine at the dentist's office and subgingival irrigation with dilute sodium hypochlorite for home-care constitute effective, safe, and affordable periodontal antimicrobial therapy . This article describes theoretical and practical guidelines for implementing rational and cost-effective antimicrobial principles in the management of periodontal disease. Life Sci, 2002 Mar 29, 70(19), 2225 - 32 Sulfite induces adherence of polymorphonuclear neutrophils to immobilized fibrinogen through activation of Mac-1 beta2-integrin (CD11b/CD18); Shigehara T et al.; Sulfite is a major air pollutant which can cause respiratory tract inflammation characterized by an influx of polymorphonuclear neutrophils (PMN) . We have previously shown that human PMN can produce sulfite either spontaneously or in response to stimulation with lipopolysaccharide . We now demonstrate that sulfite activates PMN to adhere to immobilized fibrinogen via the beta2-integrin Mac-1 (CD11b/CD18) . Mac-1 expression is not altered by treatment with this agent . Although unaffected by pertussis toxin, sulfite-triggered PMN adhesion was abrogated by pretreating cells with the membrane-impermeant sulfhydryl reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), a modifier of thiol groups on the cell surface . These results suggest that sulfite-induced PMN adhesion is dependent on a modification of thiols at the cell surface . Given its potent antioxidant and antimicrobial activities, sulfite may act as an endogenous mediator in host defense and/or inflammation. Biosci Biotechnol Biochem, 2002 Mar, 66(3), 532 - 6 Studies on the antimicrobial mechanisms of capsaicin using yeast DNA microarray; Kurita S et al.; Capsaicin is a pungent element in a variety of red peppers that are widely used as food additives and considered to be an antimicrobial factor . For our tests, we used yeast DNA micro-array methods to understand the mechanisms of inhibitory effects of capsaicin . The capsaicin treatment significantly induced 39 genes from approximately 6,000 genes . These induced genes were classified as multi-drug resistance transporter genes, membrane biosynthesis genes, genes encoding stress proteins, and uncharacterized genes . The growth abilities of the strains with the deletion of the induced genes suggest that capsaicin is pumped out of the yeast cells by the PDR5 transporter. Gen Dent, 2001 Jan-Feb, 49(1), 84 - 8 Site-specific chlorhexidine: a periodontal alternative; Fowler EB et al.; Three case reports demonstrate the clinical use of an adjunctive chlorhexidine chip capable of sustaining local antimicrobial activity for 7-10 days . The chip is easy to place, requires no additional chair time for removal, is self-adherent, and can be provided to periodontal maintenance patients on a recurring basis . This is another adjunct that can be part of the clinician's armamentarium when presented with a clinically challenging localized periodontal defect. J Antimicrob Chemother, 2002 May, 49(5), 857 - 61 Intracellular activity of ABT-773 and other antimicrobial agents against Legionella pneumophila; Jung R et al.; The intracellular activity of ABT-773 against Legionella pneumophila was compared with azithromycin and ciprofloxacin using HL-60 cells . Against L . pneumophila ATCC 33152 and three clinical isolates the MICs (mg/L) were ABT-773 0.015, ciprofloxacin 0.03 and azithromycin 0.03 . At 48 h, the mean percentage inhibition was as follows: 28.5 +/- 5.9% and 32.6 +/- 4.6% at 8 x and 16 x MIC of ABT-773; 38.1 +/- 8.6% and 48.2 +/- 7.0% at 8 x and 16 x MIC of ciprofloxacin; and 26.3 +/- 9.9% and 28.5 +/- 9.9% at 8 x and 16 x MIC of azithromycin . In this study, all three agents were highly active, with ABT-773 demonstrating similar activity to azithromycin against L . pneumophila. J Antimicrob Chemother, 2002 May, 49(5), 785 - 92 Rapid increase in macrolide resistance among penicillin non-susceptible pneumococci in Finland, 1996-2000; Pihlajamaki M et al.; The aims of this study were to evaluate the resistance patterns and serotypes/groups of penicillin non-susceptible pneumococci (PNSP) in Finland, and to determine phenotypes and resistance mechanisms of the erythromycin-resistant isolates . A total of 1190 PNSP were collected during 1996-2000 in Finland . The MICs of 18 antimicrobials were determined by the agar plate dilution method, and PCR was used to study the resistance mechanisms of the macrolide-resistant isolates . For serotyping, counterimmunoelectrophoresis and latex agglutination were used . Erythromycin resistance increased from 32% in 1996 to 62% in 2000 among PNSP in Finland . Multiresistance (co-resistance to erythromycin, tetracycline and co-trimoxazole) was present in 22% of the isolates in 1996 and in 40% in 2000 . The most common macrolide resistance phenotype was the MLS(B) phenotype (72%), 25% had the M phenotype and 3% the MS phenotype . The MLS(B) and M phenotypes increased in the same proportion during the study period . All the MLS(B) isolates had the erm(B) gene, the M isolates the mef(A) gene, and in 11 MS isolates, ribosomal mutations were the cause of resistance . The most common serotypes/groups were 14, 19 and 6 . We found a significant increase in multiresistance among PNSP within a short period of time in Finland . Although pneumococcal resistance to erythromycin was 11% in 2000, the same figure was 50% among the PNSP . The rise in erythromycin resistance is worrying, as macrolides are commonly used as first- and second-line drugs in pneumococcal infections. J Antimicrob Chemother, 2002 May, 49(5), 763 - 7 Effect of gemifloxacin on viability of Chlamydia pneumoniae (Chlamydophila pneumoniae