J Am Vet Med Assoc, 1999 Sep 15, 215(6), 815 - 7, 795-6 Antimicrobial susceptibility of Nocardia nova isolated from five cats with nocardiosis; Hirsh DC et al.; From 1992 through 1997, 5 cats were admitted to the hospital because of chronic, nonhealing lesions containing draining tracts . Exudate from 2 of the 5 cats contained macroscopically visible granules . On the basis of cytologic findings, lesions were described as pyogranulomatous . Degenerative neutrophils and activated macrophages, along with slender, branching, gram-positive, partially acid-fast microorganisms, were observed in stained smears of exudates obtained from all 5 affected cats . Nocardia nova was found in pure culture from all affected sites . Most isolates were susceptible to ampicillin, aminoglycosides (ie, amikacin, kanamycin), tetracyclines (ie, doxycycline, minocycline), macrolides (ie, erythromycin, clarithromycin), imipenem, sulfisoxazole, and trimethoprim-sulfamethoxazole . Other antimicrobials were less effective, and these included amoxicillin-clavulanic acid, the cephalosporins (ie, cefotaxime, ceftizoxime, ceftriaxone), and some aminoglycosides (ie, gentamicin, tobramycin) . Four of the 5 cats were successfully treated, 3 with a trimethoprim-sulfonamide combination, and 1 with clarithromycin . The outcome of treatment of the fifth cat is unknown . Findings in this report may be useful in diagnosis and treatment of nocardiosis caused by N nova in cats. Oral Microbiol Immunol, 1999 Jun, 14(3), 190 - 3 Immunomagnetic recovery of human neutrophil defensins from the human gingival crevice; McKay MS et al.; The human neutrophilic protein defensins are cationic, antimicrobial, cytotoxic, corticostatic chemotactic, opsonic peptides found in azurophilic granules and constitute about 5% of the total protein in human neutrophils . In the present study, defensins were recovered from the human gingival crevice using paramagnetic microspheres (beads), coated with anti-defensin antibodies . The bead-bound defensins were assayed using an enzyme-linked immunosorbent assay developed in this laboratory . Twenty sites were sampled; defensin was found in 100% of the sites and ranged in amount from 270-2000 ng/site . The large local concentrations of defensins, estimated in the mg/ml range, may have major effects on the microbiology of the gingival crevice. Dent Update, 1995 Apr, 22(3), 104 - 11 Topical antimicrobials: new horizons for management of periodontal disease in general practice? Urquhart E, Addy M. One of the most prevalent infectious diseases that dental practitioners have to treat is periodontal disease . Antimicrobial and antibiotic agents have been developed that can be applied topically with no deleterious side-effects and reaching greater concentrations at the disease site than such agents given systemically . Used in conjunction with the mechanical debridement of deep pockets of disease, these agents appear to enhance the effectiveness of treatment . This approach is likely to feature more and more in the routine management of periodontal disease. Avian Dis, 1999 Jul-Sep, 43(3), 521 - 5 The comparison of an aqueous preparation of tilmicosin with tylosin in the treatment of Mycoplasma gallisepticum infection of turkey poults; Jordan FT et al.; A virulent strain of Mycoplasma gallisepticum (MG) was used to infect groups of 40 2-day-old poults kept in separate pens of 10 each . Of the six groups, three were treated with separate concentrations of tilmicosin, one was treated with tylosin, one remained untreated, and a final group was not infected and not treated . Mortality, clinical signs, and gross lesions were significantly less (P < 0.001) in the uninfected and infected medicated groups than in the infected unmedicated group . Also, the mean body weight gain of poults surviving to the end of the experiment was greater (P < 0.005) in the uninfected and infected medicated groups . MG was not recovered from the uninfected birds, and, among the infected poults, it was recovered from significantly fewer (P < 0.05) poults in the medicated groups . Serologic results were negative for the uninfected group, and there were fewer positive reactors for the infected medicated than the infected unmedicated group . In consideration of these results, tilmicosin should prove to be a useful addition to the antimicrobials in the treatment of MG infection in poults. Eur J Pharm Sci, 1999 Oct, 9(1), 25 - 31 Synthesis, antibacterial, antifungal and anti-HIV activities of Schiff and Mannich bases derived from isatin derivatives and N-{4-(4'-chlorophenyl)thiazol-2-yl} thiosemicarbazide; Pandeya SN et al.; Isatin, its 5-chloro and 5-bromo derivatives have been reacted with N-{4-(4'-chlorophenyl)thiazol-2-yl} thiosemicarbazide to form Schiff bases and the N-Mannich bases of these compounds were synthesized by reacting them with formaldehyde and three secondary amines . Their chemical structures have been confirmed by means of IR, 1H-NMR data and by elemental analysis . Investigation of antimicrobial activity of compounds was done by agar dilution method against 28 pathogenic bacteria, 8 pathogenic fungi and anti-HIV activity against replication of HIV-1 (IIIB) in MT-4 cells . Among the compounds tested 1-{N,N-dimethylaminomethyl}-5-bromo isatin-3- inverted question mark1'-{4"-(p-chlorophenyl) thiazol-2"-yl} thio semicarbazone inverted question mark 10 showed the most favourable antimicrobial activity. Biochemistry, 1999 Sep 21, 38(38), 12313 - 9 CD spectra of indolicidin antimicrobial peptides suggest turns, not polyproline helix; Ladokhin AS et al.; Indolicidin is a 13-residue antimicrobial peptide-amide isolated from the cytoplasmic granules of bovine neutrophils that contains five Trp and three Pro residues . Falla et al . {(1996) J . Biol . Chem . 271, 19298} suggested that indolicidin forms a poly-L-proline II helix based upon the circular dichroism (CD) spectra of a closely related peptide (indolicidin methyl ester) . In contrast, we found no evidence of poly-L-proline II helix formation in the CD spectra of native indolicidin in various solvents or when bound to micelles and membranes {Ladokhin et al . (1997) Biophys . J . 72, 794} . We interpreted the spectra as arising from unordered and/or beta-turn structures, but noted a sharp negative band at 227 nm arising from the tryptophan residues that would mask spectral features characteristic of poly-L-proline II helix . We have reexamined this issue by means of CD measurements of native indolicidin and several of its analogues . None of the features characteristic of a poly-L-proline helix (or alpha- or 3(10)-helix) were observed for any of the peptides studied . To eliminate artifacts associated with tryptophan, we synthesized indolicidin-L and indolicidin-F in which all five tryptophans were replaced with leucines or phenylalanines, respectively . The changes in CD spectra of these Trp-free peptides upon transfer into membrane-like environments were found to be consistent with the formation of beta-turns . For the native indolicidin in SDS micelles, temperature increases resulted in a coupled diminution of two sharp bands, a negative one at 227 nm and a positive one at 217 nm . This phenomenon, which is absent in indolicidin-L variants with single Leu-->Trp substitutions, is consistent with exciton splitting produced by the stacking of indole rings . Type VI turns in model peptides in aqueous solution are known to be promoted by stacking interactions between cis-proline and neighboring aromatic residues {Yao et al . (1994) J . Mol . Biol . 243, 754} . Molecular modeling of indolicidin with a -Trp(6)-cis-Pro(7)-Trp(8)- type VIa turn demonstrated the feasibility of this turn conformation and revealed the possibility of an accompanying amphipathic structure . We therefore suggest that turn conformations are the principal structural motif of indolicidin and that these turns greatly enhance membrane activity. Int J Antimicrob Agents, 1999 Aug, 12(4), 355 - 8 Activity of nine fluoroquinolones against strains of Bordetella bronchiseptica; Carbone M et al.; Thirty-two strains of Bordetella bronchiseptica were tested for their antimicrobial susceptibilities to nine fluoroquinolones . The most active agents were fleroxacin, temafloxacin, ciprofloxacin (MIC90 1 microg/ml), ofloxacin, lomefloxacin and enoxacin (MIC90 2 microg/ml) . Pefloxacin and norfloxacin were active only against 59.3 and 83.1%, respectively, of the strains tested, whereas rufloxacin lacked activity against all the strains of B . bronchiseptica tested. Int J Antimicrob Agents, 1999 Aug, 12(4), 341 - 7 Metronidazole and clarithromycin resistance amongst Helicobacter pylori isolates from a large metropolitan hospital in the United States; Osato MS et al.; BACKGROUND: Metronidazole and clarithromycin-based therapies are among the most efficacious treatment regimens for H . pylori infection . Resistance to metronidazole or clarithromycin is associated with impaired therapy with these agents . We conducted a retrospective review of susceptibility data to determine the frequency of primary metronidazole and clarithromycin resistance among H . pylori isolates from a single metropolitan hospital in the United States . The database comprised 933 patients who presented at the Digestive Diseases Clinic at the Veterans Affairs Medical Center in Houston between September 1988 and January 1997 with complaints of dyspepsia, abdominal pain and peptic ulcer disease . One hundred and seventy-nine of these patients had both pharmaceutical records available for evaluation and culture and antimicrobial susceptibility data for analysis . The MICs were determined by both E-test and broth microdilution tests . The frequency of primary metronidazole resistance was 37.4% (67/179) . The level of primary clarithromycin resistance was 6.1% . Dual metronidazole and clarithromycin resistance was present in approx . 3% . The high level of primary metronidazole and clarithromycin resistance in H . pylori isolates from this metropolitan hospital is such that antimicrobial susceptibility data should be available so that informed choice can be made for specific eradication therapies, especially in patients who fail treatment. Int J Antimicrob Agents, 1999 Aug, 12(4), 319 - 23 In vitro activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with brodimoprim and dapsone, against Mycobacterium leprae; Dhople AM; The antimicrobial effects of a new dihydrofolate reductase inhibitor, epiroprim, alone and in combination with dapsone and brodimoprim against Mycobacterium leprae were evaluated in vitro in cell-free culture system . Two biochemical parameters were used to measure metabolic activity (and growth) of the organism . The minimal inhibitory activity of epiroprim against M . leprae was 10 mg/l and the action was bactericidal . When combined with dapsone, epiroprim exhibited a strong synergism; on the other hand, combination of epiroprim and brodimoprim provided only additive effects . The results suggest that epiroprim can be a component in multidrug therapy regimen in leprosy. Int J Antimicrob Agents, 1999 Aug, 12(4), 279 - 85 Association between the consumption of antimicrobial agents in animal husbandry and the occurrence of resistant bacteria among food animals; Aarestrup FM; Antimicrobial agents are used in food animals for therapy and prophylaxis of bacterial infections and in feed to promote growth . The use of antimicrobial agents for food animals may cause problems in the therapy of infections by selecting for resistance among bacteria pathogenic for animals or humans . The emergence of resistant bacteria and resistance genes following the use of antimicrobial agents is relatively well documented and it seems evident that all antimicrobial agents will select for resistance . However, current knowledge regarding the occurrence of antimicrobial resistance in food animals, the quantitative impact of the use of different antimicrobial agents on selection for resistance and the most appropriate treatment regimens to limit the development of resistance is incomplete . Surveillance programmes monitoring the occurrence and development of resistance and consumption of antimicrobial agents are urgently needed, as is research into the most appropriate ways to use antimicrobial agents in veterinary medicine to limit the emergence and spread of antimicrobial resistance. Changgeng Yi Xue Za Zhi, 1999 Jun, 22(2), 227 - 33 Spontaneous bacterial peritonitis in adult patients with primary nephrotic syndrome; Chen MC et al.; BACKGROUND: Susceptibility to bacterial infection is a common problem in nephrotic patients . Spontaneous bacterial peritonitis, although characteristic of nephrotic children, is extremely rare in adults . METHODS: A retrospective review was performed on all adult patients with the discharge diagnoses of primary nephrotic syndrome and spontaneous bacterial peritonitis treated between 1986 and 1998 at Chang Gung Memorial Hospital in Kaohsiung, Taiwan . Ten patients were included in this study, 9 of them men and one woman . The average age was 30.5 years . RESULTS: All the patients had signs of active nephrosis and presented with diffuse abdominal pain, ascites, fever and/or chills . Thirty percent (3/10) of the causative pathogens were gram-positive bacteria and 60% (6/10) were gram-negative bacteria . One patient had sterile cultures . Seven patients recovered after antibiotic treatment for 1 to 2 weeks . Three patients died of septic shock . CONCLUSION: Therefore, to improve patient outcome, it is essential to establish a diagnosis early and to initiate broad-spectrum antimicrobial therapy even before culture results are available. J Food Prot, 1999 Sep, 62(9), 1017 - 23 Antimicrobial activity of the essential oils of Thymus vulgaris L . measured using a bioimpedometric method; Marino M et al.; The essential oils obtained from Thymus vulgaris L . harvested at four ontogenetic stages were evaluated for their biological activity and chemical composition . The thyme essential oils were tested for their inhibitory effects against nine strains of gram-negative bacteria and six strains of gram-positive bacteria . The bioimpedance method was chosen for studying the antibacterial activity of the essential oils and the parameter chosen for defining and quantifying the antibacterial activity of the essential oils was the detection time . The plate counting technique was used to study the inhibitory effect by direct contact . All the thyme essential oils examined had a significant bacteriostatic activity against the microorganisms tested . This activity was more marked against the gram-positive bacteria . The oil from thyme in full flower was the most effective at stopping the growth of the microbial species examined . The oils tested were also shown to have good antibacterial activity by direct contact, which appeared to be more marked against the gram-negative bacteria . Only a few of the species were capable of recovering at least 50% of their metabolic function after contact with the inhibitor, while most of the strains were shown to have been inactivated almost completely . Escherichia coli O157:H7 was the most sensitive species, given that after contact with even the lowest concentration of oil cells could not be recovered. Biochimie, 1999 Jul, 81(7), 771 - 9 The catalytic activities of DNA topoisomerase II are most closely associated with the DNA cleavage/religation steps; Scala D et al.; DNA topoisomerase II regulates the three-dimensional organisation of DNA and is the principal target of many important anticancer and antimicrobial agents . These drugs usually act on the DNA cleavage/religation steps of the catalytic cycle resulting in accumulation of covalent DNA-topoisomerase II complexes . We have studied the different steps of the catalytic cycle as a function of salt concentration, which is a classical way to evaluate the biochemical properties of proteins . The results show that the catalytic activity of topoisomerase II follows a bell-shaped curve with optimum between 100 and 225 mM KCl . No straight-forward correlation exists between DNA binding and catalytic activity . The highest levels of drug-induced covalent DNA-topoisomerase II complexes are observed between 100 and 150 mM KCl . Remarkably, at salt concentrations between 150 mM and 225 mM KCl, topoisomerase II is converted into a drug-resistant form with greatly reduced levels of drug-induced DNA-topoisomerase II complexes . This is due to efficient religation rather than to absence of DNA cleavage as witnessed by relaxation of the supercoiled DNA substrate . In the absence of DNA, ATP hydrolysis is strongest at low salt concentrations . Unexpectedly, the addition of DNA stimulates ATP hydrolysis at 100 and 150 mM KCl, but has little or no effect below 100 mM KCl in spite of strong non-covalent DNA binding at these salt concentrations . Therefore, DNA-stimulated ATP hydrolysis appears to be associated with covalent rather than non-covalent binding of DNA to topoisomerase II . Taken together, the results suggest that it is the DNA cleavage/religation steps that are most closely associated with the catalytic activities of topoisomerase II providing a unifying theme for the biological and pharmacological modulation of this enzyme. Gac Med Mex, 1999 Jul-Aug, 135(4), 383 - 9 {Surveillance and the costs related to the prescription of antimicrobials in a pediatric hospital}; Navarrete-Navarro S et al.; INTRODUCTION: Important considerations in the selection of an antimicrobial agent include the indications for its prescription, its efficacy, toxicity and cost . However, is has been observed that up to 50% of these prescriptions are inappropriate . OBJECTIVE: To evaluate the utilization patterns and costs of restricted antimicrobial agents requiring authorization of the infectious diseases service for their prescription, in a tertiary care pediatric hospital through the use of a computer software antimicrobial use surveillance program designed by the investigators . MATERIAL AND METHODS: A one-year longitudinal descriptive and prolective survey was conducted in all patients requiring antimicrobial therapy during their hospitalization . Information on the prescription and costs of antimicrobial agents was recorded from both the medical chart and pharmacy registers . RESULTS: A total of 748 patients were prescribed at least one restricted antimicrobial agent, corresponding to 9.6% of the total number of patients hospitalized and 63.4% of the antibiotic expenditures during the study . CONCLUSIONS: Hospital surveillance of antimicrobial prescription is useful for detecting antimicrobial prescription patterns and costs . These types of studies are inexpensive and of easy access when a computerized register is available in the pharmacy. Commun Dis Public Health, 1999 Sep, 2(3), 210 - 4 Detection of antibacterial agents in warm water prawns; Willis C et al.; Samples of cooked and raw prawns intended for human consumption were collected by officers at Southampton Port Health Authority, and tested for the presence of antimicrobial agents . Antimicrobial activity was detected in 23 out of 98 cooked prawn samples but in none of the 20 raw samples collected . Samples that showed antimicrobial activity were analysed using high performance liquid chromatography and immunoassay, resulting in the presumptive identification of trimethoprim in 15 samples, and low levels of gentamicin in three samples . Prawns in which trimethoprim was putatively detected contained bacteria with significantly greater resistance to this antibiotic than samples in which no trimethoprim was found . This suggests that the presence of antibiotics in prawn samples may be correlated with increased resistance to these drugs in the associated microflora . There are currently no guidelines regarding acceptable levels of antibiotics in seafood products . These results indicate that the use of these drugs by prawn farmers may be widespread, and may be an issue that requires further attention in the future. Aliment Pharmacol Ther, 1999 Aug, 13 Suppl 3, 18 - 26 Review article: drug interactions with agents used to treat acid-related diseases; Humphries TJ et al.; Patients with acid-related diseases often need to take multiple medications . Treatment of Helicobacter pylori infection often includes either a histamine type 2 (H2)-receptor antagonist or a proton pump (H+,K(+)-ATPase) inhibitor (proton pump inhibitor), administered in conjunction with one or more antimicrobials . Also, treatment for acid-related diseases often requires extended therapy during which many concomitant medications may be administered for concurrent disease states . Polypharmacy may be the result, particularly in elderly patients, who are at increased risk for both acid-related and many other diseases . Thus, it is important to understand the potential for clinically significant drug-drug interactions in this setting . H2-receptor antagonists and proton pump inhibitors can influence the pharmacokinetic profiles of other commonly administered medications by elevating intragastric pH, which can alter drug absorption, and by interacting with the cytochrome P (CYP) 450 enzyme system, which can affect drug metabolism and clearance . Such interactions are particularly important when they affect the pharmacokinetics of drugs with narrow therapeutic ranges (e.g . warfarin, digoxin) . In these cases, drug-drug interactions can result in significant toxicity and even death . There are marked differences among H2-receptor antagonists and proton pump inhibitors in their potential for such interactions . The oldest drugs in each class, cimetidine and omeprazole, respectively, have the greatest potential to alter CYP activity and change the pharmacokinetics of other drugs . The most recently developed H2-receptor antagonist, famotidine, and the newer proton pump inhibitors, rabeprazole and pantoprazole, are much less likely to induce or inhibit CYP and thereby change the metabolism of other medications . These differences are important when choosing medications for the safe treatment of patients with acid-related diseases. Eur J Biochem, 1999 Oct 1, 265(1), 71 - 8 Myticin, a novel cysteine-rich antimicrobial peptide isolated from haemocytes and plasma of the mussel Mytilus galloprovincialis; Mitta G et al.; We report here the isolation of two isoforms of a novel cysteine-rich peptide from haemocytes (isoform A of 4.438 Da and B of 4.562 Da) and plasma (isoform A) of the mussel, Mytilus galloprovincialis . The two molecules display antibacterial activity against gram-positive bacteria, whereas only isoform B is active against the fungus Fusarium oxysporum and a gram-negative bacteria Escherichia coli D31 . Complete peptide sequences were determined by a combination of Edman degradation, mass spectrometry and cDNA cloning using a haemocyte cDNA library . The mature molecules, named myticins, comprise 40 residues with four intramolecular disulfide bridges and a cysteine array in the primary structure different to that of the previously characterized cysteine-rich antimicrobial peptides . Sequence analysis of the cloned cDNAs revealed that myticin precursors consist of 96 amino acids with a putative signal peptide of 20 amino acids, the antimicrobial peptide sequence and a 36-residue C-terminal extension . This structure suggests that myticins are synthesized as preproproteins and then processed by various proteolytic events before storage of the active peptide in the haemocytes . Myticin precursors are expressed mainly in the haemocytes as revealed by Northern blot analysis. Eur Respir J, 1999 Jul, 14(1), 221 - 9 Pharmacokinetics and pharmacodynamics of fluoroquinolones in the respiratory tract; Wise R et al.; Pharmacokinetic and pharmacodynamic features are important predictors of the therapeutic efficacy of an antibiotic . In respiratory tract infection, study of the clinical implication of pharmacodynamic features is complicated as infection occurs at several distinct sites . To ensure microbiological efficacy, antibiotics should not only be active against common respiratory pathogens but should also penetrate to the sites of infection . The newer fluoroquinolones combine good activity against Gram-negative and "atypical" organisms with extended Gram-positive activity, and are unaffected by penicillin susceptibility status and beta-lactamase production . Long terminal half-lives allow once-or twice-daily dosing, and a concentration in lung tissue at levels many times higher than is observed in the serum . Although the benefit of antibiotics in some lower respiratory tract infections has been questioned, they have proved effective in community-acquired pneumonia and acute exacerbations of chronic obstructive pulmonary disease . Early studies of oral fluoroquinolones versus intravenous or oral treatment with one or more agents in community-acquired pneumonia have shown promise . Although resistance is a potential problem with increased fluoroquinolone use, its rapid development is not anticipated . In conclusion, the broad-spectrum antimicrobial activity, tissue distribution and safety profile of fluoroquinolones suggest that they have a place in respiratory tract infection. Eur Respir J, 1999 Jul, 14(1), 218 - 20 Role of glucocorticoids on inflammatory response in nonimmunosuppressed patients with pneumonia: a pilot study; Monton C et al.; The aim of the study was to assess the potential role of glucocorticoids (GC) in modulating systemic and pulmonary inflammatory responses in mechanically ventilated patients with severe pneumonia . Twenty mechanically ventilated patients with pneumonia treated at a respiratory intensive care unit (RICU) of a 1,000-bed teaching hospital were prospectively studied . All patients had received prior antimicrobial treatment . Eleven patients received GC (mean+/-SD dose of i.v . methylprednisolone 677+/-508 mg for 9+/-7 days), mainly for bronchial dilatation . Serum and bronchoalveolar lavage fluid (BALF) tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and C-reactive protein levels were measured in all patients . The inflammatory response was attenuated in patients receiving GC, both systemically (IL-6 1,089+/-342 versus 630+/-385 pg x mL(-1), p=0.03; C-reactive protein 34+/-5 versus 19+/-5 mg x L(-1), p=0.04) and locally in BALF (TNF-alpha 118+/-50 versus 24+/-5 pg x mL(-1), p= 0.05; neutrophil count: 2.4+/-1.1 x 10(9) cells x L(-1) (93+/-3%) versus 1.9+/-1.8 x 10(9) cells x L(-1) (57+/-16%), p=0.03) . Four of the 11 (36%) patients receiving GC died compared to six (67%) who were not receiving GC (p=0.37) . The present pilot study suggests that glucocorticoids decrease systemic and lung inflammatory responses in mechanically ventilated patients with severe pneumonia receiving antimicrobial treatment. Int J Food Microbiol, 1999 Sep 15, 50(1-2), 1 - 17 Preservative agents in foods . Mode of action and microbial resistance mechanisms; Brul S et al.; Preservative agents are required to ensure that manufactured foods remain safe and unspoiled . In this review, we will discuss the mode of action of both chemical and biological (nature-derived) preservatives and the stress response mechanisms induced by these compounds in microorganisms of concern to the food industry . We will discuss the challenges that food manufacturers face with respect to the assurance of food safety and the prevention of spoilage . Following this, chemical preservatives will be discussed, in particular, weak organic acids such as sorbic and benzoic acid which are widely used in preservation . Furthermore . the mechanisms of microbial inactivation with hydrogen peroxide mediated systems and chelators such as citric acid and EDTA and their potential use in preservation will be covered . We will then address the potential of naturally occurring "preservatives" . Of the antimicrobial compounds present in nature, first to be discussed will be the nonproteinaceous compounds often present in herbs and spices and we will speculate on the stress response(s) that microorganisms may elicit to these natural compounds . Next to be addressed will be compounds that attack cell walls and membranes, for example, peptides, proteins and lytic enzymes . In discussing the resistance mechanisms against membrane and wall perturbation, the extensive knowledge of stress responses against osmotic stress and temperature stress will be refered to . Finally, in the concluding paragraphs, options for combination preservation systems are evaluated. Z Naturforsch {C}, 1999 Jul-Aug, 54(7-8), 605 - 9 Some lichen products have antimicrobial activity; Garcia Rowe J et al.; Antimicrobial activity in some lichens from south Spain has been studied . Some lichenical substances are also identified . The structures of all compounds were elucidated by physical, spectral and chemical methods . A very high activity against Gram-positive bacteria has been observed in lichens containing usnic acid. Z Naturforsch {C}, 1999 Jul-Aug, 54(7-8), 469 - 73 6,9-Dihydroxy-3(15)-caryophyllen-4,8-dione--a new antibiotic from a Marasmius species; Fabian K et al.; 6,9-Dihydroxy-3(15)-caryophyllen-4,8-dione (1), a new cytotoxic caryophyllane sesquiterpene, was isolated from fermentations of a tropical Marasmius species . The structure was established by spectroscopic methods . 1 exhibits strong cytotoxic effects on different cell lines, but only weak antimicrobial activities . 1 weakly inhibits the incorporation of leucine and thymidine into proteins and DNA of mammalian cells and interferes with the aggregation of human and bovine platelets. Zentralbl Chir, 1999, 124(8), 699 - 702 {Pathogen detection in blood culture . Contamination, colonization or infection}; Wichelhaus TA et al.; Sepsis is a severe and life-threatening disease that requires a rapid and reliable diagnosis . The detection of microorganisms in blood culture and the results of in vitro anti-microbial susceptibility testing are prerequisites for a directed and cost-effective antimicrobial therapy . Microbiological results are difficult to interpret if contamination of the blood culture with colonizing or environmental germs cannot be ruled out . The source of contamination is predominantly inappropriate withdrawal of blood . Occasionally, contamination of blood cultures occurs in the laboratory . A potentially relevant blood culture result is already indicated by the isolated pathogen itself . In addition, a short time between the collection of blood and the isolation of the microorganism as well as the detection of the same pathogen in several blood cultures even more suggest a clinically relevant result. J Clin Microbiol, 1999 Oct, 37(10), 3179 - 86 Multicenter laboratory validation of susceptibility testing of Mycobacterium tuberculosis against classical second-line and newer antimicrobial drugs by using the radiometric BACTEC 460 technique and the proportion method with solid media; Pfyffer GE et al.; In a large multicenter study involving six major study sites in the United States, Canada, and Europe, the susceptibilities of 272 Mycobacterium tuberculosis strains to classical second-line antituberculosis (anti-TB) drugs (capreomycin, cycloserine, ethionamide, and kanamycin) and newer compounds (amikacin, clofazimine, ofloxacin, and rifabutin) were determined by the radiometric BACTEC 460 procedure and the conventional proportion method on Middlebrook 7H10 agar . Previously established critical concentrations for classical second-line anti-TB drugs were compared with several concentrations in liquid medium to establish equivalence . MICs of newer compounds determined in liquid medium were either the same or up to four times lower than those determined in agar medium . After establishing critical concentrations (breakpoints) in the extended testing of clinical isolates, we obtained an excellent overall correlation between the two systems, with no errors with amikacin, kanamycin, and ofloxacin and very few major or very major errors with the other drugs; however, for cycloserine, no breakpoint concentration could be recommended due to repeatedly inconsistent results by both methods . Based on these data we conclude that the BACTEC 460 procedure is a simple and rapid method requiring 4 to 8 days on average to generate accurate antimicrobial susceptibility testing (AST) results for eight anti-TB drugs other than those considered primary ones . These data not only fill a major gap of knowledge regarding the critical test concentrations of secondary anti-TB drugs but also provide a baseline for future evaluations of M . tuberculosis AST with the more recently developed, nonradiometric broth-based culture systems. Cleve Clin J Med, 1999 Sep, 66(8), 495 - 501 'Telephone treatment' of uncomplicated acute cystitis; Campbell J et al.; Acute cystitis in women is typically uncomplicated and amenable to empiric antimicrobial therapy . We advocate a simple approach, in which women with uncomplicated cases are treated over the telephone . Such a program has been in place at the Cleveland Clinic since 1992, and has yielded good results. Vestn Ross Akad Med Nauk, 1999, (8), 54 - 7 {The development of a technology for producing a new disinfecting agent with a universal spectrum of antimicrobial action}; Buianov VV et al.; The paper summarizes the findings of the physicochemical and potency of potassium fluoride peroxohydrate (PFP-1), a new Russian disinfecting agent having a universal spectrum of antimicrobial effects . It also summarizes the results of long-term practical use for the routine and final disinfection of rooms, sanitary engineering equipment, glassware, medical instruments against both sanitary indicative microorganisms, and actual pathogens of disease in infective and somatic hospitals, tuberculous dispensaries, sanatoria, schools, kindergartens, military hospitals, maternity houses of Russian different cities, towns, and localities . The paper presents comparative data on the mechanism of action of various modifications of PFP on microbial spores, on the stability of agents and their solutions during storage, on the damaging activity on the materials of the processed objects, on toxicological and ecological risks . The results of comparative studies of the bactericidal and sporicidal activities of the modifications PFP-1, PFP-2, PFP-3 confirmed that it is necessary to develop a procedure for preparing modifications containing high levels of hydrogen peroxide in the dry preparation and that they can be obtained at the pilot unit developed to prepare PFP-1 modifications. Farmaco, 1999 Jul 30, 54(7), 475 - 8 Synthesis and antimicrobial evaluation of some 3-(substituted phenacyl)-5-{4'-(4H-4-oxo-1-benzopyran-2-yl)-benzylidene}-2,4- thiazolidinediones; Tuncbilek M et al.; Synthesis and in vitro antimicrobial activity of some 3-(substituted phenacyl)-5-{4'(4H-4-oxo-1-benzopyran-2-yl)-benzylidene}-2-4- thiazolidinedione derivatives are described . These products were synthesized by the Knoevenagel reaction from 4'-flavone carboxaldehyde and 3-substituted phenacyl-2,4-thiazolidinediones. J Chromatogr A, 1999 Aug 20, 853(1-2), 197 - 206 Development and validation of a capillary electrophoresis method for the characterization of protegrin IB-367; Chen J et al.; A capillary electrophoresis (CE) method was developed to characterize protegrin IB-367, an antimicrobial peptide being developed for the treatment of oral mucositis and for other topical applications . The electrophoretic purity and levels of potential impurities/degradation products of IB-367 drug substance are determined by CE using area normalization . Electrophoresis parameters were optimized to allow optimal resolution, reproducibility and minimal analysis time . The separation and resolution between this polycationic peptide and truncated analogs determined by the CE method was much greater than those by the HPLC methods . In addition, the CE methods separates the potential impurities/degradation products from each other while the HPLC methods failed to resolve them . The CE method was validated in the aspects of accuracy, precision, linearity, range, limit of detection, limit of quantitation, specificity, system suitability and robustness . An internal standard was used for the quantitation purpose . The selection criteria of the internal standard as well as the method validation results are presented . The truncated peptide analogs were used to demonstrate the specificity of the method . These analogs were also used to evaluate the limit of quantitation of potential impurities . The relative response factors of these analogs were assessed to determine area normalization feasibility . System suitability tests were established. Clin Ther, 1999 Aug, 21(8), 1343 - 56 Cystic fibrosis clinical score: a new scoring system to evaluate acute pulmonary exacerbation; Kanga J et al.; Although pulmonary function tests are used to evaluate acute changes in obstructive airway disease in patients with cystic fibrosis (CF), these tests are relatively difficult to perform in young children or severely ill patients and may be costly . Other standard tests (eg, the Shwachman-Kulczycki and National Institutes of Health {NIH} scoring systems) evaluate disease severity and predict prognosis but do not measure day-to-day changes in clinical status . They thus provide little information for assessing the start of acute pulmonary exacerbation . Alternative scoring systems are needed to better identify the start of pulmonary exacerbation, to predict worsening or improvement of respiratory function after intervention, and to distinguish the scores from illness severity scores . This study was undertaken to compare a new 10-component, 50-point-maximum, acute clinical scoring system with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) variables in children with CF who were experiencing an acute pulmonary exacerbation before antimicrobial therapy was initiated and until the end of therapy . One hundred thirty children aged 5 to 17 years (median age, 11 years) had a median NIH score of approximately 64 (range, 39 to 85) at admission . The cystic fibrosis clinical score (CFCS) at admission was found to correlate highly with the modified NIH score at study entry (r = -.68, P = 0.0001 ) . The total CFCS at entry was correlated inversely with both FEV1 (r = -.57, P = 0.0001) and FVC (r = -.55, P = 0.0001) measurements; crackles, dyspnea, sputum production, and respiratory rate were the 4 components most highly associated with either pulmonary function variable . The change in total CFCS from start to end of antimicrobial therapy also correlated with changes in FEV1 (r = -.31, P = 0.0016) and change in FVC (r = -.47, P = 0.0001) . Clinical improvement was observed in all patients at the end of therapy, and only 1 patient had an increase in total CFCS . Patients who experienced clinical relapse had a mean increase of 8.5 points in the CFCS from end of therapy to 2- to 4-week follow-up, indicating worsening signs and symptoms of acute exacerbation . These data suggest that the CFCS is a predictive and optional surrogate of pulmonary function in assessing the health of patients with CF . Following further validation, this scoring system could be used to evaluate health status in the outpatient setting, the need for hospitalization, and subsequent improvement during an acute pulmonary exacerbation, as well as to compare the efficacy of therapeutic regimens. Am J Physiol, 1999 Sep, 277(3 Pt 2), H1007 - 13 PR-39, a proline/arginine-rich antimicrobial peptide, prevents postischemic microvascular dysfunction; Korthuis RJ et al.; We and others have previously demonstrated that intestinal ischemia-reperfusion (I/R) is associated with a large increase in oxidant production that contributes to microvascular barrier disruption in the small bowel . It has been suggested that the bulk of tissue damage during reperfusion can be attributed to adherent, activated neutrophils . From these observations, we hypothesized that pretreatment with PR-39, an endogenous neutrophil antibacterial peptide that is also a potent inhibitor of the neutrophil NADPH oxidase, would prevent postischemic oxidant production and the development of oxidant-dependent sequelae to I/R such as increased venular protein leakage . To test this postulate, oxidant production, venular protein leakage, leukocyte adhesion, and leukocyte emigration were monitored during reperfusion in control (no ischemia) rat mesenteric venules and in mesenteric venules subjected to I/R alone or PR-39 + I/R . Treatment with a single intravenous bolus injection of PR-39 (administered at a dose to achieve an initial blood concentration of 5 microM) abolished I/R-induced leukocyte adhesion and emigration in vivo . In vitro studies indicated that PR-39 prevents platelet-activating factor-induced neutrophil chemotaxis as well as phorbol myristate acetate (PMA)-stimulated intercellular adhesion molecule-1 expression by cultured endothelial cells . PR-39 pretreatment of rat neutrophils also blocked PMA-stimulated neutrophil adhesion to activated endothelial monolayers . In vivo, I/R was associated with a marked and progressive increase in oxidant production and venular protein leakage during reperfusion, effects that were abolished by PR-39 treatment . The results of this study indicate that PR-39 completely abolishes postischemic leukocyte adhesion and emigration . The time course for inhibition of oxidant production by PR-39 suggests that its antiadhesive properties account for this effect of the peptide . PR-39 may thus be therapeutically useful for prevention of neutrophil adhesion and activation during the postischemic inflammatory response. Am J Physiol, 1999 Sep, 277(3 Pt 1), C351 - 8 Innate mechanisms of epithelial host defense: spotlight on intestine; Hecht G; The single layer of epithelial cells lining the intestinal tract is charged with a most difficult task: protecting the underlying biological compartments from both the normal commensal flora that reside within the intestinal lumen as well as the uninvited pathogens . To such an end, the intestinal epithelial cells are equipped with a panoply of defense mechanisms, both constitutive and inducible . This review focuses only on those defense mechanisms that are initiated and executed by the intestinal epithelial cell . Fitting these strict criteria are three major categories of epithelial host defense: enhanced salt and water secretion, expression of antimicrobial proteins and peptides, and production of intestinal mucins . Each of these areas is discussed in this review. Am J Gastroenterol, 1999 Sep, 94(9), 2534 - 6 Pancreatic tuberculosis with obstructive jaundice--a case report; Chen CH et al.; Isolated pancreatic tuberculosis (TB) is very rare and its treatment somewhat controversial . We report a case of pancreatic TB diagnosed as pancreatic carcinoma . An 82-yr-old man presented with right upper abdominal pain and obstructive jaundice, without fever or weight loss . Ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography showed a mass lesion in the pancreatic head, which caused stricturing of the distal common bile duct and pancreatic duct in the head of the gland . As malignancy was suspected, he underwent a Whipple procedure (pancreaticoduodenectomy) . Histological examination of the resection specimen disclosed typical features of tuberculosis in the pancreatic head, lymph nodes, and at the ampulla of Vater . The rest of the abdominal cavity was unremarkable . After receiving antimicrobial therapy for tuberculosis for 6 months, he remains well, without jaundice or a recurrent mass visible by ultrasound. Am J Gastroenterol, 1999 Sep, 94(9), 2408 - 11 The effects of bile duct obstruction on the biliary secretion of ciprofloxacin in piglets; Chen CY et al.; OBJECTIVE: The aim of this study was to evaluate the effect of bile duct obstruction on biliary secretion of ciprofloxacin and to look for useful parameters to guide clinical use of antibiotics in patients with acute cholangitis . METHODS: Twenty-five Landrace piglets were used in this study . Their common bile ducts were ligated, with a duration ranging from 1 to 7 days . The changes of liver biochemical tests, intrabiliary pressure, diameter of common bile duct, and concentration of ciprofloxacin in bile were compared among the piglets with different severity of bile duct obstruction . RESULTS: The bile-to-serum ratio of the ciprofloxacin concentration was 586.4% +/- 140.3% before the ligation of bile duct and was reduced significantly to 94.5% +/- 118.0% after 1-day obstruction . The biliary secretion of ciprofloxacin was greatly affected by the intrabiliary pressure in that the bile-to-serum ratio of ciprofloxacin concentration was reduced to 12.2% +/- 14.8% when the intrabiliary pressure reached to 32 cm H2O . The change in the intrabiliary pressure was correlated with the diameter of common bile duct, with a correlation coefficient of 0.90 (p < 0.001) . CONCLUSIONS: Biliary secretion of ciprofloxacin is decreased in proportion to the increase of intrabiliary pressure . In obstruction, a markedly dilated common bile duct usually indicates high intrabiliary pressure, and thus biliary concentrations of antibiotics will be lower than expected . Hence, our observations suggest that choosing an antibiotic with high antimicrobial activity, or establishing a biliary drainage to lower the intrabiliary pressure, would be beneficial for patients suffering from cholangitis with a dilated biliary tree. Support Care Cancer, 1999 Sep, 7(5), 343 - 6 Resource implications of febrile neutropenia in cancer patients . An international collaborative study; Harbarth S et al.; No previous study has compared countries with respect to differences in clinical practice and resource use of cancer patients with febrile neutropenic episodes (FNE) . The purpose of this international, cross-sectional pilot study conducted in tertiary care centers across Europe, Brazil and Australia was to evaluate the resource use attributable to febrile neutropenia in different countries . A total of 17 centers from eight countries provided 128 patients . The leading malignant disorders were hematological malignancies (n = 47), lymphomas (n = 27), and breast cancer (n = 26) . The median length of duration of FNE was 4 days (interquartile range, 3-8) . The incidence density of antimicrobial exposure was 4.691 days of antimicrobial therapy per 1,000 days of FNE . There were 23 patients who received a total of 280 days of G-CSF therapy . On average, 5 (+/-5.4) blood samples per patient were drawn and cultured . The most common diagnostic radiographic test was the chest X-ray, with a total of 224 such examinations performed in 82 patients . We conducted an international cross-sectional study on resource implications of febrile neutropenia in cancer patients . The records of the febrile neutropenic patients included in this study reflect clinical practice in a heterogeneous, international patient population, treated with modern supportive care and early empiric antibiotics by clinicians at different levels of expertise. Pharmazie, 1999 Aug, 54(8), 588 - 9 Synthesis and biological action of 3,4-disubstituted 5-arylsulphonylamine-1,2,4-triazoles; Modzelewska-Banachiewicz B et al.; The synthesis of 3,4-disubstituted 5-arylsulphonylamine-1,2,4-triazoles is described . The antimicrobial activities of the compounds were investigated as well as their acute toxicity. Scand J Infect Dis, 1999, 31(3), 255 - 9 Chlamydia pneumoniae is an important cause of community-acquired pneumonia in school-aged children: serological results of a prospective, population-based study; Heiskanen-Kosma T et al.; The aetiology of community-acquired pneumonia in childhood was studied in the total population of 8851 children in the area of 4 municipalities in eastern Finland . All cases of community-acquired pneumonia (n = 201) were registered during a surveillance period of 12 months between September 1, 1981 and August 31, 1982 . The diagnosis of pneumonia was verified radiologically in all identified cases . The diagnosis of chlamydial infection was based on an antibody response measured by complement fixation (CF), by enzyme immunoassay (EIA; IgG or IgM) or by microimmunofluorescence (MIF; IgG or IgM), and the diagnosis of mycoplasmal infection on CF alone . In total, 29 cases of Chlamydia sp . infection were diagnosed; 20 were caused by Chlamydia pneumoniae . Thus, C . pneumoniae was an aetiological agent in 10%, of the 201 pneumonia cases: the proportion was 9% for children aged 5-9 y and 31% for those aged 10 y or more . In the study population, the total incidence of C . pneumoniae pneumonia was 2.3/1000/y . Mycoplasma pneumoniae serology (CF) was positive in 44 patients (22%); the total incidence of M . pneumoniae pneumonia was 5.0/1000/y . Serological evidence of both Chlamydiae and M . pneumoniae was detected in 9 (41%) patients . Our results indicate that C . pneumoniae is an important cause of community-acquired pneumonia in school-aged children . Diagnostic serological response to Chlamydia species or M . pneumoniae was found in 42% of pneumonia patients between 5 and 9 y of age and in 67% of patients aged 10 y or more . Thus, we suggest that macrolides should be considered as an empirical antimicrobial treatment for community-acquired pneumonia, especially in school-aged outpatients. Kekkaku, 1999 Jul, 74(7), 563 - 70 {Effects of secretory leukocyte protease inhibitor on the production of some cytokines and nitric oxide by murine peritoneal macrophages in response to lipopolysaccharide stimulation and M . avium complex infection}; Sano C et al.; Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor abundantly found in mucous secretions of lung, is thought to serve as an important protective component in the secretory fluids at sites of degenerative and inflammatory diseases . In this study, we examined the effects of SLPI on the production of a proinflammatory cytokine, TNF-alpha, and immunosupressive cytokines, IL-10 and transforming growth factor-beta (TGF-beta) by macrophages (M phi s), in response to lipopolysaccharide (LPS)-mediated stimulation and M . avium complex (MAC) infection, using recombinant half-sized SLPI (1/2 SLPI) consisting of C-terminal domain (Arg55-Ala107) of intact SLPI . In addition, effects of SLPI on the production of nitric oxide radicals (NO), important antimicrobial effectors of M phi s against micro-organisms, by these M phi s were studied . First, when the number of TNF-alpha producing cells in the LPS-stimulated M phi population was counted by the ELISPOT assay, more than half of the M phi s acquired TNF-alpha secreting ability at 24 hr after LPS stimulation . On the other hand, MAC-infected M phi s produced detectable amounts of TNF-alpha into culture fluid during the first 24 hr . In both cases, 1/2 SLPI did not affect the LPS- or MAC-induced TNF-alpha production by M phi s . Second, when the production of IL-10 and TGF-beta by M phi s was determined by measuring the amounts of these cytokines accumulated in M phi culture fluids by ELISA, the following was observed . M phi IL-10 production was rapidly increased in the early phase of cultivation after LPS stimulation or MAC infection, peaking on day 1 and thereafter declining to normal level by day 14 . Half-sized SLPI did not affect IL-10 production of LPS-stimulated M phi s, while it caused slight enhancement of IL-10 production by MAC-infected M phi s . M phi TGF-beta production was initiated in the middle phase (day 7) of M phi cultivation and continued until day 14 . Notably, 1/2 SLPI markedly potentiated the TGF-beta producing ability of the LPS-stimulated M phi s . Moreover, 1/2 SLPI caused moderate increase in the TGF-beta production by MAC-infected M phi s . Third, significantly potentiated NO production was observed in M phi s during the first 2 days after LPS stimulation and MAC infection . Half-sized SLPI did not affect the NO production by LPS-stimulated or MAC-infected M phi s . These findings indicate that SLPI up-regulates the production of some immunoregulatory cytokines including IL-10 and TGF-beta, particularly the latter, by M phi s in response to LPS stimulation or MAC infection, thereby suggesting the possibility that SLPI may exhibit antiinflammatory effects in vivo, especially patients with bacterial infections including MAC diseases, through the modulation of M phi expression of some immunosuppressive cytokines. Kansenshogaku Zasshi, 1999 Jul, 73(7), 694 - 701 {Antibacterial effects of cacao mass on enterohemorrhagic Escherichia coli O157:H7}; Takahashi T et al.; The antimicrobial activities of aqueous cacao mass extract against enterohemorrhagic Escherichia coli (EHEC) O157:H7 006 strain were studied . Hot water extract of cacao mass (cocoa extract) was shown to inhibit the growth of EHEC O157:H7 006 strain in PBS or CAYE medium . In addition, the production of verotoxins (types 1 and 2) of EHEC O157:H7 006 strain was significantly inhibited by 8.0% cocoa extract . The cocoa extract did not neutralize the cytotoxity of verotoxins, but had inhibitory effect on adhesion of verotoxins to the target Vero cells . These results demonstrate that cacao mass has antimicrobial effects on EHEC O157:H7. Kansenshogaku Zasshi, 1999 Jul, 73(7), 646 - 51 {Clinicobacteriological studies on the nine cases with upper genital tract Mycoplasma hominis infection}; Shimada M et al.; Clinicobacteriological characteristics of nine cases isolated Mycoplasma hominis from the genital tract were studied, and the following results were obtained: elevation of IgG antibodies to M . hominis was measured by ELISA in all cases, but in the MI method only one case showed an elevation of metabolic inhibitory antibody . Convalescent sera from seven patients showed additional and high density bands which were not recognized by acute phase sera in immunoblotting . It was thought that in two patients M . hominis was a causal bacteria for pelvic inflammatory disease (PID) . In three cases, it was suggested that M . hominis was related to a premature delivery and idiopathic labor . As infectious symptoms, two patients had body temperatures of more than 38 degrees C but other cases showed 37-37.8 degrees C . Though all cases showed an elevation of CRP, six elevations were slight . As a medication beta-lactam agents were administrated, but their efficacy was not recognized . Furthermore, two patients showed spontaneous recovery in spite of improper antimicrobial agents administration or drainage combined with antimicrobial agents . From the above results . It was thought that M . hominis played a causative role in upper genital tract infection. J Biol Chem, 1999 Sep 17, 274(38), 26743 - 50 Stereochemical course and steady state mechanism of the reaction catalyzed by the GDP-fucose synthetase from Escherichia coli; Menon S et al.; Recently the genes encoding the human and Escherichia coli GDP-mannose dehydratase and GDP-fucose synthetase (GFS) protein have been cloned and it has been shown that these two proteins alone are sufficient to convert GDP mannose to GDP fucose in vitro . GDP-fucose synthetase from E . coli is a novel dual function enzyme in that it catalyzes epimerizations and a reduction reaction at the same active site . This aspect separates fucose biosynthesis from that of other deoxy and dideoxy sugars in which the epimerase and reductase activities are present on separate enzymes encoded by separate genes . By NMR spectroscopy we have shown that GFS catalyzes the stereospecific hydride transfer of the ProS hydrogen from NADPH to carbon 4 of the mannose sugar . This is consistent with the stereospecificity observed for other members of the short chain dehydrogenase reductase family of enzymes of which GFS is a member . Additionally the enzyme is able to catalyze the epimerization reaction in the absence of NADP or NADPH . The kinetic mechanism of GFS as determined by product inhibition and fluorescence binding studies is consistent with a random mechanism . The dissociation constants determined from fluorescence studies indicate that the enzyme displays a 40-fold stronger affinity for the substrate NADPH as compared with the product NADP and utilizes NADPH preferentially as compared with NADH . This study on GFS, a unique member of the short chain dehydrogenase reductase family, coupled with that of its recently published crystal structure should aid in the development of antimicrobial or anti-inflammatory compounds that act by blocking selectin-mediated cell adhesion. Phytother Res, 1999 Sep, 13(6), 494 - 7 Antimicrobial potential of Spondias mombin, Croton zambesicus and Zygotritonia crocea; Abo KA et al.; The antimicrobial activity of Spondias mombin, Croton zambesicus and Zygotritonia crocea sourced from herbalists through an ethnobotanical survey of Egbado-South in Ogun State in Nigeria is reported . The extracts of the leaf of Spondias mombin and the stem bark of Croton zambesicus exhibited wide spectrum antibacterial effects comparable to those of ampicillin and gentamycin . The antifungal effect of extracts of Zygotritonia crocea and Croton zambesicus were comparable to those of tioconazole . There is justification for the use of these little studied medicinal plants as antiinfective agents in traditional medicine . J Nat Prod, 1999 Aug, 62(8), 1185 - 7 Triterpene trimers from Maytenus scutioides: cycloaddition compounds? Gonzalez AG, Alvarenga NL, Bazzocchi IL, Ravelo AG, Moujir L. Two novel trimers, triscutins A and B (1 and 2), based on pristimerin triterpene units, were isolated and characterized from Maytenus scutioides . Their structures were determined on the basis of spectroscopic evidence, including 1H-13C heteronuclear correlation (HMQC), long-range correlation with inverse detection (HMBC), and ROESY NMR experiments; and their absolute configurations, by means of CD studies . Compounds 1 and 2 were assayed for antimicrobial and cytotoxic activities, and their possible biosynthetic route is proposed. Am J Health Syst Pharm, 1999 Aug 1, 56(15), 1521 - 4 Azithromycin versus erythromycin for community-acquired pneumonia: a cost-minimization analysis; Howard KB et al.; The costs of i.v . erythromycin versus azithromycin (in terms of medication use and treatment of adverse effects) when these drugs were used with other antimicrobials to treat community-acquired pneumonia (CAP) were compared . The medical records of patients receiving i.v . azithromycin or erythromycin as part of combination antimicrobial therapy for the treatment of CAP at a 473-bed level 1 trauma center in Kentucky were retrospectively reviewed . Data were collected for patients treated from December 1, 1997, through March 31, 1998 . Patient data collected included occurrence of phlebitis or pain at the injection site, number of line changes due to phlebitis, and culture results . Cost data collected included drug acquisition cost, pharmacy cost of drug preparation, nursing time to administer the agent, cost of drug supplies, and cost of managing complications . Three time-and-motion studies were conducted to determine technician preparation time and pharmacist verification time . The medical records of 62 patients were identified and reviewed; 50 patients were enrolled in the study (25 in the azithromycin group and 25 in the erythromycin group) . The average total days of therapy was 5.1 for the azithromycin group and 5.6 for the erythromycin group . The average total cost, including the cost of complications ($4.36 per patient in the erythromycin group), was $66.46 in the azithromycin group and $96.56 in the erythromycin group . The difference in costs between the two groups was not significant . There was no significant cost difference between azithromycin- and erythromycin-containing combination antimicrobial therapy in the treatment of CAP. Radiology, 1999 Sep, 212(3), 669 - 72 Multiple fluid collections: CT- or US-guided aspiration--evaluation of microbiologic results and implications for clinical practice; Heneghan JP et al.; PURPOSE: To determine if patients with multiple fluid collections need every collection aspirated and if cross-contamination is a risk if separate sterile procedures are not followed for each aspiration . MATERIALS AND METHODS: Records from 1,076 imaging-guided percutaneous aspirations and drainages over 39 months were retrospectively reviewed; 124 patients had multiple fluid collections drained, which yielded 287 aspirates . The patients were divided into two groups: those (n = 82) with multiple collections aspirated on any 1 day, and those (n = 61) with multiple collections aspirated over 10 days . Nineteen patients were included in both groups . Gram stain microscopy and culture results were compared between sequential aspirates in each patient, and their potential effects on antimicrobial therapy and theoretic risk for cross-contamination were evaluated . RESULTS: In 82 patients undergoing multiple aspirations on any 1 day, multiple microorganisms differed in 32 patients, which indicated a need for therapy change in 18 (22%) patients . In 61 patients undergoing aspiration on different days, microorganisms differed in 32 patients, which indicated a need for therapy change in 15 (25%) patients . Cross-contamination could have occurred in 28 of 93 (30%) aspirates from patients with a second or subsequent collection if separate sterile procedures had not been undertaken . CONCLUSION: When multiple fluid collections are identified, aspirates from all collections should be obtained through separate sterile procedures to ensure optimal antimicrobial coverage and avoid cross-contamination. Dent Update, 1999 Jan-Feb, 26(1), 7 - 14 A practical guide to antibiotic prophylaxis in restorative dentistry; Longman LP et al.; The purpose of this paper is to review the principles and practicalities of antibiotic prophylaxis in medically compromised patients who require restorative dentistry . Guidelines for the management of patients who are susceptible to infection are given . The importance of oral health and the rational use of both local and systemic antimicrobial prophylaxis is described. Am J Dent, 1998 Dec, 11(6), 259 - 70 Efficacy of a triclosan/NaF dentifrice in the control of plaque and gingivitis and concurrent oral microflora monitoring; Fine DH et al.; PURPOSE: To compare the effect of a dentifrice containing 0.3% triclosan and 1100 ppm fluoride and a control dentifrice containing 1100 ppm fluoride on plaque, gingiva and the oral microflora in a long-term study simulating clinical usage . MATERIALS AND METHODS: 159 subjects entered the clinical study and 80 were randomly selected to participate in the microbiological evaluation . 71 subjects completed the detailed evaluation of the oral microflora after 6 months use . Plaque was collected at baseline, 3 months, and 6 months, and examined by darkfield microscopy, Gram stain, immunofluorescence, and selective and non-selective media . Changes in antimicrobial susceptibilities were determined for the first 6-month period and for 6 months post-therapy for 68 subjects who completed the entire study . Susceptibilities of whole plaque samples and MIC values for two pre-designated common plaque organisms, A . viscosus and V . parvula were performed . RESULTS: Multivariate ANOVA and non-parametric analyses revealed no statistical differences for any factor tested . No detrimental shifts were found in either; (1) the compositional make up of the normal flora, (2) the periodontopathic or cariogenic flora, or (3) the opportunistic flora in either group of dentifrice users . Both treatments resulted in decreases in Gram positive cocci over time . There was a reduction in spirochetes in the triclosan/fluoride group as compared to the control group . No overgrowth in opportunists, periodontal pathogens, or cariogenic flora was found in either group . No increase in the proportion of the whole plaque flora resistant to triclosan was found nor was an increase in the MIC values of either A . viscosus or V . parvula in either group . Overall, there appeared to be a general decrease in plaque bacteria in both groups over the course of the experiment. J Immunol, 1999 Sep 15, 163(6), 3459 - 67 A novel mechanism of action of chemically modified tetracyclines: inhibition of COX-2-mediated prostaglandin E2 production; Patel RN et al.; Tetracyclines (doxycycline and minocycline) inhibit inducible NO synthase expression and augment cyclooxygenase (COX)-2 expression and PGE2 production . In contrast, chemically modified tetracyclines (CMTs), such as CMT-3 and -8 (but not CMT-1, -2, and -5), that lack antimicrobial activity, inhibit both NO and PGE2 production in LPS-stimulated murine macrophages, bovine chondrocytes, and human osteoarthritis-affected cartilage, which spontaneously produces NO and PGE2 in ex vivo conditions . Furthermore, CMT-3 augments COX-2 protein expression but inhibits net PGE2 accumulation . This coincides with the ability of CMT-3 and -8 to inhibit COX-2 enzyme activity in vitro . The action of CMTs is distinct from that observed with tetracyclines because 1) CMT-3-mediated inhibition of PGE2 production coincides with modification of COX-2 protein, which is distinct from the nonglycosylated COX-2 protein generated in the presence of tunicamycin, as observed by Western blot analysis and 2) CMT-3 and -8 have no significant effect on COX-2 mRNA accumulation . In contrast, CMT-3 and -8 do not inhibit COX-1 expression in A549 human epithelial cells at the level of protein and mRNA accumulation or modification of COX-1 protein . CMT-3 and -8 inhibit the sp . act . of COX-2 (but not COX-1) in cell-free extracts . These results demonstrate differential action of CMT-3 (Metastat) on COX-1 and -2 expression, which is distinct from other tetracyclines. Clin Infect Dis, 1999 Aug, 29(2), 312 - 7 Antibiotic prescribing by pediatricians for respiratory tract infection in children; Arnold SR et al.; To examine antimicrobial prescribing rates for viral respiratory tract infections by primary care pediatricians in the greater Toronto area, charts were reviewed for the week of 17-21 February 1997 at 61 pediatricians' offices . Antibiotics were considered appropriate if the diagnosis was compatible with bacterial infection . A total of 3,585 patient visits were reviewed . The common cold was the most common respiratory tract syndrome leading to an office visit (1,317 visits) . The overall rate of appropriate antibiotic prescribing was 89.5% . There was no significant difference in prescribing when physicians were compared by year of graduation from medical school, sex, or location of training . Diagnostic codes (ICD-9 {International Classification of Diseases, 9th edition} codes) did not match the chart diagnosis in 41% of cases . Toronto primary care pediatricians appear to have a lower rate of inappropriate antibiotic prescribing than do primary care physicians in other regions of Canada and the United States. Clin Infect Dis, 1999 Aug, 29(2), 292 - 5 Prosthetic joint infection: when can prosthesis salvage be considered? Tattevin P, Cremieux AC, Pottier P, Huten D, Carbon C. Management of prosthetic joint infection (PJI) remains a therapeutic challenge . We retrospectively studied 69 infected total hip or knee arthroplasties managed between 1980 and 1996 in our institution . Treatment failure, defined as relapse of PJI in the first year following the last antimicrobial treatment, occurred for 14 patients (20.3%) . None of the potentially contributive parameters analyzed was significantly predictive of treatment failure . Of the subgroup of 34 patients with PJI who initially underwent debridement with retention of the prosthesis, the 13 (38.2%) who did not require further surgical treatment had symptoms for a significantly shorter duration before debridement (4.85 vs . 54.24 days; P < .0001) . Because debridement with retention of the prosthesis rarely enables control of PJI, this therapeutic approach should be considered only when the duration of symptoms is very short. Clin Infect Dis, 1999 Aug, 29(2), 264 - 74 Optimal use of modern antibiotics: emerging trends; Polk R; Development of new antimicrobial drugs is an essential component in the effort to remain ahead of emerging microbial resistance . However, when new antibiotics are used with unrestrained enthusiasm, a predictable consequence is the further expansion of resistance . This problem is well known to the infectious diseases specialist and is increasingly appreciated by the nonspecialist and the public . A far more sensible strategy is to identify new ways to use these drugs to increase the duration of their usefulness . New methods to optimize antibiotic selection, dose, and duration of therapy are being investigated, and application of some of these strategies has been shown to have a favorable impact on resistance . Much of the classic thinking of how to use antibiotics is changing, and these newer strategies may result in prolongation of the era of the "antibiotic miracle." J Clin Pharm Ther, 1999 Aug, 24(4), 259 - 72 Exploring novel vaccines against Helicobacter pylori: protective and therapeutic immunization; Vyas SP et al.; Infection of human stomach by Helicobacter pylori, a gram negative spiral bacterium first isolated in 1983 from a patient with chronic active gastritis (1), causes nearly all duodenal ulcers and most gastric ulcers and is associated with an increased risk of gastric adenocarcinoma (2) . Current therapies for gastric infections include combination triple or quadruple therapy of antimicrobial and/or antiulcer agents for eradication of H . pylori infection (3) . Development of the resistant strains and ecological niche (habitant) of the bacteria may cause relapse after the termination of the therapy . However, if effective, the high cost, difficulty of patient compliance and risk of selection for resistant strains make these therapeutic regimens impractical on a large scale, though effective on the laboratory trial stages . Studies of the pathogenesis of H . pylori have led to the identification of bacterial antigens and adherin proteins as candidates for inclusion as novel vaccines against these diseases (4-7) . Both prophylactic and therapeutic vaccination have been demonstrated in animal models of H . pylori infection (8-10). Chemotherapy, 1999 Sep-Oct, 45(5), 342 - 8 In vitro bactericidal activities of antimicrobial agents and morphologic changes on Prevotella bivia; Mikamo H et al.; Prevotella bivia is common in pelvic inflammatory diseases . Parenteral antimicrobial agents have been widely used against those infections . We investigated the bactericidal activities of three cephalosporins, i.e . cefluprenam (CFLP), ceftazidime (CAZ) and cefotaxime (CTX) and of two other antimicrobial agents, i.e . clindamycin (CLDM) and imipenem (IPM) against P . bivia . We also investigated the in vitro morphological changes induced by these agents in P . bivia . Cephalosporins exhibited bactericidal activities against P . bivia and induced time- and concentration-dependent morphological changes in P . bivia (filamentation) . CLDM and IPM also had bactericidal activities, but induced different morphologic alterations: formation of spheroblasts and lysis . These results confirm the fact that each antimicrobial agent has characteristic aspects. J Antimicrob Chemother, 1999 Aug, 44(2), 163 - 77 Self-medication of antibacterials without prescription (also called 'over-the-counter' use) . A report of a Working Party of the British Society for Antimicrobial Chemotherapy; Reeves DS et al.; The availability of antimicrobial agents for self-medication may increase and could include antibacterial agents for oral or topical use . Wholesale deregulation of antibacterials would be undesirable and likely to encourage misuse of classes of agents currently important in the management of serious infections . Changed regulation from Prescription-Only Medicine (POM) to Pharmacy (P) medicine of selected agents with indications for short-term use in specific minor infections and illness is likely to have advantages to the user . However, safeguards to their use would need to be included in the Patient Information Leaflet (PIL) . Agents and indications for self-medication are discussed . Any alteration in licensed status from POM to P will require careful risk-benefit assessment, including the likely impact on bacterial resistance . Safety issues also include concerns relating to age of the user, pregnancy, underlying disease and the potential for drug interactions . The importance of appropriate information with the PIL is emphasized, as is the role of the pharmacist, while ways of improving adverse event notification and monitoring are discussed . The paucity of good denominator-controlled data on the prevalence of in-vitro resistance is highlighted, and recommendations for improving the situation are made . There are currently no levels of resistance accepted by regulatory bodies on which to base a licensing decision, be it for granting a product licence, renewal of a licence or a change in licensed status from POM to P . Due consideration should be given to: the validation of user-defined indications in comparison with those medically defined; the enhancement of pharmacy advice in the purchase of such agents; improved safety monitoring; the establishment of systematic surveillance of susceptibility data. J Biol Chem, 1999 Sep 10, 274(37), 26249 - 58 Cloning and expression of bovine neutrophil beta-defensins . Biosynthetic profile during neutrophilic maturation and localization of mature peptide to novel cytoplasmic dense granules; Yount NY et al.; beta-Defensins are microbicidal peptides implicated in host defense functions of phagocytic leukocytes and certain surface epithelial cells . Here we investigated the genetic structures and cellular expression of BNBD-4, -12, and -13, three prototypic bovine neutrophil beta-defensins . Characterization of the corresponding cDNAs indicated that BNBD-4 (41 residues) derives from a 63-amino acid prepropeptide and that BNBD-12 (38 residues) and BNBD-13 (42 residues) derive from a common 60-amino acid precursor (BNBD-12/13) . The peptides were found to be encoded by two-exon genes that are closely related to bovine epithelial beta-defensin genes . BNBD-4 and BNBD-12/13 mRNAs were most abundant in bone marrow, but were expressed differentially in certain non-myeloid tissues . In situ hybridization and immunohistochemical studies demonstrated that BNBD-4 synthesis is completed early in myelopoiesis . BNBD-12 was localized exclusively to the novel dense granules, organelles that also contain precursors of cathelicidins, antimicrobial peptides that undergo proteolytic processing during phagocytosis . In contrast to cathelicidins, Western blot analyses revealed that mature beta-defensins are the predominant organellar form in myeloid cells . Stimulation of neutrophils with phorbol myristate acetate induced secretion of BNBD-12, indicating that it is co-secreted with pro-cathelicidins . The exocytosis of BNBD-12 by activated neutrophils reveals different mobilization pathways for myeloid alpha- and beta-defensins. J Biol Chem, 1999 Sep 10, 274(37), 26172 - 8 Horseshoe crab hemocyte-derived antimicrobial polypeptides, tachystatins, with sequence similarity to spider neurotoxins; Osaki T et al.; Antimicrobial peptides, named tachystatins A, B, and C, were identified from hemocytes of the horseshoe crab Tachypleus tridentatus . Tachystatins exhibited a broad spectrum of antimicrobial activity against Gram-negative and Gram-positive bacteria and fungi . Of these tachystatins, tachystatin C was most effective . Tachystatin A is homologous to tachystatin B, but tachystatin C has no significant sequence similarity to tachystatins A and B . Tachystatins A and B showed sequence similarity to omega-agatoxin-IVA of funnel web spider venom, a potent blocker of voltage-dependent calcium channels . However, they exhibited no blocking activity of the P-type calcium channel in rat Purkinje cells . Tachystatin C also showed sequence similarity to several insecticidal neurotoxins of spider venoms . Tachystatins A, B, and C bound significantly to chitin . A causal relationship was observed between chitin binding activity and antifungal activity . Tachystatins caused morphological changes against a budding yeast, and tachystatin C had a strong cell lysis activity . The septum between mother cell and bud, a chitin-rich region, was stained by fluorescence-labeled tachystatin C, suggesting that the primary recognizing substance on the cell wall is chitin . As horseshoe crab is a close relative of the spider, tachystatins and spider neurotoxins may have evolved from a common ancestral peptide, with adaptive functions. J Antimicrob Chemother, 1999 Aug, 44(2), 209 - 16 Inhibition of potassium transport and growth of mycobacteria exposed to clofazimine and B669 is associated with a calcium-independent increase in microbial phospholipase A2 activity; Steel HC et al.; Altered phospholipase A2 (PLA2) activity and its relationship to cation (K+, Ca2+) uptake and growth were investigated in mycobacteria exposed to the riminophenazine antimicrobial agents, clofazimine and B669 (0.15-2.5 mg/L) . Microbial PLA2 activity was measured using a radiometric thin-layer chromatography procedure, whereas K+ and Ca2+ transport were measured using 86Rb+ or 42K+ and 45Ca2+, respectively . Short-term exposure (15-30 min) of Mycobacterium aurum A+ or the virulent and avirulent isolates of Mycobacterium tuberculosis H37R to the riminophenazines resulted in dose-related enhancement of microbial PLA2 activity, which was associated with inhibition of K+ influx and growth . Uptake of Ca2+ by mycobacteria was unaffected, or minimally affected, by the riminophenazines at concentrations of < or = 0.6 mg/L, whereas higher concentrations resulted in increased uptake of the cation in the setting of decreased microbial ATP concentrations . The results of kinetic studies using a fixed concentration (2.5 mg/L) of B669 demonstrated that riminophenazine-mediated enhancement of PLA2 activity and inhibition of K+ uptake in mycobacteria are rapid and probably related events that precede, by several minutes, any detectable effects on microbial ATP concentrations and uptake of Ca2+ . Inclusion of the extracellular and intracellular Ca2+-chelating agents EGTA (0.2-7.2 g/L) and BAPTA/FURA-2 (0.2-9.5 mg/L), individually or in combination, did not prevent the effects of B669 on mycobacterial PLA2 activity or K+ transport, whereas alpha-tocopherol, which neutralizes PLA2 primary hydrolysis products, antagonized the inhibitory effects of the riminophenazines on microbial K+ uptake and growth . These results demonstrate that the antimycobacterial activities of clofazimine and B669 are related to a Ca2+-independent increase in mycobacterial PLA2, leading to interference with microbial K+ transport. Novartis Found Symp, 1999, 225, 188 - 200; discussion 200-6 Peptide-lipid interactions and mechanisms of antimicrobial peptides; Huang HW; Hydrophobic matching, in which transmembrane proteins cause the surrounding lipid bilayer to adjust its hydrocarbon thickness to match the length of the hydrophobic surface of the protein, is a commonly accepted idea . To test this idea, gramicidin was embedded in dilauroyl phosphatidylcholine (DLPC) and dimyristoyl phosphatidylcholine (DMPC) bilayers at the molar ratio 1:10 . The bilayer thickness (PtP) was measured by X-ray lamellar diffraction . In the fluid phase near full hydration, PtP is 30.8 A for pure DLPC, 32.1 A for DLPC/gramicidin mixture, 35.3 A for pure DMPC and 32.7 A for a DMPC/gramicidin mixture . Gramicidin apparently stretches DLPC bilayers and thins DMPC bilayers toward a common thickness as expected by hydrophobic matching . Gramicidin pair correlations were measured by X-ray in-plane scattering . In the fluid phase, the gramicidin-gramicidin nearest-neighbour separation is 26.8 A in DLPC bilayers but shortens to 23.3 A in DMPC bilayers, thus confirming the conjecture that when proteins are embedded in a membrane, hydrophobic matching creates a strain field in the lipid bilayer that in turn gives rise to a membrane-mediated attractive potential between proteins . These results were analysed with an elasticity theory of membrane deformation . The same principle explains the 'concentration-gating' mechanism of pore formation by antimicrobial peptides via the membrane-thinning effect . Concentration-gated pore formation and membrane thinning by alamethicin and magainin have been observed. FEBS Lett, 1999 Sep 3, 457(3), 459 - 64 Novel cathelicidins in horse leukocytes(1); Scocchi M et al.; Cathelicidins are precursors of defense peptides of the innate immunity and are widespread in mammals . Their structure comprises a conserved prepropiece and an antimicrobial domain that is structurally varied both intra- and inter-species . We investigated the complexity of the cathelicidin family in horse by a reverse transcription-PCR-based cloning strategy of myeloid mRNA and by Southern and Western analyses . Three novel cathelicidin sequences were deduced from bone marrow mRNA and designated equine cathelicidins eCATH-1, eCATH-2 and eCATH-3 . Putative antimicrobial domains of 26, 27 and 40 residues with no significant sequence homology to other peptides were inferred at the C-terminus of the sequences . Southern analysis of genomic DNA using a probe based on the cathelicidin-conserved propiece revealed a polymorphic DNA region with several hybridization-positive fragments and suggested the presence of additional genes . A null eCATH-1 allele was also demonstrated with a frequency of 0.71 in the horse population analyzed and low amounts of eCATH-1-specific mRNA were found in myeloid cells of gene-positive animals . A Western analysis using antibodies to synthetic eCATH peptides revealed the presence of eCATH-2 and eCATH-3 propeptides, but not of eCATH-1-related polypeptides, in horse neutrophil granules and in the secretions of phorbol myristate acetate-stimulated neutrophils . These results thus suggest that eCATH-2 and eCATH-3 are functional genes, whereas eCATH-1 is unable to encode a polypeptide. Antimicrob Agents Chemother, 1999 Sep, 43(9), 2311 - 3 Antimicrobial susceptibility testing of Chlamydia trachomatis using a reverse transcriptase PCR-based method; Cross NA et al.; The conventional method for antimicrobial susceptibility testing of Chlamydia trachomatis is subjective and potentially misleading . We have developed a reverse transcriptase PCR (RT-PCR)-based method which is more sensitive and less subjective than the conventional method . Using 16 strains of C . trachomatis in triplicate assays, we found the RT-PCR method consistently more sensitive than the conventional technique for all eight antimicrobials tested, with resultant MICs determined by RT-PCR ranging from 1.6-fold higher (erythromycin) to >/=195-fold higher (amoxicillin). Antimicrob Agents Chemother, 1999 Sep, 43(9), 2236 - 9 In vitro activities of BMS-207147 against over 600 contemporary clinical bloodstream isolates of Candida species from the SENTRY Antimicrobial Surveillance Program in North America and Latin America; Diekema DJ et al.; We compared the in vitro activity of BMS-207147, an investigational triazole, with those of itraconazole and fluconazole against 613 clinical bloodstream isolates of Candida spp . collected from SENTRY participating hospitals during 1997 and 1998 . Overall, BMS-207147 was the most active azole against all Candida spp . While both BMS-207147 and itraconazole displayed a stepwise decrease in activity against isolates for which the fluconazole MICs were elevated, BMS-207147 had two- to fourfold greater activity than itraconazole both against Candida spp . that were dose-dependently fluconazole susceptible and against those that were fluconazole resistant. Antimicrob Agents Chemother, 1999 Sep, 43(9), 2170 - 5 A new azole derivative of 1,4-benzothiazine increases the antifungal mechanisms of natural effector cells; Pitzurra L et al.; The most widely used drug for treatment of candidiasis is fluconazole (FCZ) . Recently, a new derivative of 1,4-benzothiazine, compound FS5, was developed . FS5 had an appreciable protective effect against murine candidiasis . The present study was designed to dissect the antifungal mechanisms triggered by FS5 and to establish whether this compound could enhance the antimicrobial abilities of natural effector cells . The results show that intraperitoneal injection of FS5 in mice (i) induced an increase in circulating neutrophil levels comparable to that observed in FCZ-treated mice; (ii) enhanced phagocytosis and the killing activities of macrophages (Mphis) isolated from the spleen or peritoneal cavity, with the latter effect correlating with induction of nitric oxide synthesis and production by Mphis; and (iii) increased the levels of expression and synthesis of tumor necrosis factor alpha . These results suggest that the compound-induced synthesis of antimicrobial and proinflammatory molecules by heterogeneous Mphi populations is part of the beneficial effect of FS5 exerted against murine candidiasis. Infect Dis Clin North Am, 1999 Sep, 13(3), 735 - 50 Nosocomial bacterial meningitis, including central nervous system shunt infections; Morris A et al.; Nosocomial bacterial meningitis and CSF shunt infections result in considerable morbidity and mortality, necessitating an organized and thoughtful approach to prevention, diagnosis, and management . Prophylactic antibiotics appear to reduce the rate of postcraniotomy meningitis often caused by S . aureus . On the other hand, prophylactic antibiotics do not appear to reduce the risk of developing a CSF shunt infection . CSF shunt infections usually require shunt removal and antimicrobial chemotherapy to effect a successful outcome. Infect Dis Clin North Am, 1999 Sep, 13(3), 595 - 618 Pharmacokinetics and pharmacodynamics of antibiotics in meningitis; Andes DR et al.; The penetration of antimicrobials into the CSF is dependent on lipid solubility, molecular size, capillary and choroid plexus efflux pumps, protein binding, and the degree of inflammation . Penicillins, certain cephalosporins, carbapenems, fluoroquinolones, vancomycin, and rifampin provide the highest ratios of CSF levels to the MBC for common infecting organisms . For beta-lactam antibiotics, it is the duration of time that CSF concentrations exceed the MBC that determines the rate of bactericidal activity . It appears that levels should exceed the MBC for more than 50% of the dosing interval . The peak/MBC and AUC/MBC ratios are important determinants of efficacy for aminoglycosides and fluoroquinolones . Once-daily dosing of aminoglycosides is as effective as multiple-daily dosing regimens in experimental meningitis, probably because of drug-induced prolonged persistent effects . Fluoroquinolones do not produce as prolonged persistent effects and are slightly less effective when administered once daily . Although steroid use can reduce the penetration and decrease the bactericidal activity of some antimicrobials, such as vancomycin, in experimental meningitis, the clinical impact of steroid use in human meningitis is still unclear. Infect Dis Clin North Am, 1999 Sep, 13(3), 549 - 77, vi Models of experimental bacterial meningitis . Role and limitations; Koedel U et al.; The seriousness of bacterial meningitis has encouraged the development of animal models that characterize complex pathogenetic and pathophysiologic mechanisms, provide evaluation of pharmacokinetic and antimicrobial effects of antibiotics (especially since the worldwide emergence of multiresistant bacteria), and establish new adjuvant treatment strategies (e.g., use of anti-inflammatory agents) . The information obtained from an animal model depends on the site of inoculation . For example, using intranasal, intravenous, subcutaneous, or intraperitoneal inoculation, it is the bacterial and host factors that determine the development of bacteremia and the potential for a pathogen to invade the central nervous system that primarily are studied . In contrast, experimental models using direct inoculation into the cerebrospinal fluid can reliably produce lethal infections over a predictable time course . Furthermore, because adult animals will not reliably develop meningitis after intranasal or intraperitoneal challenge, infant animals are used . Because these models bypass the natural dissemination of bacteria from the intravascular compartment to the central nervous system, the pathogenesis is artificial . These models, however, are extremely useful for the study of pathogen and host factors leading to meningeal inflammation and resulting complications, and for evaluating potentially useful agents for treatment therapy . During the past decade, the design of clinical studies has been stimulated by findings obtained from these animal models. Cell Tissue Res, 1999 Aug, 297(2), 213 - 22 Immunocytochemical localization of substance P neurokinin-1 receptors in rat gingival tissue; Kido MA et al.; The distributions of substance P (SP) and the neurokinin-1 receptor (NK1-R), the receptor preferentially activated by SP, were examined in rat gingiva by immunocytochemical methods with light and electron microscopy . SP-immunoreactive nerve fibers were located preferentially in the junctional epithelium (JE) but few in the other oral and oral sulcular epithelia . NK1-R immunoreactivity was found in the endothelial cells (capillaries and postcapillary venules underlying the JE) . NK1-R-labeled and -unlabeled unmyelinated nerve fibers were located close to the blood vessels and partially or completely covered by a Schwann cell sheath . In the JE, labeled naked axons without Schwann cell sheaths were observed . Neutrophils and macrophages in the connective tissue underlying the JE and in the JE were also labeled with NK1-R . Furthermore, NK1-R was found in the JE cells . Basically, immunoreaction products for NK1-R were found throughout various cells (endothelial cells, neutrophils, and JE cells) at invaginations of the plasma membrane and in vesicular and granular structures that are probably endosomes and are found close to both the plasma membrane and the nucleus . This is a first report, demonstrating the presence of NK1-R in the gingival tissue in the normal nonstimulated condition . Furthermore, it is thought that SP may modulate the permeability of blood vessels beneath the JE, the production of antimicrobial agents in neutrophils, and the proliferation and endocytotic ability of JE cells through NK1-R. Aliment Pharmacol Ther, 1999 Aug, 13(8), 1079 - 84 One-week ranitidine bismuth citrate in combinations with metronidazole, amoxycillin and clarithromycin in the treatment of Helicobacter pylori infection: the RBC-MACH study; Sung JJ et al.; BACKGROUND: We have previously shown that ranitidine bismuth citrate (RBC)-based triple therapy is comparable to proton pump inhibitor-based triple therapy in eradicating Helicobacter pylori infection . AIM: To test the efficacy of different combinations of antimicrobials with RBC in the treatment of H . pylori infection . METHODS: Dyspeptic patients with H . pylori infection were prospectively randomized to receive one of the following regimens: (i) RBC 400 mg, amoxycillin 1 g, clarithromycin 500 mg {RAC}; (ii) RBC 400 mg, metronidazole 400 mg, clarithromycin 500 mg {RMC}; (iii) RBC 400 mg, metronidazole 400 mg, tetracycline 1 g {RMT} (all given twice daily for 1 week); or (iv) RBC 400 mg plus clarithromycin 500 mg twice daily for 2 weeks {RC-2} . Endoscopy (rapid urease test and culture) and 13C-urea breath test (UBT) were performed before randomization . Four weeks after finishing medication, the 13C-UBT was repeated in all cases and endoscopy was offered to patients with peptic ulcers . RESULTS: Four hundred patients were randomized but in two (one in the RAC group and one in the RMC group) H . pylori infection was not confirmed . Successful eradication of H . pylori (intention-to-treat analysis and 95% CI) of RAC (86% {79-93%}), RMC (90% {84-96%}), RMT (79% {71-87%}) and RC-2 (82% {75-90%}) were comparable, with a trend favouring clarithromycin-containing triple therapy regimens . Among 276 isolates tested for antibiotic sensitivity, primary resistance to metronidazole, clarithromycin and amoxycillin was found in 56%, 2% and 0.4%, respectively . When given RMC or RMT, patients infected by metronidazole-resistant H . pylori had success in eradicating H . pylori similar to patients infected by metronidazole-sensitive H . pylori . CONCLUSION: One-week RBC triple therapy is effective in curing H . pylori infection. Aliment Pharmacol Ther, 1999 Aug, 13(8), 1047 - 55 A systematic review of Helicobacter pylori eradication therapy--the impact of antimicrobial resistance on eradication rates; Houben MH et al.; BACKGROUND: We systematically reviewed all available data in the literature to determine the overall eradication rates of currently advised Helicobacter pylori eradication regimens and to resolve conflicting evidence on the impact of antimicrobial resistance on the eradication rates . METHODS: A comprehensive search of all published trials on H . pylori eradication therapy was carried out via an electronic database search, hand-searching and checking reference lists of pharmaceutical companies and other reviews . Full papers and abstracts in the English language which study currently advised eradication regimes were included . RESULTS: 770 study-arms were analysed . Mean eradication rates for bismuth based triple, proton pump inhibitor triple, quadruple and ranitidine bismuth citrate combination therapies vary from 65 to 92% . In case of nitroimidazole resistance, a drop in efficacy of up to 50% was found for bismuth-based triple and proton pump inhibitor-based triple therapies . For quadruple therapy, a significant difference in efficacy was found in the equal-effects analysis; however, this could not be confirmed in the random-effects analysis . In case of clarithromycin resistance, a mean drop in efficacy of 56% was found for one- and two-week clarithromycin containing proton pump inhibitor-triple therapies and of 58% for two-week ranitidine bismuth citrate combined with clarithromycin therapies . For ranitidine bismuth citrate combined with clarithromycin and nitroimidazole, no difference in efficacy was found in case of nitroimidazole or clarithromycin resistance, but data are still scarce . CONCLUSIONS: The cure rate with most regimens dropped significantly, in case of nitroimidazole-resistant strains, compared to nitroimidazole-susceptible strains . In case of clarithromycin resistance, the efficacy of most regimens is also decreased; however, data are still scarce . These data should allow physicians to make a better choice of an appropriate therapy for their patients. Proc Natl Acad Sci U S A, 1999 Aug 31, 96(18), 10086 - 91 Horseshoe crab acetyl group-recognizing lectins involved in innate immunity are structurally related to fibrinogen; Gokudan S et al.; We have characterized and cloned newly isolated lectins from hemolymph plasma of the horseshoe crab Tachypleus tridentatus, which we named tachylectins 5A and 5B (TLs-5) . TLs-5 agglutinated all types of human erythrocytes and Gram-positive and Gram-negative bacteria . TLs-5 specifically recognize acetyl group-containing substances including noncarbohydrates; the acetyl group is required and is sufficient for recognition . TLs-5 enhanced the antimicrobial activity of a horseshoe crab-derived big defensin . cDNA sequences of TLs-5 indicated that they consist of a short N-terminal Cys-containing segment and a C-terminal fibrinogen-like domain with the highest sequence identity (51%) to that of mammalian ficolins . TLs-5, however, lack the collagenous domain found in a kind of "bouquet arrangement" of ficolins and collectins . Electron microscopy revealed that TLs-5 form two- to four-bladed propeller structures . The horseshoe crab is equipped with a unique functional homologue of vertebrate fibrinogen, coagulogen, as the target protein of the clotting cascade . Our observations clearly show that the horseshoe crab has fibrinogen-related molecules in hemolymph plasma and that they function as nonself-recognizing lectins . An ancestor of fibrinogen may have functioned as a nonself-recognizing protein. J Pediatr Gastroenterol Nutr, 1999 Sep, 29(3), 302 - 7 Testing for serum IgG antibodies to Helicobacter pylori cytotoxin-associated protein detects children with higher grades of gastric inflammation; Luzza F et al.; BACKGROUND: Little information is available about the relationships between Helicobacter pylori cytotoxin-associated protein (CagA) and clinicopathologic features in children . The purpose of this study was to test whether determining serum IgG antibodies to CagA is a useful tool for detecting more severe disease . METHODS: One hundred twenty-seven consecutive children (age range, 0.75-17.8 years; median, 9.4 years) referred for gastroscopy were included in the study . Antral and corpus biopsies were taken for gastric histology and H . pylori detection . Major symptoms and endoscopic findings were recorded . A serum sample was drawn from each child and assayed for IgG antibodies CagA by a commercial enzyme-linked immunosorbent assay . RESULTS: Sixty-three (50%) children had no evidence of H . pylori infection, 28 (22%) were H . pylori positive/CagA positive, and 36 (28%) were H . pylori positive/CagA negative . There were no differences in clinical diagnosis and occurrence of any predominant symptom according to H . pylori and CagA status . Findings of antral nodularity were more frequent (p = 0.003) in H . pylori-positive/CagA-positive children than in H . pylori-positive/CagA-negative children . The gastritis score was significantly higher in H . pylori-positive/CagA-positive children than in H . pylori-positive/CagA-negative children (5.7 +/- 1.9 vs . 3.8 +/- 1.6, respectively; p = 0.0003), either in the antral (p = 0.0002) or in the corpus (p = 0.001) mucosa . Inflammation (p = 0.0001) and activity (p = 0.0001) scores were both higher in H . pylori-positive/CagA-positive children than in H . pylori-positive/CagA-negative children, but the H . pylori density score was not significantly different (p = NS) . In no case was normal gastric mucosa found in H . pylori-positive/ CagA-positive children . Lymphocytic gastritis (p = 0.0008) and lymphoid follicles (p = 0.000003) were a more frequent finding in H . pylori-positive children than in H . pylori negative children, irrespective of CagA status . CONCLUSION: Testing for serum IgG to CagA detects higher grades of gastric inflammation among children with H . pylori infection . It may be useful in targeting H . pylori-positive/ CagA-positive children for antimicrobial therapy while reducing the need for endoscopy and gastric biopsy. Immunol Res, 1999, 20(1), 15 - 27 Role of cytokines in pulmonary antimicrobial host defense; Mehrad B et al.; Host defense of the lung is characterized by a fine balance between the generation of a vigorous inflammatory response to clear pathogens and maintenance of the integrity of the alveolar gas-exchange surface . The magnitude of the inflammatory response is therefore tightly regulated by pro- and anti-inflammatory cytokine mediators . This article summarizes current information on the roles of specific cytokines in pneumonia, with particular emphasis on ongoing investigations into the role of innate immunity in bacterial and fungal pneumonia. J Pharm Pharmacol, 1999 Jul, 51(7), 797 - 801 Characterization of the carrier-mediated transport of levofloxacin, a fluoroquinolone antimicrobial agent, in rabbit cornea; Kawazu K et al.; The cornea presents a formidable barrier to drug penetration . The fluoroquinolone levofloxacin, which is an effective antimicrobial agent, has the potential to be used in the topical treatment of ocular disease . Thus, we sought to characterize how levofloxacin penetrates the cornea . To perform this characterization, we measured the time dependent permeation of levofloxacin across the isolated rabbit cornea using a diffusion chamber, and compared it with antipyrine fluxes . Levofloxacin permeation into the receiver epithelial-side bathing solution (pH = 6.5) from the donor endothelial-side (pH = 7.4) reached 3.00 nmolcm(-2) cornea after 2h, whereas in the opposite direction permeation was 1.89 nmolcm(-2) cornea . Based on the temperature-dependent effects on permeation, the calculated energy of activation for permeation, Ea, was 31.3 kcal mol(-1), whereas Ea for antipyrine, a marker of diffusion, was 11.0 kcalmol(-1) . The transport of levofloxacin from epithelium to endothelium was concentration-dependent and had both a linear and saturable component . Evaluation of the kinetic parameters, Jmax, apparent Km and k(d) showed that they were 38.78 pmol min(-1) cm(-2), 3.83 mM and 0.0135 microL min(-1) cm(-2), respectively . These results, coupled with the fact that levofloxacin permeation reached a maximum value at pH 6.5, suggest that levofloxacin transport across the cornea is carrier mediated . However, at present, it cannot be ascertained whether such a system is localized in either the corneal epithelial or the endothelial layer. J Obstet Gynaecol Res, 1999 Jun, 25(3), 205 - 7 Sonographically guided intralesional antibiotic injection for treatment of a recalcitrant pelvic abscess: a case report; Ou MC et al.; A pelvic abscess occurred in an infertile woman with an endocervical gonococcal infection after hysterosalpingographical examination . The pelvic abscess was not cured despite rigorous antimicrobial chemotherapy until two intra-abscess ceftriaxone injections were administered . This shows that antibiotics administered systemically may not reach therapeutic concentration in an abscess and an intra-abscess antibiotic injection may help to cure it. J Hosp Infect, 1999 Aug, 42(4), 303 - 12 Cost of antimicrobial treatment for nosocomial infections based on a French prevalence survey; Astagneau P et al.; An estimate of the antibiotic cost of nosocomial infections (NI) was made in a university hospital group based on data collected in adult inpatients enrolled in the French national prevalence survey in 1996 . Among the 6839 study patients, 636 (9.3%) presented with at least one NI, of these, data on antimicrobial treatment were available for 480 . The overall daily antibiotic cost was estimated between FF 49,439 and 103,526, resulting in FF 103 to 216 per infected patient . The most expensive antibiotic treatment was prescribed in intensive care patients, for pneumonia for device-related NI, or for multi-resistant bacterial infections . Non-documented NI represented about 20% of the overall antibiotic cost . Beta-lactam antibiotics, especially third generation cephalosporins, and parenteral fluoroquinolones were the most expensive antimicrobial drugs . The cost of antibiotic treatment for NI represents a significant part of hospital expenditure that should be reduced by better control of highly expensive prescriptions. Chem Biol, 1999 Sep, 6(9), 639 - 47 Interactions of (-)-ilimaquinone with methylation enzymes: implications for vesicular-mediated secretion; Radeke HS et al.; BACKGROUND: The marine sponge metabolite (-)-ilimaquinone has antimicrobial, anti-HIV, anti-inflammatory and antimitotic activities, inhibits the cytotoxicity of ricin and diptheria toxin, and selectively fragments the Golgi apparatus . The range of activities demonstrated by this natural product provides a unique opportunity for studying these cellular processes . RESULTS: Affinity chromatography experiments show that (-)-ilimaquinone interacts with enzymes of the activated methyl cycle: S-adenosylmethionine synthetase, S-adenosylhomocysteinase and methyl transferases . Known inhibitors of these enzymes were found to block vesicle-mediated secretion in a manner similar to (-)-ilimaquinone . Moreover, the antisecretory effects of (-)-ilimaquinone and inhibitors of methylation chemistry, but not brefeldin A, could be reversed in the presence of the cellular methylating agent S-adenosylmethionine . Of the enzymes examined in the activated methyl cycle, S-adenosylhomocysteinase was specifically inhibited by (-)-ilimaquinone . Consistent with these observations, (-)-ilimaquinone was shown to obstruct new methylation events in adrenocorticotrophic hormone (ACTH)-secreting pituitary cells . CONCLUSIONS: (-)-ilimaquinone inhibits cellular methylations through its interactions with S-adenosylhomocysteinase . Furthermore, these studies indicate that the inhibition of secretion by ilimaquinone is the result of the natural product's antimethylation activity . It is likely that the ability to fragment the Golgi apparatus, as well as other activities, are also related to ilimaquinone's influence on methylation chemistry. Arch Insect Biochem Physiol, 1999 Sep, 42(1), 99 - 109 Salivary glucose oxidase: multifunctional roles for helicoverpa zea? Eichenseer H, Mathews MC, Bi JL, Murphy JB, Felton GW. Labial glands of Helicoverpa zea produced a glucose oxidase (GOX), which was present in the saliva and midgut lumen . We purified GOX 23-fold by isoelectric focusing of labial gland homogenates and investigated physical and kinetic properties of the enzyme . D-glucose and 6-deoxy-D-glucose were the optimal substrates of 22 carbohydrates tested with GOX . The enzyme was not inhibited by several inhibitors of fungal GOX but was sensitive to HgCl(2) . Labial gland GOX activities varied daily during larval development with highest activities found when larvae were actively feeding . Based on pH optimum, pI, molecular weight estimate and K(m(glucose)), the insect enzyme is not derived from fungal GOXs but appears to have similar kinetic and physical attributes to other insect GOXs . Some possible functions are discussed, including antimicrobial properties, manipulating midgut O(2<B>) levels, altering host plant defense responses, and metabolizing carbohydrates . Arch . Res Microbiol, 1999 Jul-Aug, 150(6), 407 - 11 Re-evaluation of antibiotic and mercury resistance in Escherichia coli populations isolated in 1978 from Amazonian rubber tree tappers and Indians; Nascimento AM et al.; A study was carried out to assess the stability of antimicrobial susceptibility of wild isolates upon long-term storage using fifty-three Escherichia coli strains isolated in 1978 from feces of healthy children from the Amazon region in Brazil, exposed to low levels of antimicrobial agents, and examined for resistance to mercury and four antibiotics . All of the strains were kept in Lignieres medium at room temperature and were transferred to fresh media four times during this period . Thirty-five out of the 53 strains analyzed in 1978 were viable . Upon recovery, antibiotic and mercury resistance was estimated . All of the 35 strains maintained their original phenotype in a stable fashion, except for one multiresistant strain which became susceptible to kanamycin . Fifty-four percent of the strains exhibited a resistance phenotype, among which 47% had conjugative plasmids. Rozhl Chir, 1999 Mar, 78(3), 102 - 4 {Empyema of the thorax}; Vyhnanek F et al.; The authors evaluated the therapeutic procedure and results in patients with empyema of the chest . From December 1996 till June 1998 at the Surgical Clinic of the Third Medical Faculty, Charles University Prague 21 patients with empyema of the chest were hospitalized . The most frequent cause of empyema of the chest was pneumonia in 13 patients (62%) . In 16 patients (in 76%) the empyema was classified as the third stage of the disease . Decortication, the most frequent procedure, was performed in 16 patients, incl . three where it was done using videothoracoscopy . Surgical treatment was supplemented by antimicrobial treatment, either monotherapy or a combination of antimicrobial preparations . From the total number one patient died 25 days after thoracotomy and partial decortication with a mesiotheloma of the pleura . The other patients have no signs of relapse of empyema . According to the authors experience the selection of the surgical procedure depends on the stage of the disease . In the authors group decortication by the thoracotomic route was used most frequently. J Biol Chem, 1999 Sep 3, 274(36), 25330 - 4 Antimicrobial activity of a bovine hemoglobin fragment in the tick Boophilus microplus; Fogaca AC et al.; Antifungal and antibacterial activities were detected in the hemolymph and gut contents of the cattle tick, Boophilus microplus . A peptide with antibacterial activity from the tick gut contents was purified to homogeneity by reversed-phase chromatography . The molecular mass of the purified peptide was 3,205.7 Da, measured by matrix-assisted laser desorption/ionization mass spectrometry . The amino acid sequence was obtained by Edman degradation and showed that the peptide was identical to a fragment of the bovine alpha-hemoglobin . A synthetic peptide based on the sequence obtained showed characterization data identical to those of the isolated material, confirming its structure . The synthetic peptide was active in micromolar concentrations against Gram-positive bacteria and fungi . These data led us to conclude that the antibacterial activity detected in tick gut contents is the result of enzymatic processing of a host protein, hemoglobin . This activity may be used by ticks as a defense against microorganisms. Peptides, 1999, 20(5), 645 - 74 Tuftsin: on the 30-year anniversary of Victor Najjar's discovery; Siemion IZ et al.; After a short description of the results of Victor Najjar's research on tuftsin and of the discoveries done by other authors in the early stage of tuftsin investigation, the current state of work on tuftsin is presented, based mainly on the literature published in the years 1984-1997 . The presentation follows this order: the occurrence of tuftsin and retro-tuftsin sequences in proteins, their synthesis and biology, the antigenic properties of tuftsin, its influence on phagocytic cells, and other biologic activities of tuftsin, including antimicrobial, antiviral, antitumor and central effects, and the search for tuftsin superactive analogs. Cancer Lett, 1999 Aug 23, 143(1), 37 - 43 Pattern of expression of beta-defensins in oral squamous cell carcinoma; Abiko Y et al.; Human beta-defensin (hBD)-1 and hBD-2 are antimicrobial peptides that have been detected in certain types of epithelia, including the skin and oral epithelia . It has been s