Thorax, 1995 Jul, 50(7), 758 - 63 Changes in symptoms, peak expiratory flow, and sputum flora during treatment with antibiotics of exacerbations in patients with chronic obstructive pulmonary disease in general practice; Sachs AP et al.; BACKGROUND--Bacterial infections of the lower airways during an exacerbation in patients with asthma or chronic obstructive pulmonary disease (COPD) may be the cause of an exacerbation or the consequence of a viral infection or an increase in airways limitation . To determine whether bacterial infection is an important component in the pathogenesis of an exacerbation, the effects of antimicrobial treatment must be studied . METHODS--Patients with asthma or COPD seen in general practice were studied in a double blind randomised manner to investigate whether the antimicrobial drugs amoxicillin (500 mg three times daily), cotrimoxazole (960 mg twice daily), or a placebo, each when added to a short course of oral corticosteroids, can accelerate recovery from exacerbations . Patients were instructed to contact their own physician early in the morning when complaints of increased shortness of breath, wheezing, or exacerbations of cough with or without sputum production occurred . Treatment effects were evaluated over the next 14 days by studying symptom scores (wheeze, dyspnoea, cough with and without mucus production, and awakening with dyspnoea), peak expiratory flow values (PEF, expressed as % predicted), and sublingual temperature . Bacteriological study of the sputum was made at the onset of an exacerbation and 7, 21 and 35 days afterwards . RESULTS--Of 195 patients enrolled 71 (36%) contacted their physician for symptoms of an exacerbation . Symptoms improved in all three groups, improvements ranging from 0.54 to 0.75 points per day on a four point scale . PEF% predicted showed improvements in the three groups after the exacerbation, ranging from 0.34% to 0.78% predicted per day, finally returning to baseline values . Sublingual temperature did not change . Six of 71 patients consulted their physician because of a relapse between four and 24 days after the start of treatment . In only two of the 50 sputum samples, collected during an exacerbation, and which contained > or = 10(5) bacteria in culture sensitive to the chosen antibiotic given, did any benefit from antimicrobial treatment occur . During the recovery period sputum purulence improved irrespective of antibiotic treatment . CONCLUSIONS--Antibiotics given with a short course of oral prednisolone during an exacerbation do not accelerate recovery as measured by changes in peak flow and symptom scores in ambulatory patients with mild to moderate asthma or COPD when treated by their general practitioners . Moreover, antibiotics do not reduce the number of relapses after treating an exacerbation. Pediatr Infect Dis J, 1995 Jul, 14(7 Suppl), S121 - 9 Rational selection of antimicrobials for pediatric upper respiratory infections; Harrison CJ; Antibiotic selection is complicated by both emerging resistance to traditional antimicrobials in common community-acquired pathogens and increasing numbers of high potency or extended spectrum antimicrobials . This overview outlines a multistep process for antibiotic choice based on antimicrobial activity and patient acceptance . Understanding the infection (the natural history and most likely pathogens) is necessary for choosing a specific antimicrobial . Choices should be based on knowledge of local trends in and mechanisms of antimicrobial resistance . Candidate drugs should also exceed (at the site of infection) the minimum inhibitory concentration for 90% of strains of each most likely pathogen . Ideally the narrowest spectrum drug satisfying this pharmacodynamic requirement is used . However, inadequate compliance dooms even the most potent antibiotic . Therefore infrequent dosing, palatable taste or form, minimal side effects or lower cost may dictate choosing lower potency or narrower spectrum drugs to gain patient acceptance and thereby reasonable compliance. J Pharm Sci, 1995 Jul, 84(7), 895 - 902 Pefloxacine mesilate- and ofloxacin-loaded polyethylcyanoacrylate nanoparticles: characterization of the colloidal drug carrier formulation; Fresta M et al.; The entrapment of fluoroquinolones, perfloxacine mesilate (PFX) and ofloxacin (OFX), in polyalkylcyanoacrylate (PECA) nanoparticles could offer some advantages for their biological application; for examples, increasing their bioavailability, controlling the drug time-release in blood, and reducing the formation of bacterial resistance . To load these two drugs in PECA polymeric bulk, the incorporation or adsorption method was performed . These two methods were capable of influencing nanoparticle size, molecular weight, release profile, and drug-polymer association . The incorporation method, particularly for the OFX system, achieved PECA nanoparticle suspensions with a mean size value three times higher than that obtained in the absence of the drug . In contrast, negligible changes were observed for PFX systems . This preparation process also influenced the nanoparticle storage stability . The molecular weight values of the various nanoparticle preparations were also influenced; that is, the PFX-loaded systems showed an enhancement in the average molecular weight values, whereas a reduction was observed for OFX-loaded systems . The adsorption method showed no particular difference in particle size, molecular weight, and storage stability compared with nanoparticles prepared without the drugs . The nanoparticle loading capacity was higher for the colloidal systems obtained following the incorporation preparation procedure . The release of drug from the nanoparticles was biphasic for both preparation processes . The fluoro-quinolone-loaded nanoparticles showed an enhancement of the antimicrobial activity against standard bacteria strains from 2- to 50-fold compared with the free drugs. J Nat Prod, 1995 Jul, 58(7), 1047 - 55 Addition of methyl thioglycolate and benzylamine to (Z)-ligustilide, a bioactive unsaturated lactone constituent of several herbal medicines . An improved synthesis of (Z)-ligustilide; Beck JJ et al.; (Z)-Ligustilide {1} is a dihydrophthalide purported to be the active ingredient of Ligusticum plant species widely used as herbal medicines in the Orient and in Native American and Hispanic cultures . It readily underwent 1,6-conjugate addition with methyl thioglycolate in the presence of triethylamine . The methyl thioglycolate reaction also yielded a product from addition to the C-6-C-7 double bond and a diadduct from both 1,6-addition and addition to the C-6-C-7 bond . Reaction of 1 with benzylamine did not afford a 1,6-adduct, but yielded instead an N-benzyllactam, presumably formed by rearrangement from initial 1,2-addition to the carbonyl . An improved total synthesis of 1 was developed . (Z)-Ligustilide had weak antiviral properties and weak antimicrobial activity against Gram-positive, Gram-negative, and yeast microorganisms . The broad biological activity of 1 and its electrophilic reactivity are consistent with the use of Ligusticum species in folk medicine. J Med Assoc Thai, 1995 Jul, 78 Suppl 2, S91 - 4 Infusion phlebitis in medical and surgical patients in Siriraj Hospital; Danchaivijitr S et al.; A study on infusion phlebitis was done in medical and surgical departments in Siriraj Hospitals from February to April 1992 . Two hundred and eighty-one patients and 406 infusion sites were included . The infusion time was 40.6 +/- 31.9 hours . The incidence rate of phlebitis was 25.9% . There was no difference in its occurrence in medical and surgical patients . Dorsum of the hand was the site associated with low incidence and less severe phlebitis . The contrary applied to the forearm and arm . Plastic cannulae were associated with higher incidence, more severe phlebitis than steel needles, but this was not statistically significant . Intravenous antimicrobials were followed by higher incidence and more severe phlebitis . The value of early diagnosis of infusion phlebitis so as to halt its progress was also demonstrated in the study . In no case was the phlebitis, in the most severe form i.e . grade 5, encountered. J Med Assoc Thai, 1995 Jul, 78 Suppl 2, S85 - 90 Infusion-related phlebitis; Danchaivijitr S et al.; The incidence rate and risk factors of infusion-related phlebitis was studied in 1993 . Thirty-five hospitals were enrolled . Data were collected from 6,256 infusion sites . Male and female patients were almost equal . Forearms were the commonest site of infusion, followed by hand and arm respectively . In 34.1 per cent the infusion was interrupted by complications of which 6.2 per cent was phlebitis . It was mild in most cases . Increased incidence rates of infusion related phlebitis were associated with: the use of plastic cannulas, dextrose containing solutions, administration at the sites other than hand and concomitant administration of antimicrobials . The incidence rate of phlebitis rose sharply after 24 hours of infusion . It is concluded that in addition to proper insertion and good nursing care, the avoidance of the above risk factors will lead to a lower incidence of infusion-associated phlebitis. J Med Assoc Thai, 1995 Jul, 78 Suppl 2, S73 - 7 A national study on surgical wound infections 1992; Danchaivijitr S et al.; A study on SWI was done in 33 hospitals in Thailand between March 16 and May 15, 1992 involving 15,319 surgical wounds . The average incidence rate of SWI as 2.7 per cent . It was highest in provincial hospitals . Patients aged under 10 years and 51-60 years had higher rates of SWI . It was most prevalent in the surgical department followed in rank by accident and orthopaedic departments respectively . Wound types were the most important denominator of SWI; the incidence of SWI in dirty, contaminated, clean-contaminated and clean wounds were 9.7, 5.1, 1.5 and 1.3 per cent respectively . Antimicrobial prophylaxis were used in 76.7 per cent of the wounds . Ampicillin, gentamicin and cloxacillin were the commonly used drugs . Prevention of SWI needs to be improved in provincial hospitals and in the use of prophylactic antimicrobials. Chemotherapy, 1995 Jul-Aug, 41(4), 229 - 33 Concentrations of ceftibuten in bronchial secretions; Scaglione F et al.; Ceftibuten is a broad-spectrum oral cephalosporin exhibiting antimicrobial activity against a wide range of gram-negative and some gram-positive pathogens . Pharmacokinetic studies have shown that the molecule has an oral bioavailability higher than 90% of the administered dose (reaching peak serum concentrations of 5-19 mg/l after a single dose of 200 and 400 mg) . Moreover, ceftibuten has been shown to be useful in the treatment of acute lower respiratory tract infections . This study was performed to determine the distribution of ceftibuten in bronchial secretions from patients affected by the exacerbation of chronic bronchitis . Patients were treated with a single 400-mg oral dose of ceftibuten . Blood and bronchial-secretion samples were obtained just before, and at 0.5, 1, 2, 4, 8, 12, 16 and 24 h after dosing . Cells were separated from bronchial secretions by centrifugation . Ceftibuten in duplicate samples of both serum and bronchial secretion was quantified by HPLC . Ceftibuten reached peak levels 2 and 4 h after oral administration in serum and in bronchial secretions, respectively (18.12 +/- 2.13 and 9.19 +/- 3.1 mg/l, respectively) . Falling curves after the peaks showed a monoexponential decay . The absorption was very rapid both in serum and bronchial secretions, but elimination was slower in bronchial secretions than in serum. Br Vet J, 1995 Jul-Aug, 151(4), 401 - 12 Disposition of penicillin G sodium following intravenous and oral administration to Equidae; Horspool LJ et al.; The present study was designed to determine and compare the plasma disposition and pharmacokinetics of penicillin G sodium following intravenous (i.v.) administration to horses, ponies and donkeys . The plasma disposition and pharmacokinetics of penicillin G was similar in horses, ponies and donkeys (elimination half-lives--39.0, 27.3 and 31.5 min, respectively) and a dosage interval of 6-8 h would be suitable to treat infections caused by susceptible bacteria . Although penicillin G was absorbed rapidly following nasogastric administration, the systemic availability was low (0.12-0.34%), therefore oral administration would be unsuitable for systemic antimicrobial therapy in the equine . The elimination of penicillin G into the gastrointestinal tract following i.v . administration and the absorption of penicillin G from the gastrointestinal tract following oral administration were studied in two ponies with cannulated caecal fistulas . A low concentration of penicillin G (< or = 0.6 micrograms ml-1) was measured in caecal liquor following i.v . administration, however the risk of development of antimicrobial-associated colitis would be high following oral administration of penicillin G since high concentrations of drug (4.96-157.12 micrograms ml-1) were measured in caecal liquor. Br J Clin Pract, 1995 Jul-Aug, 49(4), 181 - 5 First-line treatment in acute non-dysenteric diarrhoea: clinical comparison of loperamide oxide, loperamide and placebo . UK Janssen Research Group of General Practitioners; Hughes IW; The use of antimicrobial agents for the treatment of acute diarrhoea has become more common with the introduction of quinolone compounds, which are active against most types of bacterial pathogens . Despite the fact that such drugs have been used for empirical therapy or even for prophylaxis, current opinion would restrict their use to specific groups of patients who are likely to show particular benefit from them . Non-specific therapy seems a more appropriate initial treatment for cases of acute, non-dysenteric diarrhoea . Clinical trial data are presented here comparing the effects of loperamide oxide 1 and 2 mg to those of placebo and loperamide 2 mg in this condition . All the drug preparations were significantly superior to placebo, in particular reducing the time to complete relief of symptoms to about 24 hours, as opposed to 45 hours on placebo treatment . Of these preparations, loperamide oxide 1 mg is to be preferred, as it produces fewer constipation-like episodes after treatment . The introduction of loperamide oxide 1 mg represents a useful advance in the non-specific treatment of acute, non-dysenteric diarrhoea. Boll Chim Farm, 1995 Jul-Aug, 134(7), 375 - 9 Evaluation of some arylhydrazones of p-aminobenzoic acid hydrazide as antimicrobial agents and their in vitro hepatic microsomal metabolism; Komurcu SG et al.; Benzoic acid p-amino-{(substituted phenyl/pyridyl) methylene} hydrazide derivatives were synthesised by interaction of p-aminobenzoic acid hydrazide with various aromatic aldehydes . The structures of the compounds were elucidated by use of their UV, IR, 1H-NMR and mass spectral data . These compounds were also evaluated for antimicrobial activity . The in vitro hepatic microsomal metabolism of benzoic acid p-amino-{(4-fluorophenyl)methylene}hydrazide (2d), a selected prototype from these compounds was also carried out. Antimicrob Agents Chemother, 1995 Jul, 39(7), 1489 - 92 Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648; Fujii K et al.; The mechanism of antimicrobial activity of KRM-1648 (KRM), a new rifamycin derivative with potent antimycobacterial activity, was studied . Both KRM and rifampin (RMP) inhibited RNA polymerases from Escherichia coli and Mycobacterium avium at low concentrations: the 50% inhibitory concentrations (IC50s) of KRM and RMP for E . coli RNA polymerase were 0.13 and 0.10 micrograms/ml, respectively, while the IC50s for M . avium RNA polymerase were 0.20 and 0.07 microgram/ml . Both KRM and RMP exerted weak inhibitory activity against Mycobacterium fortuitum RNA polymerase, rabbit thymus RNA polymerases, E . coli DNA polymerase I, and two types of reverse transcriptases . Uptake of 14C-KRM by M . avium reached 18,000 dpm/mg (dry weight) 1.5 h after incubation, while uptake by E . coli cells was slight . KRM was much more effective in inhibiting uptake of 14C-uracil than was RMP (IC50 of KRM, 0.04 microgram/ml; IC50 of RMP, 0.12 microgram/ml) . These findings suggest, first, that the potent antimycobacterial activity of KRM is due to inhibition of bacterial RNA polymerase and, second, that the activity of KRM against target organisms depends on target cell wall permeability. Antimicrob Agents Chemother, 1995 Jul, 39(7), 1436 - 41 Antimicrobial characterization and interrelationships of dirithromycin and epidirithromycin; Kirst HA et al.; Dirithromycin is the 9-N,11-O-oxazine adduct formed from 9(S)-erythromycylamine and 2-(2-methoxyethoxy)acetaldehyde in which the methoxyethoxymethyl substituent on the oxazine ring possesses the R configuration . Epidirithromycin is its isomer in which the methoxyethoxymethyl substituent has the opposite (S) configuration . Both compounds readily epimerize in solution, reaching an equilibrium ratio of 85:15 in favor of dirithromycin, given sufficient time . The rate of interconversion is dependent upon pH, temperature, and solvent . An enriched sample of epidirithromycin (95% purity) was synthesized by condensing erythromycylamine and 2-(2-methoxyethoxy)acetaldehyde in diethyl ether as the reaction solvent, and the product was fully characterized by nuclear magnetic resonance spectroscopy and high-pressure liquid chromatographic (HPLC) analysis . Both oxazine derivatives readily hydrolyze to erythromycylamine, so all three compounds exhibit the same antibiotic activity in vitro . In order to determine whether dirithromycin itself possesses significant antimicrobial activity without initial hydrolysis to erythromycylmine, inhibition of cell-free ribosomal protein synthesis was measured under conditions which were adapted to minimize hydrolysis, as measured by analytical HPLC in parallel experiments . Under these particular conditions, inhibition of ribosomal protein synthesis by dirithromycin was < 10% of the value measured for erythromycylamine. Biochem Biophys Res Commun, 1995 Jun 26, 211(3), 1053 - 62 Isolation and sequence determination of 6- and 8-kDa precursors of human neutrophil peptides from bone marrow, plasma and peripheral blood neutrophils; Nakazato M et al.; Human neutrophil peptides (HNPs) are 29 to 30 amino acid antimicrobial peptides localized in the azulophil granules in neutrophils . We isolated endogenous molecular forms of HNPs from normal human bone marrow, plasma and peripheral blood neutrophils and determined their primary structures to investigate their post-translational processing . HNPs initially are synthesized as 94 amino acid precursors that produce 75 amino acid pro-HNPs by cleavage of a signal peptide . The majority of pro-HNPs was processed to 56 amino acid intermediates by preaspartate proteolytic cleavage in the bone marrow then to mature HNPs in peripheral blood neutrophils . Part of pro-HNPs was released into the plasma, in which they constituted 25-30% of the HNP molecules . Pro-HNPs and their mRNAs were detected both in peripheral blood neutrophils and bone marrow . Identification of the post-translational processing products of HNPs should provide a better understanding of the biosynthesis of the peptides. Presse Med, 1995 Jun 10, 24(21), 992 - 8 {Interaction between anti-infective agents and phagocytes}; Labro MT; Metchnikoff was one of the first to suggest the need for cooperation between phagocytes and therapeutic agents for the benefit of health . After the hopes raised by the discovery and the tremendous development of antimicrobials, there is now a creeping pessimism faced with the parallel evolution of resistance strategies in the microbial world . Interest has now turned to the use of immunomodulatory drugs, alone or combined with anti-infectious agents . Another tendency is based on the possibility that antimicrobials directly interfere with the host-microbe interplay . This review is aimed at summarizing our knowledge of the interactions between antimicrobial agents and the phagocyte, still a cornerstone in the natural defence system . Despite the problems inherent in the analysis and clinical relevance of effects observed in the test tube this developing area of research could provide new therapeutic solutions beyond the year 2000. JAMA, 1995 Jun 7, 273(21), 1679 - 80 Gastroenterology and hepatology; Koff RS; Development of colon cancer is now believed to result from a series of inherited or acquired mutations in DNA . Convincing evidence that colonoscopic polypectomy prevents colorectal cancer is now available . A consensus panel recommended that all patients with duodenal and gastric ulcers who are infected with H pylori on first presentation be treated with antimicrobial agents. J Philipp Dent Assoc, 1995 Jun-Aug, 47(1), 19 - 26 An update on the non-surgical treatment of periodontal disease; Estaniel CP; For the resolution of gingivitis, the mechanical therapy of scaling and polishing in combination with an efficient plaque control system remains the most efficient therapeutic package . Topical antimicrobial, particularly mouth rinses may aid in plaque control, and irrigation devices enhance their efficacy but are not mandatory to the treatment . In the case of periodontitis, mechanical therapy in addition to the use of antimicrobial agents have proven to be highly efficient, with successful clinical parameters achieved as endpoints . Because of the strong bacterial component of the disease process, its elimination with chemotherapeutic agents becomes a reality . Delivery systems of antimicrobials to the site of action have large potential as adjunct to the existing modalities of treatment . This will especially be applicable in moderate to severe cases where access is difficult . Future directions in research lead us to the potentials of non-steroidal anti-inflammatory agents that interfere with prostaglandin metabolism . Possible alteration of the periodontal disease process at some point in time may be a reality . Inevitably, at some point, especially in severe cases, surgical intervention becomes a necessity as no mechanical therapy is possible because of inaccessibility . In which case, the point of contention is that for periodontal disease, sound principles of anti-infective therapy must be employed constantly. Scanning Microsc, 1995 Jun, 9(2), 501 - 7 The morphological effects of two antimicrobial peptides, hecate-1 and melittin, on Escherichia coli; Henk WG et al.; The effects of the 26 amino acid, cationic, amphipathic, antibacterial peptide melittin and hecate-1, a 23 amino acid analog of it, on the gram negative bacterium Escherichia coli were investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and freeze-fracture . Both peptides killed virtually all bacteria at the peptide concentration and cell density used . TEM and SEM revealed aggregates of bacteria entangled with material extruded from the bacterial surfaces . SEM revealed irregular bacterial surfaces with bleb-like projections . TEM and freeze-fracture indicate that the bacterial inner and outer membranes, as well as the peptidoglycan layer between, were extensively damaged . The cytoplasmic contents of the cells, however, did not appear radically disturbed, providing little evidence for osmotically induced cytolysis. J Chemother, 1995 Jun, 7 Suppl 2, 111 - 23 The role of aminoglycosides in modern therapy; Beaucaire G; Aminoglycosides remain a mainstay of antimicrobial therapy, especially for treatment of serious Gram-negative infections . Aminoglycosides represent cornerstone of antibiotic combination therapy and, despite their well-documented toxicity, continue to be used because of their excellent bactericidal efficacy and their limited tendency towards the development of resistance during therapy . Various factors, particularly their concentration-dependent bactericidal activity and prolonged post-antibiotic effect, indicate that aminoglycosides can be given effectively in a once-daily dosing regimen . Once-daily dosing has also been shown to reduce toxicity in animal studies . Although once-daily administration of amino-glycosides also has a number of practical advantages, questions remain concerning the indications that should be treated, the optimal peak and trough serum concentrations that should be attained, and the requirement for an initial loading dose . The present article examines the role of aminoglycosides in the treatment of serious infections and reviews the evidence presently available to answer questions on their appropriate clinical use. J S Afr Vet Assoc, 1995 Jun, 66(2), 71 - 3 Melioidosis in a goat; Van der Lugt JJ et al.; Melioidosis was diagnosed in an adult Boer goat ewe . The owner initially noticed swelling of one half of the udder . Several firm nodules developed in the affected part of the udder 2 weeks later . At necropsy, abscesses containing a creamy to yellowish-green exudate were found in the mammary gland and one of the kidneys . Pure cultures of Pseudomonas pseudomallei were isolated from the abscesses in the udder and inoculation of male guinea-pigs with the causative bacterium, produced a Shwartzman reaction in the testis and serositis as well as necrotic lesions, in parenchymatous organs . The isolate showed sensitivity to amoxycillin-clavulanate, but resistance to a number of other antimicrobials . This appears to be the first case of melioidosis in a domestic animal in South Africa. Antiviral Res, 1995 Jun, 27(3), 263 - 70 Topical treatment of recurrent mucocutaneous herpes with ascorbic acid-containing solution; Hovi T et al.; We carried out a randomized double-bind, placebo-controlled clinical trial on the topical treatment of recurrent mucocutaneous herpes with a strong water solution of Ascoxal, an ascorbic acid-containing pharmaceutical formulation with mucolytic and non-specific antimicrobial activities . The lesion was firmly pressed with a cotton wool pad soaked in drug solution 3 times for 2 min with 30-min intervals on the first day only . Evaluation of the effects was by daily recordings of several different symptoms, including the presence and severity of erythema, induration, papulae or vesicles and scab by both the patient and a trained nurse, and by virus culture . Fourteen episodes with active treatment and 18 with the placebo were analyzed . According to the patients' records, the active treatment resulted in a significantly smaller cumulative number of days with scab (P < 0.01), or with any remaining symptom (P < 0.02) and significantly fewer occasions of worsening of any symptom after the treatment (P < 0.05) . According to the nurse's records, the persistence of scabs was significantly shorter in the active treatment group (means 3.4 vs 5.9 days, P = 0.03) . Virus culture after the first day of treatment yielded herpes simplex virus significantly less frequently in the active treatment group than in the placebo group (P < 0.01) . In conclusion, a brief treatment with this ascorbic acid-containing preparation resulted in statistically significant clinical and antiviral effects, which calls for further and more extensive studies with a more intensive treatment schedule. Pathol Biol (Paris), 1995 Jun, 43(6), 483 - 7 {Effect of the molecular structure of azithromycin on pharmacokinetics and the antimicrobial activity}; Pechere JC; Azithromycin possesses in position 9 of the lactone cycle a nitrogen atom which provides a second site of protonation . Hence, and compared to erythromycin, azithromycin is more stable in the gastric environment, enjoys improved digestive absorption and improved digestive toleration, displays much higher intracellular accumulation responsible for prolonged serum and tissue half-lives, which allows simplified therapeutic schedules . It is also postulated that improved activity against Gram negative isolates such as H . influenzae and B . catarrhalis results from the same structural particularities. Mol Biochem Parasitol, 1995 Jun, 72(1-2), 11 - 22 Trypanosoma brucei dihydrofolate reductase-thymidylate synthase: gene isolation and expression and characterization of the enzyme; Gamarro F et al.; The gene encoding the bifunctional dihydrofolate reductase (DHFR) and thymidylate synthase (TS) of Trypanosoma brucei brucei has been isolated and expressed in Escherichia coli, and the enzyme has been purified and characterized . The coding sequence of the DHFR-TS is 1581 nt, encoding a 527-amino-acid protein of 58,505 Da . The gene was expressed under control of the trc promoter in pKK233-2 . The resulting expression plasmid conferred trimethoprim resistance to E . coli DH5 alpha and complemented the TS deficiency in chi 2913recA cells indicating the presence of active DHFR and TS . DHFR-TS was purified by methotrexate-Sepharose chromatography . In addition to the full-length enzyme, the purified enzyme contained 31 and 31.5-kDa forms of the enzyme that cross-reacted with anti-L . major DHFR-TS antibodies; one was truncated at the N- and C termini, and the other at only the C terminus . Despite the presence of sufficient TS for complementation, TS activity was not detectable in the crude extract or in the final purified enzyme preparation . Although the majority of the enzyme appears to be full length, it is possible that the TS domain has been degraded by one of more residues, which would inactivate the ability to synthesize thymidylate . Kinetic analysis of DHFR yielded kcat and Km values similar to those of related enzymes . The T . brucei DHFR has Ki values for antimicrobial antifolates pyrimethamine and trimethoprim which are significantly lower than the closely related T . cruzi or L . major DHFRs or than human DHFR. J Leukoc Biol, 1995 Jun, 57(6), 805 - 12 CAP37, a neutrophil-derived multifunctional inflammatory mediator; Pereira HA; Cationic antimicrobial protein of M(r) 37 kDa (CAP37) is a multifunctional protein isolated from the granules of human neutrophils, which has important implications in host defense and inflammation . CAP37 was initially recognized for its strong antibiotic activity against Gram-negative bacteria and was viewed as a component of the oxygen-independent killing mechanism of the neutrophil . However, we now know that CAP37 has more far reaching and important functions . It is a physiological protein released during inflammation with a high potential of regulating monocyte/macrophage functions, such as chemotaxis, increased survival, and differentiation . Recently, it has been demonstrated that CAP37 binds endotoxin . It has the structure of a serine esterase but lacks enzymatic activity . The bactericidal and endotoxin binding domains of the molecule have been delineated . The identification of functional peptides should provide new insight into the mechanisms of endotoxin binding, antimicrobial activity, and chemotaxis and in the long term provide key insights into therapies for treating infections and endotoxic shock. FEMS Microbiol Lett, 1995 Jun 1, 129(1), 1 - 10 Pore-forming bacteriocins of gram-positive bacteria and self-protection mechanisms of producer organisms; Abee T; Proteinaceous antimicrobial compounds are produced by a diversity of species ranging from bacteria to humans . This review focuses on the mode of action of pore-forming bacteriocins produced by Gram-positive bacteria . The mechanism of action of specific immunity proteins, which protect the producer strains from the lethal action of their own products (producer self-protection), are also discussed. Surgery, 1995 Jun, 117(6), 656 - 62 Protective effects of a novel 32-amino acid C-terminal fragment of CAP18 in endotoxemic pigs; VanderMeer TJ et al.; BACKGROUND . Cationic antimicrobial protein of 18 kd (CAP18) is a neutrophil-derived peptide that binds lipopolysaccharide (LPS) with high affinity . We hypothesized that CAP18(106-137), a novel synthetic 32-amino acid C-terminal fragment of CAP18, would neutralize the physiologic derangements induced by LPS in anesthetized swine . METHODS . Pigs were randomly allocated into three groups . Those in the LPS group (n = 6) were infused with LPS (3 micrograms/kg/hr for 4 hours) . Pigs in the LPS/CAP18 group (n = 6) were challenged with LPS (3 micrograms/kg/hr for 4 hours) and also treated with CAP18(106-137) (4 mg/kg/hr for 4 hours) . Pigs in the RL group (n = 4) received neither LPS nor CAP18(106-137) . RESULTS . Treatment with CAP18(106-137) blocked LPS-induced increases in plasma levels of 6-keto-prostaglandin F1 alpha and tumor necrosis factor-alpha and prevented LPS-induced changes in cardiac output, arterial PO2, phagocyte activation, and peripheral leukocyte count . Changes in circulating concentrations of thromboxane B2, mean pulmonary artery pressure, and dynamic pulmonary compliance were attenuated in the LPS/CAP18 group . CONCLUSIONS . Treatment with CAP18(106-137) neutralizes many of the deleterious effects of LPS in pigs. Postgrad Med, 1995 Jun, 97(6), 147 - 8, 151-4 Vertebral osteomyelitis . How to differentiate it from other causes of back and neck pain; Strausbaugh LJ; Vertebral osteomyelitis, an uncommon infection, usually presents with the very common symptom of neck or back pain . Awareness of this disorder and its distinctive features aids physicians in prompt ordering of appropriate imaging studies, which usually lead to the diagnosis . Early diagnosis, identification of the infecting microbe, and appropriate antimicrobial therapy are the keys to preventing complications and reducing the need for surgical intervention. Clin Exp Immunol, 1995 Jun, 100(3), 434 - 9 The inhibitory effects of Mycobacterium tuberculosis on MHC class II expression by monocytes activated with riminophenazines and phagocyte stimulants; Wadee AA et al.; The expression of MHC class II antigens by peripheral blood monocytes from normal individuals was investigated . Class II expression as determined by a cell ELISA was effectively induced by various phagocyte stimulants . A further aspect of our study investigated the effects of clofazimine, a riminophenazine antimicrobial agent and its analogue, B669, on class II expression . Both agents at concentrations attainable in vivo increased the expression of MHC class II antigens . A 25-kD glycolipoprotein derived from Mycobacterium tuberculosis that inhibits phagocyte functions has previously been described . This component significantly reduced the expression of MHC class II antigens induced by the riminophenazines, clofazimine and B669, interferon-gamma (IFN-gamma) or opsonised yeast when added at the initiation of experiments . The riminophenazines could not restore the decrease in class II antigen expression previously inhibited by the 25-kD mycobacterial fraction . However, cultures prestimulated with the riminophenazines or phagocyte stimulants were unaffected by the 25-kD mycobacterial fraction . The results suggest the potential use of these agents as modulators of phagocyte function. J Infect Dis, 1995 Jun, 171(6), 1491 - 6 Multiple antimicrobial resistance of pneumococci in children with otitis media, bacteremia, and meningitis in Slovakia; Reichler MR et al.; Penicillin-resistant pneumococci have been isolated from middle ear fluid, blood, cerebrospinal fluid, and nasopharyngeal secretions of several hundred children in Slovakia since 1985; 116 of these isolates were serotyped and tested for susceptibility to antimicrobial drugs at the Centers for Disease Control and Prevention . To define the prevalence of drug-resistant pneumococci and identify risk factors for infection, laboratory and medical records were reviewed . Nearly all (96%) of the resistant strains tested were serotype 14 . Of these, all were resistant to penicillin (MIC, 4-16 micrograms/mL); most were resistant to cefaclor, erythromycin, tetracycline, and chloramphenicol; and many had decreased susceptibility to trimethoprim-sulfamethoxazole and ceftriaxone . Frequent antibiotic use, prior hospitalization, and length of hospital stay (P < .001 for all 3) were associated with infection with resistant strains . These findings suggest the need for routine screening of pneumococcal isolates for penicillin resistance and highlight the importance of controlling globally the spread of resistant pneumococci. Pediatr Clin North Am, 1995 Jun, 42(3), 665 - 85 Resistance to antifungal agents; DeMuri GP et al.; The marked increase in the number of patients with AIDS and other forms of immunocompromise has resulted in the emergence of fungi as predominant pathogens in many institutions . Unfortunately, with the widespread use of antifungal agents to combat these infections, reports of resistance to antifungal agents have proliferated . In the present environment, the occurrence of resistance to antifungal agents is neither rare nor of negligible clinical importance . The expanding demand for antifungal agents mandates a new sense of vigilance for resistance . Although newly proposed standards for in vitro susceptibility testing should help to remove the ambiguity surrounding quantitative measurement of fungal resistance, lessons learned in the treatment of bacteria clearly now apply to fungi also: prolonged use of an antimicrobial agent will result in the selection of resistant organisms . The enlarging spectrum of resistance to antifungal agents must prompt aggressive searches for new modes of therapy . Strategies to inhibit fungal colonization, to augment host defenses, or to develop novel antifungal agents from Pseudomonas syringae or from peptide nanotubes are helping to solve this pressing clinical need. Pediatr Clin North Am, 1995 Jun, 42(3), 519 - 37 Antibiotic-resistant pneumococci; Schreiber JR et al.; Antibiotic-resistant pneumococci are increasing in prevalence in the United States and are present in numerous areas of the country . Simple screening methods available to identify penicillin-resistant strains and improved national surveillance programs should give more accurate data on the frequency that these resistant pneumococci are causing disease . It is logical to assume that, as the prevalence of nasopharyngeal carriage of these strains increases, more and more invasive infections in children will be caused by antibiotic-resistant pneumococci in the future . The treatment of invasive infections, particularly meningitis, caused by penicillin-resistant and multiply resistant strains, and the treatment of AOM caused by pneumococci resistant to all currently available oral preparations remains problematic . Controlled studies are necessary to determine optimal antimicrobials or other interventions necessary to treat these infections . Finally, prevention of colonization and subsequent infection by the pneumococcus assumes new urgency as antimicrobial resistance spreads . Potentially effective vaccines, such as the new polysaccharide-protein conjugate vaccines that will have efficacy in small children, are currently in early field trials and ultimately may be the best mechanism to deal with the spread of these organisms. J Pharm Pharmacol, 1995 Jun, 47(6), 503 - 9 Zinc sulphadiazines: novel topical antimicrobial agents for burns; Lee AR et al.; Two new zinc sulphadiazine (Zn(SD)2)-amine complexes, zinc sulphadiazine-methylamine (Zn(SD)2(CH3NH2)2) and zinc sulphadiazine-ethylenediamine (Zn(SD)2(C2H8N2)3.H2O), were prepared and compared with silver sulphadiazine (AgSD) . The compounds were readily obtained by reaction of zinc nitrate hexahydrate with sulphadiazine or its salt in methylamine and ethylenediamine, respectively . Structure was established by X-ray crystallography and ultraviolet-visible, infrared and nuclear magnetic resonance spectroscopy . The products were effective, in-vitro, against Gram-positive and Gram-negative bacteria as well as fungus . However, their activity is partially reversed by p-aminobenzoic acid . Further investigations in burned mice revealed that these compounds displayed a potential value in the prevention and treatment of wound healing, and diminution of mortality and weight loss . The toxicity of Zn(SD)2 derivatives was much lower than that of AgSD . The better aqueous solubility and skin permeability may explain the reason for their superiority over AgSD in the efficacy for topical therapy . Zn(SD)2(CH3NH2)2 was consistently more potent and was chosen for further development in clinical uses . The similarity in complexation between Zn(SD)2(CH3NH2)2 and AgSD may be significant to distinguish that from any other Zn(SD)2 derivative in bioactivity. Burns, 1995 Jun, 21(4), 310 - 2 Serious silver sulphadiazine and mafenide acetate dermatitis; McKenna SR et al.; Infrequently reported, serious allergic reactions to topical antimicrobial agents used in the treatment of burn injuries are a potential source of confusion . To avoid misdirected therapy, an understanding of the manifestations of such reactions is important . Two recent cases of serious allergic reactions, one to silver sulphadiazine, one to mafenide acetate, are presented and the literature is reviewed. Int J Dermatol, 1995 Jun, 34(6), 434 - 7 Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris; Shalita AR et al.; BACKGROUND . Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne . Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance . METHODS . In our double-blind investigation, the safety and efficacy of topically applied 4% nicotinamide gel was compared to 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris . Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel (n = 38) or 1% clindamycin gel (n = 38) twice daily for 8 weeks . Efficacy was evaluated at 4 and 8 weeks using a Physician's Global Evaluation, Acne Lesion Counts, and an Acne Severity Rating . RESULTS . After 8 weeks, both treatments produced comparable (P = 0.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne; 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved . Both treatments produced statistically similar reductions in acne lesions (papules/pustules; -60%, nicotinamide vs . -43%, clindamycin, P = 0.168), and acne severity (-52% nicotinamide group vs . -38% clindamycin group, P = 0.161) . CONCLUSIONS . These data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris . Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris. Vet Microbiol, 1995 Jun, 45(1), 1 - 10 In vitro efficacy of several antimicrobial combinations against Brucella canis and Brucella melitensis strains isolated from dogs; Mateu-de-Antonio EM et al.; In vitro efficacy of tetracyclines, aminoglycosides, fluoroquinolones, rifampin and macrolides and their combinations against four Brucella canis and two B . melitensis strains isolated from dogs was evaluated by means of inhibition tests: minimal inhibitory concentration (MIC) and fractional inhibitory concentrations (FIC) and by bactericidal tests: minimal bactericidal concentrations (MBC) and kill-time experiments . In inhibition studies, tetracyclines showed the lowest MICs of all compounds tested (0.06-0.50 mg/l) . However, doxycycline did not inhibit growth of B . canis D-519 strain at concentrations lesser than 1 mg/l . Most strains were resistant to macrolides . Chequerboard MIC titrations showed synergy between enrofloxacin and aminoglycosides against B . canis RM 6/66 reference strain and between doxycycline and streptomycin against B . canis D-519 strain . Combinations of tetracyclines and aminoglycosides were at the limit of synergy for B . canis RM 6/66 strain (FIC = 0.56) . Combination of doxycycline and rifampin seemed to be antagonistic against B . canis M-strain (FIC = 3) . Other combinations studied were indifferent or additive against all other strains . In bactericidal studies, aminoglycosides, fluoroquinolones and rifampin showed bactericidal activity at 1-4 x MIC but tetracyclines or macrolides did not kill brucellae below 8 x MIC . Results of kill-time experiments indicated that streptomycin was the antimicrobial agent tested which more rapid killed brucellae . In most cases, doxycycline did not kill brucellae in 96 h of incubation . Which using rifampin alone, some inocula of B . canis strains RM 6/66, D-519 and M- showed regrowth after 24 h of incubation . Retesting of these regrowing brucellae showed an increased MIC indicating development of phenotypic resistance . Testing of antimicrobial combinations in kill-time experiments indicated synergy between enrofloxacin and streptomycin and antagonism between rifampin and doxycycline both for B . canis RM 6/66 strain. J Small Anim Pract, 1995 Jun, 36(6), 267 - 70 Omental pedicle used to manage a large dorsal wound in a dog; Smith BA et al.; An eight-year-old miniature schnauzer was presented with full thickness skin necrosis over most of the back, probably caused by a chemical burn . Management consisted of debridement, bandaging, hyperbaric oxygen therapy, topical application of tris-EDTA and oral administration of antimicrobials . A pedicle created from the greater omentum was used to fill the wound and provide a vascular bed for a full thickness meshed skin graft . Despite epidermal loss from the majority of the graft, the wound healed with acceptable appearance and function . This is the first clinical case described in the veterinary literature using an omental pedicle in prepare a free skin graft bed. J Clin Microbiol, 1995 Jun, 33(6), 1492 - 5 Seroepizootiology of Helicobacter pylori gastric infection in nonhuman primates housed in social environments; Dubois A et al.; We determined the seroepizootiology of Helicobacter pylori infection in rhesus monkeys . Plasma was obtained from 196 animals (age range, 1 to 22 years) that were housed in social environments, either in indoor gang cages, in outdoor corrals, or in free-ranging forested conditions . Plasma immunoglobulin G levels were determined with a specific enzyme-linked immunosorbent assay, and the cutoff immunoglobulin G value for H . pylori seropositivity was determined from a study of 25 monkeys whose infection status was assessed by light microscopy and culture . One-year-old animals of both genders in all housing conditions had the lowest rate of positivity (60% in monkeys 1 year old versus 81% in monkeys 2 to 10 years old, P = 0.026) . In addition, females tended to have higher rates of positivity than males . Seroconversion during a 1-year observation period occurred in 7 (28%) of 25 seronegative animals . Seroreversion occurred in 3 (4%) of the 78 positive animals; all 3 of these animals had received antimicrobial agents during the year . These observations demonstrate that the epizootiology of H . pylori infection in rhesus monkeys may serve as a model for human infection. Arzneimittelforschung, 1995 Jun, 45(6), 726 - 31 Rational approach to fractionation, isolation, and characterization of polysaccharides from the lichen Cetraria islandica; Kramer P et al.; Polysaccharides, isolated from the lichen Cetraria islandica, have antimicrobial effectiveness . For pharmaceutical applications the two glucan components lichenan and isolichenan as well as the galactomannan component are of actual interest . Especially the a-glucan isolichenan ist used as an active ingredient in cough lozenges . The conditions for the extraction of the raw material, mainly pH and temperature, have a strong influence on the yield of lichenan, isolichenan, and galactomannan, and also on the amount of tannins in the extract . Target products and also by-products give higher extraction yields with increasing extraction temperatures . Hot water extraction with subsequent fractionation of the extracted polysaccharides by multiple freezing/thawing steps and water removal applying ethanol and ether permitted the isolation of the target polysaccharides in preparative quantities . Tannins were removed by reversed phase chromatography . IR and NMR spectroscopy were used for structural characterization of lichenan and isolichenan . After optimization of the hot water extraction process no significant lower extraction and fractionation yields have been obtained compared to the established tricky DMSO extraction procedure. Drugs, 1995 Jun, 49(6), 984 - 1006 Fluconazole . An update of its antimicrobial activity, pharmacokinetic properties, and therapeutic use in vaginal candidiasis; Perry CM et al.; Fluconazole is a bis-triazole antifungal drug which has a pharmacokinetic profile characterised by its high water solubility, low affinity for plasma proteins, and metabolic stability . After a single 150 mg oral dose, therapeutic concentrations in vaginal secretions are rapidly achieved and are sustained for a duration sufficient to produce high clinical and mycological responses in nonimmunocompromised patients with vaginal candidiasis (candidosis) . At this dosage, clinical and mycological responses have compared favourably with responses achieved after multiple dose regimens of other oral and intravaginal antifungal agents . Clinical efficacy rates have ranged between 92 and 99% at short term evaluation (5 days post-treatment) . At 80 to 100 days post-treatment clinical efficacy rates of 91% have been reported . In addition, limited data indicate that fluconazole is more effective than placebo as prophylactic treatment of frequently recurring vaginal candidiasis . Single oral doses of fluconazole 150 mg are well tolerated . Most frequently observed adverse events are gastrointestinal symptoms, which are generally mild and transient in nature . Thus, fluconazole is a valuable alternative to established systemic and intravaginal azole antifungal drugs which are used to treat vaginal candidiasis . Moreover, in view of its favourable patient acceptability and compliance profile compared with alternative treatments, single-dose oral fluconazole should be considered as a first-line therapeutic choice for the treatment of women with vaginal candidiasis. Fortschr Neurol Psychiatr, 1995 Jun, 63(6), 220 - 6 {Purulent meningoencephalitis--studies of disease progression and prognosis}; Zahner B et al.; The course of acute purulent meningitis and meningocephalitis was investigated in 101 patients using records and a questionnaire directed to all patients . Patients who survived meningoencephalitis were asked to come to a neurological examination . Neuropsychological status, EEG and Tc-HMPAO-Spect were also performed in these patients . The patients were treated with a combination of three antimicrobial agents which was commonly used at our hospital during the investigation time consisting of penicillin, a cephalosporine of the third generation and an aminoglycoside . 40% of the patients suffered from more or less severe neurologic sequelae; remaining cognitive deficits were also frequent . On the whole there was a tendency towards improvement in patients who suffered from less severe deficits at the time of discharge from hospital, patients with more severe deficits also showed slight improvement but generally did not reach a restitutio ad integrum . Regarding this, in our opinion a broad initial antimicrobial therapy should be used, although a statistically significant improvement of the patient's outcome by this could not be shown . Lethality as well as the frequency of complications do not seem to differ over many years although antimicrobial and intensive care treatment were improved . Thus, the outcome seems to depend largely on the occurrence of secondary focal complications or brain oedema. Wei Sheng Wu Xue Bao, 1995 Jun, 35(3), 229 - 31 {A new subspecies of Streptomyces griseoflavus}; Feng Q; In the process of research of microorganism ecology on Dun Huang freseo a strain of Streptomyces culture No . 25706 was isolated . Its morphological cultural characteristics and physiological properties as well as antimicrobial spectrum were studied . It is near to Streptomyces griseoflavus as described in the literature, but there are some significant differences between the two strains . Therefore, it was considered, to be a new subspecies and named Streptomyces griseoflavus subsp . dunhuangensis n . subsp. Nurse Pract Forum, 1995 Jun, 6(2), 99 - 105 Reproductive hazards facing female health care workers in the hospital: how the nurse practitioner can help; Sommer SM; Female health care workers are often exposed to occupational hazards that may adversely affect their reproductive health and the health of their children . This article presents an overview of the problem and, through a case study, focuses on a small sample of agents (aerosol antimicrobials, disinfectants, and infectious diseases) that represent common hospital exposures with reproductive implications . The nurse practitioner's role in identifying and counseling patients who may have exposures to reproductive hazards is discussed. Arch Dis Child, 1995 Jun, 72(6), 483 - 6 Trimethoprim-sulphamethoxazole in the treatment of persistent diarrhoea: a double blind placebo controlled clinical trial; Alam NH et al.; The efficacy of an absorbable antimicrobial agent trimethoprim-sulphamethoxazole (TMP-SMX) in the management of children with persistent diarrhoea was evaluated in a double blind, randomised, and placebo controlled trial . Of the 55 patients studied, 28 received TMP-SMX, and 27 received placebo . A trend in stool weight reduction was observed from the third day after the drug was started, and the reduction was statistically significant on day 6 and day 7 . However, the difference in total stool output (g/kg) up to day 7 was not significantly different between the two groups . The proportion of children whose diarrhoea resolved by day 7 (therapeutic success) was significantly more in the treatment group compared with the placebo group (23 v 15) . Additionally, mean duration of diarrhoea in the group that received TMP-SMX was less compared with the placebo group (6.0 v 8.3 days); this difference, however, was not significant . Hospital infection (probably nosocomial infection) was significantly less in the TMP-SMX treated group (1 v 10) . The results of our study indicate that TMP-SMX has a clinical benefit in respect of reducing the stool output, and higher recovery rate within seven days of treatment . In addition, it prevented possible hospital acquired infection. Infect Agents Dis, 1995 Jun, 4(2), 102 - 9 Prospects for use of recombinant BPI in the treatment of gram-negative bacterial infections; Elsbach P et al.; The bactericidal/permeability-increasing protein (BPI), a potent cytotoxin specific for Gram-negative bacteria and an endotoxin-neutralizing agent, is a major component of the antimicrobial arsenal of mammalian polymorphonuclear leukocytes . The antibacterial and endotoxin-neutralizing activities of the N-terminal portion (approximately 25 kDa) of BPI are at least equal to those of the holoprotein (approximately 50 kDa) . Recombinant N-terminal fragments of BPI are antibacterial and inhibit host cell responses to endotoxin in whole blood ex vivo and in animal experiments . BPI administered to both animals and man is apparently nontoxic and nonimmunogenic and acts synergistically with some antibiotics . Thus, the prospects for the therapeutic use of bioactive BPI fragments in serious Gram-negative bacterial infections are highly encouraging. Versicherungsmedizin, 1995 Jun 1, 47(3), 79 - 83 {Therapy of Lyme borreliosis}; Oschmann P et al.; Lyme Borreliosis is an infectious disorder caused directly by Borrelia burgdorferi . Secondary immunological mechanisms might play an additional pathogenetic role . The natural course of the disease in stage I and II is in most cases benign, therefore the influence of antibiotic therapy is difficult to assess . Double-blind, placebo-controlled randomized studies were performed rarely . However, by comparing untreated and treated patient groups it seems, that antibiotic therapy shortens the disease duration and prevents late complications . In stage III the course of the disease is usually chronic progressive (central nervous system, joint, skin), if no antibiotic therapy is applied . Currently performed clinical trials were up to now unable to determine the optimal antimicrobial agent, route of application, dosage and optimal duration of therapy for the different manifestations of the disease . Susceptibility testing, antimicrobial pharmacokinetic considerations (e . g . CSF penetration, half-life) and clinical experiences are therefore the basis of our recommendations . Stage I: Doxycyclin 2 x 100 mg p . o . or if contraindicated Cefuroxim 2 x 500 mg, at least 14 days . In case of systemic symptoms (e . g . fever) a intravenous therapy is indicated . Stage II and III: Ceftriaxon 1 x 2--2 x 2 g i . v . or Cefotaxim 3 x 2 g i . v., at least 14 days . Corticosteroids can be given in defined cases (pain syndrome!) additionally . Therapy failure was described regarding all used antibiotics, therefore clinical and laboratory follow up is mandatory . Residual symptoms can disappear over months and are usually not due to refractory disease.(ABSTRACT TRUNCATED AT 250 WORDS) Microbiol Rev, 1995 Jun, 59(2), 171 - 200 Bacteriocins of gram-positive bacteria; Jack RW et al.; In recent years, a group of antibacterial proteins produced by gram-positive bacteria have attracted great interest in their potential use as food preservatives and as antibacterial agents to combat certain infections due to gram-positive pathogenic bacteria . They are ribosomally synthesized peptides of 30 to less than 60 amino acids, with a narrow to wide antibacterial spectrum against gram-positive bacteria; the antibacterial property is heat stable, and a producer strain displays a degree of specific self-protection against its own antibacterial peptide . In many respects, these proteins are quite different from the colicins and other bacteriocins produced by gram-negative bacteria, yet customarily they also are grouped as bacteriocins . Although a large number of these bacteriocins (or bacteriocin-like inhibitory substances) have been reported, only a few have been studied in detail for their mode of action, amino acid sequence, genetic characteristics, and biosynthesis mechanisms . Nevertheless, in general, they appear to be translated as inactive prepeptides containing an N-terminal leader sequence and a C-terminal propeptide component . During posttranslational modifications, the leader peptide is removed . In addition, depending on the particular type, some amino acids in the propeptide components may undergo either dehydration and thioether ring formation to produce lanthionine and beta-methyl lanthionine (as in lantibiotics) or thio ester ring formation to form cystine (as in thiolbiotics) . Some of these steps, as well as the translocation of the molecules through the cytoplasmic membrane and producer self-protection against the homologous bacteriocin, are mediated through specific proteins (enzymes) . Limited genetic studies have shown that the structural gene for such a bacteriocin and the genes encoding proteins associated with immunity, translocation, and processing are present in a cluster in either a plasmid, the chromosome, or a transposon . Following posttranslational modification and depending on the pH, the molecules may either be released into the environment or remain bound to the cell wall . The antibacterial action against a sensitive cell of a gram-positive strain is produced principally by destabilization of membrane functions . Under certain conditions, gram-negative bacterial cells can also be sensitive to some of these molecules . By application of site-specific mutagenesis, bacteriocin variants which may differ in their antimicrobial spectrum and physicochemical characteristics can be produced . Research activity in this field has grown remarkably but sometimes with an undisciplined regard for conformity in the definition, naming, and categorization of these molecules and their genetic effectors . Some suggestions for improved standardization of nomenclature are offered. Int J Lepr Other Mycobact Dis, 1995 Jun, 63(2), 259 - 64 Activity of combinations of dapsone, rifampin, minocycline, clarithromycin, and sparfloxacin against M . leprae-infected mice; Gelber RH et al.; In these studies we evaluated the activity of low levels of five antimicrobials against Mycobacterium leprae-infected mice when administered singly and in all possible two- and three-drug combinations . Antibiotics studied were: dapsone (D) 0.0001% in the diet, rifampin (R) 20 mg/kg by gavage once monthly, minocycline (M) 0.004% in the diet, clarithromycin (C) 0.001% in the diet, and sparfloxacin (S) 5 mg/kg by gavage five times weekly . Singly each agent was found bacteriostatic (D + R) or partially bactericidal (M, C, and S) but not fully bactericidal . All 10 two-drug regimens were found at least bacteriostatic, 2 being "partially bactericidal" and 4 being "fully bactericidal." Of the 10 three-drug regimens, 9 were found "fully bactericidal" and the other "partially bactericidal." We conclude that combinations of antibiotics active against M . leprae are generally additive in combination. Trends Biotechnol, 1995 Jun, 13(6), 205 - 9 Amphibian skin: a promising resource for antimicrobial peptides; Barra D et al.; Amphibian skin is a rich source of biologically active compounds that are assumed to have diverse physiological and defence functions . In addition to the range of pharmacologically active peptides present, some of which have mammalian homologues, skin secretions contain a broad spectrum of antimicrobial peptides . As yet, such peptides from only a few species have been studied, and screening of other species is expected to yield further new antimicrobial activities . Natural antimicrobial peptides isolated from amphibian skin could provide lead structures for either the chemical, or rDNA synthesis of novel antimicrobials. Rev Sci Tech, 1995 Jun, 14(2), 309 - 12 Use of antimicrobial agents in official abattoirs under meat inspection in the United States of America; Patch MA; Facilities and equipment which are contaminated by a diseased carcass during slaughter and processing operations must be made free from microorganisms of human health concern before being used again . Therefore, a rapid-acting microbicidal agent is necessary to enable the swift resumption of operations . Currently, water heated to 180 degrees F (82.2 degrees C) is the antimicrobial agent of choice, as this rapidly kills microbes without leaving a residue which could jeopardize food products. Am J Reprod Immunol, 1995 Jun, 33(6), 481 - 4 Lack of magainin-like activity in human cervical tissue; Hansen KA et al.; PROBLEM: The cervix plays an integral role in innate immunity of the human reproductive tract . Magainins are antimicrobial and spermicidal peptides recently described in human submandibular glands . We investigated the human cervix for magainin-like peptides . METHOD: Histologic sections of frozen and paraffin embedded cervical tissue from nine subjects were separately incubated with two rabbit, polyclonal, anti-magainin antibodies (CB-2 and CB-7) to investigate for magainin-like activity in the human cervix . RESULTS: There was no specific staining of cervical columnar cells within the endocervical canal or in the endocervical crypts . Magainin-like immunoreactivity in the human submandibular gland confirmed previous observations . CONCLUSION: Antigen related to magainin-like peptides were not discovered in the human cervix. Vet Q, 1995 Jun, 17(2), 41 - 50 Pro-inflammatory cytokines in a ruminant model: pathophysiological, pharmacological, and therapeutic aspects; van Miert AS; Infection evokes complex changes which are thought to be caused by production and release of pro-inflammatory cytokines such as tumour necrosis factor (TNF-alpha), interferons (INFs), and interleukins (ILs) . They regulate local inflammatory reactions, but may also gain access to the circulation and induce systemic effects collectively known as the Acute Phase Response . To improve our understanding of the pathophysiology of pro-inflammatory cytokines in ruminants, studies have been performed with TNF-alpha, IL1-alpha/beta, and IFN-alpha/ gamma as well as with cytokine-inducers in dwarf goats . In relation to therapy, the following aspects may be of interest: a) Cytokine therapy given before or just after microbial challenge induces in vivo antimicrobial activity . Moreover, cytokines potentiate in vivo the antimicrobial activity of antibiotics, b) Cytokines may act as biological response modifiers for enhancing specific immunity to vaccines, and c) Cytokines may affect drug absorption, disposition, and metabolite formation in disease states . Although studies of the actions of corticosteroids, nonsteroidal anti-inflammatory and antipyretic agents, antibodies to endotoxin, TNF-alpha, or IL-1, synthetic E . coli lipid A precursors, hydrazine, isoniazid, chloroquine, polymyxin B, bicyclic imidazoles, hydroxamates, and tyrosine kinase inhibitors in endotoxaemic animals have shed further light on inflammatory processes, clinical studies in this field are urgently required to evaluate their beneficial effect. Proteins, 1995 Jun, 22(2), 182 - 6 Comparison of the effects of hydrophobicity, amphiphilicity, and alpha-helicity on the activities of antimicrobial peptides; Pathak N et al.; Multiple linear regression was used to quantify the dependence of the antimicrobial activity of 13 peptides upon three calculated or experimentally determined parameters: mean hydrophobicity, mean hydrophobic moment, and alpha-helix content . Mean hydrophobic moment is a measure of the amphiphilicity of peptides in an alpha-helical conformation . Antimicrobial activity was quantified as the reciprocal of the measured minimal inhibitory concentration (MIC) against Escherichia coli . One of the peptides was magainin 2, and the remainder were novel peptides designed for this study . The multiple linear regression results revealed that the amphiphilicity of the peptides was the most important factor governing antimicrobial activity compared to mean hydrophobicity or alpha-helix content . A better regression of the data was obtained using ln(1/MIC+constant) as the dependent variable than with either 1/MIC or ln(1/MIC) . These results should be useful in designing peptides with higher antimicrobial activity. J Ethnopharmacol, 1995 Jun, 46(3), 153 - 9 Screening of selected medicinal plants of Nepal for antimicrobial activities; Taylor RS et al.; In an ethnopharmacological screening of selected medicinal plants used in Nepal, methanol extracts from 21 plant species were assayed for activity against 8 strains of bacteria and 5 strains of fungi . Duplicate assays were conducted with and without exposure to UV-A radiation to test for light-activated or light-enhanced activity . All 21 of the extracts showed activity against at least 2 bacterial strains, and 20 showed activity against at least 2 fungi . Six extracts were active only when exposed to UV-A light, and the antibiotic or antifungal effect of 14 extracts was enhanced upon exposure to light. J Chemother, 1995 Jun, 7(3), 221 - 3 Brodimoprim, a new bacterial dihydrofolate reductase inhibitor: a minireview; Periti P; This brief review article synthesizes the principal literature regarding the clinical status of co-trimoxazole compared to monotherapy with one of the two diaminopyrimidines available commercially: trimethoprim or brodimoprim . Both these inhibitors of bacterial dihydrofolate reductase compare favorably to co-trimoxazole as antimicrobial chemotherapy . Brodimoprim is characterized by its advantageous pharmacokinetics in comparison to both co-trimoxazole and trimethoprim. J Hosp Infect, 1995 Jun, 30 Suppl, 253 - 61 Advances in rapid laboratory diagnosis of infectious endophthalmitis; Kinnear FB et al.; Infectious endophthalmitis is a serious ocular condition which always requires rapid medical or surgical intervention . At present this, in a number of situations, remains empirical as a consequence of problems inherent in unequivocal identification of the causative organism, should one be present . Aqueous humor smears and culture have limited value in diagnosis . Vitreous samples can often reveal the presence of microbes, but these may not necessarily be detected in all cases, principally due to suboptimal sampling or pretreatment with antimicrobials which render microbes non-culturable on routine media . Use of electron microscopy and/or immunocytochemistry offers an alternative means of identification, but these approaches have drawbacks principally associated with interpretation . Molecular methods which identify conserved sequences from common causative microbes of endophthalmitis, or which can specify whether the organism is a bacterium or a fungus may become especially important as diagnostic tools in this clinical scenario. J Hosp Infect, 1995 Jun, 30 Suppl, 223 - 31 Immunotherapy and immunoprophylaxis in bone marrow transplantation; Barnes RA; Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms . Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments . Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens . Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival . Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked . With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established . The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT . The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g . invasive mycoses) are rapidly becoming apparent . Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization . RhGM-CSF appears superior in these respects . The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation . As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS) J Hosp Infect, 1995 Jun, 30 Suppl, 197 - 208 Infection prevention strategies for children with cancer and AIDS: contrasting dilemmas; Chanock SJ et al.; Infectious complications represent significant challenges for children with cancer and those infected with HIV . Although both have similarities in the disease- and treatment-related alterations in host defences, there are significant differences that can have an impact on the approach to treatment and prevention of the dominant infectious complications . An important difference is that children with cancer readily recover from neutropenia . Thus, the immune deficits are interspersed with intervals of immunological recovery . On the other hand, children with HIV infection do not appreciably recover from the progressive, immunological changes associated with the underlying HIV infection . The loss of cellular and humoral immunity is generally not reversible, and thus the risk of infection only increases over time . Bacteria constitute the predominant pathogen for paediatric cancer patients but invasive mycoses, viruses and parasitic infections are emerging as important pathogens . In paediatric cancer patients, strategies have been directed at altering or suppressing the endogenous colonization patterns of pathogenic bacteria . The success of this approach has been limited and at the expense of selecting for antibiotic-resistant bacterial infections . Children with HIV infection are at risk of developing a wide spectrum of pathogens . Strategies for infection prevention in the HIV setting have been directed at specific organisms, generally using more specific antimicrobial agents and with greater success. J Clin Periodontol, 1995 Jun, 22(6), 480 - 4 The effect of triclosan on mediators of gingival inflammation; Gaffar A et al.; Triclosan (2,4,4',-trichloro-2'-hydroxydiphenylether) is a well-known and widely used nonionic antibacterial agent which has recently been introduced in toothpastes and mouthrinses . The efficacy of triclosan-containing toothpaste and mouthrinse to reduce both plaque and gingivitis in long-term clinical trials has been well documented . Until recently, it was generally assumed that triclosan's effect on gingival inflammation was due to its antimicrobial and anti-plaque effect . It has now become apparent that triclosan may have a direct anti-inflammatory effect on the gingival tissues . Several in vitro studies were conducted to evaluate the effect of triclosan on 4 primary enzymes of the pathways of arachidonic acid metabolism, cyclo-oxygenase 1, cyclo-oxygenase 2, 5-lipoxygenase and 15-lipoxygenase . These pathways lead to the production of known mediators of inflammation such as the prostaglandins, leukotrienes and lipoxins . Triclosan inhibited both cyclooxygenase 1 and cyclo-oxygenase 2 with IC-50 values of 43 microM and 227 microM, respectively . Triclosan also inhibited 5-lipoxygenase with an IC-50 of 43 microM . The 15-lipoxygenase was similarly inhibited by triclosan with an IC-50 of 61 microM . Hence, triclosan has the ability to inhibit both the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism with similar efficacy . In cell culture experiments, it was found that triclosan inhibited IL-1 beta induced prostaglandin E2 production by human gingival fibroblasts in a concentration dependent manner, and at relatively low concentrations . These data, taken together, indicate that triclosan can inhibit formation of several important mediators of gingival inflammation.(ABSTRACT TRUNCATED AT 250 WORDS) J Clin Periodontol, 1995 Jun, 22(6), 469 - 74 Periodontal pathogens on polytetrafluoroethylene membrane for guided tissue regeneration inhibit healing; Nowzari H et al.; This study determined the microbial composition of the apical parts of the expanded polytetrafluoroethylene membrane surfaces facing the gingiva and the tooth in guided tissue regeneration . Microbial and clinical features of 2-to-3 wall periodontal bony defects treated with membranes with and without concomitant use of systemic Augmentin therapy were also determined . 18 patients with 18 study sites participated . 9 patients received systemic 500 mg Augmentin 1 h prior to surgery, and 500 mg TID for 8 days thereafter . 9 patients received no systemic antimicrobial therapy . Microbiological examination was performed 1 h prior to surgery, at the time of membrane removal at week 6, and at 6 months post-surgery . Microbial morphotypes, total viable counts, and the occurrence of selected microbial species were determined by phase-contrast microscopy, selective and non-selective culture, and DNA probes . Study sites were examined for probing pocket depths and attachment levels . At baseline, no microbial or clinical parameter showed statistical differences between groups . At 6 months, the Augmentin group demonstrated a significantly higher (P = 0.032; Student t-test) mean probing attachment gain (36.5% of potential gain to the cemento-enamel junction) than the 9 control patients (22.4% of potential gain) . At the time of removal, membranes in the Augmentin group showed significantly fewer organisms than membranes in the control group (52.2 x 10(6) versus 488.6 x 10(6)) . Sites free of pathogens on the membrane surface toward the tooth gained the most clinical attachment, even in the presence of various pathogens on the gingiva-facing membrane surface.(ABSTRACT TRUNCATED AT 250 WORDS) Clin Otolaryngol, 1995 Jun, 20(3), 230 - 3 Neutrophil elastase-alpha 1-antitrypsin in middle ear fluid in chronic otitis media with effusion; Tierney P et al.; Neutrophil elastase-alpha 1-antitrypsin was quantified in samples taken from middle ear effusions collected at operation from 17 children attending for elective myringotomy and grommet insertion . At the time of surgery the effusion was classified as serous or mucoid . Children with a recent history of infection or antimicrobial therapy were excluded . The quantification of immunoreactive neutrophil elastase was by means of enzyme-linked immunosorbant assay (ELISA) . The mean value of neutrophil elastase-alpha 1-antitrypsin was 50.6 +/- 38.3 (SD) micrograms/ml in mucoid effusions, which was significantly higher (P < 0.05) than that in serous effusions (5.3 +/- 4.8 micrograms/ml) . These results indicate that a mucoid effusion may reflect a more severe inflammatory response and that persistence of neutrophil activity in the middle ear mucosa may contribute to the persistence of at least one group of middle ear effusions. J Interferon Cytokine Res, 1995 Jun, 15(6), 517 - 26 Involvement of two regulatory elements in interferon-gamma-regulated expression of human indoleamine 2,3-dioxygenase gene; Chon SY et al.; Interferon (IFN)-gamma-induced expression of indoleamine 2,3-dioxygenase (IDO) gene is implicated in the antimicrobial and antiproliferative effects of IFN-gamma in cell cultures . Earlier studies identified a 96 base pair (bp) regulatory region upstream of the IDO gene that conferred IFN-gamma response to the chloroamphenicol acetyltransferase (CAT) gene linked to herpesvirus thymidine kinase promoter . The IFN-gamma-responsive region was further narrowed to a 67 bp fragment by 3' deletion . This 67 bp fragment contains several sequence elements of potential interest, including a 14 bp sequence homologous to the ISRE sequence found in IFN-alpha-inducible genes and two palindromic sequences (PE I and PE II) homologous to the GAS sequence identified in IFN-gamma-inducible genes . Site-directed mutagenesis studies showed that IFN-gamma-induced expression of IDO-CAT constructs involved cooperation between two elements: the ISRE homolog and the PE II (but not PE I) . Either element alone with its flanking sequence was inadequate in conferring an IFN-gamma response to CAT reporter gene . Two IFN-gamma-regulated protein factors interacting with these two elements were identified . The factor binding to the ISRE region was induced with a slower kinetics, required new protein synthesis, and reacted with antibodies to IRF-1 . The factor interacting with the PE II region appeared rapidly after treatment with IFN-gamma independently of new protein synthesis, and its binding to DNA probe was blocked by antibodies to p91 factor, reported to bind to GAS element.(ABSTRACT TRUNCATED AT 250 WORDS) Clin Infect Dis, 1995 Jun, 20 Suppl 2, S372 - 5 Comparison of the activity of meropenem with that of other agents in the treatment of intraabdominal, obstetric/gynecologic, and skin and soft tissue; Pitkin D et al.; Meropenem, a new carbapenem with improved stability in the presence of human dehydropeptidase-I{1}, was evaluated in three prospective, multicenter, randomized, controlled clinical trials in North America . We compared the in vitro activity of meropenem and conventional antimicrobial agents for the treatment of intraabdominal, obstetric/gynecologic, and skin or soft tissue infections as well as the responses of pathogens to all of these agents . The trials of the drug for intraabdominal infection were double blind, and those for the obstetric/gynecologic and soft tissue infections were open labeled . Overall, MICs of meropenem for pathogens were lower, and the pathogen response rates were at least comparable to those for the following comparative agents: clindamycin plus tobramycin (for intraabdominal infections); clindamycin plus gentamicin (for obstetric/gynecologic infections); and imipenem and cilastatin (for skin or soft tissue infections) . Meropenem has high in vitro potency and covers a broad spectrum of anaerobic and aerobic pathogens. Am J Ophthalmol, 1995 Jun, 119(6), 701 - 5 The effect of povidone-iodine solution applied at the conclusion of ophthalmic surgery; Apt L et al.; PURPOSE: Povidone-iodine 5% solution decreases the incidence of postoperative endophthalmitis when used on the eye for preoperative preparation . We sought to determine whether it also minimized conjunctival bacterial flora immediately after surgery by preventing bacteria present on the surface of the eye from entering surgical wounds . METHODS: In 42 eyes of 40 patients, at the conclusion of surgery, on an alternating basis, each patient received either a drop of a broad-spectrum antibiotic solution (polymyxin B sulfate-neomycin sulfate-gramicidin) or a 5% povidone-iodine solution in the operated-on eye . Bacterial cultures were taken before and after surgery and 24 hours later . The 38 unoperated-on eyes in the unilateral cases served as control eyes . RESULTS: Relative to the control group, povidone-iodine was effective in preventing an increase in the number of colony-forming units (P = .035), while the antibiotic was not . At 24 hours after surgery, the species count was lower in the eyes receiving povidone-iodine than in the antibiotic-treated eyes (P = .034) and was increased in the antibiotic group since the completion of surgery (P = .013), but was lower in the povidone-iodine and antibiotic groups than in the control eyes for both groups (P < .01) . CONCLUSIONS: Povidone-iodine 5% solution applied to the eye at the conclusion of surgery was more effective at minimizing the number of colony-forming units and species for the first postoperative day than was a broad-spectrum antibiotic . While not true for the antibiotic, the antimicrobial effect of povidone-iodine lasted for at least 24 hours after the completion of surgery. J Indian Med Assoc, 1995 Jun, 93(6), 243 - 4, 236, 242 Experiences in case management of diarrhoea in large hospitals; Patwari AK; PIP: Scientific basis for oral rehydration therapy (ORT) has revolutionized the concepts and management of diarrheal diseases during the last 25 years . ORT is the only therapy needed in the majority of diarrhea cases . Sometimes, however, in more severe or complicated cases, the judicious use of IV therapy and antimicrobial agents is called for . This approach should form the practical guidelines for the management of diarrhea in hospitals . Indeed, such therapy practiced in Indian hospitals has resulted in fewer diarrhea-related hospital admissions and lower average expenditure per patient . Savings from the reduction in the use of IV fluid and antibiotics have been used to supply oral rehydration solution packets to mothers for use at home . Managing the more severe and complicated cases, large referral hospitals still play a central role in the practice and promotion of standard diarrhea case management (SDCM) . Medical colleges and teaching hospitals have an additional responsibility to train doctors, nurses, and health workers in SDCM . The first full-fledged diarrhea training and treatment unit (DTTU) in the country was established in Kalawati Saran Children's Hospital in January 1989 . That later served as the National Training Center for training key personnel from other medical colleges and large hospitals in SDCM . The Ministry of Health and Family Welfare trained senior physicians, pediatricians, hospital administrators, and senior nursing personnel from medical colleges, referral hospitals, and district hospitals in SDCM . There are now more than 80 DTTUs functioning in the country . Many more large/referral hospitals have no DTTU, but, nonetheless, actively practice and promote SDCM . Biochemistry, 1995 May 16, 34(19), 6521 - 6 Translocation of a channel-forming antimicrobial peptide, magainin 2, across lipid bilayers by forming a pore; Matsuzaki K et al.; A channel-forming antimicrobial peptide, magainin 2, has been shown to translocate across phospholipid bilayers by forming a pore comprising multimeric peptides . The translocation was demonstrated by four sets of experiments by use of resonance energy transfer from tryptophan introduced into the peptide to a dansyl chromophore incorporated into the lipid membrane . The translocation was coupled to pore formation, as detected by the dye efflux from the lipid vesicles; about 30% of the total peptide molecules translocated into the inner leaflets over 10 min, while 80% of the dye molecules leaked out at a lipid to peptide ratio of 57 . This novel model can explain the problems debated so far, i.e., the peptide forms an ion channel whereas the magainin helix essentially lies parallel to the membrane surface . Channel (pore) formation in the vesicles is a transient process observable mainly during the early stage of the peptide membrane interactions. Formulary, 1995 Jun, 30(6), 343 - 8 Criteria-based antimicrobial i.v . to oral conversion program; Okpara AU et al.; Collaborative efforts among several departments and the P & T Committee resulted in an IV to oral conversion program for select antimicrobials in our 580-bed county teaching hospital . This criteria-based program was designed to monitor and educate physicians on the appropriateness of parenteral antimicrobial prescribing, ensure rapid transition from IV to oral therapy, and contain costs . In the first 2 months of the program, 78 patients were converted from IV to oral administration with an estimated savings of $12,935 . Of the ordering physicians, 66 (84.6%) accepted the interventions . All patients who switched administration routes were successfully treated with an oral agent . This program also has had a positive effect on patient outcomes and physician prescribing habits. J Pept Sci, 1995 May-Jun, 1(3), 207 - 15 Determination of disulphide bridges in PG-2, an antimicrobial peptide from porcine leukocytes; Harwig SS et al.; We determined the cysteine connectivity of protegrin PG-2, a leukocyte-derived antimicrobial peptide, by performing sequential enzyme digestions with chymotrypsin and thermolysin, and monitoring each digest by direct liquid chromatography-electrospray mass spectrometric analysis . This approach resolved the disulphide pairing pattern unambiguously with only picomolar amounts of PG-2 . The inferred cysteine connectivity was confirmed by traditional amino acid composition analyses using nanomolar amounts of the protegrin . The results suggest that protegrins will assume a tachyplesin-like, disulphide-stabilized anti-parallel beta-sheet configuration in solution. Tokai J Exp Clin Med, 1995 May, 20(1), 65 - 6 Intravenous administration of vancomycin is ineffective against bacteremia following tooth extraction; Kaneko A et al.; The incidence of transient bacteremia after tooth extraction without antimicrobial prophylaxis has been reported was high as 69.2%; that with intravenous ampicillin as 4.2% (1, 2) . Currently, we tested a regime of vancomycin that was recommended by the American Heart Association as prophylaxis for oral surgery patients who were allergic to penicillin and evaluated its effectiveness . Before the surgical procedures, we started an intravenous drip infusion of vancomycin . Ten of 26 patients became blood culture positive (38.5%) . Seventeen strains of bacteria were isolated . The Minimum Inhibitory Concentrations (MICs) of vancomycin were lower than 3.13 micrograms/ml, with just one exception. J Chemother, 1995 May, 7 Suppl 1, 13 - 5 Once-a-day cephalosporins: reality or myth? Scaglione F, Dugnani S, Fraschini F. The factors that may influence the pharmacodynamics of antimicrobial agents against microorganisms at the site of infection must be considered before using once-daily antimicrobial chemotherapy in clinical practice . From a pharmacokinetic point of view, we can establish which antibiotic is suitable for once-daily therapy . For aminoglycosides and quinolones, where the bacterial killing is rapid and dose dependent, and there is a post-antibiotic effect (PAE), the pharmacodynamic objective is to maintain the tissue levels way above the minimum inhibitory concentration (MIC) for a short period . This can be achieved by giving single bolus doses at long time intervals . With beta-lactam antibiotics, however, which have a slow time-dependent antibacterial effect and do not display a PAE, the aim is to keep the antibiotic concentration above the MIC for the duration of therapy. Dtsch Tierarztl Wochenschr, 1995 May, 102(5), 193 - 5 In vitro metabolism of sulfathiazole in rumen fluid and its metabolism and disposition kinetics following intraruminal administration in sheep; Jain SK et al.; The antimicrobial agents may undergo a change in the complex stomach particularly in the rumen as a result of microbial fermentation in ruminants . Present investigation deals with the influence of ruminal fluid probably the role of ruminal microorganisms on the degradation of sulfathiazole in vitro and its metabolism and disposition following its single intraruminal administration (100 mg/kg) in adult german black head sheep . Sulfathiazole is metabolized to N4-acetyl sulfathiazole in the rumen fluid after its in vitro incubation at different concentrations (10-60 micrograms/ml) for varying time intervals (1-6 h) at a temperature of 38 +/- 0.5 degrees C . Likewise in vivo it is significantly metabolized to its N-acetyl metabolite in the rumen after an intraruminal administration . The levels of sulfathiazole are maintained above minimum effective therapeutic concentration (40 micrograms/ml) for more than 24 h in rumen fluid . The drug is poorly absorbed into the circulation after intraruminal administration since the levels in plasma could not reach up to minimum effective therapeutic concentration at any time . The biological half-life of sulfathiazole was found to be 16.7 h following single intraruminal administration . Results of this investigation suggest that oral or intraruminal application of sulfathiazole has only local effects in the rumen fluid . A systemic treatment is not possible after this path of application. Zentralbl Veterinarmed A, 1995 May, 42(3), 201 - 8 Species specific pharmacokinetics of rolitetracycline; Lashev L et al.; Comparative studies on some selected pharmacokinetic parameters of rolitetracycline (effective antimicrobial activity levels) in sheep, pigs, rabbits, chickens and pigeons were carried out after intravenous administration of the drug at a dose of 5 mg/kg . The results revealed that a two-compartment open model was usually optimal . Interspecies differences in the rate (alpha) and the volume of distribution (Vda), the area under the serum concentration time curve (AUC) and the total body clearance (ClB) were small . The values of the elimination half-life (t1/2 beta) found in sheep, pigs, rabbits, chickens and pigeons were 1.51, 3.06, 2.18, 4.33 and 2.51 h respectively . These results and data in mice, rabbits and man taken from literature were analysed to determine any correlation to body mass (W) . The log of the elimination half-life values (log t1/2 beta) of rolitetetracycline revealed a significant correlation with log values of (W) between animal species . This relationship was described by the equation t1/2 beta = 1.27.W0.29 (r = 0.93, P < 0.01, n = 5) for mammal species and t1/2 beta = 1.81.W0.24 (r = 0.78, P < 0.05, n = 7) for mammal and bird species. Bioessays, 1995 May, 17(5), 415 - 22 Seminal plasmin; Sitaram N et al.; The importance of seminal plasma in fertilization was appreciated as early as 1677 and would thus hardly seem a source for the search of antibacterial agents . The observation that seminal plasma had the ability to inhibit the growth of microorganisms in 1940 led to a systematic search for molecules possessing antimicrobial activity in addition to factors that might have a role in reproductive physiology . Extensive investigations led to the discovery in bovine seminal fluid of a 47-residue peptide, possessing potent antimicrobial activity as well as calcium transport modulatory properties in bovine sperm . We describe in this article the two, apparently unrelated, biological activities of this peptide. Br J Dermatol, 1995 May, 132(5), 800 - 4 Cutaneous infection with Mycobacterium abscessus; Fitzgerald DA et al.; Cutaneous infection with rapidly growing mycobacteria is uncommon and diagnosis may be difficult . However, the histopathological features are distinctive and may aid diagnosis . The three pathogenic species, Mycobacterium fortuitum, M . chelonae and M . abscessus, show major differences in their antimicrobial sensitivities, and species identification is therefore important . We describe a case of infection with M . abscessus, and discuss the clinical and pathological features of such infections, and approaches to their treatment. Am J Surg, 1995 May, 169(5A Suppl), 21S - 26S Clinical trials of extended spectrum penicillin/beta-lactamase inhibitors in the treatment of intra-abdominal infections . European and North American experience; Wilson SE et al.; The clinical results with the beta-lactam/beta-lactamase inhibitor class of antimicrobials in the treatment of intra-abdominal infections are reviewed . The three agents now in clinical use--ampicillin/sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam--are effective against a broad variety of gram-positive and gram-negative organisms . The beta-lactamase inhibitor is an irreversible inactivator of beta-lactamase enzymes, which are produced by many gram-negative and gram-positive organisms . Randomized, prospective, clinical trials of each agent indicate clinical cure rates > 85% that are not significantly different from those obtained with second-generation cephalosporin or aminoglycoside plus antianaerobic comparators, with the exception of one study . Piperacillin/tazobactam has also been compared with imipenem, with equivalent or superior outcomes, depending on the dose of the imipenem comparator . Side effects in the non-penicillin-allergic patient are few . The incidence of abnormal renal function tests are generally lower than that obtained with aminoglycoside plus antianaerobic therapy . Introduction of this new beta-lactam antimicrobial group provides another important strategy for the adjunctive management of surgically treated, community-acquired, intra-abdominal infection. Med Clin North Am, 1995 May, 79(3), 663 - 72 Antibiotic failure; Cunha BA et al.; There are many possible causes of antibiotic drug failure, but the most common are drug fevers, untreatable infectious diseases, noninfectious diseases, or problems with incorrect or inadequate spectrum . Failure to respond to antibiotics includes the emergence of resistant organisms, superinfections, and drug interactions . The most common mistake made with apparent antibiotic failure is to change or add additional antibiotics . The most important strategy is to analyze the cause of the antibiotic failure by careful evaluation and use of appropriate diagnostic tests to avoid needless, expensive, and potentially dangerous antimicrobial therapy. Med Clin North Am, 1995 May, 79(3), 559 - 80 Empiric therapy for infections in the febrile, neutropenic, compromised host; Giamarellou H; In the years to come, it is likely that with the advent of cytokines and even more with possibility to insert drug-resistant genes into hematopoietic stem cells, the risk of infection will be decreased because the severity and duration of neutropenia will be minimized . It is true that the ideal empiric antimicrobial regimen--a single antibiotic with a low incidence of superinfection and a low toxicity, without need for subsequent additions and readjustments--is still a wish . In the meantime and while living in the neutropenic area, physicians, for the benefit of patients, have to follow guidelines and create algorithms (see Fig . 1) . Recommendations, however, should be always adjustable to the individual characteristics of the patient and the institution and to progress in antimicrobial chemotherapy . It is inevitable that research and clinical practice should go "hand in hand" in these "difficult-to-manage" and "difficult-to-treat" patients . After all, it should never be forgotten that the ultimate goal of empiric antimicrobial regimens in febrile neutropenia is to ensure patients' survival. Med Clin North Am, 1995 May, 79(3), 551 - 8 Antibiotic treatment of sepsis; Cunha BA; Early, appropriate antibiotic therapy is critical to the treatment of the septicemic patient . The degree of organ dysfunction, underlying medical conditions, and physiologic abnormalities are important prognostic factors but are not important in initial antibiotic selection . Initial empiric therapy should be directed against the resident flora of the organ, which is primarily involved in the infectious process . Blood cultures should be obtained in all patients for the initiation of antibiotic therapy, and methods should be employed for the early detection of septicemia . Other conditions that mimic sepsis, e.g., pseudosepsis, should be ruled out initially to avoid an incorrect diagnosis and unnecessary antibiotic therapy . Monotherapy and fully recommended doses of antimicrobial drugs delivered by the intravenous route as soon as the diagnosis is established remain the cornerstone of therapy in treating the septic patient . Monotherapy with an antibiotic of the appropriate spectrum is more than adequate to treat the great majority of septicemic patients . Double-drug therapy is recommended to treat febrile leukopenic compromised hosts, serious P . aeruginosa infections, and selected cases of intra-abdominal sepsis . At the present time, corticosteroids and mediator therapy have no place in the treatment of the septic patient. Med Clin North Am, 1995 May, 79(3), 537 - 49 Considerations in antimicrobial prescribing; Ma MY et al.; Soon after antimicrobial drugs became available, it was recognized that they were being overused and misused . Reasons for concern about the inappropriate use of antimicrobials include the emergence of resistant nosocomial bacteria, which have been identified in every hospital nationwide . The presence of resistant nosocomial bacteria presents the physician with a clinical problem and increases the cost of therapy . It is clear that methods need to be implemented to help physicians improve prescribing of antimicrobial agents . As health care practitioners in all fields strive to make patient care more cost-effective, one observation has become evident: The successfully treated patient consumes fewer resources and subsequently costs the hospital less than an otherwise similar, unsuccessfully treated patient . The goal in the 1990s is to provide optimal, cost-effective care for patients without compromising quality . This goal can be achieved by collaborative efforts of physicians, pharmacists, and microbiologists working together as a team to promote quality patient care. Med Clin North Am, 1995 May, 79(3), 477 - 95 Antibiotic kinetics and dynamics for the clinician; Nicolau DP et al.; In recent decades considerable data have been acquired concerning the complex interactions of the organism-antimicrobial-host triad . Using the current understanding of drug disposition in the body, pharmacokinetics, and in vitro microbiologic activity, optimal dosing strategies can be derived to maximize clinical efficacy and minimize potential toxicities . This article discusses pharmacokinetics, pharmadynamics, and the application of this principle in clinical practice. J Toxicol Environ Health, 1995 May, 45(1), 1 - 45 Toxicity of quinolone antimicrobial agents; Takayama S et al.; An approach to minimization of toxicity of a new compound is to elucidate the mechanisms of toxicity of analogous compounds and to clarify their structure-toxicity relationships . A problem with this approach, however, is that such elucidation remains difficult . For quinolones, some improvements in this mechanistic approach have been achieved in the central nervous system (CNS), particularly with regard to their interaction with non-steroidal anti-inflammatory drugs (NSAIDs), and in genotoxicity and phototoxicity studies, particularly in comparison with other toxicities, such as to the cardiovascular, gastrointestinal, bone, reproductive, and developmental systems . This review concentrates on a description of the known effects of quinolones on various organ systems in experimental animals and humans . Given the logarithmic increase in the synthesis of new quinolones, it is questionable whether these drugs share similar safety and efficacy . Nevertheless, this mechanistic approach to the investigation and minimization of toxicity has produced satisfactory results to date and deserves to be continued. J Infect Dis, 1995 May, 171(5), 1309 - 16 Antimicrobial response of a T cell-deficient host to cytokine therapy: effect of interferon-gamma in experimental visceral leishmaniasis in nude mice; Murray HW et al.; To determine if interferon (IFN)-gamma can enhance intracellular antimicrobial defense in a T cell-deficient host, nude BALB/c mice were infected with Leishmania donovani and treated with IFN-gamma . IFN-gamma induced killing of L . donovani in livers of euthymic mice but had no effect in nude mice despite activating peritoneal macrophages in vivo . Transfer of CD4+ or CD8+ T cells permitted nude mice to respond to IFN-gamma; treatment with T cell-regulated antileishmanial cytokines (interleukin-2, granulocyte-macrophage colony-stimulating factor, or tumor necrosis factor-alpha) could not substitute for T cells . NK cells played no apparent role . In reconstituted nude mice, the antileishmanial effect of IFN-gamma correlated with markedly enhanced mononuclear cell recruitment to infected liver foci . Thus, although IFN-gamma activates macrophages in the absence of host T cells, a T cell mechanism is required for antileishmanial activity in tissue . Provided one T cell subset is adequately preserved, IFN-gamma may prove useful in intracellular infections in the T cell-deficient host. Clin Exp Immunol, 1995 May, 100(2), 219 - 22 The level of the serum opsonin, mannan-binding protein in HIV-1 antibody-positive patients; Nielsen SL et al.; The concentrations of mannan-binding protein (MBP) in consecutive samples from 10 HIV+ persons were estimated using an ELISA based on polyclonal rabbit anti-MBP . The changes in MBP with time were similar in HIV+ and HIV- persons, and did not appear to be of clinical significance . MBP was determined in a further 70 persons found HIV-1+ during a period of 2.5 years (1984-1986) . Out of the total of 80 patients, 32 have by now died from AIDS . According to the serum level of MBP the HIV-infected persons were grouped into high (> 650 ng MBP/ml), intermediate (101-650 ng/ml), and low MBP (< 101 ng/ml) . At the termination of the study the frequency of deaths/total in each of the groups were: high MBP, 14/39 (36%); intermediate MBP, 12/26 (46%); and low MBP, 6/14 (43%) . There was no association between the MBP level of the individual and the progressive loss of CD4+ T cells, and the level of MBP was not predictive for the length of time between the detection of HIV antibodies and development of AIDS, nor for the duration of AIDS before death occurred . The number of HIV+ persons without detectable MBP (10%) was significantly higher than previously reported for healthy persons (2.4%, P = 0.027) . The course of HIV infection does not seem to be influenced by the level of MBP, nor does the antimicrobial activity of MBP appear to affect the progression of AIDS . Further studies are required to substantiate the significance of absence of MBP in the susceptibility to HIV. Phys Ther, 1995 May, 75(5), 397 - 414 Pulmonary medications; Cahalin LP et al.; Many of the patients seen by physical therapists have primary or secondary diagnoses for which cardiovascular- or pulmonary-active medications may be prescribed . There is a need, therefore, for physical therapists to understand the pharmacologic treatment of such patients . This article discusses medications commonly used in the treatment of pulmonary disorders . These medications are typically divided into the following categories: bronchodilators, anti-inflammatory agents, decongestants, antihistamines, antitussives, mucokinetics, respiratory stimulants and depressants, and paralyzing and antimicrobial agents . Regardless of which group a particular medication belongs to, the rationale for its prescription centers on promoting bronchodilation or relieving bronchoconstriction, facilitating the removal of secretions from the lungs, improving alveolar ventilation or oxygenation, or optimizing the breathing pattern . The relative importance of each of these goals depends on the specific disease process involved and the resultant respiratory problem(s). J Bacteriol, 1995 May, 177(9), 2328 - 34 EmrR is a negative regulator of the Escherichia coli multidrug resistance pump EmrAB; Lomovskaya O et al.; The emrAB locus of Escherichia coli encodes a multidrug resistance pump that protects the cell from several chemically unrelated antimicrobial agents, e.g., the protonophores carbonyl cyanide m-chlorophenylhydrazone (CCCP) and tetrachlorosalicyl anilide and the antibiotics nalidixic acid and thiolactomycin . The mprA gene is located immediately upstream of this locus and was shown to be a repressor of microcin biosynthesis (I . del Castillo, J . M . Gomez, and F . Moreno, J . Bacteriol . 173:3924-3929, 1991) . There is a putative transcriptional terminator sequence between the mprA and emrA genes . To locate the emr promoter, single-copy lacZ operon fusions containing different regions of the emr locus were made . Only fusions containing the mprA promoter region were expressed . mprA is thus the first gene of the operon, and we propose that it be renamed emrR . Overproduction of the EmrR protein (with a multicopy vector containing the cloned emrR gene) suppressed transcription of the emr locus . A mutation in the emrR gene led to overexpression of the EmrAB pump and increased resistance to antimicrobial agents . CCCP, nalidixic acid, and a number of other structurally unrelated chemicals induced expression of the emr genes, and the induction required EmrR . We conclude that emrRAB genes constitute an operon and that EmrR serves as a negative regulator of this operon . Some of the chemicals that induce the pump serve as its substrates, suggesting that their extrusion is the natural function of the pump. Infect Immun, 1995 May, 63(5), 2075 - 8 Lack of involvement of nitric oxide in killing of Aspergillus fumigatus conidia by pulmonary alveolar macrophages; Michaliszyn E et al.; Nitric oxide is an important antimicrobial mechanism of phagocytes from mice and rats, but in the case of human phagocytes, secretion is still controversial . We investigated whether nitric oxide is involved in the killing of Aspergillus fumigatus conidia by human or murine pulmonary alveolar macrophages . Stimulation of the macrophages with gamma interferon and Escherichia coli lipopolysaccharide had no effect on fungicidal activity against conidia in vitro, with or without the addition of tetrahydrobiopterin . Killing of conidia (means +/- standard deviations) by murine or human alveolar macrophages, before and after stimulation, was 44% +/- 13% and 49% +/- 12% (P = 0.34) and 24% +/- 5% and 29% +/- 10% (P = 0.20), respectively . Fungicidal activity was unaltered in the presence of the competitive inhibitor NG-monomethyl L-arginine, and nitrite was undetectable in cell supernatants . Peritoneal macrophages from B6C3F1 mice produced 18 mumol of nitrite per 10(6) cells in 18 h . In conclusion, nitric oxide does not appear to be involved in the fungicidal activity of murine or human alveolar macrophages against A . fumigatus conidia. Arch Otolaryngol Head Neck Surg, 1995 May, 121(5), 566 - 72 Management of sinusitis in cystic fibrosis by endoscopic surgery and serial antimicrobial lavage . Reduction in recurrence requiring surgery; Moss RB et al.; OBJECTIVE: An effective treatment program for refractory chronic sinusitis in patients with cystic fibrosis has not been achieved . We developed a long-term management approach by combining endoscopic surgery with serial antimicrobial lavage (ESSAL) . DESIGN: In a before and after trial, results of ESSAL in 32 patients were compared with those of conventional sinus surgery without serial antimicrobial lavage in 19 patients . At least 1 year follow-up was available in all but one patient . SETTING AND PATIENTS: Patients attending the Stanford (Calif) Cystic Fibrosis Center were consecutively referred for otolaryngologic evaluation for symptoms and signs of refractory sinusitis . Those subjects who were evaluated before 1990 were treated conventionally and afterward by ESSAL . INTERVENTION: Conventionally treated patients underwent one or more of the following procedures: polypectomy, ethmoidectomy, antrostomy, or Caldwell-Luc operation . The ESSAL approach incorporated preoperative rhinosinuscopy and computed tomography, endoscopic surgery, a postoperative course of antral antimicrobial lavage, and monthly maintenance antimicrobial lavage via brief antral catheterization . MAIN OUTCOME MEASURE: Intensity and frequency of sinus surgery after initial presentation . RESULTS: The two groups were similar demographically and