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| Drug Ther Bull, 1999 Jan, 37(1), 6 - 8 New fluoroquinolone antibiotics; "Guidance for Industry: For the Submission of Chemistry et al.; The Food and Drug Administration (FDA) is announcing the availability of a document entitled "Guidance for Industry: For the Submission of Chemistry, Manufacturing and Controls and Establishment Description Information for Human Blood and Blood Components Intended for Transfusion or for Further Manufacture and For the Completion of the Form FDA 356h, 'Application to Market a New Drug, Biologic or an Antibiotic Drug for Human Use.'" This guidance document is intended to assist applicants in the preparation of the content and format of the chemistry, manufacturing, and controls (CMC) section and the establishment description section of a biologics license application (BLA), revised Form FDA 356h, for human blood and blood components intended for transfusion or for further manufacture . In addition, this guidance document provides assistance for the completion of the BLA . This action is part of FDA's continuing effort to achieve the objectives of the President's "Reinventing Government" initiatives and the Food and Drug Administration Modernization Act of 1997 (Modernization Act), to reduce unnecessary burdens for industry without diminishing public health protection. Angew Chem Int Ed Engl, 1999 Nov 2, 38(21), 3228 - 3231 Inhibition of Angiogenesis In Vivo by ets-1 Antisense Oligonucleotides-Inhibition of Ets-1 Transcription Factor Expression by the Antibiotic Fumagillin; Wernert N et al.; The inhibition of angiogenesis in vivo as a result of the inhibition of Ets-1 transcription factor expression by the ets-1 phosphorothioate antisense oligodeoxynucleotide 5'-AGATCGACGGCCGCCTTCAT-3' has been proven by experiments with chicken embryos . Thus, participation of the Ets-1 transcription factor in the formation of new blood vessels in vivo has been demonstrated . Furthermore, it is shown that the angiostatic effect of the fungal metabolite and angiogenesis inhibitor fumagillin is mainly a result of its ability to inhibit Ets-1 expression. FEBS Lett, 1999 Nov 5, 460(3), 500 - 4 Voltage-dependent interaction of the peptaibol antibiotic zervamicin II with phospholipid vesicles; Kropacheva TN et al.; The effect of a transmembrane potential on ion channel formation by zervamicin II (ZER-II) was studied in a vesicular model system . The dissipation of diffusion potential caused by addition of ZER-II to small phosphatidylcholine vesicles was monitored using fluorescent (Safranine T) and optical (Oxonol YI) probes . Cis-positive potentials facilitated channel formation, while at cis-negative potentials, ion fluxes were inhibited . A potential-independent behavior of ZER-II was observed at high peptide concentrations, most likely due to its membrane modifying property. Farmaco, 1999 Sep 30, 54(9), 594 - 9 Use of a Caco-2 cell culture model for the characterization of intestinal absorption of antibiotics; Biganzoli E et al.; The use of cell culture models, based on human cell lines derived from the intestinal epithelium, is a promising new tool for the in vitro study of oral absorption of drugs . An assay has been developed using the Caco-2 cell line with the aim of studying the in vitro permeability of antibiotics . The reproducibility of the assay conditions have been assessed by means of the transport of two different marker molecules: 3H-mannitol and fluorescein, and transepithelial electrical resistance (TEER) value for cells monolayers . The results show that cells after 21 days of culture give significantly tighter monolayers than those after 15 days with higher reproducibility . Apparent permeability coefficients (Papp) have been measured for 13 antibiotics, known to be absorbed at different rates in humans . Papp values span from 0.18 x 10(-6) cm/s for cephaloridine to 5.79 x 10(-6) cm/s for rifampicin where the corresponding bioavailability values, known from literature, span from < 3 to 98% . A Caco-2 in vitro model appears to be suitable to investigate the transport of drugs across the intestinal epithelium . This model gives no information about the metabolic phase that follows the absorption of a drug but could provide information to investigate its pharmacokinetical behavior. Scand J Prim Health Care, 1999 Sep, 17(3), 180 - 4 Medical audit changes physicians' prescribing of antibiotics for respiratory tract infections; Melander E et al.; OBJECTIVE: To reduce the prescribing of antibiotics in respiratory tract infections (RTI) . DESIGN AND SUBJECTS: The Audit Odense model for registration and quality development was used for RTI . Twenty general practitioners registered their consultations for RTIs during 4 weeks in February-March (n = 1124) and November-December (n = 926) in 1995 . Diagnosis, choice of antibiotics and diagnostic tools were registered . In between the two registrations an active intervention took place . Consultations for RTIs among 25 physicians (who had not participated in any intervention or follow-up discussion) served as a control . SETTING: General practice in southern Sweden . OUTCOME MEASURES: Prescribing of antibiotics before and after an intervention . RESULTS: The proportion of patients not receiving an antibiotic increased from the first to the second registration in both groups, in the intervention group from 45 to 55% (p < 0.001) and in the control group from 36 to 40% (p = 0.0298) . The reduction was most evident in patients diagnosed with tonsillitis and bronchitis . This was in concordance with an increase in the use of desktop diagnostics (Strep A and CRP) . CONCLUSION: These results indicate that it is possible to achieve a change in the utilisation of antibiotics in the treatment of RTIs and that the Audit Project Odense (APO) model could be a valuable tool. Prog Urol, 1999 Sep, 9(4), 721 - 6 {Fournier's gangrene involving all of the scrotum: treatment by multiple repeated surgical excisions, diversion colostomy, triple antibiotic therapy and postoperative intensive care}; Mejean A et al.; OBJECTIVES: To describe and analyse the proposed therapeutic modalities to treat a series of patients suffering from Fournier's gangrene involving the entire scrotum . MATERIAL AND METHODS: Four patients with macroscopically identical lesions of Fournier's gangrene involving the entire scrotum were managed by wide surgical debridement, diversion colostomy, triple combination antibiotic therapy, transfer to surgical intensive care, multiple repeated operations under general anaesthesia for excision of atonic tissues and mesh skin grafts . The colostomy was closed after 4 months . RESULTS: All patients survived after skin cover . Three of them were reviewed 2 months after restoration of gastrointestinal continuity and presented a good general status with a satisfactory esthetic result . The fourth patient was lost to follow-up . The mean reoperation rate was 6.5 per patient . The mean intensive care stay was 9.5 weeks . CONCLUSION: The choice of intensive treatment depends on the extent of the lesions . When the entire scrotum is involved, repeated surgical excisions and systematic colostomy, combined with the other treatment modalities appear to be necessary to manage this disease, which still has a serious prognosis. Arch Tierernahr, 1999, 52(1), 29 - 39 Comparison of the supplemental effects of Saccharomyces cerevisiae and antibiotics in low-protein and high-fibre diets fed to broiler chickens; Onifade AA et al.; Two experiments were completed to compare the supplemental effects of yeast Saccharomyces cerevisiae and sub-therapeutic antibiotics in high-fibre and low-protein diets for broiler chicks . In experiment 1, yeast was added at 1.5, 3.0 and 6.0 g kg-1 while penicillin, tylosin or neoterramycin were added at 150 mg kg-1 into different batches of a high-fibre diet containing 250 g kg-1 palm kernel meal . Saccharomyces cerevisiae and antibiotics increased BW, BWG, FCR, feed intake, carcass and breast weights above the control . Small intestine weight was reduced by antibiotics, while yeast caused a lower deposition of abdominal fat . Liver weights of different treated broilers were similar . The performance indices were superior on penicillin and 3.0 g kg-1 yeast compared to other supplements evaluated . In the second experiment, 1.5 and 3.0 g kg-1 of yeast, and 0.75 mg kg-1 of procaine penicillin, zinc bacitracin and tylosin were separately added to a 180 g kg-1 crude protein diet . Performance of the chicks with additives was compared with unsupplemented negative and positive controls containing 180 and 210 g kg-1 crude protein respectively . Broilers fed with supplements had superior BW, BWG, FCR and feed intake compared to the negative control, but carcass data were similar . Dietary penicillin increased BW, BWG, feed intake more than other supplements, but yeast stimulated higher FCR . Data from both studies indicated that Saccharomyces cerevisiae comparatively increased growth and carcass weight and reduce abdominal fat, therefore, it can serve as a natural substitute for antibiotics in broiler diet. Retina, 1999, 19(5), 437 - 41 Safety of repeated intravitreous injections of antibiotics and dexamethasone; Yoshizumi MO et al.; PURPOSE: To determine the retinotoxicity of repeated intravitreous injections of vancomycin, ceftazidime, and dexamethasone in rabbit eyes . METHODS: Twenty pigmented New Zealand rabbits were divided into two groups . In Group 1, the right eyes received repeated intravitreous injections with vancomycin 0.3 mg, ceftazidime 0.7 mg, and dexamethasone sodium phosphate 0.13 mg at three consecutive 48-hour intervals . Group 2 right eyes received three times higher dose of the same intravitreous drugs as used in Group 1, repeated at the same frequency . All left eyes served as control eyes . Retinotoxicity was monitored by slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and light and electron microscopy . RESULTS: No evidence of retinotoxicity was found in Group 1 eyes . Photopic A-waves were significantly elevated, and 30- and 50-Hz flicker fusion amplitudes were significantly depressed in Group 2 eyes . No changes were found by clinical or histopathologic examination in the retinas of either group . CONCLUSIONS: Three repeated intravitreous injections at 48-hour intervals of a combination of vancomycin, ceftazidime, and dexamethasone in rabbit eyes at dosages that approximate drug concentrations recommended for human endophthalmitis were nontoxic . Similar injections at three times higher doses resulted in mild electroretinogram changes. Morphologie, 1999 Sep, 83(262), 9 - 12 {Regenerative potential of the sensory epithelium of the mammalian organ of Corti after poisoning with ototoxic antibiotics}; Vago P et al.; Cochlear sensory hair cells are very sensitive to noxious influences such as ageing, noise and ototoxic drugs . Whereas lost auditory hair cells are replaced by new hair cells in the avian and lower vertebrates, cochlear sensory hair cells do not regenerate in mammals . Recently, we have observed transient atypical cells in the cochlea of amikacin intoxicated rats . We have related their presence to an attempt at sensory hair cell neodifferentiation . The aim of the present study was to i) investigate the mechanisms responsible for sensory hair cell losses during the intoxication and the subsequent appearance of atypical cells, ii) characterise the phenotype of these atypical cells and iii) evaluate the influence of cochlear immaturity in such an attempt at sensory hair cells neo-differentiation. J Orthop Sci, 1999, 4(5), 361 - 9 Apatite cement containing antibiotics: efficacy in treating experimental osteomyelitis; Sasaki S et al.; Osteomyelitis is generally treated by the systemic administration of antibiotics and continuous irrigation after curettage of the lesion, and bone graft is performed secondarily to treat any bone defect . This treatment is associated with major invasion, and also has adverse effects on other organs . If a superior bone filling material were to be developed that allowed high concentrations of antibiotics that acted only locally, and allowed bone formation at the same time, an ideal method of treating osteomyelitis would become available . We created an implant composed of calcium phosphate cement, gentamicin, and poly-L-lactic acid . The results of sustained-release testing in vivo and in vitro demonstrated the release of effective antibiotic concentrations over a 2-month period . Further, when an experimental model of osteomyelitis was produced in rabbits and the implant was inserted after bone marrow curettage, the implant proved effective in preventing the progression of osteomyelitis and in achieving local bone formation. Am Heart J, 1999 Nov, 138(5 Pt 2), S542 - 4 WIZARD and the design of trials for secondary prevention of atherosclerosis with antibiotics; Dunne M; Clinical trials to assess the merit of antibiotic intervention in the treatment of ischemic cardiovascular disease are now underway, spurred on by an association between Chlamydia pneumoniae and atherogenesis noted in epidemiologic investigations, histopathologic studies, and results from various animal models . The design of such clinical trials must take into account a number of issues: the primary event as strictly defined by objective criteria, the event rate in the chosen population, the potential treatment effect, the availability of patients, the underlying cause of their atherosclerotic disease, the determination of the C pneumoniae-infected population to study, the dose and duration of the antibiotic, and the length of follow-up . In the design of the WIZARD study (Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders), an attempt was made to take these issues under consideration . Patients were randomly assigned either to 600 mg/d zithromax for 3 days then 600 mg/wk for 11 additional weeks or to placebo . Patients in the study had a myocardial infarction at least 6 weeks previously, had no recent coronary artery bypass graft or percutaneous transluminal coronary angioplasty, and did not required long-term administration of antibiotics . Patients were required to have an immunoglobulin G titer to C pneumoniae of >/=1:16 . The primary end point was the time to a composite of all-cause death, myocardial infarction, a revascularization procedure, or hospitalization for angina . The study enrolled 3500 patients, sufficient to detect a 25% reduction in the presumed 8% placebo event rate with 90% power . Follow-up will continue through the prespecified number of end points. Am Heart J, 1999 Nov, 138(5 Pt 2), S537 - 8 Emerging role of antibiotics in atherosclerosis; Gurfinkel EP et al.; It has been shown that plaque composition changes significantly in the setting of acute events, macrophages and T cells being the predominant pattern at the immediate site of fissure or erosion . There appears to be a relation between physical blood stream factors, plaque morphology, and the distribution of inflammatory cells . Furthermore, there is cumulative evidence for the presence of intracellular pathogens in the arterial wall, namely Chlamydia pneumoniae and cytomegalovirus, which affect endothelial cells, monocytes, and macrophages . The ROXIS trial has shown some encouraging evidences for the potential role of intracellular pathogens in acute coronary syndromes . The ongoing WIZARD trial evaluates in a large population whether the addition of an antibiotic provides better outcome for coronary patients. Health Policy, 1999 Jul, 48(1), 29 - 45 Association between health insurance and antibiotics prescribing in four counties in rural China; Dong H et al.; A cross-sectional study was carried out at county, township and village health care facilities in four counties in rural China in order to describe and compare the effects of health financing systems on antibiotic prescribing in outpatient care . A total of 1232 outpatients at the health care facilities was selected by multi-stage random sampling and were interviewed over 2 weeks . The results showed that health financing systems appeared to influence antibiotic prescribing in outpatient care, both in terms of frequency and of the types prescribed . The insured group had lower prescribing of antibiotics at township and village health care facilities, and for respiratory tract infections, but had higher prescribing of newer antibiotics at county and village health care facilities, for respiratory tract and g-i infections . Because there was a high patient compliance rate (94.3%) in this study the prescribing of antibiotics (supply side behavior) reflected the use of antibiotics (demand side behavior) to a great extent . Thus the results imply that antibiotics prescribing and using might be biased by the patient's health financing systems and antibiotic prescribing was the result of the interaction between physicians and patients. J Chromatogr A, 1999 Oct 1, 857(1-2), 313 - 20 Micellar electrokinetic capillary chromatography of macrolide antibiotics . Separation of tylosin, erythromycin and their related substances; Tobback K et al.; The separation of tylosin by micellar electrokinetic capillary chromatography with a mixed micelle system is described . Good selectivity was obtained with sodium phosphate buffer (80 mM, pH 7.5) containing 20 mM sodium cholate and 7 mM cetyltrimethylammonium bromide (CTAB) . This method permits tylosin to be separated from its closely related substances within 15 min . The influences of type of buffer, buffer pH, the concentrations of sodium cholate and CTAB were investigated . The robustness of the method was examined for tylosin by means of a full-fraction factorial design . Quantitative results are presented . Using a similar buffer system (80 mM sodium phosphate, pH 6.0, 20 mM sodium cholate and 5 mM CTAB), separation of erythromycin and its main related substances was also obtained . However, detection sensitivity and resolution are not sufficient for analysis of related substances in erythromycin commercial samples. Electrophoresis, 1999 Sep, 20(13), 2749 - 53 Enantiomeric separations of dansyl amino acids using the macrocyclic antibiotic A35512B as a chiral selector in capillary electrophoresis; Risley DS et al.; The macrocyclic antibiotic A35512B was examined as a chiral selector for capillary electrophoresis (CE) using thirteen racemic dansyl amino acids as test analytes . The chiral selectivity of A35512B was evaluated as a function of the run buffer pH, antibiotic concentration, and organic modifier composition . After optimizing these parameters, the macrocylic antibiotic A35512B provided high resolutions of all the enantiomers for the thirteen dansyl amino acids tested in this study. Vopr Onkol, 1999, 45(4), 445 - 8 {Effectiveness of current chemotherapy in metastatic breast cancer resistant to anthracycline antibiotics}; Moiseenko VM et al.; The efficacy of different antitumor therapies was evaluated in a study involving 53 patients with metastatic breast cancer resistant to anthracyclin antibiotics . Complete and partial regression of tumor was recorded following combined administration of vinorelbin and doxorubicin (27.3%) and taxanes (21.3%) . Median therapeutic benefit duration was 22 and 28 weeks, respectively . Response frequency for mitomicin C + mitoxantron + methotrexate regimen was 11.1% . However, no objective therapeutic effects were observed in patients on ifosfamide + mitoxantron and regular 5-fluorouracil infusins. Bioorg Med Chem, 1999 Sep, 7(9), 1979 - 91 tRNA(Phe) binds aminoglycoside antibiotics; Kirk SR et al.; Aminoglycoside antibiotics have recently been found to bind to a variety of unrelated RNA molecules, including sequences that are important for retroviral replication . We report the binding of neomycin B, kanamycin A, and Neo-Neo (a synthetic neomycin-neomycin dimer) to tRNA(Phe) . Using thermal denaturation studies, fluorescence spectroscopy, Pb2+-mediated tRNA(Phe) cleavage, and gel mobility shift assays, we have established that aminoglycosides interact with yeast tRNA(Phe) and are likely to induce a conformational change . Thermal denaturation studies revealed that aminoglycosides have a substantial stabilizing effect on tRNA(Phe) secondary and tertiary structures, much greater than the stabilization effect of spermine, an unstructured polyamine . Aminoglycoside-induced inhibition of Pb2+-mediated tRNA(Phe) cleavage yielded IC50 values of: 5 microM for Neo-Neo, 100 microM for neomycin B, > 1 mM for kanamycin A, and > 10 mM for spermine . Enzymatic and chemical footprinting indicate that the anticodon stem as well as the junction of the TpsiC and D loops are preferred aminoglycoside binding sites. J Mol Biol, 1999 Sep 3, 291(5), 1025 - 34 Effect of antibiotics on large ribosomal subunit assembly reveals possible function of 5 S rRNA; Khaitovich P et al.; Functional large ribosomal subunits of Thermus aquaticus can be reconstituted from ribosomal proteins and either natural or in vitro transcribed 23 S and 5 S rRNA . Omission of 5 S rRNA during subunit reconstitution results in dramatic decrease of the peptidyl transferase activity of the assembled subunits . However, the presence of some ribosome-targeted antibiotics of the macrolide, ketolide or streptogramin B groups during 50 S subunit reconstitution can partly restore the activity of ribosomal subunits assembled without 5 S rRNA . Among tested antibiotics, macrolide RU69874 was the most active: activity of the subunits assembled in the absence of 5 S rRNA was increased more than 30-fold if antibiotic was present during reconstitution procedure . Activity of the subunits assembled with 5 S rRNA was also slightly stimulated by RU69874, but to a much lesser extent, approximately 1.5-fold . Activity of the native T . aquaticus 50 S subunits incubated in the reconstitution conditions in the presence of RU69874 was, in contrast, slightly decreased . The presence of antibiotics was essential during the last incubation step of the in vitro assembly, indicating that drugs affect one of the last assembly steps . The 5 S rRNA was previously shown to form contacts with segments of domains II and V of 23 S rRNA . All the antibiotics which can functionally compensate for the lack of 5 S rRNA during subunit reconstitution interact simultaneously with the central loop in domain V (which is known to be a component of peptidyl transferase center) and a loop of the helix 35 in domain II of 23 S rRNA . It is proposed that simultaneous interaction of 5 S rRNA or of antibiotics with the two domains of 23 S rRNA is essential for the successful assembly of ribosomal peptidyl transferase center . Consequently, one of the functions of 5 S rRNA in the ribosome can be that of assisting the assembly of ribosomal peptidyl transferase by correctly positioning functionally important segments of domains II and V of 23 S rRNA. Microbiology, 1999 Sep, 145 ( Pt 9), 2343 - 53 Genetic suppression analysis of non-antibiotic-producing mutants of the Streptomyces coelicolor absA locus; Anderson T et al.; The absA locus in Streptomyces coelicolor A3(2) was identified because mutations in it uncoupled sporulation from antibiotic synthesis: absA mutants failed to produce any of the four antibiotics characteristic of S . coelicolor . These mutants are now shown to contain point mutations in the absA1 gene which encodes the histidine kinase sensor-transmitter protein of a two-component signalling system . The absA1 non-antibiotic-producing mutants, which are unpigmented, spontaneously acquire pigmented colony sectors . Genetic analysis established that the pigmented sectors contain second-site suppressive mutations, sab (for suppressor of abs) . Phenotypic characterization showed that sab strains produce all four antibiotics; some overproduce antibiotics and are designated Pha, for precocious hyperproduction of antibiotics . A set of sab mutations responsible for suppression was localized by plasmid-mediated and protoplast fusion mapping techniques to the vicinity of the absA locus . DNA cloned from this region was used to construct phage that could transduce sab mutations . Sequence analysis of sab strains defined sab mutations in both the absA1 gene and the absA2 gene; the latter encodes the two-component system's response regulator. Jpn J Antibiot, 1999 Jul, 52(7), 517 - 23 {Effects of an oxacephem antibiotic on liver function in orthopedic surgery}; Kuroyama M et al.; The subjects were 531 patients who underwent orthopedic surgery . Flomoxef was administered, and liver function was examined before and after administration . Abnormal liver function after administration of flomoxef was found in 14.3% of patients . In male patients, a high rate of 18.8% was observed . A particularly high rate of 37.0% was obtained among patients who showed GOT values of more than 40 U/L before treatment with flomoxef . The prevalence of abnormal GOT and GPT values after administration of flomoxef was 3.6% and 13.2%, respectively . These values were significantly higher than those obtained with other cephem antibiotics . These rates of occurrence of abnormally high GOT and GPT are obviously higher than those submitted at the time of approval and reported in the drug use investigation . The prevalence of abnormal liver function values was high in patients receiving flomoxef, and particularly high in male patients and patients whose GOT was high before administration of flomoxef . Therefore, sufficient check of liver function appears important when administration of flomoxef to these types of patients is intended. Jpn J Antibiot, 1999 Jul, 52(7), 497 - 503 {Tissue penetration properties of macrolide antibiotics--comparative tissue distribution of erythromycin-stearate, clarithromycin, roxithromycin and azithromycin in rats}; Yoshida H et al.; The ability of antibiotics to penetrate the target organs is an important factor for the clinical effects and side effects in the treatment of infection . In the present study, the comparative tissue distribution of 4 kinds of macrolide antibiotics was determined in rats . After oral administration of 20 mg/kg, roxithromycin (RXM) had the highest plasma concentration, and clarithromycin (CAM) has the second highest . The Cmax of RXM and CAM were 2.7 and 1.0 micrograms/ml, respectively . On the other hand, both levels of erythromycin-stearate (EM-S) and azithromycin (AZM) were extremely low, with a Cmax of 0.1 microgram/ml . Concentration of the 4 compounds were measurable in the liver, kidney, spleen, lung and heart . The concentration in all tissues for each compound were significantly higher than those in the plasma . AZM had the most sustained and the highest tissue levels . The distribution patterns of RXM and AZM were almost similar to the case of EM-S, in that the highest tissue concentration was observed in the liver, followed in descending order by concentration in the kidney, spleen, lung and heart . On the other hand, CAM had the highest concentration in the lung, and was moderated in the liver . Major clinical indications are infections of the respiratory tracts, and commonly reported side-effects are hepatotoxity . Therefore, it is worth noting that the lung levels of CAM were significantly higher than in the liver, as the separation of clinical effects and side-effects. Ophthal Plast Reconstr Surg, 1999 Sep, 15(5), 363 - 5 Oral and topical antibiotic therapy of complete, primary acquired nasolacrimal duct obstruction in adults; Mauriello JA Jr et al.; PURPOSE: To determine whether patients with complete, acquired nasolacrimal duct obstruction may be treated with broad spectrum oral antibiotics and office lacrimal irrigation . METHODS: In a retrospective review, patients with complete, primary acquired nasolacrimal duct obstruction (NLDO) were divided by predominant symptoms and signs into two main groups: (a) those with tearing and/or mucous discharge and (b) those with previous acute dacryocystitis and/or lacrimal sac mucocele . All patients received a therapeutic trial of oral and topical antibiotics followed by lacrimal irrigation . RESULTS: Five of 55 patients with tearing and/or mucous discharge showed significant improvement after treatment with a mean follow-up of 16.5 months . A sixth patient with mucous and tearing had resolution of the mucous discharge but persistent tearing and blockage of the nasolacrimal system to irrigation . Two of 20 patients with lacrimal sac mucocele or history of acute dacryocystitis avoided surgery while 18 opted for early lacrimal surgical intervention . CONCLUSIONS: Conservative management of complete acquired NLDO consisting of oral and topical antibiotics and appropriately timed office lacrimal drainage system irrigation may be considered in selected patients. J AOAC Int, 1999 Sep-Oct, 82(5), 1083 - 95 Multiresidue analytical method for the determination of eight penicillin antibiotics in muscle tissue by ion-pair reversed-phase HPLC after precolumn derivatization; Verdon E et al.; A high-performance liquid chromatographic multiresidue method was developed for the determination of 8 penicillin compounds (benzylpenicillin, phenoxymethylpenicillin, ampicillin, amoxicillin, nafcillin, oxacillin, cloxacillin, and dicloxacillin) at trace levels in muscle tissue . This method involves extraction of the penicillins with phosphate buffer pH 9 followed by cleanup and concentration on a C18 solid-phase extraction column and reaction with benzoic anhydride at 50 degrees C for 5 min and with 1,2,4-triazole and mercury(II) chloride solution pH 9 at 65 degrees C for 10 min . The derivatized compounds are eluted on a C8 column with a mobile phase containing acetonitrile and phosphate buffer (pH 6; 0.1 mol/L) loaded with sodium thiosulfate and ion-pairing tetrabutylammonium hydrogenosulphate . The method detection limit is approximately 3-11 micrograms/kg and the limit of determination was evaluated down to 25 micrograms/kg in line with the criteria of the EU decision No . 93/256/EEC. J Arthroplasty, 1999 Sep, 14(6), 764 - 5 An inexpensive molding method for antibiotic-impregnated cement spacers in infected total hip arthroplasty; Ries MD et al.; Placement of an antibiotic-impregnated cement endoprosthesis facilitates patient mobilization and treatment of infection complicating total hip arthroplasty . Molds, particularly to form the spherical head of the cement endoprosthesis, are not readily available, however . We have found that the rubber bulb portion of an irrigation syringe can be conveniently used as a mold to shape the proximal end of a cement endoprosthesis during surgery. J Antimicrob Chemother, 1999 Sep, 44(3), 319 - 27 Pharmacokinetics of antibiotics in burn patients; Weinbren MJ; Drug pharmacokinetics are significantly altered in the burned patient but the interplay of a large number of variables is involved in deciding how an individual will deal with a drug . Consequently the burn patient population shows significant inter- and intrapatient variation . In 1976 altered aminoglycoside pharmacokinetics and the need for increased dosage in burn patients was reported but, despite this early study, a review of the currently available literature shows that for many drugs there is a paucity of information to support current dosage recommendations . In addition, many reports are based upon small numbers of patients, and even in larger studies there is no standardization of the study population with regard to the important variables known to affect drug handling . For the sub-population of burn patients who eliminate drugs extremely rapidly, a concern exists over the adequacy of antibiotic dosing . It is suggested that antibiotic serum concentrations be measured for all drugs in every patient to ascertain whether there is a significant problem with dosing . Additionally, future pharmacokinetic studies need to be standardized in burn patients. Surg Neurol, 1999 Sep, 52(3), 226 - 36; discussion 236-7 Prophylactic antibiotics with intracranial pressure monitors and external ventricular drains: a review of the evidence; Prabhu VC et al.; BACKGROUND: The role of prophylactic antibiotics (PABs) in preventing infections associated with intracranial pressure (ICP) monitors and external ventricular drains (EVD) is not well defined . METHODS: This study includes an analysis of published reports and a survey of current practices regarding the use of PABs with ICP monitors and EVDs . A computerized data search and a review of the abstracts from two major national neurosurgical meetings over the past decade yielded 85 related articles . Three independent investigators, blinded to the title, author(s), institution(s), results, and conclusions of the articles used predetermined inclusion criteria to select studies for meta-analysis . Thirty-six responses were returned from 98 questionnaires (37%) mailed to university neurosurgical programs . RESULTS: Among the articles reviewed, only two studies met the predetermined inclusion criteria for the meta-analysis, and they were of insufficient size to produce statistically significant results . Among the 36 programs that responded to the survey, 26 (72%) used PABs, mainly cephalosporins (46%) and semisynthetic penicillins (38%), with ICP monitors and EVDs . Twenty-two (85%) used one drug, and 4 (15%) used two drugs . Twenty-two (61%) of the total group reported intra-institutional variation in practices among individual staff neurosurgeons . Nineteen (53%) expressed interest in a retrospective study, and 27 (75%) expressed interest in a prospective study on the role of PABs in minor neurosurgical procedures . CONCLUSION: No consensus regarding the use of PABs with ICP monitors and EVDs is noted . Randomized controlled trials of sufficiently large size with appropriate blinding are needed to address this issue. Rapid Commun Mass Spectrom, 1999, 13(20), 2054 - 62 Liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry enantiomeric separation of dl-threo-methylphenidate, (Ritalin) using a macrocyclic antibiotic as the chiral selector; Ramos L et al.; Vancomycin, a macrocyclic antibiotic, is an amphoteric glycopeptide produced by Streptomyces orientalis which has proven to be a viable chiral selector for high performance liquid chromatograph (HPLC) (D . W . Armstrong, Y . Tang, S . Chen, Y . Zhou, C . Bagwill and J-R . Chen, Anal . Chem . (1994; 66: 1473) . While it is related to other glycopeptide antibiotics, vancomycin has a number of unique structural features, including 18 stereogenic centers, five aromatic rings, and two side chains one of which is a carbohydrate dimer . Therefore, a vancomycin-based stationary phase appears to be multimodal in that it can be utilized in both normal-phase and reversed-phase liquid chromatography . Consequently, the enantiomeric separation may be operative via several mechanisms, including pi-pi complexation, dipole stacking, inclusion, hydrogen bonding, or combinations of these interactions . LC/MS/MS is a powerful tool for quantitative analysis when evaluated on the basis of speed, specificity, reliability and sensitivity . For these reasons, the present paper explored the feasibility of bonded macrocyclic glycopeptide phases for chiral LC/MS/MS quantitative analysis . Methylphenidate was used as a model compound . A rapid chiral bioanalytical method (<7.5 min) for the determination of the enantiomers of methylphenidate was developed . A lower limit of quantification (LLOQ) of 87 pg/mL was attained for the human plasma assay . This is to our knowledge the first example of enantioselective reversed-phase LC/MS/MS for methylphenidate . The chiral column was relatively cost effective and exhibited excellent performance with no separation deterioration observed after approximately 2500 injections . Pediatr Dev Pathol, 1999 Nov-Dec, 2(6), 552 - 8 Fetal membrane histology in preterm premature rupture of membranes: comparison to controls, and between antibiotic and placebo treatment . The National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network, Bethesda, MD, USA; Bendon RW et al.; The objectives of this study were to test the hypotheses that antibiotic therapy will alter the histologic appearance of fetal membranes in preterm premature rupture of membranes (pPROM), and that the membrane histology will demonstrate distinct differences between term and preterm rupture of membranes . We also wished to test interobserver variability of pathologists . Placental membranes were sampled from 268 women participating in a randomized placebo-controlled trial of antibiotic therapy for pPROM at 24-32 weeks of gestation (cases) and from 4 control groups who were not in the randomized trial: (1) preterm labor without pPROM (n = 21), (2) term labor (n = 65), (3) term PROM (n = 21), and (4) term cesarean section (n = 27) . The cases and controls were scored for 40 histologic features by pathologists blinded to the identity of each sample (case or control) . pPROM histology of samples from patients receiving antibiotics and those receiving placebo was compared using a chi-squared test and with control groups using logistic regression . There were no histological differences between pPROM cases treated with antibiotic and those receiving placebo, nor with respect to duration of membrane rupture greater or less than 48 h . Concordance among pathologists was low for features other than acute inflammation . Logistic regression analysis controlled for race and pathologist, and demonstrated that all of the control groups had significantly fewer common markers of acute inflammation when compared with the pPROM cases . This study suggests that histopathologic evidence of infection is seen more frequently with pPROM than in preterm or term controls . The histologic features used in this study cannot be used to determine the effectiveness of antibiotic therapy. Curr Opin Chem Biol, 1999 Oct, 3(5), 598 - 606 Initiation, elongation, and termination strategies in polyketide and polypeptide antibiotic biosynthesis; Keating TA et al.; Progress in sequence analysis of biosynthetic gene clusters encoding polyketides and nonribosomal peptides and in the reconstitution of in vitro activities continues to reveal new insights into the growth of these natural products' acyl chains, which have been revealed as a series of elongating, covalent, acyl enzyme intermediates on their multimodular scaffolds . Studies that focus on the three stages of natural product biosynthesis - initiation, elongation, and termination - have yielded crucial information on monomer substrate specificity, domain and module portability, and product release mechanisms, all of which are important not only for an understanding of this exquisite enzymatic machinery, but also for the rational construction of new, functional synthetases and synthases that are a goal of combinatorial biosynthesis. Pediatrics . 1999 Oct;104(4):e45. Allergy to beta-lactam antibiotics in children; Ponvert C et al.; BACKGROUND: Skin tests with soluble beta-lactams can be used to diagnose immediate and delayed hypersensitivity (HS) reactions to beta-lactam antibiotics . Very few studies have been performed with children with suspected beta-lactam allergy . In these studies, immediate HS to beta-lactams was diagnosed by skin tests in 4.9% to 40% of children . The diagnostic and predictive values of immediate responses in skin tests are good, because very few children with negative skin test results have positive oral challenge (OC) test results . Delayed responses in skin tests (intradermal and patch tests) have been reported in adult patients and children suffering with urticaria, angioedema, and maculopapular rashes during treatments with beta-lactam antibiotics . However, the diagnostic and predictive values of late responses are unknown . Semi-late responses in skin tests with beta-lactams have never been studied in adults or children . OBJECTIVES: The aims of this study were to confirm or rule out the diagnosis of allergy to beta-lactams in children with histories of adverse reactions to these antibiotics, to determine whether allergic children were sensitized to one or several classes of beta-lactams, and to evaluate the frequency and diagnostic value of immediate, accelerated, and delayed responses in skin tests with beta-lactam antibiotics in children . METHODS: We studied 325 children with suspected beta-lactam allergy . Skin tests (prick and intradermal) were performed with soluble forms of the suspected (or very similar) beta-lactams and with one or several beta-lactams from other classes . The reaction was assessed after 20 minutes (immediate), 8 hours (accelerated), and 48 to 72 hours (delayed) . OCs with the suspected beta-lactams were performed in patients with negative skin test results, except those with severe serum sickness-like reactions and potentially harmful toxidermias . RESULTS: Skin tests and OCs led to the diagnosis of beta-lactam allergy in 24 (7.4%) and 15 (4.6%) of the children, respectively . Thus, only 12% of the children were diagnosed as allergic to beta-lactams by means of skin tests and OC . HS to beta-lactams was suspected from clinical history in 30 (9.2%) children reporting serum sickness-like reactions and potentially harmful toxidermias . In a few children, we diagnosed food allergy and intolerance to excipients or nonsteroidal antiinflammatory drugs . No cause was found in the other children . Based on skin tests and OC, the prevalences of immunoglobulin E-dependent and of semi-late or delayed sensitizations to beta-lactam assessed were similar (6.8% vs 5.2%, respectively) . Most immunoglobulin E-dependent sensitizations were diagnosed by means of skin tests (86.4%) . In contrast, most semi-late and delayed sensitizations were diagnosed by OC (70.6%) . The likelihood of beta-lactam allergy was significantly higher for anaphylaxis (42.9% vs 8.3% in other reactions) and immediate reactions (25% vs 10% in accelerated and delayed reactions) . Of the children diagnosed as allergic to beta-lactam by means of skin tests, OC, and clinical history, 11.7% were sensitized to several classes of beta-lactams . The risk was significantly higher in children with anaphylaxis (26 . 7% vs 7.5% of the children with other reactions) and in children reporting immediate reactions (33.3% vs 8.5% of the children with accelerated and delayed reactions) . Finally, age, sex, personal history of atopy, number of reactions to beta-lactams, and number of reactions to other drugs were not significant risk factors for beta-lactam allergy . CONCLUSION: The skin tests were safe, and the immediate reaction to skin tests successfully diagnosed allergy to beta-lactam antibiotics in children reporting reactions suggestive of immediate HS . In contrast, most accelerated and delayed reactions were diagnosed by OC . Thus, our results suggest that the diagnostic and predictive values of skin tests for nonimmediate HS to beta-lactams in children are low . (ABSTRACT TRU Protist, 1999 Aug, 150(2), 189 - 95 Antibiotic inhibitors of organellar protein synthesis in Plasmodium falciparum; Clough B et al.; Elongation factor Tu (EF-Tu) is encoded by the tuf gene of the plastid organelle of the malaria parasite Plasmodium falciparum . A range of structurally unrelated inhibitors of this GTP-dependent translation factor was shown to have antimalarial activity in blood cultures . The most active was the cyclic thiazolyl peptide amythiamicin A with an IC50 = 0.01 microM . Demonstrable complexes were formed in vitro between a recombinant version of P . falciparum EF-Tu(pl) and inhibitors that bind to different sites on EF-Tu; these included the antibiotics kirromycin, GE2270A and enacyloxin IIa. Eur J Gastroenterol Hepatol, 1999 Aug, 11 Suppl 2, S35 - 7; discussion S43-5 Resistance of Helicobacter pylori to antibiotics: the main limitation of current proton-pump inhibitor triple therapy; Megraud F; Data showing the clinical relevance of Helicobacter pylori resistance, as well as recent data gathered from the MACH2 study, are presented . Despite the problems associated with testing for metronidazole resistance, a correlation between resistance and eradication failure is found in most studies of proton-pump inhibitor triple therapy, in which either amoxycillin or clarithromycin is used as the second antibiotic with metronidazole . Clarithromycin resistance is still low in most communities . Current data are scarce, but indicate that when present it has a higher negative impact on treatment outcome than metronidazole resistance . Resistance frequently emerges with treatment failure, although it is not clear to what extent resistant organisms will spread . In the MACH2 study, culture was used as one of the diagnostic tests and its sensitivity compared with the urea breath test was 99% . In addition, susceptibility tests could be performed on almost all strains . The overall rates of resistance to clarithromycin and metronidazole were found to be 3% (range 1-5%) and 24% (range 16-41%), respectively . There was a 15% decrease in success rate with omeprazole-metronidazole-clarithromycin treatment (from 91 to 76%) for metronidazole-resistant strains . The addition of omeprazole improved the efficacy of metronidazole-clarithromycin dual therapy . The best way to prevent resistance is to obtain the highest possible eradication rate. Mol Gen Genet, 1999 Aug, 262(1), 102 - 14 Molecular characterization of co-transcribed genes from Streptomyces tendae Tü901 involved in the biosynthesis of the peptidyl moiety of the peptidyl nucleoside antibiotic nikkomycin; Bruntner C et al.; Six genes (nikA, nikB, nikD, nikE, nikF, and nikG) from Streptomyces tendae Tu901 were identified by sequencing the region surrounding the nikC gene, which encodes L-lysine 2-aminotransferase, previously shown to catalyze the initial reaction in the biosynthesis of hydroxypyridylhomothreonine, the peptidyl moiety of the peptidyl nucleoside antibiotic nikkomycin . These genes, together with the nikC gene, span a DNA region of 7.87 kb and are transcribed as a polycistronic mRNA in a growth-phase dependent manner . The sequences of the deduced proteins NikA and NikB exhibit significant similarity to those of acetaldehyde dehydrogenases and 4-hydroxy-2-oxovalerate aldolases, respectively, which are involved in meta-cleavage degradation of aromatic hydrocarbons . The predicted NikD gene product shows sequence similarity to monomeric sarcosine oxidases, and the deduced NikE protein belongs to the superfamily of adenylate-forming enzymes . The nikF gene and the nikG gene encode a cytochrome P450 monooxygenase and a ferredoxin, respectively . Disruption of any of the genes nikA, nikB, nikD, nikE and nikF by insertion of a kanamycin resistance cassette abolished formation of the biologically active nikkomycins I, J, X, and Z . The nikA, nikB, nikD, and nikE mutants accumulated the nucleoside moieties nikkomycins Cx and Cz . In the nikD and nikE mutants nikkomycin production (nikkomycins I, J, X, Z) could be restored by feeding with picolinic acid and hydroxypyridylhomothreonine, respectively . The nikF mutant exclusively produced novel derivatives, nikkomycins Lx and Lz, which contain pyridylhomothreonine as the peptidyl moiety . Our results indicate that the nikA, nikB, nikD, nikE, nikF, and nikG genes, in addition to nikC, function in the biosynthetic pathway leading to hydroxypyridylhomothreonine, the putative activities of each of their products are discussed. Arch Fam Med, 1999 Sep-Oct, 8(5), 426 - 30 Antibiotics for upper respiratory tract infections . Follow-up utilization and antibiotic use; Hueston WJ et al.; OBJECTIVES: To examine the effects of antibiotic prescribing during an initial visit for viral respiratory tract infections on future care seeking and the cost of care . MATERIALS AND METHODS: Retrospective analysis of recorded visits for viral respiratory tract infections (N = 49,862) between January 1, 1995, and December 31, 1997, to practices in a large network of affiliated practices that use the same electronic medical record . RESULTS: Patients receiving antibiotics at the initial visit were less likely to return for a second visit, but this difference was small (15.4% vs 17.4%, P < .001) . When returning for the second visit, those who received an antibiotic on the initial visit were prescribed more expensive antibiotics than those who had not received an antibiotic on the initial consultation . Overall, cost from initial antibiotic use outweighed any benefit from reduced utilization in adults and children . CONCLUSIONS: Antibiotic prescribing at an initial contact for a viral respiratory tract illness may reduce the likelihood that an individual will return for a subsequent visit, but adds substantial costs to care for the initial antibiotic and for more expensive antibiotics used on subsequent visits. Conn Med, 1999 Aug, 63(8), 455 - 7 Rhabdomyolysis associated with the combined use of hydroxymethylglutaryl-coenzyme A reductase inhibitors with gemfibrozil and macrolide antibiotics; Landesman KA et al.; The hydroxymethylglutaryl-coenzyme A reductase inhibitors (HMG-CoAs) are one of the most significant causes of medication induced rhabdomyolysis . The development of rhabdomyolysis is increased when the HMG-CoAs are used concurrently with certain other medications, specifically gemfibrozil and macrolide antibiotics . In this report, we describe a patient with rhabdomyolysis from the combined use of lovastatin, gemfibrozil, and clarithromycin and review the relevant literature. Gastroenterology, 1999 Oct, 117(4), 794 - 7 Antibiotic efficacy in small intestinal bacterial overgrowth-related chronic diarrhea: a crossover, randomized trial; Attar A et al.; BACKGROUND & AIMS: No controlled trial has examined the clinical efficacy of antibiotics in small bowel bacterial overgrowth . METHODS: Ten patients with bacterial overgrowth-related diarrhea underwent the following five 7-day treatment periods: untreated (control period), then placebo, and subsequently, in random order and blinded fashion, norfloxacin (800 mg/day), amoxicillin-clavulanic acid (1500 mg/day), and Saccharomyces boulardii (1500 mg/day) . A hydrogen breath test was performed on the first and last day of each period . RESULTS: Daily stool frequency was similar during the control and placebo periods (4.2 +/- 0.6 vs . 3.9 +/- 0.6 {mean +/- SEM}, respectively) . Norfloxacin and amoxicillin-clavulanic acid led to a significant reduction in daily stool frequency (2.3 +/- 0.4 and 3.0 +/- 0.5, respectively; P < 0.01 vs . placebo period) after 2.0 +/- 1.4 and 1.2 +/- 0.4 days, which was maintained for 6.1 +/- 3.7 and 6.0 +/- 9.6 days, respectively . Breath-expired H(2) volume decreased with norfloxacin (37 +/- 8 to 12 +/- 5 mL per 2 hours; P < 0.01) and amoxicillin-clavulanic acid (24 +/- 6 to 8 +/- 4 mL per 2 hours, respectively; P = 0.01), but H(2) breath test result was negative in only 3 and 5 patients . CONCLUSIONS: Norfloxacin and amoxicillin-clavulanic acid are effective in the treatment of bacterial overgrowth-related diarrhea. Electrophoresis, 1999 Sep, 20(12), 2438 - 57 Avoparcin, a new macrocyclic antibiotic chiral run buffer additive for capillary electrophoresis; Ekborg-Ott KH et al.; Avoparcin, like vancomycin, teicoplanin, and ristocetin A, belongs to the family of macrocyclic glycopeptide antibiotics . These antibiotics have all been used as effective chiral selectors for capillary electrophoresis (CE), thin-layer chromatography (TLC), and high performance liquid chromatography (HPLC) . The present work focuses on avoparcin, which has been shown to be an excellent chiral selector for the CE enantioseparation of many N-blocked amino acids, as well as several anti-inflammatory drugs of pharmaceutical importance . The use of avoparcin as a chiral run buffer additive in CE is discussed, as well as the effects of changing experimental parameters, like avoparcin concentration, pH, organic modifiers, etc . Comparisons of enantioseparations of some N-3,5-dinitrobenzoyl-derivatized amino acids, using either avoparcin, ristocetin A, teicoplanin, or vancomycin in the run buffer, are also made . In general, vancomycin had the longest migration times, and ristocetin A the shortest, while avoparcin was intermediate . Generally, at least one of the four chiral selectors produced an excellent separation, while a different macrocyclic antibiotic produced a poor separation . Currently, we see no way to predict which chiral run buffer additive will be best or worst for an individual solute. J Bacteriol, 1999 Oct, 181(19), 6142 - 51 A Streptomyces coelicolor antibiotic regulatory gene, absB, encodes an RNase III homolog; Price B et al.; Streptomyces coelicolor produces four genetically and structurally distinct antibiotics in a growth-phase-dependent manner . S . coelicolor mutants globally deficient in antibiotic production (Abs(-) phenotype) have previously been isolated, and some of these were found to define the absB locus . In this study, we isolated absB-complementing DNA and show that it encodes the S . coelicolor homolog of RNase III (rnc) . Several lines of evidence indicate that the absB mutant global defect in antibiotic synthesis is due to a deficiency in RNase III . In marker exchange experiments, the S . coelicolor rnc gene rescued absB mutants, restoring antibiotic production . Sequencing the DNA of absB mutants confirmed that the absB mutations lay in the rnc open reading frame . Constructed disruptions of rnc in both S . coelicolor 1501 and Streptomyces lividans 1326 caused an Abs(-) phenotype . An absB mutation caused accumulation of 30S rRNA precursors, as had previously been reported for E . coli rnc mutants . The absB gene is widely conserved in streptomycetes . We speculate on why an RNase III deficiency could globally affect the synthesis of antibiotics. J Am Vet Med Assoc, 1999 Sep 15, 215(6), 833 - 6 Antibiotic residues in milk samples obtained from cows after treatment for papillomatous digital dermatitis; Britt JS et al.; OBJECTIVE: To determine whether there would be detectable antibiotic residues in milk obtained from dairy cattle with papillomatous digital dermatitis (PDD) after topical treatment with oxytetracycline . DESIGN: Randomized controlled clinical trial . ANIMALS: 28 lactating Holstein cows with PDD . PROCEDURE: Cows were assigned to 2 treatment groups . Treatment 1 (n = 16) consisted of spraying of PDD lesions with 15 ml of a solution containing 100 mg of oxytetracycline/ml; lesions were sprayed twice daily for 7 days, using a garden sprayer . Treatment 2 (n = 12) consisted of a one-time application of a bandage that consisted of cotton soaked with 20 ml of a solution containing 100 mg of oxytetracycline/ml . Milk samples were obtained before and after treatment and assayed for tetracycline content by use of high-performance liquid chromatography and a commercially available tetracycline screening test . RESULTS: None of the cows in either treatment group had violative residues of oxytetracycline in milk samples . CONCLUSIONS AND CLINICAL RELEVANCE: Producers treating lactating cows that have PDD, via topical application of oxytetracycline solution at the concentrations reported in this study, have a low risk of causing violative antibiotic residues in milk. J Am Dent Assoc, 1999 Sep, 130(9), 1341 - 3 Dental therapeutic indications for the newer long-acting macrolide antibiotics; Moore PA; BACKGROUND: When treating oral infections, clinicians have used the macrolide antibiotic erythromycin as an alternative antibiotic for patients who have documented allergic reactions to penicillins . In this article, the author reports on his assessment of the pharmacology of erythromycin and the newer macrolide antibiotics, as well as of their indications for the prevention of bacterial endocarditis and their possible use for oral-dental infections . TYPES OF STUDIES REVIEWED: The author reviewed the current clinical pharmacology literature with specific emphasis on reports indicating these antibiotics' efficacy in treating oral-dental infections . RESULTS: Azithromycin, clarithromycin and dirithromycin are erythromycin analogues that are currently marketed in the United States . All three have the therapeutic advantages over erythromycin of longer durations of action, enhanced acid stabilities and improved tissue distributions . A lower incidence of gastrointestinal distress and abdominal cramping is reported for all three of these newer agents than for erythromycin . Azithromycin and dirithromycin do not appear to compete for the same hepatic drug-metabolizing enzymes as erythromycin and therefore are not associated with the same drug interactions . CONCLUSIONS AND CLINICAL IMPLICATIONS: The newer macrolide antibiotics offer the advantage of fewer adverse gastrointestinal effects than erythromycin and dosing regimens of only once or twice a day . Yet, the extremely high price of the newer macrolides compared with that of erythromycin limits their routine use. J Urol, 1999 Oct, 162(4), 1396 - 8 Ibuprofen combined with antibiotics suppresses renal scarring due to ascending pyelonephritis in rats; Huang A et al.; PURPOSE: In acute pyelonephritis renal scarring may be decreased by immediate antibiotic therapy . Unfortunately in children there is often a delay in starting treatment, which increases the likelihood of renal scarring . In rodents immediate antibiotic therapy is effective for preventing renal scar formation resulting from experimentally induced pyelonephritis . However, the same treatment beginning 72 hours after infection does not prevent renal scarring in this paradigm . We examined whether delayed administration of the nonsteroidal anti-inflammatory agent ibuprofen only or combined with antibiotics suppresses renal scarring in a model of ascending pyelonephritis in rats . MATERIALS AND METHODS: An inoculum of 5x10(9) organisms per ml . of Escherichia coli strain BH-5 was instilled into the bladder of rats and the urethra was occluded for 4 hours . Groups of animals were and were not treated with 15 mg./kg . cefadroxil or 10 mg./kg . ibuprofen given twice daily for 5 days, or the 2 drugs combined . Treatment began 72 hours after inoculation . In an additional group of rats sterile phosphate buffered saline was instilled into the bladder . In each rat the kidneys were examined grossly and microscopically 6 weeks later . RESULTS: Combined antibiotics and ibuprofen significantly inhibited gross renal scarring compared with no treatment or antibiotics only (p<0.05) . No difference in renal scarring was detected in animals that received no treatment versus those that received antibiotics or ibuprofen only (p>0.05) . CONCLUSIONS: Renal scarring resulting from acute pyelonephritis in this rat model is not decreased by delayed treatment with antibiotics only . The addition of ibuprofen to antibiotic therapy is effective for decreasing renal scarring due to acute pyelonephritis even when treatment is delayed for 72 hours. Eur J Biochem, 1999 Sep, 264(2), 577 - 81 Location of the catalytic nucleophile of phospholipase D of Streptomyces antibioticus in the C-terminal half domain; Iwasaki Y et al.; Phospholipase D (PLD) of Streptomyces antibioticus was labelled with fluorescent-labelled substrate, 1-hexanoyl-2- inverted question mark6-{(7-nitro-2-1, 3-benzoxadiazol-4-yl)-amino}hexanoyl inverted question mark-sn-glycero-3-phosphocholine, when it was incubated with the substrate and the reaction followed by SDS/PAGE . Mutant enzymes lacking the catalytic activity were not labelled under the same conditions, indicating that labelling of the PLD occurred as the result of its catalytic action . This confirmed that the labelled protein was the phosphatidyl PLD intermediate . PLDs contain two copies of the highly conserved catalytic HxKxxxxD (HKD) motif . Therefore, two protein fragments were separately prepared with recombinant strains of Escherichia coli . One of the fragments was the N-terminal half of the intact PLD containing one HKD motif, and the other was the C-terminal half with the other motif . An active enzyme was reconstructed from these two fragments, and therefore designated fragmentary PLD (fPLD) . When fPLD was subjected to the labelling experiment, only the C-terminal half was labelled . Therefore, it was concluded that the catalytic nucleophile that bound directly to the phosphatidyl group of the substrate was located on the C-terminal half of PLD, and that the N-terminal half did not contain such a nucleophile. Laryngorhinootologie, 1999 Aug, 78(8), 450 - 4 {Postoperative antibiotic therapy of cervical lymphadenitis caused by nontuberculous, atypical mycobacteria}; Jackel MC et al.; BACKGROUND: Cervical lymphadenitis caused by atypical mycobacteria is increasingly observed in immunocompetent children between 1 and 5 years of age . Surgical excision of all affected lymph nodes represents the treatment of choice . However, due to the infiltrative nature of the disease, surgery is occasionally unable to provide a complete cure and is associated with a high risk of recurrence . Such cases might derive benefit from an additional antibiotic therapy . METHODS: The study includes 4 children with demonstrated or clinically suspected nontuberculous mycobacterial lymphadenitis, in whom partial surgery had been performed . Postoperatively, two patients were treated with clarithromycin, rifabutin, and protionamide, the others with clarithromycin alone . Antibiotics were administered orally for 6-12 weeks and were continued four weeks after local signs of inflammation were no longer detectable . RESULTS: In all cases, symptoms of lymphadenitis resolved within 1-2 months and did not recur . One patient was affected by WHO grade I leukopenia after 6 weeks, which soon disappeared after administration of rifabutin and protionamid had been discontinued . CONCLUSIONS: Postoperative antibiotic therapy seems to be an effective approach to treat residual disease following incomplete surgery . It remains to be clarified, however, if such a therapy should comprise combinations of agents or if administration of clarithromycin alone might be sufficient. Am J Rhinol, 1999 Jul-Aug, 13(4), 267 - 72 A macrolide antibiotic, roxithromycin, inhibits the growth of nasal polyp fibroblasts; Nonaka M et al.; Recently, the efficacy of macrolide antibiotics in cystic fibrosis and bleomycin-induced lung injury was reported . Nasal polyposis is a chronic inflammatory disease of the upper airway characterized by structural abnormalities including stromal fibrosis . Fibroblasts are resident cells thought to play an important role in the development of fibrosis . Although the effect of Roxithromycin (RXM) on inflammatory cells is well known, there is no evidence on the effect of RXM on fibroblasts . The purpose of the present study was two-fold: to examine the effect of RXM on the growth of fibroblasts in vitro and to examine the effect of RXM on the proliferation of fibroblasts in vivo . Nasal polyp fibroblast lines were generated from untreated patients, and those who were treated with RXM (300 mg/day) for one month before biopsy . Nasal polyp fibroblast lines from untreated patients were cultured for 72 hours with or without RXM, and the direct effect of RXM on fibroblast growth in vitro was examined by cell counting and 3H thymidine uptake . Next, we examined the in vivo effect of RXM on nasal polyp fibroblasts (NPFs) by comparing the growth characteristics of NPF lines from RXM treated and untreated patients . Finally, we examined the proliferating rate of NPF lines from the same patient before and after treatment with RXM . NPF lines that were treated with RXM exhibited a lower proliferating rate in vitro as compared to those that were not treated with RXM . Treatment of NPF lines with RXM suppressed the proliferation of fibroblasts in a dose-dependent manner . In addition, NPF lines from patients treated with RXM exhibited a lower proliferating rate in vitro as compared to NPF lines from the same patient taken before RXM treatment . We demonstrated that RXM directly suppressed nasal polyp fibroblast proliferation, and that this effect of RXM on fibroblast growth was persistent, indicating that RXM may prevent the progression of nasal polyposis by inhibiting the development of fibrosis. Altern Ther Health Med, 1999 Sep, 5(5), 64 - 8 Homeopathy versus antibiotics in metaphylaxis of infectious diseases: a clinical study in pig fattening and its significance to consumers; Albrecht H et al.; CONTEXT: Due to the conditions of modern industrial pig fattening in intensive livestock farms, 24% to 69% of the animals become ill . The antibiotic metaphylaxis that is routinely administered leads to several problems in animals, human health, and the environment . OBJECTIVE: To investigate whether a homeopathic metaphylaxis is effective and potentially useful for replacing antibiotic metaphylaxis . DESIGN: Animal subjects were divided into groups of 10 per pen, 2 pens sharing 1 trough . Twenty pigs were randomly assigned within a stall and were administered either antibiotics, homeopathy, or placebo . SETTING: A typical intensive livestock farm in Northern Germany . PARTICIPANTS: 1440 piglets . INTERVENTION: Homeopathic metaphylaxis is compared with placebo, the routine low-dose antibiotic metaphylaxis, and an antibiotic metaphylaxis in therapeutic dosage . MAIN OUTCOME MEASURES: Incidence of diseases in general and of diseases of the respiratory tract . RESULTS: Homeopathic metaphylaxis is significantly effective compared with placebo and routine low-dose antibiotic metaphylaxis for incidence of disease and rate of disease of the respiratory tract among the animals studied . Only by increasing the dosage of antibiotics to a therapeutic level does antibiotic metaphylaxis surpass homeopathic metaphylaxis . CONCLUSIONS: An unacceptably high percentage of pigs in modern livestock management become ill, suffering mainly from diseases of the respiratory tract . The routine antibiotic dosage of metaphylaxis is too low to be effective . As a result, the problems of resistance and danger to human health and the environment are increasing . To confirm whether antibiotic metaphylaxis may be replaced by homeopathic metaphylaxis, this study should be repeated independently. Arch Immunol Ther Exp (Warsz), 1999, 47(4), 211 - 6 Mechanistic and clinical aspects of beta-lactam antibiotics and beta-lactamases; Kotra LP et al.; Bacterial infections have been a major cause of concern in the recent years due to the emergence of drug resistance strains and inability of the current therapeutic regimens to treat these infections in certain cases . Beta-Lactam antibiotics have been drugs of choice since the introduction of penicillin . These drugs inhibit bacterial cell-wall-synthesizing enzymes, the so-called penicillin-binding proteins (PBPs) selectively, thus providing an effective strategy for treatment of the bacterial infections . Significantly, bacteria have developed resistance mechanisms to neutralize the antibiotic action of beta-lactam drugs . Beta-Lactamases are enzymes that hydrolyze the beta-lactam moiety of these drugs, rendering them inactive . This is the primary mechanism of resistance to this class of antibiotics . There are 255 known beta-lactamases to date and the continued use of beta-lactams may select for newer variants yet . A discussion of the roles of these enzymes in the manifestation of the drug-resistant phenotype and their implications for pathogenecity of clinical strains of bacteria is presented. Antibiot Khimioter, 1999, 44(5), 12 - 6 {Enzymatic synthesis of beta-lactam antibiotics . I . Cefazolin}; Kurochkina VB et al.; Production of cefazolin by acyl transfer enzymatic synthesis with immobilised cefazolin synthetase from Escherichia coli as a biocatalyst acting in accordance with the mechanism including formation of the acyl-enzyme complex was shown possible . The process kinetic parameters and the ratio of the maximum conversion of the key amino acid and the initial concentrations of the substrate and nucleophile were determined . Correlation of the calculated and experimental data on the cefazolin yield in the enzymatic synthesis was good . The main physico-chemical properties of the substrates and the reaction products i.e . dissociation constants and solubility were investigated . The complex of the physico-chemical studies makes it possible to design a highly efficient technological process for production of cefazolin including not only the stage of the enzymatic synthesis but also the stage of separation of the reaction mixture components. Antibiot Khimioter, 1999, 44(4), 5 - 8 {Actinoplanes brasiliensis INA 3802--a producer of peptide antibiotics}; Terekhova LP et al.; In the screening programme for new antibiotics an actinomycete culture designated as 3802 was isolated from a soil sample . The culture produced a complex of peptide antibiotics belonging to the group of lantibiotics . The antibiotic complex included gardimycin (actagardin) and new antibiotics of the same group . By the taxonomic properties strain 3802 was classified as Actinoplanes brasiliensis not previously known to produce gardimycin . Conditions of the antibiotic complex biosynthesis by strain 3802, the isolation methods and biological properties were studied. J Bacteriol, 1999 Sep, 181(18), 5600 - 5 Insertional inactivation of methylmalonyl coenzyme A (CoA) mutase and isobutyryl-CoA mutase genes in Streptomyces cinnamonensis: influence on polyketide antibiotic biosynthesis; Vrijbloed JW et al.; The coenzyme B(12)-dependent isobutyryl coenzyme A (CoA) mutase (ICM) and methylmalonyl-CoA mutase (MCM) catalyze the isomerization of n-butyryl-CoA to isobutyryl-CoA and of methylmalonyl-CoA to succinyl-CoA, respectively . The influence that both mutases have on the conversion of n- and isobutyryl-CoA to methylmalonyl-CoA and the use of the latter in polyketide biosynthesis have been investigated with the polyether antibiotic (monensin) producer Streptomyces cinnamonensis . Mutants prepared by inserting a hygromycin resistance gene (hygB) into either icmA or mutB, encoding the large subunits of ICM and MCM, respectively, have been characterized . The icmA::hygB mutant was unable to grow on valine or isobutyrate as the sole carbon source but grew normally on butyrate, indicating a key role for ICM in valine and isobutyrate metabolism in minimal medium . The mutB::hygB mutant was unable to grow on propionate and grew only weakly on butyrate and isobutyrate as sole carbon sources . (13)C-labeling experiments show that in both mutants butyrate and acetoacetate may be incorporated into the propionate units in monensin A without cleavage to acetate units . Hence, n-butyryl-CoA may be converted into methylmalonyl-CoA through a carbon skeleton rearrangement for which neither ICM nor MCM alone is essential. Eur J Clin Microbiol Infect Dis, 1999 Jul, 18(7), 490 - 5 Growth characteristics and influence of antibiotics on rough/smooth phenotypic variants of Helicobacter pylori; Bertram-Drogatz PA et al.; Helicobacter pylori shows a rather high variability of several biochemical markers including lipopolysaccharide structures . This study aimed to determine whether Helicobacter pylori has a potential for phenotypic variability and to describe its effects on bacterial pathogenesis . From colonies of three clinical strains of Helicobacter pylori with rough (R) colony morphology, spontaneous phenotypic variants with smooth (S) colony morphology were isolated that occurred with a frequency of 10(-2) to 10(-3), irrespective of growth conditions . R-variant bacteria produced exclusively low-molecular-mass lipopolysaccharide . They exhibited increased lysis in the presence of plain air . In contrast, the S variants produced low- and high-molecular-mass lipopolysaccharide and did not exhibit increased lysis in the presence of plain air . Cocultivation of bacterial cells with AGS stomach cancer cells revealed that R-variant bacteria but not S-variant bacteria effected an inhibition of high molecular-weight glycoprotein biosynthesis and secretion by the host cells . Skirrow supplement added as selective agent to liquid and/or solid media was tolerated to a similar extent among R- and S-variant bacteria, while all variants proved sensitive to metronidazole, amoxicillin and clarithromycin except for the R and S isolates of strain Hp57, which showed resistance to the latter compound . It was concluded that R- and S-variants of Helicobacter pylori may have distinct roles in pathogenesis; nevertheless, these bacteria may be isolated by traditional methods and eradicated by conventional anti-infective therapy. J Antibiot (Tokyo), 1999 May, 52(5), 480 - 4 UK-2A, B, C and D, novel antifungal antibiotics from Streptomyces sp . 517-02 . IV . Comparative studies of UK-2A with antimycin A3 on cytotoxic activity and reactive oxygen species generation in LLC-PK1 cells; Takimoto H et al.; UK-2A, a novel antifungal antibiotic, is a structural relative of antimycin A3 (AA) and its mode of action is similar to that of AA which inhibits mitochondrial electron transport at complex III . In spite of their structural resemblance, AA had strong cytotoxicity while UK-2A had little cytotoxicity against LLC-PK1 cells as well as other types of cultured cells . When cells were treated with UK-2A or with AA the intracellular ATP content decreased significantly within 5 minutes in glucose-free medium to almost the same extent in both cases . Moreover, under the same conditions, UK-2A killed cells at a similar rate to AA . This suggested that UK-2A entered into the cells and, like AA, inhibited mitochondrial electron transport . On the other hand, AA stimulated reactive oxygen species (ROS) production within 5 minutes even at a low concentration of 1 microM whereas UK-2A did not show such an effect . The difference in the ROS-producing abilities of UK-2A and AA may account for the different cytotoxic effects of the two compounds. J Antibiot (Tokyo), 1999 May, 52(5), 449 - 54 High-mannose type oligosaccharide-dependent apoptosis in U937 cells induced by pradimicin, a mannose-binding antibiotic; Oki T et al.; Cell surface oligosaccharides play a role in a variety of biological events such as cell adhesion and signal transduction . We have shown that BMY-28864, a semi-synthetic analog of pradimicin, induced apoptosis of U937 cells which had been incubated with 1-deoxymannojirimycin, an inhibitor of mannosidase I . BMY-28864 was not cytotoxic to the cells which had been cultivated with other glycosidase inhibitors such as castanospermine and swainsonine . We thus propose that BMY-28864 induces apoptosis by acting on a specific mannose-rich oligosaccharide, presumably (Man)9(GlcNAc)2+. CMAJ, 1999 Aug 24, 161(4), 388 - 92 Confidential prescriber feedback and education to improve antibiotic use in primary care: a controlled trial; Hux JE et al.; BACKGROUND: Antibiotics are a medication class for which inappropriate prescribing is frequently described . We sought to assess the effectiveness of a mailed intervention combining confidential prescribing feedback with targeted educational bulletins in increasing the use of less expensive, first-line antibiotics by practising physicians . METHODS: The participants were 251 randomly selected primary care physicians from southern Ontario who consented to participate (135 in the feedback group and 116 in the control group) . Prescribing data were obtained from the claims database of the Ontario Drug Benefit program, which covers all Ontarians over age 65 years for drugs selected from a minimally restrictive formulary . Confidentially prepared profiles of antibiotic prescriptions coupled with guidelines-based educational bulletins were mailed to the intervention group every 2 months for 6 months . The control group received no intervention until after completion of the study . The main outcome measures were change from baseline in physician's median antibiotic cost and proportion of episodes of care in which a prespecified first-line antibiotic was used first . RESULTS: The median prescription cost of about $11 remained constant in the feedback group but rose in the control group (change of $0.05 v . $3.37, p < 0.002) . First-line drug use increased in the feedback group but decreased in the control group (change of 2.6% v . -1.7%, p < 0.01) . In a mailed survey of 100 feedback recipients (response rate 76%), 82% indicated that they would participate readily in another, similar program . INTERPRETATION: A simple program of confidential feedback and educational materials blunted cost increases, increased the use of first-line antibiotics and was highly acceptable to Ontario primary care physicians. Tenn Med, 1999 Sep, 92(9), 339 - 40 Accidental veterinary antibiotic injection into a farm worker; Crown LA et al.; A 29-year-old white male farm worker accidentally injected tilmicosin, a bovine antibiotic, into his finger . He developed temporary pulmonary, gastrointestinal, and neuromuscular symptomatology and a more persistent subjective asthenia. Otolaryngol Head Neck Surg, 1999 Sep, 121(3), 277 - 82 Effect of topical antibiotic therapy on recovery after tonsillectomy in adults; Mann EA et al.; OBJECTIVE: Systemic antibiotics given during the first week after tonsillectomy appear to be effective in reducing postoperative morbidity . We assessed the effectiveness of perioperative topical antibiotic rinses in reducing posttonsillectomy morbidity . METHODS: A randomized, double-blinded, placebo-controlled pilot study of 36 patients undergoing tonsillectomy was used to evaluate the effects of a standard 7-day systemic regimen of perioperative intravenous ampicillin/oral amoxicillin and 2 single-day topical antibiotic regimens: (1) clindamycin (Cleocin) and (2) amoxicillin/clavulanate (Augmentin) and ticarcillin/clavulanate (Timentin) . RESULTS: Mean aerobic and anaerobic oral bacterial counts were decreased in both topical treatment groups compared with the placebo group on the first postoperative day, achieving statistical significance with Augmentin/Timentin (aerobic and anaerobic bacterial counts) and Cleocin (aerobic counts) . Significantly less postoperative pain and mouth odor were reported for both Cleocin (P = 0.014 and P = 0.005, respectively) and Augmentin/Timentin (P = 0.026 and P = 0.05, respectively) topical treatment groups when compared with the placebo group . CONCLUSIONS: Preliminary results indicate a reduction in oral bacterial counts and postoperative morbidity in adult patients receiving topical antibiotics compared with patients receiving placebo; further investigation is warranted. Surg Clin North Am, 1999 Aug, 79(4), 759 - 65, ix Nonsurgical management of acute pancreatitis . Use of antibiotics; Runzi M et al.; In severe AP, infected necrosis is the leading cause of death . Prevention of pancreatic infection is the major goal in the treatment of patients with necrotizing pancreatitis . Adequate early antibiotic therapy seems to be promising in these patients . Their role and the optimal timing of the antibiotic therapy (e.g., benefit of prophylactic application) are discussed . Preliminary results of a study in patients with infected pancreatic necrosis and exclusively or primarily conservative treatment also are presented. Pediatrics, 1999 Sep, 104(3 Pt 1), 447 - 53 Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections; Franz AR et al.; OBJECTIVE: To examine whether the determination of interleukin 8 (IL-8) and C-reactive protein (CRP) in neonates with suspected nosocomial bacterial infection (NBI) is feasible and cost-effective in reducing antibiotic therapy . METHODS: Between April 1996 and May 1997, IL-8 was measured 260 times along with blood cultures, CRP, and immature-to-total-neutrophil (IT) ratio for suspected NBI in term and preterm neonates . All infants were retrospectively analyzed for NBI . Sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated for IL-8, CRP, and IT ratio . Receiver-operating characteristic curves were analyzed to determine optimal thresholds . Between June 1997 and June 1998, IL-8 was measured 215 times in newborn infants with suspected NBI and the decision to start antibiotic therapy was based on increased IL-8 and/or CRP values . A cost-effectiveness analysis was performed and sensitivity, specificity, and receiver-operating characteristic curves were reevaluated . RESULTS: At the first suspicion of NBI, the combination of IL-8 >/= 53 pg/mL and/or CRP >10 mg/L detected culture-proven NBI with 96% sensitivity . The combined culture-proven and clinical NBI were detected with 93% sensitivity and 80% specificity . The use of IL-8 reduced unnecessary antibiotic therapy for suspected NBI by 73% and was cost-effective when compared with initiating antibiotic therapy based on clinical signs alone or based on clinical signs and an increased IT ratio and/or CRP . CONCLUSIONS: The combination of IL-8 and/or CRP is a reliable and early test for the diagnosis of NBI in newborn infants . Using the combination of IL-8 and/or CRP to restrict antibiotic therapy to truly infected infants reduces unnecessary antibiotic therapy and is cost-effective. Chirality, 1999, 11(8), 663 - 8 Enantioseparations with the macrocyclic antibiotic ristocetin A using a countercurrent process in CE; Oswald TM et al.; The chiral selectivity of ristocetin A was examined in a countercurrent process in CE using a coated column to suppress electroosmotic flow . Excellent enantioseparations of several nonsteroidal antiinflammatories, dansylamino acids, dinitrophenyl-derivatized amino acids, and other optically active compounds were achieved . The chiral selectivity of ristocetin A also was examined as a function of antibiotic concentration and pH . Enantioresolution was found to significantly improve with a slight increase in migration time upon increasing chiral selector concentration . Enantioselectivities were found to be greatly influenced by pH of the running buffer . Folia Med (Plovdiv), 1999, 41(1), 88 - 91 Treatment of upper respiratory tract infections in the first year of life without antibiotics and antipyretics; Patchev H et al.; There is still no consensus on the question whether it is necessary to use prophylactic antibiotic therapy and on the febrile states in infectious diseases . The present study aims at solving these problems . Between 1996 and 1997, 128 children under one year of age with upper respiratory tract infections (URTI) were hospitalized in the department and examined using clinical, laboratory and instrumental methods . We found no significant difference in the percentage of complications in the children treated with or without antibiotics . We conclude that prophylactic antibiotic therapy is not justified for the predominating viral etiology of URTI in children less than one year old . URTIs can be managed without antipyretics, which entails no risk for the patients. J Pept Res, 1999 Aug, 54(2), 137 - 45 The solution structure of uperin 3.6, an antibiotic peptide from the granular dorsal glands of the Australian toadlet, Uperoleia mjobergii; Chia BC et al.; Uperin 3.6 (GVIDA5AKKVV10NVLKN15LF-NH2) is a wide-spectrum antibiotic peptide isolated from the Australian toadlet, Uperoleia mjobergii . With only 17 amino acid residues, it is smaller than most other wide-spectrum antibiotic peptides isolated from amphibians . In 50% (by vol.) trifluoroethanol, an NMR study and structure calculations indicate that uperin 3.6 adopts a well-defined amphipathic alpha-helix with distinct hydrophilic and hydrophobic faces . Examination of the activities of synthetic modifications of uperin 3.6 reveal that the three lysine residues are essential for antibiotic activity. Vet Rec, 1999 Jul 17, 145(3), 67 - 71 Efficacy of a single dose of oral antibiotic given within two hours of birth in preventing watery mouth disease and illthrift in colostrum-deficient lambs; Hodgson JC et al.; An antibiotic with a product licence limited to the treatment and control of infectious bacterial enteritis associated with Escherichia coli in piglets was tested for its ability to control watery mouth disease in neonatal lambs . Three groups of lambs were kept in conditions commonly encountered in intensive lambing systems, where high levels of environmental bacterial contamination may be expected . They were allocated at birth to: a control group (group 1) consisting of 18 colostrum-deprived lambs; group 2, consisting of 17 lambs given one feed of colostrum when they were two hours old; and group 3, consisting of 18 colostrum-deprived lambs given spectinomycin orally when they were two hours old . Nine group 1 lambs became diseased and were killed for humane reasons . Blood biochemical changes included hyperglycaemia followed by hypoglycaemia, lactacidaemia, hypoproteinaemia and metabolic acidosis, and postmortem examination of the diseased lambs showed signs consistent with endotoxaemia and a clinical diagnosis of watery mouth disease . Coliforms were isolated from the blood of all group 1 lambs and from half the lambs in groups 2 and 3, but endotoxaemia and watery mouth disease occurred only in group 1 lambs . The results for groups 2 and 3 showed that neither colostrum nor antibiotic at the rates and frequency used prevented bacteraemia, although consecutive samples were positive only on three occasions . Group 3 lambs consistently grew more rapidly than the surviving group 1 lambs and as rapidly as group 2 lambs . There was no evidence that male lambs were more prone to watery mouth disease than female lambs . The results indicated that the antibiotic spectinomycin did not induce endotoxaemia during low-grade bacteraemia and that a single oral dose given within two hours of birth protected colostrum-deprived lambs delivered into a contaminated indoor environment against watery mouth disease. Psychiatr Prax, 1999 Jul, 26(4), 205 - 6 {Symptomatic psychosis in bland sinus thrombosis and antibiotic therapy}; Hartig G et al.; It is difficult to define intracranial sinus thrombosis by clinical symptoms only . We report on a case of symptomatic psychosis which occurred in sinus thrombosis with defective blood-brain barrier during treatment with antibiotics. J Gastrointest Surg, 1998 Nov-Dec, 2(6), 496 - 503 Role of antibiotics in acute pancreatitis: A meta-analysis; Golub R et al.; In an attempt to decrease the infectious complications of acute pancreatitis and its high mortality, many investigators have conducted randomized prospective trials on the efficacy of prophylactic antibiotics . The results of these studies are conflicting, and many have called for a large multicenter study . Because multicenter trials are costly and difficult to organize, we believe that meta-analysis is a reasonable alternative . A meta- analysis of all eight previously published trials of prophylactic antibiotics in acute pancreatitis was performed . The end point was death . The Mantel-Haenszel statistic was used to summarize odds ratios across studies in a fixed effects model, after homogeneity was assessed . Sensitivity analysis was performed as appropriate . The meta-analysis of all eight trials showed a positive benefit for antibiotics in reducing mortality . Sensitivity analysis showed that the advantage was limited to patients with severe pancreatitis who received broad- spectrum antibiotics that achieve therapeutic pancreatic tissue levels . It is recommended that all patients with severe pancreatitis be treated with broad- spectrum antibiotics that achieve therapeutic levels in pancreatic tissue. Rapid Commun Mass Spectrom, 1999, 13(17), 1744 - 54 Rapid analysis of tetracycline antibiotics by combined solid phase microextraction/high performance liquid chromatography/mass spectrometry; Lock CM et al.; The technique of solid phase microextraction (SPME) combined on-line with high performance liquid chromatography/mass spectrometry (HPLC/MS) has been applied to the analysis of seven tetracycline analogues . Rapid baseline separation was achieved in under 5 min using a short 3 microm RP-18e cartridge column . Optimisation of the SPME procedure is described including choice of extracting fibre and modification of the sample by heating or salting out of the analytes . Detection limits of 4-40 ng/mL were obtained for the various analogues from extracted aqueous samples and absolute amounts of analyte extracted by the method determined using external calibration . To demonstrate the applicability of the technique for real samples the extraction of tetracycline from milk is described . J Pharmacol Exp Ther, 1999 Sep, 290(3), 1026 - 33 Stimulatory and inhibitory properties of aminoglycoside antibiotics at N-methyl-D-aspartate receptors; Masuko T et al.; The effects of aminoglycoside antibiotics on N-methyl-D-aspartate (NMDA) receptors were studied using voltage-clamp recording of recombinant NMDA receptors expressed in Xenopus oocytes . A number of aminoglycosides were found to potentiate macroscopic currents at heteromeric NR1A/NR2B receptors, but not at NR1A/NR2A, NR1A/NR2C, NR1A/NR2D, or NR1B/NR2B receptors . The degree of potentiation had a rank order neomycin B > paromomycin > gentamicin C > geneticin > kanamycin A > streptomycin . Potentiation was not seen with kasugamycin and spectinomycin . The degree of stimulation paralleled the number of the amino groups in the aminoglycosides . The stimulatory effects of aminoglycosides were more pronounced at subsaturating concentrations of glycine and at acidic pH, similar to the stimulatory effects of spermine . We measured the effects of aminoglycosides at mutant NMDA receptors to determine which amino acid residues in NMDA receptor subunits are involved in stimulation . Mutations that reduced or abolished spermine stimulation also reduced stimulation by aminoglycosides . Several aminoglycosides produced a weak voltage-dependent block of NMDA receptors, but the degree of inhibition did not appear to correlate with the number of amino groups in the molecule . The results suggest that aminoglycosides having more than three amino groups have stimulatory effects that are mediated through the spermine-binding site on NMDA receptors. Vestn Otorinolaringol, 1999, (4), 22 - 4 {Co-amoxiclav antibiotic therapy of acute otitis media, exacerbation of otitis media chronica and sinusitis in children}; Bogomil'skii MR et al.; A comparative trial was performed of two regimens of antibiotic therapy in acute otitis, exacerbation of otitis media chronica and sinusitis in children . 100 children received combined treatment with amoxycilline and clavulanic acid (amoxiclav and autmentin) . 50 control children were i.m . injected ampicilline . Oral co-amoxiclavs proved highly effective in ENT diseases in children and are superior to intramuscular ampicilline. FEBS Lett, 1999 Jul 30, 456(1), 89 - 92 Enzymatic synthesis of beta-lactam antibiotics using penicillin-G acylase in frozen media; van Langen LM et al.; Penicillin-G acylase (EC 3.5.1.11) from Escherichia coli catalyzed the synthesis of various beta-lactam antibiotics in ice at -20 degrees C with higher yields than obtained in solution at 20 degrees C . The initial ratio between aminolysis and hydrolysis of the acyl-enzyme complex in the synthesis of cephalexin increased from 1.3 at 20 degrees C to 25 at -20 degrees C . The effect on the other antibiotics studied was less, leading us to conclude that freezing of the reaction medium influences the hydrolysis of each nucleophile-acyl-enzyme complex to a different extent . Only free penicillin-G acylase could perform transformations in frozen media: immobilized preparations showed a low, predominantly hydrolytic activity under these conditions. Bioorg Med Chem Lett, 1999 Jul 19, 9(14), 2025 - 30 Synthesis and cytotoxicity of analogues of the antibiotic BE 10988 inhibitors of DNA topoisomerase II; Catrycke MO et al.; Indolequinone derivatives of the antitumour antibiotic BE 10988 were synthesized and evaluated for their cytotoxicity and action mechanism . The quinone system is essential to biological activity and the thiazole ring plays a major role in the poisoning of topoisomerase II. J Clin Invest, 1999 Aug, 104(4), 375 - 81 Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice; Barton-Davis ER et al.; Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene, leading to the absence of the dystrophin protein in striated muscle . A significant number of these mutations are premature stop codons . On the basis of the observation that aminoglycoside treatment can suppress stop codons in cultured cells, we tested the effect of gentamicin on cultured muscle cells from the mdx mouse - an animal model for DMD that possesses a premature stop codon in the dystrophin gene . Exposure of mdx myotubes to gentamicin led to the expression and localization of dystrophin to the cell membrane . We then evaluated the effects of differing dosages of gentamicin on expression and functional protection of the muscles of mdx mice . We identified a treatment regimen that resulted in the presence of dystrophin in the cell membrane in all striated muscles examined and that provided functional protection against muscular injury . To our knowledge, our results are the first to demonstrate that aminoglycosides can suppress stop codons not only in vitro but also in vivo . Furthermore, these results raise the possibility of a novel treatment regimen for muscular dystrophy and other diseases caused by premature stop codon mutations . This treatment could prove effective in up to 15% of patients with DMD. Graefes Arch Clin Exp Ophthalmol, 1999 Sep, 237(9), 705 - 13 Meta-analysis of six clinical phase III studies comparing lomefloxacin 0.3% eye drops twice daily to five standard antibiotics in patients with acute bacterial conjunctivitis; Jauch A et al.; BACKGROUND: Lomefloxacin 0.3% ophthalmic solution twice daily has been compared in patients with bacterial conjunctivitis in six randomized double-blind or investigator-masked phase III studies with either chloramphenicol 0.5% 5x/day, gentamicin 0.3% 4x/day, fusidic acid 1% 2x/day, tobramycin 0.3% 4x/day or norfloxacin 0.3% 4x/day . METHODS: A meta-analysis of all individual data of these six studies was performed . A total of 582 patients with clinically diagnosed bacterial conjunctivitis were evaluated by slit-lamp examination with grading of eight key signs and symptoms and by conjunctival swab cultures at baseline, on day 3-5 and on day 7-9 . Success of therapy, local tolerance and safety were evaluated at termination . In vitro sensitivity of the ocular isolates to 6-10 antibiotics was evaluated by disk diffusion tests . RESULTS: Two hundred and ninety patients treated with lomefloxacin 0.3% (LF) and 292 patients treated by one of the control antibiotics (combined control group, CCG) were enrolled in the studies . Two hundred and seventy-eight LF and 283 CCG patients were evaluable for the intent-to-treat (ITT) analysis, while 85 LF and 95 CCG patients had bacteria above the pathological threshold and formed the core subpopulation . The mean cumulative sum score in the LF group was 9 . 47 on day 1, and decreased by 5.70 on day 3-5 and by 8.10 on day 7-9 . In the CCG it decreased significantly less: it was 9.19 at baseline, decreased by 5.15 on day 3-5 and by 7.33 on day 7-9 . Swab counts decreased in the LF and CCG group similarly, with the major decrease observed between day 1 and day 3-5 . Most of the organisms considered resistant in vitro were still eradicated with the regimen used . Of the few surviving organisms also isolated on the next follow-up visit, one isolate in the LF group and seven in the CCG showed decreased in vitro sensitivity towards the treatment antibiotic used . Local tolerance was good or excellent, without any significant differences except for burning sensation, which lasted significantly longer in the CCG group than in the LF group . Adverse events were observed in 18 LF and 23 CCG patients; four LF and three CCG patients had to be withdrawn . All adverse events were non-serious . CONCLUSION: Lomefloxacin eye drops used with a loading dosage followed by a twice daily regimen proved as effective, safe and well tolerated as five established standard treatments used at a 2, 4 or 5 times daily regimen, caused less discomfort upon instillation, and showed a lower risk to generate or select new resistant strains. Scand J Infect Dis, 1999, 31(2), 169 - 71 Effect of antibiotics and anti-inflammatory agents on the purified protein derivative response in the rat; Kabakus N et al.; We investigated the effects of several antibiotics and anti-inflammatory agents on the purified protein derivative (PPD) response in the rat . Animals were immunized with Mycobacterium bovis vaccine BCG . Antibiotics and anti-inflammatory drugs were administered at therapeutic doses for 10 d . Chloramphenicol, erythromycin, aspirin and ibuprofen suppressed the PPD response, but penicillin and acetaminophen had no significant effects. RNA, 1999 Aug, 5(8), 1003 - 13 Peptidyl transferase antibiotics perturb the relative positioning of the 3'-terminal adenosine of P/P'-site-bound tRNA and 23S rRNA in the ribosome; Kirillov SV et al.; A range of antibiotic inhibitors that act within the peptidyl transferase center of the ribosome were examined for their capacity to perturb the relative positioning of the 3' end of P/P'-site-bound tRNA and the Escherichia coli ribosome . The 3'-terminal adenosines of deacylated tRNA and N-Ac-Phe-tRNA were derivatized at the 2 position with an azido group and the tRNAs were cross-linked to the ribosome on irradiation with ultraviolet light at 365 nm . The cross-links were localized on the rRNA within extended versions of three previously characterized 23S rRNA fragments F1', F2', and F4' at nucleotides C2601/A2602, U2584/U2585 (F1'), U2506 (F2'), and A2062/C2063 (F4') . Each of these nucleotides lies within the peptidyl transferase loop region of the 23S rRNA . Cross-links were also formed with ribosomal proteins L27 (strong) and L33 (weak), as shown earlier . The antibiotics sparsomycin, chloramphenicol, the streptogramins pristinamycin IA and IIA, gougerotin, lincomycin, and spiramycin were tested for their capacity to alter the identities or yields of each of the cross-links . Although no new cross-links were detected, each of the drugs produced major changes in cross-linking yields, mainly decreases, at one or more rRNA sites but, with the exception of chloramphenicol, did not affect cross-linking to the ribosomal proteins . Moreover, the effects were closely similar for both deacylated and N-Ac-Phe-tRNAs, indicating that the drugs selectively perturb the 3' terminus of the tRNA . The strongest decreases in the rRNA cross-links were observed with pristinamycin IIA and chloramphenicol, which correlates with their both producing complex chemical footprints on 23S rRNA within E . coli ribosomes . Furthermore, gougerotin and pristinamycin IA strongly increased the yields of fragments F2' (U2506) and F4' (U2062/C2063), respectively . The results obtained with an RNAse H approach correlate well with primer extension data implying that cross-linking occurs primarily to the bases . Both sets of data are also consistent with the results of earlier rRNA footprinting experiments on antibiotic-ribosome complexes . It is concluded that the antibiotics perturb the relative positioning of the 3' end of the P/P'-site-bound tRNA and the peptidyl transferase loop region of 23S rRNA. Orv Hetil, 1999 Jul 4, 140(27), 1529 - 32 {Effect of an antibiotic combination on the propagation of Borrelia burgdorferi, causative agent of Lyme disease}; Lakos A et al.; The effects of combined antibiotics (pefloxacin-doxycycline and pefloxacin-ceftriaxone) were tested on the most prevalent European Lyme spirochete species, Borrelia garinii by checkerboard dilution . The influence was judged both microscopically and by the measurement of the pH of the culture medium on the 5th day after inoculation . Borreliae propagated quite well at the concentration of 4 mg/l pefloxacin but the motility and the metabolism of the spirochete injured . Neither synergetic nor additive effect of the combination could be registered . Surprisingly, the pefloxacin at a concentration less than 4 mg/l activated both the propagation and the metabolism of borreliae, showing a clear antagonistic effect with doxycycline and ceftriaxone . Unless well-controlled animal model will prove the contrary, quinolones neither alone nor in combination should be used in Lyme borreliosis. J Clin Pharm Ther, 1999 Jun, 24(3), 181 - 9 Attitudes of pharmacists and physicians to antibiotic policies in hospitals; Adu A et al.; BACKGROUND: Antibiotic therapy in hospitals has substantial impact on patient outcome and the pharmacy drug budget . Antibiotic policies have been implemented by some hospitals to improve the quality of patient outcome and cost of antibiotic therapy . Antibiotic policies impose certain requirements on pharmacists and physicians . Pharmacists' and physicians' attitudes to and opinions about antibiotic policies are likely to affect the usefulness of such policies . AIM: To determine the attitudes of pharmacists and physicians to antibiotic policies in New South Wales (NSW) hospitals . METHODS: Pharmacists and physicians in NSW public hospitals were surveyed to determine their attitudes to and opinions on antibiotic policies . A simple one-stage cluster sample of 241 pharmacists and a two-stage cluster sample of 701 physicians were obtained . Factor analysis was used to identify the attitudinal dimensions . General linear modelling was used to investigate the effects of predictor variables on outcome variables . RESULTS: The response rates were 91% and 77% for pharmacists and physicians, respectively . Factor analysis identified three dimensions of attitude to antibiotic policies: that they encourage rational antibiotic use; that they improve the quality of antibiotic prescribing and that they are associated with some problems . The reliability of these factors (Cronbach's alpha) ranged from 0.71 to 0.74, and was 0.90 for the overall attitude scale . Pharmacists and physicians had a positive overall attitude to antibiotic policies . Whereas physicians recognize that antibiotic policies improve the quality of prescribing, this was highly correlated with identification of problems (alpha = 0.71) . In urban hospitals, pharmacists were more likely than physicians to associate antibiotics with problems . CONCLUSION: There was a positive overall attitude to hospital antibiotic policies expressed by pharmacists and physicians. Bull Acad Natl Med, 1999, 183(3), 601 - 9; discussion 609-13 {French National Institute for observation of prescriptions and consumption of medicines . Prescription and consumption of antibiotics in ambulatory care}; Bouvenot G; The National Research Institute for Prescriptions and Consumption of medicines which was founded under the authority of the Minister of Health, is charged with the following missions: improved evaluation of the therapeutic needs of the population; more precise knowledge of therapeutic management; the identification of possible deviations in relation to systems of reference; recommendations in favor of correct use of medicines; and the optimization of patient management . Its first report concerned the antibiotic therapy of respiratory infections . In France, the average annual increase rate of the frequency of antibiotics consumption was in the region of 3.7%, between the periods 1980-1981 and 1991-1992 . It essentially concerned cephalosporins and quinolones . Between 1991 and 1996 antibiotics sales increased on average by 2.1%, in units, per year . The increase of this consumption, which was not justified by any epidemiological evolution, is partly explained by the high frequency of antibiotic prescriptions during respiratory or ENT affections presumed to be of viral etiology: in 40% of rhinopharyngitis, 80% of acute bronchitis and more than 90% of anginas, whatever the age . Moreover the antibiotic treatments were not prescribed optimally: too long duration, insufficient dosages . Such phenomena are disturbing with regard to their consequences on the evolution of bacterial resistances . A comparison between French practices and those of Germany and the United Kingdom suggests that recourse to treatment is more frequent in France for the infectious diseases mentioned above, with more intensive utilization of antibiotics, in particular broad-spectrum penicillins . Recommendations have been made in favor of a rationalisation of practices. Zhonghua Nei Ke Za Zhi, 1997 Oct, 36(10), 689 - 92 {Hyperosmotic glucose and antibiotics induce production of plasminogen activator inhibitor and expression of TGF beta mRNA by rat peritoneal mesothelial cells}; Dong K et al.; To investigate the mechanism of fibrosis in peritoneal dialysis, we observed the effects of the hyperosmotic glucose and antibiotics such as gentamicin and cefazolin on rat peritoneal mesothelial cells with cell culture, fibrin-plate lyzing and Northern blotting analysis method . The peritoneal mesothelial cells may express PAI-1 mRNA . The expression of PAI-1 mRNA in peritoneal mesothelial cells and activities of PAI in the supernatants were enhanced by 11.2 mmol/L glucose, gentamicin and cefazolin at 12 hr . By 24 hr, the activity of PAI-1 also increased in the supernatants with 11.2 mmol/L glucose . The expression of PAI-1 mRNA and production of PAI activities by the peritoneal mesothelial cells were increased by gentamicin, and the TGF-beta mRNA increased in the peritoneal mesothelial cells was induced by 11.2 mmol/L glucose, gentamicin and cefazolin . The results suggested that 11.2 mmol/L glucose, gentamicin and cefazolin may increase the expressions or productions of PAI and TGF-beta in peritoneal mesothelial cells . So by perosmotic glucose, cefazolin and gentamicin promote the peritoneal fibrosis in patients with CAPD. Proc Natl Acad Sci U S A, 1999 Aug 3, 96(16), 9003 - 8 Direct crosslinking of the antitumor antibiotic sparsomycin, and its derivatives, to A2602 in the peptidyl transferase center of 23S-like rRNA within ribosome-tRNA complexes; Porse BT et al.; The antitumor antibiotic sparsomycin is a universal and potent inhibitor of peptide bond formation and selectively acts on several human tumors . It binds to the ribosome strongly, at an unknown site, in the presence of an N-blocked donor tRNA substrate, which it stabilizes on the ribosome . Its site of action was investigated by inducing a crosslink between sparsomycin and bacterial, archaeal, and eukaryotic ribosomes complexed with P-site-bound tRNA, on irradiating with low energy ultraviolet light (at 365 nm) . The crosslink was localized exclusively to the universally conserved nucleotide A2602 within the peptidyl transferase loop region of 23S-like rRNA by using a combination of a primer extension approach, RNase H fragment analysis, and crosslinking with radioactive {(125)I}phenol-alanine-sparsomycin . Crosslinking of several sparsomycin derivatives, modified near the sulfoxy group, implicated the modified uracil residue in the rRNA crosslink . The yield of the antibiotic crosslink was weak in the presence of deacylated tRNA and strong in the presence of an N-blocked P-site-bound tRNA, which, as was shown earlier, increases the accessibility of A2602 on the ribosome . We infer that both A2602 and its induced conformational switch are critically important both for the peptidyl transfer reaction and for antibiotic inhibition . This supposition is reinforced by the observation that other antibiotics that can prevent peptide bond formation in vitro inhibit, to different degrees, formation of the crosslink. Antimicrob Agents Chemother, 1999 Aug, 43(8), 2090 - 2 In vitro susceptibilities of four Bartonella bacilliformis strains to 30 antibiotic compounds; Sobraques M et al.; We have evaluated for the first time in vitro antibiotic susceptibilities of four human strains of Bartonella bacilliformis, the agent of Carrion's disease . Our results show that B . bacilliformis, like other Bartonella species, is highly susceptible to antibiotics, including most beta-lactams, aminoglycosides, chloramphenicol, rifampin, macrolides, tetracyclines, cotrimoxazole, and fluoroquinolones. Antimicrob Agents Chemother, 1999 Aug, 43(8), 2074 - 6 Stability of antibiotics used for antibiotic-lock treatment of infections of implantable venous devices (ports); Anthony TU et al.; Antibiotic-lock is a treatment for catheter-related bloodstream infections in which a solution containing heparin and an antibiotic dwells in the lumen of the catheter or port . We tested the stability of vancomycin, cefazolin, ticarcillin-clavulanic acid, ceftazidime, or ciprofloxacin combined with heparin after incubation in vitro at 25 or 37 degrees C for intervals of up to 10 days by bioassay . All the antibiotic solutions except ceftazidime retained >/=90% activity at both 25 and 37 degrees C . Thus, studies of antibiotic-heparin lock solutions with dwell times of up to 10 days are feasible. J Chromatogr A, 1999 Jul 2, 848(1-2), 375 - 85 Enantiomeric separations by capillary electrochromatography using a macrocyclic antibiotic chiral stationary phase; Carter-Finch AS et al.; Racemic mixtures of tryptophan and dinitrobenzoyl leucine have been successfully resolved by capillary electrochromatography (CEC) using the macrocyclic antibiotic teicoplanin, covalently bonded to a 5 microns silica support . Modification of a previously published packing procedure was required to pack reliable capillaries, capable of performing enantiomeric separations . Good levels of enantioselectivity were obtained in all cases, with optimised separations being performed in less than 6 min . Retention times, resolution and reproducibility are discussed. Angew Chem Int Ed Engl, 1999 Aug, 38(15), 2096 - 2152 Chemistry, Biology, and Medicine of the Glycopeptide Antibiotics; Nicolaou KC et al.; The war against infectious bacteria is not over! Although vancomycin and glycopeptide antibiotics have provided a strong last line of defence against many drug-resistant bacteria, their overuse has given rise to more dangerous strains of bacteria . An understanding of the chemistry and biology of these highly complex glycopeptides are destined to play a crucial role in the discovery of new antibiotics. N Engl J Med, 1999 Jul 29, 341(5), 305 - 11 A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy; Freifeld A et al.; BACKGROUND: Among patients with fever and neutropenia during chemotherapy for cancer who have a low risk of complications, oral administration of empirical broad-spectrum antibiotics may be an acceptable alternative to intravenous treatment . METHODS: We conducted a randomized, double-blind, placebo-controlled study of patients (age, 5 to 74 years) who had fever and neutropenia during chemotherapy for cancer . Neutropenia was expected to be present for no more than 10 days in these patients, and they had to have no other underlying conditions . Patients were assigned to receive either oral ciprofloxacin plus amoxicillin-clavulanate or intravenous ceftazidime . They were hospitalized until fever and neutropenia resolved . RESULTS: A total of 116 episodes were included in each group (84 patients in the oral-therapy group and 79 patients in the intravenous-therapy group) . The mean neutrophil counts at admission were 81 per cubic millimeter and 84 per cubic millimeter, respectively; the mean duration of neutropenia was 3.4 and 3.8 days, respectively . Treatment was successful without the need for modifications in 71 percent of episodes in the oral-therapy group and 67 percent of episodes in the intravenous-therapy group (difference between groups, 3 percent; 95 percent confidence interval, -8 percent to 15 percent; P=0.48) . Treatment was considered to have failed because of the need for modifications in the regimen in 13 percent and 32 percent of episodes, respectively (P<0.001) and because of the patient's inability to tolerate the regimen in 16 percent and 1 percent of episodes, respectively (P<0.001) . There were no deaths . The incidence of intolerance of the oral antibiotics was 16 percent, as compared with 8 percent for placebo (P=0.07) . CONCLUSIONS: In hospitalized low-risk patients who have fever and neutropenia during cancer chemotherapy, empirical therapy with oral ciprofloxacin and amoxicillin-clavulanate is safe and effective. Lik Sprava, 1999 Jan-Feb, (1), 85 - 8 {The effect of antibiotic therapy on the immune status of patients with nonspecific lung diseases complicated by pleural empyema}; Opanasenko NS et al.; The immunity status was studied in patients with acute pyo-destructive lung diseases complicated by purulent pleurisy (relative counts of T- and B-lymphocytes, subpopulation composition of T-cells, numbers of lymphocytes-killers, and functional state of neutrophils of the peripheral blood) . These patients revealed significant cellular immunodeficiency, rise in B-lymphocytes, and apparent changes in the activity of the peripheral blood phagocytes . The endolymphatic drug route was found out to be superior to conventional ones in that it had more expressed normalizing action on the quantitative and functional state of T-lymphocytes, their subpopulation composition (manifested by augmentation of T-cells-helpers), as well as on the level of B-lymphocytes, lymphocytes-killers, and metabolic activity of neutrophils of the peripheral blood. New Microbiol, 1999 Jul, 22(3), 233 - 9 Genetic determinants of active antibiotic-producing soil streptomycetes; Saadoun I et al.; Plasmids or covalently closed circular (CCC)-DNA molecules are abundant in the genus Streptomyces, and have been suggested to be involved in the genetic control of the production of many antibiotics in these organisms . In this study, 21 active antibiotic-producing Streptomyces isolates were screened for their plasmid content by an alkaline lysis method which revealed the presence of a small plasmid DNA in the positive control Streptomyces lividans ATCC 35287, containing pIJ702 plasmid (5.65 kb in size) . However, no low molecular weight plasmids were observed in the tested antibiotic-producing Streptomyces strains suggesting that antibiotic production in these strains is likely chromosomally encoded DNA . Treatment of 2 Streptomyces strains with 10 mM ethidium bromide (EB) resulted in the failure to produce aerial mycelia and antibiotic activity. Am J Ther, 1999 Jan, 6(1), 25 - 36 Omeprazole plus antibiotics in the eradication of Helicobacter pylori infection: a meta-regression analysis of randomized, controlled trials; Schmid CH et al.; This article presents a meta-regression analysis of published studies of omeprazole plus antibiotics (amoxicillin, clarithromycin, or an imidazole derivative) in the treatment of Helicobacter pylori . Eligible studies were all randomized, controlled trials published through April 1996 with 10 or more patients receiving omeprazole plus antibiotics for 5 or more days and testing for H . pylori eradication 4 weeks or more after treatment . Probability of eradication was calculated for each treatment arm, and logistic regression was performed using study characteristics as covariates . Seventy-four studies involving 117 treatment arms with 4,769 patients were identified . The eradication rate was 76% for omeprazole plus clarithromycin and 65% for omeprazole plus amoxicillin dual regimens (P <.0001) . Eradication rates for triple regimens were 82%, omeprazole plus amoxicillin plus clarithromycin; 83%, omeprazole plus amoxicillin plus imidazole; and 89%, omeprazole plus clarithromycin plus imidazole . In a multiple logistic regression analysis, significant factors were antibiotic, disease, omeprazole dose, and whether treatment was followed by maintenance omeprazole . A systematic overview of the best available evidence suggests that dual therapy with omeprazole plus clarithromycin is superior to omeprazole plus amoxicillin . Triple therapy is better than dual therapy . Treatment works better on ulcers than on nonulcer dyspepsia . Higher doses of omeprazole give better results . Additional trials exploring higher omeprazole doses for varying durations as well as cost, side effects, and compliance trade-offs with efficacy are recommended. Antonie Van Leeuwenhoek, 1999 Jan-Feb, 75(1-2), 41 - 78 Compartmentalization and transport in beta-lactam antibiotic biosynthesis by filamentous fungi; van de Kamp M et al.; A proper description of the biosynthesis of fungal beta-lactam antibiotics requires detailed knowledge of the cell biology of the producing organisms . This involves a delineation of the compartmentalization of the biosynthetic pathways, and of the consequential transport steps across the cell-boundary plasma membrane and across organellar membranes . Of the enzymes of the penicillin biosynthetic pathway in Penicillium chrysogenum and Aspergillus nidulans, delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) and isopenicillin N synthase (IPNS) probably have a cytosolic location . Acyl-coenzyme A:isopenicillin N acyltransferase (IAT) is located in microbodies . Of the two enzymes that may be involved in activation of the side chain, acetyl-coenzyme A synthetase (ACS) is located in the cytosol, and phenylacetyl-coenzyme A ligase (PCL) is probably located in the microbody . All enzymes of the cephalosporin biosynthesis pathway in Cephalosporium acremonium probably have a cytosolic location . The vacuole may play an ancillary role in the supply of precursor amino acids, and in the storage of intermediates . The distribution of precursors, intermediates, end- and side-products, the transport of nutrients . precursor, intermediates and products across the plasma membrane, and the transport of small solutes across organellar membranes, is discussed . The relevance of compartmentalization is considered against the background of recent biotechnological innovations of fungal beta-lactam biosynthesis pathways. Antibiot Khimioter, 1999, 44(6), 6 - 11 {Dynamics of antibiotic biosynthesis by Streptomyces chrysomallus with different plasmid status in submerged and surface culture}; Efron-Konoshenko GI; The dynamics of simultaneous production of two antibiotic substances of different structure by the same species streptomycete was studied . The comparative investigation of accumulation of actinomycin C (AC) and macrotetrolides (MTL) was performed in aerated submerged culture and on surface culture with three strains of Streptomyces chrysomallus of different plasmid status and with their bld mutants . It was shown that the dynamics of the AC and MTL production was different in the liquid medium and on the agarized medium . The maxima of the AC and MTL production were observed at different stages of the S.chrysomallus development which was likely due to different physiological roles of the two antibiotics in S.chrysomallus . The character of the MTL accumulation in the culture of bld mutants differed from that of the starting strains . By the level and dynamics of the antibiotics biosynthesis S.chrysomallus BKM Ac-590 and its mutants containing plasmids pSCH2 and pSCH3 differed from the other strains. FEMS Microbiol Lett, 1999 Jul 1, 176(1), 191 - 6 A conspicuous adaptability to antibiotics in the Escherichia coli mutator strain, dnaQ49; Tanabe K et al.; By repeating the cycle of mutagenesis and selection, the Escherichia coli dnaQ49 mutator acquired high level resistance to ampicillin (30,000 micrograms ml-1), streptomycin (26,000 micrograms ml-1) and ofloxacin (3000 micrograms ml-1) . Under the strong pressure of ofloxacin, dnaQ49 also followed the history of mutations in the gyrase and topoisomerase i.v . genes previously observed in clinical isolates of quinolone-resistant E . coli . The results of these in vitro experiments suggest that naturally existing mutators may participate in the rapid acquisition of resistance to various antibiotics in patients . A possible mechanism for the occurrence of this adaptability is discussed with special reference to the property of mutagenesis accompanying DNA replication. Rev Pneumol Clin, 1999 Apr, 55(2), 65 - 74 {Prescription and use of antibiotics in ambulatory care . Drug Agency}; Antibiotics et al.; Accident and Emergency Department, Stoke Mandeville Hospital, Aylesbury, BucksOBJECTIVES: To establish if advice concerning risks of pregnancy when taking oral contraceptive pill and antibiotics is being offered . METHOD: A retrospective audit of notes of 100 female patients aged 15-39 who were prescribed antibiotics . RESULTS: Documentation of use of contraception was noted in 3% of patients . Advice concerning risks and further precautions was noted in this 3% but not in any other records . CONCLUSION: The audit identified a gap in documentation and/or clinical practice in advising women of childbearing age of the risk of conceiving when using oral contraceptive pill and antibiotics . Recommendations are given as to how this may be addressed. J Accid Emerg Med, 1999 Jul, 16(4), 265 - 7 Oral contraceptives and oral antibiotics: interactions and advice in an accident and emergency setting; Mullan MH et al.; OBJECTIVE: (1) To determine what advice, if any, would be given by accident and emergency (A&E) doctors to women who were taking the combined oral contraceptive pill (OCP) if they had been issued with broad spectrum antibiotics and (2) after an audit programme had been instigated, whether appropriate advice was given to such women . METHODS: A questionnaire was circulated to 12 doctors working in the Exeter A&E department to assess their level of knowledge in prescribing antibiotics to women taking the OCP . Notes of women aged 15-50 who had been prescribed broad spectrum antibiotics were examined to see if a contraceptive history had been taken . If the patient was found to be taking the combined OCP it was noted whether documented advice had been given about using an additional form of contraception . Six months later after two education sessions had been held, prescriptions and notes were examined . A patient education leaflet was produced to be given to these women, indicating what additional precautions should be taken after having been prescribed antibiotics . SETTING: The A&E department of a busy district general hospital . SUBJECTS: Women aged 15-50 who had been issued with broad spectrum antibiotics . RESULTS: The level of knowledge in regard to contraceptive advice given to women taking the OCP among doctors working in an A&E department was poor . However, after educational sessions and the production of a patient information leaflet, there was an improvement in women receiving correct advice . CONCLUSIONS: The clinical significance of drug interactions between oral contraceptives and antibiotics indicates the importance of asking a full contraceptive drug history of any woman of childbearing age and documenting this in the notes . Regular audit of this topic is needed to keep it at the front of doctors' minds. J Pharmacol Exp Ther, 1999 Aug, 290(2), 672 - 7 The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1; Jariyawat S et al.; In the present study, we investigated the interactions between antibiotics, especially beta-lactam antibiotics, and rat renal organic anion transporter 1 (OAT1) . {(14)C}p-Aminohippurate (PAH) uptake via OAT1 expressed in Xenopus laevis oocytes was inhibited by all of the penicillins and cephalosporins tested . Penicillin G, carbenicillin, cephaloridine, cephalothin, cefazolin, and cephalexin inhibited {(14)C}PAH uptake via OAT1 in a competitive manner (K(i) = 0.29-2.33 mM) . Cinoxacin, a quinolone gyrase inhibitor, also inhibited PAH uptake via OAT1 . Other antibiotics, such as gentamicin, streptomycin, and vancomycin, which do not contain anionic moieties, did not interact with OAT1 . {(3)H}Penicillin G and {(14)C}cephaloridine were demonstrated to be transported via OAT1 . Using the cells that stably expressed OAT1, we analyzed the cytotoxicity of several beta-lactam antibiotics . Cells expressing OAT1 showed higher susceptibility to cephaloridine (a potentially nephrotoxic beta-lactam antibiotic) toxicity than did control cells . The present study suggests that OAT1 is the major organic anion transporter in the kidney that is responsible for the renal secretion of antibiotics, especially that of beta-lactam antibiotics . Furthermore, the culture cell system expressing OAT1 was revealed to be useful for the prediction of the nephrotoxicity of beta-lactam antibiotics. Bioconjug Chem, 1999 Jul-Aug, 10(4), 583 - 8 Molecular modeling of hapten structure and relevance to broad specificity immunoassay of sulfonamide antibiotics; Spinks CA et al.; Molecular modeling of hapten structure was used to predict and influence, through appropriate synthetic work, the outcome of an immunization program . Examination of the structures of sulfonamide antibiotics led to the development of a hypothesis and the consequent synthesis of a sulfacetamide-protein immunogen aimed at the generation of broad specificity anti-sulfonamide antibodies . The antisera generated, alongside anti-sulfachlorpyradizine antisera generated at the same time, were characterized for cross-reactions against a range of sulfonamide drugs, and were found to exhibit good but not the desired broad specificity . Discussion is presented as to the reasons for the failure of the hypothesis . Further hypotheses are developed and speculation is made as to the future of molecular modeling in immunochemical research. Rapid Commun Mass Spectrom, 1999, 13(14), 1381 - 9 Post-column metal complexation of quinolone antibiotics in a quadrupole ion trap; Shen J et al.; Post-column addition of a metal salt and an auxiliary chelating ligand via a sheath flow offers an alternative strategy for promoting electrospray ionization of analytes via metal cationization . In the present study, a high-performance liquid chromatography (HPLC) mass spectrometer interface that incorporates a modified ionspray source that allows either online metal cationization or protonation is reported . The analytical utility of metal complexation is evaluated relative to protonation as a means for efficient ionization and generation of structurally diagnostic ions during HPLC separation . To improve metal cationization, an auxiliary chelating ligand is added to the sheath flow to coordinate the metal and stabilize the resulting complexes . The methodology was verified using a series of quinolone antibiotics as model analytes . Relative reaction efficiencies were compared for the protonation vs . metal complexation modes, and it was found that metal complexation with an auxiliary chelating ligand gave a three to five times better detection limit than protonation for the quinolones . Detector linearity and optimal reaction conditions are also reported . Prostaglandins Other Lipid Mediat, 1999 Jun, 57(4), 207 - 18 Effect of different classes of antibiotics on amniotic prostaglandin E release; Vesce F et al.; Our purpose was to investigate the effects of different classes of antibiotics, namely beta-lactamines, aminoglicosides, tetracyclines, macrolides, on amniotic prostaglandin E release to clarify their role in the treatment of premature labor . The effects of these antibiotics were tested also in combination with ampicillin, whose antiprostaglandinergic action had been demonstrated previously . Ceftriaxone and gentamicin significantly and reversibly inhibit both basal and arachidonic acid- or oxytocin-stimulated prostaglandin E release from amnion, although to a different extent . On the contrary, tetracycline and erythromycin do not influence prostaglandin E output . The inhibitory effect of ampicillin is potentiated, in an additive manner, by ceftriaxone, reduced by gentamycin, and eliminated by tetracycline and erythromycin . The finding that diverse classes of antibiotics and their combinations affect amniotic prostaglandin E release should be taken into account in the management of premature labor. Laryngoscope, 1999 Jul, 109(7 Pt 1), 1081 - 3 Preoperative antibiotics and steroids in vestibular schwannoma excision; Welling DB et al.; OBJECTIVE: To examine the benefits of preoperative admission for intravenous steroids and antibiotics for patients undergoing vestibular schwannoma excision . STUDY DESIGN: Retrospective cohort study . METHODS: One hundred twenty patients with pathologically confirmed vestibular schwannoma followed for at least 1 year after surgery were included . Sixty patients were assigned to the preoperative admission group and 60 patients to the same-day-admission surgery group . The preoperative admission group was given intravenous dexamethasone (0.1 mg/kg) and intravenous cefazolin (1 g) beginning 12 hours before surgery . The same-day-surgery group received the same dosage of medication beginning at induction of anesthesia . OUTCOMES: Facial nerve function, meningitis, and wound infection rates, duration of hospital stay, and readmission rates were examined . RESULTS: There was no statistical difference in facial nerve function between the groups when controlling for tumor size . Likewise, there was no difference in meningitis or wound infection rates in the groups . As expected, hospital stay was significantly reduced but readmission rates were not affected . CONCLUSIONS: There are no apparent facial nerve function or infection control benefits to 1-day preoperative admission for intravenous steroids and antibiotics for patients undergoing vestibular schwannoma excision. Analyst, 1998 Nov, 123(11), 2263 - 6 Spectrofluorimetric study of the degradation of alpha-amino beta-lactam antibiotics catalysed by metal ions in methanol; Gutierez Navarro P et al.; The alpha-aminopenicillins ampicillin and amoxicillin and a cephalosporin, cephalothin, give rise to a fluorescent product when their methanolic solutions are incubated for prolonged time periods . The process also occurs in the presence of the metal ions Cd2+, Co2+ and Zn2+ . The effects of the different ions on the emission and excitation wavelengths and the appearance rate of the fluorophore were studied . The appearance of the fluorescent product was zero order for ampicillin and amoxicillin in metal ion-free solution and solutions with Cd2+ and Zn2+, whereas in the presence of Co2+ ion it was first order under the experimental conditions used; for cephalothin it was first order in all cases . Apparent fluorescent compound formation rates were calculated in the zero-order reactions and rate constants in the first-order reactions . The activation energy of the formation reaction of the fluorescent products of amoxicillin and ampicillin was calculated from a study of the reactions at four temperatures; all the values recorded were between 34 and 118 kJ mol-1 . As a possible mechanism for the formation of these products, cyclization of the penamaldic derivative of the antibiotic, which is formed in the first stage of the methanolytic reaction, is proposed. Infect Control Hosp Epidemiol, 1999 Jun, 20(6), 440 - 3 Implementation of a practical antibiotic policy in the Czech Republic; Kolar M et al.; We describe the antibiotic control policy at the Faculty Hospital in Olomouc, Czech Republic . Practical examples of successful implementation of the policy are provided. Acta Clin Belg, 1999 Apr, 54(2), 80 - 7 How epileptogenic are the recent antibiotics? Hantson P, Leonard F, Maloteaux JM, Mahieu P. OBJECTIVE: To review the clinical and experimental data concerning the serious neurologic adverse events, and more particularly seizures, which could be related to the administration of recent antibiotics, with special reference to cephalosporins, monobactams, carbapenems, and fluoroquinolones . DATA SOURCES: We have searched in the MEDLINE database over the years 1966-1998 the pertinent publications dealing with antibiotics related neurotoxicity . We used the thesaurus function and the following key words: antibiotics, neurotoxicity, seizures . Additional references were found in the articles sorted by the MEDLINE search . DATA SYNTHESIS: Neurotoxic manifestations following antibiotics administration are infrequently encountered under usual conditions . Experimental studies are helpful to demonstrate that these compounds might interact with a major component of the neurotransmission, the gamma aminobutyric acid (GABA) receptor complex . Structure-toxicity relationships can be described . For the clinician, the recognition of some predisposing factors related either to the patient (age, previous central nervous system disorder ...) or to the drug metabolism (reduced renal clearance, drug interactions ...) may help to minimise the risk of adverse neurologic manifestations . Several factors have to be taken into account before assessing causality: delay from administration, evolution, origin of the adverse event (risk factors, other drugs, non pharmacological origin), possibility of rechallenge, confirmation by biological testing or in vitro experiments.... Appl Microbiol Biotechnol, 1999 May, 51(5), 586 - 91 A new route to L-threo-3-{4-(methylthio)phenylserine}, a key intermediate for the synthesis of antibiotics: recombinant low-specificity D-threonine aldolase-catalyzed stereospecific resolution; Liu JQ et al.; A new enzymatic resolution process was established for the production of L-threo-3-{4-(methylthio)phenylserine} (MTPS), an intermediate for synthesis of antibiotics, florfenicol and thiamphenicol, using the recombinant low-specificity D-threonine aldolase from Arthrobacter sp . DK-38 . Chemically synthesized DL-threo-MTPS was efficiently resolved with either the purified enzyme or the intact recombinant Escherichia coli cells overproducing the enzyme . Under the optimized experimental conditions, 100 mM (22.8 g l-1) L-threo-MTPS was obtained from 200 mM (45.5 g l-1) DL-threo-MTPS, with a molar yield of 50% and a 99.6% enantiomeric excess. Antimicrob Agents Chemother, 1999 Jul, 43(7), 1808 - 10 In vitro susceptibilities of Chlamydia pneumoniae isolates from German patients and synergistic activity of antibiotic combinations; Freidank HM et al.; The susceptibilities of six Chlamydia pneumoniae type strains and of six German patient isolates to erythromycin, azithromycin, roxithromycin, clarithromycin, doxycycline, ofloxacin, and rifampin were investigated . MICs and minimal chlamydicidal concentrations were all within the ranges reported previously . Combinations of azithromycin with either ofloxacin, doxycycline, or rifampin, as well as combinations of three antibiotics (rifampin, azithromycin, and ofloxacin or doxycycline), showed synergistic activity against C . pneumoniae. Hindustan Antibiot Bull, 1997 Feb-Nov, 39(1-4), 64 - 71 Optimisation of cultural conditions for antifungal antibiotic accumulation by Streptomyces rochei G164; Chattopadhyay D et al.; To induce higher amount of antifungal antibiotic production by variation of cultural parameters has been studied . The maximum effectivity was found in sucrose as carbon source, peptone as nitrogen source and at pH 7.0 . The effect of other selected factors were also evaluated in order to judge the variables that influenced antibiotic production. Hindustan Antibiot Bull, 1997 Feb-Nov, 39(1-4), 61 - 3 Antimycotic effects of some antibiotics on the growth of some dermatophytes and other keratin degrading fungi; Singh CJ et al.; Four antibiotics have been tested against the growth of some dermatophytes and keratin degrading fungi . A gradual decrease in growth was observed with increase in concentration of all antibiotics . All, but griseofulvin observed to inhibit > 50% mycelial weight even at a lower concentration of 50 ppm . Azole derivatives were most toxic to the growth of M . gypseum at all concentrations, whereas, to that of C . tropicum at above 100 ppm . Mycostatin was the most toxic antibiotic to the growth of M . gypsea at all concentrations. Medinfo, 1998, 9 Pt 1, 549 - 53 Focusing on resistance development in a case based teleconsultation system for antibiotics therapy advice; Gierl L et al.; In this paper, we describe an approach to support physicians when they select a calculated antibiotic therapy for intensive care patients who have developed an infection as an additional complication . As advice is needed quickly and the pathogen is not yet known, we use an expected pathogen spectrum based on medical background knowledge and known resistances, which both will be adapted to the results of the laboratory . Case-Based Reasoning retrieval methods provide the advice for similar previous patients . Their solutions are adapted to be applicable to the new medical situation of the current patient . Furthermore, we present the recent resistance developments of the antibiotics to the physician. Drug Metab Dispos, 1999 Jul, 27(7), 776 - 85 An in vitro study on the metabolism and possible drug interactions of rokitamycin, a macrolide antibiotic, using human liver microsomes; Zhao XJ et al.; This in vitro study was designed to identify the enzyme(s) involved in the two major metabolic pathways of rokitamycin {formations of leucomycin A7 (LMA7) from rokitamycin and of leucomycin V (LMV) from LMA7} and to assess possible drug interactions using human liver microsomes . Formation of LMA7 or LMV was NADPH-independent . Anti-rat NADPH cytochrome P-450 (CYP) reductase serum, specific inhibitors, or substrates of CYP isoforms showed no effects on the formation of LMA7 or LMV . The mean Vmax and Vmax/Km for the formation of LMA7 from rokitamycin were much greater (P <.01) than those for the formation of LMV from LMA7 . Two esterase inhibitors, bis-nitro-phenylphosphate and physostigmine (100 microM), inhibited the formation of LMA7 or LMV by more than 85%, whereas no appreciable inhibition occurred by several substrates of carboxylesterase (EC 3.1.1.1) . Except the moderate inhibition produced by promethazine and terfenadine, theophylline, mequitazine, chlorpheniramine, and diphenhydramine showed little or no inhibition for the formation of LMA7 or LMV . Rokitamycin, LMA7, LMV, erythromycin, and clarithromycin (up to 500 microM) had no appreciable inhibition for CYP1A2-, 2C9-, and 2D6-mediated catalytic reactions . However, rokitamycin, LMA7, erythromycin, and clarithromycin inhibited the CYP3A4-catalyzed triazolam alpha-hydroxylation with IC50 (Ki) values of 5.8 (2.0), 40, 33 (20), and 56 (43) microM, respectively . It is concluded that the formations of LMA7 from rokitamycin and of LMV from LMA7 are catalyzed mainly by human esterase enzyme {possibly cholinesterase (EC3.1.1.8)} . However, whether rokitamycin would inhibit the CYP3A-mediated drug metabolism in vivo requires further investigations in patients. J Chromatogr A, 1999 Apr 16, 839(1-2), 193 - 201 Capillary electrophoresis of some tetracycline antibiotics coupled with reductive fast cyclic voltammetric detection; Zhou J et al.; The separation and quantitative performance parameters for tetracycline, chlortetracycline and oxytetracycline antibiotics were investigated by capillary zone electrophoresis coupled with fast cyclic voltammetric detection . Optimization of pH and complexation with a boric acid-sodium tetraborate buffer provided good resolution of all compounds . Detection by electrochemical reduction using fast on-line cyclic voltammetric detection with a Hg-film-microm electrode gave detection limits (2 x peak-to-peak baseline noise) of 7 x 10(-7) mol/l for tetracycline and chlortetracycline, and 1.5 x 10(-6) mol/l for oxytetracycline . The influence of electrode material, potential range and scan rate was examined and discussed . Optimal electrochemical detection was obtained at a Hg-film electrode with a waveform that consisted of an initial constant potential of -0.6 V for 200 ms followed by a cyclic voltammetry (CV) scan at 300 V/s from - 0.6 V to a vertex potential of 1.7 V . The analytical signal was obtained by plotting the integrated values of the CV current from each applied waveform as a function of time . The calibration plot (peak areas) for each separated peak was found to be linear over three-orders of magnitude. Neuroreport, 1999 May 14, 10(7), 1543 - 6 Increase of cellular hypoxic tolerance by erythromycin and other antibiotics; Huber R et al.; Antibiotics are used extensively, but in addition to their anti-infectious effects some inhibit cellular energy metabolism . We investigated hypoxic tolerance following in vivo pretreatment with erythromycin and kanamycin, or in vitro pretreatment with ampicillin . Recovery of the CA1 population spike amplitude in hippocampal slices upon 15 min hypoxia improved time-dependently following single i.p . in vivo pretreatment with erythromycin (maximum at 6 h: recovery 90+/-7% (mean s.d.) vs 30% in untreated controls; p<0.01) . The hypoxia-induced increase in NADH was smaller in slices that recovered from hypoxia . We conclude that antibiotics increase cellular hypoxic tolerance to a varying extent . Use of antibiotics in experimental studies may, therefore, distort conclusions about hypoxic sensitivity and confounding mechanisms . In contrast, antibiotics may provide an effective strategy to induce chemical preconditioning in humans. Microbiology, 1999 May, 145 ( Pt 5), 1115 - 22 Changes in Aspergillus nidulans gene expression induced by bafilomycin, a Streptomyces-produced antibiotic; Melin P et al.; In natural environments bacteria and filamentous fungi often compete for the same resources . Consequently, production of antibiotic secondary metabolites and defence mechanisms against these compounds have evolved in these organisms . An experimental model has been developed to study the response in fungi exposed to one such antibiotic . The filamentous fungus Aspergillus nidulans was treated with bafilomycin B1, a Streptomyces-produced antibiotic which reduces radial growth rate and induces morphological changes in fungi . mRNA differential display was used to study changes in fungal gene expression . For five genes, changes in abundance of the corresponding mRNAs, directly or indirectly caused by bafilomycin, were observed . Of these, three were up-regulated and two repressed . With four of these the change in mRNA abundance measured ranged from 10- to 60-fold . However, for one gene the mRNA was only detected after bafilomycin treatment . One of the down-regulated mRNAs encodes ASPND1, a glycoprotein that belongs to a known family of antigens identified in aspergilloma patients . One up-regulated mRNA shows sequence similarities, at the amino acid level, with a cell-wall protein of Saccharomyces cerevisiae . The remaining three genes were also cloned and sequenced; their sequences do not correspond to known genes in A . nidulans, and no similarities with published nucleotide or protein sequences in other organisms were found . These results indicate the feasibility of using mRNA differential display to study interactions between bacteria and filamentous fungi. Eur J Cardiothorac Surg, 1996, 10(12), 1097 - 105; discussion 1105-6 Long-term results of valve replacement using antibiotic-sterilised homografts in the aortic position; Langley SM et al.; OBJECTIVE: Antibiotic-sterilised homograft valves stored at 4 degrees C have been implanted in the subcoronary position in this unit since 1973 . This study was undertaken in order to assess the long-term function of these valves . METHODS: All 249 patients undergoing homograft aortic valve replacement (AVR) at the Wessex Cardiothoracic Centre between April 1973 and December 1994 were studied . Homograft valve sizes ranged from 15 mm to 28 mm internal diameter, 202 (81.1%) varying between 18 mm and 22 mm . The mean patient follow-up was 12.4 years with a total follow-up of 3096 patient-years . There were six early deaths (2.4%) . RESULTS: On actuarial analysis, survival was 78.5+/-2.7% (1SE) at 10 years, 65.7+/-3.3% at 15 years and 55.0+/-3.9% at 20 years . The freedom from redo AVR was 87.9+/-2.4% at 10 years, 71.7 +/-3.8% at 15 years and 49.7+/-5.6% at 20 years . The freedom from structural degeneration was 85.6+/-2.5% at 10 years, 63.6+/-4.0% at 15 years and 41.9+/-6.4% at 20 years . On multivariate analysis the risk of valve failure was significantly higher in younger patients (P<0.0001) and in those who underwent aortic root tailoring (P = 0.024) . The freedom from endocarditis was 98.4+/-0.9% at 10 years, 96.2+/-1.6% at 15 years and 95.1+/-1.9% at 20 years . Of the 249 patients, 218 had an isolated homograft AVR and were not anticoagulated . In this group there were two possible thromboembolic events . CONCLUSION: As well as the established haemodynamic benefits, this study has shown that homograft AVR with antibiotic-sterilised 4 degrees C stored homograft valves implanted in the subcoronary position, offers good long-term results. J Bacteriol, 1999 Jun, 181(12), 3824 - 9 relA is required for actinomycin production in Streptomyces antibioticus; Hoyt S et al.; The relA gene from Streptomyces antibioticus has been cloned and sequenced . The gene encodes a protein with an Mr of 93,653, which is 91% identical to the corresponding protein from Streptomyces coelicolor . Disruption of S . antibioticus relA produces a strain which grows significantly more slowly on actinomycin production medium than the wild type or a disruptant to which the intact relA gene was restored . Moreover, the disruptant was unable to accumulate ppGpp to the levels observed during the normal course of growth and actinomycin production in the wild type . The strain containing the disrupted relA gene did not produce actinomycin and contained significantly lower levels of the enzyme phenoxazinone synthase than the wild-type strain . Actinomycin synthetase I, a key enzyme in the actinomycin biosynthetic pathway, was undetectable in the relA disruptant . Growth of the disruptant on low-phosphate medium did not restore actinomycin production. Membr Cell Biol, 1998, 12(4), 537 - 55 Properties of ionic channels formed by the antibiotic syringomycin E in lipid bilayers: dependence on the electrolyte concentration in the bathing solution; Schagina LV et al.; Using the planar lipid bilayer technique, organization of ionic channels formed by the lipodepsipeptide antibiotic syringomycin E applied to one (cis) side of a lipid bilayer was studied . Low concentrations of NaCl (0.01-0.1 M) induced the opening and closing of two types of channels - "small" and "large" . The large channels had single channel conductances approximately six times greater than those of the small channels . An increase in the NaCl concentration (0.6-1.0 M) decreased almost completely the chance to reveal the large channels . Although the syringomycin channels exhibited the anion selectivity within the entire range of NaCl concentrations in the bathing solutions (from 0.001 to 1.0 M) whereas the concentration gradients across the bilayers were 2 and 4, the transfer numbers for Cl-decreased with an increase in the mean NaCl concentration (from 0.83 for 0.005 M to 0.70 for 0.5 M) . Moreover, at each mean value of NaCl concentration, all conductance levels had the same ion selectivity (identical reversal potential) . These results suggest that at low NaCl concentrations the large channels are clusters of small channels which synchronously open and close, while at high electrolyte concentrations the screening of the charged groups responsible for channel interactions prevents the cluster formation . A new theoretical approach for the estimation of the channel radius and the number of elementary charges located at its inner surface (based on the experimental curve of the dependence of transfer number on the NaCl concentration) was developed . Based on this theoretical approach, the channel radius equal to 1 nm and one elementary charge located at its inner surface were obtained. Biochim Biophys Acta, 1999 Jun 9, 1419(1), 1 - 14 The pentaene macrolide antibiotic filipin prefers more rigid DPPC bilayers: a fluorescence pressure dependence study; Castanho MA et al.; Filipin is a pentaene macrolide antibiotic which was previously shown to incorporate more extensively into DPPC bilayers below the main phase transition temperature than above this temperature . This result was extremely unusual because drugs tend to be expelled from ordered gel phases . However, such results could not be safely attributed to the phase change of the bilayer itself because the temperature was changing concomitantly . In this work we changed the bilayer phase isothermally (53 degrees C) by hydrostatic pressure variation and discovered that filipin has a slightly more extensive incorporation in the pure DPPC gel phase (P>ca . 54.4 MPa): Kp,lc approximately 3x10(3) vs . Kp,gel approximately 6x10(3) . The presence of sterols (45% molar ergosterol or cholesterol) caused an increase in the partition coefficients, regardless of pressure, ergosterol having a more pronounced effect (Kp approximately 2x10(4)-6x10(4)) . Kp was pressure dependent in both cases, but mainly with cholesterol (Kp approximately 2x10(3)-2x10(4)) . At variance with cholesterol, when ergosterol was used, no phase transition was detected . This difference cannot be due to a more extended uptake of filipin by cholesterol-containing membranes, and so must be due to specific interactions with cholesterol . In agreement with this finding, we discovered that filipin is more tightly packed (lower partial molar volume) in the cholesterol-rich phase than in the ergosterol-rich phase . Our results also point to a 2:1 DPPC:cholesterol stoichiometry in the cholesterol-rich phase (17% molar cholesterol) . All partition coefficients were calculated from steady-state fluorescence anisotropy measurements. Ther Drug Monit, 1999 Jun, 21(3), 281 - 8 Population pharmacokinetics of aminoglycoside antibiotics in patients with cystic fibrosis; Campbell D et al.; The population pharmacokinetics of gentamicin and tobramycin were investigated in a group of 51 young adults with cystic fibrosis . Their ages ranged from 14-35 years, weights from 38-82 kg, and 27 of the patients were female . None of the patients had renal impairment, but 3 patients were treated in the intensive therapy unit (ITU) during one of their courses of therapy . Data comprised 219 courses of therapy and 544 concentrations (mean: 11 per patient) . Concentration-time data were analyzed using a nonlinear mixed-effects model package (NONMEM) and were best described by a one-compartment model . Factors identified as potentially influencing aminoglycoside pharmacokinetics were added in a stepwise fashion and the best model found that drug clearance and volume of distribution were related to body surface area and admission to ITU . The mean population estimates were a clearance of 2.89 L/hr/m2 and a volume of distribution of 9.21 L/m2 with a 60% increase in patients who were admitted to ITU . Interpatient variability in clearance and volume were 14% and 8%, respectively . The results suggested that a dose of 120 mg/m2 should achieve an average 1 hour postdose peak of 10 mg/L and trough of <1 mg/L and that higher doses might be required in ITU patients. Pediatr Int, 1999 Jun, 41(3), 274 - 6 Efficacy of antibiotics against influenza-like illness in an influenza epidemic; Maeda S et al.; AIM: To determine if an antibiotic reduces the incidence of complications associated with influenza-like illness during an influenza epidemic . METHODS: During the outbreak of influenza in Kobe in 1998, 85 patients suffering from an influenza-like illness were randomly assigned to two groups . Patients received placebo or sultamicillin orally for 4 days . The incidence of complications of influenza-like illness were compared and statistically assessed . RESULTS: There was no difference in the duration of fever or the incidence of acute otitis media . However, the incidence of pneumonia was significantly lower in the sultamicillin group than the placebo group (2.4 vs 16.3%, P < 0.05) . CONCLUSION: Sultamicillin reduced the incidence of pneumonia associated with influenza-like illness during the influenza epidemic . This result suggests that antibiotics can reduce the rate of pneumonia associated with influenza. Am J Physiol, 1999 Jun, 276(6 Pt 1), L951 - 7 Cholinomimetic action of macrolide antibiotics on airway gland electrolyte secretion; Irokawa T et al.; We investigated the acute effects of erythromycin (EM) and its derivatives on ionic currents in airway glands from feline tracheae . Therapeutic concentrations of EM or clarithromycin (CAM) attenuated the whole cell currents evoked by ACh in a competitive manner . The maximally stimulated inward Cl- currents were reduced to 54 and 83% and the outward K+ currents to 55 and 84% of control values by EM and CAM, respectively, whereas the responses induced by phenylephrine, norepinephrine, caffeine, or ionomycin were unaffected by EM, CAM, or EM523, a synthetic derivative of EM . K+ channels in excised outside-out patches were not influenced by macrolides . Although therapeutic concentrations of macrolides showed no effect on the baseline currents, high concentrations of macrolides alone evoked currents mimicking the ACh response, which were abolished completely by atropine . We concluded that macrolides act as a partial agonist on cholinergic receptors, resulting in a reduction of Cl- secretion at pharmacological doses of the agents, which may exhibit a pronounced effectiveness on hypertrophied and/or cholinergically sensitized submucosal glands in pathological airways. Contraception, 1999 Feb, 59(2), 71 - 8 Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill . A literature review; Weaver K et al.; There is considerable variation in opinion about the importance of drug interactions between the combined oral contraceptive pill (COCP) and broad-spectrum antibiotics . Clinical practice varies widely, especially between doctors in Europe and those in the US . Rifampicin and griseofulvin induce hepatic enzymes and do appear to have a genuine interaction with the COCP, leading to reduced efficacy . The situation with the broad-spectrum antibiotics is less clear . There are relatively few prospective studies of the pharmacokinetics of concurrent COCP and antibiotic use and few, if any, demonstrate a convincing basis for any reduced contraceptive efficacy . There is evidence, however, that variable contraceptive steroid handling could make some women, at some times, more susceptible to COCP failure . Given the serious consequences of unwanted pregnancy, the cautious approach of using additional or alternative contraception during short courses of broad-spectrum antibiotics and the initial weeks of long-term antibiotic administration may be justified to safeguard the few unidentifiable women who may be at risk . Conflicting opinion and advice is potentially confusing to both professionals and patients, and instructions for additional precautions during and after concurrent COCP and antibiotic use are complicated . Many women are ignorant of, or confused about, the circumstances that can cause OC to fail . Health professionals who prescribe the COCP must continue to strive to educate women about the mode of action and about the times when there is the greatest danger of failure . Professionals who feel that concurrent antibiotic use represents a real threat to contraceptive efficacy of the COCP should be prepared to present the advice for additional contraceptive precautions in a simple and consistent way, backed up with written information and reinforced at regular intervals. Adolesc Med, 1997 Oct, 8(3), 443 - 448 Should Adolescents Have Over-the-Counter Access to Oral Contraceptive Pills and Antibiotics? Hewitt GD. The rate of teenage pregnancy and abortion in the U.S . is the highest in the developed world . Oral contraceptive pills (OCPs) are an effective method of contraception that has very few contraindications in healthy adolescents . This article discusses the issue of whether adolescents should be allowed access to OCPs and antibiotics for treatment of sexually transmitted diseases without prior consultation with a health care provider . The author argues that patient education and counseling that result from an interaction with a clinician are necessary for sexually active adolescents and could be greatly diminished if OCPs become available over-the-counter. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 1999 Jun, 16(3), 141 - 4 {Screening for mitochondrial 1555(G) mutation in patients with aminoglycoside antibiotic-induced deafness}; Yuan H et al.; OBJECTIVE: To identify the incidence of the 1555(G) mutation in pedigrees and sporadic patients with aminoglycoside antibiotic- induced deafness so as, to privide the theoretical evidence for establishing the method of diagnosis of this disease . METHODS: Blood samples were obtained from two pedigrees and seven sporadic patients with aminoglycoside antibiotic-induced deafness, and five mothers of the sporadic patients . DNA was extracted from the isolated leukocytes . The mitochondrial DNA fragments were amplified by PCR; 1555(G) mutation was detected by Alw26 I restriction endonuclease digestion.RESULTS: Fourteen individuals from two pedigrees carried homoplasmic 1555(G) mutation . Seven sporadic patients and the five mothers did not have 1555(G) mutation . CONCLUSION: The incidence of the 1555(G) mutation in pedigrees with aminoglycoside antibiotic-induced deafness is fairly high, while in sporadic patients is low . Screening for mitochondrial 1555(G) mutation is of potential value to clinical use. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 1999 Jun, 16(3), 138 - 40 {The relation between mitochondrial DNA mutation and aminogly- coside antibiotics-induced deafness}; Zhang L et al.; OBJECTIVE: To nvestigate the relation between mitochondrial DNA mutation and aminoglycoside antibiotics-induced deafness . METHODS: Mitochondrial DNA (mtDNA) of peripheral blood from 48 sporadic cases was analysed using PCR-BsmAI digestion and PCR-direct DNA silver sequencing . RESULTS: Six of 48 sporadic patients had A to G mutation in 12S rRNA gene of mtDNA at nucleotide 1555 . CONCLUSION: The results suggest that mtDNA 1555(G) mutation is related to the occurring of aminoglycoside antibiotics-induced deafness which can cause genetic susceptibility to aminoglycoside antibotics ototoxicity. Clin Rheumatol, 1999, 18(2), 163 - 4 Prophylactic antibiotics in recurrent parotitis in a patient with Sjogren's syndrome; Stein M et al.; We describe a 41-year-old patient with primary Sjogren's syndrome with a 16-year history of recurrent parotitis . The institution of prophylactic antibiotic coverage has succeeded, to date, in maintaining her in remission for 4 years. Schweiz Rundsch Med Prax, 1999 Apr 15, 88(16), 726 - 31 {Newer antibiotics--missed efficacy in false indications}; Vogt M; Various reports indicate conclusively that antibiotics are used much too frequently and physicians often prefer broad spectrum compounds for "safety reasons" . Symptoms of viral infections of the respiratory tract such as fever, cough and runny nose are often reason enough to start antibiotic regimens leading to increased costs and finally to development of resistance . Some newly developed antibiotics, often with unique properties will be discussed in this paper emphasizing potential problems associated with their uncritical use. Biochem Cell Biol, 1998, 76(5), 799 - 806 Differential inhibition of AE1 and AE2 anion exchangers by oxonol dyes and by novel polyaminosterol analogs of the shark antibiotic squalamine; Alper SL et al.; Oxonol and polyaminosterol drugs were examined as inhibitors of recombinant mouse AE1 and AE2 anion exchangers expressed in Xenopus laevis oocytes and were compared as inhibitors of AE1-mediated anion flux in red cells and in HL-60 cells that express AE2 . The oxonols WW-781, diBA(5)C4, and diBA(3)C4 inhibited HL-60 cell Cl-/Cl- exchange with IC50 values from 1 to 7 microM, 100-1000 times less potent than their IC50 values for red cell Cl-/anion exchange . In Xenopus oocytes, diBA(5)C4 inhibited AE1-mediated Cl- efflux several hundred times more potently than that mediated by AE2 . Several novel squalamine-related polyaminosterols were also evaluated as anion exchange inhibitors . In contrast to diBA(5)C4, polyaminosterol 1361 inhibited oocyte-expressed AE2 8-fold more potently than AE1 (IC50 0.6 versus 5.2 microM) . The 3-fold less potent desulfo-analog, 1360, showed similar preference for AE2 . It was found that 1361 also partially inhibited Cl- efflux from red cells, whereas neither polyaminosterol inhibited Cl efflux from HL60 cells . Thus, the oxonol diBA(5)C4 is >100-fold more potent as an inhibitor of AE1 than of AE2, whereas the polyaminosterols 1360 and 1361 are 8-fold more potent as inhibitors of AE2 than of AE1 . Assay conditions and cell type influenced IC50 values for both classes of compounds. Clin Perform Qual Health Care, 1998 Oct-Dec, 6(4), 168 - 71 A quality management approach to optimizing delivery and administration of preoperative antibiotics; Welch L et al.; OBJECTIVE: To optimize the process for delivering and administering preoperative antibiotics in order to prevent potential adverse patient outcomes . DESIGN: Using a multidisciplinary quality-improvement team, an evaluation of the preoperative medication order and delivery process was conducted . Charts were reviewed by selected time periods, with winter 1994 discharges for orthopedic surgeries (n = 97) and spring 1995 discharges for open heart procedures (n = 50) being used to arrive at baseline data (n = 147) . A plan was devised to mainstream the medication-use process so that it would be standardized hospitalwide . A goal of administering preoperative antibiotics within 30 to 60 minutes prior to cut time was established . Following redesign and education, a repeat chart review of orthopedic surgeries (n = 33) and open heart procedures (n = 168) was conducted during April 1997 for discharges from the same diagnosis-related groups to total (n = 201) . SETTING: A nearly 1,000-bed tertiary referral center and teaching hospital with three separate campuses . RESULTS: We identified multiple ordering mechanisms, multiple medication sources and delivery sites, multiple administration sites and administering personnel, and other logistical conflicts . Thirty-one percent of cases received antibiotics less than 30 minutes prior to start time, 39% between 30 to 60 minutes, and 30% greater than 60 minutes before start time . Following the multidisciplinary redesign and education, an increase from 39% to 61% receiving preoperative antibiotics between 30 to 60 minutes prior to surgery start time and a decrease from 31% to 18% receiving them in less than 30 minutes was documented . The percentage of patients receiving preoperative antibiotics in 60 minutes or less increased from 70% to 80% . CONCLUSION: A continuous quality-improvement approach that engages all departments involved in patient care is necessary to achieve meaningful change in complicated hospital processes. J Antimicrob Chemother, 1999 Apr, 43(4), 601 - 6 Early switch from intravenous to oral antibiotics: guidelines and implementation in a large teaching hospital; Sevinc F et al.; In recent years 'switch therapy' has been advocated: short intravenous antibiotic therapy, for 2-3 days, followed by oral treatment for the remainder of the course . Little is known about the number of patients that could benefit from early switch therapy and the consequences of introducing this strategy in everyday practice . We prospectively registered all antibiotic courses on wards for Internal Medicine, Surgery, and Pulmonology during a 2 month period, before (n = 362, inventorial phase) and after (n = 281, implementation phase) the introduction of guidelines for switching therapy . Approximately 40% of all patients who started on iv antibiotics were candidates for an early iv-oral switch . During the inventorial phase, 54% (52/97) of eligible patients were switched to oral treatment, after a median of 6 days (range 2-28 days) . After implementation of the guidelines, this percentage rose to 83% (66/80) (difference 29%, 95% CI 16-42%; P < 0.001) . Therapy was also switched earlier, after a median of 4 days (range 2 to 16 days) . In the 6 weeks after completion of the oral course, recurrence of infections, or readmissions due to reinfections did not occur . Compared with the inventorial phase, 43% of iv administrations could be avoided, that is >6000 per year . This means a potential annual reduction of dfl.60,000 (c . US$30,000) of administration costs . The potential savings in purchase costs of the antibiotics were dfl.54,000 (US$27,000) annually . In conclusion, a substantial number of patients starting on iv antibiotics were candidates for an early iv-oral switch . The guidelines were well accepted by the physicians and substantial savings in costs and nursing time were achieved. J Cardiovasc Surg (Torino), 1999 Apr, 40(2), 307 - 10 Combined use of steroid, antibiotics and early bougienage against stricture formation following caustic esophageal burns; Karnak I et al.; BACKGROUND: If an esophageal burn is diagnosed, the aim is to prevent stricture formation . The combined use of steroid, antibiotics and early bougienage (SAEB) is one of the currently used treatment protocols . The effect of SAEB treatment against stricture formation following caustic esophageal burn has been evaluated retrospectively . METHODS: Forty-nine children of 282 admitted with a history of caustic substance ingestion were found to have esophageal burns . Forty-nine children underwent treatment against stricture formation . SAEB was begun within 48 hours of ingestion . RESULTS: Eight children of 12 who ingested sodium hydroxide and five children of 20 who ingested acids developed strictures in spite of the therapy . Additionally two esophageal perforations were encountered in patients who ingested sodium hydroxide . CONCLUSIONS: This protocol has been found to carry a risk of perforation without preventing stricture formation after strong alkali ingestion . Therefore other treatment modalities for preventing strictures should be evaluated especially in children who have ingested products containing strong alkalis. Z Naturforsch {C}, 1999 Mar-Apr, 54(3-4), 163 - 8 Noroudemansin A, a new antifungal antibiotic from Pterula species 82168 and three semisynthetic derivatives; Engler-Lohr M et al.; A new antifungal (E)-beta-methoxyacrylate noroudemansin A (1), was isolated from cultures of Pterula sp . 82168 . Its biological activities were investigated and compared with oudemansin A . The structure was elucidated by spectroscopic methods . Three semisynthetic noroudemansin A derivatives were synthesized from the natural product. Drug Metab Dispos, 1999 Jun, 27(6), 724 - 30 Panipenem, a carbapenem antibiotic, enhances the glucuronidation of intravenously administered valproic acid in rats; Yamamura N et al.; Previously, a significant decrease in the trough plasma-concentration of valproic acid (VPA) owing to the concomitant administration of panipenem (PAPM)/betamipron, a carbapenem antibiotic, in epileptic patients was reported . To determine the site and mechanism of the drug interaction between VPA and PAPM, we performed in vivo and in vitro experiments using rats . A 30 mg/kg bolus dose of VPA was given i.v . to normal Sprague-Dawley rats, nephrectomized rats, and hepatectomized rats, with and without prior treatment of PAPM . PAPM treatment resulted in a significant reduction of biological half-life and a significant increase of total body clearance in normal rats . The effects of PAPM on the disposition kinetics of VPA were also observed in nephrectomized rats, whereas hepatectomy abolished the interaction completely . Thus, the site of interaction was identified as the liver . At steady state, PAPM treatment significantly increased total body clearance, the biliary excretion rate of VPA glucuronide, and the apparent metabolic clearance of VPA by glucuronidation, but did not affect the biliary excretion clearance of VPA glucuronide . Initial uptake velocity of VPA into rat hepatocytes proportionally increased as a function of VPA concentration added and was not affected by PAPM . The plasma-unbound fraction of VPA in vitro was not altered by PAPM . These data demonstrate that PAPM does not affect the uptake of VPA into the liver, the plasma-unbound fraction, and the excretion process of VPA glucuronide . Consequently, PAPM appears to enhance the rate of metabolism of VPA to VPA glucuronide in the liver. J Antibiot (Tokyo), 1999 Mar, 52(3), 319 - 24 Chemical modification of antibiotic eremomycin at the asparagine side chain; Olsufyeva EN et al.; AA3-Carboxyeremomycin 2, obtained by selective hydrolysis of antibiotic eremomycin was used as a starting compound for the eremomycin chemical modifications at the asparagine side chain to be transformed into eremomycin AA3, AA7 bis-amides (3a-c) . Bis-benzylamide 3b displayed an activity (8 microg/ml) against an E . faecium VanA strain. J Antibiot (Tokyo), 1999 Mar, 52(3), 263 - 8 Gilvusmycin, a new antitumor antibiotic related to CC-1065; Tokoro Y et al.; A new antitumor antibiotic gilvusmycin was isolated from the culture broth of Streptomyces sp . QM16 . The structure of gilvusmycin was related to CC-1065 and determined by NMR spectral analysis . Gilvusmycin exhibited antitumor activity against murine leukemia P388 in vivo. Appl Environ Microbiol, 1999 Jun, 65(6), 2703 - 9 Development of a self-cloning system for Actinomadura verrucosospora and identification of polyketide synthase genes essential for production of the angucyclic antibiotic pradimicin; Dairi T et al.; A self-cloning system for Actinomadura verrucosospora, a producer of the angucyclic antibiotic pradimicin A (PRM A), has been developed . The system is based on reproducible and reliable protoplasting and regeneration conditions for A . verrucosospora and a novel plasmid vector that consists of a replicon from a newly found Actinomadura plasmid and a selectable marker cloned from the Actinomadura strain . The system has an efficiency of more than 10(5) CFU/microgram of DNA . Using this system, we have cloned and identified the polyketide synthase (PKS) genes essential for PRM A biosynthesis from A . verrucosospora . Nucleotide sequence analysis of the 3.5-kb SalI-SphI fragment showed that ketosynthase subunits (open reading frame 1 {ORF1} and ORF2) of the essential PKS genes have strong similarities (59 to 89%) to those for angucyclic antibiotic biosynthesis. Am J Manag Care, 1999 Jan, 5(1), 53 - 9 Antibiotic therapy of Helicobacter pylori infection reduces healthcare expenditures related to duodenal ulcer; Sonnenberg A et al.; OBJECTIVE: To test whether eradication of Helicobacter pylori saves costs in the treatment of duodenal ulcer disease, compared with conventional antisecretory therapy . STUDY DESIGN: A prospective, double-blind clinical trial was conducted at 132 sites in the United States . PATIENTS AND METHODS: Adult patients with active duodenal ulcer and confirmed H pylori infection were randomized to receive treatment with clarithromycin plus omeprazole, omeprazole alone, or ranitidine alone . Utilization of ulcer-related healthcare resources was documented during 1 year following therapy . Costs were calculated by multiplying the number of health resources utilized by the cost of each resource . Resource costs were obtained from a database containing actual average costs spent by managed care organizations on outpatient and inpatient treatment . RESULTS: Of the 819 patients enrolled, 727 completed the study: 243 received clarithromycin plus omeprazole, 248 omeprazole alone, and 236 ranitidine alone . Ulcer-related health resource utilization and total ulcer-related healthcare costs were decreased after treatment with clarithromycin plus omeprazole, compared to treatment with omeprazole or ranitidine alone . In multivariate linear regression analyses, type of treatment was found to be a significant predictor of total costs . Specific costs associated with endoscopic examinations, clinic visits, and medications were also significantly reduced by treatment with clarithromycin plus omeprazole as compared to other treatment forms . CONCLUSIONS: In a managed care environment, therapy with clarithromycin and omeprazole to eradicate H pylori in patients with duodenal ulcer disease would result in significant cost savings secondary to a reduction in the utilization of healthcare resources. Manag Care Interface, 1999 Jan, 12(1), 73 - 6 The effectiveness of an antibiotic use program; Gilderman A et al.; Bacterial resistance to antibiotics continues to grow, and inappropriate diagnoses and prescriptions are to blame . The authors report on a pilot program undertaken in California that seeks to decrease the unnecessary use of antibiotics for viral-based ailments. Int J Epidemiol, 1999 Apr, 28(2), 263 - 6 Circumcision and neonatal tetanus: disclosure of risk and its reduction by topical antibiotics; Bennett J et al.; BACKGROUND: Previous case-control studies have paradoxically suggested that circumcisions protect against neonatal tetanus (NNT), but these observations have not been adjusted for differences in the length of survival of cases and controls . METHODS: Boy cases (n = 133) and their sex-matched controls (n = 399) were extracted from a population-based study of NNT undertaken in Punjab Province, Pakistan . In the resulting file, circumcisions were censored such that analysis was restricted to only those that occurred before onset in cases or before age of onset in the matched case for controls . The effect of topical antibiotics in circumcision wounds was then evaluated . RESULTS: After adjusting for confounders, circumcision before onset posed a significant risk for NNT (matched odds ratio {OR} = 3.1, 95% CI: 1.2-8.0) . The risk of NNT in those circumcised before onset and treated with topical antibiotics did not differ significantly from the referent group who had not been circumcised before onset (matched OR = 1.1, 95% CI: 0.2-6.8), whereas the lack of topical use was associated with significant risk (matched OR = 4.2, 95% CI: 1.4-12.6) . This suggests that topical antibiotics are likely to be highly effective in preventing NNT from circumcision wounds . We estimated an overall risk of about 16 fatal NNT cases per 1000 live boy births with circumcision wounds that were not protected by topical antibiotics, and that circumcision and umbilical wounds each accounted for about half of this overall risk in these boys . CONCLUSIONS: Topical antibiotics should be routinely applied to all wounds created by traditional circumcisions, to prevent NNT and sepsis from these frequently unsterile proceduresPIP: The results of previous case-control studies have suggested that circumcisions protect against neonatal tetanus (NNT) . Those observations, however, were not adjusted for differences in the length of survival of cases and controls . The authors analyzed 133 boy cases and 399 sex-matched controls extracted from a population-based study of NNT conducted in Punjab Province, Pakistan . After adjusting for confounders, circumcision before the onset of illness or NNT was a significant risk factor for NNT . The risk of NNT among those circumcised before onset and treated with topical antibiotics did not differ significantly from the control group which had not been circumcised before onset, while the lack of topical antibiotic use was associated with a considerable and significant risk, suggesting that the application of topical antibiotics is highly effective in preventing NNT arising from circumcision wounds . There was an estimated overall risk of about 16 fatal NNT cases per 1000 live boy births with circumcision wounds which were not protected by topical antibiotics, with circumcision and umbilical wounds each accounting for about half of the overall risk among these boys . J Food Prot, 1999 May, 62(5), 547 - 8 Stability of tetracycline antibiotics in raw milk under laboratory storage conditions; Podhorniak LV et al.; Raw milk samples collected from bulk milk tankers may be screened for the presence of tetracycline antibiotics using rapid screening tests . If tetracycline residues are detected, the milk may be shipped to a laboratory for high-pressure liquid chromatography (HPLC) analysis . Because the milk may be shipped on ice blocks, it is important to know whether tetracycline residues are stable at that temperature and for how long . Control raw milk samples fortified with 50 ppb each chlortetracycline, demeclocycline, methacycline hydrochloride, minocycline, oxytetracycline, and tetracycline were incubated at 4 degrees C or 25 degrees C, then analyzed using a metal chelate affinity chromatography extraction and HPLC . No loss of tetracycline was observed after 48 h of storage at 4 degrees C or 24 h at 25 degrees C . Losses ranging from 4 to 13% and 0 to 18% were noted after 72 h at 4 degrees C and 48 h at 25 degrees C, respectively. Clin Exp Allergy, 1999 Jun, 29(6), 766 - 71 Antibiotic use in early childhood and the development of asthma; Wickens K et al.; BACKGROUND AND OBJECTIVE: Recent investigations have focused on the role of infections in infancy in promoting or protecting against the subsequent development of asthma . A related hypothesis concerns the possible role of medical responses to infections, including the widespread use of antibiotics . We chose children at Rudolf Steiner schools to test this latter hypothesis because a significant proportion of parents rejects the use of conventional treatments, including antibiotics . METHODS: Seventy-five per cent (n = 456) of parents of children aged 5-10 years attending Rudolf Steiner schools throughout New Zealand completed questionnaires which included questions on the use of antibiotics and a history of asthma and wheeze in their children . RESULTS: After controlling for potential confounders, antibiotic use was significantly associated with having a history of asthma (OR = 2.74, 95% CI: 1.10-6.85) or wheeze (OR = 1 . 86, 95% CI: 1.06-3.26) but not with current wheeze (OR = 1.08, 95% CI: 0.54-2-16) . The adjusted odds ratio for asthma was 4.05 (95% CI: 1.55-10.59) if antibiotics were used in the first year of life and 1 . 64 (95% CI: 0.60-4.46) if antibiotics had been used only after the first year of life when compared with children who had never used antibiotics . The number of courses of antibiotics during the first year of life was also associated with increased odds ratios for asthma: 2.27 (95% CI: 1.14-4.51) for one to two courses and 4.02 (95% CI: 1.57-10.31) for three or more courses when compared with no antibiotic use in the first year of life . Although not significant, the association of antibiotics and hay fever (OR = 1.99 {95% CI: 0 . 93-4.26}) was of a similar strength to the association of antibiotics with a history of wheeze . Antibiotics were not significantly associated with eczema (OR = 1.23 {95% CI: 0.71-2.13}) . CONCLUSION: Antibiotic use in infancy may be associated with an increased risk of developing asthma . Further study is required to determine the reasons for this association. Clin Orthop, 1999 May, (362), 240 - 50 Development of a biodegradable antibiotic delivery system; Lin SS et al.; Antibiotic beads have been used as a drug delivery system for the treatment of various surgical infections . In this study, the copolymer 50:50 poly(DL-lactide):co-glycolide was mixed with vancomycin powder and hot compressing molded at 55 degrees C to form five types of biodegradable antibiotic beads . The beads were placed in 1 mL of phosphate buffered saline and incubated at 37 degrees C . The phosphate buffered saline was changed daily, and the removed buffer solutions were stored at -70 degrees C until the antibiotic concentration in each sample was determined by high performance liquid chromatography system assay . The concentration of vancomycin in each sample was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for more than 32 days . The release was most marked during the first 48 hours . All copolymer 50:50 poly(DI lactide):co-glycolide biodegradable beads released high concentrations of the antibiotics in vitro for the time needed to treat bone infections (4 to 6 weeks) . The diameter of the sample inhibition zone ranged from 6.5 mm to 10 mm, and the relative activity of vancomycin ranged from 12.5% to 100% . Copolymers with low heat of formation temperatures are required for making a controlled release system to prevent antibiotic decomposition, which occurs when using the hot compressing molded method . The rate and duration of release from the antibiotic beads can be adjusted by varying the diameter of the beads . This offers a convenient method to adjust the release rate to meet the specific antibiotic requirements for different patients. Res Vet Sci, 1999 Jun, 66(3), 197 - 203 Macrolide antibiotics, drug interactions and microsomal enzymes: implications for veterinary medicine; Anadon A et al.; The macrolide group of antibiotics includes natural members, pro-drugs and semi-synthetic derivatives, thus named because they are composed of a large aglycone ring (from 14 to 16 carbon atoms), to which are attached several sugars . Some of them are amino-sugars, containing a diethylamino, tertiary amine function . A number of antibiotics, including erythromycin, oleandomycin, triacetyl-oleandomycin (troleandomycin), carbomycin, spiramycin, tylosin, rosamicin, azithromycin, clarithromycin, dirithromycin and others, are members of this group . On a comparative basis, erythromycin and oleandomycin are similar, with the same basic 14-carbon lactone ring and side chain sugars . The remaining compounds contain a basic 15- or 16-carbon lactone ring and one or two side-chain sugars . Most of the macrolides are produced by Streptomyces spp bacteria . An exception is rosamicin, which is produced by Micromonospora . Clarithromycin and azithromycin are new semi-synthetic derivatives of erythromycin . Eur J Gastroenterol Hepatol, 1999 Mar, 11(3), 247 - 50 Three-day antibiotic therapy with azithromycin and tinidazole plus lansoprazole or pantoprazole to cure Helicobacter pylori infection: a pilot study; Cammarota G et al.; OBJECTIVE: The aim of the present study was to investigate and compare the effects of two proton-pump inhibitors, lansoprazole (Limpidex 30 mg, Sigmatau) vs pantoprazole (Peptazol 40 mg, Boehringer Mannheim), included in a three-day antibiotic therapy regimen with azithromycin (Zitromax 500 mg, Pfizer) and tinidazole (Fasigin 500 mg, Pfizer) . DESIGN: Seventy consecutive, H . pylori-positive patients were randomly pre-treated with lansoprazole 30 mg o.d . (once daily) or pantoprazole 40 mg o.d . for two days, and subsequently respectively assigned to one of the two following treatment regimens, given for only three days: regimen A (LAT) comprising lansoprazole 30 mg o.d . plus azithromycin 500 mg o.d . and tinidazole 500 mg b.i.d . (bis in die), or regimen B (PAT) comprising pantoprazole 40 mg o.d . plus azithromycin 500 mg o.d . and tinidazole 500 mg b.i.d . H . pylori status was evaluated by means of histology and rapid urease test at entry, and by 13C-urea breath test alone 8 weeks after treatment . MAIN OUTCOME MEASURES: Sixty-nine of the enrolled patients completed the study: 34 in the LAT group and 35 in the PAT group . One patient in the LAT group was lost to follow-up . In the LAT group, after the end of treatment, 28/34 patients were H . pylori-negative (per protocol: 82%; intention-to-treat: 80%) . In the PAT group, after treatment, 29/35 patients were H . pylori-negative (per protocol and intention-to-treat: 83%) . Mild or slight side-effects occurred in only one patient in the LAT group and in one in the PAT group . CONCLUSIONS: From this study there is no evidence that either of the two proton-pump inhibitors used is preferable in a three-day antibiotic regimen with azithromycin and tinidazole . The excellent side-effect and tolerability profiles, associated with acceptable eradication rates, make the two treatment regimens we tested particularly useful when patient compliance is difficult to achieve. Prim Dent Care, 1997 May, 4(2), 66 - 70 An audit of antibiotic prescribing in general dental practice; Steed M et al.; Clinical audit is widely recognised as the systematic and critical analysis of the quality of clinical care, including treatment regimes, the associated use of resources, and the resulting outcome and quality of life for the patient . The prescribing of antibiotics in general dental practice is an area 'wide open' for audit analysis since the profession must clearly accept its responsibility to use antibiotics sensibly; however, the definition of 'sensibly' is likely to vary from practitioner to practitioner . This audit reviews the need for antibiotic prescribing in general dental practice over two consecutive four-month periods . A consensus was achieved on the rationale for antibiotic prescribing and the number of prescriptions fell by 50% as a result. Prikl Biokhim Mikrobiol, 1999 Jan-Feb, 35(1), 55 - 9 {Effect of heat shock on biosynthesis of antibiotics by three strains of Streptomyces}; Lu H et al.; Effects of heat shock on the biosynthesis of antibiotics, actinomycin C (in cultures of Streptomyces sp . 26-115 and S . chrysomallus 23209) and antibiotics of the nonactin group (in the culture of S . werraensis 1365) were studied . After heat shock, the formation of antibiotics of the nonactin group and actinomycin C were shown to increase by 30% and 27%, respectively, in comparison to control values . Thus, heat shock stimulates the biosynthesis of antibiotics in all three strains of streptomyces studied. J Allergy Clin Immunol, 1999 May, 103(5 Pt 1), 918 - 24 Natural evolution of skin test sensitivity in patients allergic to beta-lactam antibiotics; Blanca M et al.; BACKGROUND: Subjects with immediate reactions to penicillins and positive skin test responses may lose sensitivity if penicillin is avoided . The longer the interval between the reaction and the skin test, the greater the likelihood of having a negative result . OBJECTIVE: We sought to study prospectively the evolution of skin test sensitivity in a group of subjects allergic to penicillin with positive skin test responses to different penicillin determinants . METHODS: Skin tests were performed with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin (AX), and ampicillin at the initial evaluation and repeated 1, 3, and 5 years later if the responses were still positive . Subjects were divided into 2 groups . Group A consisted of patients with a positive skin test response to benzylpenicilloyl or minor determinant mixture, and group B consisted of those with a selective response to amoxicillin and good tolerance to benzylpenicillin . RESULTS: In group A (n = 31) after 1 year, 25 patients continued to have positive responses and 6 began to have negative responses; after 3 years, 18 continued to have positive responses, 5 began to have negative responses, and 2 were lost to follow-up; and after 5 years, 12 continued to have positive responses, 5 began to have negative responses, and 1 was lost to follow-up . In group B (n = 24) 12 had positive responses, and 12 had negative responses after 1 year; 6 had positive responses, 5 had negative responses, and 1 was lost to follow-up after 3 years; and no patients had positive responses, 5 had negative responses, and 1 was lost to follow-up after 5 years . Survival analysis showed significant differences between groups (log-rank test = 12.8; P < . 0003) . CONCLUSION: Patients with a selective response to amoxicillin tended to lose sensitivity faster than those who responded to several penicillin determinants, supporting the existence of at least 2 distinct types of IgE response in patients allergic to beta-lactam. Bioorg Med Chem Lett, 1999 Apr 19, 9(8), 1209 - 14 Chemical modifications and structure activity studies of ziracin and related everninomicin antibiotics; Ganguly AK et al.; Chemical modifications of eveminomicin antibiotics, particularly ziracin (1), were carried out to study the SARs as well as the chemical properties of this class of compounds . Use of allyl ether group for protection and selective deprotection of phenolic groups provided access to a variety of novel analogs of the title compounds, some of which exhibited the same high in vitro potency as the parent compounds. Burns, 1999 May, 25(3), 256 - 61 Management of partial thickness facial burns (comparison of topical antibiotics and bio-engineered skin substitutes); Demling RH et al.; This study compared the effect of standard topical antibiotic management versus a biological skin substitute wound closure for mid-partial thickness burns of the face . Adult patients with mid-dermal facial burns produced by flash flames or flame exposure were studied using a randomized prospective study design . Total daily burn care time, pain (0-10 scale) and healing time were monitored . Immediately after partial thickness debridement, the entire face burn, including ears, was closed with a bioengineered skin substitute coated with fibronectin (TransCyte) or treated by the open technique using bacitracin ointment applied 2-3 times daily . 21 patients were studied, with 10 patients in the skin substitute group . We found a significant decrease in wound care time 0.35 +/- 0.1 versus 1.9 +/- 0.5 h, decrease in pain of 2 +/- 1 versus 4 +/- 2 and re-epithelialization time 7 +/- 2 versus 13 +/- 4 days in the skin substitute group compared to topical antibiotics . We can conclude that a bioengineered skin substitute significantly improves the management and healing rate of partial thickness facial burns, compared to the standard open topical ointment technique. Br J Pharmacol, 1999 Apr, 126(7), 1531 - 3 The antifungal antibiotic clotrimazole potently inhibits L-type calcium current in guinea-pig ventricular myocytes; Thomas GP et al.; The antimycotic agent clotrimazole (CLT) is a promising potential therapeutic agent for a variety of diseases including cancer . Although it is known that CLT alters calcium homeostasis in many cell types, its cardiac effects are virtually unknown . We investigated the effects of CLT on L-type calcium current (ICa,L) and action potentials in guinea-pig ventricular myocytes . CLT (5, 25 and 50 microM) inhibited basal ICa,L by 16, 59 and 93%, respectively . The inhibitory effect of CLT was rapid and the peak effect was attained within 3 min . At a concentration of 25 microM, the inhibitory effect of CLT was partially reversible whereas the response to 50 microM CLT persisted following drug withdrawal . CLT abbreviated action potential duration at 50 and 90% of repolarization and suppressed the plateau significantly . These results indicate that CLT may have important cardiac effects at concentrations used to induce the antiproliferative action of the drug. Chem Biol, 1999 May, 6(5), 305 - 18 In vivo processing and antibiotic activity of microcin B17 analogs with varying ring content and altered bisheterocyclic sites; Sinha Roy R et al.; BACKGROUND: The Escherichia coli peptide antibiotic microcin B17 (MccB17) contains four oxazole and four thiazole rings, and inhibits DNA gyrase . The role of individual and tandem pairs of heterocycles in bioactivity has not been determined previously . RESULTS: The two tandem 4,2-bisheterocycles in MccB17 were varied by expression of MccB17 or mutants containing altered sequences at Gly39-Ser40-Cys41 or Gly54-Cys55-Ser56 . A mixture of five-nine-ring MccB17 isoforms were separated and quantitated for antibiotic potency . Mutagenesis of the thiazole-oxazole pair significantly affected antibiotic activity compared with the upstream oxazole-thiazole, which might stabilize partially cyclized intermediates against proteolysis . CONCLUSIONS: Enzymatic heterocyclization in native MccB17 occurs distributively . Antibiotic activity correlates with the number of rings and is differentially sensitive to both the location and the identity of the 4,2-tandem heterocycle pairs in MccB17 . Such tandem heterocycles might be useful pharmacophores in combinatorial libraries. Biochem Mol Biol Int, 1999 Apr, 47(4), 587 - 95 Immunosuppressive effects of the heat shock protein 90-binding antibiotic geldanamycin; Sugita T et al.; Ansamycin antibiotic, geldanamycin has a unique pharmacological effect to bind to heat shock protein 90 (hsp90) and deplete hsp90 substrates . We investigated the immunopharmacological effects of geldanamycin . Geldanamycin depleted cellular Raf-1 of rat splenic cells without affecting the steady state levels of hsp90 and downstream mitogen activated protein (MAP) kinases, ERK1 and ERK2 . In parallel, it inhibited mitogen-induced nuclear factor-kappa B (NF-kappa B) activation in these cells . Geldanamycin also had a potent suppressive effect on recall antigen-induced T cell proliferation, with an IC50 value of 1 nM . In vivo, geldanamycin suppressed the progression of adjuvant-induced arthritis dose-dependently . These results suggest that geldanamycin exerts an immunosuppressive effect partly through destabilizing Raf-1, and raise a new strategy for the prevention of inflammatory diseases. J Paediatr Child Health, 1999 Feb, 35(1), 9 - 10 Should we now hold back from initially prescribing antibiotics for acute otitis media? Del Mar CB, Glasziou PP. The research literature provides surprisingly little evidence of benefit for initially treating acute otitis media in children with antibiotics . We show how to calculate the amount of benefit and harm from the evidence, and how this might be applied to change management practice. Arch Pediatr, 1998, 5 Suppl 1, 62s - 66s {Non-antibiotic treatments for community-acquired pneumonia in children}; Dubus JC; Besides antibiotic therapy (when warranted), treatment of acute pneumonia in children usually requires only simple measures, including: fractionated feeding, analgesic and antipyretic medications and detection of hypoxemia . There is no evidence that physical chest therapy, bronchial mucus modificators and corticosteroid therapy are really useful . The best prevention relies upon vaccinations, suppression of passive smoking, and hygiene and nutritional improvements. Antimicrob Agents Chemother, 1999 May, 43(5), 1298 - 300 In vitro activities of antibiotics alone and in combination against Brucella melitensis at neutral and acidic pHs; Akova M et al.; Brucellae survive acidic pHs in phagolysosomes . Azithromycin, streptomycin, and quinolones were active against Brucella melitensis at pH 7.0 but not at pH 5.0; rifampin and doxycycline retained activity at pH 5.0 . Regardless of pH, azithromycin-rifampin and ofloxacin-rifampin showed less synergy than established streptomycin-doxycycline and rifampin-doxycycline combinations. Pediatr Infect Dis J, 1999 Apr, 18(4), 333 - 7 A population-based study of antibiotic prescriptions for Danish children; Thrane N et al.; BACKGROUND: The aim of the study was to examine the use of systemic and topical antibiotics in relation to age and sex in Danish children . METHODS: We used the Pharmacoepidemiological Prescription Database to identify the individual prescriptions of antibiotics provided for all 0-to 15-year-old children in North Jutland County, Denmark, during 1997 . The population was approximately 95000 children . RESULTS: We identified 44640 prescriptions for systemic antibiotics . The annual prescription rate was highest in the 1- to 2-year-olds, with 945 prescriptions/1000 children/year . One-half of these children received at least 1 prescription, and 12% received 3 or more prescriptions . Among the 11- to 15-year-old children 17% received one or more prescriptions . Overall 88% of the prescriptions were penicillins and 10% were macrolides . In children younger than 3 years 57% of prescriptions were for broad spectrum penicillins, but in children older than 6 years penicillin V was the most frequently used antibiotic . We identified 12 661 prescriptions for topical antibiotics used in eye infections . The prescription rate peaked in the 1- to 2-year-old children, one-third of whom received at least 1 prescription . CONCLUSIONS: Almost two-thirds of the 0- to 2-year-old children in the population were treated with either systemic or topical antibiotics during 1 year . Physicians prescribe mostly penicillins, but the proportion of broad spectrum penicillins for young children was so high, however, that enforcement of national guidelines should be reconsidered. Postgrad Med, 1999 Apr, 105(4), 95 - 8 Antibiotics for rheumatoid arthritis? Minocycline shows promise in some patients; Alarcon GS; Rheumatoid arthritis is a painful, chronic disease that affects an estimated 2 million Americans . Although no single pharmacologic agent is completely effective against the disease, some patients have shown significant improvement when treated with minocycline . Dr Alarcon summarizes the outcomes of studies to date and offers her recommendations. Ned Tijdschr Geneeskd, 1999 Feb 13, 143(7), 336 - 41 {Management and choice of antibiotics for patients with an allergy to penicillin}; Rijnders BJ et al.; Allergic reactions to penicillin occur in 0.7-8% of treatments . Management of bacterial infections in patients allergic to penicillin depends on the availability of alternative antibiotics and on the type of allergy . Skin tests can be used to exclude the risk of IgE-mediated reactions (e.g . anaphylaxis) to subsequent penicillin administration . If penicillin is the first choice for treatment and the patient has an IgE-mediated allergy (on the basis of a positive skin test), desensitization therapy to the drug can be performed. Braz Dent J, 1998, 9(2), 67 - 76 Calcium hydroxide and a corticosteroid-antibiotic association as dressings in cases of biopulpectomy . A comparative study in dogs' teeth; Holland R et al.; The subject of this paper was to study the behavior of the periapical tissues of dogs' teeth after biopulpectomy and dressing with calcium hydroxide or a corticosteroid-antibiotic association, before root canal filling with zinc oxide eugenol (ZOE) or Sealapex sealers . The teeth were overinstrumented and dressed for 7 days before the root canal filling . The animals were sacrificed 180 days after treatment and the specimens were prepared for morphological analysis . Specimens treated with Sealapex presented a higher number of cases with biological closure than ZOE . When the root canals were filled with ZOE, better results were observed with the use of the Ca(OH)2 dressing. Aliment Pharmacol Ther, 1999 Apr, 13(4), 497 - 501 The optimal antibiotic combination in a 5-day Helicobacter pylori eradication regimen; Neville PM et al.; BACKGROUND: Current guidelines for Helicobacter pylori eradication recommend 7 days of a proton-pump inhibitor, clarithromycin (C), and either metronidazole (M) or amoxycillin (A) . A shorter course would be cheaper and could be as effective . AIM: This study was designed to investigate the efficacy of three 5-day regimens based on lansoprazole (L) . METHODS: 168 dyspepsia patients with H . pylori infection were randomized to receive a 5-day course of either LCM, LAC or CALM, and a 13C-urea breath test was performed after 4 weeks to assess eradication . RESULTS: 160 patients completed the study . Intention-to-treat eradication rates were as follows: LCM 81%, LAC 59%, CALM 88% . LCM and CALM gave significantly better eradication rates than LAC . There was no significant difference in adverse events across the three groups . Logistical regression analysis showed that the specific regimen used and the age of the patient were the only factors influencing eradication outcome . CONCLUSIONS: Five days of CALM yields acceptable eradication rates, and is cheaper than conventional 7-day proton pump inhibitor-triple therapy . It appears to offer good results in metronidazole-resistant strains of H . pylori . A randomized trial comparing 5-day CALM with conventional 7-day therapy is needed before this regimen can be recommended for routine use. Br J Clin Pharmacol, 1999 Mar, 47(3), 267 - 71 Interpretation of middle ear fluid concentrations of antibiotics: comparison between ceftibuten, cefixime and azithromycin; Scaglione F et al.; AIMS: The aim of this study was to determine the potential influence of variables such as the cell content in the fluid, and serum levels, on the concentrations of ceftibuten, cefixime and azithromycin in the middle ear fluid of patients suffering from acute otitis media . METHODS: This randomized, open study compared the penetration of ceftibuten (9 mg kg(-1) 18 patients), cefixime (8 mg kg(-1), 16 patients) and azithromycin (10 mg kg(-1) 16 patients) into the intracellular and extracellular compartments of middle ear fluid of 50 paediatric patients (aged 8-14 years) with acute otitis media . Middle ear fluid was extracted by tympanocentesis 4, 12 and 24 h after dosing and divided into two fractions: with cells (as collected) (C+) and cell-free (C-) . Antibiotics were assayed in C+ and C- samples by h.p.l.c . RESULTS: Ceftibuten achieved greater penetration into middle ear fluid than cefixime and azithromycin . Higher concentrations of ceftibuten (CTB) and cefixime (CFX) were found in the C- fraction (CTB: 4h 13.3+/-1.86; 12h 4.7+/-1.18; 24h 0.5+/-0.2 . CFX: 4h 3.2+/-1.4; 12h 1.5+/-0.5; 24h>(0.1 mgl(-1)) than in the C+ fraction (CTB:4 h 8.4+/-4.3; 12 h 2.88+/-1.19; 24 h 0.3+/-0.27 . CFX: 4 h 1.2+/-0.6; 12 h 0.8+/-0.2; 24 h>0.1 mg l(-1)) at the each time point, while the opposite was true for azithromycin (C-: 4 h 0.11+/-0.04; 12 h 0.12+/-0.08; 24 h 0.23+/-0.12 . C+: 4 h 0.38+/-0.24; 12 h 0.9+/-0.03; 24 h 1.05+/-0.3 mg l(-1)) . CONCLUSIONS: This study demonstrates that the penetration of antibiotics into the middle ear fluid is influenced by its serum concentrations as well as by the cell content in the fluid . Ceftibuten achieved higher middle ear fluid concentrations than cefixime in C+ and C- fractions at all time points . Both ceftibuten and cefixime concentrations are negatively influenced by the cell content in the fluid . In contrast the concentration of azithromycin to the middle ear fluid is positively influenced by the cell content in the fluid. Biopharm Drug Dispos, 1999 Apr, 20(3), 151 - 8 Differences in the hepatobiliary transport of two quinolone antibiotics, grepafloxacin and lomefloxacin, in the rat; Sasabe H et al.; The biliary excretion of grepafloxacin (GPFX) was compared with that of lomefloxacin (LFLX) in rats . The biliary clearances (Cl(plasma)(bile)) of GPFX was 2.9 times greater than LFLX based on the plasma concentration reached during constant intravenous (i.v.) infusion . The liver-plasma unbound concentration ratio, K(pu), of GPFX (1.7) was also higher than that of LFLX (0.7) . The hepatic uptake clearance, assessed from an integration plot analysis, of GPFX was comparable with the hepatic blood flow rate, and 1.5 times that of LFLX, indicating that membrane transport in the uptake process is more efficient for GPFX . This was also supported by the difference between the uptake clearance of GPFX and LFLX in isolated rat hepatocytes . The bile-liver unbound concentration ratio of GPFX and LFLX was approximately 6 and 3, respectively, and the biliary clearance based on the unbound liver concentration of GPFX was 1.8 times that of LFLX . These results suggest that the concentrative transport of GPFX also across the canalicular membrane was more efficient than that of LFLX . Thus, the membrane transport activity via both sinusoidal and canalicular membranes determines the net excretion of each compound. CMAJ, 1999 Apr 6, 160(7), 1013 - 7 Method of physician remuneration and rates of antibiotic prescription; Hutchinson JM et al.; BACKGROUND: Rates of antibiotic prescription in Canada far exceed generally accepted rates of bacterial infection, which led the authors to postulate that rates of antibiotic prescription depend to some extent on factors unrelated to medical indication . The associations between antibiotic prescription rates and physician characteristics, in particular, method of remuneration and patient volume, were explored . METHODS: The authors evaluated all 153,047 antibiotic prescriptions generated by 476 Newfoundland general practitioners and paid for by the Newfoundland Drug Plan over the 1-year period ending Aug . 31 1996, and calculated rates of antibiotic prescription . Linear and logistic regression models controlling for several physician characteristics, specifically age, place of education (Canada or elsewhere), location of practice (urban or rural) and proportion of elderly patients seen, were used to analyse rates of antibiotic prescription . RESULTS: Fee-for-service payment (rather than salary) and greater volume of patients were strongly associated with higher antibiotic prescription rates . Fee-for-service physicians were much more likely than their salaried counterparts to prescribe at rates above the median value of 1.51 antibiotic prescriptions per unique patient per year . The association between rate of antibiotic prescription and patient volume (as measured by number of unique patients prescribed to) was evident for all physicians . However, the association was much stronger for fee-for-service physicians . Physicians with higher patient volumes prescribed antibiotics at higher rates . INTERPRETATION: In this study factors other than medical indication, in particular method of physician remuneration and patient volume, played a major role in determining antibiotic prescribing practices. Prof Nurse, 1999 Mar, 14(6), 399 - 402 Administering intravenous antibiotics at home; Flynn S; Many patients with orthopaedic infections spend weeks or months in hospital for administration of i.v . antibiotics . Peripherally inserted central venous catheters can be used to give patients their medication at home . Some patients can be taught to administer their own antibiotics, relieving pressure of work in hospitals and the community and encouraging multidisciplinary practice. Am J Gastroenterol, 1999 Apr, 94(4), 950 - 4 The effect of antibiotic therapy on bleeding from duodenal ulcer; Sonnenberg A et al.; OBJECTIVE: We conducted this study to test whether eradication of Helicobacter pylori (H . pylori) infection prevents hemorrhage related to duodenal ulcer . METHODS: Patients with H . pylori infection and endoscopically proven duodenal ulcers without ulcer-related hemorrhage were enrolled into four randomized, double-blind, multicenter studies using the same study protocol . They were treated with clarithromycin plus omeprazole (441 patients), omeprazole alone (447 patients), or ranitidine alone (263 patients) . Success of H . pylori eradication was evaluated by the 13C-urea breath test 4-6 wk after the last dose of study drug . Follow-up continued at monthly intervals up to 1 yr after the last dose of study drug . RESULTS: Bleeding due to duodenal ulcer was not observed in any patients who received clarithromycin plus omeprazole, whereas five patients in the omeprazole treatment group and six patients in the ranitidine treatment group experienced an episode of ulcer-related hemorrhage during follow-up . All patients who experienced ulcer-related bleeding were male . When compared by bleeding, there were no significant differences with respect to ethnicity, alcohol consumption, or tobacco use . H . pylori infection was no longer detectable in 68% of patients after treatment with clarithromycin plus omeprazole, compared with 5% after treatment with omeprazole alone or 4% after treatment with ranitidine alone . CONCLUSION: In a population of duodenal ulcer patients without predisposing risk factors for ulcer bleeding, antibiotic eradication or suppression of H . pylori infection prevented the occurrence of ulcer-related hemorrhage for up to 1 yr after therapy. Biochemistry, 1999 Apr 13, 38(15), 4768 - 81 Cofactor requirements and reconstitution of microcin B17 synthetase: a multienzyme complex that catalyzes the formation of oxazoles and thiazoles in the antibiotic microcin B17; Milne JC et al.; In the maturation of the Escherichia coli antibiotic Microcin B17 (MccB17), the McbA prepro-antibiotic is modified post-translationally by the multimeric microcin synthetase complex (composed of the McbB, -C, and -D proteins), which cyclizes four cysteines and four serines to thiazoles and oxazoles, respectively . Herein, we report the purification of individual subunits of MccB17 synthetase as fusions to maltose binding protein (MBP), and the in vitro reconstitution of heterocyclization activity . Preliminary characterization of each subunit reveals McbB to be a zinc-containing protein that may catalyze the initial cyclodehydration step, and McbC to contain flavin, consistent with an anticipated role for a dehydrogenase . We have previously demonstrated that McbD is a regulated ATPase/GTPase that may function as a conformational switch . Photolabeling experiments with the McbA propeptide now identify McbD as the initial site of substrate recognition . Heterocyclization activity was reconstituted only by combining all three subunits, demonstrating that each protein is required for heterocycle formation . Titration assays indicate that the subunits bind to each other with at least micromolar affinities, although McbD affords activity only after the MBP tag is proteolytically removed . Subunit competition assays with an McbDD147A mutant, which yields a catalytically deficient synthetase in vivo, show it to be defective in complex formation, whereas the McbBC181A/C184A double mutant, which is also inactive, competitively inhibits reconstitution by native McbB . Addition of the HtpG chaperone (originally shown to copurify with MccB17 synthetase), does not stimulate synthetase reconstitution or heterocyclization activity in vitro . A model for synthetase activity is proposed. Bioorg Med Chem, 1999 Jan, 7(1), 119 - 31 Determining the occurrence of a 3(10)-helix and an alpha-helix in two different segments of a lipopeptaibol antibiotic using TOAC, a nitroxide spin-labeled C(alpha)-tetrasubstituted alpha-aminoacid; Monaco V et al.; Trichogin GA IV is a 11-residue lipopeptaibol antibiotic exhibiting membrane modifying properties . We synthesized step-by-step by solution methods three trichogin analogues, each with a double Aib (alpha-aminoisobutyric acid)-->TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) replacement . The strict similarity in the conformational propensities of Aib and TOAC allowed us to exploit these analogues in a detailed investigation of the conformation of this lipopeptaibol in different organic solvents and in a membrane-mimetic environment using in particular the double spin labeling ESR technique . We conclude that the secondary structure in solution remains essentially unchanged if compared to that previously found in the crystal state for trichogin . More specifically, the N-terminal region of the peptide folds in a 3(10)-helix, while the central and C-terminal regions are mainly alpha-helical . An additional, significant proof for the modest plasticity of the trichogin structure was obtained by an X-ray diffraction analysis of the nOct-{TOAC4,8, Leu-OMe11} analogue . For the three analogues permeability measurements revealed membrane-modifying properties comparable to those of natural trichogin. RNA, 1999 Apr, 5(4), 585 - 95 UV-induced modifications in the peptidyl transferase loop of 23S rRNA dependent on binding of the streptogramin B antibiotic, pristinamycin IA; Porse BT et al.; The naturally occurring streptogramin B antibiotic, pristinamycin IA, which inhibits peptide elongation, can produce two modifications in 23S rRNA when bound to the Escherichia coli 70S ribosome and irradiated at 365 nm . Both drug-induced effects map to highly conserved nucleotides within the functionally important peptidyl transferase loop of 23S rRNA at positions m2A2503/psi2504 and G2061/A2062 . The modification yields are influenced strongly, and differentially, by P-site-bound tRNA and strongly by some of the peptidyl transferase antibiotics tested, with chloramphenicol producing a shift in the latter modification to A2062/C2063 . Pristinamycin IA can also produce a modification on binding to deproteinized, mature 23S rRNA, at position U2500/C2501 . The same modification occurs on an approximately 37-nt fragment, encompassing positions approximately 2496-2532 of the peptidyl transferase loop that was excised from the mature rRNA using RNAse H . In contrast, no antibiotic-induced effects were observed on in vitro T7 transcripts of full-length 23S rRNA, domain V, or on a fragment extending from positions approximately 2496-2566, which indicates that one or more posttranscriptional modifications within the sequence Cm-C-U-C-G-m2A-psi-G2505 are important for pristinamycin IA binding and/or the antibiotic-dependent modification of 23S rRNA. Br J Gen Pract, 1998 Nov, 48(436), 1773 - 4 General practitioner prescribing of antibiotics for asthma; Kljakovic M et al.; Although asthma management guidelines in New Zealand do not advise prescribing antibiotics, almost a quarter of asthma consultations result in a prescription for antibiotics . This study, as part of a repeat audit of asthma care at an after-hours medical centre, describes general practitioners' perspectives on prescribing antibiotics to patients presenting with asthma . The results show that GPs have tended to overestimate the risk of bacterial infection in such patients. Toxicol Appl Pharmacol, 1999 Apr 15, 156(2), 129 - 40 Interactions of macrolide antibiotics (Erythromycin A, roxithromycin, erythromycylamine {Dirithromycin}, and azithromycin) with phospholipids: computer-aided conformational analysis and studies on acellular and cell culture models; Montenez JP et al.; The potential of 14/15 membered macrolides to cause phospholipidosis has been prospectively assessed, and structure-effects examined, using combined experimental and conformational approaches . Biochemical studies demonstrated drug binding to phosphatidylinositol-containing liposomes and inhibition of the activity of lysosomal phospholipase A1 toward phosphatidylcholine included in the bilayer, in close correlation with the number of cationic groups carried by the drugs (erythromycin A </= roxithromycin < erythromycylamine </= azithromycin) . In cultured cells (fibroblasts), phospholipidosis (affecting all major phospholipids except sphingomyelin) was observed after 3 days with the following ranking: erythromycin A </= roxithromycin < erythromycylamine < azithromycin (roxithromycin could, however, not be studied in detail due to intrinsic toxicity) . The difference between erythromycylamine and azithromycin was accounted for by the lower cellular accumulation of erythromycylamine . In parallel, based on a methodology developed and validated to study drug-membrane interactions, the conformational analyses revealed that erythromycin A, roxithromycin, erythromycylamine, and azithromycin penetrate into the hydrophobic domain of a phosphatidylinositol monolayer through their desosamine and cladinose moieties, whereas their macrocycle is found close to the interface . This position allows the aminogroups carried by the macrocycle of the diaminated macrolides (erythromycylamine and azithromycin) to come into close contact with the negatively charged phosphogroup of phosphatidylinositol, whereas the amine located on the C-3 of the desosamine, common to all four drugs, is located at a greater distance from this phosphogroup . Our study suggests that all macrolides have the potential to cause phospholipidosis but that this effect is modulated by toxicodynamic and toxicokinetic parameters related to the drug structure and mainly to their cationic character . J Bacteriol, 1999 Apr, 181(8), 2659 - 62 Sequence analysis of the four plasmid genes required to produce the circular peptide antibiotic microcin J25; Solbiati JO et al.; A 4.8-kb plasmid region carrying the four genes mcjABCD necessary for production of and immunity to the cyclic peptide antibiotic microcin J25 (MccJ25) has been sequenced . mcjA encodes the primary structure of MccJ25 as a precursor endowed with an N-terminal extension of 37 amino acids . The products of mcjB and mcjC are thought to be involved in microcin maturation, which implies cleavage of McjA and head-tail linkage of the 21-residue pro-MccJ25 . The predicted McjD polypeptide, which is highly similar to several ABC exporters, was found to be required for MccJ25 secretion, thus explaining its ability to confer immunity to MccJ25. J Med Chem, 1999 Apr 8, 42(7), 1250 - 61 Docking of cationic antibiotics to negatively charged pockets in RNA folds; Hermann T et al.; The binding of aminoglycosides to RNA provides a paradigm system for the analysis of RNA-drug interactions . The electrostatic field around three-dimensional RNA folds creates localized and defined negatively charged regions which are potential docking sites for the cationic ammonium groups of aminoglycosides . To explore in RNA folds the electronegative pockets suitable for aminoglycoside binding, we used calculations of the electrostatic field and Brownian dynamics simulations of cation diffusion . We applied the technique on those RNA molecules experimentally known to bind aminoglycosides, namely, two tobramycin aptamers (Wang, Y.; Rando, R . R . Chem . Biol . 1995, 2, 281-290): the aminoglycoside-binding region in 16S ribosomal RNA (Moazed, S.; Noller, H . F . Nature 1987, 327, 389-394) and the TAR RNA from human immunodeficiency virus (Mei, H.-Y.; et al . Bioorg . Med . Chem . Lett . 1995, 5, 2755-2760) . For the aptamers and ribosomal RNA, for which the binding sites of the aminoglycosides are known, a good agreement between negatively charged pockets and the binding positions of the drugs was found . On the basis of variations between neomycin-like and kanamycin-like aminoglycosides in the interaction with the electrostatic field of ribosomal RNA, we propose a model for the different binding specificities of these two classes of drugs . The spatial congruence between the electronegative pockets in RNA folds and binding positions of aminoglycosides was used to dock aminoglycosides to ribosomal and TAR RNAs . Molecular dynamics simulations were used to analyze possible RNA-drug interactions . Aminoglycosides inhibit the binding of the viral Tat protein to TAR RNA; however, the drug-binding sites are still unknown . Thus, our docking approach provides first structural models for TAR-aminoglycoside complexes . The RNA-drug interactions observed in the modeled complexes support the view that the antibiotics might lock TAR in a conformation with low affinity for the Tat protein, explaining the experimentally found aminoglycoside inhibition of the Tat-TAR interaction (Mei, H.-Y.; et al . Bioorg . Med . Chem . Lett . 1995, 5, 2755-2760). Hosp Pharm, 1995 Oct, 30(10), 872, 874, 876 - 7 A multidisciplinary approach to enhance documentation of antibiotic serum sampling; Sieradzan R et al.; A procedure to improve interdepartmental communication and documentation of antibiotic serum sampling data for pharmacokinetic evaluation will be presented . A prospective audit by the Pharmacokinetic Service revealed that approximately 40% of all antibiotic serum levels were improperly drawn resulting in unsuitable specimens and erroneous serum concentrations or lacked sufficient data for pharmacokinetic analysis . A lack of communication and documentation between phlebotomy and nursing personnel was found to be the most significant source of potential error in serum sampling . Once the protocol for serum sampling was revised, less than 5% of antibiotic serum levels were found to be unsuitable for evaluation and interpretation . A continuous audit for procedural compliance identifies any source of potential sampling error and provides a means to improve the overall quality of a Pharmacokinetic Service. Hosp Top, 1995 Spring, 73(2), 12 - 5 Antibiotic therapy intervention at a community hospital . Opportunities for cost and quality improvements; Thrasher CM et al.; In a one-year study, thirty-two physicians' antibiotic costs decreased significantly and were lower than those in a comparison group . The quality of patient care was not adversely affected, and the hospital's overall rate of nosocomial infection decreased . The success of the program led to its being adopted throughout the hospital . The dynamics of pharmacies' implementing cost-reduction strategies with voluntary medical staffs are discussed throughout the article. Hosp Pharm, 1995 Feb, 30(2), 132 - 4, 137 Antibiotic utilization and cost analysis in hospitalized patients with community-acquired pneumonia; Stein GE et al.; All cases of presumptive community-acquired pneumonia (CAP) in adult patients admitted to a community/teaching hospital during the first 6 months of 1993 were reviewed . A total of 67 patients ranging in age from 20-90 years (73% > 60 years) had CAP . Fifteen (22%) patients were receiving antibiotics before admission . A typical respiratory pathogen was identified in only 18 (27%) patients . Empiric parenteral antibiotics were initiated in all but 2 patients . These agents usually included cefuroxime (42%), ampicillin/sulbactam (28%), or ceftriaxone (14%) . Concomitant erythromycin (25%) or clarithromycin (17%) was used empirically in 42% of patients . Parenteral antibiotics were given for a mean of 5.2 days (median, 4 days) . The mean therapy cost of these common parenteral agents ranged from $69.50 (cefuroxime, 750 mg every 8 hours) to $271 (ceftriaxone, 1 gram every 12 hours) . Hospitalization ranged from 2-37 days (mean, 8.3 days; median, 6 days) . A total of 50 patients were switched to oral antibiotics . Prescriptions for outpatient therapy ranged from 5-21 days (mean, 8.6 days; median, 7 days) . The most common oral antibiotics included cefuroxime (33%), clarithromycin (20%), and amoxicillin/clavulanate (20%) . The mean therapy cost for these drugs ranged from $85.19 (cefuroxime, 500 mg every 12 hours) to $39.24 (clarithromycin, 500 mg every 12 hours) . This study found that empiric therapy with low-dose parenteral cefuroxime, with or without erythromycin, followed by outpatient clarithromycin was less costly than other common regimens used to treat CAP. Hosp Pharm, 1994 Jan, 29(1), 48 - 50, 53 Comprehension of antibiotic instructions in an outpatient Malaysian practice; Hassan Y et al.; Patients may not comply with antibiotic instructions because they do not understand them . The aim of this study was to assess outpatients' ability to comprehend their antibiotic prescription labels . Two hundred and five subjects on oral antibiotic regimens from an outpatient clinic and pharmacy of a district hospital were selected in this survey . All patients were interviewed by trained clinical pharmacy students . They were asked to read the labels and then how they would take their antibiotics . The results show that 119 (58.1%) patients could interpret the label . Forty-nine (23.9%) patients knew the name of antibiotics and interpreted the directions of use correctly . One hundred sixteen (56.6%) subjects were able to recall the auxiliary information . However, only 44 (21.4%) patients were able to comprehend complete antibiotic instruction . This study demonstrates that a significant proportion of patients could not interpret the labeling instruction . The comprehension level of patients was low and significantly associated (P < 0.05) with the ability of patient to read the label contents . These observations illustrate the need for physicians and pharmacists to provide antibiotic instructions and review these instructions with the patient. Hosp Formul, 1993 Sep, 28(9), 754 - 6, 761-3, 766-8 Antibiotic therapy: what to consider when treating geriatric patients; Yoshikawa TT et al.; The epidemiology, etiology, clinical manifestations, diagnostic approach, and therapeutic choices may be quite different for infections that occur in elderly patients compared with those that occur in younger adults . Given these variables, it is essential for clinicians who care for older patients to understand how to prescribe antibiotics appropriately for this population . This article examines the unique characteristics of infections in the elderly as well as provides recommendations on the use of specific antibiotic agents commonly used to treat infections in geriatric patients. Hosp Formul, 1992 May, 27(5), 509 - 10, 513-4, 516 Determining the formulary status of quinolone antibiotics: one institution's approach; Nightingale CH et al.; Streamlining antibiotic therapy--ie, simplifying regimens, route of administration, or both--is necessary in the modern treatment of hospitalized patients with infectious diseases . Due to their pharmacokinetic profiles and comparative efficacy and safety, the quinolone class of antibiotics is an ideal class for which to direct streamlining efforts . Including only one agent of this class on the formulary, however, is inadequate . Having several quinolones available, and thus expanding the local hospital market for them, enables more physicians to be contacted and educated by manufacturers' sales representatives as part of the hospital's antibiotic management program . By assisting in the education efforts, pharmaceutical representative help to conserve hospital resources, both in terms of cost and personnel . In addition, having more than one supplier of quinolones encourages competition, which favors price reductions. Hosp Pharm, 1993 Jan, 28(1), 20 - 8 Home parenteral antibiotic therapy for patients with cystic fibrosis; Munzenberger PJ et al.; Cystic fibrosis is a genetic disease that affects multiple organ systems . Pulmonary complications associated with it frequently require intense intravenous antibiotic therapy . Home care allows patients to be treated at home, reducing the disruption of family life . New drug administration devices allow the patient increased mobility and independence . With adequate family and nursing support, patients may be able to attend work or school . Reduced hospital stays are good for the patient and cost effective for the hospital . The success of home antibiotic therapy depends on careful selection of the candidate, antibiotic regimen, nursing agency, and home care company . Many patients and families, though motivated, cannot manage the additional stress and time commitment required for home intravenous antibiotic and chest physical therapy . This time commitment may be reduced somewhat by limiting the number of antibiotics and the frequency of their administration. Hosp Pharm, 1992 Oct, 27(10), 867 - 9, 872-4, 882 A multidisciplinary process to determine, communicate, and manage an antibiotic formulary; Cook AA et al.; This article describes a collaborate process developed by the Pharmacy & Therapeutics Committee to define, determine, communicate, and manage an effective antibiotic formulary . Multiple professional disciplines represented by the antibiotic subcommittee evaluated each classification of antibiotics and recommended a preferred drug(s) for each classification . Decisions were based on relative safety, efficacy, and cost with minimal duplication of therapeutic equivalent antibiotics . A therapeutic interchange policy was unnecessary because extensive communication measures developed by the committee proved effective . The strategy used strengthened pharmacist/physician working relationships . This process permitted rationality and understanding by the medical staff, which resulted in unanimous formulary acceptance. Hosp Formul, 1992 Jun, 27(6), 638 - 40, 643 Evaluation of an antibiotic restriction policy using a special drug request form; Julius HC et al.; At a university teaching hospital, a study was undertaken to assess the frequency and appropriateness of restricted antibiotic use using a special drug request (SDR) form to collect the data . The usefulness of the SDR form itself was also assessed for its ability to provide valuable information about patient care and cost effectiveness . The results of this study are presented below. Hosp Pharm, 1992 Mar, 27(3), 213 - 6 Impact of a pharmacist/physician cooperative target drug monitoring program on prophylactic antibiotic prescribing in obstetrics and gynecology; Michael KA et al.; The pharmacist's role in promoting rational, cost-effective use of drugs has been described in the literature . In a target drug monitoring program (TDMP), a single agent or group of agents becomes targeted for review . Antibiotics have been the primary focus of TDMP because of their therapeutic impact and cost considerations . The objectives of this project were to assess the prophylactic antibiotic prescribing habits of OB/GYN physicians and to evaluate the impact of a pharmacist/physician cooperative TDMP on prophylactic antibiotic prescribing and cost . The study was conducted in three phases: 1) a retrospective chart review of 150 patients, 2) an in-service education session, and 3) a concurrent chart review of 107 patients . Patient selection, timing of preoperative dose, and use of single dose prophylaxis were according to criteria in greater than 90% of patients both before and after the in-service training . Compliance with recommended regimens increased from 45 to 73% after the in-service training . A cost savings was not realized because the physicians wished to use a regimen with anti-anaerobic coverage (i.e., cefotetan) rather than a less expensive agent . However, the cost of selection of resistant organisms must be considered when discouraging the use of multiple broad spectrum agents . Active involvement of the medical staff in a pharmacy-based TDMP produces a cooperative atmosphere in which to educate clinicians and promote rational prescribing habits. Can J Hosp Pharm, 1991 Oct, 44(5), 251 - 8, 270 A pilot study of process and outcome assessment in antibiotic therapy; Ilersich AL et al.; A quality assurance survey of cefazolin therapy was conducted by pharmacists using process-related and outcome-related assessments . The purpose of this survey was to study the possibility of having pharmacists review and categorize the appropriateness and success of antibiotic therapy . During a three week period, 168 orders for cefazolin were identified and 67 prophylactic and medical therapies were selected and submitted for possible pharmacist review . Thirty-seven therapies were reviewed by staff pharmacists who scored each therapy for the acceptability of risk of adverse drug effect, the cost-effectiveness, and the overall appropriateness . An evaluation form was used, but explicit utilization criteria were not provided . The average scores (+/- SD) on a 10 centimeter visual analog scale were 9.1 (+/- 0.71), 8.7 (+/- 1.21), and 8.8 . +/- 0.79) respectively . Twenty-six (70%) of these therapies were monitored to resolution, and 24 (65%) were successful in achieving the therapeutic goal . No adverse effects were noted . The average estimated times to complete the initial review and follow-up review were 10.1 (+/- 5.60) and 3.5 (+/- 2.29) minutes respectively, less than the 19.5 minutes estimated using the Canadian Hospital Pharmacy Workload Measurement System . This survey demonstrated that pharmacists can provide both process-related and outcome-related QA data. Can J Hosp Pharm, 1990 Jun, 43(3), 116 - 22 Effectiveness of an antibiotic cost containment measure; Jung B et al.; University Hospital, University of British Columbia (UBC) Site, a 600-bed teaching hospital in Vancouver, British Columbia, adopted several cost containment measures on August 2, 1988 in an attempt to limit the rise in antibiotic expenditures . One cost containment measure involved extending the dosing intervals of cefazolin, clindamycin and metronidazole by a pharmacy-based automatic dosing interval interchange . Cefazolin and clindamycin orders were changed to an every eight-hour dosing schedule, and metronidazole orders to an every 12-hour schedule . Data were retrospectively collected and tabulated from August 1987 to February 1988 (pre-implementation or PRE period) and August 1988 to February 1989 (post-implementation or POST period) . During the POST period, the mean doses per course were significantly less for metronidazole . Estimated cost savings from the measure was $7,300 for the seven-month POST period . Annualized, the expected savings would be $12,600, which is 4.4% of 1988/1989 total antibiotic expenditures . This cost containment strategy achieved its goal of effective cost savings for University Hospital, UBC Site . Although a small reduction in total drug budget was seen, this study suggests that savings can be achieved through this cost containment measure. Eur J Biochem, 1999 Mar, 260(3), 619 - 26 Interaction of the DNA-binding antitumor antibiotics, chromomycin and mithramycin with erythroid spectrin; Majee S et al.; The aureolic acid group of antitumor antibiotics, chromomycin A3 and mithramycin, are well established as transcription inhibitors, which bind reversibly to DNA at and above physiological pH, in the presence of divalent metal ions such as Mg2+ . As part of our broad objective to elucidate their intracellular mode of action, other than association with DNA, we studied their interactions with the erythrocyte cytoskeletal protein, spectrin, in the absence and presence of magnesium . Different spectroscopic studies, such as absorbance, fluorescence and CD, have shown that both free chromomycin and mithramycin and their Mg2+ complexes bind to spectrin with an affinity higher than that reported for DNA . The affinity constants for the association of chromomycin and mithramycin (or their Mg2+ complexes) with spectrin are comparable with those for the association of spectrin with other cytoskeletal proteins, for example F-actin, ankyrin, protein 4.1, etc . The nature of the binding of the two antibiotics to spectrin is different . The mode of binding of the antibiotics with spectrin also changes in the presence of Mg2+ . The interaction leads to a change in the tertiary structure of the protein . The relevance of the results to our understanding of the mode of action of the antibiotics is discussed. Biotechnol Bioeng, 1998 Jul 5, 59(1), 73 - 9 Use of aqueous two-phase systems for in situ extraction of water soluble antibiotics during their synthesis by enzymes immobilized on porous supports; Hernandez-Justiz O et al.; Yields of kinetically controlled synthesis of antibiotics catalyzed by penicillin G acylase from Escherichia coli (PGA) have been greatly increased by continuous extraction of water soluble products (cephalexin) away from the surroundings of the enzyme . In this way its very rapid enzymatic hydrolysis has been avoided . Enzymes covalently immobilized inside porous supports acting in aqueous two-phase systems have been used to achieve such improvements of synthetic yields . Before the reaction is started, the porous structure of the biocatalyst can be washed and filled with one selected phase . In this way, when the pre-equilibrated biocatalyst is mixed with the second phase (where the reaction product will be extracted), the immobilized enzyme remains in the first selected phase in spite of its possibly different natural trend . Partition coefficients (K) of cephalexin in very different aqueous two-phase systems were firstly evaluated . High K values were obtained under drastic conditions . The best K value for cephalexin (23) was found in 100% PEG 600-3 M ammonium sulfate where cephalexin was extracted to the PEG phase . Pre-incubation of immobilized PGA derivatives in ammonium sulfate and further suspension with 100% PEG 600 allowed us to obtain a 90% synthetic yield of cephalexin from 150 mM phenylglycine methyl ester and 100 mM 7-amino desacetoxicephalosporanic acid (7-ADCA) . In this reaction system, the immobilized enzyme remains in the ammonium sulfate phase and hydrolysis of the antibiotic becomes suppressed because of its continuous extraction to the PEG phase . On the contrary, synthetic yields of a similar process carried out in monophasic systems were much lower (55%) because of a rapid enzymatic hydrolysis of cephalexin . Chem Biol, 1999 Apr, 6(4), 251 - 63 Molecular characterization and analysis of the biosynthetic gene cluster for the antitumor antibiotic mitomycin C from Streptomyces lavendulae NRRL 2564; Mao Y et al.; BACKGROUND: The mitomycins are natural products that contain a variety of functional groups, including aminobenzoquinone- and aziridine-ring systems . Mitomycin C (MC) was the first recognized bioreductive alkylating agent, and has been widely used clinically for antitumor therapy . Precursor-feeding studies showed that MC is derived from 3-amino-5-hydroxybenzoic acid (AHBA), D-glucosamine, L-methionine and carbamoyl phosphate . A genetically linked AHBA biosynthetic gene and MC resistance genes were identified previously in the MC producer Streptomyces lavendulae NRRL 2564 . We set out to identify other genes involved in MC biosynthesis . RESULTS: A cluster of 47 genes spanning 55 kilobases of S . lavendulae DNA governs MC biosynthesis . Fourteen of 22 disruption mutants did not express or overexpressed MC . Seven gene products probably assemble the AHBA intermediate through a variant of the shikimate pathway . The gene encoding the first presumed enzyme in AHBA biosynthesis is not, however, linked within the MC cluster . Candidate genes for mitosane nucleus formation and functionalization were identified . A putative MC translocase was identified that comprises a novel drug-binding and export system, which confers cellular self-protection on S . lavendulae . Two regulatory genes were also identified . CONCLUSIONS: The overall architecture of the MC biosynthetic gene cluster in S . lavendulae has been determined . Targeted manipulation of a putative MC pathway regulator led to a substantial increase in drug production . The cloned genes should help elucidate the molecular basis for creation of the mitosane ring system, as well efforts to engineer the biosynthesis of novel natural products. Schweiz Arch Tierheilkd, 1999, 141(3), 109 - 13 {Residues of antibiotics and chemotherapeutics in meat}; Jemmi T et al.; Antibiotics and chemotherapeutics in food may only be present in concentrations below a toxicologically approved level . To check the established limits laboratories depend on reliable methods: on the one hand rapid and inexpensive screening tests (biological and immunological methods), on the other hand rather costly but very specific chemical-analytical reference methods . The results of residue testing in a big slaughter plant are presented . Residues of antibiotics were mainly found in calves . The most frequently detected drugs were tetracyclines, sulfonamides and aminoglycosides. Chir Narzadow Ruchu Ortop Pol, 1998, 63(5), 463 - 7 {The influence of antibiotic content in CMWI bone cement on its bacteriostatic and mechanical properties}; Toborek J et al.; The influence of antibiotic content in CMW1 bone cement on its bacteriostatic and mechanical properties has been investigated . It was found that antibiotics (beta lactams, II and III generation cefalosporins) preserved their bacteriostatic properties within bone cement . No significant impact of antibiotic content within CMW1 on its mechanical properties has been demonstrated. Pediatr Pulmonol Suppl, 1999, 18, 146 - 9 Antibiotic therapy of childhood pneumonia; Schaad UB; Antibiotic therapy of childhood pneumonia must be based on various factors . Among them, clinical skills, diagnostic studies, knowledge of possible etiologic agents and their in-vitro susceptibility, and avoidance of antibiotic overuse are of greatest importance . The challenge of selective treatment is the reality in developed countries . The equation of pneumonia with antibiotic therapy can no longer be accepted as absolute . If antibiotic therapy is indicated, a new macrolide is usually the drug of choice. Biochem Biophys Res Commun, 1999 Apr 2, 257(1), 19 - 23 A radicicol-related macrocyclic nonaketide compound, antibiotic LL-Z1640-2, inhibits the JNK/p38 pathways in signal-specific manner; Takehana K et al.; Macrocyclic nonaketide compounds, radicicol and its two analogues, 87-250904-F1 and LL-Z1640-2, have various biological activities . Here we show that these compounds inhibit signal-dependent transcriptional activation with different specificity with distinct mechanism . Although all three compounds inhibited PMA-induced AP-1 transcriptional activity in cell-based reporter assay, these compounds exhibited differential effects in separate transcriptional reporter assays for NF-kappaB and glucocorticoid receptor . Next we found that one of these compounds, LL-Z1640-2, was a signal-specific inhibitor of the JNK/p38 pathways . In contrast to LL-Z1640-2, radicicol and 87-250904-F1 did not inhibit JNK/p38 activation . Recently, radicicol was reported as an inhibitor of activated-Ras-induced ERK activation . These results indicated that radicicol and LL-Z1640-2 showed distinct specificity to various MAP kinase pathways despite their structural similarity . Furthermore, LL-Z-1640-2 inhibited anisomycin-induced but not TNF-induced JNK/p38 activation, indicating that the inhibition mechanism is signal-specific . J Antibiot (Tokyo), 1999 Jan, 52(1), 34 - 9 Zelkovamycin, a new cyclic peptide antibiotic from Streptomyces sp . K96-0670 . II . Structure elucidation; Tabata N et al.; The structure of antibiotic zelkovamycin was elucidated as a cyclic peptide comprising glycyl, 2-aminobutanoyl, 2-amino-2-butenoyl, N-methyl glycyl, alanyl, 1,3-thiazoyl, 7-methoxytryptophanyl and 2-methyldehydrothreonyl residues . The sequence of the amino acids was established by spectroscopic studies including 1H-1H COSY, 13C-1H COSY, 13C-1H HMQC, 13C-1H HMBC, 15N-1H HMQC and 15N-1H HMBC NMR experiments. Rev Med Brux, 1999 Feb, 20(1), 43 - 7 {Overprescribing of antibiotics outside the hospital}; Sternon J et al.; Overprescription of antibiotics is evident in the community as well as in hospital, in veterinary practice or in agriculture . This leads to bacterial multiresistance and treatment failures . The limitation of this overprescription will not be obtained unless diagnostic, therapeutic and preventive guidelines are followed particularly in the management of the upper respiratory tract infections. Acta Crystallogr D Biol Crystallogr, 1999 Jan, 55 ( Pt 1), 317 - 9 Epub 1999 Jan 01. Crystallization and preliminary X-ray diffraction studies of phospholipase D from Streptomyces antibioticus; Suzuki A et al.; Phospholipase D (E.C . 3.1.4.4) from Streptomyces antibioticus has been crystallized in six crystal forms using the hanging-drop vapour-diffusion method . The type III and V crystals belong to monoclinic and hexagonal systems, respectively . All of the other crystal forms, types I, II, IV and VI, belong to orthorhombic space group P212121 . Of these four types, the type VI crystals are suitable for X-ray structure determination . Crystal data for type VI crystals are: a = 50.1, b = 98.7, c = 107.6 A, V = 532100 A3, Z = 4 and Vm = 2.47 A3 Da-1 . Type VI crystals diffract to at least 2.3 A resolution . A total of 11295 independent reflections to 3 A resolution have been collected from a type VI crystal using a conventional X-ray source, and its structural analysis is currently being conducted using isomorphous replacement methods. Clin Ther, 1999 Jan, 21(1), 148 - 59 Safety profile of sparfloxacin, a new fluoroquinolone antibiotic; Lipsky BA et al.; The safety profile of sparfloxacin, a newer fluoroquinolone antibiotic, was examined through an integrated analysis of safety data from 6 multicenter phase III trials . These consisted of 5 double-masked, randomized, comparative trials of sparfloxacin (a 400-mg oral loading dose followed by 200 mg/d for 10 days) versus standard therapies (erythromycin, cefaclor, ofloxacin, clarithromycin, and ciprofloxacin) and I open-label trial (noncomparative) in patients with: community-acquired pneumonia (2 trials); acute bacterial exacerbations of chronic bronchitis (1 trial); acute maxillary sinusitis (2 trials, one of which was the noncomparative trial); and complicated skin and skin-structure infections (1 trial) . Overall, 401 (25.3%) of 1585 patients treated with sparfloxacin and 374 (28.1%) of 1331 receiving a comparator regimen experienced at least 1 adverse event considered to be related to the study medication . Photosensitivity reactions, usually of mild-to-moderate severity, were seen more frequently with sparfloxacin (7.4%) than with comparator agents (0.5%), whereas gastrointestinal reactions (diarrhea, nausea, dyspepsia, abdominal pain, vomiting, and flatulence), insomnia, and taste perversion were more common in patients taking comparator drugs (22.3% vs 12.1%, 4.3% vs 1.5%, and 2.9% vs 1.2%, respectively) . Analysis of electrocardiographic findings showed that the mean change from baseline in QT interval corrected for heart rate (QTc) was significantly greater in sparfloxacin-treated patients (10 msec) than in patients given comparator drugs (3 msec), but no associated ventricular arrhythmias were detected . Adverse events led to discontinuation of study medication in 104 (6.6%) patients receiving sparfloxacin and 118 (8.9%) given com parator drugs . Sparfloxacin may be considered an appropriate choice for the treatment of certain community-acquired infections for patients who are not at risk for photosensitivity reactions or adverse events associated with prolongation of the QTc interval. J Pharmacol Exp Ther, 1999 Apr, 289(1), 66 - 71 Multiplicity of the H+-dependent transport mechanism of dipeptide and anionic beta-lactam antibiotic ceftibuten in rat intestinal brush-border membrane; Iseki K et al.; To elucidate the transport characteristics of the H+/dipeptide carrier that recognizes the orally active beta-lactam antibiotic ceftibuten, the uptake behaviors were compared of ceftibuten and Gly-Sar by rat intestinal brush-border membrane vesicles . The results show that 1) both the uptake of ceftibuten and that of Gly-Sar were dependent on an inwardly directed H+ gradient; 2) anionic compounds such as hippurylphenyllactic acid competitively inhibited ceftibuten uptake in the presence of H+ gradient, whereas this anion did not inhibit Gly-Sar uptake; and 3) the carrier-mediated uptake of ceftibuten did not disappear even in the presence of 20 mM Gly-Sar . The results provide an evidence that several transporters with different features are potentially responsible for the uptake of beta-lactam antibiotics into the intestinal cells . It is suggested that the dianionic beta-lactam antibiotics that carry a net negative charge such as ceftibuten use multiple H+-dependent transport systems for absorption. Arch Dis Child, 1999 Apr, 80(4), 348 - 52 Improvement of nebulised antibiotic delivery in cystic fibrosis; Wilson D et al.; AIM: To investigate deposition patterns and to assess the delivery rate of two nebuliser systems in children with cystic fibrosis (CF) . METHODS: Thirty three children with CF on regular treatment with nebulised antibiotics had radioisotope scans performed using technetium-99m labelled aerosol antibiotic generated by a Ventstream nebuliser (median mass diameter (MMD), 3.3 microm; delivery rate, 0 . 075 ml/min) under conditions similar to their routine home practice . The inhomogeneity of the images was scored on a 1-10 rating scale (a low score indicating even distribution of the antibiotic), and stomach deposition was measured as a percentage of overall deposition . Twenty patients had a repeat scan using an Optimist nebuliser (MMD, 1.8 microm; delivery rate, 0.02 ml/min) . RESULTS: The mean inhomogeneity scores were 5.4 in the Ventstream group and 3 . 5 in the Optimist group . Mean stomach deposition was 17.3% in the 33 patients using the Ventstream nebuliser . There was an inverse relation between height and stomach deposition (r = 0.69) . In the 20 patients who had both nebulisers, the mean percentages of stomach deposition for the Ventstream and Optimist nebulisers were 11.8% and 1.6%, respectively . The Ventstream nebuliser delivered antibiotic at an average 2.8 times faster rate than the Optimist nebuliser . IMPLICATIONS: A smaller particle size results in a more homogenous distribution of the antibiotic in the lungs with decreased stomach deposition . This should not be seen as a recommendation to use the Optimist nebuliser because more antibiotic was delivered to most parts of the lung with the Ventstream because of its increased delivery rate. Presse Med, 1999 Feb 20, 28(7), 343 - 50 {Prescription and consumption of antibiotics in ambulatory care}; Stimulation of free radical formation by aminoglycoside antibiotics; Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USAWe have previously shown gentamicin to form a redox-active iron chelate . This study investigates whether other aminoglycosides can likewise stimulate the generation of reactive oxygen species (free radicals) . Kanamycin, neomycin and streptomycin were compared to gentamicin in intact cells and in cell-free in vitro assays using luminescence detection with lucigenin or luminol . Neutrophils and Epstein-Barr virus-transformed lymphoblastoid cells served as cell models in which a respiratory burst of superoxide was induced by phorbol ester . The addition of millimolar amounts of any of the aminoglycosides increased the luminescence significantly . The drugs also increased the formation of free radicals in an enzymatic (hypoxanthine-xanthine oxidase) and a non-enzymatic (phenazine methosulfate-NADH) superoxide-generating system . Half-maximal stimulation was reached with (0.4 mM gentamicin, and there was an absolute requirement for an electron donor, arachidonic acid . In both intact cells and cell-free systems, gentamicin-enhanced luminosity was suppressed by iron chelators . These results demonstrate that different aminoglycoside antibiotics can stimulate the formation of free radicals in biological and in cell-free systems . Luminescence detection is a convenient assay method to investigate the redox properties of these drugs. Cell Mol Neurobiol, 1999 Feb, 19(1), 87 - 92 Antibiotics and light responses in superfused bovine retina; Walter P et al.; 1 . Our objective was to study effects of clindamycin and ciprofloxacin on the electroretinogram (ERG) of isolated bovine retinas . 2 . Electroretinograms of isolated superfused bovine retinas were recorded under normal conditions and during application of clindamycin and ciprofloxacin . The b-wave reduction was plotted against the drug concentration . In several cases retinal oxygen uptake was also measured . Clindamycin was available only in a preparation containing benzyl alcohol . To differentiate between effects caused by the antibiotic and the alcohol, ERGs were also recorded under superfusion with benzyl alcohol . To record drug effects on photoreceptors synaptic transmission was blocked using 1 mM aspartate . 3 . At concentrations between 0.3 and 10 mM clindamycin significantly reduced the amplitude of the b-wave of the ERG . A comparable reduction of retinal oxygen uptake was found at concentrations 10-fold higher . Clindamycin, 3 mM, did not affect the a-wave after preincubation with aspartate . Benzyl alcohol at concentrations of 0.3 and 1 mM did not affect the b-wave, whereas at higher concentrations the b-wave was found to be reduced . Considerable b-wave reductions were found with ciprofloxacin at concentrations of between 0.03 and 0.6 mM . All effects proved to be fully reversible and dose-dependent . 4 . Ciprofloxacin and clindamycin did both alter neural function in the isolated superfused bovine retina . The nontoxic dosages found here differ considerably from results in rabbits after intravitreal injections . This is probably due to species differences. Antibiot Khimioter, 1998, 43(12), 12 - 5 {Effect of aeration and redox potential on the biosynthesis of the antibiotic imbricin}; Sukharevich ME et al.; The relationship between imbricin biosynthesis by Streptomyces imbricatus and the medium aeration and redox potential (Eh) was studied . The influence of the oxygen dissolution velocity within the ranges of 2.9 to 0.5 g O2/l.h was investigated and it was shown that the highest yield of the antibiotic was provided by the maximum velocity . At the background of the intensive aeration (2.9 g O2/l.h) decreasing of Eh by reducing agents such as ascorbic acid, L-thyrosin or K4Fe(CN)6 stimulated the biosynthesis whereas at the lower velocities the process proved to be inhibited . Under conditions of insufficient aeration the biosynthesis stimulation could be provided by increasing the medium Eh by acidifying agents such as K2Cr2O7, K3Fe(CN)6 or KMnO4 . It was concluded that intensive synthesis of imbricin required not only efficient aeration but also definite levels of the medium redox potential. Artif Organs, 1992 Oct, 16(5), 457 - 60 Pharmacokinetics and dosage adjustment of antibiotics during continuous extracorporeal lung assistance and hemofiltration; Kroh UF et al.; Fifty-eight patients undergoing continuous volume-controlled hemofiltration (CVHF) and extracorporeal lung assistance (ECLA) received drug therapy determined by use of a new predictive algorithm in a validation study . Amikacin, netilmicin, tobramycin, ceftriaxone, vancomycin, and teicoplanin doses were given as predicted from clinical parameters . Corrections were necessary in 15 cases (e.g., CVHF 68% and ECLA 82% precision) . There were no statistical differences between predicted and monitored drug doses . The correlation coefficient gave r2 = 0.921 . Preliminary results from not yet analyzed drugs (ceftriaxone, teicoplanin) fit well into the curve . Because of rapid intraindividual changes, toxic drugs should continue to be monitored. FEMS Microbiol Lett, 1999 Feb 15, 171(2), 215 - 21 Low target site specificity of an IS6100-based mini-transposon, Tn1792, developed for transposon mutagenesis of antibiotic-producing Streptomyces; Herron PR et al.; To improve transposon mutagenesis of antibiotic-producing Streptomyces, a mini-transposon, Tn1792, was constructed, based on IS6100, originally isolated from Mycobacterium fortuitum . Easily manageable transposition assays were developed to demonstrate inducible transposition of Tn1792 into the Streptomyces genome from a temperature-sensitive delivery plasmid . Introduction of the selectable aac1 gene between the inverted repeats in Tn1792 allowed for both reliable identification of transposition events in Streptomyces, and also subsequent cloning of transposon-tagged sequences in Escherichia coli . This enabled the target site specificity of Tn1792 to be determined at nucleotide resolution, revealing no significant shared homology between different target sites . Consequently, Tn1792 is well suited for random mutagenesis of Streptomyces. FEMS Microbiol Lett, 1999 Feb 15, 171(2), 183 - 9 Identification and characterization of 6-dehydroVB-A reductase from Streptomyces antibioticus; Shikura N et al.; Streptomyces antibioticus NF-18 is a hyperproducing strain of a Streptomyces hormone, virginiae butanolide A (VB-A), that induces virginiamycin production of S . virginiae at nanomolar concentrations . To characterize the biosynthetic pathway of VB-A, we identified and characterized for the first time the 6-dehydro VB-A reductase that is responsible for the final reduction step in the biosynthesis . Assay protocols and stabilization conditions were established . The 6-dehydro VB-A reductase was found to require NADPH, not NADH, as a coenzyme . The K(m) values of the enzyme for NADPH and (+/-)-6-dehydro VB-A were determined to be 50 +/- 2 microM and 100 +/- 5 microM, respectively . Ultracentrifugation experiments revealed that 6-dehydro VB-A reductase was present almost exclusively in the 100,000 x g supernatant fraction, indicating that the enzyme is a cytoplasmic-soluble protein . The M(r) of the native 6-dehydro VB-A reductase was estimated to be 82,000 +/- 3000 by molecular sieve HPLC . The optimal pH was found to be 6.7 +/- 0.2. Biochem Pharmacol, 1999 Apr 1, 57(7), 727 - 41 A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin; Gewirtz DA; The mechanisms responsible for the antiproliferative and cytotoxic effects of the anthracycline antibiotics doxorubicin (Adriamycin) and daunorubicin (daunomycin) have been the subject of considerable controversy . This commentary addresses the potential role of DNA synthesis inhibition, free radical formation and lipid peroxidation, DNA binding and alkylation, DNA cross-linking, interference with DNA strand separation and helicase activity, direct membrane effects, and the initiation of DNA damage via the inhibition of topoisomerase II in the interaction of these drugs with the tumor cell . One premise underlying this analysis is that only studies utilizing drug concentrations that reflect the plasma levels in the patient after either bolus administration or continuous infusion are considered to reflect the basis for drug action in the clinic . The role of free radicals in anthracycline cardiotoxicity is also discussed. J Virol, 1999 Apr, 73(4), 3511 - 3 Effectiveness of polyene antibiotics in treatment of transmissible spongiform encephalopathy in transgenic mice expressing Syrian hamster PrP only in neurons; Demaimay R et al.; To date very few drugs have favorably influenced the course of transmissible spongiform encephalopathies . In previous studies, the polyene antibiotics amphotericin B (AmB) and MS-8209 prolonged the incubation time in Syrian hamsters of the 263K strain of scrapie, but AmB had no effect against other scrapie strains in Syrian hamsters . In the present experiments using transgenic mice expressing Syrian hamster PrP in neurons only, MS-8209 extended the life spans of animals infected with the 263K strain but not the DY strain . AmB was effective against both 263K and DY and prevented death in 18% of DY-infected animals . The AmB effect against strain 263K was more prominent in mice whose endogenous PrP gene had been inactivated by homologous recombination . It was unclear whether this difference was due to a change in the duration of the disease or to possible interactive effects between the mouse PrP gene and the drugs themselves . The effectiveness of treatment after intracerebral scrapie infection in transgenic mice expressing PrP only in neurons suggested that neurons are important sites of action for these drugs. J Bacteriol, 1999 Mar, 181(6), 1968 - 70 Escherichia coli outer membrane protein TolC is involved in production of the peptide antibiotic microcin J25; Delgado MA et al.; A Tn5 insertion in tolC eliminated microcin J25 production . The mutation had little effect on the expression of the microcin structural gene and presumably acted by blocking microcin secretion . The tolC mutants carrying multiple copies of the microcin genes were less immune to the microcin . TolC is thus likely a component of a microcin export complex containing the McjD immunity protein, an ABC exporter. Gene, 1999 Mar 4, 228(1-2), 147 - 53 Cloning and characterization of a Myxococcus xanthus cytochrome P-450 hydroxylase required for biosynthesis of the polyketide antibiotic TA; Paitan Y et al.; The antibiotic TA, a complex macrocyclic polyketide of Myxococcus xanthus, is produced, like many other polyketides, through successive condensations of acetate by a type I polyketide synthase (PKS) mechanism . The chemical structure of this antibiotic and the mechanism by which it is synthesized indicate the need for several post-modification steps, such as a specific hydroxylation at C-20 . Previous studies have shown that several genes, essential for TA biosynthesis, are clustered in a region of at least 36kb, which was subsequently cloned and analyzed . In this study, we report the analysis of a DNA fragment, containing a specific cytochrome P-450 hydroxylase, presumably responsible for the sole non-PKS hydroxylation at position C-20 . Functional analysis of the cytochrome P-450 hydroxylase gene through specific gene disruption confirms that it is essential for the production of an active TA molecule. Acta Ophthalmol Scand, 1999 Feb, 77(1), 110 - 3 Antibiotic-induced endotoxemia in a patient with endogenous endophthalmitis; Yamada R et al.; PURPOSE: The aim of the study is to describe a case of suspected endotoxin-induced uveitis associated with septic endogenous endophthalmitis followed by antibiotic-induced endotoxemia . METHODS: The human leukocyte antigen (HLA) typing of peripheral leukocytes was studied by lymphocytotoxicity technique . Histological and immunohistochemical studies of paraffin embedded specimen were conducted . RESULTS: Findings of HLA typing revealed positive reaction for B 51, Cw 3, DR 8, DR 11, DQ 3 . The vitreous body of an eviscerated eye was occupied by the non-specific granulomatous tissue, composed of fibroblast, plasma cells, and Sudan black staining positive foamy cells, including melaniferous phagocytes, identified as CD 68 positive macrophage . CONCLUSION: It is suggested that antibiotic-induced endotoxemia of a patient with septic endogenous endophthalmitis produced endotoxin-induced uveitis under an upregulation of HLA and endotoxin activated macrophages may release cytokines, followed by fibrin formation and subsequent granuloma. Nucleosides Nucleotides, 1999 Feb, 18(2), 153 - 9 Total synthesis of the naturally occurring antibiotic toyocamycin using new and improved synthetic procedures; Porcari AR et al.; Starting with commercially available tetracyanoethylene, we describe a more efficient and higher yielding synthesis of toyocamycin with regards to convenience, overall yield, and total reaction time than those syntheses previously reported. J Biol Chem, 1999 Mar 12, 274(11), 7316 - 24 Identifying the bicyclomycin binding domain through biochemical analysis of antibiotic-resistant rho proteins; Magyar A et al.; Mutations M219K, S266A, and G337S in transcription termination factor Rho have been shown to confer resistance to the antibiotic bicyclomycin (BCM) . All three His-tagged mutant Rho proteins exhibited similar Km values for ATP; however, the Vmax values at infinite ATP concentrations were one-fourth to one-third that for the His-tagged wild-type enzyme . BCM inhibition kinetics of poly(C)-dependent ATPase activity for the mutant proteins were non-competitive with respect to ATP (altering catalytic function but not ATP binding) and showed increased Ki values compared with His-tagged wild-type Rho . M219K and G337S exhibited increased ratios of poly(U)/poly(C)-stimulated ATPase activity and lower apparent Km values for ribo(C)10 in the poly(dC).ribo(C)10-dependent ATPase assay compared with His-tagged wild-type Rho . The S266A mutation did not show an increased poly(U)/poly(C) ATPase activity ratio and maintained approximately the same Km for ribo(C)10 in the poly(dC) . ribo(C)10-dependent ATPase assay . The kinetic studies indicated that M219K and G337S altered the secondary RNA binding domain in Rho whereas the S266A mutation did not . Transcription termination assays for each mutant showed different patterns of Rho-terminated transcripts . Tyrosine substitution of Ser-266 led to BCM sensitivity intimating that an OH (hydroxyl) moiety at this position is needed for BCM (binding) inhibition . Our results suggest BCM binds to Rho at a site distinct from both the ATP and the primary RNA binding domains but close to the secondary RNA-binding (tracking) site and the ATP hydrolysis pocket. J Arthroplasty, 1999 Feb, 14(2), 209 - 14 The in vitro elution characteristics of antibiotic-loaded CMW and Palacos-R bone cements; Penner MJ et al.; An in vitro study was carried out comparing the elution characteristics of Palacos-R and CMW acrylic cements . Three groups of 6 antibiotic-loaded cement disks were prepared, incorporating 1.0 g vancomycin and 2.4 g tobramycin per 40 g packet of cement . Palacos-R bone cement was used for group 1, CMW 1 for group 2, and CMW 3 for group 3 . The disks were placed in saline baths for 9 weeks . The baths were periodically sampled and elution rates calculated . CMW 1 released 24% less tobramycin and 36% less vancomycin than Palacos-R over the total study period (P < .05) . CMW 3 released 34% less tobramycin and 38% less vancomycin than Palacos-R (P < .05) . There was no significant difference in antibiotic release between CMW 1 and CMW 3 . The in vitro elution characteristics of Palacos-R are superior to CMW. Pharmacol Res, 1999 Jan, 39(1), 5 - 10 Effects of the ionophore antibiotic monensin on hepatic biotransformations and target organ morphology in rats; Dacasto M et al.; As a preliminary in vivo approach in order to study the mechanism of toxicity of the veterinary anticoccidial monensin, male Wistar rats were orally administered 0, 2 and 12 mg kg-1 body wt . day-1 of monensin for 7 days . At the end of the experiment, effects of the ionophore on serum creatine kinase, lactic dehydrogenase and selected drug metabolising enzyme activities were investigated . Furthermore, liver, heart and quadriceps femoris muscle samples were submitted to morphological investigations . Clinical signs or increasing levels of enzymic markers of muscle injury attributable to monensin toxicosis have never been observed in treated animals . As a matter of fact all drug metabolising enzymes activities checked have not shown significant changes, except for a significant decrease of ethoxyresorufin O-deethylase (up to 31%) and aminopyrine N-demethylase (17%) activities . Morphologically, mitochondrial cristae fragmentation and initial formation of 'myelinic sheaths-like' structures have been noticed in heart and muscle fibres . As far as rat study is concerned, these results confirm heart and muscle as target organs of monensin toxicity . In addition, these findings suggest that the inhibition of hepatic biotransformation processes following the i.p . administration of the ionophore, as reported previously by other authors, might reflect unspecific cellular toxic effects rather than a specific enzyme damage . Comp Immunol Microbiol Infect Dis, 1999 Apr, 22(2), 93 - 102 Experimental studies (in vitro) on polyene macrolide antibiotics with special reference to hamycin against Malassezia ovale; Gupte TE et al.; Hamycin activity (in vitro) against Malassezia ovale was studied and compared with old and newly discovered polyene antifungal antibiotics . Hamycin showed a marked anti-M . ovale activity which was enhanced in the presence of divalent cations like Cu++ and Zn++ . Furthermore, the absorption of hamycin onto the cell membrane or cell surface of M . ovale was also increased in the presence of divalent cations . It is suggested that hamycin alone or along with metal ions, specifically Cu++ may be useful clinically in the treatment of dandruff or seborrheic dermatitis. Pediatrics, 1999 Mar, 103(3), 627 - 31 The efficacy of routine outpatient management without antibiotics of fever in selected infants; Baker MD et al.; BACKGROUND: A previous study produced a protocol for outpatient management of febrile infants (FIs) judged to be at low risk for serious bacterial illness (SBI) . This Philadelphia protocol demonstrated that 40% of FIs seen in the emergency department could be safely managed without antibiotics at home; and it was established by the emergency department staff as the standard of care at our institution . OBJECTIVE: To determine 1) the actual practices of management of FIs 18 months after establishment of the Philadelphia protocol as the standard of care, and 2) the continued efficacy of noninvasive outpatient management of fever in FIs who, using the Philadelphia protocol, were identified as low risk for SBI . DESIGN: Thirty-six-month consecutive cohort study . SETTING: Urban pediatric emergency department . PARTICIPANTS: Four hundred twenty-two infants, 29 to 60 days of age, with rectal temperatures >/=38.0 degrees C . Interventions . After a complete history taking, physical examination, and workup for SBI, infants were managed at the discretion of the attending physician in the emergency department . Subsequently, those management practices were reviewed and compliance with the Philadelphia protocol was evaluated . In addition, the overall efficacy and safety of that standard during 8 years of use was assessed . RESULTS: Of the 422 FIs enrolled, 101 (24%) were prospectively identified as low risk for SBI, and safe for management without antibiotics . Twenty-eight (6%) FIs were managed out of accordance with the Philadelphia protocol . Seven were admitted out of accordance, 10 (2 with UTI) were discharged out of accordance, and 11 inpatients (1 with bacterial gastroenteritis) initially received no antibiotics out of accordance with the protocol . Physician failure to consider the results of the complete blood count or urinalysis accounted for errors involving FIs with SBI . None of the 43 FIs with SBI were identified by the Philadelphia protocol to be at low risk for SBI . CONCLUSIONS: The Philadelphia protocol for outpatient management without antibiotics of FIs at low risk for SBI remains practical, reliable, and safe . Because breaches do occur, physicians must carefully scrutinize protocol compliance, especially with regard to the complete blood count and urinalysis. Appl Environ Microbiol, 1999 Mar, 65(3), 1236 - 40 Organization of the gene cluster for biosynthesis of penicillin in Penicillium nalgiovense and antibiotic production in cured dry sausages; Laich F et al.; Several fungal isolates obtained from two cured meat products from Spain were identified as Penicillium nalgiovense by their morphological features and by DNA fingerprinting . All P . nalgiovense isolates showed antibiotic activity in agar diffusion assays, and their penicillin production in liquid complex medium ranged from 6 to 38 microgram . ml-1 . We constructed a restriction map of the penicillin gene cluster of P . nalgiovense and found that the organization of the penicillin biosynthetic genes (pcbAB, pcbC, and penDE) is the same as in Penicillium chrysogenum and Aspergillus nidulans . The pcbAB gene is located in an orientation opposite that of the pcbC and penDE genes in all three species . Significant amounts of penicillin were found in situ in the casing and the outer layer of salami meat during early stages of the curing process, coinciding with fungal colonization, but no penicillin was detected in the cured salami . The antibiotic produced in situ was sensitive to penicillinase. J Biol Chem, 1999 Mar 5, 274(10), 6031 - 4 Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase; Moche M et al.; In the biosynthesis of fatty acids, the beta-ketoacyl-acyl carrier protein (ACP) synthases catalyze chain elongation by the addition of two-carbon units derived from malonyl-ACP to an acyl group bound to either ACP or CoA . The enzyme is a possible drug target for treatment of certain cancers and for tuberculosis . The crystal structure of the complex of the enzyme from Escherichia coli, and the fungal mycotoxin cerulenin reveals that the inhibitor is bound in a hydrophobic pocket formed at the dimer interface . Cerulenin is covalently attached to the active site cysteine through its C2 carbon atom . The fit of the inhibitor to the active site is not optimal, and there is thus room for improvement through structure based design. Nippon Rinsho, 1999 Jan, 57(1), 81 - 6 {Antibiotic-resistant H . pylori strains in the last ten years in Japan}; Murakami K et al.; An increase in the prevalence of antibiotic-resistant H . pylori strains has been reported . We tested the sensitivity of H . pylori strains to antibiotics before and after the eradication treatment to determine primary and secondary resistance by E-test . A total of 336 H . pylori strains from 1987 to 1998 were tested for sensitivity to clarithromycin (CAM), amoxicillin (AMPC), and metronidazole (MNZ) . Primary resistance of H . pylori to CAM, MNZ, and AMPC were found in 9.5%, 26.8%, and 0.3% strains, respectively . The resistant strains to CAM and MNZ were gradually increasing in the last few years . The cure rates of triple therapy with MNZ and CAM for CAM-susceptible and CAM-resistant H . pylori isolates were 83.3% (40/48) and 30.0% (3/10) respectively, and the cure rates of triple therapy with CAM and AMPC for CAM-susceptible and CAM-resistant H . pylori isolates were 79.3% (69/87) and 12.5% (1/8) respectively . After triple therapy, secondary resistant strains to CAM and MNZ were found in 42.1% (8/19) and 31.6% (6/19) of the cases. Rapid Commun Mass Spectrom, 1998, 12(24), 2031 - 40 Electrospray ionization and tandem ion trap mass spectrometry for the confirmation of seven beta-lactam antibiotics in bovine milk; Heller DN et al.; The feasibility of a technique to confirm the presence of residues from seven beta-lactam antibiotics in bovine milk has been demonstrated . The technique makes use of electrospray ionization and tandem ion trap mass spectrometry . Residues are first extracted from milk by reversed-phase solid phase extraction . Target analytes are separated by on-line reversed-phase liquid chromatography and ionized in the electrospray interface . The product ion mass spectra are acquired following collision-induced dissociation of protonated molecules . Confirmation is based on comparison of full scan spectra between unknowns and bona fide standards . The feasibility of this technique has been demonstrated for the six beta-lactams currently approved for use in lactating dairy cattle (penicillin G, ampicillin, amoxicillin, cloxacillin, cephapirin and ceftiofur) and a drug not approved for animal use, cefazolin . The technique has been applied to control milk fortified at 5 ng/mL of penicillin G and 10 ng/mL of the other six drugs. Home Healthc Nurse, 1998 Dec, 16(12), 831 - 7 Implementation of the i.v . push method of antibiotic administration using the FOCUS/PDCA approach; Miano B et al.; Home health agencies constantly seek ways to improve patient care as part of their performance improvement program . This includes revising and updating agency policies and procedures . Changing care processes, such as administering intravenous medications, requires input from pharmacy and nursing staff as well as administration . The authors describe how one agency used this process while adopting the i.v . push method of administering certain antibiotics to home care patients. Digestion, 1999, 60 Suppl 1, 9 - 13 Role of early continuous regional arterial infusion of protease inhibitor and antibiotic in nonsurgical treatment of acute necrotizing pancreatitis; Takeda K et al.; This paper reviewed our experience with the nonsurgical management of acute necrotizing pancreatitis (ANP) by continuous regional arterial infusion (CRAI) of protease inhibitor (nafamostat mesilate, 240 mg/day) and antibiotic (imipenem, 0.5 g every 12 h) . 47 patients with ANP admitted within 7 days were treated with intensive care and CRAI for 5 days prospectively . 40 patients responded to CRAI therapy and the mortality rate in these patients was 2.5% . 7 patients (14 . 9%) did not respond to CRAI . 5 of 7 nonresponders died of multiple organ failure although pancreatic necrosis was persistently sterile . The remaining 2 patients who underwent necrosectomy for infected pancreatic necrosis recovered after surgery . In 34 patients treated with CRAI in the early stage within 72 h after the onset, 31 (91.2%) responded . The mortality rate was 5.9% and the incidence of infected pancreatic necrosis was 2.9% in these 34 patients . These results demonstrated that most patients with ANP responded to conservative management combined with CRAI with nafamostat and imipenem when employed within 72 h after the onset . Early intervention of CRAI with protease inhibitor and antibiotic has a significant role in the nonsurgical management of ANP. Mol Microbiol, 1999 Jan, 31(2), 623 - 31 The macrolide-ketolide antibiotic binding site is formed by structures in domains II and V of 23S ribosomal RNA; Hansen LH et al.; The macrolide antibiotic erythromycin interacts with bacterial 23S ribosomal RNA (rRNA) making contacts that are limited to hairpin 35 in domain II of the rRNA and to the peptidyl transferase loop in domain V . These two regions are probably folded close together in the 23S rRNA tertiary structure and form a binding pocket for macrolides and other drug types . Erythromycin has been derivatized by replacing the L-cladinose moiety at position 3 by a keto group (forming the ketolide antibiotics) and by an alkyl-aryl extension at positions 11/12 of the lactone ring . All the drugs footprint identically within the peptidyl transferase loop, giving protection against chemical modification at A2058, A2059 and G2505, and enhancing the accessibility of A2062 . However, the ketolide derivatives bind to ribosomes with widely varying affinities compared with erythromycin . This variation correlates with differences in the hairpin 35 footprints . Erythromycin enhances the modification at position A752 . Removal of cladinose lowers drug binding 70-fold, with concomitant loss of the A752 footprint . However, the 11/12 extension strengthens binding 10-fold, and position A752 becomes protected . These findings indicate how drug derivatization can improve the inhibition of bacteria that have macrolide resistance conferred by changes in the peptidyl transferase loop. Bioorg Med Chem Lett, 1999 Jan 18, 9(2), 213 - 6 RNA-aminoglycoside antibiotic interactions: fluorescence detection of binding and conformational change; Llano-Sotelo B et al.; A hammerhead ribozyme has been labeled with a fluorescein reporter dye which enables the nucleic acid to detect binding of small organic compounds such as neomycin . The fluorescent changes are associated with conformational changes in the RNA and can be used to determine the binding modes of the drugs. Fam Med, 1999 Feb, 31(2), 101 - 6 Effects of viral respiratory disease education and surveillance on antibiotic prescribing; Temte JL et al.; BACKGROUND AND OBJECTIVES: We describe a partnership between family practice residency clinics and a state public health virology laboratory that has produced comprehensive viral respiratory disease education and surveillance . Family practice residents have been provided with education on respiratory viruses and the results of ongoing viral surveillance . The preliminary effects of this program on antibiotic prescribing by senior residents are evaluated in this paper . METHODS: We used a questionnaire to assess the acceptance by family practice residents of the educational component and the utility of ongoing viral surveillance . We used chart review to evaluate rates of antibiotic prescribing and the number of patients diagnosed per year with acute upper respiratory infection and acute bronchitis by senior residents in 1992 (preexposure) and 1996 (postexposure) . RESULTS: By the third year of training, most residents (79%) reported receiving adequate training regarding common viral respiratory diseases . Moreover, residents reported that they were less likely to prescribe antibiotics to patients presenting with respiratory infections when provided with specific information on circulating viral pathogens . Antibiotic prescribing in the postexposure group was 68% lower for upper respiratory infection (URI) and 45% lower for a composite of URI and bronchitis . CONCLUSIONS: Education and monitoring of circulating respiratory viruses can result in familiarity with common disorders in primary care and reduce unnecessary antibiotic use. JAMA, 1999 Feb 3, 281(5), 427 - 31 Antibiotics and risk of subsequent first-time acute myocardial infarction; Meier CR et al.; CONTEXT: Increasing evidence supports the hypothesis of a causal association between certain bacterial infections and increased risk of developing acute myocardial infarction . If such a causal association exists, subjects who used antibiotics active against the bacteria, regardless of indication, might be at lower risk of developing acute myocardial infarction than nonusers . OBJECTIVE: To determine whether previous use of antibiotics decreases the risk of developing a first-time acute myocardial infarction . DESIGN: Population-based case-control analysis . SETTING: The United Kingdom-based General Practice Research Database comprising 350 general practices . PATIENTS: A total of 3315 case patients aged 75 years or younger with a diagnosis of first-time acute myocardial infarction between 1992 and 1997 and 13139 controls without myocardial infarction matched to cases for age, sex, general practice attended, and calendar time . MAIN OUTCOME MEASURES: Use of antibiotics among those who did or did not have a first-time acute myocardial infarction . RESULTS: Cases were significantly less likely to have used tetracycline antibiotics (adjusted odds ratio {OR}, 0.70; 95% confidence interval {CI}, 0.55-0.90) or quinolones (adjusted OR, 0.45; 95% CI, 0.21-0.95) . No effect was found for previous use of macrolides (primarily erythromycin), sulfonamides, penicillins, or cephalosporins . CONCLUSIONS: The findings from this large case-control analysis provide further, albeit indirect, evidence for an association between bacterial infections with organisms susceptible to tetracycline or quinolone antibiotics and the risk of acute myocardial infarction . These results of preliminary nature should stimulate more research to further explore the role of infections in the etiology of acute myocardial infarction. J Pharm Sci, 1999 Feb, 88(2), 277 - 80 Dose-dependent plasma clearance of MK-826, a carbapenem antibiotic, arising from concentration-dependent plasma protein binding in rats and monkeys; Wong BK et al.; After intravenous administration of MK-826, a new carbapenem antibiotic, the compound exhibited nonlinear pharmacokinetics in rats and monkeys . In both species, time-averaged plasma clearance (based on total concentrations) increased about 5-fold over the 10- to 180-mg/kg dose range . MK-826 was extensively plasma protein bound in rat and monkey plasma, and the extent of binding was concentration dependent at plasma concentrations achieved after administration of these doses . Rosenthal analysis of the plasma protein binding indicated that there were two classes of binding sites . The binding capacity of the primary site was comparable to the plasma albumin concentration, which suggested that this primary site consisted of a single site on albumin . The extent of binding of MK-826 to rat albumin was similar to that in whole plasma . Clearance values based on unbound concentrations appeared independent of dose from 10 to 180 mg/kg, which is consistent with saturation of protein binding as the primary cause of the nonlinear pharmacokinetic behavior. Pharm Res, 1999 Jan, 16(1), 55 - 61 Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux; Bretschneider B et al.; PURPOSE: This study on the intestinal transport of beta-lactam antibiotics was undertaken to investigate the correlation between cellular transport parameters and the bioavailability . METHODS: Transport of 23 beta-lactam antibiotics was characterized by measuring their ability to inhibit the uptake of glycylsarcosine into Caco-2 cells, their uptake into the cells and their total flux across the cell monolayers . RESULTS: Ceftibuten and cyclacillin were recognized by PEPT1 with affinity constants comparable to those of natural dipeptides (K(i) = 0.3 and 0.5 mM, respectively) . Cefadroxil, cefamandole, cephradine, cefaclor, cefuroxime-axetil, cefixime, cephalotin, cephalexin and ampicillin also interacted with PEPTI (K(i) = 7-14 mM) . In contrast, cefapirin, cefodizime, cefuroxime, cefmetazole, ceftazidime, benzyl-penicillin, ceftriaxone, cefpirome, cefotaxime, cefepime, cephaloridine and cefsulodin displayed no affinity to the transport system (K(i) > 20 mM) . The uptake into the cells and the transepithelial flux was highest for those beta-lactam antibiotics, which showed the strongest inhibition of {14C}Gly-Sar transport (p < 0.0001) . Exceptions were cefuroximaxetil and cephalotin . CONCLUSIONS: The probability of oral bioavailability for beta-lactam antibiotics is mainly determined by their affinity to PEPTI . A threshold K(i) value of 14 mM with respect to Gly-Sar uptake is required. J Fam Pract, 1999 Jan, 48(1), 43 - 6 Treatment of recurrent otitis media after a previous treatment failure . Which antibiotics work best? Hueston WJ, Ornstein S, Jenkins RG, Pan Q, Wulfman JS. BACKGROUND: Recurrent infection after an episode of otitis media is common in pediatric patients . If a patient experienced primary treatment failure in a preceding episode, physicians often feel pressured to prescribe a broad-spectrum, second-line agent for the next episode rather than a first-line drug . The purpose of our study was to determine whether using a second-line drug resulted in fewer treatment failures in a recurrent otitis episode following an episode of apparent resistance . METHODS: The Practice Partner Research Network database, a national research network of practices that use the same electronic medical record, was reviewed to identify all primary episodes of otitis media over a 2-year period (N = 7807) . From this, 1416 pediatric patients with presumed treatment failures were identified . The subset of those with a second otitis media episode more than 90 days after the index episode (N = 343) was selected for study . Of this group, 236 (69%) received first-line antibiotics (amoxicillin, ampicillin, penicillin, or sulfamethoxazole-trimethoprim) and the remaining 107 received a broader-spectrum, second-line antibiotic . The primary outcome was the need for an additional antibiotic for otitis media within the next 45 days . RESULTS: Patients receiving first- and second-line antibiotics did not differ in sex or age . However, those receiving second-line antibiotics had a shorter duration between episodes (231 vs 280 days, P = .007) . Failure rates for first- and second-line antibiotics in recurrent episodes were not significantly different (13% vs 19%, P = .20) . Because the duration between episodes could have affected failure rates, we stratified the time between episodes into short, intermediate, and long duration . Second-line antibiotics were not superior to first-line drugs in any stratum . CONCLUSIONS: For a new otitis media episode in a patient with a previous treatment failure, first-line drugs (amoxicillin, ampicillin, penicillin, or sulfamethoxazole-trimethoprim) are just as effective as broader-spectrum, more expensive, second-line antibiotics. J Trauma, 1999 Jan, 46(1), 97 - 103 Management of femoral diaphyseal infected nonunion with antibiotic beads local therapy, external skeletal fixation, and staged bone grafting; Ueng SW et al.; BACKGROUND: Fifteen patients with femoral shaft fractures complicated by infected nonunions were treated with a two-stage protocol . METHODS: In the first stage, radical debridement was performed along with antibiotic bead chains local therapy and external skeletal fixation . In the second stage, the debrided nonunion site was repaired with bone grafting and the external skeletal fixator was used until bony union was achieved . The time between the first and second stages of treatment was 2 to 6 weeks . The debrided bone defects ranged from 0.5 to 15 cm . Autogenous iliac cancellous bone grafting was performed in 11 patients, and microvascularized osteoseptocutaneous fibular transfer was performed in 4 patients . RESULTS: Wound healing and bone union were achieved in all 15 cases . The duration of external fixation of these patients ranged from 7 to 15 months, with an average of 9 months . Minor pin-track infection was seen in seven patients . Postoperative infection after the second-stage bone grafting occurred in three patients . These three infections were arrested by limited debridement along with 2 to 4 weeks of parenteral antibiotic therapy . In one case, stress fracture occurred at 11 months after microvascularized fibular transfer; this was managed with another 5 months of external skeletal fixation . With an aggressive physical therapy program, 10 patients achieved nearly full range of knee motion and 5 patients had relevant knee flexion deficits . The follow-up averaged 58 months (range, 40-76 months); no recurrence of osteomyelitis was observed even at 76 months . CONCLUSION: We have found that our two-stage treatment with antibiotic beads local therapy, definitive external skeletal fixation, and staged bone grafting is an acceptable treatment protocol for the management of femoral diaphyseal infected nonunion . It results in rapid recovery from osteomyelitis and a predictable recovery from nonunion. Langenbecks Arch Chir Suppl Kongressbd, 1998, 115, 854 - 60 {Prospective study of spontaneous medical utilization of antibiotics on the normal surgical ward--rationale and economic aspects}; Schmidt-Matthiesen A et al.; For 8 months, the spontaneous behaviour of the surgeons concerning the use of antibiotics (AB) was studied . The study focused on the indication itself, the chosen substance, the method of drug administration, and the treatment duration . It was evaluated whether the use of AB was rational and what the economic consequences of inadequate use of AB are . Of a total of 1168 pts 21.1% received AB, 88% of them i.v . The intention of AB treatment was therapy in 56.3%, and prophylaxis in 43.7% beside the regular perioperative single shot regimen . More than every second AB prescription was irrational . More rational behaviour (indication, therapy once daily, sequential therapy, no postoperative prophylaxis, less i.v . AB) by the prescribing surgeons would have led to a saving of more than 60% of the total costs of DM 215,000 without any loss of antiinfective efficacy . Moreover, a more rational use of AB would mean prevention of infectious hospitalism and would save a lot of staff time. J Mol Biol, 1999 Feb 12, 286(1), 33 - 43 Effect of mutations in the A site of 16 S rRNA on aminoglycoside antibiotic-ribosome interaction; Recht MI et al.; Decoding of genetic information occurs upon interaction of an mRNA codon-tRNA anticodon complex with the small subunit of the ribosome . The ribosomal decoding region is associated with highly conserved sequences near the 3' end of 16 S rRNA . The decoding process is perturbed by the aminoglycoside antibiotics, which also interact with this region of rRNA . Mutations of certain nucleotides in rRNA reduce aminoglycoside binding affinity, as previously demonstrated using a model RNA oligonucleotide system . Here, predictions from the oligonucleotide system were tested in the ribosome by mutation of universally conserved nucleotides at 1406 to 1408 and 1494 to 1495 in the decoding region of plasmid-encoded bacterial 16 S rRNA . Phenotypic changes range from the benign effect of U1406-->A or A1408-->G substitutions, to the highly deleterious 1406G and 1495 mutations that assemble into 30 S subunits but are defective in forming functional ribosomes . Changes in the local conformation of the decoding region caused by these mutations were identified by chemical probing of isolated 30 S subunits . Ribosomes containing 16 S rRNA with mutations at positions 1408, 1407+1494, or 1495 had reduced affinity for the aminoglycoside paromomycin, whereas no discernible reduction in affinity was observed with 1406 mutant ribosomes . These data are consistent with prior NMR structural determination of aminoglycoside interaction with the decoding region, and further our understanding of how aminoglycoside resistance can be conferred . Ann Thorac Surg, 1998 Dec, 66(6 Suppl), S221 - 4 Effect of antibiotic pretreatment on immunogenicity of human heart valves and component cells; Johnson DL et al.; BACKGROUND: For many years valves have been sterilized with high-dose antibiotics before implantation, but now there is an increasing trend to using "homovital" valves, which have been exposed to very low dose antibiotics . METHODS: To investigate the immunogenicity of valve tissue, before and after exposure to high- and low-dose antibiotics, peripheral blood mononuclear cells and human allogenic T cells were cocultured with antibiotic-treated valve discs, cultured valve endothelial cells, and fibroblasts . Proliferation was measured by uptake of thymidine labeled with hydrogen 3 . RESULTS: Untreated tissue pieces stimulate peripheral blood mononuclear cells (4,080+/-980 cpm) at day 0 with similar results after 1 day in Hank's balanced salt solution (4,272.4+/-1,307 cpm) reducing to 2,442+/-926 cpm after 3 days and 1,111+/-255 cpm after 5 days; antibiotic-treated pieces are less immunogenic after 1 (2,560+/-403 cpm), 3 (1,550+/-60 cpm), 5 (717+/-295 cpm), and 7 days (633+/-174 cpm) in homovital solution, whereas sterilized pieces are not immunogenic (184+/-96 cpm) after only 1 day in strong antibiotics . Histologic analysis showed that this corresponds to a reduction of class I and class II expression by human valve endothelial cells . Human valve endothelial cells but not fibroblasts are capable of causing direct stimulation of CD4+ T cells . However, human valve endothelial cells poorly stimulate CD4+ T cells after incubation in homovital solution for 24 hours . CONCLUSIONS: This study shows that valve tissue is immunogenic and this immunogenicity is mediated mainly by endothelial cells . However, the immunostimulatory potential of the valve can be reduced by incubating the solution in an antibiotic cocktail. FEBS Lett, 1999 Jan 15, 442(2-3), 215 - 20 1H NMR spectroscopy of the binuclear Cu(II) active site of Streptomyces antibioticus tyrosinase; Bubacco L et al.; The 600 MHz 1H NMR spectrum of tyrosinase (31 kDa) of Streptomyces antibioticus in the oxidized, chloride-bound form is reported . The downfield part of the spectrum (15-55 ppm) exhibits a large number of paramagnetically shifted signals . The paramagnetism is ascribed to a thermally populated triplet state . The signals derive from six histidines binding to the metals through their Nepsilon atoms . There is no evidence for endogenous bridges . The exchange coupling, -2J, amounts to 298 cm(-1) . In the absence of chloride the peaks broaden . This is ascribed to a slowing down of the electronic relaxation . The exchange coupling decreases to -2J=103 cm(-1). J Paediatr Child Health, 1998 Dec, 34(6), 498 - 9 Antibiotics for sore throats? Del Mar CB, Glasziou PP. Although not explicit, recommendations in the new edition of Therapeutic Guidelines: Antibiotic have taken a lurch towards an evidence basis . What does this mean, and what is the basis of the recommendation that antibiotics be used for sore throat in very limited circumstances? Mol Pharmacol, 1999 Feb, 55(2), 377 - 85 Enhanced binding to DNA and topoisomerase I inhibition by an analog of the antitumor antibiotic rebeccamycin containing an amino sugar residue; Bailly C et al.; Many antitumor agents contain a carbohydrate side chain appended to a DNA-intercalating chromophore . This is the case with anthracyclines such as daunomycin and also with indolocarbazoles including the antibiotic rebeccamycin and its tumor active analog, NB506 . In each case, the glycoside residue plays a significant role in the interaction of the drug with the DNA double helix . In this study we show that the DNA-binding affinity and sequence selectivity of a rebeccamycin derivative can be enhanced by replacing the glucose residue with a 2'-aminoglucose moiety . The drug-DNA interactions were studied by thermal denaturation, fluorescence, and footprinting experiments . The thermodynamic parameters indicate that the newly introduced amino group on the glycoside residue significantly enhanced binding to DNA by increasing the contribution of the polyelectrolyte effect to the binding free energy, but does not appear to participate in any specific molecular contacts . The energetic contribution of the amino group of the rebeccamycin analog was found to be weaker than that of the sugar amino group of daunomycin, possibly because the indolocarbazole derivative is only partially charged at neutral pH . Topoisomerase I-mediated DNA cleavage studies reveal that the OH-->NH2 substitution does not affect the capacity of the drug to stabilize enzyme-DNA covalent complexes . Cytotoxicity studies with P388 leukemia cells sensitive or resistant to camptothecin suggest that topoisomerase I represents a privileged intracellular target for the studied compounds . The role of the sugar amino group is discussed . The study provides useful guidelines for the development of a new generation of indolocarbazole-based antitumor agents. J Pept Sci, 1998 Dec, 4(8), 502 - 10 The crystal state conformation of Aib-rich segments of peptaibol antibiotics; Aubry A et al.; Ac-(Aib-Ala)3-OH (a protected segment of the peptaibols gliodeliquescin and paracelsin), Z-Leu-Aib-Val-Aib-Gly-OtBu (a segment of {Leu}7-gliodeliquescin), Z-Val-Aib-Aib-Gln-OtBu (a common segment of alamethicin, paracelsin, and hypelcin), and Ac-Aib-Pro-(Aib-Ala)2-OMe and Z-Aib-Pro-(Aib-Ala)2-OMe, which represent differently N(alpha)-protected 1-6 segments of alamethicin and hypelcin, have been synthesized by solution methods . The crystal-state conformations of these five Aib-containing peptides have been determined by X-ray diffraction analysis . We have confirmed that the 3(10)-helical structure is preferentially adopted by Aib-rich short peptides . An experimentally unambiguous proof for the 3(10)-->alpha-helix conversion has been provided by the two differently N-blocked -Aib-Pro-(Aib-Ala)2-OMe hexapeptides . The beta-bend ribbon conformation, commonly observed in the (Aib-Pro)n sequential oligopeptides, is not found in the -Aib-Pro-Aib-Ala-Aib-Ala-sequence . As expected on the basis of the L-configuration of the C(alpha)-monoalkylated residues, a right-handed helix screw sense was found in all peptides investigated. J Med Chem, 1999 Jan 28, 42(2), 260 - 6 Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin; Roe SM et al.; The cellular activity of several regulatory and signal transduction proteins, which depend on the Hsp90 molecular chaperone for folding, is markedly decreased by geldanamycin and by radicicol (monorden) . We now show that these unrelated compounds both bind to the N-terminal ATP/ADP-binding domain of Hsp90, with radicicol displaying nanomolar affinity, and both inhibit the inherent ATPase activity of Hsp90 which is essential for its function in vivo . Crystal structure determinations of Hsp90 N-terminal domain complexes with geldanamycin and radicicol identify key aspects of their nucleotide mimicry and suggest a rational basis for the design of novel antichaperone drugs. Antimicrob Agents Chemother, 1999 Feb, 43(2), 218 - 25 Exposure to antibiotics induces expression of the Mycobacterium tuberculosis sigF gene: implications for chemotherapy against mycobacterial persistors; Michele TM et al.; The sigF gene encodes an alternate sigma factor found in Mycobacterium tuberculosis and related pathogenic mycobacteria . Determination of conditions of sigF expression is an important step in understanding the conditional gene regulation which may govern such processes as virulence and dormancy in mycobacteria . We constructed an in-frame translational lacZ-kan fusion within the sigF gene to determine the conditions of sigF expression . This reporter construct was expressed from a multicopy plasmid in a strain of BCG harboring an integrated luciferase reporter gene under the control of the mycobacteriophage L5 gp71 promoter . Antibiotic exposure, in particular, ethambutol, rifampin, streptomycin, and cycloserine treatment, increased the level of SigF reporter specific expression in a dose-dependent fashion . The level of SigF reporter specific expression increased over 100-fold in late-stationary-phase growth compared to that in exponential growth . During the exponential phase, SigF specific expression could be induced by a number of other stresses . Anaerobic metabolism induced SigF by greater than 150-fold, particularly in the presence of metronidazole . Cold shock increased the level of SigF specific expression, while heat shock decreased it . Oxidative stress was also an important inducer of SigF specific expression; a greater induction was seen with cumene hydroperoxide than with hydrogen peroxide . Comparisons of bacterial viability as determined by the luciferase assay or by plating serial dilutions revealed that luciferase gp71-dependent activity was an unreliable predictor of the numbers of CFU during stationary-phase growth and anaerobic metabolism . The induction of sigF following antibiotic exposure suggests that this bacterial transcription factor may control genes which are important for mycobacterial persistence in the host during chemotherapy. J Vet Diagn Invest, 1999 Jan, 11(1), 79 - 86 Toxicosis in cattle from concurrent feeding of monensin and dried distiller's grains contaminated with macrolide antibiotics; Basaraba RJ et al.; Consumption of monensin-containing feed contaminated with macrolide antibiotic residues resulted in the death of cattle from multiple feedlots in south-central Kansas . Cattle were fed milo dried distiller's grains (DDG) with solubles from a common source in conjunction with the ionophore antibiotic, monensin . Deaths occurred as early as 72-96 hours after feeding and were preceded by either no premonitory signs or 1 or more of the following: anorexia, depression, dyspnea, locomotor deficits, and recumbency . Significant gross lesions were pulmonary and mesenteric edema, hepatomegaly, and generalized myocardial and skeletal muscle pallor that was confirmed histologically as acute myodegeneration and necrosis . Other significant histologic lesions included centrolobular hepatocellular necrosis, congestion, and pulmonary interstitial and alveolar edema with fibrin exudation . Animals that survived beyond 6 weeks had poor weight gain and coalescing foci of myocardial fibrosis with residual myocardial degeneration . Analysis of trace mineral supplements for monensin were within the manufacturer's label range . The DDG samples from affected feedlots had 50-1,500 ppm of erythromycin, clarithromycin, and related macrolide antibiotic analogues, which originated in the alcohol residue . In a preliminary feeding trial, cattle fed this contaminated DDG in combination with monensin had clinical signs and died with gross and histologic findings comparable to those of the field cases . Even though rations supplemented with the contaminated DDG contained approved levels of monensin, the clinical and postmortem findings were consistent with those expected for monensin toxicosis . The presence of macrolide antibiotic residues in the contaminated feed appeared to affect the biotransformation of otherwise nontoxic levels of monensin, leading to clinical ionophore toxicosis. J Am Acad Dermatol, 1999 Jan, 40(1), 69 - 72 Long-term antibiotic therapy for balanitis xerotica obliterans; Shelley WB et al.; In an open uncontrolled study of 3 patients with balanitis xerotica obliterans we have observed significant improvement after long-term systemic antibiotic therapy . Two of the patients noticed softening of the skin as well as disappearance of pruritus, tenderness, and inflammatory changes within 3 weeks of receiving oral and intramuscular penicillin . The third patient experienced the same degree of improvement after a regimen of dirithromycin, 500 mg/day . Stopping the antiobiotic for 1 month resulted in relapse, with improvement again on resumption. FEMS Microbiol Lett, 1999 Jan 1, 170(1), 221 - 7 A NusG-like transcription anti-terminator is involved in the biosynthesis of the polyketide antibiotic TA of Myxococcus xanthus; Paitan Y et al.; The antibiotic TA of Myxococcus xanthus is synthesized through a type I polyketide synthase mechanism . Previous studies have indicated that several genes essential for TA production are clustered within a 40-kb region and are transcriptionally co-regulated . In this study, we report the genetic analysis of the first gene in the TA gene cluster, identified as a NusG-like transcription anti-terminator . Functional analysis of this NusG-like anti-terminator gene by specific gene disruption confirms that it is essential for TA production but not for normal growth and development. Enferm Infecc Microbiol Clin, 1998 Dec, 16(10), 471 - 3 {Eradication of Helicobacter pylori by triple therapy in ulcerous patients: the role of endoscopy and antibiotic sensitivity}; Garrido A et al.; BACKGROUND: A protocol was conducted to evaluate the compliance and results of Helicobacter pylori infection treatment in patients with ulcer disease . To know the metronidazole, clarithromycin and amoxicillin activities of Helicobacter pylori strains from such patients . PATIENTS AND METHODS: 35 patients with ulcer disease (27 duodenal ulcer and 8 gastric ulcer) were studied . Diagnosis of Helicobacter pylori infection was performed by urease test and culture of mucosal gastric samples from patients undergoing endoscopy . The patients received the following treatment during 7 days: omeprazole (20 mg bid), clarithromycin (500 mg bid) and amoxicillin (1 g bid), OCA x 7 . Susceptibility was determined by E-test system on Wilkins-Chalgren blood agar and read after 5 days . RESULTS: 22/24 patients who had completed the protocol design eradicated Helicobacter pylori (91.7%), 11 patients (31.4%) refused second endoscopy to verify control of eradication . After treatment 10 patients presented with pyrosis "de novo" (28%) . The overall metronidazol, claritromycin and amoxicillin resistance rate was 50%, 1.5% and 0% respectively . CONCLUSIONS: OCA x 7 treatment obtains a eradication rate higher than 90% in our patients with ulcer disease, despite smoking habit, but with a significative number of patients presenting pyrosis after treatment . We recommend a non-endoscopy method to verify eradication rate, because of its poor acceptance . 3 . Metronidazol resistance rate is high in our series but clarithromycin susceptibility is maintained. Chirality, 1999, 11(1), 75 - 81 Evaluation of the macrocyclic antibiotic LY333328 as a chiral selector when used as a mobile phase additive in narrow bore HPLC; Sharp VS et al.; The macrocyclic antibiotic LY333328 has been evaluated as a chiral selector for the enantioseparation of nine dansylated amino acids . This macrocyclic glycopeptide was used as a chiral mobile phase additive (CMPA) in conjunction with narrow bore high-performance liquid chromatography (HPLC) . The key mobile phase parameters of LY333328 concentration and buffer pH were varied, along with variations in stationary phases consisting of C8, phenyl, cyano, and silica . After observing and plotting changes in retention and resolution based on corresponding variation in these parameters, a better understanding of the behavior of this chiral selector was obtained . The pKa values of the dansyl amino acid analytes and LY333328 were measured and used to gain a better understanding of the microenvironment in which these enantioseparations occur . Optimized conditions resulted in the baseline separation of eight of nine dansyl amino acids. J Antibiot (Tokyo), 1998 Oct, 51(10), 908 - 14 A new antitumor antibiotic, BE-19412A, produced by a streptomycete; Tsukamoto M et al.; A new antitumor substance, designated BE-19412A, was isolated from the culture broth of Streptomyces sp . A19412 . The active principle was extracted from the mycelium by methanol and purified by Silica gel and Sephadex LH-20 column chromatographies . BE-19412B was prepared by methylation of BE-19412A . BE-19412A and B exhibited cytotoxic activity against murine and human tumor cell lines . BE-19412A prolonged the survival of CDF1 mice bearing i.p . implanted Ehrlich carcinoma cells. Vestn Khir Im I I Grek, 1998, 157(5), 109 - 11 {Endolymphatic antibiotic therapy in the combined treatment of acute lung abscesses}; Bisenkov LN et al.; The concentration of antibiotics in the pulmonary tissue, regional lymph collectors was studied after direct and indirect endolymphatic infusions . The effectiveness of indirect endolymphatic antibiotic therapy is shown for treatment of purulent diseases of the lungs. Am J Obstet Gynecol, 1999 Jan, 180(1 Pt 1), 14 - 7 Effect of antibiotic use on the prevalence of symptomatic vulvovaginal candidiasis; Spinillo A et al.; OBJECTIVE: The purpose of the study was to evaluate the influence of antibiotic use on the prevalence of symptomatic vulvovaginal candidiasis . STUDY DESIGN: This is a case-control study of 684 women with symptomatic vulvovaginal candidiasis who were enrolled at a vaginitis clinic and 901 control subjects who attended a cytologic screening service . RESULTS: The prevalence of antibiotic use in the month preceding the visit was 19.3% (132/684) among patients with Candida infection compared with 11.9% (107/901) among control subjects (P <.001) . After adjustment by logistic regression for potential confounders (age, marital status, and contraceptive method used), the odds ratio for vulvovaginal candidiasis among patients who reported antibiotic use in the month preceding the visit was 1 . 75 (95% confidence interval 1.33 to 2.32) . No differences in risk were found by type of antibiotic used . The likelihood of vulvovaginal candidiasis was directly related to the duration of antibiotic use and was higher in patients who had a history of repeated episodes of Candida vaginal infection . CONCLUSIONS: Antibiotic use is a short-term risk factor for symptomatic vulvovaginal candidiasis, either as a first episode or in the form of recurrence . Increasing duration of antibiotic use is directly related with an increased prevalence of Candida vaginal infection. Dig Dis, 1998 Sep-Oct, 16(5), 292 - 307 Epidemiology, risk factors and treatments for antibiotic-associated diarrhea; McFarland LV; Antibiotic-associated diarrhea (AAD) is a common complication of antibiotics and recent findings on the epidemiology, etiologies and treatment strategies are reviewed . Rates of AAD vary from 5 to 39% depending upon the specific type of antibiotic . The severity of AAD may include uncomplicated diarrhea, colitis or pseudomembranous colitis . The pathogenesis of AAD may be mediated through the disruption of the normal flora and overgrowth of pathogens or through metabolic imbalances . The impact of AAD is reflected by increased hospital stays, higher medical costs and increased rates of comorbidity . The key to decreasing these consequences is prompt diagnosis followed by effective treatment and institution of control measures. Respir Med, 1998 Aug, 92(8), 1032 - 9 Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis; Omidvari K et al.; Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v . antibiotic therapy) vs . an abbreviated (2-day i.v . antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP) . We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement . Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v . every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v . every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days) . No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups . The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs . 95%, respectively) were similar in both groups . Patients who received early oral therapy had shorter hospital stays (7.3 vs . 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs . $5002, P < 0.05) . It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy . Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome. J Infect, 1998 Nov, 37(3), 224 - 8 The use of systemic antibiotics in seven community hospitals in Northern Israel; Raz R et al.; This study evaluated and compared the usage and costs of antibiotics in seven hospitals in the North of Israel and was the first of its kind . We also attempted to determine whether the presence of an Infectious Diseases Unit or Consultant affects antibiotic usage and costs. J Chromatogr B Biomed Sci Appl, 1998 Dec 11, 720(1-2), 89 - 97 Quantitative determination of the macrolide antibiotics erythromycin, roxithromycin, azithromycin and clarithromycin in human serum by high-performance liquid chromatography using pre-column derivatization with 9-fluorenylmethyloxycarbonyl chloride and fluorescence detection; Sastre Torano J et al.; A validated, highly sensitive and precise high-performance liquid chromatographic (HPLC) method for the determination of the macrolides erythromycin, azithromycin, clarithromycin and roxithromycin in human serum is described . A diethyl ether extract, obtained from serum using a saturated sodium carbonate solution, was treated with 9-fluorenylmethyl-oxycarbonyl chloride (FMOC-Cl) for 40 min at 40 degrees C and chromatographed on a base-deactivated octadecyl column, maintained at 50 degrees C during elution, using an eluent composed of acetonitrile-hydrogenphosphate buffer, pH 7.5, with 0.125% triethylamine (3:2, v/v) . Fluorescence detection was used at an excitation wavelength of 255 nm and an emission wavelength of 315 nm . Erythromycin, clarithromycin, roxithromycin and azithromycin were found to have retention times of 8.8, 15.7, 17.1 and 20.7 min, respectively . Recoveries ranging from 93 to 104% were found with reproducibility coefficients of variation of 1.1-5% . Mean correlation coefficients of 0.9997, 0.9998, 0.9996 and 0.9994 were found for the linear calibration curves (n = 2) of erythromycin (0.320-16.1 mg/l), roxithromycin (3.24-19.4 mg/l), clarithromycin (0.190-19.4 mg/l) and azithromycin (0.0988-4.94 mg/l), respectively. Biochemistry, 1999 Jan 5, 38(1), 199 - 206 Aminoglycoside antibiotics are able to specifically bind the 5'-untranslated region of thymidylate synthase messenger RNA; Tok JB et al.; The translational initiation codon for thymidylate synthase (TS) mRNA is located in a unique stem-loop structure which contains an internal cytosine-cytosine (CC) bubble . This stem-loop structure is thought to be important in the regulation of TS translation, which is itself an important target for anticancer drugs, such as 5-fluorouracil . Internal bubble or bulge structures are candidate receptors for the aminoglycoside antibiotics . It is shown here that aminoglycosides bind in a specific and saturable fashion with dissociation constants of approximately 1 microM to a TS mRNA site 1 construct and that the binding site for the aminoglycosides is located in the CC bubble region . In fact, the CC bubble, when grafted into other stem-loop structures, confers aminoglycoside binding on them . These studies reveal an additional binding domain for aminoglycosides and also suggest how novel anti-cancer drugs might be designed that affect TS mRNA translation rather than enzyme function. Infect Dis Clin North Am, 1998 Dec, 12(4), 1023 - 34, ix Quality assurance and outcomes in outpatient parenteral antibiotic therapy; Kunkel MJ; The quality improvement process in outpatient parenteral antibiotic therapy (OPAT) is driven by outcome measurement . Collection and analysis of outcome data will be an essential component of an OPAT program . Data collected must be measurable, consistently defined and transformed through analysis into understandable results that can be used to improve care. Infect Dis Clin North Am, 1998 Dec, 12(4), 995 - 1008 Outpatient antibiotic therapy in long-term care facilities; Petrak RM; OPAT in LTCFs is a viable clinical tool that should optimize patient care while limiting expenditures . Numerous opportunities exist to investigate avenues to improve this vehicle and articulate the standards by which this care should be delivered. Infect Dis Clin North Am, 1998 Dec, 12(4), 979 - 94 Infection control and outpatient parenteral antibiotic therapy; Wade BH et al.; Outpatient procedures have become more complex, requiring outpatient providers to offer technical procedures in the home, office, and clinic . This shift in health care has brought about the need for staff members to become proficient in a variety of technical procedures that were once done only in the hospital setting . Outpatient i.v . therapy has caused home health care agencies, physicians' offices, and clinics to seek education and training regarding i.v . therapy and to develop basic infection-control guidelines and guidelines related to the insertion and maintenance of i.v . devices . The goals of the outpatient provider are to prevent i.v.-related complications and to provide quality patient care . These can be accomplished by strict adherence to sound infection-control guidelines and routine monitoring of procedure techniques and complications of care . Outpatient providers may wish to seek expertise and guidance from hospital infection-control personnel, infectious diseases specialists, or other infection-control consultants to meet the demands of the complexity of outpatient care. Infect Dis Clin North Am, 1998 Dec, 12(4), 921 - 33, vii Outpatient parenteral antibiotic therapy in the management of community-acquired lower respiratory infections; Brown RB; Within the past several years, the decision to employ outpatient parenteral antibiotic therapy (OPAT) is driven by adequacy of insurance, availability of appropriate resources within the community, and the clinical stability of the patient . Current dogma is that virtually any diagnosed disease can be treated outside the hospital, provided the former criteria are met . The decision to utilize OPAT is complex and involves a number of decision points that relate to the patient, the disease and pathogen, the antibiotic, and the facilities available in the community . This article discusses the decision-making process to utilize OPAT or hospitalization for community-acquired lower respiratory infections. Verh K Acad Geneeskd Belg, 1998, 60(4), 287 - 94 {Bacterial resistance to antibiotics, an exemplary model of directed molecular evolution}; Ghuysen JM; The simplest conceivable event that can occur at the gene level can result in the development of efficacious resistance tot antibiotics . The bacterial world behaves as an enormous organism whose cells can exchange their genes very easily . Accordingly, opportunities for the exchange of genetic material in nature are probably unlimited . This knowledge cannot be ignored . It leads to the important conclusion that the antibiotics are societal drugs . A resistance gene which has appeared somewhere in the world can travel far and fast. Int J Immunopharmacol, 1998 Dec, 20(12), 765 - 79 Fosfomycin, an antibiotic, possessed TGF-beta-like immunoregulatory activities; Ishizaka S et al.; The regulatory effects of fosfomycin (FOM) were correlated closely with the multifunction of TGF-beta in the modulation of immune responses in vivo and in vitro . LPS-induced polyclonal IgM and IgG antibody responses were depressed at 3 days after the initial culture and subsequently enhanced at day 10 by FOM or TGF-beta . Neither FOM nor TGF-beta inhibited LPS-induced IgA antibody responses, whereas dexamethasone (DX) reduced polyclonal IgM, IgG and IgA antibody responses wholly . The suppression of antibody responses and Mv1Lu cell proliferation induced by FOM or TGF-beta was partly overcome with soluble TFG-beta receptors (sRIII) . Oral, i.v . and i.p . administration of FOM exhibited similar enhanced SRBC-specific antibody responses to that seen after oral administration of TGF-beta . The addition of FOM and latent TGF-beta inhibited the proliferation of Mv1Lu cells, but FOM did not lead to an increase in plasmin activities, which convert latent to active TGF-beta, and further the expression of TGF-beta receptors on the cell surface . In addition, FOM failed to enhance TGF-beta secretion . These findings suggest that immunomodulation of FOM results in increased sensitivity of cells to TGF-beta.
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