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 nucleoti