Eur J Pediatr Surg, 1995 Oct, 5(5), 282 - 5 Prophylactic antibiotics in uncomplicated appendicitis during childhood--a prospective randomised study; Soderquist-Elinder C et al.; 544 children operated upon for uncomplicated appendicitis were randomised into three groups . Group I received no antibiotics, patients in Group II were administered one single pre-operative dose of metronidazole (10 mg/kg) and patients in Group III received both both metronidazole (20 mg/kg) and cefuroxime (50 mg/kg) in a single preoperative dose . The rate of infectious complications in Group I was 6.3% but only 2.1 and 2.3 in Groups II and III, respectively . Among patients with a normal appendix or patients with simple appendicitis there was no difference in the rate of post-operative infections between the three different groups . However, in patients with gangrenous appendicitis the rate of postoperative infections was significantly lower in the two groups who received preoperative antibiotics (1.8% and 3.0% respectively) than in the group receiving no prophylactic antibiotics (infection rate 14%) . It is concluded that a single preoperative dose of metronidazole significantly decreases the rate of postoperative infectious complications in children with appendicitis . No further improvement could be demonstrated if cefuroxime against aerobic organisms was added. J Hand Surg {Br}, 1995 Oct, 20(5), 685 - 90 Post-operative infection following hand surgery . Guidelines for antibiotic use; Platt AJ et al.; An audit was designed to analyse the risk factors for developing post-operative wound infection following hand surgery . 249 consecutive patients were prospectively entered into the study . 236 (95%) patients were available for follow-up . Infection was diagnosed by clinical criteria . There was an infection rate of 10.7% in elective operations and 9.7% in emergency operations . There was no significant reduction in infection rate in the elective group with the use of antibiotics (P = 0.5) . In the emergency group of patients peri-operative antibiotic administration was associated with an 8.5-fold reduction in infection rate (P = 0.014) . The presence of a dirty wound was associated with a 13.4-fold increase in post-operative wound infection rate (P = 0.002) . A postal questionnaire of members of the British Society for Surgery of the Hand revealed a wide variation in antibiotic usage . Guidelines for antibiotic use in patients undergoing hand surgery are presented. Biosci Biotechnol Biochem, 1995 Oct, 59(10), 1835 - 41 A self-defense gene homologous to tetracycline effluxing gene essential for antibiotic production in Streptomyces aureofaciens; Dairi T et al.; By Northern blot analyses with DNA probes carrying 6-demethylchlortetracycline (6-DCT) biosynthetic genes from Streptomyces aureofaciens NRRL3203, a highly expressed gene (tcrC) was detected in a high titer producing mutant derived from the parental strain NRRL3203 by NTG mutagenesis . The analysis of the nucleotide sequence of the 2.8-kb BamHI fragment containing tcrC gene showed that the predicted tcrC gene product is a protein consisting of 512 amino acids . The deduced amino acid sequence had a high level identity with that of the self-defense gene (tet347) of Streptomyces rimosus, known to mediate oxytetracycline efflux . The tcrC gene-inactivated strains generated from strain NRRL3203 by gene replacement had a 90% decrease in the level of resistance to tetracycline and the antibiotic productivity when compared with the parental strain. Am J Respir Cell Mol Biol, 1995 Oct, 13(4), 449 - 54 Inhibition of acetylcholine-evoked Cl- currents by 14-membered macrolide antibiotics in isolated acinar cells of the guinea pig nasal gland; Ikeda K et al.; Recent clinical and experimental studies demonstrated that 14-membered macrolides suppressed fluid secretion from respiratory tract mucosa . The cellular mechanisms of acetylcholine (ACh)-induced electrolyte secretion in the acinar cell isolated from the guinea pig nasal gland were investigated by using a microfluorimetric imaging method and a patch-clamp whole-cell recording . The ACh-induced increase in intracellular Ca2+ concentration measured by the fura-2 method was little affected by three types of macrolides, josamycin (JM), erythromycin (EM), and roxythromycin (RXM) . The ACh-evoked ionic currents were not inhibited by a 16-membered macrolide, JM, whereas both 14-membered macrolides, EM and RXM, significantly inhibited membrane conductance, especially inward currents, in a concentration-dependent manner . The ACh-induced Cl- current isolated by the ionic substitutional experiments was remarkably inhibited by EM and RXM . The order of inhibition was RXM > EM >> JM . Thus, 14-membered macrolides showed a direct inhibition of the Cl- conductance activated by ACh. J Antibiot (Tokyo), 1995 Oct, 48(10), 1153 - 8 New anthracycline antibiotics 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin; Johdo O et al.; Two new anthracycline antibiotics, 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin, were photochemically obtained from anthracycline metabolites D788-1 (10-carboxy-13-deoxocarminomy-cin) and D788-3 (10-carboxy-11-deoxy-13-deoxocarminomycin) and were examined for their growth inhibitory activities on cultured L1210 leukemic cells . Effects of the S configuration of C-10 and a hydroxyl group at C-11 on the bioactivity are discussed in comparison with oxaunomycin and 11-deoxyoxaunomycin. J Antibiot (Tokyo), 1995 Oct, 48(10), 1134 - 7 Total synthesis of (+/-)-phosphonothrixin, a novel herbicidal antibiotic containing C-P bond; Nakamura K et al.; Phosphonothrixin (1) is a novel herbicidal agent produced by Saccharothrix sp . ST-888, with a unique structure possessing a C-P bond and an isoprene unit . The total synthesis of this antibiotic was accomplished from methyl (bromomethyl)acrylate in six steps. J Antibiot (Tokyo), 1995 Oct, 48(10), 1130 - 3 Phosphonothrixin, a novel herbicidal antibiotic produced by Saccharothrix sp . ST-888 . II . Structure determination; Kimura T et al.; Phosphonothrixin (1) is a novel herbicidal agent produced by Saccharothrix sp . ST-888 . This unique compound possessing a C-P bond and an isoprene unit was determined to be 2-hydroxy-2-hydroxymethyl-3-oxobutyl-phosphonic acid . Unusually rapid proton-deuterium (H-D) exchange of the methyl ketone unit of this antibiotic in D2O solution was observed . Phosphonothrixin can be classified as a new type of natural product herbicide having a C-P bond in the molecule. Aten Primaria, 1995 Sep 30, 16(5), 281 - 4 {Analysis of prescriptions of antibiotics for acute respiratory infections at a health center}; Formento Tirado JA et al.; OBJECTIVE . To analyse the prescription of antibiotics for acute respiratory infections (ARI) at our Health Centre . DESIGN . An observational crossover study . SETTING . Primary Health care . San Gregorio de Telde Health Centre, Gran Canaria . PATIENTS AND PARTICIPANTS . Systematic random sampling of 368 clinical cases with ARI . 196 women (53.26%) and 172 men (46.73%), with an average age of 33.26 +/- 1.97 . MEASUREMENTS AND MAIN RESULTS . Antibiotics were prescribed for 42.66% of ARI . Family doctors used them less than general ones (38.67% against 63.04%, p < 0.0001), and on the afternoon lists they were used less than in the morning (33.82% against 52.35%, p < 0.001) . In chronically ill patients they were used less than symptomatic treatment (42.16% against 57.83%, p < 0.001) . There were no significant differences found between their use and the appearance of complications (37.5% with Antibiotherapy against 62.5% without it) or successive consultations (45.16% with antibiotics against 54.83% without them) . They were used more in those aged over 60 (48.97%) and in those who attended less (51.56%) . Average cost per patient treated with Antibiotherapy was 2,508.48 +/- 258.80 pesetas against 694.28 +/- 78.67 pesetas for the patient treated symptomatically (p < 0.0005) . CONCLUSIONS . We are using Antibiotherapy inadequately in our field . We propose that quality control studies to detect and correct problems of this type should be undertaken . In our case corrective measures with a later reevaluation should be applied. J Med Chem, 1995 Sep 29, 38(20), 4106 - 14 Synthesis and antiproliferative and antiviral activity of 2'-deoxy-2'-fluoroarabinofuranosyl analogs of the nucleoside antibiotics toyocamycin and sangivamycin; Krawczyk SH et al.; The glycosylation of 3,4-dicyano-2-{(ethoxymethylene)amino}pyrrole (7) with 2-deoxy-2-fluoro-alpha-D-erythro-pentofuranosyl bromide (2) furnished an anomeric mixture of nucleosides (8a,b) . This mixture was separated, and the individual anomers were treated with methanolic ammonia to effect a concomitant deblocking and ring closure . This furnished both anomers of 2'-deoxy-2'-fluoro-ara-toyocamycin (9a,b) . The cyano moiety of 9b was converted to the carboxamide moiety to furnish 2'-deoxy-2'-fluoro-ara-sangivamycin (10) and to the thiocarboxamide moiety to furnish 2'-deoxy-2'-fluoro-ara-thiosangivamycin (11) . The target compounds 10 and 11 showed similar antiproliferative activity against L1210 cells in vitro, with IC50's of 3 and 5 microM . Antiviral evaluation revealed a somewhat different pattern of activity . All analogs, both alpha and beta anomers, were active against human cytomegalovirus (HCMV), albeit the beta anomers were most active . The beta anomers also were active against herpes simplex virus type 1 (HSV-1) and human immunodeficiency virus (HIV) . Compound 10 was most active in the series, ca . 10-fold more potent than 11; IC50's for 10 ranged from 4 to 25 nM for HCMV, HIV, and varicella zoster virus (VZV) and from 30 to 500 nM for HSV-1 . Even though compound 10 was cytotoxic, which will probably preclude its use as an antiviral drug (IC50's = 0.2-5.5 microM), the difference between cytotoxicity and activity against HCMV, HIV, and VZV was sufficient to indicate specific activity against a viral target. J Chromatogr A, 1995 Sep 8, 711(1), 201 - 15 Liquid chromatographic determination of D- and L-amino acids by derivatization with o-phthaldialdehyde and N-isobutyryl-L-cysteine . Applications with reference to the analysis of peptidic antibiotics, toxins, drugs and pharmaceutically used amino acids; Bruckner H et al.; In order to evaluate and extend the applicability of an analytical method that enables the quantitative and simultaneous high-performance liquid chromatographic determination of D- and L-amino acids (DL-AAs) by automated precolumn derivatization with o-phthaldialdehyde together with the chiral thiol N-isobutyryl-L-cysteine {J . Chromatogr., 666 (1994) 259} selected natural and synthetic bioactive peptides, as well as pharmaceutically used formulations of AA, were investigated and the amounts of D- and L-AA determined by fluorescence detection . Peptides containing cys(e)ine were oxidized with performic acid prior to hydrolysis with 6 M HCl, and those containing Trp were hydrolyzed with 4 M methanesulfonic acid (24 h at 110 degrees C in both cases) . Peptides analyzed were the peptide antibiotics bacitracin, gramicidins A and S, polymyxin B, metanicin C, the peptide toxin malformin A and the peptide drugs D-Arg-{Hyp3,Thi5,8,D-Phe7}-bradykinin, beta-casomorphin and alpha s1-exorphin . Further, the enantiomeric ratios of pharmaceutically used AA formulations containing racemic DL-Ser, DL-Asp and DL-Met were determined, and the AA drugs L-Asp and L-Trp were tested negatively for the presence of the respective D-enantiomers . In two aqueous formulations of L-AA used for parenteral nutrition, low amounts of D-AA (0.1-0.9% with respect to certain L-AA enantiomers and of totally 128 mg and 149 mg D-AAs per liter infusion solution) were determined. Antibiot Khimioter, 1995 Sep, 40(9), 38 - 41 {Experimental and clinical study of antibiotics administered intravitreally in endophthalmitis}; Shenderovich VA et al.; The concentrations of gentamicin and cefotaxime (claforan) in the humor of the anterior chamber and vitreous body of the eye were estimated in the study on the pharmacokinetics of the antibiotics in rabbits . The antibiotics were administered intravitreally in single doses . It was shown that the residence time of the antibiotics in the therapeutic concentrations in the eye cavity was 48 hours . Cefotaxime proved to be the most efficient agent in the prevention and treatment of postoperative endophthalmitis. Eur Respir J, 1995 Sep, 8(9), 1594 - 604 Inhalation of antibiotics in cystic fibrosis; Touw DJ et al.; Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis . However, its contribution to the improvement of lung function, infection and quality of life is not well-established . All articles published from 1965 until the present time concerning the inhalation of antibiotics in cystic fibrosis were collected by computerized literature search and analysed . Effective aerosol delivery is compromised by nebulizers with limited capacity to produce particles in the respirable range . Twelve studies concerning maintenance treatment were published . Four uncontrolled studies evaluating antibiotic aerosol maintenance treatment in stable patients indicated a beneficial effect in terms of reducing the number of hospital admissions . Eight placebo-controlled studies were found; six of these showed a significant improvement of lung function in the treatment group . Four studies showed a reduction of the number of hospital admissions . In some studies, there was a considerable negative effect of the nebulized placebo solution on the outcome, probably due to the improper choice of its osmolarity . Studies with antibiotic aerosols as adjunct to intravenous therapy in cystic fibrosis patients with an acute exacerbation showed no enhancement of the clinical effects of the intravenous antibiotic by the aerosol; sputum colony counts, however, were lower . Toxicity studies carried out so far have shown no renal or ototoxicity; however, long-term toxicity studies still have to be performed using higher dosages . Introduction or selection of resistant bacteria is relatively rare, but remains a matter of concern . Aerosol maintenance treatment with an appropriate antibiotic in high enough dosage can be recommended for patients with cystic fibrosis chronically infected with P . aeruginosa, and may improve lung function and reduce the number of hospital admissions due to an acute exacerbation. West Indian Med J, 1995 Sep, 44(3), 81 - 4 Pharmacoeconomics of intravenous antibiotic use in serious infection; Levett PN et al.; A pharmacoeconomic study of 15 antibiotics available in Barbados was performed . The antibiotics studied were amoxycillin/clavulanate, ampicillin, ampicillin/sulbactam, cefazolin, cefotaxime, ceftazidime, ceftriaxone, clindamycin, cloxacillin, cotrimoxazole, gentamicin, imipenem, metronidazole, piperacillin, piperacillin/tazobactam, and vancomycin . The costs of use of these compounds were calculated for a five-day course using a formula comprising eight categories: antibiotic purchase cost, maintenance of intravenous access, drug delivery cost, drug monitoring cost, dose readjustment, general monitoring cost, 'sharps' disposal cost and adverse effects . The costs of adverse effects were not included in this study due to lack of accurate data . The total cost of antibiotic use (in U.S . dollars) ranged from $42.52 to $463.73 per five-day course . Generic compounds were less expensive ($45.52 - $98.23) than brand-name compounds ($106.18 - $106.18 - $463.73) . Antibiotic purchase costs accounted for proportions of total costs ranging from 7 to 93% . Non-drug costs represented a much greater proportion of total costs of generic compounds . For most compounds the non-drug costs were related to the frequency of dosing, but for gentamicin the non-drug costs were relatively higher because of the need for monitoring of serum gentamicin levels . Efficacy and freedom from side-effects will remain the most important determinants in the choice of antibiotic therapy . However, pharmacoeconomic analyses can provide prescribers with the information required to make cost-effective choices for treatment of their patients. J Antibiot (Tokyo), 1995 Sep, 48(9), 954 - 61 Anguinomycins C and D, new antitumor antibiotics with selective cytotoxicity against transformed cells; Hayakawa Y et al.; The retinoblastoma protein (pRB) is inactivated during the development of a wide variety of human cancers . In the course of our screening for antitumor antibiotics by using pRB-inactivated cells, an actinomycete strain was found to produce two active substances, which were elucidated to be new members of the leptomycin-anguinomycin family by NMR spectral analysis and were designated anguinomycins C and D . The anguinomycins induced growth arrest against normal cells and induced cell death against transformed cells, in which pRB was inactivated by viral oncoproteins such as human papillomavirus E7, adenovirus E1A and simian virus 40 large T antigen. J Antibiot (Tokyo), 1995 Sep, 48(9), 1011 - 4 Biosynthetic study on the polyether carboxylic antibiotic, nigericin production and biohydroxylation of grisorixin by nigericin-producing Streptomyces hygroscopicus NRRL B-1865; Mouslim J et al.; With addition of methyl oleate, the increased yield of antibiotic production by nigericin-producing Streptomyces hygroscopicus NRRL B-1865 also resulted in the isolation of three additional polyether antibiotics . Two of these are abierixin and epinigericin, as new antibiotics . The third antibiotic is grisorixin . The production of both abierixin (opened ring A and 30-CH2OH) and grisorixin (ring A and 30-CH3) poses the problem of the identity of the last pathway precursor of the major metabolite, nigericin (ring A and 30-CH2OH) . Transformation experiments of abierixin by S . hygroscopicus gave negative results . Hydroxylation of grisorixin to nigericin by S . hygroscopicus represents the final step in nigericin biosynthesis. Anticancer Drug Des, 1995 Sep, 10(6), 441 - 50 Prodrugs of anthracycline antibiotics suited for tumor-specific activation; Azoulay M et al.; The two novel prodrugs 4 and 11 have been prepared from tetra-O-acetyl-D-galactopyranose and doxorubicin in three and six steps, respectively . Their low cytotoxicity, high stability in plasma and, in the case of 11, efficient hydrolysis in the presence of alpha-galactosidase, fulfill preliminary conditions for their use in combination with monoclonal antibody-enzyme conjugates. Orthop Nurs, 1995 Sep-Oct, 14(5), 69 - 70 Local application of antibiotics in orthopaedic infections; Gray MA; Local administration of high doses of antibiotics may be done with the use of antibiotic beads . The advantages of this treatment modality would seem to outweigh the disadvantages. J Thorac Cardiovasc Surg, 1995 Sep, 110(3), 680 - 7 Allograft heart valve sterilization: a six-year in-depth analysis of a twenty-five-year experience with low-dose antibiotics; Gall K et al.; At the Prince Charles Hospital, from a 25-year experience with allograft heart valves (1969 to 1994), a 6-year analysis from March 1988 to August 1994 of the contamination rates and efficiency of a short-duration, low-dose antibiotic sterilization protocol was made . This analysis covered 642 collections and 680 aortic and pulmonary valve implants . Tissue samples obtained at collection, valve trimming, postantibiotic incubation, and implant provided the raw data . At collection, valves retrieved in open mortuaries produced the highest contamination rate of 54% . Minimal exposure to antibiotics during transport and trimming reduced the contamination rate to 11% (p < 0.05) . This was similar to the contamination rate at trimming for valves collected in the "sterile" operating room from multiorgan donors (12%) . Antibiotic incubation at 37 degrees C for 6 hours reduced the contamination rate to 4% (p < 0.05) . Only valves that showed no contamination at cryopreservation were implanted . However, at implant, resected tissue from valves that had been incubated in antibiotics showed a contamination rate of 3%, presumably from the theater environment, compared with 15% (p < 0.05) for tissue from valves that had not been incubated . A residual antibiotic effect appears present at the time of implant in valves that have been incubated in antibiotics and may assist in the reduction of and resistance to infection in the immediate postoperative period . This is supported by the low incidence of endocarditis in the first 3 postoperative months . The simple and effective protocol of collection within 24 hours of death combined with low-dose antibiotic sterilization is sufficient to produce pathogen-free valves in the majority of cases (> 95%). Neurosurgery, 1995 Sep, 37(3), 418 - 21 Antibiotic penetration into cervical discs; Rhoten RL et al.; Antibiotics are frequently prophylactically administered in surgical procedures to reduce the incidence of infection . The penetration of antibiotics into lumbar discs has been studied with mixed results, but penetration into cervical discs has not been reviewed . In this study, we examined the penetration of two commonly used antibiotics, oxacillin and cefazolin, into cervical discs . Eighteen patients with a total of 30 discs removed were studied . Two groups, each consisting of four patients with five discs removed, received either 1 g of oxacillin or 1 g of cefazolin by a single, preoperative intravenous infusion . Two other groups, each consisting of five patients with 10 discs removed, received either 2 g of oxacillin or 2 g of cefazolin, also by a single, preoperative intravenous infusion . A blood specimen, from which serum antibiotic levels were determined, was obtained from each patient simultaneously with each discectomy . The time interval between the antibiotic infusion and discectomy/phlebotomy was also recorded . Antibiotic levels were detected in all discs removed but were quantifiable in only 12 . Nine of these 12 had been exposed to cefazolin . Of these nine discs, one was from a patient who had received 1 g whereas the other eight were from patients who had received 2 g of cefazolin . This represents 80% of the removed discs exposed to 2 g of cefazolin (10 discs total) and 20% exposed to 1 g (5 discs total) . The remaining three discs with quantifiable antibiotic levels had been exposed to 2 g of oxacillin, which represents 30% of the discs (10 total) exposed to that dose of oxacillin . Although cervical disc space infections are rare, they are serious.(ABSTRACT TRUNCATED AT 250 WORDS) Infect Dis Clin North Am, 1995 Sep, 9(3), 575 - 90 Antibiotic concerns in the elderly . A clinician's perspective; Gleckman RA; Unique antibiotic concerns exist for the management of infections in elderly patients . Issues concerning age-associated physiological alterations, compliance, drug-drug interactions, adverse drug reactions, and guidelines for empiric therapy are reviewed in this article. FEMS Microbiol Lett, 1995 Aug 15, 131(1), 27 - 34 Giant linear plasmids of beta-lactam antibiotic producing Streptomyces; Netolitzky DJ et al.; A survey of the total cellular DNA from five beta-lactam antibiotic-producing Streptomyces spp . by pulsed field gel electrophoresis was conducted to investigate the presence of linear plasmids . Streptomyces clavuligerus NRRL 3585 contained two giant linear plasmids of 120 and 430 kb, in addition to the well-characterized 11.7 kb linear plasmid . Streptomyces griseus NRRL 3851 contained a single giant linear plasmid of 120 kb, and Streptomyces jumonjinensis NRRL 5741 contained two giant linear plasmids (220 and 280 kb), and two smaller linear plasmids . No plasmids were identified in Streptomyces cattleya NRRL 3841 or Streptomyces lipmannii NRRL 3584 . Southern hybridization did not reveal any homology shared by these plasmids, and beta-lactam antibiotic synthesis gene clusters were located on the chromosome. J Pharm Technol, 1995 Sep-Oct, 11(5), 203 - 10 Use of benchmarking techniques to justify the evolution of antibiotic management programs in healthcare systems; Schentag JJ et al.; OBJECTIVE: To apply basic benchmarking techniques to hospital antibiotic expenditures and clinical pharmacy personnel and their duties, to identify cost savings strategies for clinical pharmacy services . DESIGN: Prospective survey of 18 hospitals ranging in size from 201 to 942 beds . Each was asked to provide antibiotic expenditures, an overview of their clinical pharmacy services, and to describe the duties of clinical pharmacists involved in antibiotic management activities . Specific information was sought on the use of pharmacokinetic dosing services, antibiotic streamlining, and oral switch in each of the hospitals . RESULTS: Most smaller hospitals (< 300 beds) did not employ clinical pharmacists with the specific duties of antibiotic management or streamlining . At these institutions, antibiotic management services consisted of formulary enforcement and aminoglycoside and/or vancomycin dosing services . The larger hospitals we surveyed employed clinical pharmacists designated as antibiotic management specialists, but their usual activities were aminoglycoside and/or vancomycin dosing services and formulary enforcement . In virtually all hospitals, the yearly expenses for antibiotics exceeded those of Millard Fillmore Hospitals by $2,000-3,000 per occupied bed . In a 500-bed hospital, this difference in expenditures would exceed $1.5 million yearly . Millard Fillmore Health System has similar types of patients, but employs clinical pharmacists to perform streamlining and/or switch functions at days 2-4, when cultures come back from the laboratory . CONCLUSIONS: The antibiotic streamlining and oral switch duties of clinical pharmacy specialists are associated with the majority of cost savings in hospital antibiotic management programs . The savings are considerable to the extent that most hospitals with 200-300 beds could readily cost-justify a full-time clinical pharmacist to perform these activities on a daily basis . Expenses of the program would be offset entirely by the reduction in the actual pharmacy expenditures on antibiotics. J Biol Chem, 1995 Aug 4, 270(31), 18234 - 9 Biosynthesis of the macrolide oleandomycin by Streptomyces antibioticus . Purification and kinetic characterization of an oleandomycin glucosyltransferase; Quiros LM et al.; The oleandomycin (OM) producer, Streptomyces antibioticus, possesses a mechanism involving two enzymes for the intracellular inactivation and extracellular reactivation of the antibiotic . Inactivation takes place by transfer of a glucose molecule from a donor (UDP-glucose) to OM, a process catalyzed by an intracellular glucosyltransferase . Glucosyltransferase activity is detectable in cell-free extracts concurrent with biosynthesis of OM . The enzyme has been purified 1,097-fold as a monomer, with a molecular mass of 57.1 kDa by a four-step procedure using three chromatographic columns . The reaction operates via a compulsory-order mechanism . This has been shown by steady-state kinetic studies using either OM or an alternative substrate (rosaramycin) and dead-end inhibitors, and isotopic exchange reactions at equilibrium . OM binds first to the enzyme, followed by UDP-glucose . A ternary complex is thus formed prior to transfer of glucose . UDP is then released, followed by the glycosylated oleandomycin (GS-OM). Antibiot Khimioter, 1995 Aug, 40(8), 7 - 11 {Reaction of acylation of the antineoplastic antibiotic bleomycetin}; Usol'tseva SV et al.; The reaction of benzoylation of bleomycetin, a glycopeptide antibiotic, and its cuprum complex was studied with the chloranhydride and carbodiimide methods . Acylation of the antibiotic cuprum complex by an equivalent quantity of benzoyl chloride resulted in formation of a mixture of mono- and disubstituted derivatives while with the use of a 3-fold excess of chloranhydride it was possible to obtain dibenzoylbleomycetin as a sole reaction product . Interaction of the bleomycetin cuprum complex with activated benzoic ether resulted in formation of a product monosubstituted by the antibiotic spermidine fragment . After acylation of the free antibiotic by the carbodiimide and chloranhydride methods tri- and tetrabenzoyl derivatives of bleomycetin were isolated respectively. J Indian Med Assoc, 1995 Aug, 93(8), 293 - 4, 290 Role of antibiotics in clean wounds; Hedawoo JB et al.; Two hundred twenty cases with clean surgical wounds were treated without administering any antibiotics . Majority of them (134) were hydroceles and hernias . The study included some major operation also . The infection rate was 3.6% in the present series, which is comparable with the study where antibiotics were used. Rheum Dis Clin North Am, 1995 Aug, 21(3), 817 - 34 Antibiotic therapy for rheumatoid arthritis . Scientific and anecdotal appraisals; Trentham DE et al.; Minocycline is arguably the most interesting new drug for rheumatoid arthritis since the development of methotrexate . Tetracycline compounds have long been used by rheumatologists who were considered mavericks by their peers, and recent controlled studies have demonstrated their antirheumatic activity . The reason that minocycline works is unclear, and their niche in the treatment of rheumatoid arthritis remains to be established . Nonetheless, it is clear that some patients with rheumatoid arthritis respond favorably to this form of treatment. Voen Med Zh, 1995 Aug, (8), 31 - 3, 80 {The efficacy of treating skin ulcers and burns with film dressings with antibiotics}; Morozov VM et al.; The article summarizes the results of studies conducted during the treatment of burns (108 patients), and ecthymas (85 patients) with the help of film dressing and antibiotic powder (R . Breitman's method) . During application of this method the healing process was more rapid, the administration of antibiotics was minimum, the dressing process became more easy, good cosmetic results were obtained . The period of inpatient care was shortened, cost of treatment was reduced. J Arthroplasty, 1995 Aug, 10(4), 470 - 5 Use of antibiotic-impregnated cement during hip and knee arthroplasty in the United States; Heck D et al.; A survey of practicing orthopaedists regarding their use of antibiotic(s) in bone-cement (ABC) was carried out . The initial sampling of 2,139 orthopaedists spanned the continental United States . Responses that passed fail-edit criteria were obtained from 1,015 physicians . Clinical practice patterns are highly variable . Adult reconstructive orthopaedic practitioners' belief in antibiotic(s) in bone-cement for the treatment of patients with previous sepsis is favorable . This opinion can be supported at the guideline level . Guidelines suggesting that liquid antibiotics should not be used as additions to polymethyl methacrylate are also supportable . The need for careful scientific inquiry and cost-effectiveness evaluation of the benefits and risks relating to the use of antibiotic additions to polymethyl methacrylate cement in joint arthroplasty exists . On the basis of such inquiry, educational dissemination to reduce practice variation would be indicated. J Arthroplasty, 1995 Aug, 10(4), 453 - 9 Effect of varying surface patterns on antibiotic elution from antibiotic-loaded bone cement; Masri BA et al.; In an effort to improve the antibiotic elution characteristics of the prosthesis of antibiotic-loaded acrylic cement, an in vitro study was conducted . Tobramycin-loaded bone cement blocks of three different surface patterns with different surface area-to-volume ratios were used . The elution of tobramycin over a 2-month period was investigated . There was a gradual decline in the tobramycin elution rate over time . The surface pattern with the increased surface area-to-volume ratio showed a significant increase in the tobramycin elution rate over the first week of the study . The surface pattern with ridges but no change in the surface area-to-volume ratio did not result in a statistically significant increase in the tobramycin elution rate. Cancer Lett, 1995 Aug 1, 94(2), 171 - 7 Effects of an antibiotic protease inhibitor, actinonin on the growth within collagen gels of non-metastatic and metastatic mouse mammary tumors of the same origin; Sayama K et al.; Of five autonomous sublines established independently from the transplantable hormone-dependent mouse mammary tumor, TPDMT-4, three but not two acquired metastatic potential . In in vitro culture using collagen gels, actinonin, an antibiotic protease inhibitor exerted a stronger growth-inhibiting effect on the metastatic than on the parent and non-metastatic tumors . Zymographic analysis demonstrated the active forms of gelatinases in the metastatic but not in the non-metastatic sublines and the complete inhibition of the enzyme activities by actinonin . Gelatinases/type IV collagenases might play an important role in tumor progression towards metastatic phenotype and actinonin may suppress tumor growth through inhibiting collagenase. J Antibiot (Tokyo), 1995 Aug, 48(8), 850 - 62 Structural elucidation of aculeximycin . IV . Absolute structure of aculeximycin, belonging to a new class of macrolide antibiotics; Murata H et al.; Aculeximycin (1) produced by Streptosporangium albidum possesses a 30-membered polyhydroxy macrocyclic lactone and five sugars including aculexitriose . We have described the determination of the planar structure of N-diacetylated aculeximycin (2) using degradation products, which were obtained by DBU-methanol treatment, ozonolysis and periodative oxidation . In order to determine the relative and absolute configurations of aculeximycin, first, the relative and absolute configurations of the degradation products 10, 11, 12 and 13 were determined . Rychnovsky's method was very useful to determine the relative configurations of these degradation products, and CD exciton chirality and the modified Mosher's methods were applied to determine their absolute configurations . From these results, fourteen out of the twenty asymmetric centers in aculeximycin were determined to be 5S, 17R, 20S, 21R, 23R, 24R, 29S, 30R, 31S, 34R, 35S, 36S and 37R . The absolute configurations at C-14 and C-15 on the hemiketal ring were confirmed using 12 obtained by the partial glycol bond cleavage of 9 . Absolute configurations of the remaining asymmetric centers were determined by spectral analysis of 15 and NOE experiment on 1 . From these results, the absolute configuration of 1 was determined to be 5S, 7R, 10S, 11R, 14R, 15S, 17R, 19R, 20S, 21R, 23R, 24R, 25S, 29S, 30R, 31S, 34R, 35S, 36S and 37R. J Antibiot (Tokyo), 1995 Aug, 48(8), 838 - 49 Structural elucidation of aculeximycin . III . Planar structure of aculeximycin, belonging to a new class of macrolide antibiotics; Murata H et al.; The planar structure of aculeximycin (1) produced by Streptosporangium albidum has been determined by spectral methods and chemical degradations such as 1,8-diazabicyclo{5,4,0}undec-7-ene (DBU)-methanol reaction, ozonolysis, and periodative oxidation . The antibiotic consists of a 30-membered polyhydroxy lactone ring, an alpha, beta-unsaturated ester group, an intramolecular hemiketal, an oligosaccharide (aculexitriose), a neutral sugar and an amino sugar . The structure of aculeximycin is closely related to those of sporaviridins produced by Streptosporangium viridogriseum . We consider that aculeximycin and sporaviridins belong to a new class of macrolide antibiotics, which is different from the polyol macrolides produced by Streptomyces. J Antibiot (Tokyo), 1995 Aug, 48(8), 824 - 30 Induction of differentiation of HL-60 cells by the anti-fungal antibiotic, radicicol; Shimada Y et al.; The anti-fungal antibiotic, radicicol, produced in the culture broth of Neocosmospora tenuicristata, was found to induce differentiation of HL-60 cells into macrophages from the following evidence: (1) it caused morphological changes into macrophage-like cells, (2) induced NBT (Nitrobluetetrazolium) reduction activity, (3) induced phagocytosis, and (4) induced alpha-naphthyl acetate esterase activity . The concentration of radicicol required to differentiate HL-60 cells is 50-100 ng/ml, and the incubation time required for commitment of differentiation is 16 hours . Flow cytometry analysis indicated that radicicol blocks the cell cycle of HL-60 cells at the G1 and G2 sites . In addition, radicicol induced reversal of the transformed phenotype of ras-transformed NIH3T3 cells (DT cells) at 25 ng/ml. J Antibiot (Tokyo), 1995 Aug, 48(8), 811 - 4 Resistance to the polyether ionophore antibiotic pandavir (nigericin) in two producing strains of Streptomyces; Moncheva PA et al.; In two pandavir (nigericin) producing strains, Streptomyces hygroscopicus 155 and Streptomyces albogriseolus 444, an enzyme activity was detected leading to inactivation of the antibiotic in the presence of ATP-Na2 . Apparently, the observed inactivation is specific for the antibiotic produced by these strains . The nigericin producing strains were also found to be less permeable to pandavir than their non-producing variants. J Clin Anesth, 1995 Aug, 7(5), 425 - 39 Antibiotic therapy and the anesthesiologist; Cheng EY et al.; The anesthesiologist is frequently responsible for administering antibiotics in the immediate preoperative and intraoperative periods . Anesthesiologists often are not trained in the administration of antibiotics, which can be associated with both acute and long-term complications including potentiation of neuromuscular blocking agents, allergic reactions, and end-organ toxicity . The indications for perioperative antibiotics, proper method of administration, and occurrence and treatment of major side effects of the more commonly recommended prophylactic antibiotics are discussed. J R Soc Health, 1995 Aug, 115(4), 231 - 4 Compliance with short-term antibiotic therapy among patients attending primary health centres in Riyadh, Saudi Arabia; al-Shammari SA et al.; Non-compliance results in several undesired consequences . Admissions due to non-compliance have been estimated to account for up to 10.5% of all admissions to hospital . There seems to be very little data about compliance in Saudi Arabia . The present study addressed the problem of non-compliance with short-term antibiotic therapy in patients attending Primary Health Centres (PHC) . The data were collected from five different centres selected randomly from the 53 centres in the Riyadh area, Saudi Arabia . A five-part questionnaire was designed and used to collect data . Different parts were required to be completed by patient, doctor, pharmacist and social worker . At the end of the study period 414 questionnaires were suitable for evaluation . Paediatric patients (< 15 years old) constituted 65.9% of the sample . Compliance was noted in 67.8% . Those who missed three doses or less and more than three doses were 22.7% and 9.4% respectively . Factors which appeared to enhance patient compliance were: parental involvement (p < 0.001), unemployment (p < 0.01), absence of psychiatric illness (p < 0.02) and early improvement of symptoms (p < 0.05) . Reasons most frequently mentioned by patients for non-compliance were: rapid improvement of symptoms, bitter taste of drug(s), forgetfulness and frequent dosing . These reasons accounted for 73.7% of reasons for non-compliance . Our findings suggest that approximately two thirds of patients were compliant with their medications . It is also worth noting that approximately three quarters of patients were not compliant for reasons which could be minimised or removed by good patient counselling and effective communication with patients.(ABSTRACT TRUNCATED AT 250 WORDS) Microbiology, 1995 Aug, 141 ( Pt 8), 1793 - 803 A new Myxococcus xanthus gene cluster for the biosynthesis of the antibiotic saframycin Mx1 encoding a peptide synthetase; Pospiech A et al.; The gene cluster for the biosynthesis of the heterocyclic quinone antibiotic saframycin Mx1 of Myxococcus xanthus DM504/15 was inactivated and tagged by Tn5 insertions . The tagged genes were cloned in Escherichia coli and used to select overlapping cosmid clones spanning 58 kb of the M . xanthus genome . Gene disruption experiments defined a > or = 18 kb contiguous DNA region involved in saframycin biosynthesis . Sequencing of part of this region revealed a large ORF containing two 600-amino-acid domains with similarity to peptide synthetase amino-acid-activating sequences, suggesting that saframycin Mx1 is synthesized by a nonribosomal multienzyme complex, similar to other bioactive peptides. Pancreas, 1995 Aug, 11(2), 132 - 40 Therapeutic regimens in acute experimental pancreatitis in rats: effects of a protease inhibitor, a beta-agonist, and antibiotics; Araida T et al.; The osmolality of contrast injected retrograde into the rat pancreatic duct did not affect the severity of the pancreatitis (Urografin, 1,300 mOsm/kg, and Hexabrix, 580 mOsm/kg) . The severity of the pancreatitis induced in rats was assessed by survival rate, histologic grading, wet lung ratio, and serum levels of amylase, lipase, and trypsin-like activity . Rats with pancreatitis induced by retrograde injected Urografin, lipopolysaccharide, taurocholic acid plus enterokinase were treated with either intravenous (i.v.) FUT-175 (Nafamstat Mesilate), FUT-175 administered by retrograde pancreatic injection, i.v . terbutaline, i.v . piperacillin sodium, piperacillin sodium by retrograde pancreatic duct injection, or a combination of FUT-175 plus terbutaline and piperacillin . Survival among the rats was increased and the incidence of pancreatic infection reduced in rats treated with i.v . piperacillin or with a combination of FUT-175 plus i.v . terbutaline, plus i.v . piperacillin compared to controls. Biochemistry, 1995 Jul 25, 34(29), 9632 - 44 Conformation of A82846B, a glycopeptide antibiotic, complexed with its cell wall fragment: an asymmetric homodimer determined using NMR spectroscopy; Prowse WG et al.; Proton NMR assignments were determined for the asymmetric dimer complex of A82846B with the pentapeptide cell-wall fragment . A total of 683 experimental constraints, both distance and dihedral, were collected from NOESY and COSY data sets . From these constraints, a total of 80 structures were calculated using standard X-PLOR protocols . These structures were subsequently refined using the full CHARMm potential and the addition of water molecules in the calculation . The CHARMm structures occupied more conformational space than did the X-PLOR structures and were utilized for the structure analysis . From the structures, a unique set of interactions for the dALA-5 carboxylate pocket was observed, having backbone amides from residues 2 and 3 hydrogen bonding one carboxylate oxygen while amide 4 and the side chain amide from Asn-3 hydrogen bond the other oxygen . Also, near the N-terminal region of the ligand, the GGLU-2's carboxylate forms a hydrogen bond with the asymmetric disaccharide dyad, which helps to define the interactions seen for this part of the ligand. Biochem Biophys Res Commun, 1995 Jul 17, 212(2), 428 - 32 A DNA-binding antitumor antibiotic binds to spectrin; Majee S et al.; Aureolic acid group of antibiotics inhibit transcription by reversible binding to DNA in presence of divalent magnesium . We for the first time report binding of the one of such antitumor antibiotic, mithramycin (MTR), to the major protein component of erythrocyte cytoskeleton, spectrin . A reasonably high apparent dissociation constant was estimated to be 1.5 microM . The binding of mithramycin in the absence of any divalent cation to the large cytoskeletal protein led to quenching in the tryptophan fluorescence of the protein . Stern-Volmer quenching of the tryptophan residues by acrylamide revealed conformational change in the MTR-bound spectrin . This preliminary study might be useful in understanding other possible sites of actions after translocation. Carbohydr Res, 1995 Jul 10, 271(1), 55 - 63 The complete 1H NMR assignments of aminoglycoside antibiotics and conformational studies of butirosin A through the use of 2D NMR spectroscopy; Cox JR et al.; The complete proton assignments of the aminoglycoside antibiotics, butirosin A, kanamycin A and kanamycin B, at pH 6.5 have been made through the use of various homonuclear and heteronuclear 2D NMR methods . Butirosin A NOESY experiments suggest a stacking arrangement between the xylose and 2,6-diamino-2,6-dideoxyglucose rings, while the 2-deoxystreptamine ring and its substituent, the (S)-4-amino-2-hydroxybutyryl group, extend away from the stacked rings . Informative long-range NOEs were observed for butirosin A but not with kanamycin A or kanamycin B . Many intra-ring NOEs were observed with all three aminoglycosides that confirm the proton assignments made in this study. Biochim Biophys Acta, 1995 Jul 6, 1237(1), 1 - 5 Formation of membrane channels by chrysospermins, new peptaibol antibiotics; Grigoriev P et al.; The four homologous chrysospermins (Ia-d) are new 19 amino acid peptaibols which form cation selective ion channels in artificial lipid bilayer membranes . Conductance of channels formed by chrysospermins B (Ib) and D (Id) was twice as high (640 pS in 100 mM KCl) as found with chrysospermins A (Ia) and C (Ic) . Single channel current traces were recorded for each of the four peptides even at very low (even zero) membrane voltages suggesting that non-gated channels are formed. EMBO J, 1995 Jul 3, 14(13), 3247 - 51 Enhancement of Neurospora VS ribozyme cleavage by tuberactinomycin antibiotics; Olive JE et al.; Several examples of inhibition of the function of a ribozyme or RNA-protein complex have shown that certain antibiotics can interact specifically with RNA . There are, however, few examples of antibiotics that have a positive, rather than a negative, effect on the function of an RNA . We have found that micromolar concentrations of viomycin, a basic, cyclic peptide antibiotic of the tuberactinomycin group, enhance the cleavage of a ribozyme derived from Neurospora VS RNA . Viomycin decreases by an order of magnitude the concentration of magnesium required for cleavage . It also stimulates an otherwise insignificant transcleavage reaction by enhancing interactions between RNA molecules . The ability of viomycin to enhance some RNA-mediated reactions but inhibit others, including translation and Group I intron splicing, demonstrates the potential for natural selection by small molecules during evolution in the 'RNA world' and may have broader implications with respect to ribozyme expression and activity in contemporary cells. Anal Chem, 1995 Jul 1, 67(13), 2088 - 95 Effect of micelles and mixed micelles on efficiency and selectivity of antibiotic-based capillary electrophoretic enantioseparations; Rundlett KL et al.; Vancomycin (an oligophenolic, glycopeptide, macrocyclic antibiotic) has been shown to be a superb chiral selector for anionic and neutral compounds . It was found that adding sodium dodecyl sulfate to the run buffer increased efficiency by over 1 order of magnitude, decreased analysis times, and reversed the elution order of the enantiomers . This allows for control of the retention order as well as the resolution of enantiomers in complex mixtures in a single run . A mechanism is proposed which explains all of the observed effects and is verified experimentally . Since vancomycin is present in both the micelle and in free solution, previously proposed micelle-selector models are, at best, limiting cases . A general equation is derived which can be used to describe all possible interactions, including those with the capillary wall, if needed . Also, it is shown that electrophoretic mobilities and not migration times must be used to calculate binding constants of a solute to the micelle, the chiral selector, or both . Furthermore, it is shown that a neutral marker molecule cannot be used to accurately correct mobilities that have been altered due to changes in solution viscosity . While this work utilizes the practical vancomycin-micelle system, the general conclusions and theory apply to most other analogous CE systems as well. Antibiot Khimioter, 1995 Jul, 40(7), 25 - 9 {Effect of antibiotics on glucocorticoid receptor function}; Golikov PP; The effects of penicillin G and cefazolin (cefamezin) on the function of the types II and III glucocorticoid receptors of the liver cytosol were studied on Wistar male rats weighing 180-200 g . The Scatchard and Lineweaver--Berk analysis showed that penicillin G and cefazolin (0.1-10.0 mM) induced a dose-dependent increase in the density of the type III glucocorticoid receptors and a decrease in the affinity of 3H-corticosterone with the type III glucocorticoid receptors . The activation of the function of the type III glucocorticoid receptor by penicillin G and cefazolin was not competitive . Penicillin G had no significant effect on the function of the type II glucocorticoid receptors . The increase in the density of the type II glucocorticoid receptors under the effect of cefazolin was dose-dependent though Ka and Kd did not significantly change . The results were indicative of the fact that penicillins and cephalosporins had a strong action on the most important regulatory system of homeostasis, i.e . the glucocorticoid function which is the decisive one in the pathogenesis of inflammation. Med Clin North Am, 1995 Jul, 79(4), 919 - 33 Antibiotic dosing in renal failure; Maderazo EG; The Dosing in Renopathy by Easy-To-Use Multipliers (DREM) System is a simple method for dose adjustments of anti-infectives in renal insufficiency . The simple 2-step method involves: (1) estimating creatinine clearance (CLcr) from age, sex, and serum creatinine, and (2) calculating the adjusted dose or dosing interval with the use of multipliers . By multiplying the normal dose or dosing interval with the dose (CLcr/100) or interval (100'CLcr) multiplier, the adjusted dose or dosing interval is obtained, respectively . Dose estimates with this method are reasonably accurate and compare favorably with previously published methods of correction. Cornea, 1995 Jul, 14(4), 382 - 7 An in vitro comparison of the susceptibilities of bacterial isolates from patients with conjunctivitis and blepharitis to newer and established topical antibiotics; Everett SL et al.; This retrospective study compared new and established topical antibiotics with regard to the in vitro susceptibility of bacterial isolates recovered from patients with conjunctivitis (n = 385) and blepharitis (n = 173) using the National Committee for Clinical Laboratory Standards-approved disk diffusion method . The percent susceptibility of recovered isolates to single antibiotic agents or combinations were ranked from greatest to least: chloramphenicol, bacitracin/polymyxin B, ofloxacin, sulfa, ciprofloxacin, trimethoprim/polymyxin B, norfloxacin, gentamicin, bacitracin, trimethoprim, tobramycin, neomycin, erythromycin, and polymyxin B . We determined that none of the available topical antibiotics provided 100% broad spectrum coverage in vitro . Established antibiotics often provided coverage comparable to the newer drugs . Due to the unproven value of in vitro testing as a predictor of clinical outcome in bacterial blepharitis and conjunctivitis, the ophthalmologist should choose therapy based on clinical experience, ongoing critical evaluation of available antibiotics, and cost-effectiveness. J Ind Microbiol, 1995 Jul, 15(1), 49 - 54 Bioconversion capacity of Streptomyces sp GE44282, a producer of the antibiotics heneicomycin and aurodox; Marinelli F et al.; Streptomyces sp GE44282 was isolated in the course of a screening program for novel antibiotics . It co-produces heneicomycin and aurodox, two kirromycin-type antibiotics, which differ by the presence of an hydroxyl group at the C30 position of aurodox . Heneicomycin is converted into aurodox both by growing and resting cells of Streptomyces sp GE44282 and by the producer of aurodox, Streptomyces goldiniensis ATCC 21386 . This bioconversion of heneicomycin is substrate-specific and is not observed using the producer of heneicomycin, Streptomyces filippiniensis NRRL 11044 . The three strains show very similar taxonomic characteristics . These results suggest that heneicomycin is a precursor of aurodox, the production of which depends on the bioconversion capability expressed by the strain. Trop Doct, 1995 Jul, 25(3), 115 - 7 Aggressive fluid resuscitation and broad spectrum antibiotics decrease mortality from typhoid ileal perforation; Mock C et al.; One of the most severe complications of typhoid enteritis is perforation of ileal ulcerations . The typically high mortality rates from these perforations are in part due to extremely limited supportive care in hospitals in typhoid endemic areas . In the setting of a rural African hospital, this study demonstrated a decrease in overall mortality rate from 40% with one layer closure and chloramphenicol alone to 19% with two-layer closure and chloramphenicol, gentamicin and metronidazole . This was primarily due to a decrease in late (> 24 h) mortality . There was also a decrease in overall mortality rate from 43% with < 10 ml/kg of intraoperative fluid administration to 14% with > 10 ml/kg . This was primarily due to a decrease in early (< 24 h) mortality . Even within the constraints of the rural developing world, more aggressive initial fluid resuscitation can decrease early mortality, while broader spectrum antibiotics and two-layer closure can decrease late mortality from typhoid ileal perforation. J Antibiot (Tokyo), 1995 Jul, 48(7), 683 - 95 Synthesis of new pseudodisaccharide aminoglycoside antibiotics from carbohydrates; Pelyvas IF et al.; Novel pseudodisaccharide-type aminocyclitol antibiotic models, built up from D-arabinose, D-ribose, D-glucosamine, L-ristosamine and L-acosamine have been synthesized by the glycosylation of suitably protected (azido)deoxyinosose aglycones derived by the Ferrier carbocyclic ring transformation of carbohydrate precursors . An alternative approach to related pseudodisaccharides, based on the Ferrier carbocyclization of reducing disaccharides, has also been elaborated . This latter method extends the scope of the Ferrier reaction, by demonstrating that acid-labile 2-deoxydisaccharides can also be readily transformed into the corresponding pseudodisaccharides under the slightly acidic conditions of this ring-transformation. J Antibiot (Tokyo), 1995 Jul, 48(7), 614 - 8 Fusacandins A and B; novel antifungal antibiotics of the papulacandin class from Fusarium sambucinum . II . Isolation and structural elucidation; Hochlowski JE et al.; Two novel antifungal compounds of the papulacandin class, named fusacandins A and B, have been isolated from Fusarium sambucinum . Each compound contains two units of galactose and one of glucose, the latter connected as a C-glycoside to an aromatic moiety . Fusacandin A is esterified at two sites with long-chain, unsaturated fatty acids and fusacandin B at only one site . The structures of the fusacandins were elucidated through analysis of mass spectral and 1-D and 2-D homonuclear and heteronuclear NMR data. Free Radic Biol Med, 1995 Jul, 19(1), 31 - 7 Hydrogen peroxide as a potent bacteriostatic antibiotic: implications for host defense; Hyslop PA et al.; Host defense against bacterial pathogens in higher organisms is mediated in part by the generation of reactive oxygen species (ROS) by PMN . In this study, we determined the following effects of exposure of constant concentrations of H2O2 on E . coli in a culture continuously monitored for H2O2 concentration, numbers, and viabilities of cells: (1) E . coli growth rates monitored for 1 h were profoundly affected by concentrations of H2O2, between 25-50 microM . (2) Complete bacteriostasis was observed at 100 microM . (3) Significant cell killing was not observed until the concentration of H2O2 was greater than 500 microM . (4) Bacteriostatic (25-50 microM) concentrations of H2O2 appeared not to be toxic to human skin fibroblasts for a 2-h exposure . (4) Bacteriostasis by H2O2 could not be explained by metabolic inhibition, because intracellular ATP levels were not compromised at bacteriostatic doses of H2O2 . (5) Measurements of H2O2 concentrations in subcutaneous abscess fluid infected with both E . coli and S . aureus indicated prevailing concentrations of the oxidant consistent with a proposed role of H2O2 in host defense. J Pharmacol Exp Ther, 1995 Jul, 274(1), 194 - 9 Effects of nephrotoxic beta-lactam antibiotics on the mitochondrial metabolism of monocarboxylic substrates; Tune BM et al.; The nephrotoxic beta-lactam antibiotics (beta-lactams) cephaloridine, cephaloglycin and imipenem are toxic to the mitochondrial transport and (secondarily) oxidation of succinate and other dicarboxylic substrates . However, compared to cephaloglycin, cephaloridine is minimally toxic to the mitochondrial uptake and uncoupled oxidation of the short-chain fatty anion butyrate . Further studies were therefore done to compare the early effects of nephrotoxic doses (300 mg/kg body weight) of imipenem, cephaloridine and cephaloglycin on the mitochondrial metabolism of three important monocarboxylic substrates, butyrate, valerate and pyruvate, in rabbit renal cortex . The following was found: 1) imipenen reduces the oxidation of all three monocarboxylates, within 0.5 to 1 hr after administration . 2) The respiratory toxicity of cephaloglycin is essentially the same as that of imipenem with all three substrates . 3) cephaloridine causes little or no toxicity to pyruvate or butyrate oxidation and is significantly less toxic than imipenem or cephaloglycin to valerate oxidation . 4) The effects of the three beta-lactams on butyrate and pyruvate uptake parallel their effects on butyrate and pyruvate oxidation . CONCLUSIONS: Imipenem and cephaloglycin have essentially the same patterns of toxicity to the mitochondrial metabolism of all metabolic substrates that have been tested . Although cephaloridine has similar effects on dicarboxylic substrates, it is significantly less toxic to the mitochondrial metabolism of pyruvate and the short-chain fatty anions . It is proposed that cephaloridine's zwitterionic charge may restrict its ability to acylate monocarboxylic and other anionic carriers, resulting in less nephrotoxicity than might otherwise result from its uniquely high intracellular concentrations and singular ability among the toxic beta-lactams to produce oxidative injury. J Thorac Cardiovasc Surg, 1995 Jul, 110(1), 224 - 38 A comparison of failure modes of glutaraldehyde-treated versus antibiotic-preserved mitral valve allografts implanted in sheep; Tamura K et al.; Morphologic studies and calcium analyses were made on mitral valve allografts from 12 juvenile sheep surviving 12 to 24 weeks after mitral valve replacement . Before implantation, the allografts were treated with 0.625% glutaraldehyde (group I, n = 4) or with cold antibiotic solution (group II, n = 8) . Three group I animals died 12 to 19 weeks after implantation because of dysfunction of calcified valves; the surviving animal also had extensive allograft calcification . One group II animal died of mitral regurgitation; the valves of the other seven (including five with regurgitation shown by Doppler and ventriculographic studies) were explanted at 19 to 24 weeks . Chordal rupture related to calcific deposits was found in all group I valves . Leaflet perforations (n = 4) and ruptured chordae (n = 4), each caused by connective tissue deterioration, were found in group II valves . Inflammatory reaction was absent or minimal in group I valves but moderate or severe in group II valves . Fibrous sheaths were thicker in group II than in group I valves . Calcium levels were much higher in group I than in group II valves . Calcification in group I valves was diffuse and involved collagen, elastic fibers, and connective tissue cells and matrix; in group II valves, it was localized in connective tissue cells . Thus glutaraldehyde-treated allografts failed because of extensive calcification, whereas antibiotic-preserved allografts underwent deterioration of connective tissue and infiltration by inflammatory cells. J Med Microbiol, 1995 Jul, 43(1), 37 - 44 Dexamethasone treatment of lipopolysaccharide-induced meningitis in rabbits that mimics magnification of inflammation following antibiotic therapy; Rooney P et al.; The objective of adjunct anti-inflammatory therapy of bacterial meningitis is the containment of heightened inflammation caused by lysis of bacteria by antibiotics . This can be modelled by giving two consecutive intra-cisternal injections of lipopolysaccharide (LPS) to rabbits, the first at 0 h to induce inflammation to mimic that occurring during the proliferation of bacteria in the cerebrospinal fluid (CSF), and the second at 6 h to mimic inflammation subsequent to antibiotic-induced bacterial lysis . Injection of 2.5 ng of LPS induced pleocytosis at 4 h which was preceded by a peak of tumour necrosis factor (TNF) activity at 2 h . A subsequent injection of 25 ng of LPS at 6 h induced second peaks of pleocytosis and CSF TNF . Dexamethasone (1.5 mg/kg, i.v.) administered 15 min or 1 h before the second injection of LPS tended only to reduce CSF TNF, but effectively prohibited further pleocytosis . Brain TNF alpha mRNA levels were unchanged at 6 and 7 h after LPS injection, and were unaffected by dexamethasone . These results indicate that the subarachnoid space is distinct from the general circulation in that the TNF-producing cells present do not display a hypo-responsive state towards LPS as occurs when LPS is injected systemically . Furthermore, dexamethasone is able to attenuate the secondary inflammatory response resulting from a second LPS injection without eliminating a second peak of TNF activity. Am J Emerg Med, 1995 Jul, 13(4), 396 - 400 Antibiotics to prevent infection of simple wounds: a meta-analysis of randomized studies; Cummings P et al.; A meta-analysis was conducted to determine whether prophylactic systemic antibiotics prevent infection in patients with nonbite wounds that are managed in the emergency department (ED) . A literature search was performed to identify published, randomized trials of prophylactic antibiotics for nonbite wounds . Blinded review of trial methods was used to select trials that randomly assigned patients to antibiotic or control groups and analyzed results by intention to treat . Of 9 randomized trials, 7 (with 1,734 study subjects) were accepted for analysis . The odds ratio for infection in treated patients compared with controls was used as the measure of effect, and a summary odds ratio was calculated . Patients treated with antibiotics had a slightly greater incidence of infection compared with untreated controls: odds ratio 1.16 (95% confidence interval {CI} 0.77 to 1.78) . Even among patients treated with a penicillinase-resistant antibiotic (5 trials with 1,204 patients), there was no benefit from treatment; odds ratio 1.00 (95% CI 0.59 to 1.71) . In conclusion, there is no evidence in published trials that prophylactic antibiotics offer protection against infection of nonbite wounds in patients treated in EDs. J AOAC Int, 1995 Jul-Aug, 78(4), 978 - 86 Identification and measurement of beta-lactam antibiotic residues in milk: integration of screening kits with liquid chromatography; Harik-Khan R et al.; A procedure for identifying and quantitating violative beta-lactams in milk is described . This procedure integrates beta-lactam residue detection kits with the multiresidue automated liquid chromatographic (LC) cleanup method developed in our laboratory . Spiked milk was deproteinized, extracted, and subjected to reversed-phase LC using a gradient program that concentrated the beta-lactams . Amoxicillin, ampicillin, cephapirin, ceftiofur, cloxacillin, and penicillin G were, thus, separated into 5 fractions that were subsequently tested for activity by using 4 kits . beta-lactams in the positive fractions were quantitated by analytical LC methods developed in our laboratory . The LC cleanup method separated beta-lactam antibiotics from each other and from interferences in the matrix and also concentrated the antibiotics, thus increasing the sensitivity of the kits to the beta-lactam antibiotics . The procedure facilitated the task of identifying and measuring the beta-lactam antibiotics that may be present in milk samples. J Vet Diagn Invest, 1995 Jul, 7(3), 374 - 9 Influence of the antibiotics lincomycin and tylosin on aflatoxicosis when added to aflatoxin-contaminated diets of growing swine; Harvey RB et al.; Effects of dietary aflatoxin (AF) and the antibiotics lincomycin (L) and tylosin (T) were evaluated in growing crossbred pigs . Six barrows (3 replicates of 2 each, mean body weight 14.0 kg) per group were assigned to 1 of 6 treatment groups (for a total of 36): 0 mg L, 0 mg T, and 0 mg AF/kg of feed (control); 220 mg L/kg of feed (200 g/ton); 110 mg T/kg of feed (100 g/ton); 2.5 mg AF/kg of feed; 2.5 mg AF plus 220 mg L/kg of feed; 2.5 mg AF plus 110 mg T/kg of feed . Barrows were administered their respective diets for 28 days . Body weight, body weight gain, and feed consumption were reduced by the AF alone, the AF plus L, and the AF plus T treatments, compared with control, L, and T treatments . Altered serum biochemical or hematologic measurements induced by AF treatments included increased serum activities of alkaline phosphatase and gamma-glutamyltransferase, increased hematocrit, hemoglobin, RBC count, WBC count, and mean cell hemoglobin, decreased serum concentrations of albumin, cholesterol, inorganic phosphorus, unsaturated iron binding capacity, total protein, and urea nitrogen, and decreased lymphoblastogenic response . Liver weight was increased, and microscopic lesions were consistent with those observed in cases of aflatoxicosis . With some other minor exceptions for hematologic and immunologic variables, these data indicate that the feed antibiotics lincomycin and tylosin, when added to aflatoxin-contaminated diets, do not have beneficial or detrimental effects on aflatoxicosis in growing swine. New Microbiol, 1995 Jul, 18(3), 325 - 9 In vitro effects of novel glycopeptide antibiotics on the reactivity of the lipopolysaccharide (LPS) of S . minnesota R595; Matera G et al.; Four novel glycopeptide antibiotics, namely MDL 62708, MDL 63155, MDL 62827, MDL 62873 (mideplanin), plus teicoplanin, which differ in their chemical structure, were used to examine the relationship between the structure of glycopeptides and their LPS neutralization activity . Compound MDL 62708 (100 micrograms/ml) significantly reduced (P < 0.01 vs . antibiotic-free LPS, by Fisher's PLSD Test) metachromatic reactivity of S . minnesota R595 LPS (500 micrograms/ml) as evaluated by the DMB test . The remaining glycopeptides showed a significant reduction of the metachromatic reactivity, although at concentrations (333 and 1000 micrograms/ml) higher than MDL 62708 . Data obtained with LAL test appeared in accordance with those of the other techniques: all the glycopeptides used (100 and 1000 micrograms/ml) significantly (P < 0.05) reduced the reactivity of S . minnesota R595 LPS (50 pg/ml), and the lowest concentration of MDL 62708 (10 pg/ml) used produced a substantial, although not significant, reduction of the LPS reactivity with LAL . The antibiotic/LPS ratios associated to a significant reduction of LPS reactivity were 3.3/5 (wt/wt) and 2/1 (wt/wt) for DMB and LAL tests respectively . Such ratio appeared to be even lower for MDL 62708 . In conclusion, the four new glycopeptides, when tested at an antibiotic/LPS ratio about 1000 times lower than that which can be found in vivo, were able to reduce the reactivity of LPS in the in vitro models used . Teicoplanin aglycone MDL 62708, which also lacks the teicoplanin fatty acid, seems to have the same anti-LPS activity as the parental antibiotic, thus suggesting an important role for the glycopeptide backbone and NH2 groups in LPS-neutralizing effect. Rev Med Brux, 1995 Jul-Aug, 16(4), 320 - 4 {Health economics and antibiotic therapy}; Leclercq P et al.; In the field of antibiotic therapy, particularly the methods of economic evaluation hold one's attention within the wide range of health economics' applications . Several tools allow a comparison of the outcomes of alternative strategies and thereby guide choices to the most appropriate solutions . After a brief recall of the methods classically used to evaluate health care strategy, the authors stress the importance and difficulty of fixing and applying a correct and satisfactory procedure for evaluation . An evaluation example of antibiotic therapy allows to illustrate the application of the principles confronting a field in which competition is intense and economic stakes stay large--a fact which naturally yields to seek after objective decision making criteria . The health care policies drawn by public authorities as well as the marketing strategies of the health sector trade are partly based on such evaluations . If these techniques are not intended for the practitioner in the first place, they should not be indifferent to him since they influence health authorities and thereby indirectly affect the therapeutic freedom of the physician. Arch Biochem Biophys, 1995 Jun 20, 320(1), 177 - 81 The influence of antibiotics and antitumor agents on the relaxation activity of Pisum sativum leaf chloroplast topoisomerase I; Zagariya AM et al.; DNA topoisomerase was isolated from pea leaf chloroplasts . The relaxation activity of this topoisomerase was Mg2+ dependent and sensitive to ethidium bromide and novobiocin, a gyrase inhibitor . Chloroplast topoisomerase (Topo I) was ATP independent, as shown by the characteristic gel distribution of topoisomers . Topoisomerase, compared with the known eucaryotic topoisomerase I, was not stimulated by polyamines as are spermidine, spermine, and cadaverine . Ethidium bromide, DAPI, heparin, nalidixic acid, and m-AMSA (but not camptothecin) were able to inhibit the relaxation activity of chloroplast topo I . Nalidixic acid, novobiocin, m-AMSA, camptothecin, and amiloride were tested for their effects on the topoisomerase-catalyzed "cleavage complex" between DNA and chloroplast DNA topoisomerase I. Antibiot Khimioter, 1995 Jun, 40(6), 3 - 6 {Induction of antibiotic formation by inactive cultures of actinomycetes . A mutant strain of Streptomyces helvaticus, a new producer of bruneomycin}; Malkina ND et al.; After exposure of an inactive actinomycete to ethidium bromide a stable mutant producing an antibiotic on a solid medium was isolated . The exposure to methylnitrosoguanidine provided the isolation of a more productive variant synthesizing the antibiotic in a liquid medium . By UV, IR, NMR and mass spectroscopy the antibiotic was identified as bruneomycin (streptonigrin) . The taxonomic investigation of the culture showed that it belongs to Streptomyces helvaticus which is a new culture producing bruneomycin (streptonigrin) . Previously it did not synthesize the antibiotic. Pathol Biol (Paris), 1995 Jun, 43(6), 524 - 8 {The particular case of azalides: antibiotic diapedesis . Experimental data from a murine model of pneumococcal pneumonia}; Veber B et al.; The relations between the clinical efficacy, phagocytic transport phenomena, tissular and sera kinetics have been assessed in a pneumonia murine model . At first, the correlation between the clinical efficacy and pharmacokinetics characteristics has been studied for the erythromycin, spiramycin, roxithromycin, clarithromycin and azithromycin . An in vivo clinical efficacy hierarchy has been established (azi > ery > roxi = azi > spira) . A hierarchy identical to the clinical efficacy, has been recognised for the pulmonary elimination half lives and the pulmonar AUC . These could be considered as predictive of these antibiotics activity in the respiratory infections . In a second time, the tissular pharmacokinetics of the azithromycin in leukopenic mice allowed to confirm the leukocytes role in the transport and release of this antibiotic in the midst of the infections site . Finally, this antibiotic demonstrated its efficacy in a bacterienic infection even when administered at a low dosage thus allowing to have sera concentrations identical to those obtained in human clinical case and close to MIC's for S . pneumoniae . The pharmacokinetic novelty displayed by its strong tissular penetration can explain its remarkable efficacy. Appl Environ Microbiol, 1995 Jun, 61(6), 2302 - 7 Overexpression of the robA gene increases organic solvent tolerance and multiple antibiotic and heavy metal ion resistance in Escherichia coli; Nakajima H et al.; Escherichia coli K-12 OST3410 was isolated previously as a stable cyclohexane-tolerant mutant derived from cyclohexane-sensitive strain JA300 . A plasmid which provides cyclohexane tolerance to strain JA300 was isolated from the OST3410 genomic library . Subcloning and sequence analysis showed that the plasmid contained the robA gene, whose gene product was reported to bind specifically to the right border of oriC . We observed that the robA gene on the multicopy plasmid generally increased the organic solvent tolerance of several E . coli strains . We also observed an increase in the organic solvent tolerance of JA300 carrying the lac-robA fusion gene on a low-copy plasmid by isopropyl-beta-D-thiogalactopyranoside induction . Strain JA300 carrying the multicopy robA plasmid also showed an increase in resistance to a number of unrelated antibiotics and heavy metal ions, and the spectrum of resistance was significantly similar to that of the soxS-overexpressing strain. J Bacteriol, 1995 Jun, 177(11), 3323 - 5 The peptide antibiotic microcin 25 is imported through the TonB pathway and the SbmA protein; Salomon RA et al.; Selection of spontaneous mutants for insensitivity to the peptide antibiotic microcin 25 led to the isolation of five categories of mutants . Phenotypic and mapping studies showed the mutations to be located in the fhuA, exb, tonB, and sbmA genes . The latter encodes a cytoplasmic membrane protein which is also required for the penetration of microcin B17. J Antibiot (Tokyo), 1995 Jun, 48(6), 484 - 7 Production of the new antibiotic tetrahydrokalafungin by transformants of the kalafungin producer Streptomyces tanashiensis; Kakinuma S et al.; The new antibiotic tetrahydrokalafungin was produced by the transformants of kalafungin producing S . tanashiensis and kalafungin-nonproducing mutants carrying the recombinant plasmid pKU523 . This plasmid consists of pKU501 (J . Antibiotics 44: 995 approximately 1005, 1991) which contains the gene cluster for kalafungin biosynthesis, and additional 5 kb stability region of SCP2*. J Antibiot (Tokyo), 1995 Jun, 48(6), 471 - 8 Thiazinotrienomycins, new ansamycin group antibiotics; Hosokawa N et al.; New triene-ansamycins designated thiazinotrienomycins A, B, C, D and E were isolated from culture broth of Streptomyces sp . MJ672-m3 for their activities against cervical cancer cell lines . The structures and some biological and biochemical properties of the antibiotics were determined. Fam Pract, 1995 Jun, 12(2), 166 - 70 Antibiotic use in upper respiratory tract infections in New Zealand; McGregor A et al.; Upper respiratory tract infections (URTIs) are a common reason for presentation to general practitioners . The current study used computerised consultation records of 100,222 patients from 17 general practices in New Zealand for the 12-month period 1 July 1991-30 June 1992 . URTIs were noted in 8.9% of all consultations: 44.1% of cases were children aged less than 10 years . Females presented more frequently than males for all ages above five years . Fifteen different antibiotics were prescribed for URTIs, but in 22.5% of cases no antibiotic was prescribed . There was no statistically significant difference in the likelihood of a successful outcome with or without antibiotic therapy (chi 2 = 0.76, P > 0.05) . The treatment failure profile of some antibiotics highlights the need for more prescriber education, especially as the range of medications available for general practitioner prescribing increases. Antimicrob Agents Chemother, 1995 Jun, 39(6), 1292 - 4 Evaluation of antibiotic therapies for eradication of Helicobacter hepaticus; Foltz CJ et al.; The newly recognized murine pathogen Helicobacter hepaticus is known to colonize the ceca and colons of several strains of mice from a variety of commercial suppliers . Additionally, the organism persistently infects mice, causes a chronic hepatitis, and is linked to hepatic tumors in the A/JCr inbred mouse strain . For this reason, eradication of the organism from infected mouse colonies is desirable . Treatment modalities for eradication of H . hepaticus from the gastrointestinal system consisted of oral administration of various antibiotic combinations previously evaluated for eradication of experimental H . felis gastric infection in mice . A/JCr mice (8 to 10 weeks old) naturally infected with H . hepaticus were divided into six treatment groups of 10 animals each . Animals received monotherapy of amoxicillin, metronidazole, or tetracycline or triple therapy of amoxicillin-metronidazole-bismuth (AMB) or tetracycline-metronidazole-bismuth (TMB) . All medications were administered by oral gavage three times daily for 2 weeks . One month after the final treatment, mice were euthanatized and livers, ceca, and colons were cultured for H . hepaticus . All untreated control animals had H . hepaticus isolated from the cecum and/or colon . H . hepaticus was not recovered from the livers, ceca, or colons of the AMB or TMB treatment groups . All animals receiving the various antibiotic monotherapies had H . hepaticus isolated from the cecum and colon . We conclude that at the doses and the route evaluated, AMB and TMB triple therapies are effective for eradication of H . hepaticus in 8- to 10-week old A/JCr mice. Kansenshogaku Zasshi, 1995 Jun, 69(6), 684 - 95 {Therapeutic evaluation of combination therapy using human native immunoglobulin preparation for i.v . administration, with antibiotics and G-CSF in severe infections in the field of internal medicine}; Kitamura K et al.; A human native immunoglobulin liquid preparation for intravenous injection, was used in combination with antibiotics and G-CSF to study its efficacy and safety in 49 patients with severe infections (Granulocyte counts were <or= 1000/ microliters, Body temperature was >or= 38 degrees C) which had not responded to antibiotic and G-CSF therapy of a 3-day or more duration . As a result of the Committee judgment, 49 patients were included in this study; 30 (61.7%) were included in efficacy and safety analysis . The analysis of 30 patients consisted of 9 patients (30.0%) with suspected septicemia, 5 (16.7%) with pneumonia, and 4 (13.3%) with septicemia . All patients had severe underlying diseases such as leukemia and malignant lymphoma . Clinical efficacy of Immunoglobulin preparation was judged by the doctors in charge to be "excellent" and "good" in 70.0% of the total cases . The rate of effectiveness was calculated from the results of the Committee judgment was 83.3% when "excellent" and "good" cases were included . No side effects were observed in all cases . Our results suggest that the immunoglobulin in combination with G-CSF is very effective on patients with severe infections. Nucleic Acids Res, 1995 May 11, 23(9), 1524 - 30 Novel DNA photocleaving agents with high DNA sequence specificity related to the antibiotic bleomycin A2; Kuroda R et al.; We have designed and synthesized a series of novel DNA photocleaving agents which break DNA with high sequence specificity . These compounds contain the non-diffusible photoactive p-nitrobenzoyl group covalently linked via a dimethylene (or tetramethylene) spacer to thiazole analogues of the DNA binding portion of the antibiotic bleomycin A2 . By using a variety of 5' or 3' 32P-end labeled restriction fragments from plasmid pBR322 as substrate, we have shown that photoactive bithiazole compounds bind DNA at the consensus sequence 5'-AAAT-3' and induce DNA cleavage 3' of the site . Analysis of cleavage sites on the complementary DNA strand and inhibition of DNA breakage by distamycin A indicates these bithiazole derivatives bind and attack the minor groove of DNA . A photoactive unithiazole compound was less specific inducing DNA breakage at the degenerate site 5'-(A/T)(AA/TT)TPu(A/T)-3' . DNA sequence recognition of these derivatives appears to be determined by the thiazole moiety rather than the p-nitrobenzoyl group: use of a tetramethylene group in place of a dimethylene spacer shifted the position of DNA breakage by one base pair . Moreover, much less specific DNA photocleavage was observed for a compound in which p-nitrobenzoyl was linked to the intercalator acridine via a sequence-neutral hexamethylene spacer . The 5'-AAAT-3' specificity of photoactive bithiazole derivatives contrasts with that of bleomycin A2 which cleaves DNA most frequently at 5'-GPy-3' sequences . These results suggest that the cleavage specificity exhibited by bleomycin is not simply determined by its bithiazole/sulphonium terminus, and the contributions from other features, e.g . its metal-chelating domain, must be considered . The novel thiazole-based DNA cleavage agents described here should prove useful as reagents for probing DNA structure and for elucidating the molecular basis of DNA recognition by bleomycin and other ligands. Arch Intern Med, 1995 May 8, 155(9), 922 - 8 Costs of duodenal ulcer therapy with antibiotics; Sonnenberg A et al.; BACKGROUND: Intermittent or maintenance therapy with histamine2 antagonists, highly selective vagotomy, or antibiotic therapy to eradicate Helicobacter pylori all represent distinct, viable options to manage duodenal ulcer disease . Comparing the costs associated with these four approaches could help in deciding among them . METHODS: The decision model of a Markov chain was used to compare the costs of the four approaches and their influence on the natural course of duodenal ulcers . Direct costs were calculated from the average wholesale prices of drugs and from charges for medical services submitted to and allowed by the Health Care Financing Administration . Average annual income was used to estimate indirect costs . RESULTS: The model predicted that after antibiotic therapy, 99.7% of patient time is spent free of duodenal ulcer . The corresponding percentages were 96.6% for maintenance therapy, 94.4% for vagotomy, 89.4% for intermittent therapy, and 82.8% without therapy . For an individual patient after 15 years, the expected total costs of a treatment approach involving antibiotics are $995, compared with $10,350 for intermittent therapy with histamine2 antagonists, $11,186 for maintenance therapy with histamine2 antagonists, and $17,661 after vagotomy . Incorporating upper gastrointestinal tract endoscopy to verify eradication of H pylori raises the costs of the antibiotic therapy option to $2426 . Increasing the annual infection rate of H pylori from baseline 1% to 10% raises the expected costs after 15 years to $3431 . Decreasing the H pylori eradication rate from baseline 80% to 50% raises the costs to $2679 . CONCLUSIONS: Compared with other options, antibiotics to eradicate H pylori are the cheapest therapy for duodenal ulcer and provide the least time spent with an active ulcer . From an economic perspective, antibiotics represent the treatment of choice. Acta Pol Pharm, 1995 May-Jun, 52(3), 187 - 92 Electrochemical studies of some quinolone antibiotics . Part I . Qualitative analysis on mercury and carbon electrodes; Warowna-Grzeskiewicz M et al.; Direct current polarography and cyclic voltammetry was used to study quinolone antibiotics: ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin on a mercury and carbon electrode . The dependence of limiting currents and half-wave potentials on the pH of the solution, mercury head, temperature, ionic strength of the solution, methyl cellulose concentration, scan rate and quinolone concentration was studied . The optimal parameters and background solutions have been chosen . It was concluded that on mercury electrode quinolones are reduced in two one-electron waves and the process of the reduction is accompanied by an acid-base equilibrium . An anodic peak observed on graphite electrode is probably caused by the oxidation of piperazine ring in the molecule. Indian Pediatr, 1995 May, 32(5), 529 - 31 Routine antibiotic cover for newborns intubated for aspirating meconium: is it necessary? Krishnan L, Nasruddin, Prabhakar P, Bhaskaranand N. A retrospective analysis was performed on 215 babies to evaluate the incidence of septicemia in babies intubated at birth for aspirating meconium from the trachea . Only term, appropriate for gestational age babies were included . Babies with any known perinatal risk factor for infection were excluded from the study and none of the babies had been put on "prophylactic antibiotics." There were 88 babies in the intubated group in a one year period from January 1991 to December 1991 . One hundred and twenty seven babies were taken as controls . There was no significant difference in the incidence of early septicemia in the two groups . There were no deaths in either group . It is concluded that well term babies who are intubated for aspirating meconium need not be put on routine antibiotic cover. Antibiot Khimioter, 1995 May, 40(5), 35 - 7 {The possibility for obtaining sorbents from the mycelial wastes of antibiotic production}; Iakubova AR et al.; A technological process for production of a sorbent based on the mycelial waste of penicillin manufacture was developed . The process and its parameters are described . The exploitation conditions determine whether a strong sorbent with low sorption properties or a sorbent with higher sorption properties and lower granule strength is prepared. J Antibiot (Tokyo), 1995 May, 48(5), 391 - 8 Structures and absolute configurations of antibiotics of the oligosporon group from the nematode-trapping fungus Arthrobotrys oligospora; Anderson MG et al.; Spectroscopic data define the structures of three new antibiotics, 4',5'-dihydro-oligosporon (4), hydroxyoligosporon (5) and 10',11'-epoxyoligosporon (6) from the nematode-trapping fungus Arthrobotrys oligospora, and confirm the structures of the recently reported antibiotics oligosporon (1) and oligosporol B (3) . The absolute configuration of the substituted 7-oxabicyclo{4.1.0}hept-3-ene nucleus of these metabolites is determined by circular dichroic spectroscopy . Oligosporon (1) and its dihydro-derivative (4) represent the second and most complex structural type of nematocidal metabolite to be characterised from cultures of nematophagous fungi. Laryngoscope, 1995 May, 105(5 Pt 1), 472 - 4 Safety of ototopical antibiotics; Welling DB et al.; A prospective randomized study analyzing the safety and efficacy of a single dose of ototopical antibiotics following human middle ear tympanostomy tube insertion was performed . Fifty children undergoing bilateral tympanostomy tube insertion were studied by the placement of 0.5 mL of Cortisporin Otic Suspension (COS; Burroughs Wellcome Co., Research Triangle Park, N.C.) to one middle ear space by random assignment . Preoperative and postoperative audiograms were obtained, and the presence of otorrhea was noted . In one patient sensorineural hearing loss of 6 dB developed bilaterally, which was symmetric in both the treated and the untreated ear . This preliminary study showed no statistical difference in hearing loss or postoperative otorrhea associated with a single application of Cortisporin to the middle ear space. Med Clin North Am, 1995 May, 79(3), 463 - 76 Antibiotic formulary selection; Crowe HM et al.; Physicians worldwide are being forced to consider economics in the care of patients . In most hospitals, antibiotics are a steadily increasing segment of the pharmacy budget . This article discusses how the authors used drug pharmacokinetics, restriction policies, and cost benefit analysis to design a cost-effective antibiotic formulary. FEMS Microbiol Lett, 1995 May 1, 128(2), 101 - 6 Effect of the lipopeptide antibiotic, iturin A, on morphology and membrane ultrastructure of yeast cells; Thimon L et al.; The effects of iturin A, at fungicidal concentrations, on yeast cells were studied by scanning electron microscopy and by transmission electron microscopy . A depression, observed in each iturin A-treated cell, was the consequence of the release of electrolytes and other cytoplasmic components . Iturin A passes through the cell wall and disrupts the plasma membrane with the formation of small vesicles and the aggregation of intramembranous particles . Moreover, iturin A passes through the plasma membrane and interacts with the nuclear membrane and probably with membranes of other cytoplasmic organelles. Therapie, 1995 May-Jun, 50(3), 243 - 5 {Drug interactions and antibiotics}; Jourdan J et al.; Situations that require the use of systemic antibiotic therapy are common and drug interactions are potentially frequent . These interactions may be deleterious and lead to reduction of therapeutic index, enhancement of toxic risk or may be favourable, with optimization of pharmacokinetics or pharmacodynamics . The mechanisms of these interactions are discussed. Br Poult Sci, 1995 May, 36(2), 265 - 75 Influence of dietary enzyme complex on the performance of broilers fed on diets with and without antibiotic supplementation; Vranjes MV et al.; 1 . The aim of the experiment was to test the possible interactions of an enzyme complex and a food antibiotic on the growth and metabolism, carcase yield, whole body composition and nutrient deposition in broilers . The basal diet contained 400 g/kg barley . The four treatments were as follows: O--without supplements (control), E--enzyme complex Roxazyme G, 200 mg/kg, A--antibiotic avoparcin, 10 mg/kg, EA--Roxazyme G, 200 mg/kg plus avoparcin, 10 mg/kg . 2 . Roxazyme G positively influenced weight gain, food conversion efficiency, energy metabolisability, fat and nitrogen utilisation and the dry matter content of droppings . Fat and energy deposition in the whole body were also increased, whereas protein deposition and carcase yield were not influenced . 3 . Avoparcin increased energy metabolisability and fat utilisation, but had no influence on nitrogen utilisation . No significant improvements from avoparcin were seen in growth or in nutrient deposition in the body . The fibre degradability (NDF and ADF fraction) was significantly depressed by antibiotic supplementation . 4 . The inclusion of both supplements to the diet did not have a fully additive effect on growth, energy metabolisability, or fat and nitrogen utilisation . The interaction between enzyme and antibiotic for food conversion efficiency during the first experimental period (7 to 21 d) was nearly significant (P = 0.053) . Except for fibre degradability (P < or = 0.01), no other significant interactions between enzyme and antibiotic were found. Int J Clin Pharmacol Ther, 1995 May, 33(5), 266 - 76 Pharmacokinetic development of quinolone antibiotics; Schaefer HG et al.; A prerequisite for the pharmacokinetic development of quinolone antibiotics is a sensitive and accurate method for the quantification of the drug in biological fluids . Both, a drug specific (e.g . HPLC) and a drug non-specific but effect related assay (e.g . bioassay) should be used during early clinical development to detect major active metabolites . The basic pharmacokinetic behavior of the drug is investigated as part of the early phase I program, where single and multiple ascending dose studies are performed to characterize the safety and tolerability of the quinolone in healthy volunteers . Further pharmacokinetic studies are performed to describe the absolute bioavailability, dose proportionality, pharmacokinetics in young and elderly, male and female volunteers . The suitability of the clinical dosage from must be evaluated in comparison to an oral solution and by quantification of the effect of food on bioavailability . The characterization of the absorption in different parts of the gastrointestinal tract may be valuable for dosage form optimization . In order to start phase IIb clinical trials, the potential of possible drug-drug interactions with antacids, cimetidine, theophylline and warfarin has to be evaluated . This can be done by in vitro and in vivo preclinical experiments, before formal clinical-pharmacology studies are performed . Further pharmacokinetic characterization (e.g . studies in special subpopulation, extended interaction studies, total recovery using 14C-labelled compound, blister fluid penetration) will be done parallel to the phase II/III development program . During these efficacy and safety trials blood samples should be obtained and PK-parameters can be calculated using sparse data analysis methods like non-linear mixed effect modeling (NONMEM) or Bayesian methods to characterize the pharmacokinetics in the target population. Vnitr Lek, 1995 May, 41(5), 332 - 5 {Ambulatory parenteral antibiotic therapy}; Pospisilova Y; The paper sums up the current knowledge on the outpatient parenteral antibiotic therapy, the information is based on the experience with this type of treatment in the USA . The introduction gives the reasons for outpatient as opposed to inpatient therapy . The first part of the paper discusses the indications and the contraindications of outpatient parenteral antibiotic therapy, the choice of the adequate antibiotic, the organisation of this treatment and the cooperation between the doctors, nurses and patients . The second part of the paper deals with specific diseases and the possibility of their treatment by means of outpatient parenteral antibiotic therapy. Urol Nefrol (Mosk), 1995 May-Jun, (3), 11 - 4 {Tubular interstitial disorders in the nephrotoxic action of antibiotics}; Potapova AV et al.; Experimental and clinical evaluation of antibiotic nephrotoxicity suggest a conclusion that these drugs may cause tubular damage in relatively unaffected function of tubular apparatus . Progression of tubular dysfunction results from accumulation of high concentrations of antibiotics in renal parenchyma due to tubular filtration and secretion of the drug by tubular epithelium cells . In the majority of patients the disease manifestations were directly associated with antibiotics administration . Tubular dysfunctions present as concentration, acid-excretion, glucose transport and beta 2-microglobulin reabsorption abnormalities . Though renal lesions proved benign, there were occasional cases of acute renal insufficiency in the absence of arterial hypertension. J Antimicrob Chemother, 1995 May, 35(5), 669 - 74 Quantitation of antibiotic effects on bacteria by bioluminescence, viable counting and quantal analysis; Soren L et al.; Discrepant results are obtained when antibiotic-induced bacterial killing is quantitated by viable counting or bioluminescence assay of intracellular ATP . In this study the killing of bacteria exposed to amikacin or imipenem was quantitated by viable counting and bioluminescence assay of intracellular ATP and also by quantal analysis . The results of quantal analysis and viable counting agreed very well, whereas a much lower degree of bacterial killing was recorded by bioluminescence. Drug Metab Dispos, 1995 May, 23(5), 542 - 7 The antibiotic tiamulin is a potent inducer and inhibitor of cytochrome P4503A via the formation of a stable metabolic intermediate complex . Studies in primary hepatocyte cultures and liver microsomes of the pig; Witkamp RF et al.; Tiamulin is a semisynthetic antibiotic frequently used in agricultural animals . The drug has been shown to produce clinically important--often lethal--interactions with other compounds that are simultaneously administered . To explain this, it has been suggested that tiamulin selectively inhibits oxidative drug metabolism via the formation of a cytochrome P450 metabolic intermediate complex . The aim of the present study was to provide further support for this hypothesis . When hepatic microsomes and cultured primary pig hepatocytes were incubated with tiamulin, a maximum in the absorbance spectrum at 455 nm was observed, which disappeared after adding KFe(CN)6 . When hepatocytes were incubated with tiamulin for 72 hr, cytochrome P450 content and cytochrome P4503A apoprotein levels were increased . Tiamulin strongly inhibited and concentration dependently inhibited the hydroxylation rate of testosterone at the 6 beta-position in both microsomes and hepatocytes, and the microsomal N-demethylation rate of ethylmorphine . Other testosterone hydroxylations were inhibited to a lesser extent or not affected . The relative inhibition of the hydroxylation of testosterone at the 6 beta-position was more pronounced in microsomes from rifampicin- and triacetyloleandomycin-treated pigs . The results indicate that cytochrome P450 complex formation can at least partly explain the interactions observed with tiamulin . Tiamulin seems to be a strong, probably selective, inhibitor of the cytochrome P4503A subfamily and an interesting tool for further research. Mol Microbiol, 1995 May, 16(3), 385 - 95 Beta-lactamases and bacterial resistance to antibiotics; Frere JM; The efficiency of beta-lactam antibiotics, which are among our most useful chemotherapeutic weapons, is continuously challenged by the emergence of resistant bacterial strains . This is most often due to the production of beta-lactamases by the resistant cells . These enzymes inactivate the antibiotics by hydrolysing the beta-lactam amide bond . The elucidation of the structures of some beta-lactamases by X-ray crystallography has provided precious insights into their catalytic mechanisms and revealed unsuspected similarities with the DD-transpeptidases, the bacterial enzymes which constitute the lethal targets of beta-lactams . Despite numerous kinetic, structural and site-directed mutagenesis studies, we have not completely succeeded in explaining the diversity of the specificity profiles of beta-lactamases and their surprising catalytic power . The solutions to these problems represent the cornerstones on which better antibiotics can be designed, hopefully on a rational basis. Acta Gastroenterol Belg, 1995 May-Aug, 58(3-4), 290 - 6 Hepatotoxicity of antibiotics; Hautekeete ML; Several antibiotics can cause severe hepatic injury . It is the purpose of this paper to review the main antibiotics that can cause hepatic injury and discuss the presentation, pattern, and outcome of hepatic injury . In the case of the penicillins, the combination amoxycillin-clavulanate and the penicillinase-resistant penicillins oxacillin, (di-)cloxacillin, and flucloxacillin can cause (mainly cholestatic) hepatitis . Cephalosporins have little hepatotoxicity; ceftriaxone can cause drug-induced gallstones . The potential of erythromycin and several other macrolides to cause (usually cholestatic) hepatitis is well established . Tetracyclines can cause a syndrome mimicking acute fatty liver of pregnancy, but this complication has virtually disappeared . Quinolones seem to be able to cause cholestasis . Sulfamethoxazole/trimethoprim can cause severe hepatotoxicity, especially in patients with acquired immunodeficiency syndrome (AIDS) . Finally, nitrofurantoin can cause acute cholestatic and hepatocellular reactions as well as chronic hepatitis mimicking chronic auto-immune hepatitis. Presse Med, 1995 Apr 29, 24(16), 750 - 2 {Critical serum concentration of antibiotics . A therapeutic tool and means of comparative evaluation}; Potel G et al.; It is difficult to predict the clinical activity of antibiotics solely on the basis of in vitro data . Experimental models measuring the relationship between serum concentration and in vivo activity are essential for comparing the activity of different compounds currently available . The critical serum concentration can be used to compare the intrinsic activity of antibiotics on a given bacterial strain . When compared with the minimal inhibiting concentration measured in vitro, "activity loss" can be determined for each antibiotic placed in contact with bacteria in an infected tissue . The relevance of this therapeutic tool in comparison with other methods is discussed. Eur J Pharmacol, 1995 Apr 28, 289(2), 321 - 33 Aminoglycoside antibiotics induce aggregation but not fusion of negatively-charged liposomes; Van Bambeke F et al.; The binding of aminoglycoside antibiotics to acidic phospholipids of membranes is an essential step in the development of both their renal and auditory toxicities, which could be associated with critical modifications of the membrane properties . This work examines the capacity of aminoglycosides to induce membrane aggregation and fusion . Three techniques were used in parallel: (i) measurement of the dequenching rate of a lipid-soluble fluorescent probe (octadecylrhodamine B) incorporated at self-quenched concentration in membranes; (ii) measurement of the increase in the energy transfer between two fluorescent derivatives of phospholipids; and (iii) electron microscopy of negatively-stained replicas . The results were compared with those obtained with spermine (an aggregating polycation) and melittin (a fusogenic peptide) . The three approaches indicate that aminoglycosides induce liposomes aggregation, but not fusion . Aggregation is related to the capacity of each drug studied to bind phosphatidylinositol, as evaluated by its energy of interaction with this acidic phospholipid, and to its toxic potential . Membrane aggregation occurring in vivo could therefore contribute to, or be a determinant of this toxicity, which could rationally be screened for new derivatives by the methods applied here. Microb Drug Resist, 1995 Spring, 1(1), 5 - 8 Antibiotic-resistant pneumococci in pediatric disease; Klugman KP et al.; The surveillance of pneumococcal resistance in nasopharyngeal isolates is a practical way to determine the prevalence of resistant strains and is a reasonable predictor of resistance in systemic isolates . The increasing prevalence of resistance is shifting the distribution of invasive pneumococcal serotypes toward those included in conjugate vaccines . If these vaccines reduce carriage, they may eliminate or greatly reduce the prevalence of resistant strains . Meningitis is the most important infection caused by PRP for which penicillin or ampicillin therapy is inappropriate . Although the extended spectrum cephalosporins will be effective for most cases of PRP meningitis, it is clear that such therapy is not foolproof . It is important for the laboratory to test CSF isolates not only for penicillin resistance but also for resistance to the cephalosporins . beta-Lactam antibiotics can still be considered appropriate empiric therapy for otitis media, pneumonia, or sepsis . However, occasional treatment failures with these agents may necessitate use of alternative therapeutic strategies. Bioorg Med Chem, 1995 Apr, 3(4), 429 - 36 On the conformation of Phe78 of a chromoprotein antibiotic, neocarzinostatin; Imajo S et al.; A structure of neocarzinostatin, an antitumor chromoprotein antibiotic, has been built using X-ray crystallographic data and NMR data, particularly NOE data observed between the apoprotein and the chromophore . Chemical shift changes of protons of the chromophore upon binding to the apoprotein indicated that the aromatic plane of Phe52 has the conformation almost perpendicular to the C-2-C-3 triple bond of the core of the chromophore while Phe78 takes multiple conformations in solution although one of the stable conformations has been assigned for Phe78 in a crystal structure. Br J Rheumatol, 1995 Apr, 34(4), 380 - 2 Role of prophylactic antibiotics in the prevention of late infection of prosthetic joints . Results of a questionnaire and review of the literature; Averns HL et al.; A postal survey has revealed wide variation in attitudes towards the need for prophylactic antibiotics in patients with implants who develop intercurrent infections, or who undergo surgical procedures . The available evidence is insufficient to reach any firm conclusions, however any patient who has an implant should receive swift treatment for intercurrent infections. J Antibiot (Tokyo), 1995 Apr, 48(4), 293 - 9 RS-22A, B and C: new macrolide antibiotics from Streptomyces violaceusniger . II . Physico-chemical properties and structure elucidation; Ubukata M et al.; RS-22A, B and C are novel 36-membered macrolide antibiotics produced by Streptomyces violaceusniger . The structures of these antibiotics were unambiguously determined by 1D and 2D NMR and tandem-mass analysis of the oxidative derivative of RS-22C. Toxicol Lett, 1995 Apr, 76(3), 239 - 43 Correlation between in vitro and in vivo models of proconvulsive activity with the carbapenem antibiotics, biapenem, imipenem/cilastatin and meropenem; Day IP et al.; The present study evaluated the proconvulsant liability of biapenem, a novel carbapenem antibiotic, in in vitro and in vivo experiments, in comparison with the carbapenems, imipenem/cilastatin and meropenem . Imipenem/cilastatin is a carbapenem antibiotic with known proconvulsive liability in man and in animal experiments . In in vivo studies imipenem/cilastatin, at doses of 400/400 mg/kg i.v., significantly lowered the convulsive threshold of pentylenetetrazol (PTZ) in mice and shifted the dose-response curve of PTZ . The effects of biapenem (400 mg/kg i.v.) and another reference carbapenem, meropenem (400 mg/kg i.v.), in the mouse PTZ model were not significantly different from control . In in vitro experiments the carbapenems were tested for their ability to inhibit {3H}muscimol (1.3 mM) binding to rat brain homogenates at concentrations of 1-10 mM . Similar to in vivo results, when compared to imipenem/cilastatin, biapenem and meropenem did not inhibit {3H}muscimol binding to the GABAA receptor complex in brain homogenates while i