Curr Opin Biotechnol, 1993 Oct, 4(5), 531 - 7 Genetic engineering of Streptomyces to create hybrid antibiotics; Hopwood DA; Over the past year, dramatic developments in the technology for isolating and manipulating genes for polyketide synthases have been reported . Significant progress has been made in understanding the mechanisms by which these complex enzymes generate the carbon chains of the polyketides, a highly versatile class of natural products . With the demonstration of the production of novel metabolites by synthase engineering, the stage is excitingly set for rationally manipulating synthase 'programming' to generate tailor-made carbon chains. J Chromatogr, 1993 Sep 22, 619(2), 319 - 23 Rapid determination of tetracycline antibiotics in serum by reversed-phase high-performance liquid chromatography with fluorescence detection; Iwaki K et al.; A rapid and accurate determination of tetracycline antibiotics in human serum by reversed-phase high-performance liquid chromatography with fluorescence detection has been developed, based on protein precipitation in serum . Various reagents for precipitation were investigated, and 24% trichloroacetic acid in methanolic solution gave the maximum recovery (at least 94.3%) and interference-free chromatograms of different three tetracyclines . At a concentration of 0.5 micrograms/ml, the precision (relative standard deviation) ranged from 1.12 to 1.94% . In the range 0.04-10.0 micrograms/ml for oxytetracycline and chlorotetracycline and 0.01-10.0 micrograms/ml for tetracycline, linear responses were observed . The detection limits of this method were 10-35 ng/ml for all three antibiotics . The proposed method was applied to the determination of serum concentrations in subjects receiving tetracycline antibiotics. Biochem Biophys Res Commun, 1993 Sep 15, 195(2), 659 - 66 Specific interaction between a novel enediyne chromophore and apoprotein in macromolecular antitumor antibiotic C-1027; Matsumoto T et al.; The DNA cleavage experiments show that C-1027 chromophore is selectively incorporated into C-1027 apoprotein and is strongly protected by the apoprotein from loss of its DNA cleaving activity . Fluorescence and circular dichroism spectra reveal (1) important participation of tertiary structure of C-1027 apoprotein for the chromophore binding, (2) specific 1:1 binding of C-1027 chromophore to the apoprotein, and (3) significant interaction of the benzoxazine group in the chromophore-apoprotein complex . On the other hand, C-1027 apoprotein does not contribute to sequence-specificity DNA cleavage by C-1027 antibiotics. J Immunol Methods, 1993 Sep 15, 164(2), 165 - 73 Production of highly specific monoclonal antibodies to monensin and development of a microELISA to detect this antibiotic; Pauillac S et al.; Monensin, a polyether antibiotic of molecular weight 671 Da, was converted into a hemisuccinate and covalently linked to bovine serum albumin via the mixed anhydride method . Using this immunogen, polyclonal anti-monensin antibodies were raised in rabbits and monoclonal antibodies were prepared from mice . The specificity of the anti-monensin antibodies was examined by using several structural analogues as the immunogen and by performing direct binding and competitive microELISA assays on Terasaki plates . Rabbit polyclonal antibodies had a dissociation constant (KD) of 5.5 x 10(-8) M for monensin and reacted with nigericin, an antibiotic structurally related to monensin . In contrast, a mouse monoclonal antibody, 2H8, reacted only with monensin and had a much lower KD = 3 x 10(-8) M for monensin . Monoclonal antibody 2H8 was used to develop a competitive microELISA able to detect as little as 5 ng/ml of monensin in solution which corresponds to 75 pg or 110 fmol of this hapten per Terasaki well. Cas Lek Cesk, 1993 Sep 13, 132(17), 529 - 31 {Systemic administration of antibiotics in therapy of brain abscesses . Present trends and possibilities}; Kolar M et al.; The authors describe possibilities as regards selection of antibiotics in the general treatment of brain abscesses . They mention the most frequent aetiological agents of the disease in relation to predisposing factors and site . Systemic antibiotherapy along with surgery is considered by the authors decisive in the therapy of these conditions. Nucleic Acids Res, 1993 Sep 11, 21(18), 4174 - 9 A molecular basis for human hypersensitivity to aminoglycoside antibiotics; Hutchin T et al.; We have investigated the distribution of mitochondrial DNA polymorphisms in a rare maternally transmitted genetic trait that causes hypersensitivity to aminoglycoside antibiotics, in the hope that a characterization of its molecular basis might provide a molecular and cellular understanding of aminoglycoside-induced deafness (AGD) . Here we report that the frequency of a particular mitochondrial DNA polymorphism, 1555G, is associated nonrandomly with aminoglycoside-induced deafness in two Japanese pedigrees, bringing the frequency of this polymorphism to 5 occurrences in 5 pedigrees of AGD, and in 4 of 78 sporadic cases in which deafness was thought to be the result of aminoglycoside exposure; both frequencies are significantly different from the occurrence of this mutation in the hearing population, which was 0 in 414 individuals surveyed . The 1555G polymorphism occurred in none of 34 aminoglycoside-resistant individuals . We propose a specific molecular mechanism for aminoglycoside hypersensitivity in individuals carrying the 1555G polymorphism, based on the three-dimensional structure of the ribosome, in which the 1555G polymorphism favors aminoglycoside binding sterically, by increasing access to the the ribosome cleft. J Orthop Res, 1993 Sep, 11(5), 627 - 32 In vitro pharmacokinetics of antibiotic release from locally implantable materials; Miclau T et al.; Local deposition of antibiotics has became increasingly popular in the management of open fractures or osteomyelitis, and several substances have been employed as the vehicle for delivery . Although the elution characteristics of some substances have been documented, a comparative study of the characteristics of the commonly used substances could establish the clinical indications for particular vehicles . Cylindrical pellets of uniform size (6 x 4 mm) were prepared from bone graft (BG), demineralized bone matrix (DBM), plaster of Paris (POP), or polymethylmethacrylate (PMMA), with 25 mg of tobramycin/g of substance in each pellet . The pellets were suspended in phosphate buffered saline, and the antibiotic concentration in the buffer was determined at various time intervals by an enzyme immunoassay . BG and DBM eluted 70 and 45% of their antibiotic load by 24 h, and negligible amounts were detected at 1 week; POP released 17% of its load by 24 h, with trace amounts detected at 3 weeks; and PMMA eluted 7% at 24 h, with trace amounts detected for as long as 14 days . These findings suggest that the optimal vehicle for local deposition of antibiotic depends on the clinical setting . BG and DBM may be best employed when brief antibiotic coverage is required (as for acute contaminated open fractures), whereas POP and PMMA may be better suited for long-term coverage (such as for established osteomyelitis). J Orthop Res, 1993 Sep, 11(5), 619 - 26 Treatment of experimental osteomyelitis with antibiotic-impregnated bone graft substitute; Cornell CN et al.; The model of Norden was used to induce osteomyelitis in the left tibia of New Zealand White rabbits . Twenty-one days following inoculation, the animals had primary debridement and then were randomized into one of three treatment groups . Group I received no additional treatment; in Group II, plain hydroxyapatite beads were packed into the defect; and in Group III, gentamicin crobefat-loaded hydroxyapatite beads were packed into the defect . The animals were observed for 40 days after the primary debridement and then were killed . The intensity of infection was determined by swab cultures and quantitative bacterial cultures of the debrided material . At primary debridement, all of the animals in each group were equally infected . At the time of secondary debridement, only the animals in Group III had a statistically significant reduction in infection (p < 0.001) . In this study, we demonstrated that an antibiotic-loaded osteoinductive ceramic bead can effectively eliminate bacteria from an osteomyelitic cavity. J Oral Maxillofac Surg, 1993 Sep, 51(9), 982 - 5; discussion 986 Clinical evaluation of antibiotic-supplemented bone allograft; Petri WH 3rd et al.; Antibiotic-supplemented bone allograft (ASBA) was originally developed for treatment of combat-acquired, avulsive defects of the oral and maxillofacial skeleton . Earlier findings in experimental wound models showed that ASBA resulted in significantly improved wound repair of infected osseous defects when compared with conventional treatment . In this study, ASBA was evaluated in paired, comparable, mandibular third molar sockets and compared with the findings following conventional surgical removal . The results of this assessment showed that wound healing was significantly improved with the use of ASBA . Evidence produced by this clinical evaluation of ASBA suggests its potential use for other surgical bone defects when grafting is precluded by the risk of infection as a result of contamination by oral flora. Vet Q, 1993 Sep, 15(3), 112 - 7 Elimination of aminoglycoside antibiotics in milk following intramammary administration; Moretain JP et al.; The elimination in cow milk of aminoglycoside antibiotic residues (neomycin, dihydrostreptomycin, kanamycin and gentamicin) was studied after intramammary administration of eight drug formulations marketed in France . Quantitative residue analysis was performed by a cylinder plate method . The sensitivity was 0.15 microgram/ml for neomycin, dihydrostreptomycin, kanamycin and 0.025 microgram/ml for gentamicin . The mean elimination periods ranged between 4 and 13 milkings . Several ways of assessing withdrawal times are discussed. J Parenter Sci Technol, 1993 Sep-Oct, 47(5), 205 - 10 An approach to the determination of endotoxin in anesthetics and antibiotics: use of an ultrafiltration system and enzymatic LAL reaction; Justicia H et al.; An ultrafiltration system is used to obtain an endotoxin-free buffer for the LAL test . The procedure is combined with a kinetic LAL reaction of high sensitivity . This approach allows for the easy determination of endotoxin levels in parenterals with LAL-interfering substances, reducing the maximum valid dilution necessary for use in product development. J AOAC Int, 1993 Sep-Oct, 76(5), 952 - 6 Solubility of antibiotics used in animal feeds in selected solvents; Salvatore MJ et al.; The solubility of antibiotics used in animal feeds in organic solvents was determined . The solubility data could be used in identification of classes and in some cases individual members of the same class of antibiotics, and in differential step(s) in the analysis of these antibiotics . A universal solvent was developed to extract all antibiotics from animal feeds. Antimicrob Agents Chemother, 1993 Sep, 37(9), 2027 - 9 Lincosamide antibiotics stimulate dissociation of peptidyl-tRNA from ribosomes; Menninger JR et al.; At nonpermissive temperatures the peptidyl-tRNA hydrolase of pth(Ts) bacterial mutants is inactivated, and cells accumulate peptidyl-tRNA and die . Doses of erythromycin, lincomycin, or clindamycin that inhibited the growth of antibiotic-hypersensitive DB-11 pth+ cells accelerated the killing of DB-11 pth(Ts) cells at nonpermissive temperatures . Erythromycin and lincomycin also stimulated the accumulation of peptidyl-tRNA . Lincomycin and clindamycin stimulated peptidyl-tRNA dissociation from ribosomes. J Antibiot (Tokyo), 1993 Sep, 46(9), 1421 - 7 CL307-24, a new antibiotic complex from Saccharopolyspora aurantiaca sp . nov . II . Physico-chemical and biological properties; Fabre B et al.; CL307-24I, the main component of the CL307-24 complex produced by Saccharopolyspora aurantiaca sp . nov., was found to be a potent inhibitor of yeast mitochondrial ATPase . CL307-24I displayed a high degree of activity towards some coryneform bacteria and also has been shown to possess an insecticidal activity . Its biological and physico-chemical properties clearly distinguish it from previously known ATPase inhibitors. Biull Eksp Biol Med, 1993 Sep, 116(9), 272 - 4 {The cellular acid phosphatase activity in yeast-like fungi of the genus Candida exposed to ultrasound, polyene antibiotics and dyes}; Sergeev PV et al.; The activity of one of the lysosomal membrane marker enzymes--acid phosphatase from the Candida yeast fungi on their exposure to ultrasound (US), polyenic antibiotics (amphotericin B and nystatin) dye antiseptics (ethacridine lactate, methylene blue), and their combinations was assayed . The impact of US and the drugs, in particular their combination, was found to be followed by activation of the fungal lysosomal apparatus function and increases in their catabolic processes . The highest rise in lysosomal catabolic activity was found when the polyenic antibiotics were used in combination with US, which reflects the higher damaging effect of this combination against Candida lysosomal membranes than the dyes and of these antibiotics and US alone . The studies provide strong evidence for the preference of the combined use of US and the polyenic antibiotics in candidiasis as a factor enhancing their fungicidal effect against Candida yeast fungi. Ann Ital Chir, 1993 Sep-Oct, 64(5), 527 - 32 The role of the administration time of prophylactic antibiotic therapy in colorectal cancer surgery: a review of 6,069 patients from 36 randomized clinical trials; Cosimelli M et al.; The aim of the present report was to establish the effectiveness of different prophylactic antibiotic regimens and administration times in colorectal cancer surgery . Six thousand and sixty nine patients from 36 selected randomized clinical trials, published between 1980 and 1989, were reviewed . The occurrence of septic events, isolated bacterial strains, fever and postoperative hospitalization times were also analyzed . The therapeutic schedules that included the perioperative administration of antibiotics provided better results that those that did not (p . less than .0001 for infections both specifically related and unrelated to colorectal surgery) . The number of postoperative administrations did not affect the clinical results, even if the predominant choice was to give more than one administration of antibiotics . A factorial design demonstrated that prolonging the perioperative administrations up to the postoperative period provided statistically significant benefits (p less than .0001) only with regard to the risk of infections that were not specifically related to colorectal surgery. Biol Pharm Bull, 1993 Sep, 16(9), 908 - 11 Distinct effects of clinically used anthracycline antibiotics on ras oncogene-expressed cells; Tsuchiya KS et al.; Doxorubicin, pirarubicin, and FAD-104, but not aclarubicin or MX 2, flattened the morphology of NIH3T3 cells that had been transformed by human H-ras and K-ras . The effect appeared on almost all cells, as early as 2 d following exposure to the antibiotics at concentrations inhibiting cell growth by 50% or more . The morphological alteration accompanied other normal cell phenotypes, such as the restoration of actin stress fibers, anchorage dependence of cell growth and an increase in nucleoside diphosphate (NDP) kinase activity . NIH3T3 cells transformed by src and other tumor cell lines responded less prominently, if at all. Biochemistry, 1993 Aug 17, 32(32), 8068 - 74 Structure of the altromycin B (N7-guanine)-DNA adduct . A proposed prototypic DNA adduct structure for the pluramycin antitumor antibiotics; Sun D et al.; Altromycin B belongs to the pluramycin family of antitumor antibiotics, which also includes kidamycin, hedamycin, pluramycin, neopluramycin, DC92-B, and rubiflavin A . These potent antitumor compounds react with DNA in as yet imprecisely determined ways . In the present investigation, we have used gel electrophoresis methods in combination with nuclear magnetic resonance and mass spectrometry to determine the structure of the altromycin B-DNA adduct . High-resolution gel electrophoresis demonstrated that guanine was the reactive base, and N7 was implicated from experiments in which N7-deazaguanine was used in place of guanine in a strand breakage assay . Experiments using supercoiled DNA demonstrated that altromycin B and related drugs intercalated into DNA, which implicated this as a common mechanism for binding of the pluramycin antibiotics to DNA . The altromycin B-guanine adduct was isolated from calf thymus DNA after thermal depurination of the alkylated DNA . Mass spectrometry confirmed that altromycin alkylated DNA through guanine, and 1H- and 13C-NMR was used to confirm the covalent linkage sites between altromycin B and guanine . On the basis of these results, we propose that altromycin B first intercalates into DNA via a threading mechanism, reminiscent of nogalamycin, to insert the disaccharide into the minor groove and position the epoxide in the major groove in proximity to N7 of guanine . Nucleophilic attack from N7 of guanine leads to an acid-catalyzed opening of the epoxide, resulting in the altromycin B-DNA adduct . On the basis of these results, a general mechanism for the interaction of the pluramycin family of antibiotics with DNA is proposed. Gene, 1993 Aug 16, 130(1), 107 - 16 Hybridization and DNA sequence analyses suggest an early evolutionary divergence of related biosynthetic gene sets encoding polyketide antibiotics and spore pigments in Streptomyces spp; Blanco G et al.; The whiE gene cluster of Streptomyces coelicolor, which is related to gene sets encoding the biosynthesis of polycyclic aromatic polyketide antibiotics, determines a spore pigment . Southern blotting using probes from three different parts of the whiE cluster revealed related gene sets in about half of a collection of diverse Streptomyces strains . A 5.2-kb segment of one such cluster, sch, previously shown to determine spore pigmentation in Streptomyces halstedii, was sequenced . Seven open reading frames (ORFs), two of them incomplete, were found . Six of the ORFs resemble the known part of the whiE cluster closely . The derived gene products include a ketosynthase (= condensing enzyme) pair, acyl carrier protein and cyclase, as well as two of unidentified function . The seventh ORF diverges from the main cluster and encodes a protein that resembles a dichlorophenol hydroxylase . Comparison with sequences of related gene sets for the biosynthesis of antibiotics suggests that gene clusters destined to specify pigment production diverged from those destined to specify antibiotics early in the evolution of the Streptomyces genus. Nucleic Acids Res, 1993 Aug 11, 21(16), 3671 - 5 A quantitative assay to measure the relative DNA-binding affinity of pyrrolo{2,1-c} {1,4}benzodiazepine (PBD) antitumour antibiotics based on the inhibition of restriction endonuclease BamHI; Puvvada MS et al.; An assay has been developed (restriction endonuclease digestion assay--RED100) based on inhibition of the restriction endonuclease BamHI that is capable of quantitative evaluation of the relative DNA-binding affinity of pyrrolo{2,1-c} {1,4}benzodiazepine (PBD) antitumour antibiotics . This method provides comparable results to those obtained from thermal denaturation and ethidium bromide displacement assays but is much more sensitive, discriminating between molecules of similar structure such as DC-81, iso-DC-81 and neothramycin . The results reveal a trend between relative DNA-binding affinity and in vitro cytotoxicity for the PBDs in two tumour cell lines studied. Biochem Pharmacol, 1993 Aug 3, 46(3), 542 - 6 Interaction of the orally active dianionic cephalosporin cefixime with the uptake system for oligopeptides and alpha-amino-beta-lactam antibiotics in rabbit small intestine; Kramer W et al.; The uptake of two orally active beta-lactam antibiotics of different chemical structure, the zwitterionic alpha-aminocephalosporin cephalexin and the dianionic carboxymethoxyimino-cephalosporin cefixime, by brush border membrane vesicles obtained from rabbit small intestine and their molecular interaction with the H+/oligopeptide transport system were investigated . The uptake of both compounds was stimulated by an inwardly directed H(+)-gradient with a profound pH-maximum for cephalexin at pH 6outside and pH 7.4inside whereas cefixime uptake was maximal below pH 5outside . Modification of histidyl residues of membrane proteins led to a complete loss of pH dependence of transport of both cephalosporins . The uptake of cephalexin was competitively inhibited by cefixime and dipeptides and vice versa that of cefixime by cephalexin and dipeptides . The uptake of cefixime was trans-stimulated by cephalexin and glycyl-L-proline whereas cephalexin uptake could only be trans-stimulated by glycyl-L-proline, not by cefixime . Photoaffinity labeling with {3H}benzylpenicillin as a direct photoaffinity probe of the H+/oligopeptide transport system demonstrated a direct molecular interaction of both cephalexin and cefixime with this transporter in the pH range of 5-8 . Thermal pretreatment of membrane vesicles inhibited the cephalexin transport system temperature-dependently, whereas cefixime uptake was not inhibited, but stimulated . Taken together we conclude that dianionic cephalosporins like cefixime bind to the transport system shared by oligopeptides and alpha-amino-beta-lactam antibiotics . Their transport across the enterocyte brush border membrane, however, may occur to a significant extent by a different transport system. Fundam Appl Toxicol, 1993 Aug, 21(2), 164 - 73 Tapetal effect of an azalide antibiotic following oral administration in beagle dogs; Fortner JH et al.; An azalide antibiotic (CP-62,993) was administered at 100 mg/kg by oral gavage once daily for 35 consecutive days to 3 normal Beagle dogs (tapetal) and 3 Beagle dogs lacking a clinically apparent ocular tapetum (atapetal) . The total dose delivered was approximately 100-fold the recommended clinical dose . Bilateral ophthalmoscopic changes were observed in the treated tapetal dogs on Day 36, consisting of mild to moderate tapetal decoloration with loss of the normal color change at the junction with the nontapetal fundus and muting of reflectivity of the normally highly reflective tapetum; treated atapetal and all control tapetal and atapetal dogs had no ophthalmoscopic changes . Microscopic examination of ocular tissue revealed rudimentary tapetal cell layers in the correct location in untreated, clinically atapetal eyes . Tapetal cells from treated tapetal and atapetal dogs were swollen and vacuolated, and contained intracytoplasmic, electron-dense debris but no recognizable tapetal rodlets . Lysosomal lamellar bodies were observed in the retinal ganglion cells of both treated groups and were neither enhanced nor reduced by the presence of a functional tapetum . Necrosis and inflammation were not observed in any ocular tissue . The altered ophthalmoscopic appearance of treated tapetal dogs was not influenced by the retinal changes because any effect on retinal transparency would have been seen in treated atapetal dogs . The decoloration and muting of reflectivity observed clinically in the tapetal fundus of dogs following prolonged exposure to high levels of CP-62,993 result from unique changes within the ocular tapetum itself and cannot be interpreted to be of consequence to nontapetal species including humans. Cesk Farm, 1993 Aug, 42(4), 173 - 6 {Polyvalent antibiotics in ambulatory practice}; Blahutova A et al.; The present paper analyzes the consumption of antibiotics from the viewpoint of the diagnosis, specialization of the prescribing physician, and the age and sex of the out-patients . The analysis concerns the prescription within two months in a pharmacy at a policlinic . The results are presented according to the frequency of diagnosis, polyvalence of the antibiotics and the specialization of the prescribing physician. J Parasitol, 1993 Aug, 79(4), 553 - 8 Glycoside antibiotics alone and combined with tetracyclines for prophylaxis of experimental cryptosporidiosis in neonatal BALB/c mice; Fayer R et al.; Glycoside antibiotics including the macrolide antibiotics azithromycin, clarithromycin, and erythromycin and the aminoglycoside paromomycin were administered alone or combined with doxycycline, minocycline, or tetracycline to neonatal BALB/c mice experimentally infected with Cryptosporidium parvum . Glycosides at 100 or 200 mg/kg of body weight and tetracyclines at 50 mg/kg of body weight were dissolved in dimethylsulfoxide (DMSO), which was then diluted with phosphate-buffered saline (PBS) and given orally by gavage . Drugs were administered at 0, 24, 48, and 72 hr postinfection (PI) for prophylaxis . Histologic sections of ileum, cecum, and colon from tissues fixed at 96 hr PI were examined microscopically to determine the number of developing parasites and assign a quantitative score based on infectivity . All groups that received glycosides had significantly (P < 0.01) lower scores than controls that received only DMSO/PBS . A range in efficacy was apparent . None or extremely few parasites were found in paromomycin- and azithromycin-treated groups, whereas few to moderate numbers of parasites were found in erythromycin- and clarithromycin-treated groups . The addition of tetracyclines did not consistently result in significantly lower scores. Immun Infekt, 1993 Aug, 21(4), 111 - 4 {Antibiotic therapy in pregnancy}; Friese K; Antibiotics are the most frequently prescribed medications in pregnancy, their application and choice should be made according to the highest criteria . Penicillins and cephalosporins can be safely used in pregnancy, however, their side effects such as allergic reactions present a greater therapeutic problem . Tetracyclines, chloramphenicol and quinolones are strictly contraindicated in pregnancy . 5-nitroimidazole derivatives, aminoglycosides and sulfonamides are indicated only in severe infections . Not only the risk of malformation is increased in the embryonic stage, i.e . in the first 8 weeks of gestation, but also at the time of delivery with the use of drugs as sulfonamides, which can cause icterus. J Med Microbiol, 1993 Aug, 39(2), 147 - 54 The application of flow cytometry to the study of bacterial responses to antibiotics; Gant VA et al.; Experiments were performed to determine whether a modern flow cytometer could be used to study bacterial populations in suspension, with particular reference to their morphological characteristics and their responses to antibiotics . The FACScan, a commercial benchtop flow cytometer fitted with an air-cooled laser, designed primarily for the study of eukaryotic peripheral blood mononuclear cells, yielded reproducible data relating to bacterial shape and internal architecture . It was sensitive enough to detect changes in bacterial morphology on entry into the growth cycle and after exposure to antibiotics . Antibiotic-induced morphological changes affecting subpopulations of bacteria were sufficiently specific to allow differentiation between antibiotics with different cell-wall enzyme targets . Simultaneously, the effect of such antibiotics on the integrity of the outer cell membrane of Escherichia coli was assessed by measurement of the association of the nucleic acid-binding dye propidium iodide with the bacteria . These experiments demonstrated complex patterns of probable cell-wall leakage, related to the modes of action of the antibiotics . The FACScan is a useful and sensitive tool for the study of the morphology and physiology of bacterial populations in suspension, and is especially applicable to the study of antibiotic action. J Med Microbiol, 1993 Aug, 39(2), 100 - 6 Influence of subinhibitory levels of antibiotics on expression of Escherichia coli lipopolysaccharide and binding of anti-lipopolysaccharide monoclonal antibodies; Nelson D et al.; The expression of Escherichia coli lipopolysaccharide (LPS) and the binding capacity of anti-LPS monoclonal antibodies (MAbs) to E . coli grown in the presence or absence of subinhibitory concentrations of various antibiotics was studied . Four E . coli strains (three clinical blood-culture isolates and an isogenic, non-capsulate mutant of the O18:K1 parent) were grown in the presence of the beta-lactam antibiotic, ampicillin, the aminoglycoside gentamicin, the fluoroquinolone ciprofloxacin and chloramphenicol . The techniques of silver staining, immunoblotting, whole-cell ELISA and flow cytometry were all used to monitor the expression of LPS on the bacteria and the binding of the anti-LPS MAbs . Treatment with ampicillin, chloramphenicol and ciprofloxacin resulted in enhanced binding of anti-core reactive MAbs to most E . coli strains . Overall, treatment with gentamicin produced the least effect on MAb binding . The presence of chloramphenicol decreased the expression of high molecular mass O-antigen or increased the expression of low molecular mass substituted E . coli LPS or both . These results further illustrate that LPS core, especially the inner-core region, becomes more accessible to antibodies when bacteria are grown in the presence of certain antibiotics . Possible synergy between antibodies and antibiotics for treatment of septicaemia and septic shock remains an intriguing possibility. Jpn J Antibiot, 1993 Aug, 46(8), 736 - 47 {Criteria for clinical evaluation of antibiotics in pediatrics . The purpose and process for establishing the criteria}; Fujii R et al.; This paper describes the purpose and process for establishing "Criteria for Clinical Evaluation of Antibiotics in the Pediatric Field", which was reported in the Japanese Journal of Antibiotics Vol . 46, May, 1993 . The Criteria Committee was organized in November 1991 . Four meetings were held to establish the draft criteria . The criteria were applied to the evaluation of oral cephem S-1108 and parenteral cephem SCE-2787 . When the criteria were compared with the conventional criteria, the results indicated that no difference was obtained in the efficacy rate as a whole, the sum of "Good" and "Excellent" cases, but there was a difference in the cases judged to be "Excellent" . Partial alteration was made to the draft criteria and the Committee produced the final version of the criteria . However, the criteria are far from complete, so it will be subjected to further revision it accordance with future advance in chemotherapy. Eur J Clin Microbiol Infect Dis, 1993 Aug, 12(8), 622 - 5 Computerised calculation of the true costs of antibiotic therapy; Kerr JR et al.; A system for computerised calculation of the drug costs and hidden costs of antibiotic therapy is described . A previously developed method for costing antibiotic therapy was used to quantify hidden costs arising from intravenous administration, labour, serum antibiotic assays, monitoring of haematological and biochemical indices, and disposal of sharp instruments . These calculations were installed into a software system using spreadsheets (Microsoft Excel/Windows) . Cost calculations were simplified as a result of automated calculation with centralised cost updating, a facility for new antibiotics, a facility for atypical regimens, availability to a number of users, password protection and a facility for multiple courses of intravenous antibiotic therapy. Aliment Pharmacol Ther, 1993 Aug, 7(4), 463 - 6 Short report: treatment of Helicobacter pylori-associated duodenal ulcer with omeprazole plus antibiotics; McCarthy CJ et al.; Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common . Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse . This study investigates the effect of omeprazole with antibiotics in H . pylori-associated duodenal ulceration . Forty-three patients with endoscopically proven duodenal ulcer and H . pylori entered this study . Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s . and 500 mg tetracycline t.d.s . Four weeks after completing the treatment, 81% (35/43) had a healed duodenal ulcer, and 58% (25/43) had H . pylori eradication . In those who healed, at one year 21 remained H . pylori-negative, 12 had persistent H . pylori infection and 2 had re-infection . The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re-infected, and only 1 was H . pylori-negative . This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer relapse than omeprazole alone. Respir Med, 1993 Aug, 87(6), 449 - 54 Effect of antibiotics on sputum inflammatory contents in acute exacerbations of bronchiectasis; Ip M et al.; We studied the changes in sputum neutrophil chemotactic activity (NCA) and elastolytic activity (EA) in acute exacerbations of bronchiectasis before and after treatment with oral antibiotics . Twelve patients who chronically produced sputum were assessed in the stable state, and when they subsequently developed symptoms of acute exacerbations, prior to initiation of antibiotics, during 2 weeks of antibiotics, and at 2 and 6 weeks after stopping antibiotics . NCA was measured using modified Boyden's technique with multiwell chemotaxis chamber, and EA with N-succinyl-trialanine-p-nitroanilide as elastase substrate . All 12 patients had NCA (49.3 +/- 8.69% FMLP response) and EA (50.5 +/- 17.1 mU per 100 microliters) in their sputum in the stable state . At acute exacerbation, there was significant increase in NCA (P < 0.001) and EA (P < 0.05) . All responded clinically after 1 week of antibiotics, and this was associated with a decrease in NCA and EA back to the levels in stable state . A further week of antibiotics did not result in further decline of NCA or EA . Three patients had another acute exacerbation clinically between 2-6 weeks after stopping antibiotics and their NCA and EA rose again . In the other nine patients, both NCA and EA at 2 and 6 weeks post-treatment were similar to pre-exacerbation levels . Our findings suggest that short course antibiotics effectively control the upsurge in inflammatory activity in acute exacerbations, but has little effect on chronic airway inflammation.(ABSTRACT TRUNCATED AT 250 WORDS) J Hosp Infect, 1993 Aug, 24(4), 309 - 11 Setting standards--antibiotic policies; Gerken A; It is important to choose appropriate topics for audit in order to produce satisfactory results and maintain interest and enthusiasm . A trail of incomplete audit cycles is unhelpful and demoralizing . The audit should be carefully designed and a vital stage is choosing appropriate standards upon which to measure current performance . An agreed policy provides a practical standard against which to audit the use of antibiotics. J Pharm Pharmacol, 1993 Aug, 45(8), 756 - 8 Effect of macrolide antibiotics on ciliary motility in rabbit airway epithelium in-vitro; Takeyama K et al.; We have studied ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method in-vitro . Addition of erythromycin and roxithromycin increased CBF in a dose-dependent fashion, whereas clarithromycin was without effect . The rank order potency of macrolide was roxithromycin > erythromycin >> clarithromycin . The roxithromycin-induced increase in CBF was not altered by propranolol, AA-861, or verapamil, but partially attenuated by indomethacin . Roxithromycin increased intracellular cAMP concentrations . These results suggest that certain macrolides can stimulate airway ciliary motility probably via prostaglandin- and cAMP-dependent regulatory pathways, which may affect mucociliary transport function in the respiratory tract. Cancer Res, 1993 Jul 15, 53(14), 3336 - 42 Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics; Hinman LM et al.; The calicheamicin family of antitumor antibiotics are capable of producing double-stranded DNA breaks at sub-picomolar concentrations . Their potency suggested that the calicheamicins would be excellent candidates for targeted delivery and a hydrazide prepared from the most potent and abundant of the naturally occurring derivative, gamma 1I, was linked to oxidized sugars on CT-M-01, an internalizing anti-polyepithelial mucin antibody . The conjugates retained the immunoreactivity of the unmodified antibody and were specifically cytotoxic toward antigen positive tumor cells in vitro and in vivo . Hydrazide analogues of less potent calicheamicin derivatives were also prepared and conjugated to CT-M-01 . Comparison of the therapeutic efficacy of the conjugates against the MX-1 xenograft tumor implanted s.c . in nude mice showed that conjugates of derivatives missing the rhamnose, a sugar residue that is part of the DNA binding region of the drug, were not as promising as antitumor therapies . However, conjugates of two derivatives, alpha 3I and N-acetyl-gamma 1I, in which the rhamnose residue is present but the amino sugar residue of the parent drug is either missing or modified, significantly inhibited tumor growth over a 4-fold dose range and produced long-term tumor-free survivors . Sterically hindering methyl groups adjacent to the disulfide in the linker further increased the therapeutic window of these potent conjugates. FEBS Lett, 1993 Jul 12, 326(1-3), 95 - 100 Retention of native-like structure in an acyclic counterpart of a beta-sheet antibiotic; Maplestone RA et al.; An acyclic derivative of the cyclic peptide antibiotic, ramoplanin, has been prepared . In aqueous solution, two-dimensional NMR spectroscopy indicates that the acyclic form adopts a threshold population of conformers in which at least part of the beta-sheet characteristic of the intact ramoplanin persists . Thus, despite losing the entropic benefit which the macrocycle must lend to beta-sheet formation, the polypeptide chain of the acyclic ramoplanin appears to display an innate tendency to adopt a native-like conformation. Clin Orthop, 1993 Jul, (292), 210 - 4 Prophylaxis with systematic antibiotics versus gentamicin bone cement in total hip arthroplasty . A ten-year survey of 1,688 hips; Josefsson G et al.; In 1976, nine Swedish orthopedic departments started a prospective, randomized, and controlled study in which the prophylactic effect of systematic antibiotics (SAs) was compared with gentamicin bone cement (GBC) in 1,688 consecutive total hip arthroplasties (THAs) . After ten years, 13 deep infections had occurred in the SA group and nine in the GBC group . The earlier reported significant difference at two and five years in favor of GBC no longer existed . No allergic or toxic reactions have been reported in the GBC group. J Clin Gastroenterol, 1993 Jul, 17(1), 14 - 7 Are antibiotics useful in the management of nontoxic severe ulcerative colitis? Peppercorn MA. Severely ill patients with ulcerative colitis are usually treated with parenteral corticoids . Those with signs of systemic toxicity usually receive antibiotics as well . However, the role of antibiotics in patients without high fever, profound leukocytosis, peritoneal signs or megacolon is not clear . Since 1985, seven patients who were admitted to the hospital with severe ulcerative colitis but without signs of toxicity have received broad spectrum antibiotics . The patients ranged in age from 21 to 65 years: four were male; all were white . Stools for infectious agents were negative . Each patient received intravenous prednisolone at a dose of 60 mg/24 h . After 7 days, each patient continued to have eight to 10 bloody stools per day with low-grade fever and leukocytosis . Institution of broad-spectrum antibiotics was associated with a striking resolution of bloody diarrhea and normalization of temperature . No patient has required colectomy in follow-up of 2-9 years . Whether the antibiotics are treating an undetected pathogen or eliminating non-pathogenic bacteria contributing to the inflammatory process is not clear . I suggest that severely ill patients with ulcerative colitis deserve a trial of antibiotics before being considered failures of medical therapy. Geburtshilfe Frauenheilkd, 1993 Jul, 53(7), 488 - 91 {Clarithromycin, a new macrolide antibiotic . Effectiveness in puerperal infections and pharmacokinetics in breast milk}; Sedlmayr T et al.; The aims of this study were, to determine the pharmacokinetic parameters of clarithromycin and to study the passage of the drug into breast milk . Twelve patients (age 24 to 38; weight 44 to 83 kg), suffering from puerperal infections, were treated orally with 250 mg clarithromycin b.i.d . for 6 days . Samples of blood and breast milk were taken at timed intervals . The specimens were assayed for clarithromycin and its active metabolite 14-hydroxy-clarithromycin by HPLC and electrochemical detection . Serum concentrations of clarithromycin in the investigated patients were higher than those reported in healthy volunteers . The mean peak concentrations of clarithromycin and 14-hydroxy-clarithromycin in breast milk were about 25%, and 75% respectively of the corresponding serum concentrations . All patients recovered within 2 to 4 days and no drug-associated side effects (eg . gastrointestinal) were noted . Clarithromycin appears to be an appropriate antibiotic for the treatment of puerperal infections and (because of its considerable concentrations in breast milk) for puerperal mastitis as well. J Antibiot (Tokyo), 1993 Jul, 46(7), 1139 - 44 PC-766B, a new macrolide antibiotic produced by Nocardia brasiliensis . II . Isolation, physico-chemical properties and structure elucidation; Kumagai K et al.; A new macrolide antibiotic, PC-766B, was isolated from the cells of Nocardia brasiliensis SC-4710 by acetone extraction, and purified by gel filtration, silica gel chromatography, HPLC and TLC . The structure of PC-766B was determined by NMR spectral analysis to be a new class of the hygrolidin family antibiotics . PC-766B had a 16-membered macrocyclic lactone ring, a 6-membered hemiketal ring and a 2-deoxy-D-rhamnose moiety . DL-alpha-Tocopherol, known as an antioxidant agent, significantly improved the stability of PC-766B and prevented the decomposition of PC-766B during the storage of the antibiotic. J Antibiot (Tokyo), 1993 Jul, 46(7), 1076 - 81 Vicenistatin, a novel 20-membered macrocyclic lactam antitumor antibiotic; Shindo K et al.; A new antitumor antibiotic vicenistatin was isolated from the culture broth of Streptomyces sp . HC34 . The structure of vicenistatin was elucidated by NMR spectral analysis . Vicenistatin exhibited antitumor activity against human colon carcinoma Co-3 in the xenograft model. Int J Biomed Comput, 1993 Jul, 33(1), 65 - 81 Modeling and simulating the evolution of resistance against antibiotics; Massad E et al.; An epidemiological model is proposed for the spread of resistance against antibiotics in populations of bacterial pathogens . The host population, which is assumed to be constant, is divided into three compartments, viz . susceptible, hosts infected by an antibiotic-sensitive strain and hosts infected by a resistant strain . It is further assumed that susceptibles can be infected by either strain and that there is a possibility for cross-infection between hosts infected by the two strains . The rate of cross-infection can be enhanced by mutations or the transfer of plasmids conferring resistance . Equilibrium analysis was performed in order to determine which of the strain 'wins' the competition by the host . It is assumed that the eventual shift in the competition between the two strains is due to treatment by antibiotic (selective pressure). Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 48 - 51; discussion 63-4 Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Health maintenance organization; Miller Z; HMOs can provide economical outpatient parenteral antibiotic therapy that takes advantage of existing nursing and physician staff as well as centralized pharmacy services . Reimbursement problems are nonexistent . Treatment is possible in the home or clinic . In the model presented, the therapeutic program is initiated and supervised by infectious disease specialists. Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 44 - 7; discussion 62-3 Outpatient parenteral antibiotic therapy . Managemnt of serious infections . Part II: Amenable infections and models for delivery . Emergency department and urgent care center; Lindbeck G; Two approaches to outpatient parenteral antibiotic therapy are commonly used in the emergency care setting . One is daily administration of a parenteral antibiotic followed by oral therapy if clinical response has been satisfactory . The other is administration of a single parenteral dose to initiate a course of oral therapy . Both treatment strategies have proved effective in preliminary studies. Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 31 - 5; discussion 59-60 Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Pyelonephritis; Millar LK; Outpatient therapy is currently recommended for women with uncomplicated pyelonephritis, not those with sepsis, renal insufficiency or pathology, or significant underlying disease . Parenteral therapy is usually initiated in the emergency department, followed by oral therapy at home . Pregnant patients are hospitalized, though studies suggest that outpatient therapy may be appropriate. Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 25 - 30; discussion 58-9 Outpatient parenteral antibiotic therapy . Management of serious infections, Part II: Amenable infections and models for delivery . Pelvic inflammatory disease; Sweet RL; Due to its polymicrobial origins and potential for causing infertility and ectopic pregnancy, pelvic inflammatory disease (PID) is a particularly challenging infection to treat . Treatment of mild PID has long been standardized: a single dose of an IM antibiotic followed by oral therapy . Patients with advanced PID requiring long-term therapy may be candidates for outpatient parenteral therapy. Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 20 - 4, discussion 58 Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Pneumonia and chronic lung disease; Trowbridge JF; The need for medical support is the determining factor when selecting patients with acute pneumonia for outpatient therapy . Patients are often too old or too sick for early discharge, but a large subgroup can continue parenteral therapy as outpatients . Other pneumonia patients, as well as patients with infectious flares of chronic lung disease, can be treated with outpatient therapy alone. Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 15 - 9; discussion 57-8 Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Meningitis; Bradley JS; Children with bacterial meningitis are ideal candidates for outpatient parenteral antibiotic therapy; most recover from the acute infection within five days and do not require skilled nursing observation of neurologic status during the entire course of therapy . Before discharge, the child should be afebrile, show a good response to therapy, and demonstrate no neurologic abnormalities. Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 10 - 4; discussion 57 Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Cellulitis; Lindbeck G et al.; Most patients with cellulitis can be managed on an outpatient basis, frequently with a single dose of parenteral antibiotic followed by oral therapy . Cellulitis must first be differentiated from more serious soft tissue infections that require aggressive inpatient therapy and perhaps surgery . Patients with preexisting medical conditions, such as diabetes, need to be carefully followed if treated as outpatients. Indian J Pediatr, 1993 Jul-Aug, 60(4), 591 - 4 Antibiotic associated colitis; Ahmad SH et al.; It is a prospective study based on 100 consecutive cases of diarrhea following antibiotic therapy admitted to the pediatric services of J.N . Medical College, A.M.U., Aligarh between January to December 1987 . They had C . penicillin (50), chloramphenicol (34), ampicillin (34), gentamicin (34), cephalosporin (4) and cotrimoxazole (4) for 3 days to 3 weeks prior to the onset of diarrhea . Apart from routine and special investigations, naked eye and microscopic examination of stool, its culture for pathogens including Cl . difficile were carried out in all cases . Presence of Cl . difficile cytotoxin was demonstrated by observing the cytopathic . Effect on veru cell culture, 18 grew Cl . difficile (14 cyto toxin positive) . Frequency of fever, vomiting, abdominal distension, dehydration and duration of diarrhea was not different (p > 0.05) in the two groups . Purge rate and presence of mucus and blood in Cl . difficile positive patients was significantly higher (p < 0.05) . Eight Cl . difficile positive (7 cytotoxin+ve) were subjected to endoscopy . Three of them showed P.M . colitis and 2 non specific colitis . Chloromycetin, gentamicin and penicillin were the main culprits responsible for AAC . None of the patients given ampicillin alone suffered from AAC . The mortality was 5%. Gig Sanit, 1993 Jul, (7), 42 - 3 {Effect of industrial noise and ototoxic antibiotics on ear function in man}; Anichin VF et al.; Fifty workers of the 166 ones examined were occupationally exposed to noise; 26 of them were treated with ototoxic antibiotics . Workers of treated with antibiotics most often (69.2%) developed deterioration of acoustic function. Biopharm Drug Dispos, 1993 Jul, 14(5), 443 - 54 Toxicokinetic approach for evaluating respiratory depression effect of aminoglycoside antibiotics: species differences in drug susceptibility; Komiya I et al.; The respiratory depression effect of aminoglycoside antibiotics was studied by a toxicokinetic approach, and species differences in drug susceptibility were elucidated based on plasma concentrations . An allometric relationship was obtained between total body clearance of arbekacin, a novel aminoglycoside antibiotic, and animal body weight . The power was 0.714, less than unity, which means smaller animals have higher ability to eliminate the drug from the body and need higher doses to attain a certain steady-state plasma concentration . When the infusion rate of arbekacin was altered, the total dose required to cause the toxicologic endpoint for respiratory depression (60 per cent loss of respiratory rates) changed greatly, but the plasma concentration of arbekacin at the toxicologic endpoint remained at almost a constant level . The concentration at the toxicologic endpoint was similar for all of the animal species examined and was 650-950 micrograms ml-1, even though the total dose required to cause the toxicologic endpoint varied greatly among the animal species . These findings suggest that the toxicologic effect compartment for respiratory depression is indistinguishable from the plasma compartment, and that species differences in the total dose are due to differences in pharmacokinetics of the drug, mainly in the total body clearance, but not to differences in intrinsic susceptibility to the drug. Q J Med, 1993 Jul, 86(7), 419 - 24 The risks of symptomatic vaginal candidiasis after oral antibiotic therapy; MacDonald TM et al.; It is generally accepted that antibiotic use can result in vaginal fungal overgrowth, although evidence estimating the extent to which this causes symptomatic vaginitis is scant . In a study using the prescription of vaginal antifungal preparations as a surrogate measure of vaginal candidiasis, a cohort of women taking antibiotics had a higher incidence of vaginal candidiasis after antibiotic exposure than beforehand (relative risk 2.3; 95% confidence interval 1.9-3.0); this risk was highest in those aged 36-40 years (RR 6.0, 95% CI 2.9-12.5) . The attributable risk was highest among those who were taking cephalosporins (AR 12.8%, 95% CI 9.1-16.5) . In a case-control study, comparing previous antibiotic exposure among women using vaginal antifungal agents and matched controls, antibiotic exposure was higher among those using vaginal antifungal agents during the previous 28 days, with an odds ratio of 5.5 (95% CI 3.8-7.9). Antibiot Khimioter, 1993 Jul, 38(7), 7 - 10 {A novel antibiotic of the aureolic acid group . Isolation, physicochemical and biological properties, identification}; Fedorova GB et al.; An antibiotic complex was extracted from the culture fluid of Streptomyces phaeofaciens, strain 51 . By the physicochemical properties it was referred to the group of aureolic acid . The complex was separated to chromatographically pure components by column chromatography . The main component was designated as antibiotic 51-I . Its physicochemical and biological properties were studied . Comparison of the data on the study of antibiotic 51-I with the respective characteristics of the described antibiotics of the group of aureolic acid suggested that antibiotic 51-I is a new representative of this group. Antibiot Khimioter, 1993 Jul, 38(7), 37 - 9 {Therapeutic effect of azlocillin and its combinations with other antibiotics in experimental plague infection}; Markovskaia EI et al.; The therapeutic effect of azlocillin and its combinations with other antibiotics was studied in a model of experimental plague of albino mice . Azlocillin was shown to be efficient in the prophylaxis and treatment of the experimental plague infection . The optimal doses of azlocillin were determined . The protective action of the drug depended on the dose and the time of its administration . The therapeutic effect was mainly defined by the antibiotic dose . The use of azlocillin in not sufficiently active doses in combination with aminoglycosides (gentamicin, sisomicin and amikacin), rifampicin or doxycycline significantly increased the percentage of the animal survival by comparison with that after the use of every antibiotic alone . A synergistic effect was observed when azlocillin was used in combination with rifampicin or amikacin. Neurosurgery, 1993 Jul, 33(1), 44 - 9 Penetration of intravenous antibiotics into brain abscesses; Yamamoto M et al.; INTRA-ABSCESS CONCENTRATIONS OF the intravenously administered latamoxef (LMOX, moxalactam in the United States) and cefotetan (CTT), were studied in 11 patients with intracranial abscess . None of these patients underwent surgical ablation of the abscess . In all cases, the abscess was aspirated, and multiple aspirations were required in five patients . Antibiotic concentrations in 18 aspirates were, therefore, determined by the agar well method . LMOX concentrations in 16 aspirates drawn from nine brain abscess cases ranged from 0 to 10.9 micrograms/ml, with a mean (standard deviation) of 4.18 (3.04) micrograms/ml . The CTT concentration in one patient with a brain abscess was 8.51 micrograms/ml, and the LMOX concentration in the one remaining patient with subdural empyema was 5.20 micrograms/ml . In one patient, the serum-to-pus penetration rate of LMOX was estimated to be 0.11 against the peak value of the concentration in serum or 0.44 against the simultaneously obtained level in serum . Significantly higher concentrations of LMOX were produced in abscess cavities with multiple-dose administration or by prior drainage of pus . More-advanced stages of local inflammation, as demonstrated by computed tomography, correlated with higher concentrations . However, the routine indexes of systemic inflammation, such as body temperature, white blood cell count, and level of C-reactive protein in serum, cannot be used to predict the concentration present in intracerebral pus . A tendency for LMOX concentrations in pus obtained after single dose-administration to decrease with increasing duration from symptom onset to sampling was observed but was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) Nat Genet, 1993 Jul, 4(3), 289 - 94 Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness; Prezant TR et al.; Maternally transmitted non-syndromic deafness was described recently both in pedigrees with susceptibility to aminoglycoside ototoxicity and in a large Arab-Israeli pedigree . Because of the known action of aminoglycosides on bacterial ribosomes, we analysed the sequence of the mitochondrial rRNA genes of three unrelated patients with familial aminoglycoside-induced deafness . We also sequenced the complete mitochondrial genome of the Arab-Israeli pedigree . All four families shared a nucleotide 1555 A to G substitution in the 12S rRNA gene, a site implicated in aminoglycoside activity . Our study offers the first description of a mitochondrial rRNA mutation leading to disease, the first cases of non-syndromic deafness caused by a mitochondrial DNA mutation and the first molecular genetic study of antibiotic-induced ototoxicity. Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 40 - 3; discussion 61-2 Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Infusion center, office, and home; Poretz DM; Outpatient parenteral antibiotic therapy (OPAT) administered in an infusion center often offers the advantages but not the expense of the hospital setting . Office-based OPAT maintains the physician-patient relationship but may be impractical for the physician . Home administration is ideal for selected patients, but when it is provided by an infusion company, the physician may be sidestepped. Science, 1993 Jun 4, 260(5113), 1500 - 3 Footprinting the sites of interaction of antibiotics with catalytic group I intron RNA; von Ahsen U et al.; Aminoglycoside inhibitors of translation have been shown previously to inhibit in vitro self-splicing by group I introns . Chemical probing of the phage T4-derived sunY intron shows that neomycin, streptomycin, and related antibiotics protected the N-7 position of G96, a universally conserved guanine in the binding site for the guanosine cofactor in the splicing reaction . The antibiotics also disrupted structural contacts that have been proposed to bring the 5' cleavage site of the intron into proximity to the catalytic core . In contrast, the strictly competitive inhibitors deoxyguanosine and arginine protected only the N-7 position of G96 . Parallels between these results and previously observed protection of 16S ribosomal RNA by aminoglycosides raise the possibility that group I intron splicing and transfer RNA selection by ribosomes involve similar RNA structural motifs. Postgrad Med, 1993 Jun, 93(8), 173 - 80 Antibiotics for nursing home residents . When are they appropriate? Katz PR. Antibiotics are used often in nursing homes in response to high rates of infection . Physicians and nursing home administrators and staff need to work in concert to avoid inappropriate prescription of antibiotics in this setting . Physicians need to know how infection presents in frail, institutionalized elderly patients; strive to prevent infection; and prescribe antibiotics only in situations in which clear benefit has been demonstrated . Nursing home administrators and staff must institute comprehensive infection control programs, adopt specific guidelines for antibiotic use, and keep physicians informed about the number and types of infections and antibiotic susceptibility patterns. Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 6 - 10 Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . The team concept; Tice AD; The delivery of outpatient parenteral antibiotic therapy is a team effort that, at minimum, requires a physician, a nurse, and a pharmacist . Other specialists may be added as needed . The team may be structured in several different ways, but two basic models emerge: physician-directed and nonphysician-directed . Whatever the structure, the physician should maintain a leadership role in the care of the patient. Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 52 - 7 Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Legal issues; Lawton SE; The tremendous growth of outpatient services has spurred closer legal scrutiny of patient referrals to physician-owned companies (self-referral) . Federal "safe harbor" regulations protect certain arrangements, but much of the law remains vague . Future legislation is likely to be more specific, however . Physicians should obtain legal counsel before entering into any ownership or investment opportunities in home infusion therapy. Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 44 - 51 Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Reimbursement; Tierce JC; Reimbursement for outpatient parenteral antibiotic therapy (OPAT), like that for all health care, is regulated by a multitude of private and public policies . Not all payers reimburse all aspects of OPAT, and with those that do, obtaining payment can be a daunting task . A key to prompt payment is the correct billing code . An overview of office-based, home-based, and hospital-based OPAT reimbursement is presented. Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 39 - 43 Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Costs and benefits; Milkovich G; The costs of outpatient parenteral antibiotic therapy are outweighed by the benefits to all involved: provider, payer, patient, and society . Simple comparisons of inpatient and outpatient charges are not a true measure of costs . Recent in-depth cost-benefit analyses reveal a significant saving when indirect benefits, such as increased productivity and quality of life, are included . Even so, financial issues remain to be addressed. Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 33 - 8 Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Quality assurance; Kunkel MJ; At present, there are no accepted guidelines for quality assurance in the outpatient setting, although they are being developed . Greater emphasis is being placed on ongoing rather than retrospective improvement of quality, as measured by the care-giving process and outcome . Thus, programs need to incorporate sound methods for teamwork, communication, and documentation of services. Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 28 - 32 Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Pediatric considerations; Bradley JS; Outpatient parenteral antibiotic therapy (OPAT) is less threatening to children than in-hospital treatment and most likely reduces the risk of nosocomial infection . Most pediatric infections can be treated in the home if patients are medically stable, parents are motivated to help with therapy, and appropriate resources, such as skilled pediatric nursing, are available . The cost of pediatric OPAT is similar to that of adult OPAT. Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 21 - 7 Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Advances in i.v . delivery; Kravitz GR; Physicians who prescribe outpatient parenteral antibiotic therapy must remain abreast of advances in intravenous catheters and infusion pumps so they can select equipment that realizes the full potential of therapy and suits the patient's needs for comfort, reliability, and safety . The cost of equipment and installation can vary greatly and is thus another important consideration when choosing these devices. Clin Orthop, 1993 Jun, (291), 303 - 12 The effects of antibiotic-impregnated autogeneic cancellous bone graft on bone healing; Lindsey RW et al.; Autogeneic cancellous bone graft has been recommended as a vehicle for local antibiotic delivery . Its effect on graft incorporation, however, is unknown . The healing of defects grafted with tobramycin-impregnated cancellous bone were compared with those grafted with cancellous bone alone . Plane roentgenographs, microradiographs, bone density analyses, histologic examination, and biomechanical testing were performed on specimens throughout the course of healing . The presence of large concentrations of local tobramycin does not appear to affect the normal healing characteristics of cancellous bone graft. Biochemistry, 1993 Jun 1, 32(21), 5548 - 53 Some characteristics of DNA strand scission by macromolecular antitumor antibiotic C-1027 containing a novel enediyne chromophore; Sugiura Y et al.; A new macromolecular antitumor antibiotic, C-1027, shows potent cytotoxic effects and DNA cutting activity . The DNA cleaving properties of C-1027 are compared with those of other enediyne compounds such as neocarzinostatin, esperamicin A1, and calicheamicin gamma 1 . Even in the absence of thiols or reductants, the antibiotic C-1027 has high DNA breakage ability . Of special interest is the fact that C-1027 causes strand breaks two base pairs apart at specific sites such as 5'-TAT/3'-ATA and 5'-AGA/3'-TCT (cleavage sites in italics) in the two strands . This novel double-stranded cleavage fashion is different from that of calicheamicin gamma 1, which is found to have a 3-bp separation between cleavage sites on the two strands . The asymmetric cleavage pattern to the 3'-side and a competitive experiment with distamycin A reveal minor-groove interaction of double-helical DNA with C-1027 . This antibiotic appears to oxidize DNA through hydrogen abstraction predominantly at the C-4' carbon of deoxyribose . The activation mechanism of C-1027, which contains an enediyne chromophore of the esperamicin/calicheamicin type, has been proposed. J Infect Dis, 1993 Jun, 167(6), 1336 - 43 Effect of antibiotic class and concentration on the release of lipopolysaccharide from Escherichia coli; Evans ME et al.; The ability of six antibiotics from different classes to release radiolabeled lipopolysaccharide (LPS) from a phenotypically smooth galE mutant of Escherichia coli O111:B4 was examined . Antibiotic concentrations were 0.0625-512 micrograms/mL . LPS release increased as a function of the antibiotic concentration, reaching a limit at or near the concentration that killed the majority of bacteria . The maximum amount of LPS released by polymyxin B was 40.6% +/- 0.9%, by gentamicin 58.2% +/- 2.5%, by ciprofloxacin 65.8% +/- 2.5%, by ceftazidime 73.1% +/- 0.9%, by tetracycline 75.3% +/- 10.0%, and by imipenem 79.7% +/- 2.3% . In timed experiments, ceftazidime released 61.9% +/- 1.2%, imipenem 51.1% +/- 8.8%, and tetracycline 39.7% +/- 4.4% of the LPS within the first hour of incubation, whereas polymyxin B released 13.5% +/- 1.9%, gentamicin 9.8% +/- 3.6%, and ciprofloxacin 12.7% +/- 2.6% of the LPS (P < .05) . Fluoro-radiography and immunoblot analyses revealed similar migration patterns for antibiotic-released and cell-bound LPS on SDS-PAGE gels, suggesting similar O-polysaccharide content in the two LPS fractions . The amount and rate of LPS release from an E . coli strain was dependent upon antibiotic class and concentration. J Neurosurg, 1993 Jun, 78(6), 938 - 43 Epileptogenic effect of antibiotic drugs; Grondahl TO et al.; The epileptogenicity of antibiotic drugs represents a clinical problem, and it is well known that the use of penicillin and certain other preparations can induce seizures . In the present study, the authors investigated the epileptogenic properties of different concentrations of 12 commonly used antibiotic medications belonging to seven separate groups . The drugs were tested in the hippocampus, which has a low threshold for the development of epileptiform activity . The hippocampal slice technique, using rat tissue, was employed since absence of the blood-brain barrier allows administration of the drugs in known concentrations . The preparation was exposed to antibiotics in known concentrations and the amplitude and number of population spikes were recorded . Penicillin G was used as a reference substance . Cloxacillin (> or = 1 gm/liter), cephalothin (> or = 1 gm/liter), gentamicin (> or = 80 mg/liter), chloramphenicol (> or = 1 gm/liter), ciprofloxacin (> or = 50 mg/liter), erythromycin (> or = 1 gm/liter), and ampicillin (> or = 1 gm/liter) showed moderate to marked epileptogenic effects, whereas cefuroxime, clindamycin, cefotaxime, vancomycin, and tobramycin had no epileptogenic effects. Cesk Farm, 1993 Jun, 42(3), 143 - 4 {Preparation of the first peroral antibiotic, Anginol-tablet}; Novacek L; In 1892-1896 Ivan Honl and Jaroslav Bukovsky successfully tested pyocyaneoprotein (pyocynase), later used as the pharmaceutical preparation Tonsilan, in the therapy of crural ulcers and other bacterial diseases . In 1911 Honl prepared pyocyaneoprotein as the first antibiotic in the form of tablets called Anginol-tablets . Anginol was used in the Czech Lands in infectious diseases of the pharynx and larynx, particularly in tonsillitis, until the end of the Second World War . The present paper reports the procedure of compounding Anginol-tablets and their composition. Crit Care Nurs Clin North Am, 1993 Jun, 5(2), 313 - 23 Antibiotic agents in critical care; McCraney S et al.; The practice of infectious disease and the use of antibiotics are becoming more and more complex in the critical care patient . Critical care nurses continue to play an important role in the safe administration and the postadministration monitoring of antibiotics . Important issues include the choice of drug for specific infections, the effect of pharmacokinetics, methods for safe administration, and the postadministration monitoring for effectiveness and for adverse effects. Ann Plast Surg, 1993 Jun, 30(6), 525 - 30 Investigation of a biodegradable, implantable antibiotic delivery system on rate of wound infection; Sasmor MT et al.; Biodel, a bioabsorbable polymer, may be adapted to serve as an antibiotic delivery system for high local concentrations of drugs . In an autocontaminated, irradiated wound model with a high intrinsic infection rate, implanted gentamicin-impregnated Biodel beads prevented wound infections in the submental area of rats. J Antibiot (Tokyo), 1993 Jun, 46(6), 942 - 51 Respinomycins A1, A2, B, C and D, a novel group of anthracycline antibiotics . II . Physico-chemical properties and structure elucidation; Ubukata M et al.; Respinomycins A1, A2, B, C and D were revealed to be novel anthracycline antibiotics with molecular formulae of C51H72N2O20, C43H58N2O15, C35H43NO14, C36H45NO14 and C51H70N2O22, respectively . Their structures were determined by means of 1H-1H COSY, 13C-1H COSY and HMBC spectra . The structure of the aglycone of respinomycins was unambiguously determined by LSPD experiments and NOESY . The common skeleton of respinomycins is a new type and is distinguished from that of the nogalamycin group. J Antibiot (Tokyo), 1993 Jun, 46(6), 928 - 35 Verucopeptin, a new antitumor antibiotic active against B16 melanoma . II . Structure determination; Sugawara K et al.; The structure of a new antibiotic verucopeptin has been determined by the spectroscopic analyses and chemical degradation studies . It is a 19-membered cyclodepsipeptide which is structurally related to azinothricin and A83586C. J Antibiot (Tokyo), 1993 Jun, 46(6), 921 - 7 Verucopeptin, a new antitumor antibiotic active against B16 melanoma . I . Taxonomy, production, isolation, physico-chemical properties and biological activity; Nishiyama Y et al.; A new antitumor antibiotic verucopeptin was isolated from the culture broth of Actinomadura verrucosospora Q886-2 . It should potent cytotoxicity and specific in vivo activity against B16 melanoma . Maximum T/C value (162%) was obtained by Q1D x 1 treatment schedule. Br J Dermatol, 1993 Jun, 128(6), 619 - 26 Selective generation of CD8+ T-cell clones from the peripheral blood of patients with cutaneous reactions to beta-lactam antibiotics; Hertl M et al.; The presence, phenotype, and functional characteristics of peripheral blood penicillin-specific T lymphocytes in individuals with cutaneous allergic reactions to penicillin were investigated using in vitro long-term culture techniques . Peripheral blood mononuclear cells from two penicillin-allergic patients were stimulated in vitro with penicillin, and T-cell blasts were clonally expanded by limiting dilution . Seven T-cell clones were derived, all of which were CD3+ CD4- CD8+ HLA-DR+, and produced IL-2 and IFN-gamma upon stimulation . T-cell proliferation required the presence of antigen and autologous, but not allogeneic, antigen-presenting cells . In addition to the parent compound, the T-cell clones also developed a proliferative response to penicilloyl, the major metabolite of penicillin . The cloned T-cell lines were found to exhibit marked suppressor activity for Con A mitogenesis . The observed suppressor activity required cell-to-cell contact, as supernatants from these T-cell clones had no comparable inhibitory effect . These findings indicate that there is a predominance of penicillin-specific CD8+ T cells in the peripheral blood of individuals sensitized to beta-lactam antibiotics. Antimicrob Agents Chemother, 1993 Jun, 37(6), 1377 - 9 Elimination of quinolone antibiotic carryover through use of antibiotic-removal beads; Zabinski RA et al.; To prove the utility of antibiotic-removal beads in separating antibiotics from bacterial samples, Escherichia coli ATCC 25922 was exposed to five separate quinolones before and after each was exposed to antibiotic-removal beads . Plates treated with antibiotic solutions that were exposed to beads demonstrated antibiotic removal, and plates treated with antibiotic solutions that were not exposed to beads demonstrated antibiotic carryover . After exposure to beads, fluoroquinolone concentrations decreased from 5 micrograms/ml to 0.14 micrograms/ml (ciprofloxacin), 0.04 micrograms/ml (temafloxacin), < 0.01 microgram/ml (ofloxacin), < 0.01 microgram/ml (sparfloxacin), and 0.02 micrograms/ml (clinafloxacin) . These data indicate that antibiotic carryover can be successfully circumvented through the use of antibiotic-removal beads. Zentralbl Bakteriol, 1993 Jun, 279(2), 157 - 66 Metabolism of phosphate-limited cultures of Streptomyces . IV . Protein-phosphorylation of antibiotics-producing cultures; Ozegowski JH et al.; It has been demonstrated that in the cellular proteins of Streptomyces hygroscopicus JA 6599 and Streptomyces noursei JA 3890 b, the producers of the antibiotics turimycin and nourseothricin, respectively, phosphorylated proteins are present . Numbers and concentrations of phosphorylated proteins decreased during the idiophase as characterized by phosphate limitation, antibiotic biosynthesis and phosphatase formation . Phosphoamino acids of serine, threonine and tyrosine were found in the hydrolysates of proteins . Protein tyrosyl kinase was demonstrated in the cellular extracts . The results supports the hypothesis that protein phosphorylation possesses a function in the regulation of growth and secondary product formation. Antibiot Khimioter, 1993 Jun, 38(6), 8 - 11 {Use of the protoplast fusion and regeneration method for screening antibiotic producers among inactive strains of Streptomyces}; Malanicheva IA et al.; Intraspecies fusion of protoplasts of two strains of Streptomyces fradiae, i.e native protoplasts of an inactive strain INA 00708 and heat inactivated protoplasts of a neomycin-producing strain ATCC 10745, and regeneration of the protoplasts of the inactive strain INA 00708 resulted in formation of clones producing neomycin and clones synthesizing antibiotics of an unknown nature differing from neomycin . All the active clones were unstable and lost their antibiotic activity in subcultures . Regeneration of the protoplasts of 4 different inactive strains of Streptomyces sp . also resulted in formation of active clones which were unstable and lost their capacity for the antibiotic synthesis after the first subculture . The data in principal indicate to the possible use of protoplast fusion and regeneration in screening of cultures producing new antibiotics among inactive strains of streptomycetes . However, the efficiency of such procedures is low since the experiments are labor-consuming and the resulting active clones are genetically unstable. J R Coll Surg Edinb, 1993 Jun, 38(3), 167 - 9 Audit of antibiotic policy and wound infection in neck surgery; Murdoch DA et al.; Neck surgery on 100 consecutive patients in a unit with an established antibiotic policy was studied . An infection rate of 3% was recorded, comparing well with previously published studies . There were no major sequelae in the infected cases . A policy of no perioperative antibiotics for 'clean' surgery for benign disease, cefuroxime for 'clean' surgery for malignant disease and cefuroxime plus metronidazole for 'clean contaminated' surgery is vindicated. FEMS Microbiol Lett, 1993 May 15, 109(2-3), 123 - 9 Synchronous germination of Streptomyces antibioticus spores: tool for the analysis of hyphal growth in liquid cultures; Miguelez EM et al.; We have devised a method for obtaining synchronous and dispersed growth of Streptomyces antibioticus in liquid cultures . After ultrasonic treatment, most of the spores germinated at the same time, yielding hyphae very similar in length . Dispersed growth was achieved in media without Ca2+ and in which the levels of Fe2+ and Mg2+ were carefully controlled . Studies on the kinetics of growth carried out with synchronous cultures of young hyphae revealed a multiphasic pattern of hyphal elongation, with successive periods of linear growth and changes in growth rate at defined intervals. Thromb Haemost, 1993 May 3, 69(5), 503 - 8 Beta-lactam antibiotics inhibit agonist-stimulated platelet calcium influx; Burroughs SF et al.; beta-lactam antibiotics cause platelet dysfunction with reversible agonist-receptor inhibition, irreversible {14C}-penicillin binding, and inhibition of agonist-stimulated elevation in cytosolic Ca2+ ({Ca2+}i), occurring after 24 h exposure in vitro and after in vivo treatment . We investigated beta-lactam antibiotic-induced inhibition of rises in {Ca2+}i stimulated by thrombin, sodium arachidonate or A23187 to determine whether Ca2+ influx or intracellular release was primarily affected . The mean rise in {Ca2+}i, measured with fura-2-AM, was inhibited 43.7-84.1% by penicillin when the extracellular Ca2+ concentration ({Ca2+}e) was 1 mM, but was significantly less inhibited when {Ca2+}e was < 1 microM . NiCl2 (2 mM), that blocks Ca2+ influx, caused inhibition comparable to penicillin . MnCl2 (1 mM), that quenches the intracellular fura-2 signal, significantly decreased the rise in 1 mM {Ca2+}i when {Ca2+}e was 1 mM, but did not increase the inhibition caused by penicillin . Penicillin did not inhibit the rise in {Ca2+}i stimulated by inositol-1,4,5-trisphosphate or GTP gamma S . Therefore, beta-lactam antibiotics inhibit agonist-induced elevations of {Ca2+}i primarily through inhibition of Ca2+ influx, which probably accounts for the irreversible inhibition of platelet function seen after prolonged in vitro or in vivo treatment. J Antibiot (Tokyo), 1993 May, 46(5), 791 - 802 Conformation studies on and assessment by spectral analysis of the protein-chromophore interaction of the macromolecular antitumor antibiotic C-1027; Otani T; Characterization of the secondary structure of the antitumor antibiotic C-1027 has been made from a comparison of C-1027 and its apoprotein by various analytical means . The results indicated the antibiotic to be abundant in beta-structure by measurements of Fourier-transform infrared (FT-IR) spectroscopy and the circular dichroism (CD) spectrum, and by a prediction of the secondary structure based on the amino acid sequence of the peptide . In comparison of the IR spectra of their proteins in D2O, the apoprotein exhibited a faster H-D exchange than C-1027, indicating an increase in the "non-motile parts" of the beta-sheets formed through the protein-chromophore interaction in holo-C-1027 . The prediction of hydropathic index indicated the hydrophobic residues of the apoprotein to be predominantly located in the beta-sheet structures, suggesting hydrophobic interaction in the binding between chromophore and apoprotein . Further, the interaction between chromophore and apoprotein was detected by a fluorescence method . The result showed the dissociation constant (Kd) to be 6.88 x 10(-5) M, indicating that the chromophore is tightly bound to the protein moiety. J Bone Joint Surg Am, 1993 May, 75(5), 714 - 20 Antibiotic-leaching from polymethylmethacrylate beads; Seligson D et al.; Aminoglycoside-impregnated polymethylmethacrylate beads, which are used to deliver antibiotic directly to infected sites in the musculoskeletal system, are available as a manufactured product or they can be mold-made by a pharmacy or hand-rolled by the orthopaedist in the operating suite . We investigated the leaching of antibiotic from each of these types of beads . Our hypothesis was that the elutions of antibiotic from the three types of beads are similar . Three study groups (hand-made, mold-made, and manufactured beads), each composed of four five-bead subsets, were formed so that twenty beads of each type were tested . Each bead was leached daily in a two-milliliter aliquot of normal saline solution throughout a sixty-day period, and the aminoglycoside concentration in twenty of these aliquots was determined . Analysis of variance showed no statistically significant differences when the antibiotic elutions within each subset, between the different subsets, and between the three groups were compared . The clinically important finding of this investigation is that the leaching characteristics of the three types of aminoglycoside-impregnated beads are equivalent when the beads have been fabricated out of comparable materials. Prof Nurse, 1993 May, 8(8), 510 - 2 Be alert to an avoidable problem . Management and prevention of antibiotic-acquired diarrhoea; Robinson B; Antibiotic-associated diarrhoea is an unpleasant and distressing problem for patients and health professionals alike . Although this condition can be treated with drugs, patient relapses are common . Implementation of rigorous infection control policies are therefore required. J Clin Anesth, 1993 May-Jun, 5(3), 212 - 5 Interaction of antibiotics on pipecuronium-induced neuromuscular blockade; de Gouw NE et al.; STUDY OBJECTIVE: To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug) . DESIGN: Prospective, randomized, placebo-controlled study . SETTING: Inpatient gynecologic and gastroenterologic service at a university medical center . PATIENTS: Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia . INTERVENTIONS: Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen . Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response . At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo . MEASUREMENTS AND MAIN RESULTS: The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist . RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test . Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin . CONCLUSIONS: When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism. J Pharm Sci, 1993 May, 82(5), 518 - 20 Extraction and analysis by high-performance liquid chromatography of antibiotics in a drug delivery system for farmed fish; Rogstad A et al.; Simple assays for extraction and determination of the concentrations of the antibiotics oxytetracycline, oxolinic acid, and flumequine in a drug dosage form for farmed fish are described . HPLC with UV detection was used in the analyses . The recovery of all three drugs was approximately 100%, and the precision varied from 0.5-3.0% . The methods are applicable to the production control, quality control, and stability control of the products. Hear Res, 1993 May, 67(1-2), 13 - 9 Aminoglycoside antibiotics inhibit maxi-K+ channel in single isolated cochlear efferent nerve terminals; Takeuchi S et al.; Patch clamp recordings were obtained from isolated cochlear efferent nerve terminals . The effect of aminoglycoside antibiotics on single maxi-K+ channels was determined . At positive voltages (cytosol with respect to extracellular side), neomycin, streptomycin, and kanamycin significantly reduced the single channel current amplitude of the maxi-K+ channel from the cytosolic side . The IC50 for neomycin was 9.10(-4) M from the cytosolic side and >> 10(-3) M from the extracellular side . Streptomycin and kanamycin were less potent . No significant difference in inhibition of the single channel current amplitude by 2.5.10(-4) M cytosolic neomycin was observed between 7.10(-4) M and 10(-6) M free cytosolic Ca2+ . Neomycin had no significant effect on the open probability of the maxi-K+ channel either from the cytosolic or from the extracellular side . These findings demonstrate that the maxi-K+ channel in cochlear efferent nerve terminals can be a site of action for aminoglycoside antibiotics. J Antimicrob Chemother, 1993 May, 31 Suppl D, 1 - 16 Pharmacokinetics of antibiotics in natural and experimental superficial compartments in animals and humans; Ryan DM; Transcapillary exchange of antibiotics and other small molecules is diffusion driven and occurs in the capillary beds of the tissues . Small polar molecules are ionized at physiological pH and diffusion is pore-mediated . More lipophilic substances can also leave capillaries by the transcellular route . Splanchnic tissues have fenestrated capillary walls while somatic tissues have mainly micropores in their capillary walls . Under normal physiological conditions the ratio of capillary surface area to volume of fluid present (SA/V) is very large (> 100) and the rate of exchange of substances between capillaries, interstitial fluid and tissue fluid is extremely rapid . The structure of the interstitial space or ground substance, linking the capillary to the tissue cells, is designed to regulate the exchange of water, albumen and other solutes between the plasma and tissues . Interstitial space fluid (tissue fluid) is not simply an ultrafiltrate of plasma and has a specific chemical imbalance with plasma . Some antibiotics bind to serum albumen and it is claimed that this impairs their ability to penetrate into tissue fluids . However, the reduced concentration of albumen in the tissue fluid, relative to the plasma, is the main reason why percentage tissue penetration data based on total levels present are misleading and perpetuate the misconception that highly bound antibiotics (> 80%) have a reduced penetration potential . The majority of infections are localized in extracellular fluid . Several models have been developed to sample serially the extracellular compartment . They have yielded diverse concentration/time profiles even for the same antibiotic at similar sites (skin and subcutaneous tissues) . It has been shown that the various profiles are a direct consequence of compartment SA/V, which can range from > 100 to < 10 . In the preclinical situation, the blister model has proven popular and reproducible but it should be remembered that the delayed profile seen is an artefact of blister geometry (SA/V < 10) . On the evidence available it is likely that bacterial infections, in the presence of acute inflammation, will enhance the rate of entry of agents, while the reverse is true in areas of chronic inflammation where pathological barriers are already in place. J Antimicrob Chemother, 1993 May, 31(5), 739 - 47 Evaluation of delayed type hypersensitivity to beta-lactam antibiotics in mice; Hattori H et al.; This study was designed to determine whether delayed type hypersensitivity could be evoked by protein-unconjugated beta-lactam antibiotics emulsified with Freund's complete adjuvant (FCA) in mice . The method providing the strongest sensitization was assessed by measuring footpad swelling induced by several biweekly intervals of subcutaneous injections of 0.8 mg/mouse cephalothin with FCA, followed by intradermal challenge with 1.0 mg/site cephalothin into the footpad in four different strains of female mice . A total of three and four injections, once every two weeks, in BDF1 and DBA/2 mice, respectively, produced the greatest potential for swelling . This swelling could be reinduced by the local passive transfer of cephalothin-primed splenocytes into the footpad of naive recipient mice . Moreover, the reaction was diminished by the addition of anti-Thy-1.2 monoclonal antibody with low-toxicity rabbit complement to cephalothin-primed splenocytes . Swelling in the footpad was therefore induced via the delayed type hypersensitivity reaction, indicating T-lymphocyte dependence . When the potential for beta-lactam antibiotics to elicit delayed type hypersensitivity was investigated in BDF1 mice, eight of the nine agents employed showed a 10-90% positive incidence . This result had a significant correlation (r = 0.76) with the data for skin reaction in guinea pigs, the method generally used for estimating allergenicity . These results suggest that this procedure may be a useful tool for evaluating delayed type hypersensitivity induction during the early development of novel antibiotics, since not only can sensitization be induced with protein-unconjugated antibiotic, but also because assessment can be made using a small amount of sample. Mol Microbiol, 1993 May, 8(3), 571 - 82 Streptomyces antibioticus contains at least three oleandomycin-resistance determinants, one of which shows similarity with proteins of the ABC-transporter superfamily; Rodriguez AM et al.; Three different DNA fragments of an oleandomycin producer, Streptomyces antibioticus, conferring oleandomycin resistance were cloned in plasmid pIJ702 and expressed in Streptomyces lividans and in Streptomyces albus . These oleandomycin resistance determinants were designated as oleA (pOR400), oleB (pOR501) and oleC (pOR800) . oleA and oleC are closely linked in the chromosome as they were both obtained together in two cosmid clones that were isolated from a genomic library . Sequencing of the oleC resistance determinant revealed four complete open reading frames (ORFs) and the C-terminal end of a fifth . The functions of orf1 and orf2 are unknown since they did not show significant similarity with other sequences in the data bases . The orf3 gene product has similarity with some proteins involved in iron and vitamin B12 uptake in bacteria . The orf4 gene product had a hydrophilic profile and showed important similarity with proteins containing typical ATP-binding domains characteristic of the ABC-transporter superfamily and involved in membrane transport and, particularly, with several genes conferring resistance to various macrolide antibiotics and anticancer drugs . The last gene, orf5, is translationally coupled to orf4 and codes for a hydrophobic polypeptide containing several transmembrane domains characteristic of integral membrane proteins . Subcloning and deletion experiments limited the resistance determinant to a 0.9 kb PstI-SphI fragment and only orf4 is included in this fragment . These results suggest that resistance to oleandomycin conferred by oleC (orf4) is probably due to an efflux transport system of the ABC-transporter superfamily. J Pharm Pharmacol, 1993 May, 45(5), 466 - 72 Evaluation of the inhibitory activity on serine and aspartic proteases of 4-amino-4H-1,2,4-triazole and 5-aminothiazole derivatives structurally related to beta-lactam antibiotics; Vilain AC et al.; Twenty new derivatives of 4-amino-4H-1,2,4-triazole and 5-aminothiazole have been examined for their inhibitory potential towards serine and aspartic proteases . Upon prolonged incubation with enzyme, the phenylacetylaminothiazolium salts exhibit progressive, time-dependent inhibition of chymotrypsin according to a first-order process . The formation of a tetrahedral transition state-like complex by attack of the active-site serine at the C2-position of the pseudobase form of the thiazolium may be responsible for the observed effect . Triazolium salts appeared to be simple competitive inhibitors of this enzyme, effective in the mM range concentration . Poor inhibitions of trypsin and pepsin were also obtained in the triazolium series . In spite of their structural analogy with beta-lactams, the selected derivatives failed to inhibit human leucocyte elastase. Clin Exp Immunol, 1993 May, 92(2), 218 - 24 Therapeutic effect of granulocyte colony-stimulating factor and cephem antibiotics against experimental infections in neutropenic mice induced by cyclophosphamide; Wakiyama H et al.; Effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) against severe infections in cyclophosphamide (CY)-induced neutropenic mice were investigated by its single use or by its combination with cephem antibiotics . Treatment with rhG-CSF increased the number of peripheral blood leucocytes and strikingly shortened the duration of the neutropenic state . Most of the regained population in the peripheral blood leucocytes were neutrophils . Functions of neutrophils, such as phagocytic activity, superoxide release, and expression of Mac-1 molecules, were remarkably enhanced by administration of rhG-CSF . When rhG-CSF was administered to CY-induced neutropenic mice before infection, protective effects against various kinds of bacteria were remarkable . On the other hand, such remarkable effects were not observed when rhG-CSF was administered after infections . However, even in the case of post-infectious treatment, a combination therapy of rhG-CSF with cephem antibiotics, particularly with Cefodizime (CDZM), showed a significant improvement in the survival rate and a decrease in the number of viable bacteria in the liver . These results suggest that a combination therapy of rhG-CSF with cephem antibiotics, especially with CDZM, is an efficient regime against severe infections in patients with neutropenia induced by a heavy anti-tumour chemotherapy. Am J Ophthalmol, 1993 Apr 15, 115(4), 471 - 7 Comparison of topical ciprofloxacin to conventional antibiotic therapy in the treatment of ulcerative keratitis; Parks DJ et al.; We evaluated the efficacy of ciprofloxacin (3 mg/ml) as the sole topical antibiotic used to treat infectious keratitis in 14 patients . We compared the ciprofloxacin-treated group to a retrospective control group of 30 consecutive culture-positive patients treated with conventional therapy in which cefazolin (50 mg/ml) and fortified gentamicin sulfate (9.1 mg/ml) solutions were used . We found no remarkable difference between the control group and the ciprofloxacin-treated group regarding patient age, risk factors, need for hospitalization, and virulence of organism isolated . The average time to healing in culture-positive ciprofloxacin-treated patients was 34 +/- 33 days vs 45 +/- 71 days in the control group and this difference was not statistically significant . The duration of antibiotic therapy in the culture-positive ciprofloxacin-treated group was 27 +/- 15 days vs 33 +/- 50 days in the control group . Four of the 30 control patients required modification of their antibiotic regimen, whereas no ciprofloxacin-treated patient required a change . Ciprofloxacin appears to be an effective single agent in the treatment of ulcerative keratitis. J Biol Chem, 1993 Apr 5, 268(10), 6831 - 4 Combined purification of actinomycin synthetase I and 3-hydroxyanthranilic acid 4-methyltransferase from Streptomyces antibioticus; Jones GH; Actinomycin synthetase I, which activates the precursor of the chromophore of actinomycin, has been purified nearly 1000-fold from extracts of Streptomyces antibioticus . The enzyme has an M(r) of 45,000 and appears to function as a single polypeptide chain . The formation of the enzyme is repressed when S . antibioticus mycelium is grown on glucose as a carbon source . Several benzoic acid derivatives, including intermediates in the putative pathway for actinomycin biosynthesis, were capable of supporting ATP-pyrophosphate exchange catalyzed by actinomycin synthetase I . Interestingly, three synthetic phenoxaziones also functioned as substrates in the exchange reaction . It proved possible to purify a second enzyme involved in actinomycin biosynthesis, 3-hydroxyanthranilic acid 4-methyltransferase, from the same extracts prepared for the purification of actinomycin synthetase I and by similar procedures . Streptomyces lividans, previously shown to contain a silent gene for the enzyme phenoxazione synthase, apparently does not contain a silent pathway for the complete synthesis of actinomycin since neither actinomycin synthetase I nor the methyltransferase could be detected in strains containing a cloned sequence that activates phenoxazione synthase expression. Ulster Med J, 1993 Apr, 62(1), 50 - 7 Antibiotic pharmacoeconomics: an attempt to find the real cost of hospital antibiotic prescribing; Kerr JR et al.; Antibiotics account for a large part of all hospital pharmacy budgets, but the actual cost of their prescription is unknown . These costs include intravenous administration, labour, serum antibiotic assay, monitoring of haematological and biochemical indices, disposal of sharps and adverse effects . An in-house method of costing antibiotic therapy is presented, to quantify these hidden expenses . Since not only an awareness, but an accurate quantification, of hidden costs is required, a study of various hospital procedures relating directly to antibiotic therapy was undertaken in an acute medical ward; this involved the identification of particular staff members performing various procedures, consumables used and time taken . The cost of five-day courses of gentamicin, penicillin G, ampicillin, flucloxacillin, cefuroxime, ceftotaxime and erythromycin has been calculated; drug and hidden costs for each are presented graphically for comparison . The breakdown cost for gentamicin is presented to illustrate the method . The costing of adverse effects has not been attempted . We suggest that costings of this sort are used in cost-benefit analysis of antibiotic use . These calculations have been incorporated into a computer spreadsheet and this costing service will be offered to clinical areas of our hospital. J Antibiot (Tokyo), 1993 Apr, 46(4), 598 - 605 Pradimicins T1 and T2, new antifungal antibiotics produced by an actinomycete . II . Structures and biosynthesis; Hasegawa T et al.; Pradimicins T1 and T2 are new members of the pradimicin family of antibiotics produced by an actinomycete strain AA3798 . Pradimicins T1 and T2 are dihydrobenzo{a}naphthacenequinones substituted with 3 and 2 sugar moieties, respectively . The salient feature in their structures is an L-xylose attached to the phenolic hydroxyl group at C-11 . Bioconversion experiments using a blocked mutant B-54 of strain AA3798 not only explored a plausible biosynthetic pathway of pradimicins T1 and T2, but also provided evidence of 5S,6S configuration. Int J Syst Bacteriol, 1993 Apr, 43(2), 297 - 301 Kibdelosporangium albatum sp . nov., producer of the antiviral antibiotics cycloviracins; Tomita K et al.; A new species of the genus Kibdelosporangium is described . This soil organism forms long straight spore chains and numerous sporangium-like structures on the aerial mycelium . The new species has type IV cell walls and pattern A whole-cell sugars (meso-diaminopimelic acid, arabinose, and galactose are present), type PII phospholipids, MK-9(H4) as the major menaquinone, and no mycolic acids . On the basis of morphology and chemotaxonomy, the single isolate is assigned to the genus Kibdelosporangium . The isolate differs from two previously described species of the genus in fatty acid composition, the absence of melanin formation, and many physiological and biochemical characteristics and is identified as a new species . Accordingly, the name Kibdelosporangium albatum sp . nov . is proposed for this isolate . The type strain is R761-7 (= ATCC 55061). Gut, 1993 Apr, 34(4), 466 - 9 Short and long term outcome of Helicobacter pylori positive resistant duodenal ulcers treated with colloidal bismuth subcitrate plus antibiotics or sucralfate alone; Bianchi Porro G et al.; Thirty two patients with Helicobacter pylori positive duodenal ulcers resistant to treatment were randomly assigned to 4 weeks' treatment with sucralphate 4 g/day or colloidal bismuth subcitrate 480 mg/day plus amoxycillin from days 1 to 7 and tinidazole from days 8 to 14 . After 4 weeks, patients with unhealed ulcers were crossed over to the other form of treatment for a further 4 week period . Patients with healed ulcers were followed up for 1 year without maintenance therapy with clinical and endoscopic investigations 3, 6, and 12 months after healing . Complete healing rates at 4 weeks were 88% (15 of 17) in the colloidal bismuth subcitrate plus antibiotics group and 40% (six of 15) in the sucralphate group (p < 0.05) . After cross over, overall healing rates were 88% (22 of 25) and 47% (eight of 17), respectively (p < 0.05) . H pylori eradication occurred in 83% of patients treated with the triple therapy . Cumulative relapse rates at 12 months were 12% (two of 17) in patients in whom H pylori had been eradicated and 100% (10 of 10) in those with persistent infection after short term therapy (p < 0.05) . These results show that a colloidal bismuth subcitrate plus antibiotics regimen is highly effective in the short term treatment of resistant duodenal ulcers and that H pylori eradication can change the natural tendency to early recurrence of these ulcers. Am J Obstet Gynecol, 1993 Apr, 168(4), 1239 - 46 Antibiotics in the treatment of preterm labor; Kirschbaum T; OBJECTIVE: Clinical evidence for a relationship between chorioamnionitis and the onset of preterm labor, supported by well developed biochemical models of that interaction, motivated a review of prospective, randomized trials of antibiotic use in its prevention . STUDY DESIGN: A literature search was made of antibiotic trials applied to women at risk for preterm labor and with a clinical diagnosis of preterm labor after premature preterm rupture of membranes . A review of two retrospective case-control studies conducted on pregnant women with positive cultures for Chlamydia trachomatis is also included . RESULTS AND CONCLUSION: Results of antibiotic use in women with preterm premature rupture of membranes supports significant prolongation of the interval from rupture of membranes to delivery and improvement and neonatal outcome in treated patients. J Clin Periodontol, 1993 Apr, 20(4), 299 - 303 Prevention of transmission of resistant bacteria between periodontal sites during subgingival application of antibiotics; Preus HR et al.; This study was designed to investigate whether antibiotic resistant micro-organisms are able to contaminate and survive on syringe tips used for subgingival deposition of antibiotics, and to test simple and effective means of disinfecting the syringe tip between applications . In the first part of the study, syringe tips used for application of Minocycline subgingival formula in 20 adult periodontitis patients were cultured for bacteria resistant to this drug before and after disinfecting them with ethanol . The results showed that 80% of the unwashed syringes were culture positive for minocycline resistant bacteria, whereas only 1 ethanol washed syringe tip was contaminated . In part II of the study, after dispensing minocycline periodontal formula in 20 patients, 10 of the syringe tips were washed with ethanol while 10 were left untreated . All syringes were stored in a refrigerator for 8 days, whereafter the tips were sampled for resistant bacteria . 20% of the unwashed tips were contaminated after 8 days incubat