Brain Res, 1985 Mar 25, 330(2), 349 - 52 The aminoglycoside antibiotic, gentamicin, fails to block increases in miniature endplate potential frequency induced by the sulfhydryl reagent, N-ethylmaleimide, in low calcium solutions; Carlson CG et al.; N-ethylmaleimide (NEM) increases the frequency of miniature endplate potentials (MEPPs) at the adult rat hemidiaphragm . This sulfhydryl-alkylating agent produces comparable effects in the absence of added calcium (2 mM EGTA), suggesting that the drug releases calcium from internal stores, or promotes calcium-independent release by depolarizing the nerve terminal or interacting more directly with the release mechanism . These increases in frequency are not blocked by the aminoglycoside antibiotic, gentamicin; although the latter agent reduces quantal content and the elevations in MEPP frequency induced by high potassium solutions . The results suggest that gentamicin and NEM act at different sites at the presynaptic terminal, and that the aminoglycosides block voltage-dependent presynaptic calcium influx. JAMA, 1985 Mar 22-29, 253(12), 1774 - 6 Persistence of improvement in antibiotic prescribing in office practice; Ray WA et al.; We evaluated persistence of the prescribing improvement seen in a previous statewide controlled trial, which measured improvement in the prescribing of contraindicated antibiotics and oral cephalosporins in the year after an educational intervention . Doctors visited by physician-counselors substantially improved their prescribing of both classes of drugs . The beneficial effect of the physician-counselors persisted throughout year 2, with attributable reductions in prescribing of 30% and savings of $950 for each doctor visited . The marked and lasting improvement in prescribing produced by the physician-counselors suggests using this model to develop ongoing programs to improve prescribing. Hinyokika Kiyo, 1985 Mar, 31(3), 533 - 8 {Studies on antibiotics distribution in the post-operative cavity}; Kamidono S et al.; In 17 post-operative patients, serum and operation cavity exudate levels after 2 g administration of various cephems (CZX, LMOX, CTX, and CPZ) by one hour drip infusion were evaluated . Drug concentration in exudate (actual levels) was corrected by using an equation for the purpose of excluding blood contamination . After 2 hours from the start of infusion, theoretical levels generally were similar to actual levels . CZX: Peak exudate level was 38.9 micrograms/ml at 4 hours . Maximum exudate level/maximum serum level (E/S) was 0.31 . LMOX: Peak in exudate was 41.4 micrograms/ml at 4 hours . E/S was 0.59 . CTX: Exudate peak level was 30.8 micrograms/ml at 2 hours, and E/S was 0.53 . CPZ: Peak level in exudate was 74.0 micrograms/ml at 4 hours . E/S was 0.36 . Generally, peaks occurred at 4 hours (3 hours later than serum peaks), and their range was between 30 and 80 micrograms/ml . At 8 hours, drug levels in exudate were 10 approximately 60 micrograms/ml, and they were higher than the corresponding serum level at that time. J Gen Microbiol, 1985 Mar, 131 ( Pt 3), 561 - 70 Incorporation of fluorotryptophan into triostin antibiotics by Streptomyces triostinicus; Cornish A et al.; The quinoxaline chromophores of the antibiotics produced by Streptomyces triostinicus are derived from tryptophan . Protoplasts of this organism made novel products when they were incubated with DL-5-fluorotryptophan or DL-6-fluorotryptophan . When added to batch cultures of the organism, DL-5-fluorotryptophan, at concentrations as low as 10 microM, inhibited both mycelial growth and triostin production, but gave rise to novel products . These have been characterized, using fast atom bombardment mass spectrometry, as novel triostins in which one or both of the quinoxaline rings contain an atom of fluorine . The chromatographic properties of the triostins arising from the incorporation of DL-5-fluorotryptophan are very similar to those of triostins containing chlorine or bromine at position 6 of the quinoxaline ring; they are clearly different from those having a chlorine atom at position 7 . Accordingly, it is suggested that the carbon atom at position 5 of the indole ring of tryptophan ends up at position 6 of the quinoxaline ring system in triostins A and C. Antibiot Med Biotekhnol, 1985 Mar, 30(3), 163 - 6 {Macrotetrolide antibiotics from mycelia of Streptomyces chrysomallus}; Nefelova MV et al.; White crystalline antibiotically active substances identified as macrotetrolides were isolated from the mycelium of four actinomycetous strains, i.e . S . chrysomallus var . I, S . chrysomallus var . III, S . chrysomallus var . carotenoides and S . chrysomallus var . macrotetrolidi . The component composition of the macrotetrolide antibiotics of all four strains was identical . It was characterized by predominance of nonactin, a lower homologue . The composition ratio was the following: 69-79 per cent of nonactin, 19-29 per cent of monactin, 1-3 per cent of dinactin and the traces of trinactin and tetranactin . The strains differed in the intensity of production of the macrotetrolides and the ability to synthesize other biologically active substances. J Pharmacobiodyn, 1985 Mar, 8(3), 167 - 74 Effect of extracellular water volume on the distribution kinetics of beta-lactam antibiotics as a function of age; Tsuji A et al.; The distribution kinetics of cefazolin in rats has been examined at four different ages (1, 7, 50 and 100 weeks) . The steady state distribution volume of cefazolin, estimated from the plasma time course after i.v . injection of 20 mg/kg, varied between 136 ml/kg (50-week-old rats) and 297 ml/kg (1-week-old rats) . The extracellular fluid volume, obtained from the steady state distribution volume of inulin, varied between 126 ml/kg (50-week-old rats) and 370 ml/kg (1-week-old rats) . There was a good correlation between the steady state distribution volume of cefazolin and extracellular fluid volume (r = 0.977) . The influence of changes on the value of the plasma unbound fraction and extracellular fluid volume on the tissue-to-plasma partition coefficient of beta-lactam antibiotics was simulated by using a physiological pharmacokinetic model . The results of the simulation showed that extracellular fluid volume is an important factor affecting the distribution volume of beta-lactam antibiotics and that plasma binding plays a minor role on it . The experimental and simulation results suggested that the change in the interstitial fluid volume is a determinant factor in the age-related changes in the distribution volume of beta-lactam antibiotics. J Clin Hosp Pharm, 1985 Mar, 10(1), 67 - 72 Stability of metronidazole and ten antibiotics when mixed with magnesium sulphate solutions; Das Gupta V et al.; The chemical stabilities of metronidazole (in water) and ten antibiotics (ampicillin, carbenicillin, cefamandole, cefazolin, cefoxitin, moxalactam, nafcillin, penicillin G, piperacillin, and ticarcillin) in 5% dextrose injection (except ampicillin which was in 0.9% sodium chloride) with magnesium sulphate were studied at 25 degrees C . The clarity of the solutions did not change in 20 h . The pH values of metronidazole, nafcillin and penicillin G solutions containing magnesium sulphate were lower (at 0 and 20 h) by up to 1.2 units as compared with solutions without magnesium sulphate . The decomposition of nafcillin and penicillin G solutions was hastened significantly by magnesium sulphate due to effect on the pH values of the solutions. Antimicrob Agents Chemother, 1985 Mar, 27(3), 337 - 9 Comparison of moxalactam and cefazolin as prophylactic antibiotics during cesarean section; Rayburn W et al.; Prophylactic antibiotics have been shown to be effective in decreasing the incidence of febrile morbidity associated with cesarean section after labor . However, the relative effectiveness of different single antibiotics has been studied infrequently, and these investigations have been limited by small patient samples . Several new, broad-spectrum antibiotics are now available, and any further benefit from more traditional antibiotics for surgical prophylaxis remains untested . A randomized prospective double-blind therapeutic trial was therefore undertaken to compare the value of a first-generation cephalosporin (cefazolin) with a new third-generation cephalosporin (moxalactam) . Between July 1981 and June 1983, 254 qualifying women who underwent primary cesarean section after labor were randomly chosen for either of the two treatment groups . Although not statistically significant, the rates of febrile morbidity, wound infection, and endometritis were less for those treated with cefazolin (4.0, 3.2, and 0.8%, respectively) than for those treated with moxalactam (9.2, 7.7, and 1.6%, respectively) . No serious adverse effects were apparent in the mother and newborn infant from short-term exposure to either drug . Although the newer, more expensive, and broader-spectrum cephalosporin, moxalactam, was associated with a low postoperative febrile morbidity rate and short postpartum hospitalization, it was no more beneficial than cefazolin. J Trauma, 1985 Mar, 25(3), 224 - 7 Effectiveness of prophylactic antibiotics in the outpatient treatment of burns; Boss WK et al.; We compared wound infection rates in 133 outpatient burns treated with prophylactic antibiotics in our emergency room and 161 similar, untreated burns . Infection rates in the treated and untreated groups were 3.8% (5/133) and 3.1% (5/161), respectively . Since this was an observational cohort study, it was necessary to demonstrate the comparability of treated and untreated groups with respect to risk factors for infection, including patient age, size, location, and etiology of the burn injury, time since injury, and presence of co-morbidity . The groups were found to be comparable for all risk factors except size of burn: larger burns were over-represented in the treated group (p less than 0.05) . Even after controlling for size, antibiotic use did not lower the infection rate . These results argue strongly against routine use of systemic antibiotics in the treatment of outpatient burns. Am J Physiol, 1985 Mar, 248(3 Pt 1), G320 - 5 Structure-activity relation among macrolide antibiotics in initiation of interdigestive migrating contractions in the canine gastrointestinal tract; Itoh Z et al.; The relation between the chemical structure of commercially available macrolide antibiotics and their activity in inducing interdigestive migrating contractions (IMC) was studied in conscious dogs . It was found that the 14-membered macrolides erythromycin and oleandomycin are active in inducing IMC in the stomach in association with the endogenous release of motilin . These erythromycin- and oleandomycin-induced contractions in the stomach migrated through the small intestine in a caudad direction . Conversely, 16-membered macrolide antibiotics such as leucomycin, acetylspiramycin, and tylosin do not induce any contractions in the stomach or stimulate endogenous release of motilin . These findings suggest that the IMC-inducing activity in macrolides seems to be closely related to their chemical configuration, i.e., the structure of 14-membered macrolides with dimethylaminosugar (desosamine) bound at C-5 and neutralsugar at C-3 in glycosidic linkage in parallel is likely to be necessary for IMC-inducing activity . The mechanisms by which erythromycin and oleandomycin stimulate endogenous motilin release are not known. Surg Gynecol Obstet, 1985 Mar, 160(3), 259 - 63 Prophylactic antibiotics and closed tube thoracostomy; LeBlanc KA et al.; A prospective randomized study of 85 patients who had sustained trauma to the chest requiring closed tube thoracostomy is reported . They were segregated into two groups, one of which did not receive prophylactic cephapirin sodium . Although the series is somewhat abbreviated, it would appear that the use of prophylactic antibiotics merely for the presence of a chest tube is an unsettled issue and of no definitely proved benefit. Rev Infect Dis, 1985 Mar-Apr, 7(2), 189 - 99 Successful treatment of multiple brain abscesses with antibiotics alone; Boom WH et al.; Seven adults with multiple brain abscesses were successfully treated with antibiotic therapy alone at The George Washington University Medical Center, Washington, D.C., during 1976-1981 . Fever, meningismus, and focal neurologic signs were common presenting features . No patient presented with coma or obtundation . Etiologic agents were identified in only three cases . Computerized tomographic (CT) scans were valuable in diagnosing and monitoring the response to therapy . Decrease in the size of the lesions was noted two to nine weeks after initiation of antibiotic therapy . In all patients, clinical signs of improvement preceded evidence of resolution of lesions on CT scan . These results indicate that, in carefully selected patients in whom surgical drainage is not feasible because of the anatomic location and/or multiplicity of lesions, a prolonged course of high-dose intravenous antibiotics alone can lead to a successful outcome. JPEN J Parenter Enteral Nutr, 1985 Mar-Apr, 9(2), 220 - 4 Piggyback compatibility of antibiotics with pediatric parenteral nutrition solutions; Watson D; The compatibility of 28 parenteral antibiotics with a pediatric parenteral nutrition solution was tested using a piggyback injection technique . The parenteral nutrition solution, apparatus, and antibiotic doses simulated central venous administration to 5- and 30-kg patients . All antibiotics were injected into a running parenteral nutrition solution, distal to an in-line filter . After passing through a central venous catheter, immersed in a heated water bath, the effluent was collected, analyzed for pH, and visually inspected for precipitate formation . The effluent was not evaluated for the presence of microscopic precipitates . When given as piggyback injections, five of the 28 antibiotics increased the pH of the original parenteral nutrition solution . These were ampicillin, cefamandole, cephalothin, cephradine, and oxacillin . Two of these, ampicillin and cephradine, produced a heavy visible precipitate, found to consist of calcium and phosphorus . The injections of certain antibiotics promote the formation of an insoluble calcium phosphate precipitate . When calcium and phosphate are present in a parenteral nutrition solution, a flush procedure is recommended when injecting antibiotics which increase the pH of the original parenteral nutrition solution. Mol Gen Mikrobiol Virusol, 1985 Mar, (3), 3 - 14 {Genetic control of Actinomycetes resistance to antibiotics}; Fedorenko VA et al.; The results of studies on genetic control of resistance to antibiotics in Streptomyces strains are discussed . Cloning and sequence analysis of resistance genes yield information concerning their expression in homo- and heterologous systems, allow analysis of signal sequences responsible for initiation of transcription and translation . Cloning of genes coding for resistance to neomycin,viomycin, thiostrepton in Streptomyces and Bac . licheniformis ermD gene made them convenient selective markers for constructing vector molecules, useful for identification of homology regions in S . fradiae aph gene and TnS of E . coli; the site homologous to ermD gene has been thus revealed in S . erythreus chromosome . Possibilities of the studies aimed at elucidation of instability of many actinomycete characters using determinants of natural multiple resistance to antibiotics as a model are demonstrated . It has been shown that genetic instability is not related to the loss of plasmids and is associated with genes having chromosomal location . Simultaneous high frequency loss of a number of resistance characters determined by non-linked genes suggests the participation in gene activity regulation of actinomycete genome rearrangements . This is confirmed by evidence for such rearrangements found in strains with mutant phenotypes, including deletions in tyrosinase and streptomycin phosphotransferase genes in Mel- and StrS strains of S . reticuli and S . glaucescens. Jpn J Antibiot, 1985 Mar, 38(3), 615 - 33 {Clinical studies on TMS-19-Q.O tablets, the preparation of a new macrolide antibiotic, in the field of oral surgery}; Sasaki J et al.; Multicenter clinical trial or TMS-19-Q.O tablet was performed to evaluate the usefulness in oral surgery . The results obtained were as follows: Clinical efficacy was assessed by clinical points . The patients entered into the trial were 77 cases with periodontitis, 23 with pericoronitis, 92 with osteitis of jaw and 18 with other infections, and the each effective rates were 80.5, 60.9, 83.7 and 72.2%, respectively . Overall effective rate was 79.0% . Isolation frequency of organisms were 33.8% in periodontitis, 34.8% in osteitis of jaw and 17.4% in pericoronitis . Bacteria isolated were aerobic organisms (63.1%) and anaerobic organisms (36.9%) . TMS-19-Q.O tablet was well tolerated, and no adverse reaction was observed. Pathol Biol (Paris), 1985 Mar, 33(3), 205 - 12 {Antibiotic sensitivity of Mycoplasma pathogenic for man}; Quentin C et al.; Human pathogen mycoplasmas (Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum) are intrinsically resistant to antibiotics which inhibit the cell wall biosynthesis (beta-lactams, vancomycin, bacitracin), to polymyxins, rifamycins, sulfonamides, trimethoprim, 5-nitroimidazoles, nitrofurans and to presently available quinolones . These three species are moderately susceptible to aminoglycosides, susceptible to chloramphenicol and highly susceptible to tetracyclines . M . pneumoniae is susceptible to macrolides, lincosamins and streptogramins . M . hominis is resistant to early macrolides (erythromycin, oleandomycin, spiramycin) and susceptible to new macrolides (josamycin, midecamycin, rosaramicin), lincosamins and streptogramins . U . urealyticum is resistant to lincosamins and susceptible to macrolides and streptogramins . Discordant results from various reports can be explained by differences in methods and breakpoint concentration values . In M . pneumoniae species, two strains resistant to macrolides and lincosamins have been described . In M . hominis species, one strain resistant to tetracyclines and another one resistant to tetracyclines and chloramphenicol have been reported . Two to ten percent of U . urealyticum strains are resistant to tetracyclines . These resistances are likely to be plasmid-mediated. Handchir Mikrochir Plast Chir, 1985 Mar, 17(2), 69 - 72 {In vitro studies on Geliperm Dry as a vehicle for antibiotics and antiseptics in local burn therapy}; von Castelberg B et al.; Geliperm is a synthetic skin substitute, consisting of polysaccharid-polyacrylic plates . It is available as a soaked or a dried form (Geliperm dry) . Geliperm dry can be soaked in antibiotic or antiseptic solutions . The in vitro inhibition of bacterial growth has been measured . The optimal concentrations have been evaluated . Geliperm dry soaked in antibiotic or antiseptic solutions can be used in the treatment of burns, but does not replace early excision of burned tissue or infected necrosis. J Am Intraocul Implant Soc, 1985 Mar, 11(2), 185 - 6 Prevention of endophthalmitis by intraocular solution filtration and antibiotics; Gills JP; Gentamicin sulfate was used in a millipore-filtered irrigating solution for 12,000 cases of anterior segment surgery (extracapsular cataract extraction with posterior chamber lens implantation) without one occurrence of endophthalmitis . One instance of endophthalmitis occurred in eight cases in which unfiltered gentamicin sulfate solution was used . No side effects have been associated with the use of the millipore-filtered irrigating solution. Jpn J Antibiot, 1985 Mar, 38(3), 634 - 42 Cephem antibiotics and alcohol metabolism; Yanagihara M et al.; Mechanisms of the disulfiram-like reaction of cephem antibiotics were studied . Changes in ethanol (EtOH) and acetaldehyde (AcH) levels in the blood with EtOH loading following daily intravenous administration of cephem antibiotics were determined in rats and the following were found: The daily intravenous injection of cefazolin, cefotiam (CTM), cefsulodin, cefoxitin or ceftizoxime in no way varied the changes in the EtOH and AcH levels in the blood with EtOH loading . The daily intravenous injection of cefmetazole, cefoperazone, cefamandole, latamoxef, cefmenoxime or cefotetan caused the AcH level in the blood to be elevated significantly until at least 8 hours after the EtOH loading, but was inert on the EtOH level on the blood . The daily administration of 1-methyl-2-tetrazoline-5-thione (TZ), a compound having a partial structure similar to those of the cephem antibiotics elevating the AcH level in the blood on EtOH loading, was inert on the EtOH level in the blood but elevated the AcH level in the blood . The daily administration of 1-(2-dimethylaminoethyl)-2-tetrazoline-5-thione (MTZ), a compound having a partial structure similar to that of CTM, was inert either on the EtOH or AcH level in the blood . The cephem antibiotics elevating the AcH level in the blood all had a (1-methyl-1H-tetrazol-5-yl) thiomethyl group in the 3 position of the aminocephalosporanic acid nucleus . It was though that the disulfiram-like reaction caused by the cephem antibiotics was derived from the elevation of AcH level in the blood.(ABSTRACT TRUNCATED AT 250 WORDS) J Antibiot (Tokyo), 1985 Mar, 38(3), 302 - 11 Structure of alahopcin (nourseimycin), a new dipeptide antibiotic; Horii S et al.; The structure of alahopcin (nourseimycin) (1), a new dipeptide antibiotic isolated from Streptomyces, has been established to be (2S, 3R)-2-{(L-alanyl)amino}-4-formyl-3-(hydroxy-aminocarbonyl)butyric acid . 1 exists in two cyclic hemiacetal type tautomers formed by intramolecular ring closure between the hydroxyamino group and the formyl group in aqueous solution . The structure of the new weakly acidic amino acid (2), a constituent of 1, is revealed to be (2S, 3R)-2-amino-4-formyl-3-(hydroxyaminocarbonyl)butyric acid, and 2 also exists in two cyclic hemiacetal type tautomers in aqueous solution. Antibiot Med Biotekhnol, 1985 Mar, 30(3), 179 - 82 {Anti-amebic effect of polyenic antibiotics}; Liubimova LK et al.; All-Union Research technological Institute of Antibiotics and Medical Enzymes, Leningrad . Institute of Epidemiology, Virology and medical parasitology, Ministry of Health of the Armenian SSR . The effect of polyenic antibiotics made in the USSR on development of E . histolytica and E . moshkovski was studied . The following antibiotics were used: levorin and its derivatives, mycoheptin, amphotericin B, amphoglucamine and nystatin . The antibiotics were compared with emetine and metronidazole . Some drugs of the imidazole group were also included into the study . On the whole 15 drugs were tested for their antiamebic activity . All the polyenic antibiotics showed a high antiamebic activity . Levorin and its derivatives were the most active . Their MICs ranged from 0.1 to 5.38 micrograms/ml . The most active of the new imidazoles was 100 times less effective than sodium levorin . The studies show that the polyenic antibiotics have an antiamebic activity and a broad antiprotozoal spectrum. J Antibiot (Tokyo), 1985 Mar, 38(3), 415 - 9 Mildiomycin: a nucleoside antibiotic that inhibits protein synthesis; Feduchi E et al.; Mildiomycin, a new nucleoside antibiotic, selectively inhibits protein synthesis in HeLa cells, and is less active in the inhibition of RNA or DNA synthesis . An increased inhibition of translation by mildiomycin is observed in cultured HeLa cells when they are permeabilized by encephalomyocarditis virus . This observation suggests that this antibiotic does not easily pass through the cell membrane, as occurs with other nucleoside and aminoglycoside antibiotics . The inhibition of translation is also observed in cell-free systems, such as endogenous protein synthesis in a rabbit reticulocyte lysate or the synthesis of polyphenylalanine directed by poly (U) . Finally the mode of action of mildiomycin was investigated and the results suggest that the compound blocks the peptidyl-transferase center. Biochem Pharmacol, 1985 Feb 15, 34(4), 481 - 90 Superoxide radical reactions with anthracycline antibiotics; Nakazawa H et al.; The reaction of superoxide with daunorubicin or its aglycones in the aprotic solvents dimethyl sulfoxide and dimethylformamide was studied . This interaction generated the blue anthracycline phenolate anion as monitored by u.v.-visible spectrometry and molecular oxygen as determined by a modified Clark-type oxygen electrode . The visible spectrum of the phenolate anion (gamma max 604, 652 nm) was subject to considerable shifts dependent on the size of the cation present . The phenolate anion could be further oxidized by molecular oxygen to generate the C-6, C-11 (B-ring) semiquinone as detected by a weak electron paramagnetic resonance spectrometry signal . These results raise the possibility that similar reactions of superoxide with anthracyclines in vivo may play a role in the antitumor activity and/or the etiology of the toxic side effects of this class of drugs. Hosp Formul, 1985 Mar, 20(3), 310 - 2 Improvement in antibiotic use secondary to a small hospital antibiotic review; Strahl DA et al.; An ongoing antibiotic review was instituted in a 144-bed, community teaching hospital . The objectives were to establish criteria defining the use of antibiotics and to identify and quantify antibiotic use not fulfilling these criteria . Through medical staff review of this data on antibiotic use, utilization was then changed to conform with established criteria or was identified as an exception to the criteria . A 45% improvement in antibiotic use was noted when data from the first 9 months of the audit were compared with the second 9-month period . This report shows that a pharmacy-directed antibiotic review can have a positive effect on drug utilization in a small community hospital. Am J Med, 1985 Feb 8, 78(2A), 19 - 26 Investigation into the immunologic cross-reactivity of aztreonam with other beta-lactam antibiotics; Saxon A et al.; The cross-reactivity between the monobactam antibiotic aztreonam and the commonly used beta-lactam antibiotics, penicillins, and cephalosporins was investigated . Antibodies to aztreonam, penicillin, and cephalothin were raised in rabbits . The ability of the homologous or heterologous drug or drug conjugates to inhibit antibody binding was assessed in a solid-phase radioimmunoassay . Aztreonam demonstrated very little ability to interact with anti-penicillin or anti-cephalothin antibodies as it required 10,000-fold higher concentrations than other beta-lactams to achieve equivalent blocking . Similarly, penicillin and cephalothin conjugates did not cross-react, to any significant degree, with anti-aztreonam rabbit antiserums . Interestingly, free aztreonam was as effective as conjugated aztreonam in reacting with antibodies raised against conjugated aztreonam . This result suggested that, in contrast to the other beta-lactams, antibodies to aztreonam recognize the side chain rather than the nuclear structures . Studies with other beta-lactam analogs confirmed that the IgG rabbit anti-aztreonam binding was indeed side chain-specific . Thirty-six volunteers were given a seven-day course of therapeutic doses of aztreonam and in none did any detectable IgE anti-aztreonam antibodies develop . Four of these subjects had evidence of preexisting IgG antibodies cross-reactive with aztreonam, but the levels rose in only one patient following drug exposure . This human IgG anti-aztreonam was also directed to the side chain and did not cross-react with cephalothin or penicillin . The ability of aztreonam to cross-react with human IgE to various penicillin determinants was also investigated . Aztreonam determinants analogous to the penicillin determinants (penicillin, penicilloyl, and penicilloate) were constructed and the maximal concentration that did not evoke false-positive skin test results was determined to be 6 X 10(-3) mol/liter . None of 41 patients with documented IgE-reactive skin tests to various penicillin determinants concurrently demonstrated reproducible reactivity to any aztreonam reagents . IgE anti-penicilloyl antibodies from three persons were also tested in vitro for their ability to cross-react with conjugated or free aztreonam . Minimal, if any, reactivity was observed between the IgE anti-penicilloyl and any of the aztreonam materials . These results indicate that there is very little cross-reactivity between the monobactam aztreonam and other beta-lactam antibiotics. Antibiot Med Biotekhnol, 1985 Feb, 30(2), 96 - 9 {Calculated rates of the filtration of antibiotic suspensions in leaf filters with horizontal filtering elements}; Sinitsyn MA et al.; A procedure for calculating sediment distribution on horizontal filtering elements of multileaf filters used for separation of antibiotic suspensions, as well as for calculation of the filtration time in such apparatus is described . The correlations derived on the basis of this procedure may be used for preliminary technological evaluation of the stage of suspension filtration in production of antibiotic powders for injection with the use of closed air-tight apparatus schemes including multileaf filters. Antibiot Med Biotekhnol, 1985 Feb, 30(2), 122 - 4 {Study of the stability of pyrimido-{5,4-e}-1,2,4-triazine antibiotics in acid-base media by NMR spectroscopy}; Esipov SE et al.; A comparative study of the NMR 1H and 13C spectra of reumycin, fervenulin and xanthothricin in aqueous acid-base media showed that at pH or pD ranging from 8.0 to 1.0 the antibiotics were chemically stable . By the ratio of the 1H and 13C chemical shifts of reumycin at pH 4.0-10.0 the pKa values of this antibiotic were determined: 6.7 in aqueous (D2O) solution and 8.76 in dimethylsulfoxide media . Alkalization of the solutions of reumycin (pH 12.0), fervenulin (pH 9.0) and xanthothricin (pH 8.0) resulted in irreversible chemical transformation of the antibiotics . The analysis of the chemical shifts in the PMR spectra of the transformation products revealed transformation of the uracil ring in reumycin and uracil and triazine rings in fervenulin and xanthothricin . Alkalization of the xanthothricin solutions resulted also in demethylation with formation of reumycin. Antibiot Med Biotekhnol, 1985 Feb, 30(2), 103 - 6 {Macrolide antibiotics: characteristics of their interaction with organoids, intracellular distribution and the effect of sulfalene}; Guliaev AE et al.; Interaction of erythromycin and oleandomycin with isolated subcellular fractions of rat liver homogenates and intracellular distribution of the antibiotics were studied . It was found that the macrolides were bound by the cell organoids . The binding was partially reversible . The intracellular distribution was characterized by accumulation of erythromycin and oleandomycin in the mitochondrial fraction while erythromycin preserved higher activity in cytosol as compared to oleandomycin . Sulfalen induced redistribution of the macrolides . It decreased absorption of the macrolides by the organoids and increased the concentration of free erythromycin and especially oleandomycin in cytosol. Antibiot Med Biotekhnol, 1985 Feb, 30(2), 101 - 2 {Possible use of exclusive ghosts of autologous erythrocytes for directed transport of antibiotics}; Gening TP et al.; Incorporation of rubomycin into exclusive shades of erythrocytes amounted to 7.1 per cent, that of tetracyclines to 6.9-8.9 per cent . Determination of stability of the erythrocyte containers showed that leakage of the antibiotics proceeded during the first 30 minutes of incubation at 37 degrees C when titrated with the Hanks solution . It varied with respect to different antibiotics . With the use of blood serum for titration stability of the erythrocyte containers probably increased . After incubation for 30 minutes only traces of the tetracycline derivatives were detected in the supernatant liquid while rubomycin was not detectable at all . Therefore, the study showed that the exclusive shades of autologous erythrocytes may be in principle used for transport of water-soluble antibiotics. J Antibiot (Tokyo), 1985 Feb, 38(2), 236 - 41 The photodeactivation of hedamycin, an antitumor antibiotic of the pluramycin type; Fredenhagen A et al.; The cytotoxicities of hedamycin and photohedamycin A as well as of kidamycin and isokidamycin were determined using HeLa cell cultures . Photohedamycin A proved to be 15 times less cytotoxic than hedamycin thus explaining the loss of biological activity observed for solutions of hedamycin left in daylight . The fact that photohedamycin A is less active than hedamycin, and isokidamycin less than kidamycin points to the important role the rings E and F play in the biological activity of hedamycin and kidamycin. J Anim Sci, 1985 Feb, 60(2), 462 - 9 Feed additive studies with newly weaned pigs: efficacy of supplemental copper, antibiotics and organic acids; Edmonds MS et al.; Six experiments involving 706 newly weaned 28- to 32-d-old pigs were conducted to evaluate the efficacy of copper (Cu) sulfate (to provide 250 mg/kg Cu), antibiotic-sulfa combinations {chlortetracycline, 110 mg/kg + penicillin, 55 mg/kg + sulfamethazine, 110 mg/kg; i.e., Aureo-Sulfa-Penicillin (ASP) or tylosin, 110 mg/kg + sulfamethazine, 110 mg/kg; i.e., Tylosin-Sulfa (TS)} and anhydrous citric or fumaric acid (.75 to 1.5% of the diet) . The basal experimental diet was a 19% crude protein (CP)-fortified corn-soybean meal diet (1.08% lysine) containing 7% dried whey and 3% fish meal . Marked and consistent gain and gain/feed responses occurred from the Cu supplement, particularly during the first week postweaning . The antibiotic-sulfa combinations were less efficacious than Cu during the 1-wk postweaning stress period . During either the 1- or 3-wk growth periods, ASP and TS showed additivity with Cu in promoting rate and efficiency of weight gain . Liver Cu was increased by Cu addition to the diet, but neither ASP nor TS affected Cu deposition in the liver . In a factorial experiment involving 17% (1.01% lysine) or 20% CP (1.23% lysine) corn-soybean meal diets containing either no dried whey or an addition of 25% whey, Cu supplementation elicited marked improvements in rate and efficiency of weight gain, particularly in diets without added whey . Likewise, whey addition improved pig performance, especially when added to the diets containing no supplemental Cu.(ABSTRACT TRUNCATED AT 250 WORDS) South Med J, 1985 Feb, 78(2), 223 - 4 Oral antibiotic therapy for osteomyelitis of the foot in diabetic patients; Wilson KH et al.; Although osteomyelitis of the foot in diabetic patients is generally considered a difficult infection to cure, the literature contains few reports comparing various treatment regimens . We have described two diabetic patients with osteomyelitis of the foot treated with oral antibiotics chosen on the basis of their broad activity against the pathogens commonly found in such infections . Both patients responded well to therapy and have shown no evidence of active osteomyelitis for 11 and four months, respectively. J Antibiot (Tokyo), 1985 Feb, 38(2), 224 - 9 Antitumor activity of a new antibiotic, kazusamycin; Komiyama K et al.; The antitumor activity of a new antibiotic, kazusamycin, against various murine tumors was studied by various treatment schedules . Single, intermittent, and successive injections of the antibiotic were almost equally effective against Ehrlich carcinoma, IMC carcinoma and sarcoma 180 tumor, but successive injections showed more efficacy than the other schedules against Meth A fibrosarcoma and Lewis lung carcinoma . Interestingly, there was no clear dose response for the efficacy of kazusamycin on murine tumors . When HeLa cells were exposed to kazusamycin for 72 hours in vitro, the IC50 value was about 1 ng/ml, however the cytotoxicity of the antibiotic depended on the incubation time. J Antibiot (Tokyo), 1985 Feb, 38(2), 220 - 9 Structural study of a new antitumor antibiotic, kazusamycin; Komiyama K et al.; The structure of a new antitumor antibiotic, kazusamycin produced by Streptomyces sp . No . 81-484, was determined on the basis of its spectral and chemical properties . Kazusamycin has a structure characteristic of an unsaturated, branched-chain fatty acid with a terminal delta-lactone ring. Zh Mikrobiol Epidemiol Immunobiol, 1985 Feb, (2), 41 - 5 {Antibiotic sensitivity of the erythromycin-resistant strain E of Rickettsia prowazekii cultured in the vector's body}; Klimchuk ND et al.; Experiments on the laboratory cultures of lice infected by Weigl's method revealed that the spontaneous, erythromycin-resistant mutant of R . prowazekii strain E, adapted to the vector's organism, retained its resistance to erythromycin during 50 successive passages without the maintenance concentrations of this antibiotic . The above strain remained sensitive to tetracycline and levomycetin . Its level of sensitivity to the latter antibiotics was similar to that of R . prowazekii strains cultivated in the vector's organism for a long time. Postgrad Med, 1985 Feb 1, 77(2), 105 - 8, 111 Outpatient intravenous antibiotic therapy . Ten years' experience; Kind AC et al.; The experience within the past ten years at Methodist Hospital and Park Nicollet Medical Center, Minneapolis, has clearly demonstrated that outpatient intravenous (IV) antibiotic therapy can be undertaken with relative ease and results in substantial cost savings . During this time, no significant morbidity and no mortality associated with this modality have occurred . Patients of all ages with bone, joint, skin, or soft-tissue infection and other infectious diseases such as meningitis have participated . Patient compliance and enthusiasm have been high . Necessary elements for such a program include an enthusiastic medical staff, a central admixture service, and a team of nurses or other health care professionals available for IV cannula care . Careful patient selection, education, and follow-up are also essential . We believe use of outpatient IV antibiotic therapy will continue to grow in the future, in part because of changes in the financing of medical care. J Natl Cancer Inst, 1985 Feb, 74(2), 275 - 81 Combined cytotoxicity effect of hyperthermia and anthracycline antibiotics on human tumor cells; Ohnoshi T et al.; The effects of temperature on the anthracycline antibiotics-induced cell kill of DND-1A human malignant melanoma (MM) and DND-39A Burkitt's lymphoma (BL) cell lines were studied by means of a clonogenic assay . The two cell lines differed in sensitivity when exposed to heat: The MM cells were unaffected by hyperthermia (42 degrees C), whereas BL cells were sensitive to this temperature . With the MM cells, hyperthermia potentiated the cytotoxic effects of doxorubicin (ADM), daunorubicin, mitoxantrone (DHAD), and quelamycin but did not enhance that of aclacinomycin (ACM) . Conversely, the exposure of cells to the anthracycline compounds at 0 degree C resulted in almost complete disappearance of cell kill effects except with ACM; ACM retained substantial cell kill effects even at the given low temperature . For BL cells, ADM- or DHAD-induced cell lethality was also potentiated by hyperthermia; ACM produced only additive cell kill . At 0 degree C, ACM's effects virtually disappeared . These data indicate that human tumor cell lines have a substantial variety in heat sensitivity and that not every anthracycline antitumor agent is potentiated by temperature . ACM's thermoresponse is unique among anthracycline antibiotics studied . Additionally, it was shown that normothermic cell kill by ADM was not affected by hyperthermic preheating; however, preheating of appropriate duration produced important influence on subsequent hyperthermic ADM-induced cell kill. J Antibiot (Tokyo), 1985 Feb, 38(2), 175 - 80 The structure of amphotericin A . II . The complete structure of the antibiotic; Sowinski P et al.; The structure of amphotericin A without the configuration of asymmetric carbon atoms has been elucidated . The stereochemistry of the sugar moiety has been determined . On the basis of homoscalar correlated 2D 1H spectra . of amphotericin A the position of the hemiketal moiety has been located, and the chemical shifts of all the protons in the antibiotic molecule have been determined. Schweiz Med Wochenschr, 1985 Jan 19, 115(3), 90 - 2 {Antibiotic therapy in bronchopulmonary infections}; Schadelin J; The causative agent of lower respiratory tract infection cannot always be determined even with invasive techniques . In most clinical situations an empirical choice of antibiotics is indicated, if only for early institution of therapy . Next to the often misleading clinical picture, consideration of the epidemiological setting and specific risk of underlying diseases is of value in selecting empirical therapy. J Biol Chem, 1985 Jan 10, 260(1), 344 - 8 Biosynthetic studies on saframycin A, a quinone antitumor antibiotic produced by Streptomyces lavendulae; Mikami Y et al.; The biosynthesis of saframycin A, a heterocyclic quinone antitumor antibiotic isolated from Streptomyces lavendulae 314, was studied by feeding experiments with 14C and 13C precursors . Highly increased production of saframycin A and prolongation of the maximum production period of saframycin A were attained by constant pH control of the culture and by addition of chloramphenicol to the culture . The biosynthetic origin of the quinone skeleton common to the saframycin group was confirmed to be two tyrosine molecules which condense to generate the basic ring system of saframycin A . Feeding experiments with {1-13C}tyrosine showed specific labeling of C-11 and C-21 carbons of saframycin A, and the enrichment of the carbons was 40-fold over natural abundance . Two O- and two C-methyl and one N-methyl carbons arose directly from methionine, and alanine and glycine were the precursors for the pyruvoyl amide side chain of saframycin A. J Membr Biol, 1985, 88(1), 15 - 23 Transport of potassium ions across planar lipid membranes by the antibiotic, grisorixin: I . The equilibrium state and self-diffusion K+ fluxes; Amblard G et al.; 42K+ tracer flux and steady-state conductance measurements were carried out with bilayer lipid membranes containing grisorixin, a carboxylic polyether antibiotic . When the membranes are placed between two bulk aqueous solutions of identical composition, the exchange or self-diffusion transmembrane flux of potassium is measured by a method which allows the characterization of the bilayer K+ permeability at the equilibrium state . The K+ self-diffusion flux increases with the pH in the range pH 6 to pH 9 and reaches a constant value for values above 9 . This can be directly related to the increase of the surface concentration of the 1:1 complex formed by K+ and the deprotonated polyether at both bilayer membrane interfaces . The transport model initially proposed by Pressman and co-workers (Proc . Natl . Acad . Sci . USA 58:1949-1956, 1967) is again taken into consideration in the quantitative analysis of the flux data . The transmembrane transport of K+ results from the translocation of its neutral complex with grisorixin and the association-dissociation of the antibiotic with either potassium or protons taking place at both interfacial space layers while the turnover of the mobile carrier is accomplished under asymmetrical conditions by a translocation process of the acidic grisorixin . Using the data of some previous studies for mixed ionophore-lipid monolayers at the air/water interface and the present results for the self-diffusion flux measurements, it was possible to propose an evaluation of the more important parameters characterizing the transport; namely, the total surface concentration of grisorixin, the interfacial pK and the translocation rate constant of its potassium neutral complex.(ABSTRACT TRUNCATED AT 250 WORDS) Nahrung, 1985, 29(7), 665 - 70 The effect of certain antibiotics on the keeping quality of bolti fish (Tilapia nilotica); el-Bedawey AE et al.; Fresh bolti fish (Tilapia nilotica), caught in the river Nile was immersed in 10 and 20 ppm tetracycline (TC) solutions for 10 and 15 min respectively and in 500 and 1000 R.U . nisin/g fish for 20 and 30 min respectively . Total volatile bases (TVN) showed in both fish treated with TC and nisin a slow increase at the first stage and after that a fast increase . There was an increase in trimethylamine (TMA) during the storage period, but the fish treated with TC and nisin contained less TMA than the control . Starting from 6 h the residual TC decreased gradually till the third day, when it disappeared completely . There is no change in pH values in both control and treated fish . Optical density (OD) of gills extract increased gradually as the storage period progresses . The treated fish showed lower OD values than the controls . The refractive index of muscle fluids and the OD of muscle extract showed no significant differences between the control and treated fish. Int Orthop, 1985, 8(4), 299 - 302 Complications with antibiotics used prophylactically in joint replacement surgery: a case report of cephradine-induced pseudomembranous colitis; Roberts AP et al.; A woman underwent joint replacement surgery with prophylactic antibiotic cover, and subsequently died as a result of pseudomembranous colitis . We have noted a high incidence of antibiotic diarrhoea with cephradine, and suggest that if administration of prophylactic antibiotics is restricted to 3 days or less, the incidence of diarrhoea would diminish, and the therapeutic value of the antibiotics would be maintained. Rev Chir Orthop Reparatrice Appar Mot, 1985, 71(2), 79 - 86 {Preventive antibiotic therapy and postoperative infection in orthopedic surgery . 1983 total hip prostheses}; Marotte JH et al.; In a previous paper the authors studied the role of aerobio-contamination in the rate of post-operative infections . In the present study, the results of 1,172 total hip prostheses performed between 1979/1982 with prophylactic antibiotics were compared with those obtained in 811 cases performed before 1979 without antibiotics . In the 1979/1982 series, there was 0,5 p . 100 of post-operative infection and in the pre- 1979 series, 3,3 p . 100 . During the two periods the peri-operative environment was identical and the surgical technique was the same . The rate of infection in more than 8,000 other surgical procedures performed in the same hospital remained the same . The use of prophylactic antibiotics appears to be a valid approach . They should be used only in high-risk procedures to avoid the selective production of resistant organisms. Rev Chir Orthop Reparatrice Appar Mot, 1985, 71(2), 73 - 8 {Osteogenesis induced by the addition of demineralized bone matrix to plaster pellets with antibiotics . Animal experiment}; Varlet A et al.; The authors have previously shown the role of antibiotic loaded plaster-of-Paris pellets in the treatment of bone loss . In the present paper, a study has been made of the effects of osteogenesis of added decalcified bone matrix in powder . The experiment was made by the implantation of pellets in the muscles of rabbits . It was shown that bone induction by pellets of bone matrix was slightly lower when Rifamycin was added and was not modified by the addition of Fucidin or Gentamycin . The exudation of antibiotics was not diminished by the addition of bone matrix to plaster-of-Paris pellets . The double action, on infection and on bone induction, of composite pellets of plaster-of-Paris with antibiotics and bone matrix may lead to their use in the treatment of septic bone cavities since the pellets are absorbable. Vet Med Nauki, 1985, 22(3), 48 - 53 {Chemical composition of the meat of chickens treated with antibiotics}; Ionova I et al.; Studies were carried out on the chemical composition of meat obtained from a total of 150 Leghorn birds at the age of four weeks, treated with nine antibiotic preparations . When the antibiotics were applied at therapeutic rates certain changes took place in the amount of total nitrogen as well as in the amino acids tryptophane and hydroxi-proline, which depended on the type of the antibiotic used . The study of muscle samples from the test groups revealed negligible rise (P greater than 0.05) of the fats and water to the detriment of total nitrogen as against the values of the same indices of the controls . Demonstrated was the higher biologic value of white meat proteins as shown by the control group as compared with the test groups . The withdrawal time was found to be six days during which full elimination of the antibiotic preparations from the body of the birds was achieved, and there was no rise both of the total nitrogen and of the index of the tryptophane/hydroxi-proline ratio. Scand J Infect Dis, 1985, 17(1), 131 - 2 Rapid determination of antibiotic susceptibility by a disc diffusion test for urgent clinical situations; Midtvedt K et al.; Employing the PDM method, disc diffusion antibiotic susceptibility tests were read after 4 and 8 h and compared to traditional readings after 18 h . Four hours of incubation was not found suitable . After 8 h of incubation, all the 74 strains tested showed visible growth and more than 75% of the readings fell in the same sensitivity groups . Nearly all the discrepancies observed could be classified as minor, and reading the plates after 8 h of incubation should be considered as a valuable alternative when the clinical need for rapid information is obvious. Int J Clin Pharmacol Ther Toxicol, 1985 Jan, 23(1), 47 - 51 Comparative study on renal accumulation of aminoglycoside antibiotics; Fujita K et al.; Antibiotic activities in the subcellular fractions of rat kidney were determined after a single intraperitoneal injection of streptomycin, gentamicin and amikacin in the doses of 100 mg/kg of body weight . The concentration in the sediment fraction, which consisted mainly of lysosome and mitochondria, is a valuable index for renal accumulation and subsequent toxicity . Half-lives of the aminoglycosides in this fraction were in the order of amikacin (2.34 h), streptomycin (5.86 h), and gentamicin (9.26 h). Antimicrob Agents Chemother, 1985 Jan, 27(1), 42 - 5 Antibiotic uptake by alveolar macrophages of smokers; Hand WL et al.; Cigarette smoking, particularly when associated with chronic pulmonary disease, increases the risk of respiratory tract infection . Thus, we elevated the uptake of antibiotics by alveolar macrophages (AM) obtained by bronchoalveolar lavage from persons who smoke and have associated pulmonary abnormalities, circumstances which adversely affect certain macrophage functions . The entry of radiolabeled drugs into AM was determined by a velocity-gradient centrifugation technique, and uptake was expressed as the ratio of cellular to extracellular antibiotic concentration (C/E) . Cefamandole and penicillin G were taken up poorly by the AM obtained from smokers (C/E less than or equal to 1) . Cellular levels of isoniazid, gentamicin, and tetracycline were similar to their extracellular concentrations . The lipid-soluble drugs lincomycin, chloramphenicol, and rifampin were concentrated severalfold by the AM from smokers (C/E = 3 to 11) . Ethambutol also entered macrophages readily (C/E = 11) . Erythromycin and clindamycin were massively concentrated by the AM from smokers (C/E = 23 to 56) . The AM of smokers accumulated a lipid-soluble antibiotic (rifampin) and actively transported agents (erythromycin propionate, clindamycin) more avidly than did the AM of nonsmokers . Augmented uptake of these antibiotics by the AM of smokers may be related to structural and functional alterations induced by smoking. J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 59 - 75 General principles of antibiotic tissue penetration; Barza M et al.; It is well established that, at equilibrium, the concentrations of free drug on either side of a porous capillary are equal . However, the dynamic factors which operate on the way to achieving this equilibrium, while drug levels fluctuate in serum and extravascular sites, have been less well studied . This paper reviews some of the physical principles relating to diffusion through capillary pores and permeation through capillary membranes . Emphasis has been placed on the importance of the surface area-to-volume ratio in determining the time required to reach various stages of equilibrium . The effects of infection have been considered . At equilibrium, the AUC of free drug in serum and non-specialized extravascular compartments must be equal . Therefore, although the mode of administration (e.g . continuous infusion versus intermittent bolus) will affect the profile of the concentration-time curve in extravascular loci, it will not affect the overall AUC of drug in these sites . We have derived an equation to estimate the levels of drug within an abscess when bacteria are destroying the drug . Brief consideration has been given to transport in specialized sites with non-porous capillaries and with active transport systems . Throughout the analysis, we have focused on the application of these principles to in-vitro models and the potential use of in-vitro models to substantiate these principles. Ophthalmology, 1985 Jan, 92(1), 97 - 9 The effect of therapeutic soft contact lenses on antibiotic delivery to the cornea; Matoba AY et al.; The effects of high (71%) and low (38.6%) water content lenses on antibiotic delivery to the cornea were studied in rabbits by measuring corneal tobramycin concentrations 1, 2, 4 and 6 hours after topical application at intervals of 15 minutes . In the presence of the low water content lens corneal drug levels were higher than in control corneas for every time point assayed . This difference was only significant at 4 hours (P less than 0.05) . In eyes wearing the high water content contact lens corneal drug concentration was also higher at every time point tested except one hour . The difference was significant only at 4 hours (P less than 0.01) . The data suggest that in the normal, noninflammed eye, the presence of a therapeutic soft contact lens will not compromise aminoglycoside delivery to the cornea. J Antibiot (Tokyo), 1985 Jan, 38(1), 24 - 30 Structure of the quinone antibiotic EM5519 and the behavior of quinones in fast atom bombardment mass spectrometry; Cooper R et al.; Fast atom bombardment (FAB) mass and MS/MS spectra of a novel quinone antibiotic are presented . Their interpretation is based upon the examination of reductive behavior of model quinones in FAB solvents. Nauchnye Doki Vyss Shkoly Biol Nauki, 1985, (1), 81 - 8 {Kinetics of Streptomyces baarnensis growth and antibiotic synthesis in batch and dialysis cultures}; Panikov NS et al.; The kinetics of biomass and antibiotic formation in batch and dialysis culture of Streptomyces baarnensis at various initial concentrations limiting the substrate growth (glucose) has been studied . The antibiotic substances were synthesized by actively growing culture, its concentration in the cultural media was maximum in the log-phase . In continuous dialysis culture on the background of biomass lianer growth in the course of time the constant antibiotic concentration in the media proportional to the glucose input concentration has been established . The inactivation (decomposition) of antibiotic was immediately initiated after discontinuation of substrate supply and followed first kinetics order . Observed features were used for construction of kinetical model of antibiotic biosynthesis . A conclusion has been made that the dialysis culture gives opportunity for more effective antibiotic synthesis as compared with the batch one. Am J Emerg Med, 1985 Jan, 3(1), 19 - 23 The use of antibiotics in the initial management of recent dog-bite wounds; Rosen RA; The use of antibiotics in the initial management of dog-bite wounds presented within eight hours of injury was studied . Of 211 wounds occurring in 150 patients seen during the study period, 66 wounds occurring in 33 patients comprised the study sample . All wounds were managed according to a strict protocol that included cleaning, debridement, and pressure irrigation . The wounds studied were randomly assigned to either an antibiotics (penicillinase-resistant penicillin or erythromycin) or placebo group . Two of the 35 antibiotic-treated wounds became infected, and three of the 31 placebo-treated wounds became infected . There was no significant difference in outcome between antibiotic and placebo groups . Hand wounds became infected significantly more often than other wounds . The administration of a penicillinase-resistant antibiotic is not indicated in the initial management of dog-bite wounds presented within eight hours of injury. Biochem Pharmacol, 1985 Jan 1, 34(1), 81 - 4 Transport of cefadroxil, an aminocephalosporin antibiotic, across the small intestinal brush border membrane; Kimura T et al.; The transport characteristics of cefadroxil, an aminocephalosporin antibiotic, across the brush border membrane of rat small intestine were investigated by a rapid filtration technique . The uptake of cefadroxil was not affected by Na+ gradient, suggesting the absence of a cotransport system between cefadroxil and Na+ in the brush border membrane . The uptake was slightly inhibited by HgCl2 pretreatment and stimulated by the countertransport effect, where cyclacillin played a role as an elicitor . These results suggest the existence of a carrier-mediated transport system for cefadroxil in the brush border membrane, which is shared with cyclacillin . Papain treatment increased the specific transport activities for the antibiotic . This may be the first step of purification of the cefadroxil transport carrier. Vet Med Nauki, 1985, 22(9), 78 - 84 {Electrophoretic method of demonstrating antibiotic residues in meat and eggs}; Ionova I et al.; Studies were carried out on Smither and Vanghan's electrophoretic method with the use of high voltage . The method was found to be readily reproducible and to have good sensitivity . It could be successfully used in the demonstration and identification of residual amounts of antibiotics in meat and eggs . It was also established that with the use of agarose of pH 6.0 amino glycosides, beta-lactams, flavomycin, spectinomycin, and monensin showed higher migration capacity . The same value of pH was contributive to increasing the migration distances with macrolites, zincbacitracin, and tetracyclines . It was demonstrated that the use of electric current at 50 MA made it more favourable to separate and identify antibiotics . B . subtilis BGA was found to be more sensitive than B . mycoides v . cereus ATCC 11778 with regard to the antibiotics used and it could be made use of in the demonstration of minimal amounts. Gene, 1985, 37(1-3), 101 - 10 The nucleotide sequence of the tyrosinase gene from Streptomyces antibioticus and characterization of the gene product; Bernan V et al.; The sequence of a 1.56-kb DNA fragment containing the tyrosinase gene (mel) from Streptomyces antibioticus was determined and the Mr (30612) and amino acid (aa) sequence of the protein were deduced from the nucleotide (nt) sequence . Intracellular and extracellular tyrosinase from S . antibioticus, transformed with pIJ702 (containing mel), were purified to homogeneity; the Mr (29 500), as determined by Sephadex G-75 chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was consistent with the value derived from the nt sequence . Edman degradation established that the N-terminal sequence of both the intracellular and extracellular forms of tyrosinase are identical and correspond to the aa sequence derived from the structural gene . In addition, this sequence exhibits striking homology to the N-terminal region of the intracellular and extracellular enzyme purified from Streptomyces glaucescens (Crameri et al., 1982) . An additional open reading frame (ORF438) upstream of the mel gene, was also identified that appears to code for a protein (Mr = 14 754) with a putative signal sequence. Zentralbl Mikrobiol, 1985, 140(4), 325 - 32 Purification and identification of Streptomyces aureofaciens lD13 antibiotic; Saleh EA et al.; Complete extraction of S . aureofaciens lD13 antibiotic was achieved by adding n-butanol to the clarified culture filtrate (v/2v) at pH 8.0 . Using the column chromatography technique, 85.7% of the initial amount of the antibiotic was obtained in a purified form . Data of the Rf values of the antibiotic in different organic solvents revealed that it belongs to the tetracycline group . The antibiotic was chromatographically analyzed, using the thin-layer technique . UV and IR spectra, optical rotation, melting point as well as 15 colour reactions were also determined. Microbios, 1985, 42(169-170), 145 - 53 Effect of phospholipid enrichment on nystatin action: differences in antibiotic sensitivity between in vivo and in vitro conditions; Rao TV et al.; Polyene-nystatin had a selective effect on the transport of glutamic acid and lysine in phosphatidylcholine-, or phosphatidylethanolamine-enriched cells of Saccharomyces cerevisiae . However, liposomes prepared from lipid extracts from the same cells did not mimic the results of in vivo studies . Our in vitro results demonstrated that factors other than sterols, e.g . phospholipid enrichment, protein lipid interactions and lipid bilayer asymmetry may also affect the overall susceptibility of polyene antibiotics. Cell Biol Toxicol, 1985 Jan, 1(2), 87 - 101 Formation of DNA-adducts and induction of DNA-crosslinks and chromosomal aberrations by the new potent anthracycline antitumor antibiotics: morpholinodaunomycin, cyanomorpholinodaunomycin and cyanomorpholinoadriamycin; Westendorf J et al.; The DNA-interaction of three newly developed semisynthetic anthracyclines with high antitumor potency MoDNM3, CNMoDNM, and CNMoADM, was investigated . When primary rat hepatocytes were incubated with tritium labeled MoDNM and CNMoDNM and their DNA was purified and enzymatically hydrolized, the formation of DNA-adducts could be demonstrated by the HPLC chromatography of the resulting mononucleoside mixtures . The parent compound, daunomycin (DNM), also formed covalent adducts with hepatocyte DNA, but to a lesser extent . These findings correlate well with earlier observations that MoDNM and CNMoDNM are potent inducers of DNA-repair in primary rat hepatocytes, whereas DNM is only weakly active in this regard . Alkaline elution studies were performed with L 1210 mouse leukemia cells and V79 Chinese hamster fibroblasts . The cyanomorpholinyl derivatives showed dose-dependent DNA crosslinking activities in both cell lines at concentrations greater than or equal to 5 nMol/l . The formation of crosslinks began a few minutes after treatment of the cells and reached a maximum after 1 hr . In contrast, MoDNM, at concentrations of up to 10 muMol/l, had only a limited capacity to induce single strand breaks in L 1210 cells but did not induce DNA-crosslinks . In addition, chromosomal aberrations (chromatid breaks and translocations) were induced by the treatment of Friend and L 1210 leukemia cells with CNMoADM at concentrations between 0.07-0.6 nMol/l . At higher doses, chromosome clumping was observed . These results indicate that the high capacity of MoDNM, CNMoDNM and CNMoADM to induce DNA repair in primary rat hepatocytes is due to the formation of covalent adducts with DNA . The cyanomorpholino compounds have alkylating capacities also in cell lines such as L 1210 and V79, whereas MoDNM requires rat hepatocytes for activation . The ready formation of DNA crosslinks and chromosomal aberrations could be responsible for the high cytotoxicity of these compounds. Circ Shock, 1985, 16(3), 265 - 77 Corticosteroid/antibiotic treatment of adrenalectomized dogs challenged with lethal E . coli; Hinshaw LB et al.; Adrenalectomized animals are extremely sensitive to endotoxin and die quickly when given small doses . A six hour administration of the corticosteroid, methylprednisolone sodium succinate (MPSS), combined with the antibiotic, gentamicin sulfate (GS), promotes complete recovery of dogs with intact adrenals administered LD100 E . coli . The aim of the present study was to determine if this early administered treatment would protect adrenalectomized dogs from overwhelming lethal doses of E . coli . Dogs were infused with MPSS from fifteen minutes to six hours after the onset of E . coli administration and with GS after administration of all E . coli . Animals given only E . coli died in 2.6 (+/- 0.3) hours, while those given no E . coli, or E . coli plus steroid/antibiotic, survived longer than 100 hours . Arterial pressure, pH, pO2, hematocrit, lactate, and glucose concentrations were maintained near control values in animals receiving steroid/antibiotic infusions . Adrenalectomized dogs infused with corticosteroid/antibiotic recovered completely from shock even though the treatment period was limited to the first 6 hours after lethal E . coli infusion . Findings indicate that animals treated with MPSS/GS after E . coli ultimately succumbed to adrenal insufficiency rather than from the E . coli insult and thus recovery from shock itself was complete. Acta Neurochir (Wien), 1985, 76(3-4), 94 - 8 Treatment of deep brain abscesses by stereotactic implantation of an intracavitary device for evacuation and local application of antibiotics; Broggi G et al.; Complete recovery from deep brain abscesses was achieved in four patients treated by a specialized stereotactic method . In one patient the lesion was in the right thalamus, in two patients within the brain stem and in one case in the right rolandic cortex . The technique consists in the stereotactic implantation of a chronic intracavitary catheter connected to a subcutaneous reservoir to allow postoperative multiple evacuations and local antibiotic irrigations . Serial CT scan examinations guided the timing of intracavitary treatment and the removal of the catheter . No recurrence developed . The diagnostic and therapeutic advantages of this stereotactic technique are emphasized. Zentralbl Chir, 1985, 110(9), 532 - 8 {Perioperative antibiotic prevention in colon and rectum surgery . A randomized study on the value of single dose prevention}; Athanasiadis S et al.; In a prospective randomized trial clinical results of one-shot-prophylaxis with Tinidazole (Group I, n = 50) versus 9 doses of Metronidazole (Group II, n = 50) as perioperative short-time-prophylaxis were compared . The rate of postoperative wound infections was not significantly different in the groups (p = 0,09) . (1/50 in Group I = 2%, 5/50 in Group II = 10%) . Postoperative complications clearly occurred less frequently in the first group than in the second one (12% versus 34%, p0,01) . Our investigation indicates that prophylactic treatment with Tinidazole as a preoperative high and single dose is important for preventing postoperative infection in patients undergoing bowel surgery. Antimicrob Agents Chemother, 1985 Jan, 27(1), 21 - 7 Oxygen- and time-dependent effects of antibiotics and selected mitochondrial inhibitors on Plasmodium falciparum in culture; Divo AA et al.; Several antibiotics which inhibit protein synthesis on 70S ribosomes, including clindamycin, pirlimycin, 4'-pentyl-N-demethyl clindamycin, four tetracyclines, chloramphenicol, thiamphenicol, and erythromycin, had antimalarial effects against Plasmodium falciparum in culture which were greatly influenced by the duration of drug exposure and by oxygen tension . In 96-h incubations, potency was increased by a factor of up to 10(6) over the first 48-h period and by a factor of up to 10(4) in 15% O2 versus 1% O2 . Two aminoglycosides, kanamycin and tobramycin, had no antimalarial activity . Rifampin and nalidixic acid, which inhibit nucleic acid synthesis, were not similar to the 70S inhibitors . The mitochondrial inhibitors Janus Green, rhodamine 123, antimycin A1, and 8-methylamino-8-desmethyl riboflavin had activities which were influenced by the duration of exposure and oxygen tension . Quinoline-containing antimalarial agents, ionophores, and other antimalarial drugs were influenced to a minor extent by the duration of exposure but were not affected by oxygen tension . These data can best be explained by the hypothesis that antimalarial 70S ribosome-specific protein synthesis inhibitors are toxic to the parasites by acting on the mitochondrion. J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 197 - 9 Penetration of antibiotics through cell culture monolayers; Haller I; Commercial tissue culture chambers were modified in such a way that they contained two portions of medium separated by a horizontal membrane . When grown on this membrane, Vero (monkey kidney) cells formed continuous cell monolayers . By comparing the penetration of antibiotics through monolayer-covered and cell-free membranes, the retention brought about by the cell layer could be measured . Only minor differences were seen between oxacillin, mezlocillin and ciprofloxacin . Penetration of polymyxin B through the cell layer proved to be reduced by about 40% in comparison to oxacillin. J Periodontol, 1985 Jan, 56(1), 18 - 20 Inhibition of oral contraceptive effectiveness by concurrent antibiotic administration . A review; Barnett ML; The use of antibiotics in periodontal therapy has received increasing attention in recent years . Although generally safe, certain antibiotics, including tetracycline and ampicillin, have been shown to interact indirectly with oral contraceptives, with a resultant decrease in oral contraceptive efficacy . This paper reviews the nature of antibiotic-oral contraceptive inter-actions, as well as the precautions that have been suggested for patients taking oral contraceptives for whom certain antibiotics have been prescribed. J Antimicrob Chemother, 1985 Jan, 15(1), 23 - 30 In-vitro susceptibility of Nocardia asteroides to 21 beta-lactam antibiotics, in combination with three beta-lactamase inhibitors, and its relationship to the beta-lactamase content; Kitzis MD et al.; Twelve strains of Nocardia asteroides were studied for their susceptibility to 21 beta-lactam antibiotics, alone or in combination with clavulanic acid, sulbactam, or BLP 2013, and for their content of beta-lactamase . Eleven strains were shown to have beta-lactamase activities, which gave three different patterns after analytical isoelectric focusing . The only strain with no detectable beta-lactamase was the most susceptible to the antibiotics tested . The other strains containing beta-lactamases showed almost the same susceptibility profile . Clavulanic acid was the only beta-lactamase inhibitor to show a significant synergistic effect when combined with penicillins. J Antimicrob Chemother, 1985 Jan, 15(1), 115 - 8 Susceptibility of 126 isolates of Escherichia coli from the cerebrospinal fluid of neonates to five antibiotics; Mulder CJ et al.; One hundred and twenty-six clinical isolates of Escherichia coli from the CSF of neonates, obtained in the Netherlands during 1976 to 1982, were tested for sensitivity to five antibiotics . The usefulness of the generally recommended initial therapy, a combination of ampicillin and gentamicin, is supported in the majority of cases . On the basis of the in-vitro results, cefotaxime would have been effective as a therapy for all cases . Ampicillin and cefuroxime resistance occurred mostly in neonates who had received antibiotics prophylactically, neonates whose mothers had fever during labour or in neonates who had been nursed in incubators for more than one week. Chemotherapy, 1985, 31(1), 76 - 82 Antibiotic infection prophylaxis in gallbladder surgery--a prospective randomized study; Harnoss BM et al.; In the course of 1 year, 180 patients undergoing elective surgery for confirmed cholelithiasis were included in a prospective randomized study in which they either received 2 g of preoperatively applied ceftriaxon intravenously at the beginning of anesthesia or, as an alternative, no antibiotic at all . Infectious wound-healing disturbances occurred postoperatively in 11% in the control group and in no case in the prophylaxis group . The difference is statistically significant. Clin Pharmacokinet, 1985 Jan-Feb, 10(1), 63 - 79 Pharmacokinetic interactions of the macrolide antibiotics; Ludden TM; The macrolide antibiotics erythromycin and triacetyloleandomycin (troleandomycin) are prescribed for many types of infections . As such they are often added to other preexisting drug therapy . Thus, there are frequent opportunities for the interaction of these antibiotics with other drugs . Both erythromycin and triacetyloleandomycin appear to have the potential to inhibit drug metabolism in the liver and also drug metabolism by micro-organisms in the gut, either through their antibiotic effect or through complex formation and inactivation of microsomal drug oxidising enzymes . Of the two agents, triacetyloleandomycin appears to be the more potent inhibitor of microsomal drug metabolism . Published studies indicate that triacetyloleandomycin can significantly decrease the metabolism of methylprednisolone, theophylline and carbamazepine . Its ability to cause ergotism in patients receiving ergot alkaloids and cholestatic jaundice in patients on oral contraceptives may also be related to its inhibitory effect on drug metabolism . Erythromycin appears to be a much weaker inhibitor of drug metabolism . There are numerous reports describing apparent interactions of erythromycin with theophylline and a lesser number of reports dealing with carbamazepine, warfarin methylprednisolone and digoxin . There are sufficient data to suggest that erythromycin can, in some individuals, inhibit the elimination of methylprednisolone, theophylline, carbamazepine and warfarin . The mean change in drug clearance is about 20 to 25% in most cases, with some patients having a much larger change than others . Like tetracycline, erythromycin also appears to have the potential for increasing the bioavailability of digoxin in patients who excrete high amounts of reduced digoxin metabolites, apparently through destruction of the gut flora that form these compounds . Concurrent administration of triacetyloleandomycin with drugs whose metabolism is known to be affected or that could potentially be affected should be avoided unless appropriate adjustments in dosage are made . Coadministration of erythromycin with drugs believed to interact should be undertaken with caution and with appropriate patient monitoring . Among the other macrolide antibiotics, josamycin has seldom been involved in causing drug interactions, while midecamycin and the older derivative spiramycin have not so far been incriminated. Br J Surg, 1985 Jan, 72(1), 66 - 7 Treatment of acute abscesses by incision, curettage and primary suture without antibiotics: a controlled clinical trial; Stewart MP et al.; One hundred and thirty-seven consecutive acute superficial abscesses were randomly allocated to incision, curettage and primary suture without parenteral antibiotics (64 cases) or to conventional treatment with incision, drainage and dressings (73 cases) . Wound healing was faster; 7.0 days: 25.1 days (P less than 0.01, Wilcoxon's rank sum test), the number of hospital visits was smaller; 3.8 visits: 11.1 visits (P less than 0.01) and the time off work was shorter; 4.0 days: 14.1 days (P less than 0.01) in the group treated by primary closure compared with those managed conventionally . In this study no complications attributable to the withholding of antibiotics occurred . Incision and primary closure of abscesses is safe and more economic than conventional drainage . Routine antibiotic cover is not necessary. Ann Otolaryngol Chir Cervicofac, 1985, 102(7), 499 - 502 {Concentrations of antibiotics (josamycin, trioleandomycin and amoxicillin) in the secretions of the ear, sinus and adenoids}; Berezin A et al.; This was a comparative study of antibiotics in the pus of otitis and from the sinuses as well as in the adenoids . Three antibiotics were chosen: Trioleandomycin, Josamycin, Amoxicillin . The study protocol was strict . Results obtained were as follows: high concentrations of macrolids in discharge of otitis and the sinuses as well as in the adenoids . Concentrations were higher than serum concentrations . By contrast, in the case of amoxicillin tissue concentrations were lower than the serum concentration . This leads to the conclusion that there is good penetration of infectious ENT sites by macrolids. Microbiol Immunol, 1985, 29(9), 803 - 9 Relationship between beta-lactamase activity and resistance to beta-lactam antibiotics in Mycobacterium smegmatis; Yabu K et al.; Penicillin-susceptible mutants and beta-lactamase-negative mutants were isolated from Mycobacterium smegmatis after nitrosoguanidine mutagenesis . Both the mutants were found to be susceptible to low levels of penicillin and cephalosporins by twofold dilution testing . Clavulanic acid reduced the minimal inhibitory concentrations of beta-lactamase-labile beta-lactams for the penicillin-susceptible mutants and the parent strain, but had no effect on the susceptibility of the beta-lactamase-negative mutants . Comparison of the beta-lactamase activities found in these mutants and the parent strain indicated that there was a rough correlation between the beta-lactamase level in these organisms and their susceptibility to beta-lactams. Ciba Found Symp, 1985, 111, 171 - 87 Creation of novel chiral synthons with enzymes: application to enantioselective synthesis of antibiotics; Ohno M; Retrosynthesis was carried out to generate, from a target molecule, a symmetric diester in the prochiral or meso form . The symmetric diester was subjected to asymmetric hydrolysis with pig liver esterase to create the corresponding chiral half-ester . The chiral half-ester was converted into the target molecule by organic synthesis . Thus, various types of carbapenem antibiotics, negamycin, showdomycin, 6-azapseudouridine, cordycepin, aristeromycin, neplanocin A, and precursors of fortimicin were efficiently synthesized with the desired absolute configuration . The methods for asymmetric synthesis starting from substrates with sigma-symmetry have been extensively developed. Mol Gen Genet, 1985, 201(2), 168 - 73 Methylation of 16S ribosomal RNA and resistance to the aminoglycoside antibiotics gentamicin and kanamycin determined by DNA from the gentamicin-producer, Micromonospora purpurea; Thompson J et al.; When DNA fragments from Micromonospora purpurea (the producer of gentamicin) were cloned in Streptomyces lividans, a gentamicin-resistant strain was obtained in which the ribosomes were highly resistant both to gentamicin and to kanamycin . Reconstitution analysis revealed that such resistance resulted from some property of their 16S RNA . Extracts from the clone contained methylase activity which acted on 16S RNA within E . coli 30S ribosomal subunits and rendered them resistant to gentamicin and kanamycin. Infection, 1985, 13 Suppl 1, S156 - 60 Renal tolerance of imipenem/cilastatin and other beta-lactam antibiotics in rats; Sack K et al.; Imipenem is inactivated by the renal dehydropeptidase I, which can be inhibited by cilastatin . Therefore, both compounds are administered in combination . According to the manufacturers, they are not nephrotoxic in rats . 70 female Wistar rats (n = 10/test series) were treated over five days at dosage intervals of 12 hours with intraperitoneal injections (injection volume: 10 ml/200 g body weight) of isotonic 0.9% NaCl, cilastatin (1000 mg/kg/day), imipenem (500 and 1000 mg/kg/day), cilastatin + imipenem (500 or 1000 mg/kg/day each) and cefsulodin (1000 mg/kg/day) . The nocturnal excretion of renal tubular cells was determined . Furthermore, three rats in each test were treated intraperitoneally with 150 mg/kg imipenem or with the combination of imipenem and cilastatin (150 mg/kg each) . Imipenem concentrations were measured over four hours in the blood of the tail vein . Commencing on the second day of study, cilastatin, imipenem and the combination of both substances induced significant surplus excretion of tubular cells compared to the control group . The tubulotoxic effects of imipenem and imipenem + cilastatin in combination were dose-dependent . The toxic effects of imipenem, imipenem + cilastatin and cefsulodin did not significantly differ . Cilastatin prolonged the half-life of imipenem in the blood from 0.4 to 0.9 h and increased the AUC of imipenem from 156 to 325 mg/l/h.(ABSTRACT TRUNCATED AT 250 WORDS) Mol Gen Genet, 1985, 200(3), 415 - 21 Methylation of 16S ribosomal RNA and resistance to aminoglycoside antibiotics in clones of Streptomyces lividans carrying DNA from Streptomyces tenjimariensis; Skeggs PA et al.; A single gene from Streptomyces tenjimariensis, conferring resistance to kanamycin, apramycin and sisomicin, has been cloned in Streptomyces lividans . The mechanism of resistance involves methylation of 16S RNA in the 30S ribosomal subunit. Scand J Infect Dis Suppl, 1985, 44, 46 - 51 Long-standing otitis media with effusion--a convenient model for the study of antibiotic penetration to respiratory tract secretions; Eden T; In long-standing otitis media with effusion, myringotomy with aspiration of the middle ear exsudate is an established therapeutical procedure, which can be performed under carefully planned conditions . This common disease thus offers convenient advantages for the study of antibiotic concentrations in the middle ear . This is exemplified by a review of studies with erythromycin, doxycycline and cefaclor . A delayed penetration into the middle ear was demonstrated for all these antibiotics, especially for erythromycin . The elimination from the middle ear was slower than from serum, at least with erythromycin and doxycycline . With these two antibiotics, the middle ear concentrations were close to the peak serum levels, with only small fluctuations between doses during a course of treatment . With cefaclor, peak middle ear concentrations were less than 40% of peak serum levels . By using this model, data from a natural disease in humans are obtained . Since the mucosa anywhere in the respiratory tract reacts in a uniform manner to an inflammatory stimulus, results from studies on long-standing otitis media with effusion can disclose some aspects on antibiotic pharmacokinetics in respiratory tract secretions in general. Scand J Infect Dis Suppl, 1985, 44, 16 - 23 Antibiotic accumulation in human polymorphonuclear leucocytes and lymphocytes; Forsgren A et al.; Human polymorphonuclear leucocytes and lymphocytes were incubated with 10 different radiolabelled antibiotics (10 micrograms/ml) for 2 hours . The ratio of cellular concentration to extracellular concentration of the drugs was determined after centrifugation . For beta-lactam antibiotics and gentamicin the ratios were less than 1.0 . The ratios for doxycycline, erythromycin, fusidic acid and rifampicin were 13, 4.3, 7-10 and 2.5 respectively indicating a cellular accumulation of these drugs . Erythromycin, fusidic acid and rifampicin were rapidly released from the cells in antibiotic free medium, while doxycycline was partly irreversibly bound. Cancer Chemother Pharmacol, 1985, 15(2), 153 - 60 Comparative murine metabolism and disposition of class II anthracycline antibiotics; Dodion P et al.; The metabolism and tissue distribution of aclacinomycin A (ACL), marcellomycin (MCM), and musettamycin (MST), three new anthracycline antibiotics, were compared after IV administration to mice . In plasma, total MCM- and ACL-derived fluorescence declined according to first-order kinetics, whereas an initial decline followed by a rebound was observed for MST . In plasma, MCM remained the predominant compound . ACL was eliminated more quickly, and was replaced by two metabolites, the reduced glycoside M1, and an aglycone . In the case of MST, two unidentified metabolites were observed in concentrations equivalent to that of the parent drug . The three drugs were distributed widely to organs, but only ACL achieved measurable concentrations in the brain . Initially, high concentrations of all three drugs were present in the lungs, but these decreased quickly to values similar to those present in the liver and kidneys . Intermediate concentrations of the three drugs were measured in heart and skeletal muscle . Splenic concentrations of all three drugs rose progressively, reaching a maximum at 8 h after injection in the case of ACL and MST, and at 24 h after injection in the case of MCM . Concentrations of the metabolites of MCM and MST were low in all organs except liver and kidney, where the aglycones 7-deoxypyrromycinone and bisanhydropyrromycinone were seen . The metabolism of ACL was extensive . Aglycones were dominant in the liver and kidneys, whereas reduced glycosides predominated in the spleen . These observations indicate that the murine pharmacology of these three structurally similar drugs differs markedly. Ann N Y Acad Sci, 1985, 446, 390 - 402 Selective toxicity and enhanced therapeutic index of liposomal polyene antibiotics in systemic fungal infections; Juliano RL et al.; Incorporation of the polyene antibiotic amphotericin B (AMB) in liposomes results in a marked reduction in drug toxicity with no loss of antifungal potency . Nephrotoxicity, the dose-limiting side effect of AMB, is almost abolished when the drug is utilized in a liposomal carrier . Because of reduced toxicity, high doses of liposomal AMB can be used, resulting in superior therapy of systemic fungal infections in mice . The improved therapeutic index of liposomal AMB versus free AMB is also manifest in infected neutropenic animals . The reduced toxicity of liposomal AMB is due to a fundamental alteration in the interaction of the drug with mammalian cell membranes . AMB transfers effectively from donor liposomes to fungal cell walls and membranes and is thus toxic to fungi . By contrast, AMB does not transfer from liposomes to mammalian cells and thus is not toxic to these cells . Thus, the use of liposomal AMB may offer a marked improvement in the therapy of systemic fungal infection in cancer patients and other immunodebilitated individuals. Ann Rech Vet, 1985, 16(3), 245 - 53 {Antibiotic-resistant coliforms in a purification station on a pig-breeding farm}; Avignon M et al.; The survival of antibiotic-resistant enteric bacteria in the effluent treatment plant of a pig farm was studied by quantitative determinations of resistant and sensitive populations at different sites of the effluent purification process . The effluent treatment system, combining storage and aeration tanks, reduced the concentration of enteric organisms in the output of the plant to about one-tenth of the concentration found in the incoming untreated slurry . This reduction occurred mainly at the level of the aerated tank and was observed for the total population of enteric organisms as well as for the various populations resistant to ampicillin, chloramphenicol, kanamycin, streptomycin and tetracycline respectively . Moreover, no particular sequence of resistances seems to have been selected during treatment . Storage and aeration of pig slurry before disposal reduces the risk of dissemination of antibiotic-resistant bacteria of animal origin in the environment, as compared to the frequent direct spreading of untreated effluents. Scand J Infect Dis, 1985, 17(4), 395 - 400 The distribution of labeled antibiotics in normal and infected rat brain: an autoradiographic study; Kourtopoulos H et al.; The penetration and distribution of labeled benzylpenicillin and cefuroxime into normal and infected rat brain was studied . 15 rats were injected intravenously with radiolabeled antibiotic; 5 of these served as uninfected controls and 10 were previously infected by stereotactic deposition of 10(11) B . fragilis in the right frontal lobe inducing bacterial cerebritis . The animals were killed after administration of antibiotic . The brains were immediately frozen and cut into 20/micron sections . Autoradiographic recordings showed that benzylpenicillin was mainly distributed in the cerebrospinal fluid and pial vessels but no activity was found in the deeper grey or white matter . In contrast, cefuroxime was found not only in the surrounding but also in the centre of the infected area . The autoradiographic technique provides a valuable method for studies of the distribution of antibiotics in the brain. Nucleic Acids Symp Ser, 1985, (16), 81 - 3 Synthesis and biological activity of nucleoside antibiotics, ascamycin and its amino acid analogs; Ubukata M et al.; Synthesis of an alanylsulfamoyl nucleoside antibiotic, ascamycin was achieved by the condensation of N6-t-butyloxycarbonyl-2-chloro-9-(2',3'-O-isopropylidene-5'-O-sulfamoyl- beta-D- ribofuranosyl)adenine(3) with t-butyloxycarbonyl-L-alanylimidazole in the presence of NaH in DMF . Deprotection with 90% trifluoroacetic acid gave ascamycin in 61% overall yield . This procedure may be applicable for preparation of a number of amino acid analogs of ascamycin. Adv Enzyme Regul, 1985, 24, 263 - 74 Interaction of the antibiotic adriamycin with the plasma membrane; Hickman JA et al.; The antitumor antibiotic adriamycin was found to be a potent modulator of the human erythrocyte discocyte echinocyte transition . Incubation of discocytes for 10 min with 10 microM adriamycin inhibited calcium-induced echinocytosis by 90 per cent . Adriamycin itself had no effect on erythrocyte morphology, a feature which distinguished it from other amphipaths which bring about the formation of a cupped cell morphology . Additionally, adriamycin differed from amphipaths such as the phenothiazines in that concentrations which prevented echinocytosis had no effects on calmodulin, as measured by effects on calmodulin-stimulated 45Ca2+ uptake into inside-out red cell vesicles . Adriamycin, paradoxically, appeared to cause a fall in the levels of erythrocyte polyphosphoinositides, but prevented further breakdown induced by calcium loading . This fall in inositides may be apparent rather than real, as the drug did not cause breakdown of the inositides to either inositol di- or triphosphates in red cell vesicles . Instead, it inhibited breakdown . It is possible that adriamycin may complex out the inositides and thus maintain levels of the inositide polyphosphates, congruent with the maintenance of the discocyte morphology . Interference with inositol lipid metabolism may be an important aspect of the pharmacology of adriamycin. Bioorg Khim, 1985 Jan, 11(1), 132 - 4 {Localization of mutation leading to resistance of E . coli RNA polymerase to the antibiotic streptolydigin in the gene rpoB coding for the beta-subunit of the enzyme}; Lisitsyn NA et al.; For the first time a mutation of streptolydigin resistance was localized . It was discovered to be a double substitution, namely Gly544----Asp, Phe545----Ser, in the region where most rif-r mutations are located . One may suppose that this region takes part in the formation of both elongation NTP binding site, blocked by streptolydigin, and RNA chain binding and translocation site that is blocked by rifampicin. Chemotherapy, 1985, 31(2), 138 - 45 Influence of beta-lactam antibiotics, fosfomycin and vancomycin on the adherence (hemagglutination) of Escherichia coli-containing different adhesins; Klein U et al.; The adherence of Escherichia coli of certain adhesin types can be influenced by subinhibitory concentrations of beta-lactam antibiotics . Subinhibitory concentrations (1/4MIC) of those penicillin and cephalosporin compounds which lead to filament formation increase mannose-sensitive adhesion (MS+) . Antibiotics with ovoid cell formation did not change or only slightly reduced MS+ adherence . Strains with mannose-resistant (MR+) adhesins were not affected by these antibiotics . Only azthreonam increased the adherence of both MS+ and MR+ strains . Vancomycin and fosfomycin reduced the adherence of all strains tested . The degree of change was strain and antibiotic specific . No relation could be detected between the changes of adherence and the changes of hydrophobicity under the influence of antibiotics . Electron microscopic investigation has not yet yielded an explanation of the observed phenomenon. Antimicrob Agents Chemother, 1985 Jan, 27(1), 84 - 92 Diffusion of beta-lactam antibiotics through the porin channels of Escherichia coli K-12; Yoshimura F et al.; Diffusion rates of various beta-lactam antibiotics through the OmpF and OmpC porin channels of Escherichia coli K-12 were measured by the use of reconstituted proteoliposomes . The results can be interpreted on the basis of the gross physicochemical properties of the antibiotics along the following lines . (i) As noted previously (Nikaido et al., J . Bacteriol., 153:232-240, 1983), there was a monotonous dependence of the penetration rate on the hydrophobicity of the molecule among the classical monoanionic beta-lactams, and a 10-fold increase in the octanol-water partition coefficient of the uncharged molecule decreased the penetration rate by a factor of 5 to 6 . (ii) Compounds with exceptionally bulky side chains, such as mezlocillin, piperacillin, and cefoperazone, showed much slower penetration rates than expected from their hydrophobicity . (iii) The substituted oxime side chain on the alpha-carbon of the substituent group at position 7 of the cephem nucleus decreased the penetration rate almost by an order of magnitude; this appears to be largely due to the steric effect . (iv) The presence of a methoxy group at position 7 of the cephalosporins also reduced the penetration rate by 20%, probably also due to the steric hindrance . (v) Zwitterionic compounds penetrated very rapidly, and the correlation between the rate and hydrophobicity appeared to be much weaker than with the monoanionic compounds . Imipenem showed the highest permeability among the compounds tested, presumably due, at least in part, to its compact molecular structure . (vi) Compounds with two negative charges penetrated more slowly than did analogs with only one negatively charged group . Among them, only moxalactam, ceftriaxone, and azthreonam showed penetration rates corresponding to, or higher than, 10% of that of imipenem. J Antibiot (Tokyo), 1985 Jan, 38(1), 99 - 110 Amplification of the antibiotic effects of the bleomycins, phleomycins and tallysomycins: its dependence on the nature of the variable basic groups; Grigg GW et al.; The bleomycins, phleomycins and tallysomycins are structurally similar glycopeptide antibiotics . Within each class, individual members differ only in the structure of a basic group . The antibiotic effect of phleomycin (Bristol batch A9331-648) against Escherichia coli is amplified substantially by a number of simple heterocyclic and aromatic compounds . In this paper a sample of 26 such compounds were tested for this property with 25 different phleomycins, bleomycins and tallysomycins . The nature of the variable basic group of the phleomycins, bleomycins and tallysomycins determined the response obtained with all amplifiers, although variation of response was much less marked with caffeine which potentiated the cytotoxic effects of all the phleomycins, bleomycins and tallysomycins tested . Phleomycins and bleomycins having two or three guanidino groups in the variable basic group, or phleomycins having a secondary amino group within a methylene chain and a terminal 2-phenylethyl substituent, were amplified by most compounds, whereas the cytotoxicity of others was enhanced little or not at all . Similar phleomycins, having a secondary amino and a terminal guanidino group and no 2-phenylethyl substituent showed little enhancement, and in these cases the inclusion of a 2-phenylethyl substituent had a major influence in determining amplifiability . Bleomycins and phleomycins having identical basic groups were amplified to similar extents by the sample of 26 amplifying agents used. Gan To Kagaku Ryoho, 1984 Dec, 11(12 Pt 2), 2640 - 52 {New anthracycline antibiotics and derivatives}; Tatsuta K; Studies of anthracycline antibiotics which have been carried out for the purpose of finding compounds useful in the treatment of cancer are described . Synthetic development of derivatives and analogs which have stronger activities and lower characteristic toxicities than parent antitumor antibiotics such as daunomycin, adriamycin, etc., have been illustrated namely: (1) syntheses of 4'-O-derivatives such as 4'-O-tetrahydropyranyl-adriamycin; (2) syntheses of N-alkyl derivatives such as 3'-deamino-3'-morpholino-adriamycin; and (3) syntheses of 11-deoxy-adriamycin . Notably, 4'-O-tetrahydropyranyl-adriamycin having a (2" R)-configuration has been confirmed to have stronger activity and lower toxicity than adriamycin by Phase II study . New, naturally occurring anthracycline antibiotics (decilorubicin, arugomycin, ditrisarubicin, etc.) have also been reviewed. Am Surg, 1984 Dec, 50(12), 666 - 7 Assessment of pancreatic ductal penetration of antibiotics; Wallace JR et al.; Pancreatic ductal penetration of antibiotics is not uniform . Antibiotic therapy for pancreatic and pancreatic related infections, theoretically, is enhanced by drugs that reach the ductal system . The pancreatic ductal penetrance of Cefamandol (1 gm), Amikacin (7.5 mg/kg), and Chloramphenicol (1 gm) given as a single intravenous dose prior to endoscopic retrograde cholangiopancreatography was studied in ten patients . Serum and pancreatic juice were collected simultaneously, frozen, and later assayed for antibiotic concentration . Each antibiotic achieved its expected therapeutic serum level . In contrast, pancreatic ductal levels of Cefamandol and Amikacin were subtherapeutic, whereas Chloramphenicol levels were therapeutic . Further studies are needed to identify other antibiotics with good pancreatic ductal penetrance. Arch Tierernahr, 1984 Dec, 34(12), 841 - 50 {Effect of the polyether antibiotic "monensin" on fattening and slaughtering performance as well as protein and energy retention in bulls}; Richter G et al.; In an individual feeding experiment (150-500 kg live weight) the influence of the polyether antibiotic Monensin on the fattening, slaughtering and retention performances of crossbreeding dairy bulls (genotype 31) and fattening hybrids (genotype 61) was ascertained . The supplementation of the polyether antibiotic on average resulted in a decrease by approximately equal to 11% of the dry matter and energy expenditure per kg weight gain due to a lower feed intake and a higher live weight gain . The slaughtering parameter investigated and the chemical composition of the empty body remained uninfluenced . The daily nutrient retention values were positively influenced by the Monensin supplementation since the fattening bulls of the test group required 30 days less to achieve the attempted fattening weight . The additional retention of protein, fat and energy per animal and day in the dairy bulls approximately equal to 10.9; 13.5 and 16.4% and in the fattening hybrids 1.9; 3.2 and 2.6% . Due to a higher energy retention at a lower level of feed and energy intake after Monensin supplementation an average of approximately equal to 11.3 and 15.4% resp . more of the consumed digestible protein and the digestible energy resp . were retained in the empty bodies . One can conclude that Monensin improved the utilisation of feed energy; obviously the effect of the polyether antibiotic is due to its influence on processes in the rumen or directly or indirectly on metabolism. J Antibiot (Tokyo), 1984 Dec, 37(12), 1664 - 9 Biosynthesis of astromicin and related antibiotics . I . Biosynthetic studies by bioconversion experiments; Itoh S et al.; Biosynthesis of astromicin, a unique pseudodisaccharide aminoglycoside antibiotic containing 1,4-diaminocyclitol component, was investigated by isolating a variety of possible precursor compounds from mutants of Micromonospora olivasterospora in which biosynthetic pathways for astromicin were blocked . Washed mycelia of M . olivasterospora mutants converted these compounds to astromicin, which was detected by thin-layer chromatography . Since astromicin possesses one glycyl and three methyl groups, {14C}glycine and {14C}methionine should be incorporated into precursors to form astromicin . To confirm the biosynthetic pathway, formation of labeled astromicin from the precursors was examined using {1-14C}-glycine or {methyl-14C}methionine . From above results, we propose the biosynthetic pathway for astromicin as shown in Fig . 2. J Antibiot (Tokyo), 1984 Dec, 37(12), 1596 - 9 Stereochemistry of the epoxydon group antibiotic G7063-2 isolated from a Streptomyces species HPL Y-25711; Reddy GC et al.; The absolute configuration of the ring system of the antibiotic G7063-2 has been established as being the same as that reported for terreic acid, based on circular dichroism data . During structure elucidation experiments, reaction with ethereal diazomethane gave an adduct whose structure is proposed. J Antibiot (Tokyo), 1984 Dec, 37(12), 1566 - 71 PD 114,759 and PD 115,028, novel antitumor antibiotics with phenomenal potency . I . Isolation and characterization; Bunge RH et al.; The isolation of two new antibiotics, PD 114,759 and PD 115,028, exhibiting in vivo antitumor activity at extremely low doses is described . The physico-chemical properties of these sulfur-containing compounds show that they represent a novel class of antitumor agents. J Antibiot (Tokyo), 1984 Dec, 37(12), 1546 - 54 Cephabacins, new cephem antibiotics of bacterial origin . III . Structural determination; Tsubotani S et al.; The structures of 15 new cephem antibiotics, cephabacin F1-9 and H1-6, were determined by their spectroscopic analyses and decomposition studies . They are consisted of a cephalosporin nucleus and a di, tri or tetrapeptide including a new amino acid which is bound at the position 3 with an ester bond . The components, F1-9, showed unique biological activities by the presence of a formylamino group at the position 7. Antimicrob Agents Chemother, 1984 Dec, 26(6), 863 - 9 Gastrointestinal motor-stimulating activity of macrolide antibiotics and analysis of their side effects on the canine gut; Itoh Z et al.; For clarification of the nature of the side effects of macrolide antibiotics on the gastrointestinal tract, the motor-stimulating activity of these agents was studied in unanesthetized dogs . The results showed that erythromycin and oleandomycin, the 14-membered macrolides with two side chain sugars combined at C3 and C5 in a glycosidic linkage in parallel, strongly stimulate gastrointestinal motor activity, an action accompanied by vomiting at large doses . On the other hand, leucomycin, acetylspiramycin, and tylosin, belonging to a 16-membered macrolide with two side chain sugars in series combined at C5 of the lactone ring, did not induce contractions of the gastrointestinal tract . Motor-stimulating activity by erythromycin and oleandomycin was greatly inhibited by atropine sulfate . These results point to structure-physiological activity relationships. Antimicrob Agents Chemother, 1984 Dec, 26(6), 841 - 4 Intra- and extracellular susceptibility of Mycobacterium avium-intracellulare complex to aminoglycoside antibiotics; Nozawa RT et al.; We developed a rapid, quantitative culture method to estimate the replication of Mycobacterium avium-intracellulare complex (MAIC) in human peripheral blood mononuclear cells . Mononuclear cells were plated in a 96-well tray, infected with clinically isolated strains of MAIC in the presence of autologous plasma, and further cultivated for 1 to 2 weeks in a tissue culture medium . No MAIC cells proliferated extracellularly, since human plasma inhibited extracellular growth of the mycobacteria . The mononuclear cells were lysed through a brief treatment with alkali, and surviving intracellular mycobacteria were diluted and plated with tissue culture medium in a 96-well tray . Mycobacterial colonies were counted under a microscope after a 5-day incubation . The number of viable MAIC cells continuously increased, reaching 10 times the number of inoculated cells in a week . Thus, mononuclear phagocytes were the permissive site for the replication of MAIC . Intra- and extracellular susceptibilities of seven MAIC strains to four aminoglycoside antibiotics were then studied . The mycobacteria were most susceptible in vitro to dibekacin (MICs, 3.13 to 12.5 micrograms/ml) . Dibekacin at 12.5 micrograms/ml was bacteriostatic to five of seven strains in the monocytes . Also, intracellular replication of the other two strains was greatly suppressed by that concentration of dibekacin. Antibiotiki, 1984 Dec, 29(12), 897 - 901 {Elimination of admixtures from antibiotic sediments during their treatment with solvents}; Sinitsyn MA et al.; A model for determination of the admixture concentration in the secondary mother solution was developed . The concentration was determined depending on the solvent volume used for repulping the precipitate and on the impurity level of the initial antibiotic paste . When the values of X1 and X2 are known it is possible to estimate the amount of the admixtures remaining in the paste layer after separation of the secondary mother solution with regard to the volume of the latter in the precipitate pores . Optimization of paste repulping should be considered in combination with displacement washing and the apparatus used for separation of the phases, as well as the requirements for the purity level of the finished product. Antibiotiki, 1984 Dec, 29(12), 884 - 92 {Structure of the