Am J Hosp Pharm, 1988 Mar, 45(3), 584 - 8 Attitudes of house physicians concerning various antibiotic-use control programs; Murray MD et al.; Medical and surgical house physicians at three teaching hospitals with different antibiotic control programs (ACPs) were surveyed to determine their attitudes about and preferences for these programs . Questionnaires were mailed to resident physicians who had trained at all three hospitals . One hospital had no antibiotic prescribing policy (open prescribing), one employed an infectious-disease physician consultant who discussed antibiotic orders for certain reserved drugs with prescribing physicians but did not otherwise restrict access to the drugs (educational ACP), and the third hospital required approval of an infectious-disease physician for dispensing of reserved drugs by the pharmacy department (restrictive ACP) . The survey response was 77% after one follow-up mailing to nonrespondents . Regardless of hospital type, physicians preferred the educational ACP to either open prescribing or the restrictive ACP . Based on personal experiences, significantly fewer physicians encountered patient-care problems with the educational ACP than with either open antibiotic prescribing or the restrictive ACP . Significantly more physicians perceived that the educational ACP was more beneficial for patient antibiotic therapy and will be more beneficial for future antibiotic prescribing than the restrictive ACP . Most respondents believed that ACPs save hospitals money, that ACPs can be implemented without compromising either patient care or physician performance, and that they would encounter similar ACPs in the future . Educational ACPs should be considered at teaching hospitals with interested infectious-disease consultants. Antimicrob Agents Chemother, 1988 Mar, 32(3), 341 - 5 Cycloheximide efflux in antibiotic-adapted cells of the fungus Mucor racemosus; Shearer G Jr et al.; Mucor racemosus cells adapted to either cycloheximide or trichodermin were approximately 40-fold more resistant to cycloheximide than nonadapted cells . Ribosomes isolated from adapted and nonadapted cells were equally sensitive to cycloheximide in an in vitro poly(U) translation assay . There was no detectable modification of cycloheximide by adapted cells . Uptake of drug by nonadapted and adapted cells was characterized by a rapid initial accumulation during the first 2 min of incubation with {3H}cycloheximide, followed by a steady-state intracellular drug concentration well below that of the medium . The steady-state drug concentration was approximately 10-fold lower in adapted cells than in nonadapted cells . Treatment of cells with sodium azide or dinitrophenol abolished the difference between uptake of drug by nonadapted and adapted cells and resulted in intracellular drug levels equal to that of the medium . Direct efflux measurements showed that adapted cells loaded with cycloheximide were able to excrete the drug far more rapidly than nonadapted cells . These results suggest that both nonadapted and adapted cells possess an energy-dependent efflux mechanism for transporting cycloheximide and that resistance in adapted cells is due to increased efficiency of transport. Antimicrob Agents Chemother, 1988 Mar, 32(3), 314 - 8 Comparative toxicities of cephalosporin antibiotics in a rabbit kidney cell line (LLC-RK1); Williams PD et al.; The rabbit kidney cell line LLC-RK1 was tested for its ability to discriminate the toxicities of six cephalosporin antibiotics according to their in vivo nephrotoxic potentials in rabbits . With the exception of cephalothin, which was markedly toxic to kidney cells in vitro, a good correlation between in vitro toxicity and in vivo nephrotoxicity was obtained, yielding the following toxicity rank order: ceftazidime less than cefazolin approximately cefoperazone less than cephaloglycin approximately cephaloridine . The addition of a kidney microsomal S9 fraction to the cell cultures desacetylated cephalothin as occurs in vivo and detoxified this antibiotic, providing it with the proper toxicity relative to the other cephalosporins . When compared with parent structures, desacetylated derivatives of other cephalosporins such as cephapirin were similarly found to be less toxic to LLC-RK1 cells . The acetylated cephalosporin cephaloglycin was not detoxified by the kidney S9 fraction and was desacetylated three to four times slower than cephalothin by renal esterases . Thus, the rate and extent of desacetylation of cephalosporins may play a role in their in vivo nephrotoxic potential . Our results further suggest that LLC-RK1 cells will provide a useful model for evaluating the potential nephrotoxicity of new cephalosporin antibiotics before in vivo studies. J Antimicrob Chemother, 1988 Mar, 21(3), 345 - 54 Quantitative study of the interaction between two antibiotics by agar diffusion; Lauzer J et al.; In order to quantify the interaction between two antibiotics by agar diffusion, a fractional critical concentration (FCC) index, analogous to the fractional inhibitory concentration (FIC) index, was defined . Two pairs of filter paper strips, containing different concentrations of each of two antibiotics, were placed at right angles on an agar plate . After 2 h of diffusion the strips were removed and the plate was inoculated with bacteria . The FCC index was calculated after overnight incubation . Three combinations of antibiotics were studied: trimethoprim-sulphamethoxazole, tobramycin-cefazolin and vancomycin-rifampicin . Over 80% agreement was obtained between the FCC indices and the FIC indices obtained by the chequerboard microdilution technique . The novel diffusion method thus appears promising and warrants further evaluation. J Bone Joint Surg Br, 1988 Mar, 70(2), 322 - 4 The timing of tourniquet application in relation to prophylactic antibiotic administration; Bannister GC et al.; Antibiotic levels in bone and fat were measured in patients undergoing knee replacement to determine the time that should elapse between intravenous injection and tourniquet inflation . The tissue levels increased progressively with time, and there was wide variation in absorption rate between patients and between the two cephalosporins assessed . Five minutes should probably be left between systemic injection and inflation of the tourniquet, though two minutes may be long enough for drugs which are rapidly absorbed. Prikl Biokhim Mikrobiol, 1988 Mar-Apr, 24(2), 182 - 6 {Antibiotic activity and heterogeneity of a population of Azotobacter chroococcum}; Pozmogova et al.; Antibiotic activity of Azotobacter chroococcum was determined depending on the morphological composition of the population . The population was divided by the sedimentary properties into 2 fractions: heavy (H) and light (L) . A higher amount of azochroomycin (up to 170%) could be extracted from the H-fraction consisting mainly of medium size cells (1.3-1.9 nm in diameter) as compared to that from the L-fraction consisting predominantly of the cells of 0.7-1.3 nm in diameter; the activity of the L-fraction counted as 100%. Rev Infect Dis, 1988 Mar-Apr, 10(2), 365 - 76 Role of empiric parenteral antibiotics prior to lumbar puncture in suspected bacterial meningitis: state of the art; Talan DA et al.; The performance of lumbar puncture (LP) in patients with suspected meningitis is often delayed if, for example, the clinical presentation suggests a need for prior computed tomographic (CT) scan or if patients are initially examined at settings with limited clinical facilities . The role of empiric parenteral antibiotic therapy prior to LP under these circumstances has not been critically analyzed . Review of the literature suggests that in cases of bacterial meningitis (1) the existing data are inadequate to assess the effect of a short delay of therapy on mortality and morbidity; (2) a short period of antibiotic therapy prior to LP does not change cerebrospinal fluid (CSF) white blood cell count, protein, or glucose; (3) the yield of CSF gram stain and culture may be somewhat reduced by a short period of antibiotic therapy, but these tests often remain positive; and (4) adjunctive tests, including blood cultures and CSF antigen tests, can often independently identify the bacterial meningopathogen . The available evidence suggests that if bacterial meningitis is suspected and LP must be delayed, intravenous antibiotics are warranted before CSF is obtained. Gan To Kagaku Ryoho, 1988 Mar, 15(3), 369 - 79 {The structure and antitumor activity of antitumor antibiotics--recent progress}; Otake N; Effort looking for new antitumor antibiotics useful for the treatment of curing cancer resulted to the discovery of a number of new compounds with newer action mechanism as well as newer structural feature . The antibiotics which have been discovered since 1984 are discussed under classifications of action mechanism and structural feature, as well . The first group, which belong to a novel class of antibiotics containing a bicyclodiynene carbon skeleton in the molecules exhibited the most strong anti-tumor activity comparing with the antitumor antibiotics so far discovered . The action mechanism of this was explained by the diradical formation of diynene-cyclization, which led to the scission of double strand DNA . Amongst, esperamicin A seems of great interest in view of the therapeutic development . Moreover, elsamicin A, a member of chatarin antibiotics, and FR-900482 compound, an antibiotic having a polycyclic alkalodal skeleton are under development for the new chemotherapeutic agents . Rhizoxin, the metabolite of Rhizopus chinensis is also a promising candidate as anticancer agent . Its action mechanism was classified as an inhibitor of mitosis by binding to the microtibline proteins . Rhizoxin A shows no cross resistance with vincristine . MX2 (KRN 8602), the morpholino derivative of 13-deoxo-10-hydroxy-carminomycin, shows anticancer activity against tumor cells resistant to P388/ADM as well as low cardial toxicity . Miscellaneous compounds whose action mechanism are unknown are described. South Med J, 1988 Mar, 81(3), 412 - 3 Cure of brain abscess caused by Nocardia asteroides resistant to multiple antibiotics; Fried J et al.; A 29-year-old man with pulmonary infiltrates due to pulmonary alveolar proteinosis had Nocardia asteroides pneumonia and brain abscess . The nocardial infections persisted after therapy with sulfonamides, minocycline, and cefotaxime . Based on the susceptibility studies and serum antibiotic concentrations, he was treated with minocycline, 400 to 600 mg daily, cefotaxime, 12 to 30 gm daily, and probenecid for 15 months . Proteinuria observed near the completion of therapy was transient . Three years after therapy, the infections appear to have been cured. Arch Surg, 1988 Mar, 123(3), 333 - 9 Duration of preventive antibiotic administration for open extremity fractures; Dellinger EP et al.; The necessary duration of antibiotic administration after open fracture has not been established . In a double-blind prospective trial we randomized 248 patients with open fractures to receive one or five days of cefonicid sodium therapy or five days of cefamandole nafate therapy as part of the initial treatment . Rates of fracture-associated infections in the three groups were ten (13%) of 79, ten (12%) of 85, and 11 (13%) of 84, respectively . The 95% confidence limit for the difference in infection rates between the one-day group and the combined five-day groups was 0% to 8.3% . The actual difference was 0.2% . A brief course of antibiotic administration is not inferior to a prolonged course of antibiotics for prevention of postoperative fracture-site infections. Immunology, 1988 Mar, 63(3), 471 - 5 Immunosuppressive and anti-proliferative effects of a macrotetrolide antibiotic, tetranactin; Tanouchi Y et al.; The macrotetrolide tetranactin suppressed the appearance of experimental autoimmune uveoretinitis induced in Lewis rats with a soluble retinal antigen (S-antigen) . The drug at 1 ng/ml inhibited the mitogen activation of unfractionated lymphocytes; incorporation of radiolabelled precursors such as thymidine, uridine and leucine into the cells was markedly reduced . The synthesis and release of IL-2 by mitogen-activated lymphocytes was significantly suppressed in the presence of tetranactin . Incorporation of 45Ca was also inhibited, while intracellular Na+ levels were increased . In view of the ionophore property of tetranactin, it was suggested that the drug might demonstrate its immunosuppressive effect by affecting intracellular cation concentrations. Cell Biol Toxicol, 1988 Mar, 4(1), 123 - 33 Induction of erythroid differentiation by the anthracycline antitumor antibiotic pyrromycin; Steinheider G et al.; The oligosaccharide-anthracyclines, aclacinomycin A, marcellomycin and musettamycin, are potent inducers of erythroid differentiation in hemopoietic cells lines of rodent and human origin . The present studies revealed that pyrromycin, a closely related monosaccharide-anthracycline, induced erythroid differentiation in Friend leukemia cells and in the human leukemia cell line K 562 . Pyrromycin, marcellomycin and musettamycin, which possess an identical aglycone structure containing a Cl-hydroxyl group, exhibited relatively low optimal inductive concentrations . In contrast, the optimal inductive concentration of aclacinomycin A, which lacks the Cl-hydroxyl group, was markedly higher, i.e., the differentiation inducing capacity was lower . It should be noted, however, that the yield of differentiated cells following treatment with the monosaccharide-anthracycline pyrromycin was distinctly lower than that after treatment with the oligo-saccharide-anthracyclines, aclacinomycin A, marcellomycin or musettamycin . Thus, our data indicate that the efficacy of anthracyclines to induce erythroid differentiation is related to a) the presence of a Cl-hydroxyl group in the aglycone and b) the presence of an oligosaccharide side chain. Anticancer Drug Des, 1988 Mar, 2(4), 371 - 85 An alternative concept for the molecular nature of the peroxidating ability of anthracycline anti-tumor antibiotics and anthracenodiones; Tempczyk A et al.; Quantum chemical calculations of model anthraquinone molecules using the CNDO/2 method have revealed that superoxide anion radical formation following the single electron transfer mediated by anthraquinone anti-tumor antibiotics may occur in aerobic conditions as a result of the direct addition of an electron to the anthraquinone-oxygen low energy charge transfer complex that is formed with singlet oxygen . Cyclovoltammetric measurements have been performed in order to provide experimental evidence supporting the hypothesis . The structural requirements for an anthraquinone molecule not exhibiting peroxidating ability by the above mechanism have been postulated . They include maximum symmetry of electron density distribution (symmetry of the molecule), a decrease of the electron density of the pi electron system and an increase in the rigidity of the molecule. Antibiot Khimioter, 1988 Mar, 33(3), 211 - 7 {Antibiotic production by variants of Penicillium chrysogenum isolated after protoplast formation and exposure to mutagens at the protoplast stage}; Sotnikova IV et al.; A procedure for protoplast formation in the penicillin-producing organism Penicillium chrysogenum was developed . The yield of the protoplasts was high, the protoplasts were stable and capable of regeneration . Two types of the protoplast regeneration were revealed . The spores and protoplasts were treated with UV light and N-nitroso-N'-methyl biuret and their effect on production of the antibiotic by the isolated variants was studied . It was shown that the protoplasts of P . chrysogenum were more liable to the mutagenic effect of UV light and nitroso methyl biuret than the fungus conidia . It is possible to use this specific feature in intensification of selection aimed at isolation of highly productive strains of P . chrysogenum. Antibiot Khimioter, 1988 Mar, 33(3), 185 - 9 {Selection of strains of Streptomyces griseus Kr., the producer of a streptothricin antibiotic grisin, using the method of protoplast fusion}; Kuklin VV et al.; The effect of protoplasting on antibiotic activity of the grisin-producing organism was shown . High frequency of Grn- mutants after strain VG307f protoplasting and no capacity in these mutants for reversion to the initial Grn+ phenotype were shown . The reversion frequency was less than 10(-8) . Moreover, it was shown that all the Grn- mutants lost their stability (GrnR) to the effect of their own antibiotic . With respect to strain VG212 there was noted a significant increase in the number of both the minus and the plus variants after the protoplast formation and regeneration . Fusing of protoplasts of strains VG307f and VG212 belonging to the divergent lines in selection of S . griseus Kr . yielded the phage stable strain VG7849 with high levels of the antibiotic production and improved technological properties. Compr Ther, 1988 Mar, 14(3), 10 - 3 Update: antibiotic therapy; King CH; Although these new antibiotics are powerful broad-spectrum agents, the decision to use new antibiotics should be based on careful assessment of the patient's clinical status and need for therapy, the known resistance patterns of the hospital or community, and cost-benefit factors . Indiscriminate widespread use will limit or abolish their usefulness and needlessly increase the cost of hospital therapy. Drug Metab Dispos, 1988 Mar-Apr, 16(2), 296 - 301 Metabolism of cyclosporin A . III . Interaction of the macrolide antibiotic, erythromycin, using rabbit hepatocytes and microsomal fractions; Fabre I et al.; The interaction between cyclosporin A (CsA) and the macrolide antibiotic, erythromycin, has been studied in freshly isolated rabbit hepatocytes and in rabbit liver microsomal fractions . In hepatocytes, CsA was rapidly accumulated inside the cells and metabolized to its different groups of derivatives (mono- and/or dihydroxylated and/or N-demethylated metabolites) {Fabre, Bertault-Peres, Fabre, Maurel, Just, and Cano: Drug Metab . Dispos . 15, 384 (1987)} . In the presence of erythromycin in the extracellular compartment, CsA metabolism was inhibited in a concentration-dependent manner . However, erythromycin did not affect intracellular CsA accumulation and binding of CsA to its intracellular protein binding site(s) . Since CsA was specifically metabolized by the cytochrome P-450 LM3c isozyme {Bertault-Peres, Bonfils, Fabre, Just, Cano, and Maurel: Drug Metab . Dispos . 15, 391 (1987)}, we further studied the effect of erythromycin on CsA metabolism by liver microsomal fractions . In the presence of erythromycin, CsA metabolism was also decreased . Lineweaver-Burk analysis of erythromycin-CsA interaction demonstrated that erythromycin was a competitive inhibitor (Ki = 156 microM) of CsA metabolism (Km = 0.43 microM; Vmax = 4.8 nmol/min) . In agreement with these data, CsA inhibited (i) erythromycin N-demethylation to a large extent and (ii) the appearance of the erythromycin-cytochrome P-450 LM3c complex . We could conclude that the interaction between CsA and erythromycin most likely results from the fact that both drugs are extensively metabolized by the same cytochrome P-450 form: P-450 LM3c or P-450 III A4 according to the new nomenclature.(ABSTRACT TRUNCATED AT 250 WORDS) Antimicrob Agents Chemother, 1988 Mar, 32(3), 308 - 13 Polycation binding to isolated lipopolysaccharide from antibiotic-hypersusceptible mutant strains of Escherichia coli; Rocque WJ et al.; Lipopolysaccharide (LPS) samples isolated from a parent and two antibiotic-hypersusceptible mutant strains of Escherichia coli were analyzed for polycation affinity and level of binding . Purified salts of the LPSs from the parent strain, UB1005, and from one of the mutant strains, DC1, bound similar amounts of sodium and magnesium, but the samples from the second mutant strain, DC2, had significantly greater amounts of counterions bound per phosphate than did the other two isolates . The 31P nuclear magnetic resonance spectra indicated that, compared with LPS from the parental strain, the sample from strain DC1 was similar but the DC2 sample contained fewer diphosphodiester and more diphosphomonoester groups . Motion within the lipid A head group regions of the magnesium salts of the three isolates was dramatically different, as revealed by an electron spin resonance probe . The binding of the cations to the LPS aggregates was measured by the displacement of this cationic spin probe from the LPS samples . The polycations polymyxin, gentamicin, and spermine displaced more probe from samples of the two mutant strains than from that of the parental strain . The sample from the most antibiotic-susceptible strain, DC2, had the highest affinity for all the polyvalent cations tested . The results indicate that antibiotic hypersusceptibility can result from at least two distinct alterations in LPS structure . The decrease in diphosphodiesters and increase in diphosphomonoesters in the LPS of the DC2 sample resulted in more acidic phosphate moieties and a more antibiotic-susceptible cell . In contrast, the alterations in the LPS of DC1 that resulted in antibiotic hypersusceptibility of the cell were not in the phosphate substituents . In both mutants, however, hypersusceptibility resulted in an alteration in LPS structure that increased the affinity of the molecules for polycations. Biochem Biophys Res Commun, 1988 Feb 15, 150(3), 947 - 54 Inhibition of protein synthesis by aminoglycoside antibiotics in polyamine-requiring bacteria; Nastri HG et al.; The effect of streptomycin and other aminoglycosides on protein synthesis has been studied using various streptomycin-sensitive strains unable to synthesize polyamines . We have confirmed and extended our previous results showing that the strong inhibition of translation caused by the antibiotic in polyamine-supplemented bacteria was markedly reduced in polyamine-starved cells . The analysis of polypeptides synthesized in the absence and presence of streptomycin in bacteria grown with and without putrescine has shown that the antibiotic provoked the accumulation of low molecular weight peptides partially bound to ribosomes in polyamine-unstarved cells . On the contrary, the drug did not induce major alterations in the patterns of proteins obtained from polyamine-depleted bacteria . The addition of the antibiotic did not evoke any change of proteolytic activity. J Toxicol Sci, 1988 Feb, 13(1), 41 - 7 Effect of beta-lactam antibiotics on hepatocellular glutathione levels in vitro and in vivo; Higaki J et al.; Incubation of isolated rat hepatocytes with high concentration of beta-lactam antibiotics, cephaloridine (CER), flomoxef (FMOX) or cephamandole (CMD), resulted in significant reduction of cellular glutathione (GSH) levels, though cell viability was not affected during the incubation period . I.v . injection of a large dose, 300 mg/kg, of these beta-lactam antibiotics to rats did not affect the hepatic GSH levels . The concentration of beta-lactam antibiotics in the body fluid of the rats were found to be much lower than the amounts which causes GSH depletion in vitro. Jpn J Pharmacol, 1988 Feb, 46(2), 165 - 72 In vitro effects of various heterocyclic thiol compounds and beta-lactam antibiotics on vitamin K-dependent gamma-glutamylcarboxylation activity in liver microsomes; Oka T et al.; The in vitro effect of N-methyltetrazolethiol (NMTT), one of the common substituents at the 3'-position of the cephem in various beta-lactam antibiotics, on liver microsomal gamma-glutamylcarboxylation (gamma-carboxylation) activity was examined using solubilized rat liver enzyme . The enzyme activity was inhibited by coexisting with NMTT and NADH, and this inhibitory activity could be suppressed by the addition of a sulfhydryl compound such as dithiothreitol (DTT), glutathione or cysteine . Various five-membered heterocyclic thiol compounds exhibited concentration-dependent inhibition of microsomal gamma-carboxylation activity . These inhibitory actions diminished markedly in the presence of 1 mM DTT . In vitro gamma-carboxylation activity also decreases upon addition of various beta-lactam antibiotics at 1 or 10 mM, depending upon the concentration of the drug . Among the heterocyclic thiol compounds, there is a correlation between their inhibitory activities and hydrophobicities . Thus, the in vitro inhibitory activity of heterocyclic thiol compounds and beta-lactam antibiotics on microsomal gamma-carboxylation activity is not correlated with their molecular structures, but rather depends on their hydrophobicities and with the concentrations in the reaction mixture. Antibiot Khimioter, 1988 Feb, 33(2), 96 - 9 {Selection of the seeding media and the age and quantity of mycelia providing simultaneous biosynthesis of an antibiotic and pigment by the fungus Hypomyces rosellus}; Toropova EG et al.; The authors observed maximum simultaneous biosynthesis of antibiotic and pigment in the microphilic fungus with using 48-hour seed mycelium having the specific growth rate of 0.008-0.011 h-1 in an amount of 5-7 per cent (v) . The Balling 4 degrees wart and Chapek medium with 1 per cent of soybean flower and 1 per cent of corn steep liquor may be used for growing the seed mycelium . No significant effect of the seed medium composition and seed mycelium age on the pigment production was observed. Jpn J Antibiot, 1988 Feb, 41(2), 196 - 200 {An application of a new antibiotic, ceftriaxone, during the perinatal period}; Tateno M; 1 . Ceftriaxone (CTRX) was not transferred well into cerebrospinal fluid in healthy individuals . 2 . The transplacental passage and the transfer of CTRX into amniotic fluid were very good, and CTRX seems useful for the treatment of perinatal infections . 3 . Clinically, CTRX was very effective against amniotic infections and infections of the puerperal uterus: Clinical efficacies were excellent in 1 case and good in 3 out of 4 cases (efficacy rate: 100%) . 4 . No side effects or laboratory abnormalities were observed. Antimicrob Agents Chemother, 1988 Feb, 32(2), 159 - 63 Simple spectrophotometric assay for measuring protein binding of penem antibiotics to human serum; Gootz TD et al.; The binding of antibiotics to plasma (serum) proteins through hydrogen bonding can significantly influence the biological characteristics of these drugs . A rapid spectrophotometric assay has been developed that measures the level of free (unbound) penem antibiotic in serum ultrafiltrates . Whole human serum was adjusted to a standard concentration of antibiotic and then filtered by centrifugation through a Centrifree (Amicon Corp., Lexington, Mass.) filter that retained greater than 99.9% of serum protein . The degree of penem protein binding was determined spectrophotometrically by measuring the level of unbound drug in the ultrafiltrate at 322 nm . At this wavelength, no interfering absorption from residual protein was detected in the ultrafiltrate, and penem absorption was linear over a wide concentration range . The method gave protein-binding values comparable to those obtained by a high-pressure liquid chromatography assay but was more rapid, since it did not require solvent extraction and high-pressure liquid chromatography calibration procedures . The spectrophotometric assay has been used to assay over 100 penems to determine the structure-activity relationships that are involved with the high serum protein binding of these agents . As with penicillins and some cephalosporins, the nonpolar nature of the penem side chain at the C-2 position strongly influenced the degree of penem binding to serum proteins. Ann Intern Med, 1988 Feb, 108(2), 289 - 92 Stopping antibiotic therapy in neutropenic patients; DiNubile MJ; Infection is the major cause of death in neutropenic patients . Because of the lack of acute inflammatory cells, the usual signs of infection are often absent in these patients . Therefore, unexplained fever in a neutropenic patient requires prompt initiation of antibiotic therapy . Many physicians advocate continuing antibiotic therapy until neutropenia resolves . However, prolonged treatment with broad-spectrum antibiotics increases the risks of drug toxicity and superinfection with resistant bacteria and fungi . Based on a critical review of the literature and a large personal clinical experience, I offer tentative guidelines for withdrawing antibiotic therapy in persistently neutropenic patients . When antibiotic therapy is discontinued, frequent and careful monitoring of these patients and a low threshold for reinstituting antibiotic therapy are essential. Plast Reconstr Surg, 1988 Feb, 81(2), 162 - 70 Experimental evaluation of the antibiotic carrying capacity of a muscle flap into a fibrotic cavity; Russell RC et al.; A study was undertaken to determine the antibiotic carrying capacity of a transferred muscle flap into a fibrotic cavity using a tissue cage model in rabbits . Blood and chamber fluid antibiotic levels were determined after intramuscular hindlimb gentamicin injection up to 56 days following muscle transfer . This study suggests that muscle flaps increase the concentration of antibiotics that can be achieved within a fibrotic cavity . The measurable peak level decreases with time, probably due to increased scarring around the muscle . This model should enable the study of many different classes of antibiotics with different protein binding and other administration schedules using multiple timed doses or a combination of agents. J Clin Pharmacol, 1988 Feb, 28(2), 136 - 40 Glycopeptide antibiotics; Parenti F; Numerous glycopeptides continue to be described in the literature . They all share a similar heptapeptidic structure with a fixed spatial configuration that forms the basis of their ability to recognize D-alanyl-D-alanine-containing structures in the cell wall . This complexation results in block of peptiglycan elongation; hence, inhibition of growth; and, eventually, cell death . The great variety of substituents on the heptapeptide forms the basis of a wide gradation of physico-chemical characteristics, namely net charge and lipophilicity, which, in turn, might explain the widely differing pharmacologic properties. Biokhimiia, 1988 Feb, 53(2), 227 - 32 {Relation between respiration and swelling of liver mitochondria induced by anthracycline antibiotics}; Suslova AI et al.; The anthracycline antibiotics rubomycin (daunorubicin) and carminomycin at concentrations which stimulate mitochondrial respiration in the absence of ADP induce the swelling of rat liver mitochondria . Under these conditions, the lipid peroxidation (LPO) inhibitor ionol slows down both the respiration and swelling of mitochondria . This suggests that stimulation of respiration and swelling under effects of the antibiotics largely depend on LPO . In the presence of the respiration inhibitor antimycin no effect of ionol is observed . Adriamycin (doxorubicin) stimulates mitochondrial respiration in a lesser degree than rubomycin and carminomycin and fails to induce mitochondrial swelling. J Hosp Infect, 1988 Feb, 11 Suppl A, 251 - 8 Prophylactic antibiotics in traumatic wounds; Sacks T; There is well-documented evidence justifying, perhaps demanding, the obligatory use of early, anticipatory treatment in open fractures and in penetrating abdominal wounds, and equally convincing evidence that they are not indicated in fractures of the base of the skull with CSF leaks, in thermal injuries, or in simple lacerations . As far as penetrating chest wounds, and bites are concerned, the evidence is perhaps as yet inconclusive, but antibiotics are probably not indicated in these situations. Biochem Biophys Res Commun, 1988 Jan 15, 150(1), 384 - 90 Conformational change on calcium binding by the lipopeptide antibiotic amphomycin . A C.D . and monolayer study; Lakey JH et al.; The acidic linear lipopeptide amphomycin is a calcium dependent antibiotic which is thought to bind to carrier lipids such as dolichol monophosphate . The actual role of Ca++ is not definitely established and in this article we have examined the peptides interactions with a range of divalent cations . By CD we have shown that a conformational change is induced by Ca++, Sr++ and Ba++ but not by Mg++, Zn++, Cd++ or Gd+++ . Monolayer studies show a decrease in molecular area and an increase in film stability when the subphase contains Ca++ . The ensemble of results provides preliminary evidence for the formation of a beta hairpin structure on ion binding (Ka (Ca++) = 2.4 x 10(3)M-1) which could enhance amphomycin's bilayer solubility. Br J Haematol, 1988 Jan, 68(1), 63 - 6 The development of hypoprothrombinaemia following antibiotic therapy in malnourished patients with low serum vitamin K1 levels; Cohen H et al.; A group of nine well-nourished patients, with normal serum vitamin K1 levels (mean 546, range 310-1350 pg/ml), maintained normal prothrombin times (PTs) and factor VII clotting activities throughout a 7 d course of i.v . cefotetan disodium, an N-methyl-thiotetrazole (NMTT) containing cephalosporin antibiotic . However, 11 of 20 patients, with acute intra-abdominal sepsis and initially normal PTs who underwent emergency surgery, developed prolonged PTs (INR 1.4-3.1) associated with reduction in factor VII activities (0.74-0.38 u/ml) after 3-7 d of antibiotic therapy . Nine of these 11 patients had clinical evidence of malnutrition and nine had subnormal serum vitamin K1 levels (mean 119, range 43-354 pg/ml) on admission . Seven received cefotetan but four were treated with a non-NMTT-containing cephalosporin or antibiotics belonging to other groups . The nine patients who maintained normal PTs all had normal nutritional status and normal serum vitamin K1 levels (mean 279, range 103-915 pg/ml) at presentation . The PT is a relatively insensitive indicator of vitamin K stores, and malnourished patients with low serum vitamin K1 levels are at risk of developing hypoprothrombinaemia following intravenous antibiotic therapy. Zentralbl Gynakol, 1988, 110(9), 570 - 4 {Value of the preventive use of antibiotics following vaginal obstetric operations}; Rechlin D et al.; For a period of 6 years 838 puerperal cases after vaginal obstetric operations (forceps delivery, vacuum extraction, delivery with speculum, manual placenta separation, palpation of the uterus) were critically analysed . The result of the studies suggest that an antibiotic or chemoprophylaxis after vaginal obstetric operations is not successful because of the relatively low infectious morbidity . In obstetrics this prophylaxis is indicated only in delivery by caesarean section as a perioperative short-time prophylaxis. Folia Microbiol (Praha), 1988, 33(3), 238 - 40 The antibiotic PSX-1 produced by Penicillium stipitatum is identical with botryodiplodin; Fuska J et al.; Antibiotic PSX-1 exhibiting antitumour activity, formerly isolated from the filtrate of a culture of Penicillium stipitatum, was shown to be identical with botryodiplodin. Drugs, 1988, 35 Suppl 2, 208 - 13 Computer modelling antibiotic therapy costs . Impact of therapeutic range; Gladen HE; Computer modelling techniques were used to examine the economic consequences of intravenous chemotherapy of serious infection . Acquisition cost of the drug was found to be a poor predictor of global cost, since inclusion of the preparation and administration costs and projected laboratory and drug complication costs narrow, or even reverse, apparent cost differentials between drugs . Thus, the cost per day for acquisition/total treatment (in US dollars) are: penicillin $5/$30, gentamicin $1/$46, amikacin $26/$63, clindamycin $38/$57, metronidazole $12/$20 and cefotaxime $47/$60 . 'Triple therapy' involving gentamicin ($0.40/dose) resulted in higher hospital costs than the equivalent regimen involving cefotaxime ($16/dose) . Even when the purchase price is high, humanitarian considerations advocate the use of safe, predictable, efficacious drugs . Fortunately, the present analysis suggests that such drugs frequently result in the lowest total treatment cost . Current cost containment efforts that are based on acquisition costs only are flawed and may result in both suboptimal care and higher actual costs. Drugs, 1988, 35 Suppl 2, 100 - 5 Preventative antibiotics for penetrating abdominal trauma--single agent or combination therapy? Bivins BA, Crots L, Sorensen VJ, Obeid FN, Horst HM. In this open, prospective, comparative study, 75 patients who sustained penetrating abdominal trauma were randomised to receive 1 of 3 antibiotic regimens preoperatively and for 3 to 5 days postoperatively . Group I received cefotaxime 2g 8-hourly, group II received cefoxitin 2g 6-hourly and group III received clindamycin (900 mg 8-hourly) and gentamicin 3 to 5 mg/kg/day in divided doses 8-hourly . The 3 groups were not statistically different in terms of age, sex, severity of injury, number of organs injured, colon injuries, shock, blood transfusions or positive intra-operative cultures . Septic complications occurred in 8% of patients in group I, in 4% of group II patients and in 8% of group III patients . Cefotaxime was the least costly regimen, followed by cefoxitin, then clindamycin and gentamicin . It may be concluded that single agent therapy with a broad spectrum cephalosporin is preferable to combination therapy on the basis of equivalent effectiveness, less toxicity and lower costs. Chemotherapy, 1988, 34(2), 90 - 5 Determination of antibiotic lipophilicity with a micromethod: application to brain permeability in man and rats; Meulemans A et al.; Lipophilicity of the injectable form of some antibiotics was measured with a micromethod . The antibiotic was dissolved in a small volume (1 ml) of phosphate buffer at a physiological pH (pH = 7.4) and was extracted by a small volume of octanol (1 ml) . HPLC determinations of the antibiotic were performed in the two phases . log P ranged from +1.3 for chloramphenicol to -4.3 for ceftriaxone . A linear relationship was established for a few antibiotics between the log P values found in our experiments and the log permeability calculated from data in the literature for human and rat brain . This linear relationship enabled the brain concentrations of antibiotics to be predicted in man and rats. J Pharmacobiodyn, 1988 Jan, 11(1), 9 - 17 Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects . (5) . Interaction of tobramycin with latamoxef in vitro; Kojima R et al.; Interaction of tobramycin (TOB) with latamoxef (LMOX) was studied in vitro . Solutions containing TOB alone, LMOX alone or both of these compounds in varying molar ratios (TOB:LMOX = 1:1, 1:2, 1:4 and 2:1) were incubated at 37 degrees C for 0.5, 1, 3 and 5 h after adjusting to pH 7.4 . Aliquots sampled at a suitable time were subjected to paper electrophoresis (PE) and thin layer chromatography (TLC) . In PE, the spots of TOB and LMOX were observed as single spots on the cathode and anode sides, respectively . However, the spot associated with TOB overlapped with that associated with LMOX on the cathode side when aliquots of the solution containing both TOB and LMOX were analyzed . It seemed that the degree of overlapping became stronger with an increase in incubation time, and there were no spots corresponding to TOB alone in the mixture of TOB-LMOX (1:4) . TLC analysis showed that the spot of LMOX radiated fluorescence with Rf value 0.38 . On the other hand, in the mixtures, there was a definite decrease in fluorescence of LMOX at the position of Rf value 0.38, compared with that of LMOX alone . Furthermore, the spot associated with LMOX, which overlapped with that associated with TOB, also appeared at the origin on the TLC plate . The ultraviolet spectrum of the mixture of TOB-LMOX (1:2) showed a decrease in the intensity of absorption of LMOX at 268 nm . These interactions between TOB and LMOX were also observed in rat serum and its filtrate in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) Int J Clin Pharmacol Res, 1988, 8(2), 101 - 5 Effect of flurithromycin, a new macrolide antibiotic, on carbamazepine disposition in normal subjects; Barzaghi N et al.; The effects of flurithromycin, a new macrolide antibiotic, on the disposition of a single oral dose of carbamazepine (CBZ) (400 mg) were investigated in seven normal subjects . Flurithromycin (2 x 250 mg thrice daily for 10 days) caused a slight increase in the CBZ area under the serum concentration curve and a moderate reduction in carbamazepine-10, 11-epoxide (CBZ-E) levels . These results suggest that flurithromycin can inhibit the conversion of CBZ to CBZ-E, although, at the dosage tested, the magnitude of this effect was significantly smaller than that observed after administration of erythromycin in the same subjects. Antibiot Khimioter, 1988 Jan, 33(1), 51 - 60 {Methodological aspects of an experimental multifactorial study of the combined use of antibiotics and immunomodulators}; Nikitin AV et al.; Methodological approaches to investigation of the protective effect of natural immunomodulators are described . The use of multifactorial experiment design, a model of infectious processes and immunomodulators alone or in combination with antibiotics is implied . Theoretical preconditions for rational choosing of the experimental factors and their levels, as well as specific designs are discussed . Potentialities of polynomial statistic model analysis in development of optimal regimens for combined chemoimmunotherapy are shown. Antibiot Khimioter, 1988 Jan, 33(1), 40 - 2 {Rheological research in creating cellulose ester-based hydrogels with antibiotics}; Kagan EZ et al.; Rheological properties of antibiotic hydrogels based on cellulose ethers were studied . It was shown possible to use methylcellulose and sodium carboxymethylcellulose as bases for hydrogels with erythromycin and fusidic acid. Eksp Onkol, 1988, 10(1), 52 - 5 {Pharmacokinetics of anthracycline antibiotics deposited by polymers}; Rusakov IG et al.; An increase of doxorubicin concentration in different organs and tissues and its decrease in the peripheral blood were observed when studying pharmacokinetics of this drug administered in the 10% solution of polyvinylpyrrolidone . A prolonged and stable release of carminomycin from glue composition MK-10-0 "carminacryl" confirms an expediency of alpha-cyanoacrylate use for deposition of anthracycline antibiotics with the aim of loco-regional chemotherapy. J Neurol, 1988 Jan, 235(3), 140 - 2 Chronic borrelia encephalomyeloradiculitis with severe mental disturbance: immunosuppressive versus antibiotic therapy; Kollikowski HH et al.; A 57-year-old male was repeatedly admitted to hospital because of complex neurological symptoms, including radicular pain, disturbance of micturition, seizures, and severely impaired mental state . The diagnosis was encephalomyeloradiculitis possibly of viral origin, and treatment with immunosuppressants was initiated . An alternating course with a tendency towards improvement ensued . Two and a half years after the occurrence of the initial symptoms, identification of specific antibodies in the blood and CSF led to the diagnosis of borreliosis with CNS involvement . High-dose therapy with penicillin rapidly reduced the symptoms, beginning with those of radicular pain and followed by an improvement of the mental state . Attention is directed to the wide spectrum of clinical symptoms of chronic borreliosis with CNS involvement . Previous reports that immunosuppression may result in some improvement but with a tendency towards relapse are confirmed . Our encouraging treatment results support those of other reports that penicillin therapy may lead to improvement even at late chronic stages in patients with severe CNS deficits. Nauchnye Doki Vyss Shkoly Biol Nauki, 1988, (2), 84 - 8 {Development of a synthetic medium for the growth of the mycophilous fungus Hypomyces rosellus 94/77 and its synthesis of an antibiotic and a pigment}; Piskunkova NF et al.; Using the method of mathematical design of an experiment the synthetic medium ensuring the growth of the mycophilous fungus Hypomyces rosellus 94/77 and its production of antibiotic and pigment has been worked out. J Orthop Res, 1988, 6(3), 311 - 6 Effect of irrigation and tourniquet application on aminoglycoside antibiotic concentrations in bone; MacMillan M et al.; Preoperative antibiotics are an important measure taken to prevent infection in joint replacement surgery . The local availability of these antibiotics in the operative site is absolutely necessary to ensure adequate prophylaxis against contaminant bacteria . Because pulsatile-lavage rapid-recovery systems have become a routine technique of bone preparation in joint reconstruction, we chose to study the effect of these systems on local antibiotic concentrations . We further investigated the effect of irrigation with and without use of a limb tourniquet . For our study, we obtained 23 bone specimens in 16 patients undergoing joint reconstruction (14) or amputation (2) . The patients were classified into one of four groups based on whether a tourniquet was applied during the procedure and whether the bone specimens were irrigated . In addition, matched blood samples were obtained to establish that therapeutic serum levels were achieved . Nine patients contributed 13 bone specimens, which underwent vigorous irrigation in vitro . None of these specimens had detectable levels of antibiotics, regardless of whether a tourniquet was used . Seven patients yielded 10 bone specimens, which were not irrigated . Five of these seven patients had detectable levels of antibiotics . In addition, the specimens from limbs without tourniquets had levels that averaged 0.51 microgram/ml while those with tourniquets averaged below 0.2 microgram/ml . Therefore, the use of vigorous irrigation in bone preparation has a significant deleterious effect on the local presence of previously administered systemic antibiotics . This effect is compounded if the operative site is isolated from continuous blood flow by use of a tourniquet . We therefore recommend that additional measures be taken to ensure that adequate antibiotic levels are present.(ABSTRACT TRUNCATED AT 250 WORDS) J Antimicrob Chemother, 1988 Jan, 21(1), 125 - 31 Antibiotic dispensing by drug store personnel in Bangkok, Thailand; Thamlikitkul V; The current pattern of antibiotic use by drug store personnel in Bangkok was examined . Ten well-trained medical students (simulated patients) presented to 40 randomly selected drug stores with common complaints, namely urethral discharge, acute watery diarrhoea, fever with sore throat, coryza, skin infection and acute dysuria . Analysis of medications obtained revealed that 50-100% of drug stores dispensed antibiotics for each condition . Co-trimoxazole, ampicillin, chloramphenicol, penicillin V and tetracycline were commonly given . Most antibiotics were dispensed inappropriately with respect to choice of drug and duration of treatment . The cost per treatment varied from 20 cents to 6 $US . Strategies to promote rational use are proposed. Drug Intell Clin Pharm, 1988 Jan, 22(1), 58 - 61 Absorption of intraperitoneal antibiotics; Morse GD et al.; The treatment of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) usually includes the repeated administration of intraperitoneal (ip) antibiotics . The initial segment of this study (15 noninfected CAPD patients) examined the ip administration of four structurally different agents that represent the common types of antibiotics prescribed for peritonitis: an aminoglycoside (tobramycin), a glycopeptide (vancomycin), a beta-lactam (cefamandole), and an oxa-beta-lactam (moxalactam) . Subsequently, 16 CAPD patients with peritonitis received either vancomycin (30 mg/kg) or cefamandole (1 g) in two liters of dialysate over a six-hour dwell period . Vancomycin and cefamandole were absorbed more rapidly in patients with peritonitis as indicated by a more rapid decline in dialysate concentrations, and higher serum concentrations that occurred earlier than in the noninfected patients . Although a higher percentage of the ip dose of vancomycin and cefamandole was absorbed during peritonitis, peak serum concentrations at the end of the drug administration dwell period were not significantly different . Numerous factors influence the absorption of ip antibiotics, including the dialysate drug concentration, the dwell period, protein binding, distribution volume, and presence or absence of peritonitis. Am J Hosp Pharm, 1988 Jan, 45(1), 122 - 5 Multidisciplinary cost-containment program promoting oral metronidazole for treatment of antibiotic-associated colitis; Briceland LL et al.; A multidisciplinary cost-containment program for promoting oral metronidazole in place of oral vancomycin as initial therapy of antibiotic-associated colitis (AAC) is described . The pharmacy department and the division of infectious diseases implemented the program in two phases . In the first phase, a one-year retrospective drug-use review in patients with AAC treated with oral vancomycin was conducted to determine the average cost of therapy per treatment course . In the second phase, the use of oral metronidazole instead of oral vancomycin for initial treatment of AAC was promoted using inservice-education programs and distribution of pocket-size brochures containing AAC treatment guidelines to medical staff . The pharmacy and therapeutics committee supported the program by endorsing metronidazole as the drug of choice for AAC and by distributing follow-up progress reports of the program to medical staff . Pharmacists on the nursing units were responsible for enforcing the program stipulations regarding vancomycin and metronidazole use and for collecting data on patient-specific drug use . Six months after implementation of the program, the average cost of drug therapy for AAC had decreased by 89%, from $343.24 per patient to $37.50 per patient . The projected annual savings resulting from the program was $38,829.02 . All prescribing physicians and dispensing pharmacists complied 100% with the program stipulations regarding drug use . The multidisciplinary program described here was successful in promoting the use of oral metronidazole for initial therapy of AAC. Thromb Res, 1988 Jan 1, 49(1), 79 - 90 Inhibition by the antilipogenic antibiotic cerulenin of thrombin-induced activation of human platelets; Matsushima Y et al.; Upon incubation with an antibiotic cerulenin, human platelets lost their abilities to aggregate and to release serotonin or ATP in response to various stimuli such as thrombin, ADP, collagen and platelet activating factor . The loss of activities was dependent on both incubation time and cerulenin concentrations . As judged by 14C-serotonin release, concentrations of cerulenin required for the half-maximal inhibition of thrombin-induced activation were 5-10 and 70 micrograms/ml in the incubation for 120 min at 37 degrees C for washed platelets and those in platelet rich plasma, respectively . The cerulenin treatment also resulted in a significant inhibition of 14C-acetate incorporation into the lipid fraction of platelets, suggesting that de novo synthesis of fatty acids was inhibited by the treatment . No release of lactate dehydrogenase activity nor morphological changes in platelet structure was detected upon cerulenin treatment . When effects of cerulenin on intracellular Ca2+ concentration were examined, mobilization of intracellular Ca2+ by thrombin was significantly depressed in the cerulenin-treated platelets as judged by Fura2, Quin2 or chlortetracycline fluorescence . Since the influx of external Ca2+ is not essential to the thrombin-induced platelet activation (Rink, T . J . et al . FEBS Lett . 148 21-26, 1982), the results suggest that cerulenin-treatments affect the platelet function through the inhibition of intracellular Ca2+ mobilization. J Antibiot (Tokyo), 1988 Jan, 41(1), 68 - 72 New aureolic acid antibiotics . II . Structure determination; Koenuma M et al.; Structure determination using NMR spectroscopy of new aureolic acid analogues, demethylchromomycins A2 and A3 and demethylolivomycins A and B produced by Streptomyces aburaviensis PA-39856, is described. Pediatr Res, 1988 Jan, 23(1), 50 - 3 Lack of inhibition of intestinal heme oxygenase by antibiotics and tin-protoporphyrin; Hintz SR et al.; We assessed the in vivo and in vitro effects of antibiotics and tin-protoporphyrin (TP) on intestinal heme oxygenase (HO) activity using a gas chromatographic assay . This method measures the carbon monoxide produced from heme in the presence of NADPH . After in vivo administration of kanamycin (10 mg/kg body weight), ampicillin (200 mg/kg body weight) or neomycin (60 mg/kg body weight) with or without TP (65 mumol/kg body weight) to suckling rats, no significant difference in HO activity along the small intestine was observed . In vitro exposure of adult rat intestinal preparations to the antibiotics showed no significant decrease in HO activity between control and experimental tissue preparations . A concentration-dependent stimulatory effect of neomycin was observed . Subcutaneous administration of TP (25 mumol/kg body weight) to adult male Wistar rats revealed no significant inhibition of the intestine . However, in vitro addition of TP (12.5 microM) to the control tissue preparations of adult Wistar rats revealed highly significant inhibition in liver and spleen when compared to the unexposed control tissues . In contrast, when TP was added to control intestinal preparations no inhibition was observed . These findings suggest that suckling rat intestinal heme oxygenase is not inhibited by in vivo treatment with high concentrations of kanamycin, ampicillin, or neomycin . Furthermore, these antibiotics are not in vitro inhibitors of adult rat intestinal HO . Finally, adult rat intestinal HO is not inhibited either in vivo or in vitro by a concentration of TP that significantly inhibits liver and spleen activity. Am J Obstet Gynecol, 1988 Jan, 158(1), 23 - 7 Transcervical amnioinfusion of antibiotics: a basic study for managing premature rupture of membranes; Ogita S et al.; To determine the best method of preventing ascending infection in the management of premature rupture of membranes, antibiotics such as latamoxef sodium, cefoperazone sodium, and cefotaxime sodium were infused directly into the amniotic cavity in 64 patients undergoing induction of labor at term . A single infusion of 100 or 500 mg of each drug resulted in a concentration of 200 to 1000 micrograms/ml immediately after infusion, and the concentration remained above 10 micrograms/ml for about 24 hours without significant increase in fetal or maternal blood levels . Consequently, a daily single dose of 100 mg or more is probably effective prophylaxis in cases of premature rupture of membranes . When intrauterine infection is suspected, the dose can be increased to 500 mg or more, and transplacental administration may be added to achieve a higher concentration in fetal blood . The present study simulates well premature rupture of membranes, and an amnioinfusion of antibiotics will be reliable and effective in managing premature rupture of membranes. Clin Orthop, 1988 Jan, (226), 222 - 30 Local delivery of antibiotics via an implantable pump in the treatment of osteomyelitis; Perry CR et al.; Twenty-one patients with osteomyelitis were treated with surgical debridement and local antibiotic therapy . Amikacin (19 patients) or netilmicin (2 patients) was delivered locally via a pump implanted subcutaneously . The outflow catheters were led from the pump subcutaneously to the infected area and placed in the defect created by the surgical debridement . The pump was refilled at intervals, on an outpatient basis . The pump was surgically removed at the conclusion of therapy . Follow-up evaluation was for 12-27 months . The duration of hospitalization was five to 52 days (mean, 23 days) . The infusions were sustained for 32-140 days (mean, 63 days) . Systemic levels of antibiotics were always below acceptable trough levels . Levels in the wound drainage of the 11 patients who drained after operation were always greater than the upper limit of the assay . Nephrotoxicity and ototoxicity were determined using pre- and posttherapy creatinine clearances and audiograms . Two patients exhibited minimal nephrotoxicity (creatinine clearance of 66 ml/minute and 55 ml/minute; normal, 70 ml/minute) . There were no other adverse effects of the antibiotics . Sixteen patients have not drained since removal of the pumps. Annu Rev Med, 1988, 39, 171 - 84 Oral antibiotic therapy for serious infections; Smith AL; After a pathogen has been identified and the antibiotic susceptibility determined, parenteral antibiotic administration can be replaced by the oral route for certain patients with meningitis, brain abscess, endocarditis, and skeletal infections . Antibiotics should be administered with the stomach empty and accompanied by 3 ml/kg of water . Direct instillation into the lumen of the small intestine may be advantageous with selected patients . Documenting adequate antibiotic absorption and ensuring compliance are essential to efficacious therapy. Genetika, 1988 Jan, 24(1), 53 - 9 {Yeast resistance to polyene antibiotics . VI . Isolation and biochemical analysis of strains of Saccharomyces cerevisiae yeasts with mutations in the 2 nystatin-resistance genes}; Ogorodnikova TE et al.; The comparative analysis of sterol content in the yeast Saccharomyces cerevisiae strains singly or doubly defective in nystatin resistance genes was carried out . The strains with two mutations in NYS genes were shown to accumulate the sterol mixture, similar to that of the parental singly defective mutant . This type of gene interaction allows to define the main biochemical order of reaction in ergosterol synthesis: methylation in C24 (NYS1), delta 8----delta 7 isomerization (NYS2), C5 (6) and C22 (23) desaturation (NYS3 and NYSX). Antimicrob Agents Chemother, 1988 Jan, 32(1), 153 - 5 Increase in permeability of Escherichia coli outer membrane by local anesthetics and penetration of antibiotics; Labedan B; The MICs of several antibiotics (both hydrophobic and hydrophilic) which penetrate very poorly into intact Escherichia coli cells were found to be 2- to 10-fold decreased in the presence of low doses of various local anesthetics (procaine, dibucaine, tetracaine, chlorpromazine, and quinine) . The concentrations of anesthetics necessary for this effect have no adverse effect on cell growth and are markedly lower than those concentrations used clinically. J Orthop Res, 1988, 6(2), 279 - 86 Comparative evaluation of the diffusion of tobramycin and cefotaxime out of antibiotic-impregnated polymethylmethacrylate beads; Wilson KJ et al.; Both tobramycin and cefotaxime diffuse from antibiotic-impregnated polymethylmethacrylate (PMMA) beads in quantities sufficient to inhibit the growth of bacteria on agar lawns or in broth cultures over a 28-day period . Extraction of antibiotic from tobramycin or cefotaxime-impregnated PMMA beads revealed that substantial amounts of both antibiotics remained within the beads despite 28 days of diffusion . Diffusion of antibiotic from the PMMA beads during the initial 3-5 days is much greater than occurs for the remainder of the 4-week period . The results of the study suggest that perhaps tobramycin of cefotaxime-impregnated PMMA beads would produce local levels of antibiotic high enough to sterilize a given dead space for a period of 28 days. J Reprod Fertil, 1988 Jan, 82(1), 135 - 43 Effects of antibiotics and medium supplements on steroidogenesis in cultured cow luteal cells; Poff JP et al.; Corpora lutea were removed from regularly cycling dairy cows, dissociated with collagenase and cultured for 8 or 10 days in Ham's F-12 medium . In Exp . 1 treatment with insulin, or an insulin-transferrin-selenium combination (ITS), increased progesterone production from basal levels on Day 4 of culture to 234% (P less than 0.01) above controls on Day 10 . LH alone increased progesterone production 45% above controls on Day 10 (P greater than 0.05) . When LH was combined with insulin or ITS, progesterone production was stimulated to an average of 1802% (P less than 0.01) above controls on Day 10 of culture . Transferrin or selenium without insulin did not allow LH to stimulate progesterone synthesis . In Exp . II, LH alone or LH plus gentamicin or penicillin-streptomycin increased progesterone production from basal levels on Day 2 steadily to an average of 468% (P less than 0.01) above controls (no antibiotics) by Day 8 of culture . The addition of amphotericin-B, alone or in combination with the other antibiotics, inhibited all LH-stimulated progesterone synthesis, but did not affect basal progesterone levels . We conclude that insulin is essential for maximal steroidogenesis in a bovine luteal cell culture system, and that LH-stimulated progesterone production is inhibited in the presence of amphotericin-B, but is not inhibited by gentamicin or penicillin-streptomycin . The elimination of amphotericin-B, coupled with the addition of insulin to the cell culture system increased the responsiveness of the cells to LH . These culture conditions represent the first report in which LH increased total progesterone production for 10 days, maintaining luteal function in a chemically-defined culture system. Am J Med, 1988 Jan, 84(1), 68 - 74 Cefoperazone versus combination antibiotic therapy of hospital-acquired pneumonia; Mangi RJ et al.; Cefoperazone monotherapy was compared with combination antibiotic therapy in a randomized prospective evaluation of patients with hospital-acquired pneumonia . Cefoperazone was as effective as either clindamycin/gentamicin or cefazolin/gentamicin (cure rate: 45 of 52 cefoperazone-treated patients {87 percent}, versus 44 of 61 combination-therapy patients {72 percent}, p = 0.069) . With the exception of hypoprothrombinemia in those patients who did not receive prophylactic vitamin K, there was no difference in the incidence of side effects . In addition, no difference was noted in the incidence of superinfections or secondary pneumonias . When antibiotic costs, administration costs, and laboratory costs were considered, cefoperazone monotherapy was the least expensive antibiotic regimen . Cefoperazone is a suitable alternative to combination antibiotic therapy for the treatment of hospital-acquired pneumonia. Chem Biol Interact, 1988, 68(3-4), 179 - 88 In vivo and in vitro effects of a new macrolide antibiotic roxithromycin on rat liver cytochrome P-450: comparison with troleandomycin and erythromycin; Delaforge M et al.; The effects of a new macrolide antibiotic (Roxithromycin) and one of its major metabolite (RU 39001) on rat hepatic drug metabolizing enzymes were compared to those of erythromycin, erythralosamine and troleandomycin (TAO) both in vitro and in vivo . In contrast to erythromycin, erythralosamine and TAO, roxithromycin and its metabolite RU 39001 exhibit: (i) a very poor affinity for rat liver cytochrome P-450, (ii) an unability to be metabolized into a stable inhibitory metabolite-cytochrome P-450 complex and (iii) a decreased ability to induce liver cytochrome P-450 PCNE, an isozyme implicated in drug associations involving some macrolide antibiotics. Scand J Infect Dis Suppl, 1988, 55, 1 - 61 Neurotoxicity of beta-lactam antibiotics . Experimental kinetic and neurophysiological studies; Schliamser SE; The neurotoxic potential of intravenous administered benzylpenicillin (BPC) was studied in rabbits with intact blood-CNS barriers and rabbits with experimental E . coli meningitis . At onset of epileptogenic EEG activity or seizures, serum, CSF and brain tissue were collected for assay of BPC . Based on the fact that, in tissues, BPC seems to remain extracellularly, brain concentrations of BPC were expressed as brain tissue fluid (BTF) levels, calculated as 10x the concentration in whole brain tissue . Neurotoxicity could be precipitated in all rabbits . In normal rabbits BTF levels of BPC were considerably higher than those in CSF indicating a better penetration across the blood-brain barrier (BBB) . BPC penetrated better to CSF and BTF in meningitic rabbits than in normal controls, suggesting some degree of damage of the BBB concomitant with meningeal inflammation . E . coli meningitis did not increase the neurotoxicity of BPC . In control rabbits the intracisternal injection of saline resulted in some degree of pleocytosis . Unmanipulated animals are therefore preferable as controls . Epileptogenic EEG-changes was the most precise of the two variables used for demonstration of neurotoxicity . EEG-changes were therefore used as neurotoxicity criterion in the following rabbit experiments . To evaluate the effect of uraemia alone and uraemia plus meningitis on the neurotoxity of BPC in rabbits, cephaloridine was used to induce uraemia . Meningitis was induced by intracisternal inoculation of a cephalosporin resistant strain of E . cloacae . Untreated rabbits were used as controls . Uraemia resulted in increased BTF penetration of BPC, possibly explained by permeability changes in the BBB and/or decreased binding of BPC to albumin . Uraemia did not result in increased penetration of BPC into the CSF of non-meningitic rabbits . Uraemic non-meningitic rabbits had the highest BTF levels of BPC at the criterion, indicating that cephaloridine-induced renal failure increased the epileptogenic threshold in these rabbits . The combination of uraemia and meningitis increased the neurotoxicity of BPC since the criterion was reached at considerably lower BTF levels of BPC . Meningitis, either alone or together with uraemia, did not increase the neurotoxicity in comparison to control rabbits . Higher BTF levels of BPC were found in meningitic rabbits than in controls with intact blood-CNS barriers at onset of EEG-changes . In all groups of rabbits there was a pronounced variability of BPC levels in the CSF while the intra-group variations in BTF levels were much smaller . Thus, BTF and not CSF levels were decisive for the neurotoxicity of BPC.(ABSTRACT TRUNCATED AT 400 WORDS) J Arthroplasty, 1988, 3(4), 369 - 77 Two-stage reimplantation of septic total knee arthroplasty . Report of three cases using an antibiotic-PMMA spacer block; Cohen JC et al.; The management of an infected total knee implant is a major challenge to the orthopaedic surgeon . This article reviews the use of antibiotic-PMMA spacer block in two-stage reimplanation of septic total knee arthroplasties . In addition to serving as an antibiotic delivery system between the time of component removal and reimplantation, the antibiotic-impregnated spacer block imparts mechanical stability to the joint and decreases the morbidity during the period before reimplantation . This temporary "interposition arthroplasty" facilitates the patient's ambulation and also simplifies dissection at the time of reimplantation . Furthermore, osteoporotic bone at the time of resection becomes firm, good-quality bone by the time of reimplantation. Free Radic Res Commun, 1988, 5(3), 149 - 58 Oxidative damage to DNA and deoxyribose by beta-lactam antibiotics in the presence of iron and copper salts; Quinlan GJ et al.; beta-lactam antibiotics in the presence of certain metal ions damage deoxyribose and DNA with the release of thiobarbituric acid-reactive material . This damage can be substantially prevented by catalase, metal chelators and some scavengers of the hydroxyl radical . Ferric salts in the presence of certain beta-lactam antibiotics were effective in degrading deoxyribose but they did not appear to damage DNA . In contrast copper salts and beta-lactam antibiotics were extremely effective in damaging both DNA and deoxyribose. Ann Rech Vet, 1988, 19(4), 259 - 66 {Immunomodulator effects of 2 antibiotics, chloramphenicol and kitasamycin, in the chicken}; Laval A et al.; One-day-old chickens treated via drinking water with kitasamycin (0.7 g/l for 6 days then 0.35 g/l for 15 days) or with chloramphenicol (1 g/l for 6 days the 0.5 g/l for 15 days), were immunized at the 24th day with sheep red blood cells . Body and spleen growths were recorded and compared to control every week for 5 weeks after immunization . Humoral and cell-mediated immune responses were measured by hemagglutinating antibodies titration, direct and indirect plaque forming cells (PFC) numeration, and graft versus host reaction (GVHR) . Both antibiotics reduce antibody response and number of PFC, chloramphenicol being significantly more suppressive than kitasamycin . A short stimulation of cellular response is shown with kitasamycin, which stimulates GVHR, whereas chloramphenicol has a negative effect. Nucleic Acids Symp Ser, 1988, (19), 101 - 4 Differential scanning calorimetry of antitumor antibiotics-plasmid DNA interaction; Maeda Y et al.; Differential scanning calorimetry (DSC) can detect stepwise melting of plasmid DNA along the molecular chain with high resolution . This method was applied to study interaction of some antitumor antibiotics with the plasmid pJL3-TB5 DNA (5277 base-pairs in length) . Analysis of DSC curves of the plasmid DNA in the presence of, for example, adriamycin, an antitumor antibiotics of anthracycline group, together with theoretical analysis of the DNA melting curves obtained by calculation from the entire base sequence, led to the conclusion that adriamycin bound preferentially to the four particular regions with high G + C content . The DSC method would thus be useful for the study of properties of drugs which bind to DNA. Int J Immunopharmacol, 1988, 10(8), 919 - 24 Macrolidic antibiotics: effects on primary in vitro antibody responses; Villa ML et al.; The effect of two macrolidic antibiotics, josamycin and erythromycin, on the primary immune response in cultures of human peripheral blood mononuclear cells (PBMC), were studied using a soft agar hemolytic plaque assay . Both compounds induced an appreciable reduction in the primary antibody response in total PBMC cultures . The removal of plastic-adherent cells, however, profoundly modified the effect of macrolides on the immune response . Both josamycin and, to a lesser extent, erythromycin enhanced, rather than suppressed, the antibody response . Furthermore, the macrolide-induced immunodepression in cultures of total PBMC was completely reversed by the addition of catalase (8000 U/ml) . Taken together, these findings suggest that the macrolide-induced depression of the antibody response depends upon the presence of adherent monocytic cells and is mediated by the production of hydrogen peroxide. Chemotherapy, 1988, 34(4), 345 - 53 Analytical studies on beta-lactam antibiotics . II . Displacement effect of beta-lactam antibiotics on bilirubin bound to human serum albumin; Matsuura A et al.; We established a method for determining the KD value as a measure of the bilirubin-displacing effect for drugs by using bilirubin oxidase, which is produced by Myrothecium verrucaria MT-1 . This method makes it possible to conduct measurements of many beta-lactam antibiotics, including those which could not be determined by Brodersen's method . The KD values of latamoxef reported by many investigators based on Brodersen's method were higher than the true value owing to interaction of the drug with peroxidase and H2O2 . Our KD value under the new enzyme conditions was 2.6 X 10(3) . Little or no interaction of drug with the enzyme system was tentatively confirmed . Flomoxef, a newly developed drug, and 7432-S, under development in our company, had KD values of 0.4 X 10(3) and 2.8 X 10(3), respectively. Chemotherapy, 1988, 34(4), 272 - 6 Effect of medium chain glycerides on enteral and rectal absorption of beta-lactam and aminoglycoside antibiotics; Unowsky J et al.; The rat enteral and rabbit rectal models were utilized to study the effect of Capmul (medium chain glycerides) on the absorption of a selection of beta-lactam and aminoglycoside antibiotics . All tested non-orally available beta-lactam antibiotics (cefamandole, cefotaxime, moxalactam, cefoxitin, mezlocillin, carumonam, penicillin G and amdinocillin) showed increased absorption enterally in rats and rectally in rabbits when formulated with Capmul . The orally available beta-lactam antibiotics, cephalexin and cephradine, were not enhanced in their enteral or rectal absorption by Capmul in the two model systems . Ampicillin absorption was enhanced rectally and enterally by Capmul . Rectal absorption of the aminoglycoside antibiotics, tobramycin and gentamycin, was enhanced by Capmul while enteral absorption was not. Int Urol Nephrol, 1988, 20(4), 375 - 81 A re-appraisal of antibiotic susceptibility tests in the management of bacterial prostatitis; Kazanci G et al.; In a material of fifty cases of chronic prostatitis the effectiveness of antibiotic susceptibility tests has been evaluated in the management of bacterial prostatitis . Limitations of the therapy are discussed, and factors effecting drug diffusion across the prostatic membrane are reviewed. Chemotherapy, 1988, 34(2), 142 - 8 High concentrations of antibiotic obtained for a short time excel more long-standing lower levels in the therapy of gonorrhoea . Implications of an in vitro model; Korting HC et al.; During recent decades there has been a controversial discussion if comparable plasma level profiles which are rather constant or those which show a high peak are more efficient for the cure of gonorrhoea . So far, investigations in this field were not based on the Grasso apparatus . Although the findings with cefotiam and ceftizoxime do not allow to formulate a general hypothesis without any restriction, it can be stated that on the basis of an identical area under the antibiotic level time curve, 'peak concentration' profiles are more favourable. Bioorg Khim, 1988 Jan, 14(1), 103 - 13 {Effect of the molecular structure of natural anthracycline antibiotics on their relative hydrophobicity}; Baranov EP et al.; Relative hydrophobicities of anthracycline antibiotics, adriamycin, rubomycin and carminomycin, have been measured by the two-phase distribution method . Two different biphasic systems were used for this purpose . Possible reasons of discrepancies between results obtained and other authors, data are discussed . It was established that the relative hydrophobicities of the compounds investigated contradict the theory of increment additivity . The results are compared with quantum-chemical calculations. Jpn J Antibiot, 1988 Jan, 41(1), 48 - 52 {Tissue distribution of beta-lactam antibiotics, cefotiam and cefmenoxime in the lungs of sheep}; Hirai K et al.; The present study was performed to investigate the distribution of beta-lactam antibiotics, cefotiam (CTM) and cefmenoxime (CMX) in pulmonary tissue of sheep . The animals were prepared to form chronic lung-lymph fistula for the collection of lung lymph . CTM and CMX were administered bolus-intravenously at doses of 20 mg/kg and 40 mg/kg, respectively, and serum and lymph levels of each drug were measured by bioassay method . Antibiotic levels of serum or lymph increased to a peak within 15 minutes after injection and then decreased rapidly . Measurable concentrations persisted for 240 minutes after the injection . Ratios of lung lymph to serum concentrations of CTM and CMX within 1 hour after the injection ranged 0.7 to 1.3, and 0.9 to 1.3, respectively . In addition, CMX levels in serum, lung lymph and tissues of both right and left lung were compared in anesthetized sheep to which CMX 50 mg/kg was given . Ratios of lung lymph and tissue concentrations of CMX in right and left lung to serum concentration were 0.76, 0.14 and 0.13, respectively . These results indicate that CTM and CMX were well distributed in interstitial fluid (lung lymph), and the levels of CMX in tissues of both right and left lung were markedly lower than those of lung lymph. Dis Colon Rectum, 1988 Jan, 31(1), 28 - 32 Comparison of short-term antibiotic cover with a third-generation cephalosporin against conventional five-day therapy using metronidazole with an aminoglycoside in emergency and complicated colorectal surgery; Tudor RG et al.; In a prospective, randomized control trial, 152 consecutive patients requiring emergency or complicated colorectal surgery were allocated either to two doses of cefotetan or to five-day cover with gentamicin, and a single dose of metronidazole . Twenty-one patients received 6 gm of cefotetan before prolongation of prothrombin time dictated a change in the dose regimen such that all remaining patients (N = 55) received only 4 gm of cefotetan . The groups were well matched for diagnosis and surgical procedure . Rates of postoperative infection did not differ significantly between the groups, with wound infection rates occurring in 17 of 75 patients receiving gentamicin and metronidazole (22.7 percent) compared with ten of 75 receiving cefotetan (13 percent) . Although wound infection rates were lower in the cefotetan group, the incidence of intra-abdominal abscess was similar in both groups . Eight patients receiving cefotetan developed intra-abdominal abscesses (11 percent), compared with seven receiving gentamicin and metronidazole (9 percent) . Prolongation of prothrombin time in excess of 13 seconds occurred in six patients receiving cefotetan compared with no patients receiving gentamicin and metronidazole . None of these patients developed clinical bleeding, however. Acta Microbiol Hung, 1988, 35(2), 81 - 8 Antibiotic effects on growth and heterocyst differentiation of the cyanobacterium Nostoc muscorum; Pattanaik U et al.; In a medium free of combined nitrogen, 1.0-6.0 micrograms/ml chloramphenicol gradually decreased the growth of the nitrogen-fixing cyanobacterium Nostoc muscorum; at 2.0 micrograms/ml the culture appeared yellowish, heterocyst frequency was not evident up to 3.0 micrograms/ml, whereas 4.0 micrograms/ml suppressed heterocyst differentiation . Lower concentrations (0.0125-0.75 microgram/ml) of rifampicin suppressed the growth but had no significant effect on heterocyst frequency in liquid medium, whereas on solid medium 0.02 micrograms/ml produced chains of heterocysts in filaments . The growth and heterocyst frequency declined gradually with increasing doses of puromycin and 6.0 micrograms/ml suppressed the heterocyst differentiation . Actinomycin-D did not affect significantly growth and heterocyst frequency even at 10.0 and 20.0 micrograms/ml. Chemotherapy, 1988, 34(5), 415 - 8 Elimination of antibiotic-resistant plasmids by quinolone antibiotics; Fu KP et al.; Of 7 plasmids we tested, the plasmid pORF2 was eliminated in vitro with the most efficiency by treatment with subinhibitory concentrations of novobiocin, coumermycin and 10 quinolones . It showed a cure rate of 43% by enoxacin; 12% by novobiocin, pefloxacin, ciprofloxacin and CI-934; 7% by coumermycin and ofloxacin; 9% by amifloxacin; and 4% by AM-833 . On the other hand, pSC194, pBR322 and pMH612 were poorly cured in vitro by quinolones, except pSC194 which was cured 33% by enoxacin . R1, pP1603, and pUB110 were unaffected by the treatment . Mice were challenged intraperitoneally with a 2XLD50 of Escherichia coli carrying the ORF2 plasmid and were treated per os with 1 X or 1/2 X ED50 of either enoxacin or CI-934 . The frequency of loss of ampicillin resistance determined 3 h after treatment shows curing effects of 92% for CI-934, 89% for enoxacin and 20% for untreated control. Pediatr Pulmonol, 1988, 4(2), 84 - 9 Cost savings and economic considerations using home intravenous antibiotic therapy for cystic fibrosis patients; Kane RE et al.; Our Cystic Fibrosis (CF) Center made an effort to utilize home intravenous antibiotic therapy (HIVAT) as an alternative to continued hospitalization during a 1-year study . After thorough individual clinical and financial evaluation, 27 of 41 CF patients admitted for treatment, including antibiotic therapy, were selected for HIVAT to complete a 14- to 21-day treatment course (mean 15.1 days) . The 27 patients (6-28 years old, mean 16 years) incurred a total of $698,587 in hospital charges and physician fees during 96 admissions . The average charge for 974 inpatient days was $717/day ($7,280 per admission) . After an average of 10.2 days of inpatient care, the 27 patients underwent 79 courses of HIVAT for an additional 8 days; 21 additional HIVAT courses in six of these patients were initiated on an outpatient basis between frequent readmissions . The 811 days of HIVAT resulted in $85,027 total charges by two home care companies . The charges per day of HIVAT by one company were almost twice that of the other . The average daily cost of HIVAT was $108/day . If the HIVAT patients had remained hospitalized to complete the course of intravenous antibiotic therapy, the projected inpatient costs would have been $589,271 . Therefore, the 811 days of HIVAT over a 1-year period resulted in total estimated direct cost savings of $501,770 . The average savings per course of HIVAT was $5,017, or $618/day.(ABSTRACT TRUNCATED AT 250 WORDS) J Reprod Med, 1988 Jan, 33(1 Suppl), 144 - 8 Overview of therapeutic and prophylactic antibiotics in obstetrics and gynecology; Herbst AL et al.; Infection in the obstetrics-gynecology patient remains an important source of concern . Advances in the identification of pathogenic organisms have led to improvements in the diagnosis of pelvic infections . Important considerations in the selection of antibiotics for established infections include prior hospitalization status, the size of the bacterial inoculum causing the infection, the etiologic organisms and, in the case of prophylaxis, the type of operative procedure . The antibiotic must also be cost effective. Pediatr Infect Dis J, 1988 Jan, 7(1), 23 - 6 Cost effectiveness in the choice of antibiotics for the initial treatment of otitis media in children: a decision analysis approach; Weiss JC et al.; If the initial use of amoxicillin fails to cure otitis media, a family will be burdened with medical costs for a second medication, additional office visit fees and time lost from employment . For some families the initial choice of a more expensive but more effective antibiotic may be more cost effective . Using a decision analysis approach we compared the cost effectiveness of amoxicillin and cefaclor . As the amoxicillin efficacy rate decreases or as parental salaries are increased, the cost-effective advantage moves towards cefaclor . With the decision analysis method described, a practitioner can use costs and efficacy rates relevant to his or her practice to determine the most cost-effective initial antibiotic for a child with otitis media. J Clin Invest, 1988 Jan, 81(1), 142 - 8 Experimental chemotherapy-induced skin necrosis in swine . Mechanistic studies of anthracycline antibiotic toxicity and protection with a radical dimer compound; Averbuch SD et al.; The reactivity of antitumor anthracycline and mitomycin C antibiotics with the oxomorpholinyl radical dimers, bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (TM3) and bi(3,5-dimethyl-5-hydroxymethyl-2-oxomorpholin-3-yl) (DHM3), was studied in vitro . The oxomorpholinyl radical reduced daunorubicin to a quinone methide intermediate that reacted with solvent to form 7-deoxydaunorubicinone . The solvolysis reaction followed first order kinetics, and the reactivity rate constants (k2) measured for seven anthracycline analogues ranged from 2 X 10(-2) s-1 to 8.0 X 10(-4) s-1 . The chemical reactivity of each anthracycline quinone methide correlated with the total skin toxicity caused by the respective parent anthracycline following injection into swine skin . Microscopic examination of experimental lesions in swine skin resemble those observed in humans after inadvertant chemotherapy extravasation . Hydrocortisone sodium succinate was not effective for the treatment of doxorubicin-induced skin necrosis, whereas DHM3 was effective for the treatment of skin necrosis caused by all seven anthracyclines and by the quinone containing antibiotic, mitomycin C. G Batteriol Virol Immunol, 1988 Jan-Dec, 81(1-12), 117 - 28 {Antibiotic-resistant bacterial strains, their spread and social and economic implications}; Cavallo G; The policies, laws, regulations governing the prescription and the use of antibiotics in 41 countries are examined . The enforcement of restrictions and the relations with the emergence of resistant strains are discussed . Emergence and spread of antibiotic-resistant bacteria result augmented in developing countries . Efforts to improves, in these nations, sanitation, nutrition, right information, education and usage of antibiotics must be taken into consideration. Microbios, 1988, 56(227), 105 - 21 An analysis of intracellular proteinases from antibiotic-producing cells of Penicillium urticae; Rollins MJ et al.; Two distinct patterns of activity obtained with the substrates azocasein and azocollagen suggested that Penicillium urticae produces at least two intracellular proteinases during its antibiotic-production phase . Cell extracts fractionated using high resolution gel filtration actually separated three major activities . These three pooled fractions contained predominantly cysteine-type proteinases, as indicated by their sensitivities to inhibitors and by the enhancement of their activities with dithiothreitol and ethylenediamine-tetracetic acid . One of these fractions also appeared to contain significant levels of serine-type proteinases . The three pools could be differentiated from one another by changes in their substrate specificities over a range of pH values, and by their stabilities during storage and at elevated temperatures . Further purification by non-denaturing polyacrylamide gel electrophoresis, revealed that two of the fractions each contained five apparently different activities while in the third pooled fraction, thirteen individual activities were detected . The range of properties displayed by these proteinases is consistent with their probable involvement in general protein degradation, a crucial process which during starvation sustains the supply of substrate necessary for secondary enzyme synthesis as well as contributing to the short lifetime of these same secondary enzymes. Drugs Exp Clin Res, 1988, 14(7), 467 - 72 Unique mechanism of action of an antifungal antibiotic RI-331; Yamaki H et al.; An amino acid antibiotic RI-331, (S)-2-amino-5-hydroxy-4-oxopentanoic acid, produced by a Streptomyces sp., is a novel antifungal agent . Biochemical studies on the mechanism of action of the antibiotic were carried out with a susceptible yeast Saccharomyces cerevisiae . In growing yeast cells, RI-331 inhibited protein synthesis to a greater extent than RNA or DNA synthesis . However, polypeptide synthesis by a cell-free preparation from yeasts was refractory to the antibiotic . The inhibition of protein synthesis by RI-331 was revealed to be due to the depletion of several amino acids such as threonine, methionine, isoleucine and serine in the cellular pool . These results suggest the possibility that some steps in amino acid metabolic pathways, especially those involved in biosynthesis of threonine, methionine and isoleucine, may constitute a primary target of RI-331 action. Crit Rev Biotechnol, 1988, 8(1), 1 - 32 Peptide antibiotics, beta-lactams, and related compounds; Kleinkauf H et al.; In the field of natural peptides, beta-lactams, and related compounds, recent exciting developments are discussed . The increasing interest in this class of bioactive amino-acid derived structures has been attributed to the use of new directed screens (enzyme inhibition assays, beta-lactam detection, immunomodulator studies), new and improved applications (antibiotic, transplantation, and cancer chemotherapy), and advances in functional studies (DNA binding peptides, nucleotide complexones, cell wall and protein processing inhibitors) . Peptides offer unique access to modifications and analog production by in vivo (directed biosynthesis) and in vitro procedures (enzymatic synthesis) due to their general linear precursors permitting point replacements . Of special interest are recent developments in the genetics of these compounds (cyclic peptides and beta-lactams), which will find applications in production methods in the near future. Ann N Y Acad Sci, 1988, 539, 324 - 45 Antibiotic therapy of early European Lyme borreliosis and acrodermatitis chronica atrophicans; Weber K et al.; In a study on 121 consecutive patients with erythema migrans, 65 patients obtained oral penicillin, 36 tetracyclines, and 20 amoxicillin-clavulanic-acid . Follow-up was carried out for a median of 29, 17, and 7 months, respectively . In another limited trial on 29 patients with acrodermatitis chronica atrophicans (ACA), 14 patients received oral penicillin, 9 parenteral penicillin, and 6 tetracyclines . There was no statistically significant difference among treatment groups in both therapeutic trials, with the exception of different follow-ups due to the nonrandomized study design and different occurrence of the Jarisch-Herxheimer reaction in patients with erythema migrans . Later extracutaneous manifestations developed in 27% of the patients with erythema migrans and in 47% of the patients with ACA despite antibiotic therapy . We could not prove the superiority of any antibiotic tested in either early or late European Lyme borreliosis. Eur Urol, 1988, 14(5), 398 - 401 Reappraisal of antibiotic susceptibility tests in the management of chronic bacterial prostatitis; Kazanci G et al.; In view of 50 cases of chronic bacterial prostatitis the efficacy and limitations of antibiotic susceptibility tests have been evaluated and factors affecting passage of drugs across the prostatic cell membrane have been discussed. Med Oncol Tumor Pharmacother, 1988, 5(2), 103 - 5 Double-blind, placebo-controlled lithium treatment in chemotherapy induced aplasia for AML: reduced antibiotic requirement; Collado S et al.; A double-blind placebo-controlled study on lithium (Li) therapy after chemotherapy-induced bone marrow aplasia was undertaken in 53 patients with acute myeloblastic leukemia (AML) . No difference was observed between the two groups for the duration of aplasia, the number of units of platelets or RBC transfused, the complete remission rate or the disease free survival . However, a statistically significant reduction in the number of days of antibiotic therapy required was found in the treated group (10.55 +/- 2.72 vs 12.73 +/- 3.60, P less than 0.05). Audiology, 1988, 27(3), 137 - 46 Pharmacokinetics of aminoglycoside antibiotics in blood, inner-ear fluids and tissues and their relationship to ototoxicity; Henley CM 3rd et al.; This review critically evaluates the literature on aminoglycoside pharmacokinetics in order to answer the question how fluid and tissue levels of the drugs relate to the development of ototoxic and nephrotoxic side effects . We will summarize the evidence that: (1) aminoglycosides do not accumulate in inner-ear fluids; (2) aminoglycoside levels in fluids do not correlate with the ototoxic potential of a drug, and (3) selective toxicity cannot be explained by selective tissue penetration of the drugs . We suggest that studies of drug disposition at the cellular level after chronic aminoglycoside treatment be conducted to establish whether a cell-specific uptake contributes to the selective toxicity of the aminoglycoside antibiotics . A sequence of biochemical events that may lead to the development of toxicity at the molecular level is briefly described. J Hosp Infect, 1988 Jan, 11(1), 16 - 25 Measuring the saving attributable to an antibiotic prescribing policy; Stevenson RC et al.; An analytical framework is suggested for the economic evaluation of policies to improve the management of hospital infection . Consideration of the costs and benefits to be expected from improved policies implies the existence of an optimal infection rate which is higher than the minimum attainable . It follows that hospitals can and probably do spend too much on infection control in, at least, some areas . This optimal approach is not operational at present but its data requirements might be thought of as an agenda for future research . In the meantime, progress in infection control economics depends on a piecemeal approach . An example is given in the estimation of the cost savings attributable to an improved antibiotic prescribing policy at the Royal Liverpool Hospital. Chemotherapy, 1988, 34(1), 36 - 9 Bordetellae and charcoal horse blood agar: inactivation of antibiotics in agar during prolonged incubation for susceptibility testing; Hoppe JE et al.; We examined the degree of inactivation of 22 antibiotics caused by prolonged incubation at 36 degrees C of agar plates during agar dilution susceptibility testing of Bordetellae . Fresh antibiotic-containing plates of charcoal horse blood agar and plates which had been held at 36 degrees C for 2 or 3 days prior to inoculation were inoculated with strains of Bordetella pertussis and Bordetella parapertussis and incubated for 2 days . Then the MICs were compared . Most antibiotics showed a loss of activity of up to four dilution steps after prolonged incubation . Further studies with other slow-growing organisms and other complex media are needed. Biol Met, 1988, 1(2), 112 - 6 A five-coordinate copper complex with superoxide dismutase mimetic activity from Streptomyces antibioticus; Schechinger T et al.; A Cu(II) complex of desferrithiocin from Streptomyces antibioticus was prepared and characterized . The first shell atoms, including one nitrogen and four oxygens, were arranged around the copper in a square-planar pyramide . Due to the axially Jahn-Teller-distorted Cu-O distance at 224.7 pm, a distinct Cu2Zn2superoxide dismutase mimetic activity was measured . The Cu-complex survived 600 microM bovine serum albumin and the thermodynamic stability (pK = 17.4) was not very different from that of Cu-EDTA . The electronic absorption properties, circular dichroism and electron paramagnetism were in accordance with those of the type-II copper species. Free Radic Biol Med, 1988, 5(5-6), 341 - 8 Hydroxyl radical generation by the tetracycline antibiotics with free radical damage to DNA, lipids and carbohydrate in the presence of iron and copper salts; Quinlan GJ et al.; Tetracycline antibiotics caused the degradation of carbohydrate in the presence of a ferric salt at pH 7.4 . This degradation appeared to involve hydroxyl radicals since the damage was substantially reduced by the presence of catalase, superoxide dismutase, scavengers of the hydroxyl radical and metal chelators . Similarly, the tetracycline antibiotics in the presence of a ferric salt greatly stimulated the peroxidation of liposomal membranes . This damage, which did not implicate the hydroxyl radical, was significantly reduced by the addition of chain-breaking antioxidants and metal chelators . Only copper salts in the presence of tetracycline antibiotics, however, caused substantial damage to linear duplex DNA . Studies with inhibitors suggested that damage to DNA did involve hydroxyl radicals. Arch Microbiol, 1988, 150(2), 184 - 92 A second streptomycin resistance gene from Streptomyces griseus codes for streptomycin-3"-phosphotransferase . Relationships between antibiotic and protein kinases; Heinzel P et al.; Two genes, aphE and orf, coding for putative Mr 29,000 and Mr 31,000, proteins respectively, were identified in the nucleotide sequence of a 2.8 kbp DNA segment cloned from Streptomyces griseus N2-3-11 . The aphE gene expressed streptomycin (SM) resistance and a SM phosphorylating enzyme in S . lividans strains . The two genes were found to be in opposite direction and seemed to share a common region of transcription termination . The aphE gene shows significant homology to the aph gene, encoding aminoglycoside 3'-phosphotransferase, APH(3'), from the neomycin-producing S . fradiae . The enzymatic specificity of the aphE gene product was identified to be SM 3"-phosphotransferase, APH(3") . The primary structure of the APH(3") protein is closely related to the members of the APH(3') family of enzymes . However, the APH(3") enzyme did not detectably phosphorylate neomycin or kanamycin . There is only low similarity of the protein to the APH(6) group of SM phosphotransferases . An evolutionary relationship between antibiotic and protein kinases is proposed. Cancer Chemother Pharmacol, 1988, 22(3), 246 - 50 In vitro antitumor activity of mitomycin C derivative (RM-49) and new anticancer antibiotics (FK973) against lung cancer cell lines determined by tetrazolium dye (MTT) assay; Horiuchi N et al.; Seven small- (SCLC) and four non-small-cell (NSCLC) lung cancer cell lines were used to examine the in vitro cytotoxicity of cytotoxic drugs such as (1aS-(1a alpha,8 beta,8a alpha,8b alpha}-8-{aminocarbonyl)oxy)methyl)-4,8a- dimethoxy-1,1a,2,8,8a,8b-hexahydro-7-hydroxy-5-methyl-6- nitrosoazirino(2',3':3,4)-pyrrolo-(1,2-a)indole (RM-49) and 11-acetyl-8-carboxymethyl-4-formyl-14oxa-1,11-diaze- tetracyclo(7.4.1.0(2,7),0(10,12}tetradeca-2-4-6-trien-6,9-++ +diyl-diacetate (FK973) . In vitro cytotoxicities of RM-49 and FK973 were compared with those of mitomycin C (MMC), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP16), adriamycin (ADM) and vindesin (VDS) . Drug sensitivity was determined using a tetrazolium (MTT)-based assay . Average IC50 values of these two drugs were not statistically different compared with that of MMC, although FK973 showed strong antitumor activity against SCLC cell lines such as LT3, N857, and H69 at the same concentration . The predicted peak plasma concentration (predicted PPC) calculated by the formula proposed by Scheithauer, log (predicted PPC) = -0.788 + (0.755 x log(LD50}, and relative antitumor activity, RAA (PPC/IC50), of RM-49 were higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P less than or equal to 0.05), and those of FK973 were also higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P less than or equal to 0.05) . Based on these promising in vitro studies, the clinical trials of RM-49 and FK973 were warranted. EMBO J, 1988 Jan, 7(1), 277 - 82 Resistance to macrolides, lincosamides and streptogramin type B antibiotics due to a mutation in an rRNA operon of Streptomyces ambofaciens; Pernodet JL et al.; Streptomyces ambofaciens produces spiramycin, a macrolide antibiotic and expresses an inducible resistance to macrolides, lincosamides and streptogramin B antibiotics (MLS) . From a mutant of S.ambofaciens exhibiting a constitutive MLS resistance phenotype a resistance determinant was cloned on a low copy number vector (pIJ61) through its expression in Streptomyces lividans . Further characterization has shown that this determinant corresponded to a mutant rRNA operon with a mutation in the 23S rRNA gene . In different organisms, mutations leading to MLS resistance have been located at a position corresponding to the adenine 2058 of Escherichia coli 23S rRNA . In the 23S rRNA from S.ambofaciens a similar position for the mutation has been postulated and DNA sequencing of this region has shown an adenine to guanine transition at a position corresponding to 2058 . S.ambofaciens possesses four rRNA operons which we have cloned . In Streptomyces, contrary to other bacteria, a mutation in one among several rRNA operons confers a selectable MLS resistance phenotype . Possible reasons for this difference are discussed. Am J Otolaryngol, 1988 Jan-Feb, 9(1), 1 - 5 Inflammatory effects of topical antibiotic suspensions containing propylene glycol in chinchilla middle ears; Vassalli L et al.; This study examines the occurrence of inflammatory changes and cholesteatoma in the middle ears of seven chinchillas after the application of topical antibiotic suspensions containing two different concentrations of propylene glycol . The preparations used were Cortisporin otic suspension, which contains neomycin, polymyxin B, hydrocortisone, and 10.5% propylene glycol, and Cortisporin ophthalmic suspension, containing the same ingredients, but only a 2% concentration of propylene glycol . Six weeks after the administration of the Cortisporin preparations, applied to the middle ear through a transbulla approach, no cholesteatomas were found in the seven ears treated with the ophthalmic suspension . Evidence of mild inflammation was present in only two of these ears . In the seven contralateral ears treated with the otic suspension, middle ear adhesions were found in six, cholesteatoma was present in four, serous effusions were found in three, and one had a large tympanic membrane perforation . The ears that showed cholesteatomas also had histologic evidence of squamous metaplasia, granulation tissue, and erosion of the underlying bone . We submit that the pathologic responses of the middle ear mucosa treated with the otic suspension, were due to an inflammatory response to the higher concentration of propylene glycol compared to that of the ophthalmic suspension. Vopr Onkol, 1988, 34(11), 1348 - 55 {Results of a cooperative clinical study of the Russian antineoplastic antibiotic bleomycetin}; Sokolov IuN et al.; Cooperative clinical trials of a newly-developed antibiotic--bleomycetin (a purified fraction of bleomycin A5) conducted in 172 patients at 7 oncological centers revealed a spectrum of antitumor activities similar to that displayed by Japanese-made bleomycin . When administered by intravenous or intramuscular injection in single or total doses amounting to only 50-70% of those of bleomycin (bleocin), bleomycetin proved effective in the treatment of extended squamous cell carcinoma of the head and neck, skin, cervix uteri, embryonal cancer of the testicle and, particularly, recurrent Hodgkin's disease and non-Hodgkin's lymphoma . Single administration of 15-50 mg bleomycetin (total dose--50-150 mg) to serous cavities was followed by the cure of specific pleurisy and ascites in 47% . Unlike bleomycin, bleomycetin treatment was free of pulmonary toxicity, and skin hyperpigmentation, hyperkeratosis, vomiting and alopecia were significantly less frequent. Exp Gerontol, 1988, 23(1), 35 - 41 The peculiarities of protein and RNA syntheses in the hepatic mitochondria of young and old animals: studies without the use of an antibiotic; Adenuga GA et al.; Pulse-labelling in the presence of antibiotics is so widely used for studying mitochondriogenesis that the shortcomings of the method is usually overlooked . In this article, we present the results of experiments on the biogenesis of mitochondria done without the use of antibiotics . The method of Kitagawa and Sugimoto (1980) for the estimation of in vivo translational activity of rat liver mitochondria without the use of antibiotics was employed . The syntheses of RNA and protein in rat liver mitochondria of young and old animals was investigated . Incorporation of 14C-ATP into the RNA of isolated mitochondria occurs at the same level in both young and old animals . However, the incorporation of 14C-leucine into the two fractions of mitochondria, i.e . mitochondria protein of nucleo-cytoplasmic origin and those of intrinsic mitochondrial origin are at the same level for young animals . In old animals, the incorporation of the tracer into mitochondrial protein of intrinsic mitochondrial origin (which is at the same level as that of young animals) is three times greater than the incorporation of the tracer into mitochondrial protein of nucleo-cytoplasmic origin . These findings suggest that the role of the mitochondrial genome in the biogenesis of mitochondria increases at senesence and that the synthesis of corresponding regulatory proteins which are of nucleo-cytoplasmic origin decreases at senesence. Neurosurgery, 1988 Jan, 22(1 Pt 1), 97 - 100 Antibiotic therapy for infected Ommaya reservoir systems; Siegal T et al.; The major complication of prolonged use of a permanently implanted Ommaya reservoir system is bacterial infection, encountered in 3 to 15% of patients . The best therapeutic approach to ventriculitis and meningitis occurring in the presence of this device is still a subject of debate . We reviewed our experience in 66 consecutive patients receiving intraventricular therapy via the Ommaya reservoir for leptomeningeal metastases or for subacute sclerosing panencephalitis . Eight episodes of infection occurred during the period of treatment, and all of them responded to systemic antibiotics with or without intraventricular treatment . Removal of the Ommaya reservoir was avoided, and therapy via the device for the underlying disease was resumed as soon as the infection was controlled . No relapse of infection occurred during a minimal follow-up of 40 days . On the basis of our experience and review of the literature, we challenge the concept that the Ommaya device, as a foreign body, must be removed to treat such infections successfully. Hear Res, 1987 Dec 31, 31(3), 217 - 22 Nutritional status, glutathione levels, and ototoxicity of loop diuretics and aminoglycoside antibiotics; Hoffman DW et al.; Chinchillas deprived of food for 48 h prior to the administration of a combined dose of ethacrynic acid (10 mg/kg) and kanamycin (100 mg/kg) suffered a profound hearing loss . Fed animals did not demonstrate any hearing loss at the same dose levels . Drug metabolism may be the common pathway by which ototoxic agents interact, by a mechanism which is common to both the cochlea and the kidney . Glutathione (GSH) is a tripeptide which is involved in several pathways in the detoxification of active oxygen and reactive species formed during xenobiotic metabolism . The enhanced auditory dysfunction was paralleled by one-third decline in hepatic glutathione levels in the food-deprived animals . Manipulation of endogenous GSH levels may mitigate the toxicities of many of these drugs, which otherwise limit their clinical usefulness . These results also indicate that nutritional status may have important clinical implications during drug therapy. J Chromatogr, 1987 Dec 18, 411, 313 - 23 Improvement of chemical analysis of antibiotics . XIII . Systematic simultaneous analysis of residual tetracyclines in animal tissues usin