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Showing papers in "Antimicrobial Agents and Chemotherapy in 1973"


Journal ArticleDOI
TL;DR: The genetic basis for resistance to a number of antibiotics was examined in Rhizobium japonicum, and resistance to penicillin G, neomycin, and chloramphenicol appears to be mediated by an extrachromosomal element similar to that found in the Enterobacteriaceae.
Abstract: The genetic basis for resistance to a number of antibiotics was examined in Rhizobium japonicum. Resistance to penicillin G, neomycin, and chloramphenicol appears to be mediated by an extrachromosomal element similar to that found in the Enterobacteriaceae. Resistance to these antibiotics was eliminated from cells by treatment with acridine orange, and resistance to all three antibiotics could be transferred en bloc to Agrobacterium tumefaciens under conditions excluding transformation or transduction as possible genetic mechanisms.

250 citations


Journal ArticleDOI
TL;DR: Transfer experiments to E. coli K-12 indicate that these strains are infected with two different R factors, one causing CM, TC, SM, and SU resistance and the other causing AM or AM and KM resistance.
Abstract: During 1972 a large epidemic, in excess of 10,000 cases, of typhoid fever occurred in Mexico City, Pachuca, and other communities of Mexico. The main characteristic of the epidemic, in addition to the large number of persons affected, was the prevalence of a strain of Salmonella typhi which was highly resistant to chloramphenicol both in vivo and in vitro, and which belonged to a single phage type, Vi degraded approaching type A. Of 493 strains of S. typhi studied during the outbreak, 452 (91.7%) were resistant to chloramphenicol (CM), tetracycline (TC), streptomycin (SM), and sulfonamides (SU). The epidemic strain owes its resistance to an R factor which is easily transferable to Escherichia coli K-12 and which appears to be stable. In the third month of the outbreak, a strain of S. typhi resistant to CM, TC, SM, SU, ampicillin (AM), and kanamycin (KM) was isolated from a patient with severe typhoid fever. During the following 9 months, six additional strains of S. typhi resistant to AM, CM, TC, SM, and SU were also isolated. Transfer experiments to E. coli K-12 indicate that these strains are infected with two different R factors, one causing CM, TC, SM, and SU resistance and the other causing AM or AM and KM resistance. The frequency of transfer of the resistance in overnight crosses was in the order of 10(-4) for CM, TC, SM, and SU and 10(-6) for AM or AM, and KM. The appearance of these strains resistant both to chloramphenicol and ampicillin was a cause for concern for the clinicians; fortunately, they have remained an infrequent cause of disease.

193 citations


Journal ArticleDOI
TL;DR: A modification of the broth-disk method of Schneierson allowed us to determine antibiotic susceptibility in a completely anaerobic environment and there was good correlation between results obtained by this broth- disk method and minimal inhibitory concentrations.
Abstract: The most commonly used method for testing the antibiotic susceptibility of aerobic and facultative bacteria is the disk diffusion method. However, some anaerobic bacteria do not grow well enough in anaerobic jars for performance of disk diffusion tests. A modification of the broth-disk method of Schneierson allowed us to determine antibiotic susceptibility in a completely anaerobic environment. Commercial antibiotic disks were added anaerobically to tubes of prereduced brain heart infusion broth to achieve a concentration of each antibiotic approximating that attainable in blood. The tubes were then inoculated and incubated for 18 h. Resistance or susceptibility to each antibiotic was determined according to the amount of growth in each tube as compared with a control culture without the antibiotic. There was good correlation between results obtained by this broth-disk method and minimal inhibitory concentrations.

166 citations


Journal ArticleDOI
TL;DR: Although the microscopic procedure does not allow species identification of mycobacteria or differentiation between viable and nonviable cells, it often provided, within hours rather than days or weeks, useful information on the residual burden of acid-fast bacilli in sputum during chemotherapy.
Abstract: A method for precise microscopic enumeration of acid-fast bacilli in the sputum of patients with pulmonary tuberculosis is described. The total number of acid-fast bacilli and the number of culturable cell units of tubercle bacilli per milliliter of sputum were determined in 269 specimens from 28 patients collected prior to and/or during chemotherapy, to establish the usefulness of the procedure for evaluation of the effects of chemotherapy. Prior to or very early in the course of therapy, there was good agreement between microscopically and culturally measurable bacilli in 27 of 28 patients. Thereafter, there were systematic divergences in five patients and occasional divergences in most others. Yet, in general, in 20 of the 28 patients, the microscopically determined population provided a useful measure of the number of culturable tubercle bacilli present. Although the microscopic procedure does not allow species identification of mycobacteria or differentiation between viable and nonviable cells, it often provided, within hours rather than days or weeks, useful information on the residual burden of acid-fast bacilli in sputum during chemotherapy. The nature of the disease in those patients in whom microscopy failed to provide useful information is discussed.

165 citations


Journal ArticleDOI
TL;DR: Parallel experiments indicated Virazole to have at least a comparable degree of activity, and it was also active against a wider variety of viruses than any of these known active materials.
Abstract: Virazole (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a highly soluble new synthetic nucleoside having significant, reproducible activity against a broad spectrum of deoxyribonucleic acid and ribonucleic acid viruses in vitro. The drug inhibited viral cytopathogenic effects in monolayers of cells infected for 3 days with type 3 adeno, types 1 and 2 herpes, myxoma, cytomegalo, vaccinia, infectious bovine rhinotracheitis, types 1A, 2, 8, 13, and 56 rhino, types 1 and 3 parainfluenza, vesicular stomatitis, subacute sclerosing panencephalitis, Semliki Forest, Newcastle disease, and measles viruses. Hemagglutinin production by influenza A(2), influenza B, and type 1 parainfluenza viruses in chicken embryo cells was reduced by Virazole treatment. Recoverable intra- and extracellular virus titers were reduced by the drug in experiments with type 1 herpes, vaccinia, type 3 parainfluenza, and vesicular stomatitis viruses. Plaque formation by type 1 herpesvirus was also inhibited by exposure of the infected cells to Virazole. Pretreatment of cells with the compound, followed by its removal before addition of type 1 herpesvirus, severely lessened the antiviral activity; the compound was still moderately effective in reducing the viral effects on the cells when added as long as 22 hr after the virus. Parallel experiments, in which the antiviral activity of a number of known active drugs was compared, indicated Virazole to have at least a comparable degree of activity, and it was also active against a wider variety of viruses than any of these known active materials. The CCED(50) of Virazole to chicken embryo cells was approximately 1,000 mug/ml, although concentrations as low as 10 mug/ml caused slight (15%) inhibition in total cellular protein after 72 hr of incubation.

162 citations


Journal ArticleDOI
TL;DR: A single R-factor type may have been maintained in the Burns Unit between the two Pseudomonas outbreaks as a plasmid conferring resistance to ampicillin in K. aerogenes.
Abstract: An outbreak of R-factor-mediated carbenicillin resistance in Pseudomonas aeruginosa in burned patients in March 1969 was followed by a second outbreak 6 months later. No R-factor-carrying P. aeruginosa strains were detected in the intervening period but R-factor-determined lactamase was commonly encountered, particularly in Klebsiella aerogenes strains. A comparison of the molecular properties of the R factors in pseudomonads from the first and second phases with those in the Klebsiella strains from the intervening period showed them to be very closely related. A single R-factor type therefore may have been maintained in the Burns Unit between the two Pseudomonas outbreaks as a plasmid conferring resistance to ampicillin in K. aerogenes .

139 citations


Journal ArticleDOI
TL;DR: It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin, as increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum.
Abstract: Penicillins can be metabolized to penicilloic acids in man, the extent being dependent on the penicillin structure. In the phenoxy penicillin series, phenoxymethyl penicillin was found to be particularly unstable, but the higher homologues were more stable. In the isoxazolyl series, oxacillin was unstable, and progressive insertion of halogen in the phenyl ring increased stability. Ampicillin and amoxycillin showed some instability, ampicillin possibly being the more stable. After intramuscular administration, carbenicillin was very stable in the body, ampicillin was fairly stable, and benzyl penicillin was unstable. It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin. Increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum. Penicilloic acids seemed to be more slowly cleared from the body than penicillins. The liver is probably the site of inactivation.

124 citations


Journal ArticleDOI
TL;DR: Aphidicolin is an antibiotic of novel structure produced by the mold Cephalosporium aphidicola that is active against iododeoxyuridine-resistant herpes virus, and does not itself readily induce the formation of drug-resistant strains of herpesvirus.
Abstract: Aphidicolin is an antibiotic of novel structure produced by the mold Cephalosporium aphidicola. It is a potent inhibitor of cellular deoxyribonucleic acid synthesis, and it also strongly inhibits the growth of herpes simplex virus both in tissue culture and in the rabbit eye. Aphidicolin is active against iododeoxyuridine-resistant herpes virus, and does not itself readily induce the formation of drug-resistant strains of herpesvirus.

124 citations


Journal ArticleDOI
TL;DR: A broth dilution method was used to determine the minimal inhibitory concentration of a series of fatty acid esters of polyhydric alcohols against gram-negative and gram-positive organisms.
Abstract: A broth dilution method was used to determine the minimal inhibitory concentration of a series of fatty acid esters of polyhydric alcohols against gram-negative and gram-positive organisms. Gram-negative organisms were not affected. Gram-positive organisms were inhibited as follows. Of the monoglycerol esters, monoglycerol laurate was the most active. Esters of polyglycerols (tri-, hexa-, and decaglycerol esters) were generally active when the fatty acid had chain lengths of 8 to 12 carbon atoms. Sucrose esters, when active, except for laurate, are more active than the free fatty acid. The spectrum of antimicrobial action of esters of polyhydric alcohols is narrower when compared with the free acids.

122 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the modified test is applicable to susceptibility determinations with representative, commercially available antimicrobial disks, indicating that themodified method could provide rapid in vitro guidelines for in vivo therapy.
Abstract: A rapid (6-7 hr), modified Kirby-Bauer disk-susceptibility method, by which derivatives of tetrazolium dyes are used to enhance delineation between areas of growth and zones of inhibition, has been developed. Inoculated petri plates, prepared by the Kirby-Bauer method, were sprayed, after 6 to 7 hr of incubation (37 C), with aqueous solutions of MTT-tetrazolium or INT-tetrazolium resulting in readily detectable zones of inhibition. Excellent correlation was obtained between the modified test and the standard Kirby-Bauer test when challenged with a variety of gram-negative bacteria and Staphylococcus aureus strains. Additionally, the modified test has demonstrated reproducibility comparable to the standard Kirby-Bauer test. It is demonstrated that the modified test is applicable to susceptibility determinations with representative, commercially available antimicrobial disks. This applicability indicates that the modified method could provide rapid in vitro guidelines for in vivo therapy.

111 citations


Journal ArticleDOI
TL;DR: BB-K8 generally showed the greatest ratio between achieveable mean peak serum levels and concentrations needed to inhibit each group of organisms tested and was active against six of seven highly gentamicin-resistant strains.
Abstract: The in vitro susceptibility to BB-K8, butirosin, gentamicin, sisomicin, and tobramycin of seven groups of clinically significant gram-negative bacilli and Staphylococcus aureus was assessed by using the International Collaborative Study-World Health Organization criteria. The activity of gentamicin, sisomicin, and tobramycin generally paralleled each other. Sisomicin was the most potent compound by weight and usually demonstrated the most rapid rate of killing. BB-K8 and butirosin were less potent, but higher serum levels may be achieved with these agents. BB-K8 generally showed the greatest ratio between achieveable mean peak serum levels and concentrations needed to inhibit [Formula: see text] of each group of organisms tested. Additionally, BB-K8 was active against six of seven highly gentamicin-resistant strains. All of these antibiotics showed diminished activity at pH 6.4 but only gentamicin and sisomicin showed occasionally enhanced activity at pH 8.4.

Journal ArticleDOI
TL;DR: Nearly 100 isolates of Lactobacillus were obtained from human and animal sources and one of these, L. helveticus strain LP27, was shown to produce a potent bacteriocin called lactocin 27, which was isolated from the culture supernatant fluid as a protein-lipopolysaccharide complex.
Abstract: Nearly 100 isolates of Lactobacillus were obtained from human and animal sources. Screening tests with the isolates revealed seven possible bacteriocinogenic strains and 26 strains sensitive to one or more of these inhibitory strains. Three homofermentative strains were selected for additional study after it was shown that their inhibitory substances differed in activity spectrum and in susceptibility to inactivation by proteolytic enzymes. One of these, L. helveticus strain LP27, was shown to produce a potent bacteriocin called lactocin 27. The lactocin was isolated from the culture supernatant fluid as a protein-lipopolysaccharide complex. In the presence of sodium dodecyl sulfate the complex was dissociated, and the activity was found to reside in a small glycoprotein (molecular weight 12,400). The amino acid composition of purified lactocin 27 is similar to that of the L. fermenti bacteriocin; neither requires disulfide bonds for activity.

Journal ArticleDOI
TL;DR: The sulfur-containing antibiotic thiolutin has been shown to be a potent, reversible inhibitor of the growth of Saccharomyces cerevisiae and may prove to be of use in studies of various stages of yeast growth.
Abstract: Thesulfur-containing antibiotic thiolutin hasbeenshowntobea potent, reversible inhibitor ofthegrowth ofSaccharomyces cerevisiae. Viability was unaffected overtheconcentration rangeof4to100ug/ml. Atconcentrations as lowas2 sg/ml, thedruginhibited ribonucleic acid(RNA)andprotein synthesis inwholecells andspheroplasts. Atthese lowconcentrations, protein synthesis continued for ashort period oftimeafter RNAsynthesis was completely stopped. Withhigher drugconcentrations (greater than20;g/ml) protein synthesis was inhibited; concentrations ofthiolutin up to100,ug/ml didnotaffect translocation orpeptide bondformation incell-free protein-synthesizing systemsfromyeast. Theeffect ofthiolutin on theactivity ofpartially purified deoxyribonucleic acid-dependent RNA polymerases was examined, andthedrug was found tobea potentinhibitor ofRNA synthesis invitro. Inhibition was greatest whenthe polymerase was preincubated withthiolutin. Several mechanisms arediscussed toexplain themultiple effects ofthiolutin onS.cerevisiae. Since theaction ofthe drugiseasily reversed, thiolutin may provetobeofuse instudies ofvarious stages ofyeastgrowth. Inbacteria, antibiotics haveplayed useful roles inproviding genetic markers foranumber ofmacromolecules andhavealso beenusedin dissecting theroles ofmacromolecules inconcerted reactions. Theuseofantibiotics inyeast hasnotbeenexploited tothesameextent. This isdue,inpart, tothefactthatmanyofthe better-characterized antibiotics donotaffect Saccharomyces cerevisiae, presumably because theyeastcell isimpermeable tothese compounds. Manyantifungal compounds havebeen isolated during theprocess ofscreening for antimicrobial agents, and,although theymay notbemedically useful because oftheir toxicity properties, itisquite possible that someofthese compounds mayhavebiochemical applications. Thisreport describes ourinitial studies onthe modeofaction ofonesuchantifungal agent, thiolutin.

Journal ArticleDOI
TL;DR: It is suggested that silver sulfadiazine may be useful as a broad-spectrum antimicrobial substance for the prevention and treatment of infections of burns and wounds.
Abstract: Isolates (657) representing 22 bacterial species were tested for susceptibility to silver sulfadiazine. All of the strains tested were inhibited by concentration levels of the drug which are easily achieved topically. It is suggested that silver sulfadiazine may be useful as a broad-spectrum antimicrobial substance for the prevention and treatment of infections of burns and wounds.

Journal ArticleDOI
TL;DR: Cefamandole was the most active of the four agents against Haemophilus species and gram-negative bacilli susceptible to cephalosporins, but had no useful activity against Pseudomonas species.
Abstract: The in vitro antibacterial activity of cefamandole, a new cephalosporin antibiotic, was compared with that of cephaloridine, cephalothin, and cephalexin against 1,213 strains of gram-positive and gram-negative bacteria recently isolated from clinical sources. The decreasing order of activity of the four agents against gram-positive cocci was cephaloridine, cephalothin, cefamandole, and cephalexin. However, cefamandole was the most active of the four against Haemophilus species and gram-negative bacilli susceptible to cephalosporins. It was also active against many strains resistant to the other cephalosporins, such as Enterobacter species and indole-positive Proteus species, but there was a marked inoculum effect with all of these organisms, and minimal bactericidal concentrations were usually considerably higher than minimal inhibitory concentrations. Cefamandole, like other cephalosporins, had no useful activity against Pseudomonas species.

Journal ArticleDOI
TL;DR: The number and location of amino groups on the hexoses and the site of attachment of the other rings to deoxystreptamine have been shown to exert a profound effect on the ability of these compounds to inhibit or to cause misreading of polypeptide synthesis in vitro.
Abstract: The close structural similarity of several of the deoxystreptamine-containing aminoglycoside antibiotics (gentamicins, neomycins, kanamycins, tobramycin) and the recent isolation of enzymatically N-acetylated aminoglycosides have permitted a systematic comparison of the structure-activity relationships in this group of antibiotics The number and location of amino groups on the hexoses and the site of attachment of the other rings to deoxystreptamine have been shown to exert a profound effect on the ability of these compounds to inhibit or to cause misreading of polypeptide synthesis in vitro The conclusions allow certain predictions to be made concerning the interaction of these compounds with the bacterial ribosome

Journal ArticleDOI
TL;DR: Five of these six isolates also had acquired massive resistance to 5-fluorouracil (5-FU), suggesting that a mutation in the uridine-5′-monophosphate pyrophosphorylase was responsible for drug resistance.
Abstract: Isolates of Cryptococcus neoformans from six patients were obtained before and after unsuccessful therapy with 5-fluorocytosine (5-FC). Post-therapy isolates exhibited massive and stable 5-FC resistance. The frequency of drug-resistant mutants in susceptible isolates of C. neoformans was <0.001% (70.4 +/- 17.9 per 10(7) cryptococci), whereas mutant frequencies in resistant isolates approached 100%. Non-drug-induced, spontaneously appearing 5-FC resistant mutants were documented in four susceptible isolates of C. neoformans by use of the statistical method of fluctuation analysis. Mutation rates on these same four isolates ranged from 1.2 x 10(-7) to 4.8 x 10(-7). Total intracellular uptake and incorporation of cytosine-5-(3)H (CyH(3)) and 5-fluorocytosine-2-(14)C (5-FC(14)) into a trichloroacetic acid-insoluble fraction were markedly reduced in six isolates with in vivo-acquired resistance when compared with susceptible pretreatment strains from the same patients. Five of these six isolates also had acquired massive resistance to 5-fluorouracil (5-FU), suggesting that a mutation in the uridine-5'-monophosphate pyrophosphorylase was responsible for drug resistance. The sixth isolate, which remained susceptible to 5-FU, appeared to have a defect in a cytosine-specific permease accounting for 5-FC resistance. A single isolate with in vitro-acquired 5-FC and 5-FU resistance had no reduction in uptake or incorporation of CyH(3) or 5-FC(14). The mechanism of resistance in this isolate is discussed.

Journal ArticleDOI
TL;DR: The size of the inoculum markedly affected the MIC of sulfonamides and had variable effects on other agents, and Marked synergy of erythromycin with ampicillin was demonstrated for nearly all strains tested.
Abstract: A method for preparing uniformly dispersed cultures of Nocardia asteroides for use in tests for susceptibility to antimicrobial agents is described. The minimal inhibiting concentration (MIC) of 45 agents for cultures thus prepared was determined with the use of a replica-inoculating apparatus. Minocycline at a concentration of 3.1 μg or less/ml inhibited 90% of the strains tested, and all were inhibited by 6.3 μg/ml. An erythromycin concentration of 0.8 μg or less/ml inhibited 40% of the strains, but the MIC for most of the others was > 100 μg/ml. The other agents were generally less active. Chemically related analogues varied in activity to different degrees. Also, the MIC of each antibiotic against different strains generally varied over a wide range. Sulfonamides and trimethoprim were not active against most strains in the method used. The size of the inoculum markedly affected the MIC of sulfonamides and had variable effects on other agents. Marked synergy of erythromycin with ampicillin was demonstrated for nearly all strains tested.

Journal ArticleDOI
TL;DR: The discrepancy between the extremely low concentration of diumycin required to inhibit the in vitro system from E. coli and the much higher concentration needed to inhibit growth of the organism is noteworthy.
Abstract: Diumycin, janiemycin, nisin, and subtilin inhibited peptidoglycan synthesis catalyzed by particulate enzyme systems from Bacillus stearothermophilus and Escherichia coli. All of these, except for nisin, also induced accumulation of the lipid intermediate in peptidoglycan synthesis. Concentrations required for 50% inhibition of peptidoglycan synthesis were less than 0.1 mug/ml for diumycin and in the range of 10 to 100 mug/ml for janiemycin, nisin, and subtilin in both organisms. The discrepancy between the extremely low concentration of diumycin required to inhibit the in vitro system from E. coli and the much higher concentration required to inhibit growth of the organism is noteworthy.

Journal ArticleDOI
TL;DR: The kinetic parameters governing the distribution and elimination of BB-K8 and kanamycin after an im dose were similar to those obtained for iv dosing and indicate desirable dose-independent kinetics, according to a human pharmacokinetic study.
Abstract: Comparative studies in beagle dogs suggested that the pharmacokinetic profiles of BB-K8 and kanamycin are similar. After intravenous (iv) administration to dogs, BB-K8 and kanamycin were rapidly distributed in plasma and tissue fluids; their "apparent" volumes of distribution comprised approximately 23% of the total body volume. Like kanamycin, BB-K8 had a plasma half-life of about 0.8 h which paralleled the urinary excretion rate. Approximately 92% of the dose was excreted as unchanged drug within 6 h of dosing, and clearance appeared to be primarily by glomerular filtration. After intramuscular (im) administration to dogs, BB-K8 and kanamycin were totally and rapidly absorbed; peak concentrations in the plasma occurred 0.5 to 1.0 h after dosing. The kinetic parameters governing the distribution and elimination of BB-K8 and kanamycin after an im dose were similar to those obtained for iv dosing and indicate desirable dose-independent kinetics. A human pharmacokinetic study indicated that the kinetic profiles of BB-K8 and kanamycin are similar in man after im dosing. Like kanamycin, BB-K8 is rapidly absorbed, yielding peak serum concentrations of about 20 mug/ml at 1 h after a 500-mg im dose. The plasma half-life of these two drugs was approximately 2.3 h. Clearance in man was primarily by glomerular filtration, and the urinary excretion of BB-K8 and kanamycin accounted for 83% of the dose.

Journal ArticleDOI
TL;DR: With three independent techniques (absorption spectrophotometry, measurement of the deoxyribonucleic acid [DNA] melting temperature, and equilibrium dialysis), no evidence has been found for the binding of nalidixic acid to purified DNA and the hypothesis that nalidxic acid is permanently modified to a new, active compound by the bacterial cell is not supported.
Abstract: With three independent techniques (absorption spectrophotometry, measurement of the deoxyribonucleic acid [DNA] melting temperature, and equilibrium dialysis), no evidence has been found for the binding of nalidixic acid to purified DNA. Also, no evidence has been found to support the hypothesis that nalidixic acid is permanently modified to a new, active compound by the bacterial cell. By using an in vitro DNA replication system developed by Bonhoeffer and colleagues, soluble extracts from nalidixic acid-sensitive cells have been shown to confer nalidixic acid sensitivity on the DNA synthesis of lysates from nalidixic acid-resistant cells. The activity in the extracts is only present in sensitive cells and is nondialyzable and heat sensitive. Finally, two known nalidixic acid-resistant mutants of Escherichia coli, mapping at nal A and nal B, respectively, have been tested to determine whether either of them is a transport mutant. It has been shown that nal B(r) is a transport mutant whereas nal A(r) is not.

Journal ArticleDOI
TL;DR: Findings support the conclusion that the antibiotic effects of cerulenin are due to a specific inhibition of fatty acid synthesis.
Abstract: The antibiotic cerulenin markedly inhibits the growth of Escherichia coli. The effects of the antibiotic on cellular syntheses were studied by measuring the incorporation of labeled precursors into lipids and macromolecules. During the first 40 min after the addition of cerulenin to a culture of growing cells, lipid synthesis was inhibited more than 90% and ribonucleic acid and deoxyribonucleic acid synthesis about 25%, whereas protein synthesis was not affected. At later periods after cerulenin addition (1 to 2 h), the inhibition of cell growth and of lipid and protein synthesis was complete. Upon removal of cerulenin from the culture, growth was restored and lipid synthesis resumed more rapidly than did the synthesis of protein. Addition of both palmitate and oleate, but not of either fatty acid alone, reversed the inhibition of growth by cerulenin. These findings support the conclusion that the antibiotic effects of cerulenin are due to a specific inhibition of fatty acid synthesis.

Journal ArticleDOI
TL;DR: R+ bacteria in the hospital discharge were also resistant to a broader spectrum of drugs than those in city sewage, and such drug-resistant pathogens in the water environment could be of particular concern.
Abstract: The number and properties of drug-resistant coliform bacteria in hospital and city sewage were compared. There was little difference in the counts of organisms with nontransferable resistance to one or more of 13 commonly used drugs. An average of 26% of coliforms in hospital waste water had transferable resistance to at least one of the drugs ampicillin, chloramphenicol, streptomycin, sulfonamide, or tetracycline as compared to an average of 4% in city sewage. R(+) bacteria in the hospital discharge were also resistant to a broader spectrum of drugs than those in city sewage. In both effluents, the occurrence of fecal Escherichia coli among R(+) coliforms was twice as high as among coliforms with nontransferable resistance. Resistance was transferable to Salmonella typhi, and such drug-resistant pathogens in the water environment could be of particular concern. The significance of the results with regard to environmental pollution with R(+) bacteria and the dissemination of these organisms is discussed.

Journal ArticleDOI
TL;DR: The combination of vancomycin and gentamicin or vancomYcin and streptomycin (where in vitro studies demonstrate synergism) may be a useful alternate therapy in enterococcal endocarditis.
Abstract: The in vitro activity of vancomycin and combinations of vancomycin-gentamicin and vancomycin-streptomycin against enterococci was investigated. The minimal inhibitory concentration of vancomycin for 99 of 100 enterococcal strains isolated clinically was 3.12 mug or less/ml. When cultures of eight strains were incubated with vancomycin, regardless of the inoculum size (10(6), 10(5), or 10(4)) and concentration of vancomycin (10 or 20 mug/ml), there was no significant reduction in the number of viable enterococci at 6, 24, and 48 h. Gentamicin and streptomycin in concentrations attainable clinically were not effective against enterococci. Vancomycin combined with gentamicin or streptomycin was tested against 41 enterococcal strains. With the combination of vancomycin at 10 mug/ml and gentamicin at 4 mug/ml or vancomycin at 5 mug/ml and gentamicin at 4 mug/ml, synergism was demonstrated against all 41 strains at 6 h. The combination of vancomycin at 10 mug/ml and streptomycin at 10 mug/ml was only synergistic against 25 of 41 strains at 6 h, and only 22 of 41 strains were affected synergistically at 6 h by vancomycin at 5 mug/ml with streptomycin at 10 mug/ml. With few exceptions, the enhanced killing was more pronounced at 24 and 48 h. The combination of vancomycin and gentamicin or vancomycin and streptomycin (where in vitro studies demonstrate synergism) may be a useful alternate therapy in enterococcal endocarditis.

Journal ArticleDOI
TL;DR: R factor R931 exists as a naturally occurring high-frequency transfer system in P. aeruginosa strains 931 and 1310, however, in strain 280 it acts as if subject to fertility repression, and other members of the P-2 compatibility group also are high- frequencies transfer systems in the natural host and in strain 1310.
Abstract: R factors were detected in 3.3% of 233 hospital isolates of Pseudomonas aeruginosa using P. aeruginosa recipients in conjugations. Transferred markers included streptomycin, tetracycline, and sulfonamide resistance. Gentamicin resistance was transferred from two strains previously shown to acetylate gentamicin. A group of R factors exemplified by R931 were characterized by failure to transfer to Escherichia coli recipients. Such R factors formed a single compatibility group when examined in a P. aeruginosa recipient. Other P. aeruginosa R factors, including RP4, showed stable coexistence with the R931 group. It is proposed that RP4 and similar R factors be members of the P-1 compatibility group and that R931, R3108, R209, and R130 be members of a group termed P-2. The buoyant densities of all R factors examined were similar, about 1.716 to 1.719 g/cm 3 . The content of R-factor deoxyribonucleic acid (DNA) relative to the total DNA varied among the different R factors, ranging from about 18 ± 2% in log-phase cells of 931 (R931) to undetectable for 679 (R679). However, R679, which transferred from strain 679 at extremely low and irregular frequencies to an E. coli host, was shown to represent about 4% R-factor DNA in that host. The relative DNA content of R931 appeared to decline in the stationary growth phase of 931 (R931) or 280 (R931). R931 covalently closed circular DNA was isolated by ethidium bromide-CsCl gradient centrifugation and examined by electron microscopy. Two major molecular distributions existed, having contour lengths of 0.5 and 12.4 μm. The molecular weights were estimated to be 10 6 and 25 × 10 6 . Both molecules were under relaxed replication control. R factor R931 exists as a naturally occurring high-frequency transfer system in P. aeruginosa strains 931 and 1310. However, in strain 280 it acts as if subject to fertility repression. Other members of the P-2 compatibility group also are high-frequency transfer systems in the natural host and in strain 1310. RP4 is restricted from recipient strain 1310. Some additional recipient effects were noted in that strains 1310 or 280 sometimes differed in recipient effectiveness with a given donor. Agglutination reactions with absorbed antiserum were able to distinguish between two members of the same R-factor compatibility group, R931 and R3108. Images

Journal ArticleDOI
TL;DR: It is recommended that all Kirby-Bauer tests be incubated at a temperature of 35 C to insure detection of methicillin-resistant S. aureus strains.
Abstract: Heteroresistant (methicillin-resistant) and nonheteroresistant strains of Staphylococcus aureus were tested for their susceptibility to penicillinase-resistant penicillins at incubation temperatures of 37, 35, and 30 C. Susceptibilities were determined by agar dilution and by the standard Kirby-Bauer agar diffusion tests. Minimal inhibitory concentrations were higher at 35 and 30 C than at 37 C. Heteroresistance could be detected with the Kirby-Bauer test if the incubation temperature was 30 or 35 C instead of 37 C, when tests were performed against methicillin, oxacillin, or nafcillin, because the resistant organisms grew up to the disks even though the susceptible organisms were inhibited. At 37 C, the resistance was detectable with some strains but not with others. When cloxacillin disks were used, the temperature effect was not seen. The incubation temperature did not affect results with nonheteroresistant strains. Therefore, it is recommended that all Kirby-Bauer tests be incubated at a temperature of 35 C to insure detection of methicillin-resistant S. aureus strains. Detection of these strains is of increasing importance because the incidence of infections with these organisms is increasing, particularly in hospitalized patients.

Journal ArticleDOI
TL;DR: A rapid and accurate enzymatic assay has been developed for the determination of blood serum levels of BB-K8 and other suitable aminoglycoside antibiotics.
Abstract: A rapid and accurate enzymatic assay has been developed for the determination of blood serum levels of BB-K8 and other suitable aminoglycoside antibiotics.

Journal ArticleDOI
TL;DR: The serum half-life of tobramycin was found to be the same as that of gentamicin in patients with similar renal function and both drugs were readily removed from the serum by the Kiil artificial kidney, with a 70% reduction in serum concentrations during a 12-hr dialysis period.
Abstract: The serum half-life of tobramycin was found to be the same as that of gentamicin in patients with similar renal function. The values ranged from 2 hr in normal volunteers to 53.4 hr in anephric patients. Both drugs were readily removed from the serum by the Kiil artificial kidney, with a 70% reduction in serum concentrations during a 12-hr dialysis period.

Journal ArticleDOI
TL;DR: The susceptibility of 100 or more strains of Bacteroides fragilis to six antibiotics was determined by standardized agar dilution and disc diffusion tests, and good correlation of results was obtained with chloramphenicol, clindamycin, lincomycin, penicillin, and vancomYcin.
Abstract: The susceptibility of 100 or more strains of Bacteroides fragilis to six antibiotics was determined by standardized agar dilution and disc diffusion tests. Good correlation of results of the two methods was obtained with chloramphenicol, clindamycin, lincomycin, penicillin, and vancomycin. Correlation of results with erythromycin was not as good. A great deal of overlapping of zone diameters among strains classed as susceptible, intermediate, and resistant occurred with both erythromycin and lincomycin, making interpretation of disc diffusion tests difficult. All strains tested were susceptible to chloramphenicol; 94% were susceptible to clindamycin at concentrations readily achieved with ordinary dosage, and all strains were inhibited by 6.2 μg/ml, a level which is achieved with somewhat more intensive therapy. Only 7% were shown to be susceptible to erythromycin and 13% to lincomycin under the conditions of our testing procedure. Only a small percentage of the strains were susceptible to penicillin, and none was susceptible to vancomycin.

Journal ArticleDOI
TL;DR: Topical application of 1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole) significantly inhibited the development of herpetic keratitis in the eyes of rabbits, as determined by both infectivity and Draize scoring parameters.
Abstract: Topical application of 1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole) significantly inhibited the development of herpetic keratitis in the eyes of rabbits, as determined by both infectivity and Draize scoring parameters. Significant inhibition of the infection was demonstrated with 10% concentrations of Virazole; a 1% solution had a moderate effect, whereas doses of 0.1 and 0.01% had little activity in this system. A 5% concentration of Virazole similarly inhibited vaccinia keratitis in rabbits. Encephalitis-induced mortality in hamsters initially infected intraocularly with herpesvirus was significantly prevented or inhibited by topical application of 5, 10, and 20% concentrations of Virazole. Surviving, treated hamsters had no signs of herpes keratitis. The 20% concentration was the approximate LD 50 in hamsters. Virazole administered subcutaneously or intraperitoneally to mice did not appreciably alter the course of herpes virus- or vaccinia virus-induced encephalitis in these animals, although in a herpesvirus experiment direct injection of the drug into the brains 3 hr prior to virus inoculation resulted in a significant survivor increase.