Antimicrobial Agents and Chemotherapy

Korfhagen, T. R.; Loper, J. C.

doi: 10.1128/AAC.pmid: 806259

R factor RPL11 from Pseudomonas aeruginosa determines multiple drug resistance including resistance to gentamicin and carbenicillin. The host range and incompatibility properties of RPL11 are those of incompatibility group P-2. Strains harboring the factor are not altered with respect to the major immunotypes 1 through 7 of Parke-Davis, or with respect to pyocin type by using the 18 indicators of Jones and co-workers. Analytical ultracentrifugation of crude extracts of R factor-containing strains shows a band of satellite DNA with a buoyant density of 1.717 g/cm 3 . Antimicrob Agents Chemother. 1975 January; 7(1): 69-73 Copyright © 1975 American Society for Microbiology . All Rights Reserved.

Rodriguez, Victorio; Bodey, Gerald P.; Valdivieso, Manuel; Feld, Ronald

doi: 10.1128/AAC.pmid: 1137357

Studies were conducted in 30 patients with neoplastic diseases. Twelve patients received sisomicin intramuscularly at doses of 20 mg/m 2 and 40 mg/m 2 . The mean peak serum concentration occurred at 1 h and was 2.5 µg/ml and 4.0 µg/ml, respectively. Ten patients received intravenous sisomicin at doses of 30 mg/m 2 during 30-min infusion. Mean peak serum level determined at 30 min was 5.1 µg/ml. The levels gradually decreased and at 6 h was 0.6 µg/ml. The serum half-life was 160 min. Serum levels determined in eight patients who received sisomicin by continuous infusion at doses of 30 mg/m 2 every 6 h were greater than 1.4 µg/ml during the 6-h period. The urinary excretion of sisomicin during the 6-h period after intramuscular administration of 20 mg/m 2 and 40 mg/m 2 was 49 and 61%, respectively. The pharmacology of sisomicin is similar to gentamicin. Antimicrob Agents Chemother. 1975 January; 7(1): 38-41 Copyright © 1975 American Society for Microbiology . All Rights Reserved.

Howarth, William R.; Tewari, Ram P.; Solotorovsky, Morris

doi: 10.1128/AAC.pmid: 1137359

The in vitro antifungal activity of amphotericin B methyl ester (AME), a water-soluble derivative of amphotericin B, was compared to that of the parent compound against a variety of pathogenic and potentially pathogenic fungi. AME has a significant antifungal activity, but the activity of AME was slightly lower than that of amphotericin B. Among the yeast-like organisms, only the yeast cells of Sporothrix schenckii were more resistant than others to both antibiotics, with a minimal fungicidal concentration of 5 to 10 µg/ml. The yeast cells of other fungi were killed at concentrations of 1 µg or less of either antibiotic per ml. The filamentous forms of S. schenckii and Oidiodendron kalrai were more resistant than the filamentous forms of other dimorphic fungi to both drugs. The minimal fungicidal concentration for S. schenckii was 10 µg/ml and for O. kalrai , 50 µg/ml. The dermatophytes, phycomycetes, and dematacious and other potentially pathogenic fungi were inhibited fairly well by both drugs, but up to 50 µg/ml was required for fungicidal action. The water solubility and wide spectrum of antifungal activity of AME warrant evaluation of its chemotherapeutic activity against experimental fungal infections. Antimicrob Agents Chemother. 1975 January; 7(1): 58-63 Copyright © 1975 American Society for Microbiology . All Rights Reserved.

Ferone, R.; Bushby, S. R. M.; Burchall, J. J.; Moore, W. D.; Smith, D.

doi: 10.1128/AAC.pmid: 1169907

Rich media support the growth of bacteria in the presence of concentrations of sulfonamides and diaminopyrimidines that are highly inhibitory when the organisms are grown on minimal media. Many such rich media can be made more suitable for susceptibility testing by the incorporation of lysed horse blood. Harper and Cawston characterized the active substance, Harper-Cawston factor (HCF), and later studies indicated it to be a protein. It has now been identified as thymidine phosphorylase. The identification follows from the identical purification pattern of HCF and thymidine phosphorylase activities from horse blood to a high degree of purity. Blood of goats, sheep, oxen, geese, chickens, cows, dogs, rats, and humans had neither biological activity. The identification of HCF as thymidine phosphorylase is consistent with the earlier findings of Koch and Burchall (1971) that most of the interfering effects of rich media could be accounted for by their thymidine contents, and that thymidine is much more active in this respect than is thymine. Antimicrob Agents Chemother. 1975 January; 7(1): 91-98 Copyright © 1975 American Society for Microbiology . All Rights Reserved.

Chopra, I.

doi: 10.1128/AAC.pmid: 1137361

The mechanism of plasmid-mediated resistance to cadmium in Staphylococcus aureus was investigated. Protein synthesis in cell-free extracts from resistant or susceptible bacteria was equally susceptible to inhibition by Cd 2+ , but spheroplasts from resistant bacteria retained their resistance. Resistant bacteria did not have a decreased affinity for cations in general, nor was active metabolism required for exclusion of Cd 2+ . The kinetics of Cd 2+ uptake into susceptible and resistant bacteria suggested that the conformation of membrane proteins in resistant bacteria may be important in the exclusion of Cd 2+ . Antimicrob Agents Chemother. 1975 January; 7(1): 8-14 Copyright © 1975 American Society for Microbiology . All Rights Reserved.

Pien, F. D.; Williams, R. D.; Vosti, K. L.

doi: 10.1128/AAC.pmid: 1137355

The use of serum rather than broth as the diluent in the serum bactericidal test results in a significant decrease in the test level among patients receiving highly protein-bound semisynthetic penicillins. Antimicrob Agents Chemother. 1975 January; 7(1): 113-114 Copyright © 1975 American Society for Microbiology . All Rights Reserved.

Paterniti, James R., Jr.; Wilkie, David; Eaton, Norman R.

doi: 10.1128/AAC.pmid: 1094943

Cells of Saccharomyces cerevisiae showed differential growth inhibition when cultured on various carbon sources in the presence of the proline analogue thiazolidine-4-carboxylic acid (TZ). On 0.5% yeast extract, 2% glucose and TZ (10 mg/ml) medium, growth lags from 8 to 10 h were observed, after which cells recovered and growth proceeded normally. Growth was totally inhibited on a medium of 0.5% yeast extract, 3% ethanol, and 5 mg of TZ per ml. This inhibition was not due to the inability of cells to undergo aerobic respiration, since similar media containing glycerol instead of ethanol allowed growth. Proline added to the culture medium reversed the lag on glucose and TZ medium but did not promote recovery on ethanol and TZ medium. TZ was found to have two probable modes of action in yeast. It was a noncompetitive inhibitor of yeast alcohol dehydrogenase, and it was also found to be incorporated into cellular protein. Uptake studies using 14 C-labeled TZ showed that the recovery on glucose was correlated with the progressive exclusion of the analogue from cells. Antimicrob Agents Chemother. 1975 January; 7(1): 25-31 Copyright © 1975 American Society for Microbiology . All Rights Reserved.

Reusser, Fritz

doi: 10.1128/AAC.pmid: 1094944

Lincomycin does not affect initiation factor-dependent formation of 70 S initiation complexes formed with fmet-tRNA F , the initiation triplet A-U-G, and 70 S ribosomes, whereas its 7-chloro-derivative clindamycin substantially stimulates this process. Conversely, lincomycin stimulates nonenzymatic formation of the 70 S complex, but clindamycin does not. Both antibiotics stimulate the assembly of non-enzymatically formed 70 S initiation complexes with R 17 phage ribonucleic acid and exert little effect on those formed in the presence of initiation factors. The formation of 30 S initiation complexes is stimulated or remains unaffected by lincomycin or clindamycin except when initiation occurs in the presence of very low Mg 2+ concentrations. In this case, both antibiotics inhibit the assembly of the 30 S complexes regardless of the messenger present. Antimicrob Agents Chemother. 1975 January; 7(1): 32-37 Copyright © 1975 American Society for Microbiology . All Rights Reserved.

Hale, E. M.; Hinsdili, R. D.

doi: 10.1128/AAC.pmid: 1137360

Staphylococcin 462 is a proteinaceous inhibitor produced by Staphylococcus aureus strain 462. In broth cultures, susceptible S. aureus strain 140 and 19 respond to treatment with the bacteriocin by stopping growth and cell division. Examination of macromolecular synthesis by measuring the incorporation of radioactive precursors revealed that S. aureus 140 stops synthesizing protein immediately. After exposure to staphylococcin 462, the synthesis of deoxyribonucleic acid and ribonucleic acid is quickly inhibited also, but not as completely. Treatment of S. aureus 140 with the inhibitor causes a rapid drop in cellular adenosine 5'-triphosphate level to about 60% of control levels. Of the 70 strains of gram-positive bacteria tested for susceptibility to staphylococcin 462, 24 (34%), distributed among 7 genera, were susceptible. FOOTNOTES

Bartlett, John G.; Bustetter, Larry A.; Gorbach, Sherwood L.; Onderdonk, Andrew B.

doi: 10.1128/AAC.pmid: 1094945

Antibiotic-induced changes in the fecal microflora after oral administration of tetracycline hydrochloride and doxycycline for 8 to 10 days were compared. A significant difference was noted in the concentrations of Escherichia coli resistant to tetracyclines. With tetracycline hydrochloride, there was a mean increase of approximately 10 4 resistant strains per g compared to only 10 1 /g for doxycycline. This difference is ascribed to reduced intestinal concentrations of bioactive drug with recommended oral dosage for doxycycline. Antimicrob Agents Chemother. 1975 January; 7(1): 55-57 Copyright © 1975 American Society for Microbiology . All Rights Reserved.