Assuntos
Asiático , Controle de Doenças Transmissíveis , Programas de Rastreamento , Refugiados , Adulto , Camboja/etnologia , Humanos , Rhode IslandRESUMO
Quinolone antimicrobial agents are known to interact with DNA gyrase, but the mechanism by which bacterial cell death occurs is not fully understood. In order to determine whether there is a correlation between quinolone-induced inhibition of early (i.e., 10 to 15 min) DNA synthesis and potency (MICs and MBCs), we measured the rate of DNA synthesis in log-phase Escherichia coli K-12 by using [3H]thymidine incorporation. Three quinolones (ciprofloxacin, norfloxacin, and difloxacin) were selected based on their decreasing activity against reference strain KL16. All three quinolones caused an early 50% inhibition of DNA synthesis which was proportional to MICs and MBCs (r greater than 0.99). Furthermore, 50% inhibition of DNA synthesis and MICs were nearly identical for mutant strains with an altered quinolone target (gyrA) or with decreased [nfxB(ompF)] or increased (acrA) permeability. There were significant differences (P less than 0.001) between individual quinolones in the degree of DNA synthesis inhibition in nalidixic acid-resistant gyrA and nfxB(ompF) mutant strains. The comparison of the three mutants with the wild-type strain permitted an in vivo examination of the effects of alterations of the drug target or entry on the activity determined by DNA synthesis inhibition and MICs.
Assuntos
Anti-Infecciosos/farmacologia , DNA Bacteriano/biossíntese , Escherichia coli/efeitos dos fármacos , Fluoroquinolonas , Ciprofloxacina/análogos & derivados , Ciprofloxacina/farmacologia , DNA Bacteriano/efeitos dos fármacos , Relação Dose-Resposta a Droga , Escherichia coli/genética , Escherichia coli/metabolismo , Mutação , Norfloxacino/farmacologiaRESUMO
In vitro studies of tircarcillin or cefsulodin combined with [3H]tobramycin were performed with Pseudomonas aeruginosa. The rate of bacterial killing, the uptake of tobramycin, and the effects on optical density were measured. Both beta-lactams increased the uptake of subinhibitory concentrations of tobramycin. This result was quantitatively associated with a 2- to 4-h time-kill potentiation and confirmed earlier studies on the mechanism of beta-lactam-aminoglycoside synergy in Escherichia coli (P. H. Plotz and B. D. Davis, Science 135:1067-1068, 1962).
