ABSTRACT
The activities of three antibiotics in both Mueller-Hinton broth (MHB) and pooled human urine were compared by using an in vitro pharmacodynamic model. Clinical and reference strains of Escherichia coli were exposed to antibiotics at concentrations achievable in human urine. The rate of bacterial killing (time to a reduction of 3 log10 CFU/ml) and the extent of bacterial killing at 24 h were examined. Between MHB and urine, there were no significant differences in the rate or extent of bacterial killing for both ampicillin and ciprofloxacin. For trimethoprim-sulfamethoxazole there was no significant difference in the extent of bacterial killing in urine compared with that in MHB (P > 0.1); however, there was a significant decrease in the rate of bacterial killing in urine compared with that in MHB (P < 0.001). We conclude that with ampicillin and ciprofloxacin, activity against E. coli in MHB is predictive of the effects in human urine. The activity of trimethoprim-sulfamethoxazole in MHB predicts the extent but not the rate of bacterial killing in human urine.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/urine , Culture Media/pharmacology , Ampicillin/pharmacology , Ampicillin/urine , Anti-Infective Agents/pharmacology , Anti-Infective Agents/urine , Anti-Infective Agents, Urinary/pharmacology , Anti-Infective Agents, Urinary/urine , Ciprofloxacin/pharmacology , Ciprofloxacin/urine , Escherichia coli/drug effects , Humans , Microbial Sensitivity Tests , Penicillins/pharmacology , Penicillins/urine , Predictive Value of Tests , Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology , Trimethoprim, Sulfamethoxazole Drug Combination/urineABSTRACT
The accumulation of radiolabelled pefloxacin, norfloxacin, and lomefloxacin was determined in Staphylococcus aureus during log phase growth, the postantibiotic effect (PAE), and at 1, 4 and 6 h post PAE. Uptake in actively growing cells was consistent with a non-saturable passive diffusion process. The addition of metabolic inhibitors significantly increased accumulation consistent with the presence of an energy dependent efflux system. Accumulation of all three fluoroquinolones in PAE phase cells was significantly increased compared to that which occurred in actively growing cells. In contrast to cells in the log phase, addition of metabolic inhibitors to PAE phase cells did not result in a significant increase in drug accumulation. Uptake kinetics 1 h and 4 h post PAE were similar to those found during the PAE phase. Organisms required 6 h after the end of the PAE phase before normal uptake kinetics of fluoroquinolones resumed.
