Selection of ciprofloxacin resistance in Escherichia coli in an in vitro kinetic model: relation between drug exposure and mutant prevention concentration
| Autor: | Patricia Komp Lindgren, Sara K. Olofsson, Otto Cars, Linda L. Marcusson, Diarmaid Hughes |
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| Rok vydání: | 2006 |
| Předmět: |
Microbiology (medical)
medicine.drug_class Antibiotics Cmax Colony Count Microbial Drug resistance Microbial Sensitivity Tests Biology medicine.disease_cause Models Biological Microbiology Antibiotic resistance immune system diseases Ciprofloxacin Drug Resistance Bacterial medicine Escherichia coli Humans Pharmacology (medical) Selection Genetic Escherichia coli Infections Antibacterial agent Pharmacology biology.organism_classification Enterobacteriaceae Anti-Bacterial Agents Infectious Diseases DNA Gyrase Area Under Curve Mutation Urinary Tract Infections medicine.drug |
| Zdroj: | The Journal of antimicrobial chemotherapy. 57(6) |
| ISSN: | 0305-7453 |
| Popis: | To evaluate the mutant prevention concentrations (MPCs) of ciprofloxacin for two susceptible and one first-step gyrA resistant mutant Escherichia coli strains in an in vitro kinetic model and to identify the pharmacodynamic index that best predicts prevention of resistance emergence.An in vitro kinetic model was used to measure MPC with static antibiotic concentrations and to test different dosing profiles to study pharmacokinetics/pharmacodynamics indices important to prevent the growth of resistant mutants. In one set of kinetic experiments the starting concentration was equal to the MPC and the TMPC was varied before antibiotic dilution was begun. In a second set of kinetic experiments C(max) was varied and dilution of the antibiotic was started at time zero.From the static experiments we calculated MPC values of 0.128 mg/L for both the susceptible strains (16x MIC) and 0.188 mg/L (4x MIC) for the first-step resistant (gyrA) strain. The kinetic experiments showed that the TMPC needed to prevent the growth of resistant bacteria was shorter with an increased C(max). When resistance was selected, several subpopulations with different levels of susceptibility to ciprofloxacin emerged.Neither TMPC nor C(max) proved to be single correlates for preventing resistance development. For the two investigated wild-type strains, an AUC/MPC ratio ofor =22 was the single pharmacodynamic index that predicted prevention of resistant mutant development. |
| Databáze: | OpenAIRE |
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