Selection of linezolid-resistant Enterococcus faecium in an in vitro dynamic model: protective effect of doxycycline
| Autor: | Irene Yu Lubenko, Stephen H. Zinner, Alexander A. Firsov, Deborah Gilbert, Kenneth Greer |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Microbiology (medical)
medicine.drug_class Enterococcus faecium Antibiotics Microbial Sensitivity Tests Biology Models Biological Microbiology chemistry.chemical_compound Pharmacokinetics Acetamides Drug Resistance Bacterial medicine Humans Pharmacology (medical) Oxazolidinones Antibacterial agent Pharmacology Doxycycline Linezolid Area under the curve biochemical phenomena metabolism and nutrition bacterial infections and mycoses biology.organism_classification Infectious Diseases chemistry Pharmacodynamics bacteria medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 61:629-635 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | Objectives: To relate the enrichment of linezolid-resistant Enterococcus faecium with linezolid pharmacokinetics, the pharmacodynamics of linezolid and its ability to prevent the selection of resistant mutants were studied in an in vitro model that simulates antibiotic concentrations in and out of the mutant selection window (MSW), i.e. the concentration range from the MIC to the mutant prevention concentration (MPC). Methods: A clinical isolate of E. faecium (MIC 1.8mg/L and MPC 7mg/L) at a starting inoculum of 8 log cfu/mL was exposed to twice-daily linezolid, alone and in combination with once-daily doxycycline (MIC 0.2 mg/L and MPC 3.4 mg/L), for 3 consecutive days in a hollow-fibre two-compartment model. Results: The ratios of 24 h area under the curve (AUC 24 ) to MIC of linezolid were estimated at 70, 100 and 230 h and those of doxycycline were estimated at 230 and 720 h. At the two lower AUC 24/ MIC ratios of linezolid given alone, E. faecium resistant to 2 x MIC-16 x MIC and 2 x MIC-8 x MIC of linezolid, respectively, were selectively enriched with a concomitant slight loss in susceptibility. Neither growth on linezolid-containing media nor changes in susceptibility occurred at the high AUC 24 /MIC ratio. A similar protective effect was observed with the minimal AUC 24 /MIC ratio of linezolid (70 h) combined with doxycycline at an AUC 24 /MIC of 230 h. Conclusions: This study suggests that selection of linezolid-resistant enterococci can be predicted from the MSW concept and can be prevented by linezolid given in combination with doxycycline, each at suboptimal AUC 24 /MIC ratios. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|