AUC(0-t)/MIC is a continuous index of fluoroquinolone exposure and predictive of antibacterial response for Streptococcus pneumoniae in an in vitro infection model
| Autor: | Siyao Sun, Godfrey K. M. Harding, Robert E. Ariano, Sheryl A. Zelenitsky, Harris Iacovides |
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| Rok vydání: | 2003 |
| Předmět: |
Microbiology (medical)
Ofloxacin medicine.drug_class Antibiotics Moxifloxacin Levofloxacin Microbial Sensitivity Tests Biology Pharmacology medicine.disease_cause Models Biological Pneumococcal Infections Microbiology Anti-Infective Agents Predictive Value of Tests Streptococcus pneumoniae Drug Resistance Bacterial medicine Pharmacology (medical) Antibacterial agent Aza Compounds Dose-Response Relationship Drug medicine.disease Culture Media Pneumococcal infections Infectious Diseases Pharmacodynamics Area Under Curve Quinolines medicine.drug Fluoroquinolones |
| Zdroj: | The Journal of antimicrobial chemotherapy. 51(4) |
| ISSN: | 0305-7453 |
| Popis: | Objective: To conduct a comprehensive pharmacodynamic analysis of moxifloxacin and levofloxacin against Streptococcus pneumoniae in an in vitro infection model. Methods: In dose escalation studies, single doses with peak concentrations equivalent to 1 x, 2 x, 4 x, 8 x, 16 x and 32 x MIC against two isolates of S. pneumoniae were studied over 24 h. Traditional pharmacodynamic indices, including peak concentration divided by MIC (peak/MIC), time of concentration above MIC (T> MIC) and AUC 24 /MIC, were estimated for all regimens. As a continuous index of fluoroquinolone exposure, AUC 0-t /MIC was also calculated, as AUC from time 0 to 1, 2 and 6 h divided by MIC. Correlations between pharmacodynamic indices and antibacterial effects were examined using linear and non-linear methods. In validation experiments, the pharmacodynamic model was used to predict bacterial kill curves, produced by simulated clinical doses of moxifloxacin and levofloxacin against two other S. pneumoniae isolates. Results: Peak/MIC was most predictive of early bacterial kill, whereas T> MIC was significantly associated with final bacterial counts at 24 h. Antibacterial effects were bacteriostatic when T > MIC was 48% and bactericidal when values exceeded 55%. AUC 0-t /MIC was strongly associated with bacterial kill throughout the dosing interval. Bactericidal activity and bacterial eradication were associated with AUC 0-t /MICs of 28 and 135, respectively. AUC 0-t /MIC was also highly predictive of bacterial kill curves produced by simulated clinical doses of moxifloxacin and levofloxacin (precision 0.36 log 10 cfu/mL, bias 0.02 log 10 cfulmL). Conclusion: This study demonstrated the novel application of AUC 0-t /MIC as a continuous index of antibiotic activity, and provided extensive characterization of fluoroquinolone pharmacodynamics against S. pneumoniae. |
| Databáze: | OpenAIRE |
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