Pharmacodynamic comparison of linezolid, teicoplanin and vancomycin against clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci collected from hospitals in Brazil

Abstract

Pharmacodynamic exposures, measured as the ratio of steady-state total drug area under the curve to MIC (AUC/MIC), were modelled using a 5000-patient Monte-Carlo simulation against 119 non-duplicate clinical isolates of Staphylococcus aureus and 82 coagulase-negative staphylococci (CNS) collected from hospitals in Brazil between 2003 and 2005. Pharmacodynamic targets included an AUC/MIC >82.9 for linezolid and >345 for teicoplanin and vancomycin, as well as a free drug AUC/MIC >180 for vancomycin. The cumulative fractions of response (CFRs) against all S. aureus isolates were 96.0%, 30.1%, 71.6%, 48.0% and 65.1% for linezolid 600 mg every 12 h, teicoplanin 400 mg every 24 h and 800 mg every 24 h, and vancomycin 1000 mg every 12 h and every 8 h, respectively. Using a free drug target for vancomycin improved the CFR to 94.6% for the high-dose regimen, but did not substantially alter results for the lower dose. CFRs against all CNS isolates were 97.8%, 13.4%, 34.6%, 10.9% and 31.3%, respectively, for the same antibiotic regimens. The CFR was reduced for all compounds among the methicillin-resistant isolates, except for linezolid against methicillin-resistant CNS. Sensitivity analyses did not alter the final order of pharmacodynamic potency against these isolates. Although higher doses of vancomycin and teicoplanin increased the CFR, the likelihood of achieving bactericidal targets was still lower than with linezolid. The results for the high-dose vancomycin regimen were highly dependent on the pharmacodynamic target utilised. These data suggest that linezolid has a greater probability of attaining its requisite pharmacodynamic target than teicoplanin and vancomycin against these staphylococci.

Proposal of a Pharmacokinetically Optimized Dosage Regimen of Antibiotics in Patients Receiving Continuous Hemodiafiltration

“…The MIC of the pathogen (e.g., methicillin-resistant Staphylococcus aureus [MRSA]) was set at 1 or 2 mg/liter (19,36). In the same manner, the dosage regimens of TEC were calculated to achieve an AUC 0-24 h /MIC of 345 (23). The target C trough of TEC was set at 10 to 60 mg/liter because a C trough of Ͻ10 mg/liter is considered suboptimal and a C trough of Ͼ60 mg/liter is toxic (43).…”

Glycopeptides

“…The CFR was reduced among the methicillin-resistant isolates. Higher doses of teicoplanin increased the CFR (Kuti et al 2008 ).…”

Antibacterial effects of brand-name teicoplanin and generic products against clinical isolates of methicillin-resistant Staphylococcus aureus

“…Simulated administration of each drug was set to a twicedaily 0.5-h infusion of 400 mg on the first day and 400 mg once daily on the following 2 days. The pharmacokinetic parameter related to teicoplanin efficacy against MRSA infection is AUC/MIC ratio [7]. The AUC from 0 to 72 h (AUC 0-72 ) was analyzed by setting body weight at 60 kg and creatinine clearance (Ccr) at either 80 m/min (normal) or 20 m/min (renal dysfunction).…”