Pharmacodynamic comparison of linezolid, teicoplanin and vancomycin against clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci collected from hospitals in Brazil.
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.
Kuti
J L
JL
Center for Anti-Infective Research and Development, Hartford Hospital, CT, USA.
Kiffer
C R V
CR
Mendes
C M F
CM
Nicolau
D P
DP
D000081:Acetamides / Q000493:pharmacokinetics / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001938:Brazil; D003030:Coagulase; D000069349:Linezolid; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009010:Monte Carlo Method; D023303:Oxazolidinones / Q000493:pharmacokinetics / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013210:Staphylococcus / Q000187:drug effects* / Q000302:isolation & purification; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D017334:Teicoplanin / Q000493:pharmacokinetics / Q000494:pharmacology; D014640:Vancomycin / Q000493:pharmacokinetics / Q000494:pharmacology
D000081:Acetamides; D000890:Anti-Infective Agents; D003030:Coagulase; D023303:Oxazolidinones; D017334:Teicoplanin; D014640:Vancomycin; D000069349:Linezolid