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

Abstract number: 1733_872

Kiffer C., Kuti J., Mendes C., Sinto S., Koga P., Nicolau D.

Objectives: The association of MIC distribution and pharmacokinetic (PK) data derived from microbiological and human studies through the use of pharmacodynamic (PD) models offers a more developed tool for prediction of infection outcome. The probability of obtaining critical PD targets was determined and compared by the use of Monte Carlo simulation for Linezolid (L), Teicoplanin (T), and Vancomycin (V) against non-duplicate clinical isolates of Staphylococcus spp. collected from 3 hospitals in São Paulo, Brazil between 2003 and 2005.

Methods: MICs were determined for 201 Staphylococcus aureus (SA) and coagulase negative staphylococci (CNS) isolates by Etest method for L, T, and V. Interpretations were done according to established CLSI criteria. Methicillin resistance (MR) was confirmed by oxacillin and cefoxitin disc diffusion. PD exposures, measured as steady-state total drug AUC/MIC, were modeled via a 5,000 patient Monte Carlo simulation for the following: L 600 mg q12h, T 400 mg q24h (T6), T 800 mg q24h (T8), V 1 g q12h, and V 1 g q8h using PK from patients. PD targets included AUC/MIC >82.9 for L and >345 for T and V. The bactericidal cumulative fraction of response (CFR) was calculated for each regimen against each specific population: methicillin-susceptible (MS) and MR, for both SA and CNS.

Results: There were 40/119 MRSA and 74/82 MR-CNS isolates. The SA isolates were fully susceptible to T (MIC90 = 2 mg/mL) and L (MIC90 = 1 mg/mL). There was one SA isolate with intermediate susceptibility to V (MIC = 3 mg/mL) (MIC90 = 1.5 mg/mL). The CNS isolates were fully susceptible to V (MIC90 = 3 mg/mL) and L (MIC90 = 1 mg/mL), and 13.4% resistant to T (MIC90 = 32 mg/mL). CFR against all SA were 96.0%, 30.1%, 71.6%, 48.0%, and 65.1% for L, T6, T12, V q12h, and V q8h, respectively. CFR against all CNS were 97.8%, 13.4%, 34.6%, 10.9%, and 31.3% for L, T6, T12, V q12h, and V q8h, respectively. The CFR was reduced for all compounds among the MR versus the MS strains, except for L against the MR-CNS (94.9% MS-CNS and 98.1% MR-CNS).

Conclusion: Although MR was not expected to affect MIC, these isolates did present with higher MICs than the MS isolates, thereby contributing to lower CFR for MR strains. These data suggest that L has a greater probability of attaining its requisite PD target than V and T against these staphylococci. Although higher doses of V and T increased the CFR for both SA and CNS, the bactericidal targets achieved still appeared insufficient.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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