Determination of pharmacokinetic/pharmacodynamic index for patients treated with high-dose vancomycin by continuous infusion
Abstract number: O26
Ampe E., Tulkens P., Delaere B., Hecq J.D., Glupczynski Y.
Background and Aims: Over the past 10 years, the susceptibility of Staphylococci to vancomycin (VAN) has decreased. In parallel, it has been suggested that an AUC24 h/MIC ratio of at least 400 h-1 is necessary for optimal therapy (Moise-Broder et al. Clin Pharmacokinet. 2004;43:92542). Since continuous infusion (CI) is easier both for nursing and for monitoring than conventional Q12 h dosing, we have examined whether it can be applied to patients with infections caused by organisms with increased MICs.
Methods: 54 patients (40 documented infections) were enrolled to receive VAN by CI with a target concentration of 2530 mg/L, a value above which significant increase in the risk of nephrotoxicity has been reported (Ingram et al., J Antimicrob Chemother. 2008;62:16871). We used a loading dose of 20 mg/kg and an infusion rate of 2.5 g/day (adapted to renal function and corrected by therapeutic drug monitoring of actual serum levels [immuno-assay Architect, Abbot Diagnostics, Solna, Sweden]). MICs were measured by E-test (AB BIODISK, Solna, Sweden)
Results: Treatment duration ranged from 1 to 37 days (mean: 12±10). The left figure shows that the target concentration range was reached and remained constant as an average after the first 48 h (with correction of the infusion rate). However, intra-individual variability was quite important between successive determinations in individual patients (middle). MIC's of isolates (MRSA, 14; MSSA, 6; coagulase negative Staphylococci, 16; others, 4) ranged between 0.25 and 3 mg/L. A mean AUC24 h/MIC of 400 h-1 (calculated over the whole duration of treatment) was reached in about half of the cases, with lower values seen mainly for patients infected by organisms with an MIC of 1.5 mg/L of greater (right).
Conclusion: High dose vancomycin by CI with adjustment based on therapeutic drug monitoring does not allow reaching a pharmacodynamic/pharmacokinetic index sufficient for optimal therapy in all patients. Patients infected with organisms having MIC's >1.5 mg/L should be considered at risk for treatment failure. The PK/PD data observed in this study further suggest that lowering the current EUCAST susceptibility breakpoint of VAN (S 4/R > 8 mg/L) is warranted.
|Session name:||19th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Helsinki, Finland, 16 - 19 May 2009|
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