Abstract
BackgroundExisting data are not consistently supportive of improved clinical outcome when vancomycin dosing regimens aimed at achieving target trough levels are used. A retrospective, post hoc, subgroup analysis of prospectively collected data from the Phase 3 ATTAIN trials of telavancin versus vancomycin for treatment of nosocomial pneumonia was conducted to further investigate the relationship between vancomycin serum trough levels and patient outcome.MethodsStudy patients were enrolled in 274 study sites across 38 countries. A total of 98 patients had Staphylococcus aureus nosocomial pneumonia and vancomycin serum trough levels available. These patients were grouped according to their median vancomycin trough level; < 10 μg/mL, 10 μg/mL to < 15 μg/mL, and ≥ 15 μg/mL.ResultsClinical cure rates in the < 10 μg/mL, 10 μg/mL to < 15 μg/mL, and ≥ 15 μg/mL vancomycin trough level groups were 70% (21/30), 55% (18/33), and 49% (17/35), respectively (p = 0.09), and the frequencies of patient death were 10% (3/30), 15% (5/33), and 20% (7/35), respectively (p = 0.31). Renal adverse events were more frequent in the ≥ 15 μg/mL (17% [6/35]) than the < 10 μg/mL (0%) and 10 μg/mL to < 15 μg/mL (3% [1/33]) trough level groups (p < 0.01). When patients with acute renal failure or vancomycin exposure within 7 days prior to study medication were excluded, clinical cure rates in the < 10 μg/mL, 10 μg/mL to < 15 μg/mL, and ≥ 15 μg/mL vancomycin trough level groups (71% [12/17], 60% [9/15], and 27% [3/11], respectively; p = 0.04) and the number of deaths (12% [2/17], 20% [3/15], and 45% [5/11], respectively; p = 0.07) demonstrated a trend towards worse outcomes in the higher vancomycin trough level groups.ConclusionsThe findings of our study suggest that higher vancomycin trough levels do not result in improved clinical response but likely increase the incidence of nephrotoxicity.Trial registrationNCT00107952 and NCT00124020
Highlights
Existing data are not consistently supportive of improved clinical outcome when vancomycin dosing regimens aimed at achieving target trough levels are used
Staphylococcus aureus has emerged as a major cause of nosocomial pneumonia (NP), with rates of methicillinresistant strains (MRSA) as high as 70% reported in some US studies [1]
The results of the Phase 4 ZEPHyR trial comparing vancomycin with linezolid for MRSA NP found that higher trough levels of vancomycin were associated with lower cure rates [6]
Summary
Existing data are not consistently supportive of improved clinical outcome when vancomycin dosing regimens aimed at achieving target trough levels are used. A retrospective, post hoc, subgroup analysis of prospectively collected data from the Phase 3 ATTAIN trials of telavancin versus vancomycin for treatment of nosocomial pneumonia was conducted to further investigate the relationship between vancomycin serum trough levels and patient outcome. Vancomycin serum trough levels of 5–15 μg/mL have previously been targeted to optimize clinical outcome in patients with NP, more recent literature suggests a vancomycin trough level of 15–20 μg/mL [3] This range of trough concentrations is required to achieve the presumed optimal vancomycin AUC/MIC (area under the curve/minimum inhibitory concentration) target of > 400 for S. aureus with MIC values ≤ 1 μg/mL [3]. Existing data are not consistently supportive of improved clinical outcome when vancomycin dosing regimens aimed at achieving this AUC/MIC target are used [4,5]. The results of the Phase 4 ZEPHyR trial comparing vancomycin with linezolid for MRSA NP found that higher trough levels of vancomycin were associated with lower cure rates [6]
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