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Open Access Highly Accessed Research article

Effect of vancomycin serum trough levels on outcomes in patients with nosocomial pneumonia due to Staphylococcus aureus: a retrospective, post hoc, subgroup analysis of the Phase 3 ATTAIN studies

Steven L Barriere1*, Martin E Stryjewski2, G Ralph Corey3, Fredric C Genter1 and Ethan Rubinstein4

Author Affiliations

1 Theravance, Inc., South San Francisco, CA, 94080, USA

2 Centro de Educación Médica e Investigaciones Clinicas (CEMIC) Norberto Quirno, Buenos Aires, Argentina

3 Duke Clinical Research Institute and Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, 27710, USA

4 Section of Infectious Diseases, Department of Internal Medicine and Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada

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BMC Infectious Diseases 2014, 14:183  doi:10.1186/1471-2334-14-183

Published: 4 April 2014

Abstract

Background

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.

Methods

Study 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.

Results

Clinical 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.

Conclusions

The 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 registration

NCT00107952 and NCT00124020

Keywords:
Vancomycin; Trough levels; Nosocomial pneumonia; Staphylococcus aureus