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

BMC Infectious Diseases

Ethan Rubinstein⁴  Fredric C Genter²  G Ralph Corey¹  Martin E Stryjewski³  Steven L Barriere² 

[1] Duke Clinical Research Institute and Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, 27710, USA;Theravance, Inc., South San Francisco, CA, 94080, USA;Centro de Educación Médica e Investigaciones Clinicas (CEMIC) Norberto Quirno, Buenos Aires, Argentina;Section of Infectious Diseases, Department of Internal Medicine and Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada

关键词: Staphylococcus aureus;    Nosocomial pneumonia;    Trough levels;    Vancomycin;   

Others  :  1134182
DOI  :  10.1186/1471-2334-14-183

 received in 2013-06-24, accepted in 2014-03-31,  发布年份 2014

【 摘 要 】

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

【 授权许可】

   
2014 Barriere et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]DeRyke CA, Lodise TP Jr, Rybak MJ, McKinnon PS: Epidemiology, treatment, and outcomes of nosocomial bacteremic Staphylococcus aureus pneumonia. Chest 2005, 128(3):1414-1422.
• [2]American Thoracic Society; Infectious Diseases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005, 171(4):388-416.
• [3]Rybak MJ, Lomaestro BM, Rotschafer JC, Moellering RC, Craig WA, Billeter M, Dalovisio JR, Levine DP: Vancomycin therapeutic guidelines: a summary of consensus recommendations from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis 2009, 49(3):325-327.
• [4]Jeffres MN, Isakow W, Doherty JA, McKinnon PS, Ritchie DJ, Micek ST, Kollef MH: Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices. Chest 2006, 130(4):947-955.
• [5]Hermsen ED, Hanson M, Sankaranarayanan J, Stoner JA, Florescu MC, Rupp ME: Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections. Expert Opin Drug Saf 2010, 9(1):9-14.
• [6]Kunkel M, Chastre JE, Kollef MH, Niederman MS, Shorr AF, Wunderink RG, McGee W, Olvey S, Reisman A, Baruch A: Linezolid vs vancomycin in the treatment of nosocomial pneumonia proven due to methicillin-resistant Staphylococcus aureus (abstract LB-49). Canada: Vancouver, BC; 2010. [Infectious Diseases Society of America (IDSA) 48th Annual Meeting]
• [7]Jeffres MN, Isakow W, Doherty JA, Micek ST, Kollef MH: A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia. Clin Ther 2007, 29(6):1107-1115.
• [8]Lodise TP, Patel N, Lomaestro BM, Rodvold KA, Drusano GL: Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis 2009, 49(4):507-514.
• [9]Patel N, Pai MP, Rodvold KA, Lomaestro B, Drusano GL, Lodise TP: Vancomycin: we can't get there from here. Clin Infect Dis 2011, 52(8):969-974.
• [10]Rubinstein E, Lalani T, Corey GR, Kanafani ZA, Nannini EC, Rocha MG, Rahav G, Niederman MS, Kollef MH, Shorr AF, Lee PC, Lentnek AL, Luna CM, Fagon JY, Torres A, Kitt MM, Genter FC, Barriere SL, Friedland HD, Stryjewski ME, for the ATTAIN Study Group: Telavancin versus vancomycin for hospital-acquired pneumonia due to gram-positive pathogens. Clin Infect Dis 2011, 52(1):31-40.
• [11]Wong-Beringer A, Joo J, Tse E, Beringer P: Vancomycin-associated nephrotoxicity: a critical appraisal of risk with high-dose therapy. Int J Antimicrob Agents 2011, 37(2):95-101.
• [12]Bosso JA, Nappi J, Rudisill C, Wellein M, Bookstaver PB, Swindler J, Mauldin PD: Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial. Antimicrob Agents Chemother 2011, 55(12):5475-5479.
• [13]Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A: High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med 2006, 166(19):2138-2144.