This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (54)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in this journal  Topic Collections  • Drug Therapy, Other  • Bacterial Infections  • Alert me on articles by topic

Efficacy and Toxicity

Levita K. Hidayat, PharmD; Donald I. Hsu, PharmD; Ryan Quist, PhD; Kimberly A. Shriner, MD; Annie Wong-Beringer, PharmD

Arch Intern Med. 2006;166:2138-2144.

Background  Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 µg/mL.

Methods  A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (2 vs <2 µg/mL) for efficacy and high vs low trough (15 vs <15 µg/mL) for nephrotoxicity analyses.

Results  Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents.

Conclusions  High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 µg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 µg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.

Author Affiliations: University of Southern California, Los Angeles (Drs Hidayat and Wong-Beringer), Huntington Memorial Hospital, Pasadena (Drs Hidayat, Shriner, and Wong-Beringer), and Western University, Pomona (Drs Hsu and Quist), Calif.

RELATED LETTERS

Alternative Agents for the Treatment of Invasive Infections Due to Methicillin-Resistant Staphylococcus aureus Strains With Reduced Susceptibility to Vancomycin
Pierre Tattevin, Cédric Arvieux, and Christian Michelet
Arch Intern Med. 2007;167(11):1206.
EXTRACT | FULL TEXT  

Is High Minimal Inhibitory Concentration of Vancomycin a Predictor of Poor Response in MRSA Infections?
Gustavo Faulhaber, Alexandre Zavascki, and Sandra Costa Fuchs
Arch Intern Med. 2007;167(11):1206-1207.
EXTRACT | FULL TEXT  

Treatment of MRSA Infections With Older Molecules: A Reasonable Option for Investigation
Houssem Hmouda, Chaker Ben Salem, Kamel Bouraoui, and Letaief Jemni
Arch Intern Med. 2007;167(11):1207-1208.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Relationship between Vancomycin MIC and Failure among Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia Treated with Vancomycin
Lodise et al.
Antimicrob. Agents Chemother. 2008;52:3315-3320.
ABSTRACT | FULL TEXT  

Microbiological and Genotypic Analysis of Methicillin-Resistant Staphylococcus aureus Bacteremia
McCalla et al.
Antimicrob. Agents Chemother. 2008;52:3441-3443.
ABSTRACT | FULL TEXT  

Characterization of Vancomycin-Heteroresistant Staphylococcus aureus from the Metropolitan Area of Detroit, Michigan, over a 22-Year Period (1986 to 2007)
Rybak et al.
J. Clin. Microbiol. 2008;46:2950-2954.
ABSTRACT | FULL TEXT  

Predictors of high vancomycin MIC values among patients with methicillin-resistant Staphylococcus aureus bacteraemia
Lodise et al.
J Antimicrob Chemother 2008;0:dkn329v1-4.
ABSTRACT | FULL TEXT  

Daptomycin Is Effective in Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus
Marco et al.
Antimicrob. Agents Chemother. 2008;52:2538-2543.
ABSTRACT | FULL TEXT  

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates in Urban Detroit
Chua et al.
J. Clin. Microbiol. 2008;46:2345-2352.
ABSTRACT | FULL TEXT  

Larger Vancomycin Doses (at Least Four Grams per Day) Are Associated with an Increased Incidence of Nephrotoxicity
Lodise et al.
Antimicrob. Agents Chemother. 2008;52:1330-1336.
ABSTRACT | FULL TEXT  

Staphylococcus aureus: The new adventures of a legendary pathogen
REHM
Cleveland Clinic Journal of Medicine 2008;75:177-192.
ABSTRACT | FULL TEXT  

Relationships between vancomycin pharmacodynamics and the emergence of vancomycin-intermediate Staphylococcus aureus (VISA) from heterogeneous VISA in an in vitro pharmacodynamic model
Rose et al.
J Antimicrob Chemother 2008;0:dkn037v1-6.
ABSTRACT | FULL TEXT  

Inhibitory Activities of 11 Antimicrobial Agents and Bactericidal Activities of Vancomycin and Daptomycin against Invasive Methicillin-Resistant Staphylococcus aureus Isolates Obtained from 1999 through 2006
Holmes and Jorgensen
Antimicrob. Agents Chemother. 2008;52:757-760.
ABSTRACT | FULL TEXT  

Microbiological effects of prior vancomycin use in patients with methicillin-resistant Staphylococcus aureus bacteraemia
Moise et al.
J Antimicrob Chemother 2008;61:85-90.
ABSTRACT | FULL TEXT  

Vancomycin MIC creep in non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates from 2001 05
Steinkraus et al.
J Antimicrob Chemother 2007;60:788-794.
ABSTRACT | FULL TEXT  

Methicillin-Resistant Staphylococcus aureus Pneumonia Treatment: Do Not Confuse Pharmacokinetics and Pharmacodynamics
Moine and Bedos
Chest 2007;132:1101-1101.
FULL TEXT  

Appropriate Pharmacokinetic Index for Outcome in Staphylococcus aureus Pneumonia
Potoski et al.
Chest 2007;132:1101-1103.
FULL TEXT  

Alternative Agents for the Treatment of Invasive Infections Due to Methicillin-Resistant Staphylococcus aureus Strains With Reduced Susceptibility to Vancomycin
Tattevin et al.
Arch Intern Med 2007;167:1206-1206.
FULL TEXT  

Vancomycin Levels, Efficacy, and Toxicity
Johnson
Arch Intern Med 2007;167:1207-1207.
FULL TEXT  

Treatment of MRSA Infections With Older Molecules: A Reasonable Option for Investigation--Reply
Wong-Beringer et al.
Arch Intern Med 2007;167:1208-1209.
FULL TEXT  

Is High Minimal Inhibitory Concentration of Vancomycin a Predictor of Poor Response in MRSA Infections?
Faulhaber et al.
Arch Intern Med 2007;167:1206-1207.
FULL TEXT  

Treatment of MRSA Infections With Older Molecules: A Reasonable Option for Investigation
Hmouda et al.
Arch Intern Med 2007;167:1207-1208.
FULL TEXT  

Pharmacologic Treatment Options for Nosocomial Pneumonia Involving Methicillin-Resistant Staphylococcus aureus
Maclayton and Hall II
The Annals of Pharmacotherapy 2007;41:235-244.
ABSTRACT | FULL TEXT  

Vancomycin Therapy for MRSA Infections
JWatch Infect. Diseases 2006;2006:3-3.
FULL TEXT