Relationship of vancomycin minimum inhibitory concentration to mortality in patients with methicillin-resistant Staphylococcus aureus hospital-acquired, ventilator-associated, or health-care-associated pneumonia

Chest. 2010 Dec;138(6):1356-62. doi: 10.1378/chest.09-2453. Epub 2010 Jun 17.

Abstract

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health-care-associated pneumonia (HCAP). These infections are associated with significant morbidity, mortality, and cost. The impact of vancomycin minimum inhibitory concentration (MIC) on mortality for patients with MRSA pneumonia has not been determined.

Methods: Adult patients in ICUs with a diagnosis of MRSA HAP, VAP, or HCAP were entered in the study. Clinical and laboratory information were prospectively collected. Vancomycin MIC and heteroresistance were determined for each MRSA isolate. Data were collected from February 2006 through August 2007. The primary outcome variable was all-cause mortality at day 28. A propensity score approach was used to adjust for confounding variables.

Results: The study sample consisted of 158 patients. All-cause mortality at day 28 was 32.3%. The majority of MRSA isolates had a vancomycin MIC ≥ 1.5 mg/mL (115/158, 72.8%). Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 mg/mL (P ≤ .001). Heteroresistance to vancomycin, demonstrated in 21.5% isolates, was not associated with mortality.

Conclusions: Mortality in patients with MRSA HAP, VAP, and HCAP increases as a function of the vancomycin MIC, even for strains with MIC values within the susceptible range. Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia. The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 mg/mL should be undertaken with caution, and alternative therapies should be considered.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cause of Death
  • Cross Infection / drug therapy
  • Cross Infection / microbiology
  • Cross Infection / mortality
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Hospital Mortality
  • Humans
  • Intensive Care Units
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Microbial Sensitivity Tests
  • Middle Aged
  • Pneumonia, Ventilator-Associated / drug therapy*
  • Pneumonia, Ventilator-Associated / microbiology
  • Pneumonia, Ventilator-Associated / mortality*
  • Prospective Studies
  • Staphylococcal Infections / diagnosis
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / mortality*
  • Survival Analysis
  • Treatment Outcome
  • Vancomycin / pharmacology
  • Vancomycin / therapeutic use*

Substances

  • Vancomycin