title: The impact of serum vancomycin levels and minimum inhibitory concentrations of methicillin-resistant Staphylococcus aureus on mortality in patients with nosocomial pneumonia.
abstract: BACKGROUND
  Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure is not uncommon, even when the minimum inhibitory concentration (MIC) of the MRSA strain is within the susceptible range for vancomycin.
  
  
  OBJECTIVE
  To describe the relationship between molecular markers such as the mecA and agrII genes, serum vancomycin levels and vancomycin MICs, and the 30-day mortality rate of patients with nosocomial MRSA pneumonia in an intensive care unit (ICU).
  
  
  METHODS
  The present study was a prospective cohort study including all patients with MRSA hospital-acquired pneumonia or ventilator-associated pneumonia who were admitted to the ICU of a tertiary care hospital between June 2009 and December 2011. The MIC for vancomycin was determined using the E-test and broth microdilution methods. Variables analyzed included age, sex, comorbid conditions, serum vancomycin trough concentration, the Acute Physiology and Chronic Health Evaluation II (APACHE) score and the presence of the agrII gene. The primary outcome was mortality at 30 days.
  
  
  RESULTS
  Thirty-six (42.4%) patients died within 30 days of the index MRSA culture. A multiple regression analysis that included the variables of MIC (determined using the E-test or broth microdilution methods), APACHE II score, serum vancomycin level and the presence of agrII revealed that only the APACHE II score was related to the 30-day mortality rate (P=0.03). Seven patients (9.0%) with isolates exhibiting an MIC ≥1.5 μg/mL according to the E-test method died, and nine patients (11.6%) survived (P=0.76). Of the patients for whom MICs were determined using the broth microdilution method, 11 (14.1%) patients with MICs of 1.0 μg/mL died, and 16 (20.5%) survived (P=0.92). The median APACHE II score of survivors was 22.5, and the median score of nonsurvivors was 25.0 (P=0.03). The presence of the agrII gene was not related to the 30-day mortality rate.
  
  
  CONCLUSIONS
  Patients with severe hospital-acquired pneumonia presented with MRSA isolates with low to intermediate vancomycin MICs in the ICU setting. At the Hospital de Clínicas de Porto Alegre (Porto Alegre, Brazil), the 30-day mortality rate was high, and was similar among patients with severe hospital-acquired pneumonia infected with MRSA isolates that exhibited MICs of ≤1.5 μg/mL determined using the E-test method and ≤1.0 μg/mL determined using the broth microdilution method in those who achieved optimal serum vancomycin levels. The APACHE II scores which provides an overall estimate of ICU mortality were independently associated with mortality in the present study, regardless of the MICs determined. Molecular markers, such as the agrII gene, were not associated with higher mortality in the present study.
authors.affiliation: Section of Infectious Diseases and Infection Control Hospital Committee, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Denise Pires
authors.initials: DP
authors.lastname: Machado
authors.affiliation: Section of Infectious Diseases and Infection Control Hospital Committee, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Luciano Z
authors.initials: LZ
authors.lastname: Goldani
authors.affiliation: Section of Infectious Diseases and Infection Control Hospital Committee, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Rodrigo Minuto
authors.initials: RM
authors.lastname: Paiva
authors.affiliation: Section of Infectious Diseases and Infection Control Hospital Committee, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Valério Rodrigues
authors.initials: VR
authors.lastname: Aquino
authors.affiliation: Section of Infectious Diseases and Infection Control Hospital Committee, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: de-Paris
authors.affiliation: Section of Infectious Diseases and Infection Control Hospital Committee, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Lisboa
authors.affiliation: Section of Infectious Diseases and Infection Control Hospital Committee, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Jung
authors.affiliation: Section of Infectious Diseases and Infection Control Hospital Committee, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Rodrigo Pires
authors.initials: RP
authors.lastname: Dos Santos
keywords: Methicillin-resistant Staphylococcus aureus; Nosocomial pneumonia; Vancomycin