Ventilator-associated pneumonia by methicillin-susceptible Staphylococcus aureus: do minimum inhibitory concentrations to vancomycin and daptomycin matter?

Abstract

The use of vancomycin minimum inhibitory concentration (MIC) as an outcome predictor in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia has become an important topic for debate in the last few years. Given these previous results, we decided to investigate whether MICs to vancomycin or daptomycin had any effect on the evolution of patients with ventilator-associated pneumonia (VAP) due to MSSA. An observational, retrospective, multicenter study was conducted among patients with MSSA VAP. We analyzed the relationship between vancomycin and daptomycin MICs and early clinical response (72 h), 30-day mortality, intensive care unit (ICU) length of stay (LOS), and duration on mechanical ventilation. Univariate and multivariate analyses were performed. Sixty-six patients from 12 centers were included. Twenty-six patients (39%) had an infection due to MSSA strains with a vancomycin MIC ≥1.5 μg/mL. Daptomycin MIC was determined in 58 patients, of whom 17 (29%) had an MIC ≥1.0 μg/mL. Ten patients (15%) did not respond to first-line treatment. Only daptomycin MIC ≥1.0 μg/mL had a significant association [odds ratio (OR): 30.00; 95% confidence interval (CI): 2.91-60.41] with early treatment failure. The 30-day mortality was 12% (n = 8). Any variable was associated with mortality in the multivariate analysis. None of the variables studied were associated with ICU LOS or duration on mechanical ventilation. In patients with MSSA VAP, vancomycin MIC does not influence the response to antibiotic treatment or the 30-day mortality. Daptomycin MIC was directly related to early treatment failure.

Nebulization of Vancomycin Provides Higher Lung Tissue Concentrations than Intravenous Administration in Ventilated Female Piglets with Healthy Lungs

“…• The hypothesis that lung tissue vancomycin concentrations will be higher after administration as an inhaled aerosol than after intravenous administration was tested in healthy, anesthetized, mechanically ventilated female piglets • One hour after administration of a 37.5 mg/kg aerosol dose, the median lung tissue vancomycin concentration (161 µg/g) was 13 times that after intravenous administration of 15 mg/kg (12 µg/g) • Twelve hours after aerosol administration, the median lung tissue vancomycin concentration was 63 µg/g, while 12 h after intravenous administration, vancomycin was undetectable in 60% of lung specimens M ethicillin-resistant Staphylococcus aureus is one of the main causal agents of ventilator-associated pneumonia. 1,2 This pathogen often presents resistance to other antimicrobials, which is a concern in relation to the treatment options. 3 Vancomycin is the recommended treatment, 4 but this standard therapy results in poor clinical outcomes, not exceeding 57% of clinical success rate.…”