Activity of Pulmonary Vancomycin Exposures versus Planktonic and Biofilm Methicillin-Resistant Staphylococcus aureus Isolated from Cystic Fibrosis Sputum.

Abstract Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection in patients with cystic fibrosis (CF) lung disease; however, there are limited data to support the in vitro activity of this agent against MRSA isolated from CF sputum. The primary objective of this study was to evaluate the activity of vancomycin at pulmonary concentrations (intravenous and inhaled) against 4 clinical MRSA CF sputum isolates in planktonic and biofilm time-kill (TK) experiments. Vancomycin minimum inhibitory concentrations (MICs) were determined for these isolates at standard inoculum (SI; ∼106 colony-forming units [CFU]/mL) and high inoculum (HI; ∼108 CFU/mL), and in biofilms cultivated using physiologic media recapitulating the microenvironment of the CF lung. Vancomycin concentrations of 10, 25, 100, and 275 µg/mL were evaluated in TK experiments against planktonic MRSA at varying inocula and versus biofilm MRSA. Vancomycin MICs increased from 0.5 µg/mL at SI to 8-16 µg/mL when tested at HI. Vancomycin MICs were further increased to 16-32 µg/mL in biofilm studies. In TK experiments, vancomycin displayed bactericidal activity (≥ 3 log10 killing at 24 h) against 1/4 and 0/4 planktonic MRSA isolates at SI and HI, respectively. Against MRSA biofilms, vancomycin was bactericidal against 0/4 isolates. Based on these findings, vancomycin monotherapy appears unlikely to eradicate MRSA from the respiratory tract of patients with CF, even at high concentrations similar to those observed with inhaled therapy. Novel vancomycin formulations with enhanced biofilm penetration or combination therapy with other potentially synergistic agents should be explored.