α-Hemolysin activity of methicillin-susceptible Staphylococcus aureus predicts ventilator-associated pneumonia

Abstract

Rationale: Colonization of lower airways by Staphylococcus aureus is a risk factor for the development of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). However, little is known about the virulence factors of methicillin-sensitive and -resistant S. aureus (MSSA and MRSA) that may influence host colonization and progression to VAT and VAP.

Objectives: We evaluated MRSA and MSSA endotracheal aspirates (ETA) for genotype and α-hemolysin activity in relation to the development of VAT and VAP.

Methods: Serial S. aureus ETA isolates from ventilated patients were analyzed for methicillin resistance, molecular type by Multi-Locus Sequence Typing and spa-typing, and α-hemolysin activity by semiquantitative analysis of hemolysis on sheep blood agar and quantitative measurement of cytolysis of human lung epithelial cells. The virulence of selected strains was assessed in mice by intranasal challenge.

Measurements and main results: We detected S. aureus from ETA samples in a quarter of the 231 ventilated patients analyzed; one-third of them developed VAP. VAP patients (n = 15) were mainly infected by MSSA strains (87%), whereas colonized individuals (n = 18) not progressing to disease mainly carried MRSA strains (68%). MSSA isolates from colonized or VAT patients exhibited significantly lower α-hemolysin activity than those from VAP cases; however, no such relationship was found with MRSA strains. α-Hemolysin activity of S. aureus isolates was predictive for virulence in mouse pneumonia model.

Conclusions: MSSA strains with strong blood agar hemolysis and high α-hemolysin activity are markers for VAP, but not VAT, and might be considered in differential diagnosis and initiation of therapy.

Keywords: Staphylococcus aureus; biomarker; ventilator-associated pneumonia; α-hemolysin.