LY146032 in a hamster model of Staphylococcus aureus pneumonia--effect on in vivo clearance and mortality and in vitro opsonophagocytic killing.

The effect of the new peptolide LY146032 (LY) was studied in a hamster model of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. In vivo, after infection with one of two well-encapsulated strains of MRSA, A83 and A116 (type 8 and type 5), LY was protective only in A116 pneumonia. An in vitro assay of the effect of subinhibitory concentrations of LY on opsonophagocytic killing by pulmonary phagocytes demonstrated marked enhancement of killing of A116 (92.6 and 63.8% kill with 1/10 MIC and 1/50 MIC LY; no kill in the absence of LY). This effect was dependent on the presence of fresh serum. LY in subinhibitory concentrations produces a surface effect that may allow complement binding and activation and subsequent phagocytosis and killing to take place. The opsonizing effect of subinhibitory concentrations of LY was not demonstrable for the A83 strain. Differences in capsular types may be determinants of response to therapy of MRSA infections.