Pharmacodynamic activity of the lantibiotic MU1140

This study evaluated the pharmacodynamics of the lantibiotic MU1140 and the ability of selected organisms to develop resistance to this antibiotic. MU1140 demonstrated activity against all Gram-positive organisms tested, including oxacillin- and vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis (VREF). No activity was observed against Gram-negative bacteria or yeast. Time-kill studies revealed that MU1140 was rapidly bactericidal against Streptococcus pneumoniae and multidrug-resistant S. aureus, whilst it was bacteriostatic against VREF. In vitro resistance development to MU1140, tested by sequential subculturing in subinhibitory concentrations of MU1140, revealed a stable threefold increase in the minimum inhibitory concentration (MIC) for S. aureus and S. pneumoniae. Subsequent subculturing of the strains with elevated MICs in antibiotic-free media for 7 days did not result in a reduction of their MIC values for MU1140. Collectively, our findings illustrate the therapeutic potential of MU1140 for management of Gram-positive infections.