Activity of the anti-MRSA carbapenem razupenem (PTZ601) against Enterobacteriaceae with defined resistance mechanisms.

BACKGROUND: Razupenem (previously known as PTZ601, PZ-601, SMP-601 or SM-216601) is a novel carbapenem, active against Enterobacteriaceae as well as Gram-positive bacteria including methicillin-resistant staphylococci and enterococci.

METHODS: We examined the effect of extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases on the activity of razupenem, using the CLSI agar dilution method to measure MICs for mutants, transconjugants and isolates with and without these enzymes.

RESULTS: ESBLs had no effect on the activity of razupenem against Escherichia coli and Klebsiella spp., and only a small effect when coupled with outer membrane impermeability. Inducible or, more especially, derepressed AmpC enzymes gave some protection, with most AmpC-derepressed Enterobacter and Citrobacter spp. requiring MICs of approximately 8 mg/L. This relative resistance was further increased when porins were lost, restricting drug uptake. Metallo- and class A-carbapenemases conferred resistance, with MICs > or =16 mg/L.

CONCLUSIONS: Razupenem has good activity against ESBL producers, but is affected by AmpC enzymes, especially when derepressed and coupled with outer membrane impermeability; its activity is also compromised by carbapenemases.