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.
Livermore
David M
DM
Antibiotic Resistance Monitoring & Reference Laboratory, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London, NW9 5EQ, UK. david.livermore@hpa.org.uk
Mushtaq
Shazad
S
Warner
Marina
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000378:metabolism / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D015780:Carbapenems; C500116:SM-216601; D001618:beta-Lactamases