In vitro and in vivo Transferrable β‐Lactam Resistance Due to a New Plasmid‐Mediated Oxyiminocephalosporinase from a Clinical Isolate of Proteus mirabilis

Abstract

A new plasmid‐mediated β‐lactamase (FPM‐1) with an isoelectric point of 7.2 and a molecular weight of 26,000 was found in a cefuroxime‐resistant clinical isolate of Proteus mirabilis strain 6003. FPM‐1 can be classified as a type I oxyiminocephalosporinase on the basis of its substrate specificity and inhibition pattern by clavulanic acid etc., and it conferred resistance on both the strain and transconjugants against most oxyme‐type cephalosporins as well as the older ones but not against cefamycins and a few exceptional oxyme‐type cephalosporins such as ceftizoxime, ceftazidime and cefixime. In a murine systemic infection model, only these FPM‐1‐stable drugs exhibited protective activity against the FPM‐1‐producing P. mirabilis 6003 similar to that against a nonproducing derivative strain. The FPM‐1‐mediated cefuroxime resistance in P. mirabilis 6003 was transferred to co‐infected Escherichia coli 7004 at frequencies between 3.8 × 10 −3 and 4.0 × 10 −2 in a murine ascending urinary tract infection model. In the same infection model due to the FPM‐1‐producing E. coli transconjugant, FPM‐1‐stable cefixime was significantly more effective than FPM‐1‐labile cefteram pivoxil, although both drugs had similar therapeutic effect against its FPM‐1‐nonproducing counterpart strain.