title: In vitro and in vivo transferrable beta-lactam resistance due to a new plasmid-mediated oxyiminocephalosporinase from a clinical isolate of Proteus mirabilis.
abstract: A new plasmid-mediated beta-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 oxyimino-cephalosporinase on the basis of its substrate specificity and inhibition pattern by clavulanic acid etc., and its 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 x 10(-3) and 4.0 x 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.
authors.affiliation: Department of Bacteriology, Juntendo University School of Medicine, Tokyo.
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: Y
authors.initials: Y
authors.lastname: Higashi
authors.forename: Y
authors.initials: Y
authors.lastname: Wakai
authors.forename: Y
authors.initials: Y
authors.lastname: Mine
mesh_terms: D000818:Animals; D002444:Cefuroxime / Q000494:pharmacology; D002510:Cephalosporinase / Q000032:analysis / Q000302:isolation & purification*; D002511:Cephalosporins / Q000627:therapeutic use; D004269:DNA, Bacterial / Q000032:analysis; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D010957:Plasmids; D011512:Proteus Infections / Q000188:drug therapy; D011513:Proteus mirabilis / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D014552:Urinary Tract Infections / Q000188:drug therapy; D001618:beta-Lactamases / Q000032:analysis / Q000302:isolation & purification*
chemical_list: D002511:Cephalosporins; D004269:DNA, Bacterial; D002510:Cephalosporinase; C070716:PPM-1 beta-lactamase; D001618:beta-Lactamases; D002444:Cefuroxime