title: Effect of clavulanic acid on activity of beta-lactam antibiotics in Serratia marcescens isolates producing both a TEM beta-lactamase and a chromosomal cephalosporinase.
abstract: An isolate of Serratia marcescens that produced both an inducible chromosomal and a plasmid-mediated TEM-1 beta-lactamase was resistant to ampicillin and amoxicillin and also demonstrated decreased susceptibility to extended-spectrum beta-lactam antibiotics (ESBAs). Clavulanic acid did not lower the MICs of the ESBAs, but it decreased the MICs of the penicillins. The TEM-1-producing plasmid was transferred to a more susceptible S. marcescens strain that produced a well-characterized inducible chromosomal beta-lactamase. The MICs of the ESBAs remained at a low level for the transconjugant. Ampicillin and amoxicillin which were good substrates for the plasmid-mediated enzyme, were not well hydrolyzed by the chromosomal enzymes; the ESBAs were hydrolyzed slowly by all the enzymes. When each of the S. marcescens strains was grown with these beta-lactam antibiotics, at least modest increases in chromosomal beta-lactamase activity were observed. When organisms were grown in the presence of clavulanic acid and an ESBA, no enhanced induction was observed. The increases in the MICs of the ESBAs observed for the initial clinical isolate may have been due to a combination of low inducibility, slow hydrolysis, and differences in permeability between the S. marcescens isolates. When clavulanic acid and a penicillin were added to strains that produced both a plasmid-mediated TEM and a chromosomal beta-lactamase, much higher levels of chromosomal beta-lactamase activity were present than were observed in cultures induced by the penicillin alone. This was due to the higher levels of penicillin that were available for induction as a result of inhibition of the TEM enzyme by clavulanate.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08540.
authors.forename: K
authors.initials: K
authors.lastname: Bush
authors.forename: R K
authors.initials: RK
authors.lastname: Flamm
authors.forename: S
authors.initials: S
authors.lastname: Ohringer
authors.forename: S B
authors.initials: SB
authors.lastname: Singer
authors.forename: R
authors.initials: R
authors.lastname: Summerill
authors.forename: D P
authors.initials: DP
authors.lastname: Bonner
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000378:metabolism; D002510:Cephalosporinase / Q000096:biosynthesis*; D002876:Chromosomes, Bacterial / Q000201:enzymology*; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology*; D003227:Conjugation, Genetic / Q000502:physiology; D004352:Drug Resistance, Microbial / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010957:Plasmids; D016868:Serratia Infections / Q000382:microbiology; D012706:Serratia marcescens / Q000187:drug effects* / Q000201:enzymology; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D002969:Clavulanic Acids; D019818:Clavulanic Acid; D002510:Cephalosporinase; D001618:beta-Lactamases