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 _j-lactamase was resistant to ampicillin and amoxicillin and also demonstrated decreased susceptibility to extended-spectrum P-lactam antibiotics (ESBAs). Clavulanic acid did not lower the MICs of the ESBAs, but it decreased the MICs of the penicillins. The TEM-l-producing plasmid was transferred to a more susceptible S. marcescens strain that produced a well-characterized inducible chromosomal 13-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 3-lactam antibiotics, at least modest increases in chromosomal 3-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 P-lactamase, much higher levels of chromosomal j3-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.Resistance to P-lactam antibiotics is caused to a great extent by the presence of P-lactamases, enzymes that are capable of destroying the antibacterial activities of many of these agents. Clavulanic acid has become a useful supplement to penicillins that are susceptible to hydrolysis by plasmid-mediated P-lactamases. This 3-lactamase inactivator works well when it is combined with amoxicillin or ticarcillin to treat infections caused by bacteria that produce many kinds of penicillinases or P-lactamases with broadspectrum hydrolyzing activities (1, 17). However, recent reports indicate that occasional antagonism of penicillin activity has been observed when antibiotic combinations with clavulanic acid are added to selected gram-negative rods (19,21). In certain isolates, the lack of synergy observed has been attributed to the induction of chromosomal cephalosporinases (10, 12, 22), P-lactamases that are not well inhibited by clavulanate. Although most studies have included organisms that produce only a single inducible chromosomal cephalosporinase, some resistant isolates have been identified as strains that produce multiple P-lactamases (8,19 Bio-Rad (Richmond, Calif.).Organisms. S. marcescens SC 15071, which produces cephalosporinase S1 and the plasmid-mediated TEM-1 P-lactamase (plasmid pSVA071), was from a group of clinical isolates selected at the Seattle Ve...

Occurrence and Phenotypic Characteristics of Extended-Spectrum β-Lactamases among Members of the Family Enterobacteriaceae at the Tel-Aviv Medical Center (Israel) and Evaluation of Diagnostic Tests

“…Note that by being based on phenotypic testing, the tests we conducted may have shown false-negative results due to the coexistence of chromosomal beta-lactamases (4,7) or to the presence of plasmid-mediated enzymes that are not inhibited by beta-lactamase inhibitors (5,14). In addition, it is very likely that the particular enzymes harbored by the tested organisms might influence test performance.…”

Outbreak of TEM-24-producing Enterobacter aerogenes in an intensive care unit and dissemination of the extended-spectrum beta-lactamase to other members of the family enterobacteriaceae

“…There are many reports of production of extended-spectrum ␤-lactamases (ESBla) among Klebsiella pneumoniae (2,9,13,17,20) but only a few among Enterobacter aerogenes or Enterobacter cloacae (7,8,19). Detection of ESBla in such strains is more difficult than with other species of Enterobacteriaceae, in part because of the production of the cephalosporinase (3). Over a 7-month period, 10 strains of E. aerogenes were isolated in three departments: seven in an intensive care unit (ICU), one in a medicine unit (on the same floor as the ICU), and two in a geriatric department (in another town-district).…”

In Vitro Susceptibility of Characterized β-Lactamase-Producing Strains Tested with Avibactam Combinations

“…Quality control organisms were Pseudomonas aeruginosa ATCC 27853 for ceftazidime, meropenem, aztreonam, and aztreonam-avibactam; Klebsiella pneumoniae ATCC 700603 for ceftazidime, ceftazidime-avibactam, and ceftaroline-avibactam; Staphylococcus aureus ATCC 29213 for ceftaroline; and Escherichia coli ATCC 35218 for piperacillin-tazobactam. The 57 strains used in the study were from the laboratory collections of the authors Jacoby (10-12) and Bush (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). They include both laboratory-constructed strains and clinical isolates (Table 1), which had been transferred among multiple laboratories and which did not always contain all the secondary enzymes originally reported in the primary literature.…”