ABSTRACT. The incidence of pulmonary infections in children with cystic fibrosis caused by Pseudomonas cepacia, an organism which may possess an inducible 8-lactamase, has increased since 1978. Seven of 13 sputum isolates of P. cepacia from children with cystic fibrosis were classified as inducible by quantitative enzyme production following preincubation with 100, 200, or 400 pg/ml of cefoxitin. The recovery of inducible strains tended to be associated with recent ceftazidime therapy. Susceptibility to aztreonam, ceftazidime, and piperacillin alone or combined with the b-lactamase inhibitors. YTR 830 or sulbactam, and isoelectric focusing for /3-lactamase were performed. Inducible isolates produced significantly more /3-lactamase than noninducible strains with or wihtout the addition of cefoxitin. Noninducible isolates were more susceptible than inducible isolates to 8 pg/ml of piperacillin, a difference that was eliminated with the addition of either P-lactamase inhibitor. Twelve of 13 strains produced a Plactamase band in the pH range of 7.9-8.1; no differences in satellite patterns were noted between the two groups of organisms. Increased production of /3-lactamase in the absence of an inducer may account for piperacillin resistance in P. cepacia in children with cystic fibrosis. creased since 1978 and is now recovered from 20% of patients in some centers (3, 4).Sputum isolates of P. cepacia from children with cystic fibrosis are resistant to most P-lactam agents in vitro. In an in vitro study comparing the susceptibilities of 62 consecutive sputum isolates, concentrations of 64 pg/ml of aztreonam and piperacillin were required to inhibit 79 and 87.1 % of the bacterial population, respectively; 90% of the isolates were inhibited by 8 pg/ml of ceftazidime (5). In vitro, ceftazidime has proven more active against P. cepacia than piperacillin, aztreonam, HR-810, or BMY-28 142 (5, 6). Although the mechanism(s) of resistance of P. cepacia to Plactam agents is unclear, at least three, inducible, isoelectrically distinct p-lactamases have been identified (9-1 1). Hirai et al. (10) noted that the enzyme produced by Pseudomonas cepacia GN I 1 164 hydrolyzed cefuroxime, cefotaxime, and cefamandole. The purpose of this study was to ascertain the role played by inducible enzyme production in resistance to piperacillin, aztreonam, and ceftazidime by sputum isolates of P. cepacia from patients with cystic fibrosis. MATERIALS AND METHODSTest strains. Thirteen isolates of P. cepacia recovered from the sputum of 12 children admitted to Rainbow Babies and Children's Hospital with pulmonary exacerbations of cystic fibrosis were studied. With one exception, all of the test strains were recovered between April and December 1984. Seven of the 13 test strains were recovered during or immediately after ceftazidime therapy; two isolates were recovered following ciprofloxacin therapy, one isolate after aztreonam therapy, and three isolates were obtained prior to parenteral antibiotic therapy. Pseudomonas aeruginosa ATCC 27853 was use...
Pseudomonas cepacia, a significant pulmonary pathogen among children with cystic fibrosis (CF), often possesses an inducible beta-lactamase. The beta-lactamase isoelectric focusing pattern and beta-lactam susceptibility of CF and non-CF isolates of P. cepacia were compared. Against all of the test strains, ceftazidime and piperacillin were more effective than aztreonam. More CF isolates were resistant to 8 micrograms/ml of ceftazidime than non-CF isolates. Isoelectric focusing of cefoxitin-induced, cell-free preparations of the CF isolates produced significantly more bands than comparable preparations of non-CF isolates. Organisms producing a beta-lactamase band that focused in the pH range of 8.5 to 8.7 were significantly more resistant to 8 micrograms/ml of ceftazidime than other isolates. The increased resistance of CF isolates of P. cepacia to ceftazidime may be the result of the production of a specific bacterial beta-lactamase.
YTR 830, a new beta-lactamase inhibitor, is synergistic with amoxycillin in vitro against a number of beta-lactamase-producing organisms. The combination of amoxycillin-YTR 830 was compared to amoxycillin-clavulanate in the treatment of experimental Staphylococcus aureus, Citrobacter freundii and Proteus mirabilis infections in mice. Both combinations were synergistic with amoxycillin against all three test organisms. The amoxycillin-clavulanate combination was superior against S. aureus and C. freundii while amoxycillin-YTR 830 was more effective against P. mirabilis. The difference in efficacy between the two drug combinations appears to relate to the degree of protection afforded the animals by the beta-lactamase inhibitor alone. YTR 830 is a promising new agent and should undergo further investigation.
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