Differences in drug susceptibility between isolates of <i>pseudomonas cepacia</i> recovered from patients with cystic fibrosis and other sources and its relationship to beta‐lactamase focusing pattern

Aronoff, Stephen C.; Labrozzi, Pauline H.

doi:10.1002/ppul.1950020609

Cited by 7 publications

(4 citation statements)

References 26 publications

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“…Levels of P-lactamase production by all of the strains were comparable and well below l000 U, the specific enzyme activity associated with derepressed enzyme production (2). All of the strains produced a major P-lactamase band that focused in the pH range of 7.9 to 8.1, similar to previous observations and comparable to the 3-lactamase focusing pattern of the derepressed strain, 75-26z (2,4,8). The MICs of piperacillin and ceftazidime against the CF isolates (619i and 16901) and the resistant mutant (75-26Mc) were comparable and higher than the MICs of these two compounds against strain 75-26.…”

Section: Resultssupporting

confidence: 72%

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Outer membrane permeability in Pseudomonas cepacia: diminished porin content in a beta-lactam-resistant mutant and in resistant cystic fibrosis isolates

Aronoff

1988

Antimicrob Agents Chemother

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Since ,B-lactam resistance is a feature of Pseudomonas cepacia isolates causing pulmonary infections in cystic fibrosis (CF), this study was undertaken to determine whether alterations in 1-lactam permeability mediate drug resistance in this species. A P-lactam-susceptible non-CF isolate (strain 75-26), a resistant mutant derived from 75-26 by selection for cross-resistance to ciprofloxacin and ceftazidime, and two resistant CF isolates of P. cepacia were used. Permeability constants were calculated from the rate of nitrocefin hydrolysis in intact bacterial cells. Qualitative changes in outer membrane proteins were determined electrophoretically. The permeability constants of the mutant and the resistant CF isolates were lower than the value for the reference strain, 75-26. Whereas the lipopolysaccharide side chains were present in the test and reference strains, the resistant mutant and the CF isolates contained reduced amounts of the 36-kilodalton (kDa) outer membrane protein and failed to express the 27-kDa outer membrane protein. These observations suggest that the 27-kDa outer membrane protein may be a major porn or a major protein component of the porin complex in P. cepacia and that decreased expression of the 36-kDa outer membrane and loss of the 27-kDa porin are associated with high-level (3-lactam resistance in some CF isolates of P. cepacia.Pseudomonas cepacia has emerged as a significant cause of pulmonary infections among children with cystic fibrosis (CF) (14,23). Most CF sputum isolates of P. cepacia are ,B-lactam resistant (3, 9, 15); furthermore, significantly more CF isolates than non-CF isolates of P. cepacia are resistant to ceftazidime, the most active agent against this species (4). The mechanism(s) that mediates high-level ,B-lactam resistance in CF isolates of P. cepacia is not known. Most CF and non-CF isolates of P. cepacia contain a chromosomal P-lactamase which focuses on isoelectric gels in the pH 7.9 to 8.1 range (4). A resistant mutant, developed from a ,-lactam-susceptible parental strain of P. cepacia by selection on ceftazidime-containing agar, was highly resistant to piperacillin and ceftazidime and produced 40 times more chromosomal ,-lactamase than did the drug-susceptible parent (2). Among 13 CF isolates of P. cepacia, moderate increases in base-line chromosomal ,B-lactamase content far below the levels observed in the derepressed mutant were associated with low-level piperacillin resistance only. Nevertheless, 12 of these strains were resistant to ceftazidime (8). These observations suggest that although derepressed production of chromosomal ,B-lactamase in P. cepacia can mediate high-level P-lactam resistance, this mechanism does not appear frequently in resistant CF isolates of this organism.In a resistant mutant of Pseudomonas aeruginosa, loss of the outer membrane porin (F protein) decreased passive diffusion of ,B-lactam antibiotics into the bacterial cell and resulted in drug resistance (17). Since either of two P. cepacia outer membrane proteins may function as a por...

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Section: Resultssupporting

confidence: 72%

“…P-lactamase which focuses on isoelectric gels in the pH 7.9 to 8.1 range (4). A resistant mutant, developed from a ,-lactam-susceptible parental strain of P. cepacia by selection on ceftazidime-containing agar, was highly resistant to piperacillin and ceftazidime and produced 40 times more chromosomal ,-lactamase than did the drug-susceptible parent (2).…”

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confidence: 99%

Outer membrane permeability in Pseudomonas cepacia: diminished porin content in a beta-lactam-resistant mutant and in resistant cystic fibrosis isolates

Aronoff

1988

Antimicrob Agents Chemother

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“…Of the 13 strains studied in this report, 12 produced bands which focused in the pH range of 7.8 to 8.1. In a previous study, isoelectric focusing of 23 CF isolates of P. cepacia from three centers in North America and 17 isolates from patients without cystic fibrosis and from the environment demonstrated P-lactamase bands in the 7.9 to 8.1 pH range for most strains (19). The production of a (3-lactamase band in this pH range appears to be common in P. cepacia isolated from all sources, including children with cystic fibrosis, and is independent of the inducibility of the organism.…”

Section: Methodsmentioning

confidence: 99%

Decreased Baseline β-Lactamase Production and Inducibility associated with Increased Piperacillin Susceptibility of Pseudomonas cepacia Isolated from Children with Cystic Fibrosis

1986

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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...

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“…Some patients are apparently colonized with P. cepacia in the absence of worsened respiratory symptoms (17,31), whereas other patients with P. cepacia rapidly progress to respiratory failure and death (31). Isolates of P. cepacia isolated from CF patients tend to be more resistant than non-CF isolates to commonly used antipseudomonal antibiotics (1,2). It is the increased prevalence of this multiply-resistant pathogen capable of causing significant morbidity among patients with advanced pulmonary disease which has made P. cepacia important in CF patients (9,10,17).…”

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confidence: 99%

Subgrouping of Pseudomonas cepacia by cellular fatty acid composition

Mukwaya

Welch

1989

J Clin Microbiol

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The cellular fatty acid compositions were determined for 42 strains of Pseudomonas cepacia from five cystic fibrosis centers in North America. All isolates contained significant (20%) amounts of hexadecanoic (C16:0), and cis-9 hexadecenoic (Cl6:1 cis9) acids and an isomer of octadecenoic acid (Cl8,:). None had hydroxy acids containing fewer than 14 carbon atoms. The quantitative data from the fatty acid analysis were highly reproducible and provided a basis for numerical analysis. Five subgroups comprising all the strains were obtained by cluster analysis and further characterized by principal-component analysis. With minor exceptions, the predominant subgroup identified in each center was different from that identified in other centers and accounted for one-half of the isolates within each center. Cellular fatty acid composition is a useful adjunct to biochemical characterization for the identification of P. cepacia isolated from cystic fibrosis patients. Numerical analysis of the fatty acid data can separate P. cepacia into subgroups, which may provide useful epidemiologic information or a basis for further analysis by more complex techniques such as DNA probe analysis.

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Differences in drug susceptibility between isolates of pseudomonas cepacia recovered from patients with cystic fibrosis and other sources and its relationship to beta‐lactamase focusing pattern

Cited by 7 publications

References 26 publications

Outer membrane permeability in Pseudomonas cepacia: diminished porin content in a beta-lactam-resistant mutant and in resistant cystic fibrosis isolates

Outer membrane permeability in Pseudomonas cepacia: diminished porin content in a beta-lactam-resistant mutant and in resistant cystic fibrosis isolates

Decreased Baseline β-Lactamase Production and Inducibility associated with Increased Piperacillin Susceptibility of Pseudomonas cepacia Isolated from Children with Cystic Fibrosis

Subgrouping of Pseudomonas cepacia by cellular fatty acid composition

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