Detection of clonally related Escherichia coli isolates producing different CMY β-lactamases from a cystic fibrosis patient

Crémet, Lise; Caroff, Nathalie; Giraudeau, Cécile; Reynaud, Alain; Caillon, Jocelyne; Corvec, Stéphane

doi:10.1093/jac/dks520

Cited by 23 publications

(13 citation statements)

References 19 publications

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“…With the exception of PDC-77 found in ST175 isolates from 3 distant cities (i.e., which suggests a geographical diffusion of a single clone), our results provide evidence that the ESACs emerged locally in genotypically distinct and rather prevalent P. aeruginosa clones (see Table S1). Since 15 (48.4%) ESACproducing isolates came from chronically infected patients with cystic fibrosis (n ϭ 10) or chronic obstructive pulmonary disease (COPD [n ϭ 5]), we asked whether hypermutability, which is common in these diseases (37), was required for the emergence of ESAC-associated mutations, as suggested elsewhere (23,38). Actually, only 1 (CF isolate 12.1111) out of 10 randomly selected ESAC strains (the other 9 strains including 5 CF, 1 COPD, and 3 non-CF, non-COPD isolates) turned out to give rise to rifampinresistant mutants at rates significantly higher (Ն20-fold) than those of reference strain PAO1 (10 Ϫ8 ) and to fit with the definition of hypermutator (39; data not shown).…”

Section: Identification Of New Ampc Variants Sequencing Of Genementioning

confidence: 99%

Mutations in β-Lactamase AmpC Increase Resistance of Pseudomonas aeruginosa Isolates to Antipseudomonal Cephalosporins

Berrazeg

Jeannot

Enguéné

et al. 2015

Antimicrob Agents Chemother

216

171

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b Mutation-dependent overproduction of intrinsic ␤-lactamase AmpC is considered the main cause of resistance of clinical strains of Pseudomonas aeruginosa to antipseudomonal penicillins and cephalosporins. Analysis of 31 AmpC-overproducing clinical isolates exhibiting a greater resistance to ceftazidime than to piperacillin-tazobactam revealed the presence of 17 mutations in the ␤-lactamase, combined with various polymorphic amino acid substitutions. When overexpressed in AmpC-deficient P. aeruginosa 4098, the genes coding for 20/23 of these AmpC variants were found to confer a higher (2-fold to >64-fold) resistance to ceftazidime and ceftolozane-tazobactam than did the gene from reference strain PAO1. The mutations had variable effects on the MICs of ticarcillin, piperacillin-tazobactam, aztreonam, and cefepime. Depending on their location in the AmpC structure and their impact on ␤-lactam MICs, they could be assigned to 4 distinct groups. Most of the mutations affecting the omega loop, the R2 domain, and the C-terminal end of the protein were shared with extended-spectrum AmpCs (ESACs) from other Gramnegative species. Interestingly, two new mutations (F121L and P154L) were predicted to enlarge the substrate binding pocket by disrupting the stacking between residues F121 and P154. We also found that the reported ESACs emerged locally in a variety of clones, some of which are epidemic and did not require hypermutability. Taken together, our results show that P. aeruginosa is able to adapt to efficacious ␤-lactams, including the newer cephalosporin ceftolozane, through a variety of mutations affecting its intrinsic ␤-lactamase, AmpC. Data suggest that the rates of ESAC-producing mutants are >1.5% in the clinical setting. Pseudomonas aeruginosa is a well-known cause of acute and chronic infections in fragile patients. One of the most remarkable traits of this opportunistic pathogen is its ability to evolve and become resistant to many antibiotics through a variety of mutational and transferable mechanisms (reviewed in reference 1). Some mechanisms tend to prevent the interaction of drugs with their cognate cellular targets, while others result in drug inactivation (1). Like several other Gram-negative species, P. aeruginosa harbors a chromosomal drug-inducible gene, bla AmpC , encoding a wide-spectrum class C ␤-lactamase (2). This enzyme contributes to the natural resistance of the microorganism toward labile and inducing molecules, such as aminopenicillins, first-and secondgeneration cephalosporins (3). More importantly, when overproduced as a result of mutations altering the peptidoglycan recycling process, AmpC becomes a major cause of resistance to widely used antipseudomonal penicillins (ticarcillin and piperacillin), monobactams (aztreonam), and third-generation (ceftazidime) and fourth-generation (cefepime) cephalosporins (4-7). The so-called "derepressed mutants" are common in the clinical setting and account for a large proportion of strains resistant to ceftazidime and cefepime in various studies (8-11)....

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Section: Identification Of New Ampc Variants Sequencing Of Genementioning

confidence: 99%

Mutations in β-Lactamase AmpC Increase Resistance of Pseudomonas aeruginosa Isolates to Antipseudomonal Cephalosporins

Berrazeg

Jeannot

Enguéné

et al. 2015

Antimicrob Agents Chemother

216

171

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“…Indeed, no tailored clinical definitions have been provided so far for chronic lung infection due to Enterobacteriaceae such as K. pneumoniae and Escherichia coli. This lack of definitions reflects the fact that these organisms have classically been considered to have a minor chronic pathogenic role in CF, since their long-term persistence in the lung of CF patients has seldom been described (11)(12)(13). However, in a recent study by Barillova et al, the prevalence of persistent E. coli isolation (i.e., for longer than 6 months) from sputum samples was as high as 11% among 176 German CF patients, thus supporting a previously unrecognized role of members of the Enterobacteriaceae as possible CF pathogens (14).…”

Section: Case Reportmentioning

confidence: 99%

First Report of Chronic Pulmonary Infection by KPC-3-Producing and Colistin-Resistant Klebsiella pneumoniae Sequence Type 258 (ST258) in an Adult Patient with Cystic Fibrosis

et al. 2015

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“…5 Several cases of multidrug-resistant Enterobacteriaceae chronic infections have recently been reported. [6][7][8] The purpose of this study was to characterize antimicrobial susceptibility trends among organisms isolated from the respiratory tract of CF patients.…”

mentioning

confidence: 99%

Increasing Incidence of Multidrug Resistance Among Cystic Fibrosis Respiratory Bacterial Isolates

Rutter

Burgess

2017

Microbial Drug Resistance

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Pseudomonas aeruginosa and Staphylococcus aureus are common pathogens in cystic fibrosis (CF) patients with increasing multidrug resistance (MDR). This study characterized antimicrobial susceptibility trends among organisms isolated from the respiratory tract of CF patients. Microbiological culture and sensitivity results for all CF patients were collected from January 2010 through December 2014. Minimum inhibitory concentrations were obtained using Phoenix and Etest methods. Clinical and Laboratory Standards Institute guidelines were used to remove duplicate isolates and develop antimicrobial susceptibility reports. MDR was defined as resistance to one agent in three or more antibiotic classes or oxacillin resistance in S. aureus. Overall, 542 bacterial isolates from 376 cultures were analyzed for trends. P. aeruginosa (41%), S. aureus (40%), and Stenotrophomonas maltophilia (8%) were the most commonly isolated organisms. Multidrug-resistant organism isolation increased from 39% to 49% (r = 0.76, p = 0.13), while representing 47.6% of all isolates. Multidrug-resistant P. aeruginosa incidence increased each year from 26% to 43% (r = 0.89, p = 0.046), while P. aeruginosa isolation decreased from 47% to 38% over the study period (r = -0.93, p = 0.02). MRSA accounted for 62.6% of all S. aureus isolated, while overall multidrug-resistant S. aureus incidence was 73.1% in all cultures. MDR among common pathogens in CF continues to increase. Empiric therapy for CF exacerbations should be targeted to previous antimicrobial susceptibility, and P. aeruginosa and S. aureus should be empirically covered.

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Detection of clonally related Escherichia coli isolates producing different CMY β-lactamases from a cystic fibrosis patient

Abstract: Our study shows that, similarly to Pseudomonas aeruginosa, E. coli can undergo phenotypic and genomic changes in the CF context. For the first time, we identified an in vivo expanded-spectrum evolution of the CMY-2 β-lactamase, during bacterial persistence in the CF lung.

Cited by 23 publications

References 19 publications

Mutations in β-Lactamase AmpC Increase Resistance of Pseudomonas aeruginosa Isolates to Antipseudomonal Cephalosporins

Mutations in β-Lactamase AmpC Increase Resistance of Pseudomonas aeruginosa Isolates to Antipseudomonal Cephalosporins

First Report of Chronic Pulmonary Infection by KPC-3-Producing and Colistin-Resistant Klebsiella pneumoniae Sequence Type 258 (ST258) in an Adult Patient with Cystic Fibrosis

Increasing Incidence of Multidrug Resistance Among Cystic Fibrosis Respiratory Bacterial Isolates

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