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Examining the activity of cefepime-taniborbactam against Burkholderia cepacia complex and Burkholderia gladioli isolated from cystic fibrosis patients in the United States.

ABSTRACT: The novel clinical-stage β-lactam-β-lactamase inhibitor combination, cefepime-taniborbactam, demonstrates promising activity toward many Gram-negative bacteria producing class A, B, C, and/or D β-lactamases. We tested this combination against a panel of 150 Burkholderia cepacia complex (Bcc) and Burkholderia gladioli strains. The addition of taniborbactam to cefepime shifted cefepime minimum inhibitory concentrations toward the provisionally susceptible range in 59% of the isolates tested. Therefore, cefepime-taniborbactam possessed similar activity as first-line agents, ceftazidime and trimethoprim-sulfamethoxazole, supporting further development.

SUBMITTER: Mojica MF

PROVIDER: S-EPMC10648927 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Examining the activity of cefepime-taniborbactam against Burkholderia cepacia complex and Burkholderia gladioli isolated from cystic fibrosis patients in the United States.

Mojica Maria F MF Zeiser Elise T ET Becka Scott A SA LiPuma John J JJ Six David A DA Moeck Greg G Papp-Wallace Krisztina M KM

Antimicrobial agents and chemotherapy 20230928 11

The novel clinical-stage β-lactam-β-lactamase inhibitor combination, cefepime-taniborbactam, demonstrates promising activity toward many Gram-negative bacteria producing class A, B, C, and/or D β-lactamases. We tested this combination against a panel of 150 Burkholderia cepacia complex (Bcc) and Burkholderia gladioli strains. The addition of taniborbactam to cefepime shifted cefepime minimum inhibitory concentrations toward the provisionally susceptible range in 59% of the isolates ...[more]

PMID: 37768313

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Project description:In persons with cystic fibrosis (CF), airway infection with Burkholderia cepacia complex (Bcc) species or Burkholderia gladioli presents a significant challenge due to inherent resistance to multiple antibiotics. Two chromosomally encoded inducible β-lactamases, a Pen-like class A and AmpC are produced in Bcc and B. gladioli Previously, ceftazidime-avibactam demonstrated significant potency against Bcc and B. gladioli isolated from the sputum of individuals with CF; however, 10% of the isolates tested resistant to ceftazidime-avibactam. Here, we describe an alternative antibiotic combination to overcome ceftazidime-avibactam resistance. Antimicrobial susceptibility testing was performed on Bcc and B. gladioli clinical and control isolates. Biochemical analysis was conducted on purified PenA1 and AmpC1 β-lactamases from Burkholderia multivorans ATCC 17616. Analytic isoelectric focusing and immunoblotting were conducted on cellular extracts of B. multivorans induced by various β-lactams or β-lactam-β-lactamase inhibitor combinations. Combinations of piperacillin-avibactam, as well as piperacillin-tazobactam plus ceftazidime-avibactam (the clinically available counterpart), were tested against a panel of ceftazidime-avibactam nonsusceptible Bcc and B. gladioli The piperacillin-avibactam and piperacillin-tazobactam-ceftazidime-avibactam combinations restored susceptibility to 99% of the isolates tested. Avibactam is a potent inhibitor of PenA1 (apparent inhibitory constant [Kiapp] = 0.5 μM), while piperacillin was found to inhibit AmpC1 (Kiapp = 2.6 μM). Moreover, piperacillin, tazobactam, ceftazidime, and avibactam, as well as combinations thereof, did not induce expression of blapenA1 and blaampC1 in the B. multivorans ATCC 17616 background. When ceftazidime-avibactam is combined with piperacillin-tazobactam, the susceptibility of Bcc and B. gladioli to ceftazidime and piperacillin is restored in vitro Both the lack of blapenA1 induction and potent inactivation of PenA1 by avibactam likely provide the major contributions toward susceptibility. With in vivo validation, piperacillin-tazobactam-ceftazidime-avibactam may represent salvage therapy for individuals with CF and highly drug-resistant Bcc and B. gladioli infections.

Project description:BackgroundChronic infection with Burkholderia cepacia complex species remains a significant problem for clinicians treating people with cystic fibrosis. Colonisation with Burkholderia cepacia complex species is linked to a more rapid decline in lung function and increases morbidity and mortality. There remain no objective guidelines for strategies to eradicate Burkholderia cepacia complex in cystic fibrosis lung disease, as these are inherently resistant to the majority of antibiotics and there has been very little research in this area. This review aims to examine the current treatment options for people with cystic fibrosis with acute infection with Burkholderia cepacia complex and to identify an evidence-based strategy that is both safe and effective. This is an updated version of the review.ObjectivesTo identify whether treatment of Burkholderia cepacia complex infections can achieve eradication, or if treatment can prevent or delay the onset of chronic infection. To establish whether following eradication, clinical outcomes are improved and if there are any adverse effects.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Last search: 12 March 2019.We also searched electronic clinical trials registers for the USA and Europe.Date of last search: 12 March 2019.Selection criteriaRandomised or quasi-randomised studies in people with cystic fibrosis of antibiotics or alternative therapeutic agents used alone or in combination, using any method of delivery and any treatment duration, to eradicate Burkholderia cepacia complex infections compared to another antibiotic, placebo or no treatment.Data collection and analysisTwo authors independently assessed for inclusion in the review the eligibility of 52 studies (79 references) identified by the search of the Group's Trial Register and the other electronic searches.Main resultsNo studies looking at the eradication of Burkholderia cepacia complex species were identified.Authors' conclusionsThe authors have concluded that there was an extreme lack of evidence in this area of treatment management for people with cystic fibrosis. Without further comprehensive studies, it is difficult to draw conclusions about a safe and effective management strategy for Burkholderia cepacia complex eradication in cystic fibrosis. Thus, while the review could not offer clinicians evidence of an effective eradication protocol for Burkholderia cepacia complex, it has highlighted an urgent need for exploration and research in this area, specifically the need for well-designed multi-centre randomised controlled studies of a variety of (novel) antibiotic agents.

Dataset Information

Examining the activity of cefepime-taniborbactam against Burkholderia cepacia complex and Burkholderia gladioli isolated from cystic fibrosis patients in the United States.

Publications

Examining the activity of cefepime-taniborbactam against <i>Burkholderia cepacia</i> complex and <i>Burkholderia gladioli</i> isolated from cystic fibrosis patients in the United States.

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