Time-kill evaluation of antibiotic combinations containing ceftazidime-avibactam against extensively drug-resistant Pseudomonas aeruginosa and their potential role against ceftazidime-avibactam-resistant isolates

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• dc.contributor.author Montero, Maria Milagro
• dc.contributor.author Domene Ochoa, Sandra
• dc.contributor.author López-Causapé, Carla
• dc.contributor.author Luque, Sonia
• dc.contributor.author Sorlí, Luisa
• dc.contributor.author Campillo Ambrós, Núria
• dc.contributor.author López Montesinos, Inmaculada
• dc.contributor.author Padilla, Eduardo
• dc.contributor.author Prim, Núria
• dc.contributor.author Angulo-Brunet, Ariadna
• dc.contributor.author Grau Cerrato, Santiago
• dc.contributor.author Oliver, Antoni
• dc.contributor.author Horcajada Gallego, Juan Pablo
• dc.date.accessioned 2022-03-30T07:18:50Z
• dc.date.available 2022-03-30T07:18:50Z
• dc.date.issued 2021
• dc.description.abstract Ceftazidime-avibactam (CZA) has emerged as a promising solution to the lack of new antibiotics against Pseudomonas aeruginosa infections. Data from in vitro assays of CZA combinations, however, are scarce. The objective of our study was to perform a time-kill analysis of the effectiveness of CZA alone and in combination with other antibiotics against a collection of extensively drug-resistant (XDR) P. aeruginosa isolates. Twenty-one previously characterized representative XDR P. aeruginosa isolates were selected. Antibiotic susceptibility was tested by broth microdilution, and results were interpreted using CLSI criteria. The time-kill experiments were performed in duplicate for each isolate. Antibiotics were tested at clinically achievable free-drug concentrations. Different treatment options, including CZA alone and combined with amikacin, aztreonam, meropenem, and colistin, were evaluated to identify the most effective combinations. Seven isolates were resistant to CZA (MIC ≥ 16/4 mg/liter), including four metallo-β-lactamase (MBL)-carrying isolates and two class A carbapenemases. Five of them were resistant or intermediate to aztreonam (MIC ≥ 16 mg/liter). Three isolates were resistant to amikacin (MIC ≥ 64 mg/liter) and one to colistin (MIC ≥ 4 mg/liter). CZA monotherapy had a bactericidal effect in 100% (14/14) of the CZA-susceptible isolates. Combination therapies achieved a greater overall reduction in bacterial load than monotherapy for the CZA-resistant isolates. CZA plus colistin was additive or synergistic in 100% (7/7) of the CZA-resistant isolates, while CZA plus amikacin and CZA plus aztreonam were additive or synergistic in 85%. CZA combined with colistin, amikacin, or aztreonam was more effective than monotherapy against XDR P. aeruginosa isolates. A CZA combination could be useful for treating XDR P. aeruginosa infections, including those caused by CZA-resistant isolates. IMPORTANCE The emergence of resistance to antibiotics is a serious public health problem worldwide and can be a cause of mortality. For this reason, antibiotic treatment is compromised, and we have few therapeutic options to treat infections. The main goal of our study is to search for new treatment options for infections caused by difficult-to-treat resistant germs. Pseudomonas aeruginosa is a Gram-negative bacterium distributed throughout the world with the ability to become resistant to most available antibiotics. Ceftazidime-avibactam (CZA) emerged as a promising solution to the lack of new antibiotics against infections caused by P. aeruginosa strains. This study intended to analyze the effect of CZA alone or in combination with other available antibiotics against P. aeruginosa strains. The combination of CZA with other antibiotics could be more effective than monotherapy against extensively drug-resistant P. aeruginosa strains.
• dc.format.mimetype application/pdf
• dc.identifier.citation Montero MM, Domene Ochoa S, López-Causapé C, Luque S, Sorlí L, Campillo N, López Montesinos I, Padilla E, Prim N, Angulo-Brunet A, Grau S, Oliver A, Horcajada JP. Time-kill evaluation of antibiotic combinations containing ceftazidime-avibactam against extensively drug-resistant Pseudomonas aeruginosa and their potential role against ceftazidime-avibactam-resistant isolates. Microbiol Spectr. 2021 Sep 3;9(1):e0058521. DOI: 10.1128/Spectrum.00585-21
• dc.identifier.doi http://dx.doi.org/10.1128/Spectrum.00585-21
• dc.identifier.issn 2165-0497
• dc.identifier.uri http://hdl.handle.net/10230/52801
• dc.language.iso eng
• dc.publisher American Society for Microbiology
• dc.relation.ispartof Microbiol Spectr. 2021 Sep 3;9(1):e0058521
• dc.rights © 2021 Montero et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Pseudomonas aeruginosa
• dc.subject.keyword Amikacin
• dc.subject.keyword Aztreonam
• dc.subject.keyword Ceftazidime-avibactam
• dc.subject.keyword Colistin
• dc.subject.keyword Combination therapy
• dc.title Time-kill evaluation of antibiotic combinations containing ceftazidime-avibactam against extensively drug-resistant Pseudomonas aeruginosa and their potential role against ceftazidime-avibactam-resistant isolates
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion