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. 2025 Apr 28;25(1):622.
doi: 10.1186/s12879-025-10891-w.

Assessment of in vitro antimicrobial activities of ceftolozane/tazobactam and ceftazidime/avibactam against carbapenem-resistant Pseudomonas aeruginosa clinical isolates

Dalia Salem  1 , Ahmed El-Shenawy  2 , Heba Dahroug  2 , Manar Zaiton  2 , Doaa Gamal  2 , Manal Diab  2
Affiliations

Assessment of in vitro antimicrobial activities of ceftolozane/tazobactam and ceftazidime/avibactam against carbapenem-resistant Pseudomonas aeruginosa clinical isolates

Dalia Salem et al. BMC Infect Dis. .

Abstract

Background: Carbapenem resistant Pseudomonas aeruginosa (P. aeruginosa) is a global health concern that poses a challenge to treat in health care facilities. Ceftazidim/avibactam and ceftolozane/tazobactam have a potential role in treatment of multi-drug resistant phenotypes including carbapenem resistant P. aeruginosa. Therefore, we aimed to assess the in vitro antimicrobial activity of ceftazidime/avibactam and ceftolozane/tazobactam against carbapenem-resistant P. aeruginosa (CRPA) strains with different β-lactamase/carbapenemase genes.

Methods: Sixty CRPA isolates identified from clinical samples were examined for antimicrobial susceptibility including ceftazidim/avibactam and ceftolozane/tazobactam by Vitek2 compact system, and carbapenemase production by modified carbapenem inactivation method (mCIM) test and carbapenemase producing genes by polymerase chain reaction (PCR).

Results: Isolates were resistant to imipenem in 96.7% and meropenem in 88.3%. of isolates. Carbapenemase production by mCIM test was 70% compared to 73.3% by (PCR). Carbapenemase encoding genes blaNDM, blaVIM and blaOXA-48 were detected in 60%, 41.7% and 25% respectively while blaIMP and blaKPC weren't identified in this study. Among CRPA, both ceftazidim/avibactam and ceftolozane/tazobactam; were sensitive in only 11.7% of the isolates. Resistance to ceftazidim/avibactam and ceftolozane/tazobactam in isolates owning blaNDM, blaVIM, blaOXA-48 and those having combined blaNDM, blaVIM and blaOXA-48 carbapenemase resistance genes were 97.2%, 92%, 100% and 100% respectively.

Conclusion: Modified carbapenem inactivation method test gave satisfactory results and could be used as an alternative to expensive genotypic methods. Ceftazidim/avibactam and ceftolozane/tazobactam were unsuccessful against carbapenem resistant P. aeruginosa isolates carrying carbapenemase genes especially metallo-β lactamase genes. Therefore, it is essential to detect susceptibility patterns to newly introduced β-Lactam/β-Lactamase inhibitor combinations due to the emerging resistance to these therapeutics.

Keywords: Carbapenem resistant P. aeruginosa; Ceftazidim/avibactam; Ceftolozane/tazobactam; Modified carbapenem inactivation method test; β-Lactam/β-Lactamase inhibitor combinations.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The protocol of work was approved by institutional review board (FWA00010609), and the work has been carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for Experiments in Humans. The Research Ethics Committee of Theodor Bilharz Research Institute waived informed consent as working was carried out on unidentified isolates. Patients data and hospital details were anonymized by using codes instead of identifying information. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Antimicrobial susceptibility profile of the studied 60 CRPA isolates using Vitek2 compact system. TIC: Ticarcilin, T/C: Ticarcillin/Clavulanic, TZP: Piperacillin/Tazobactam, CAZ: Ceftazidim, CZA: Ceftazidim/avibactam, C/T: Ceftolozane/tazobactam, FEP: Cefepime, AK: Amikacin, CN: Gentamycin, TOB: Tobramycin, CIP: Ciprofloxacin, ATM: Aztreonam, IMP: Imipenem, MEM: Meropenem
Fig. 2
Fig. 2
MIC distribution of ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), for 60 CRPA isolates. Breakpoints for (CZA) were ≤ 8 µg/ml susceptible and ≥ 16 µg/ml resistant, for (C/T) were of ≤ 4 µg/ml susceptible, 8 µg/ml intermediate, and ≥ 16 µg/ml resistant, according to CLSI, 2023
Fig. 3
Fig. 3
Agarose gel electrophoresis of PCR products of CRPA blaNDM positive gene (621 bp) Lane 1: Molecular weight marker (100 bp), Lane 2: Molecular weight marker (ladder 50 bp), Lane 3: Positive control, Lane 4: Negative control, Lane (5, 8, 9,13, 14, 15,16): Positive DNA samples blaNDM PCR amplification product
Fig. 4
Fig. 4
Agarose gel electrophoresis of PCR products of CRPA blaVIM positive gene (258 bp) Lane 1: Molecular weight marker (ladder 50 bp). Lane 2: Negative control. Lane 3: Positive control. Lane (6, 7, 12, 13, 14, 15,16): Positive DNA samples blaVIM PCR amplification product
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