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. 2025 Feb 11;15(1):5102.
doi: 10.1038/s41598-025-88965-7.

Synergistic combination of ceftazidime and avibactam with Aztreonam against MDR Klebsiella pneumoniae in ICU patients

Sally Khattab  1 , Aya Mohamed Askar  2 , Hidi A A Abdellatif  3   4   5 , Amira A A Othman  6 , Amal H Rayan  7   8 , Hasnaa Azab  1
Affiliations

Synergistic combination of ceftazidime and avibactam with Aztreonam against MDR Klebsiella pneumoniae in ICU patients

Sally Khattab et al. Sci Rep. .

Abstract

The proliferation of multidrug-resistant, metallo-beta-lactamase-producing Klebsiella pneumoniae (MBL-producing K. pneumoniae) poses a major threat to public health resulting in increasing treatment costs, prolonged hospitalization, and mortality rate. Treating such bacteria presents substantial hurdles for clinicians. The combination of Aztreonam (ATM) and ceftazidime/avibactam (CAZ/AVI) is likely the most successful approach. The study evaluated the in vitro activity of CAZ/AVI in combination with ATM against MBL-producing K. pneumoniae clinical isolates collected from Suez Canal University Hospital patients. Carbapenem-resistant K. pneumoniae were isolated and identified from different specimens. The presence of metallo-β-lactamases was detected phenotypically by modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) testing, and genotypically for the three metallo-β-lactamase genes: blaNDM, blaIMP, and blaVIM by conventional PCR method. The synergistic effect of CAZ/AVI with ATM against MBL-producing K. pneumoniae was detected by ceftazidime-avibactam combination disks and E-test for antimicrobial susceptibility testing. Out of the 65 K. pneumoniae isolates recovered, 60% (39/65) were carbapenem-resistant (CRKP). According to the mCIM and eCIM tests, 89.7% (35/39) of CRKP isolates were carbapenemase-positive, and 68.6% (24/35) were metallo-β-lactamase (MBL)-positive. By using the conventional PCR, at least one of the MBL genes was present in each metallo-bata-lactamase-producing isolate: 8.3% carried the blaVIM gene, 66.7% the blaNDM, and 91.7% the blaIMP gene. After doing the disk combination method for ceftazidime-avibactam plus Aztreonam, 62.5% of the isolates shifted from resistance to sensitivity. Also, ceftazidime/avibactam plus Aztreonam resistance was reduced markedly among CRKP using the E-test. The addition of Aztreonam to ceftazidime/avibactam is an effective therapeutic option against MBL-producing K. pneumoniae.Clinical Trials Registry: Pan African Clinical Trials Registry. Trial No.: PACTR202410744344899. Trial URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=32000.

Keywords: Klebsiella pneumoniae; Carbapenemase; E-test; Synergy; eCIM; mCIM.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Human ethics and consent to participate: Ethical approval was obtained from the Research Ethics Committee of the Faculty of Medicine, Suez Canal University, Egypt, #5060. The patients provided informed consent, which addressed all the steps of the study and their right to withdraw at any time. The minor patient’s informed consent was obtained from a parent, which addressed all the steps of the study and their right to withdraw at any time. It is declared that: All methods were carried out by relevant guidelines and regulations. It was performed according to the recommendations of Good Clinical Practice and the Declaration of Helsinki (2013).

Figures

Fig. 1
Fig. 1
mCIM and eCIM testing showed an increase of zone diameter ≥ 5 mm after adding EDTA and they were considered as metallo-β-lactamase positive isolates.
Fig. 2
Fig. 2
Detection of metallo-beta lactamase genes by agarose gel electrophoresis. Lane M shows a 100 bp molecular strand DNA ladder, (A) blaNDM gene; All Lanes show positive specimens (236 bp), except lane (3, 5), (B) blaIMP gene; All Lanes show positive specimens (587 bp), (C) blaVIM gene; 2 Lanes show positive specimens (382 bp).
Fig. 3
Fig. 3
Antibiotic susceptibility pattern of the 39 CRKP isolates by Kirby-Bauer disk diffusion method.
Fig. 4
Fig. 4
MIC of ceftazidime/avibactam alone and in combination with aztreonam by E-test strip.
Fig. 5
Fig. 5
Antibiotic susceptibility by using E-test strips showing ceftazidime/avibactam strip alone and ceftazidime/avibactam combined with aztreonam.
See this image and copyright information in PMC

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