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. 2022 Jul 6:15:3537-3548.
doi: 10.2147/IDR.S371248. eCollection 2022.

Carbapenem-Resistant Klebsiella pneumoniae Among Patients with Ventilator-Associated Pneumonia: Evaluation of Antibiotic Combinations and Susceptibility to New Antibiotics

Raghdaa A Ramadan  1 , Aya M Bedawy  1 , Essamedin M Negm  2 , Tarek H Hassan  3 , Dalia A Ibrahim  3 , Somia M ElSheikh  1 , Rania M Amer  1
Affiliations

Carbapenem-Resistant Klebsiella pneumoniae Among Patients with Ventilator-Associated Pneumonia: Evaluation of Antibiotic Combinations and Susceptibility to New Antibiotics

Raghdaa A Ramadan et al. Infect Drug Resist. .

Abstract

Background: Carbapenemase-producing Gram-negative bacteria, particularly Klebsiella pneumoniae (K. pneumoniae), are at the forefront of the list of causative agents of ventilator-associated pneumonia (VAP). The treatment options for such infections are limited, and various antimicrobial combinations have been suggested as alternatives in clinical practice. New antibiotics, such as ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol, have shown advantages in both in vitro and clinical studies.

Purpose: To evaluate the in vitro effect of meropenem-ciprofloxacin and meropenem-colistin combinations on carbapenem-resistant (CR) K. pneumoniae VAP isolates and to determine their susceptibility to new antibiotics.

Methods: Seventy-three K. pneumoniae isolates from 176 endotracheal samples from VAP cases were studied. Antibiotic susceptibility testing and phenotypic detection of extended-spectrum β lactamase (ESBL) and carbapenemase production were done. CR K. pneumoniae isolates were tested for the five predominant carbapenemase genes (bla KPC, bla OXA-48, bla NDM, bla VIM, and bla IMP). In vitro evaluation of meropenem-ciprofloxacin and meropenem-colistin combinations was done by MIC test strips. Susceptibility to new antibiotics was tested by disk diffusion method.

Results: Sixty-three (86.3%) of the isolates were ESBL producers and 52 (71.2%) were carbapenem resistant. Bla NDM was the most prevalent carbapenemase gene (50%), followed by bla OXA-48, (36.5%) then bla KPC in (11.5%). Bla VIM and bla IMP were not detected. Meropenem-ciprofloxacin combination showed indifferent effect on all isolates, while meropenem-colistin combination showed 25% synergism, 15.4% addition and 59.6% indifference. All (100%) CR K. pneumoniae isolates were resistant to ceftolozane/tazobactam and 79% were resistant to ceftazidime/avibactam, while 96% were sensitive to cefiderocol.

Conclusion: A high rate of carbapenem resistance exists among VAP K. pneumoniae isolates. Meropenem-colistin combination and cefiderocol appear to be potential treatment options for infections caused by CR K. pneumoniae. Resistance to the tested new β-lactam/β-lactamase inhibitors was high, signifying a major threat.

Keywords: Klebsiella pneumoniae; carbapenem resistant; carbapenemases; combination; new antibiotics; ventilator-associated pneumonia.

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Conflict of interest statement

The authors report no conflicts of interest in relation to this work.

Figures

Figure 1
Figure 1
Results of mCIM/eCIM test of 2 CR K. pneumoniae isolates. The two isolates show positive mCIM/eCIM test results indicating MBL production.
Figure 2
Figure 2
PCR results for carbapenemase genes. (A) Agarose gel electrophoresis of blaKPC and blaOXA-48 amplicons. Lane (1): DNA ladder 100 bp, lanes (2, 5, 6, 7): positive for blaOXA-48 gene (438bp), lane (8): positive for blaKPC gene (789bp). (B) Agarose gel electrophoresis of blaNDM amplicons. Lane (1): DNA ladder 100 bp, lanes (2–4): positive for blaNDM gene (621bp).
Figure 3
Figure 3
Meropenem–colistin combination testing. This was a synergistic effect. Meropenem MIC was >32 μg/mL when tested alone but was 0.25 μg/mL in combination. Colistin MIC was 8 μg/mL when tested alone but was 1.5 μg/mL in combination.
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