Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Pozuelo-Carrascosa DP, Cobo-Cuenca AI, Carmona-Torres JM, Laredo-Aguilera JA, Santacruz-Salas E, Fernandez-Rodriguez R. Body position for preventing ventilator-associated pneumonia for critically ill patients: a systematic review and network meta-analysis. J Intensive Care. 2022;10(1):9. doi:10.1186/s40560-022-00600-z - DOI - PMC - PubMed
    1. Erfani Y, Rasti A, Janani L. Prevalence of Gram negative bacteria in ventilator-associated pneumonia in neonatal intensive care units: a systematic review and meta-analysis protocol. BMJ Open. 2016;6(10):e012298. doi:10.1136/bmjopen-2016-012298 - DOI - PMC - PubMed
    1. Bush K. Alarming β-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae. Curr Opin Mirobiol. 2010;13(5):558–564. doi:10.1136/bmjopen-2016-012298 - DOI - PubMed
    1. El-Herte R, Kanj S, Matar G, Araj G. The threat of carbapenem resistant Enterobacteriaceae in Lebanon: an update on the regional and local epidemiology. J Infect Public Health. 2012;5(3):233–243. doi:10.1016/j.jiph.2012.02.003 - DOI - PubMed
    1. Laishram S, Pragasam AK, Bakthavatchalam YD, Veeraraghavan B. An update on technical, interpretative and clinical relevance of antimicrobial synergy testing methodologies. Indian J of Med Microbiol. 2017;35(4):445–468. doi:10.4103/ijmm.IJMM_17_189 - DOI - PubMed