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

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 beta 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 beta-lactam/beta-lactamase inhibitors was high, signifying a major threat.