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 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.