Carbapenem-Resistant Klebsiella pneumoniae Among Patients with Ventilator-Associated Pneumonia: Evaluation of Antibiotic Combinations and Susceptibility to New Antibiotics
Raghdaa A. Ramadan, Aya Bedawy, Essamedin M. Negm, Tarek Hamdy Hassan, Dalia Ibrahim, Somia M ElSheikh, Rania Amer
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: ventilator-associated pneumonia, Klebsiella pneumoniae , carbapenem resistant, carbapenemases, combination, new antibiotics