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

• Published in: Infection and drug resistance 2022-07, Vol.15, p.3537-3548
• Main Authors: Ramadan, Raghdaa A, Bedawy, Aya M, Negm, Essamedin M, Hassan, Tarek H, Ibrahim, Dalia A, ElSheikh, Somia M, Amer, Rania M
• Format: Article
• Language: English
• Subjects: Analysis; Bacterial pneumonia; Beta lactamases; carbapenem resistant; carbapenemases; Ciprofloxacin; combination; Diagnosis; Drug therapy; Health aspects; klebsiella pneumoniae; Medical research; Medicine, Experimental; new antibiotics; Original Research; Pneumonia; ventilator-associated pneumonia
• ISSN: 1178-6973; 1178-6973
• DOI: 10.2147/IDR.S371248

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.sub.KPC], [bla.sub.OXA-48], [bla.sub.NDM], [bla.sub.VIM], and [bla.sub.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. BlaNDM was the most prevalent carbapenemase gene (50%), followed by [bla.sub.OXA-48], (36.5%) then [bla.sub.KPC] in (11.5%). BlaVIM and [bla.sub.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. Keywords: ventilator-associated pneumonia, Klebsiella pneumoniae, carbapenem resistant, carbapenemases, combination, new antibiotics