In Vitro Activities of Cefiderocol, Ceftazidime–Avibactam, Meropenem–Vaborbactam, Imipenem–Relebactam and Eravacycline Against Carbapenem-Resistant Klebsiella pneumoniae

Abstract

AIM/BACKGROUND

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a significant global threat due to the limited treatment options. In this study, in vitro activities of novel antimicrobial agents were investigated against CRKP strains.

METHODS

Eighty-five CRKP clinical isolates were included in the study. The most common carbapenemase resistance genes (KPC, OXA-48, NDM, VIM, IMP) were investigated with the Xpert Carba-R Assay (Cepheid,USA). Cefiderocol susceptibility was detected by DD and broth microdilution (BMD) method using iron-depleted cation-adjusted Mueller-Hinton broth. Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam and eravacycline susceptibilities were detected by disk diffusion (DD) and gradient-test. Results were evaluated to FDA breakpoints for eravacycline and EUCAST breakpoints for others.

RESULTS

The most prevalent resistance gene was OXA-48 (55.2%), followed by NDM+OXA48 (32.9%), KPC (5.8%) and NDM (4.7%). Eravacycline was the most active agent with 97.6% susceptibility by DD and with MIC50/MIC90 results of 0.38/1 mg/L by gradient-test. Cefiderocol susceptibility was 43.5% by DD and 56.5% by BMD. Ceftazidime-avibactam susceptibility was 63.5% by both methods. Ceftazidime-avibactam inhibited all KPC and OXA-48 producers, while all NDM/NDM+OXA48 producers were resistant to ceftazidime-avibactam, except for one NDM+OXA-48 producer. Both meropenem-vaborbactam and imipenem-relebactam susceptibilities were 7% by DD, while 18.8% and 21.2% by gradient-test, respectively; these agents were resistant to all NDM/NDM+OXA48 producers except five isolates for meropenem-vaborbactam by gradient-test (Table).

CONCLUSIONS

Eravacycline and cefiderocol are promising in the treatment of CRKP, especially for MBL-producers. Ceftazidime-avibactam is a good treatment option for CRKP except for MBL-producers. Reasons behind the high cefiderocol MICs in resistant isolates need to be further investigates.