In Vitro Activity of Cefiderocol, Cefepime-Zidebactam, and β-Lactam Combinations Versus Other Antibiotic Classes Against Various Sequence Types of Clinically Isolated Carbapenemase-Producing Klebsiella pneumoniae.

Abstract

Aim: This study aimed to establish the in vitro efficacy and susceptibility profiles of new β-lactam antibiotics against clinically isolated carbapenemase-producing Klebsiella pneumoniae (CPKP) strains. Materials and Methods: A total of 117 nonduplicated CPKP isolates were tested against cefiderocol, cefepime-zidebactam, ceftazidime-avibactam, tigecycline, and other 20 antibiotics by broth microdilution. The carbapenemase genes were identified using PCR and sequencing, while multilocus sequence typing established the bacterial strains. Results: Three significant sequence types (STs), including ST147, ST16, and ST11, were shown to be the dominant STs, which occupied ∼90% of the tested population. Three carbapenemase genes, bla_NDM-1, bla_OXA-181, and bla_OXA-232, were detected. The bla_NDM-1 was found in ST147 and ST16 but not in ST11, while the bla_OXA-232 was not detected in ST147. The majority of ST16 isolates contained both bla_NDM-1 and bla_OXA-232, which was not seen in other strains. Cefiderocol, cefepime-zidebactam, and tigecycline were the most active agents against CPKP. Both MIC₅₀ and MIC₉₀ of these three antibiotics remained within the susceptible categories, while nearly all other antibiotics were in the resistant levels. However, in ST11, which carried only bla_OXA genes without bla_NDM-1, ceftazidime-avibactam was effective with the MIC₉₀ at 2 μg/mL. In addition, amikacin was shown to have good activity in ST11. In contrast, gentamicin was active in only ST16 and ST147. Conclusions: This study is the first report that demonstrates the prevalence of CPKP, distribution of strains, resistant genes, and antimicrobial susceptibility profiles in northern Thailand. These data would contribute to appropriate individual treatment and the selection of infection control strategies.