Epidemiology and in vitro activity of ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, eravacycline, plazomicin, and comparators against Greek carbapenemase-producing Klebsiella pneumoniae isolates

Abstract

Background The increase in carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is of great concern because of limited treatment options. New antimicrobials were recently approved for clinical therapy. This study evaluated the epidemiology of carbapenemase-producing K. pneumoniae isolates collected at a Greek university hospital during 2017-2020, and their susceptibilities to ceftazidime-avibactam (CAZ/AVI), meropenem-vaborbactam (M/V), imipenem-relebactam (I/R), eravacycline, plazomicin, and comparators. Methods Minimum inhibitory concentrations (MICs) were evaluated by Etest. Only colistin MICs were determined by the broth microdilution method. Carbapenemase genes were detected by PCR. Selected isolates were typed by multilocus sequence typing (MLST). Results A total of 266 carbapenemase-producing K. pneumoniae strains were isolated during the 4-year study period. Among them, KPC was the most prevalent (75.6%), followed by NDM (11.7%), VIM (5.6%), and OXA-48 (4.1%). KPC-producing isolates belonged mainly to ST258 and NDM producers belonged to ST11, whereas OXA-48-and VIM producers were polyclonal. Susceptibility to tigecycline, fosfomycin, and colistin was 80.5%, 83.8%, and 65.8%, respectively. Of the novel agents tested, plazomicin was the most active inhibiting 94% of the isolates at ≤ 1.5 μg/ml. CAZ/AVI and M/V inhibited all KPC producers and I/R 98.5% of them. All OXA-48 producers were susceptible to CAZ/AVI and plazomicin. The novel β-lactam/β-lactamase inhibitors (BLBLIs) tested were inactive against MBL-positive isolates, while eravacycline inhibited 61.3% and 66.7% of the NDM and VIM producers, respectively. Conclusions KPC remains the predominant carbapenemase among K. pneumoniae, followed by NDM. Novel BLBLIs, eravacycline, and plazomicin are promising agents for combating infections by carbapenemase-producing K. pneumoniae. However, the emergence of resistance to these agents highlights the need for continuous surveillance and application of enhanced antimicrobial stewardship.

Epidemiology, Drug Resistance, and Risk Factors for Mortality Among Hematopoietic Stem Cell Transplantation Recipients with Hospital-Acquired Klebsiella pneumoniae Infections: A Single-Center Retrospective Study from China

“…However, the emergence of some resistance also reminds the need to monitor antimicrobial activity and strengthen management. 40 Moreover, for the efficacy evaluation of some “classical” antibiotics, a meta-analysis showed that the resistance rates of CRKP to colistin, polymyxin B, gentamicin and fosfomycin were 31.1%, 9.8%, 35.7% and 47.3%, respectively. 41 That, in addition to newer agents, some relatively “old” drugs still retain a certain (or even good) effect on CRKP infections.…”

Drug development concerning metallo-β-lactamases in gram-negative bacteria

“…For this reason, plazomicin maintains its activity against many MDR Enterobacteriaceae and was approved in 2018 by the FDA for the treatment of complicated urinary tract infections related to E. coli, K. pneumoniae, Enterobacter cloacae, and Proteus mirabilis (Serio et al, 2019). Several studies in vitro have confirmed its antibacterial activity on MBL-producing Enterobacteriaceae at a concentration of 0.75-2 µg/ml (Serio et al, 2019;Johnston et al, 2021;Maraki et al, 2022). No study on its antibacterial activity against MBL-producing P. aeruginosa or A. baumannii was found.…”

“…Recently, eravacycline has been approved for use in complicated intra-abdominal infections, including infections caused by MBL producers (Solomkin et al, 2019 ). Eravacycline at 1–4 μg/ml exerts potent antibacterial activity on all or most of the tested Enterobacteriaceae strains producing MBLs (Zhang et al, 2016 ; Johnston et al, 2020 ; Maraki et al, 2022 ). However, no relevant studies have been conducted to test its antibacterial activity in MBL-producing P. aeruginosa or A. baumannii thus far.…”

Multicenter Clinical Evaluation of ETEST Eravacycline for Susceptibility Testing of Enterobacteriaceae and Enterococci

“…Emergence of resistance among enterococci is also possible due to a combination of rpsJ mutations and horizontal transfer of tet genes ( 5 ). Indeed, the emergence of resistance to promising agents such as ERV and plazomicin highlights the need for continuous surveillance and application of enhanced antimicrobial stewardship ( 11 ).…”