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

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 ß-lactam/ß-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.

Ceftazidime-avibactam, meropenen-vaborbactam, and imipenem-relebactam in combination with aztreonam against multidrug-resistant, metallo-ß-lactamase-producing Klebsiella pneumoniae.

The spread of multidrug-resistant (MDR), metallo-ß-lactamase (MBL)-producing Klebsiella pneumoniae represents a major therapeutic challenge. The newly introduced ß-lactam-ß-lactamase inhibitors (BLBLIs), ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (M/V), and imipenem/relebactam (I/R) are inactive against MBLs. The aim of this study was to evaluate the in vitro efficacy of aztreonam (ATM) in combination with CAZ/AVI, M/V, and I/R against 40 MDR, MBL-producing, and serine-ß-lactamases co-producing Klebsiella pneumoniae using the Etest method. Synergy was defined as a fractional inhibitory concentration index ≤0.5. All isolates were resistant to ATM, CAZ/AVI, and I/R and 38/40 (95%) were resistant to M/V. Synergy was observed in 97.5% in the combinations CAZ/AVI-ATM, and I/R-ATM and in 72.5% in the combination M/V-ATM. Further clinical studies are required to confirm the efficacy of these antimicrobial combinations.