TY - JOUR
TI - In vitro comparative activity of the new beta-lactamase inhibitor
taniborbactam with cefepime or meropenem against Klebsiella pneumoniae
and cefepime against Pseudomonas aeruginosa
metallo-beta-lactamase-producing clinical isolates
AU - Meletiadis, Joseph
AU - Paranos, Paschalis
AU - Georgiou,
AU - Panagiota-Christina
AU - Vourli, Sofia
AU - Antonopoulou, Stavroula and
AU - Michelaki, Aikaterini
AU - Vagiakou, Eleni
AU - Pournaras, Spyros
JO - International Journal of Antimicrobial Agents
PY - 2021
VL - 58
TODO - 5
SP - null
PB - Elsevier
SN - 0924-8579
TODO - 10.1016/j.ijantimicag.2021.106440
TODO - beta-lactamase inhibitor; metallo-beta-lactamase-producing isolates; K.
pneumoniae; P. aeruginosa
TODO - Metallo-beta-lactamase (MBL)-producing Gram-negative bacteria are
increasing worldwide and very few agents are active against these
pathogens. Taniborbactam (formerly VNRX-5133) is a newly developed
bicyclic boronate beta-lactamase inhibitor that directly inhibits all
four Ambler classes of beta-lactamases. In the present study the in
vitro activity of cefepime or meropenem combined with taniborbactam
against 100 Klebsiella pneumoniae and cefepime combined with
taniborbactam against 100 Pseudomonas aeruginosa molecularly
characterized MBL-producing strains were investigated using ISO standard
broth microdilution assays and compared with a panel of antimicrobial
agents that are used in clinical practice (amikacin, aztreonam,
ciprofloxacin, levofloxacin, gentamicin, piperacillin/tazobactam,
imipenem, tigecycline, ceftolozane-tazobactam, cefepime-tazobactam,
meropenem-vaborbactam, ceftazidime-avibactam). For K. pneumoniae
isolates, the MIC90 values were >= 64 mg/L for all drugs except
cefepime-taniborbactam (16 mg/L; 87% inhibited at <= 8/4 mg/L),
meropenem-taniborbactam (4 mg/L; 94% inhibited at <= 8/4 mg/L) and
tigecycline (8 mg/L), with high levels of resistance (>= 65%) found for
all approved comparator antimicrobials tested. For P. aeruginosa, the
MIC90 values were >= 64 mg/L for all drugs except aztreonam (32 mg/L),
cefepime-taniborbactam (32 mg/L; 88% inhibited at <= 16/4 mg/L) and
ciprofloxacin (32 mg/L), with high levels of resistance (>= 73%) for
all approved drugs except aztreonam (27%). Taniborbactam reduced
cefepime and meropenem MICs by a median 5 and 7 two-fold dilutions to <=
8 mg/L in 87% and 94% of MBL-producing K. pneumoniae isolates, and
cefepime MICs by a median 5 two-fold dilutions to <= 16 mg/L in 86% of
MBL-producing P. aeruginosa, respectively . The combinations
cefepime-taniborbactam and meropenem-taniborbactam are promising
alternative treatment options for infections by MBL-producing isolates.
(C) 2021 Elsevier Ltd and International Society of Antimicrobial
Chemotherapy. All rights reserved.
ER -