Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 66, Issue 3, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/aac.02161-21
Keywords
cefepime-taniborbactam susceptibility; carbapenemase-producing Enterobacterales; carbapenemase-producing Pseudomonas aeruginosa
Categories
Funding
- Venatorx Pharmaceuticals
- Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority [HHSO100201900007C]
- Plan Nacional de [I1D 1 i 2013-2016]
- Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases [RD16/0016/0001, RD16/0016/0004, RD16/0016/0006, RD16/0016/0007, RD16/0016/0008, RD16/0016/0010, REIPI RD16/0016/0011]
- European Development Regional Fund A Way to Achieve Europe (ERDF)
- CIBER en Enfermedades Infecciosas (CIBERINF) [CB21/13/00084]
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This study evaluated the activity of cefepime-taniborbactam against carbapenemase-producing bacteria and found it to be effective against both Enterobacterales and Pseudomonas species.
Novel beta-lactam-beta-lactamase inhibitor combinations currently approved for clinical use are poorly active against metallo-beta-lactamase (MBL)-producing strains. We evaluated the in vitro activity of cefepime-taniborbactam (FTB [formerly cefepime-VNRX-5133]) and comparator agents against carbapenemase-producing Enterobacterales (n = 247) and carbapenem-resistant Pseudomonas species (n = 170) clinical isolates prospectively collected from different clinical origins in patients admitted to 8 Spanish hospitals. FTB was the most active agent in both Enterobacterales (97.6% MICFTB, <= 8/4 mg/L) and Pseudomonas (67.1% MICFTB, <= 8/4 mg/L) populations. Novel beta-lactam-beta-lactamase inhibitor combinations currently approved for clinical use are poorly active against metallo-beta-lactamase (MBL)-producing strains. We evaluated the in vitro activity of cefepime-taniborbactam (FTB [formerly cefepime-VNRX-5133]) and comparator agents against carbapenemase-producing Enterobacterales (n = 247) and carbapenem-resistant Pseudomonas species (n = 170) clinical isolates prospectively collected from different clinical origins in patients admitted to 8 Spanish hospitals. FTB was the most active agent in both Enterobacterales (97.6% MICFTB, <= 8/4 mg/L) and Pseudomonas (67.1% MICFTB, <= 8/4 mg/L) populations. The MICFTB was >8 mg/L in 6/247 (2.4%) Enterobacterales isolates (3 KPC-producing Klebsiella pneumoniae isolates, 1 VIM-producing Enterobacter cloacae isolate, 1 IMP-producing E. cloacae isolate, and 1 NDM-producing Escherichia coli isolate) and in 56/170 (32.9%) Pseudomonas isolates, 19 of them carbapenemase producers (15 producers of VIM, 2 of GES, 1 of GES+VIM, and 1 of GES+KPC). Against the Enterobacterales isolates with meropenem MICs of >2 mg/L (138/247), FTB was the most active agent against both serine-beta-lactamases (107/138) and MBL producers (31/138) (97.2 and 93.5% MICFTB, <= 8/4 mg/L, respectively), whereas the activity of comparators was reduced, particularly against the MBL producers (ceftazidime-avibactam, 94.4 and 12.9%, meropenem-vaborbactam, 85.0 and 64.5%, imipenem-relebactam, 76.6 and 9.7%, ceftolozane-tazobactam, 1.9 and 0%, and piperacillin-tazobactam, 0 and 0%, respectively). Among the meropenem-resistant Pseudomonas isolates (163/170; MIC, >2 mg/L), the activities of FTB against serine-beta-lactamase (35/163) and MBL (43/163) producers were 88.6 and 65.1%, respectively, whereas the susceptibilities of comparators were as follows: ceftazidime-avibactam, 88.5 and 16.0%, meropenem-vaborbactam, 8.5 and 7.0%, imipenem-relebactam, 2.9 and 2.3%, ceftolozane-tazobactam, 0 and 2.3%, and piperacillin-tazobactam, 0 and 0%, respectively. Microbiological results suggest FTB as a potential therapeutic option in patients infected with carbapenemase-producing Enterobacterales and carbapenem-resistant Pseudomonas isolates, including MBL producers.
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