Enmetazobactam is a penicillanic acid sulfone extended-spectrum β-lactamase (ESBL) inhibitor. It is an N-methylated tazobactam derivative ideveloped at Orchid Pharma (India) and then out-licensed to Allecra Therapeutics. It has broad-spectrum activity against most Gram-positive and Gram-negative bacteria, including those the bacteria causing urinary tract infections such as pyelonephritis.
Enmetazobactam is soluble in DMSO.
| Molecular Formula | C11H14N4O5S |
| Mechanism of Action | Enmetazobactam has a cefepime-sparing function by preventing cefepime's breakdown by bacterial extended-spectrum β-lactamases (ESBLs). ESBLs are a group of bacterial serine beta-lactamases that hydrolyze third-generation cephalosporins (3GC) leading to the development of 3GC-resistant bacteria. When used in combination with cefepime, Enmetazobactam protects cefepime from degradation by ESBLs and therefore prevents antibiotic resistance. It can inhibit representatives of all serine β-lactamase (SBL) classes without undergoing substantial scaffold fragmentation, |
| Spectrum | Enmetazobactam is active against most Gram-positive and Gram-negative bacteria. |
| Microbiology Applications |
Bacterial ESBL enzymes can hydrolyze important antibiotics like penicillins, broad-spectrum cephalosporins and monobactams, so ESBL-producing bacteria pose many challenges. When used in combination with cefepime (ie cefepime/enmetazobactam) it can prevent cefepime's breakdown by bacterial ESBL enzymes. Enmetazobactam in combination with cefepime was active against 223 Enterobacteriaceae clinical isolates including multidrug-resistant Escherichia coli and Klebsiella pneumoniae isolates; MIC50 is 0.125 mg/L (Crandon and Nicolau, 2015). |
| References |
Crandon JL and Nicolau DP (2015) In vitro activity of Cefepime/AAI101 and comparators against Cefepime non-susceptible Enterobacteriaceae. Pathogens. 4(3):620-625 PMID 26295262 Lanier C, Melton T, Covert K (2025) Cefepime-Enmetazobactam: A drug review of a novel beta-cactam/beta-lactamase inhibitor. Ann Pharmacother. 59(6):570-576 PMID 39329253 Lang PA et al (2022) Studies on Enmetazobactam clarify mechanisms of widely used β-lactamase inhibitors, Proc. Natl. Acad. Sci. U.S.A. 119 (18) e2117310119 Upadhyay JR, Gajjar AK, Chokshi A (2026) Enmetazobactam: an extended-spectrum beta-lactamase inhibitor in countering antimicrobial resistance. Eds. Yu B and Zhan P. Drug Discovery Stories Vol 2, Elsevier, pp. 181-192 |