The FDA has approved Allecra Therapeutics’ novel antibiotic combination, EXBLIFEP (cefepime/enmetazobactam), to treat complicated urinary tract infections (cUTIs), including acute pyelonephritis (AP), in patients ≥ 18 years of age caused by the following gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex. Designed as a “carbapenem-sparing” treatment for multi-drug resistant (MDR) gram-negative infections, EXBLIFEP represents an important new therapeutic option in the battle against antimicrobial resistance (AMR), says GlobalData, a leading data and analytics company.

In addition to the FDA approval, EXBLIFEP has also been submitted for marketing approval in the EU and received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in January 2024. The CHMP’s positive opinion included treatment of cUTIs, AP, hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and bacteremia associated with any of those infections. The European Medicines Agency (EMA) is expected to make a final decision in March this year.

The current standard of care (SOC) for treating cUTIs, piperacillin/tazobactam (TZP), is under threat from the growing prevalence of extended-spectrum β-lactamase (ESBL) mediated resistance. ESBL-producing pathogens are often resistant to most fluoroquinolone, aminoglycoside, and β-lactam antibiotics. This led to the use of carbapenem antibiotics to treat drug-resistant cUTIs.

Nancy Jaser, Senior Infectious Disease Analyst at GlobalData, comments: “Carbapenems are highly effective against MDR pathogens and are typically reserved as last resort treatment options to limit the growth of carbapenem-resistant bacterial strains. However, the increased use in cUTIs resulted in the emergence of carbapenem-resistant Enterobacterales (CRE). Therefore, a critical need exists for “carbapenem-sparing” options, such as EXBLIFEP, to treat cUTIs caused by ESBL-producing bacteria and other resistant infections.”

EXBLIFEP was designed to provide a novel therapeutic “carbapenem-sparing” option to address the serious threat of increasing ESBL prevalence. The FDA’s approval of EXBLIFEP was highly influenced by Phase III pivotal clinical data that demonstrated its efficacy against AMR mediated by ESBLs in gram-negative bacteria. EXBLIFEP further demonstrated superiority to piperacillin/tazobactam with respect to the trial’s primary endpoints of clinical cure and microbiological eradication in cUTI patients.

Jaser concludes: “ESBL mediated AMR is an urgent global threat. EXBLIFEP has the potential to serve as a replacement for piperacillin/tazobactam in treating cUTIs and an alternative to carbapenem use. Monitoring for the emergence of enmetazobactam-resistant bacterial strains should be prioritized to ensure continued efficacy against ESBL pathogens. However, it is unlikely that EXBLIFEP can solve this issue alone. A significant need remains for the continued development of novel therapeutic options to effectively treat drug-resistant infections in the long term.”