Beta-lactamases are a family of enzymes involve in bacterial resistance to β-lactam antibiotics. Beta-lactamases act by breaking the beta-lactam ring that allows Penicillin-like antibiotics to work. Nowadays, β-lactamase inhibitors prevents bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

VNRX-5133 is a cyclic boronate β-lactamase inhibitor. Especially, VNRX-5133 enhances the activity of Cefepime against resistant Enterobacteriaceae and P. aeruginosa isolates in a neutropenic mouse-thigh infection model. Particularly, VNRX-5133 greatly enhances the activity of Cefepime against many difficult to treat organisms. These organisms include cephalosporin and carbapenem resistant Enterobacteriaceae and Pseudomonas aeruginosa. Researchers evaluate the activity of Cefepime in combination with VNRX-5133 against recent clinical isolates. VNRX-5133/Cefepime is highly active against emerging multidrug-resistant Enterobacteriaceae.

In this study, Denis Daigle, et al show that Cefepime/VNRX-5133 is highly active against multidrug-resistant (MDR)-P. aeruginosa clinical isolates. VNRX-5133/Cefepime is highly active against five Ceftazidime/Avibactam-resistant K. pneumoniae clinical isolates with MIC ranging from 0.5 to 4 mg/L. Besides, VNRX-5133/Cefepime is also active against all five clinical isolates of Ceftolozane/Tazobactam-resistant P. aeruginosa. Moreover, VNRX-5133/Cefepime shows potent in vitro activity against all Enterobacteriaceae, with an MIC90 of 0.5 mg/L, compared to Cefepime, Levofloxacin, Piperacillin, and Tazobactam. As a result, VNRX-5133/Cefepime inhibits 99% of all Enterobacteriaceae, which includes 99% of extended spectrum β-lactamase-producers and 93% of meropenemnon-susceptible (CRE) isolates.

All in all, VNRX-5133 restores the activity of Cefepime against highly resistance gram-bacteria by inhibiting a broad spectrum of serine and metallo β-lactamases.

Denis Daigle, PhD, et al. 1370. Cefepime/VNRX-5133 Broad-Spectrum Activity Is Maintained Against Emerging KPC- and PDC-Variants in Multidrug-Resistant K. pneumonia and P. aeruginosa. Open Forum Infect Dis. 2018 Nov; 5(Suppl 1): S419-S420.