Vaborbactam: perspective of a new β-lactamase inhibitor in the antimicrobial chemotherapy

Infections due to carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii constitute a global public health threat and are associated with high morbidity and mortality rates. Resistance is mainly due to the production of various types of carbapenemases. Vaborbactam is a novel boronic acid-based β-lactamase inhibitor with high potency against class A carbapenemases, including KPC variants. Combined with meropenem, it almost fully restores its activity against KPC carbapenemase-producing Enterobacterales. However, it has limited activity against carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clinical efficacy and safety of the combination were evaluated in two clinical trials, TANGO I and II: it was proved to be non-inferior compared to other therapeutic options. It was also found safe, having few serious adverse effects, especially in terms of nephrotoxicity. Based on available in vitro and in vivo data it appears to retain a low propensity for resistance selection. Vaborbactam exhibits pharmacokinetic properties similar to those of meropenem. Meropenem-vaborbactam has been approved for use in adults with complicated urinary tract and intrabdominal infections, hospital-acquired and ventilator-associated pneumonia, as well as infections due to aerobic Gram-negative organisms in adults with limited treatment options. Studies regarding its use in real-life settings show promising clinical cure rates and lower rates of adverse effects, even when it comes to cases of very fragile patients.