Game Changers: New β-Lactamase Inhibitor Combinations Targeting Antibiotic Resistance in Gram-Negative Bacteria

Recent regulatory approvals for the beta-lactam inhibitor combinations of ceftazidime avibactam and meropenem-vaborbactam have provided two novel therapeutic options for the treatment of multidrug-resistant infections caused by Gram-negative bacteria. Most importantly, these combination agents have satisfied an important medical need related to antibiotic resistant Klebsiella pneumoniae that produce serine carbapenemases, especially the Klebsiella pneumoniae carbapenemase (KPC) enzymes. Both combinations contain non-beta-lactam beta-lactamase inhibitors of novel chemical classes not previously developed as antibacterial agents, the diazabicyclooctanes and cyclic boronic acid derivatives. Their rapid development and approval programs have spurred a number of similar inhibitor combinations that will need to differentiate themselves for commercial success. Gaps still exist for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa, Acinetobacter spp., and metallo-beta-lactamase-producing pathogens. Overall, the new beta-lactamase inhibitor combinations have infused new life into the search for new antibacterial agents to treat multidrug-resistant bacteria.