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The latest advances in β-lactam/β-lactamase inhibitor combinations for the treatment of Gram-negative bacterial infections

ABSTRACT Introduction: Antimicrobial resistance in Gram-negative pathogens is a significant threat to global health. β-Lactams (BL) are one of the safest and most-prescribed classes of antibiotics on the market today. The acquisition of β-lactamases, especially those which hydrolyze carbapenems, is eroding the efficacy of BLs for the treatment of serious infections. During the past decade, significant advances were made in the development of novel BL-β-lactamase inhibitor (BLI) combinations to target β-lactamase-mediated resistant Gram-negatives. Areas covered: The latest progress in 20 different approved, developing, and preclinical BL-BLI combinations to target serine β-lactamases produced by Gram-negatives are reviewed based on primary literature, conference abstracts (when available), and US clinical trial searches within the last 5 years. The majority of the compounds that are discussed are being evaluated as part of a BL-BLI combination. Expert opinion: The current trajectory in BLI development is promising; however, a significant challenge resides in the selection of an appropriate BL partner as well as the development of resistance linked to the BL partner. In addition, dosing regimens for these BL-BLI combinations need to be critically evaluated. A revolution in bacterial diagnostics is essential to aid clinicians in the appropriate selection of novel BL-BLI combinations for the treatment of serious infections.