Infections à bacilles à Gram négatif résistants : nouvelles molécules, nouvelles associations

Infections caused by multidrug-resistant Gram-negative bacilli (GNB) are dramatically increasing, with significant morbidity and mortality. However, the number of novel antibiotics approved in clinics is shrinking, strongly limiting therapeutic options. In 2010, IDSA has launched the “10 × '20 initiative” aiming to promote the development of 10 new antimicrobial agents by 2020. To date, 7 new molecules or combinations have reached phase II or III clinical studies for the treatment of infections caused by GNB, including 4 β-lactam-β-lactamase inhibitor combinations (ceftolozane/tazobactam, ceftazidime/avibactam, ceftaroline/avibactam, and imipenem/MK-7655), 2 protein synthesis inhibitors (plazomicin and eravacycline) and 1 molecule with a novel mechanism of action (brilacidin). Other candidates also are promising, including 1 in halted phase II and 2 in advanced phases I. The majority of these new products is active against Enterobacteriaceae producing ESBL, cephalosporinases, or class A carbapenemases (i.e., KPC). Nonetheless, their activity is variable against Pseudomonas aeruginosa and generally limited against Acinetobacter baumannii. None of them (except one candidate currently in phase I) is active in vitro against metallo-β-lactamase producers. Finally, clinical evaluation of these new compounds for the treatment of bloodstream infections is lacking.