Investigational antimicrobial drugs for bloodstream infections

Bloodstream infections, especially those arising from multidrug-resistant strains, are an alarming public health threat requiring continuous efforts for new drug development. In this review, antibiotics at an advanced development stage for the treatment of patients with bloodstream infections are identified through a search of the available literature sources. Eight compounds currently undergoing phase II and/or phase III trials were identified. Isavuconazole, a triazole, is undergoing a phase III trial for the potential treatment of candidemia. Ceftobiprol medocaril, which belongs to the cephalosporin class, is undergoing regulatory review for the treatment of skin infections. Three lipoglycopeptides, oritavancin, dalbavancin and telavancin, are being tested against Gram-positive cocci in clinical trials. Also, human lactoferrin peptide 1-11, which appears to be a promising agent, is being tested in patients with Staphylococcus epidermidis bacteremia and in patients with candidemia. Iclaprim, a novel dihydrofolate reductase inhibitor, has completed two phase III trials for complicated skin and skin structure infections. The revival of an old class of antibiotics, polymyxins, in an effort to combat resistance, has also necessitated further investigation of these agents; colistin (polymyxin E) is at the forefront of this class of compounds, and is being assessed in a phase III efficacy trial. This overview of investigational antibiotics for bloodstream infections highlights that the pace of antimicrobial drug research and development is slower than the evolution of resistance. Only eight relevant compounds were identified in the pipeline of antibiotic research, none of which demonstrate a novel mechanism of action.