Antibacterial agents active against Gram Negative Bacilli in phase I, II, or III clinical trials

Antimicrobial resistance is a major threat to modern healthcare, and it is often regarded that the antibiotic pipeline is 'dry.'Antimicrobial agents active against Gram negative bacilli in Phase I, II, or III clinical trials were reviewed.Nearly 50 antimicrobial agents (28 small molecules and 21 non-traditional antimicrobial agents) active against Gram-negative bacilli are currently in clinical trials. These have the potential to provide substantial improvements to the antimicrobial armamentarium, although it is known that 'leakage' from the pipeline occurs due to findings of toxicity during clinical trials. Significantly, a lack of funding for large phase III clinical trials is likely to prevent trials occurring for the indications most relevant to loss of life attributed to antimicrobial resistance such as ventilator-associated pneumonia. Non-traditional antimicrobial agents face issues in clinical development such as a lack of readily available and reliable susceptibility tests, and the potential need for superiority trials rather than non-inferiority trials. Most importantly, concrete plans must be made during clinical development for access of new antimicrobial agents to areas of the world where resistance to Gram negative bacilli is most frequent.