Antibiotics in the clinical pipeline at the end of 2015

Abstract

There is growing global recognition that the continued emergence of multidrug-resistant bacteria poses a serious threat to human health. Action plans released by the World Health Organization and governments of the UK and USA in particular recognize that discovering new antibiotics, particularly those with new modes of action, is one essential element required to avert future catastrophic pandemics. This review lists the 30 antibiotics and two β-lactamase/β-lactam combinations first launched since 2000, and analyzes in depth seven new antibiotics and two new β-lactam/β-lactamase inhibitor combinations launched since 2013. The development status, mode of action, spectra of activity and genesis (natural product, natural product-derived, synthetic or protein/mammalian peptide) of the 37 compounds and six β-lactamase/β-lactam combinations being evaluated in clinical trials between 2013 and 2015 are discussed. Compounds discontinued from clinical development since 2013 and new antibacterial pharmacophores are also reviewed.

Enhancement of antibiotic-activity through complexation with metal ions - Combined ITC, NMR, enzymatic and biological studies

“…AgNO 3 had an antibacterial effect against all examined strains in contrast to CuCl 2 and Zn(OAc) 2 where only a very low antimicrobial effect was visible.…”

“…Careless use of antibiotics has led to the evolution of multi-drug resistant (MDR) bacteria resulting in untreatable infections, and this rise and spread of resistant bacteria is a serious threat for health systems across the globe. [1] With the ongoing increase in drug resistance, the treatment of bacterial diseases by antibiotics is becoming less effective, and there are very few new antibiotics in the clinical pipeline, [2] necessitating the development of alternative approaches. [3] The possibility of modifying existing commercially available drugs to overcome MDR is a favorable approach, saving costs and time compared to the design and development of completely new drugs.…”

Novel drug delivery systems to combat antimicrobial resistance

“…Unless drastic measures are taken soon, grim predictions estimate the annual worldwide death toll may increase to 10 million per year by 2050 [5]. To exacerbate the situation, the drive towards the development of newer antibiotics has slowed down [6]. The Food and Drug Administration (FDA) approved 49 new antibiotics during 1981-2000 period, out of which 24…”

“…The drop in approvals may indicate, either a changing, stricter FDA approval process, fewer submissions, or a lack of pharmaceutical industry support for development. Out of the new drugs approved, five were totally new classes of antibiotics, but none were targeted against gram negative bacteria [6].…”

“…Worldwide, during the period from 2000-2015 30 new antibiotics were marketed along with two new β-lactam/β-lactamase inhibitor combinations (BBLIC) [6] (Figure 1). Note that β-lactamase will breakdown penicillin and lead to resistance.…”