Multidrug-resistant gram-negative organisms: a review of recently approved antibiotics and novel pipeline agents
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REVIEW ARTICLE
Multidrug‑resistant gram‑negative organisms: a review of recently approved antibiotics and novel pipeline agents A. Provenzani1 · A. R. Hospodar2 · A. L. Meyer2 · D. Leonardi Vinci3 · E. Y. Hwang2 · C. M. Butrus2 · P. Polidori1 Received: 27 February 2020 / Accepted: 23 June 2020 © Springer Nature Switzerland AG 2020
Abstract Background The discovery of antibiotics several decades ago was a defining moment in history. They were used to treat previously incurable diseases and save many lives. However, the use of antibiotics is not benign. Antibiotic resistance occurs due to the natural evolution of bacteria and gene transfer between bacteria via vertical and horizontal routes, resulting in protective mechanisms that render antibacterial agents ineffective. Aim of the review To list and describe current, novel pipeline antibiotics indicated for multidrug-resistant gram-negative bacteria. This review discusses the limited number of novel pipeline drugs available to combat the rapidly increasing number of multidrug-resistant bacteria and the need for initiatives to research and discover more novel antibiotics. Method A search of MEDLINE/PubMed using the search terms antibacterial pipeline OR antibiotic pipeline including publications between 1 January 2018 through 23 January 2020 resulted in 230 items. The results obtained were narrowed by adding the search term AND multi-drug resistant which resulted in 12 items. Then, ClinicalTrials.gov was searched for phase 2–3 “interventional” trials registered between 1 January 2018 and 23 January 2020 with the status “recruiting” or “completed” function and including World Health Organization-defined priority pathogens in the “condition or disease” field. The search process was then completed by introducing the term antibacterial agents in the “other terms” field. The trials search and selection resulted in 13 items. Relevant English-language studies and those conducted in humans were considered. Those drugs belonging to new antibiotic classes or to antibiotic classes already known but with new chemical structure were defined as “novel antibiotics”. Results The studies selected and reviewed were those referring to a novel antibiotics. Thus, from MEDLINE/PubMed, we found only 1 item referred to a novel chemical class (Murepavadin n = 1). From ClinicalTrials.gov a total of 4 citations were identified (Ftortiazinon n = 1, Zoliflodacin n = 1, Gepotidacin n = 1, ETX2514 + sulbactam n = 1). Conclusion The antibiotics annually approved by the Food and Drug Administration (FDA) mostly belong to existing classes of antibiotics and have specific indications, limiting their use in many multidrug-resistant infections. There are limited novel drug classes targeting gram-negative infections in the pipeline. Providers must be vigilant with the use of current antibiotics, especially until research and development (R&D) advancements are made. Keywords Antibiotics · Antimicrobial resistance · Multidrug-resistant gram-negative organisms · Novel antibiotics · Pipeline
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