Perspectives on synthetic pharmacotherapy for the treatment of nosocomial pneumonia

Expert Opin Pharmacother. 2019 Aug;20(12):1439-1448. doi: 10.1080/14656566.2019.1617852. Epub 2019 May 16.

Abstract

Introduction: Nosocomial pneumonia is the second most common infection in hospital settings, resulting in substantial increases in morbidity, mortality, and length of hospital stay. The rapid increase in resistance of nosocomial pathogens to many antibiotics and the high dissemination of resistance genes highlight the need for innovative approaches to combat difficult-to-treat nosocomial respiratory infections. Areas covered: This review summarizes the synthetic antimicrobials that are currently in development for the treatment of nosocomial pneumonia, focusing on antibiotics in the final phases of clinical development and on the strategies employed by novel synthetic antimicrobial peptides. Expert opinion: Several novel synthetic antimicrobials are currently in the pipeline, and it appears that new antimicrobial peptides or mimetics will soon be made available, expanding the opportunities to treat nosocomial pneumonia. However, the approval process for use in the treatment of nosocomial pneumonia is arduous. Given that significant investments by pharmaceutical companies have ended in failure to obtain the approval of regulatory agencies, novel platforms for antimicrobial discovery are needed. The identification of new and fully synthetic chemical structures with activity against nosocomial pathogens needs to be followed by preclinical studies in large animals and by pharmacokinetic and pharmacodynamic studies in specific critically ill populations to assess lung penetration.

Keywords: Synthetic antimicrobials; antimicrobial peptides; hospital-acquired pneumonia; host-defense peptide mimetics; pharmacotherapy; ventilator-associated pneumonia.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Chemistry Techniques, Synthetic / methods
  • Chemistry Techniques, Synthetic / trends
  • Cross Infection / drug therapy*
  • Cross Infection / epidemiology
  • Drug Discovery / methods
  • Drug Discovery / trends
  • Drug Therapy / methods
  • Drug Therapy / trends*
  • Healthcare-Associated Pneumonia / drug therapy*
  • Healthcare-Associated Pneumonia / epidemiology
  • Humans
  • Pneumonia / drug therapy
  • Pneumonia / epidemiology

Substances

  • Anti-Bacterial Agents