Antimicrobial resistance and treatment: an unmet clinical safety need

Expert Opin Drug Saf. 2018 Jul;17(7):669-680. doi: 10.1080/14740338.2018.1488962. Epub 2018 Jun 22.

Abstract

Introduction: Infections due to multidrug-resistant (MDR) bacteria are burdened by high mortality rates. The development of new compounds to face the global threat of resistance is urgently needed. Combination regimens including "old" high-dose antimicrobials are currently limited by the risk of toxicity, resistance selection, and reduced efficacy. Following the Infectious Diseases Society of America call to develop 10 new antibacterials by 2020, new molecules are currently under development or have become available for use in clinical practice.

Areas covered: We have reviewed safety characteristics and tolerability of old antimicrobials that are currently employed in combination regimens as well as new antimicrobials, including beta-lactams/beta-lactamase inhibitors, new cephalosporins, quinolones, and aminoglycosides.

Expert opinion: The availability of new compounds that show in vitro efficacy against MDR represents a unique opportunity to face the threat of resistance and to optimize the current use of antimicrobials, potentially reducing toxicity. Agents that are potentially active against MDR Gram-negatives are ceftozolane/tazobactam, new carbapenems and cephalosporins, the combination of avibactam with ceftazidime, and plazomicin. Further data from clinical trials and post-marketing studies for drugs targeting MDR pathogens are crucial to confirm their efficacy and safety.

Keywords: Multidrug-resistant gram-negative infections; colistin; drug toxicity; fosfomycin; new antibiotics; tigecycline.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacology
  • Drug Design*
  • Drug Resistance, Multiple, Bacterial
  • Drug Therapy, Combination
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans

Substances

  • Anti-Bacterial Agents