Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

Clin Infect Dis. 2019 Nov 13;69(Suppl 7):S565-S575. doi: 10.1093/cid/ciz830.

Abstract

Antimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

Keywords: antimicrobial stewardship; carbapenemase; multidrug resistance; rapid diagnostics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Antimicrobial Stewardship
  • Carbapenems / therapeutic use*
  • Clinical Trials as Topic
  • Drug Resistance, Bacterial*
  • Forecasting
  • Gram-Negative Bacterial Infections / drug therapy*
  • Humans
  • Public Health

Substances

  • Anti-Bacterial Agents
  • Carbapenems