Novel pharmacotherapy for the treatment of hospital-acquired and ventilator-associated pneumonia caused by resistant gram-negative bacteria

Expert Opin Pharmacother. 2018 Mar;19(4):397-408. doi: 10.1080/14656566.2018.1438408. Epub 2018 Feb 19.

Abstract

Introduction: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are among the most prevalent infections in hospitalized patients, particularly those in the intensive care unit. Importantly, the frequency of multidrug resistant (MDR) Gram-negative (GN) bacteria as the bacteriologic cause of HABP/VABP is increasing. These include MDR Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem resistant Enterobacteriaceae (CRE). Few antibiotics are currently available when such MDR Gram-negatives are encountered and older agents such as polymyxin B, colistin (polymyxin E), and tigecycline have typically performed poorly in HABP/VABP.

Areas covered: In this review, the authors summarize novel antibiotics which have reached phase 3 clinical trials including patients with HABP/VABP. For each agent, the spectrum of activity, pertinent pharmacological characteristics, clinical trial data, and potential utility in the treatment of MDR-GN HABP/VABP is discussed.

Expert opinion: Novel antibiotics currently available, and those soon to be, will expand opportunities to treat HABP/VABP caused by MDR-GN organisms and minimize the use of more toxic, less effective drugs. However, with sparse clinical data available, defining the appropriate role for each of the new agents is challenging. In order to maximize the utility of these antibiotics, combination therapy and the role of therapeutic drug monitoring should be investigated.

Keywords: Acinetobacter baumannii; Pseudomonas aeruginosa; aminoglycosides; beta-lactam/beta-lactamase inhibitors; carbapenem-resistant Enterobacteriaceae; fosfomycin.

Publication types

  • Review

MeSH terms

  • Administration, Inhalation
  • Amikacin / pharmacology
  • Amikacin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use*
  • Ceftazidime / pharmacology
  • Ceftazidime / therapeutic use
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use
  • Clinical Trials as Topic
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / isolation & purification
  • Humans
  • Pneumonia, Ventilator-Associated / drug therapy*
  • Pneumonia, Ventilator-Associated / microbiology
  • Sisomicin / analogs & derivatives
  • Sisomicin / pharmacology
  • Sisomicin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • ceftolozane
  • Amikacin
  • Ceftazidime
  • plazomicin
  • Sisomicin