Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management

Pharmacotherapy. 2015 Oct;35(10):949-62. doi: 10.1002/phar.1636.


Infections caused by resistant gram-negative bacteria are becoming increasingly prevalent and now constitute a serious threat to public health worldwide because they are difficult to treat and are associated with high morbidity and mortality rates. In the United States, there has been a steady increase since 2000 in rates of extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii, particularly among hospitalized patients with intraabdominal infections, urinary tract infections, ventilator-associated pneumonia, and bacteremia. Colonization with resistant gram-negative bacteria is common among residents in long-term care facilities (particularly those residents with an indwelling device), and these facilities are considered important originating sources of such strains for hospitals. Antibiotic resistance is associated with a substantial clinical and economic burden, including increased mortality, greater hospital and antibiotic costs, and longer stays in hospitals and intensive care units. Control of resistant gram-negative infections requires a comprehensive approach, including strategies for risk factor identification, detection and identification of resistant organisms, and implementation of infection-control and prevention strategies. In treating resistant gram-negative infections, a review of surveillance data and hospital-specific antibiograms, including resistance patterns within local institutions, and consideration of patient characteristics are helpful in guiding the choice of empiric therapy. Although only a few agents are available with activity against resistant gram-negative organisms, two recently released β-lactam/β-lactamase inhibitor combinations - ceftolozane/tazobactam and ceftazidime/avibactam - have promising activity against these organisms. In this article, we review the epidemiology, risk factors, and antibiotic resistance mechanisms of gram-negative organisms. In addition, an overview of treatment options for patients with these infections is provided.

Keywords: avibactam; carbapenemase; ceftolozane; extended-spectrum β-lactamase; gram-negative bacteria; multidrug resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use
  • Cross Infection / epidemiology
  • Cross Infection / microbiology
  • Drug Resistance, Multiple, Bacterial / physiology*
  • Drug Therapy, Combination
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / epidemiology*
  • Humans
  • Infection Control / organization & administration
  • Microbial Sensitivity Tests
  • Risk Factors
  • United States
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamase Inhibitors / therapeutic use


  • Anti-Bacterial Agents
  • Carbapenems
  • beta-Lactamase Inhibitors