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

Abstract

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.