Addressing the Emergence and Impact of Multidrug-Resistant Gram-Negative Organisms: A Critical Focus for the Next Decade
Approximately 10% of hospitalizations are complicated by a healthcare-associated infection, and up to 75% of these are due to organisms resistant to first-line antimicrobial therapy.1,2 Furthermore, antimicrobial-resistant bacterial infections are associated with significant increases in morbidity and mortality and incur upward of $20 billion in annual healthcare costs.1,2 Antimicrobial resistance has increased significantly in all spheres of patient care: acute care hospitals, long-term acute care hospitals, long-term care, and the community. Despite these sobering facts, we remain woefully unprepared to address both current and future resistant organisms.
Although antimicrobial resistance has been noted in nearly all bacterial pathogens, multidrug resistance among gram-negative bacteria represents a unique and immediate threat. In the past decade, there has been a dramatic increase in the prevalence of various types of antimicrobial-resistant gram-negative bacteria, including extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii.3-6 Infections due to these organisms have been associated with significantly worse clinical outcomes, with mortality rates up to 4 times higher than infections caused by susceptible strains.7-9 Furthermore, the potential for widespread and rapid transmission of these pathogens and/or the underlying genetic determinants of their resistance is of great concern.
What makes the emergence of multidrug-resistant gram-negative organisms uniquely compelling is the fact that few antimicrobial agents currently exist for treatment of these infections (eg, polymyxins, tigecycline).10-14 Indeed, clinical cases in which an infecting organism is effectively resistant to all available antimicrobial agents are increasingly common. Further compounding this issue is the well-recognized lack of new agents active against these organisms currently in development.15 While several new agents targeting resistant gram-positive organisms have been brought to market in the past 10 years, virtually no new agents specifically addressing resistant gram-negative pathogens have been introduced.
Given the lack of new antimicrobial development, it is critical that efforts target the preservation of currently available agents. As such, studies that elucidate those key aspects of the epidemiology of multidrug-resistant gram-negative pathogens are vitally important. Unfortunately, funding for the study of significant bacterial pathogens is limited, particularly in comparison to the burden of disease caused by these organisms.16 Thus, it is not surprising that studies that have addressed these issues have often been hampered by small sample size, limitation to 1 medical center, significant heterogeneity in patient populations, failure to differentiate between infection versus colonization, and inability to control for important potential confounders. In addition to these limitations, it is worth noting that the vast majority of studies conducted to date have been performed in acute care hospitals. In this light, it is important to highlight the fact that multidrug-resistant organisms are as common, if not more so, in post–acute care clinical sites such as long-term care facilities and long-term acute care hospitals.17,18 Understanding the epidemiology of multidrug-resistant gram-negative organisms in these settings is critical for controlling the emergence of resistance in these settings and also because of the frequent transfer of patients between different healthcare facilities.
It is in this context that this special issue of Infection Control and Hospital Epidemiology is presented. Papers included in this issue address a variety of important emerging pathogens, including carbapenem-resistant Enterobacteriaceae, multidrug-resistant A. baumannii, and ESBL-producing Enterobacteriaceae. An important component of addressing these organisms is better defining the scope of the problem. To this end, several papers (Reno et al, Brennan et al, Mathers et al, Pfeiffer et al, Fitzpatrick et al, Johnson et al, Pereira et al, and Shaw et al) describe novel strategies for conducting surveillance for target pathogens. Before interventions to curb the emergence of these organisms might be devised, it is important to elucidate the knowledge base, attitudes, and practices of healthcare providers regarding multidrug-resistant pathogens. A few papers in this issue (Drees et al, Lyles et al, Rajapakse et al) focus on more clearly defining how clinicians, infection preventionists, and hospitals approach patients colonized or infected with these organisms. Strategies to control the spread of multidrug-resistant gram-negative organisms rely on identifying potential reservoirs. Several studies (Havill et al, Rock et al, Rosa et al, Stewardson et al, Cochard et al) seek to elucidate the potential impact of such reservoirs as food sources, healthcare workers, and the environment in the emergence of these organisms. Much can also be learned from reports of efforts to control the spread of multidrug-resistant organisms both in endemic and epidemic situations as well as from studies evaluating treatment and prevention strategies (Fitzpatrick et al, Epson et al, Pisney et al, Drekonja et al, Pfeiffer et al, Lin et al, Rajapakse et al). Finally, the emergence of multidrug-resistant gram-negative pathogens has been widespread across not only adult acute care hospitals but also other practice sites (eg, long-term acute care hospitals) and populations (eg, pediatrics, long-term care). This issue also contains several papers addressing these important populations contributing to the emergence of antimicrobial resistance (Dirajlal-Fargo et al, Bhargava et al, Mortensen et al, Cochard et al, Lyles et al).
The incidence and distribution of multidrug resistance in gram-negative pathogens has steadily increased in recent years. If successful efforts to curb the further emergence of these organisms are to be devised, elucidating key factors needed to inform prevention and treatment efforts is critical. The papers included in this special issue provide important insights into various aspects of this critical problem. In addition, they raise questions that will guide future scientific endeavors in this critically important area. Importantly, they also highlight the epidemic of multidrug-resistant gram-negative infections and, we hope, lay the groundwork for future national and global responses to these pathogens that threaten the very foundations of our healthcare systems.
Financial support. This work was partially supported by the National Institutes of Health grant K24-A1080942 (to E.L.).
Potential conflicts of interest. All authors report no conflicts of interest relevant to this study. All authors submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and the conflicts that the editors consider relevant to this article are disclosed here.
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