The Relationship between Antimicrobial Resistance and Patient Outcomes: Mortality, Length of Hospital Stay, and Health Care Costs

SUPPLEMENT ARTICLE The Relationship between Antimicrobial Resistance and Patient Outcomes: Mortality, Length of Hospital Stay, and Health Care Costs Sara E. Cosgrove Division of Infectious Diseases, The Johns Hopkins Medical Institutions, Baltimore, Maryland There is an association between the development of antimicrobial resistance in Staphylococcus aureus, enterococci, and gram-negative bacilli and increases in mortality, morbidity, length of hospitalization, and cost of health care. For many patients, inadequate or delayed therapy and severe underlying disease are primarily responsible for the adverse outcomes of infections caused by antimicrobial-resistant organisms. Patients with infections due to antimicrobial-resistant organisms have higher costs (∼$6,000–$30,000) than do patients with infections due to antimicrobial-susceptible organisms; the difference in cost is even greater when patients infected with antimicrobial-resistant organisms are compared with patients without infection. Strategies to prevent nosocomial emergence and spread of antimicrobial-resistant organisms are essential. Awareness of the prevalence of antimicrobial resistance is growing among the medical community and the general public, and the impact of antimicrobial resistance on clinical and economic outcomes is the subject of ongoing investigation. An awareness of the effect of antimicrobial resistance on outcomes has several potential benefits. First, knowledge about the implications of resistance with regard to patient outcomes may prompt hospitals and health care providers to begin and support initiatives to prevent such infections (e.g., infection-control programs and antimicrobial agent management programs). Second, data can be used to influence health care providers to follow guidelines about isolation and to make rational choices with regard to the use of antimicrobial agents. Third, data can guide policy makers who make decisions about the funding of programs to track and prevent the spread of antimicrobial-resistant organisms. Fourth, such knowledge may stimulate interest in developing new antimicrobial agents and therapies. Finally, information Reprints or correspondence: Dr. Sara E. Cosgrove, Div. of Infectious Diseases, The Johns Hopkins Medical Institutions, Osler 425, 600 N. Wolfe St., Baltimore, MD 21287 (). Clinical Infectious Diseases 2006; 42:S82–9  2005 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2006/4202S2-0004$15.00 S82 • CID 2006:42 (Suppl 2) • Cosgrove about resistance may be important in defining the prognosis for individual patients with infection. In the present article, methodological issues that influence the results of studies of antimicrobial resistance outcomes will be acknowledged, and associations between resistance in specific pathogens and adverse outcomes, including increased mortality, length of hospital stay, and cost, will be reviewed. METHODOLOGICAL ISSUES IN STUDIES OF ANTIMICROBIAL RESISTANCE OUTCOMES Various methodological issues can influence the conduct and results of studies of antimicrobial resistance outcomes, as discussed in detail elsewhere [1–3]. The types of outcomes examined, the perspective of the study, the reference groups within the study, adjustments for confounding factors, and the type of economic assessment are among the factors that should be considered (table 1) [2]. With regard to outcomes, morbidity and cost, rather than mortality, may be the most sensitive measures with which to quantify the impact of antimicrobial resistance. The perspective of an outcome study determines the end points measured and affects how the economic impact of infection with resistant organisms is estimated. The cost for individual patients (relevant to the Table 1. Influences on studies assessing the impact of infection with antimicrobial-resistant bacteria. Methodologic issue, factor Outcome Mortality Morbidity Economic Outcome perspective Hospital Third-party payer Patient Societal Aspects In hospital, attributable to infection; in hospital and after discharge, all-cause Length of hospitalization, need for ICU care, need for surgery or other procedures, activity level at discharge, and loss of functional status (loss of work) Hospital costs, hospital charges, resource utilization, total health care costs, skilled nursing, and other outpatient costs Inpatient morbidity, mortality, and/or costs Inpatient and outpatient health care costs Decreased functional status, loss of work, and fewer antimicrobial agent options Total health care costs of antimicrobial resistance and loss of antimicrobial classes Choice of reference group Patients infected with susceptible strains Uninfected patients Patients colonized with resistant strains Confounding factors Length of hospital stay … … … APACHE score, McCabe/Jackson score, and Charlson comorbidity scorea Underlying severity of illness Comorbid conditions … … NOTE. ICU, intensive care unit. Adapted and reprinted with permission from Cosgrove and Carmeli [2]. a APACHE is a severity of disease classification system that uses a point score based on initial values of 12 routine physiologic measurements, age, and previous health status. It is a validated tool to predict mortality for patients in the ICU. The McCabe/Jackson score uses a simple 3-category score to predict mortality for patients with bacteremia due to gram-negative organisms. The Charlson comorbidity score is a simple, readily applicable, and valid method of estimating risk of death from comorbid disease. perspective of the hospital or third-party payers) pales in the face of the societal impact, which was estimated to be in the billions of dollars a decade ago [4]. Some of the most important influences on the patient and society, such as the gradual loss of efficacy of antimicrobial classes, are difficult to measure. It is essential to select the appropriate reference group (i.e., individuals infected with susceptible strains, colonized with resistant strains, or uninfected), control for the length of hospital stay, and adjust for the severity of the underlying illness and comorbidities before infection, because each of those factors can have a significant effect on outcomes measures. OUTCOMES OF INFECTIONS WITH ANTIMICROBIAL-RESISTANT GRAM-POSITIVE PATHOGENS Methicillin-resistant Staphylococcus aureus (MRSA). The impact of methicillin resistance on mortality rates among patients infected with S. aureus has been studied primarily in patients with bacteremia, and results of studies have varied [5– 17]. To further address this issue, we conducted a meta-analysis of studies with relevant mortality data published between 1980 and 2000 [18]. When data from all studies (31 cohort studies including 3963 patients [34% of whom were infected with methicillin-resistant strains]) were pooled with a random-effects model, a significant increase in mortality associated with MRSA bacteremia, relative to methicillin (...truncated)