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Developing Strategies to Prevent Antimicrobial Resistance Marin H Washington University School of Medicine Digital Commons@Becker Open Access Publications 2006 The intensive care unit as a research laboratory: Developing strategies to prevent antimicrobial resistance Marin H. Kollef Washington University School of Medicine in St. Louis Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Kollef, Marin H., ,"The intensive care unit as a research laboratory: Developing strategies to prevent antimicrobial resistance." Surgical infections.7,2. 85-99. (2006). https://digitalcommons.wustl.edu/open_access_pubs/3172 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. SURGICAL INFECTIONS Volume 7, Number 2, 2006 © Mary Ann Liebert, Inc. Surgical Infection Society Twenty-Fifth Annual Altemeier Lecture The Intensive Care Unit as a Research Laboratory: Developing Strategies to Prevent Antimicrobial Resistance MARIN H. KOLLEF ABSTRACT Objective: To assemble the available clinical data on the prevention of antimicrobial resis- tance in the intensive care unit (ICU) setting. Data Source: A MEDLINE database search and references from identified articles were em- ployed to obtain the literature relating to the prevention of antimicrobial resistance in the ICU. Conclusions: The ICU presents a unique environment for the conduct of clinical research. The closed physical space with centralized patient management and efficient data recovery allows important clinical questions to be evaluated in a timely manner. Antimicrobial resis- tance has emerged as an important determinant of mortality for patients in the ICU. Addi- tionally, there is currently a limited pipeline of new agents for the treatment of emerging bac- teria with new resistance genes that pose an increasing threat to the ICU patient. Effective strategies for the prevention of antimicrobial resistance within ICUs are available and should be implemented aggressively. These strategies can be divided into non-pharmacologic infec- tion-control strategies (e.g., routine hand hygiene, infection-specific prevention protocols) and antibiotic management strategies (e.g., shorter courses of appropriate antibiotics, narrowing of the antimicrobial spectrum on the basis of culture results). Additional studies conducted in ICUs are needed urgently to identify the optimal approaches for the management of an- tibiotics in order to balance the need for efficacy with the ability to minimize resistance. NTIMICROBIAL RESISTANCE HAS EMERGED as an tions [4–12]. In many circumstances, particularly Aimportant issue influencing patient mortal- with methicillin-resistant Staphylococcus aureus ity and overall resource utilization in the inten- (MRSA), Enterococcus faecium, and gram-nega- sive care unit (ICU) setting [1–3]. Intensive care tive bacteria producing extended-spectrum units worldwide are faced with increasingly beta-lactamase (ESBL) enzymes with resistance rapid emergence and spread of antibiotic-resis- to multiple other antibiotics, few agents remain tant bacteria. Both gram-negative and gram-pos- for effective treatment [13–20]. itive bacteria resistant to antibiotics are reported Intensive care units are an important area for as important causes of hospital-acquired infec- the emergence of antimicrobial resistance be- Pulmonary and Critical Care Division, Washington University School of Medicine, Barnes Jewish Hospital, St. Louis, Missouri. Presented at the Twenty-Fifth Annual Meeting of the Surgical Infection Society/Second Joint Meeting with the Sur- gical Infection Society–Europe, Miami Beach, Florida, May 5, 2005. 85 86 KOLLEF cause of the frequent use of broad-spectrum an- invasive devices such as endotracheal tubes and tibiotics, the crowding of patients with high intravascular catheters, possibly because of the levels of disease acuity within relatively small formation of biofilms on their surfaces; resi- specialized areas, reductions in nursing and dence in long-term treatment facilities; and in- other support staff because of economic pres- adequate infection control practices [22]. The sures (increasing the likelihood of person-to- emergence of new strains of existing pathogens person transmission of microorganisms), and within the community has created additional the presence of more chronically and acutely ill stressors favoring the entry of resistant mi- patients who require prolonged hospitalization croorganisms into the ICU. This has been and often harbor antibiotic-resistant bacteria demonstrated most recently by the identifica- [2,21,22]. Therefore, it makes sense to employ tion and spread of community-associated me- the ICU as a model for the conduct of clinical thicillin-resistant S. aureus (CA-MRSA) [34,35]. research aimed at curbing or at least minimiz- However, prolonged regimens of antimicrobial ing this problem. Many of the strategies de- agents appear to be the most important factor scribed below have been developed in the ICU promoting the emergence of antibiotic resis- setting but also are applicable in other areas of tance, one that is potentially amenable to inter- the hospital. In general, these interventions vention [36,37]. simply attempt to balance the somewhat-com- peting goals of providing appropriate antimi- crobial treatment to critically ill patients while ANTIBIOTIC RESISTANCE AS A avoiding the unnecessary administration of an- DETERMINANT OF HOSPITAL tibiotics. It is this balance that needs to drive MORTALITY AND HIGHER future clinical research in the area of resistance. HEALTH CARE COSTS The strategies described in this review adhere to the Centers for Disease Control and Preven- Antimicrobial regimens lacking activity tion 12-step program for the prevention of an- against identified microorganisms causing se- timicrobial resistance (http://www.cdc.gov/ rious infections (i.e., inappropriate antimicro- drugresistance/healthcare). One of the key el- bial therapy) are associated with greater hos- ements in this strategy is to consult experts in pital mortality [38–47]. More recently, the same the field of antimicrobial resistance (e.g., infec- finding has been demonstrated for patients tious disease experts, infection control practi- with severe sepsis [48–51]. Unfortunately, tioners, microbiologists) when designing inter- changing antimicrobial therapy to an appro- ventions aimed at minimizing the emergence priate regimen after susceptibility data become of antimicrobial resistance. available does not improve clinical outcomes [40,44,46]. These studies suggest that escalating resistance has led to greater overall hospital ANTIBIOTIC EXPOSURE IS THE MAIN mortality, in part through the administration of RISK FACTOR FOR ANTIMICROBIAL less effective antimicrobial agents. The recent RESISTANCE Infectious Diseases Society of America/Amer- ican Thoracic Society (IDSA/ATS) guidelines A number of investigators have demonstrated for the treatment of ventilator-associated pneu- a close association between the use of antibiotics monia (VAP) emphasize the importance of in- and the emergence of subsequent antibiotic re- appropriate antimicrobial therapy as a de- sistance in both gram-negative and gram-posi- terminant of hospital mortality [52]. These tive bacteria [23–33]. Therefore, strategies aimed guidelines also stress the importance of main- at limiting or modifying the administration of taining local, frequently updated antibiograms antimicrobial agents have the greatest likelihood within individual hospitals and ICUs to ensure of preventing resistance to these agents. Other the appropriateness of antibiotic coverage and factors promoting antimicrobial resistance in- the use of proper drug doses to optimize the clude prolonged hospitalization; the presence of tissue concentrations of antibiotics. TWENTY-FIFTH ANNUAL ALTEMEIER LECTURE 87 In addition to increased hospital mortality, an- WHAT STRATEGIES PREVENT timicrobial resistance is associated with excess ANTIMICROBIAL RESISTANCE? costs. Most of this cost is associated with the ac- quisition of nosocomial infections, many of which Infection control strategies are potentially caused by antibiotic-resistant bac- In general, strategies aimed at the prevention teria [33,53]. However, resistance may actually of nosocomial infections caused by antibiotic- confer added morbidity and costs as well. For ex- resistant bacteria should be employed routinely ample, MRSA infections are associated with in all ICUs (Table 1). These interventions can be worse clinical outcomes than those attributable to separated into two broad categories: Specific in- methicillin-sensitive S. aureus (MSSA). Cosgrove terventions aimed at the primary prevention of et al., in a meta-analysis of 30 investigations fo- nosocomial infections (e.g., catheter-associated cusing on bacteremia, concluded that MRSA bac- bacteremia, VAP) and the use of infection con- teremia independently increased the risk of death trol practices to prevent horizontal transmission [54]. Similarly, Blot et al. observed that the mor- of antibiotic-resistant bacteria. tality difference attributable to MRSA relative to MSSA was approximately 25% [55]. Hand hygiene and protective barriers All of these efforts have been limited by lack of information about two key confounders: Hand hygiene is still the most important Severity of illness and administration of inap- and
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