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II. Background

MDRO definition. For epidemiologic purposes, MDROs are defined as microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents (1). Although the names of certain MDROs describe resistance to only one agent (e.g., MRSA, VRE), these pathogens are frequently resistant to most available antimicrobial agents . These highly resistant organisms deserve special attention in healthcare facilities (2). In addition to MRSA and VRE, certain GNB, including those producing extended spectrum beta-lactamases (ESBLs) and others that are resistant to multiple classes of antimicrobial agents, are of particular concern.1 In addition to Escherichia coli and Klebsiella pneumoniae, these include strains of Acinetobacter baumannii resistant to all antimicrobial agents, or all except imipenem,(6-12), and organisms such as Stenotrophomonas maltophilia (12-14), Burkholderia cepacia (15, 16), and Ralstonia pickettii(17) that are intrinsically resistant to the broadest-spectrum antimicrobial agents. In some residential settings (e.g., LTCFs), it is important to control multidrug-resistant S. pneumoniae (MDRSP) that are resistant to penicillin and other broad-spectrum agents such as macrolides and fluroquinolones (18, 19). Strains of S. aureus that have intermediate susceptibility or are resistant to vancomycin (i.e., vancomycin-intermediate S. aureus [VISA], vancomycin-resistant S. aureus [VRSA]) (20-30) have affected specific populations, such as hemodialysis patients.

Clinical importance of MDROs. In most instances, MDRO infections have clinical manifestations that are similar to infections caused by susceptible pathogens. However, options for treating patients with these infections are often extremely limited. For example, until recently, only vancomycin provided effective therapy for potentially life-threatening MRSA infections and during the 1990's there were virtually no antimicrobial agents to treat infections caused by VRE. Although antimicrobials are now available for treatment of MRSA and VRE infections, resistance to each new agent has already emerged in clinical isolates(31-37). Similarly, therapeutic options are limited for ESBL-producing isolates of gram-negative bacilli, strains of A. baumannii resistant to all antimicrobial agents except imipenem(8-11, 38) and intrinsically resistant Stenotrophomonas sp.(12-14, 39). These limitations may influence antibiotic usage patterns in ways that suppress normal flora and create a favorable environment for development of colonization when exposed to potential MDR pathogens (i.e., selective advantage)(40).

Increased lengths of stay, costs, and mortality also have been associated with MDROs (41- 46). Two studies documented increased mortality, hospital lengths of stay, and hospital charges associated with multidrug-resistant gram-negative bacilli (MDR-GNBs), including an NICU outbreak of ESBL-producing Klebsiella pneumoniae (47) and the emergence of thirdgeneration cephalosporin resistance in Enterobacter spp. in hospitalized adults (48). Vancomycin resistance has been reported to be an independent predictor of death from enterococcal bacteremia(44, 49-53). Furthermore, VRE was associated with increased mortality, length of hospital stay, admission to the ICU, surgical procedures, and costs when VRE patients were compared with a matched hospital population (54). However, MRSA may behave differently from other MDROs. When patients with MRSA have been compared to patients with methicillin-susceptible S. aureus (MSSA), MRSAcolonized patients more frequently develop symptomatic infections(55, 56). Furthermore, higher case fatality rates have been observed for certain MRSA infections, including bacteremia(57-62), poststernotomy mediastinitis(63), and surgical site infections(64). These outcomes may be a result of delays in the administration of vancomycin, the relative decrease in the bactericidal activity of vancomycin(65), or persistent bacteremia associated with intrinsic characteristics of certain MRSA strains (66). Mortality may be increased further by S. aureus with reduced vancomycin susceptibility (VISA) (26, 67). Also some studies have reported an association between MRSA infections and increased length of stay, and healthcare costs(46, 61, 62), while others have not(64). Finally, some hospitals have observed an increase in the overall occurrence of staphylococcal infections following the introduction of MRSA into a hospital or special-care unit(68, 69).

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