Hospital-Based Strategies for Combating Resistance

Robert C. Owens Jr. 1 2 Louis Rice .) 0 0 Medical Service, Louis Stokes Cleveland Veterans Affairs Medical Center , Cleveland, Ohio 1 Departments of Infectious Diseases and Clinical Pharmacy, Maine Medical Center , Portland 2 Department of Medicine, University of Vermont College of Medicine , Burlington Selective pressures generated by the indiscriminate use of b-lactam antibiotics have resulted in increased bacterial resistance across all b-lactams classes. In particular, the use of third-generation cephalosporins has been associated with the emergence of extended-spectrum b-lactamase-producing and AmpC b-lactamaseproducing Enterobacteriaceae and vancomycin-resistant enterococci. Conversely, b-lactams (e.g., cefepime, piperacillin-tazobactam, and ampicillin-sulbactam) have not demonstrated such strong selective pressures. Chief among institutional strategies to control outbreaks of multidrug-resistant bacteria are infection-control measures and interventional programs designed to minimize the use of antimicrobial agents that are associated with strong relationships between use and resistance. Successful programs include antimicrobial stewardship programs (prospective audit and feedback), formulary interventions (therapeutic substitutions), formulary restrictions, and vigilant infection control. Fourth-generation cephalosporins, such as cefepime, have proven to be useful substitutes for third-generation cephalosporins, as a part of an overall strategy to minimize the selection and impact of antimicrobial-resistant organisms in hospital settings. - The management of nosocomial infections has become an urgent health care priority. Hospital-acquired infections cause increases in mortality, morbidity, and length of hospital stay and have an enormous impact on health care costs. By one estimate, the average excess cost attributable to each such infection is 1$15,000 [1]. An increasing number of nosocomial infections are due to multidrug-resistant pathogens that may require the use of more expensive agents or may be treatable only with relatively toxic agents. The cost burden is further aggravated by such pathogens, because hospital stays are generally longer for patients with infections caused by resistant organisms [2]. Controlling the development and spread of multidrug-resistant bacteria in the hospital setting requires a combination of approaches that need to be applied in a disciplined and coordinated manner. This review will discuss selected experiences, as reported in the medical literature, of hospitals and health care facilities that have confronted the problems associated with nosocomial drug-resistant pathogens. The relative merits of hospital-based strategies for controlling outbreaks of resistant organisms and for treating the infections that they cause will also be discussed. A particular emphasis will be placed on approaches to the prevention and management of infections caused by extended-spectrum b-lactamase (ESBL)producing and AmpC b-lactamaseproducing bacteria. THE IMPORTANCE OF INFECTIONCONTROL MEASURES In general, antimicrobial resistance develops from a confluence of factors: failures of institutional hygiene; enhancement of resistance mechanisms in well-established clones through gene-capture genetic units, such as plasmids, integrons, or transposons; and facilitation of the coselective process under different selective pressures [3, 4]. At least one-third of all nosocomial infections, whether caused by susceptible or resistant pathogens, are thought to be preventable through infection-control programs [5]. In cases in which isolation precautions for controlling the dissemination of multidrug-resistant bacteria have been established, compliance may nevertheless be poor, which undermines the usefulness of such measures. A study in a Paris university hospital [6] found that, in general, caregivers poorly adhered to infection-control practices aimed at containing multidrug-resistant bacteria and that physicians wrote isolation orders for only 4 of 10 patients who required such measures. Personnel were also notably deficient in complying with hand-washing guidelines and with proper glove and gown use. High rates of patient transfer between units and between hospitals may intensify an outbreak of resistant bacteria [7]. However, initiating barrier precautions to contain the spread of resistant organisms often is not practical for hospitals that must contend with a highly mobile patient population. A study of risk factors for colonization with ESBL-producing Escherichia coli and Klebsiella species found that the duration of hospitalization was the only independent risk factor for colonization with these organisms [8]. It was also noted that a large proportion of colonized patients had been admitted from another health care facility. Interhospital transmission of resistant bacteria was demonstrated in a study of 15 hospitals in Brooklyn, New York [9]. Isolates of Acinetobacter baumannii and Pseudomonas aeruginosa were collected from the hospitals over the course of a 3month period in 1999. A high proportion of A. baumannii isolates were multidrug resistant. Ribotyping revealed that a single clone accounted for 160% of the A. baumannii isolates, which were recovered from patients at all 15 hospitals. For P. aeruginosa, 3 clones accounted for nearly half of the multidrugresistant isolates and were shared by most hospitals. In another report of clonal dissemination of a resistant pathogen, a hospital in Italy identified P. aeruginosa containing a metallo-b-lactamase gene; the strains appeared to be clonally related [10]. Transmission of resistance to broad-spectrum b-lactams does not occur solely by migration of a single clone. In Japan, an outbreak of metallo-b-lactamaseproducing P. aeruginosa resistant to broad-spectrum b-lactams and carbapenems was found to have proliferated multifocally, by plasmid-mediated dissemination of the metallo-b-lactamase gene in pseudomonal strains of different genetic backgrounds [11]. On the basis of this and other evidence, the interhospital spread of resistant strains emphasizes why control measures aimed at suppressing the emergence of such strains are not merely the responsibility of a single hospital or localized group of medical centers [12]. In addition to large hospitals with mobile populations, long-term care facilities are another high-risk environment for bacteria with multidrug resistance. For residents in a skilled-care unit, Trick et al. [13] determined the frequency of and risk factors for colonization with several antimicrobialresistant bacterial species. Approximately 1 of 4 residents who were culture positive for a resistant bacterial species also was cocolonized by 11 resistant species. Risk factors for colonization varied by pathogen, with total dependence on health S174 CID 2006:42 (Suppl 4) Owens, Jr. and Rice care workers being a specific risk factor for colonization with ESBL-producing Klebsie (...truncated)