Neil O. Fishman

Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship

Timothy H. Dellit, Robert C. Owens, John E. McGowan, Jr., Dale N. Gerding, Robert A. Weinstein, John P. Burke, W. Charles Huskins, David L. Paterson, Neil O. Fishman, Christopher F. Carpenter, P. J. Brennan, Marianne Billeter, and Thomas M. Hooton Harborview Medical Center and the University of Washington, Seattle; Maine Medical Center, Portland; Emory University, Atlanta, Georgia; Hines Veterans Affairs Hospital and Loyola University Stritch School of Medicine, Hines, and Stroger (Cook County) Hospital and Rush University Medical Center, Chicago, Illinois; University of Utah, Salt Lake City; Mayo Clinic College of Medicine, Rochester, Minnesota; University of Pittsburgh Medical Center, Pittsburgh, and University of Pennsylvania, Philadelphia, Pennsylvania; William Beaumont Hospital, Royal Oak, Michigan; Ochsner Health System, New Orleans, Louisiana; and University of Miami, Miami, Florida

Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae: Risk Factors for Infection and Impact of Resistance on Outcomes

The prevalence of antibiotic resistance among extended-spectrum beta-lactamase (ESBL)--producing Escherichia coli and Klebsiella pneumoniae has increased markedly in recent years. Thirty-three patients with infection due to ESBL-producing E. coli or K. pneumoniae (case patients) were compared with 66 matched controls. Total prior antibiotic use was the only independent risk factor for ESBL-producing E. coli or K. pneumoniae infection (odds ratio, 1.10; 95% confidence interval, 1.03--1.18; P=.006). Case patients were treated with an effective antibiotic a median of 72 hours after infection was suspected, compared with a median of 11.5 hours after infection was suspected for controls (P<.001). ESBL-producing E. coli or K. pneumoniae infection was associated with a significantly longer duration of hospital stay and greater hospital charges (P=.01 and P<.001, respectively). Finally, many ESBL-producing E. coli and K. pneumoniae isolates were closely related. ESBL-producing E. coli and K. pneumoniae infections have a significant impact on several important clinical outcomes, and efforts to control outbreaks of infection with ESBL-producing E. coli and K. pneumoniae should emphasize judicious use of all antibiotics as well as barrier precautions to reduce spread.

Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

Policy Statement on Antimicrobial Stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS)

Antimicrobial resistance has emerged as a significant healthcare quality and patient safety issue in the twenty-first century that, combined with a rapidly dwindling antimicrobial armamentarium, has resulted in a critical threat to the public health of the United States. Antimicrobial stewardship programs optimize antimicrobial use to achieve the best clinical outcomes while minimizing adverse events and limiting selective pressures that drive the emergence of resistance and may also reduce excessive costs attributable to suboptimal antimicrobial use. Therefore, antimicrobial stewardship must be a fiduciary responsibility for all healthcare institutions across the continuum of care. This position statement of the Society for Healthcare Epidemiology of America, the Infectious Diseases Society of America, and the Pediatric Infectious Diseases Society of America outlines recommendations for the mandatory implementation of antimicrobial stewardship throughout health care, suggests process and outcome measures to monitor these interventions, and addresses deficiencies in education and research in this field as well as the lack of accurate data on antimicrobial use in the United States.

Epidemiological Investigation of Fluoroquinolone Resistance in Infections Due to Extended-Spectrum β-Lactamase—Producing Escherichia coli and Klebsiella pneumoniae

The incidence of infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) has increased markedly in recent years. Treatment is difficult because of frequent multidrug resistance. Although fluoroquinolones offer effective therapy for ESBL-EK infections, their usefulness is threatened by increasing fluoroquinolone resistance. To identify risk factors for fluoroquinolone resistance in ESBL-EK infections, a case-control study of all patients with ESBL-EK infections from 1 June 1997 through 30 September 1998 was conducted. Of 77 ESBL-EK infections, 43 (55.8%) were resistant to fluoroquinolones. Independent risk factors for fluoroquinolone resistance were fluoroquinolone use (odds ratio [OR], 11.20; 95% confidence interval [CI], 1.99-63.19), aminoglycoside use (OR, 5.83; 95% CI, 1.12-30.43), and long-term care facility residence (OR, 3.39; 95% CI, 1.06-10.83). The genotypes of fluoroquinolone-resistant ESBL-EK isolates were closely related. Efforts should be directed at modification of these risk factors to preserve the utility of fluoroquinolones in the treatment of ESBL-EK infections.

Risk Factors and Clinical Impact of Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae

BACKGROUND Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is an emerging pathogen with serious clinical and infection control implications. To our knowledge, no study has specifically examined risk factors for KPC-producing K. pneumoniae or its impact on mortality. METHODS To identify risk factors for infection or colonization with KPC-producing K. pneumoniae, a case-control study was performed. Case patients with KPC-producing K. pneumoniae were compared with control subjects with carbapenem-susceptible K. pneumoniae. A cohort study evaluated the association between KPC-producing K. pneumoniae and in-hospital mortality. RESULTS Fifty-six case patients and 863 control subjects were identified. In multivariable analysis, independent risk factors for KPC-producing K. pneumoniae were (1) severe illness (adjusted odds ratio [AOR], 4.31; 95% confidence interval [CI], 2.25-8.25), (2) prior fluoroquinolone use (AOR, 3.39; 95% CI, 1.50, 7.66), and (3) prior extended-spectrum cephalosporin use (AOR, 2.55; 95% CI, 1.18, 5.52). Compared with samples from other anatomic locations, K. pneumoniae isolates from blood samples were less likely to harbor KPC (AOR, 0.33; 95% CI, 0.12, 0.86). KPC-producing K. pneumoniae was independently associated with in-hospital mortality (AOR, 3.60; 95% CI, 1.87-6.91). CONCLUSIONS KPC-producing K. pneumoniae is an emerging pathogen associated with significant mortality. Our findings highlight the urgent need to develop strategies for prevention and infection control. Limiting use of certain antimicrobials, specifically fluoroquinolones and cephalosporins, use may be effective strategies.

Clinical and Microbiological Outcomes of Serious Infections with Multidrug-Resistant Gram-Negative Organisms Treated with Tigecycline

Eighteen patients received tigecycline as treatment for infection due to multidrug-resistant gram-negative bacilli, including Acinetobacter baumannii and Klebsiella pneumoniae carbapenemase- and extended-spectrum beta-lactamase-producing Enterobacteriaceae. Pretherapy minimum inhibitory concentration values for tigecycline predicted clinical success. Observed evolution of resistance during therapy raises concern about routine use of tigecycline in treatment of such infections when other therapies are available.

Impact of a Hospital-Based Antimicrobial Management Program on Clinical and Economic Outcomes

Inappropriate use of antimicrobial agents results in unnecessary exposure to medication, persistent or progressive infection, emergence of resistance, and increased costs. We implemented a program to control use of restricted agents while improving care. This study compared 2 major mechanisms for improving use of antimicrobial agents: (1) recommendations made by the Antimicrobial Management Team (AMT), which included a clinical pharmacist backed up by a physician from the Division of Infectious Diseases (ID), and (2) recommendations made by ID fellows. Outcome measures included appropriateness of recommendations, cure rate, number of treatment failures, and cost of care, which were assessed for 180 patients. The AMT outperformed the ID fellows in all outcomes examined by the study (including appropriateness [87% vs. 47%; P<.001], cure rate [64% vs. 42%; P=.007], and treatment failures [15% vs. 28%; P=.03]), although the differences in economic outcomes between cases managed by the AMT and those managed by the ID fellows were not statistically significant. In an academic setting with a restricted formulary, the AMT demonstrated better antimicrobial prescribing than ID fellows.

Discovery research: the scientific challenge of finding new antibiotics

The dwindling supply of new antibiotics largely reflects regulatory and commercial challenges, but also a failure of discovery. In the 1990s the pharmaceutical industry abandoned its classical ways of seeking antibiotics and instead adopted a strategy that combined genomics with high-throughput screening of existing compound libraries. Too much emphasis was placed on identifying targets and molecules that bound to them, and too little emphasis was placed on the ability of these molecules to permeate bacteria, evade efflux and avoid mutational resistance; moreover, the compound libraries were systematically biased against antibiotics. The sorry result is that no antibiotic found by this strategy has yet entered clinical use and many major pharmaceutical companies have abandoned antibiotic discovery. Although a raft of start-up companies-variously financed by venture capital, charity or public money--are now finding new antibiotic compounds (some of them very promising in vitro or in early trials), their development through Phase III depends on financial commitments from large pharmaceutical companies, where the discouraging regulatory environment and the poor likely return on investment remain paramount issues.

Systematic Review and Cost Analysis Comparing Use of Chlorhexidine with Use of Iodine for Preoperative Skin Antisepsis to Prevent Surgical Site Infection

OBJECTIVE To compare use of chlorhexidine with use of iodine for preoperative skin antisepsis with respect to effectiveness in preventing surgical site infections (SSIs) and cost. METHODS We searched the Agency for Healthcare Research and Quality website, the Cochrane Library, Medline, and EMBASE up to January 2010 for eligible studies. Included studies were systematic reviews, meta-analyses, or randomized controlled trials (RCTs) comparing preoperative skin antisepsis with chlorhexidine and with iodine and assessing for the outcomes of SSI or positive skin culture result after application. One reviewer extracted data and assessed individual study quality, quality of evidence for each outcome, and publication bias. Meta-analyses were performed using a fixed-effects model. Using results from the meta-analysis and cost data from the Hospital of the University of Pennsylvania, we developed a decision analytic cost-benefit model to compare the economic value, from the hospital perspective, of antisepsis with iodine versus antisepsis with 2 preparations of chlorhexidine (ie, 4% chlorhexidine bottle and single-use applicators of a 2% chlorhexidine gluconate [CHG] and 70% isopropyl alcohol [IPA] solution), and also performed sensitivity analyses. RESULTS Nine RCTs with a total of 3,614 patients were included in the meta-analysis. Meta-analysis revealed that chlorhexidine antisepsis was associated with significantly fewer SSIs (adjusted risk ratio, 0.64 [95% confidence interval, [0.51-0.80]) and positive skin culture results (adjusted risk ratio, 0.44 [95% confidence interval, 0.35-0.56]) than was iodine antisepsis. In the cost-benefit model baseline scenario, switching from iodine to chlorhexidine resulted in a net cost savings of