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President Obama’s recent proposal to nearly double funding for antibiotic resistance programs to $1.2 billion in the 2016 federal budget confirms that the battle against “superbugs” is indeed moving up the government agenda.
GoldsteinPresident Obama’s recent proposal to nearly double funding for antibiotic resistance programs to $1.2 billion in the 2016 federal budget confirms that the battle against “superbugs” is indeed moving up the government agenda. Clearly, there is greater awareness of the serious implications of antibiotic resistance for public health.
Antibiotic resistance is now seen in all parts of the world and threatens the effective prevention and treatment of an ever-increasing range of common infectious diseases as well as the more complicated infections. The development of some resistance should be no surprise, of course, as it occurs naturally as microorganisms replicate and, through horizontal gene transfer, is able to mobilize any resistance gene. The ongoing use and misuse of antibiotics, however, accelerates the emergence of drug-resistant strains. Add this phenomenon to poor infection control and suboptimal sanitary conditions, and you have a potent recipe for the development of multidrug-resistant bacteria-the so-called superbugs.
Related: Optimize antibiotic stewardship
According to the World Health Organization, it’s no longer alarmist to warn that without urgent, coordinated action, the world is heading toward a postantibiotic era in which common infections and minor injuries, treatable for decades, can once again kill.1 In the United States alone, the Centers for Disease Control and Prevention (CDC) estimates that each year at least 2 million individuals acquire serious infections with bacteria that are now resistant to 1 or more antibiotics designed specifically to treat those infections. Annually, at least 23,000 die as a direct result of resistant bacteria, but many more die from other conditions that arise from an antibiotic-resistant infection.2
Antibiotic resistance imposes considerable costs on the already overburdened healthcare system. Estimates vary, but in 2008 dollars, excess direct healthcare costs may be as high as $20 billion, with up to $35 billion in additional costs for lost productivity due to hospitalizations and sick days.2
Published in September 2014, the report by the President’s Council of Advisors on Science and Technology (PCAST) sets out practical steps that the US government should take to bring the antibiotic-resistance crisis under control. The report includes recommendations for stronger federal coordination and oversight, effective surveillance, and basic and clinical research. PCAST also advocates that, by the end of 2017, federal regulations should require US hospitals, critical access hospitals, and long-term care and nursing home facilities to develop and implement robust antibiotic stewardship programs (ASPs) consistent with best clinical practices.3
Antibiotics are prescribed for the majority of patients hospitalized in US acute care hospitals, presumptively to treat infections. Alarmingly, 30% to 50% of these prescriptions may be inappropriate mainly because they are unnecessary or have incorrect antibiotic dosing or duration of therapy.4 By reducing unnecessary and inappropriate antibiotic use and promoting optimal therapy, ASPs are a key weapon against the growing threat of antibiotic resistance and have been clearly shown to improve clinical outcomes, including reductions in mortality.5
The National Foundation for Infectious Diseases offers a wealth of information and guidance for formulary managers responsible for delivering ASPs in their facilities.6 However, it’s also valuable to “show and tell,” in other words, to share practical lessons with colleagues about their frontline experiences of ASPs. Where better to do this than at Infectious Diseases Week (IDWeek).
Each year, IDWeek brings together the expertise of members of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Antibiotic resistance and ASPs were key topics at IDWeek 2014 in Philadelphia, with more than 300 reports of clinical experience not only from the United States but also from the rest of the world. There were, however, some overarching predominant themes.
When used as part of an ASP, de-escalation of antibiotic therapy can reduce inappropriate antibiotic use, cost, and adverse events. Other possible benefits of shortened antimicrobial treatment include a lower risk for superinfections, antimicrobial-related organ toxicity, and improved regimen compliance. De-escalation is often implemented with clinical-decision-support system (CDSS) software, but resource limitations may mean that some community hospitals must implement ASPs without this type of support.
Lisa Dumkow, PharmD (Grand Rapids, Mich.), described the first 6 months of an ASP in a 280-bed community teaching hospital that used a daily computer-generated list of all patients receiving antimicrobials.7 Over the course of the study, an infectious disease-trained pharmacist reviewed about 7,500 charts and recommended 1,600 interventions, 90% of which were accepted by physicians. The most common interventions were de-escalation/discontinuation, followed by conversion from intravenous to oral administration, and dose optimization. During implementation, carbapenem and levofloxacin utilization declined by 64% and 49%, respectively, and Clostridium difficile infections fell by one third.
After the first 3 days of antibiotic therapy, the CDC advocates a time out (TO) to review the need for continued treatment once clinical microbiologic data become available. Matthew Bidwell Goetz, MD (Los Angeles), reported the impact of a TO program in which physicians in acute medical wards and surgical and medical intensive care units used a self-guided, decision-support system to gain reapproval for vancomycin and piperacillin/tazobactam therapy.8
Self-approval resulted in a 13% decline in vancomycin use but no significant change in use of piperacillin/tazobactam. Prior policy at the facility required reapproval by the antibiotic stewardship team. These results show how engaging physicians in TO reviews within an ASP can help to further optimize in-hospital antibiotic prescribing.
As part of ASPs, auto-stop features in electronic health records (EHR) enable mandatory removal of an antibiotic from the current medications list after completion of the approved length of therapy. The clinical impact of the EHR-based auto-stop feature for antibiotic prescribing at Children’s Hospital of Philadelphia was described by Rachael Ross, MPH (Philadelphia).9
With 4 years’ experience of auto-stop in 26,300 patients, there were no changes in hospital all-cause mortality, length of stay, or readmission rates at 14 and 30 days. There were, however, no negative clinical effects. Further studies are needed to examine the effects of EHR-based auto-stop on antimicrobial use. The study did not evaluate the impact on pharmacy workload of removing the need to approve further medication under restricted antibiotic orders that remained after expiry of ASP-approved length of therapy in the hospital’s previous system.
Care bundles aim to provide a systematic method to improve and monitor the delivery of clinical care processes by grouping together key elements of care for procedures and the management of specific diagnoses. The Institute for Healthcare Improvement’s 100K Lives Campaign, launched in 2004, consists of 6 care bundles. Three address the need to reduce the rate of hospital-acquired infections, but none include the role of ASPs.
Speaking during an IDWeek symposium, Elizabeth Dodds-Ashley, PharmD (Rochester, New York), underlined that ASPs are an indispensable component of the bundle approach because they foster a multidisciplinary perspective and incorporation of evidence-based guidelines.10 In particular, targeted antibiotic stewardship within a care bundle approach can deliver more rapid and more appropriate antibiotic therapy within hospitals.
To optimize antibiotic prescribing, the ASP team needs both recent local susceptibility data and long-term studies to track resistance trends. The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a global surveillance study initiated by Merck in 2002. It is designed to monitor trends in the in vitro susceptibility to 12 commonly used antibiotics. With more than 170 sites, including 20 in the United States, SMART is one of the world’s largest programs for tracking trends in antibiotic resistance.11
SMART data presented by Robert Badal (Kenilworth, New Jersey) highlight the value of susceptibility data in guiding more informed antibiotic selection. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli rates and susceptibility were monitored from intra-abdominal infections in the Untied States, Canada, and Mexico from 2009 to 2013. ESBL+ E. coli rates are highest and continuing to rise significantly in Mexico (40%–59%), but are also increasing significantly in the US (from 6%–12%) and Canada (9%–11%). In 2013, only amikacin, ertapenem, and imipenem demonstrated greater than 90% susceptibility rates in all 3 countries. These findings suggest that the United States and its neighbors must exert continued efforts, such as restricting quinolone use, to contain the expansion of ESBL+ E. coli.12
The major thrust of IDWeek 2014 was to provide clinical evidence and guidance from infectious disease experts to help formulary managers and their colleagues to maximize ASP development and implementation. Pharmacy professionals will also need long-term studies to track resistance trends, however, along with local susceptibility data to optimize antibiotic prescribing by physicians. In the meantime, the message from IDWeek in Philadelphia is that implementation of an ASP offers health facilities the opportunity not only to stem antibiotic resistance and improve patient outcomes but also to lower treatment costs. ASPs may be one significant option to turn the tide of antibiotic resistance and improve the effective prevention and treatment of an ever-increasing range of common infectious diseases as well as the more complicated infections.
1. World Health Organization. Antimicrobial resistance: global report on surveillance 2014. http://www.who.int/drugresistance/documents/surveillancereport/en/. Accessed February 17, 2015.
2. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf. Accessed February 17, 2015.
3. Executive Office of the President. President’s Council of Advisors on Science and Technology. Report to the President on combating antibiotic resistance. September 2014.
. Accessed February 17, 2015.
4. Fridkin S, Baggs J, Fagan R, et al; Centers for Disease Control and Prevention. Vital signs: improving antibiotic use among hospitalized patients. MMWR Morb Mortal Wkly Rep. 2014;63(9):194–200.
5. Rosa RG, Goldani LZ, dos Santos RP. Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort study. BMC Infect Dis. 2014;14:286.
6. National Foundation for Infectious Diseases. Antimicrobial resistance. http://www.nfid.org/links/antimicrobial-resistance. Accessed February 17, 2015.
7. Dumkow L, Galang M, Egwuatu N. Early impact of a pharmacist-led antimicrobial stewardship program conducted without clinical decision-support software at a community teaching hospital. Abstract 611 presented at: IDWeek 2014; October 8-12; Philadelphia, PA.
8. Jones M, Graber C, Butler J, et al. Decreased vancomycin use after implementation of a decision support program for antibiotic time outs. Abstract 1328 presented at: IDWeek 2014; October 8-12; Philadelphia, PA.
9. Ross R, Metjian TA, Beus J, et al. Impact of an antimicrobial order auto-stop on clinical outcomes at a single institution. Abstract 1329 presented at: IDWeek 2014; October 8-12; Philadelphia, PA.
10. Dodds-Ashley E. Bundles – combining stewardship with processes from other disciplines to optimize effect. Symposium: antimicrobial stewardship-the latest trends and opportunities. Presentation 546 at: IDWeek 2014; October 8-12; Philadelphia, PA.
11. Morrissey I, Hackel M, Badal R, et al. A review of ten years of the Study for Monitoring Antimicrobial Resistance Trends (SMART) from 2002 to 2011. Pharmaceuticals (Basel). 2013;6(11):1335–1346.
12. Badal R, Lob S, Hackel M, et al. Comparison of ESBL rates and susceptibility of E. coli from IAI in the USA, Canada, and Mexico 2009-2013. Abstract 417 presented at: ID Week 2014; October 8-12; Philadelphia, PA.
Dr Goldstein is the director of R.M. Alden Research Laboratory, a Clinical Professor of Medicine at UCLA School of Medicine and Clinical Section Editor for Clinical Infectious Diseases