The battle with drug-resistant bacteria has evolved into an all-out war in many hospitals, and fighting back with newer drugs no longer seems like the best defensive strategy. Instead, hospitals are deploying multidisciplinary teams to spread the word about prevention through judicious use of antibiotics.
These so-called “antimicrobial stewardship” teams are looking not only at antibiotic use as it relates to a patient's particular disease profile, but also focusing on how the case fits into hospital-wide trends of infection and resistance. The goal is to create an environment in which everyone, from techs to nurses to doctors to pharmacists, takes ownership of the idea that antibiotics should be used judiciously, both for the sake of the patient and the hospital.
“Antimicrobial stewardship is about taking infection control practices and marrying them with appropriate antibiotic use. The two go hand in hand,” said Joseph Alessandrini, a pharmacist who is administrative director for the department of pharmaceutical care and drug information services at South Jersey Healthcare-Regional Medical Center, a community hospital in Vineland, N.J.
Most physicians would agree that overuse of antibiotics is feeding the epidemic of drug-resistance, and studies have shown that upwards of 50% of antimicrobial use is unnecessary or inappropriate. But that doesn't necessarily mean doctors are quick to change.
“The challenge is how do you get physicians to think globally? How do you get them to think about resistance instead of just about their own patient?” said Neil O. Fishman, MD, an infectious disease specialist and director of the antimicrobial stewardship program at the Hospital of the University of Pennsylvania in Philadelphia.
Finding the right fit
Hospitals are learning that they need to find what model of stewardship works best for them. At Temple University Hospital, in Philadelphia, the antibiotic stewardship initiative began as a “point of initiation” approval program that entailed a single contact between the pharmacist and the clinician at the onset of treatment.
Now the program has evolved into a system that involves a case-specific review of antibiotic use, either at day one or day three of an admission, depending on the drug.
Thomas Fekete, FACP, the hospital's chief of infectious diseases and liaison to the stewardship program, said the new approach has fostered a closer relationship between the medical staff and the pharmacy and promotes the hospital's educational mission by allowing for more discussion of patient cases between the clinician and a pharmacist trained in infectious disease.
Under the pre-approval system, he said, doctors learned how to “game the system” to get clearance for antibiotics they were determined to use, and the approval process sometimes was contentious, in part because it required on-the-spot decisions by the pharmacist.
“As time went on, people lost faith in the system,” he said. Now, with the follow-up approach, “it becomes not a confrontation, but a consultation,” with an infectious disease doctor acting as tie breaker if the doctor and the pharmacist can't agree.
There's more opportunity for education between the consulting parties and patient safety has been enhanced by an emphasis on adjusting drug dosing and duration, Dr. Fekete said. The aim isn't to achieve a specific ratio of antibiotics or to put a cap on a given drug, he said. Rather, “the idea is that we don't want to undertreat and we don't want to overtreat. We want to hit just the right sweet spot.” For instance, if an isolate for E. coli is found to be susceptible to ampicillin, the patient likely would be taken off cefepime, a broader agent.
Premier Inc., a quality and cost-improvement alliance of about 2,000 U.S. hospitals, offers members a Web-based tracking tool called SafetySurveillor, which provides alerts on lab results, keeps tabs on infection and prescribing trends, and helps simplify the job of reporting infection- related data to government entities and others. “Software like this is bringing people together throughout the hospital to think collaboratively about solutions,” sand Salah Qutaishat, PhD, an epidemiologist and Premier's director of infection prevention.
The University of Wisconsin Hospital and Clinics uses the Premier system to flag cases that warrant a closer look, said Sarah Bland, senior clinical pharmacist. Each day, Ms. Bland gets a report of about 75 cases in which antimicrobial orders need to be evaluated for appropriateness, whittles it down to 10 to 15 cases that require more information and then talks to pharmacists and doctors on the wards.
Among the cases where she has intervened:
- Antibiotics that have run longer than needed for a given condition. For example, 14 days of antibiotics ordered for hospitalacquired pneumonia not caused by Pseudomonas aeruginosa.
- Antibiotics that are either too broad or not effective against the identified organism. For example, piperacillin-tazobactam (Zosyn) prescribed to treat Haemophilus influenzae (too broad) or Stenotrophomonas maltophilia (doesn't cover it).
- The use of multiple antibiotics when one will suffice. For example, tigecycline (Tygacil) can be used to treat polymicrobial infections.
“Physicians know we're not just there to play ‘gotcha.’ We're there to provide help for the patient,” Ms. Bland said. “We don't tell doctors what to do, but we say, ‘From an infectious disease perspective, this is something you should think about.’” While her hospital's stewardship efforts aren't strictly financially driven, they are paying off. Expenditures on anti-infective drugs went from $183.26 per admission in fiscal year 2005 to a projected $159.53 in fiscal January 2009, a decline of nearly 13%.
The University of Pennsylvania's antimicrobial stewardship program, started in 1992, includes representatives from pharmacy, microbiology lab, infectious diseases and epidemiology. It also maintains an up-to-date Web site relating to antibiotic guidelines, and operates a call-in system, staffed by clinical pharmacists in the day and infectious disease fellows in the evening, for cases in which an antibiotic needs to be preapproved.
Dr. Fishman said his team intervenes in about 80% of the calls it gets, which leads to more appropriate use of antibiotics, better infection cure rates and fewer unwanted side effects. The hospital saved about $302,000 on antibiotics in one year alone, $533,000 on infection-related expenses and $4.25 million in total costs, mostly because patients spent less time in the ICU.
“We have built a level of credibility with the staff, and we have data to show that patients do better,” Dr. Fishman said. “We've always tried to keep this a positive thing. We all have the goal of providing quality care to patients and improving clinical outcomes.”
Feeling their way
There has been little research on whether antibiotic stewardship programs can limit the growth of resistance, though some early promising reports have emerged from small studies and in-house reviews.
Guidelines published in January 2007 by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America offer a framework for a stewardship program, including assembling a multidisciplinary team that includes experts from infectious disease, pharmacy and microbiology. The guidelines also focus on the potential benefits of formulary restriction, preauthorization requirements, antimicrobial order forms and physician feedback mechanisms, and the importance of measuring outcomes.
In addition, the guidelines call for more research to prove what methods work best to reduce resistance. “A lot of what is being done is not evidence-based. I don't think we have the perfect formula and one size does not fit all,” said Henry Blumberg, FACP, professor of medicine (division of infectious diseases) and epidemiology at Emory University School of Medicine and hospital epidemiologist at Grady Memorial Hospital in Atlanta.
One area where hospitals have seen some success is in dealing with Methicillin-resistant Staphylococcus aureus (MRSA), but there are plenty of other worries, including Clostridium difficile, which is showing up as a more resistant and virulent strain requiring the use of vancomycin, traditionally considered a lastresort antibiotic.
A study presented in November 2008 at a meeting of the Association for Professionals in Infection Control and Epidemiology concluded that on a typical day in U.S. hospitals, 13 of every 1,000 patients are either colonized or infected with C. diff, with infections often happening as a result of other antibiotic treatment. Researchers said that rate was higher than some previous studies had shown.
Gram-negative organisms also are proving formidable. According to CDC testimony to Congress in June 2008, “a small but growing subset of the gram-negative bacterial strains that cause healthcare-associated infections, like Acinetobacter baumannii and Pseudomonas aeruginosa, have become resistant to all available antimicrobial agents.”
While stewardship proponents preach the need for more judicious use of antimicrobials, new data suggests there is much work to be done.
A study published in November 2008 in Archives of Internal Medicine found that antibiotic use in adult patients at a consortium of 35 university teaching hospitals rose 7% from 2002 to 2006, with the acceleration driven by more use of broad-spectrum agents and vancomycin. There was a 59% increase in carbapenem use and an 84% increase in the use of piperacillintazobactam during the five-year period.
Many of the hospitals surveyed had an antimicrobial stewardship program, but the study did not detect significantly lower use of broad-spectrum agents at those centers. The study was not designed to look at the impact of stewardship programs, so it's possible there was an effect that wasn't measured. However, the study's authors are still convinced that the programs can have an effect.
“With few new antibacterials in development, antimicrobial stewardship programs in concert with aggressive infection control efforts represent the best chance for control of resistant pathogens,” the study concluded.
Study co-author Ronald E. Polk, chair of the department of pharmacy at Virginia Commonwealth University's School of Pharmacy, said the results illustrate the spiraling effect occurring in hospitals: The increasing presence of resistant organisms leads to increasing use of broad-spectrum antibiotics, which in turn leads to more resistance problems. Dr. Polk said more research is needed to identify optimal antimicrobial use, including whether the drugs can be given for fewer days without compromising patient care.
“The sad secret is that for most infectious diseases we don't know the optimal duration of therapy,” he said.