Antibiotic Stewardship Curbs Microbe Resistance, Saves Money

Daniel M. Keller, PhD

October 27, 2011

October 27, 2011 (Boston, Massachusetts) — In one of the longest-running antibiotic stewardship programs (ASPs), researchers have observed a direct correlation between antibiotic usage and susceptibility of pathogens to antimicrobial drugs, with better susceptibility accompanying lower drug use, Derick Gross, PharmD, a clinical pharmacist in adult medicine at the 760-bed tertiary care Wesley Medical Center (WMC) in Wichita, Kansas, told poster session attendees here at the Infectious Diseases Society of America (IDSA) 49th Annual Meeting.

Dr. Gross said no published study has reported on the effects of an ASP on antibiotic usage and pathogen susceptibilities for as long as theirs. "We've had our stewardship program since 1993. It's always been a multidisciplinary program, very consistent with current IDSA guidelines, which were released in 2007 as far as being multidisciplinary [with] prospective audits."

The WMC ASP team consists of an infectious disease physician, a full-time pharmacist, microbiology laboratory services, and infection prevention and involves all the hospital physicians as well.

When the program began in 1993, and after discussions with infectious disease physicians, pharmacists made therapy recommendations, including intravenous (IV) to oral (PO) conversions, drug substitution, broadening or narrowing coverage, length of therapy, and dose optimization.

By 2000, the medical center had hired a pharmacist trained in infectious disease and had automatic IV to PO conversions and automatic formulary therapeutic substitutions performed by the pharmacist. Currently, there are automatic renal dose adjustments of antibiotics, automatic discontinuation of postoperative prophylaxis at 24 hours (48 hours for cardiac surgery), and no formulary restrictions or any antibiotic preauthorization required.

In this retrospective observational study using susceptibility data from WMC antibiograms and antibiotic usage data from pharmacy records covering 1993 to 2009, Dr. Gross and coworkers found that the proportion of the pharmacy budget dedicated to antibiotic purchases decreased from 22% in the year before the ASP began to 14% in the first year of the program and remained relatively stable over the years despite fluctuations in drug costs and availability.

Stewardship Leads to Improved Antibiotic Susceptibilities

The researchers observed direct correlations between antibiotic usage and susceptibilities. "In some cases we saw dramatic improvements in susceptibilities associated with decreases in usage, and other times we just saw consistent susceptibilities associated with consistent usage," Dr. Gross said. "In some cases we saw gradual changes. In other cases, for example with gentamicin and Pseudomonas aeruginosa, we saw very abrupt changes. As we decreased usage we saw almost that exact same year improvements in susceptibilities."

In 2003, only 66% of Pseudomonas aeruginosa isolates were susceptible to gentamicin, but by 2009 susceptibility had risen to 92%. At the same time, P aeruginosa susceptibility to ceftazidime increased from 68% to 90%. These decreases in resistance mirror a reduction in the use of these drugs.

The majority of these isolates remained highly susceptible to tobramycin and piperacillin-tazobactam (88% of isolates or greater). Total use of fluoroquinolones remained steady over the period of observation, and so did the susceptibility of P aeruginosa to these drugs.

Similar increases in susceptibility of Escherichia coli and Klebsiella pneumonia to ampicillin-sulbactam occurred over the same period, in concert with decreased usage of the drug combination. E coli and K pneumoniae showed minimal resistance, with only rare occurrences of extended-spectrum β-lactamase–producing isolates (less than 1%). Susceptibilities of these organisms to other antibiotics were similar over the course of the study.

The ASP has saved money in terms of the percentage of the pharmacy budget going for antibiotics. In the last year of the pre-ASP period, 1992, the proportion was 22%, dropping to 14% in 1993, and gradually decreasing each year through 2006, when it was 9.8%. Between 2007 and 2009, the proportion spent on antibiotics has ranged from 9.2% to 12.1%.

The authors said that this study provides the first long-term data on the effectiveness of an ASP. With few novel antimicrobial agents in the pipeline and in an era of cost containment, they concluded that antibiotic stewardship can be an effective tool against antibiotic resistance and can save pharmacy costs at the same time.

Coauthor Mandelin Cooper, PharmD, also from WMC, warned that antibiotic stewardship is a moving target and therefore an ongoing endeavor. "Right now we have a lot of drug shortages, so we have a lot of problems with that. You also have problems with new drugs coming on the market. How are you going to use them? You have more resistance coming along. So there are always new challenges. There are always new problems, and there's always something else to work on," she said.

She commented that the medical center's ability to keep its budget for antimicrobial agents in check "is definitely attributable to stewardship because we have been able to maintain this despite the facts that we have had drug shortages [and] we have had very expensive medications come on the market. Drugs go off, and then they come back, and they're 5 times more expensive than they were. We've been able to maintain it despite everything else that's happened."

WMC does not now and has never had formulary restrictions as part of its ASP. "We do it all through education," Dr. Cooper said. "Any physician in our hospital can order any drug they want to. However, we do make recommendations on appropriateness."

Not everyone agrees that a "no restrictions" policy is best, and "restriction" does not mean "prohibition." David Gilbert, MD, professor of medicine at the Oregon Health Science University in Portland and past president of the IDSA, said restrictions may be appropriate when new drugs are approved that are safe and effective for treating the worst pathogens.

He commented to Medscape Medical News, "If we just allow the drugs to be used willy-nilly, we know that the bugs have a conference. The bacteria get together and say, 'We got a new problem here. Let's figure out how to become resistant,' and they become resistant very quickly or at least potentially can become resistant very quickly."

He advised, "The drugs in the category we're talking about are usually restricted to use by critical care doctors and infectious disease doctors. So, it's not saying you can't get them. We have a little filter which has the opportunity of education as well as helping the doctors manage the care of the patient."

The study received no commercial funding. Dr. Gross, Dr. Cooper, and Dr. Gilbert have disclosed no relevant financial relationships.

Infectious Diseases Society of America (IDSA) 49th Annual Meeting. Abstract #177. Presented October 21, 2011.

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