SAN ANTONIO, TEX—“We have seen that we can control epidemics of resistant organisms in outbreak situations with antibiotic management,” said David L. Paterson, MD, arguing for the benefits of antibiotic-restricting strategies in the ICU. A debate, held during the annual meeting of the Society of Critical Care Medicine in San Antonio, Texas, saw Dr. Paterson, Director of the Antibiotic Management Program at the University of Pittsburgh Medical Center, face off against Philip S. Barie, MD, who maintained that formulary control measures were too restrictive.[1]

Dr. Barie, Chief of the Division of Critical Care and Trauma at Weill Medical College of Cornell University in New York City, countered, “Outbreaks can occur so suddenly, formulary control programs may not be nimble enough to respond to an urgent situation.” In addition, he gave evidence that some types of controls may increase resistance, not prevent it. However, both speakers agreed on the value of antibiotic heterogeneity and education in judicious use of antibiotics.

FOR FORMULARY CONTROL

Using data from the CDC’s National Nosocomial Infections Surveillance System, Dr. Paterson, who is also an Associate Professor of Medicine (Infectious Diseases), showed that antibiotic resistance among both gram-negative and gram-positive organisms is fairly common in ICUs in the United States. Although there are many drugs under development to combat resistant gram-positive organisms, for the gram-negatives “there is nothing coming down the pipeline in the next five years,” he said. The lack of promising new therapies, combined with the emergence of completely resistant gram-negative organisms, such as some strains of Pseudomonas, are the most pressing concerns.

So, what options are available now? There are two, said Dr. Paterson. The first is traditional infection control. This involves patient isolation, scrupulous hand washing by ICU personnel, and the cleaning of everything that has been in contact with the patient. Unfortunately, he observed, “In busy, understaffed units, I don’t believe that infection control truly works.” He continued, “I advocate infection control, but I don’t believe it is going to be the way [to] control antibiotic resistance in our ICUs.”

The second option is antibiotic control, centered on restrictions within the formulary. Dr. Paterson described both front-end and back-end formulary control. In front-end control, the physician must get approval before beginning therapy with a particular antibiotic. In back-end control, the physician may initiate treatment with a specific antibiotic but needs formulary approval to continue therapy past a certain point. Back-end control can be used in conjunction with reevaluation of the patient after a few days of antibiotic treatment, and therapy can be stopped if it is not appropriate. Reevaluation can help eliminate the use of antibiotics for an excessive duration.

Dr. Paterson used an example from his hospital, where there had been an outbreak of resistant Clostridium difficile colitis. “We told people which antibiotics were implicated in our outbreak.… We had a massive educational campaign. But use of the implicated antibiotics was reduced by only 10%. It was only when there was a hurdle—when [physicians] had to call to request use of the implicated antibiotics—that things started to come under control,” he said. These measures resulted in a greater than 50% reduction in the use of the implicated antibiotics.

FORMULARY IS TOO CONTROLLING

Even though many hospitals already have antibiotic control programs in place, multidrug resistance is still a problem, observed Dr. Barie, who is also a Professor of Surgery and Public Health. He took issue with front-end formulary control measures that make it difficult for physicians to prescribe certain drugs. In some cases, Dr. Barie said, “these programs withhold information from clinicians and withhold drugs from the patients.” He added that outbreaks can occur so suddenly that formulary plans may not be flexible enough to respond to an urgent situation in an ICU.

Often, said Dr. Barie, when hospitals with formulary restrictions identify noncompliance, the pharmacy will flat-out refuse to dispense the antibiotic. “This is front-end restriction in the extreme,” he argued, adding that all too often such an approach results in a delay in patient treatment and a host of potential problems, both medical and legal, because of that delay.

Dr. Barie also addressed back-end control, specifically the practice of requiring physicians to call the pharmacy to request continued antibiotic therapy. “Who’s the expert?” he asked. “The person at the other end of the telephone who has never seen the patient or the person who is at the foot of the bed, struggling to make the patient better?”

Although Dr. Paterson cited several studies showing that formulary control works, Dr. Barie pointed out that there are just as many studies showing it doesn’t work. He and Dr. Paterson both used published accounts describing hospital outbreaks of resistant organisms. When the antibiotics in question were restricted, different ones took their place. Susceptibility to the restricted antibiotics increased, but resistance to the replacement antibiotics increased as well.

Is formulary restriction simply replacing one problem with another? “You can’t restrict everything,” said Dr. Barie, who noted that if clinicians are denied one antibiotic, they will simply use something else.

HETEROGENEITY

Both Drs. Paterson and Barie agreed that heterogeneity when prescribing antibiotics is highly desirable. However, Dr. Paterson warned that using equal amounts of a wide variety of antibiotics at the same time in an ICU may, in fact, be the major disadvantage of a program designed to promote heterogeneity. He asked, “What is the baseline susceptibility to certain antibiotics in a given ICU? Not only do patients enter the ICU with different susceptibilities, susceptibility patterns differ among ICUs.” Like Dr. Barie, he also questioned the loss of autonomy for surgeons and physicians. “Who decides what will be prescribed?”

Dr. Barie remarked that “prescribing ruts” are what promote resistance, and this is what formulary restriction does when formulary control measures are not calibrated precisely. There is increasing evidence that limited formulary choice can promote the emergence of resistance. Furthermore, he said that open formularies and unfettered prescribing do not always lead to trouble.

EDUCATION AND TEAMWORK

Dr. Barie suggested that education may be the best way to manage antibiotic prescribing. Quoting from a paper by Joseph A. Paladino,[2] Dr. Barie concluded, “ ‘Antimicrobial management programs should be directed at ensuring the most appropriate use of antimicrobials rather than focusing on limiting choices.’ ”

Along with education, Dr. Paterson stressed teamwork. He envisioned an antibiotic management team, made up of representatives from critical care medicine, pharmacy, and infectious diseases. “We need to jointly produce guidelines, and we need to agree that this is what we are going to follow.”

—Gale Jurasek

References
1. Paterson DL, Barie PS. Pro/con: antibiotic restricting strategies are appropriate in the ICU. Presented at: 32nd Congress of the Society of Critical Care Medicine; February 1, 2003; San Antonio, Tex.
2. Paladino JA. Economic justification of antimicrobial management programs: implications of antimicrobial resistance. Am J Health Syst Pharm. 2000;57(suppl 2):S10-S12.

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