Stopping Antibiotic Overprescribing: What Works?

Laird Harrison

Disclosures

June 21, 2016

Not a Knowledge Problem

Infectious disease specialist Brad Spellberg, MD, was on consult at Los Angeles County-University of Southern California Medical Center in Los Angeles, California, when he got a panicked call from the hospital's chief resident. The resident wanted to treat a patient's perforated appendix with piperacillin/tazobactam.

Dr Spellberg, the hospital's chief medical officer, assured the resident that the patient's persistent signs and symptoms didn't mean an infection with highly resistant hospital-acquired bacteria. Piperacillin/tazobactam is reserved for that purpose, said Dr Spellberg. But the resident wasn't mollified. "In any other hospital, we would be allowed to broaden treatment," he shot back.

And after he got off the phone, Dr Spellberg found himself wondering what would happen if he was wrong. "I've published tons on antibiotics, and I'm starting to be afraid," he said.

To Dr Spellberg, this story gets to the crux of the problem with antibiotic overprescription. Doctors already know that every antibiotic prescription increases the chances of developing resistance. But when faced with a suffering patient, they disregard concerns for the population and reach for whatever tools might help the individual.

"This is not a knowledge problem," Dr Spellberg says. "People know. This is a fear problem. It's about being afraid of being wrong and being afraid of hurting patients."

Although some smaller-scale antibiotic stewardship initiatives have helped, Dr Spellberg and others would like to see more strategic efforts on the part of professional societies and government agencies to address the problem of antibiotic overprescribing.

Antibiotics can cause side effects beyond allergic reactions or gastrointestinal distress. Some evidence suggests they can increase the risk for serious cardiac arrhythmias, death, and childhood obesity.[1] But the biggest problem is the development of resistance. Every year in the United States, at least 2 million people acquire infections with antibiotic-resistant bacteria and 23,000 people die as a result.[2]

Bacteria are rapidly developing resistance even to the drugs that have been held in reserve. In May, the US Department of Defense reported the first known case of a US patient infected with Escherichia coli resistant to colistin, the weapon of last resort for bacteria that can survive everything else.[3] (See First US Case of E coli Resistant to Last-Resort Antibiotic.)

Although other factors, such as the use of antibiotics in livestock, have contributed to the problem, overprescription plays a key role.[4] Clinicians appear to be ignoring guidelines designed to restrain them from inappropriate prescribing. In the 2010-2011 National Ambulatory Medical Care Survey, it was estimated that 506 prescriptions were written for every 1000 persons. By matching the prescriptions to guidelines, they found that only 353 per 1000 people were appropriate.[5]

What's to Be Done?

Lecturing physicians won't help much, says Marian McDonagh, PharmD, a professor of medical informatics and medical epidemiology at Oregon Health & Science University in Portland, Oregon.

McDonagh recently led a systematic review of efforts to stop overprescribing antibiotics for acute respiratory tract infections, the indication for which most antibiotics are prescribed.[1] "I think that clinicians are trained," she says. "They do know when you should and shouldn't prescribe an antibiotic."

Physicians want to help patients, and research has shown that patients are more likely to go home satisfied if they have a prescription in their pockets, she says. Dr Spellberg agrees, "Increasingly, physicians are being judged on patient satisfaction surveys."

But some studies have shown that a combination of public education for patients and clinicians improved appropriate prescribing, with an overall 7% reduction in overall prescribing, with similar rates of complications and satisfaction.[1]

For example, at the walk-in clinic at the Denver Health Medical Center in Denver, Colorado, physicians attended a 1-hour education program based on Centers for Disease Control and Prevention guidelines about antibiotic use in respiratory tract infections. Posters in each of the clinic's examination rooms either explained the lack of effectiveness of antibiotics in treating acute bronchitis or listed respiratory infections for which antibiotics are not indicated and presented graphics showing the increase in drug resistance in recent years.

Patients spent about 17 minutes on average completing a computer-based education program in basic English or Spanish that explained self-care strategies for respiratory illness and the role of antibiotics (or lack thereof). The patient entered signs, symptoms, and medical history into the program and received a likely diagnosis. This was followed by an education session for the patient, based on his or her likely diagnosis, and a printout for the patients to take to their providers.

The researchers analyzed records of 554 adults from October to December 2000 and 964 during the study period from January to April 2011. They found that among patients with acute bronchitis who completed the computer module, the proportion who were given antibiotics declined from 58% at baseline to 24% during the study period—a statistically significant difference (P < .001). Antibiotic prescriptions for nonspecific upper respiratory tract infections also declined, from 14% to 1%.[6]

A similar clinic-based education of parents resulted in a 21% reduction in antibiotic prescribing for children, without affecting return visits.[1] Electronic decision support systems, such as reminders in electronic health records, resulted in a 5%-9% reduction in overall prescribing without affecting complication rates and healthcare use.[1]

Changing Behavior

Dr Spellberg is a fan of one such intervention. In a randomized trial,[7] researchers at six centers, including the University of Southern California in Los Angeles, randomly assigned 47 primary care practices with a total of 248 clinicians to one of three behavioral interventions involving changes to the electronic prescribing system or to a control practice.

In the first type of change, electronic prescribing software automatically suggested alternatives to electronic order sets. In the second, the prescriber was prompted to enter justifications for prescribing antibiotics. And in the third, clinicians periodically received emails that compared their antibiotic prescribing rates with the lowest rates among their colleagues.

At baseline, all of the practices were prescribing antibiotics in 20%-24% of visits. Over the next 18 months, antibiotic prescribing declined in all practices—by 11% in the control group, 16% in the suggested alternative group, 18% in the accountable justification group, and 16% in the peer comparison group. The difference between the control and the intervention was statistically significant only for the accountable justification and peer comparison groups.

Clinicians might be less likely to prescribe antibiotics if they had greater certainty about when patients really needed them. One method for making this determination is to test for procalcitonin, a precursor of the hormone calcitonin, which rises in response to bacterial infection.[1] Studies showing that prescribers who used the tests for procalcitonin in adults wrote 12%-72% fewer antibiotic prescriptions than prescribers who didn't use the tests, with no difference in the patients' symptoms, activity, missed work, adverse events, hospitalization, or mortality.[1]

However, procalcitonin assays are not easy to obtain in the United States, Dr McDonagh says. And there is evidence that using adult procalcitonin algorithms actually resulted in increased antibiotic prescribing in children.

More Than One Approach

The research so far leaves a lot of questions unanswered, Dr McDonagh says. First, many studies measured a reduction in prescriptions of antibiotics but didn't try to determine how this reduction affected patients. That was the case with tests for streptococcal antigen and rapid multiviral testing in adults.

Second, other approaches yielded insufficient evidence or mixed results. That was what Dr McDonagh and her colleagues found when they looked at delayed prescribing—for example, requiring patients to make a return visit to get a prescription. And they found the same problem with tests for C-reactive protein and attempts to teach clinicians how to communicate better with their patients.

Finally, many studies failed to measure the effects of an intervention over the long term. A jolt of improvement in inappropriate prescribing can tail off after months or years.

Intuitively, it makes sense to combine approaches. But few studies have examined this tactic. On a policy level, Dr McDonagh would like guidelines from professional societies to address antibiotic overprescription much more directly. Most guidelines don't take into account the latest information on how to avoid overprescribing, and when they do, they are vague. She cites delayed prescribing as an example. Many guidelines don't mention it at all, and those that do don't explain how to go about it, she says, adding, "The guidelines don't read like they have a clear mission to reduce prescribing in a real way."

Dr Spellberg believes that high-level initiatives offer the best hope for taming overprescribing. "We're not aligning the psychology of the provider with the needs of the society," he says. "We need a grand strategic approach." He would like to see public reporting of antibiotic use similar to the public reporting of hospital-associated infection rates, perhaps linked to physicians' bonuses. "You watch how quickly the C suite hops to when there is public reporting," he predicts.

Dr Spellman has also proposed changing the scope of the US Food and Drug Administration beyond safety and efficacy to restricting the use of broad-spectrum antibiotics, keeping them mostly in reserve for bacteria that are resistant to narrow-spectrum drugs. "Once I give an indication, the indication legally allows marketing for that purpose," he says. "Marketing drives physician behavior."

The National Quality Forum has been studying measures of antibiotic use, and the Centers for Medicaid & Medicare Services is considering adopting such measures in how providers are reimbursed, says Dr Spellberg. Such initiatives could finally reverse the trend that is depriving patients of the most successful class of medications ever invented, he believes. "That's a huge step forward. It's entirely possible that we'll get there."

Disclosures: Brad Spellberg, MD, has disclosed the following relevant financial relationships:
Received consulting fees from: Cempra; The Medicines Company; MedImmune/AstraZeneca; PTC Therapeutics; Entasis; Tetraphase; Merck; Genentech
Received data safety and monitoring board fees: Dipexium
Owned equity in: Motif; BioAIM; Synthetic Biologics
Marian McDonagh, PharmD, has disclosed no relevant financial relationships.

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