Choosing formulary antimicrobials? Your expertise should be the key

Merely considering cost-effectiveness can undermine effective choices

Cutting the costs of wholesale antimicrobials may not be the best way to save money for hospital pharmacy directors under the gun to make formularies cost-effective. It’s an especially difficult challenge in the area of antimicrobials, where the market offers wide spread choices coupled with the ongoing threats of resistance and nosocomial infections.

But there may be a more important bottom line than the financial one, according to Joseph Paladino, PharmD, clinical associate professor at State University of New York in Buffalo. "The cost of medication contributes less than 8% to overall health care costs," says Paladino, co-author of a recent study on the influence of fluoroquinolone purchasing patterns on hospi - tal antimicrobial expenditures and on Pseudomonas aeruginosa susceptibility.

"Antimicrobials are 20% of that, so antimicrobials constitute 2% of overall health care costs," he says. "When we study the costs of treating an infected patient, the antimicrobial is 2.5% to 5% of treatment costs for a hospitalized patient. That is a small part of the overall treatment costs. So it is wrong to look only at the cost of the drug."

The fluoroquinolone study looked at the influence of using ofloxacin in place of ciprofloxacin on hospital fluoroquin olone expenditures and total antimicrobial expenditures. It also looked at how this affected the fluoroquinolone susceptibility of P. aeruginosa.

The study found that hospitals using ciprofloxacin as their primary fluoroquinolone experienced greater savings in antimicrobial expenditures than institutions primarily using ofloxacin. In addition, the use of ciprofloxacin was associated with lower rates of ciprofloxacin-resistant P. aeruginosa despite the fact that ofloxacin has been marketed as a lower-cost alternative to ciprofloxacin.

"When hospitals make a choice to use one drug over another on the basis of saving money, they may not actually get lower expenditures," says Paladino. "Cost-shifting will occur as physicians turn to other medications. Also, using a less-effective medication will increase the chance of bacterial resistance, and that, in turn, causes a patient to stay sicker for a longer period of time, and that costs more money and potentially exposes them to more infections. Outpatients go back to the doctor and the pharmacy more often, and inpatients stay in the hospital longer. Also, there’s an increase in mortality as well as morbidity, so the human cost is measurable."

Look for the true cost

Paladino says hospitals should look at the cost of treating the patient, not the cost of the drug. The appropriate outcome measure, he says, is how well the drug is working.

"The cheaper drug may have expensive side effects. Maybe it doesn’t work as quickly, so the patient stays sicker longer and uses more health care. We need cost-effectiveness in the real sense. The difference between economics and mere cost-containment is based on patient outcomes, and we can put a figure on that. Failure is more expensive than success, and success rewards good patient care."

Another part of this equation, Paladino says, is the importance of optimizing doses for individual patients through the use of pharmacokinetics and pharmacodynamics.

"I think the future value of pharmacists is grounded in this clinical contribution, rather than distributive functions or warehouse stocking of drugs. Pharmacists must get into this for their own survival. If they believe their only job is to cut costs, they will be asked to cut more and more, and inevitably, the administrator is going to be disappointed when there is no more opportunity to cut costs. So this is for their own survival. Also, they are not demonstrating their value if they do this. The only way to show value is to show the positive impact of patient outcomes. We need to take clinical pharmacy to the bedside."

Develop an infection control plan

According to the Centers for Disease Control and Prevention in Atlanta, nosocomial infections affect some 2 million patients a year in acute care facilities in the United States at an annual patient care cost of more than $3 billion. Those infections are difficult to treat because the microorganisms that cause them are becoming increasingly resistant to traditional antimicrobial agents.

CDC epidemiologist Lennox Archibald, MD, says preventing the transmission of resistant pathogens in hospitals is crucial. "You need infection control guidelines to do this. Hospitals should have infection control committees with representatives from all departments: doctors, nurses, pharmacy, everyone. And there should be a concerted plan. The committee must identify common infections, develop surveillance methods, and get feedback to those who need to know."

Archibald cites a recent survey that found getting feedback to surgeons actually reduces surgical wound infections.

According to the CDC, studies indicate a third of nosocomial infections could be prevented by well-organized infection control programs, but only 6% to 9% actually are prevented. One of the stated goals of the CDC’s hospital infections program is addressing the discrepancy between what can be prevented and what is being prevented.

"Another key is to avoid triggering events, exposures to certain antimicrobials," Archibald says. "Be sure to use the best specific antimicrobial. Be aware that the cheapest isn’t necessarily the best. Consideration while prescribing is key. Don’t give the patient an antibiotic if there is a chance the condition is caused by a virus."

Lance Peterson, MD, professor of medicine and pathology at Northwestern University in Chicago, says there are several considerations when choosing an antimicrobial.

"You need to decide which class to use and then which is the optimal agent. And that really depends on where you are, whether you are somewhere with high levels of resistance. You need to know how much resistance there is in your area. Then you must decide whether the infection is truly bacterial and pick the appropriate specific agent."

Experts say those factors also must be considered when choosing which antimicrobials to include in the formulary and which to cut.

Patient education also is important. Archibald says patients, especially parents concerned about their children, still pressure physicians to prescribe an antibiotic when it’s not indicated. Pharmacists can help educate parents about resistance, he says.

Patients also need to know how important it is to take antimicrobials properly, as prescribed. They should be advised to take an entire prescription course and not save the medication to self-prescribe later.

New weapons in the arsenal

Bayer Corporation’s Avelox (moxifloxacin hydrochloride) has been approved for use against respiratory tract infections, including acute bacterial exacerbations of common bronchitis, community-acquired pneumonia of mild to moderate severity, and acute bacterial sinusitis. The U.S. Food and Drug Administration approved Avelox on Dec. 13, 1999.

Bayer officials say the drug helps fill a void created by the pathogens’ increased resistance to commonly prescribed antibiotics. For now, it will be used mainly in outpatient settings because there is not yet an IV formulation.

"Because of resistance to commonly used agents, there is growing concern about choosing the correct antimicrobial," says Peterson. "Prac ti tioners are turning to quinolones when resistance is a factor. And the unique thing about Avelox is that it has two or three initial targets, which makes it harder for the organism to become resistant."

Peterson says quinolones are particularly appropriate for older patients who have underlying diseases or true bacterial pneumonia, as well as for patients in densely populated urban areas where there are high levels of resistance. He says if you are going to use a fluoroquinolone, Avelox is least likely to cause resistance, and it is up to physicians to help keep it that way.

"If you don’t use it in patients who don’t need antimicrobials, and you use the correct dose, and use it only where you are sure you have a bacterial infection, you will delay resistance. You can’t prevent resistance, but you can delay it," he explains.

Avelox was studied in clinical trials involving nearly 8,000 patients. Bayer says the drug is safe and well-tolerated and does not cause photosensitivity or serious liver toxicity. The most common adverse reactions were nausea and diarrhea.

Avelox is contraindicated in patients with a known hypersensitivity to moxifloxacin or any quinolone antimicrobial. It also should be used with caution in patients with known or suspected nervous system disorders or predisposition to seizures.

The recommended dosage for Avelox is 400 mg daily for five or 10 days, depending on the specific infection. Bayer says it is not metabolized by the enzyme system that breaks down many other drugs and therefore can be taken safely with a wide variety of other medications. In addition, it has a half-life of 12 to 14 hours and does not need to be taken at any particular time, nor does it need to be taken with meals.

Peterson says the drug is a good candidate for a managed care formulary. "I don’t think it is priced higher than other agents, and the data presented to the FDA suggest quinolones decrease mortality and hospitalization. The Avelox data also indicated lower hospitalization rates, and keeping patients out of the hospital decreases costs."

Last year, the FDA also approved the injectable antibiotic quinupristin-dalfopristin (Synercid I.V., Rhone-Poulenc Rorer) for use against serious infections associated with vancomycin-resistant Enterococcus faecium (VRE) bacteremia, making it the first streptogramin approved for marketing in the United States. Synercid works by inhibiting bacterial protein synthesis, thereby eradicating the infection.

The urgency of providing safe and effective treatment for VRE allowed quinupristin-dalfopristin to qualify for approval under the FDA’s accelerated approval process. The agency based its decision on a surrogate marker — the drug’s ability to clear VRE from the bloodstream — rather than on the more rigorous requirement of clinical benefit.

Synercid also is labeled for use in the treatment of complicated skin and skin-structure infections caused by Streptococcus pyogenes and methicillin-susceptible Staphylococcus aureus.

The recommended dosage is 7.5 mg/kg administered every eight hours for treatment of VRE infections and every 12 hours for skin and skin-structure infections.

Quinupristin-dalfopristin first went before the FDA’s anti-infective drugs advisory panel in 1998. The committee’s deliberations emphasized the need for more antimicrobials active against VRE. The drug was studied worldwide in clinical trials and an FDA-sanctioned emergency-use program. Possible side effects include local irritation, muscle aches, and general malaise.

Gram-positive bacteria such as E. faecium and S. aureus are considered serious public health threats because of their resistance to commonly used antibiotics. In addition, they are among the most common causes of nosocomial infections.

He also says he’s seen limiting resistance become a real priority for physicians and patients over the past five years, which is an accomplishment if you consider the time span.

"These organisms have been around for a very long time, and we’ve only had the ability to manage them for a short time. So things have changed a lot. Physicians and patients are much more aware of the issue and open to talking about it. I think things have changed a lot, and limiting resistance is now a priority and a major concern."

Joseph A. Paladino, PharmD, FCCP, Clinical Associate Professor, State University of New York at Buffalo, and Director of Pharmacokinetics and Pharmacoecon omics, Millard Fillmore Suburban Hospital, Williams ville, NY. Telephone: (716) 645-2828.

Lennox Archibald, MD, Epidemiologist, Hospital Infections Program, Centers for Disease Control and Prevention, Atlanta. Telephone: (404) 639-3311.

Lance Peterson, MD, Professor of Medicine and Pathology, Northwestern University Medical School, Chicago. Telephone: (312) 503-8649.