Decades of campaigns against antibiotic overuse have produced only marginal reductions in use.
From 1995 to 2005, the top 90% of oral systemic antimicrobial prescriptions dispensed by U.S. retail pharmacies decreased by 8.1%, according to the team Johann-Liang worked with. But trends varied widely from one drug to another and from one physician or other prescriber specialty to another.
Johann-Liang reported on the study at the recent National Foundation for Infectious Diseases' conference on antimicrobial resistance in Bethesda, Md. The research was based on two proprietary databases: Verispan LLC's Vector One: National (VONA), which integrates outpatient retail pharmacy prescription activity; and Physician Drug and Diagnosis Audit (PDDA), a monthly survey of office-based prescribers on disease states and prescribing habits. The researchers looked to those databases to confirm and update the National Ambulatory Medical Care Survey (NAMCS), which reported an overall antimicrobial prescribing decline over the 1990s. But NAMCS had also shown that as use of older antimicrobials decreased, the newer broad-spectrum drugs were used more often.
Working on the proprietary data for the 11.5 years ending in June 2006, the FDA found that most of the cuts in prescribing were accounted for by the older drugs, including the cephalosporins and penicillins. But, Johann-Liang noted, "when we really looked at the FDA for five to seven years-at all of the compiled clinical trials data on upper respiratory tract infections-clinical trials data with non-inferiority design showed that new drugs are not necessarily shown to be superior to older drugs, or placebo for that matter, for self-resolving diseases."
But physicians seem to like the newer drugs. Use of macrolides increased by 25.8%; use of fluoroquinolones by 128.1%. Johann-Liang said that azithromycin alone increased from 2.2% of total prescription share in 2005 to 16.3% in 2005, and five indications accounted for half of all use: otitis media (13% of the total share), sinusitis (11%), bronchitis (10%), urinary tract disorders (7%), and acute pharyngitis (6%).
Antimicrobial prescribing is concentrated in a few specialties, as well, Johann-Liang said, and not in infectious disease so much as in general practice. Over the decade ending in 2005, more than two-thirds of oral systemic antimicrobials were prescribed by four practice areas: general practice, family medicine, and osteopathy (28.8%); pediatrics (15.12%); internal medicine (13.64%); and dentistry (10.29%). Pediatricians decreased use by 34.9%; general practice, family medicine, and osteopathic doctors by 27.6%; and internal medicine by 10.5%. Dentists actually increased their use by 7.2%. And although physician assistants and nurse practitioners each made up only about 1.4% of antimicrobial prescribing, their increases in use were eye-opening: 461.2% for physician assistants and 862.4% for nurse practitioners.
Room for concern
From 2002 to 2005 antimicrobial prescribing increased by 2.3%, rising for the majority of specialties who use the most antimicrobials. It is difficult to know how to educate physicians, said Jeffrey Linder, M.D., M.P., assistant professor at Brigham and Women's Hospital, who also spoke at the meeting. Most interventions with physicians cut inappropriate prescribing by only about 10%. But Linder said a recent review found that "multidimensional interventions involving physicians and patients appear more effective than clinician educational interventions."
In addition, Johann-Liang said, "research targeted to specific indications-including rapid diagnostics and quantification of benefit to risk-will provide tools needed for public health efforts on judicious antimicrobial use." All drugs, she said, "have issues with adverse drug events, but antimicrobials are unique in that they confer drug safety issues to somebody else, the implications for antimicrobial resistance."
THE AUTHOR is a writer based in the Washington, D.C., area.