- Despite widespread azithromycin use, no audit has targeted this drug to date. Azithromycin was audited in primary military clinics between July 1, 2003 and December 31, 2003 (period 1). Consumption (defined daily doses/1000 visits) and economic expenditure of penicillin V, amoxicillin, erythromycin, and azithromycin were evaluated. An educational intervention was performed (dissemination of local guideline regarding indications for azithromycin use) and its impact was assessed between July 1, 2004 and December 31, 2004 (period 2). During periods 1 and 2, 105 and 31 patients were prescribed azithromycin. Azithromycin was appropriately chosen in 5.7% vs. 70.9% of cases (p < 0.0001), but unnecessary in 90.5% vs. 16.2 (p < 0.0001). Azithromycin prescription during period 1 resulted in extrapolated excess expenditure of 420,000 New Israeli shekels/year (1 U.S. dollar = 4.5 New Israeli shekels). There was an attributable decrease of 82.1% in azithromycin consumption (adjusted attributable cost reduction 38.1%), but an increase in amoxicillin consumption (20.2%). Intervention decreased azithromycin consumption and expenditure but its effect was offset by increased consumption of other agents, mainly amoxicillin. Interventions in primary care settings should target prescribing behavior through a multifaceted approach to increase efficacy while preventing a trade-off effect.