Cumulative Incidence of and Risk Factors for Unnecessary Use of Double Anaerobic Coverage Therapy

Background: Beta-lactam/beta-lactamase inhibitors (BLIs) can be used as monotherapy for mixed aerobic and anaerobic infection. The only rational indication of adding metronidazole to BLIs in inpatients is for treatment of C. difficile associated disease (CDAD). Unnecessary double anaerobic coverage therapy (DACT) may lead to emergence of antimicrobial resistance as well as increased antibiotic adverse events. To counter this inappropriate prescribing pattern, it is critical to understand and evaluate the context in which such patterns occur.  

Objective: To ascertain the cumulative incidence of and risk factors for unnecessary DACT use.

Methods: A nested case-control study was conducted at the Hospital of the University of Pennsylvania (HUP). We focused on the most commonly used BLI in our institution (i.e., ampicillin-sulbactam). DACT was defined as co-administration of ampicillin-sulbactam and metronidazole. All DACT prescriptions were considered unnecessary unless it was given for treatment of CDAD. All hospitalized patients treated with ampicillin-sulbactam for at least 2 days were enrolled as the study population. Cases were those patients treated with unnecessary DACT. Controls were subjects not treated with DACT or who were treated with necessary DACT. All eligible controls were included. 

Results: From October 1, 2007 through September 30, 2009, a total of 1783 subjects (41 cases and 1742 controls) were included. The cumulative incidence of unnecessary DACT was 2.3% [95%CI; 1.7-3.1]. Independent risk factors for unnecessary DACT [adjusted odds ratio (95%CI); p-value] were: 1) hospitalization on a surgical ward [3.51 (1.03-12.02); p=0.002]; 2) hospitalization on an obstetrics and gynecology ward [9.07 (2.54-32.40); p=0.002]; and 3) underlying metastatic malignancy [3.18 (1.38-7.09); p=0.006].  

We also evaluated the association between unnecessary DACT and type of antibiotic stewardship program (ASP) in place. During the first half of study period, prescriptions of ampicillin-sulbactam if administered for > 3 days, and parenteral metronidazole (if administered at any frequency other than every 12 hours) required pre-approval from the ASP. During the second half of study period, these requirements were no longer in place. Segmented regression analysis did not find a significant difference between these two study periods [0.23 (-1.06-1.51); p=0.73]. Additionally, there was no significant trend change after the change in pre-approval program [0.07 (-0.12-0.25);p=0.48).

Conclusions: Although uncommon, unnecessary DACT does occur. Partial discontinuation of antibiotic pre-approval program did not seem to aggravate unnecessary DACT use at HUP which has a comprehensive ASP. Based on our study results, educational programs to eliminate this practice should focus on services where it is particularly common.