Antibiotics and Risk of Community-Associated C. difficile Infection
The Article: Brown, KA, et al. “Meta-Analysis of Antibiotics and the Risk of Community-Associated Clostridium difficile Infection” Antimicrobial Agents and Chemotherapy 2013;57:2326-2332.
Bottom line: Outpatient clindamycin, fluoroquinolones, cephalosporins, monobactams, and carbapenems are associated with high risk of C. diff infection. Outpatient macrolides, sulfonamides and trimethoprim, and penicillins are associated with lower risk of C. diff infection. Outpatient tetracycline use is NOT associated with significant risk of C. diff infection.
The Idea: Incidence of community-acquired C. diff infections continue to increase. There is a meta-analysis and a systematic review studying inpatient antibiotic use and subsequent risk of C. diff infection, but there is no systematic review studying the relationship between outpatient antibiotic use and subsequent risk of C. diff infection. The authors argue that this is an important distinction since non-hospitalized patients are generally younger, have less exposure to patients with symptomatic C. diff infection, and have different infections and antibiotic regimens.
The Study: A systematic review including 7 studies (from 1988 to 2007), excluding studies analyzing hospital/healthcare-acquired diseased and risk factors for severe/relapsing C. diff in patients already diagnosed with C. diff. Antibiotics were classified as tetracyclines, sulfonamides and trimethoprim, penicillins, macrolides, cephalosporins/monobactams/carbapenems, fluoroquinolones, or clindamycin.
Primary meta-analysis was performed on the 5 of 7 included studies that had a true control group (i.e. no antibiotic exposure). Odds ratios were calculated for antibiotic classes relative to no antibiotic exposure.
Secondary analysis was performed on the 2 of 7 included studies that did not have a true control group. Odds ratios were calculated for antibiotic classes using penicillin as a control.
Results: Outpatient tetracyclines were not associated with significant risk of C. diff infection [OR 0.92 (95% confidence interval 0.61-1.40)]. Outpatient penicillins [OR 2.71 (1.75-4.21)], sulfonamides and trimethoprim [OR 1.81 (1.34-2.43)], and macrolides [OR 2.65 (1.92-3.64)] were associated with a small risk of C. diff infection. Outpatient cephalosporins/monobactams/carbapenems [OR 5.68 (2.12-15.23)], fluoroquinolones [OR 5.50 (4.26-7.11)], and clindamycin [OR 16.80 (7.48-37.76)] were associated with a high risk of C. diff infection. Pooled data suggested that any antibiotic use increased risk of C. diff infection by OR 3.55 (2.56-4.94). Similar findings were noted in the secondary analysis.
The Takeaway: This study suggests that outpatient antibiotic regimens increase risk of C. diff infection, and that different antibiotic classes carry different risks. Tetracyclines did not carry a significant risk of C. diff infection, while penicillins, sulfas, and macrolides carried a small risk. Cephalosporins/monobactams/carbapenems, fluoroquinolones, and clindamycin carried the highest risk of C. diff infection. This study had many limitations, notably: incomplete exclusion of exposure to hospital setting or inpatient antibiotics, possible alternative etiology of diarrhea in C. diff (+) patient, variable onset post-antibiotic exposure, and simultaneous use of multiple antimicrobials.