Lower Risk of C Difficile Infection With Tetracycline Use

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c diff_PHIL_16787
Researchers conducted a systemic review and meta-analysis to determine which antibiotics for systemic use were associated with the lowest risk of C difficile infection.

Tetracycline antibiotics, specifically doxycycline, were shown to be associated with a lower risk of Clostridium difficile infection compared with other antibiotics, according to the results of a recent study published in Clinical Infectious Diseases.

In this meta-analysis and systematic review researchers considered studies between 1993 and 2012 that evaluated tetracycline use and the risk of C difficile infection. Articles that compared tetracycline with other antibiotics and with no antibiotics were included in the analysis. Of the 6 included studies, 4 were case-control and 2 were cohort. Overall, 5322 cases of C difficile infections and 412,208 controls were included in this random-effects meta-analysis.

After adjustment for the use of gastric acid suppression medications and various other demographics (depending on the study), tetracyclines were associated with a lower risk of C difficile infection (adjusted odds ratio [OR] 0.62; 95% CI, 0.47-0.81; P <.001).

Although no publication bias was noted, the researchers reported a high level of heterogeneity in the studies (I2 53%), which was attributed to variations in study setting. Tetracyclines were more likely to decrease the risk of C difficile infections in studies that included inpatients only (OR 0.55, 95% CI, 0.40-0.75; P <.001) compared with studies that included both inpatients and outpatients (OR 0.92, 95% CI 0.58-1.46; P =.72).

Half of the studies included in the meta-analysis (n=3) evaluated doxycycline specifically. In a subgroup analysis, doxycycline was associated with a lower risk of C difficile infection (OR 0.55, 95% CI 0.40-0.75; P <.001).

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Dr Sahil Khanna, of the division of internal medicine at Rochester General Hospital in New York and lead  study investigator, noted that the results were “very comforting and not completely surprising, as individual studies hinted at a possible protective effect of tetracyclines for C difficile infection.” He mentioned, however, that future prospective studies are needed to determine whether the findings can be replicated.


Tariq R, Cho J, Kapoor S, et al. Low risk of primary Clostridium difficile infection with tetracyclines: a systematic review and meta-analysis [published online September 18, 2017]. Clin Infect Dis. doi:10.1093/cid/cix833.