Tetracyclines Associated with Lower Risk of CDI

A recent study has shown that, compared with other antibiotics, tetracyclines may be associated with a reduced risk of Clostridium difficile infection (CDI).

Raseen Tariq, MBBS, Mayo Clinic, Rochester, Minnesota, and colleagues published the results of their systematic review and meta-analysis online September 18, 2017, in the journal Clinical Infectious Diseases.

“In this meta-analysis, we found that the use of tetracyclines was associated with a 38% lower risk of CDI compared with the use of other antibiotics,” the authors write.

The toxin-producing bacterium Clostridium difficile is the most significant cause of hospital-acquired infections in the United States, causing almost half a million infections and approximately 29,000 deaths each year.

Antibiotic exposure is the main risk factor for the development of CDI, although the degree of risk varies among the different classes of antibiotics. Clindamycin, third-generation cephalosporins, penicillin, and fluoroquinolones are considered high-risk antibiotics, while tetracyclines have been infrequently associated with CDI.

However, clinicians remain challenged to select appropriate antibiotics to treat systemic infections in patients with a high risk of CDI because studies evaluating the impact of antibiotic exposure on CDI have produced inconsistent results. Some studies have indicated that tetracyclines may be associated with a lower risk of CDI than other antibiotics are, while others have shown conflicting findings, the authors say.

Dr. Tariq and colleagues, therefore, conducted a systematic review and meta-analysis to compare the risk of CDI in patients receiving tetracyclines with the risk in those receiving other antibiotics.

They included 6 studies with patient recruitment periods between 1993 and 2012. The studies involved a total of 5,322 CDI cases and 412,208 controls.

The researchers found that patients who received tetracyclines had a lower risk of CDI compared to those who received other antibiotics (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.47 to 0.81; P<.001).

In a subgroup analysis, they found that doxycycline therapy alone also had a protective effect against CDI (OR, 0.55; 95% CI, 0.40 to 0.75; P<.001).

Although the mechanism by which tetracycline use may lower the risk of CDI remains unclear, the authors suggest that it may be due to several reasons, including its in vitro activity against C. difficile, its accumulation in high concentrations in the bowel, or its relatively brief disruptive effect on the gut microbiota compared with other antibiotics.

The authors emphasize, however, that the protective effect of tetracycline against CDI development was consistent in cohort studies and studies involving inpatients only. No effect of tetracycline treatment was found in case-control studies, they say; similarly, subgroup analysis of studies involving mixed populations of inpatients and outpatients showed no effect of tetracycline treatment on CDI development, although, tetracycline did have a protective effect in the inpatient population.

Because of these discrepancies, the authors stress the need for additional prospective studies to examine the role of tetracyclines in reducing the risk of primary and recurrent CDI, and to compare the effect in inpatients versus outpatients, as well as against community-acquired versus hospital-acquired CDI.

“Until that time, clinicians may wish to consider doxycycline over alternative antimicrobials where appropriate,” Dr. Tariq and colleagues conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.