ICAAC: Tetracycline May Protect Against C. difficile Colitis

SAN FRANSICO, Sept. 28 -- Though antibiotic exposure typically increases the risk of Clostridium difficile colitis, tetracycline may protect against it, researchers reported here.

Tetracycline decreased the risk C. difficile colitis (odds ratio [OR] 0.6, (95% confidence interval [CI] 0.5 to 0.9) while other antibiotics, particularly imipenem, raised the risk, according to a case-control study presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy in an oral session.

Antibiotics with the highest risk included:

• imipenem (OR 3.31, CI 1.27 to 8.62, P=0.02)
• ceftazidime (OR 2.45, CI 1.48 to 4.07, P<0.01)
• clindamycin (OR 2.02, P<0.01)
• moxifloxacin (OR 1.66, P=0.03)

"In hospitals with high rates of C. difficile, physicians should consider using antibiotics with lower associated risk," said Roger Baxter, M.D., of Kaiser Permanente Northern California in Oakland.

Surprisingly, meropenem had one of the lowest associated risks (OR 1.05) though imipenem in the same class of drugs had the highest risk. The lowest risks were from tetracycline (OR: 0.6, CI: 0.5 to 0.9), doxycycline, ampicillin (often faulted as the main cause of C. difficile, noted Dr. Baxter), metronidazole, and erythromycin.

Antibiotics in the middle range with increased risk of C. difficile colitis, though not significantly so due to wide confidence intervals, included piperacillin/tazobactam, cefotetan, ampicillin/sulbactam, ceftriaxone and others.

Many earlier studies looking at risk from individual antibiotics had problems with sample size. Dr. Baxter and colleagues drew data from the Kaiser Permanente Northern California system of 54 clinics and 16 hospitals that have the advantage of consistent inter-institution infection-control standards.

The retrospective study included 696 cases seen from 2000 through 2004 of first-time C. difficile toxin assay positive infection in patients who had been exposed to antibiotics in the 60 days prior to the positive C. difficile test. Each patient was matched with eight controls (total 2,058) with the same number of days in the same hospital in the same year and quarter, same diagnosis at discharge, and who had also been exposed to antibiotics.

About half of the patients were male and the average age was 68 years for both cases and controls. However, cases had more hospitalized days (14 versus 9) and more proton pump inhibitor use (42% versus 30%).

All odds ratios were determined after controlling for prior hospitalization days, number of prior different antimicrobials and proton pump inhibitor use in a regression analysis.

Dr. Baxter cautioned that these results are somewhat different than other studies have found because of the limited power due to matching criteria. Further study will be needed to confirm the findings with regard to ceftriaxone, which has been much higher on other studies' risk findings, and the apparent protective effect of tetracylines.

Also, the newer antimicrobials like linezolid, tigecycline and daptomycin were not used frequently enough to make statistical comparisons with other agents, he said.

This study confirmed what clinicians thought was true, that broad-spectrum antibiotics increase the risk of colitis more and, therefore, are particularly going to be problematic in hospitals where there is C. difficile exposure, Dr. Baxter concluded.

Other risk factors identified in the study were older age, number of hospital days in the 60 days prior to index date, and high medical costs in the year prior to index date.