Initial Vancomycin Monotherapy is Associated With Higher Rates of Subsequent Clostridium difficile Infection in Inflammatory Bowel Disease Population

Abstract

BACKGROUND: Screening and treatment for latent tuberculosis (TB) before the use of antiTNF therapy has decreased the risk of active TB. In Spain, which has a high prevalence of TB, the recommended TB screening according to national guidelines includes 2-step tuberculin skin test (TST) and chest X-ray. No data are available on the risk of developing a positive response in serial TST in inflammatory bowel disease (IBD) patients receiving long-term infliximab therapy whose initial 2-step TST was negative. The aim of this study was to determine the likelihood of detecting latent TB by the positive conversion of serial TST in a cohort of IBD patients treated with infliximab. The outcome of patients with positive conversion in the TST was also investigated. METHODS: This prospective single-center study included all consecutive IBD patients with negative 2-step TST before starting infliximab treatment. TST was positive if induration was ≥5 mm in first test or the induration was ≥5 mm in the second test (if the first TST was <5mm but provided a booster effect). We performed annual serial TST in all patients. Patients with a positive result in any serial TST were treatedwith a complete therapeutic regimen for latent TBwhile continuing on infliximab. These patients were followed to assess clinical outcomes. RESULTS: Sixty two patients (mean age 41 years, 39% male) with either Crohn's disease (n=33) or ulcerative colitis (n=29) were enrolled. Eight patients had a positive TST during follow-up (mean TST induration 13 mm, range 9-20 mm). At one year, positive conversion had occurred in 5/62 (8.1%; 95% CI: 2.7-17.8) patients. At two and three years, 2/27 (7.4%; 95% CI: 0.9-24.2) patients and 1/ 11 (9.1%; 95% CI: 0.2-41.2) patients had a positive TST, respectively. The cumulative two year risk of positive conversion of TST was 7/32 (21.8%; 95% CI: 6-37.8) patients. The patients with positive conversion of TST received a 9month course of isoniazid and continued with infliximab therapy. An occupational exposure to TB was identified in only 1/8 patients. After a median of 16 months (range 3-30 months) follow-up, none of the patients with positive conversion of TST had clinical or radiological signs of active TB. CONCLUSION: Patients with IBD treated with infliximab were at high risk of conversion in the serial TST, even when the initial 2-step TST was negative. Although the exact significance of these positive conversions is not well known, annual TST is advisable as false negative responses to latent TB or new TB contacts are possible in IBD patients receiving long-term infliximab therapy, especially in countries with a high prevalence of TB.