rifampin and Colitis--Ulcerative

Topics: Anti-Inflammatory Agents; Clarithromycin; Colitis, Ulcerative; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Humans; Immunocompromised Host; Infliximab; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Rifampin

Tamoxifen, a common anti-estrogen breast cancer medication, is a prodrug that undergoes bioactivation via cytochrome P450 enzymes, CYP2D6 and to a lesser degree, CYP3A4 to form the active metabolite endoxifen. With an increasing use of oral anti-cancer drugs, the risk for drug-drug interactions mediated by enzyme inhibitors and inducers may also be expected to increase. Here we report the first case demonstrating a potent drug-drug interaction in a real-world clinical setting between tamoxifen and rifampin in a breast cancer patient being treated concurrently for ulcerative colitis.. We describe a patient on adjuvant tamoxifen therapy for breast cancer that was prescribed rifampin for TB prophylaxis prior to initiation of an anti-tumor necrosis factor (TNF)-α agent due to worsening ulcerative colitis. This 39 year old Caucasian woman had been followed by our personalized medicine clinic where CYP2D6 genotyping and therapeutic monitoring of tamoxifen and endoxifen levels had been carried out. The patient, known to be a CYP2D6 intermediate metabolizer, had a previous history of therapeutic endoxifen levels. Upon admission to hospital for a major flare of her ulcerative colitis a clinical decision was made to initiate an anti-TNFα biological agent. Due to concerns regarding latent TB, rifampin as an anti-mycobacterial agent was initiated which the patient was only able tolerate for 10 days. Interestingly, her plasma endoxifen concentration measured 2 weeks after cessation of rifampin was sub-therapeutic at 15.8 nM and well below her previous endoxifen levels which exceeded 40 nM.. Rifampin should be avoided in patients on tamoxifen therapy for breast cancer unless continued tamoxifen efficacy can be assured through endoxifen monitoring. Drug-drug interactions can pose a significant risk of sub-therapeutic benefit in tamoxifen patients.

Topics: Adult; Breast Neoplasms; Colitis, Ulcerative; Comorbidity; Drug Antagonism; Female; Humans; Rifampin; Tamoxifen; Treatment Outcome

Escherichia coli is implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a nonabsorbable derivative of rifampin effective against E. coli, improves symptoms in mild-to-moderate IBD. However, rifaximin resistance can develop in a single step in vitro. We examined the prevalence and mechanisms of rifaximin resistance in 62 strains of E. coli isolated from the ileal mucosa of 50 patients (19 with ileal Crohn's disease [L1+L3], 6 with colonic Crohn's disease [L2], 13 with ulcerative colitis [UC], 4 with symptomatic non-IBD diagnoses [NI], and 8 healthy [H]). Resistance (MIC > 1,024 mg/liter) was present in 12/48 IBD-associated ileal E. coli strains. Resistance correlated with prior rifaximin treatment (P < 0.00000001) but not with the presence of ileal inflammation (P = 0.73) or E. coli phylogroup. Mutations in a 1,057-bp region of rpoB, which encodes the bacterial target of rifaximin, were identified in 10/12 resistant strains versus 0/50 sensitive strains (P < 0.000000001) and consisted of seven amino acid substitutions. The efflux pump inhibitor Phe-Arg-β-naphthylamide (PAβN) lowered the MIC of 9/12 resistant strains 8- to 128-fold. Resistance was stable in the absence of rifaximin in 10/12 resistant strains after 30 passages. We conclude that IBD-associated ileal E. coli frequently manifest resistance to rifaximin that correlates with prior rifaximin use, amino acid substitutions in rpoB, and activity of PAβN-inhibitable efflux pumps, but not with the presence of ileal inflammation or E. coli phylogroup. These findings have significant implications for treatment trials targeting IBD-associated E. coli.

Topics: Amino Acid Substitution; Anti-Bacterial Agents; Anti-Infective Agents; Colitis, Ulcerative; Crohn Disease; Dipeptides; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Proteins; Humans; Ileum; Intestinal Mucosa; Membrane Transport Proteins; Microbial Sensitivity Tests; Mutation; Rifampin; Rifamycins; Rifaximin

Topics: Aged; Aged, 80 and over; Antibiotics, Antitubercular; Colitis, Ulcerative; Female; Humans; Male; Rifampin

Topics: Colitis, Ulcerative; Humans; Remission Induction; Rifampin

Topics: Adult; Colitis, Ulcerative; Humans; Male; Rifampin

We report a case of secondary skin tuberculosis due to endogenous secondary infection in a 27-year-old subject affected by ulcerative colitis. The clinical appearance the lesion was atypical and its classification uncertain. The morphology of the lesion and the fact that the primary tubercular complex, at pulmonary level, was masked by a simultaneous candidiasis infection were probably due to cell-mediated immunodeficiency consequent to the ulcerative colitis and on-going therapy (Salazopyrin and prednisone). Rapid remission of cutaneous and pulmonary lesions was achieved following specific therapy (rifampicin, isoniazid, ethambutol).

Topics: Adult; Colitis, Ulcerative; Ethambutol; Humans; Isoniazid; Prednisone; Rifampin; Sulfasalazine; Tuberculosis, Cutaneous; Tuberculosis, Pulmonary

We report on a case, ulcerative colitis and another of Crohn's disease. During a relapse which was unresponsive to conventional therapy, acid-fast bacilli were found in colonic biopsies. Conventional therapy was substituted with antimycobacterial chemotherapy (rifampicin, isoniazid and ethambutol) which was responsible for a marked improvement. However, a relapse occurred during chemotherapy and no acid-fast bacilli were found. The patients became responsive to sulphasalazine and corticosteroid therapy once again. It appears that Mycobacteria play a collateral role in inflammatory bowel disease and that once they have been eliminated the original disease re-emerges.

Topics: Adult; Anti-Bacterial Agents; Colitis, Ulcerative; Crohn Disease; Ethambutol; Female; Humans; Isoniazid; Male; Mycobacterium; Rifampin; Sulfasalazine

Topics: Bile; Bile Duct Neoplasms; Cholangitis; Cholelithiasis; Cholestasis; Colitis, Ulcerative; Humans; Rifampin