gms | German Medical Science

Background: Metronidazole has been considered as the first line therapy for the Clostridium difficile-associated diarrhea (CDAD). In refractory cases or severe cases oral vancomycin serves as an alternative therapy. However, oral vancomycin is not available in our country, and also vancomycin resistant enterococci (VRE) is of concern in centers which use vancomycin in the treatment of CDAD. Tigecycline is minocycline which has been approved for the treatment of complicated skin-soft tissue infections, intra-abdominal infections and community acquired pneumonia. Tigeycline was found to be active against C. difficile strians in vitro, and few case reports showed that tigecycline can be used as an alternative in the treatment of CDAD. Here, we aimed to share our experience in the treatment of CDAD with tigecycline in hematopoetic stem cell recepients.

Patients and Methods: Hematopoetic stem cell transplant patients who had uniform stools more than 3 times a day, are tested by ELISA test for C. difficile as a part of etiological investigation of diarrhea in our center. Each CDAD episode was considered mild to moderate if the white blood cell (WBC) count was <15,000 cells/mm³ and the serum creatinine (SCr) level was <1.5X the baseline value. Severe disease was defined as a WBC count of ≥15,000 cells/mm³ or an SCr level that was >1.5X the baseline value. Response to therapy against CDAD was defined as resolution of diarrhea, and no further need for anti-CDAD therapy. CDAD recurrence was defined as diarrhea within 8 weeks of the end of therapy accompanied by a positive C. difficile toxin test.

Results: Between January 2012 and September 2013 a total of 19 hematopoetic stem cell recepients with CDAD were detected. 11 out of 19 patients were successfully treated with metronidazole. However, 8 (42.1%) patients did not respond to the therapy. The median age of the patients with metronidazole failure were 25.5 years (range, 20-56 years), and six were male. 6 out of 8 patients underwent allogenic stem cell transplantation, and 2 of them received autologous stem cell transplantation.Three of them were diagnosed as gastrointerstinal graft versus host disease (GVHD) and patient was diagnosed as skin GVHD before diagnosis of CDAD. Patients with GVHD received corticosteroids, mycophenolate mofetil ± cyclosporin. Six out eight patients were under metronidazole prophylaxis for gastrintestinal GVHD before CDAD were diagnosed and two patients received metranidazole as the first line treatment for CDAD. Two of the eight patients had severe CDAD, however, neutrophil count was below 500/mm³ in four patients who don’t meet the criteria for severe CDAD. Clinical improvement was detected six out of eight patients who received tigecycline. Median duration tigecycline was 14 days (range; 3-12 days). One patient died due to respiratory insufficiency at the fifth day of tigecycline therapy and skin rash developed in an other patient which was resolved after tigecycline was stopped. New-onset VRE colonization was not noted after tigecycline therapy. None of the patients had recurrent CDAD up to six month follow up.

Conclusion: Tigecycline can serve as an effective treatment option for CDAD in patients with stem cell transplantation.