Bone Marrow Transplantation, (1999) 23 , 1039–1042  1999 Stockton Press All rights reserved 0268–3369/99 $12.00 http:/ / www.stockton-press.co.uk/ bmt Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation S Bilgrami, JM Feingold, D Dorsky, RL Edwards, RD Bona, AM Khan, F Rodriguez-Pinero, J Clive and PJ Tutschka Bone Marrow Transplant Program, University of Connecticut Health Center, Farmington, CT, USA Summary: A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of infection with Clostridium difficile. The diag- nosis was confirmed in 14 patients with diarrhea (15 episodes) at a median of 33 days after stem cell infusion. Five patients were neutropenic at the time of diagnosis. Every individual had adverse known risk factors such as recent or current use of antibiotic, corticosteroid and antiviral therapy, recent administration of myelo- ablative chemotherapy and numerous, prolonged periods of hospitalization. Diarrhea, frequently hemorrhagic, was the most common presenting feature along with fever, abdominal cramps and abdominal dis- tention. Diagnosis was established by the stool-cytotoxin test. Response to standard treatment with oral vanco- mycin or metronidazole was prompt despite the pres- ence of several adverse prognostic features in these patients. There was only one instance of relapse which was also treated successfully. Several transplant-related variables such as age, sex, underlying malignancy, myelo-ablative regimen, duration of neutropenia, and prophylactic use of oral ampicillin underwent statistical analysis but failed to be predictive of C. difficile infec- tion in such a setting. Finally, C. difficile is not uncom- mon after autologous PBSCT and must be included in the differential diagnosis in any such patient with diarrhea. Keywords: Clostridium difficile; autologous stem cell transplant Clostridium difficile is a gram-positive, spore-forming ana- erobe which has been implicated in antibiotic-associated diarrhea or colitis, or pseudomembranous colitis (PCM). Only enterotoxin-producing strains are pathogenic. 1 The pathogenesis of this infection involves several steps includ- ing alteration of the normal colonic flora by antibiotic ther- apy, colonization of the gut by C. difficile, and finally, intes- tinal mucosal damage and inflammation due to enterotoxin production by these organisms. 1,2 Broad-spectrum anti- Correspondence: Dr S Bilgrami, University of Connecticut Health Center, MC-1315, 263 Farmington Avenue, Farmington, CT 06030, USA Received 18 August 1998; accepted 13 January 1999 microbial agents such as clindamycin, sulfonamides, tetra- cyclines, penicillins and cephalosporins can all disrupt the normal colonic flora and lead to an intestinal environment that is conducive to the overgrowth of C. difficile. 3–5 Fur- thermore, a suitable external environment is provided by hospitals and nursing facilities which act as an exogenous source of C. difficile organisms and spores. 1,6–13 However, not every case of C. difficile infection is preceded by anti- biotic therapy. Other risk factors include recent cancer chemotherapy 14 and anti-viral chemotherapy. 15 Patients undergoing bone marrow transplantation (BMT) or periph- eral blood stem cell transplantation (PBSCT) appear to be a group at particularly high risk because they are treated with numerous antibiotics, are hospitalized for prolonged periods of time, receive myelo-ablative chemotherapy caus- ing severe pancytopenia, and are severely immunocompro- mised for several months to years. Surprisingly, there are few prior reports of C. difficile infection occurring in this setting. 16,17 We evaluated 200 individuals with a variety of malignancies who received high-dose chemotherapy fol- lowed by autologous PBSCT. The incidence, clinical fea- tures, treatment and outcome of C. difficile infection in these patients is described. Materials and methods Two hundred consecutive patients who underwent autolog- ous PBSCT between March 1993 and August 1996, at the University of Connecticut Health Center, Farmington, CT, USA, were eligible for this retrospective evaluation. Clini- cal data were obtained from comprehensive chart reviews in all patients (Table 1). The underlying malignancies included carcinoma of the breast (n = 99), non-Hodgkin’s lymphoma or Hodgkin’s disease (n = 65), multiple myeloma (n = 14), ovarian cancer (n = 7), acute leukemia (n = 6) and miscellaneous solid tumors (n = 9). During the 30 days preceding the initiation of myeloablative conditioning chemotherapy, all 200 patients received a stem cell mobilizing chemotherapy regi- men as follows: etoposide 60 mg/kg intravenously (n = 40); cyclophosphamide 3 g/m 2 intravenously (n = 3); etoposide 60 mg/kg intravenously and cyclophosphamide 3 g/m 2 intravenously (n = 17); and etoposide 60 mg/kg intra- venously, cyclophosphamide 3 g/m 2 intravenously, and paclitaxel 200 mg/m 2 intravenously (n = 140). Every patient received prophylactic ciprofloxacin 500 mg orally twice daily from the completion of chemotherapy until