title: Risk factors, preemptive therapy, and antiperistaltic agents for Clostridium difficile infection in cancer patients.
abstract: BACKGROUND
  Clostridium difficile infection (CDI) is a serious complication of chemotherapy including high-dose regimens with autologous stem cell transplantation (ASCT). Antiperistaltic agents are contraindicated in CDI and preemptive CDI therapy is not recommended. We assessed the incidence, risk factors, and outcomes of CDI in patients with newly diagnosed multiple myeloma (MM) receiving similar antineoplastic therapy and supportive care including antiperistaltic agents and preemptive CDI antibiotics for significant diarrhea.
  
  
  METHODS
  A total of 303 consecutive MM patients (2004-2007) were enrolled in a protocol consisting of induction chemotherapy, tandem melphalan (MEL)-ASCT, and consolidation. Patients with grade 2-4 diarrhea were simultaneously tested for CDI, and initiated on antiperistaltic agents (loperamide) and preemptive anti-CDI therapy. Risk factors, including prior CDI and MM immunoglobulin (Ig) isotype, were evaluated. Multinomial logistic regression was used to compute the relative risk ratio (RRR) and 95% confidence intervals (CIs).
  
  
  RESULTS
  There were 43 cases of CDI (14.2%) during 1529 chemotherapy courses (536 ASCT). IgA MM protected against CDI (RRR 0.35; 95% CI 0.13-0.93, P = 0.04) whereas CDI during first induction markedly increased the risk of recurrence during second induction (RRR = 10.94; 95% CI 1.90, 62.92, P = 0.01) and following MEL-ASCT (RRR = 6.63; 95% CI 1.51, 29.12, P = 0.01). No CDI-related surgical intervention or death ensued despite use of antiperistaltic agents.
  
  
  CONCLUSIONS
  CDI was not uncommon in cancer patients receiving chemotherapy. IgA myeloma appears to be protective. Concurrent antiperistaltic (loperamide) and preemptive CDI therapies were associated with excellent outcomes. Prior CDI history increased the risk for recurrence during successive chemotherapy courses.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; Department of Gastroenterology, Hepatology and Nutrition, Ohio State University Medical Center, Columbus, Ohio, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Krishna
authors.forename: W
authors.initials: W
authors.lastname: Zhao
authors.forename: S K
authors.initials: SK
authors.lastname: Apewokin
authors.forename: K
authors.initials: K
authors.lastname: Krishna
authors.forename: P
authors.initials: P
authors.lastname: Chepyala
authors.forename: E J
authors.initials: EJ
authors.lastname: Anaissie
mesh_terms: D000328:Adult; D000368:Aged; D000930:Antidiarrheals / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*; D000075202:Contraindications; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008139:Loperamide / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000628:therapy; D016017:Odds Ratio; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000930:Antidiarrheals; D008139:Loperamide
keywords: Clostridium difficile; anti-motility drugs; antiperistaltic drugs; chemotherapy; loperamide; lower alimentary tract mucositis; multiple myeloma; stem cell transplantation