Clostridium difficile Infection Associated with Antineoplastic Chemotherapy: A Review

Abstract

Colitis and infection due to Clostridium difficile have been reported in patients receiving antineoplastic chemotherapy for cancer without prior antibiotic treatment. Chemotherapeutic agents can alter the normal bowel flora and cause extensive intestinal inflammatory changes, potentiating both the growth of C. difficile and its production of toxin. This review includes all 23 known reported cases of C. difficile infection associated with antineoplastic chemotherapy and examines the pathogenesis, clinical features, and management of this condition. Chemotherapy-associated C. difficile colitis has been documented in association with a variety of neoplasms. Various classes of antineoplastic agents have been incriminated, methotrexate most commonly. A spectrum of illness ranging from mild to fulminant has been reported. Symptoms, management, and outcome have appeared to be no different than for antibiotic-associated cases, but the available data are limited. Chemotherapy-associated infection with C. difficile may be underreported because it is not suspected and/or because frequent concomitant use of antibiotics masks its true incidence. C. difficile infection should be kept in mind whenever a patient undergoing antineoplastic chemotherapy develops diarrhea. Prompt, appropriate diagnostic testing and early treatment may avert morbidity and death.

Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality

“…Methotrexate and fluorouracil have been incriminated most frequently in anti-neoplasticassociated C. difficile infection. 2 However, the use of short course methotrexate in our study was not associated with an increased incidence of C. difficile infection.…”

Peri‐transplant clostridium difficile infections in patients undergoing allogeneic hematopoietic progenitor cell transplant

“…A study found that gastrointestinal colonization with toxigenic Clostridium difficile occurred in 12% of recipients of HPC transplant on admission to the hospital [6]. In addition, these patients are immunocompromised, receive extensive exposure to broad spectrum antimicrobials before and after HPC transplant, have compromise of the integrity of the intestinal mucosa due to the high dose chemoradiation given to the patients as part of transplant preparative regimens, and also often have very prolonged hospital stay [7][8][9]. Studies have shown the association of CDI with the development of acute Graft-versus-host disease (GVHD) [10,11] and increased non-relapse mortality [10] after allogeneic HPC transplant.…”

Risk factors, outcomes and epidemiology associated with Clostridium difficile infection in patients with haematological malignancies in a tertiary care hospital in China

“…Several studies have shown that antineoplastic agents, such as methotrexate and doxorubicin, have intrinsic antimicrobial activity, alter the bowel flora and precipitate an overgrowth of C. difficile (Anand & Glatt, 1993).…”

“…Antineoplastic drugs can also damage the gut and induce severe inflammatory changes, promote an anaerobic environment, and decrease degradation of C. difficile toxins by promoting an accumulation of albumin and other protein-rich fluids in the lumen of the gut (Anand & Glatt, 1993;Jarvis & Shevchuk, 1997). Reports show a 76-91 % incidence of diarrhoea in HSCT recipients (Tomblyn et al, 2002), and the incidence of CDI in these patients can be as high as 20 % (Bobak et al, 2008).…”