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Clostridium difficile infection in cancer patients
Med Clin (Barc). 2017;148(2):91–94
www.elsevier.es/medicinaclinica
Scientific letters Clostridium difficile infection in cancer patients夽 Infección por Clostridium difficile en pacientes con cáncer Dear Editor, We read with great interest the scientific letter by GarcíaLozano et al.,1 regarding Clostridium difficile infection (CDI) in cancer patients. Concerning the same, we would like to make some observations. We agree with the authors that cancer patients in active treatment have a higher incidence of CDI compared with other type of patients (7 vs 1–2%),2 this is attributable to many factors among which age, repeated contact with the health system, prolonged hospitalization, broad-spectrum antibiotic treatments, bone marrow and hematopoietic stem cell transplantation, neutropenia, anticancer treatments (methotrexate, 5-fluorouracil, DNA topoisomerase inhibitors), previous episodes of CDI and blood transfusions2–5 stand out. CDI complicates the progression of cancer patients and makes the implementation of chemotherapy or radiotherapy difficult. In addition, there may be an underdiagnosis of CDI in cancer patients because diarrhea and fever can be side effects of anticancer drugs. In our healthcare environment, up to 17.3% of diarrhea episodes in hospitalized cancer patients are caused by CDI.3 The good clinical progression of all patients in the first episode of CDI (3 untreated patients and 17 with oral metronidazole), the low rate of recurrence (2 in 20 patients) and the absence of complications or death1 is highlighted in García-Lozano et al.’s series. These progression data are better than those described in general hospital patients, with 18% recurrence, 22% mortality and 9% mortality attributable to CDI.5 Progression results are more unfavorable in other cancer patient series, (8.2% recurrence, mortality attributable to CDI 19.7% and treatment failure 29.5%), and rates of response to antibiotic treatment for CDI are lower (53.7% for metronidazole and 50% for vancomycin).2 The benign course of the García-Lozano et al. series is probably attributable to dealing with episodes of mild and moderate CDI, as 3 patients were cured without specific treatment for CDI, and no patient had <500 neutrophils/mm,3 but we do not have this information. The clinical practice recommendations on CDI of the Infectious Diseases Society of America (IDSA)4 and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID)5 recommend early identification of the CDI episode’s severity, depending on the existence of a number of predictors (clinical, laboratory and radiological) to improve the adequacy of treatment. However,
夽 Please cite this article as: Sánchez-Munoz ˜ LA, Martín Asenjo M, Martín Guerra J. Infección por Clostridium difficile en pacientes con cáncer. Med Clin (Barc). 2017;148:91.
the reliability of these predictors in cancer patient series seems improvable.2 The reasons can be many: (1) some predictors of severity are leukocytosis,4,5 the left shift5 and fever >38.5 ◦ C.5 Since cancer patients frequently experience neutropenia (up 44.3%),2 inadequate response of the bone marrow to infection and fever and/or diarrhea secondary to concurrent infections or chemotherapy rather than as a consequence of CDI, these predictors of severity may underestimate it; and (2) neutropenia appears as an independent risk factor for CDI-associated mortality in recent studies,2 therefore, alternative definitions of severity that include neutropenia would be needed in order to enhance their accuracy. Finally, in the recent ESCMID guide, cancer is one of the comorbidities considered a poor prognostic outcome marker.5 This causes CDI to be severe in a patient with cancer (or at increased risk of developing severe CDI) and the recommended treatment would be, in this order, vancomycin 125 mg/6 h oral 10 days (AI), fidaxomicin 200 mg/12 h oral 10 days (B-I) and metronidazole 500 mg/8 h oral 10 days (D-I).5 In short, although CDI episodes in this series show a positive progression with metronidazole, the ESCMID guide5 recommends to consider CDI episodes in cancer patients as serious or potentially serious. More studies are needed in order to make a proper stratification of severity in these patients. References 1. García-Lozano T, Aznar-Oroval E, Martín-Utrilla S. Recurrencias en infecciones por Clostridium difficile en pacientes con cáncer. Med Clin (Barc). 2016;147:417–8. 2. Yoon YK, Kim MJ, Sohn JW, Kim HS, Choi YJ, Kim JS, et al. Predictors of mortality attributable to Clostridium difficile infection in patients with underlying malignancy. Support Care Cancer. 2014;22:2039–48. ˜ 3. Rodriguez-Garzotto A, Mérida-García A, Munoz-Unceta N, Galera-López MM, Orellana-Miguel MA, Díaz-García CV, et al. Risk factors associated with Clostridium difficile infection in adult oncology patients. Support Care Cancer. 2015;23:1569–77. 4. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31: 431–55. 5. Debast SB, Bauer MP, Kuijper EJ, European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20 Suppl. 2:S1–26.
˜ ∗ , Miguel Martín Asenjo, Luis Angel Sánchez-Munoz Javier Martín Guerra Servicio de Medicina Interna, Hospital Clínico Universitario de Valladolid, Valladolid, Spain ∗ Corresponding
author. ˜ E-mail address: [email protected] (L.A. Sánchez-Munoz). 2387-0206/ ˜ S.L.U. All rights reserved. © 2016 Elsevier Espana,
www.elsevier.es/medicinaclinica
Scientific letters Clostridium difficile infection in cancer patients夽 Infección por Clostridium difficile en pacientes con cáncer Dear Editor, We read with great interest the scientific letter by GarcíaLozano et al.,1 regarding Clostridium difficile infection (CDI) in cancer patients. Concerning the same, we would like to make some observations. We agree with the authors that cancer patients in active treatment have a higher incidence of CDI compared with other type of patients (7 vs 1–2%),2 this is attributable to many factors among which age, repeated contact with the health system, prolonged hospitalization, broad-spectrum antibiotic treatments, bone marrow and hematopoietic stem cell transplantation, neutropenia, anticancer treatments (methotrexate, 5-fluorouracil, DNA topoisomerase inhibitors), previous episodes of CDI and blood transfusions2–5 stand out. CDI complicates the progression of cancer patients and makes the implementation of chemotherapy or radiotherapy difficult. In addition, there may be an underdiagnosis of CDI in cancer patients because diarrhea and fever can be side effects of anticancer drugs. In our healthcare environment, up to 17.3% of diarrhea episodes in hospitalized cancer patients are caused by CDI.3 The good clinical progression of all patients in the first episode of CDI (3 untreated patients and 17 with oral metronidazole), the low rate of recurrence (2 in 20 patients) and the absence of complications or death1 is highlighted in García-Lozano et al.’s series. These progression data are better than those described in general hospital patients, with 18% recurrence, 22% mortality and 9% mortality attributable to CDI.5 Progression results are more unfavorable in other cancer patient series, (8.2% recurrence, mortality attributable to CDI 19.7% and treatment failure 29.5%), and rates of response to antibiotic treatment for CDI are lower (53.7% for metronidazole and 50% for vancomycin).2 The benign course of the García-Lozano et al. series is probably attributable to dealing with episodes of mild and moderate CDI, as 3 patients were cured without specific treatment for CDI, and no patient had <500 neutrophils/mm,3 but we do not have this information. The clinical practice recommendations on CDI of the Infectious Diseases Society of America (IDSA)4 and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID)5 recommend early identification of the CDI episode’s severity, depending on the existence of a number of predictors (clinical, laboratory and radiological) to improve the adequacy of treatment. However,
夽 Please cite this article as: Sánchez-Munoz ˜ LA, Martín Asenjo M, Martín Guerra J. Infección por Clostridium difficile en pacientes con cáncer. Med Clin (Barc). 2017;148:91.
the reliability of these predictors in cancer patient series seems improvable.2 The reasons can be many: (1) some predictors of severity are leukocytosis,4,5 the left shift5 and fever >38.5 ◦ C.5 Since cancer patients frequently experience neutropenia (up 44.3%),2 inadequate response of the bone marrow to infection and fever and/or diarrhea secondary to concurrent infections or chemotherapy rather than as a consequence of CDI, these predictors of severity may underestimate it; and (2) neutropenia appears as an independent risk factor for CDI-associated mortality in recent studies,2 therefore, alternative definitions of severity that include neutropenia would be needed in order to enhance their accuracy. Finally, in the recent ESCMID guide, cancer is one of the comorbidities considered a poor prognostic outcome marker.5 This causes CDI to be severe in a patient with cancer (or at increased risk of developing severe CDI) and the recommended treatment would be, in this order, vancomycin 125 mg/6 h oral 10 days (AI), fidaxomicin 200 mg/12 h oral 10 days (B-I) and metronidazole 500 mg/8 h oral 10 days (D-I).5 In short, although CDI episodes in this series show a positive progression with metronidazole, the ESCMID guide5 recommends to consider CDI episodes in cancer patients as serious or potentially serious. More studies are needed in order to make a proper stratification of severity in these patients. References 1. García-Lozano T, Aznar-Oroval E, Martín-Utrilla S. Recurrencias en infecciones por Clostridium difficile en pacientes con cáncer. Med Clin (Barc). 2016;147:417–8. 2. Yoon YK, Kim MJ, Sohn JW, Kim HS, Choi YJ, Kim JS, et al. Predictors of mortality attributable to Clostridium difficile infection in patients with underlying malignancy. Support Care Cancer. 2014;22:2039–48. ˜ 3. Rodriguez-Garzotto A, Mérida-García A, Munoz-Unceta N, Galera-López MM, Orellana-Miguel MA, Díaz-García CV, et al. Risk factors associated with Clostridium difficile infection in adult oncology patients. Support Care Cancer. 2015;23:1569–77. 4. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31: 431–55. 5. Debast SB, Bauer MP, Kuijper EJ, European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20 Suppl. 2:S1–26.
˜ ∗ , Miguel Martín Asenjo, Luis Angel Sánchez-Munoz Javier Martín Guerra Servicio de Medicina Interna, Hospital Clínico Universitario de Valladolid, Valladolid, Spain ∗ Corresponding
author. ˜ E-mail address: [email protected] (L.A. Sánchez-Munoz). 2387-0206/ ˜ S.L.U. All rights reserved. © 2016 Elsevier Espana,