Recurrence and death after Clostridium difficile infection: gender-dependant influence of proton pump inhibitor therapy

SpringerPlus, Apr 2016

Goals To determine whether patients with a pre-existing PPI treatment had a higher risk of poor evolution (recurrence or death) when diagnosed with a toxicogenic Clostridium difficile digestive infection. Background Previous studies identified pump proton inhibitor (PPI) prescription as a risk factor for C. difficile infection. The influence of PPI on the outcome of C. difficile infection is controversial. Study This was a retrospective monocentric cohort study. All cases of patients in our center with a symptomatic infection by a toxicogenic C. difficile strain during the years 2012 and 2013 were retrospectively analyzed. The primary endpoint was the occurrence of a recurrence or C. difficile infection -related death within 2 months after diagnosis. Results 373 patients were included in this study (198 men and 175 women), with a mean age of 70.1 ± 18.6 years (2–100 years). Fourteen (3.7 %) patients died secondarily to C. difficile infection (median survival time 5 days), and 88 (23.6 %) experienced recurrence (after a median delay of 30 days). One hundred and ninety eight (53.1 %) patients were already receiving PPI at the time of the C. difficile infection (including 156 patients with a prescription >1 month). When analyzing separately men and women, male patients were more likely to experience recurrence or death in case of pre-existing PPI prescription [HR = 2.32 (1.26–4.27)]; this was not observed in female patients [HR = 0.62 (0.31–1.22)]. Conclusions Pre-existing PPI therapy may increase the risk of recurrence or death in male patients with a toxicogenic C. difficile infection. PPI risk–benefit ratio should be carefully assessed.

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Recurrence and death after Clostridium difficile infection: gender-dependant influence of proton pump inhibitor therapy

Dos Santos‑Schaller et al. SpringerPlus Recurrence and death after Clostridium difficile infection: gender‑dependant influence of proton pump inhibitor therapy Ophélie Dos Santos‑Schaller 2 3 Sandrine Boisset 1 2 Arnaud Seigneurin 4 5 Olivier Epaulard OEpaulard@chu‑grenoble.fr 0 2 3 0 Service des Maladies Infectieuses , CHU de Grenoble, CS10217, 38043 Grenoble Cedex 09 , France 1 Laboratory of Bacteriology, Grenoble University Hospital , Grenoble , France 2 Faculty of Medicine, Grenoble Institute of Clinical , Biological and Epidemio‐ logical Infectiology, Grenoble , France 3 Infectious Disease Unit, Grenoble University Hospital , Grenoble , France 4 Computational and Mathematical Biology, TIMC‐IMAG UMR 5525 , Grenoble , France 5 Quality Science and Medical Evalu‐ ation Unit, Grenoble University Hospital , Grenoble , France Goals: To determine whether patients with a pre‑ existing PPI treatment had a higher risk of poor evolution (recurrence or death) when diagnosed with a toxicogenic Clostridium difficile digestive infection. Background: Previous studies identified pump proton inhibitor (PPI) prescription as a risk factor for C. difficile infection. The influence of PPI on the outcome of C. difficile infection is controversial. Study: This was a retrospective monocentric cohort study. All cases of patients in our center with a symptomatic infection by a toxicogenic C. difficile strain during the years 2012 and 2013 were retrospectively analyzed. The primary endpoint was the occurrence of a recurrence or C. difficile infection ‑ related death within 2 months after diagnosis. Results: 373 patients were included in this study (198 men and 175 women), with a mean age of 70.1 ± 18.6 years (2-100 years). Fourteen (3.7 %) patients died secondarily to C. difficile infection (median survival time 5 days), and 88 (23.6 %) experienced recurrence (after a median delay of 30 days). One hundred and ninety eight (53.1 %) patients were already receiving PPI at the time of the C. difficile infection (including 156 patients with a prescription >1 month). When analyzing separately men and women, male patients were more likely to experience recurrence or death in case of pre‑ existing PPI prescription [HR = 2.32 (1.26-4.27)]; this was not observed in female patients [HR = 0.62 (0.31-1.22)]. Conclusions: Pre‑ existing PPI therapy may increase the risk of recurrence or death in male patients with a toxicogenic C. difficile infection. PPI risk-benefit ratio should be carefully assessed. Proton pump inhibitor; Clostridium difficile; Death; Recurrence; Gender Background Clostridium difficile infection (CDI) has become a common cause of acute diarrhea in adults. Over the last years, CDI incidence has increased three to eight times in the USA (Lessa et al. 2015; Gilca et al. 2010) , along with the risk of complications (Pepin et  al. 2004); in Europe, the rise of an hypervirulent C. difficile strain (027 or NAP1) has been observed, this strain being responsible for more severe clinical forms and more recurrences (Davies et  al. 2014; Loo et  al. 2005) . CDI has various clinical forms, from relatively benign afebrile or febrile diarrhea, to simple colitis, pseudomembranous colitis, severe sepsis, toxic megacolon, and  organ perforation; mortality rate of severe form reaches 50  % (Venugopal et al. 2013). Classical risk factors of CDI are recent hospitalization, antibiotic prescription, age over 65 years, and immunosuppression (Pacheco and Johnson 2013) . In the last years, it has been suspected that proton pump inhibitor (PPI) therapy may be a risk factor for CDI (Kwok et  al. 2012; Janarthanan et  al. 2012) . PPI are widely prescribed; in the USA, more than 11 million patients are treated with PPI (as a long term treatment) (Fashner and Gitu 2013), and overuse has been documented in Europe (Ramirez et al. 2010) . The purpose of this study was to determine whether patients with a pre-existing PPI treatment had a higher risk of CDI recurrence or CDI-related death when diagnosed with a toxicogenic C. difficile strain. Results Population From January 2012 to December 2013, Clostridium difficile was detected in feces of 592 patients. Three hundred and seventy-three patients meeting the inclusion criteria (clinical symptoms including at least diarrhea, and fecal samples positive for toxicogenic C. difficile) were included. One hundred and ninety eight (53.1 %) patients were men and 175 (46.9  %) were women. The mean age was 70.1 ± 51.5–88.7 (2–100 years). Among the included patients, 5 were carrying the 027 C. difficile strain. Among the 373 included patients, 198 (53.1  %) were receiving PPI before CDI; PPI therapy was initiated more than 1  month before CDI in 156 patients (41.8  %). Two hundred and seventy (72.4 %) patients received antibiotics within a month before the infection, 269 (72.1 %) had been hospitalized in the 3 months prior to the CDI, and 72 (19.3 %) were receiving long term immunosuppressive therapy ( (...truncated)


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Ophélie Dos Santos-Schaller, Sandrine Boisset, Arnaud Seigneurin, Olivier Epaulard. Recurrence and death after Clostridium difficile infection: gender-dependant influence of proton pump inhibitor therapy, SpringerPlus, 2016, pp. 430, Volume 5, Issue 1, DOI: 10.1186/s40064-016-2058-z