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)