Acid Suppression Therapy Does Not Predispose to Clostridium difficile Infection: The Case of the Potential Bias

Abstract

ObjectiveAn adverse effect of acid-suppression medications on the occurrence of Clostridium difficile infection (CDI) has been a common finding of many, but not all studies. We hypothesized that association between acid-suppression medications and CDI is due to the residual confounding in comparison between patients with infection to those without, predominantly from non-tested and less sick subjects. We aimed to evaluate the effect of acid suppression therapy on incidence of CDI by comparing patients with CDI to two control groups: not tested patients and patients suspected of having CDI, but with a negative test.MethodsWe conducted a case-control study of adult patients hospitalized in internal medicine department of tertiary teaching hospital between 2005–2010 for at least three days. Controls from each of two groups (negative for CDI and non-tested) were individually matched (1∶1) to cases by primary diagnosis, Charlson comorbidity index, year of hospitalization and gender. Primary outcomes were diagnoses of International Classification of Diseases (ICD-9)–coded CDI occurring 72 hours or more after admission.ResultsPatients with CDI were similar to controls with a negative test, while controls without CDI testing had lower clinical severity. In multivariable analysis, treatment by acid suppression medications was associated with CDI compared to those who were not tested (OR = 1.88, p-value = 0.032). Conversely, use of acid suppression medications in those who tested negative for the infection was not associated with CDI risk as compared to the cases (OR = 0.66; p = 0.059).ConclusionsThese findings suggest that the reported epidemiologic associations between use of acid suppression medications and CDI risk may be spurious. The control group choice has an important impact on the results. Clinical differences between the patients with CDI and those not tested and not suspected of having the infection may explain the different conclusions regarding the acid suppression effect on CDI risk.

Clostridium difficile infection

“…Given that disruption of the intestinal flora persists for >3 months after antibiotic therapy, patients can remain susceptible to CDI development long after ending the treatment 28 . Acid suppression by proton pump inhibitors (commonly used for dyspepsia, peptic ulcer disease and gastroesophageal reflux disease) has frequently been associated with CDI 158,159 but the precise role of proton pump inhibitors in CDI (and a causal relationship) remains unclear 160,161 . Of all patients with antibiotic-associated diarrhoea, 20–30% is caused by C. difficile 162 .…”

Changing epidemiological pattern of hospital and community borne Clostridium difficile infections: A cause for public health concern

“…In general, gastric acid suppression is believed to aid the reach of more vegetative organisms to the colon; however, the spores of C. difficile are acid-resistant and capable of remaining viable at the low pH gastric juice. Although some investigators have reported the increase in risk of CDI with acid suppression [28], the others have not agreed with this [37,46]. A study investigating CDI in patients aged 67 to 92 years old observed that all of these patients were non-surgical and haemodialysis and intensive care unit stay were not risk factors [39].…”

Faktori rizika za nastanak bolesti povezanе sa Clostridium difficile

“…Studije koje su se do sada bavile ispitivanjem potencijalne veze između CDAD i lekova koji smanjuju lučenje hlorovodonične kiseline, pre svega inhibitora protonske pumpe, često su dolazile do potpuno kontradiktornih rezultata. Dok su neki autori sugerisali na povezanost primene ovakve terapije sa CDAD, drugi su nakon određenih prilagođavanja potpuno negirali postojanje takve veze [39,40].…”