Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.

Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication

Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.

Did the severe acute respiratory syndrome-coronavirus 2 pandemic cause an endemic Clostridium difficile infection?

BACKGROUND Clostridium difficile infection(CDI)has increased in prevalence during the last years.The coronavirus disease 2019(COVID-19)pandemic has negatively influenced patient outcomes.The majority of the severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)-infected patients received antibiotics during hospitalization.AIM To analyze the factors that influenced CDI development after SARS-CoV-2 infection.METHODS Between March 2020 to December 2020,we performed a prospective observational study including 447 patients diagnosed with CDI who were admitted to our tertiary referral university hospital.The diagnosis of CDI was based on the presence of diarrhea(≥3 watery stools within 24 h)associated with Clostridium difficile toxins A or B.We excluded patients with other etiology of acute diarrhea.RESULTS Among the total 447(12.5%)patients with CDI,most were male(54.3%)and mean age was 59.7±10.8 years.Seventy-six(17.0%)had history of COVID-19,most being elderly(COVID-19:62.6±14.6 years vs non-COVID-19:56.8±17.6 years,P=0.007),with history of alcohol consumption(43.4%vs 29.4%,P=0.017),previous hospitalizations(81.6%vs 54.9%,P<0.001)and antibiotic treatments(60.5%vs 35.5%,P<0.001),requiring higher doses of vancomycin and prone to recurrent disease(25.0%vs 13.1%,P=0.011).Age over 60 years[odds ratio(OR):2.591,95%confidence interval(CI):1.452-4.624,P=0.001],urban residence(OR:2.330,95%CI:1.286-4.221,P=0.005),previous antibiotic treatments(OR:1.909,95%CI:1.083-3.365,P=0.025),previous hospitalizations(OR:2.509,95%CI:1.263-4.986,P=0.009)and alcohol consumption(OR:2.550,95%CI:1.459-4.459,P=0.001)were risk factors of CDI in COVID-19.CONCLUSION CDI risk is unrelated to history of SARS-CoV-2 infection.However,previous COVID-19 may necessitate higher doses of vancomycin for CDI.