Use of Acid-Suppressing Drugs and the Risk of Bacterial Gastroenteritis

doi:10.1016/j.cgh.2007.09.010

Clinical Gastroenterology and Hepatology

Volume 5, Issue 12, December 2007, Pages 1418-1423

https://doi.org/10.1016/j.cgh.2007.09.010 Get rights and content

Background & Aims: Gastric acid is a defense mechanism against gastrointestinal infections caused by ingested bacteria. Studies have suggested that the use of acid-suppressing drugs may increase the risk of gastroenteritis (GE). Methods: Patients aged 20−74 years with an episode of acute bacterial GE (n = 6414) were identified. A control group from the same study population without a diagnosis of GE (n = 50,000) was frequency-matched by age, sex, and calendar year to the case group. Unconditional logistic regression was used to calculate the adjusted relative risk (RR) of GE in patients using proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H₂RAs). Results: Current use of PPIs was associated with an increased risk of bacterial GE compared with nonuse, regardless of the treatment duration (RR, 2.9; 95% confidence interval [CI], 2.5−3.5), whereas no association was observed with H₂RA use (RR, 1.1; 95% CI, 0.9−1.4). Doubling the PPI dose further increased the risk of developing bacterial GE (RR, 5.0; 95% CI, 2.7−9.3). The effect of PPI use did not vary significantly with regard to treatment indication. The increased risk associated with PPI use was similar for both omeprazole (RR, 3.0; 95% CI, 2.5−3.7) and lansoprazole (RR, 2.1; 95% CI, 1.4−3.0), whereas neither cimetidine nor ranitidine showed any increased risk. Campylobacter (n = 4124) and Salmonella (n = 1885) were the 2 species most frequently responsible for GE episodes in the case group. When analyzed separately, both species reproduced the increased risk associated with PPI use and not H₂RA use. Clostridium GE cases were rare (n = 31). Conclusions: This study suggests that gastric acid suppression induced by PPIs but not H₂RAs is associated with an increased risk of Campylobacter and Salmonella GE.

Section snippets

Study Design

We conducted a nested case-control study using the General Practice Research Database. The General Practice Research Database is a population-based database in the United Kingdom where general practitioners store their practice database with clinical information on their patients including demographics, diagnoses, and free text comments, referral information, and records of all prescriptions issued by them.⁶ Data on about 3 million patients are recorded systematically and sent anonymously to

Results

Selected characteristics of cases and controls are presented in Table 1. Because of the matching, cases and controls had a similar distribution of age and sex. Excessive alcohol consumers presented a greater risk than abstainers, as shown in Table 1. The risk of developing gastroenteritis was more than twice as great in summer than in the colder seasons. Leanness (body mass index < 20) conferred a close to 25% reduced risk of bacterial GE compared with normal-weight individuals. Current use of

Discussion

This large population-based study found that PPI use is associated with an increased risk of bacterial gastroenteritis. The hazard of GE quickly returns to the background level after cessation of PPI treatment, is relatively constant over treatment duration, is greater with double-dose PPI therapy, and is of similar magnitude with the use of omeprazole and lansoprazole. By contrast, consumption of H₂RA did not carry a greater risk of bacterial GE. All these associations were reproduced when

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Cited by (110)

Acute Bacterial Gastroenteritis
2021, Gastroenterology Clinics of North America
Citation Excerpt :
Medications that counter fundamental host defenses against invading enteric pathogens can put patients at increased risk. Proton pump89 inhibitors may increase the risk for symptomatic infection90 with several enteric pathogens, including NTS and Campylobacter,91,92 by reducing gastric acidity, an essential first line of host defense. Similarly, prior antibiotic use has been shown to promote infection by both of these pathogens, presumably by removing the colonization resistance of competing normal flora or by fostering the selection of resistant organisms.24,93
Long-term use of proton pump inhibitors as a risk factor for various adverse manifestations
2021, Therapies
The long-term use of proton pump inhibitors (PPIs) can lead to increased gastric pH, hypochlorhydria and in some cases to achlorhydria when compared to other acid-suppressing agents like histamine-2 (H2) receptor blockers and antacids. These consequences by the use of long-term PPIs may lead to significant vitamin (B₁₂ and C) and mineral (iron, calcium and magnesium) deficiencies which needs gastric acid for their absorption and bioavailability. Long-term use of PPIs by the pregnant patients may impose a potential risk of congenital malformations. Various studies have recommended the life style modifications and antacid use as first choice among pregnant womens by preserving PPIs (omeprazole as a safe choice of PPI) for severe conditions of gastroesophageal reflux disease. The long-term acid suppression by PPIs can also lead to enteric, respiratory and urinary tract infections. The hypochlorhydria by chronic PPIs use may induce hypergastrinemia, which ultimately mediates the gastric polyps, gastric carcinoids and gastric cancer. The concomitant use of PPIs with antiplatelet drugs like clopidogrel can impose the patients to major adverse cardiac events. This review has enlisted the comprehensive information regarding the adverse effects induced by long-term use of PPIs and their possible relations. Considerable studies like case-control, randomized trials, cohort studies and meta-analysis were reported in supporting these adverse effects. The clinicians and patients should be cautious about these effects so that they can avoid the serious outcomes. PPIs should be avoided for long-term use mainly in older adults unless there is a proper indication.
Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis – An international cohort study
2020, Pancreatology
Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP.
We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018.
Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality.
Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.
Gastroesophageal Reflux
2020, Pediatric Gastrointestinal and Liver Disease, Sixth Edition
Esophageal reflux is a common finding in infants and children. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition have developed guidelines for the management of infants and children with this condition. In children with prolonged or severe symptoms, determination of the underlying etiology enables appropriate therapeutic intervention.
Impact of an evaluation of the professional practices on the relevance of proton pump inhibitors prescriptions pertinence at the hospital
2018, Revue de Medecine Interne
Les inhibiteurs de la pompe à protons (IPP) sont largement prescrits pour des indications non reconnues, à forte dose, pour une durée prolongée, malgré des effets indésirables et des interactions médicamenteuses nombreux. En 2009, la HAS a publié des recommandations de bonne prescription mais ces dernières sont peu respectées. Dans ce contexte de surprescription et de surcoût pour la société, nous avons réalisé une évaluation des pratiques professionnelles sur le modèle de la roue de Deming. L’objectif de ce travail était d’optimiser la pertinence des prescriptions des IPP dans deux services de médecine interne et de gériatrie grâce à une évaluation des pratiques professionnelles. Toutes les prescriptions d’IPP étaient analysées qu’elles aient été initiées en externe ou durant l’hospitalisation.
Le recueil des données était prospectif, sur deux périodes de 2 mois et incluait 163 (première phase) puis 139 patients (deuxième phase). Une grille d’évaluation des prescriptions d’IPP était remplie par les médecins concernant le principe actif, la posologie, la durée et l’indication de la prescription. La pertinence correspondait aux prescriptions d’IPP avec une indication et une durée conformes et aux prescriptions non recommandées arrêtées. À la suite de la première période de recueil des données, une information des internes et médecins sur la pertinence de leurs prescriptions au regard des recommandations actuelles et la distribution de plaquettes d’aide à la prescription étaient faites dans le but d’améliorer les pratiques avant la seconde période d’évaluation (deuxième phase).
Lors de la première phase, seulement 25 % des prescriptions pré-hospitalières et 33 % des prescriptions hospitalières respectaient les recommandations de la HAS. La principale indication des IPP était la prévention d’ulcères gastroduodénaux dans un contexte de prise médicamenteuse estimée à risque. Une amélioration de la pertinence des prescriptions était observée après la sensibilisation des prescripteurs : pertinence de 26 % lors de la première phase à 60 % après rappel auprès des prescripteurs (p < 0,012). Lors de la seconde phase, la part des prescriptions d’IPP initiées à l’hôpital diminuait de 33 à 17 % et l’arrêt de l’exposition non recommandée avec information des médecins correspondants augmentait de 6 à 33 % (p < 0,001). Cependant, lors de la deuxième phase, 33 % des prescriptions initiées en hospitalisation étaient toujours non recommandées et 61 % des prescriptions débutées en externe non conformes étaient toujours poursuivis à la sortie, probablement par manque d’information suffisante pour arrêter la prescription d’IPP.
Notre étude souligne le non-respect fréquent des recommandations dans la prescription des IPP. De manière intéressante, une évaluation des pratiques professionnelles a permis une amélioration de la pertinence des prescriptions avec un arrêt plus fréquent des expositions chroniques non conformes et une baisse des prescriptions hors indications. Notre étude suggère qu’il est primordial de poursuivre la sensibilisation des internes et des médecins hospitaliers et de ville dans leur prescription d’IPP. Une information des patients sur les indications et la durée limitée de la prescription, les effets indésirables potentiellement graves d’une prise prolongée et le risque d’interactions médicamenteuses reste également nécessaire pour faciliter l’arrêt de l’exposition et limiter l’automédication.
Proton pump inhibitors (PPI) are widely prescribed for unrecognized indications, at high a dose and for a long duration, in spite of side effects and numerous drug interactions. In 2009, the HAS (French Health Authority) published recommendations of good prescription but the latter are poorly respected. In this context of over prescription and additional cost for the society, we performed a professional practice evaluation of on the model of the Deming wheel. The objective of this work was to optimize the relevance of the prescriptions of the IPP in two services of internal medicine and geriatrics through an evaluation of the professional practices. All PPI prescriptions introduced in outpatient visits or during hospitalization were analyzed.
Data collection was prospective, over two periods of 2 months and included 163 (first phase), then 139 patients (second phase). An assessment grid of PPI prescriptions was completed by physicians regarding the active substance, the dose, the duration and the indication of the prescription. The relevance of the prescription corresponded to PPI with a conformed indication and duration and to the prescriptions no recommended stopped. Following the first period of data collection, information was given to medical students and physicians on the relevance of their prescriptions with regard to the current recommendations and informative flyers were offered with the aim of improving the practices before the second period of evaluation (second phase).
During the first phase, only 25% of the pre-hospital prescriptions and 33% of the hospital prescriptions respected the HAS recommendations. The main indication of the PPI was the prevention of peptic ulcers in a context of associated drug estimated at risk. An improvement of the global relevance of prescription was observed after awareness of the physicians: 26% relevance during the first phase and 60% in the second one (P < 0.012). During the second phase, the part of PPI prescriptions introduced at hospital decreased from 33 to 17% and the discontinuation of the not corresponding prescriptions increased from 6 to 33%, with an additional information given to the general practitioner (P < 0.001). However, during the second phase, 33% of the prescriptions introduced in hospitalization were always not corresponding and 61% of the not corresponding prescriptions begun in outpatient visits were always pursued on discharge, probably due to the lack of sufficient information to stop the prescription.
Our study underlines the frequent disrespect of the indications in the prescription of PPI. Interestingly, a professional practices evaluation improved the relevance of the prescriptions with a more frequent withdrawal of the not corresponding exposure and a decrease in global not corresponding prescriptions. Our study suggests that it is crucial to regularly inform physicians on the good prescription of PPI. Patient information focused on the indications and the limited duration of PPI prescription, potentially severe side effects of chronic exposure and on the risk of drug interactions also remains necessary in order to facilitate the stop of the exposure and restrict self-medication.
Bowel symptoms in patients that receive proton pump inhibitors. Results of a multicenter survey in Mexico
2019, Revista de Gastroenterologia de Mexico
Los IBP se han asociado con sobrepoblación bacteriana del intestino delgado, lo cual se incrementa con el tiempo de uso, y esta se ha asociado con síndrome de intestino irritable (SII).
Investigar la prevalencia de síntomas intestinales en pacientes tratados con IBP en México.
Gastroenterólogos de 36 ciudades encuestaron pacientes tratados con IBP utilizando un instrumento ad hoc para determinar la presencia de síntomas intestinales y SII.
Doscientos quince médicos incluyeron 1,851 pacientes. La indicación de IBP fue gastritis (48.8%), reflujo gastroesofágico (38.5%), úlcera péptica (6.2%) y otras (6.5%); el 77.5% recibió tratamiento por ≤ 6 meses y 11.9% por ≥ 1 año. El 92.3% reportó síntomas: evacuaciones anormales (90%), distensión subjetiva (82%), dolor abdominal (63%), flatulencia (58%), malestar abdominal (53%) y el 67.5% llenó criterios de Roma III para SII. En el 55.9% los síntomas se presentaron antes y en 44.1% después de IBP (p < 0.005). En los primeros predominó el estreñimiento (63.8%), en los segundos diarrea (56.5%) (p < 0.0001). Los tratamientos recetados para manejar estos síntomas fueron antiespasmódicos, antibióticos, procinéticos y antiflatulentos, sin embargo los pacientes consideraron la mayor satisfacción con antibióticos (rifaximina mayormente) (p < 0.0001).
La asociación de IBP con síntomas intestinales y SII es frecuente en México. Predominan la diarrea y la distensión subjetiva, y los antibióticos producen la mayor satisfacción al tratamiento. Lo anterior sugiere la sobrepoblación bacteriana del intestino delgado o disbiosis como causa de estos síntomas por IBP, lo cual debe ser confirmado.
Proton pump inhibitors (PPIs) have been associated with small intestinal bacterial overgrowth (SIBO), which increases with prolonged PPI use, and SIBO has been associated with irritable bowel syndrome (IBS).
The aim of the present study was to study the prevalence of bowel symptoms in patients treated with PPIs in Mexico.
Gastroenterologists in 36 cities surveyed patients treated with PPIs, utilizing an ad hoc questionnaire to determine the presence of bowel symptoms and IBS.
Two hundred and fifteen physicians interviewed 1,851 patients. PPI indications were gastritis (48.8%), gastroesophageal reflux (38.5%), peptic ulcer (6.2%), and others (6.5%). A total of 77.5% of the patients received treatment for ≤ 6 months and 11.9% for ≥ 1 year. Symptoms were reported in 92.3% of the patients: abnormal bowel habits (90%), bloating (82%), abdominal pain (63%), flatulence (58%), and abdominal discomfort (53%). A total of 67.5% of the patients fit the Rome III criteria for IBS. Symptoms presented in 55.9% of the patients before PPI intake and in 44.1% of the patients after PPI use (P < .005). Constipation (63.8%) predominated in the former, and diarrhea (56.5%) in the latter (P < .0001). The treatments prescribed for managing those symptoms were antispasmodics, antibiotics, prokinetics, and antiflatulents, but patients stated greater satisfaction with antibiotics (mainly rifaximin) (P < .0001).
The association of PPIs with bowel symptoms and IBS is frequent in Mexico. Diarrhea and bloating predominate, and antibiotics produce the greatest treatment satisfaction, suggesting that SIBO or dysbiosis is the cause of the PPI-related bowel symptoms. However, that remains to be confirmed.

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: This study was partially supported by a research grant from AstraZeneca R&D (Sweden).

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Clinical Gastroenterology and Hepatology

Section snippets

Study Design

Results

Discussion

References (21)

The comparative effects of lansoprazole, omeprazole, and ranitidine in suppressing gastric acid secretion

Clin Ther

Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease

Gastroenterology

Impact of alcohol abuse in the etiology and severity of community-acquired pneumonia

Chest

Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies

CMAJ

Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease

JAMA

Omeprazole as a risk factor for campylobacter gastroenteritis: case-control study

BMJ

Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors

Aliment Pharmacol Ther

Review article: proton pump inhibitors and bacterial overgrowth

Aliment Pharmacol Ther

Use of the UK General Practice Research Database for pharmacoepidemiology

Br J Clin Pharmacol

The General Practice Research Database: quality of morbidity data

Popul Trends

Cited by (110)

Acute Bacterial Gastroenteritis

Long-term use of proton pump inhibitors as a risk factor for various adverse manifestations

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis – An international cohort study

Gastroesophageal Reflux

Impact of an evaluation of the professional practices on the relevance of proton pump inhibitors prescriptions pertinence at the hospital

Bowel symptoms in patients that receive proton pump inhibitors. Results of a multicenter survey in Mexico

Original article—alimentary tractUse of Acid-Suppressing Drugs and the Risk of Bacterial Gastroenteritis

Section snippets

Study Design

Results

Discussion

Clin Ther

Gastroenterology

Chest

Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies

CMAJ

Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease

JAMA

Omeprazole as a risk factor for campylobacter gastroenteritis: case-control study

BMJ

Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors

Aliment Pharmacol Ther

Review article: proton pump inhibitors and bacterial overgrowth

Aliment Pharmacol Ther

Use of the UK General Practice Research Database for pharmacoepidemiology

Br J Clin Pharmacol

The General Practice Research Database: quality of morbidity data

Popul Trends

Original article—alimentary tract
Use of Acid-Suppressing Drugs and the Risk of Bacterial Gastroenteritis