Systematic review of the risk of enteric infection in patients taking acid suppression
Abstract
CONTEXT: Proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RAs) have become the mainstay of therapy in acid-related upper gastrointestinal disorders. There have been concerns raised about the possible association of PPIs with enteric infections. OBJECTIVE: We conducted a systematic review to evaluate any association between acid suppression and enteric infection. We also assessed differences between types of enteric infections and the type of acid suppression. DATA SOURCES: Electronic searches of MEDLINE (1966-2005), EMBASE (1988-2005), and CINAHL (1982-2005) were undertaken using a combination of subject headings and text words related to PPI therapy, H(2)RAs, and enteric infections. STUDY SELECTION: All observational studies were eligible, including cross-sectional, case control, and cohort studies that evaluated risk of enteric infection associated with antisecretory therapy. Eligibility assessment was made by two independent researchers. DATA EXTRACTION: Information on study design, patient population, type of acid suppression, type of infection, and outcomes was collected. The odds ratio (OR) of taking acid suppression therapy in cases and controls was calculated and results were synthesized using a random effects model (DerSimonian and Laird, Stats direct version 2.4.4). DATA SYNTHESIS: A total of 12 papers evaluating 2,948 patients with Clostridium difficile were included in the review. There was an increased risk of taking antisecretory therapy in those infected with C. difficile (pooled OR 1.94, 95% CI 1.37-2.75). There was significant heterogeneity between the studies (P= 0.0006) that was not explained by planned subgroup analysis. The association was greater for PPI use (OR 1.96, 95% CI 1.28-3.00) compared with H(2)RA use (OR 1.40, 95% CI 0.85-2.29). A total of six studies evaluated Salmonella, Campylobacter, and other enteric infections in 11,280 patients. There was an increased risk of taking acid suppression in those with enteric infections (OR 2.55, 95% CI 1.53-4.26). There was significant heterogeneity between the studies (P < 0.0001) that was not explained by subgroup analysis. The association was greater for PPI use (OR 3.33, 95% CI 1.84-6.02) compared with H(2)RA use (OR 2.03, 95% CI 1.05-3.92). CONCLUSION: There is an association between acid suppression and an increased risk of enteric infection. Further prospective studies on patients taking long-term acid suppression are needed to establish whether this association is causal.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A growing body of evidence has linked acid-reducing medications such as proton pump inhibitors and histamine H2 antagonists with increased risk of enteric infections such as clostridium difficile and profound alterations.
“Supporting the importance of such mechanisms, a growing body of evidence has linked acid-reducing medications such as proton pump inhibitors and histamine H2 antagonists, with increased risk of enteric infections such as clostridium difficile[248–250] and profound alterations”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [249]
PPIs can influence the onset of enteric infections, resulting in an increased risk of Clostridium difficile infection (CDI), as well as Salmonella, Campylobacter and diarrheagenic Escherichia coli.
“PPIs can influence the onset of enteric infections, resulting in an increased risk of Clostridium difficile infection (CDI), as well as Salmonella, Campylobacter and diarrheagenic Escherichia coli (E. coli)[110-113].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [112]
Cites
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722 · see citing works
Meta-analysis in clinical trials
DerSimonian, R., & Laird, N. (1986) · Controlled Clinical Trials · doi:10.1016/0197-2456(86)90046-2 · Cited by 39,552 · see citing works
Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs
Concato, J., Shah, N., & Horwitz, R. I. (2000) · New England Journal of Medicine · doi:10.1056/nejm200006223422507 · Cited by 3,563 · see citing works
Publication and related bias in meta-analysis
Sterne, J. A. C., Gavaghan, D., & Egger, M. (2000) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(00)00242-0 · Cited by 2,282 · see citing works
Loo, V. G., Poirier, L., Miller, M. A., Oughton, M., Libman, M., Michaud, S., Bourgault, A., Nguyen, T. T., Frenette, C. H., Kelly, M., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051639 · Cited by 1,944 · see citing works
Dial, S. (2005) · JAMA · doi:10.1001/jama.294.23.2989 · Cited by 954 · see citing works
Risk of Community-Acquired Pneumonia and Use of Gastric Acid–Suppressive Drugs
Laheij, R. J. F. (2004) · JAMA · doi:10.1001/jama.292.16.1955 · Cited by 879 · see citing works
Muto, C. A., Pokrywka, M., Shutt, K. A., Mendelsohn, A. B., Nouri, K., Posey, K., Roberts, T. L., Croyle, K. S., Krystoflak, S., Patel-Brown, S., et al. (2005) · Infection Control and Hospital Epidemiology · doi:10.1086/502539 · Cited by 619 · see citing works
Dial, S. (2004) · Canadian Medical Association Journal · doi:10.1503/cmaj.1040876 · Cited by 577 · see citing works
Consensus Recommendations for Managing Patients with Nonvariceal Upper Gastrointestinal Bleeding
Barkun, A. N., Bardou, M., Marshall, J. K., & for the Nonvariceal Upper GI Bleeding Consensus Conference Group* (2003) · Annals of Internal Medicine · doi:10.7326/0003-4819-139-10-200311180-00012 · Cited by 540 · see citing works
Prevention of NSAID-induced gastroduodenal ulcers
Rostom, A., Dube, C., Wells, G. A., Tugwell, P., Welch, V. A., Jolicoeur, E., McGowan, J., Lanas, Á., Rushton, E., & Shukla, T. (2002) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002296 · Cited by 470 · see citing works
American Gastroenterological Association Technical Review on the Evaluation of Dyspepsia
Talley, N. J., Vakil, N. B., & Moayyedi, P. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.09.020 · Cited by 436 · see citing works
Gastro-oesophageal reflux disease
Moayyedi, P., & Talley, N. J. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68932-0 · Cited by 433 · see citing works
Clostridium difficile-associated diarrhea in adults
Poutanen, S. M. (2004) · Canadian Medical Association Journal · doi:10.1503/cmaj.1031189 · Cited by 415 · see citing works
Gerding, D. N. (1986) · Archives of Internal Medicine · doi:10.1001/archinte.1986.00360130117016 · Cited by 368 · see citing works
Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea
Cunningham, R., Dale, B., Undy, B., & Gaunt, N. (2003) · Journal of Hospital Infection · doi:10.1016/s0195-6701(03)00088-4 · Cited by 331 · see citing works
Underlying Disease Severity as a Major Risk Factor for Nosocomial Clostridium difficile Diarrhea
Kyne, L., Sougioultzis, S., McFarland, L. V., & Kelly, C. P. (2002) · Infection Control and Hospital Epidemiology · doi:10.1086/501989 · Cited by 241 · see citing works
Armstrong, D., Marshall, J. K., Chiba, N., Enns, R., Fallone, C. A., Fass, R., Hollingworth, R., Hunt, R. H., Kahrilas, P. J., Mayrand, S., et al. (2005) · Canadian Journal of Gastroenterology · doi:10.1155/2005/836030 · Cited by 237 · see citing works
Risk Factors for Clostridium difficile Toxin-Associated Diarrhea
Brown, E., Talbot, G. H., Axelrod, P. I., Provencher, M., & Hoegg, C. L. (1990) · Infection Control and Hospital Epidemiology · doi:10.1086/646173 · Cited by 190 · see citing works
DOORDUYN, Y., VAN DEN BRANDHOF, W. E., VAN DUYNHOVEN, Y. T. H. P., WANNET, W. J. B., & VAN PELT, W. (2006) · Epidemiology and Infection · doi:10.1017/s0950268805005406 · Cited by 183 · see citing works
Omeprazole as a risk factor for campylobacter gastroenteritis: case-control study: Table 1
Neal, K. R., Scott, H. M., Slack, R. C., & Logan, R. F. (1996) · BMJ · doi:10.1136/bmj.312.7028.414 · Cited by 161 · see citing works
Moayyedi, P., Forman, D., Braunholtz, D., Feltbower, R. G., Crocombe, W., Liptrott, M., Axon, A., & on behalf of the Leeds HELP Study Group (2000) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2000.2126_1.x · Cited by 151 · see citing works
Infection Due to Clostridium difficile Among Elderly Residents of a Long-Term-Care Facility
Simor, A. E., Yake, S. L., & Tsimidis, K. (1993) · Clinical Infectious Diseases · doi:10.1093/clinids/17.4.672 · Cited by 127 · see citing works
Moayyedi, P., Forman, D., Braunholtz, D., Feltbower, R. G., Crocombe, W., Liptrott, M., & Axon, A. T. R. (2000) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2000.02126.x · Cited by 121 · see citing works
Albumin, Length of Stay, and Proton Pump Inhibitors
Al-Tureihi, F. I. J., Hassoun, A., Wolf‐Klein, G. P., & Isenberg, H. D. (2005) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2005.01.003 · Cited by 116 · see citing works
Quinolone Use as a Risk Factor for Nosocomial Clostridium difficile-Associated Diarrhea
Yip, C., Loeb, M. B., Salama, S. E., Moss, L., & Olde, J. (2001) · Infection Control and Hospital Epidemiology · doi:10.1086/501954 · Cited by 105 · see citing works
Neal, R., Brij, O. S., Slack, B. C. R., Hawkey, J. C., & Logan, R. F. (1994) · BMJ · doi:10.1136/bmj.308.6922.176 · Cited by 103 · see citing works
Risk Factors for Clostridium difficile Toxin-Associated Diarrhea
Brown, E., Talbot, G. H., Axelrod, P. I., et al. (1990) · Infection Control and Hospital Epidemiology · doi:10.2307/30145487 · Cited by 96 · see citing works
Neal, K. R., & Slack, R. C. (1997) · Epidemiology and Infection · doi:10.1017/s0950268897008224 · Cited by 92 · see citing works
Gastric acid suppression does not promote clostridial diarrhoea in the elderly
Shah, S. (2000) · QJM · doi:10.1093/qjmed/93.3.175 · Cited by 88 · see citing works
Nelson, D. E., Auerbach, S. B., Baltch, A. L., Desjardin, E. K., Beck‐Sagué, C. M., Rheal, C., Smith, R. P., & Jarvis, W. R. (1994) · Infection Control and Hospital Epidemiology · doi:10.1086/646867 · Cited by 86 · see citing works
Meta-analysis: Can We Mix Apples and Oranges?
Moayyedi, P. (2004) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2004.40948.x · Cited by 72 · see citing works
Clostridium difficile Among Hospitalized Patients Receiving Antibiotics A Case-Control Study
Modena, S., Bearelly, D., Swartz, K., & Friedenberg, F. K. (2005) · Infection Control and Hospital Epidemiology · doi:10.1086/502603 · Cited by 67 · see citing works
Banatvala, N., Cramp, A. G., Jones, I. R., & Feldman, R. A. (1999) · Cited by 56 · see citing works
Possible Foodborne Transmission in a Case of Pseudomembranous Colitis Due to Clostridium difficile
Gurian, L. E., Ward, T. T., & Katon, R. M. (1982) · Gastroenterology · doi:10.1016/s0016-5085(82)80345-4 · Cited by 54 · see citing works
Salmonellosis in North Thames (East), UK: associated risk factors
Banatvala, N., CRAMP, A., Jones, I. R., & Feldman, R. A. (1999) · Epidemiology and Infection · doi:10.1017/s0950268899002162 · Cited by 53 · see citing works
The Impact of Clostridium difficile on a Surgical Service
Kent, K. C., Rubin, M. S., Lissin, L. W., Hanff, P. A., & Silen, W. (1998) · Annals of Surgery · doi:10.1097/00000658-199802000-00021 · Cited by 52 · see citing works
Gurian, L. E., Ward, T. T., & Katon, R. M. (1982) · PubMed · Cited by 51 · see citing works
Gastric Acid, Acid-Suppressing Drugs, and Bacterial Gastroenteritis
Alberto, L., Rodríguez, G., & Ruigómez, A. (1997) · Epidemiology · doi:10.1097/00001648-199709000-00016 · Cited by 48 · see citing works
Nelson, D. E., Auerbach, S. B., Baltch, A. L., Desjardin, E. K., Beck‐Sagué, C. M., Rheal, C., Smith, R. P., & Jarvis, W. R. (1994) · Infection Control and Hospital Epidemiology · doi:10.2307/30145537 · Cited by 47 · see citing works
The impact of illness in patients with moderate to severe gastro-esophageal reflux disease
El-Dika, S. S., Guyatt, G. H., Armstrong, D., Degl’Innocenti, A., Wiklund, I. E., Fallone, C. A., Tanser, L., van Zanten, S. V., Heels-Ansdell, D., Wahlqvist, P., et al. (2005) · BMC Gastroenterology · doi:10.1186/1471-230x-5-23 · Cited by 29 · see citing works
Increased incidence of bacterial diarrhoea in patients taking gastric acid antisecretory drugs
Nwokolo, C. U., Loft, D. E., HOLDER, R. L., & Langman, M. J. S. (1994) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-199408000-00009 · Cited by 27 · see citing works
Jensen, G. L., Bross, J. E., Bourbeau, P. P., Naumovitz, D. W., Streater, M., & Gianferante, L. E. (1994) · The Journal of Infectious Diseases · doi:10.1093/infdis/170.1.227 · Cited by 19 · see citing works
Watanakunakorn, P. W., WATANAKUNAKORN, C., & Hazy, J. (1996) · Infection Control and Hospital Epidemiology · doi:10.1086/647286 · Cited by 13 · see citing works
Nath, S. K., Salama, S. E., Persaud, D., Thornley, J. H., Smith, I., Foster, G., & Rotstein, C. (1994) · Canadian Journal of Infectious Diseases and Medical Microbiology · doi:10.1155/1994/207601 · Cited by 12 · see citing works
Risk factors for the development of Clostridium difficile toxin‐associated diarrhoea: a pilot study
Aziz, E. E., Ayis, S. A., Gould, F. K., & Rawlins, M. D. (2001) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.598 · Cited by 6 · see citing works
Watanakunakorn, P. W., Watanakunakorn, C., & Hazy, J. (1996) · Infection Control and Hospital Epidemiology · doi:10.2307/30141026 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Dellinger, R. P., Levy, M. M., Rhodes, A., Annane, D., Gerlach, H., Opal, S. M., Sevransky, J., Sprung, C. L., Douglas, I. S., Jaeschke, R., et al. (2013) · Intensive Care Medicine · doi:10.1007/s00134-012-2769-8 · Cited by 7,282 · see citing works
Alhazzani, W., Møller, M., Arabi, Y., Loeb, M., Gong, M., Fan, E., Oczkowski, S., Levy, M., Derde, L., Dzierba, A., et al. (2020) · Critical Care Medicine · doi:10.1097/ccm.0000000000004363 · Cited by 2,448 · see citing works
Proton pump inhibitors affect the gut microbiome
Imhann, F., Bonder, M. J., Vich Vila, A., Fu, J., Mujagic, Z., Vork, L., Tigchelaar, E. F., Jankipersadsing, S. A., Cenit, M. C., Harmsen, H. J. M., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310376 · Cited by 1,371 · see citing works
Interaction between drugs and the gut microbiome
Weersma, R. K., Zhernakova, A., & Fu, J. (2020) · Gut · doi:10.1136/gutjnl-2019-320204 · Cited by 988 · see citing works
Proton pump inhibitors alter the composition of the gut microbiota
Jackson, M. A., Goodrich, J. K., Maxan, M.-E., Freedberg, D. E., Abrams, J. A., Poole, A. C., Sutter, J. L., Welter, D., Ley, R. E., Bell, J. T., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310861 · Cited by 895 · see citing works
The Changing Epidemiology of Clostridium difficile Infections
Freeman, J., Bauer, M. P., Baines, S. D., Corver, J., Fawley, W. N., Goorhuis, A., Kuijper, E. J., & Wilcox, M. H. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00082-09 · Cited by 825 · see citing works
Risk of Clostridium difficile Infection With Acid Suppressing Drugs and Antibiotics: Meta-Analysis
Kwok, C. S., Arthur, A. K., Anibueze, C. I., Singh, S., Cavallazzi, R., & Loke, Y. K. (2012) · The American Journal of Gastroenterology · doi:10.1038/ajg.2012.108 · Cited by 579 · see citing works
Gut Microbiota and Colonization Resistance against Bacterial Enteric Infection
Ducarmon, Q. R., Zwittink, R. D., Hornung, B. V. H., van Schaik, W., Young, V. B., & Kuijper, E. J. (2019) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00007-19 · Cited by 566 · see citing works
Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis
Janarthanan, S., Ditah, I., Adler, D. G., & Ehrinpreis, M. N. (2012) · American Journal of Gastroenterology · doi:10.1038/ajg.2012.179 · Cited by 538 · see citing works
Moayyedi, P., Eikelboom, J. W., Bosch, J., Connolly, S. J., Dyal, L., Shestakovska, O., Leong, D. P., Anand, S. S., Störk, S., Branch, K. R., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.05.056 · Cited by 487 · see citing works
Complications of Proton Pump Inhibitor Therapy
Vaezi, M. F., Yang, Y., & Howden, C. W. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.04.047 · Cited by 484 · see citing works
Control of Gastric Acid Secretion in Health and Disease
Schubert, M. L., & Peura, D. A. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.05.021 · Cited by 480 · see citing works
for the SIF-AIGO-FIMMG Group, Scarpignato, C., on behalf of the Italian Society of Pharmacology, T. I. A. O. H. G., Gatta, L., Zullo, A., & Blandizzi, C. (2016) · BMC Medicine · doi:10.1186/s12916-016-0718-z · Cited by 469 · see citing works
Salmonella infections in immunocompromised adults
Gordon, M. A. (2008) · Journal of Infection · doi:10.1016/j.jinf.2008.03.012 · Cited by 453 · see citing works
Increased Incidence of Small Intestinal Bacterial Overgrowth During Proton Pump Inhibitor Therapy
Lombardo, L., Foti, M., Ruggia, O., & Chiecchio, A. (2010) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.12.022 · Cited by 350 · see citing works
Proton Pump Inhibitor Use and the Risk of Small Intestinal Bacterial Overgrowth: A Meta-analysis
Lo, W., & Chan, W. W. (2013) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.12.011 · Cited by 353 · see citing works
Overutilization of proton-pump inhibitors: what the clinician needs to know
Heidelbaugh, J. J., Kim, A. H., Chang, R., & Walker, P. C. (2012) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x12437358 · Cited by 327 · see citing works
Safety of the long-term use of proton pump inhibitors
Thomson, A. B. R. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i19.2323 · Cited by 314 · see citing works
Adverse Effects of Long-Term Proton Pump Inhibitor Therapy
Sheen, E., & Triadafilopoulos, G. (2011) · Digestive Diseases and Sciences · doi:10.1007/s10620-010-1560-3 · Cited by 307 · see citing works
World Gastroenterology Organisation Global Guidelines
Hunt, R. H., Armstrong, D., Katelaris, P., Afihene, M., Bane, A., Bhatia, S. J., Chen, M., Choi, M., de Melo, A. C., Fock, K. M., et al. (2017) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000000854 · Cited by 306 · see citing works
Proton-pump inhibitors: understanding the complications and risks
Malfertheiner, P., Kandulski, A., & Venerito, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.117 · Cited by 297 · see citing works
Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications
Le Bastard, Q., Al‐Ghalith, G. A., Grégoire, M., Chapelet, G., Javaudin, F., Dailly, E., Batard, E., Knights, D., & Montassier, E. (2018) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14451 · Cited by 263 · see citing works
Trifan, A., Stanciu, C., Girleanu, I., Stoica, O. C., Singeap, A. M., Maxim, R., Chiriac, S. A., Ciobica, A., & Boiculese, L. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i35.6500 · Cited by 286 · see citing works
Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015
Iwakiri, K., Kinoshita, Y., Habu, Y., Oshima, T., Manabe, N., Fujiwara, Y., Nagahara, A., Kawamura, O., Iwakiri, R., Ozawa, S., et al. (2016) · Journal of Gastroenterology · doi:10.1007/s00535-016-1227-8 · Cited by 284 · see citing works
Drug-microbiota interactions: an emerging priority for precision medicine
Zhao, Q. C., Chen, Y., Huang, W., Zhou, H., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01619-w · Cited by 296 · see citing works
The role of protein digestibility and antacids on food allergy outcomes
Untersmayr, E., & Jensen‐Jarolim, E. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.04.025 · Cited by 270 · see citing works
Mechanisms and therapeutic effectiveness of lactobacilli
Cerbo, A. D., Palmieri, B., Aponte, M., Morales‐Medina, J. C., & Iannitti, T. (2015) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2015-202976 · Cited by 264 · see citing works
Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified
Bruno, G., Zaccari, P., Rocco, G., Scalese, G., Panetta, C., Porowska, B., Pontone, S., & Severi, C. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i22.2706 · Cited by 258 · see citing works
Ranitidine is Associated With Infections, Necrotizing Enterocolitis, and Fatal Outcome in Newborns
Terrin, G., Passariello, A., Curtis, M. D., Manguso, F., Salvia, G., Lega, L., Messina, F., Paludetto, R., & Canani, R. B. (2011) · PEDIATRICS · doi:10.1542/peds.2011-0796 · Cited by 253 · see citing works
Oral–Gut Microbiome Axis in Gastrointestinal Disease and Cancer
Park, S.-Y., Hwang, B.-O., Lim, M., Ok, S.-H., Lee, S., Chun, K., Park, K.-K., Hu, Y., Chung, W., & Song, N. (2021) · Cancers · doi:10.3390/cancers13092124 · Cited by 237 · see citing works
Biology of <i>Clostridium difficile</i>: Implications for Epidemiology and Diagnosis
Karen C., C., & John G., B. (2011) · Annual Review of Microbiology · doi:10.1146/annurev-micro-090110-102824 · Cited by 233 · see citing works
C. difficile Infection: Changing Epidemiology and Management Paradigms
Vindigni, S. M., & Surawicz, C. M. (2015) · Clinical and Translational Gastroenterology · doi:10.1038/ctg.2015.24 · Cited by 236 · see citing works
The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
Kahrilas, P. J., & Boeckxstaens, G. E. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.038 · Cited by 234 · see citing works
Side Effects of Long‐Term Proton Pump Inhibitor Use: A Review
Haastrup, P., Thompson, W., Søndergaard, J., & Jarbøl, D. E. (2018) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13023 · Cited by 231 · see citing works
Novel concepts in the pathophysiology and treatment of functional dyspepsia
Wauters, L. I., Talley, N. J., Walker, M. M., Tack, J. F., & Vanuytsel, T. (2019) · Gut · doi:10.1136/gutjnl-2019-318536 · Cited by 231 · see citing works
Systematic review: hypomagnesaemia induced by proton pump inhibition
Hess, M. W., Hoenderop, J. G. J., Bindels, R. J. M., & Drenth, J. P. H. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2012.05201.x · Cited by 223 · see citing works
Invasive Non‐TyphiSalmonellaDisease in Africa
Morpeth, S. C., Ramadhani, H. O., & Crump, J. A. (2009) · Clinical Infectious Diseases · doi:10.1086/603553 · Cited by 219 · see citing works
Safety of Proton Pump Inhibitor Exposure
Yang, Y., & Metz, D. C. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.08.023 · Cited by 215 · see citing works
The Occurrence and Prevention of Foodborne Disease in Vulnerable People
Lund, B. M., & O’Brien, S. J. (2011) · Foodborne Pathogens and Disease · doi:10.1089/fpd.2011.0860 · Cited by 215 · see citing works
Deshpande, A., Pant, C., Pasupuleti, V., Rolston, D. D. K., Jain, A., Deshpande, N., Thota, P., Sferra, T. J., & Hernández, A. V. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.09.030 · Cited by 211 · see citing works
Long-term Safety Concerns with Proton Pump Inhibitors
Ali, T., Roberts, D. N., & Tierney, W. M. (2009) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.04.014 · Cited by 198 · see citing works
The influence of proton pump inhibitors and other commonly used medication on the gut microbiota
Imhann, F., Vila, A. V., Bonder, M. J., Manosalva, A. G. L., Koonen, D. P. Y., Fu, J., Wijmenga, C., Zhernakova, A., & Weersma, R. K. (2017) · Gut Microbes · doi:10.1080/19490976.2017.1284732 · Cited by 195 · see citing works
Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors
Almario, C. V., Chey, W. D., & Spiegel, B. M. R. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000798 · Cited by 190 · see citing works
Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186 · see citing works
Eze, P., Balsells, E., Kyaw, M. H., & Nair, H. (2017) · Journal of Global Health · doi:10.7189/jogh.07.010417 · Cited by 186 · see citing works
Proton pump inhibitors in GORDAn overview of their pharmacology, efficacy and safety
Savarino, V., Mario, F. D., & Scarpignato, C. (2008) · Pharmacological Research · doi:10.1016/j.phrs.2008.09.016 · Cited by 185 · see citing works
Koop, H., Fuchs, K., Labenz, J., Jansen, P. L., Messmann, H., Miehlke, S., Schepp, W., Wenzl, T., & der Leitliniengruppe, U. D. M. (2014) · Zeitschrift für Gastroenterologie · doi:10.1055/s-0034-1385202 · Cited by 172 · see citing works
A comparison of the gut microbiome between long‐term users and non‐users of proton pump inhibitors
Clooney, A. G., Bernstein, C. N., Leslie, W. D., Vagianos, K., Sargent, M., Laserna‐Mendieta, E. J., Claesson, M. J., & Targownik, L. E. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13568 · Cited by 166 · see citing works
Proton Pump Inhibitor Use in the U.S. Ambulatory Setting, 2002–2009
Rotman, S. R., & Bishop, T. F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056060 · Cited by 168 · see citing works
Overutilization of Proton Pump Inhibitors: A Review of Cost-Effectiveness and Risk in PPI
Heidelbaugh, J. J., Goldberg, K. L., & Inadomi, J. M. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.49 · Cited by 165 · see citing works
Meta‐analysis: proton pump inhibitor use and the risk of community‐acquired pneumonia
Johnstone, J., Nerenberg, K. A., & Loeb, M. B. (2010) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2010.04284.x · Cited by 163 · see citing works
Association of Gastric Acid Suppression With Recurrent Clostridium difficile Infection
Tariq, R., Singh, S., Gupta, A., Pardi, D. S., & Khanna, S. (2017) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2017.0212 · Cited by 160 · see citing works
von Rosenvinge, E. C., Song, Y., White, J. R., Maddox, C., Blanchard, T. G., & Fricke, W. F. (2013) · The ISME Journal · doi:10.1038/ismej.2013.33 · Cited by 153 · see citing works
Rieder, F., Biancani, P., Harnett, K. M., Yerian, L. M., & Falk, G. W. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00454.2009 · Cited by 155 · see citing works
Alshamsi, F. E., Belley‐Côté, E. P., Cook, D., Almenawer, S. A., Alqahtani, Z., Perri, D., Thabane, L., Al‐Omari, A., Lewis, K. A., Guyatt, G. H., et al. (2016) · Critical Care · doi:10.1186/s13054-016-1305-6 · Cited by 151 · see citing works
García-Mazcorro, J. F., Suchodolski, J. S., Jones, K. R., Clark‐Price, S. C., Dowd, S. E., Minamoto, Y., Markel, M. E., Steiner, J. M., & Dossin, O. (2012) · FEMS Microbiology Ecology · doi:10.1111/j.1574-6941.2012.01331.x · Cited by 150 · see citing works
Tleyjeh, I. M., Abdulhak, A. A. B., Riaz, M. A., Alasmari, F. A., Garbati, M. A., Alghamdi, M. A. A., Khan, A. R., Al-Tannir, M. A., Erwin, P. J., Ibrahim, T., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050836 · Cited by 148 · see citing works
Acid and the basis for cellular plasticity and reprogramming in gastric repair and cancer
Sáenz, J. B., & Mills, J. C. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2018.5 · Cited by 138 · see citing works
Adverse Effects Associated with Proton Pump Inhibitor Use
Yibirin, M., Oliveira, D. D., Valera, R. J., Plitt, A. E., & Lutgen, S. (2021) · Cureus · doi:10.7759/cureus.12759 · Cited by 141 · see citing works
Abraham, N. S. (2012) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e328358d5b9 · Cited by 140 · see citing works
Proton pump inhibitor therapy and potential long-term harm
Corleto, V. D., Festa, S., Giulio, E. D., & Annibale, B. (2013) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000031 · Cited by 134 · see citing works
Implication of Gut Microbiota in Nonalcoholic Fatty Liver Disease
Boursier, J., & Diehl, A. M. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1004559 · Cited by 134 · see citing works
Adverse effects of proton pump inhibitor drugs: clues and conclusions
McCarthy, D. M. (2010) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e32833ea9d9 · Cited by 132 · see citing works
Acid peptic diseases: pharmacological approach to treatment
Mejia, A. V., & Kraft, W. K. (2009) · Expert Review of Clinical Pharmacology · doi:10.1586/ecp.09.8 · Cited by 129 · see citing works
The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors
Minalyan, A., Gabrielyan, L., Scott, D. R., Jacobs, J. P., & Pisegna, J. R. (2017) · Current Gastroenterology Reports · doi:10.1007/s11894-017-0577-6 · Cited by 132 · see citing works
Nichols, G. L., Richardson, J. F., Sheppard, S. K., Lane, C., & Sarran, C. E. (2012) · BMJ Open · doi:10.1136/bmjopen-2012-001179 · Cited by 127 · see citing works
Vincent, C., Stephens, D. A., Loo, V. G., Edens, T. J., Behr, M. A., Dewar, K., & Manges, A. R. (2013) · Microbiome · doi:10.1186/2049-2618-1-18 · Cited by 123 · see citing works
Compare, D., Pica, L., Rocco, A., De Giorgi, F., Cuomo, R., Sarnelli, G., Romano, M., & Nardone, G. (2011) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2010.02419.x · Cited by 122 · see citing works
Gastrointestinal Complications of Cystic Fibrosis
Gelfond, D., & Borowitz, D. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.11.006 · Cited by 121 · see citing works
Moayyedi, P., & Leontiadis, G. I. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2011.272 · Cited by 121 · see citing works
Safety of long-term PPI therapy
Reimer, C. (2013) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2013.06.001 · Cited by 117 · see citing works
Importance of gastrin in the pathogenesis and treatment of gastric tumors
Burkitt, M. D., Varró, A., & Pritchard, D. M. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.15.1 · Cited by 117 · see citing works
Micromotors for drug delivery in vivo: The road ahead
Srivastava, S. K., Clergeaud, G., Andresen, T. L., & Boisen, A. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.09.005 · Cited by 118 · see citing works
Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study
Hart, E. J., Dunn, T. E., Feuerstein, S. G., & Jacobs, D. M. (2019) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2235 · Cited by 115 · see citing works
Gut Microbiota Composition Before and After Use of Proton Pump Inhibitors
Hojo, M., Asahara, T., Nagahara, A., Takeda, T., Matsumoto, K., Ueyama, H., Matsumoto, K., Asaoka, D., Takahashi, T., Nomoto, K., et al. (2018) · Digestive Diseases and Sciences · doi:10.1007/s10620-018-5122-4 · Cited by 114 · see citing works
Lee, C., Im, J. P., Kim, J. W., Kim, S., Ryu, D. Y., Cha, J. M., Kim, E. Y., Kim, E. R., & Chang, D. K. (2013) · Surgical Endoscopy · doi:10.1007/s00464-013-2979-3 · Cited by 114 · see citing works
Stress-Induced Ulcer Bleeding in Critically Ill Patients
Ali, T., & Harty, R. F. (2009) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2009.03.002 · Cited by 111 · see citing works
Toxicity of long-term use of proton pump inhibitors in children
Bruyne, P. D., & Ito, S. (2017) · Archives of Disease in Childhood · doi:10.1136/archdischild-2017-314026 · Cited by 111 · see citing works
Trikudanathan, G., Israel, J., Cappa, J., & O’Sullivan, D. M. (2011) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2011.02650.x · Cited by 110 · see citing works
Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use
Naito, Y., Kashiwagi, K., Takagi, T., Andoh, A., & Inoüe, R. (2018) · Digestion · doi:10.1159/000481813 · Cited by 109 · see citing works
Krag, M., Perner, A., Wetterslev, J., Wise, M. P., Borthwick, M., Bendel, S., McArthur, C. J., COOK, D., Nielsen, N., Pelosi, P. P., et al. (2015) · Acta Anaesthesiologica Scandinavica · doi:10.1111/aas.12508 · Cited by 107 · see citing works
Huang, H., Jiang, W., Wang, C.-Y., Qin, H., & Du, B. (2018) · Critical Care · doi:10.1186/s13054-017-1937-1 · Cited by 107 · see citing works
Goel, G., Deshpande, A., López, R., Hall, G. S., van Duin, D., & Carey, W. D. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.11.019 · Cited by 105 · see citing works
Proton pump inhibitors as a risk factor for paediatric Clostridium difficile infection
TURCO, R., Martinelli, M., Miele, E., Roscetto, E., Pezzo, M. D., Greco, L., & Staiano, A. (2009) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2009.04229.x · Cited by 104 · see citing works
Johnson, D. A., & Oldfield, E. C. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.11.031 · Cited by 101 · see citing works
Walker, M. M., & Talley, N. J. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12666 · Cited by 101 · see citing works
Depression, antidepressant medications, and risk of Clostridium difficileinfection
Rogers, M. A. M., Greene, M. T., Young, V. B., Saint, S. K., Langa, K. M., Kao, J. Y., & Aronoff, D. M. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-121 · Cited by 101 · see citing works
The Efficacy of Proton Pump Inhibitors for the Treatment of Asthma in Adults
Chan, W. W., Chiou, E., Obstein, K. L., Tignor, A. S., & Whitlock, T. L. (2011) · Archives of Internal Medicine · doi:10.1001/archinternmed.2011.116 · Cited by 100 · see citing works
Choudhry, M., Soran, H., & Ziglam, H. M. (2008) · QJM · doi:10.1093/qjmed/hcn035 · Cited by 99 · see citing works
Ahrens, D., Behrens, G., Himmel, W., Kochen, M. M., & Chenot, J. (2012) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2012.02973.x · Cited by 98 · see citing works
van Woerkom, M., Piepenbrink, H., Godman, B., de Metz, J., Campbell, S., Bennie, M., Eimers, M., & Gustafsson, L. L. (2012) · Journal of Comparative Effectiveness Research · doi:10.2217/cer.12.52 · Cited by 97 · see citing works
Willems, R. P. J., van Dijk, K., Ket, J. C. F., & Vandenbroucke‐Grauls, C. M. J. E. (2020) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2020.0009 · Cited by 96 · see citing works
Recent advances in Clostridium difficile-associated disease
Monaghan, T. M., Boswell, T., & Mahida, Y. (2008) · Postgraduate Medical Journal · doi:10.1136/gut.2007.128157 · Cited by 95 · see citing works
Dalton, B., LYE‐MACCANNELL, T., Henderson, E. A., MacCannell, D., & Louie, T. (2008) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2008.03924.x · Cited by 94 · see citing works
Barletta, J. F., Bruno, J. J., Buckley, M. S., & Cook, D. J. (2016) · Critical Care Medicine · doi:10.1097/ccm.0000000000001872 · Cited by 94 · see citing works
Leonard, C. E., Freeman, C. P., Newcomb, C. W., Reese, P. P., Herlim, M., Bilker, W. B., Hennessy, S., & Strom, B. L. (2012) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.3329 · Cited by 92 · see citing works
Morrison, R. H., Hall, N. S., Said, M., Rice, T., Groff, H. L., Brodine, S. K., Slymen, D. J., & Lederman, E. R. (2011) · Clinical Infectious Diseases · doi:10.1093/cid/cir668 · Cited by 89 · see citing works
Proton Pump Inhibitor Use and Enteric Infections
Dial, M. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.46 · Cited by 89 · see citing works
Barletta, J. F., & Sclar, D. A. (2014) · Critical Care · doi:10.1186/s13054-014-0714-7 · Cited by 87 · see citing works
Kallen, A. J., Thompson, A. D., Ristaino, P., Chapman, L., Nicholson, A. C., Sim, B.-T. T., Lessa, F. C., Sharapov, U. M., Fadden, E., Boehler, R., et al. (2009) · Infection Control and Hospital Epidemiology · doi:10.1086/595694 · Cited by 87 · see citing works
- Authors
- Leonard, J., Marshall, J. K., & Moayyedi, P.
- Affiliations
- McMaster University (CA)
- Venue
- The American Journal of Gastroenterology
- Published
- 2007-09
- Volume
- 102
- Issue
- 9
- Pages
- 2047-2056
- ISSN
- 0002-9270 (ISSN-L)
- 1572-0241
- OpenAlex
- W2114271048
- Cited by
- 633
- References
- 46
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 22 · 2023: 24 · 2022: 32 · 2021: 35 · 2020: 39 · 2019: 29 · 2018: 35 · 2017: 41 · 2016: 30 · 2015: 28 · 2014: 30 · 2013: 63 · 2012: 55
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Keywords
- acid suppression, proton pump inhibitors, H2 receptor antagonists, gastrointestinal infections, Clostridium difficile infection, Salmonella, Campylobacter, Clostridium difficile-associated diarrhea, antisecretory therapy, infection risk, drug safety, Helicobacter pylori, Helicobacter heilmannii
- MeSH terms
- Bacterial Infections, Gastric Acid, Gastrointestinal Diseases, Histamine H2 Antagonists, Humans, Risk Factors, Proton Pump Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review