Defining Appropriate Use of Proton-Pump Inhibitors Among Medical Inpatients

Pappas, Matt; Jolly, Sanjay; Vijan, Sandeep

doi:10.1007/s11606-015-3536-7

Cited by 24 publications

(24 citation statements)

References 48 publications

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“…While prior antibiotic therapy is associated with the largest risk of contracting a CDI, proton pump inhibitor (PPI) use has been identified as an independent risk factor associated with the development of a CDI (37). The use of PPIs has become exceptionally common for both inpatient and outpatient settings for the treatment of numerous conditions related to upper gastrointestinal complications, stress ulcer prophylaxis, and functional dyspepsia (38)(39)(40). PPIs, by design, increase the pH of the upper gastrointestinal tract, including the stomach and the proximal duodenum (41).…”

Section: Discussionmentioning

confidence: 99%

Germinant Synergy Facilitates Clostridium difficile Spore Germination under Physiological Conditions

Kochan

Shoshiev

Hastie

et al. 2018

mSphere

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is a Gram-positive obligate anaerobe that forms spores in order to survive for long periods in the unfavorable environment outside a host. is the leading cause of nosocomial infectious diarrhea worldwide. infection (CDI) arises after a patient treated with broad-spectrum antibiotics ingests infectious spores. The first step in pathogenesis is the metabolic reactivation of dormant spores within the gastrointestinal (GI) tract through a process known as germination. In this work, we aim to elucidate the specific conditions and the location within the GI tract that facilitate this process. Our data suggest that germination occurs through a two-step biochemical process that is regulated by pH and bile salts, amino acids, and calcium present within the GI tract. Maximal germination occurs at a pH ranging from 6.5 to 8.5 in the terminal small intestine prior to bile salt and calcium reabsorption by the host. Germination can be initiated by lower concentrations of germinants when spores are incubated with a combination of bile salts, calcium, and amino acids, and this synergy is dependent on the availability of calcium. The synergy described here allows germination to proceed in the presence of inhibitory bile salts and at physiological concentrations of germinants, effectively decreasing the concentrations of nutrients required to initiate an essential step of pathogenesis. is an anaerobic spore-forming human pathogen that is the leading cause of nosocomial infectious diarrhea worldwide. Germination of infectious spores is the first step in the development of a infection (CDI) after ingestion and passage through the stomach. This study investigates the specific conditions that facilitate spore germination, including the following: location within the gastrointestinal (GI) tract, pH, temperature, and germinant concentration. The germinants that have been identified in culture include combinations of bile salts and amino acids or bile salts and calcium, but , these function at concentrations that far exceed normal physiological ranges normally found in the mammalian GI tract. In this work, we describe and quantify a previously unreported synergy observed when bile salts, calcium, and amino acids are added together. These germinant cocktails improve germination efficiency by decreasing the required concentrations of germinants to physiologically relevant levels. Combinations of multiple germinant types are also able to overcome the effects of inhibitory bile salts. In addition, we propose that the acidic conditions within the GI tract regulate spore germination and could provide a biological explanation for why patients taking proton pump inhibitors are associated with increased risk of developing a CDI.

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Section: Discussionmentioning

confidence: 99%

Germinant Synergy Facilitates Clostridium difficile Spore Germination under Physiological Conditions

Kochan

Shoshiev

Hastie

et al. 2018

mSphere

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“…However, up to one third of patients in the community and 60% of hospitalised patients receiving PPI do not have any indication documented. [1][2][3][4] This is relevant as emerging data suggest that PPI are not without adverse effects. 3,[5][6][7][8][9][10][11][12][13] Haematology patients represent a unique population as there are often multiple potential risk factors for gastrointestinal (GI) bleeding, including intensive steroid use, anticoagulation, thrombocytopenia and mucositis from chemotherapy and neutropenia.…”

Section: Introductionmentioning

confidence: 99%

Is there a role for proton pump inhibitor prophylaxis in haematology patients?

Leitinger

Hui

Grigg

2019

Internal Medicine Journal

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While proton pump inhibitors (PPI) are widely prescribed as prophylaxis in selected haematology inpatient and outpatients, an informal survey of haematology units around Australia found wide variations in the specific indications for their use. This is consistent with a literature review which showed a paucity of robust evidence to support their use, specifically in chemotherapy‐induced mucositis, thrombocytopenia or administration of high dose glucocorticosteroids in the absence of additional risk factors. Rationalising PPI prescribing is clinically important from both a cost and safety perspective, given the emerging evidence of adverse events associated with prolonged PPI administration. A review of prescribing practices at our institution over a 14‐month period found that approximately 60% of myeloma, lymphoma and autograft patients received PPI prophylaxis during and beyond chemotherapy without an accepted indication. We encourage institutions to review their PPI prescribing practices with the intent of rationalising their use, and to conduct studies aiming to fill the substantial gaps in our knowledge.

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“…4) In the cardiovascular field, previous studies have focused on whether PPIs may increase cardiovascular risks in patients with coronary artery disease who are taking clopidogrel. 5) Currently, these risks may extend from patients with coronary artery disease to the general population.…”

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confidence: 99%

Potential Cardiovascular Risks of Proton Pump Inhibitors in the General Population

Zhu

Hong

2017

Int. Heart J.

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SummaryProton pump inhibitors (PPIs) are the most effective gastric acid-suppressing agents and the mainstay medical therapy for a series of acid peptic diseases. In general, the safety profile of PPIs is excellent. However, with long-term drug administration, the safety and potency of PPIs has been questioned. In the cardiovascular field, drug-drug interactions related to PPIs have been identified with particular attention regarding the use of PPIs combined with clopidogrel in patients with acute coronary syndrome. Currently, cardiovascular risks from PPIs may extend from patients with coronary artery disease to the general population. This review summarizes the possible cardiovascular risks in PPI users with no history of cardiovascular diseases and discusses possible biological mechanisms. (Int Heart J 2017; 58: 163-166)

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Defining Appropriate Use of Proton-Pump Inhibitors Among Medical Inpatients

Cited by 24 publications

References 48 publications

Germinant Synergy Facilitates Clostridium difficile Spore Germination under Physiological Conditions

Germinant Synergy Facilitates Clostridium difficile Spore Germination under Physiological Conditions

Is there a role for proton pump inhibitor prophylaxis in haematology patients?

Potential Cardiovascular Risks of Proton Pump Inhibitors in the General Population

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