Risk of Clostridium difficile Infection With Acid Suppressing Drugs and Antibiotics: Meta-Analysis

Kwok, Chun Shing; Arthur, Aaron Kobina; Anibueze, Chukwudubem Ifeanyichukwu; Singh, Sonal; Cavallazzi, Rodrigo; Loke, Yoon K.

doi:10.1038/ajg.2012.108

Cited by 515 publications

(398 citation statements)

References 62 publications

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“…A meta-analysis of 29 studies of patients with CDI found that PPI increased the risk of CDI (pooled odds ratio = 2.15, 95 % confidence interval (CI) 1.81 -2.55) ( 234 ). Two recent meta-analyses confi rm association and strengthen the evidence that PPI use is associated with an increased risk of CDI ( 7,8 ). Th e risk factors for recurrent CDI are slightly diff erent from those for initial CDI.…”

Section: Conflict Of Interestmentioning

confidence: 97%

See 1 more Smart Citation

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

Surawicz

Brandt

Binion

et al. 2013

American Journal of Gastroenterology

1,465

1,408

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Clostridium diffi cile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system. Patients with CDI typically have extended lengths-of-stay in hospitals, and CDI is a frequent cause of large hospital outbreaks of disease. This guideline provides recommendations for the diagnosis and management of patients with CDI as well as for the prevention and control of outbreaks while supplementing previously published guidelines. New molecular diagnostic stool tests will likely replace current enzyme immunoassay tests. We suggest treatment of patients be stratifi ed depending on whether they have mild-to-moderate, severe, or complicated disease. Therapy with metronidazole remains the choice for mildto-moderate disease but may not be adequate for patients with severe or complicated disease. We propose a classifi cation of disease severity to guide therapy that is useful for clinicians. We review current treatment options for patients with recurrent CDI and recommendations for the control and prevention of outbreaks of CDI. Am J Gastroenterol 2013; 108:478-498; doi: 10.1038/ajg.2013 12. In patients in whom oral antibiotics cannot reach a segment of the colon, such as with Hartman's pouch, ileostomy, or colon diversion, vancomycin therapy delivered via enema should be added to treatments above until the patient improves. (Conditional recommendation, low-quality evidence)13. The use of anti-peristaltic agents to control diarrhea from confi rmed or suspected CDI should be limited or avoided, as they may obscure symptoms and precipitate complicated disease. Use of anti-peristaltic agents in the setting of CDI must always be accompanied by medical therapy for CDI. (Strong recommendation, low-quality evidence) Management of severe and complicated CDI14. Supportive care should be delivered to all patients and includes intravenous fl uid resuscitation, electrolyte replacement, and pharmacological venous thromboembolism prophylaxis. Furthermore, in the absence of ileus or signifi cant abdominal distention, oral or enteral feeding should be continued. 17. Vancomycin delivered orally (500 mg four times per day) and per rectum (500 mg in a volume of 500 ml four times a day) plus intravenous metronidazole (500 mg three times a day) is the treatment of choice for patients with complicated CDI with ileus or toxic colon and / or signifi cant abdominal distention. (Strong recommendation, low-quality evidence)18. Surgical consult should be obtained in all patients with complicated CDI. Surgical therapy should be considered in patients with any one of the following attributed to CDI: hypotension requiring vasopressor therapy; clinical signs of sepsis and organ dysfunction (renal and pulmonary); mental status changes; white blood cell count ≥ 50,000 cells / μ l, lactate ≥ 5 mmol / l; or failure to improve on medical therapy after 5 days. (Strong recommendation, moderate-quality evidence) Management of recurrent CDI (RCDI)19. The fi rst recurrence of CDI can be treated ...

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Section: Conflict Of Interestmentioning

confidence: 97%

“…Th e two biggest risk factors are exposure to antibiotics and exposure to the organism; others are comorbid conditions, gastro intestinal tract surgery, and medications that reduce gastric acid, including proton-pump inhibitors (PPIs) ( 7,8 ). More information on epidemiology is in the appendix.…”

Section: Epidemiology and Risk Factorsmentioning

confidence: 99%

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

Surawicz

Brandt

Binion

et al. 2013

American Journal of Gastroenterology

1,465

1,408

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“…Multiple observational studies have linked the prolonged use of PPI to a multitude of adverse events including infections, electrolyte imbalances such as hypomagnesemia, kidney disease, osteoporosis, bone fractures, and dementia [81 –89] (Table 5). …”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

“…One plausible explanation of these adverse events, especially infections, is that prolonged, PPI-induced acid suppression may result in alterations in the gut flora, as well as microbiome changes, leading to increased load of bacterial pathogens, and hence increasing the risk of infections [90,91]. A large meta-analysis (Table 5) including 43 studies found an association with incident and recurrent C. difficile and PPI use [81]. This prompted the FDA to issue a safety alert warning of C. difficile association with PPI use [92].…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

177

172

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Introduction: Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism.Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy.Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.

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“…Son múltiples los factores de riesgo, pero los más importantes son el uso previo de antibióticos (8,9) y la exposición al germen (7). Además, se han reconocido otros factores asociados, como la edad mayor de 65 años (8), el tiempo de hospitalización (10,11), la estancia previa en la unidad de cuidados intensivos (12), la gravedad de la condición de salud, la hipoalbuminemia (<2,5 g/dl) (11), el uso previo de quimioterapia, la manipulación del tubo digestivo (incluido el paso de sondas de nutrición) (13) y el uso de medicamentos que suprimen el ácido gástrico (bloqueadores de la histamina 2 o inhibidores de la bomba de protones) (12,14,15 Entre las complicaciones de la infección por C. difficile están la alteración electrolítica, el megacolon tóxico, la perforación intestinal con peritonitis y el choque séptico, las cuales pueden llevar a la muerte (14).…”

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Clinical and demographic profile and risk factors for Clostridium difficile infection

Carvajal¹,

Pacheco²,

Jaimes³

2017

biomedica

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Contribución de los autores:Todos los autores participaron en igual medida en todos los aspectos del estudio y la redacción del manuscrito. Introducción. La enfermedad asociada a Clostridium difficile es la principal causa de diarrea infecciosa adquirida en el hospital; su creciente incidencia, las menores tasas de respuesta al tratamiento inicial y la mayor tasa de recaídas han incrementado la carga de la enfermedad. Objetivo. Determinar las características clínicas de los pacientes hospitalizados con enfermedad asociada a C. difficile. Materiales y métodos. Se hizo un estudio de casos anidado en una cohorte. Se revisaron las historias clínicas de pacientes con diarrea iniciada durante su hospitalización a quienes se les había practicado la prueba de detección de la toxina A-B de C. difficile, entre febrero de 2010 y febrero de 2012. Se definió como caso al paciente hospitalizado con diarrea y prueba de Enzyme Linked Fluorescent Assay (ELFA) positiva para la toxina y, como control, a aquel con resultado negativo para la toxina. Se recolectaron los datos demográficos y clínicos, así como la información sobre los factores asociados, la estancia hospitalaria, el tratamiento y las complicaciones. Perfil clínico y demográfico y factores de riesgo frente a la infección por Clostridium difficileResultados. Durante el periodo de seguimiento se recolectaron datos de 123 pacientes, de los cuales 30 fueron positivos para la toxina. La edad media en la población de estudio fue de 49 años y el 60 % correspondía a hombres. Los síntomas predominantes fueron el dolor abdominal (35 %) y la fiebre (34 %). Las principales complicaciones fueron la alteración electrolítica y la sepsis grave asociada con disfunción renal. La mortalidad total fue de 13 % y los factores independientes asociados con la aparición de la infección fueron el uso de inhibidores de la bomba de protones y la cirugía gastrointestinal previa. Conclusiones. El uso de inhibidores de la bomba de protonesy la cirugía gastrointestinal previa fueron factores asociados con la infección por C. difficile. Clinical and demographic profile and risk factors for Clostridium difficile infectionIntroduction: Clostridium difficile infection is the leading cause of nosocomial infectious diarrhea. The increasing incidence added to a lower rate of response to the initial treatment and higher rates of relapse has generated a higher burden of the disease. Objective: To determine the clinical characteristics of hospitalized patients with C. difficile infection. Materials and methods:We made a nested case-cohort study. We reviewed medical records of the patients with nosocomial diarrhea for whom an assay for toxin A-B of C. difficile had been requested from February, 2010, to February, 2012. We defined case as a patient with diarrhea and a positive assay for the toxin, and control as those patients with a negative assay for the toxin. We collected data on demographic and clinical characteristics, risk factors, hospital length of stay, treatment, and complications. Results: We collec...

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Risk of Clostridium difficile Infection With Acid Suppressing Drugs and Antibiotics: Meta-Analysis

Abstract: Despite the substantial statistical and clinical heterogeneity, our findings indicate a probable association between PPI use and incident and recurrent CDI. This risk is further increased by concomitant use of antibiotics and PPI, whereas H2RAs may be less harmful.

Cited by 515 publications

References 62 publications

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Clinical and demographic profile and risk factors for Clostridium difficile infection

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