Posts filed under ‘Infecciones gastrointestinales’

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence

Clinical Infectious Diseases September 1, 2018 V.67 N.5 P.649–656

Dale N Gerding; Ciaran P Kelly; Galia Rahav; Christine Lee; Erik R Dubberke …

Subgroup analyses from MODIFY confirmed that prior Clostridium difficile infection (CDI), age ≥65 years, infection with 027/078/244 strain, compromised immunity, and severe CDI are risk factors for recurrent CDI. Bezlotoxumab reduced CDI recurrence in participants with ≥1 risk factor compared with placebo.

Background

Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI.

Methods

The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented.

Results

The majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI.

Conclusions

The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit.

Clinical Trials Registration NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

FULL TEXT

https://academic.oup.com/cid/article/67/5/649/4925796

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September 2, 2018 at 10:33 am

Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Trial in China

Antimicrobial Agents and Chemotherapy September 2018 V.62 N.9

Yong Xie, Zhenhua Zhu, Jiangbin Wang, Lingxia Zhang, Zhenyu Zhang, Hong Lu, Zhirong Zeng, Shiyao Chen, Dongsheng Liu, Nonghua Lv

The objective of this study was to investigate the efficacy and safety of 10-day bismuth quadruple therapy with amoxicillin, tetracycline, or clarithromycin and different doses of rabeprazole for first-line treatment of Helicobacter pylori infection.

This multicenter, randomized, parallel-controlled clinical trial was conducted between March 2013 and August 2014.

A total of 431 H. pylori-infected patients with duodenal ulcers were enrolled and randomized into four treatment groups (1:1:1:1) for 10 days, as follows: (i) a group receiving a low dose of rabeprazole of 10 mg twice a day (b.i.d.) (LR dose) plus bismuth, amoxicillin, and clarithromycin (LR-BAC); (ii) a group receiving LR plus bismuth, amoxicillin, and tetracycline (LR-BAT); (iii) a group receiving a high dose of rabeprazole of 20 mg b.i.d. (HR dose) plus bismuth, amoxicillin, and clarithromycin (HR-BAC); and (iv) a group receiving HR-BAT. Antimicrobial susceptibility was assessed by the Etest method.

The primary outcome was H. pylori eradication at 4 weeks after the treatment. The per-protocol (PP) eradication rates in the LR-BAC, LR-BAT, HR-BAC, and HR-BAT groups were 94.1%, 91.9%, 94.8%, and 91.9%, respectively, while the intention-to-treat (ITT) eradication rates in those groups were 87.2%, 87.2%, 87.7%, and 86%, respectively.

There was no significant difference between the four groups in PP analysis (P = 0.799) and ITT analysis (P = 0.985). The efficacies of four-treatment therapy were not affected by antibiotic resistance.

The adverse events in the four treatment groups were similar; central nervous system (CNS) and gastrointestinal symptoms were the most common reported.

Bismuth-containing quadruple therapy with low-dose rabeprazole, amoxicillin, and tetracycline is a good option for first-line treatment of H. pylori infection in a population with high antibiotic resistance.

(This study is registered at Chinese Clinical Trials Registry [www.chictr.org.cn] under number ChiCTR1800014832.)

FULL TEXT

https://aac.asm.org/content/62/9/e00432-18?etoc=

PDF

https://aac.asm.org/content/aac/62/9/e00432-18.full.pdf

August 29, 2018 at 3:41 pm

Shotgun Metagenomic Detection of Pathogens: a Micro-Comic Strip

Journal of Clinical Microbiology  August 2018 V.56 N.8

Editorial

Alexander J. McAdam

Next-generation sequencing has made shotgun metagenomic testing of primary clinical specimens for detection of pathogens feasible (1).

These technologies can routinely detect a range of pathogens (bacterial, viral, fungal, and eukaryotic parasites), allowing for hypothesis-free testing, in which test selection does not depend on knowing what pathogens are likely to be present.

Such testing has been applied for detecting infections or colonization of the nervous system (2–4), gastrointestinal tract (5, 6), prosthetic joints (7, 8), and blood or serum (9, 10).

Shotgun metagenomic testing for pathogens is now available for patient testing at a small number of academic and commercial laboratories, and it is expensive compared to other microbiology tests.

Where do the cost of and diversity of pathogens detected by shotgun metagenomic testing fit into the range of available microbiology tests?

FULL TEXT

http://jcm.asm.org/content/56/8/e00799-18?etoc

PDF

http://jcm.asm.org/content/56/8/e00799-18.full.pdf+html

July 28, 2018 at 6:32 pm

Durability and Long-term Clinical Outcomes of Fecal Microbiota Transplant Treatment in Patients With Recurrent Clostridium difficile Infection

Clinical Infectious Diseases June 1, 2018 V.66 N.11 P.1705–1711

EDITOR’S CHOICE

Yafet Mamo; Michael H Woodworth; Tiffany Wang; Tanvi Dhere; Colleen S Kraft

Background

Fecal microbiota transplant (FMT) appears safe and effective for treatment of recurrent Clostridium difficile infection (RCDI). However, durability, long-term clinical outcomes, and patient satisfaction after FMT are not well described.

Methods

Eligible patients who received FMT for RCDI at Emory Hospital between 1 July 2012 and 31 December 2016 were contacted via telephone for a follow-up survey. Of 190 eligible patients, 137 (72%) completed the survey.

Results

Median time from last FMT to follow-up was 22 months. Overall, 82% (113/137) of patients at follow-up had no recurrence of C. difficile infection (CDI) post-FMT (non-RCDI group) and 18% (24/137) of patients had CDI post-FMT (RCDI group). Antibiotic exposure for non-CDI infections after FMT was more common in the RCDI group compared to the non-RCDI group (75% vs 38%, P = .0009). Overall, 11% of patients reported improvement or resolution of diagnoses not related to CDI post-FMT, and 33% reported development of a new medical condition or symptom post-FMT. Ninety-five percent of patients (122/128) indicated that they would undergo FMT again, and 70% of these 122 reported that they would prefer FMT to antibiotics as initial treatment if they were to have a CDI recurrence.

Conclusions

In this follow-up survey of outcomes after FMT at a median of 22 months follow-up, 82% of patients had durable cure of CDI. Patients with recurrence had more post-FMT antibiotic exposure, underscoring the need for thoughtful antibiotic use and a potential role for prophylactic microbiome enrichment to reduce recurrence.

FULL TEXT

https://academic.oup.com/cid/article/66/11/1705/4762674

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June 10, 2018 at 7:17 pm

Enterotoxigenic Escherichia coli blood group A interactions intensify diarrheal severity

The Journal of Clinical Investigation 2018

Pardeep Kumar, Mark Donowitz, James M. Fleckenstein

Enterotoxigenic Escherichia coli (ETEC) infections are highly prevalent in developing countries where clinical presentations range from asymptomatic colonization to severe cholera-like illness. The molecular basis for these varied presentations, that may involve strain-specific virulence features as well as host factors, have not been elucidated. We demonstrated that when challenged with ETEC strain H10407, originally isolated from a case of cholera-like illness, blood group A human volunteers developed severe diarrhea more frequently than individuals from other blood groups. Interestingly, a diverse population of ETEC strains, including H10407, secrete the EtpA adhesin molecule. As many bacterial adhesins also agglutinate red blood cells, we combined the use of glycan arrays, biolayer inferometry, and non-canonical amino acid labeling with hemagglutination studies to demonstrate that EtpA is a dominant ETEC blood group A specific lectin/hemagglutinin. Importantly, we have also shown that EtpA interacts specifically with glycans expressed on intestinal epithelial cells from blood group A individuals, and that EtpA-mediated bacterial-host interactions accelerate bacterial adhesion and effective delivery of both the heat-labile and heat-stable toxins of ETEC. Collectively, these data provide additional insight into the complex molecular basis of severe ETEC diarrheal illness that may inform rational design of vaccines to protect those at highest risk.

abstract

https://www.jci.org/articles/view/97659/pdf

PDF (CLIC en DOWNLOAD)

https://dm5migu4zj3pb.cloudfront.net/manuscripts/97000/97659/cache/97659.1-20180507184523-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf

May 21, 2018 at 8:38 am

Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

Clinical Infectious Diseases April 1, 2018 V.66 N.7 P.987-994

IDSA FEATURE

L Clifford McDonald; Dale N Gerding; Stuart Johnson; Johan S Bakken; Karen C Carroll …

Un panel de expertos fue convocado por la Sociedad de Enfermedades Infecciosas de América (IDSA) y la Sociedad de Epidemiología de Salud de Estados Unidos (SHEA) para actualizar la guía de práctica clínica 2010 sobre la infección por Clostridium difficile (CDI) en adultos.

La actualización, que ha incorporado recomendaciones para niños (siguiendo las recomendaciones de adultos para epidemiología, diagnóstico y tratamiento), incluye cambios significativos en el tratamiento de esta infección y refleja la controversia en evolución sobre los mejores métodos para el diagnóstico.

Clostridium difficile sigue siendo la causa más importante de diarrea asociada a la asistencia sanitaria y se ha convertido en la causa más común de infección asociada al cuidado de la salud en adultos en los EUU. Además, C. difficile se ha establecido como un patógeno comunitario importante.

Aunque la prevalencia de la epidemia y virulenta cepa ribotype 027 ha disminuido notablemente junto con las tasas globales de CDI en partes de Europa, sigue siendo una de las cepas más comúnmente identificadas en los EEUU, donde causa una minoría considerable de CDI, especialmente asociados al cuidado de la salud. Esta guía actualiza las recomendaciones sobre epidemiología, diagnóstico, tratamiento, prevención de infecciones y gestión ambiental.

FULL TEXT

https://academic.oup.com/cid/article/66/7/987/4942452

PDF (CLIC en PDF)

 

April 1, 2018 at 3:23 pm

Risk Factors for Community-Associated Clostridium difficile Infection in Adults: A Case-Control Study

Open Forum Infectious Diseases Fall 2017 V.4 N.4

EDITOR’S CHOICE

Alice Y Guh; Susan Hocevar Adkins; Qunna Li; Sandra N Bulens; Monica M Farley …

Fundamento

Una proporción cada vez mayor de infecciones por Clostridium difficile (CDI) en los EEUU están asociadas a la comunidad (CA). Llevamos a cabo un estudio de casos y controles para identificar los factores de riesgo CA-CDI.

Métodos

Ingresamos participantes de 10 sitios de EEUU entre octubre 2014 y marzo 2015. Los pacientes se definieron como personas > 18 años con una muestra positiva de C. difficile recogida de forma ambulatoria o dentro de los 3 días de la hospitalización y que no tenían otro ingreso a un centro de atención de salud en las 12 semanas anteriores y sin diagnóstico previo de CDI. Cada paciente se comparó con un caso-control (personas sin CDI). Los participantes fueron entrevistados sobre exposiciones relevantes; se realizaron regresiónes logísticas condicionales multivariadas.

Resultados

De 226 el 70.4% eran mujeres y el 52.2% tenían ≥ 60 años. Más casos de pacientes que de controles tuvieron una atención ambulatoria de la salud (82,1% vs a 57,9%, p <0,0001) y ATB (62,2% vs a 10,3%, p <0,0001). En el análisis multivariado, la exposición a ATB, es decir, cefalosporina (odds ratio ajustados ajustados [AmOR], 19,02, IC del 95%, 1,13 a 321,39), clindamicina (AmOR, 35,31, IC del 95%, 4,01 a 311,14), fluoroquinolona (AmOR, 30.71; IC del 95%, 2.77-340.05) y combinación de betalactámicos y/o inhibidores de la betalactamasa (AmOR, 9.87; IC 95%, 2.76-340.05), – consulta al servicio de emergencia (AmOR, 17.37; IC 95%, 1.99 -151.22), raza blanca (AmOR 7.67, IC 95%, 2.34-25.20), enfermedad cardíaca (AmOR, 4.87, IC 95%, 1.20-19.80), enfermedad renal crónica (AmOR, 12.12, IC 95%, 1.24-118.89 ), y la enfermedad inflamatoria intestinal (AmOR, 5.13, IC 95%, 1.27-20.79) se asoció con CA-CDI.

Conclusiones

Los ATB siguen siendo un factor de riesgo importante para CA-CDI, lo que subraya la importancia de una adecuada prescripción ambulatoria. Los servicios de emergencia pueden ser una fuente ambiental de CDI; se necesita una mayor investigación de su contribución a la transmisión de CDI.

FULL TEXT

https://academic.oup.com/ofid/article/4/4/ofx171/4460109

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April 1, 2018 at 3:14 pm

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