Posts filed under ‘Infecciones gastrointestinales’

Review – Role of cephalosporins in the era of Clostridium difficile infection

Journal of Antimicrobial & Chemotherapy January 1, 2017 V.72 N.1 P.1-18

Mark H. Wilcox, James D. Chalmers, Carl E. Nord, Jane Freeman, and Emilio Bouza

1Leeds Institute of Biomedical and Clinical Sciences, Faculty of Medicine and Health, University of Leeds, and Microbiology, Leeds Teaching Hospitals, Leeds, UK

2Tayside Respiratory Research Group, University of Dundee, Dundee, UK

3Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden

4Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise.

This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011–12 to 2012–13, respectively.

While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence.

Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI.

Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations.

We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes.

PDF

http://jac.oxfordjournals.org/content/72/1/1.full.pdf+html

August 19, 2017 at 10:33 am

From Expert Protocols to Standardized Management of Infectious Diseases

Clinical Infectious Diseases  15 August 2017  V.65 N.suppl 1 S12–S19

Jean-Christophe Lagier; Camille Aubry; Marion Delord; Pierre Michelet; Hervé Tissot-Dupont …

We report here 4 examples of management of infectious diseases (IDs) at the University Hospital Institute Méditerranée Infection in Marseille, France, to illustrate the value of expert protocols feeding standardized management of IDs.

First, we describe our experience on Q fever and Tropheryma whipplei infection management based on in vitro data and clinical outcome.

Second, we describe our management-based approach for the treatment of infective endocarditis, leading to a strong reduction of mortality rate.

Third, we report our use of fecal microbiota transplantation to face severe Clostridium difficile infections and to perform decolonization of patients colonized by emerging highly resistant bacteria.

Finally, we present the standardized management of the main acute infections in patients admitted in the emergency department, promoting antibiotics by oral route, checking compliance with the protocol, and avoiding the unnecessary use of intravenous and urinary tract catheters.

Overall, the standardization of the management is the keystone to reduce both mortality and morbidity related to IDs.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/65/suppl_1/10.1093_cid_cix403/3/cix403.pdf?Expires=1502372492&Signature=LVAbXU3YuwNx~UkUFnKvXaFmayq1aLSWpor6xnVqc2jGiKuNc69M1UqI4xbuqSgRoOKoPhupwLOXRmDGZRMNfu1ydEj9NXbJnqvpBSeWUzfnWw~jYh2w3Y37B92GZwGPSe4XelatYtvhE7i8mqlvzzKKpL2cpkgYhApfvdGjdPIJ-cWZCHuU8dzEdHMOzmEjV-sJI1rBrwSqK4XlRyFojeLEKx5yBZxDukcIP2GQbPvbL1BYugZA~MAyA8mGR2GpExfsI14HZhD4mnTkj9UwjfA63wbptXdFn8jPuhfRCDI6Q52VtmEonPn~V4RR88mRqcV~l63vhtFfzysOXOk83A__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

August 9, 2017 at 8:50 am

Case Report: Benefits and Challenges of Long-term Eculizumab in Atypical Hemolytic Uremic Syndrome

Pediatrics June 2015 V.135 N.6

Noelle Cullinan, Kathleen Mary Gorman, Michael Riordan, Mary Waldron, Timothy H.J Goodship, Atif Awan

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, leading to complement overactivation. A humanized anti-C5 monoclonal antibody, eculizumab, has been available for the treatment of aHUS since 2011.

The long-term safety and efficacy of this novel drug in the pediatric population remain under review.

We present a child with a hybrid CFH/CFHR3 gene who, having had multiple disease relapses despite optimal treatment with plasma exchange, commenced eculizumab therapy in August 2010.

She remains relapse free in follow-up at 52 months, and treatment has been well tolerated. The risk of meningococcal disease during this treatment is recognized.

Despite vaccination against meningococcal disease and appropriate antibiotic prophylaxis, our patient developed meningococcal bacteremia 30 months into treatment.

She presented with nonspecific symptoms but recovered without sequelae with appropriate treatment. We recommend that children be vaccinated against invasive meningococcal infection before beginning eculizumab therapy and take appropriate antibiotic prophylaxis during treatment, and we suggest that vaccine responses should be checked and followed annually.

Clinicians need to maintain a high index of suspicion for invasive meningococcal disease. Neither vaccination nor antibiotic prophylaxis provides complete protection in patients on eculizumab therapy.

The appropriate dosage of eculizumab needed to achieve remission in aHUS in the pediatric population is unknown.

Having achieved remission in our patient, we monitor eculizumab and CH50 levels to evaluate ongoing blockade of the terminal complement cascade. Such information may help guide dosing intervals in the future….

FULL TEXT

http://pediatrics.aappublications.org/content/135/6/e1506

PDF

http://pediatrics.aappublications.org/content/pediatrics/135/6/e1506.full.pdf

July 27, 2017 at 8:09 am

Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study

Lancet Infectious Diseases July 2017 V.17 N.7

Dr Richard J Vickers, PhD’, Glenn S Tillotson, PhD, Richard Nathan, MD, Sabine Hazan, MD, John Pullman, MD, Christopher Lucasti, DO, Kenneth Deck, MD, Prof Bruce Yacyshyn, MD, Benedict Maliakkal, MD, Yves Pesant, MD, Bina Tejura, MD, Prof David Roblin, FRCP, Prof Dale N Gerding, MD, Prof Mark H Wilcox, MD for the show CoDIFy study group†

Background

Clostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment of C difficile infection.

Methods

We did a phase 2, randomised, double-blind, active-controlled, non-inferiority study. Participants with signs and symptoms of C difficile infection and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned (1:1) to receive oral ridinilazole (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was achievement of a sustained clinical response, defined as clinical cure at the end of treatment and no recurrence within 30 days, which was used to establish non-inferiority (15% margin) of ridinilazole versus vancomycin. The primary efficacy analysis was done on a modified intention-to-treat population comprising all individuals with C difficile infection confirmed by the presence of free toxin in stool who were randomly assigned to receive one or more doses of the study drug. The study is registered with ClinicalTrials.gov, number NCT02092935.

Findings

Between June 26, 2014, and August 31, 2015, 100 patients were recruited; 50 were randomly assigned to receive ridinilazole and 50 to vancomycin. 16 patients did not complete the study, and 11 discontinued treatment early. The primary efficacy analysis included 69 patients (n=36 in the ridinilazole group; n=33 in the vancomycin group). 24 of 36 (66·7%) patients in the ridinilazole group versus 14 of 33 (42·4%) of those in the vancomycin group had a sustained clinical response (treatment difference 21·1%, 90% CI 3·1–39·1, p=0·0004), establishing the non-inferiority of ridinilazole and also showing statistical superiority at the 10% level. Ridinilazole was well tolerated, with an adverse event profile similar to that of vancomycin: 82% (41 of 50) of participants reported adverse events in the ridinilazole group and 80% (40 of 50) in the vancomycin group. There were no adverse events related to ridinilazole that led to discontinuation.

Interpretation

Ridinilazole is a targeted-spectrum antimicrobial that shows potential in treatment of initial C difficile infection and in providing sustained benefit through reduction in disease recurrence. Further clinical development is warranted.

Funding

Wellcome Trust and Summit Therapeutics.

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30235-9.pdf

 

Lancet Infectious Diseases July 2017 V.17 N.7

COMMENT – Expanding the armamentarium for the treatment of Clostridium difficile infection 

Simon D Goldenberg

In The Lancet Infectious Diseases, Richard Vickers and colleagues1 report results of a phase 2 study of ridinilazole, a promising new drug for the treatment of Clostridium difficile infection. Although efforts to improve infection control practices and antimicrobial stewardship have led to significant reductions in some countries, C difficile infection remains a substantial problem worldwide.

All-cause 30-day mortality associated with C difficile infection has been reported to be in the region of 9–38%.3, 4 Furthermore, cases are associated with excess length of hospital stay of approximately 7 days (and 12 days in severe cases). C difficile infection usually occurs following disruption of the intestinal microbiota resulting from exposure to antibiotics. The risk of C difficile infection increases by up to six times during antibiotic therapy and in the month thereafter.

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30237-2.pdf

June 23, 2017 at 7:56 am

Real-Time Electronic Tracking of Diarrheal Episodes and Laxative Therapy Enables Verification of Clostridium difficile Clinical Testing Criteria and Reduction of Clostridium difficile Infection Rates

Journal of Clinical Microbiology May 2017 V.55 N.5 P.1276-1284

Cynthia Y. Truong, Saurabh Gombar, Richard Wilson, Gopalakrishnan Sundararajan, Natasa Tekic, Marisa Holubar, John Shepard, Alexandra Madison, Lucy Tompkins, Neil Shah, Stan Deresinski, Lee F. Schroeder, and Niaz Banaei

aDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA

bDigital Solutions, Stanford Health Care, Stanford, California, USA

cDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA

dInfection Control and Prevention, Stanford Health Care, Stanford, California, USA

eStanford Antimicrobial Safety and Sustainability, Stanford Health Care, Stanford, California, USA

fDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA

gClinical Microbiology Laboratory, Stanford Health Care, Stanford, California, USA

Health care-onset health care facility-associated Clostridium difficile infection (HO-CDI) is overdiagnosed for several reasons, including the high prevalence of C. difficile colonization and the inability of hospitals to limit testing to patients with clinically significant diarrhea. We conducted a quasiexperimental study from 22 June 2015 to 30 June 2016 on consecutive inpatients with C. difficile test orders at an academic hospital. Real-time electronic patient data tracking was used by the laboratory to enforce testing criteria (defined as the presence of diarrhea [≥3 unformed stools in 24 h] and absence of laxative intake in the prior 48 h). Outcome measures included C. difficile test utilization, HO-CDI incidence, oral vancomycin utilization, and clinical complications. During the intervention, 7.1% (164) and 9.1% (211) of 2,321 C. difficile test orders were canceled due to absence of diarrhea and receipt of laxative therapy, respectively. C. difficile test utilization decreased upon implementation from an average of 208.8 tests to 143.0 tests per 10,000 patient-days (P < 0.001). HO-CDI incidence rate decreased from an average of 13.0 cases to 9.7 cases per 10,000 patient-days (P = 0.008). Oral vancomycin days of therapy decreased from an average of 13.8 days to 9.4 days per 1,000 patient-days (P = 0.009). Clinical complication rates were not significantly different in patients with 375 canceled orders compared with 869 episodes with diarrhea but negative C. difficile results. Real-time electronic clinical data tracking is an effective tool for verification of C. difficile clinical testing criteria and safe reduction of inflated HO-CDI rates.

PDF

http://jcm.asm.org/content/55/5/1276.full.pdf+html

May 9, 2017 at 8:23 am

Commentaries – Strategies for Optimizing the Diagnostic Predictive Value of Clostridium difficile Molecular Diagnostics

Journal of Clinical Microbiology May 2017 V.55 N.5 P.1244-1248

Larry K. Kociolek

Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Division of Infectious Diseases, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA

Because nucleic acid amplification tests (NAATs) do not distinguish Clostridium difficile infection (CDI) and asymptomatic C. difficile carriage, the diagnostic predictive value of NAATs is limited when used in patients with a low probability of CDI. In this issue of the Journal of Clinical Microbiology, Truong et al. (J. Clin. Microbiol., 55:1276–1284, 2017, https://doi.org/10.1128/JCM.02319-16) report significant reductions in hospital-onset CDI and oral vancomycin utilization at their institution following implementation of a novel intervention that leveraged their clinical bioinformatics resources to prevent C. difficile testing of stools from patients without clinically significant diarrhea and in patients with recent laxative use….

PDF

http://jcm.asm.org/content/55/5/1244.full.pdf+html

May 9, 2017 at 8:22 am

CMV infection complicating the diagnosis of Crohn’s disease in an immunocompetent patient.

BMJ Case Rep. 2012 May 8;2012. pii: bcr1120115254. doi: 10.1136/bcr.11.2011.5254.

Shahani L1.

1Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois, USA. lokesh83@hotmail.com

Abstract

Cytomegalovirus (CMV) affects the gastrointestinal tract commonly; however CMV colitis is uncommon in patients who are not severely immunocompromised.

The author reports a 51-year-old Caucasian female who was admitted to the hospital with exacerbation of her chronic diarrhoea. CAT scan of the abdomen and pelvis showed thickening of the wall of the terminal ileum with inflammatory stranding and follow-up colonoscopy showed extensive circumferential ulceration in the terminal ileum.

Biopsies confirmed diagnosis of CMV infection and the patient was started on appropriate antimicrobial agents. CMV viremia showed response to the medication; however the patient’s intestinal symptoms failed to improve.

Nodular lesions consistent with erythema nodusum were noticed and promethus test was consistent with Crohn’s disease.

The patient showed good response to immunosuppressive therapy. CMV infections are known to exacerbate symptoms of inflammatory bowel disease and hence Crohn’s disease should be suspected in an immunocompetent patient presenting with CMV ileitis.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351665/pdf/bcr.11.2011.5254.pdf

February 9, 2017 at 2:51 pm

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