78 research outputs found
Clostridium difficile infection among veterans health administration patients
OBJECTIVETo report on the prevalence and incidence of Clostridium difficile infection (CDI) from 2009 to 2013 among Veterans Healthcare Administration patientsDESIGNA retrospective descriptive analysis of data extracted from a large electronic medical record (EMR) databaseSETTINGData were acquired from VHA healthcare records from 2009 to 2013 that included outpatient clinical visits, long-term care, and hospitalized care as well as pharmacy and laboratory information.RESULTSIn 2009, there were 10,207 CDI episodes, and in 2013, there were 12,143 CDI episodes, an increase of 19.0%. The overall CDI rate increased by 8.4% from 193 episodes per 100,000 patient years in 2009 to 209 episodes per 100,000 patient years in 2013. Of the CDI episodes identified in 2009, 58% were identified during a hospitalization, and 42% were identified in an outpatient setting. In 2013, 44% of the CDI episodes were identified in an outpatient setting.CONCLUSIONThis is one of the largest studies that has utilized timely EMR data to describe the current CDI epidemiology at the VHA. Despite an aging population with greater burden of comorbidity than the general US population, our data show that VHA CDI rates stabilized between 2011 and 2013 following increases likely attributable to the introduction of the more sensitive nucleic acid amplification tests (NAATs). The findings in this report will help establish an accurate benchmark against which both current and future VA CDI prevention initiatives can be measured.Infect. Control Hosp. Epidemiol. 2015;36(9):1038–1045</jats:sec
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Acid Suppression Therapy Does Not Predispose to Clostridium difficile Infection: The Case of the Potential Bias
Objective: An adverse effect of acid-suppression medications on the occurrence of Clostridium difficile infection (CDI) has been a common finding of many, but not all studies. We hypothesized that association between acid-suppression medications and CDI is due to the residual confounding in comparison between patients with infection to those without, predominantly from non-tested and less sick subjects. We aimed to evaluate the effect of acid suppression therapy on incidence of CDI by comparing patients with CDI to two control groups: not tested patients and patients suspected of having CDI, but with a negative test. Methods: We conducted a case-control study of adult patients hospitalized in internal medicine department of tertiary teaching hospital between 2005–2010 for at least three days. Controls from each of two groups (negative for CDI and non-tested) were individually matched (1∶1) to cases by primary diagnosis, Charlson comorbidity index, year of hospitalization and gender. Primary outcomes were diagnoses of International Classification of Diseases (ICD-9)–coded CDI occurring 72 hours or more after admission. Results: Patients with CDI were similar to controls with a negative test, while controls without CDI testing had lower clinical severity. In multivariable analysis, treatment by acid suppression medications was associated with CDI compared to those who were not tested (OR = 1.88, p-value = 0.032). Conversely, use of acid suppression medications in those who tested negative for the infection was not associated with CDI risk as compared to the cases (OR = 0.66; p = 0.059). Conclusions: These findings suggest that the reported epidemiologic associations between use of acid suppression medications and CDI risk may be spurious. The control group choice has an important impact on the results. Clinical differences between the patients with CDI and those not tested and not suspected of having the infection may explain the different conclusions regarding the acid suppression effect on CDI risk
Efficacy of bezlotoxumab in participants receiving metronidazole, vancomycin, or fidaxomicin for treatment of Clostridioides (Clostridium) difficile infection
Background: In phase 3 MODIFY I/II trials, bezlotoxumab significantly reduced recurrence of
Methods: In MODIFY I/II (NCT01241552/NCT01513239), participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment. Using pooled data from MODIFY I/II, initial clinical cure (ICC) and rCDI were assessed in metronidazole-, vancomycin-, and fidaxomicin-treated subgroups.
Results: Of 1554 participants in MODIFY I/II, 753 (48.5%) received metronidazole, 745 (47.9%) vancomycin, and 56 (3.6%) fidaxomicin. Fewer participants receiving metronidazole had a prior CDI episode in the previous 6 months (12.9%) or ≥1 risk factor for rCDI (66.0%) vs participants receiving vancomycin (41.2% and 83.6%, respectively) and fidaxomicin (55.4% and 89.3%, respectively). ICC rates were similar in the bezlotoxumab (metronidazole, 81.0%; vancomycin, 78.5%; fidaxomicin, 86.7%) and placebo groups (metronidazole, 81.3%; vancomycin, 79.6%; fidaxomicin, 76.9%). In placebo-treated participants, the rCDI was lower in the metronidazole subgroup vs the vancomycin and fidaxomicin subgroups (metronidazole, 28.0%; vancomycin, 38.4%; fidaxomicin, 35.0%). When analyzed by subsets based on history of CDI, rCDI rates were similar in the metronidazole and vancomycin groups. rCDI rates were lower in all antibiotic subgroups for bezlotoxumab vs placebo (metronidazole: rate difference [RD], -9.7%; 95% confidence interval [CI], -16.4% to -3.1%; vancomycin: RD, -15.4%; 95% CI, -22.7% to -8.0%; fidaxomicin: RD, -11.9%; 95% CI, -38.1% to 14.3%).
Conclusion: Bezlotoxumab reduces rCDI vs placebo in participants receiving metronidazole and vancomycin, with a similar effect size in participants receiving fidaxomicin
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The Monoclonal Antitoxin Antibodies (Actoxumab–Bezlotoxumab) Treatment Facilitates Normalization of the Gut Microbiota of Mice with Clostridium difficile Infection
Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab–bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials. Although the main mechanism of protection is through direct neutralization of the toxins, the impact of MK-3415A on gut microbiota and its restoration has not been examined. Using a CDI murine model, we compared the bacterial diversity of the gut microbiome of mice under different treatments including MK-3415A, vancomycin, or vancomycin combined with MK-3415A, sampled longitudinally. Here, we showed that C. difficile infection resulted in the prevalence of Enterobacter species. Sixty percent of mice in the vehicle group died after 2 days and their microbiome was almost exclusively formed by Enterobacter. MK-3415A treatment resulted in lower Enterobacter levels and restoration of Blautia, Akkermansia, and Lactobacillus which were the core components of the original microbiota. Vancomycin treatment led to significantly lower survival rate than the combo treatment of MK-3415A and vancomycin. Vancomycin treatment decreased bacterial diversity with predominant Enterobacter and Akkermansia, while Staphylococcus expanded after vancomycin treatment was terminated. In contrast, mice treated by vancomycin combined with MK-3415A also experienced decreased bacterial diversity during vancomycin treatment. However, these animals were able to recover their initial Blautia and Lactobacillus proportions, even though episodes of Staphylococcus overgrowth were detected by the end of the experiments. In conclusion, MK-3415A (actoxumab–bezlotoxumab) treatment facilitates normalization of the gut microbiota in CDI mice. It remains to be examined whether or not the prevention of recurrent CDI by the antitoxin antibodies observed in clinical trials occurs through modulation of microbiota
A qualitative examination of apathy and physical activity in Huntington's and Parkinson's disease
Aim: In Huntington's disease (HD) and Parkinson's disease (PD), apathy is a frequently cited barrier to participation in physical activity. Current diagnostic criteria emphasize dissociable variants of apathy that differentially affect goal-directed behavior. How these dimensions present and affect physical activity in HD and PD is unknown. Methods: Using a qualitative approach, we examined the experience of apathy and its impact on physical activity in 20 people with early-manifest HD or idiopathic PD. Results: Two major themes emerged: the multidimensionality of apathy, including initiation or goal-identification difficulties, and the interplay of apathy and fatigue; and facilitators of physical activity, including routines, safe environments and education. Conclusion: Physical activity interventions tailored to apathy phenotypes may maximize participant engagement
Myth or Memory? Recollections of Penal Times in Irish Folklore
Stories of priests being hunted down and murdered at Mass Rocks by priest catchers and soldiers during the Penal era in Ireland persist to the present day. Using Ó Ciosáin’s (2004) tripartite taxonomy of memory this paper explores the reasons why these images continue to dominate and reflect persecuted nature of Catholicism
WSES guidelines for management of Clostridium difficile infection in surgical patients
In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe
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Update on the immunologic basis of Helicobacter pylori gastritis
PURPOSE OF REVIEWHelicobacter pylori is a ubiquitous bacterial pathogen that has evolved to chronically infect the gastric mucosal surface, evade host immune clearance, and cause peptic ulcer disease or gastric neoplasia in a significant minority of infected individuals. Understanding the colonization, persistence, and virulence determinants of the bacterium as well as the innate and adaptive immune responses of the host are critically important if we are to develop novel treatment strategies for eradication of infection and prevention of H. pylori-induced gastroduodenal disease. RECENT FINDINGSSubstantial progress has been made in understanding the role of CagA in altering gastric epithelial cell signaling pathways. Intracellular CagA has been shown to activate the Ras/MEK/ERK mitogen activated protein kinase cascade and to associate with epithelial tight-junction scaffolding protein ZO-1. CagA was shown to regulate cellular responses and possibly contribute to gastritis by phosphorylation-dependent pathways. A phosphorylation-independent mechanism for CagA intracellular effects has also been proposed. The potential for CagA to disrupt the apical junctional barrier and for the outer membrane protein oipA to promote IL-8 secretion and gastric inflammation have also been explored. A number of different mechanisms by which H. pylori escapes and evades host immune attack to cause chronic indolent inflammation have been uncovered. Meanwhile, the examination and development of new adjuvants and vaccine delivery mechanisms to induce mucosal immune responses against key bacterial antigens has been a continuing focus of investigation in both animal and human studies. SUMMARYH. pylori induces gastritis through production of a variety of antigens, virulence factors, and soluble mediators. The bacterium also dysregulates, disarms, and evades host immune responses to maintain chronic colonization of the gastric mucosa. Understanding the mechanisms of its growth and survival in the human stomach are essential for the development of an effective vaccine and other novel eradication strategies
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