Efficacy of Secondary #Prophylaxis With Vancomycin for Preventing Recurrent #Clostridium difficile Infections

http://www.nature.com/ajg/journal/vaop/ncurrent/full/ajg2016417a.html

CONCLUSIONS:

Oral vancomycin appears as an effective strategy for decreasing the risk of further CDI recurrence in patients with a history of recurrent CDI who are re-exposed to antibiotics.

Receipt of #Antibiotics in Hospitalized Patients and Risk for #Clostridium difficile Infection in Subsequent Patients Who Occupy the Same Bed

http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2565687

Conclusions and Relevance Receipt of antibiotics by prior bed occupants was associated with increased risk for CDI in subsequent patients. Antibiotics can directly affect risk for CDI in patients who do not themselves receive antibiotics.

Effects of control #interventions on #Clostridium difficile infection in England: an observational study

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(16)30514-X/fulltext

Restricting fluoroquinolone prescribing appears to explain the decline in incidence of C difficile infections, above other measures, in Oxfordshire and Leeds, England. Antimicrobial stewardship should be a central component of C difficile infection control programmes.

#Bezlotoxumab for Prevention of Recurrent #Clostridium difficile Infection

http://www.nejm.org/doi/full/10.1056/NEJMoa1602615

Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy.

Comparative Effectiveness of #Vancomycin and Metronidazole for the Prevention of Recurrence and Death in Patients With #Clostridium difficile Infection

http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2601079

Recurrence rates were similar among patients treated with vancomycin and metronidazole. However, the risk of 30-day mortality was significantly reduced among patients who received vancomycin. Our findings may further justify the use of vancomycin as initial therapy for severe CDI.

Effects of #control interventions on #Clostridium difficile infection in England: an observational study

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(16)30514-X/abstract

Restricting fluoroquinolone prescribing appears to explain the decline in incidence of C difficile infections, above other measures, in Oxfordshire and Leeds, England. Antimicrobial stewardship should be a central component of C difficile infection control programmes.

Timely use of #Probiotics in Hospitalized Adults Prevents #Clostridium difficile Infection: a Systematic Review with Meta-Regression Analysis

http://www.gastrojournal.org/article/S0016-5085(17)30136-1/abstract?referrer=http%3A%2F%2Fwww.jwatch.org%2Fna43601%2F2017%2F03%2F06%2Fprobiotics-prevent-c-difficile-infection-hospitalized%3Fijkey%3DPERK4MOUVye3s%26keytype%3Dref%26siteid%3Djwatch%26variant%3Dfull-text

In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by more than 50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395

Enhanced terminal room #disinfection and acquisition and infection caused by multidrug-resistant organisms and #Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study
http://thelancet.com/journals/lancet/article/PIIS0140-6736(16)31588-4/abstract

The primary outcome was not statistically lower with bleach (n=101; 41·6 cases per 10 000 exposure days; RR 0·85, 95% CI 0·69–1·04; p=0·116), or bleach and UV (n=131; 45·6 cases per 10 000 exposure days; RR 0·91, 95% CI 0·76–1·09; p=0·303) among exposed patients. Similarly, the incidence of C difficile infection among exposed patients was not changed after adding UV to cleaning with bleach (n=38 vs 36; 30·4 cases vs 31·6 cases per 10 000 exposure days; RR 1·0, 95% CI 0·57–1·75; p=0·997).

Effect of #antibiotic stewardship on the incidence of infection and colonisation with antibiotic-#resistant bacteria and #Clostridium difficile infection: a systematic review and meta-analysis
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30325-0/abstract

Antibiotic stewardship programmes significantly reduce the incidence of infections and colonisation with antibiotic-resistant bacteria and C difficile infections in hospital inpatients. These results provide stakeholders and policy makers with evidence for implementation of antibiotic stewardship interventions to reduce the burden of infections from antibiotic-resistant bacteria.

Multiply #Recurrent #Clostridium difficile Infection in the United States: A Cohort Study
http://annals.org/aim/article/2636751/increasing-incidence-multiply-recurrent-clostridium-difficile-infection-united-states-cohort

Clostridium difficile infection (CDI), the most common health care–associated infection, often recurs. Fecal microbiota transplantation is increasingly used to treat multiply recurrent CDI (mrCDI). From 2001 to 2012, the annual incidence of CDI and mrCDI per 1000 person-years increased by 42.7% (from 0.4408 to 0.6289 case) and 188.8% (from 0.0107 to 0.0309 case), respectively. The increase in mrCDI incidence was independent of known risk factors for CDI. Those who developed mrCDI were older (median age, 56.0 vs. 49.0 years; adjusted odds ratio aOR per 10-year increase in age, 1.25 95% CI, 1.21 to 1.29) and were more likely to be female (63.8% vs. 58.7%; aOR, 1.24 CI, 1.11 to 1.38) and to have used antibiotics (72.3% vs. 58.8%; aOR, 1.79 CI, 1.59 to 2.01), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 CI, 1.01 to 1.29), or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 CI, 1.00 to 1.32) within 90 days of CDI diagnosis. Chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 CI, 1.24 to 1.80) and diagnosis in a nursing home (2.1% vs. 0.6%; aOR, 1.99 CI, 1.34 to 2.93) were also associated with increased risk for mrCDI.

Conclusion:
Relative to CDI, mrCDI incidence has disproportionately increased, indicating a rising demand for mrCDI therapies.

Systematic review with meta-analysis: the efficacy of faecal microbiota #transplantation for the treatment of recurrent and refractory #Clostridium difficile infection
http://onlinelibrary.wiley.com/doi/10.1111/apt.14201/abstract;jsessionid=F8304BE6332A57344642B0BBD9C57DFA.f03t02

Clostridium difficile infection (CDI) is the commonest nosocomial cause of diarrhoea. Faecal microbiota transplantation (FMT) is an approved treatment for recurrent or refractory CDI but there is uncertainty about its use.

FMT was more effective than vancomycin (RR: 0.23 95%CI 0.07-0.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95%CI 89%-94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95%CI 92%-97%) vs 88% (95%CI 82%-94%) respectively (P=.02). There was no difference between fresh and frozen FMT 92% (95%CI 89%-95%) vs 93% (95%CI 87%-97%) respectively (P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect.

Conclusion
Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery.

The long-term effects of faecal #microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent #Clostridium difficile infection
http://onlinelibrary.wiley.com/doi/10.1111/apt.14443/abstract

Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection. In short-term the treatment has been shown to be safe, however, there are no large, long-term follow-up studies looking into the potential adverse effects There was no difference in the incidence of severe diseases (inflammatory bowel disease, cancer, autoimmune disease, allergy, neurological diseases) between the patient groups. In addition, weight gain did not differ between treatment groups. The FMT treated patients reported that their bowel habits improved significantly faster, they had less irregular bowel function and less symptoms of upper GI-tract when compared to the patients treated with antibiotics. Significantly more patients in FMT-group reported that their mental health improved after the treatment. The willingness to receive FMT treatment for potential new C. difficile infection was significantly higher in both treatment groups compared to other treatment options.

Conclusion
Our study highlights that FMT is a durable, safe and acceptable treatment option for patients with recurrent C. difficile infection also in long term, and it shows potential benefits over antimicrobial treatment

Evaluating the risk factors for #hospital-onset #Clostridium difficile infections in a large healthcare system
https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/cix1112/4767819

In this multicenter retrospective cohort study of over 1 million patients at 150 US hospitals, proton pump inhibitors increased the odds of a patient having hospital-onset Clostridium difficile infection as did third and fourth generation cephalosporins, carbapenems, and piperacillin/tazobactam. These findings support appropriate prescribing of acid-suppression therapy and high-risk antibiotics.

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)

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/cix1085/4855916

Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.

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Risk of meticillin resistant #Staphylococcus aureus and #Clostridium difficile in patients with a documented #penicillin allergy: population based matched cohort study

https://www.bmj.com/content/361/bmj.k2400


The primary outcome was risk of incident MRSA and C difficile. Secondary outcomes were use of β lactam antibiotics and β lactam alternative antibiotics.

Results Among 64 141 adults with penicillin allergy and 237 258 matched comparators, 1365 developed MRSA (442 participants with penicillin allergy and 923 comparators) and 1688 developed C difficile (442 participants with penicillin allergy and 1246 comparators) during a mean 6.0 years of follow-up. Among patients with penicillin allergy the adjusted hazard ratio for MRSA was 1.69 (95% confidence interval 1.51 to 1.90) and for C difficile was 1.26 (1.12 to 1.40). The adjusted incidence rate ratios for antibiotic use among patients with penicillin allergy were 4.15 (95% confidence interval 4.12 to 4.17) for macrolides, 3.89 (3.66 to 4.12) for clindamycin, and 2.10 (2.08 to 2.13) for fluoroquinolones. Increased use of β lactam alternative antibiotics accounted for 55% of the increased risk of MRSA and 35% of the increased risk of C difficile.

Conclusions Documented penicillin allergy was associated with an increased risk of MRSA and C difficile that was mediated by the increased use of β lactam alternative antibiotics. Systematically addressing penicillin allergies may be an important public health strategy to reduce the incidence of MRSA and C difficile among patients with a penicillin allergy label.

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Microbial Preparations (#Probiotics) for the Prevention of #Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants

https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/microbial-preparations-probiotics-for-the-prevention-of-clostridium-difficile-infection-in-adults-and-children-an-individual-patient-data-metaanalysis-of-6851-participants/A450208CAAFACC500BE2CE7BAA468DB2

Probiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio OR 0.37; 95% confidence interval CI, 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.

CONCLUSIONS
Moderate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.

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Development and Validation of a Prediction Model for Mortality and Adverse Outcomes Among Patients With Peripheral #Eosinopenia on Admission for #Clostridium difficile Infection

https://jamanetwork.com/journals/jamasurgery/article-abstract/2698956

Those with an undetectable eosinophil count at admission had increased in-hospital mortality in both the training (odds ratio OR, 2.01; 95% CI, 1.08-3.73; P = .03) and validation (OR, 2.26; 95% CI, 1.33-3.83; P = .002) cohorts in both univariable and multivariable analysis. Undetectable eosinophil counts were also associated with indicators of severe sepsis, such as admission to monitored care settings (OR, 1.40; 95% CI, 1.06-1.86), the need for vasopressors (OR, 2.08; 95% CI, 1.32-3.28), and emergency total colectomy (OR, 2.56; 95% CI, 1.12-5.87). Other significant predictors of mortality at admission included increasing comorbidity burden (for each 1-unit increase: OR, 1.13; 95% CI, 1.05-1.22) and lower systolic blood pressures (for each 1-mm Hg increase: OR, 0.99; 95% CI, 0.98-1.00). In a subgroup analysis of patients presenting without initial tachycardia or hypotension, only patients with undetectable admission eosinophil counts, but not those with an elevated white blood cell count, had significantly increased odds of inpatient mortality (OR, 5.76; 95% CI, 1.99-16.64).

Conclusions and Relevance This study describes a simple, widely available, inexpensive model predicting CDI severity and mortality to identify at-risk patients at the time of admission.

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Para- #cresol production by #Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007191

C. difficile is transmitted by spores, which are able to survive in harsh environments for long periods of time. After initial treatment for C. difficile, up to 35% of patients develop the disease again, thus requiring additional and more successful treatment.

Here, we use novel techniques to show that C. difficile produces a compound, p-cresol, which has detrimental effects on the natural protective gut bacteria. We show that p-cresol selectively targets certain bacteria in the gut and disrupts their ability to grow.

By removing the ability of C. difficile to produce p-cresol, we show that it makes C. difficile less able to recolonise after an initial infection. This is linked to significant alterations in the natural healthy bacterial composition of the gut. Our study provides new insights into the effects of p-cresol production on the healthy gut microbiota and how it contributes to C. difficile survival and pathogenesis.

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Cost savings following faecal #microbiota transplantation for recurrent #Clostridium difficile infection

https://journals.sagepub.com/doi/10.1177/1756284819843002

Recurrent Clostridium difficile infection (rCDI) is becoming increasingly common. Faecal microbiota transplantation (FMT) is effective for rCDI, but the costs of an FMT and hospital cost savings related to FMT are unknown. The aim of this study was to calculate the cost of an FMT and the total hospital costs before and after FMT.

The average cost of an outpatient FMT procedure if donor faeces were applied by colonoscopy was €3,326 per patient and €2,864 if donor faeces were applied using a nasojejunal tube. The total annual pre-FMT hospital costs per patient were €56,415 (95% confidence interval (CI) 41,133–71,697), and these costs dropped by 42% to €32,816 (22,618–42,014) post-FMT (p = 0.004). The main cost driver was hospital admissions. Sensitivity analyses demonstrated cost reductions in all scenarios.

Conclusions:
In a public hospital with an implemented FMT service, the average cost of FMT applied by either colonoscopy or nasojejunal tube was €3,095. Total hospital costs dropped by 42% the first year after FMT. The reduction was mainly caused by reductions in the number of hospital admissions and in length of stay

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A Phase 2 Study Evaluating the Safety, Tolerability, and Immunogenicity of Two 3-Dose Regimens of a #Clostridium difficile #Vaccine in Healthy US Adults Aged 65 to 85 Years

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciz153/5498282

Clostridium difficile causes toxin-mediated nosocomial diarrhea and community-acquired infections; no preventive vaccine is licensed.

The 200-μg dose level elicited higher immune responses than the 100-µg dose level across regimens. Compared with the day regimen, the month regimen induced stronger and more persistent immune responses that remained elevated 12 months after dose 3. Responses peaked at month 7 (month regimen) and day 37 (day regimen). LRs (primarily injection site pain) were more frequent in vaccine recipients than controls; SE frequency was similar across groups. More related AEs were reported in the day regimen group than the month regimen group..

Conclusions
The C. difficile vaccine was safe, well tolerated, and immunogenic in healthy US adults aged 65–85 years. Immune responses were particularly robust in the 200-μg month regimen group. These results support continued vaccine development.