Dataset Information

Prevention of Clostridium difficile Infection and Associated Diarrhea: An Unsolved Problem.

ABSTRACT: For many years, it has been known that Clostridium difficile (CD) is the primary cause of health-care-associated infectious diarrhea, afflicting approximately 1% of hospitalized patients. CD may be simply carried or lead to a mild disease, but in a relevant number of patients, it can cause a very severe, potentially fatal, disease. In this narrative review, the present possibilities of CD infection (CDI) prevention will be discussed. Interventions usually recommended for infection control and prevention can be effective in reducing CDI incidence. However, in order to overcome limitations of these measures and reduce the risk of new CDI episodes, novel strategies have been developed. As most of the cases of CDI follow antibiotic use, attempts to rationalize antibiotic prescriptions have been implemented. Moreover, to reconstitute normal gut microbiota composition and suppress CD colonization in patients given antimicrobial drugs, administration of probiotics has been suggested. Finally, active and passive immunization has been studied. Vaccines containing inactivated CD toxins or components of CD spores have been studied. Passive immunization with monoclonal antibodies against CD toxins or the administration of hyperimmune whey derived from colostrum or breast milk from immunized cows has been tried. However, most advanced methods have significant limitations as they cannot prevent colonization and development of primary CDI. Only the availability of vaccines able to face these problems can allow a resolutive approach to the total burden due to this pathogen.

SUBMITTER: Principi N

PROVIDER: S-EPMC7690700 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Prevention of <i>Clostridium difficile</i> Infection and Associated Diarrhea: An Unsolved Problem.

Principi Nicola N Gnocchi Margherita M Gagliardi Martina M Argentiero Alberto A Neglia Cosimo C Esposito Susanna S

Microorganisms 20201023 11

For many years, it has been known that <i>Clostridium difficile</i> (CD) is the primary cause of health-care-associated infectious diarrhea, afflicting approximately 1% of hospitalized patients. CD may be simply carried or lead to a mild disease, but in a relevant number of patients, it can cause a very severe, potentially fatal, disease. In this narrative review, the present possibilities of CD infection (CDI) prevention will be discussed. Interventions usually recommended for infection control ...[more]

PMID: 33114040

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Project description:Antibiotic usage is the most commonly cited risk factor for hospital-acquired Clostridium difficile infections (CDI). The increased risk is due to disruption of the indigenous microbiome and a subsequent decrease in colonization resistance by the perturbed bacterial community; however, the specific changes in the microbiome that lead to increased risk are poorly understood. We developed statistical models that incorporated microbiome data with clinical and demographic data to better understand why individuals develop CDI. The 16S rRNA genes were sequenced from the feces of 338 individuals, including cases, diarrheal controls, and nondiarrheal controls. We modeled CDI and diarrheal status using multiple clinical variables, including age, antibiotic use, antacid use, and other known risk factors using logit regression. This base model was compared to models that incorporated microbiome data, using diversity metrics, community types, or specific bacterial populations, to identify characteristics of the microbiome associated with CDI susceptibility or resistance. The addition of microbiome data significantly improved our ability to distinguish CDI status when comparing cases or diarrheal controls to nondiarrheal controls. However, only when we assigned samples to community types was it possible to differentiate cases from diarrheal controls. Several bacterial species within the Ruminococcaceae, Lachnospiraceae, Bacteroides, and Porphyromonadaceae were largely absent in cases and highly associated with nondiarrheal controls. The improved discriminatory ability of our microbiome-based models confirms the theory that factors affecting the microbiome influence CDI. IMPORTANCE The gut microbiome, composed of the trillions of bacteria residing in the gastrointestinal tract, is responsible for a number of critical functions within the host. These include digestion, immune system stimulation, and colonization resistance. The microbiome's role in colonization resistance, which is the ability to prevent and limit pathogen colonization and growth, is key for protection against Clostridium difficile infections. However, the bacteria that are important for colonization resistance have not yet been elucidated. Using statistical modeling techniques and different representations of the microbiome, we demonstrated that several community types and the loss of several bacterial populations, including Bacteroides, Lachnospiraceae, and Ruminococcaceae, are associated with CDI. Our results emphasize the importance of considering the microbiome in mediating colonization resistance and may also direct the design of future multispecies probiotic therapies.

Project description:BackgroundRecent meta-analyses of the efficacy of probiotics for preventing diarrhea associated with Clostridium difficile have concluded there is a large effect favouring probiotics. We reexamined this evidence, which contradicts the results of a more recent large randomized controlled trial that found no benefit of Lactobacillus probiotics for preventing C. difficile-associated diarrhea.MethodsWe performed a systematic review of the efficacy of treatment with Lactobacillus probiotics for preventing nosocomial C.?difficile-associated diarrhea in adults and carried out a meta-analysis using a Bayesian hierarchical model. We used credibility analysis and meta-regression to characterize the heterogeneity between studies.ResultsTen studies met our inclusion criteria. The pooled risk ratio was highly statistically significant, at 0.25 (95% credible interval 0.08-0.47). However, the 95% prediction interval for the risk ratio in a future study, 0.02-1.34, was wider than the credible interval, owing to heterogeneity between studies. Furthermore, a credibility analysis showed that the strength of the evidence was weaker than the observed number of cases of C. difficile-associated diarrhea across studies would suggest. Meta-regression suggested that the beneficial effect of probiotics was more likely to be reported in studies with an increased risk of C. difficile-associated diarrhea in the control group, although this association was not statistically significant.InterpretationAccounting for between-study heterogeneity showed that there is considerable uncertainty regarding the apparently large efficacy estimate associated with Lactobacillus probiotic treatment in preventing C. difficile-associated diarrhea. Most studies to date have been carried out in populations with a low risk of C. difficile-associated diarrhea, such that the evidence is inconclusive and inadequate to support a policy concerning routine use of probiotics in to prevent this condition.

Dataset Information

Prevention of Clostridium difficile Infection and Associated Diarrhea: An Unsolved Problem.

Publications

Prevention of <i>Clostridium difficile</i> Infection and Associated Diarrhea: An Unsolved Problem.

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