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Advances in the diagnosis and treatment of Clostridium difficile infections.

ABSTRACT: Clostridium difficile is a leading cause of antibiotic-associated diarrhea worldwide. The diagnosis of C. difficile infection (CDI) requires both clinical manifestations and a positive laboratory test for C. difficile and/or its toxins. While antibiotic therapy is the treatment of choice for CDI, there are relatively few classes of effective antibiotics currently available. Therefore, the development of novel antibiotics and/or alternative treatment strategies for CDI has received a great deal of attention in recent years. A number of emerging agents such as cadazolid, surotomycin, ridinilazole, and bezlotoxumab have demonstrated activity against C. difficile; some of these have been approved for limited clinical use and some are in clinical trials. In addition, other approaches such as early and accurate diagnosis of CDI as well as disease prevention are important for clinical management. While the toxigenic culture and the cell cytotoxicity neutralization assay are still recognized as the gold standard for the diagnosis of CDI, new diagnostic approaches such as nucleic acid amplification methods have become available. In this review, we will discuss both current and emerging diagnostic and therapeutic modalities for CDI.

SUBMITTER: Peng Z

PROVIDER: S-EPMC5837143 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Advances in the diagnosis and treatment of Clostridium difficile infections.

Peng Zhong Z Ling Lifen L Stratton Charles W CW Li Chunhui C Polage Christopher R CR Wu Bin B Tang Yi-Wei YW

Emerging microbes & infections 20180207 1

Clostridium difficile is a leading cause of antibiotic-associated diarrhea worldwide. The diagnosis of C. difficile infection (CDI) requires both clinical manifestations and a positive laboratory test for C. difficile and/or its toxins. While antibiotic therapy is the treatment of choice for CDI, there are relatively few classes of effective antibiotics currently available. Therefore, the development of novel antibiotics and/or alternative treatment strategies for CDI has received a great deal o ...[more]

PMID: 29434201

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Project description:ImportanceSince 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased.ObjectiveTo review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥ 18 years).Evidence reviewOvid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process.FindingsLaboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI).Conclusions and relevanceDiagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient's risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.

Project description:BackgroundThe epidemiology of Clostridium difficile-associated infection (CDI) has changed, and it is evident that susceptibility is related not only to exposures and bacterial potency, but host factors as well. Several small studies have suggested that CDI after trauma is associated with a different patient phenotype. The purpose of this study was to examine and describe the epidemiologic factors associated with C. difficile in blunt trauma patients without traumatic brain injury using the Trauma-Related Database as a part of the "Inflammation and Host Response to Injury" (Glue Grant) and the University of Florida Integrated Data Repository.MethodsPreviously recorded baseline characteristics, clinical data, and outcomes were compared between groups (67 C. difficile and 384 uncomplicated, 813 intermediate, and 761 complicated non-C. difficile patients) as defined by the Glue Grant on admission and at days seven and 14.ResultsThe majority of CDI patients experienced complicated or intermediate clinical courses. The mean ages of all cohorts were less than 65 y and CDI patients were significantly older than uncomplicated patients without CDI. The CDI patients had increased days in the hospital and on the ventilator, as well as significantly higher new injury severity scores (NISS), and a greater percentage of patients with NISS >34 points compared with non-CDI patients. They also had greater Marshall and Denver multiple organ dysfunction scores than non-CDI uncomplicated patients, and greater creatinine, alkaline phosphatase, neutrophil count, lactic acid, and PiO2:FiO2 compared with all non-CDI cohorts on admission. In addition, the CDI patients had higher glucose concentrations and base deficit from uncomplicated patients and greater leukocytosis than complicated patients on admission. Several of these changes persisted to days seven and 14.ConclusionAnalysis of severe blunt trauma patients with C. difficile, as compared with non-CDI patients, reveals evidence of increased inflammation, immunosuppression, worse acute kidney injury, higher NISS, greater days in the hospital and on the ventilator, higher organ injury scores, and prolonged clinical courses. This supports reports of an increased prevalence of CDI in a younger population not believed previously to be at risk. This unique population may have specific genomic or inflammation-related risk factors that may play more important roles in disease susceptibility. Prospective analysis may allow early identification of at-risk patients, creation of novel therapeutics, and improved understanding of how and why C. difficile colonization transforms into infection after severe blunt trauma.

Project description:Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and contain the spread of resistance and to ensure an efficacious therapy for CDI.

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Advances in the diagnosis and treatment of Clostridium difficile infections.

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Advances in the diagnosis and treatment of Clostridium difficile infections.

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