South African Society of Clinical Microbiology Clostridioides difficile infection diagnosis, management and infection prevention and control guideline.
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ABSTRACT:
SUBMITTER: Nana T
PROVIDER: S-EPMC8378053 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Agents in development for the prevention or treatment of Clostridioides difficile infection can be split into three broad categories: antibiotics, microbiome restoration, and vaccines. Given the extensive list of agents currently in development, this narrative review will focus on agents that have progressed into late-stage clinical trials, defined as having a Phase III clinical trial registered on ClinicalTrials.gov. These agents include one antibiotic (ridinilazole), three live biotherapeutic products (LBPs) (CP101, RBX2660, and SER109), and two toxoid vaccines (PF06425090 and a second toxoid vaccine). As new prevention and treatment strategies enter the market, clinicians and administrators will need knowledge of these products to make rational decisions on how best to adopt them into clinical practice.
| S-EPMC9841950 | biostudies-literature
Project description:This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.
| S-EPMC7111242 | biostudies-literature
Project description:BackgroundClostridioides difficile (CD) is the most common healthcare-associated enteric infection. There is currently limited epidemiological evidence on CD incidence in South Africa.AimTo estimate the burden of CD infection (CDI) in the South African public sector between 1 July 2016 and 30 June 2017.MethodsA retrospective cohort study utilizing secondary data was conducted to describe the epidemiology of CD in South Africa. We assessed the patient-level association between variables of interest, CD, and CD recurrence, by undertaking both univariate and multivariable analysis. Adjusted incidence rate ratios (aIRR) were calculated utilizing multivariable Poisson regression. The incidence of CD, CD recurrence and CD testing was estimated by Poisson regression for various levels of care and provinces.ResultsA total of 14 023 samples were tested for CD during the study period. After applying exclusion criteria, we were left with a sample of 10 053 of which 1 860 (18.50%) tested CD positive. A positive and significant association between CDI and level of care is found, with patients treated in specialized tuberculosis (TB) hospitals having a five-fold increased adjusted incidence risk ratio (aIRR) for CDI (aIRR 4.96 CI95% 4.08-6.04,) compared to those managed in primary care. Patients receiving care at a secondary, tertiary, or central hospital had 35%, 66% and 41% increased adjusted incidence of CDI compared to those managed in primary care, respectively. National incidence of CDI is estimated at 53.89 cases per 100 000 hospitalizations (CI95% 51.58-56.29), the incidence of recurrence at 21.39 (CI95% 15.06-29.48) cases per 1 000 cases and a recurrence rate of 2.14% (CI95% 1.51-2.94).ConclusionCompared to European countries, we found a comparable incidence of CD. However, our estimates are lower than those for the United States. Compared to high-income countries, this study found a comparatively lower CD recurrence.
| S-EPMC8610264 | biostudies-literature
Project description:Clostridioides (Clostridium) difficile is the major cause of healthcare antibiotic-associated diarrhoea. However, extra-intestinal manifestations of Clostridioides (Clostridium) difficile infection (CDI) (including bacteremia and tissue infection) are extremely rare. We report a case of extraintestinal CDI after surgery. The isolate of C. difficile was not the PCR ribotype 027. However, this isolate produced toxins A and B. The patient underwent a follow-up examination 30 days after discharge, which showed complete recovery. This case report adds to existing knowledge of CDI.
| S-EPMC7475194 | biostudies-literature
Project description:BackgroundClostridioides difficile infection (CDI) is an infectious nosocomial disease caused by Clostridioides difficile, an opportunistic pathogen that occurs in the intestine after extensive antibiotic regimens.ResultsNine C. difficile strains (CBA7201-CBA7209) were isolated from nine patients diagnosed with CDI at the national university hospital in Korea, and the whole genomes of these strains were sequenced to identify their genomic characteristics. Comparative genomic analysis was performed using 51 reference strains and the nine isolated herein. Phylogenetic analysis based on 16S rRNA gene sequences confirmed that all 60 C. difficile strains belong to the genus Clostridioides, while core-genome tree indicated that they were divided into five groups, which was consistent with the results of MLST clade analysis. All strains were confirmed to have a clindamycin antibiotic resistance gene, but the other antibiotic resistance genes differ depending on the MLST clade. Interestingly, the six strains belonging to the sequence type 17 among the nine C. difficile strains isolated here exhibited unique genomic characteristics for PaLoc and CdtLoc, the two toxin gene loci identified in this study, and harbored similar antibiotic resistance genes.ConclusionIn this study, we identified the specific genomic characteristics of Korean C. difficile strains, which could serve as basic information for CDI prevention and treatment in Korea.
| S-EPMC8447795 | biostudies-literature
Project description:Background:Bezlotoxumab is approved for prevention of recurrence of Clostridioides difficile infection (CDI) in adults receiving standard of care (SoC) therapy based on findings from MODIFY clinical trials. However, utilization practices and validation of trial results in the real world are limited. Methods:Records of patients receiving bezlotoxumab between April 2017 and December 2018 across 34 infusion centers in the United States were retrospectively reviewed. Recurrent CDI (rCDI), defined as diarrhea lasting??2 days resulting in treatment, was assessed 90 days postbezlotoxumab. Results:The study cohort included 200 patients (median age, 70 years; 66% female; median Charlson comorbidity index, 5), of whom 86% (n?=?173) had prior CDI episodes and 79% (n?=?158) had??2 risk factors for rCDI. SoC antibiotics included vancomycin (n?=?137, 68%), fidaxomicin (n?=?60, 30%), and metronidazole (n?=?3, 2%). Median time from C. difficile stool test to bezlotoxumab and initiation of SoC to bezlotoxumab were 15 days and 11 days, respectively. Within 90 days, 31 of 195 patients (15.9%) experienced rCDI, which corresponds to a success rate of 84.1%. Patients with??2 CDI recurrences prebezlotoxumab had a higher risk of subsequent rCDI compared with those with 1 recurrence or primary CDI (hazard ratio, 2.77; 95% confidence interval, 1.14-6.76; P?=?.025). Conclusions:This real-world multicenter study demonstrated successful prevention of rCDI with bezlotoxumab comparable to clinical trial results regardless of type of SoC and timing of infusion. Multiple prior CDI recurrences were associated with a higher risk of subsequent rCDI, supporting the use of bezlotoxumab earlier in the disease course.
| S-EPMC7186524 | biostudies-literature
Project description:ImportanceThe effect of rationally defined nonpathogenic, nontoxigenic, commensal strains of Clostridia on prevention of Clostridioides difficile infection (CDI) is unknown.ObjectiveTo determine the efficacy of VE303, a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence. The primary objective was to determine the recommended VE303 dosing for a phase 3 trial.Design, setting, and participantsPhase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from February 2019 to September 2021 at 27 sites in the US and Canada. The study included 79 participants aged 18 years or older who were diagnosed with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence (defined as aged ≥75 years or ≥65 years with ≥1 risk factors: creatinine clearance <60 mL/min/1.73 m2, proton pump inhibitor use, remote [>6 months earlier] CDI history).InterventionsParticipants were randomly assigned to high-dose VE303 (8.0 × 109 colony-forming units [CFUs]) (n = 30), low-dose VE303 (1.6 × 109 CFUs) (n = 27), or placebo capsules (n = 22) orally once daily for 14 days.Main outcomes and measuresThe primary efficacy end point was the proportion of participants with CDI recurrence at 8 weeks using a combined clinical and laboratory definition. The primary efficacy end point was analyzed in 3 prespecified analyses, using successively broader definitions for an on-study CDI recurrence: (1) diarrhea consistent with CDI plus a toxin-positive stool sample; (2) diarrhea consistent with CDI plus a toxin-positive, polymerase chain reaction-positive, or toxigenic culture-positive stool sample; and (3) diarrhea consistent with CDI plus laboratory confirmation or (in the absence of a stool sample) treatment with a CDI-targeted antibiotic.ResultsBaseline characteristics were similar across the high-dose VE303 (n = 29; 1 additional participant excluded from efficacy analysis), low-dose VE303 (n = 27), and placebo (n = 22) groups. The participants' median age was 63.5 years (range, 24-96); 70.5% were female; and 1.3% were Asian, 1.3% Black, 2.6% Hispanic, and 96.2% White. CDI recurrence rates through week 8 (using the efficacy analysis 3 definition) were 13.8% (4/29) for high-dose VE303, 37.0% (10/27) for low-dose VE303, and 45.5% (10/22) for placebo (P = .006, high-dose VE303 vs placebo).Conclusions and relevanceAmong adults with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence, high-dose VE303 prevented recurrent CDI compared with placebo. A larger, phase 3 study is needed to confirm these findings.Trial registrationClinicalTrials.gov Identifier: NCT03788434.
| S-EPMC10105904 | biostudies-literature
Project description:Pneumonia remains a major cause of morbidity and mortality amongst South African children. More comprehensive immunisation regimens, strengthening of HIV programmes, improvement in socioeconomic conditions and new preventive strategies have impacted on the epidemiology of pneumonia. Furthermore, sensitive diagnostic tests and better sampling methods in young children improve aetiological diagnosis. To produce revised guidelines for pneumonia in South African children under 5 years of age. The Paediatric Assembly of the South African Thoracic Society and the National Institute for Communicable Diseases established seven expert subgroups to revise existing South African guidelines focusing on: (i) epidemiology; (ii) aetiology; (iii) diagnosis; (iv) antibiotic management and supportive therapy; (v) management in intensive care; (vi) prevention; and (vii) considerations in HIV-infected or HIVexposed, uninfected (HEU) children. Each subgroup reviewed the published evidence in their area; in the absence of evidence, expert opinion was accepted. Evidence was graded using the British Thoracic Society (BTS) grading system. Sections were synthesized into an overall guideline which underwent peer review and revision. Recommendations include a diagnostic approach, investigations, management and preventive strategies. Specific recommendations for HIV infected and HEU children are provided. The guideline is based on available published evidence supplemented by the consensus opinion of SA paediatric experts. Recommendations are consistent with those in published international guidelines.
| S-EPMC7433705 | biostudies-literature
Project description:Effect on gene transcript levels upon up- or down-regulation of two component system WalRK (Wal-ON and Wal-OFF)
2022-04-09 | GSE200346 | GEO
Project description:Clostridioides difficile (CD) is responsible for nosocomial diarrhea syndrome with possible severe progression. Recurrence of the disease induces higher health system costs, as well as exposes patients to additional health risks. Patients with recurrence of this disease are difficult to identify, so the purpose of this study is to quantify various demographic, clinical, and treatment factors that could prevent further progression to recurrence of the disease. In the period 2018-2019, about 195 patients were diagnosed with more than one episode of CDI in the three months following the first episode. The recurrence rate for CDI was 53.84% (60.95% for one episode and 39.05% for multiple episodes). Most commonly afflicted were 60-69-year-old patients, or those with higher Charlson Comorbidity Index (CCI). Multiple analyses associated cardiovascular (odds ratios (OR) = 3.02, 95% confidence intervals (CI) = 1.23-7.39, p = 0.015), digestive (OR = 3.58, 95% CI = 1.01-12.63, p = 0.047), dementia (OR = 3.26, 95% CI = 1.26-8.41, p = 0.014), immunosuppressive (OR = 3.88, 95% CI = 1.34-11.21, p = 0.012) comorbidities with recurrences. Risk factor identification in the first episode of CDI could lead to the implementation of treatment strategies to improve the patients' quality of life affected by this disease.
| S-EPMC7551610 | biostudies-literature