Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults.
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SUBMITTER: Nelson RL
PROVIDER: S-EPMC6464548 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC6561347 | biostudies-literature
Project description:Diarrhoea is common in Intensive Care Unit (ICU) patients, with a reported prevalence of 15-38%. Many factors may cause diarrhoea, including Clostridium difficile, drugs (e.g. laxatives, antibiotics) and enteral feeds. Diarrhoea impacts on patient dignity, increases nursing workload and healthcare costs, and exacerbates morbidity through dermal injury, impaired enteral uptake and subsequent fluid imbalance. We analysed a cohort of 9331 consecutive patients admitted to a mixed general intensive care unit to establish the prevalence of diarrhoea in intensive care unit patients, and its relationship with infective aetiology and clinical outcomes. We provide evidence that diarrhoea is common (12.9% (1207/9331) prevalence) in critically ill patients, independently associated with increased intensive care unit length of stay (mean (standard error) 14.8 (0.26) vs 3.2 (0.09) days, p < 0.001) and mortality (22.0% (265/1207) vs 8.7% (705/8124), p < 0.001; adjusted hazard ratio 1.99 (95% CI 1.70-2.32), p < 0.001) compared to patients without diarrhoea even after adjusting for potential confounding factors, and infrequently caused by infective aetiology (112/1207 (9.2%)) such as Clostridium difficile (97/1048 (9.3%) tested) or virological causes (9/172 (5.7%) tested). Our findings suggest non-infective causes of diarrhoea in ICU predominate and pathophysiology of diarrhoea in critically ill patients warrants further investigation.
| S-EPMC4837391 | biostudies-literature
Project description:BackgroundColonization by the pathogen Clostridium difficile often occurs in the background of a disrupted microbial community. Identifying specific organisms conferring resistance to invasion by C. difficile is desirable because diagnostic and therapeutic strategies based on the human microbiota have the potential to provide more precision to the management and treatment of Clostridium difficile infection (CDI) and its recurrence.MethodsWe conducted a longitudinal study of adult patients diagnosed with their first CDI. We investigated the dynamics of the gut microbiota during antibiotic treatment, and we used microbial or demographic features at the time of diagnosis, or after treatment, to predict CDI recurrence. To check the validity of the predictions, a meta-analysis using a previously published dataset was performed.ResultsWe observed that patients' microbiota "before" antibiotic treatment was predictive of disease relapse, but surprisingly, post-antibiotic microbial community is indistinguishable between patients that recur or not. At the individual OTU level, we identified Veillonella dispar as a candidate organism for preventing CDI recurrence; however, we did not detect a corresponding signal in the conducted meta-analysis.ConclusionAlthough in our patient population, a candidate organism was identified for negatively predicting CDI recurrence, results suggest the need for larger cohort studies that include patients with diverse demographic characteristics to generalize species that robustly confer colonization resistance against C. difficile and accurately predict disease relapse.
| S-EPMC5684761 | biostudies-literature
Project description:Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by C. difficile-directed antibiotics is virtually uninvestigated. In this study, diarrheal stool samples were collected from 20 hospitalized patients, half of whom were confirmed to have CDI. Analyzing tissue ex vivo and in duplicate, CDI and non-CDI fecal samples (n = 176) were either not antibiotic treated or treated with metronidazole, vancomycin, or fidaxomicin, the three most common CDI therapies. The microbial community composition, interactions, and predicted metabolic functions were assessed by 16S rRNA gene and internal transcribed spacer sequencing, bipartite network analysis, and phylogenetic investigation of communities by reconstruction of unobserved states. Our results demonstrate that while all C. difficile-directed antibiotics were associated with similar reductions in alpha diversity, beta diversity significantly differed on the basis of the particular antibiotic, with differentiating relative abundances of bacterial and fungal assemblages. With the exception of fidaxomicin, each antibiotic was associated with the emergence of potentially pathogenic fungal operational taxonomic units, with predicted bacterial functions enriched for xenobiotic metabolism that could perpetuate the dysbiosis driving CDI. Toxin-independent mechanisms of colitis related to the relative abundance of pathogenic bacteria and fungi were also noted. This study suggests that a transkingdom interaction between fungi and bacteria may be important in CDI pathophysiology, including being a factor in the historically high persistence and recurrence rates associated with this disease. IMPORTANCE Using human fecal samples and including sequencing for both bacterial and fungal taxa, this study compared the conventional antibiotics used to treat C. difficile infection (CDI) from the perspective of the microbiome, which is particularly relevant, given the relationship between dysbiotic states and the development of CDI. Sequencing and imputed functional analyses suggest that C. difficile-directed antibiotics are associated with distinct forms of dysbiosis that may be influential in the course of CDI. Further, a role for fungal organisms in the perpetuation of the causal dysbiosis of CDI is discussed, suggesting a previously unappreciated, clinically relevant transkingdom interaction that warrants further study.
| S-EPMC5760750 | biostudies-literature
Project description:IntroductionHelicobacter pylori (HP) infection is associated with many gastrointestinal disorders, including gastric cancer, and consensus guidelines recommend eradication after detection. There is a theoretical, yet uninvestigated, concern that HP treatment could increase the risk of Clostridium difficile infection (CDI). Using the data from a large cohort of patients with HP, we investigated whether HP eradication is associated with CDI.MethodsA retrospective cohort study within the Veterans Health Administration on 38,535 patients (median age 61.8 years; 91.8% men) with detected HP between January 1, 1994, and December 31, 2018 was conducted. Primary outcome was a positive laboratory test for CDI within 3 months of HP detection. Multivariable logistic regression evaluated the following: patient demographics, previous CDI, recent hospitalization, and whether the patient received HP eradication therapy (by antibiotic and regimen, and including proton pump therapy). Secondary analysis of those treated evaluated whether eradication of HP was associated with CDI.ResultsAmong 38,535 patients, 28,818 (74.8%) were treated for HP and 284 (0.74%) developed CDI. In multivariable analysis, prominent factors included hospital discharge within 12 weeks (odds ratio [OR] 2.15; 95% confidence interval [CI]: 1.22-3.77) and 4 weeks (OR 3.46; 95% CI: 2.18-5.48), P < 0.001, and previous CDI (OR 12.5; 95% CI: 9.21-17.0, P < 0.001). Treatment of HP was not associated with future CDI. In secondary analysis of those treated, confirmation of eradication was not associated with future CDI (OR 1.49; 95% CI: 0.67-3.29).DiscussionIn a large study of US patients with HP, we demonstrate that neither treatment nor eradication of HP is associated with CDI. Previous C. difficile infection and recent hospital discharge, established risk factors for CDI, are strongly associated. These findings suggest that treatment should be continued to be prescribed when HP is detected (http://links.lww.com/AJG/B507).
| S-EPMC7202442 | biostudies-literature
Project description:Antibodies for the treatment of Clostridium difficile infection (CDI) have been demonstrated to be effective in the research and clinical environments. Early uncertainties about molecular and treatment modalities now appear to have converged upon the systemic dosing of mixtures of human IgG1. Although multiple examples of high-potency monoclonal antibodies (MAbs) exist, significant difficulties were initially encountered in their discovery. This minireview describes historical and contemporary MAbs and highlights differences between the most potent MAbs, which may offer insight into the pathogenesis and treatment of CDI.
| S-EPMC4097441 | biostudies-literature
Project description:BackgroundAntibiotics are commonly given for the treatment of childhood diarrhoea, but are not indicated in most cases. Antibiotics modify the gastrointestinal microbiota, which may have unanticipated effects on the risk of subsequent diarrhoea.MethodsIn a prospective observational cohort study, we assessed the effect of caregiver-reported antibiotic treatment for diarrhoea on the timing of a child's next episode among 434 children followed from birth to 3 years of age in Vellore, India. We estimated median time differences and time ratios from inverse probability of exposure-weighted Kaplan-Meier curves for the time to next diarrhoea episode, comparing children who did and did not receive antibiotics for the previous episode.ResultsStudy children had more than five diarrhoea episodes on average in the first 3 years of life, and more than a quarter of all episodes were treated with antibiotics. Children who received antibiotics for their first diarrhoea episode had their second episode on average 8 weeks earlier (median time difference: -8, 95% confidence interval: -10, -3) than children who did not receive antibiotics. The effects of antibiotics on subsequent diarrhoea were greatest at earlier episodes and younger ages, and cefixime had a slightly larger effect compared with cotrimoxazole.ConclusionsAntibiotic treatment of diarrhoea was associated with reduced time to a subsequent diarrhoea episode, especially among younger infants. Whereas rational use of antibiotics has been advocated to reduce antimicrobial resistance in populations, we show that overuse of antibiotics may also have a direct adverse effect on individual patients.
| S-EPMC4607743 | biostudies-literature
Project description:OBJECTIVES:The incidence and severity of Clostridium difficile infection (CDI) have increased rapidly over the past 2 decades, particularly in elderly patients with multiple comorbidities. This study sought to characterize the incidence and risks of these infections in cardiac surgery patients. METHODS:A total of 5158 patients at 10 Cardiothoracic Surgical Trials Network sites in the US and Canada participated in a prospective study of major infections after cardiac surgery. Patients were followed for infection, readmission, reoperation, or death up to 65 days after surgery. We compared clinical and demographic characteristics, surgical data, management practices, and outcomes for patients with CDI and without CDI. RESULTS:C difficile was the third most common infection observed (0.97%) and was more common in patients with preoperative comorbidities and complex operations. Antibiotic prophylaxis for >2 days, intensive care unit stay >2 days, and postoperative hyperglycemia were associated with increased risk of CDI. The median time to onset was 17 days; 48% of infections occurred after discharge. The additional length of stay due to infection was 12 days. The readmission and mortality rates were 3-fold and 5-fold higher, respectively, in patients with CDI compared with uninfected patients. CONCLUSIONS:In this large multicenter prospective study of major infections following cardiac surgery, CDI was encountered in nearly 1% of patients, was frequently diagnosed postdischarge, and was associated with extended length of stay and substantially increased mortality. Patients with comorbidities, longer surgery time, extended antibiotic exposure, and/or hyperglycemic episodes were at increased risk for CDI.
| S-EPMC5808431 | biostudies-literature
Project description:Antibiotic therapy is the principal risk factor for Clostridium difficile infection (CDI), but little is known about how risks cumulate over the course of therapy and abate after cessation. We prospectively identified CDI cases among adults hospitalized at a tertiary hospital between June 2010 and May 2012. Poisson regression models included covariates for time since admission, age, hospitalization history, disease pressure, and intensive care unit stay. Impacts of antibiotic use through time were modeled using 4 measures: current antibiotic receipt, time since most recent receipt, time since first receipt during a hospitalization, and duration of receipt. Over the 24-month study period, we identified 127 patients with new onset nosocomial CDI (incidence rate per 10,000 patient days [IR] = 5.86). Of the 4 measures, time since most recent receipt was the strongest independent predictor of CDI incidence. Relative to patients with no prior receipt of antibiotics in the last 30 days (IR = 2.95), the incidence rate of CDI was 2.41 times higher (95% confidence interval [CI] 1.41, 4.13) during antibiotic receipt and 2.16 times higher when patients had receipt in the prior 1-5 days (CI 1.17, 4.00). The incidence rates of CDI following 1-3, 4-6 and 7-11 days of antibiotic exposure were 1.60 (CI 0.85, 3.03), 2.27 (CI 1.24, 4.16) and 2.10 (CI 1.12, 3.94) times higher compared to no prior receipt. These findings are consistent with studies showing higher risk associated with longer antibiotic use in hospitalized patients, but suggest that the duration of increased risk is shorter than previously thought.
| S-EPMC4144891 | biostudies-literature
Project description:Perturbations in the gastrointestinal microbiome caused by antibiotics are a major risk factor for Clostridium difficile infection (CDI). Probiotics are often recommended to mitigate CDI symptoms; however, there exists only limited evidence showing probiotic efficacy for CDI. Here, we examined changes to the GI microbiota in a study population where probiotic treatment was associated with significantly reduced duration of CDI diarrhea. Subjects being treated with standard of care antibiotics for a primary episode of CDI were randomized to probiotic treatment or placebo for 4 weeks. Probiotic treatment consisted of a daily multi-strain capsule (Lactobacillus acidophilus NCFM, ATCC 700396; Lactobacillus paracasei Lpc-37, ATCC SD5275; Bifidobacterium lactis Bi-07, ATCC SC5220; Bifidobacterium lactis B1-04, ATCC SD5219) containing 1.7 x 1010 CFUs. Stool was collected and analyzed using 16S rRNA sequencing. Microbiome analysis revealed apparent taxonomic differences between treatments and timepoints. Subjects administered probiotics had reduced Verrucomicrobiaceae at week 8 compared to controls. Bacteroides were significantly reduced between weeks 0 to 4 in probiotic treated subjects. Ruminococcus (family Lachnospiraceae), tended to be more abundant at week 8 than week 4 within the placebo group and at week 8 than week 0 within the probiotic group. Similar to these results, previous studies have associated these taxa with probiotic use and with mitigation of CDI symptoms. Compositional prediction of microbial community function revealed that subjects in the placebo group had microbiomes enriched with the iron complex transport system, while probiotic treated subjects had microbiomes enriched with the antibiotic transport system. Results indicate that probiotic use may impact the microbiome function in the face of a CDI; yet, more sensitive methods with higher resolution are warranted to better elucidate the roles associated with these changes. Continuing studies are needed to better understand probiotic effects on microbiome structure and function and the resulting impacts on CDI.
| S-EPMC6161886 | biostudies-literature