Path of least recurrence: A systematic review and meta-analysis of fidaxomicin versus vancomycin for Clostridioides difficile infection.

STUDY OBJECTIVE: Current Clostridioides difficile infection (CDI) treatment guidelines recommend either fidaxomicin or vancomycin as first-line therapy for initial and recurrent CDI. The objective of this study was to compare recurrence rates of fidaxomicin and vancomycin for the treatment of CDI in clinically relevant and real-world subgroups via systematic review and meta-analysis. DESIGN & DATA SOURCES: A systematic literature review was performed by searching PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to September 1, 2021, for randomized and observational studies comparing vancomycin and fidaxomicin for CDI treatment in adults. The meta-analysis was performed with Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) using a random-effects model. The primary end point was CDI recurrence after treatment with fidaxomicin or vancomycin. Subgroup analyses were conducted. PATIENTS, INTERVENTION, MEASUREMENTS & MAIN RESULTS: The literature search identified six randomized controlled trials and eight observational trials, with a total of 3944 patients (fidaxomicin 32%; vancomycin 68%) included in the meta-analysis. The mean age of study patients ranged from 46 to 75 years. The CDI recurrence rate was 22.4% (fidaxomicin 16.1%, vancomycin 25.4%). Compared to vancomycin, treatment with fidaxomicin was associated with a 31% reduction in the risk of recurrence (risk ratio 0.69; 95% confidence interval: 0.52-0.91, I2  = 62%). This reduction in recurrence risk was also seen in subgroup analyses for patients with initial CDI, first recurrent CDI, non-severe and severe CDI, and in both inpatient and outpatient settings. CONCLUSION: Our systematic review and meta-analysis found fidaxomicin was consistently associated with a lower risk of CDI recurrence than vancomycin. These results confirm CDI guideline recommendations and indicate that fidaxomicin may be preferred over vancomycin to minimize CDI recurrence across multiple clinical scenarios, although further studies are warranted.

Treatment of Severe Hypertriglyceridemia With Insulin Infusions in Severe COVID-19: A Case Series.

PURPOSE: Rapid onset of severe hypertriglyceridemia was quickly recognized in critical COVID-19 patients. Associated causes have been due to secondary hemophagocytic lymphohystiocytosis (HLH) syndrome, medication-induced, or acute liver failure. Statins, omega-3 polyunsaturated acids, niacin, and fibrates are common oral lipid lowering therapy options in patients at risk for hypertriglyceridemia. The severity of hypertriglyceridemia in COVID-19 patients with triglyceride values reaching greater than 1,000 mg/dL put them at a heightened risk of pancreatitis and therefore an essential need to acutely lower their levels. We present a case series of 5 patients who achieved rapid triglyceride lowering through continuous insulin infusion therapy. METHODS: A retrospective chart review of 48 critical COVID-19 patients who were admitted from March 22 to April 15, 2020 was conducted. Inclusion criteria consisted of mechanical ventilation and continuous insulin infusion to treat severe hypertriglyceridemia resulting with 5 eligible patients in this case report. RESULTS AND CONCLUSION: In addition to standard oral lipid lowering therapies, continuous insulin infusion successfully treated severe hypertriglyceridemia in critically ill COVID-19 patients. None of the patients experienced pancreatitis or hypoglycemia necessitating cessation of insulin. Further studies are needed to show the optimum dose and duration of insulin infusion as monotherapy and in combination with oral therapies.