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 http://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.

Background Directed antibiotic locks have the potential to treat orthopedic infections due to the ability to bypass specific systemic absorption allowing for higher antimicrobial concentrations. With limiting antimicrobial options to treat biofilm commonly associated with bone and joint infections, our aim is to understand and further test the relevance of utilizing standard systemic MIC values to direct therapy. Methods Using our previously described biofilm assay with six unique spa-type (t004, t018, t062, t064, t1340, t008) MRSA isolates, biofilm was grown for 4, 6, and 24hrs at 6 log10 CFU/mL in TSB per CLSI guidance adding dextrose 1.25% for biofilm promotion. MIC were run using CLSI guidance. Planktonic cells were removed by irrigation, simulating debridement. 24hr treatment assays, simulating antibiotic locks included levofloxacin (5 mg/mL) in d5W solution and vancomycin (5 mg/mL) in NS. Results Levofloxacin by definition of standard MIC values was found to be resistant in five out of the six MRSA isolates (MIC ranging from 1 – 312mcg.mL). However, at 16-25,000 times the MIC, levofloxacin demonstrated a decrease in biofilm growth on mature 24-hr established biofilm by 9-130%. Similarly, vancomycin heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA), at 3000-6000 the MIC demonstrated a decrease of 53-190% mature biofilm growth. Conclusion All isolates produced consistent biofilm as previously tested as a low or high biofilm-producer when there was no antibiotic present. Levofloxacin and vancomycin at least 1000X the MIC nearly eradicated all established MRSA biofilm. Our next steps will be to evaluate if the MIC values have any effect on additional antibiotics in a lock solution. Disclosures Kerry L. LaPlante, Pharm.D., FCCP, FIDSA, FIDP, AbbVie Inc.: Grant/Research Support|Gilead Sciences, Inc.: Grant/Research Support|Melinta Therapeutics, Inc.,: Grant/Research Support|Merck & Co., Inc.: Advisor/Consultant|Merck & Co., Inc.: Grant/Research Support|Nabriva Therapeutics US, Inc.,: Grant/Research Support|Ocean Spray Cranberries, Inc.: Grant/Research Support|Pfizer Pharmaceuticals: Grant/Research Support|Shionogi, Inc.: Grant/Research Support|Tetraphase Pharmaceuticals.: Grant/Research Support.