Novel Fidaxomicin Treatment Regimens for Patients With Multiple Clostridium difficile Infection Recurrences That Are Refractory to Standard Therapies (original) (raw)
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Clinical outcomes of fidaxomicin vs oral vancomycin in recurrent Clostridium difficile infection
Journal of Clinical Pharmacy and Therapeutics, 2018
Clostridium difficile infection (CDI) is the most common cause of health care-associated infection in the United States and has witnessed an epidemic shift in the early 2000s. 1 Coinciding with this shift is the emergence of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain. 1,2 The NAP1 strain is highly virulent and causes higher morbidity, recurrence rates, and mortality. 3-5 Oral vancomycin and metronidazole have been the mainstays of therapy for CDI for over 25 years. 3 Most patients with an initial episode of CDI respond to either treatment choice; however, overall recurrence in infection occurs in 20%-30% of patients. 6,7 Clostridium difficile treatment guidelines from the Infectious Diseases Society of America (IDSA) published in 2010 recommend treating first
Safety and Efficacy of Fidaxomicin in Patients With Clostridium Difficile Infection
Clinical Medicine Insights: Therapeutics, 2013
Fidaxomicin is a bactericidal macrolide that is indicated for the treatment of Clostridium difficile infection (CDI) in adults. Fidaxomicin is not effective for the treatment of systemic infections due to minimal systemic absorption. Until recently, oral vancomycin was the only medication with United States Food and Drug Administration (FDA) approval for the treatment of CDI. In clinical studies, fidaxomicin demonstrated noninferiority to vancomycin for the treatment of CDI. Lower recurrence rates of CDI with fidaxomicin than with oral vancomycin were observed. The lower recurrence rates were not observed with highly virulent strains of C. difficile. Lower recurrence rates of CDI with fidaxomicin are believed to be associated with its narrow spectrum of activity. Fidaxomicin was approved for use after publication of the most recent guideline from the Society for Healthcare Epidemiology of America (SHEA) and Infectious Diseases Society of America (IDSA). However, its current place in...
Clinical Infectious Diseases, 2012
Our study sought to compare the strain types of Clostridium difficile causing initial and recurrent episodes of C. difficile infection (CDI) in adult patients with a first episode of CDI or 1 prior episode of CDI within the previous 90 days. Strains originated from patients who had been entered into two phase 3 randomized clinical trials of fidaxomicin versus vancomycin. Isolates of C. difficile from the initial and recurrent episodes within 28 (±2) days of cure of CDI were compared using restriction endonuclease analysis (REA) typing. Paired isolates were available from 90 of 194 (46%) patients with recurrent CDI. Patients with isolates available were significantly younger (P = .008) and more likely to be from Canadian sites (P = .0001), compared with patients without isolates. In 75 of 90 subjects (83.3%), the identical REA type strain was identified at recurrence and the initial episode (putative relapse). Early recurrences (0-14 days after treatment completion) were relapses in 86.7% and a new strain (reinfection) in 13.3%. Later recurrences (15-31 days after treatment) were relapses in 76.7% and reinfections in 23.3%. Mean time (± standard deviation) to recurrence was 12.2 (±6.4) days for relapses and 14.7 (±6.8) days for reinfections (P = .177). The most common BI/NAP1/027 group and the previous US epidemic REA group J/NAP2/001 had a significantly higher combined rate of recurrence with the same strain (relapse), compared with the other REA groups (39 of 42 [93%] vs 36 of 48 [75%], respectively; P = .023). We found a higher than historic rate of recurrent CDI caused by the same isolate as the original episode, a finding that may be related to the relatively short observation period in this study and the high frequency of isolation of epidemic strains, such as groups BI and J, for which relapse rates may be higher than for other REA groups. Caution in generalizing these observations is required, because the patients studied were younger and more likely to be from Canadian sites than were patients with recurrence who did not provide isolates.
Clinical Microbiology and Infection, 2018
Objectives: This study was conducted to compare clinical outcomes of fidaxomicin versus oral vancomycin in the management of severe Clostridium difficile infection (CDI). Methods: The investigation was a retrospective, multicentre, propensity score-matched analysis using a national clinical administrative database. Veterans treated for severe CDI from any Veterans Affairs Medical Center between 1 June 2011 and 30 June 2017 were included if they received fidaxomicin or an oral vancomycin regimen for treatment. The two groups were matched by the nearest-neighbour method from a propensity score derived from independent variables associated with the selection of a fidaxomicin course. Results: Propensity score matching resulted in two well-matched cohorts consisting of 213 fidaxomicin and 639 oral vancomycin courses. No statistically-significant difference was found for the primary outcome of combined clinical failure or recurrence (68/213 (31.9%) versus 163/639 (25.5%), respectively, p 0.071). Additionally, no statistically significant differences were found for the secondary outcomes of 30day (23/213 (10.8%) versus 75/639 (11.7%), respectively, p 0.71), 90-day (48/213 (22.5%) versus 140/639 (21.9%), respectively, p 0.85), and 180-day mortality (62/213 (29.1%) versus 186/639 (29.1%), respectively, p 1.0) between the two treatment groups. Conclusions: Courses of fidaxomicin or oral vancomycin for severe CDI resulted in similar treatment outcomes. Study findings are consistent with current treatment guideline recommendations for the use of either agent in the management of severe CDI. C.A. Gentry, Clin Microbiol Infect 2019;▪:1 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.
Central European Journal of Public Health, 2018
Objective: Clostridium difficile infection (CDI) has become one of the most common causes of hospital-acquired infections. Fidaxomicin is one of the latest antibiotics used in the treatment of CDI, however, treatment cost affects recommendations for its use in several countries. We have analysed the treatment of our patients with CDI, treated by fidaxomicin since it was introduced to the market in 2018 and became available in the second biggest Slovak hospital, University Hospital of L. Pasteur. Our aim was to determine efficacy and safety of fidaxomicin in the treatment of CDI in Slovak patients. Methods: We reviewed all courses of fidaxomicin use in our hospital (n = 60). Fidaxomicin was used for first recurrence (12 times), second recurrence (4 times), third recurrence (2 times), and fifth recurrence (1 patient). 41 patients received fidaxomicin first-line. Results: Success of fidaxomicin treatment was recorded at 86.7% within the whole cohort. In the recurrent Clostridium difficile infection (rCDI) subgroup, fidaxomicin was 63% effective with three patients dying (15.7%) and two patients developing subsequent rCDI. During the duration of the study, 6 patients in total died. Only one of three patients, with three or more recurrences of CDI, had no further presentations after eight weeks of completion of treatment. Conclusions: The biggest benefit from fidaxomicin treatment was shown in a cohort of patients with primary CDI infection demonstrating a low recurrence rate and significant reduction of fidaxomicin effectiveness in preventing a recurrence when treating patients with multiple rCDI.
Infection, 2017
recurrence (32 vs. 7%; p < 0.01). Fidaxomicin was used as a first line for 83% of the patients with recurrence and for only 52% of first episodes even though 86% had recurrence's risk factors. Conclusion Compared with RCTs, fidaxomicin in real world is used for patients with more severe and recurrent CDI, but clinical cure and recurrence rates were similar. Comparative studies are needed in these specific subgroups. Our data also illustrate clinicians' difficulty to define a "patient at risk for recurrence" among the first episodes. Finally, we showed that binary toxin could be important in the screening for severity and recurrence risks.
Fidaxomicin in Clostridium difficile infection: latest evidence and clinical guidance
Therapeutic Advances in Chronic Disease, 2013
The incidence of Clostridium difficile infection (CDI) has risen 400% in the last decade. It currently ranks as the third most common nosocomial infection. CDI has now crossed over as a community-acquired infection. The major failing of current therapeutic options for the management of CDI is recurrence of disease after the completion of treatment. Fidaxomicin has been proven to be superior to vancomycin in successful sustained clinical response to therapy. Improved outcomes may be due to reduced collateral damage to the gut microflora by fidaxomicin, bactericidal activity, inhibition of Clostridial toxin formation and inhibition of new sporulation. This superiority is maintained in groups previously reported as being at high risk for CDI recurrence including those: with relapsed infection after a single treatment course; on concomitant antibiotic therapy; aged >65 years; with cancer; and with chronic renal insufficiency. Because the acquisition cost of fidaxomicin far exceeds th...
Antimicrobial agents and chemotherapy, 2015
We studied the clinical and economic impact of a protocol encouraging fidaxomicin first-line for Clostridium difficile infection (CDI) in patients hospitalized during a two-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for fidaxomicin via a protocol that encouraged its use for select patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (p=0.027). In a multivariate analysis that included severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (aOR 0.33, 95% CI 0.12-0.9...
A multi-center study of fidaxomicin use for Clostridium difficile infection
SpringerPlus, 2016
Fidaxomicin use in real-world clinical practice, especially for severe Clostridium difficile infection (CDI), is mainly based on single-center observational studies. The purpose of this pharmacoepidemiology study was to assess outcomes of patients given fidaxomicin based on episode number and use of concomitant antibiotics. Fidaxomicin use over time across included hospitals in the United States was assessed using a large inpatient drug utilization database. A multicenter retrospective chart review was also conducted of hospitalized patients with CDI that received fidaxomicin between 2011 and 2013. Fidaxomicin utilization and clinical outcomes were stratified by use of fidaxomicin for first or second episode (early episodes) versus greater than or equal to episodes (later episodes). The overall fidaxomicin use rate was 2.16 % which increased from 0.22 % in the last two quarters of 2011 to 3.16 % in the first two quarters of 2013. A total of 102 hospitalized patients that received fi...