A multi-center study of fidaxomicin use for Clostridium difficile infection

Shah et al. SpringerPlus (2016) 5:1224 DOI 10.1186/s40064-016-2825-x Open Access RESEARCH A multi‑center study of fidaxomicin use for Clostridium difficile infection Dhara N. Shah1*, Fay S. Chan1, Nandita Kachru2, Krutina P. Garcia1, Holly E. Balcer3, April P. Dyer4, John E. Emanuel5, Michelle D. Jordan6, Katherine T. Lusardi7, Geri Naymick8, Radhika S. Polisetty9, Lanny Sieman10, Ashley M. Tyler11, Michael L. Johnson2 and Kevin W. Garey1 Abstract Purpose: 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. Methods: 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). Results: 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 fidaxomicin from 11 hospitals were identified in the multicenter study. Sixty-nine patients received fidaxomicin for early (68 % with severe CDI) and 33 received for later episodes. The majority of patients received other CDI therapy including 61 patients (88 %) for early episodes and 27 (82 %) for later episodes. Concomitant non-CDI antibiotics were received by 48 patients (47 %). Rates of clinical outcomes were similar regardless of CDI episode. Conclusion: This study demonstrated a slow but steady increase in fidaxomicin utilization over time; most of which was combined with other systemic antibiotics. Antimicrobial stewardship teams should provide guidance on appropriate use of fidaxomicin to optimize therapy and assess the need to continue other antibiotics during CDI treatment. Keywords: Pharmacoepidemiology, Anaerobe infections, Real-world study, Treatment, Clinical practice Background According to the Centers for Disease Control and Prevention (CDC), the annual incidence of CDI in the United States exceeds 500,000 hospitalized cases with 29,000 deaths (Lessa et al. 2015). Treatment options for CDI are limited. Metronidazole and oral vancomycin have been utilized as the mainstay therapy for CDI (Kelly and LaMont 2008; Cohen et al. 2010). However, morbidity and mortality including the recurrence of CDI *Correspondence: 1 Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 1441 Moursund Street, Houston, TX 77030, USA Full list of author information is available at the end of the article continues to be a major concern with recurrence rate up to 25 % after discontinuation of treatment (McFarland et al. 1999). Moreover, patients with at least one recurrence have a higher probability of experiencing further recurrences (Sheitoyan-Pesant et al. 2016). CDI is also associated with increased healthcare costs due to longer hospitalizations and re-hospitalizations (Lawrence et al. 2007; Kyne et al. 2002). Fidaxomicin, a narrow spectrum macrocyclic antibiotic, displays many favorable qualities including inhibition of spore formation (Babakhani et al. 2012), preservation of intestinal microbiota (Louie et al. 2012), and reduced acquisition of VRE and candida in patients treated with fidaxomicin (Nerandzic et al. 2012). In © 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Shah et al. SpringerPlus (2016) 5:1224 two, large phase III studies, fidaxomicin was shown to decrease recurrent CDI compared to oral vancomycin in patients given the drug during their first occurrence or first recurrence of CDI disease (Louie et al. 2011; Cornely et al. 2012a, b; Crook et al. 2012). The current practice guidelines by the Society for Healthcare Epidemiology of America (SHEA) and Infectious Disease Society of America (IDSA) 2010 clinical practice guidelines (Cohen et al. 2010) was published prior to the Food and Drug Administration (FDA) approval of fidaxomicin. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines have mentioned fidaxomicin as one of the mainstay CDI therapy and is recommended as one of the options for initial, non-severe CDI, initial, severe CDI, first recurrent CDI, and in patients at a risk for recurrent CDI based on limited evidence (Debast et al. 2014). A case study published after its approval reported limited benefit of fidaxomicin when used for multiple recurrent CDI (Orenstein 2012). Two other studies have demonstrated positive benefits on the use of fidaxomicin using a pre-defined protocol (Goldenberg et al. 2016; Gallagher et al. 2015). Despite these findings, there seems to be a lack of consensus on the optimal time to utilize fidaxomicin for CDI management. Furthermore, data regarding fidaxomicin utilization in real-world clinical practice. The objective of this study was to evaluate fidaxomicin use nationwide in the real-world clinical setting. The specific aims of the study was (1) to evaluate fidaxomicin use and overall utilization rate stratified by regions, hospital location, and hospital type and CDI therapy utilization in the United States; (2) to evaluate fidaxomicin use based on CDI episode number, use of other CDI therapy and concomitant non-CDI antibiotic use. Methods The use of fidaxomicin was assessed using a nationally representative database and a multisite, chart review study of all patients receiving fidaxomicin. For specific aim 1, the Premier Perspective Database (Safavi et al. 2014) was used to identify patients with CDI. Premier Perspective Database is a largest inpatient drug utilization database, consists of data from a network of approximately 3400 United States hospitals, including >45 million inpatients and >200 million outpatients. Data from 372 hospitals contain date-stamp log of all billing files that includes drug billing data at the individual patient level. The database encompasses events during hospitalizations such as diagnoses and medication administration information directly from electronic health records. Each encounter of a patient is given a unique identifier. Data collection included information Page 2 of 8 from the third quarter of (...truncated)