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

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.

Echinocandins: the newest class of antifungals.

OBJECTIVE: To review the mechanism of action, antifungal spectrum of activity, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety of the echinocandins. DATA SOURCES: A MEDLINE search (1982-May 2009) was conducted for articles published in the English language using the key words caspofungin, micafungin, anidulafungin, and echinocandins. STUDY SELECTION AND DATA EXTRACTION: Medicinal chemistry, in vitro, and animal studies, as well as human trials were reviewed for information on the pharmacodynamics, pharmacokinetics, efficacy, and safety of each echinocandin. Clinical trials were reviewed and included to compare and contrast the available echinocandins. DATA SYNTHESIS: Three echinocandin antifungal agents are currently approved for use in the US: caspofungin, micafungin, and anidulafungin. The echinocandins have a unique mechanism of action, inhibiting beta-(1,3)-D-glucan synthase, an enzyme that is necessary for the synthesis of an essential component of the cell wall of several fungi. The echinocandins display fungistatic activity against Aspergillus spp. and fungicidal activity against most Candida spp., including strains that are fluconazole-resistant. The echinocandins have been shown to be efficacious for the treatment of esophageal candidiasis, candidemia, and invasive candidiasis. In addition, caspofungin has demonstrated efficacy as empiric treatment of febrile neutropenia and salvage therapy for the treatment of invasive aspergillosis, and it is the only echinocandin approved for use in pediatric patients. Micafungin is the only echinocandin approved for use as prophylaxis against Candida infections in patients undergoing hematopoietic stem cell transplantation. Overall, resistance to echinocandins is still rare, and all agents are well tolerated, with similar adverse effect profiles and few drug-drug interactions. CONCLUSIONS: Echinocandins, the newest addition to the arsenal of antifungals, offer potential advantages over other classes of agents. Clinicians should assess their distinguishing characteristics, including route of metabolism, drug interaction profile, and approved indications for use, when determining which agent to include on a formulary.

Update on prevention of meningococcal disease: focus on tetravalent meningococcal conjugate vaccine.

OBJECTIVE: To review the immunogenicity, efficacy, safety, and new recommendations for routine use of the tetravalent meningococcal conjugate vaccine (MCV4). DATA SOURCES: A MEDLINE search (1966-June 2005) was conducted using the key words Neisseria meningitidis and meningococcal vaccines for clinical trials limited to human research published in the English language. STUDY SELECTION AND DATA EXTRACTION: Randomized, controlled, multicenter trials were reviewed and included to evaluate the safety and efficacy of MCV4. Additional open-label trials on the use of MCV4 in children less than 24 months of age are included since these studies may be used to support the approval of the vaccine for use in children. Literature on epidemiology and pathology of meningococcal meningitis and the Advisory Committee on Immunization Practices (ACIP) recommendations were also reviewed. DATA SYNTHESIS: MCV4 is approved for active immunization of adolescents and adults between the ages of 11 and 55 years for the prevention of disease caused by N. meningitidis serogroups A, C, Y, and W-135. MCV4 has been shown to have comparable immunogenicity and a similar adverse reaction profile to the tetravalent meningococcal polysaccharide vaccine (MPSV4). It is expected that MCV4 will provide a longer duration of protection from meningococcal disease than MPSV4. CONCLUSIONS: Based on lished immunogenicity, efficacy, and safety data, as well as the recent recommendations by the ACIP for its routine use, MCV4 is the preferred meningococcal vaccine for persons between 11 and 55 years of age and should be included on pharmacy formularies.