Tiffany Bias

Sofosbuvir: A Nucleotide NS5B Inhibitor for the Treatment of Chronic Hepatitis C Infection

OBJECTIVE To review the use of sofosbuvir for the treatment of chronic hepatitis C virus (HCV). DATA SOURCES Review and nonreview articles were identified through MEDLINE (1996-April 2014), citations of articles, and meeting abstracts using keywords, including NS5B polymerase inhibitor, GS-7977, sofosbuvir, direct-acting antiviral (DAA), and others. STUDY SELECTION AND DATA EXTRACTION Phase 1, 2, and 3 studies describing dose-ranging potential, pharmacokinetics, efficacy, safety, and tolerability of sofosbuvir were identified. DATA SYNTHESIS Sofosbuvir is an NS5B polymerase inhibitor that was approved for use by the Food and Drug Administration in December 2013 for the treatment of chronic HCV in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) for genotype 1. Additionally, it has been evaluated with other oral DAAs, such as simeprevir and others in the pipeline. It is not recommended as monotherapy because of lower sustained virological response (SVR) rates in clinical studies. Most of the treatment regimens are 12 weeks in duration; however, certain populations require a longer duration. Sofosbuvir has activity against all 6 genotypes, although most clinical trials evaluated genotypes 1 to 3. Sofosbuvir has a favorable safety and tolerability profile, making it a recommended first-line agent for chronic HCV infection. CONCLUSION In clinical trials, 12 weeks of sofosbuvir with concomitant peg-IFN and RBV therapy in treatment-naïve and experienced HCV genotype 1 patients resulted in SVR rates of >90%. An all-oral regimen of sofosbuvir and RBV is highly effective for genotype 2 and 3 patients. Sofosbuvir was found to be tolerable with minimal adverse effects (AEs), and no treatment discontinuations occurred secondary to drug related AEs..Objective: To review the use of sofosbuvir for the treatment of chronic hepatitis C virus (HCV). Data Sources: Review and nonreview articles were identified through MEDLINE (1996-April 2014), citations of articles, and meeting abstracts using keywords, including NS5B polymerase inhibitor, GS-7977, sofosbuvir, direct-acting antiviral (DAA), and others. Study Selection and Data Extraction: Phase 1, 2, and 3 studies describing dose-ranging potential, pharmacokinetics, efficacy, safety, and tolerability of sofosbuvir were identified. Data Synthesis: Sofosbuvir is an NS5B polymerase inhibitor that was approved for use by the Food and Drug Administration in December 2013 for the treatment of chronic HCV in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) for genotype 1. Additionally, it has been evaluated with other oral DAAs, such as simeprevir and others in the pipeline. It is not recommended as monotherapy because of lower sustained virological response (SVR) rates in clinical studies. Most of the treatment regimens are 12 weeks in duration; however, certain populations require a longer duration. Sofosbuvir has activity against all 6 genotypes, although most clinical trials evaluated genotypes 1 to 3. Sofosbuvir has a favorable safety and tolerability profile, making it a recommended first-line agent for chronic HCV infection. Conclusion: In clinical trials, 12 weeks of sofosbuvir with concomitant peg-IFN and RBV therapy in treatment-naïve and experienced HCV genotype 1 patients resulted in SVR rates of >90%. An all-oral regimen of sofosbuvir and RBV is highly effective for genotype 2 and 3 patients. Sofosbuvir was found to be tolerable with minimal adverse effects (AEs), and no treatment discontinuations occurred secondary to drug related AEs..

Multicenter Study of Outcomes with Ceftazidime-Avibactam in Patients with Carbapenem-Resistant Enterobacteriaceae Infections

ABSTRACT Ceftazidime-avibactam is a novel cephalosporin–beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review for 60 patients who received ceftazidime-avibactam for a CRE infection. In-hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option.

Impact of an antimicrobial stewardship initiative on time to administration of empirical antibiotic therapy in hospitalized patients with bacteremia

PURPOSE The impact of an antimicrobial stewardship initiative on time to first antibiotic dose and clinical outcomes in bacteremic patients was evaluated. METHODS A single-center, retrospective study was conducted for adult inpatients who received antibiotics before and after implementation of a rapid administration of antimicrobials by an infectious diseases specialist (RAIDS) protocol. Patients admitted to an inpatient service from June to October 2011 (pre-RAIDS protocol) and from December 2011 to February 2012 (post-RAIDS protocol) were eligible for inclusion if (1) they were age 18 years or older, (2) their infection occurred two or more days after hospital admission, and (3) they had a blood culture growing an organism other than common skin contaminants (i.e., coagulase-negative staphylococci, Bacillus species). The primary outcome was the time to the first antibiotic dose (TFAD), defined as the time that elapsed from a positive blood culture result to administration of the first empirical antimicrobial dose. RESULTS A total of 111 bacteremic patients were included in the analysis. Implementation of the RAIDS protocol led to significantly faster antibiotic order entry, verification, and administration of empirical antibiotics in patients with bacteremia. The median TFAD was approximately 8 hours faster in the post-RAIDS group than in the pre-RAIDS group (9:09 hr:min versus 1:23 hr:min, p < 0.001). Patients in the post-RAIDS group had a significant reduction in infection-related mortality (p = 0.047), though all-cause 30-day mortality was similar. CONCLUSION Early notification of an infectious diseases pharmacist about positive blood cultures using the RAIDS protocol led to increased appropriateness of empirical drug selection and a dramatic reduction in the administration of antibiotics and was associated with decreased infection-related mortality.

Incidence of Antiretroviral Drug Interactions During Hospital Course The Role of a Pharmacist-Led Antiretroviral Stewardship Program

Background: Human immunodeficiency virus (HIV) providers are treating more comorbid conditions with additional pharmacologic agents, resulting in patients with HIV being disproportionately at risk for clinically significant drug–drug interactions (CSDDIs). There is a potential to overlook these interactions and ultimately place patients at risk for drug toxicity, resistance, and virologic failure. Objective: To assess the burden of CSDDIs among patients receiving antiretroviral therapy (ART) within 24 hours of admission and to evaluate the effect of a clinical pharmacist operating through an antiretroviral stewardship (ARVSP) program in identifying and correcting potential drug interactions. Methods: Adult HIV-positive patients receiving ART who were admitted to The Brooklyn Hospital Center from November 2010 through January 2012 were included in the analysis. Drug interactions were categorized according to time frame (ie, within 24 hours of admission vs after 24 hours of admission) and type (ie, contraindicated combinations, dosage modifications, and frequency alterations). The Liverpool HIV drug reference, Micromedex drug database, and the Department of Health and Human Services Guidelines were used as comprehensive tools for identification of antiretroviral drug errors. Results: Eighty-four CSDDIs were identified from 252 admissions among 158 patients receiving ART during the study period. Of the identified CSDDIs, 61 (73%) occurred within 24 hours of admission and 23 (27%) later in the hospital course. Forty-eight drug interactions (57%) represented contraindicated drug combinations. Protease inhibitor–based regimens were associated with the highest percentage of CSDDIs (98%). Of all CSDDIs, the most common interacting drug class was acid-suppressive therapy (63%). Clinical pharmacists identified and intervened in 80% of the CSDDIs that occurred on patient admission with all interventions accepted. Conclusions: CSDDIs are common among patients receiving ART at the time of admission and throughout the hospital course. Interventions including medication review by clinical pharmacists are critical in the prevention of CSDDIs on admission.

Association of tenofovir disoproxil fumarate with primary allograft survival in HIV-positive kidney transplant recipients

Tenofovir disoproxil fumarate (TDF) is an antiretroviral agent frequently used to treat human immunodeficiency virus (HIV). There are concerns regarding its potential to cause acute kidney injury, chronic kidney disease, and proximal tubulopathy. Although TDF can effectively suppress HIV after kidney transplantation, it is unknown whether use of TDF‐based antiretroviral therapy (ART) after kidney transplantation adversely affects allograft survival.