Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D.

BACKGROUND: In a phase 3 trial, bulevirtide monotherapy led to a virologic response in patients with chronic hepatitis D. Pegylated interferon (peginterferon) alfa-2a is recommended by guidelines as an off-label treatment for this disease. The role of combination therapy with bulevirtide and peginterferon alfa-2a, particularly with regard to finite treatment, is unclear. METHODS: In this phase 2b, open-label trial, we randomly assigned patients to receive peginterferon alfa-2a alone (180 µg per week) for 48 weeks; bulevirtide at a daily dose of 2 mg or 10 mg plus peginterferon alfa-2a (180 µg per week) for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks; or bulevirtide at a daily dose of 10 mg alone for 96 weeks. All the patients were followed for 48 weeks after the end of treatment. The primary end point was an undetectable level of hepatitis D virus (HDV) RNA at 24 weeks after the end of treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group. RESULTS: A total of 24 patients received peginterferon alfa-2a alone, 50 received 2 mg and 50 received 10 mg of bulevirtide plus peginterferon alfa-2a, and 50 received 10 mg of bulevirtide monotherapy. At 24 weeks after the end of treatment, HDV RNA was undetectable in 17% of the patients in the peginterferon alfa-2a group, in 32% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15 to 50; P<0.001). At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% of the patients in the peginterferon alfa-2a group, in 26% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. The most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia. The majority of adverse events were of grade 1 or 2 in severity. CONCLUSIONS: The combination of 10-mg bulevirtide plus peginterferon alfa-2a was superior to bulevirtide monotherapy with regard to an undetectable HDV RNA level at 24 weeks after the end of treatment. (Funded by Gilead Sciences; MYR 204 ClinicalTrials.gov number, NCT03852433.).

Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase 3 randomized trial.

BACKGROUND & AIMS: Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24. METHODS: In this ongoing, open-label, randomized phase 3 study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log10 IU/mL from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA. RESULTS: Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independent of virologic response. Adverse events (AEs) were mostly mild, with no serious AEs related to BLV. CONCLUSIONS: Virologic and biochemical responses were maintained and/or increased with longer-term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96. IMPACT AND IMPLICATIONS: In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2-mg and 10-mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96. GOV IDENTIFIER: NCT03852719.

Efficacy and Safety of Sofosbuvir/Velpatasvir Plus Ribavirin in Patients with Hepatitis C Virus-Related Decompensated Cirrhosis.

A fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) plus weight-based ribavirin (RBV) for 12 weeks is recommended for the treatment of patients with hepatitis C virus (HCV)-associated decompensated cirrhosis. However, large global studies, while confirming the effectiveness of SOF/VEL in a broad range of patients, often exclude these patients. This Phase 2, single-arm, open-label study in adult patients with HCV-associated decompensated cirrhosis in France and the USA aimed to provide further data on the safety and efficacy of SOF/VEL plus RBV for 12 weeks in this population. Patients were treated with a fixed-dose combination of SOF 400 mg/VEL 100 mg plus weight-based RBV once daily for 12 weeks. The inclusion criteria were chronic HCV infection (≥6 months), quantifiable HCV RNA at screening, Child-Turcotte-Pugh class B or C cirrhosis, and liver imaging within 6 months of Day 1 to exclude hepatocellular carcinoma. Among 32 patients who initiated treatment, 78.1% achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Failure to achieve SVR12 was due to non-virologic reasons (investigator discretion, n = 1; death, n = 6). All 25 patients in the per-protocol population achieved SVR12 and all but one achieved sustained virologic response 24 weeks after the end of treatment. Adverse events (AEs) were as expected for a patient population with advanced liver disease. All Grade 3-4 and serious AEs and deaths were deemed unrelated to treatment. In patients with HCV-associated decompensated cirrhosis, SOF/VEL plus RBV achieved high SVR12 rates and was generally well tolerated.

MIC Discrepancies between Parenteral and Oral Anti-Staphylococcal Beta-Lactams among MSSA.

INTRODUCTION: Recent evidence has shown that oral antibiotic therapy is not inferior to IV antibiotic therapy in the treatment of complicated Staphylococcus aureus infections. Therefore, oral antibiotic therapy is now frequently prescribed in clinical practice due to cost benefit, ease of administration, decreased complication rate, and lack of need for IV access. In vitro susceptibility testing for ß-lactam oral antibiotics is not routinely performed as the guidelines provided by the Clinical and Laboratory Standards Institute (CLSI) recommend using oxacillin and cefoxitin as surrogate markers. Hence, oral antibiotic susceptibilities for cephalexin and dicloxacillin are not reported and implied based on oxacillin and cefoxitin. The objective of the current study was to determine whether susceptibilities among S. aureus isolates are predictable when comparing commonly used IV and oral beta-lactams. METHODS: Cefazolin, cephalexin, dicloxacillin, and oxacillin broth microdilution minimum inhibitory concentrations (MICs) were determined for 100 clinical isolates of methicillin-sensitive S. aureus by broth microdilution following CLSI guidelines. RESULTS: Among these isolates, median MICs for cephalexin were eight-fold higher than cefazolin MICs and median MICs for dicloxacillin were four-fold less than oxacillin MICs. Ten percent of more strains studied had a major or very major error in its susceptibility reporting when cephalexin was compared to its surrogate marker oxacillin. DISCUSSIONS/CONCLUSIONS: The variations in MICs observed compounded with the dosing and pharmacokinetic differences of oral versus IV ß-lactam suggests that establishing breakpoints for oral ß-lactam antibiotics is necessary to ensure adequate therapy is selected for the treatment of complex S. aureus infections.

Examining the Combination of Cefixime and Amoxicillin/Clavulanate against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Isolates.

INTRODUCTION: Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have limited oral therapeutic options and pose significant clinical challenges. The goal of this study was to evaluate the in vitro synergy between CFM and AMC against ESBL E. coli with aims to identify an oral treatment option for UTIs. METHODS: Minimum inhibitory concentrations (MICs) of CFM in the presence of AMC were determined for 46 clinical isolates by placing a CFM Etest on a plate with AMC impregnated in the agar. Isolates with CFM MIC ≤1 µg/mL in the presence of AMC were considered susceptible to the CFM and AMC combination. Five isolates were then selected for further testing using time-kill analysis in the presence of CFM, AMC, and CFM with AMC. Time-kill curves were plotted to determine synergy over 24 h. RESULTS: AMC improved the activity of CFM against ESBL E. coli isolates by 128-fold in the Etest analysis with 85% of tested isolates being susceptible to the combination. A fourfold or greater reduction in CFM MIC was exhibited in 44 of 46 (96%) isolates when in the presence of AMC. Synergy and bactericidal activity between CFM and AMC were exhibited in each of the five isolates tested by time-kill analysis. DISCUSSION/CONCLUSION: This study found that AMC improves the activity of CFM against ESBL E. coli and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL E. coli UTIs.

Sofosbuvir-velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan.

BACKGROUND & PURPOSE: Protease-free regimens for chronic hepatitis C virus (HCV) infection are safe and effective for persons with either compensated or decompensated cirrhosis. We examined the efficacy and safety of sofosbuvir-velpatasvir in participants with HCV and compensated cirrhosis in Japan. METHODS: This was a Phase 3, multi-center, open-label study. At 20 sites, 37 individuals with chronic HCV infection of any genotype and compensated cirrhosis received sofosbuvir-velpatasvir (400 mg/100 mg) daily for 12 weeks. Participants were treatment-naïve or treatment-experienced with interferon-based treatments with or without HCV NS3/4A protease inhibitors. Prior exposure with HCV NS5A or NS5B inhibitors was prohibited. The primary study endpoint was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: Among participants, 62% had HCV genotype 1 infection, and 38% had HCV genotype 2. More than three quarters (29/37, 78%) were HCV treatment naïve. All participants (37/37, 100%) achieved SVR12. Seventeen participants (46%) and three participants (8%) had pretreatment resistance-associated substitutions to HCV NS5A and NS5B nucleoside inhibitors respectively, yet no on-treatment breakthrough or relapse occurred. Sofosbuvir-velpatasvir for 12 weeks treatment was safe and well tolerated. The most commonly reported adverse events were headache (8%, 3/37) and diarrhea (5%, 2/37). One serious adverse event, patella fracture, occurred and was considered not treatment related. No participants discontinued study treatment due to an adverse event. Three participants (8%) had a Grade 3 laboratory abnormality; all were hyperglycemia. CONCLUSION: Sofosbuvir-velpatasvir resulted in high SVR rates and was well tolerated among Japanese patients with HCV and compensated cirrhosis. This single-tablet regimen offers a highly effective, protease-inhibitor free regimen for treating HCV. CLINICALTRIALS: gov Identifier: NCT04112303.

The role of nonprescription syringe sales in ending the human immunodeficiency virus epidemic.

In 2019, the executive branch of the United States released "Ending the Human Immunodeficiency Virus (HIV) Epidemic: A Plan for America" (EHE). EHE proposes to end the HIV epidemic in the United States by 2030. To do so requires a multifaceted effort from all health care providers addressing every possible avenue of HIV transmission. An important aspect of this mission is to increase access to sterile syringes for people who inject drugs (PWID). For many PWID, access to Syringe Service Programs is limited because of hours, location, and state laws. Pharmacies are able to provide clean syringes in a safe, clean, climate-controlled atmosphere with access to a health professional. Although published research shows pharmacist ambivalence toward the nonprescription sales of syringes, pharmacist involvement in states with established guidance and support from departments of health suggests that pharmacists are interested in this public health effort. However, without proper support from departments of health and access to training on the dignified delivery of services, pharmacies will continue to be an ineffective avenue for prevention of HIV spread through the provision of sterile syringes.

Emergence of Resistance in Klebsiella aerogenes to Piperacillin-Tazobactam and Ceftriaxone.

We examined the effects of piperacillin-tazobactam (TZP) concentration and bacterial inoculum on in vitro killing and the emergence of resistance in Klebsiella aerogenes The MICs for 15 clinical respiratory isolates were determined by broth microdilution for TZP and by Etest for ceftriaxone (CRO) and cefepime (FEP). The presence of resistance in TZP-susceptible isolates (n = 10) was determined by serial passes over increasing concentrations of TZP-containing and CRO-containing agar plates. Isolates with growth on TZP 16/4-µg/ml and CRO 8-µg/ml plates (n = 5) were tested in high-inoculum (HI; 7.0 log10 CFU/ml) and low-inoculum (LI; 5.0 log10 CFU/ml) time-kill studies. Antibiotic concentrations were selected to approximate TZP 3.375 g every 8 h (q8h) via a 4-h prolonged-infusion free peak concentration (40 µg/ml [TZP40]), peak epithelial lining fluid (ELF) concentrations, and average AUC0-24 values for TZP (20 µg/ml [TZP20] and 10 µg/ml [TZP10], respectively), the ELF FEP concentration (14 µg/ml), and the average AUC0-24 CRO concentration (6 µg/ml). For HI, FEP exposure significantly reduced 24-h inocula against all comparators (P ≤ 0.05) with a reduction of 4.93 ± 0.64 log10 CFU/ml. Exposure to TZP40, TZP20, and TZP10 reduced inocula by 0.81 ± 0.43, 0.21 ± 0.18, and 0.05 ± 0.16 log10 CFU/ml, respectively. CRO-exposed isolates demonstrated an increase of 0.42 ± 0.39 log10 CFU/ml compared to the starting inocula, with four of five CRO-exposed isolates demonstrating TZP-nonsusceptibility. At LI after 24 h of exposure to TZP20 and TZP10, the starting inoculum decreased by averages of 2.24 ± 1.98 and 2.91 ± 0.50 log10 CFU/ml, respectively. TZP demonstrated significant inoculum-dependent killing, warranting dose optimization studies.

Treatment of patients with HIV or hepatitis C by pharmacist clinicians in a patient-centered medical home.

PURPOSE: This report describes an innovative pharmacy practice model assisting in the care of patients living with or at risk of acquiring human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). SUMMARY: In the state of New Mexico, pharmacists can obtain prescribing privileges through a Pharmacist Clinician (PhC) license. The license allows PhCs to assess patients, order laboratory/diagnostic tests, prescribe medication, and bill select insurances. PhCs have developed a practice model for patients living with or at risk of HIV and/or HCV at a Level 3 National Committee for Quality Assurance Patient-Centered Medical Home in Albuquerque, New Mexico. In 2015, 5 PhCs, employed part time, were involved with 8 different clinics: (1) HIV Adherence and Complex Care, (2) HIV Transitions of Care, (3) HCV Mono- and Co-Infection, (4) HIV Pre-Exposure Prophylaxis (PrEP), (5) HIV Primary Care and Cardiovascular Risk Reduction, (6) Young Adult Clinic, (7) Perinatal HIV, and (8) Pediatric HIV. In 2015, PhCs at the clinic billed for 774 direct patient encounters. CONCLUSION: Pharmacists with the PhC license are able to provide high-quality medical care to patients living with or at risk of HIV and/or HCV infections within an interprofessional medical home model.

Adjuvant ß-Lactam Therapy Combined with Vancomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: Does ß-Lactam Class Matter?

We analyzed the impact of vancomycin (VAN) combined with adjuvant ß-lactam therapy (Combo) on persistent (≥5 days) methicillin-resistant Staphylococcus aureus bacteremia versus VAN alone by using pooled data from two previously published observational studies (n = 156). Combo was inversely associated with persistent bacteremia (adjusted odds ratio, 0.460; 95% confidence interval, 0.229 to 0.923). Acute kidney injury was more common with Combo than with VAN (18.9% and 7.6%, respectively; P = 0.062).

Exploring the Role of Piperacillin and Tazobactam in Combination with Vancomycin against Methicillin-Resistant Staphylococcus aureus.

Previous studies have demonstrated synergy between piperacillin (PIP)-tazobactam (TAZ) (TZP) and vancomycin (VAN) against methicillin-resistant Staphylococcus aureus (MRSA). However, it is unknown whether PIP and/or TAZ synergizes with VAN against MRSA. We sought to determine whether PIP and/or TAZ synergizes with VAN against MRSA in vitro. The activity of PIP and/or TAZ with and without VAN (1/2 the minimum inhibitory concentration) was tested against 5 clinical MRSA isolates using a 24-h time-kill methodology. Antibiotic susceptibilities, accessory gene regulator (agr) operon functionality, and US strain type were also determined for the isolates. The combination of VAN and TZP was bactericidal against 3/5 isolates and synergistic against 4/5 isolates tested. Neither PIP nor TAZ alone combined with VAN demonstrated a significant reduction in bacterial growth. The combination of TZP and VAN was less active against the lone isolate with agr dysfunction. In summation, the combination of VAN with both PIP and TAZ was required for synergy against MRSA. This antibiotic combination may not be effective against unique MRSA strain types.

Clinical Impact of a Rapid Streptococcal Antigen Test on Antibiotic Use in Adult Patients.

INTRODUCTION: Adult pharyngitis is rarely attributable to group A streptococci. Utilization of a rapid streptococcal antigen test (RADT) may improve appropriate prescribing for bacterial pharyngitis. METHODS: Clinic 1 performed RADTs with subsequent Group A DNA probe test (GADNA) from November 2014-March 2015 and November 2015-March 2016 while Clinic 2 was the control clinic, then implemented the RADT with a GADNA from November 2015-March 2016. All GADNA results were obtained for each clinic from October 2013-March 2016. RESULTS: At Clinic 1, 22.2% versus 8.5% of patients received inappropriately prescribed antibiotics for a GADNA or RADT result, respectively (p=0.048). For Clinic 2, 51.1% compared to 21.4% of patients were inappropriately prescribed antibiotic for a GADNA or RADT result, respectively (p=0.038). Overall, the total GADNA without RADT testing or RADTs with subsequent GADNA testing, 41.6% versus 11% of patients were inappropriately prescribed antibiotics, respectively (p=<0.0001). CONCLUSION: Utilizing the RADT prevented unnecessary prescribing of antibiotics in adults.

Clinical and Economic Effects of a Pharmacist-Administered Antiretroviral Therapy Adherence Clinic for Patients Living with HIV.

BACKGROUND: Pharmacists have demonstrated the ability to improve patient adherence to antiretroviral therapy (ART). OBJECTIVE: To determine the clinical and economic effects of a pharmacist-administered ART adherence clinic for patients living with human immunodeficiency virus (HIV). METHODS: This pilot study with a pretest-posttest design examined the effect of a pharmacy adherence clinic on patient HIV viral load and CD4 count over a 6-month period. Patients with documented adherence problems were referred to the clinic. The pharmacist counseled patients at baseline and met with patients 1-2 weeks, 6 weeks, 3 months, and 6 months after starting ART. A societal perspective net cost analysis of the pharmacy adherence clinic was conducted to assess the economic efficiency of the intervention. RESULTS: Twenty-eight patients were enrolled in the study, and 16 patients reached completion. Median HIV RNA significantly decreased from 48,000 copies/mL (interquartile range [IQR] = 16,750-139,000) to undetectable (< 20 copies/mL) at 6 months for all study participants who completed the full intervention (P = 0.001). In the 3 months following the intervention, we estimated that it prevented approximately 0.13 secondary HIV infections among the sexual partners of the 16 participants who completed the intervention. The total cost of the intervention was $16,811 ($1,051 per patient), which was less than the future savings in averted HIV-related medical care expenditures ($49,702). CONCLUSIONS: A pharmacy adherence clinic that focused on early and sustained ART adherence interventions helped patients with documented medication adherence problems achieve an undetectable HIV RNA. The intervention was highly cost saving, with a return of nearly $3 in future medical care savings per dollar spent on the intervention. DISCLOSURES: This work was supported in part by a research grant to Dilworth, Mercier, and Borrego from the American Society of Health-System Pharmacists Foundation. Klein and Pinkerton were supported in part by grants T32-MH19985 and P30-MH52776, respectively, from the National Institute of Mental Health. No funding bodies had any role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Health Resources and Services Administration. The authors have no conflicts of interest to disclose. Study concept and design were contributed primarily by Dilworth, Mercier, and Borrego, along with the other authors. Dilworth took the lead in data collection, along with Pinkerton, Klein, Mercier, and Jakeman. Data interpretation was performed by Dilworth and Pinkerton, along with the other authors. The manuscript was written by Dilworth, Klein, and Jakeman, with assistance from the other authors, and revised by Dilworth, Jakeman, and Klein, with assistance from the other authors. The results from this study were presented in part at the 2015 United States Conference on AIDS in Washington, DC, on September 10-13, 2015.

Host-Pathogen-Treatment Triad: Host Factors Matter Most in Methicillin-Resistant Staphylococcus aureus Bacteremia Outcomes.

Previous studies have separately emphasized the importance of host, pathogen, and treatment characteristics in determining short-term or in-hospital mortality rates for patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections. Less is known about the relative importance of these factors and their interactions in determining short-, medium-, and long-term mortality rates. This is an observational cohort study in which data for all patients admitted to the University of New Mexico (UNM) Health Sciences Center (HSC) between July 2002 and August 2013 with MRSA-positive blood cultures were recorded. We collected patients' demographics and treatment data, as well as data on genetic markers of the MRSA isolates. Outcomes of interest were determinants of short-term (within 30 days), medium-term (30 to 90 days), and long-term (>90 days) mortality rates. This study included 273 patients with MRSA bacteremia. Short-, medium-, and long-term mortality rates were 18.7%, 26.4%, and 48%, respectively. Thirty-day mortality rates were influenced by host variables and host-pathogen interaction characteristics. Pitt bacteremia scores, malignancy, and health care exposure contributed to 30- to 90-day mortality rates, while treatment duration of >4 weeks had a protective effect. Age remained a significant risk factor for death at >90 days, while admission leukocytosis was protective. Infection represented the most frequent cause of death for all three time frames; rates varied from 72.6% in the first 30 days and 60% for 30 to 90 days to 35.7% for >90 days (P = 0.003). Host characteristics affect short-, medium-, and long-term mortality rates for MRSA bloodstream infections more than do pathogen genetic markers and treatment factors.

Potential Ceiling Effect of Healthcare Worker Influenza Vaccination on the Incidence of Nosocomial Influenza Infection.

OBJECTIVE To evaluate the effect of healthcare worker (HCW) influenza vaccination on the incidence of nosocomial influenza DESIGN Retrospective cross-sectional study SETTING A 550-bed tertiary-care academic medical center METHODS All admitted patients with a direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) assay positive for influenza ordered between October 1 and May 31 from 2010 to 2015 were eligible for inclusion. Nosocomial influenza was defined as a positive influenza test collected ≥48 hours after admission in patients without influenza-like illness present within 24 hours of admission. Relative nosocomial influenza frequency was calculated by dividing the number of nosocomial cases by the total number of admitted patients with influenza for each season. A univariate logistic regression was used to determine the association between HCW influenza vaccination coverage and nosocomial influenza. RESULTS Over 5 seasons, 533 patients had positive influenza tests during their hospitalization; 29 of these patients (5.4%) acquired influenza during their hospitalization. HCW vaccination coverage increased over the 5 seasons from 47% to 90% (P<.001). Despite an initial decrease in relative nosocomial influenza frequency during the first year (9% to 4.9%), subsequent seasons failed to show an additional decrease in nosocomial infections (4.3%, 5.2%, and 4.8%, respectively); the overall decrease in nosocomial influenza from the first season to the final season was not significant (P=.282). No association was detected between HCW vaccination coverage and nosocomial influenza (odds ratio [OR], 0.990; 95% confidence interval [CI], 0.970-1.011). CONCLUSION HCW vaccination >50% may not have a significant effect on nosocomial influenza. Infect Control Hosp Epidemiol 2016;37:840-844.

Complementary and Alternative Medicine and Therapy Use in a Diverse New Mexican Population.

OBJECTIVE: To describe differences, attitudes, and experiences in use of complementary and alternative medicines and therapy (CAMT) in people living in New Mexico (NM). DESIGN: Cross-sectional survey study. SETTING: Clinics staffed by the University of New Mexico College of Pharmacy faculty between September 2009 and August 2011 in Albuquerque, NM. PARTICIPANTS: Patients 18 years of age or older or parents of patients younger than age 18 years. OUTCOME MEASURES: Descriptive statistics for survey results and mean scores for attitudinal items. Chi-square, t-test, and analysis of variance were used to compare differences between groups across demographic variables. RESULTS: A convenience sample yielded 263 completed surveys. Of the respondents, 62% were male, 39% were single, and 50% were Hispanic. Nearly 56% of respondents used CAMT in the previous 6 months; 38% used CAMT in addition to and 11% used CAMT instead of prescription medications. Average number of CAMT used per respondent was 2.3 ± 1.6. A majority of respondents indicated that their CAMT use in the previous 6 months was useful, a good idea, easy to use, and likely to continue. CAMT use was significantly higher in female respondents (p = 0.03), those with a higher education level (p < 0.01), and those with a higher household income level (p = 0.03). CONCLUSION: Prevalence of CAMT is high in a diverse population of patients. Older respondents were more likely to use CAMT in addition to prescription medications, and younger respondents were more likely to use CAMT instead of prescription medications. Providers need to consider CAMT use when discussing treatment options with patients.

An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection.

BACKGROUND: Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers. METHODS: The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge. RESULTS: No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9% to the total hospitalization cost, compared with 6.4% for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95% confidence interval [CI], 0.249-0.997; P < 0.05). CONCLUSION: This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01419184 (Date: August 16, 2011).

Evaluating community pharmacists' HIV testing knowledge: A cross-sectional survey.

OBJECTIVES: To assess community pharmacists' knowledge of human immunodeficiency virus (HIV), antiretroviral therapy, and new in-home oral fluid HIV test. METHODS: A cross-sectional questionnaire administered to pharmacists, student pharmacists, and technicians before an education program at the New Mexico Pharmacists Association 2013 Mid-Winter Meeting in Albuquerque, NM. The main outcome measure was community pharmacists' correct response rate of 75% or more. RESULTS: Overall survey response rate of attendees was 89% (173/194 attendees). Among them 87 participants were community pharmacists; 87% of community pharmacists responded correctly when asked how HIV antiretroviral medications work and 84.3% correctly identified known sources of HIV infection. The 75% predefined adequate knowledge threshold was not met on any HIV screening or in-home HIV test knowledge items. Only 65.1% of community pharmacists correctly identified the minimum number of antiretroviral drugs that should be included in an ideal HIV treatment regimen. The only variable that positively influenced pharmacists' knowledge was age. An inverse relationship between pharmacist age and HIV knowledge was observed among study participants. CONCLUSION: Community pharmacists from urban and rural areas in New Mexico possessed adequate basic HIV knowledge, but did not demonstrate adequate HIV screening or in-home HIV test knowledge. Future educational interventions aimed at improving pharmacist knowledge in this area are warranted.

Iohexol transmembrane clearance during modeled continuous renal replacement therapy.

BACKGROUND/AIMS: Urea clearance during continuous renal replacement therapy (CRRT) is not representative of middle molecular weight solute clearances. We aimed to characterize iohexol, molecular weight 821 Da, clearance during continuous hemofiltration (CH) and continuous hemodialysis (CHD). METHODS: Using an in vitro model, iohexol sieving coefficients (SC) and saturation coefficients (SA) were determined with the M100 membrane at ultrafiltration/dialysate rates of 1, 2, 3, 4, and 6 l/h. Iohexol transmembrane clearance was calculated using the measured SC and SA. RESULTS: During CH, the value of iohexol SC remained approximately 1 at all ultrafiltration rates studied. In contrast, during CHD iohexol the mean SA was 1.02 ± 0.05 at a dialysate rate 1 l/h and decreased significantly with higher dialysate rates to a mean SA of 0.57 ± 0.12 at a dialysate rate of 6 l/h. CONCLUSIONS: At higher effluent flow rates, CH was more effective in removing iohexol than CHD. CH transmembrane clearance of iohexol appears to approximate the ultrafiltration rate.

Antimicrobial Stewardship Intervention and Feedback to Infectious Disease Specialists: A Case Study in High-Dose Daptomycin.

Infectious Diseases specialists have used high-dose daptomycin (≥6 mg/kg/day) in select patients with difficult to treat methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) infections to optimize outcomes. Antimicrobial stewardship programs enforce antimicrobial formulary restrictions; however, interventions specifically aimed at Infectious Disease specialists can be particularly challenging. The purpose of this study was to create a high-dose daptomycin algorithm for Infectious Disease specialists that are consistent with best-practices. Daptomycin prescribing habits pre- and post-daptomycin algorithm implementation were evaluated using a quasi-experimental study design. Patients were included if ≥18 years of age and received daptomycin for ≥48 h. Patients were excluded if daptomycin was initiated on an outpatient setting. During the 12-month pre-intervention phase, 112 patients were included, with 73 patients in the 12-month post-intervention phase. A statistically significant decrease in the mean daptomycin dose from 9.01 mg/kg to 7.51 mg/kg (p < 0.005) was observed, resulting in an annual drug cost-savings of over $75,000 without adversely affecting readmission rates due to infection. Creation of a daptomycin algorithm with consideration of pathogen, disease state, and prior treatment, is an effective means of influencing prescribing habits of Infectious Disease specialists.