Effectiveness of oral antibiotics for definitive therapy of non-Staphylococcal Gram-positive bacterial bloodstream infections.

BACKGROUND: Data on the effectiveness of definitive oral (PO) antibiotics for BSIs in preparation for discharge from hospital are lacking, particularly for Gram-positive bacterial BSIs (GP-BSI). The objective of this study was to determine rates of treatment failure based on bioavailability of PO antimicrobial agents used for GP-BSI. METHODS: This was a single-center, retrospective cohort study of adult inpatients admitted to an academic medical center over a three-year period. Patients with a non-staphylococcal GP-BSI who received intravenous antibiotics and were then switched to PO antibiotics for at least a third of their treatment course were included. The cohort was stratified into high (⩾90%) and low (<90%) bioavailability groups. The primary endpoint was the proportion of patients experiencing clinical failure in each group. Secondary endpoints included clinical failure stratified by antibiotic group, bactericidal versus bacteriostatic PO agents, and organism. RESULTS: A total of 103 patients met criteria for inclusion, which failed to reach the a priori power calculation. Of the patients included, 26 received high bioavailability agents and 77 received low bioavailability agents. Infections originated largely from a pulmonary source (30%) and were caused primarily by streptococcal species (75%). Treatment failure rates were 19.2% in the high bioavailability group and 23.4% in the low bioavailability group (p = 0.66). Clinical failure stratified by subgroups also did not yield statistically significant differences. CONCLUSIONS: Clinical failure rates were similar among patients definitively treated with high or low bioavailability agents for GP-BSI, though the study was underpowered to detect such a difference.

HIV Clinical Updates: New Single-Tablet Regimens.

OBJECTIVE: To review the pharmacokinetics, safety, common drug-drug interactions (DDIs), and advantages and disadvantages of new single-tablet regimens (STRs) approved since September 2016 for HIV-1 infection. DATA SOURCES: A search using PubMed was conducted (2004 through May 2018) using the following keywords: single tablet regimen AND HIV. Additionally, a PubMed search was conducted for each individual STR using the generic names of the agents. For specific STRs, additional search terms were added to narrow results. Articles were evaluated for content, and additional references were identified from a review of literature citations. Conference abstracts from national and international HIV conferences were also searched. STUDY SELECTION AND DATA EXTRACTION: Studies included were published randomized controlled trials and observational studies that evaluated STR approved since September 2016. Relevant conference abstracts were included if the study design was a randomized controlled trial or observational study pertaining to the STRs included. DATA SYNTHESIS: Four new STRs are available, including the first dual antiretroviral therapy (ART) regimen for virologically suppressed patients. Of the STRs, only 1 is a new molecular entity, and others include new combinations of existing agents that result in distinct advantages and disadvantages. Relevance to Patient Care and Clinical Practice: The treatment of HIV-1 continues to improve with new agents developed rapidly. These agents should be analyzed in regard to efficacy, safety, DDIs, and appropriateness for specific patients on an individual basis. CONCLUSIONS: STRs and agents in the pipeline continue to simplify ART regimens, increase medication adherence, and minimize toxicities.

Single-Tablet Regimens for the Treatment of HIV-1 Infection.

OBJECTIVE: To review the pharmacokinetics, safety, drug-drug interactions, and advantages and disadvantages of currently available single-tablet regimens (STRs) for HIV-1 infection. DATA SOURCES: A search using PubMed was conducted (up to September 2016) using the following keywords: single tablet regimen AND HIV. Additionally, a PubMed search was conducted for each individual STR using the generic names of the agents. Articles were evaluated for content, and additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: Studies included were predominantly phase III clinical trials with the exception of tenofovir alafenamide because phase I and phase II trials were also relevant for this new antiretroviral agent. DATA SYNTHESIS: Six STRs are currently available for the treatment of HIV-1. Each agent has unique pharmacokinetic, safety, and drug-drug interaction profiles that result in distinct advantages and disadvantages. Three of these agents are first-line recommended therapies per national guidelines because of high virological efficacy and tolerability. CONCLUSIONS: STRs have significantly advanced HIV management by minimizing pill burden and improving patient compliance. It is important to consider the nuances of each STR in regard to renal and hepatic function, drug interactions, and tolerability, to ensure safe and effective use.

Depression, Resource Utilization, and Outcomes Following Liver Transplant.

CONTEXT: There is evidence that depression after liver transplant (LTX) is associated with increased morbidity and mortality; however, the effect of depression treatment on LTX outcomes has not been well established. OBJECTIVE/SETTING/DESIGN: This single-center, longitudinal cohort study aimed to determine whether depression treatment influences outcomes after LTX. Depression diagnosis was based on medical history and documentation from psychosocial providers. PATIENTS/INTERVENTION/MAIN OUTCOME MEASURES: Patients were studied from October 2010 to June 2013 and separated into 3 groups for analysis: no depression, adequately treated depression, and inadequately treated depression. Adequacy of depression treatment was determined using the Antidepressant Treatment History Form. RESULTS: Of the 161 patients included in the analysis, 103 did not have depression, 24 had adequately treated depression, and 34 had inadequately treated depression. Baseline demographics were similar between the groups. Patients with inadequately treated depression had significantly more encounters with a health-care provider (P = .03). Graft loss tended to be higher in these patients (27% in the inadequately treated group, 17% in the adequately treated, and 14% in the no depression group, P = .25). The adequately treated group was more likely than the inadequately treated group to be on antidepressants at 30 days post-LTX (P = .001). The inadequately treated group was more likely to be on a sleep aid 30 days post-LTX (P = .01). CONCLUSION: Inadequately treated depression led to increased health-care resource utilization. Patients with adequately treated depression had similar outcomes as those with no depression. Use of sleep aids early post-LTX may be a surrogate indicator of inadequately treated depression.

Voriconazole concentration monitoring at an academic medical center.

PURPOSE: Results of a study of the relationship among voriconazole dosages, serum concentrations, adverse effects, and clinical outcomes are presented. METHODS: A retrospective chart review was conducted that included all patients who had at least one voriconazole concentration drawn between July 1, 2009, and August 15, 2014, at a single academic medical center. The primary outcome was the proportion of patients with initial voriconazole concentrations in the target range. RESULTS: Forty-seven of 88 patients (53%) had an initial voriconazole concentration within the target range, 27% (24 of 88) of patients had a concentration above the range, and 19% (17 of 88) had a concentration below the range. Sixty-seven percent of patients with above-target concentrations had adverse effects. Voriconazole was discontinued in 9% of patients, and dosages were reduced in 11% of patients because of adverse effects. Voriconazole for treatment versus prophylaxis was analyzed in a subgroup, as was obesity and nonobesity. Twenty-four percent of patients died during their hospital admission, and 14% were not discharged on voriconazole therapy. The within-target group had the highest proportion of patients discharged on voriconazole and the lowest proportion of deaths. CONCLUSION: A retrospective study in one institution revealed that the first measured voriconazole concentration was within the target range in 53% of patients and that dosage was modified in only 51% of patients whose concentration was outside of that range. The majority of patients with above-target concentrations had an adverse effect, and this result was particularly common in patients with a body mass index of ≥35 kg/m(2).

Use of fluoxetine in anorexia nervosa before and after weight restoration.

OBJECTIVE: To examine the evidence for the use of fluoxetine in treatment of underweight and weight-restored patients with anorexia nervosa (AN) and provide recommendations for the clinical usefulness of fluoxetine in AN. DATA SOURCES: Literature was accessed via PubMed through June 2013 using the terms fluoxetine and anorexia nervosa. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials published in English identified from the data sources were evaluated. Studies including the use of fluoxetine in underweight or weight-restored patients with AN were included. Studies of fluoxetine in preclinical animal models of anorexia nervosa were excluded. DATA SYNTHESIS: AN is a serious psychiatric illness with no currently approved medication therapy. Because patients with AN frequently display symptoms of major depressive and obsessive-compulsive disorders, medication therapy is commonly used in attempts to improve these symptoms and prevent relapses of AN. Antidepressants such as fluoxetine are the most frequently used medications for these symptoms. The evidence for fluoxetine in the treatment of AN is controversial, particularly in patients who remain underweight. One theory of inefficacy is that underweight patients do not have the nutrients required to make serotonin, therefore preventing selective serotonin reuptake inhibitors from taking effect. Another theory involves dysregulation of the serotonin receptor. Despite the lack of evidence, fluoxetine may still be useful in certain underweight and weight-restored patients. CONCLUSIONS: The risk-benefit ratio of fluoxetine in underweight and weight-restored patients with AN is undefined by clinical trials; therefore, clinical experience must be applied for its use in this patient population.