A Comparison of Outcomes With and Without Infectious Diseases Consultation for Enterococcal Bacteraemia in a Multicenter Healthcare System.

INTRODUCTION: It is unknown whether infectious diseases consultation improves outcomes for enterococcal bacteraemia in a multicentre healthcare system. METHODS: This retrospective multicentre observational cohort study included 250 adult patients with enterococcal bacteraemia between July 2016 and December 2020. The primary endpoint was a composite of clinical failure, including persistent bacteraemia, persistent fever, and in-hospital mortality. Secondary endpoints included adherence to a treatment bundle (appropriate empiric and definitive antibiotics, appropriate planned treatment duration, obtaining repeat blood cultures and an echocardiogram). RESULTS: Clinical failure occurred in 35 of 155 patients (22.6%) with an infectious diseases consultation and 16 of 95 patients (16.8%) without an infectious diseases consultation (P = 0.274). Multivariate analysis identified vasopressors as the only independent predictor of the primary outcome. Infectious diseases consultation resulted in higher adherence to a treatment bundle, including echocardiogram (75.5% vs. 34.7%; P < 0.0001), repeat blood cultures (85.2% vs. 68.4%; P = 0.002), appropriate definitive antibiotics (70.5% vs. 91.6%; P < 0.0001) and appropriate planned durations of therapy (81.1% vs. 94.2%; P = 0.001). More patients in the consult group were treated with ampicillin (47.1% vs. 22.1%; P < 0.0001) and fewer were treated with vancomycin (17.4% vs. 24.2%; P = 0.068). CONCLUSION: Despite finding no difference in clinical failure between groups, this study highlights important benefits of infectious diseases consultation in enterococcal bacteraemia.

Early diagnosis with sequencing and successful treatment of Bipolaris prosthetic valve endocarditis.

We present a case of a 48-year-old man with congenital bicuspid aortic valve, history of Ross procedure, prosthetic pulmonary valve and homograft with rapid molecular diagnosis and prompt surgical and medical treatment for Bipolaris fungal endocarditis with excellent outcome with early valve replacement, debridement, combination antifungal therapy, ongoing suppressive therapy after treatment.

Nitrosamine Impurities in Angiotensin Receptor Blockers.

Nitrosamines are known carcinogens which have been recently discovered in several angiotensin receptor blockers (ARBs). This led to the recall of valsartan in the United States in 2018, and afterward, the recall of other ARBs as well as unrelated medications (e.g., ranitidine). The presence of nitrosamine in ARBs was likely a result of changes in the manufacturing process, although nitrosamine contamination is believed to occur by different mechanisms with other medications. The United States Food and Drug Administration has since taken steps to identify products affected by nitrosamine contamination and mitigate this concern going forward. Despite the contamination of some drug products, studies estimate that the overall risk to patients is low enough to not necessitate changes in prescribing patterns at this time.

Tafamidis: A Novel Treatment for Transthyretin Amyloid Cardiomyopathy.

Transthyretin (TTR) amyloid cardiomyopathy is a life-threatening condition in which amyloid fibrils accumulate in the heart, eventually leading to cardiac symptomatology and death. To date, treatment of this condition has been directed at symptom relief due to a lack of effective treatment options which target the cause of the disease. The discovery that amyloid deposition was a result of dissociation of the TTR protein structure allowed for the development of tafamidis, which acts by stabilizing the TTR tetramer. Due to the rare nature of the disease, there is limited clinical trial data with tafamidis, with the largest clinical trial enrolling only 441 patients. Nonetheless, that trial demonstrated tafamidis to reduce all-cause mortality as well as cardiovascular hospitalizations compared to placebo with a comparable adverse effect profile, although not all subgroups of patients received benefit. The United States Food and Drug Administration subsequently granted Fast Track review status to tafamidis, leading to its approval in May 2019. Important questions still remain, however, such as which patient groups will receive the most benefit with this drug, how the exceptionally high cost of the drug will be handled by third-party payers, and how the therapeutic role of tafamidis will evolve as competing or perhaps complementary medications complete their ongoing clinical trials and move into the marketplace.

Review and Validation of Bayesian Dose-Optimizing Software and Equations for Calculation of the Vancomycin Area Under the Curve in Critically Ill Patients.

BACKGROUND: Vancomycin area under the concentration-time curve (AUC) has been linked to efficacy and safety. An accurate method of calculating the AUC is needed. METHODS: Bayesian dose-optimizing software programs available for clinician use and first-order pharmacokinetic equations were evaluated for their ability to estimate vancomycin AUC. A previously published rich pharmacokinetic data set of 19 critically ill patients was used for validation of the AUC estimation. The AUC estimated using subsets of the full data set by Bayesian software and equations was compared with the reference AUC. Accuracy (ratio of estimated AUC to the reference AUC) and bias (percentage difference of estimated AUC to reference AUC) were calculated. RESULTS: Five Bayesian dose-optimizing software programs (Adult and Pediatric Kinetics [APK], BestDose, DoseMe, InsightRx, and Precise PK) and two first-order pharmacokinetic equations were included. Of the Bayesian programs, InsightRx was the most adaptable, visually appealing, easiest to use, and had the most company support. Utilizing only the trough, accuracy (range 0.79-1.03) and bias (range 5.1-21.2%) of the Bayesian dose-optimizing software were variable. Precise PK and BestDose had the most accurate estimates with the accuracy values of BestDose exhibiting the most variability of all the programs; however, both programs were more difficult to use. Precise PK was the least biased (median 5.1%). Using a single nontrough value produced similar results to that of the trough for most programs. The addition of a second level to the trough improved the accuracy and bias for DoseMe and InsightRx but not Precise PK and BestDose. APK did not reliably estimate the AUC with input of two levels. Using two levels, the pharmacokinetic equations produced similar or better accuracy and bias as compared with Bayesian software. CONCLUSION: Bayesian dose-optimizing software using one or more vancomycin levels and pharmacokinetic equations utilizing two vancomycin levels produce similar estimates of the AUC.