Among patients with a BL allergy, use of BL antibiotics is associated with a lower rate of clinical failure. The low rate of hypersensitivity provides further evidence about the risk of cross-reactivity between BL classes. These results support the practice of using a BL from an alternative class for patients in need of gram-negative antibiotic coverage.

Despite growing evidence and promise as a cost-effective strategy for reducing cardiovascular risk, chronotherapy is not uniformly recommended in the treatment of hypertension. Careful selection of patients and antihypertensives for chronotherapy is required. Further investigation is needed to evaluate the definitive impact of chronotherapy on cardiovascular outcomes.

The use of novel oral anticoagulants (NOACs) with rapid onset and offset is desirable in patients post-heart transplant (post-OHT) due to frequently scheduled biopsies; however, the safety of these agents in combination with calcineurin inhibitors (CNIs) is not well established. While apixaban (A) and rivaroxaban (R) are major substrates of CYP3A4, dabigatran (DTI) is a major substrate of p-glycoprotein (PGP). Both CNIs are PGP inhibitors, conferring a theoretical risk of increased bleeding and increased CNI troughs with DTI use not present with the Anti-Xa oral agents (AXa). This study aims to determine the drug-drug interactions between NOACs and CNIs in heart transplant recipients. Methods: This was a retrospective, single-center cohort study. The electronic outpatient transplant system was queried to identify all post-OHT patients with concurrent orders for NOACs and a CNI from 1/2011-8/2015. Patients taking additional CYP3A4 or PGP inhibitors were excluded. Major bleeding events were recorded utilizing outpatient notes and patient admissions. CNI doses and troughs in relation to the start of the NOAC were also recorded. Results: A total of 27 patients were found to have concurrent NOAC (A= 1, R= 17, DTI= 9) and CNI (tacrolimus= 25, CsA= 2) orders. Four rivaroxaban patients were excluded from the main analysis for concurrent dilitiazem therapy. At baseline patients did not differ in age, weight, renal function, indication (AF= 48%, VTE= 35%), or duration of therapy. Of the 23 included patients, major bleeds occurred in two patients (DTI= 2/9 v. AXa= 0/14, p= 0.065). Patients prescribed DTI were more likely to have a decrease in tacrolimus dose during NOAC therapy than AXa (5/9 (55.6%) v. 2/14 (14.3%), p= 0.036). When including diltiazem-treated patients receiving NOAC with CNI, patients receiving AXa were found to have an increased risk of major bleed when treated with concurrent CNI and diltiazem therapy (2/4 v. 0/14, p= 0.039). Conclusion: These limited results indicate a trend towards increased risk of major bleeds with DTI and CNI combination therapy when compared to AXa and CNI use. Dabigatran's competition with CNI at the PGP site may also increase CNI levels, leading to a decrease in required CNI dose. Additionally, AXa use concurrent with CNI and diltiazem, possibly by CYP3A4 interaction, may increase risks of bleeding in these patients.

Objectives We evaluated clinical outcomes associated with ESA use in LVAD-supported patients. Background Use of erythropoiesis stimulating agents (ESAs) in patients with left ventricular assist devices (LVADs) may minimize blood transfusions and decrease allosensitization. ESAs increase thrombotic events which is concerning as LVADs are sensitive to pump thrombosis (PT). Methods We retrospectively reviewed 221 patients at our center who received a HeartMate II® LVAD between 1/2009 and 6/2013. Patients were divided into those who received ESAs during index admission (n = 121) and those who did not (n = 100). Suspected PT was defined as evidence of thrombus in the LVAD or severe hemolysis (LDH > 1,000 mg/dL or plasma free hemoglobin > 40mg/dL). Outcomes were compared between cohorts using inverse probability-weighted analyses. Results During a mean follow-up of 14.2 ± 11.9 months, suspected PT occurred in 37 patients (ESA 23%, no-ESA 12%; P =0.03). The ESA cohort received ESAs 13.9 ± 60.9 days after LVAD implantation. At 180-days, event-free rates for suspected PT were ESA 78.6% vs. no-ESA 94.5% (P < 0.001). ESA use had higher rates of suspected PT (HR 2.35, 95% CI 1.38-4.00; P = 0.002). For every 100 unit increase in cumulative ESA dosage, the hazard of suspected PT increased by 10% (HR 1.10, 95% 1.04-1.16; P < 0.001). After inverse probability weighting, ESA use was associated with a significantly higher rate of all-cause mortality (HR 1.62, 95% 1.12-2.33; P = 0.01). Conclusions ESA use in LVAD patients is associated with higher rates of suspected PT.