Acute Portal and Superior Mesenteric Vein Thrombosis with Topical Testosterone Therapy: An Adverse Drug Event Case Report.

This is a case report of a 55-year-old Caucasian male prescribed topical testosterone therapy for 12 months prior to admission, when he was diagnosed with acute thrombosis in the portal vein (PVT) and superior mesenteric vein (SMV). The patient had a negative thrombophilia workup, including Factor V Leiden, Prothrombin G20210A, and JAK2 V617F mutations. There were no other pertinent laboratory markers that raised concern for the cause of thrombus. No strong familial history of venous thromboembolism (VTE) was reported during the patient's initial workup. With this in mind, the patient's use of topical testosterone therapy was considered the most likely risk factor for the PVT and SMV thrombus. During hospitalization, the patient was initiated on therapeutic anticoagulation with a heparin drip and discharged to home on apixaban for 3 months with extended therapy to be determined by outpatient hematologist. With no other identified VTE risk factors, probability that this patient's VTE was attributed to testosterone was evaluated using the Naranjo scale with a calculated score of 6, which classifies the adverse reaction as "likely." Clinicians should be aware of the possibility that topical testosterone therapy may be a risk factor for venous thrombosis in unusual sites.

Amikacin target achievement in adult cystic fibrosis patients utilizing Monte Carlo simulation.

AIM: Pseudomonas aeruginosa (PsA) is a common pathogen in cystic fibrosis (CF). Management of an acute pulmonary exacerbation (APE) caused by PsA is dual anti-pseudomonal antibiotics, a beta-lactam plus aminoglycoside. Aminoglycoside dosing in CF differs from the general population due to altered pharmacokinetics. The primary objective of this study was to utilize pharmacokinetic data from adult CF patients that received amikacin to determine the probability of target attainment for APEs caused by PsA. METHODS: This was a single-center, non-randomized, retrospective cohort study of patients >18 years with CF that received intravenous amikacin between January 2010 and July 2016. Amikacin dose, frequency, and serum concentrations were used to calculate pharmacokinetic parameters assuming a one-compartment model. Monte Carlo simulation was conducted with MIC values from CF patients with a PsA positive sputum culture between January 2014 and September 2016 to predict concentration-time profiles for different doses of amikacin. RESULTS: This study included pharmacokinetic parameters for 14 amikacin courses administered to six unique patients. The average empiric dose of amikacin was 24.3 ± 14.6 mg/kg, achieving a peak:MIC ratio ≥8 at a rate of 37% (median 5.87; IQR 3.05-10.96). A dose of 45 mg/kg/day was needed to achieve target peak:MIC ratios 90% of the time for a PsA MIC of 8 mg/L. CONCLUSION: Our data suggests it may not be clinically feasible to utilize amikacin for PsA isolates with a MIC of 16 mg/L. Current guideline dosing recommendations of amikacin 30-35 mg/kg/day are only adequate for PsA with a MIC ≤4 mg/L.