Home-Based Peanut Oral Immunotherapy for Low-Risk Peanut-Allergic Preschoolers During the COVID-19 Pandemic and Beyond

The coronavirus disease 2019 (COVID-19) pandemic has led to the deprioritization of non-emergency services, such as oral food challenges and the initiation of oral immunotherapy (OIT) for food-allergic children. Recent studies have suggested that home-based peanut OIT could be a safe and effective option for low-risk peanut-allergic children. In the period between September 1, 2020, and January 31, 2021, nine preschoolers with a history of mild allergic reactions to peanut underwent home-based peanut OIT. Eight of them (88.9%) completed the build-up phase at home in 11–28 weeks, tolerating a daily maintenance dose of 320 mg peanut protein. During the build-up, six patients (75.0%) reported urticaria, three (33.3%) reported gastrointestinal tract symptoms, and one (14.3%) reported oral pruritis. None of the patients developed anaphylaxis, required epinephrine, or attended emergency services related to OIT. One or two virtual follow-up visits were completed per patient during the build-up phase. Our case series shows that home-based OIT could be offered to the low-risk preschoolers during the COVID-19 pandemic when non-emergency services are limited and could be considered beyond the pandemic, especially for the families living in the rural or remote areas that may otherwise be unable to access OIT.

1576. Delaying the Start of Maintenance Vancomycin After a Loading Dose to Avoid a High 0–24h AUC

Background Vancomycin dosing guidelines recommend loading doses (LDs) (25–30 mg/kg TBW), and a maintenance regimen, usually started after a time period equal to the dosing interval. Studies of vancomycin exposure and nephrotoxicity conclude that a 0 to 24-hour area under the serum concentration–time curve (0–24AUC) > 677 mg-hour/L results in a 3- to 4-fold increased risk of nephrotoxicity (Zasowski EJ, Antimicrob Agents Chemother 2018). For vancomycin LDs we compare the calculated LD and the maintenance dose, and delay initiation of the maintenance regimen when the LD exceeds the daily maintenance dose by > 50%. This study assessed the pharmacokinetic outcomes from this technique. Methods We retrospectively reviewed 68 consecutive adult patients receiving therapeutic doses of vancomycin. Patient age, sex, height, weight, serum creatinine, and indication were used to calculate the daily dose/intervals for a steady-state 24-hr AUC of 400 or 600 mg-hour/L. The total 0–24AUC was calculated by adding the 0–24 AUC from a 25 mg/kg LD (max: 3 gm) to the 0–24AUC(s) for maintenance dose(s) within the first 24 hours. We compared the total 0-24AUC when the first maintenance dose was timed for the next dosing interval (“scheduled”) to that when the maintenance dose was delayed according to our protocol (“delayed”). We tested the proportion of patients who would be exposed to a vancomycin 0-24AUC > 677 mg-hour/L. Results 16/68 patients were diagnosed with SSTI (goal 24 hr AUC: 400 mg-hour/L) and 52/68 with sepsis, bacteremia/endocarditis, or pneumonia (24 hr AUC: 600 mg-hour/L). Median daily maintenance dose was 1750 mg (range: 875–4,000 mg). For patients with a goal AUC of 400, the 0-24AUC was > 677 mg-hour/L in one patient using the “scheduled” process and in none of the patients using the “delayed” protocol. However, for patients with a goal AUC of 600, the 0-24AUC was > 677 mg-hour/L in 22/52 patients via the “scheduled” process vs. 4/52 patients via the “delayed” protocol. Conclusion For patients with severe gram-positive bacterial infections requiring aggressive dosing of vancomycin, delaying the start of maintenance dosing following a large LD is an effective way to ensure attainment of goal therapeutic AUC within the first 24 hr without placing the patient at increased risk for nephrotoxicity. Disclosures All authors: No reported disclosures.

Cytochrome P450 2B6 and 2C9 genotype polymorphism – a possible cause of prasugrel low responsiveness

SummaryThe cytochrome P450 (CYP) isoenzymes are essential for the metabolic activation of the prodrug prasugrel. Little is known about the impact of polymorphism of these isoenzymes on the prevalence of prasugrel low responsiveness (PLR) in patients with coronary artery disease. We investigated the frequency of PLR and the question whether PLR is associated with decreased/non-function polymorphisms of the CYP isoenzymes (2C9*2, 2C9*3, 2C19*2, 2C19*3, and 2B6*6). Our study included 355 patients who underwent percutaneous coronary stenting. The patients were initially treated with either prasugrel (n=90; 60/10 mg: loading/daily maintenance dose) or 600/75 mg clopidogrel hydrogensulfate (n=265) in combination with 500/100 mg acetylsalicylic acid (ASA). Platelet function was tested by impedance aggregometry 48 hours after taking the loading dose. Prasugrel achieved on the average significantly higher levels of platelet inhibition as compared to clopidogrel (mean 27.3 U vs 41.2 U). The frequencies of low response for prasugrel, clopidogrel and ASA were 9.8%, 35.1% and 14.9%, respectively. We identified only body mass index to be associated with PLR. PLR was not caused by a loss of ADP P2Y12-receptor function. Half of the patients with PLR were carriers of the reducedfunction allele CYP2B6*6, and 41.7% had the genetic variant CYP2C9*2. The allele CYP2C9*3 was detected in three patients with PLR (25%) and two patients with PLR (16.7%) carried the gene variant CYP2C19*2. In conclusion, the rate of low responders was significantly lower among patients treated with prasugrel than with clopidogrel. PLR are more often carriers of CYP2C9*2 (50% in PLR) than when compared to the prevalence described in literature. Also, there is a trend to an increased frequency of CYP2B6*6 in PLR. In conclusion, CYP2B6 and CYP2C9 polymorphisms seem to be associated with prasugrel low-response.

Predicting Daily Maintenance Dose of Fluindione, an Oral Anticoagulant Drug

SummaryDue to large inter-individual variations, the dose of vitamin K antagonist required to target the desired hypocoagulability is hardly predictible for a given patient, and the time needed to reach therapeutic equilibrium may be excessively long. This work reports on a simple method for predicting the daily maintenance dose of fluindione after the third intake. In a first step, 37 patients were delivered 20 mg of fluindione once a day, at 6 p.m. for 3 consecutive days. On the morning of the 4th day an INR was performed. During the following days the dose was adjusted to target an INR between 2 and 3. There was a good correlation (r = 0.83, p<0.001) between the INR performed on the morning of day 4 and the daily maintenance dose determined later by successive approximations. This allowed us to write a decisional algorithm to predict the effective maintenance dose of fluindione from the INR performed on day 4. The usefulness and the safety of this approach was tested in a second prospective study on 46 patients receiving fluindione according to the same initial scheme. The predicted dose was compared to the effective dose soon after having reached the equilibrium, then 30 and 90 days after. To within 5 mg (one quarter of a tablet), the predicted dose was the effective dose in 98%, 86% and 81% of the patients at the 3 times respectively. The mean time needed to reach the therapeutic equilibrium was reduced from 13 days in the first study to 6 days in the second study. No hemorrhagic complication occurred. Thus the strategy formerly developed to predict the daily maintenance dose of warfarin from the prothrombin time ratio or the thrombotest performed 3 days after starting the treatment may also be applied to fluindione and the INR measurement.