Background: Prescribing errors related to the COVID-19 oral antiviral agent nirmatrelvir-ritonavir have been reported and are primarily due to improper renal dosing and significant drug–drug interactions. These patient safety issues are particularly concerning in the long-term care facility (LTCF) population. The Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) is a unique collaborative partnership involving the University of Nebraska Medical Center, Nebraska Medicine, and the Nebraska Department of Health and Human Services (DHHS). ASAP is funded through the Nebraska DHHS healthcare-associated infections and antimicrobial resistance (HAI/AR) program and was established in 2016, with a primary focus of promoting safe and effective antimicrobial use in Nebraska. In 2022, ASAP developed a statewide pharmacist-led service to assist LTCFs in evaluating prescriptions for COVID-19 oral therapeutics. We studied the impact of ASAP pharmacist intervention on COVID-19 oral antiviral prescriptions. Methods: ASAP created a centralized LTCF treatment request process for oral antivirals. A REDCap survey hosted on a dedicated program webpage was used to collect requests for treatment submitted by any LTCF in Nebraska, including assisted living facilities. An ASAP pharmacist reviewed each survey submission for renal and hepatic function, drug–drug interactions, date of symptom onset, and ability to take oral medications. After pharmacist approval, delivery of the appropriate COVID-19 therapeutic to the LTCF was coordinated with the dispensing pharmacy. The pharmacists recorded the specific interventions for each treatment in the program database. Descriptive analyses were used to study the program impact. Results: In total, 630 courses of oral COVID-19 antivirals were administered to Nebraska LTCF residents through the ASAP program in 2022. The median patient age was 84 years, and 59% were female. Most dispensed courses (n = 410, 65%) needed pharmaceutical interventions upon review for 506 individual interventions. The most frequent intervention was to hold or adjust doses of concomitant medications in 205 patients (33%), followed by antiviral dose adjustment for renal function in 117 patients (19%), and selecting an alternative COVID-19 therapy due to drug–drug interactions in 108 patients (17%). COVID-19 therapeutic agents were changed upon ASAP intervention to be in compliance with the National Institute of Health COVID-19 treatment guidelines in 37 patients (6%). Conclusions: Pharmacist review of oral antiviral prescriptions for COVID-19 through a public health–supported initiative identified and prevented potential patient safety issues in LTCF residents. Future studies should analyze the impact of similar interventions on patient outcomes.

Disclosures: None

Background: A penicillin allergy guidance document containing an algorithm for challenging penicillin allergic patients with β-lactams was developed by the antimicrobial stewardship program (ASP). As part of this algorithm, a “graded challenge” order set was created containing antimicrobial orders and safety medications along with monitoring instructions. The process is designed to challenge patients at low risk of reaction with infusions of 1% of the target dose, then 10%, and finally the full dose, each 30 minutes apart. We evaluated outcomes from the order set. Methods: Orders of the graded challenge over 17 months (March 2018 through July 2019) were reviewed retrospectively. Data were collected on ordering and outcomes of the challenges and allergy documentation. Use was evaluated based on ASP-recommended indications: history of IgE-mediated or unknown reaction plus (1) no previous β-lactam tolerance and the reaction occurred >10 years ago, or (2) previous β-lactam tolerance, now requiring a different β-lactam for treatment. Only administered challenges were included and descriptive statistics were utilized. Results: Of 67 orders, 57 graded challenges were administered to 56 patients. The most common allergies were penicillins (87.7%) and cephalosporins (38.6%), with the most common reactions being unknown (41.7%) or hives (22%). The most common antibiotics challenged were ceftriaxone (43.9%), cefepime (21.1%), and cefazolin (5.3%). Antibiotics given prior to challenge included vancomycin (48.2%), fluoroquinolones (35.7%), carbapenems (21.4%), aztreonam (19.6%), and clindamycin (12.5%). The median duration of challenged antibiotic was 6 days. The infectious diseases service was consulted on 59.6% of challenges and 75.4% of challenges were administered in non-ICU settings. There was 1 reaction (1.8%) involving a rash with the second infusion, which was treated with oral diphenhydramine and had no lasting effects. Based on indications, 80.7% of challenges were aligned with ASP guidance criteria. The most common use outside of these criteria was in patients without IgE-mediated reactions (10.5%). Most of these had minor rashes and could have received a full dose of a cephalosporin. Allergy information was updated in the electronic health record after 91.2% of challenges. Conclusions: We demonstrated the utility of a graded challenge process at our academic medical center. It was well tolerated, ordered frequently by noninfectious diseases clinicians, administered primarily in non-ICU settings, and regularly resulted in updated allergy information in the medical record. With many patients initially receiving broad-spectrum antibiotics with high costs or increased rates of adverse effects, graded challenges can potentially prevent the use of suboptimal therapies with minimal time and resource investment.

Funding: None

Disclosures: Scott Bergman reports a research grant from Merck.

Encephalitis causes high morbidity and mortality. An incidence of 4.3 cases of encephalitis/100 000 population has been reported in the UK. We performed a retrospective evaluation of the diagnosis and management of adults admitted to hospital with a clinical diagnosis of encephalitis/meningoencephalitis. Clinical, laboratory and radiological data were collated from electronic records. Thirty-six patients, median age 55 years and 24 (67%) male were included. The aetiology was confirmed over nine months in 25 (69%) of whom 16 were infections (six viral, seven bacterial, two parasitic and one viral and parasitic co-infection); 7 autoimmune; 1 metabolic and 1 neoplastic. Of 24 patients with fever, 15 (63%) had an infection. The median time to computed topography, magnetic resonance imaging and electroencephalography (EEG) was 1, 8 and 3 days respectively. Neuroimaging was abnormal in 25 (69%) and 17 (89%) had abnormal EEGs. Only 19 (53%) received aciclovir treatment. Six (17%) made good recoveries, 16 (44%) had moderate disability, 8 (22%) severe disability and 6 (17%) died. Outcomes were worse for those with an infectious cause. In summary, a diagnosis was made in 69.4% of patients admitted with encephalitis/meningoencephalitis. Autoimmune causes are important to consider at an early stage due to a successful response to treatment. Only 53% of patients received aciclovir on admission. Neuroimaging and EEG studies were delayed. The results of this work resulted in further developing the clinical algorithm for managing these patients.

We aim to re-prove a theorem conjectured by Gauss, namely there are exactly nine imaginary quadratic fields $\mathbf{Q}(\sqrt{-q})$ with class number one: specifically the list is $q\in \{3,4,7,8,11,19,43,67,163\}$. Our method initially follows an idea of Goldfeld, but rather than using an elliptic curve of analytic rank three (provided by the Gross–Zagier theorem), we instead use an elliptic curve of analytic rank two, where this $L$-function vanishing can be proven by modular symbols rather than a difficult height formula. It is already clear that Goldfeld’s work yields a constant lower bound for the class number by such means, but unfortunately it seems that even for the best choice of elliptic curve this numerical constant is less than 1, unless one can show non-trivial cancellation in the $L$-function coefficients restricted to values taken by quadratic forms. To show the latter, we consider a specific analytic rank-two elliptic curve with complex multiplication by $\mathbf{Q}(\sqrt{-1})$, and then by adapting a result of Hooley’s regarding equi-distrbution of roots of a quadratic polynomial to varying moduli, are able to show that there is indeed sufficient coefficient cancellation, giving an effective resolution of class number one. As we use various aspects of the principal form, our proof seems inapplicable for larger class numbers. We also comment on the possibility of using spectral techniques (following Templier and Tsimerman) to show the desired coefficient cancellation, though postpone the details of this to elsewhere.