1101. Implementing a Beta-Lactam Therapeutic Drug Monitoring Program: Experience from a Large Academic Medical Center

Background Beta-lactams (BL) are the cornerstone of antimicrobial treatment for infections. Beta-lactam therapeutic drug monitoring (BL-TDM) optimizes drug concentrations to ensure maximal efficacy and minimal toxicity. The goals of this study were to describe the implementation process of a BL-TDM program and to further describe our experience using BL-TDM in clinical practice. Methods This was a retrospective review of adult patients with available BL-TDM between January 2016 and November 2019 at the University of Florida (UF) Health Shands Hospital. Total serum concentrations of BL were measured in the Infectious Diseases Pharmacokinetics Lab (IDPL) at UF, using a validated ultrahigh pressure liquid chromatography assay with triple quadrupole mass spectroscopy (LC-MS-MS). At our institution, TDM is available for 11 BLs and in-house assays are performed from Mon-Fri for most BLs. Results A total of 3,030 BL concentrations were obtained. An analysis was performed on the first BL-TDM encounter in 1,438 patients. The median age was 57 years (IQR, 41-69) and the median BMI was 27.5 kg/m2 (IQR, 22.5-34.5). On the day of BL-TDM, the median serum creatinine was 0.83 (IQR, 0.59-1.30). Fifty-one percent of patients (n=735) were in an ICU at the time of BL-TDM with a median SOFA score of 6 (IQR, 3-9). BL-TDM was most frequently performed on cefepime (61%, n=882), piperacillin (15%, n=218), and meropenem (11%, n=151). The BL was administered as a continuous infusion in 211 (15%) patients. An interim analysis of 548 patients showed that BL-TDM was performed a median of 2 days (IQR, 1-4) from the start of BL therapy and resulted in a dosage adjustment in 26% (n=145). Conclusion BL-TDM was performed in older, non-obese patients with normal renal function. Over half of the evaluated patients were in an ICU at the time of TDM. This finding emphasizes the value of BL-TDM in the ICU setting because altered pharmacokinetics during critical illness has been linked to enhanced BL clearance. Interestingly, BL-TDM resulted in dosage adjustment in 1 in 4 patients who were receiving licensed BL dosing regimens, thus highlighting the role of TDM in dose individualization. BL-TDM was performed most commonly within the 72-hours of therapy initiation. Early BL-TDM has been shown to improve patient outcomes and should be promoted. Disclosures Venugopalan Veena, PharmD, Melinta (Other Financial or Material Support, Received a stipend for participation in a drug registry)Merck (Other Financial or Material Support, Received a stipend for participation in a drug registry) Charles A. Peloquin, Pharm.D., Nothing to disclose

1257. Re-Evaluation of Cefepime or Piperacillin-Tazobactam to Decrease Use of Carbapenems in ESBL-Producing Enterobacterales Urinary Tract Infections (REDUCE-UTI)

Background Carbapenems (CBP) are considered first-line for infections caused by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). However, recent literature suggests that cefepime (FEP) and piperacillin-tazobactam (TZP) may produce similar outcomes vs. CBPs for the treatment of ESBL-E urinary tract infections (UTIs). The goal of this study was to determine if non-carbapenem (NCBP) therapy with FEP or TZP is as effective as CBPs for the treatment of ESBL-E UTIs. Methods This was a retrospective observational study of patients admitted to the hospital from January 1st, 2016 to June 30th, 2020 with a urine culture positive for ESBL-E. Patients were included if they received a study antibiotic (meropenem, ertapenem, TZP, or FEP). Patients were excluded if they had any of the following: absence of pyuria, prior receipt of study antibiotic, CBP-resistant organism isolated in urine culture, polymicrobial urine culture, end-stage renal disease, or concomitant gram-negative infection. The primary outcome was clinical cure defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days, and resistance within 30 days. Results A total of 133 patients were included based on definitive therapy received; 69 (52%) received CBP and 64 (48%) received NCBP therapy. Of the total patient population, 17 (13%) were admitted to the intensive care unit, 84 (63%) had a complicated UTI, and 64 (48%) had pyelonephritis. Baseline characteristics were similar between the two groups. There was no difference in clinical cure between the CBP and NCBP therapy groups (96% vs. 97%, p = 1.0). Additionally, no differences in secondary outcomes were observed. Subgroup analyses were performed in patients with specific pathogens, uncontrolled genitourinary source, complicated UTI, and pyelonephritis. These analyses did not reveal any differences in primary or secondary outcomes between the two groups. Conclusion FEP and TZP may be reasonable CBP-sparing alternatives for the treatment of ESBL-E UTIs as clinical and microbiological outcomes were similar with these NCBP agents vs. CBPs in this study population. Disclosures Venugopalan Veena, PharmD, Melinta (Other Financial or Material Support, Received a stipend for participation in a drug registry)Merck (Other Financial or Material Support, Received a stipend for participation in a drug registry)

Retrospective analysis of prescriptions for the treatment of cardiovascular diseases in the program «Affordable medicines» on the example of a pharmacy

Improving access and affordability for patients of essential drugs in the treatment of cardiovascular diseases is a priority because mortality and a morbidity rates are high in Ukraine. In April 2017, the government launched the reimbursement program «Affordable medicines», which included drugs to treat cardiovascular disease. The aim of the study was a retrospective analysis of released prescriptions on the example of the pharmacy № 1 in Vynohradiv, Transcarpathian region, which serves patients from the city and Vynohradiv district, which allowed us to analyze and compare the structure of the appointments of primary care physicians and to identify the main INN, stocks of which should be a priority in pharmacies for the treatment of cardiovascular diseases. The objects of study were the records of the pharmacies about drugs released in the program for 24 months, the Orders of the Ministry of Health of Ukraine, the CMU Decisions, the Drug Registry for cardiovascular diseases, the cost for reimbursement in the program «Affordable Medicines» as well. Frequency analysis methods, ATC/DDD methodology, as well as methods of comparative, logical and content analysis were used. Data for the selected period were analyzed using frequency analysis methods and ATC/DDD method, and it was found that enalapril, spironolactone and clopidogrel were in the lead. It was found that the majority of patients in 2017 chose free drugs (more than 80%), and in 2018–2019 this rate was only 60%. According to prescriptions, about 92% are patients from Vynohradiv district, which confirms the improvement of access to drugs in the program «Affordable Medicines» for the rural population. The results were verified by comparing the released e-prescriptions for cardiovascular diseases in the city and district and found that the structure of prescriptions for cardiovascular diseases on e-prescriptions from April 2019 to April 2020 remains stable and the main share is 4 INN: clopidogrel, enalapril, amlodipine and bisoprolol. It is determined that in order for the «Affordable Medicines» program, the provision and convenience of patients, the pharmacies need to have an expanded list of trade names and a sufficient supply of enalapril, spironolactone, clopidogrel and bisoprolol.

OP0288 ANTI-IL1 TREATMENT IN COLCHICINE RESISTANT PEDIATRIC FMF PATIENTS-REAL LIFE DATA FROM THE HELIOS REGISTRY

Background:FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine resistant/intolerant FMF patients.Objectives:We aimed to investigate the efficacy and safety of anti-IL1 treatment in pediatric FMF patients in our local (HELIOS) registry.Methods:HELIOS (Hacettepe univErsity eLectronIc research fOrmS) is a web-based biological drug registry for pediatric rheumatology patients (helios.hacettepe.edu.tr). Data were recorded at biological treatment onset (month 0), at month 6 and yearly thereafter in patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agent.Results:Forty pediatric FMF patients were included to the study group (67% female).Thirty-four patients received continous anti-IL1 treatment. The mean age at the start of the colchicine was 5.55±3.87 years. Age at onset of the anti-IL1 treatment was 11.47±5.41 with a mean follow-up duration of 3.87±1.96 years. Apart from two patients, all of them had biallelic exon-10 mutations.We have also given anti-IL1 treatment on an on-demand basis in six adolescent patients. Five of them were having very severe attacks during menstrual periods and one was having attacks during extreme stress periods along with very high CRP levels. The quality of life has markedly improved and these patients no longer reveal any CRP elevation.Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients were treated with canakinumab. Anti-IL1 treatment decreased the CRP levels, number and severity of the attacks. (Figure 1.) There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leukopenia with anakinra and one patient had thrombocytopenia with canakinumab. We have discontinued anti-IL1 treatment until the cytopenia subsided. We have switched to on-demand therapy in one patient, started the same treatment and gradually increased the dose in the other two patients. There were no malignancy or other severe adverse reactions.Figure 1.Conclusion:Anakinra and canakinumab are efficient and safe alternatives in colchicine resistant and intolerant pediatric FMF patients. We also for the first time, report on-demand use of anti-IL1 in pediatric FMF patients. We suggest that on-demand treatment should be considered under certain circumstances where the trigger is known and short-lasting (such as menstruation and periods of extreme stress)Acknowledgments:Authors would like to thank Elif Arslanoglu Aydin, Armagan Keskin, Kubra Yuksel and Emil Aliyev for their contribution to the HELIOS registryDisclosure of Interests:Erdal Sag Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Fuat Akal Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Erdal Atalay Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ummusen Kaya Akca Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Selcan Demir Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Dilara Demirel Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ezgi Deniz Batu Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Yelda Bilginer Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis

Anti-IL1 treatment in colchicine-resistant paediatric FMF patients: real life data from the HELIOS registry

Objectives FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine-resistant/intolerant FMF patients. We aimed to investigate the efficacy and safety of anti-IL1 treatment in paediatric FMF patients in our local [Hacettepe univErsity eLectronIc research fOrmS (HELIOS)] registry. Methods HELIOS is a web-based biologic drug registry for paediatric rheumatology patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agents. Results Forty paediatric FMF patients (34 continuous and six on-demand use) were included. Among the continuously treated group (61.7% female), the mean age at the start of colchicine was 5.55 (3.87) years. Age at onset of the anti-IL1 treatment was 11.47 (5.41) years with a mean follow-up duration of 3.87 (1.96) years. Apart from two, all patients had biallelic exon-10 mutations. We also gave anti-IL1 treatment on an on-demand basis in six patients. Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients with canakinumab. Anti-IL1 treatment decreased the CRP levels and number and severity of the attacks. There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leucopenia with anakinra and one patient had thrombocytopenia with canakinumab. There was no malignancy or other severe adverse reactions. Conclusion Anakinra and canakinumab are efficient and safe alternatives in colchicine-resistant or -intolerant paediatric FMF patients. We also, for the first time, report on-demand use of anti-IL1 in paediatric FMF patients.

Long-Distance Skiing and Incidence of Hypertension

Background: Hypertension is the leading risk factor for death worldwide, and high levels of physical activity are associated with a lower incidence of hypertension. The associations of excessive levels of exercise and incidence of hypertension are less well known. We aim to compare the incidence of hypertension among 206 889 participants in a long-distance cross-country skiing event and 505 542 people randomly sampled from the general population (matched to the skiers on age, sex, and place of residence). Methods: Skiers’ best performance (in percent of winning time) and number of completed races during the study period were associated with incidence of hypertension after participation in Vasaloppet. Hypertension was defined as prescription of blood pressure–lowering drugs as obtained from the national drug registry. Models were adjusted for sex, age, education, and income (total effect). Results: During a median time of risk of 8.3 years, skiers had a lower incidence of hypertension compared with nonskiers (hazard ratio [HR], 0.59 [95% CI, 0.58–0.60]). Among the skiers, better performance (in percent of winning time) in Vasaloppet was strongly associated with a lower incidence of hypertension (fastest fifth: HR, 0.41 [95% CI, 0.39-0.42]; slowest fifth: HR, 0.78 [95% CI, 0.75–0.81]). The association was nearly linear and did not differ between sexes. Among the skiers, a weaker association was seen between the number of completed races during the study period and the incidence of hypertension (1 race: HR, 0.63 [95% CI, 0.62–0.65]; >5 races: HR, 0.51 [95% CI, 0.50–0.53]). A subanalysis of 10 804 participants including adjustment for lifestyle factors showed similar results. Conclusions: Participation in a long-distance skiing event was associated with a 41% lower incidence of hypertension over the next 8 years compared with nonparticipation. A near linear association between performance and incidence of hypertension was observed. This adds to the list of beneficial effects of intensive training, because hypertension is the leading risk factor of premature death globally.

Ataluren use in patients with nonsense mutation Duchenne muscular dystrophy: patient demographics and characteristics from the STRIDE Registry

Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (DMD) in clinical practice (NCT02369731). Here, we describe the initial demographic characteristics of the registry population. Patients & methods: Patients will be followed up from enrollment for ≥5 years or until study withdrawal. Results & conclusion: As of 9 July 2018, 213 DMD boys were enrolled from 11 countries. Mean (standard deviation) ages at first symptoms and at study treatment start were 2.7 (1.7) years and 9.8 (3.7) years, respectively. Corticosteroids were used by 190 patients (89.2%) before data cut-off. Mean (standard deviation) ataluren exposure was 639.0 (362.9) days. Six patients withdrew. STRIDE is the first drug registry for patients with DMD and represents the largest real-world registry of patients with nmDMD to date.