272. Clinical Utility of Sulfamethoxazole Serum Level Monitoring in the Treatment of Brain Abscesses due to Nocardia Species

Background Although trimethoprim-sulfamethoxazole (TMP-SMX) has consistently demonstrated significant interindividual variability, therapeutic drug monitoring is used to optimize dosing and avoid adverse reactions that may contribute to treatment interruption. While data exists on the use of SMX level monitoring in pneumocystis, there is a lack of data in SMX serum monitoring utility for invasive Nocardia infections. Methods We retrospectively reviewed adults who received TMP-SMX to treat nocardial brain abscess (BA) and underwent SMX testing level from January 2010 to December 2020. Results Overall, 24 patients had Nocardia spp. BA; Twenty-two (91.7%) were treated with TMP-SMX, and 16/22 (72.7%) had a documented SMX serum level. The median age was 64 (IQR 58-69) years, and the majority were males (77.3%). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a higher prevalence of hemodialysis (HD, 42.9% vs. 33%; P=.99) and malignancy (50% vs. 33.3%; P=.65). The most common BA location was the frontal lobe (43.8% vs. 33.3%; P=.99), with a single (68.8% vs. 50%; P=.62) and smaller (1.3 vs. 1.9 cm; P=.58) brain fluid collection, and with fewer midline shift (6.3% vs. 16.7%; P=.48), respectively. The median TMP-SMX duration was 350 days (P=.31). The most common dosing was 2-double strength, three times a day (31.8%). The SMX median level was 158.5 (IQR 120-218) mcg/mL, collected at two hours (75%) post-administration in the induction phase (81.3%). The most common recommendation was to continue therapy based on the level results. Eleven (46%) patients had a level >150 mcg/mL, and 5 (45.5%) reported drug toxicity, including nausea in 3, acute kidney injury in 2, and thrombocytopenia in 2 patients. Ninety-four percent of the patients with SMX levels had surgical intervention for therapeutic purposes vs. 83% of those without it (P=.65). A total of 11 (50%) patients were cured, 3 (18.8%) relapsed, and 2 (12.5%) died. Conclusion Patients with SMX serum level monitoring are more likely to be on HD, during the induction phase and among those with higher and more frequent dosing. About half of patients with SMX levels >150 mcg/mL experienced drug toxicity; however, SMX levels did not impact patient outcome and length of treatment. Disclosures All Authors: No reported disclosures

Depression as is Seen by Molecular Spectroscopy. Phospholipid- Protein Balance in Affective Disorders and Dementia

There is an expanding field of research investigating the instrumental methods to measure the development of affective disorders. The goal of the commentary is to turn the attention of medical practitioners at the molecular spectroscopy techniques (FTIR, Raman and UV-Vis) that can be applied for monitoring and quantification of the phospholipid-protein balance in human blood serum of depressed patients. Even facial overview of cited original research strongly suggests that disturbed phospholipid-protein balance could be one of the biomarkers of affective disorders. The blood serum monitoring of depressed patients would serve as a tool for more effective holistic therapy.

Detection of p53 mutation and serum monitoring alert caused by Marek's disease virus

Background Marek’s disease (MD), as a chicken neoplastic disease, brings huge economic losses to the global poultry industry. The tumor suppressor gene, wild type P53 plays a key role in blocking cell cycle, promoting apoptosis and maintaining stability of genome. The p53 function could change to that of an oncogene from a tumor inhibitory role, if a mutation happened. It will increase risk of cancer incidence. Results It was found that the mutation rate of p53 was 60 percent in experimentally infected and naturally infected chickens. The mutations included point-mutation and deletions, and mostly located in the DNA-binding domain. The most common point mutation happened in five sites, which were 651, 786, 828, 864 and 879 respectively. The mutated P53 can be expressed in tumors of various tissues in an infected chicken because of the lengthening of the half-life of mutated P53. Due to the loss of nuclear localization function, most of mutated P53 were expressed in cytoplasm. The concentration of P53 was decrease in serum of MD infected chicken. Conclusions Results of the current study suggested that p53 mutations with different types were common in MD, and most of mutated P53 were expressed in cytoplasm. Detecting the concertation of P53 and P53 antibody in serum could be helpful for diagnosis and monitor of MD.

Closing the Gap in Surveillance and Audit of Invasive Mold Diseases for Antifungal Stewardship Using Machine Learning

Clinical audit of invasive mold disease (IMD) in hematology patients is inefficient due to the difficulties of case finding. This results in antifungal stewardship (AFS) programs preferentially reporting drug cost and consumption rather than measures that actually reflect quality of care. We used machine learning-based natural language processing (NLP) to non-selectively screen chest tomography (CT) reports for pulmonary IMD, verified by clinical review against international definitions and benchmarked against key AFS measures. NLP screened 3014 reports from 1 September 2008 to 31 December 2017, generating 784 positives that after review, identified 205 IMD episodes (44% probable-proven) in 185 patients from 50,303 admissions. Breakthrough-probable/proven-IMD on antifungal prophylaxis accounted for 60% of episodes with serum monitoring of voriconazole or posaconazole in the 2 weeks prior performed in only 53% and 69% of episodes, respectively. Fiberoptic bronchoscopy within 2 days of CT scan occurred in only 54% of episodes. The average turnaround of send-away bronchoalveolar galactomannan of 12 days (range 7–22) was associated with high empiric liposomal amphotericin consumption. A random audit of 10% negative reports revealed two clinically significant misses (0.9%, 2/223). This is the first successful use of applied machine learning for institutional IMD surveillance across an entire hematology population describing process and outcome measures relevant to AFS. Compared to current methods of clinical audit, semi-automated surveillance using NLP is more efficient and inclusive by avoiding restrictions based on any underlying hematologic condition, and has the added advantage of being potentially scalable.

P15 Lacosamide monitoring in the serum of children with refractory epilepsy

BackgroundLacosamide is indicated for various types of refractory epilepsy and as adjunctive therapy to other antiepileptic medications. Data on monitoring serum levels of lacosamide in pediatric patients is scarce.ObjectiveTo evaluate the correlation between serum levels of lacosamide and the tolerability in children with refractory epilepsy.MethodsThe medical records of 22 children with refractory epilepsy treated with lacosamide at Assaf Harofeh Medical Center were reviewed. Trough serum levels of lacosamide was measured using HPLC and correlated with its efficacy and safety.ResultsMean age of the children was 11 ± 4 (3–18) years. Median lacosamide daily dose was 9.3 (6.6–11) mg/kg and median plasma concentration was 7.1 (5.9–11.9) ug/ml. The therapeutic range of lacosamide serum concentration is 10 to 20 ug/ml. No change in seizures frequency was reported in 21.4% of children with lacosamide concentrations below 10 ug/ml. However, in 40% of the children, reduction of the seizures frequency was reported when serum concentration was above 10 ug/ml. No serious adverse events were reported during therapy. The prospective part of the study was initiated, and the first patients were recruited.ConclusionLarge studies, preferably prospective, on lacosamide serum monitoring including information on correlation with efficacy and safety are warranted.Disclosure(s)Nothing to disclose