Mean Duration Of Therapy Research Articles

Effectiveness and tolerability of methotrexate monotherapy in Crohn's disease patients: a multicenter observational study.

Methotrexate monotherapy is recommended as a maintenance therapy for Crohn's disease (CD). However, long-term follow-up data are scarce. We aimed to examine the effectiveness and tolerability of methotrexate monotherapy in 94 CD patients from three inflammatory bowel disease Clinics in Korea. This was a multicenter retrospective observational study. Patients with active CD treated with methotrexate monotherapy were included. Clinical characteristics, laboratory indicators, endoscopy indices were evaluated at baseline, 6, 12, and 24 months. Independent factors associated with long-term clinical and endoscopic outcomes were determined. Methotrexate was administered orally (70.2%) or parenterally (29.8%). The mean methotrexate induction dose was 15.3 ± 0.4 mg/week, and the mean duration of therapy was 26.2 months. Of 76 patients who were treated for >6 months, the clinical remission rates were 76.3%, 74.6%, and 80.0% at 6, 12, and 24 months, respectively, by per-protocol analysis. The mean CRP levels were 7.5 ± 1.3, 5.3 ± 1.2, 3.8 ± 0.7, and 2.6 ± 0.5 mg/L at 0, 6, 12, and 24 months, respectively. Of 31 patients who underwent follow-up endoscopy after 27.5 months, the endoscopic remission rate was 38.7%. Baseline hemoglobin level <10 g/dL was a significant independent factor negatively associated with clinical remission at 6 [odds ratio (OR): 0.023, 95% confidence interval (CI): 0.003-0.206, p = 0.001] and 12 (OR: 0.079, 95% CI: 0.009-0.699, p = 0.023) months. Parenteral administration was a significant independent factor positively associated with clinical remission (OR: 11.231, 95% CI: 1.027-122.811, p = 0.047) and endoscopic remission (hazard ratio: 4.711, 95% CI: 1.398-15.874, p = 0.012) at 12 months. Methotrexate monotherapy was effective and tolerable as a maintenance therapy in CD patients.

Subglottic hemangioma—prevalence, clinical presentation and treatment

This retrospective study aimed to investigate the clinical features and treatment of pediatric subglottic hemangioma (SH), identify risk factors for treatment-induced adverse effects, and identify a strategy for timely therapy discontinuation in children diagnosed with SH at the national pediatric center. Medical records of patients presented with stridor from 2010 to 2020 were retrieved and assessed, the diagnosis of SH was established via flexible bronchoscopy, and the patients were treated using propranolol with a subsequent gradual dose increase to 3 mg/kg body weight daily. A two-week oral steroids trial was added for those with circumferential lesions. Early indicators of a good therapeutic response included decreased stridor and primary lesion size on follow-up bronchoscopy performed one week after propranolol commencement. Duration of therapy, tailored individually based on bronchoscopy findings, and at least twelve months of treatment were the two main criteria for deciding therapy termination. Outpatient visits were arranged at least every three months. Our results showed that SH was the third most frequent cause of stridor (15/137 patients), and biphasic stridor was uniformly present as a typical symptom. Both clinical improvement and bronchoscopy findings confirmed the efficacy of the treatment. The mean therapy duration was 17 months. The only significant adverse event observed was hypoglycemic seizures in one infant. Contributory factors were all prematurity, high propranolol dose (3 mg/kg) and poor oral intake. Collectively, defining a safe and timely protocol for therapy cessation and avoidance of risk factors for adverse effects is the mainstay of SH treatment.

680. Utility of Cefoxitin for the Treatment of ESBL-producing E. coli Urinary Tract Infections

Abstract Background Carbapenems are regarded as first-line agents for the treatment of ESBL-producing bacterial infections, even when in vitro activity to other beta lactams is demonstrated. However, overuse is associated with the selection of beta-lactamases that can hydrolyze carbapenems. Patients with isolated urinary tract infections due to ESBL–producing E. coli potentially have a lower burden of infection ("low inoculum"). These patients are frequently less ill and may benefit from non-carbapenem therapy. Cephamycins have in vitro activity against ESBL–producing Enterobacterales, and may be useful in the treatment of ESBL E. coli urinary tract infections as a carbapenem sparing agent. Methods Patients 18 years of age and older, hemodynamically stable with negative blood cultures and who demonstrated signs and symptoms of a urinary tract infection with a urine culture showing ESBL E. coli, were eligible to participate. Patients were started on initial antimicrobial therapy at the discretion of the admitting physician, and if the urine culture showed ESBL E. coli with an MIC of less than 8, the antimicrobial stewardship team requested to switch the patient to Cefoxitin 2 g intravenously every 6 hours, via extended infusion. The dose was renally adjusted as appropriate, and patients with beta-lactam allergies were excluded. Results 46 patients were evaluated between May 2017-April 2022. Patients received antibiotics for 2.6+1 day before the switch to Cefoxitin. The mean duration of therapy with Cefoxitin was 4.5+2.2 days. All 46 patients had resolution of fever and dysuria. Six patients were readmitted within 30 days, but none were due to a urinary tract infection. 30 patients had a repeat urinalysis at 48 hours, and all demonstrated reduction in pyuria. 39 patients had a repeat urine culture following completion of therapy, and 36 had converted to culture-negative status. Conclusion Cefoxitin is a useful agent for the treatment of ESBL E. coli urinary tract infections. The optimal dose appears to be 2 g intravenously every 6 hours, via extended infusion, in patients with normal creatinine clearance. Further larger studies, involving patients with pyelonephritis, are needed to validate these findings. Disclosures Ramesh V. Nathan, MD, Eli Lilly: Grant/Research Support|PPD: Grant/Research Support.

1745. Drilling Down on Antibiotic Use in Dental Clinics

Abstract Background Dentists are the third highest prescribers of antibiotics in outpatient settings in the US with reported suboptimal prescribing rates between 30 and 85%. The 2019 American Dental Association guidelines provide guidance for antibiotic use based on the presence of dental pain and/or swelling and whether definitive conservative dental treatment is immediately available. Our primary objective was to assess the appropriateness of systemic antibiotic use in our institution’s dental clinics based on these guidelines. Our secondary objectives were to describe antibiotic choice, duration of therapy, and use of non-first line antibiotics. Methods From January 2021 through December 2021 data on antibiotics prescribed during all patient encounters in our institution’s dental clinics were abstracted from the electronic medical record. Detailed review was performed on a randomly generated sample of 120 unique patient encounters (10 each month). First line antibiotics included penicillin, amoxicillin, and amoxicillin-clavulanate. Results Of 14,381 dental clinic encounters, 2,413 (16%) resulted in one or more antibiotic prescriptions (total of 2788 prescriptions). Non-first line antibiotics accounted for 402 (14%) of all antibiotic prescriptions (Table). Sixty-nine (17%) of non-first line antibiotics were prescribed for patients with no documented beta-lactam allergy. Of the 333 non-first line antibiotics prescribed for patients with a documented beta-lactam “allergy”, a first line antibiotic or cephalexin could have been used in 120 (36%). Of 120 patient encounters undergoing detailed review, antibiotics were prescribed for treatment (not prophylaxis) in 115 (96%). Antibiotics were indicated in only 16 of 108 (14%) evaluable patients. The mean duration of therapy was 7.2 days. Eleven percent of prescriptions were longer than 7 days. Conclusion At our institution most antibiotics prescribed from our dental clinics were for treatment, were commonly not indicated, and were usually prescribed for 7 days or more. First line antibiotics and cephalexin could have replaced nearly half of the non-first line antibiotics prescribed. Developing a clinical pathway incorporating updated guidelines and management of patients with beta-lactam “allergies” may improve patient care. Disclosures All Authors: No reported disclosures.

Follicle-stimulating hormone effectiveness in male idiopathic infertility: What happens in daily practice?

To assess the effectiveness of follicle-stimulating hormone (FSH) administration in male idiopathic infertility in a clinical setting. A retrospective real-world study was carried out, including all consecutive FSH-treated infertile men attending the Andrology Unit of Modena (Italy) from June 2015 to May 2022. Medical history, physical and andrological examinations, hormonal and seminal parameters, therapeutic management and pregnancy data were collected. The primary endpoint was the number of pregnancies obtained after FSH administration, whereas semen parameters change was the secondary outcome. A total of 194 of 362 (53.6%) infertile men, eligible according to the Italian Health System regulations, were treated with FSH (mean age 37.9±6.1 years). Following FSH administration (mean therapy duration 9.1±7.1 months), 43 pregnancies were recorded (27.6%), of which 22 occurred naturally and 21 after assisted reproduction. A significant increase in sperm concentration (9.9±12.2 vs. 18.9±38.9 million/mL, p=0.045) was detected after treatment, together with a significant increase in normozoospermia (from 1.0% to 5.1%, p=.044) and a reduction in azoospermia rate (from 9.8% to 7%, p=0.044). Dividing the cohort in FSH-responders and non-responders, in terms of pregnancy achieved, higher sperm concentrations (15.7±26.6 vs. 22.2±25.7 million/mL, p=0.033) and progressive sperm motility (18.0±18.2 vs. 27.3±11.3, p=0.044) were found in pregnancy group. Our experience suggests that FSH, empirically administered to men with idiopathic infertility, leads to pregnancy in one out of four patients and increases sperm concentration. Although the expected limits because of a real-world data study, the number of FSH-treated patients required to achieve one pregnancy seems to be lower in clinical setting if compared to previously published data.

ODP242 Safety of SGLT2-Inhibitors in Patients with Multiple Myeloma and Diabetes

Abstract Background An estimated 10-20% of patients with multiple myeloma (MM) have type 2 diabetes (T2DM). About half of patients with MM will experience renal insufficiency,the risk of which increases in the setting of T2DM. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) are beneficial in patients with chronic kidney disease (CKD) due to diabetic or hypertensive nephropathy, the role of SGLT2i in MM-related CKD is unknown. Moreover, as MM therapies target the immune system, concurrent use with SGLT2i may increase the risk of adverse events such as infections. The current work is the first to examine the potential benefit and safety of SGLT2i in patients with MM and T2DM. Methods This study was approved by the Institutional Review Board. A retrospective cohort study was performed on patients aged 18 years or older with MM who received SGLT2i therapy between March 2013 and December 2020 at a quaternary academic medical center. Electronic medical records were reviewed for the following data: demographics, comorbidities, MM parameters, medication and medical history, SGLT2i usage and duration, and hemoglobin A1c(HbA1c) and serum creatinine pre- and post-SGLT2i initiation. Data are presented as mean ± standard deviation or counts and percentages, and was analyzed using SPSS software (version 25. 0, IBM Corp). Results In total, 50 patients were identified. Patients who were diagnosed with MM after initiation of SGLT2i (n= 12), did not have any MM data available (n=1), or for whom SGLT2i usage could not be verified (n= 4) were excluded. Thirty-three patients were included in the final analysis. The mean age was 63 (±7.8) years, 63.6% were male, and 87.9% had active MM or MM in remission. Most had received stem-cell transplantation (55. 0%) and multiple lines of chemotherapy (63.6%) prior to SGLT2i initiation. The average HbA1c was 7.4% (±1.2%) and 20% of patients had CKD prior to SGLT2i initiation. The overall SGLT2i discontinuation rate was 42.4%, and the mean duration of therapy was 2.2(±1.5) years. Notably, 21.4% of discontinuation events were due to an increase in creatinine; however, for the entire cohort, there were no statistically significant changes in serum creatinine, total body weight, HbA1c, or 24-hour urine protein at 15 months’ follow-up. Other reasons for SLGT2i discontinuation included loss to follow-up, change of health insurance coverage for SGLT2i, and unrelated hospital admission. Genitourinary infection was not cited as a reason for any SGLT2i discontinuation. Conclusion SGLT2i therapy may be safe in patients with MM and T2DM, but no benefit was found with respect to serum creatinine, HbA1c, or 24-hour urine protein. Prospective research is required to further evaluate the potential benefit and safety of SGLT2i therapy in this population. Presentation: No date and time listed

ODP259 Evaluating the Efficacy and Safety of Long-Acting GLP-1 Receptor Agonist in T1DM Patients

Abstract Introduction GLP-1 receptor agonist is a medication class that mimics the endogenous incretin hormone GLP-1. Short-acting GLP-1 agents were studied as adjunct therapies in type 1 diabetes (T1DM) but not approved due to concern of increased diabetic ketoacidosis (DKA) risk. Long-acting GLP-1 medications are still commonly prescribed for T1DM patients. One study has assessed the impact of a long-acting GLP-1 in 11 T1DM patients. No hospitalizations were observed, and time in range was not reported. [1] Our study aims to evaluate the efficacy and safety of long-acting GLP-1 medications in a larger cohort of T1DM patients. Methodology We conducted a retrospective chart review of T1DM patients taking a long-acting GLP-1 for at least three months. ICD-10 code E10. Type 1 diabetes mellitus was used to search our institution's Electronic Health Record system (EPIC). Primary parameters collected included A1C and glycemic trends. Data analysis was done by averaging values over a two-year period before and after starting the medication. Results We identified 27 participants with T1DM (mean age 42yrs, mean T1DM duration 18.1yrs) on a long-acting GLP-1 (semaglutide 70.4%, dulaglutide 33.3%, long-acting exenatide 3.7%, albiglutide 3.7%). Mean therapy duration was 24.28±19. 01mo. A1C values decreased significantly from7.61±1. 08% to 7.16±0.73% (p=0. 015, N=25). Per CGM data, average time in range (TIR) increased significantly from48.82±22.35% to64.70±16.58% (p=0. 0002, N=15), average time in hyperglycemia decreased from42.39±23.32% to 31.58±16.65% (p=0. 019, N=14) and 14-day blood mean glucose decreased from 190.40±38.42 mg/dl to 167. 06±25.86 mg/dl (p=0. 001, N=17). There were no statistically significant differences in time in hypoglycemia and incidence of DKA. Hyperglycemic and hypoglycemic episodes were defined per patients’ individualized CGM settings (most commonly Blood Glucose levels&amp;gt;180 and &amp;lt;70 respectively). Patients’ weight decreased non-significantly from182. 00±50.92 lbs to 170.88±51.37 lbs (p=0.128, N=8). There were no ER visits or hospitalizations for DKA while on GLP-1 therapy. Conclusion There is an urgent need for strategies to improve glycemic control and reduce morbidity and mortality in T1DM. Long-acting GLP-1s are a promising adjunct to insulin. Our study is the first to demonstrate significant A1C reduction and TIR increase without increased hypoglycemia and DKA risk in 27 T1DM patients on long-acting GLP-1s. Longer prospective studies are warranted. Presentation: No date and time listed

S1457 Endoscopic Vacuum Therapy for Treatment of Bariatric Surgery Complications: A Systematic Review and Meta-Analysis

Introduction: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are 2 common bariatric surgeries for treatment of obesity. Although the complication rate for post-bariatric surgery gastric leaks are low, given how frequently these surgeries are being performed, having safe and effective therapies available for complications is crucial for patient outcomes. Revisional surgeries can significantly increase the risk of mortality in these patients so avoiding them is ideal but if revisional surgery does occur, having post-op management options would be valuable. Endoscopic vacuum therapy (EVT) has emerged in recent years as a potential option for management of luminal wounds. EVT is based upon endoscopically applying sponges to the area of a leak and negative pressure is applied to draw off fluid and promote granulation tissue formation along with healing. In this study we aim to review and analyze all currently available data on applying EVT to post-bariatric surgery leaks specifically focusing on success rate, complication rate, mean duration of therapy, and number of sponge changes to see if it’s a therapy warranting further research. Methods: Pubmed, Embase, and Cochrane were searched from inception to through May 2022 for studies reporting success and complication rates for EVT used for bariatric surgery associated gastric leaks whether it was for initial therapy or after revisional therapy for SG and RYGB surgeries. We included both retrospective and prospective studies in our analysis. Using I2 we assessed heterogeneity and calculated 95% confidence intervals using fixed or random effect models. Results: Six studies, totaling 81 patients, were included in the analysis. The total clinical success rate was 89.5% (CI: 83-96%. P < 0.001). The adverse event rate among all studies was 4.5% (95% CI: 0.2-8.7%. P = 0.041). There were 6 adverse events related to EVT noted in this review. The one mortality event that occurred in this review was presumed to be secondary to deconditioning during the recovery period and not EVT itself and thus wasn’t counted in adverse outcomes. EVT associated complications were related to bleeding and abscess formation. Conclusion: Based upon our currently available data, EVT appears to be a viable and safe option for the treatment of post-bariatric surgery (specifically SG and RYGB) gastric leaks. Larger prospective studies appear reasonable and would allow for a more powerful meta-analysis to further evaluate EVT as a potential therapy.Figure 1.: Success and adverse event rates for endoscopic vacuum therapy

Comparison of Two Endoscopic Therapeutic Interventions as Primary Treatment for Anastomotic Leakages after Total Gastrectomy.

Simple SummaryAn esophagojejunal anastomotic leak after oncological gastrectomy is a life-threatening complication. Endoscopic treatment offers the possibility of minimally invasive diagnosis and immediate effective therapy in one session. A retrospective, single-center analysis of two different endoscopic strategies as first-line treatment options was performed.Introduction: An esophagojejunal anastomotic leak following an oncological gastrectomy is a life-threatening complication, and its management is challenging. A stent application and endoscopic negative pressure therapy are possible therapeutic options. A clinical comparison of these strategies has been missing until now. Methods: A retrospective analysis of 14 consecutive patients endoscopically treated for an anastomotic leak after a gastrectomy between June 2014 and December 2019 was performed. Results: The mean time of the diagnosis of the leakage was 7.14 days after surgery. Five patients were selected for a covered stent, and nine patients received endoscopic negative pressure therapy. In the stent group, the mean number of endoscopies was 2.4, the mean duration of therapy was 26 days, and the mean time of hospitalization was 30 days. In patients treated with endoscopic negative pressure therapy, the mean number of endoscopies was 6.0, the mean days of therapy duration was 14.78, and the mean days of hospitalization was 38.11. Treatment was successful in all patients in the stent-based therapy group and in eight of nine patients in the negative pressure therapy group. Discussion: Good clinical results in preserving the anastomosis and providing sepsis control was achieved in all patients. Stent therapy resulted in anastomosis healing with a lower number of endoscopies, a shorter time of hospitalization, and rapid oral nutrition.

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies-Insights From a Retrospective Case Series.

BackgroundDespite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations.MethodsWe retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0–281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases).ResultsTen patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5–65). The mean sirolimus level was 8.52 ng/ml (range, 5.38–12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4–6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor—advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course.ConclusionIn the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms.

Can Beta-D-Glucan testing as part of the diagnostic pathway for invasive fungal infection reduce anti-fungal treatment costs?

Invasive fungal infection increases the risk of death in very sick people. So, treatment is started before test results are known. Beta-D-Glucan (BDG) test is faster than standard blood culture tests. We estimate that using BDG tests in how patients are diagnosed could save about £1643 per patient.

Real-World Evidence of Efficacy and Safety of Levonadifloxacin (Oral and IV) in the Management of Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Findings of a Retrospective, Multi-Center Study.

BackgroundAntimicrobial resistance by bacteria poses a substantial threat to the success in the treatment of acute bacterial skin and skin structure infections (ABSSSI). Levonadifloxacin is a novel benzoquinolizine subclass of quinolone which has a broad spectrum of activity, available in both oral and intravenous formulations for the treatment of skin structure infections caused by Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA).Patients and methodsThis prescription event monitoring study captured data of 227 patients receiving levonadifloxacin (oral and/or IV) in a real-world setting to assess the safety and efficacy in the treatment of ABSSSI. Study outcomes were a clinical and microbial success at the end of therapy and safety was assessed based on adverse events reported.ResultsOne hundred and forty patients received IV levonadifloxacin therapy, 76 patients received oral alalevonadifloxacin, and 11 received IV followed by oral therapy. The mean duration of therapy was 7.3 days. Out of 227 patients, MRSA isolates were identified in 79 patients. Clinical success rates with oral, IV, and IV followed by oral levonadifloxacin therapy were 97.3%, 97.8%, and 100% respectively. The overall microbial success rate was 99.2% and only two patients reported two adverse events.ConclusionsThe excellent safety and efficacy profile of levonadifloxacin on oral and/or intravenous therapy, makes it a desirable treatment modality for management of ABSSSI. Unique features of levonadifloxacin such as availability of both IV and oral form, minimal drug-drug interactions, exemption from dosage adjustment in renal and hepatic impaired patients and a broad spectrum of coverage, makes it a suitable agent meeting several unmet clinical needs in contemporary patients.

Mucosal healing with methotrexate versus azathioprine treatment in pediatric Crohn's disease as reflected by fecal calprotectin.

The current treatment goal for inflammatory bowel disease (IBD) is achievement of mucosal healing (MH). While established with biologic or azathioprine (AZA) therapies, the data on MH with methotrexate (MTX( treatment is scarce. We aimed to compare MH rate as reflected by FC in children with Crohn's disease (CD) treated with either MTX or thiopurines monotherapy. A cross-sectional multicenter study including children with CD (<18 years), with documented mucosal ulcerations/erosions on their first endoscopy, who were in clinical and biochemical remission for at least 6 months on MTX or AZA/6-MP monotherapy and had fecal calprotectin (FC) measurements during remission. Clinical remission was defined as PCDAI<10 and normal C-reactive-protein (CRP) level. FC < 100 μg/gr was used as a marker of MH. Demographic, clinical and laboratory data were retrieved from the medical charts. 64 patients (41 males, age 16.6±4.2 years) were included; 36 with MTX, 26 with AZA and 2 with 6-MP treatment. The mean treatment dose was 14.0±1.8 mg/m2 for MTX, and 1.8±0.66 mg/kg for AZA, and mean therapy duration was 22 ±17.1 months. MH (FC < 100 μg/gr) was demonstrated in 14/36 (39%) and 18/28 (64%) of patients on MTX and AZA/6-MP therapy, respectively (p=0.04). Rates of FC < 300 μg/gr were comparable [27/36 (75%) MTX, 24/28 (86%) AZA/6-MP, p=0.29]. MH was associated with longer treatment duration (p=0.03). MH as reflected by FC < 100 μg/gr, was higher with AZA/6-MP compared to MTX treatment in pediatric CD.

Rifampin Pharmacokinetics/Pharmacodynamics in the Hollow-Fiber Model of Mycobacterium kansasii Infection.

ABSTRACTThere is limited high-quality evidence to guide the optimal treatment of Mycobacterium kansasii pulmonary disease. We retrospectively collected clinical data from 33 patients with M. kansasii pulmonary disease to determine the time-to-sputum culture conversion (SCC) upon treatment with a standard combination regimen consist of isoniazid-rifampin-ethambutol. Next, MIC experiments with 20 clinical isolates were performed, followed by a dose-response study with the standard laboratory strain using the hollow-fiber system model of M. kansasii infection (HFS-Mkn). The inhibitory sigmoid maximum effect (Emax) model was used to describe the relationship between the bacterial burden and rifampin concentrations. Finally, in silico clinical trial simulations were performed to determine the clinical dose to achieve the optimal rifampin exposure in patients. The SCC rate in patients treated with combination regimen containing rifampin at 10 mg/kg of body weight/day was 73%, the mean time to SSC was 108 days, and the mean duration of therapy was 382 days. The MIC of the M. kansasii laboratory strain was 0.125 mg/L, whereas the MICs of the clinical isolates ranged between 0.5 and 4 mg/L. In the HFS-Mkn model, a maximum kill (Emax) of 7.82 log10 CFU/mL was recorded on study day 21. The effective concentration mediating 80% of the Emax (EC80) was calculated as the ratio of the maximum concentration of drug in serum for the free, unbound fraction (fCmax) to MIC of 34.22. The target attainment probability of the standard 10-mg/kg/day dose fell below 90% even at the MIC of 0.0625 mg/L. Despite the initial kill, there was M. kansasii regrowth with the standard rifampin dose in the HFS-Mkn model. Doses higher than 10 mg/kg/day, in combination with other drugs, need to be evaluated for better treatment outcome.

Success rate of surface-treated and non-treated orthodontic miniscrews as anchorage reinforcement in the lower arch for the Herbst appliance: A single-centre, randomised split-mouth clinical trial.

Surface treatment of miniscrews was implemented to determine whether its application increased bone-to-surface contact and enhanced the interlock between the device and the surrounding bone. To compare the success rate of surface-treated and non-treated orthodontic miniscrews used as reinforcement of anchorage during treatment with the Herbst appliance. Split-mouth design with an allocation ratio of 1:1. Eligibility criteria to enrol patients were skeletal and dental class II patients with a retrusive chin, use of the Herbst appliance to correct malocclusion, need for skeletal anchorage using a miniscrew both in the left and right side of the mouth, absence of systemic diseases, absence of using drugs that alter bone metabolism, and good oral hygiene. Patients received self-drilling miniscrews without surface treatment and with surface treatment. Both types presented a 1.4 or 1.2 mm diameter. Miniscrews were inserted between the first molar and second premolars or between the two premolars. The force applied to the screws was an elastic chain from the head of the miniscrews to a direct button applied on the canines. The success rate of each type of miniscrew was considered the primary outcome, and the association of success with demographical, clinical, and geometrical characteristics was investigated. Differences were tested by the generalised linear mixed effects model for the split-mouth design. Differences with a P-value &lt; 0.05 were selected as significant. A randomisation list was created for the mouth side assignment. The study was single blinded with regard to the statistical analysis. Thirty-nine miniscrews of the non-treated type and 39 miniscrews of the surface-treated type were inserted in 39 patients (23 female and 16 male, mean age: 15.55 ± 7.91) recruited between March 2018 and December 2020 with a split-mouth study design. The mean therapy duration was 9.3 months (SD = 1.31). No differences in failure rate were observed between miniscrew types. No serious harm was observed. The success rate of surface-treated and non-treated miniscrews showed no significant differences. This trial was not registered.

Predictors of Duration of Phenobarbitone Therapy in Seizures of Neonates with Hypoxic-Ischemic Encephalopathy

Objective: Perinatal asphyxia with hypoxic-ischemic encephalopathy associated with seizures is one of the leading cause of neonatal mortality and morbidity in Bangladesh. Phenobarbitone remains the drug of choice in treatment of neonatal seizures. This study was conducted to determine the predictors of duration of Phenobarbitone therapy in seizures of neonates with Hypoxic-Ischemic Encephalopathy (HIE). Methodology: The study was conducted in Neonatal Intensive Care Unit (NICU) of East West Medical College Hospital from 1st february 2016 to 31st january 2017 on fifty neonates with HIE and seizures. The dose and duration of phenobarbitone therapy for initial control of seizure was noted. Total duration of phenobarbitone therapy after control of seizure to prevent further recurrences was also noted. Follow up was given up to 3 months of age to see any recurrence of seizures. Results: Out of the 50 neonates,25 cases (50%) responded well within 24 hours. Mean duration of phenobarbitone therapy after initial control of seizure was 4.70 ± 2.93days and Mean total duration of therapy was 6.89 ± 3.58 days in cases who responded well within 24 hours.. 3 (6%) cases had recurrence of seizures. The recurrence cases required more than 72 hours for initial control of seizure (p 0.006) and had poor primitive reflexes and activity after initial control of seizure (p 0.0002). Mean duration of phenobarbitone therapy after initial control of seizures was 6.33 ± 6.11 days and Mean total duration of phenobarbitone therapy was also longer 9.67 ± 7.37 days. Conclusion: Neonates who have good initial response and have better reflexes required short duration of phenobarbitone therapy. It should be discontinued soon after control of seizure. Neonates with HIE III, those requiring more than 72 hours for initial response and poor reflexes after initial control of seizure may require longer duration of phenobarbitone therapy (more than 7 days) to prevent recurrence of seizures. Thus, judicious use of phenobarbitone will minimize the unnecessary non-specific treatment.

1367. Management of Patients Presenting with Purulent Skin and Soft Tissue Infections in the Emergency Department (ED)

Abstract Background Incision and drainage (I&amp;D) is the primary treatment for purulent skin and soft tissue infection (SSTI). Empiric adjunctive treatment of purulent SSTI targets methicillin-resistant Staphylococcus aureus (MRSA). In light of increasing antibiotic resistance, culture and sensitivity (C&amp;S) from drained specimen and consideration of the local antibiogram are recommended.1 Our primary objective was to assess the utilization of C&amp;S from drained specimen in out institution’s ED. Our secondary objectives were to describe antibiotic choice and duration of therapy upon discharge, to evaluate the appropriateness of antibiotic choice based on C&amp;S and local antibiogram, and to assess the need for adjunctive antibiotic based on available literatures. Methods A retrospective cohort study was performed on a random sample of unique patients who underwent I&amp;D procedure in the ED from January 2019 through December 2019. Demographic and clinical data were collected from the electronic medical record. Results Of 120 patients evaluated, only 14 patients (11.7%) had C&amp;S performed on the initial I&amp;D specimen (Table 1). Five patients received inappropriate antibiotic(s) based on C&amp;S. Of 108 patients who were discharged from ED, antibiotic(s) was prescribed in 97 patients (Table 2). Mean duration of therapy was 7.8 days with 27.8% of patients prescribed a duration of therapy longer than 7 days. Despite high clindamycin resistant rate for MRSA (35%), clindamycin was the second most prescribed antibiotic. Adjunctive antibiotic(s) may have been unnecessary in 9.5% patients. Five patients reported possible adverse reaction related to prescribed antibiotic. Additional antibiotic course was prescribed in 15 patients for the same infection. Fifteen patients were readmitted to ED within 30 days and five of them required hospital admission Conclusion At our institution, majority of patients were discharged after I&amp;D with adjunctive antibiotic(s) without microbiologic testing. Despite high local clindamycin resistance, it was the second most commonly prescribed empiric treatment. Developing a clinical pathway that emphasizes the importance of timely microbiologic testing and local antibiogram consideration along with the need for appropriate adjunctive antibiotics may improve patient outcomes. Disclosures All Authors: No reported disclosures

1151. Clinical Characteristics of Persistent Staph Aureus Bacteremia in Children

BackgroundPersistent Staphylococcus aureus bacteremia (pSAB) is a poorly defined entity, but associated with significant morbidity and mortality in children. We aim to better describe the epidemiological features of this clinical entity.MethodsWe performed a retrospective case series analysis of pediatric patients with pSAB at a single center children’s hospital using electronic medical data from 2016 – 2020. Bacterial persistence was defined as culture growth > 72 hours after first blood culture. ResultsTwenty-two patients with pSAB were included in the analysis. Sources of persistent infection were endovascular infection (n=11, 50%), osteoarticular infection (n=6, 27%,), isolated central line associated blood stream (n=4, 18%), isolated skin and soft tissue infection (n=2, 9%), and no known primary infectious site (n=1). Methicillin resistance occurred in 41% (n=9) of cases of pSAB. Total duration of therapy varied, with a median of 4 weeks from negative cultures (range of 2 – 8 weeks). Total days of positive cultures in pSAB were not significantly associated with methicillin susceptibility of the bacterial isolate, use of double gram-positive coverage, nor presence of a central venous catheter. Use of double gram-positive coverage occurred in 50% of cases with a mean duration of therapy of 11 days, most frequently in cases of septic thrombophlebitis (Table 1). Rifampin and gentamicin were the most commonly used agents. Table 1. Clinical Characteristics of Children Treated with Double Gram-Positive Coverage ConclusionChildren presenting with persistent S. aureus bacteremia present with a heterogenous group of underlying conditions and epidemiological features. While pediatric recommendations for double gram-positive coverage for synergy have not been established, their use for pSAB is common, especially in endovascular infections where culture persistence is often an expected outcome. Further research should examine risk factors for pSAB and define optimal treatment modalities and duration. Disclosures All Authors: No reported disclosures

Novel home use of mechanical negative pressure wound therapy in diabetic foot ulcers.

Mechanical negative pressure wound therapy is an ultraportable, light weight and disposable single-use device that has been shown to promote wound healing. This study evaluated home use of a mechanically powered negative pressure wound therapy (NPWT) in diabetic foot wounds. Patients underwent revascularisation and/or debridement or amputation before starting mechanical NPWT. Wound outcomes and images of the wounds were recorded at each follow-up visit by the wound nurse. Patients were followed up until wound closure or end of therapy. A total of 12 patients (each with one wound) were included in the study. Of the 12 wounds, 33.3% (n=4) of wounds achieved primary wound closure while the remaining 66.6% (n=8) of wounds demonstrated a mean wound size reduction of 37.5±0.13%. Of the closed wounds, mean time to healing was 4.75±2.50 weeks. There was 100% limb salvage with no further debridement or amputations, and no 30-day unplanned readmissions. Mean length of hospital stay before starting home NPWT was 9.75±6.31 days. Mean number of NPWT changes was 8.33±2.67 sessions, while mean duration of therapy was 4.0±1.54 weeks. Mean cost of home NWPT therapy was US$1904±731 per patient. The home use of mechanically powered NPWT in diabetic foot wounds demonstrated excellent wound healing rates and 100% limb salvage, with no complications.