Sequential Intravenous-Oral Therapy for Pediatric Streptococcus anginosus Intracranial Infections

Introduction Streptococcus anginosus group is a common cause of pediatric intracranial infections but treatment recommendations, including use of oral therapy, are poorly defined. Methods We performed a retrospective review from 2004-2019 of all patients with Streptococcus anginosus group pyogenic intracranial infections at Children’s Hospital Colorado, highlighting patients transitioned to oral therapy. The primary endpoint was worsening infection necessitating intravenous antibiotics or a source control procedure after transition to oral therapy. Results Of 107 patients with Streptococcus anginosus intracranial infections, 61 were transitioned to exclusive oral therapy after a median intravenous duration of 37 days, overwhelmingly with a levofloxacin-based regimen. Only one failure was noted in a patient who did not fill their prescription. Patients with epidural infections were more likely to be transitioned to oral therapy within the first 28 days of treatment (defined as “early”). Patients with parenchymal infections, bacteremia, co-pathogens, higher inflammatory markers, and requiring >1 source control procedure were less likely to be transitioned early to oral therapy. Complications of a central catheter and/or intravenous medications contributed to 56% of oral transitions. Conclusions Levofloxacin-based oral regimens were effective and well-tolerated. Patients with less severe infections were more likely to be transitioned early to oral therapy. Criteria for transitioning patients to oral antibiotics for intracranial infections should be established to minimize risks inherent with central catheters.

Ponesimod oral therapy for the treatment of relapsing forms of multiple sclerosis in adults and its precautions in cardiovascular disease patients

The ponesimod oral therapy was approved in March 2021 by the United States Food and Drug Administration for relapsing forms multiple sclerosis (MS). Ponesimod is a sphingosine 1-phosphate (S1P) receptor 1 modulator that acts selectively as an anti- inflammatory agent and provides a suitable microenvironment for the function of the other neuroprotective agents. Ponesimod is contraindicated in patients who in the last 6 months, have experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure. Also contraindicated in patients who have the presence of Mobitz type II second-degree, third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker. This article briefs the information about dosage, precautions and warnings required in cardiovascular disease patients before initiation of ponesimod oral therapy.

Efficacy of Outpatient Infusion Therapy in Pediatric Patients With Post-Concussive Headaches

ObjectiveThe objective of this study is to determine the relative efficacy of an intravenous therapy for post-concussive headaches in a pediatric population, as compared to oral therapy.BackgroundPost traumatic headache is extremely common in the acute and chronic phases after concussion. To date, there is still not significant evidence-based treatment protocols defined for treatment.Design/MethodsPediatric patients who were treated for post-concussive headaches at an outpatient infusion clinic from 2016 to 2018 were selected for inclusion in the study. Clinic visits before and after infusions were reviewed to determine changes in headache score (HA), symptom severity score (SSS), and self-reported symptom relief. The control group received only oral therapy for their headaches. The infusion consisted of parenteral ketorolac, compazine, diphenhydramine, and a normal saline bolus (20 mg/kg). Of the 95 patients who were treated in clinic, 53 patients were selected for a retrospective chart review.ResultsFollowing infusion therapy, overall mean HA and SSS scores were both reduced (1.6346, SD 1.8997, p < 0.0001 and 23.0385, SD 29.4971, p < 0.0001 respectively). Oral therapy demonstrated a similar mean overall reduction in HA and SS scores (1.4151, SD 1.4992, p < 0.0001 and 25.4906, SD 30.2042, p < 0.0001). While both groups achieved a reduction in HA and SS scores, there was not a statistically significant difference in reduction of symptoms scores between the oral and infusion groups.ConclusionsInfusion therapy is as effective at reducing HA and SSS as established oral therapies. It is hypothesized that infusion therapy may have a shorter time to headache abortion than oral therapy based on pharmacokinetics. Further, some physicians are unwilling to allow an athlete to return to play while taking suppressive medication. Future studies may show that an infusion could allow a more rapid return to play and resolution of symptoms.

A Case of Extensive Grover’s Disease in a Patient with a History of Multiple Non-Melanoma Skin Cancers

We report on a 69-year-old man who presented with itching and erythematous papules on his torso and extremities, which were resistant to topical therapy with antibiotics and steroids. Physical examination revealed multiple erythematous papules on his back, neckline, and lower extremities. The lesions had appeared 4 years earlier and usually worsened with heat or extensive sweating. Histopathology of previous skin biopsies had shown multiple cutaneous squamous cell carcinomas or was non-conclusive. Thus, a re-biopsy was performed, revealing acanthosis and focal acantholytic dyskeratosis. These clinical and anamnestic findings lead to the diagnosis of extensive Grover’s disease (GD). Oral therapy with isotretinoin 30-mg QD led to the regression of the skin lesions. Topical adapalene, as well as topical corticosteroids, were later prescribed for maintenance therapy.

Childhood Furuncular Cutaneous Myiasis Associated with Seborrheic Dermatitis: A Case Report

Myiasis is a parasitic infection caused by dipterous fly larvae that can affect various organs in both human and animals. Cutaneous myiasis is the most common type of myiasis and can be classified into three categories, localized furuncular myiasis, migratory myiasis, and wound myiasis. One of the risk factors for myiasis is seborrheic dermatitis. The definitive treatment for the condition requires complete extraction of larvae, in combination with oral therapy, and localized occlusion to promote hypoxia. This paper reports a case of a 12-year-old girl with furuncular cutaneous myiasis associated with seborrheic dermatitis on the occipital region that showed significant improvements after manual extraction of larvae after local anesthesia injection of 2% lidocaine on the base of the lesion, in combination with oral and topical therapies

219. Outcomes with Low- vs. High-bioavailability Oral Antibiotics in Treatment of Uncomplicated Gram-Negative Bacteremia

Background High-bioavailability (HIGH-BIO) oral agents (i.e. trimethoprim-sulfamethoxazole, fluoroquinolones) are increasingly utilized for definitive treatment of uncomplicated gram-negative (UGN) bloodstream infections (BSI). Literature supports use of HIGH-BIO agents as step-down therapy, but few studies have assessed use of low-bioavailability (LOW-BIO) agents (i.e. beta-lactams). Increased recurrence of BSI has been associated with LOW-BIO agents; suboptimal dosing of beta-lactam agents may have impacted outcomes. Trials have not assessed whether high-dose beta-lactams (HD-BL) improve clinical outcomes over low-dose beta-lactams (LD-BL) for UGN BSI. Methods This retrospective cohort study conducted between December 2016 and December 2020 included adults with UGN BSI administered oral step-down therapy for at least 1/3rd the total antibiotic duration. The primary outcome was incidence of treatment failure of HIGH-BIO compared to LOW-BIO agents within 90 days of completing oral therapy. Treatment failure was a composite of all-cause mortality, recurrent BSI, reinfection of the primary site, or transition to IV antibiotics after initiating oral therapy. Secondary outcomes were incidence of treatment failure of HIGH-BIO compared to HD-BL agents, and of HD-BL compared to LD-BL agents. Results Of 225 patients, 67 (29.8%) received a HIGH-BIO and 158 (70.2%) a LOW-BIO agent; of those in the LOW-BIO arm 126 (79.7%) received a HD-BL. The most common source of BSI was urinary (202 [89.8%]); transition to oral therapy occurred after a mean of 5 ± 2.39 days. No difference in treatment failure was observed (8 [11.9%] HIGH-BIO vs. 25 [15.8%] LOW-BIO, P = 0.45). A numerically higher number of patients in the LOW-BIO arm had recurrent BSI (4 [2.5%] LOW-BIO vs. 0 [0%] HIGH-BIO, P = 0.18). No difference in treatment failure was observed between HIGH-BIO and HD-BL agents (8 [11.9%] vs. 20 [15.9%], P = 0.46), or HD-BL and LD-BL agents (20 [15.9%] vs. 5 [15.6%], P = 0.97). Conclusion No difference in treatment failure was observed between groups; further study is needed due to failure to reach statistical power. A numerical trend towards increased recurrence of BSI was observed with LOW-BIO agents. Beta-lactams may be reasonable for step-down therapy of UGN BSI if HIGH-BIO agents are contraindicated. Disclosures All Authors: No reported disclosures

232. Safety and Effectiveness of Intravenous to Oral De-escalation Compared to Continued Vancomycin Therapy in Orthopedic Infections

Background The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial determined oral antibiotics administered during the first six weeks of therapy were non-inferior to parenteral antibiotics. There was no difference in the incidence of serious adverse effects. The objective of this study was to evaluate the safety and effectiveness of de-escalating to oral therapy compared to continuing parenteral vancomycin therapy in patients with orthopedic infections in a real-world setting. Methods We conducted a single-center, retrospective cohort study of patients discharged between April 1, 2018 and April 1, 2020 with an orthopedic infection, a prescription for at least four weeks of parenteral vancomycin, and documented follow-up. The primary outcome was incidence of adverse events defined as provider documentation of the event and changes to therapy. The secondary outcome was incidence of 6-month treatment failure defined as repeat surgical intervention or therapy escalation. Results One hundred fifty-seven patients were included. Twenty-nine (18.5%) patients were de-escalated to oral therapy. Three (10%) patients in the oral therapy group had an adverse event compared to 35 (27%) in the vancomycin group (p=0.058). Of the 35 patients with an adverse event in the vancomycin group, eight were due to parenteral access-related complications. Treatment failure occurred in three (10%) patients in the oral therapy group compared to 27 (21%) patients in the vancomycin group (p=0.29). Three (10%) patients in the oral therapy group had an unplanned readmission compared to 25 (20%) patients in the vancomycin group (p=0.24). Baseline Characteristics, Unplanned Readmission Rates, and Incidence of Adverse Events and 6-Month Treatment Failure Conclusion Patients de-escalated to oral therapy had fewer adverse events and similar incidences of treatment failure compared to patients maintained on parenteral vancomycin. Switching to oral therapy avoids some adverse events related to parenteral access. Our results in an uncontrolled, real-world setting are consistent with the OVIVA trial. Though limited by sample size, our data indicate switching to oral therapy in patients with an orthopedic infection improves safety outcomes without compromising effectiveness compared to continued parenteral vancomycin therapy. Disclosures Russell J. Benefield, PharmD, Paratek Pharmaceuticals (Grant/Research Support)