107. A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Oteseconazole (VT-1161) Oral Capsules versus Fluconazole and Placebo in the Treatment of Acute Vulvovaginal Candidiasis Episodes in Subjects with Recurrent Vulvovaginal Candidiasis (ultraViolet)

Abstract Background Recurrent vulvovaginal candidiasis (RVVC) affects nearly 138 million women globally each year. Currently there are no FDA approved treatments. The study was conducted to evaluate the efficacy of oral oteseconazole (VT-1161) in the prevention of culture-verified acute VVC episodes through Week 50 and compare the efficacy of oteseconazole and fluconazole in treatment of an acute VVC episode in RVVC subjects. Methods 219 subjects with history of RVVC (≥ 3 acute episodes within prior 12 months) were enrolled at 51 US sites. The study consisted of two phases. Induction Phase: Subjects who presented with a vulvovaginal signs and symptoms score of ≥ 3 and positive KOH test identifying Candida were randomized to either: • 600 mg oteseconazole on Day 1, 450 mg oteseconazole on Day 2 and matching placebo capsules; OR • 3 sequential 150 mg doses (every 72 hours) of over-encapsulated fluconazole together with matching placebo capsules Maintenance Phase: 185 subjects with resolved acute VVC infections (clinical signs and symptoms score of < 3) on Day 14 received: • 150 mg oteseconazole or placebo weekly for 11 weeks • then 37-week Follow-up period Results Study achieved primary and secondary efficacy endpoints. Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with ≥ 1 culture-verified acute VVC episode through Week 50 in the intent-to-treat (P < 0.001). The average percentage of subjects with ≥ 1 culture-verified acute VVC episode through Week 50 was lower in the oteseconazole group (5.1%) compared to the fluconazole/placebo group (42.2%). Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at Day 14; 93.2% oteseconazole group, 95.8% fluconazole/placebo group. The percentage of subjects who had ≥ 1 treatment-emergent adverse event (TEAE) was similar; oteseconazole (54%), fluconazole/placebo (64%). Most TEAEs experienced were mild or moderate severity in both groups and no drug-related SAEs or adverse effects on liver function or QT intervals. Conclusion Oteseconazole was shown to be safe and effective in treatment of acute VVC, treatment of RVVC and prevention of recurrence of acute VVC episodes in RVVC subjects. Oteseconazole was non-inferior to fluconazole for treatment of acute VVC in subjects with RVVC. Disclosures Bassem Maximos, MD, Evofem Biosciences (Scientific Research Study Investigator, Speaker's Bureau)Mycovia Pharmaceutical (Scientific Research Study Investigator)Sage Therapeutics (Scientific Research Study Investigator, Speaker's Bureau) Thorsten Degenhardt, Ph.D, Mycovia Pharmaceuticals (Employee, Shareholder) Karen Person, M.S., Mycovia Pharmaceuticals, Inc. (Employee)Mycovia Pharmaceuticals, Inc. (Employee) Mahmoud Ghannoum, PhD, Mycovia Pharmaceuticals (Grant/Research Support, Research Grant or Support) Stephen Brand, Ph.D, Mycovia Pharmaceuticals (Employee)

Background. Autoimmune encephalitis is an urgent treatable etiology that needs to be differentiated from viral encephalitis. Prompt recognition and therapy is of utmost importance.
Methods. We performed a retrospective cohort of encephalitis cases in 16 hospitals in Houston, Texas, between January 2005 and December 2019.
Results. A total of 1,310 adult (age ≥18 years) inpatient hospital admissions were identified by the presence of an encephalitis-related discharge diagnosis per the International Classification of Disease 9 th edition codes. Of these, only 279 cases met the 2013 International Encephalitis Consortium criteria for probable encephalitis. A laboratory confirmed diagnosis of autoimmune encephalitis or viral encephalitis was identified in 36 (12.9%) and 88 (31.5%) cases, respectively. There were 155 cases (55.5%) that had no identifiable cause and were considered idiopathic.
As compared to viral encephalitis, patients with autoimmune encephalitis were more likely to be younger (< 60 years old), have a subacute (6-30 days) or chronic ( >30 days) presentation, have seizures, and have psychiatric and/or memory complaints (P< 0.001). Furthermore, patients with autoimmune encephalitis were less likely to be febrile and to lack inflammatory cerebrospinal fluid (CSF) (defined as white blood cells < 50 per microliter or protein < 50 milligrams per deciliter) [See Table 1]. In the multivariable logistic regression model, subacute/chronic presentation, psychiatric and/or memory complaints, and lack of inflammatory CSF were significantly associated with autoimmune encephalitis. Using these 3 variables, patients were classified into 3 risk categories for autoimmune encephalitis: low risk (0-1 variables); 0%; intermediate risk (2 variables); 16%; and high risk (3 variables); 83% (P value < 0.001).

Conclusion.
Adults with encephalitis can be accurately stratified for the risk of having autoimmune encephalitis using clinical variables available upon presentation. Methods. 219 subjects with history of RVVC (≥ 3 acute episodes within prior 12 months) were enrolled at 51 US sites. The study consisted of two phases.
Induction Phase: Subjects who presented with a vulvovaginal signs and symptoms score of ≥ 3 and positive KOH test identifying Candida were randomized to either: • 600 mg oteseconazole on Day 1, 450 mg oteseconazole on Day 2 and matching placebo capsules; OR • 3 sequential 150 mg doses (every 72 hours) of over-encapsulated fluconazole together with matching placebo capsules Maintenance Phase: 185 subjects with resolved acute VVC infections (clinical signs and symptoms score of < 3) on Day 14 received: • 150 mg oteseconazole or placebo weekly for 11 weeks • then 37-week Follow-up period Results. Study achieved primary and secondary efficacy endpoints. Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with ≥ 1 culture-verified acute VVC episode through Week 50 in the intent-to-treat (P < 0.001).
The average percentage of subjects with ≥ 1 culture-verified acute VVC episode through Week 50 was lower in the oteseconazole group (5.1%) compared to the fluconazole/placebo group (42.2%). Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at Day 14; 93.2% oteseconazole group, 95.8% fluconazole/placebo group.
The percentage of subjects who had ≥ 1 treatment-emergent adverse event (TEAE) was similar; oteseconazole (54%), fluconazole/placebo (64%). Most TEAEs experienced were mild or moderate severity in both groups and no drug-related SAEs or adverse effects on liver function or QT intervals.
Background. Diabetic foot osteomyelitis (DFO) remains a significant comorbidity in diabetes and often requires both surgical and medical interventions. Surgical bone resection with proximal margins is performed for treatment at our institution to guide antimicrobial therapy. Optimal antibiotic duration often remains unclear, along with clinical outcomes with negative margins. We evaluate if negative bone margins predict outcomes of DFO at one year in our county hospital.
Methods. A retrospectively cohort study assessed adult patients undergoing DFO amputations between 9/2016 to 9/2019. Patient data collected included demographics, smoking history, hemoglobin A1c (HbA1c), basic labs, microbiology, antibiotic duration, bone margin pathology. Physician review of records determined if intervention was successful. Primary outcome was met if no further amputation at the same site was required in the following 12 months.
Results. Of 92 patients, 57 had negative margins and 35 had positive margins for pathology confirmed osteomyelitis. Smoking history was significant in positive margins (35.1% vs 57.1%; p=0.038). Patients with negative margins had a successful outcome at 12 months compared to positive margins (86% vs 66%; p=0.003), but no significant differences in outcome at 6 months. Antibiotic days was reduced in negative margin individuals (mean 18 vs 30 days; p=0.001). Negative margins also demonstrated significant lower rates of readmission at 12 months (p=0.015). Staphylococcus aureus was notable in positive vs negative margins (57.1% vs 29.8%; p=0.017). MSSA was significantly noted in positive margins (45.7% vs 14%; p=0.001). MRSA was similar regardless of margin results (15.8% vs 11.4%; p=0.399). Initial ESR, CRP and HbA1c were similar between groups.
Conclusion. Our study noted that negative proximal bone margins resulted in more successful outcomes at 12 months and less days of antimicrobial therapy. Patients with negative margins had lower rates of readmission at 12 months for surgical site complications. Negative proximal bone margins results can guide antibiotic therapy and improve outcomes of resections. Presence of S. aureus was significant in positive margins and likely warrant consideration for further aggressive intervention. Background. In China, the prevalence of infections due to multidrug-resistant gram-negative bacteria is high and additional treatment options for complicated intra-abdominal infections (cIAI) are needed. This study compared the efficacy and safety of ceftolozane/tazobactam (C/T) + metronidazole (MTZ) versus meropenem (MEM) + placebo (pbo) for the treatment of cIAI in adult Chinese participants.
Methods. This was a phase 3, double-blind study conducted at 21 centers in China (NCT03830333). Participants aged 18-75 years with cIAI requiring surgical intervention within 24 hours of study drug administration were stratified by site of infection and randomized 1:1 to receive 1.5 g C/T (1 g ceftolozane and 0.5 g tazobactam) + 0.5 g MTZ administered intravenously (IV) every 8 hours (q8h) or 1 g MEM + pbo administered IV q8h for 4-14 days. The primary endpoint was clinical cure at test of cure (TOC) in the clinically evaluable (CE) population. Secondary endpoints included rates of clinical cure, per-participant microbiologic response, per-pathogen microbiologic response, and adverse events (AE). Non-inferiority for clinical cure at TOC in the CE population was confirmed if the lower bound of the 2-sided 95% CI for the between-treatment difference in the clinical cure rate was larger than −12.5%.