DIAGNOSIS AND OUTCOMES IN PATIENTS WITH ATYPICAL PATHOGENS IN A PHASE-3 COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA TRIAL COMPARING DELAFLOXACIN TO MOXIFLOXACIN

Abstract

SESSION TITLE: Monday Electronic Posters 1 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: An etiological agent is often not identified at the time of diagnosis of community-acquired bacterial pneumonia (CABP) and as such, the Infectious Diseases Society of America/American Thoracic Society Guidelines recommend that empirical treatment cover atypical pathogens. Fluoroquinolones (FQ) have a spectrum of activity that covers gram-positive, gram-negative and atypical pathogens common in CABP. Delafloxacin (DLX) is a new FQ with activity against many Gram-positive FQ-resistant strains. A Phase 3 global, randomized, double-blind, active-controlled study was recently completed to evaluate IV-to-oral DLX compared with moxifloxacin (MOX) in the treatment of CABP. We report the clinical outcomes among patients with atypical pathogens. METHODS: CABP patients were randomized to receive 5-10 days of either DLX or MOX and could switch from IV to oral dosing after Day 3. Serologic diagnosis of Legionella pneumophila (Lp), Mycoplasma pneumoniae (Mp), and Chlamydophila pneumoniae (Cp) was made using paired acute and convalescent sera showing at least a 4-fold increase in titer. Additionally, Lp could be diagnosed by sputum culture or urinary antigen and Mp could be diagnosed by culture of oropharyngeal swabs. Susceptibility testing was performed on Lp and Mp isolates. Efficacy assessments were performed at 96 (±24) hours for Early Clinical Response (ECR) and at the Test of Cure (TOC) visit 5-10 days after the end of treatment. RESULTS: 859 patients were enrolled from sites in 18 countries, and a microbiological diagnosis (all pathogens) was established in 60.5% of patients. In the patients with baseline pathogens, Lp, Mp and Cp were detected in 11.9, 12.5 and 7.9% of these patients, respectively. Overall, 13.1% of microbial diagnoses were monomicrobial infections with atypical pathogens. DLX had potent activity against Mp and Lp. The DLX MIC90 was 0.5 μg/mL for Mp and the MICs ranged from 0.00025-0.001 μg/mL (n=4) for Lp. Overall DLX was non-inferior to MOX for the treatment of CABP in the primary outcome of ECR and by-pathogen success rates were high. In the evaluable population, ECR (DLX vs. MOX) was 93.1% vs. 87.5% for Lp, 85.7% vs. 96.7% for Mp, and 96.0% vs 87.5% for Cp. At the TOC visit, clinical success was 93.1% vs. 100% for Lp, 96.7% vs. 100% for Mp, and 100% vs 100% for Cp. CONCLUSIONS: Atypical pathogens were frequently identified in this Phase 3 study in CABP, including as monomicrobial infections. DLX, which is approved for treatment of acute bacterial skin and skin structure infections in the US, was confirmed as efficacious in monotherapy for CABP and provided comparable outcomes to MOX for the treatment of patients with atypical pathogens. CLINICAL IMPLICATIONS: DLX may be a useful treatment option for monotherapy in CABP on either an inpatient or outpatient basis when empirical coverage of atypical pathogens is desired. DISCLOSURES: Employee relationship with Melinta Please note: >$100000 Added 03/03/2019 by Sue Cammarata, source=Web Response, value=Salary Employee relationship with Melinta Therapeutics, Inc. Please note: >$100000 Added 03/04/2019 by Kara Keedy, source=Web Response, value=Salary Stock holder relationship with Melinta Therapeutics, Inc. Please note: $1001 - $5000 Added 03/12/2019 by Kara Keedy, source=Web Response, value=stock Employee relationship with Melinta Therapeutics Please note: >$100000 Added 03/12/2019 by Laura LAWRENCE, source=Web Response, value=Salary No relevant relationships by Yang Li, source=Web Response Employee $100000 Added 03/12/2019 by Sandra McCurdy, source=Web Response, value=Salary<br former employee relationship with Melinta Therapeutics Please note: >$100000 Added 03/12/2019 by Ashley Nenninger, source=Web Response, value=salary and stock Employee relationship with Melinta Therapeutics, Inc. Please note: >$100000 Added 03/12/2019 by Megan Quintas, source=Web Response, value=Salary Employee relationship with Melinta Therapeutics Inc Please note: >$100000 Added 03/12/2019 by Amanda Sheets, source=Web Response, value=Salary Stock holder relationship with Melinta Therapeutics Inc Please note: $1-$1000 Added 03/12/2019 by Amanda Sheets, source=Web Response, value=Consulting fee Removed 03/12/2019 by Amanda Sheets, source=Web Response Stock holder relationship with Melinta Therapeutics Inc Please note: $1001 - $5000 Added 03/12/2019 by Amanda Sheets, source=Web Response, value=Stock