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Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial
Delafloxacin is a novel fluoroquinolone with activity against Gram-positive, Gram-negative, and atypical pathogens, including fluoroquinolone-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA). The microbiological results of a phase 3 clinical trial in adults with community-acquired p...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038307/ https://www.ncbi.nlm.nih.gov/pubmed/31844013 http://dx.doi.org/10.1128/AAC.01949-19 |
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author | McCurdy, Sandra Keedy, Kara Lawrence, Laura Nenninger, Ashley Sheets, Amanda Quintas, Megan Cammarata, Sue |
author_facet | McCurdy, Sandra Keedy, Kara Lawrence, Laura Nenninger, Ashley Sheets, Amanda Quintas, Megan Cammarata, Sue |
author_sort | McCurdy, Sandra |
collection | PubMed |
description | Delafloxacin is a novel fluoroquinolone with activity against Gram-positive, Gram-negative, and atypical pathogens, including fluoroquinolone-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA). The microbiological results of a phase 3 clinical trial in adults with community-acquired pneumonia (CAP) comparing delafloxacin (300 mg intravenously [i.v.] with the option to switch to 450 mg orally every 12 h) to moxifloxacin (400 mg i.v. with the option to switch to 400 mg orally once a day [QD]) were determined. Patients from 4 continents, predominately Europe but also South America and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 520 patients, and 60.5% of these patients had a bacterial pathogen identified. Multiple diagnostic methods were employed, including culture, serology, PCR, and urinary antigen tests. Based on baseline MIC(90) values, delafloxacin exhibited at least 16-fold greater activity than moxifloxacin for Gram-positive and fastidious Gram-negative pathogens. Delafloxacin retained activity against resistant phenotypes found in Streptococcus pneumoniae (penicillin-, macrolide-, and multiple-drug resistant), Haemophilus species (β-lactamase producing and macrolide nonsusceptible), and S. aureus (MRSA and fluoroquinolone-nonsusceptible methicillin-susceptible S. aureus [MSSA]). The microbiological success rates were 92.7% for S. pneumoniae (87.5% for penicillin-resistant S. pneumoniae [PRSP]), 92.6% for S. aureus (100% for MRSA), 100% for Escherichia coli, 82.4% for Klebsiella pneumoniae, 100% for Klebsiella oxytoca, 100% for Moraxella catarrhalis, 91.7% for Haemophilus influenzae, 88.6% for Haemophilus parainfluenzae, 96.7% for Mycoplasma pneumoniae, 93.1% for Legionella pneumophila, and 100% for Chlamydia pneumoniae. There was little correlation between MICs and outcomes, with a high proportion of favorable outcomes observed across all delafloxacin baseline MIC values. Delafloxacin may be considered a treatment option as monotherapy for CAP in adults, where broad-spectrum coverage including MRSA activity is desirable. |
format | Online Article Text |
id | pubmed-7038307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-70383072020-03-06 Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial McCurdy, Sandra Keedy, Kara Lawrence, Laura Nenninger, Ashley Sheets, Amanda Quintas, Megan Cammarata, Sue Antimicrob Agents Chemother Clinical Therapeutics Delafloxacin is a novel fluoroquinolone with activity against Gram-positive, Gram-negative, and atypical pathogens, including fluoroquinolone-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA). The microbiological results of a phase 3 clinical trial in adults with community-acquired pneumonia (CAP) comparing delafloxacin (300 mg intravenously [i.v.] with the option to switch to 450 mg orally every 12 h) to moxifloxacin (400 mg i.v. with the option to switch to 400 mg orally once a day [QD]) were determined. Patients from 4 continents, predominately Europe but also South America and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 520 patients, and 60.5% of these patients had a bacterial pathogen identified. Multiple diagnostic methods were employed, including culture, serology, PCR, and urinary antigen tests. Based on baseline MIC(90) values, delafloxacin exhibited at least 16-fold greater activity than moxifloxacin for Gram-positive and fastidious Gram-negative pathogens. Delafloxacin retained activity against resistant phenotypes found in Streptococcus pneumoniae (penicillin-, macrolide-, and multiple-drug resistant), Haemophilus species (β-lactamase producing and macrolide nonsusceptible), and S. aureus (MRSA and fluoroquinolone-nonsusceptible methicillin-susceptible S. aureus [MSSA]). The microbiological success rates were 92.7% for S. pneumoniae (87.5% for penicillin-resistant S. pneumoniae [PRSP]), 92.6% for S. aureus (100% for MRSA), 100% for Escherichia coli, 82.4% for Klebsiella pneumoniae, 100% for Klebsiella oxytoca, 100% for Moraxella catarrhalis, 91.7% for Haemophilus influenzae, 88.6% for Haemophilus parainfluenzae, 96.7% for Mycoplasma pneumoniae, 93.1% for Legionella pneumophila, and 100% for Chlamydia pneumoniae. There was little correlation between MICs and outcomes, with a high proportion of favorable outcomes observed across all delafloxacin baseline MIC values. Delafloxacin may be considered a treatment option as monotherapy for CAP in adults, where broad-spectrum coverage including MRSA activity is desirable. American Society for Microbiology 2020-02-21 /pmc/articles/PMC7038307/ /pubmed/31844013 http://dx.doi.org/10.1128/AAC.01949-19 Text en Copyright © 2020 McCurdy et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Clinical Therapeutics McCurdy, Sandra Keedy, Kara Lawrence, Laura Nenninger, Ashley Sheets, Amanda Quintas, Megan Cammarata, Sue Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial |
title | Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial |
title_full | Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial |
title_fullStr | Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial |
title_full_unstemmed | Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial |
title_short | Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial |
title_sort | efficacy of delafloxacin versus moxifloxacin against bacterial respiratory pathogens in adults with community-acquired bacterial pneumonia (cabp): microbiology results from the delafloxacin phase 3 cabp trial |
topic | Clinical Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038307/ https://www.ncbi.nlm.nih.gov/pubmed/31844013 http://dx.doi.org/10.1128/AAC.01949-19 |
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