Delafloxacin––A novel fluoroquinolone for the treatment of ciprofloxacin‐resistant Pseudomonas aeruginosa in patients with cystic fibrosis

Abstract Introduction Fluoroquinolone antibiotics, namely ciprofloxacin and levofloxacin, play an important role in treating infection in cystic fibrosis (CF) and ciprofloxacin remains the last widely used and orally available antipseudomonal agent. Recently, a new fluoroquinolone, delafloxacin, has...

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Main Authors: Beverley Cherie Millar, John McCaughan, Jacqueline C. Rendall, John E. Moore
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:The Clinical Respiratory Journal
Subjects:
Online Access:https://doi.org/10.1111/crj.13262
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author Beverley Cherie Millar
John McCaughan
Jacqueline C. Rendall
John E. Moore
author_facet Beverley Cherie Millar
John McCaughan
Jacqueline C. Rendall
John E. Moore
author_sort Beverley Cherie Millar
collection DOAJ
description Abstract Introduction Fluoroquinolone antibiotics, namely ciprofloxacin and levofloxacin, play an important role in treating infection in cystic fibrosis (CF) and ciprofloxacin remains the last widely used and orally available antipseudomonal agent. Recently, a new fluoroquinolone, delafloxacin, has been approved by the FDA for the indication of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). This antibiotic is a novel dual‐targeting anionic fluoroquinolone and differs from previous agents in its class, as it lacks a protonatable substituent. To date, there are no reports of its use or activity against Pseudomonas aeruginosa in CF. Alarmingly, fluoroquinolone resistance is increasing among CF P aeruginosa isolates. The aims of the study were to (a) examine in vitro susceptibility of delafloxacin against a population of P. aeruginosa (n = 52) isolated from adult CF patients at our CF centre, (b) to compare delafloxacin and ciprofloxacin in vitro susceptibilities against CF P. aeruginosa and (c) to evaluate where delafloxacin may add benefit in treating CF P aeruginosa. Methods In vitro susceptibilities were examined on 52 non‐mucoid P. aeruginosa and P. aeruginosa ATCC™ 27853 reference strain, by employing Etest® gradient test strips for delafloxacin (range:0.002 ‐ 32 mg/L) and ciprofloxacin (0.002 ‐ 32 mg/L), as per manufacturer's instructions (Biomerieux). Results MIC range, MIC50 and MIC90 for delafloxacin were 0.064 → 32 mg/L, 0.56 mg/L and 2.19 mg/L, respectively. For ciprofloxacin, these were 0.047 → 32 mg/L, 1.69 mg/L and 8.0 mg/L, respectively. Overall, isolates were statistically more sensitive to delafloxacin (p = 0.0005) than ciprofloxacin. Of note, 4/12 (33.3%) isolates with intermediate resistance to ciprofloxacin were sensitive to delafloxacin. Similarly, 10/28 (35.7%) isolates resistant to ciprofloxacin were sensitive to delafloxacin, with only 17.9% isolates resistant to ciprofloxacin, resistant to delafloxacin. Conclusion Given similar breakpoints of these fluoroquinolones, these data show that delafloxacin has greater activity than ciprofloxacin. While delafloxacin and ciprofloxacin were equally effective with sensitive isolates, the value of delafloxacin was noted with more resistant isolates to ciprofloxacin. While ciprofloxacin should remain the first line fluoroquinolone for treating CF P aeruginosa, delafloxacin shows potential in treating ciprofloxacin‐resistant P aeruginosa.
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spelling doaj.art-12c1f10319174305af2a93954873a67d2022-12-22T02:35:01ZengWileyThe Clinical Respiratory Journal1752-69811752-699X2021-01-0115111612010.1111/crj.13262Delafloxacin––A novel fluoroquinolone for the treatment of ciprofloxacin‐resistant Pseudomonas aeruginosa in patients with cystic fibrosisBeverley Cherie Millar0John McCaughan1Jacqueline C. Rendall2John E. Moore3Department of Bacteriology Northern Ireland Public Health Laboratory Belfast City Hospital Belfast UKDepartment of Medical Microbiology The Royal Group of Hospitals Belfast UKNorthern Ireland Regional Adult Cystic Fibrosis Centre Level 8 Belfast City Hospital Belfast UKDepartment of Bacteriology Northern Ireland Public Health Laboratory Belfast City Hospital Belfast UKAbstract Introduction Fluoroquinolone antibiotics, namely ciprofloxacin and levofloxacin, play an important role in treating infection in cystic fibrosis (CF) and ciprofloxacin remains the last widely used and orally available antipseudomonal agent. Recently, a new fluoroquinolone, delafloxacin, has been approved by the FDA for the indication of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). This antibiotic is a novel dual‐targeting anionic fluoroquinolone and differs from previous agents in its class, as it lacks a protonatable substituent. To date, there are no reports of its use or activity against Pseudomonas aeruginosa in CF. Alarmingly, fluoroquinolone resistance is increasing among CF P aeruginosa isolates. The aims of the study were to (a) examine in vitro susceptibility of delafloxacin against a population of P. aeruginosa (n = 52) isolated from adult CF patients at our CF centre, (b) to compare delafloxacin and ciprofloxacin in vitro susceptibilities against CF P. aeruginosa and (c) to evaluate where delafloxacin may add benefit in treating CF P aeruginosa. Methods In vitro susceptibilities were examined on 52 non‐mucoid P. aeruginosa and P. aeruginosa ATCC™ 27853 reference strain, by employing Etest® gradient test strips for delafloxacin (range:0.002 ‐ 32 mg/L) and ciprofloxacin (0.002 ‐ 32 mg/L), as per manufacturer's instructions (Biomerieux). Results MIC range, MIC50 and MIC90 for delafloxacin were 0.064 → 32 mg/L, 0.56 mg/L and 2.19 mg/L, respectively. For ciprofloxacin, these were 0.047 → 32 mg/L, 1.69 mg/L and 8.0 mg/L, respectively. Overall, isolates were statistically more sensitive to delafloxacin (p = 0.0005) than ciprofloxacin. Of note, 4/12 (33.3%) isolates with intermediate resistance to ciprofloxacin were sensitive to delafloxacin. Similarly, 10/28 (35.7%) isolates resistant to ciprofloxacin were sensitive to delafloxacin, with only 17.9% isolates resistant to ciprofloxacin, resistant to delafloxacin. Conclusion Given similar breakpoints of these fluoroquinolones, these data show that delafloxacin has greater activity than ciprofloxacin. While delafloxacin and ciprofloxacin were equally effective with sensitive isolates, the value of delafloxacin was noted with more resistant isolates to ciprofloxacin. While ciprofloxacin should remain the first line fluoroquinolone for treating CF P aeruginosa, delafloxacin shows potential in treating ciprofloxacin‐resistant P aeruginosa.https://doi.org/10.1111/crj.13262antibiotic resistanceciprofloxacincystic fibrosisdelafloxacinfluoroquinolonePseudomonas aeruginosa
spellingShingle Beverley Cherie Millar
John McCaughan
Jacqueline C. Rendall
John E. Moore
Delafloxacin––A novel fluoroquinolone for the treatment of ciprofloxacin‐resistant Pseudomonas aeruginosa in patients with cystic fibrosis
The Clinical Respiratory Journal
antibiotic resistance
ciprofloxacin
cystic fibrosis
delafloxacin
fluoroquinolone
Pseudomonas aeruginosa
title Delafloxacin––A novel fluoroquinolone for the treatment of ciprofloxacin‐resistant Pseudomonas aeruginosa in patients with cystic fibrosis
title_full Delafloxacin––A novel fluoroquinolone for the treatment of ciprofloxacin‐resistant Pseudomonas aeruginosa in patients with cystic fibrosis
title_fullStr Delafloxacin––A novel fluoroquinolone for the treatment of ciprofloxacin‐resistant Pseudomonas aeruginosa in patients with cystic fibrosis
title_full_unstemmed Delafloxacin––A novel fluoroquinolone for the treatment of ciprofloxacin‐resistant Pseudomonas aeruginosa in patients with cystic fibrosis
title_short Delafloxacin––A novel fluoroquinolone for the treatment of ciprofloxacin‐resistant Pseudomonas aeruginosa in patients with cystic fibrosis
title_sort delafloxacin a novel fluoroquinolone for the treatment of ciprofloxacin resistant pseudomonas aeruginosa in patients with cystic fibrosis
topic antibiotic resistance
ciprofloxacin
cystic fibrosis
delafloxacin
fluoroquinolone
Pseudomonas aeruginosa
url https://doi.org/10.1111/crj.13262
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