Delafloxacin – A Novel fluoroquinolone for the treatment of ciprofloxacin-resistant pseudomonas aeruginosa in patients with cystic fibrosis (CF)

Link to article at PubMed

Clin Respir J. 2020 Aug 13. doi: 10.1111/crj.13262. Online ahead of print.


INTRODUCTION: Fluoroquinolone antibiotics, namely ciprofloxacin and levofloxacin, play an important role in treating infection in cystic fibrosis (CF) and ciprofloxacin remains the last orally available antipseudomonal agent. Recently, a new fluoroquinolone, delafloxacin, has been approved by the FDA for skin infections. 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 (PA) in CF. Alarmingly, fluoroquinolone resistance is increasing amongst CF PA isolates. The aims of the study were to (i) examine in vitro susceptibility of delafloxacin against a population of PA (n=52) isolated from adult CF patients at our CF centre, (ii) to compare delafloxacin and ciprofloxacin susceptibilities and (iii) to evaluate where delafloxacin may add benefit in treating CF PA.

METHODS: In vitro susceptibilities were examined on 52 non-mucoid PA and ATCC™ 27853 reference strain, by employing Etest® gradient 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, this data shows that delafloxacin has greater activity than ciprofloxacin. Whilst delafloxacin and ciprofloxacin were equally effective with sensitive isolates, the value of delafloxacin was noted with more resistant isolates to ciprofloxacin. Whilst ciprofloxacin should remain the first line fluoroquinolone for treating CF PA, delafloxacin shows potential in treating ciprofloxacin-resistant PA.

PMID:32790958 | DOI:10.1111/crj.13262

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