Delafloxacin--A novel fluoroquinolone for the treatment of ciprofloxacin-resistantPseudomonas aeruginosain patients with cystic fibrosis

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 againstPseudomonas aeruginosain CF. Alarmingly, fluoroquinolone resistance is increasing among CFP aeruginosaisolates. The aims of the study were to (a) examine in vitro susceptibility of delafloxacin against a population ofP. aeruginosa(n = 52) isolated from adult CF patients at our CF centre, (b) to compare delafloxacin and ciprofloxacin in vitro susceptibilities against CFP. aeruginosaand (c) to evaluate where delafloxacin may add benefit in treating CFP aeruginosa. Methods In vitro susceptibilities were examined on 52 non-mucoidP. aeruginosaandP. aeruginosaATCC (TM) 27853 reference strain, by employing Etest(R)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, MIC(50)and MIC(90)for delafloxacin were 0.064 (R) 32 mg/L, 0.56 mg/L and 2.19 mg/L, respectively. For ciprofloxacin, these were 0.047 (R) 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 CFP aeruginosa, delafloxacin shows potential in treating ciprofloxacin-resistantP aeruginosa.