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Article Dans Une Revue Journal of Antimicrobial Chemotherapy Année : 2024

In vitro activity of delafloxacin against clinical levofloxacin-resistant Helicobacter pylori isolates

Activité in vitro de la Délafloxacine sur les isolats cliniques de H. pylori résistant à la lévofloxacine.

Résumé

Background: Increasing antibiotic resistance in Helicobacter pylori necessitates research on new active molecules. In 2017, delafloxacin, a new fluoroquinolone with chemical properties of activity under acidic conditions, was approved for treatment of community-acquired bacterial pneumonia and acute bacterial skin and soft-tissue infections. Mutations in gyrA are responsible for fluoroquinolone resistance, but certain clinical isolates of H. pylori appear to display a dual phenotype: resistance to levofloxacin associated with very low delafloxacin MICs.
Objectives: To estimate epidemiological cut-off (ECOFF) values and to identify mutations in the gyrA gene, specific to FQ resistance, without increasing the MICs of delafloxacin. Methods Clinical strains (n = 231) were collected in the bacteriology laboratory of Poitiers University Hospital over a 2 year period to determine the ECOFF of delafloxacin. Retrospectively, 101 clinical strains with an levofloxacin-resistant phenotype (MIC > 1 mg/L) were selected from 2018 to 2022 for delafloxacin MIC determination and QRDR (gyrA) sequencing.
Results: The estimated ECOFF of delafloxacin was ≤0.125 mg/L. No H. pylori isolate showed a levofloxacin-sensitive phenotype with a delafloxacin MIC of >0.125 mg/L. Among the levofloxacin-resistant H. pylori isolates, 53.5% had delafloxacin MICs of ≤0.125 mg/L. The N87I mutation was associated with dual levofloxacin/delafloxacin resistance (P < 0.001) in contrast to the N87K and D91N mutations (P > 0.05). Mutations D91G and D91Y were not associated with a delafloxacin resistance phenotype (P > 0.05).
Conclusions: Delafloxacin seems to be a therapeutic alternative for levofloxacin-resistant strains with greater in vitro activity. However, further clinical/biological investigations are required to determine its efficacy in H. pylori eradication.
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hal-04670899 , version 1 (23-08-2024)

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Victor Luzarraga, Julie Cremniter, Chloé Plouzeau, Anthony Michaud, Lauranne Broutin, et al.. In vitro activity of delafloxacin against clinical levofloxacin-resistant Helicobacter pylori isolates. Journal of Antimicrobial Chemotherapy, 2024, ⟨10.1093/jac/dkae269⟩. ⟨hal-04670899⟩

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