In vitro characterization of delafloxacin activity against intracellular Legionella: Exploring new treatment options for Legionnaires' disease

Abstract

Objectives: Delafloxacin is a fourth-generation fluoroquinolone that is currently approved in Europe and the United States for bacterial infections of the skin and skin structures and for community-acquired pneumonia, including cases where it is caused by atypical pathogens. It has demonstrated superior efficacy against a broad spectrum of bacteria and fewer adverse effects compared with other quinolones, such as levofloxacin, a current first-line treatment against Legionnaires' disease. This study aimed to characterize for the first time the intracellular activity of delafloxacin compared with levofloxacin against various serogroups of Legionella pneumophila and species of Legionella in terms of culturability and viability.

Methods: The infectious capacity of 10 Legionella strains was evaluated individually to ensure a percentage of viable infected macrophage post-infection. Then, the extracellular concentration inhibiting intracellular multiplication (MIEC₉₀) of the antibiotic was determined by gradient antibiotic incubations in the in vitro infection model through culturability assays. Finally, the viability of intracellular Legionella was studied by quantitative polymerase chain reaction after antibiotic treatment at MIEC₉₀ value.

Results: Delafloxacin decreased the culturability of Legionella from five to 10 times more than levofloxacin. The MIEC₉₀ obtained was 0.025 mg/l for levofloxacin and 0.005 mg/l for delafloxacin for all strains tested, except L. longbeachae; the same concentration for both antibiotics was required. The bactericidal effect of both antibiotics was confirmed by viability quantitative polymerase chain reaction.

Conclusions: Based on the results obtained, the higher intracellular activity of delafloxacin compared with levofloxacin and its better safety profile should be confirmed in phase IV clinical real-life cases of Legionnaires' disease.

Keywords: Delafloxacin; Intracellular activity; Legionella; Levofloxacin; Macrophages; Minimum inhibitory extracellular concentration.