The antibiotic delafloxacin emerges as a potential therapeutic alternative against Legionella

A study led by researchers at the Germans Trias i Pujol Research Institute (IGTP) shows, in an experimental laboratory model, that delafloxacin inhibits the intracellular replication of Legionella more effectively than one of the current standard treatments. The findings provide new evidence of its potential therapeutic value and support the need for future clinical studies in patients with Legionnaires' disease.

Legionnaires' disease is a severe form of pneumonia caused by bacteria of the genus Legionella, which are transmitted through the inhalation of aerosols from contaminated water. In Europe, its incidence has increased markedly in recent years, rising in just five years from 2.4 to 3.5 infections per 100,000 inhabitants. This increase has been linked to factors such as climate change, which promotes the proliferation of the bacteria in water systems, as well as greater awareness and improvements in the detection and reporting of cases.

The treatment of this disease is based on antibiotics that are able to act effectively inside human cells, as Legionella is an intracellular pathogen that replicates within macrophages. Among the current therapeutic options, levofloxacin is one of the reference antibiotics, although its use may require high doses and is associated with some adverse effects characteristic of fluoroquinolones.

Exploring new therapeutic options against Legionella

In this context, the Clinical and Environmental Infectious Diseases Study Group (CEID) at IGTP evaluated the efficacy of delafloxacin against different Legionella species and compared it with that of levofloxacin. To do so, the team used an in vitro model of intracellular infection in human macrophages, analysing ten representative strains of the genus.

The results, published in the International Journal of Infectious Diseases, show that delafloxacin displays greater intracellular activity, except in one specific species, Legionella longbeachae, for which both antibiotics showed similar efficacy. In most of the strains analysed, delafloxacin reduced the intracellular multiplication of Legionella at concentrations five to ten times lower than those required with levofloxacin.

In addition, the researchers confirmed that the observed effect is bactericidal and does not induce a viable but non-culturable (VBNC) state, an aspect of particular relevance for Legionella, as this state can hinder detection and control in clinical and environmental settings. To this end, the team combined culturability assays with viability PCR techniques, demonstrating a genuine reduction in bacterial viability following antibiotic treatment.

"As an intracellular pathogen, Legionella requires antibiotics that effectively penetrate host cells, and delafloxacin has demonstrated promising intracellular activity that supports further clinical investigation as a potential improvement over current treatments", explains Roger Cortès-Tarragó, first author of the study.

Scope and next steps

The authors stress, however, that this is an in vitro study conducted with a limited number of strains, and therefore the results cannot be directly translated into clinical practice. Future work will need to confirm these findings in more complex models and, in particular, in clinical studies to assess whether the greater intracellular activity of delafloxacin translates into clinical benefits for patients with Legionnaires' disease.

The work also highlights the value of collaboration between academia and the pharmaceutical industry. "This study is the result of collaboration between a research group and an internationally relevant pharmaceutical company. The findings underline the importance of public-private partnerships and reflect the translational orientation of the research carried out at our centre, providing valuable information for future clinical application", says Noemí Párraga-Niño, corresponding author and supervisor of the study.

Overall, the study provides new evidence supporting the potential of delafloxacin as an alternative therapeutic option against Legionella and justifies the need for clinical studies comparing its efficacy and safety with currently available treatments.

Reference

Cortès-Tarragó R, Arqué E, Vinyeta L, Basart Altieri M, Elizondo SM, Sopena N, Reynaga E, Díez de Los Ríos J, Quero S, Párraga-Niño N, Pedro-Botet L. In vitro characterization of delafloxacin activity against intracellular Legionella: Exploring new treatment options for Legionnaires' disease. Int J Infect Dis. 2025 Nov 2;162:108165. DOI: 10.1016/j.ijid.2025.108165.

Funding

This study was partially funded by Laboratorios Menarini S.A., which granted the research group to carry out part of this study as a part of collaboration between the Germans Trias i Pujol Institute and the pharmaceutical company. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

This project has been funded by a grant from the JMC Arrival Fund of the Germans Trias i Pujol University Hospital and promoted by the Universitat Autònoma de Barcelona. CIBERES is an initiative of Instituto de Salud Carlos III. Germans Trias i Pujol Research Institute are included in the CERCA Programme/Generalitat de Catalunya.