Hidden Selection of Bacterial Resistance to Fluoroquinolones In Vivo: The Case of Legionella pneumophila and Humans

• Legionellosis is a pneumonia caused by the inhalation of aerosols containing Legionella, mainly L. pneumophila.
• Its average mortality rate is 10%, despite availability of effective antibiotics such as the macrolides and the fluoroquinolones.
• Using modern molecular approaches, we identified the selection of fluoroquinolone resistance in L. pneumophila in patients under fluoroquinolone therapy.
• This may lead to reduction of treatment efficacy and prognosis worsening.
• Our findings should lead to revised guidelines for therapeutic management and prognosis evaluation of legionellosis.

BackgroundInfectious diseases are the leading cause of human morbidity and mortality worldwide. One dramatic issue is the emergence of microbial resistance to antibiotics which is a major public health concern. Surprisingly however, such in vivo adaptive ability has not been reported yet for many intracellular human bacterial pathogens such as Legionella pneumophila.MethodsWe examined 82 unrelated patients with Legionnaire's disease from which 139 respiratory specimens were sampled during hospitalization and antibiotic therapy. We both developed a real time PCR assay and used deep-sequencing approaches to detect antibiotic resistance mutations in L. pneumophila and follow their selection and fate in these samples.FindingsWe identified the in vivo selection of fluoroquinolone resistance mutations in L. pneumophila in two infected patients treated with these antibiotics. By investigating the mutational dynamics in patients, we showed that antibiotic resistance occurred during hospitalization most likely after fluoroquinolone treatment.InterpretationIn vivo selection of antibiotic resistances in L. pneumophila may be associated with treatment failures and poor prognosis. This hidden resistance must be carefully considered in the therapeutic management of legionellosis patients and in the control of the gradual loss of effectiveness of antibiotics.