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

EBioMedicine

卷:2

Jean-François Timsit¹  Carole Schwebel¹  Sylvie Larrat²  Iyad Almahmoud³  Lubana Shadoud³  Max Maurin³  Dominique Schneider³  Sophie Jarraud⁴  Jérôme Etienne⁴ 

[1] CHU Grenoble, Réanimation Médicale, Grenoble, France;

[2] Unit of Virus host Cell Interactions (UVHCI), UMI 3265, Univ. Grenoble Alpes, European Molecular Biology Laboratory (EMBL), Centre National de la Recherche Scientifique (CNRS), Grenoble, France;

[3] Univ. Grenoble Alpes, Laboratoire Adaptation et Pathogénie des Microorganismes (LAPM), F-38000 Grenoble, France;

[4] Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France;

关键词: Legionella pneumophila;    Legionellosis;    Fluoroquinolone resistance;    In vivo selection;    Resistance detection;    Next generation sequencing;   

DOI  :  10.1016/j.ebiom.2015.07.018

来源: DOAJ

【 摘 要 】

Background: Infectious 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.Methods: We 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.Findings: We 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.Interpretation: In 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.

【 授权许可】

Unknown