Antimicrobial susceptibility and epidemiological types of Legionella pneumophila human isolates from Italy (1987-2020)

Objectives: Although antimicrobial resistance has not yet emerged as an overarching problem for Legionella pneumophila (L. pneumophila) infection, the description of clinical and environmental strains resistant to fluoroquinolones and macrolides is a cause of concern. This study aimed to investigate the antimicrobial susceptibility of L. pneumophila human isolates in Italy. Methods: A total of 204 L. pneumophila clinical isolates were tested for sensitivity to 9 antibiotics using the broth microdilution assay (BMD). All isolates were typed by sequence-based typing, and Legionella pneumophila serogroup 1 (Lp1) isolates by monoclonal antibody subgrouping. Minimum inhibitory concentration (MIC) data were correlated with the possible source of infection and geographical distribution. The presence of the lpeAB efflux pump genes was also investigated. The genome sequences of a subpopulation of isolates showing reduced susceptibility to azithromycin were also analysed. Results: The L. pneumophila isolates did not show significant resistance to the tested antibiotics, although a trend toward reduced sensitivity to azithromycin was observed in a subpopulation of 46 strains, most of which belonged to sequence type 1 (ST1), the second most widespread ST in Italy. An amplicon of the expected size overlapping the lpeAB genes was obtained only in the 46-subpopulation above mentioned. In 4 of the 46 isolates, sequencing analysis showed the occurrence of amino-acid substitutions already described in other strains. No further mutation was found. Conclusions: The presence of L. pneumophila strains with reduced susceptibility or resistance to azithromycin should be monitored to predict future trends and suggest to physicians a combined therapy with fluoroquinolones when a poor response to azithromycin is observed.