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Antimicrobial agent susceptibilities of Legionella pneumophila MLVA-8 genotypes

Yehonatan Sharaby¹, Orna Nitzan^2,3, Ingrid Brettar⁴

¹Department of Evolutionary and Environmental Biology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel.

Scientific Reports

|April 18, 2019

Abstract:

Legionella pneumophila causes human lung infections resulting in severe pneumonia. High-resolution genotyping of L. pneumophila isolates can be achieved by multiple-locus variable-number tandem-repeat analysis (MLVA-8). Legionella infections in humans occur as a result of inhalation of bacteria-containing aerosols, thus, our aim was to study the antimicrobial susceptibilities of different MLVA-8 genotypes to ten commonly used antimicrobial agents in legionellosis therapy. Epidemiological cut-off values were determined for all antibiotics. Significant differences were found between the antimicrobial agents' susceptibilities of the three studied environmental genotypes (Gt4, Gt6, and Gt15). Each genotype exhibited a significantly different susceptibility profile, with Gt4 strains (Sequence Type 1) significantly more resistant towards most studied antimicrobial agents. In contrast, Gt6 strains (also Sequence Type 1) were more susceptible to six of the ten studied antimicrobial agents compared to the other genotypes. Our findings show that environmental strains isolated from adjacent points of the same water system, exhibit distinct antimicrobial resistance profiles. These differences highlight the importance of susceptibility testing of Legionella strains. In Israel, the most extensively used macrolide for pneumonia is azithromycin. Our results point at the fact that clarithromycin (another macrolide) and trimethoprim with sulfamethoxazole (SXT) were the most effective antimicrobial agents towards L. pneumophila strains. Moreover, legionellosis can be caused by multiple L. pneumophila genotypes, thus, the treatment approach should be the use of combined antibiotic therapy. Further studies are needed to evaluate specific antimicrobial combinations for legionellosis therapy.

Insights

Different Legionella pneumophila genotypes show varying antimicrobial resistance. Genotype Gt4 was most resistant, while Gt6 was more susceptible, highlighting the need for Legionella susceptibility testing in pneumonia treatment.

Area of Science:

Microbiology
Infectious Diseases
Antimicrobial Resistance

Background:

Legionella pneumophila causes severe pneumonia through aerosol inhalation.
Multiple-locus variable-number tandem-repeat analysis (MLVA-8) is a high-resolution genotyping method for L. pneumophila.
Understanding antimicrobial susceptibilities of different L. pneumophila genotypes is crucial for effective legionellosis therapy.

Purpose of the Study:

To investigate the antimicrobial susceptibilities of three distinct L. pneumophila MLVA-8 genotypes (Gt4, Gt6, Gt15) against ten common antibiotics.
To determine epidemiological cut-off values for these antibiotics in legionellosis treatment.
To assess the impact of genotypic variation on antimicrobial resistance profiles in environmental L. pneumophila strains.

Main Methods:

Genotyping of L. pneumophila isolates using MLVA-8.
Antimicrobial susceptibility testing against ten commonly used antimicrobial agents.
Determination of epidemiological cut-off values for each antibiotic.
Statistical analysis to compare susceptibility profiles between genotypes.

Main Results:

Significant differences in antimicrobial susceptibility were observed among the three studied genotypes (Gt4, Gt6, Gt15).
Gt4 strains (Sequence Type 1) exhibited significantly higher resistance to most tested antimicrobial agents.
Gt6 strains (Sequence Type 1) demonstrated greater susceptibility to six of the ten antibiotics compared to other genotypes.
Environmental strains from the same water system displayed distinct antimicrobial resistance profiles.

Conclusions:

Environmental L. pneumophila strains, even from the same source, can possess unique antimicrobial resistance patterns.
Susceptibility testing for Legionella strains is essential for guiding appropriate pneumonia treatment.
Clarithromycin and trimethoprim-sulfamethoxazole (SXT) showed the highest efficacy against the studied L. pneumophila strains.
Combined antibiotic therapy is recommended for legionellosis due to the potential involvement of multiple L. pneumophila genotypes.

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