Antibiotic Resistance of Legionella pneumophila in Clinical and Water Isolates—A Systematic Review

Abstract

The current systematic review investigates the antibiotic susceptibility pattern of Legionella pneumophila isolates from the 1980s to the present day, deriving data from clinical and/or water samples from studies carried out all over the world. Eighty-nine papers meeting the inclusion criteria, i.e., “Legionella pneumophila” and “resistance to antibiotics”, were evaluated according to pre-defined validity criteria. Sixty articles referred to clinical isolates, and 18 articles reported water-related L. pneumophila isolates, while 11 articles included both clinical and water isolates. Several methods have been proposed as suitable for the determination of MICs, such as the E-test, broth and agar dilution, and disk diffusion methods, in vivo and in vitro, using various media. The E-test method proposed by the European Society of Clinical Microbiology and Infectious Diseases (EUCAST) seems to be the second most frequently used method overall, but it is the preferred method in the most recent publications (2000–2019) for the interpretation criteria. Erythromycin has been proved to be the preference for resistance testing over the years. However, in the last 19 years, the antibiotics ciprofloxacin (CIP), erythromycin (ERM), levofloxacin (LEV) and azithromycin (AZM) were the ones that saw an increase in their use. A decrease in the sensitivity to antibiotics was identified in approximately half of the reviewed articles.

Antimicrobial susceptibility profiles and tentative epidemiological cutoff values of Legionella pneumophila from environmental water and soil sources in China

“…The epidemiological cutoff value (ECOFF) is used to distinguish isolates with resistant mechanisms and acts as a reference in clinical treatment when an approved clinical breakpoint is not determined ( Kahlmeter, 2014 ), which is usually the highest MIC for microorganisms lacking phenotypically detectable acquired resistance mechanisms and can be obtained from pooled MIC distributions by using the statistical goodness-of-fit tests ( Turnidge et al, 2006 ; Karatuna et al, 2020 ). In the past few decades, many antimicrobial susceptibility tests (ASTs) have been conducted on L. pneumophila ( García et al, 2000 ; Choi et al, 2010 ; Bruin et al, 2012 ; De Giglio et al, 2015 ; Xiong et al, 2016 ; Vandewalle-Capo et al, 2017 ; Koshkolda and Lück, 2018 ; Wilson et al, 2018 ; Jia et al, 2019 ; Natas et al, 2019 ; Sharaby et al, 2019 ; Assaidi et al, 2020 ; Pappa et al, 2020 ; Cocuzza et al, 2021 ); however, sufficient data to establish comprehensive ECOFFs are not currently available due to the limited number of wild-type (WT) isolates ( Koshkolda and Lück, 2018 ). Meanwhile, a small number (dozens to hundreds) of L. pneumophila isolates from samples confined to a small region tested for the minimum inhibitory concentration (MIC) distribution and ECOFFs were a noteworthy issue ( Al-Matawah et al, 2012 ).…”

Sensitivity of Legionella pneumophila to phthalates and their substitutes

“…In order to assess whether an exposure to phthalates modulates the antibiotic resistance pattern of L. pneumophila Paris, four antibiotics (Azithromycin, Clarithromycin, Levofloxacin and Rifampicin) most commonly used in clinical treatment of legionellosis 71 were selected (Table 2 ).…”

Bacterial persistence in Legionella pneumophila clinical isolates from patients with recurring legionellosis

“…Treatment failure of legionellosis is still a serious issue today with a 5-10% mortality rate ( Herwaldt and Marra, 2018 ). To date, natural antibiotic resistant Lp are rarely characterised compared to other bacterial pathogens ( Pappa et al., 2020 ; Ginevra et al., 2022 ). Even though macrolide resistant clones can be easily obtained during in vitro evolution ( Descours et al., 2017 ), these resistance-associated mutations are not recovered in Lp clinical isolates issued from patients with relapsing legionellosis ( Pouderoux et al., 2020 ).…”