{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:19:38Z","timestamp":1790752778627,"version":"4.1.0"},"reference-count":106,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T00:00:00Z","timestamp":1597104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>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., \u201cLegionella pneumophila\u201d and \u201cresistance to antibiotics\u201d, 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\u20132019) 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.<\/jats:p>","DOI":"10.3390\/ijerph17165809","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T09:28:57Z","timestamp":1597138137000},"page":"5809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Antibiotic Resistance of Legionella pneumophila in Clinical and Water Isolates\u2014A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"given":"Olga","family":"Pappa","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of West Attica, 12243 Egaleo, Greece"},{"name":"Central Public Health Laboratory, National Public Health Organization, EL-15123 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimosthenis","family":"Chochlakis","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Microbiology and Microbial Pathogenesis, School of Medicine, University of Crete, 71500 Heraklion, Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilios","family":"Sandalakis","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Microbiology and Microbial Pathogenesis, School of Medicine, University of Crete, 71500 Heraklion, Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrysa","family":"Dioli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of West Attica, 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Psaroulaki","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Microbiology and Microbial Pathogenesis, School of Medicine, University of Crete, 71500 Heraklion, Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena","family":"Mavridou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of West Attica, 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1128\/MMBR.00016-10","article-title":"Origins and evolution of antibiotic resistance","volume":"74","author":"Davies","year":"2010","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_2","unstructured":"O\u2019Neill, J. (2019, November 22). Tackling Drug-Resistant Infections Globally: Final Report and Recommendations. The Review on Antimicrobial Resistance. Available online: https:\/\/wellcomecollection.org\/works\/thvwsuba."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Manyi-Loh, C., Mamphweli, S., Meyer, E., and Okoh, A. (2018). Antibiotic use in agriculture and its consequential resistance in environmental sources: Potential public health implications. Molecules, 23.","DOI":"10.3390\/molecules23040795"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jes.2019.02.023","article-title":"Abundance of antibiotic resistance genes and their association with bacterial communities in activated sludge of wastewater treatment plants: Geographical distribution and network analysis","volume":"82","author":"Zhang","year":"2019","journal-title":"J. Environ. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109837","DOI":"10.1016\/j.ecoenv.2019.109837","article-title":"Antibiotic Resistance Genes in drinking water of China: Occurrence, distribution and influencing factors","volume":"188","author":"Zhang","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.scitotenv.2019.03.162","article-title":"Antibiotic resistance in drinking water systems: Occurrence, removal, and human health risks","volume":"669","author":"Sanganyado","year":"2019","journal-title":"Sci. Total. Environ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.chemosphere.2018.11.106","article-title":"Response of microorganisms in biofilm to sulfadiazine and ciprofloxacin in drinking water distribution systems","volume":"218","author":"Wang","year":"2019","journal-title":"Chemosphere"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.micpath.2017.05.004","article-title":"Comparison of biofilm formation and antibiotic resistance pattern of Pseudomonas aeruginosa in human and environmental isolates","volume":"109","author":"Gholami","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"02116","DOI":"10.1128\/AAC.02188-16","article-title":"Ribosomal mutations conferring macrolide resistance in legionella pneumophila","volume":"61","author":"Descours","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/S0140-6736(78)91507-6","article-title":"Outbreak of legionnaires\u2019 disease diagnosed in 1977 clinical and epidemiological features","volume":"312","author":"Terranova","year":"1978","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2165\/00003495-199346010-00005","article-title":"Treatment of legionnaires\u2019 disease","volume":"46","author":"Roig","year":"1993","journal-title":"Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/jac\/41.2.289","article-title":"Activity of azithromycin, clarithromycin, roxithromycin, dirithromycin, quinupristin\/dalfopristin and erythromycin against Legionella species by intracellular susceptibility testing in HL-60 cells","volume":"41","author":"Stout","year":"1998","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/jac\/dki391","article-title":"In vitro activity of pazufloxacin, tosufloxacin and other quinolones against Legionella species","volume":"56","author":"Higa","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1086\/511159","article-title":"Infectious diseases society of America\/American thoracic society consensus guidelines on the management of community-acquired pneumonia in adults","volume":"44","author":"Mandell","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1111\/j.1469-0691.2011.03672.x","article-title":"Guidelines for the management of adult lower respiratory tract infections\u2014Full version","volume":"17","author":"Woodhead","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1378\/chest.125.6.2135","article-title":"Levofloxacin efficacy in the treatment of community-acquired Legionellosis","volume":"125","author":"Yu","year":"2004","journal-title":"Chest"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1086\/428059","article-title":"Clinical outcomes for hospitalized patients with legionella pneumonia in the antigenuria era: The influence of levofloxacin therapy","volume":"40","author":"Mykietiuk","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1086\/428049","article-title":"Antimicrobial chemotherapy for legionnaires disease: Levofloxacin versus macrolides","volume":"40","author":"Garrido","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1378\/chest.128.3.1401","article-title":"Fluoroquinolones vs macrolides in the treatment of legionnaires disease","volume":"128","author":"Roig","year":"2005","journal-title":"Chest"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"353","DOI":"10.2169\/internalmedicine.46.6006","article-title":"Intravenous ciprofloxacin versus erythromycin in the treatment of Legionella pneumonia","volume":"46","author":"Haranaga","year":"2007","journal-title":"Intern. Med."},{"key":"ref_21","first-page":"495","article-title":"Macrolides versus quinolones in Legionella pneumonia: Results from the Community-Acquired Pneumonia Organization international study","volume":"14","author":"Griffin","year":"2010","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1093\/jac\/dkm055","article-title":"The ORION statement: Guidelines for transparent reporting of Outbreak Reports and Intervention studies Of Nosocomial infection","volume":"59","author":"Stone","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., G\u00f8tzsche, P.C., Ioannidis, J.P.A., Clarke, M., Devereaux, P., Kleijnen, J., and Moher, D. (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med., 6.","DOI":"10.2427\/5768"},{"key":"ref_24","unstructured":"Gilbert, D.N., Eliopoulos, G.M., Chambers, H.F., Saag, M.S., and Pavia, A.T. (2020). The Sanford Guide to Antimicrobial Therapy 2020: 50 Years: 1969-2019, Antimicrobial Therapy. [50th ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4172\/2332-0877.1000e103","article-title":"Antibiotic susceptibility surveillance of environmental legionella Strains: Application of the E-Test to bacteria isolated from hospitals in Greece","volume":"2","author":"Alexandropoulou","year":"2014","journal-title":"J. Infect. Dis. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Alexandropoulou, I., Parasidis, T., Konstantinidis, T., Panopoulou, M., and Constantinidis, T. (2019). A Proactive environmental approach for preventing legionellosis in infants: Water sampling and antibiotic resistance monitoring, a 3-Years Survey Program. Health, 7.","DOI":"10.3390\/healthcare7010039"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/jac\/44.5.693","article-title":"In-vitro activity of antibiotics against Legionella pneumophila isolates from water systems","volume":"44","author":"Tsakris","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"678","DOI":"10.2166\/wh.2014.217","article-title":"Minimum inhibitory concentration distribution in environmental Legionella spp. isolates","volume":"12","author":"Sandalakis","year":"2014","journal-title":"J. Water Health"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.diagmicrobio.2011.09.016","article-title":"Wild-type MIC distribution and epidemiological cut-off values in clinical Legionella pneumophila serogroup 1 isolates","volume":"72","author":"Bruin","year":"2012","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6138","DOI":"10.1038\/s41598-019-42425-1","article-title":"Antimicrobial agent susceptibilities of Legionella pneumophila MLVA-8 genotypes","volume":"9","author":"Sharaby","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_31","unstructured":"(2019, November 22). Antimicrobial Wild Type Distributions of Microorganisms. Available online: https:\/\/mic.eucast.org\/Eucast2\/SearchController\/search.jsp%3Faction=init."},{"key":"ref_32","unstructured":"EUCAST (2019, November 22). General Consultation on Considerations in the Numerical Estimation of Epidemiological Cutoff (ECOFF) Values. Available online: https:\/\/www.eucast.org\/documents\/consultations\/."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/j.1469-0691.2006.01377.x","article-title":"Statistical characterisation of bacterial wild-type MIC value distributions and the determination of epidemiological cut-off values","volume":"12","author":"Turnidge","year":"2006","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1128\/AAC.13.1.78","article-title":"In vitro activity of antimicrobial agents on legionnaires disease bacterium","volume":"13","author":"Thornsberry","year":"1978","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1128\/jcm.30.3.537-539.1992","article-title":"Cefamandole-susceptible strains of Legionella pneumophila serogroup 1: Implications for diagnosis and utility as an epidemiological marker","volume":"30","author":"Vickers","year":"1992","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/BF01989985","article-title":"Antimicrobial activity of ten macrolide, linsosamine and streptogramin drugs tested against Legionella species","volume":"11","author":"Johnson","year":"1992","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"568","DOI":"10.2105\/AJPH.77.5.568","article-title":"Pontiac fever outbreak associated with a cooling tower","volume":"77","author":"Friedman","year":"1987","journal-title":"Am. J. Public Health"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.envres.2015.08.013","article-title":"Antibiotic susceptibility of Legionella pneumophila strains isolated from hospital water systems in Southern Italy","volume":"142","author":"Napoli","year":"2015","journal-title":"Environ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jiac.2018.01.018","article-title":"In vitro activity of various antibiotics against clinical strains of Legionella species isolated in Japan","volume":"24","author":"Miyashita","year":"2018","journal-title":"J. Infect. Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"936","DOI":"10.26719\/2013.19.11.936","article-title":"Isolation and identification of Legionella pneumophila from drinking water in Basra governorate, Iraq","volume":"19","author":"Yehyazarian","year":"2013","journal-title":"East. Mediterr. Health J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.envres.2018.02.030","article-title":"Environmental surveillance and in vitro activity of antimicrobial agents against Legionella pneumophila isolated from hospital water systems in Campania, South Italy: A 5-year study","volume":"164","author":"Torre","year":"2018","journal-title":"Environ. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1469-0691.1997.tb00627.x","article-title":"Susceptibility testing by E-test and agar dilution of 30 strains of Legionella spp. isolated in Portugal","volume":"3","author":"Marques","year":"1997","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s10661-009-1293-y","article-title":"In vitro activity of antimicrobial agents against Legionella isolated from environmental water systems: First results from Turkey","volume":"171","author":"Erdogan","year":"2010","journal-title":"Environ. Monit. Assess."},{"key":"ref_44","first-page":"138389","article-title":"Detection and quantification of legionella pneumophila from water systems in kuwait residential facilities","volume":"2012","author":"Qasem","year":"2012","journal-title":"J. Pathog."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.2166\/wh.2016.056","article-title":"Antibiotic susceptibility of Legionella strains isolated from public water sources in Macau and Guangzhou","volume":"14","author":"Xiong","year":"2016","journal-title":"J. Water Health"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"66","DOI":"10.5604\/12321966.1234048","article-title":"Assessment of antibiotic susceptibility of Legionella pneumophila isolated from water systems in Poland","volume":"24","author":"Sikora","year":"2017","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0732-8893(99)00095-4","article-title":"Susceptibility of Legionella species to five antibiotics and development of resistance by exposure to erythromycin, ciprofloxacin, and rifampicin","volume":"36","author":"Nielsen","year":"2000","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"661","DOI":"10.2217\/fmb-2019-0049","article-title":"Antibiotic susceptibility of environmental Legionella pneumophila isolated in India","volume":"14","author":"Sreenath","year":"2019","journal-title":"Futur. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ijmm.2013.11.002","article-title":"Mixed infection by Legionella pneumophila in outbreak patients","volume":"304","author":"Colomina","year":"2014","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"40114","DOI":"10.1038\/srep40114","article-title":"Comparison of sputum microbiome of legionellosis-associated patients and other pneumonia patients: Indications for polybacterial infections","volume":"7","author":"Mizrahi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_51","unstructured":"(1967). Establishment of a provisional National Committee on Clinical Laboratory Standards, NCCLS, Department of Helath, Education and Welfare, Public Health Service Burea of Disease Prevention and Environmental Control, National Communicable Disease Center. Available online: https:\/\/clsi.org\/about\/clsis-history\/."},{"key":"ref_52","unstructured":"Clinical and Laboratory Standards Institute (2019, November 22). Available online: https:\/\/clsi.org\/about\/clsis-history\/."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Jia, X., Ren, H., Nie, X., Li, Y., Li, J., and Qin, T. (2019). Antibiotic resistance and azithromycin resistance mechanism of legionella pneumophila serogroup 1 in China. Antimicrob. Agents Chemother., 63.","DOI":"10.1128\/AAC.00768-19"},{"key":"ref_54","unstructured":"(2019, November 22). The European Committee on Antimicrobial Susceptibility Testing\u2019 (EUCAST), Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 7.1. Available online: http:\/\/www.eucast.org\/ast_of_bacteria\/."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1128\/AAC.18.3.403","article-title":"Susceptibility of Legionella pneumophila to twenty antimicrobial agents","volume":"18","author":"Edelstein","year":"1980","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1128\/AAC.36.11.2387","article-title":"In vitro activities of fleroxacin against clinical isolates of Legionella spp., its pharmacokinetics in guinea pigs, and use to treat guinea pigs with L. pneumophila pneumonia","volume":"36","author":"Edelstein","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1128\/AAC.38.2.200","article-title":"In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species","volume":"38","author":"Edelstein","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1128\/AAC.40.2.314","article-title":"Activity of trovafloxacin (CP-99,219) against Legionella isolates: In vitro activity, intracellular accumulation and killing in macrophages, and pharmacokinetics and treatment of guinea pigs with L. pneumophila pneumonia","volume":"40","author":"Edelstein","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/jac\/40.3.427","article-title":"In-vitro activities of ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin, pefloxacin, sparfloxacin and trovafloxacin against gram-positive and gram-negative pathogens from respiratory tract infections","volume":"40","year":"1997","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0732-8893(87)90180-5","article-title":"Antimicrobial activity of imipenem and SCH34343 against Legionella species","volume":"6","author":"Jones","year":"1987","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1365-2672.2008.03765.x","article-title":"Multiresistant waterborne pathogens isolated from water reservoirs and cooling systems","volume":"105","author":"Blasco","year":"2008","journal-title":"J. Appl. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1128\/AAC.28.1.15","article-title":"Susceptibility of Legionella pneumophila to ofloxacin in vitro and in experimental Legionella pneumonia in guinea pigs","volume":"28","author":"Saito","year":"1985","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1093\/jac\/46.3.385","article-title":"The effect of azithromycin on intracellular Legionella pneumophila in the Mono Mac 6 cell line at serum concentrations attainable in vivo","volume":"46","author":"Jonas","year":"2000","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s101560070004","article-title":"Evaluation of the activity of antimicrobial agents against Legionella pneumophila multiplying in a human monocytic cell line, THP-1, and an alveolar epithelial cell line, A549","volume":"6","author":"Kunishima","year":"2000","journal-title":"J. Infect. Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/jac\/23.1.37","article-title":"Susceptibility of Legionella pneumophila to eight antimicrobial agents including four macrolides under different assay conditions","volume":"23","author":"Liebers","year":"1989","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1128\/AAC.01639-13","article-title":"Antimicrobial Activity of Solithromycin against Clinical Isolates of Legionella pneumophila Serogroup 1","volume":"58","author":"Mallegol","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ijantimicag.2004.08.019","article-title":"Comparative activity of quinolones, macrolides and ketolides against Legionella species using in vitro broth dilution and intracellular susceptibility testing","volume":"25","author":"Stout","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1086\/320526","article-title":"Persistently positive culture results in a patient with community-acquired pneumonia due to Legionella pneumophila","volume":"32","author":"Tan","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0732-8893(97)00174-0","article-title":"Comparative activity of ciprofloxacin, ofloxacin, levofloxacin, and erythromycin against legionella species by broth microdilution and intracellular susceptibility testing in HL-60 Cells","volume":"30","author":"Stout","year":"1998","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s15010-009-9253-1","article-title":"Hospital-acquired pneumonia and bacteremia caused by legionella pneumophila in an immunocompromised patient","volume":"38","author":"Lai","year":"2010","journal-title":"Infection"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.ebiom.2015.07.018","article-title":"Hidden selection of bacterial resistance to fluoroquinolones in vivo: the case of legionella pneumophila and humans","volume":"2","author":"Shadoud","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0732-8893(89)90073-4","article-title":"In vitro activity of lomefloxacin (SC 47111 or NY-198) against isolates of Legionella spp.","volume":"12","author":"Dubois","year":"1989","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_73","first-page":"463","article-title":"Susceptibility ofLegionella spp. to imipenem and 27 other beta-lactam antibiotics","volume":"3","author":"Ruckdeschel","year":"1984","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1128\/jcm.35.11.3004-3006.1997","article-title":"Comparison of charcoal- and starch-based media for testing susceptibilities of Legionella species to macrolides, azalides, and fluoroquinolones","volume":"35","author":"Pendland","year":"1997","journal-title":"J. Clin. Microbiol."},{"key":"ref_75","first-page":"69","article-title":"In vitro susceptibility of 98 clinical and environmental isolates of Legionella pneumophila to ciprofloxacin, norfloxacin and ofloxacin","volume":"4","author":"Carsia","year":"1991","journal-title":"Rev. Esp. Quimiterap."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1093\/jac\/39.6.815","article-title":"Lack of resistance to erythromycin, rifampicin and ciprofloxacin in 98 clinical isolates of Legionella pneumophila","volume":"39","author":"Onody","year":"1997","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/jac\/43.suppl_2.25","article-title":"The in-vitro activity of moxifloxacin against Legionella species and the effects of medium on susceptibility test results","volume":"43","author":"Ruckdeschel","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1128\/AAC.49.4.1468-1476.2005","article-title":"Comparative antimicrobial characterization of LBM415 (NVP PDF-713), a new peptide deformylase inhibitor of clinical importance","volume":"49","author":"Fritsche","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e00004-17","DOI":"10.1128\/mSphere.00004-17","article-title":"Fluorocycline TP-271 is potent against complicated community-acquired bacterial pneumonia pathogens","volume":"2","author":"Grossman","year":"2017","journal-title":"mSphere"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1128\/AAC.48.10.3697-3701.2004","article-title":"Antimicrobial evaluation of nocathiacins, a thiazole peptide class of antibiotics","volume":"48","author":"Pucci","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1128\/AAC.01315-06","article-title":"In vitro and in vivo antibacterial activities of heteroaryl isothiazolones against resistant gram-positive pathogens","volume":"51","author":"Pucci","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1007\/BF01960892","article-title":"Comparative in vitro activity of clarithromycin","volume":"11","author":"Loza","year":"1992","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"59","DOI":"10.13005\/bpj\/1081","article-title":"Antimicrobial resistance properties of legionella pneumophila isolated from the cases of lower respiratory tract infections","volume":"10","author":"Rahimi","year":"2017","journal-title":"Biomed. Pharmacol. J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/BF01711076","article-title":"FatalLegionella pneumophila pneumonia: Treatment failure despite early sequential oral-parenteral amoxicillin-clavulanic acid therapy","volume":"20","author":"Hohl","year":"1992","journal-title":"Infection"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.diagmicrobio.2013.03.001","article-title":"Correlation of MIC value and disk inhibition zone diameters in clinical Legionella pneumophila serogroup 1 isolates","volume":"76","author":"Bruin","year":"2013","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1128\/AAC.44.8.2176-2178.2000","article-title":"In vitro activities of gemifloxacin versus five quinolones and two macrolides against 271 Spanish isolates of legionella pneumophila: Influence of charcoal on susceptibility test results","volume":"44","author":"Pelaz","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.envres.2018.06.045","article-title":"Legionella pneumophila recurrently isolated in a Spanish hospital: Two years of antimicrobial resistance surveillance","volume":"166","author":"Graells","year":"2018","journal-title":"Environ. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0732-8893(94)90110-4","article-title":"Evaluations of the etest for antimicrobial susceptibility testing of Legionella pneumophila, including validation of the imipenem and sparfloxacin strips","volume":"20","author":"Rhomberg","year":"1994","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/jac\/dks001","article-title":"Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs)","volume":"67","author":"Sader","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1111\/j.1469-0691.2007.01717.x","article-title":"Activity of telithromycin and comparators against isolates of Legionella pneumophila collected from patients with community-acquired respiratory tract infections: PROTEKT Years 1\u20135","volume":"13","author":"Dunbar","year":"2007","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s12223-012-0161-2","article-title":"Postantibiotic effect of various antibiotics on Legionella pneumophila strains isolated from water systems","volume":"57","author":"Zeybek","year":"2012","journal-title":"Folia Microbiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1179\/joc.2004.16.5.502","article-title":"In vitro activity of thiamphenicol, erythromycin and fluoroquinolones against legionella pneumophila","volume":"16","author":"Bonfiglio","year":"2004","journal-title":"J. Chemother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.ijantimicag.2010.01.026","article-title":"Antimicrobial characterisation of CEM-101 activity against respiratory tract pathogens, including multidrug-resistant pneumococcal serogroup 19A isolates","volume":"35","author":"Farrell","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/BF02490181","article-title":"In vitro and in vivo evaluation of the antimicrobial activity of azithromycin against legionella species","volume":"3","author":"Koide","year":"1997","journal-title":"J. Infect. Chemother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1476-0711-8-35","article-title":"Microbiological evaluation of the efficacy of two new biodetergents on multidrug-resistant nosocomial pathogens","volume":"8","author":"Liguori","year":"2009","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.eimc.2018.11.006","article-title":"Epidemiological surveillance and wild-type MIC distribution of Legionella pneumophila in north-western Spain. 2003\u20132016","volume":"37","author":"March","year":"2019","journal-title":"Enfermedades Infecciosas y Microbiolog\u00eda Cl\u00ednica"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1128\/AAC.47.3.1081-1087.2003","article-title":"Use of the microbial growth curve in postantibiotic effect studies of legionella pneumophila","volume":"47","author":"Smith","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/MD.0b013e31827f6104","article-title":"Community-acquired legionella pneumophila pneumonia","volume":"92","author":"Viasus","year":"2013","journal-title":"Medicine"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.cegh.2018.12.002","article-title":"Prevalence and molecular distribution of Legionella pneumophila in cold water taps across Alborz province, Iran","volume":"7","author":"Yaslianifard","year":"2019","journal-title":"Clin. Epidemiol. Glob. Health"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/jac\/dkx386","article-title":"Antibiotic susceptibility of clinical Legionella pneumophila serogroup 1 strains isolated in Germany","volume":"73","author":"Koshkolda","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/jac\/47.2.147","article-title":"Efficacy of moxifloxacin, trovafloxacin, clinafloxacin and levofloxacin against intracellular Legionella pneumophila","volume":"47","author":"Jonas","year":"2001","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1128\/AAC.04659-14","article-title":"Moxifloxacin pharmacokinetic profile and efficacy evaluation in empiric treatment of community-acquired pneumonia","volume":"59","author":"Hardlei","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_103","unstructured":"Murdoch, D. (2019, November 22). Treatment of Legionaires\u2019 Disease (Legionella pneumonia) 2020. Available online: https:\/\/www.uptodate.com\/contents\/treatment-and-prevention-of-legionella-infection."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1111\/bph.13936","article-title":"The macrolide antibiotic renaissance","volume":"174","author":"Dinos","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_105","first-page":"567","article-title":"Long term treatment with macrolides in chronic lung diseases","volume":"155","author":"Shteinberg","year":"2016","journal-title":"Harefuah"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e122","DOI":"10.1097\/MJT.0000000000000138","article-title":"Azithromycin and risk of cardiovascular death","volume":"22","author":"Khan","year":"2015","journal-title":"Am. J. Ther."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/16\/5809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:59:13Z","timestamp":1760176753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/16\/5809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,11]]},"references-count":106,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijerph17165809"],"URL":"https:\/\/doi.org\/10.3390\/ijerph17165809","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,11]]}}}