Treatment and prevention of Legionella infection
- Victor L Yu, MD
Victor L Yu, MD
- Professor of Medicine
- University of Pittsburgh Medical Center
- Nieves Sopena Galindo, MD
Nieves Sopena Galindo, MD
- Assistant Professor of Medicine
- Universitat Autònoma de Barcelona
The mortality of community-acquired Legionnaires' disease ranges from 16 to 30 percent if untreated or treated with inactive antibiotics; the mortality for nosocomial Legionnaires' disease can approach 50 percent given the underlying illness of the patient . With the advent of improved diagnostic methods leading to earlier diagnosis and more potent therapies, mortality has been reduced to less than 10 percent in patients with community-acquired legionellosis [2-5].
The treatment of Legionella infection will be reviewed here. The epidemiology, pathogenesis, clinical manifestations, and diagnosis of this entity are discussed separately. (See "Epidemiology and pathogenesis of Legionella infection" and "Clinical manifestations and diagnosis of Legionella infection".)
In vitro susceptibility results are not readily interpretable for Legionella since methods have not been standardized. Conventional in vitro susceptibility methods in broth and agar have proven unreliable. For example, the charcoal in buffered charcoal yeast extract agar used for Legionella isolation binds antibiotics, and, thus, activity of these antibiotics against the organism is falsely minimized. Also, many commercially available antibiotics, which have excellent in vitro activity against Legionella by conventional testing (eg, beta-lactam agents and aminoglycosides), have proven to be relatively ineffective in patients with Legionnaires' disease.
The intracellular location of the pathogen is relevant to the efficacy of the antibiotic. Antibiotics capable of achieving intracellular concentrations higher than the minimum inhibitory concentration are more effective clinically than antibiotics with poor intracellular penetration . Antibiotics with intracellular penetration include the macrolides, quinolones, tetracyclines, and rifampin.
The empiric finding that tetracycline and erythromycin appeared to be more effective than beta-lactam agents and aminoglycosides in early outbreaks of Legionnaires' disease was consistent with in vitro results in intracellular [7-11] and animal models of Legionnaires' disease [12-14]. Determination of the susceptibility of Legionella spp to antimicrobial agents is now based upon such intracellular and animal models of Legionella infection [6,15].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Fraser DW, Tsai TR, Orenstein W, et al. Legionnaires' disease: description of an epidemic of pneumonia. N Engl J Med 1977; 297:1189.
- Benin AL, Benson RF, Besser RE. Trends in legionnaires disease, 1980-1998: declining mortality and new patterns of diagnosis. Clin Infect Dis 2002; 35:1039.
- Fernández JA, López P, Orozco D, Merino J. Clinical study of an outbreak of Legionnaire's disease in Alcoy, Southeastern Spain. Eur J Clin Microbiol Infect Dis 2002; 21:729.
- Blázquez Garrido RM, Espinosa Parra FJ, Alemany Francés L, et al. Antimicrobial chemotherapy for Legionnaires disease: levofloxacin versus macrolides. Clin Infect Dis 2005; 40:800.
- Mykietiuk A, Carratalà J, Fernández-Sabé N, et al. Clinical outcomes for hospitalized patients with Legionella pneumonia in the antigenuria era: the influence of levofloxacin therapy. Clin Infect Dis 2005; 40:794.
- Edelstein PH. Antimicrobial chemotherapy for legionnaires' disease: a review. Clin Infect Dis 1995; 21 Suppl 3:S265.
- Takemura H, Yamamoto H, Kunishima H, et al. Evaluation of a human monocytic cell line THP-1 model for assay of the intracellular activities of antimicrobial agents against Legionella pneumophila. J Antimicrob Chemother 2000; 46:589.
- Stout JE, Arnold B, Yu VL. Comparative activity of ciprofloxacin, ofloxacin, levofloxacin, and erythromycin against Legionella species by broth microdilution and intracellular susceptibility testing in HL-60 cells. Diagn Microbiol Infect Dis 1998; 30:37.
- Stout JE, Arnold B, Yu VL. Activity of azithromycin, clarithromycin, roxithromycin, dirithromycin, quinupristin/dalfopristin and erythromycin against Legionella species by intracellular susceptibility testing in HL-60 cells. J Antimicrob Chemother 1998; 41:289.
- Baltch AL, Smith RP, Franke MA, Michelsen PB. Antibacterial effects of levofloxacin, erythromycin, and rifampin in a human monocyte system against Legionella pneumophila. Antimicrob Agents Chemother 1998; 42:3153.
- Gómez-Lus R, Adrián F, del Campo R, et al. Comparative in vitro bacteriostatic and bactericidal activity of trovafloxacin, levofloxacin and moxifloxacin against clinical and environmental isolates of Legionella spp. Int J Antimicrob Agents 2001; 18:49.
- Edelstein PH, Edelstein MA, Lehr KH, Ren J. In-vitro activity of levofloxacin against clinical isolates of Legionella spp, its pharmacokinetics in guinea pigs, and use in experimental Legionella pneumophila pneumonia. J Antimicrob Chemother 1996; 37:117.
- Edelstein PH, Shinzato T, Doyle E, Edelstein MA. In vitro activity of gemifloxacin (SB-265805, LB20304a) against Legionella pneumophila and its pharmacokinetics in guinea pigs with L. pneumophila pneumonia. Antimicrob Agents Chemother 2001; 45:2204.
- Fraser DW, Wachsmuth I, Bopp C, et al. Antibiotic treatment of guinea-pigs infected with agent of Legionnaires' disease. Lancet 1978; 1:175.
- Sabria M, Yu VL. Legionella pneumophila. In: Therapy and Vaccines, Yu VL, Weber R, Raoult D (Eds), Apple Trees Productions, New York 2002. p.395.
- Miller AC. Erythromycin in legionnaires' disease: a re-appraisal. J Antimicrob Chemother 1981; 7:217.
- Vergis EN, Indorf A, File TM Jr, et al. Azithromycin vs cefuroxime plus erythromycin for empirical treatment of community-acquired pneumonia in hospitalized patients: a prospective, randomized, multicenter trial. Arch Intern Med 2000; 160:1294.
- Genné D, Siegrist HH, Humair L, et al. Clarithromycin versus amoxicillin-clavulanic acid in the treatment of community-acquired pneumonia. Eur J Clin Microbiol Infect Dis 1997; 16:783.
- File TM Jr, Segreti J, Dunbar L, et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother 1997; 41:1965.
- Tanaseanu C, Bergallo C, Teglia O, et al. Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia. Diagn Microbiol Infect Dis 2008; 61:329.
- Sabrià M, Pedro-Botet ML, Gómez J, et al. Fluoroquinolones vs macrolides in the treatment of Legionnaires disease. Chest 2005; 128:1401.
- Haranaga S, Tateyama M, Higa F, et al. Intravenous ciprofloxacin versus erythromycin in the treatment of Legionella pneumonia. Intern Med 2007; 46:353.
- Gershengorn HB, Keene A, Dzierba AL, Wunsch H. The association of antibiotic treatment regimen and hospital mortality in patients hospitalized with Legionella pneumonia. Clin Infect Dis 2015; 60:e66.
- Chidiac C, Pires-Croneberger S, Brun-Buisson C, et al. Antibiotic therapy for Legionnaires' disease: results of a French study in 595 hospital patients. #L-915 (abstract) In: ICAAC/IDSA Annual Meeting, Washington, DC, October 2008.
- Pedro-Botet ML, García-Cruz A, Tural C, et al. Severe Legionnaires' disease successfully treated with levofloxacin and azithromycin. J Chemother 2006; 18:559.
- Pedro-Botet ML, Yu VL. Treatment strategies for Legionella infection. Expert Opin Pharmacother 2009; 10:1109.
- Kuzman I, Soldo I, Schönwald S, Culig J. Azithromycin for treatment of community acquired pneumonia caused by Legionella pneumophila: a retrospective study. Scand J Infect Dis 1995; 27:503.
- Yu VL, Greenberg RN, Zadeikis N, et al. Levofloxacin efficacy in the treatment of community-acquired legionellosis. Chest 2004; 125:2135.
- Plouffe JF, Breiman RF, Fields BS, et al. Azithromycin in the treatment of Legionella pneumonia requiring hospitalization. Clin Infect Dis 2003; 37:1475.
- Morley JN, Smith LC, Baltch AL, Smith RP. Recurrent infection due to Legionella pneumophila in a patient with AIDS. Clin Infect Dis 1994; 19:1130.
- Blatt SP, Dolan MJ, Hendrix CW, Melcher GP. Legionnaires' disease in human immunodeficiency virus-infected patients: eight cases and review. Clin Infect Dis 1994; 18:227.
- Pedro-Botet ML, Sabrià M, Sopena N, et al. Legionnaires disease and HIV infection. Chest 2003; 124:543.
- Heath CH, Grove DI, Looke DF. Delay in appropriate therapy of Legionella pneumonia associated with increased mortality. Eur J Clin Microbiol Infect Dis 1996; 15:286.
- Gacouin A, Le Tulzo Y, Lavoue S, et al. Severe pneumonia due to Legionella pneumophila: prognostic factors, impact of delayed appropriate antimicrobial therapy. Intensive Care Med 2002; 28:686.
- Pedro-Botet ML, Sabria-Leal M, Sopena N, et al. Role of immunosuppression in the evolution of Legionnaires' disease. Clin Infect Dis 1998; 26:14.
- Matute AJ, Schurink CA, Hoepelman IM. Is a 5 day course of azithromycin enough for infections caused by Legionella pneumophila? J Antimicrob Chemother 2000; 45:930.
- Tan JS, File TM Jr, DiPersio JR, et al. Persistently positive culture results in a patient with community-acquired pneumonia due to Legionella pneumophila. Clin Infect Dis 2001; 32:1562.
- Lettinga KD, Verbon A, Nieuwkerk PT, et al. Health-related quality of life and posttraumatic stress disorder among survivors of an outbreak of Legionnaires disease. Clin Infect Dis 2002; 35:11.
- Stout JE, Muder RR, Mietzner S, et al. Role of environmental surveillance in determining the risk of hospital-acquired legionellosis: a national surveillance study with clinical correlations. Infect Control Hosp Epidemiol 2007; 28:818.
- Fiore AE, Butler JC, Emori TG, Gaynes RP. A survey of methods used to detect nosocomial legionellosis among participants in the National Nosocomial Infections Surveillance System. Infect Control Hosp Epidemiol 1999; 20:412.
- Johnson JT, Yu VL, Best MG, et al. Nosocomial legionellosis in surgical patients with head-and-neck cancer: implications for epidemiological reservoir and mode of transmission. Lancet 1985; 2:298.
- Joly J, Alary M. Occurrence of nosocomial Legionnaires' disease in hospitals with contaminated potable water supply. In: Current Status and Emerging Perspectives, Barbaree JD, Breiman RF, Dufour AP (Eds), American Society for Microbiology, Washington, DC 1994. p.39.
- Sabrià M, Mòdol JM, Garcia-Nuñez M, et al. Environmental cultures and hospital-acquired Legionnaires' disease: a 5-year prospective study in 20 hospitals in Catalonia, Spain. Infect Control Hosp Epidemiol 2004; 25:1072.
- Stout JE, Yu VL. Experiences of the first 16 hospitals using copper-silver ionization for Legionella control: implications for the evaluation of other disinfection modalities. Infect Control Hosp Epidemiol 2003; 24:563.
- Lin YE, Stout JE, Yu VL. Controlling Legionella in hospital drinking water: an evidence-based review of disinfection methods. Infect Control Hosp Epidemiol 2011; 32:166.
- Srinivasan A, Bova G, Ross T, et al. A 17-month evaluation of a chlorine dioxide water treatment system to control Legionella species in a hospital water supply. Infect Control Hosp Epidemiol 2003; 24:575.
- Zhang Z, McCann C, Stout JE, et al. Safety and efficacy of chlorine dioxide for Legionella control in a hospital water system. Infect Control Hosp Epidemiol 2007; 28:1009.
- Flannery B, Gelling LB, Vugia DJ, et al. Reducing Legionella colonization in water systems with monochloramine. Emerg Infect Dis 2006; 12:588.
- SUSCEPTIBILITY TESTING
- SELECTION OF ANTIMICROBIAL AGENTS
- Quinolones versus macrolides
- Monotherapy versus combination therapy
- Oral versus parenteral and duration of therapy
- Empiric therapy for community-acquired pneumonia
- Nosocomial pneumonia
- Transplant recipients
- Endocarditis and extrapulmonary legionellosis
- HIV infection
- Pontiac fever
- Approach to therapy
- Nosocomial disease
- - Disinfection of the water supply
- Community-acquired disease
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS