Legionella: macrolides or quinolones?

Following the first outbreaks of legionnaire's disease, erythromycin emerged as the treatment of choice without the foundation of rigorous clinical trials. The number of therapeutic failures with erythromycin, as well as the side-effects and drug interactions, led to the consideration of other drugs such as the new macrolides and quinolones for the treatment of legionnaire's disease in the 1990s. In this article, 19 studies in in-vitro intracellular models and seven animal studies that compared macrolides to quinolones were reviewed. Quinolones were found to have greater activity in intracellular models and improved efficacy in animal models compared with macrolides. No randomised trials comparing the clinical efficacy of the new macrolides and new quinolones have ever been performed. Three observational studies totalling 458 patients with legionnaire's disease have compared the clinical efficacy of macrolides (not including azithromycin) and quinolones (mainly levofloxacin). The results suggested that quinolones may produce a superior clinical response compared with the macrolides (erythromycin and clarithromycin) with regard to defervescence, complications, and length of hospital stay. Little data exist for direct comparison of quinolones and azithromycin.

[1]  M. Pedro-Botet,et al.  Fluoroquinolones vs macrolides in the treatment of Legionnaires disease. , 2005, Chest.

[2]  J. Powers,et al.  Levofloxacin and macrolides for treatment of Legionnaires disease: multiple comparisons give few answers. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[3]  O. Cars,et al.  Pharmacodynamic studies of moxifloxacin and erythromycin against intracellular Legionella pneumophila in an in vitro kinetic model. , 2005, The Journal of antimicrobial chemotherapy.

[4]  L. Bopp,et al.  Antibacterial activities of gemifloxacin, levofloxacin, gatifloxacin, moxifloxacin and erythromycin against intracellular Legionella pneumophila and Legionella micdadei in human monocytes. , 2005, The Journal of antimicrobial chemotherapy.

[5]  V. Yu,et al.  Comparative activity of quinolones, macrolides and ketolides against Legionella species using in vitro broth dilution and intracellular susceptibility testing. , 2005, International journal of antimicrobial agents.

[6]  J. Dorca,et al.  Clinical outcomes for hospitalized patients with Legionella pneumonia in the antigenuria era: the influence of levofloxacin therapy. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  M. Segovia Hernández,et al.  Antimicrobial chemotherapy for Legionnaires disease: levofloxacin versus macrolides. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  V. Yu,et al.  Levofloxacin efficacy in the treatment of community-acquired legionellosis. , 2004, Chest.

[9]  M. García-nuñez,et al.  Legionnaires disease and HIV infection. , 2003, Chest.

[10]  D. Snydman,et al.  An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  P. Edelstein,et al.  In Vitro Activity of Gemifloxacin (SB-265805, LB20304a) against Legionella pneumophila and Its Pharmacokinetics in Guinea Pigs with L. pneumophila Pneumonia , 2001, Antimicrobial Agents and Chemotherapy.

[12]  L. Mandell,et al.  Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. The Canadian Community-Acquired Pneumonia Working Group. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  Michael J Fine,et al.  Practice Guidelines for the Management of Community-Acquired Pneumonia in Adults , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  P. Edelstein,et al.  In Vitro Activity of the Ketolide HMR 3647 (RU 6647) for Legionella spp., Its Pharmacokinetics in Guinea Pigs, and Use of the Drug To Treat Guinea Pigs withLegionella pneumophila Pneumonia , 1999, Antimicrobial Agents and Chemotherapy.

[15]  M. Franke,et al.  Antibacterial Effects of Levofloxacin, Erythromycin, and Rifampin in a Human Monocyte System againstLegionella pneumophila , 1998, Antimicrobial Agents and Chemotherapy.

[16]  D. Navarro,et al.  A comparative study on the efficacy of the new quinolone alatrofloxacin in the treatment of experimental Legionellosis in guinea pigs , 1998, European Journal of Clinical Microbiology and Infectious Diseases.

[17]  Yu Vl,et al.  Legionella: a major opportunistic pathogen in transplant recipients. , 1998, Seminars in respiratory infections.

[18]  V. Yu,et al.  Activity of azithromycin, clarithromycin, roxithromycin, dirithromycin, quinupristin/dalfopristin and erythromycin against Legionella species by intracellular susceptibility testing in HL-60 cells. , 1998, The Journal of antimicrobial chemotherapy.

[19]  R. Smith,et al.  Effect of levofloxacin, erythromycin or rifampicin pretreatment on growth of Legionella pneumophila in human monocytes. , 1997, The Journal of antimicrobial chemotherapy.

[20]  T. Nichterlein,et al.  Excellent activity of newer quinolones on Legionella pneumophila in J774 macrophages. , 1997, Zentralblatt fur Bakteriologie : international journal of medical microbiology.

[21]  B. Marston,et al.  Surveillance for Legionnaires' disease. Risk factors for morbidity and mortality. , 1994, Archives of internal medicine.

[22]  J. Frottier,et al.  Unsuccessful treatment of Legionella pneumophila infection with a fluoroquinolone. , 1993, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  A. Saito,et al.  Inhibition of Legionella pneumophila in guinea pig peritoneal macrophages by new quinolone, macrolide and other antimicrobial agents. , 1991, The Journal of antimicrobial chemotherapy.

[24]  P. Edelstein,et al.  In vitro activity of azithromycin against clinical isolates of Legionella species , 1991, Antimicrobial Agents and Chemotherapy.

[25]  P. Edelstein,et al.  In vitro activity of sparfloxacin (CI-978; AT-4140) for clinical Legionella isolates, pharmacokinetics in guinea pigs, and use to treat guinea pigs with L. pneumophila pneumonia , 1990, Antimicrobial Agents and Chemotherapy.

[26]  P. Edelstein,et al.  WIN 57273 is bactericidal for Legionella pneumophila grown in alveolar macrophages , 1989, Antimicrobial Agents and Chemotherapy.

[27]  H. Forst,et al.  Brief report: Ciprofloxacin in the treatment of legionellosis in critically III patients including those cases unresponsive to erythromycin , 1989 .

[28]  A. Tzianabos,et al.  Pathogenesis and chemotherapy of experimental Legionella pneumophila infection in the chick embryo. , 1989, Zentralblatt fur Bakteriologie : international journal of medical microbiology.

[29]  W. Graninger,et al.  Failure of treatment of legionella pneumonia with ciprofloxacin. , 1988, The Journal of antimicrobial chemotherapy.

[30]  R. Fitzgeorge,et al.  The effect of ofloxacin on the intracellular growth of Legionella pneumophila in guinea pig alveolar phagocytes. , 1988, The Journal of antimicrobial chemotherapy.

[31]  L. Saravolatz,et al.  Effect of quinolones and other antimicrobial agents on cell-associated Legionella pneumophila , 1987, Antimicrobial Agents and Chemotherapy.

[32]  K. Yamaguchi,et al.  The antimicrobial activity of ciprofloxacin against Legionella species and the treatment of experimental Legionella pneumonia in guinea pigs. , 1986, The Journal of antimicrobial chemotherapy.

[33]  K. Yamaguchi,et al.  Susceptibility of Legionella pneumophila to ofloxacin in vitro and in experimental Legionella pneumonia in guinea pigs , 1985, Antimicrobial Agents and Chemotherapy.

[34]  R. Fitzgeorge The effect of antibiotics on the growth of Legionella pneumophila in guinea-pig alveolar phagocytes infected in vivo by an aerosol. , 1985, The Journal of infection.

[35]  D. Frappaz,et al.  Failure of erythromycin/rifampicin treatment of legionella pneumonia. , 1985, The Journal of infection.

[36]  E. Wing,et al.  Failure of erythromycin in treatment of Legionella micdadei pneumonia. , 1984, The American journal of medicine.

[37]  A. Chonko,et al.  Failure of oral erythromycin therapy for Legionnaires' disease in a renal transplant recipient. , 1981, Southern medical journal.

[38]  S. Finegold,et al.  Legionnaires' Disease: Report of Sixty‐five Nosocomially Acquired Cases and Review of the Literature , 1980, Medicine.

[39]  J. Feeley,et al.  ANTIBIOTIC TREATMENT OF GUINEAPIGS INFECTED WITH AGENT OF LEGIONNAIRES' DISEASE , 1978, The Lancet.

[40]  A. Lees,et al.  LEGIONNAIRES' DISEASE , 1977, The Lancet.

[41]  P. Brachman,et al.  Legionnaires' disease. , 1977, Disease-a-month : DM.

[42]  J. Fleurette,et al.  LEGIONNAIRE'S DISEASE , 1977, The Lancet.

[43]  M. Fine,et al.  Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. , 2001, American journal of respiratory and critical care medicine.

[44]  L. Mandell,et al.  Summary of Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Disease Society and the Canadian Thoracic Society. , 2000, The Canadian journal of infectious diseases = Journal canadien des maladies infectieuses.

[45]  V. Yu,et al.  Comparative activity of ciprofloxacin, ofloxacin, levofloxacin, and erythromycin against Legionella species by broth microdilution and intracellular susceptibility testing in HL-60 cells. , 1998, Diagnostic microbiology and infectious disease.

[46]  J. Morera,et al.  Role of immunosuppression in the evolution of Legionnaires' disease. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[47]  V. Yu,et al.  Legionella: a major opportunistic pathogen in transplant recipients. , 1998, Seminars in respiratory infections.

[48]  P. Edelstein,et al.  In-vitro activity of levofloxacin against clinical isolates of Legionella spp, its pharmacokinetics in guinea pigs, and use in experimental Legionella pneumophila pneumonia. , 1996, The Journal of antimicrobial chemotherapy.

[49]  H. Forst,et al.  Ciprofloxacin in the treatment of legionellosis in critically ill patients including those cases unresponsive to erythromycin. , 1989, The American journal of medicine.

[50]  P. Rajagopalan,et al.  Efficacy of pefloxacin in comparison with erythromycin in the treatment of experimental guinea pig legionellosis. , 1986, The Journal of antimicrobial chemotherapy.

[51]  M. Horwitz,et al.  Intracellular multiplication of Legionnaires' disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin. , 1983, The Journal of clinical investigation.

[52]  V. Yu,et al.  Nosocomial outbreak of Legionnaire's disease at the Pittsburgh Veterans Administration Medical Center. , 1980, Transactions of the Association of American Physicians.

[53]  G F Mallison,et al.  Legionnaires' disease: description of an epidemic of pneumonia. , 1977, The New England journal of medicine.