Advertisement

Chlamydia pneumoniae and asthma and atherosclerosis: role of macrolides

  • Margaret R. Hammerschlag
Chapter
  • 492 Downloads
Part of the Milestones in Drug Therapy MDT book series (MDT)

Abstract

Chlamydia pneumoniae was first described as a respiratory tract pathogen by Grayston and colleagues in 1986 [1]. The genus Chlamydiae is a group of obligate intracellular parasites that have a unique developmental cycle with morphologically distinct infectious and reproductive forms. All members of the genus have a gram-negative envelope without peptidoglycan, share a genus-specific lipopolysaccharide (LPS) antigen, and utilize host ATP for the synthesis of chlamydial protein. The genus now contains four species: Chlamydia psittaci, C. trachomatis, C. pneumoniae, and C. pecorum. Macrolide antibiotics have long been used for treatment of infections due to C. trachomatis, and, by extrapolation, they have been used for treatment of C. pneumoniae infections. Macrolide antibiotics, especially the newer agents, have a number of properties that make them ideal agents for the treatment of infections due to intracellular pathogens such as C. pneumoniae. They achieve high concentrations in tissue and cells, including polymorphonuclear leukocytes and macrophages. These drugs also have long half-lives in tissue, allowing once-daily dosing and shorter duration of therapy. However, data on the treatment of even respiratory infection due to C. pneumoniae is limited. Although currently available macrolides have good activity against C. pneumoniae in vitro, the majority of published treatment studies have relied on serologic diagnosis, and thus microbiological efficacy has not been assessed [2].

Keywords

Antimicrob Agent Macrolide Antibiotic Obligate Intracellular Parasite Respiratory Tract Pathogen Chlamydia Psittaci 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Grayston JT, Kuo CC, Wang SP, Altman J (1986) A new Chlamydia psittaci strain, isolated in acute respiratory tract infections. N Engl J Med 315: 161–168PubMedCrossRefGoogle Scholar
  2. 2.
    Hammerschlag, MR (1994) Antimicrobial susceptibility and therapy of infections caused by Chlamydia pneumoniae. Antimicrob Agents Chemother 38: 1873–1878PubMedCrossRefGoogle Scholar
  3. 3.
    Jackson M, White N, Giffard P, Timms P (1999) Epizootiology of chlamydia infections in two free-range koala populations. Vet Microbiol 65: 255–264PubMedCrossRefGoogle Scholar
  4. 4.
    Grayston JT, Campbell LA, Kuo CC, Mordhorst CH, Saikku P, Thom DH, Wang SP (1990) A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR. J Infect Dis 161: 618–625PubMedCrossRefGoogle Scholar
  5. 5.
    Hammerschlag MR(1999)Community-acquired Pneumonia Due To Atypical Organisms In Adults:Diagnosis and treatment. Infect Dis Clin Pract 8: 232–240CrossRefGoogle Scholar
  6. 6.
    Marston BJ, Plouff JF, File Jr. TM, Hackman BA, Salstrom SJ, Lipman HB, Kolczak MS, Breiman RF (1997) Incidence of community-acquired pneumonia requiring hospitalization. Arch Intern Med 157: 1709–1718PubMedCrossRefGoogle Scholar
  7. 7.
    Norrby SR (1997) Atypical pneumonia in the nordic countries: aetiology and clinical results of a trial comparing fleroxacin and doxycycline. J Antimicrob Chemother 39: 499–508CrossRefGoogle Scholar
  8. 8.
    Block S, Hedrick J, Hammerschlag MR, Cassell GH, Craft JC (1995) Mycoplasma pneumonie and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of clarithromycin vs. erythromycin ethylsuccinate. Pediatric Infect Dis J 14: 471–477CrossRefGoogle Scholar
  9. 9.
    Harris JS, Kolokathis A, Campbell M, Cassell GH, Hammerschlag MR (1998) Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children. Pediatr Infect Dis 17: 865–871CrossRefGoogle Scholar
  10. 10.
    Wubbel L, Muniz L, Ahmed A, Trujillo M, Carubelli C, McCoig C, Abramo T, Leinonen M, McCracken GH (1999) Etiology of community-acquired pneumonia in ambulatory children. Pediatr Infect Dis J 18:98–104PubMedCrossRefGoogle Scholar
  11. 11.
    Emre U, Roblin PM, Gelling M, Dumomay W, Rao M, Hammerschlag MR, Schachter J (1994) The association of Chlamydia pneumoniae infection and reactive airway disease in children. Arch Pediatr Adolesc Med 148: 727–732PubMedCrossRefGoogle Scholar
  12. 12.
    Block S, Hammerschlag MR, Hedrick J, Tyler R, Smith A, Robin P, Gaydos C, Pham D, Quinn TC, Palmer R et al (1997) Chlamydia pneumoniae in acute otitis media. Pediatr Infect Dis J 16: 858–862PubMedCrossRefGoogle Scholar
  13. 13.
    Grayston JT, Aldous MB, Easton A, Wang SP, Kuo CC, Campbell LA, Altman J (1993) Evidence that Chlamydia pneumoniae causes pneumonia and bronchitis. J Infect Dis 168: 1231–1235PubMedCrossRefGoogle Scholar
  14. 14.
    Hyman CL, Roblin PM, Gaydos CA, Quinn TC, Schachter J, Hammerschlag MR (1995) Prevalence of asymptomatic nasopharyngeal carriage of Chlamydia pneumoniae in subjectively healthily adults: assessment of polymerase chain reaction-enzyme immunoassay and culture. Clin Infect Dis 20: 1174–1178PubMedCrossRefGoogle Scholar
  15. 15.
    Hammerschlag MR, Chirgwin K, Roblin PM, Gelling M, Dumomay W, Mandel L, Smith P, Schachter J (1992) Persistent infection with Chlamydia pneumoniae following acute respiratory illness. Clin Infect Dis 14:178–182PubMedCrossRefGoogle Scholar
  16. 16.
    Dean D, Roblin PM, Mandel L, Schacter J, Hammerschlag MR (1998) Molecular evaluation of serial isolates from patients with persistent Chlamydia pneumoniae infections. In: Stephens RS, Byrne GI, Christiansen G, Eds. Chlamydia infections: Proceedings of the Ninth International Symposium on Human Chlamydia Infection. San Francisco: USCF, 219–223Google Scholar
  17. 17.
    Wong YK, Gallagher PJ, Ward ME (199) Chlamydia pneumoniae and atherosclerosis. Heart 82:232–238Google Scholar
  18. 18.
    Fenelon LE, Mumtaz G, Ridgway GL (1990) The in vitro antibiotic susceptibility of Chlamydia pneumoniae. J Antimicrob Chemother 26: 763–767PubMedCrossRefGoogle Scholar
  19. 19.
    Cooper MA, Baldwin D, Matthews RS, Andrews JM, Wise R (1991) In vitro susceptibility of Chlamydia pneumoniae (TWAR) to seven antibiotics. J Antimicrob Chemother 28: 407–413PubMedCrossRefGoogle Scholar
  20. 20.
    Ridgway GL, Mumtaz G, Fenelon L (1991) The in vitro activity of clarithromycin and other macrolides against the strain of Chlamydia pneumoniae (TWAR). J Antimicrob Chemother 27: 43–45PubMedCrossRefGoogle Scholar
  21. 21.
    Agacfidan A, Moncada J, Schachter J (1993) In vitro activity of azithromycin (CP-62,993) against Chlamydia trachomatis and Chlamydia pneumoniae. Antimicrob Agents Chemother 37: 1746–1748PubMedCrossRefGoogle Scholar
  22. 22.
    Hammerschlag MR, Khaldoon KQ, Roblin PM (1992) In vitro activities of azithromycin, clarithromycin, L-ofloxacin, and other antibiotics against Chlamydia pneumoniae. Antimicrob Agents Chemother 36: 1573–1574PubMedCrossRefGoogle Scholar
  23. 23.
    Welsh LE, Gaydos CA, Quinn TC (1992) In vitro evaluation of activities of azithromycin, erythromycin, and tetracycline against Chlamydia trachomatis and Chlamydia pneumoniae. Antimicrob Agents Chemother 36: 291–294PubMedCrossRefGoogle Scholar
  24. 24.
    Niki Y, Kimura M, Miyashita N, Soejima R (1994) In vitro and in vivo activities of azithromycin, and new azalide antibiotic, against chlamydia. Antimicrob Agents Chemother 38: 2296–2299PubMedCrossRefGoogle Scholar
  25. 25.
    Roblin PM, Montalban G, Hammerschlag MR (1994) Susceptibilities to clarithromycin and erythromycin of isolates of Chlamydia pneumoniae from children with pneumonia. Antimicrob Agents Chemother 38: 1588–1589PubMedCrossRefGoogle Scholar
  26. 26.
    Welsh L, Gaydos C, Quinn TC (1996) In vitro activities of azithromycin, clarithromycin, erythromycin and tetracycline against 13 strains of Chlamydia pneumoniae. Antimicrob Agents Chemother 40: 212–214PubMedGoogle Scholar
  27. 27.
    Kuo CC, Jackson LA, Lee A, Graystron JT (1996) In vitro activities of azithromycin, clarithromycin, and other antibiotics against Chlamydia pneumoniae. Antimicrob Agents Chemother 40: 2669–2670PubMedGoogle Scholar
  28. 28.
    Miyashita N, Niki Y, Kishimoto T, Nakajima M, Matsushima T (1997) In vitro and in vivo activities of AM-1155, a new fluoroquinolone, against Chlamydia spp. Antimicrob Agents Chemother 41: 1331–1334PubMedGoogle Scholar
  29. 29.
    Roblin PM, Kutlin A, Sokolovskaya N, Hammerschlag MR (1997) In vitro activity of dirithromycin against Chlamydia pneumoniae. J Antimicro Chemother 39: 647–649CrossRefGoogle Scholar
  30. 30.
    Roblin PM, Hammerschlag MR (1998) Microbiologic efficacy of azithromycin and susceptibilities to azithromycin of isolates of Chlamydia pneumoniae from adults and children with community-acquired pneumonia. Antimicrob Agents Chemother 42: 194–196PubMedGoogle Scholar
  31. 31.
    Roblin PM, Hammerschlag MR (1998) In vitro activity of a new ketolide antibiotic, HMR 3647, against Chlamydia pneumoniae. Antimicrob Agents Chemother 42: 1515–1516PubMedGoogle Scholar
  32. 32.
    Strigil S, Roblin PM, Reznik T, Hammerschlag MR (2001). In vitro activity of ABT 773, a new ketolide antibiotic, against Chlamydia pneumoniae. Antimicrob Agents Chemother; in press.Google Scholar
  33. 33.
    Freidank HM, Losch P, Vogele H, Weidmann-Al-Ahmad M (1999) In vitro susceptibilities of Chlamydia pneumoniae isolates from German patients and synergistic activity of antibiotic combinations. Antimicrob Agents Chemother 43: 1808–1810PubMedGoogle Scholar
  34. 34.
    Nystrom-Rosander C, Hulten K, Gustayson I, Cars 0, Engstrand L, Hjelm E (1997) Susceptibility of Chlamydia pneumoniae to azithromycin and doxycycline: methodological aspects on the determination of minimal inhibitory and minimal bactericidal concentrations. Scand J Infect Dis 29: 513–516PubMedCrossRefGoogle Scholar
  35. 35.
    Gnarpe J, Eriksson K, Gnarpe H (1996) In vitro activities of azithromycin and doxycycline against 15 isolates of Chlamydia pneumoniae. Antimicrob Agents Chemother 40: 1843–1845PubMedGoogle Scholar
  36. 36.
    Malinverni R, Kuo CC, Campbell LA, Lee A, Grayston JT (1995) Effects of two antibiotic regimens on course and persistence of experimental Chlamydia pneumoniae TWAR pneumonitis. Antimicrob Agents Chemother 39: 45–49PubMedCrossRefGoogle Scholar
  37. 37.
    Masson ND, Toseland CDN, Beale AS (1995) Relevance of Chlamydia pneumoniae murine pneumonitis model to evaluation of antimicrobial agents. Antimicrob Agents Chemother 39: 1959–1964PubMedCrossRefGoogle Scholar
  38. 38.
    Wolf K, Malinverni R (1999) Effect of azithromycin plus rifampin versus that of azithromycin alone on the eradication of Chlamydia pneumoniae from lung tissue in experimental pneumonitis. Antimicrob Agents Chemother 43: 1491–1493PubMedGoogle Scholar
  39. 39.
    Kutlin A, Roblin PM, Hammerschlag MR (1999) In vitro activities of azithromycin and ofloxacin against Chlamydia pneumoniae in a continuous-infection model. Antimicrob Agents Chemother 43: 2268–2272PubMedGoogle Scholar
  40. 40.
    File Jr. TM, Segrett J, Dunbar L, Player R, Kohler R, Williams RR, Kojak C, Rubin A (1997) 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 penumonia. Antimicrob Agents Chemother 41: 1965–1972PubMedGoogle Scholar
  41. 41.
    Leophonte P, Baldwin RJT, Pluck N (1998) Trovafloxavin versus amoxicillin/clavulanic acid in the treatment of acute exacerbations of chronic obstructive bronchitis. Eur J Clin Microbiol Infect Dis 17: 434–440PubMedCrossRefGoogle Scholar
  42. 42.
    Danesh J, Collins R, Peto R (1997) Chronic infections and coronary heart disease: is there a link? Lancet 350: 430–436PubMedCrossRefGoogle Scholar
  43. 43.
    Hammerschlag MR (1998) Current knowledge of Chlamydia pneumoniae and atherosclerosis. Eur J Clin Microbiol Infect Dis 17 305–308PubMedGoogle Scholar
  44. 44.
    Hahn DL (1999) Chlamydia pneumoniae, asthma and COPD: what is the evidence? Ann Allergy Asthma Immun 83: 271–292CrossRefGoogle Scholar
  45. 45.
    Cook PJ, Davies P, Tunnicliffe W, Ayres JG, Honeyboume D, Wise R (1998) Chlamydia pneumoniae and asthma. Thorax 53: 254–259PubMedCrossRefGoogle Scholar
  46. 46.
    Larsen FO, Nom S, Mordhorst CH, Skov P, Stahl P, Milman N, Clementsen P (1998) Chlamydia pneumoniae and possible relationship to asthma: serum immunoglobulins and histamine release in patients and controls. APMIS 106: 928–934PubMedCrossRefGoogle Scholar
  47. 47.
    Hahn DL (1995) Treatment of Chlamydia pneumoniae infection in adult asthma: a before-after trial. J Pam Pract 41:345–351Google Scholar
  48. 48.
    Scaglione F, Rossoni G (1998) Comparative anti-inflammatory effects of roxithromycin azithromycin and clarithrommycin. J Antimicrob Chemother 41: 47–50PubMedCrossRefGoogle Scholar
  49. 49.
    Takizawa H, Desaki M, Ohtoshi T, Kawasaki S, Kohyama T, Sato M, Nakajima J, Yanagisawa M, Ito K (1999) Erythromycin and clarithromycin attenuate cytokine-induced endothelin-1 expression in human bronchial epithelial cells. Thorax 54: S58¡ªS62Google Scholar
  50. 50.
    Ridker P (1999) Are associations between infection and coronary disease causal or due to confounding? Am J Med 106: 376–377PubMedCrossRefGoogle Scholar
  51. 51.
    Danesh, J (1999) Coronary heart disease, Helicobacter pylori, dental disease, Chlamydia pneumoniae, and cytomegalovirus: Meta-analyses of prospective studies. Am Heart J 138: S434¡ªS437CrossRefGoogle Scholar
  52. 52.
    Weiss SM, Hammerschlag, MR (1997) Are heart attacks infectious? A critical look at the link between Chlamydia pneumoniae and atherosclerosis. Bull Institut Pasteur 95:107–113CrossRefGoogle Scholar
  53. 53.
    Ramirez JA (1996) Isolation of Chlamydia pneumoniae from the coronary artery of a patient with coronary atherosclerosis. Ann Intern Med 125: 979–982PubMedGoogle Scholar
  54. 54.
    Jackson LA, Campbell LA, Kuo CC, Rodriguez DI, Lee A, Grayston JT (1997) Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen. J Infect Dis 176: 292–295PubMedCrossRefGoogle Scholar
  55. 55.
    Maass M, Gieffers J, Krause E, Engel PM, Bartels C, Solbach W (1998) Poor correlation between microimmunofluorescence serology and polymerase chain reaction for detection of vascular Chlamydia pneumoniae infection in coronary artery disease patients. Med Microbiol Immunol 187: 103–106PubMedCrossRefGoogle Scholar
  56. 56.
    Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm J (1997) Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 96: 404–407.PubMedCrossRefGoogle Scholar
  57. 57.
    Gurfinkel E, Bozovich G, Darcoa A, Beck E, Mautner B (1997) Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study. Lancet 350: 404–407PubMedCrossRefGoogle Scholar
  58. 58.
    Gurfinkel E, Bozovich G, Beck E, Testa E, Livellara B, Mautner B (1999) Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes. Eur Heart J 20: 121–127PubMedCrossRefGoogle Scholar
  59. 59.
    Anderson JL, Muhlestein JB, Carlquist J, Allen A, Trehan S, Nielson C, Hall S, Brady J, Egger M, Horne B et al (1999) Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: the azithromycin in coronary artery disease: elimination of myocardial infection with chlamydia (ACADEMIC) study. Circulation 99: 1540–1547PubMedCrossRefGoogle Scholar
  60. 60.
    Leah AJ, Shelby-James TM, Mayo M, Gratten M, Laming AC, Currie BY, Matthews JD (1997) A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae. Clin Infect Dis 24: 356–362CrossRefGoogle Scholar
  61. 61.
    Jackson LA, Stewart DK, Wang SP, Cooke DB, Cantrell T, Grayston JT (1999) Safety and effect on anti-Chlamydia pneumoniae antibody titres of a 1 month course of daily azithromycin in adults with coronary artery disease. J Antimicrob Chemother 44: 411–414PubMedCrossRefGoogle Scholar
  62. 62.
    Michael Dunne (1999) WIZARD and the design of trials for secondary prevention of atherosclerosis with antibiotics. Am Heart J 138: S542¡ªS544CrossRefGoogle Scholar
  63. 63.
    Muhlestein JB, Anderson JL, Hammon EH, Zhao L, Trehan S, Schwobe BS, Carlquist JF (1998) Infection with Chlamydia pneumoniae accelerates the development of artherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation 97: 633–636PubMedCrossRefGoogle Scholar
  64. 64.
    Fong IW, Chiu B, Vira E, Jang D, Fong MW, Peeling R, Mahony JB (1999) Can an antibiotic (macrolide) prevent Chlamydia pneumoniae induced atherosclerosis in a rabbit model? Clin Diag 6:891–894Google Scholar
  65. 65.
    Richardson M, De Reske M, Delaney K, Fletch A, Wilcox LH, Kinlough-Rathbone RL (1997) Respiratory infection in lipid-fed rabbits enhances sudanophilia and the expression of VCAM-1. Am J Pathol 151: 1009–1017PubMedGoogle Scholar
  66. 66.
    Moazed TC, Kuo CC, Grayston JT, Campbell LA (1998) Evidence of systemic dissemination of Chlamydia pneumoniae via macrophages in the mouse. J Infect Dis 177: 1322–1325PubMedCrossRefGoogle Scholar
  67. 67.
    Meier CR, Derby LE, Jick SS, Vasilaksi C, Jick H (1999) Antibiotics and risk subsequent first-time acute myocardial infarction. JAMA 281: 427–431PubMedCrossRefGoogle Scholar
  68. 68.
    Jackson LA, Smith NL, Heckbert SR, Grayston JT, Siscovick DS, Psaty BM (1999) Lack of association between first myocardial infarction and past use of erythromycin, tetracycline, or doxycycline. Emerg Infect Dis 5: 281–284PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2002

Authors and Affiliations

  • Margaret R. Hammerschlag
    • 1
  1. 1.Division of Infectious Diseases,Department of PediatricsSUNY Health Science Center at BrooklynBrooklynUSA

Personalised recommendations