Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1995 Dec;50(12):1246–1252. doi: 10.1136/thx.50.12.1246

Long term effect of erythromycin therapy in patients with chronic Pseudomonas aeruginosa infection.

T Fujii 1, J Kadota 1, K Kawakami 1, K Iida 1, R Shirai 1, M Kaseda 1, S Kawamoto 1, S Kohno 1
PMCID: PMC1021345  PMID: 8553295

Abstract

BACKGROUND--Diffuse panbronchiolitis is a chronic infection of the lower respiratory tract common among the Japanese people, with a persistent Pseudomonas aeruginosa infection in the late stage and sustained neutrophil retention in the airways. The long term effect of erythromycin was examined retrospectively in a group of patients with diffuse panbronchiolitis, with and without P aeruginosa infection, and the relationship between drug-induced bacterial clearance and clinical improvement was investigated. METHODS--The history, daily volume of sputum, type of organisms in sputum cultures, pulmonary function tests, arterial blood gas tensions, and chest radiographs were compared in 16 patients with diffuse panbronchiolitis with P aeruginosa infection and 12 without. The total and differential cell counts in the bronchoalveolar lavage (BAL) fluid were compared in 14 of the 28 patients (five of whom were infected with P aeruginosa) before and after 1-12 months of treatment with erythromycin (600 mg/day). The outcome of treatment in patients showing clearance of organisms on repeated sputum cultures was compared with that in those demonstrating persistence of bacteria in the sputum and patients with normal flora. RESULTS--Erythromycin improved respiratory function and arterial blood gas tensions irrespective of the presence or absence of P aeruginosa in the sputum. Treatment also resulted in a reduction in the BAL fluid total cell count and the percentage of neutrophils in both groups of patients. There were no differences between patients in whom the bacteria cleared and those with persistent bacteria or patients with a normal flora with regard to the degree of improvement of respiratory function, arterial blood gas tensions, and BAL fluid cell composition. CONCLUSION--The results suggest that the efficacy of erythromycin in diffuse pan-bronchiolitis may be due to anti-inflammatory effect, independent of P aeruginosa infection or bacterial clearance.

Full text

PDF
1246

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Buret A., Cripps A. W. The immunoevasive activities of Pseudomonas aeruginosa. Relevance for cystic fibrosis. Am Rev Respir Dis. 1993 Sep;148(3):793–805. doi: 10.1164/ajrccm/148.3.793. [DOI] [PubMed] [Google Scholar]
  2. Cantin A. M., North S. L., Fells G. A., Hubbard R. C., Crystal R. G. Oxidant-mediated epithelial cell injury in idiopathic pulmonary fibrosis. J Clin Invest. 1987 Jun;79(6):1665–1673. doi: 10.1172/JCI113005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Goswami S. K., Kivity S., Marom Z. Erythromycin inhibits respiratory glycoconjugate secretion from human airways in vitro. Am Rev Respir Dis. 1990 Jan;141(1):72–78. doi: 10.1164/ajrccm/141.1.72. [DOI] [PubMed] [Google Scholar]
  4. Homma H., Yamanaka A., Tanimoto S., Tamura M., Chijimatsu Y., Kira S., Izumi T. Diffuse panbronchiolitis. A disease of the transitional zone of the lung. Chest. 1983 Jan;83(1):63–69. doi: 10.1378/chest.83.1.63. [DOI] [PubMed] [Google Scholar]
  5. Høiby N. Diffuse panbronchiolitis and cystic fibrosis: East meets West. Thorax. 1994 Jun;49(6):531–532. doi: 10.1136/thx.49.6.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ichikawa Y., Ninomiya H., Koga H., Tanaka M., Kinoshita M., Tokunaga N., Yano T., Oizumi K. Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients. Am Rev Respir Dis. 1992 Jul;146(1):196–203. doi: 10.1164/ajrccm/146.1.196. [DOI] [PubMed] [Google Scholar]
  7. Kadota J., Sakito O., Kohno S., Abe K., Shirai R., Kawakami K., Iida K., Morikawa T., Kusano S., Hara K. [Roxithromycin treatment in patients with chronic lower respiratory tract disease--its clinical efficacy and effect on cytokine]. Kansenshogaku Zasshi. 1994 Jan;68(1):27–33. doi: 10.11150/kansenshogakuzasshi1970.68.27. [DOI] [PubMed] [Google Scholar]
  8. Kadota J., Sakito O., Kohno S., Sawa H., Mukae H., Oda H., Kawakami K., Fukushima K., Hiratani K., Hara K. A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis. Am Rev Respir Dis. 1993 Jan;147(1):153–159. doi: 10.1164/ajrccm/147.1.153. [DOI] [PubMed] [Google Scholar]
  9. Kudoh S., Uetake T., Hagiwara K., Hirayama M., Hus L. H., Kimura H., Sugiyama Y. [Clinical effects of low-dose long-term erythromycin chemotherapy on diffuse panbronchiolitis]. Nihon Kyobu Shikkan Gakkai Zasshi. 1987 Jun;25(6):632–642. [PubMed] [Google Scholar]
  10. Lapa e Silva J. R., Guerreiro D., Noble B., Poulter L. W., Cole P. J. Immunopathology of experimental bronchiectasis. Am J Respir Cell Mol Biol. 1989 Oct;1(4):297–304. doi: 10.1165/ajrcmb/1.4.297. [DOI] [PubMed] [Google Scholar]
  11. Lee C. T., Fein A. M., Lippmann M., Holtzman H., Kimbel P., Weinbaum G. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome. N Engl J Med. 1981 Jan 22;304(4):192–196. doi: 10.1056/NEJM198101223040402. [DOI] [PubMed] [Google Scholar]
  12. Liu P. V. The roles of various fractions of Pseudomonas aeruginosa in its pathogenesis. 3. Identity of the lethal toxins produced in vitro and in vivo. J Infect Dis. 1966 Oct;116(4):481–489. doi: 10.1093/infdis/116.4.481. [DOI] [PubMed] [Google Scholar]
  13. MORIHARA K., TSUZUKI H., OKA T., INOUE H., EBATA M. PSEUDOMONAS AERUGINOSA ELASTASE. ISOLATION, CRYSTALLIZATION, AND PRELIMINARY CHARACTERIZATION. J Biol Chem. 1965 Aug;240:3295–3304. [PubMed] [Google Scholar]
  14. Masutani T., Sawaki M., Mikasa K., Konishi M., Yagyu Y., Narita N., Harikane O., Sano R., Munekawa Y., Mase T. [Inhibitory effect of erythromycin on elastase producing ability of Pseudomonas aeruginosa]. Kansenshogaku Zasshi. 1989 Oct;63(10):1212–1214. doi: 10.11150/kansenshogakuzasshi1970.63.1212. [DOI] [PubMed] [Google Scholar]
  15. McCord J. M., Fridovich I. The biology and pathology of oxygen radicals. Ann Intern Med. 1978 Jul;89(1):122–127. doi: 10.7326/0003-4819-89-1-122. [DOI] [PubMed] [Google Scholar]
  16. Mikasa K., Sawaki M., Kita E., Konishi M., Maeda K., Hamada K., Takeuchi S., Masutani T., Sano R., Kunimatsu M. [Long-term chemotherapy using erythromycin (EM) for chronic lower airway infection: effectiveness of clarithromycin in EM ineffective cases--the fourth report]. Kansenshogaku Zasshi. 1992 Aug;66(8):1097–1104. doi: 10.11150/kansenshogakuzasshi1970.66.1097. [DOI] [PubMed] [Google Scholar]
  17. Mohammed J. R., Mohammed B. S., Pawluk L. J., Bucci D. M., Baker N. R., Davis W. B. Purification and cytotoxic potential of myeloperoxidase in cystic fibrosis sputum. J Lab Clin Med. 1988 Dec;112(6):711–720. [PubMed] [Google Scholar]
  18. Monroe P. W., Muchmore H. G., Felton F. G., Pirtle J. K. Quantitation of microorganisms in sputum. Appl Microbiol. 1969 Aug;18(2):214–220. doi: 10.1128/am.18.2.214-220.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nagai H., Shishido H., Yoneda R., Yamaguchi E., Tamura A., Kurashima A. Long-term low-dose administration of erythromycin to patients with diffuse panbronchiolitis. Respiration. 1991;58(3-4):145–149. doi: 10.1159/000195915. [DOI] [PubMed] [Google Scholar]
  20. Nagaki M., Shimura S., Tanno Y., Ishibashi T., Sasaki H., Takishima T. Role of chronic Pseudomonas aeruginosa infection in the development of bronchiectasis. Chest. 1992 Nov;102(5):1464–1469. doi: 10.1378/chest.102.5.1464. [DOI] [PubMed] [Google Scholar]
  21. Oda H., Kadota J., Kohno S., Hara K. Erythromycin inhibits neutrophil chemotaxis in bronchoalveoli of diffuse panbronchiolitis. Chest. 1994 Oct;106(4):1116–1123. doi: 10.1378/chest.106.4.1116. [DOI] [PubMed] [Google Scholar]
  22. Oishi K., Sonoda F., Kobayashi S., Iwagaki A., Nagatake T., Matsushima K., Matsumoto K. Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases. Infect Immun. 1994 Oct;62(10):4145–4152. doi: 10.1128/iai.62.10.4145-4152.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pirtle J. K., Monroe P. W., Smalley T. K., Mohr J. A., Rhoades E. R. Diagnostic and therapeutic advantages of serial quantitative cultures of fresh sputum in acute bacterial pneumonia. Am Rev Respir Dis. 1969 Dec;100(6):831–838. doi: 10.1164/arrd.1969.100.6.831. [DOI] [PubMed] [Google Scholar]
  24. Poletti V., Patelli M., Poletti G., Bertanti T., Spiga L. Diffuse panbronchiolitis observed in an Italian. Chest. 1990 Aug;98(2):515–516. doi: 10.1378/chest.98.2.515. [DOI] [PubMed] [Google Scholar]
  25. Randhawa P., Hoagland M. H., Yousem S. A. Diffuse panbronchiolitis in North America. Report of three cases and review of the literature. Am J Surg Pathol. 1991 Jan;15(1):43–47. [PubMed] [Google Scholar]
  26. Sakata K., Yajima H., Tanaka K., Sakamoto Y., Yamamoto K., Yoshida A., Dohi Y. Erythromycin inhibits the production of elastase by Pseudomonas aeruginosa without affecting its proliferation in vitro. Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):1061–1065. doi: 10.1164/ajrccm/148.4_Pt_1.1061. [DOI] [PubMed] [Google Scholar]
  27. Sawaki M., Mikami R., Mikasa K., Kunimatsu M., Ito S., Narita N. [The long term chemotherapy with erythromycin in chronic lower respiratory tract infections--second report: including cases with Pseudomonas infections]. Kansenshogaku Zasshi. 1986 Jan;60(1):45–50. doi: 10.11150/kansenshogakuzasshi1970.60.45. [DOI] [PubMed] [Google Scholar]
  28. Stutts M. J., Schwab J. H., Chen M. G., Knowles M. R., Boucher R. C. Effects of Pseudomonas aeruginosa on bronchial epithelial ion transport. Am Rev Respir Dis. 1986 Jul;134(1):17–21. doi: 10.1164/arrd.1986.134.1.17. [DOI] [PubMed] [Google Scholar]
  29. Takeda H., Oogaki N., Kikuchi N., Kobayashi H., Akashi T. [A study to clarify the mechanism of the usefulness of the macrolides--the influence of clarithromycin to biofilm with P. aeruginosa]. Kansenshogaku Zasshi. 1992 Oct;66(10):1454–1461. doi: 10.11150/kansenshogakuzasshi1970.66.1454. [DOI] [PubMed] [Google Scholar]
  30. Tamaoki J., Isono K., Sakai N., Kanemura T., Konno K. Erythromycin inhibits Cl secretion across canine tracheal epithelial cells. Eur Respir J. 1992 Feb;5(2):234–238. [PubMed] [Google Scholar]
  31. Weiland J. E., Davis W. B., Holter J. F., Mohammed J. R., Dorinsky P. M., Gadek J. E. Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am Rev Respir Dis. 1986 Feb;133(2):218–225. doi: 10.1164/arrd.1986.133.2.218. [DOI] [PubMed] [Google Scholar]
  32. Yamamoto M., Kondo A., Tamura M., Izumi T., Ina Y., Noda M. [Long-term therapeutic effects of erythromycin and newquinolone antibacterial agents on diffuse panbronchiolitis]. Nihon Kyobu Shikkan Gakkai Zasshi. 1990 Oct;28(10):1305–1313. [PubMed] [Google Scholar]
  33. Yamasaki T. [Adherence of Pseudomonas aeruginosa to mouse tracheal epithelium--the effect of antimicrobial agents]. Kansenshogaku Zasshi. 1990 May;64(5):575–583. doi: 10.11150/kansenshogakuzasshi1970.64.575. [DOI] [PubMed] [Google Scholar]
  34. Yasuda H., Ajiki Y., Koga T., Kawada H., Yokota T. Interaction between biofilms formed by Pseudomonas aeruginosa and clarithromycin. Antimicrob Agents Chemother. 1993 Sep;37(9):1749–1755. doi: 10.1128/aac.37.9.1749. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES