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. 1992 Jun;36(6):1198–1203. doi: 10.1128/aac.36.6.1198

Efficacy of erythromycin lactobionate for treating Pseudomonas aeruginosa bacteremia in mice.

Y Hirakata 1, M Kaku 1, K Tomono 1, K Tateda 1, N Furuya 1, T Matsumoto 1, R Araki 1, K Yamaguchi 1
PMCID: PMC190317  PMID: 1416819

Abstract

We induced endogenous Pseudomonas aeruginosa bacteremia by administering cyclophosphamide and ampicillin to specific pathogen-free mice fed P. aeruginosa. Using this model, we evaluated the efficacy of erythromycin lactobionate (EML) in treating P. aeruginosa bacteremia. Treatment with EML at 50 and 100 mg/kg of body weight per day twice a day for 14 days significantly increased the survival rate. The most effective dose was 100 mg/kg/day, with a survival rate of 80% compared with a 20% survival rate in the control. However, the administration of EML at 500 mg/kg/day rather decreased the survival rate. In a model of intravenous infection, treatment with EML at 100 mg/kg/day twice a day for 7 days before the bacterial challenge also enhanced the survival rate. EML levels in serum, liver, and stool were apparently lower than the MIC (512 micrograms/ml). These observations suggest that EML is effective against P. aeruginosa bacteremia despite a lack of specific activity for this pathogen. Although the protective mechanism is still unclear, it is possible that a subinhibitory level of EML may affect the virulence of P. aeruginosa and enhance the host defense system.

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Selected References

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

  1. Adinolfi L. E., Bonventre P. F. Enhanced phagocytosis, killing, and serum sensitivity of Escherichia coli and Staphylococcus aureus treated with sub-MICs of imipenem. Antimicrob Agents Chemother. 1988 Jul;32(7):1012–1018. doi: 10.1128/aac.32.7.1012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson R., Fernandes A. C., Eftychis H. E. Studies on the effects of ingestion of a single 500 mg oral dose of erythromycin stearate on leucocyte motility and transformation and on release in vitro of prostaglandin E2 by stimulated leucocytes. J Antimicrob Chemother. 1984 Jul;14(1):41–50. doi: 10.1093/jac/14.1.41. [DOI] [PubMed] [Google Scholar]
  3. Andreana A., Perna P., Utili R., Dilillo M., Ruggiero G. Increased phagocytosis and killing of Escherichia coli treated with subinhibitory concentrations of cefamandole and gentamicin in isolated rat livers. Antimicrob Agents Chemother. 1984 Feb;25(2):182–186. doi: 10.1128/aac.25.2.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bailly S., Pocidalo J. J., Fay M., Gougerot-Pocidalo M. A. Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin. Antimicrob Agents Chemother. 1991 Oct;35(10):2016–2019. doi: 10.1128/aac.35.10.2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bryan C. S., Reynolds K. L., Brenner E. R. Analysis of 1,186 episodes of gram-negative bacteremia in non-university hospitals: the effects of antimicrobial therapy. Rev Infect Dis. 1983 Jul-Aug;5(4):629–638. doi: 10.1093/clinids/5.4.629. [DOI] [PubMed] [Google Scholar]
  6. Collins H. H., Cross A. S., Dobek A., Opal S. M., McClain J. B., Sadoff J. C. Oral ciprofloxacin and a monoclonal antibody to lipopolysaccharide protect leukopenic rats from lethal infection with Pseudomonas aeruginosa. J Infect Dis. 1989 Jun;159(6):1073–1082. doi: 10.1093/infdis/159.6.1073. [DOI] [PubMed] [Google Scholar]
  7. Eyraud A., Descotes J., Lombard J. Y., Laschi-Loquerie A., Tachon P., Veysseyre C., Evreux J. C. Effects of erythromycin, josamycin and spiramycin on rat polymorphonuclear leukocyte chemotaxis. Chemotherapy. 1986;32(4):379–382. doi: 10.1159/000238438. [DOI] [PubMed] [Google Scholar]
  8. Fernandes A. C., Anderson R., Theron A. J., Jooné G., Van Rensburg C. E. Enhancement of human polymorphonuclear leucocyte motility by erythromycin in vitro and in vivo. S Afr Med J. 1984 Aug 4;66(5):173–177. [PubMed] [Google Scholar]
  9. Fraschini F., Scaglione F., Ferrara F., Marelli O., Braga P. C., Teodori F. Evaluation of the immunostimulating activity of erythromycin in man. Chemotherapy. 1986;32(3):286–290. doi: 10.1159/000238425. [DOI] [PubMed] [Google Scholar]
  10. Grimwood K., To M., Rabin H. R., Woods D. E. Inhibition of Pseudomonas aeruginosa exoenzyme expression by subinhibitory antibiotic concentrations. Antimicrob Agents Chemother. 1989 Jan;33(1):41–47. doi: 10.1128/aac.33.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hentges D. J., Stein A. J., Casey S. W., Que J. U. Protective role of intestinal flora against infection with Pseudomonas aeruginosa in mice: influence of antibiotics on colonization resistance. Infect Immun. 1985 Jan;47(1):118–122. doi: 10.1128/iai.47.1.118-122.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hirakata Y., Tomono K., Tateda K., Matsumoto T., Furuya N., Shimoguchi K., Kaku M., Yamaguchi K. Role of bacterial association with Kupffer cells in occurrence of endogenous systemic bacteremia. Infect Immun. 1991 Jan;59(1):289–294. doi: 10.1128/iai.59.1.289-294.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Ishiguro M., Koga H., Kohno S., Hayashi T., Yamaguchi K., Hirota M. Penetration of macrolides into human polymorphonuclear leucocytes. J Antimicrob Chemother. 1989 Nov;24(5):719–729. doi: 10.1093/jac/24.5.719. [DOI] [PubMed] [Google Scholar]
  15. Kita E., Sawaki M., Nishikawa F., Mikasa K., Yagyu Y., Takeuchi S., Yasui K., Narita N., Kashiba S. Enhanced interleukin production after long-term administration of erythromycin stearate. Pharmacology. 1990;41(4):177–183. doi: 10.1159/000138716. [DOI] [PubMed] [Google Scholar]
  16. Kita E., Sawaki M., Oku D., Hamuro A., Mikasa K., Konishi M., Emoto M., Takeuchi S., Narita N., Kashiba S. Suppression of virulence factors of Pseudomonas aeruginosa by erythromycin. J Antimicrob Chemother. 1991 Mar;27(3):273–284. doi: 10.1093/jac/27.3.273. [DOI] [PubMed] [Google Scholar]
  17. Nelson S., Summer W. R., Terry P. B., Warr G. A., Jakab G. J. Erythromycin-induced suppression of pulmonary antibacterial defenses. A potential mechanism of superinfection in the lung. Am Rev Respir Dis. 1987 Nov;136(5):1207–1212. doi: 10.1164/ajrccm/136.5.1207. [DOI] [PubMed] [Google Scholar]
  18. Neu H. C. The role of Pseudomonas aeruginosa in infections. J Antimicrob Chemother. 1983 May;11 (Suppl B):1–13. doi: 10.1093/jac/11.suppl_b.1. [DOI] [PubMed] [Google Scholar]
  19. Ozaki Y., Ohashi T., Minami A., Nakamura S. Enhanced resistance of mice to bacterial infection induced by recombinant human interleukin-1a. Infect Immun. 1987 Jun;55(6):1436–1440. doi: 10.1128/iai.55.6.1436-1440.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pocidalo J. J., Albert F., Desnottes J. F., Kernbaum S. Intraphagocytic penetration of macrolides: in-vivo comparison of erythromycin and spiramycin. J Antimicrob Chemother. 1985 Jul;16 (Suppl A):167–173. doi: 10.1093/jac/16.suppl_a.167. [DOI] [PubMed] [Google Scholar]
  21. Warren R. L., Baker N. R., Johnson J., Stapleton M. J. Selective inhibition of the accumulation of extracellular proteases of Pseudomonas aeruginosa by gentamicin and tobramycin. Antimicrob Agents Chemother. 1985 Apr;27(4):468–472. doi: 10.1128/aac.27.4.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wood R. E., Boat T. F., Doershuk C. F. Cystic fibrosis. Am Rev Respir Dis. 1976 Jun;113(6):833–878. doi: 10.1164/arrd.1976.113.6.833. [DOI] [PubMed] [Google Scholar]
  23. van der Waaij D., Berghuis J. M., Lekkerkerk J. E. Colonization resistance of the digestive tract of mice during systemic antibiotic treatment. J Hyg (Lond) 1972 Dec;70(4):605–610. doi: 10.1017/s0022172400022464. [DOI] [PMC free article] [PubMed] [Google Scholar]

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