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. 1994 Nov;49(11):1134–1138. doi: 10.1136/thx.49.11.1134

Concentration of amoxycillin and clavulanate in lung compartments in adults without pulmonary infection.

P J Cook 1, J M Andrews 1, J Woodcock 1, R Wise 1, D Honeybourne 1
PMCID: PMC475276  PMID: 7831630

Abstract

BACKGROUND--The efficacy of an antibiotic is usually predicted from serum levels and MIC90 values for likely pathogens, but in the lung tissue concentrations may be more informative. This study compares concentrations of amoxycillin and clavulanate in serum, epithelial lining fluid (ELF), alveolar macrophages, and bronchial mucosa in 15 adults. METHODS--Amoxycillin 500 mg and clavulanic acid 250 mg were given 1-2 hours before diagnostic bronchoscopy for haemoptysis or radiological abnormality. Mucosal biopsy samples were taken from macroscopically normal sites, alveolar macrophages harvested by lavage, and ELF volume derived from urea concentrations in bronchial lavage fluid and blood. Amoxycillin was assayed by inhibition of growth of Micrococcus lutea, and clavulanate (in serum, ELF, and bronchial mucosa) by inhibition of growth of Klebsiella pneumoniae; in macrophages clavulanate was measured by high performance liquid chromatography. RESULTS--The median concentrations in serum were 6.90 mg/l for amoxycillin and 5.25 mg/l for clavulanate. The median bronchial mucosal concentration of amoxycillin was 2.99 mg/l and of clavulanate was 1.65 mg/l; the median concentrations in ELF were 0.89 and 0.96 mg/l, and in macrophages 0 and 0.76 mg/l, respectively. In macrophages amoxycillin levels were undetectable in 10 of 14 subjects (71%); by contrast, only 6 of 14 subjects (43%) had no detectable clavulanate. CONCLUSIONS--Clavulanate levels exceeded quoted MIC90 values (around 0.25 mg/l) for Legionella pneumophila both in ELF and in macrophages. Amoxycillin-clavulanate may therefore have a clinical role in infections with Legionella pneumophila.

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Selected References

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

  1. Baldwin D. R., Andrews J. M., Ashby J. P., Wise R., Honeybourne D. Concentrations of cefixime in bronchial mucosa and sputum after three oral multiple dose regimens. Thorax. 1990 May;45(5):401–402. doi: 10.1136/thx.45.5.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baldwin D. R., Honeybourne D., Wise R. Pulmonary disposition of antimicrobial agents: methodological considerations. Antimicrob Agents Chemother. 1992 Jun;36(6):1171–1175. doi: 10.1128/aac.36.6.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baldwin D. R., Maxwell S. R., Honeybourne D., Andrews J. M., Ashby J. P., Wise R. The penetration of cefpirome into the potential sites of pulmonary infection. J Antimicrob Chemother. 1991 Jul;28(1):79–86. doi: 10.1093/jac/28.1.79. [DOI] [PubMed] [Google Scholar]
  4. Bergogne-Berezin E. Penetration of antibiotics into the respiratory tree. J Antimicrob Chemother. 1981 Sep;8(3):171–174. doi: 10.1093/jac/8.3.171. [DOI] [PubMed] [Google Scholar]
  5. Brambilla C., Kastanakis S., Knight S., Cunningham K. Cefuroxime and cefuroxime axetil versus amoxicillin plus clavulanic acid in the treatment of lower respiratory tract infections. Eur J Clin Microbiol Infect Dis. 1992 Feb;11(2):118–124. doi: 10.1007/BF01967062. [DOI] [PubMed] [Google Scholar]
  6. Cunha B. A. Amoxicillin/clavulanate therapy of respiratory tract infections: a microbiologic perspective. Clin Ther. 1992 May-Jun;14(3):418–425. [PubMed] [Google Scholar]
  7. Effros R. M., Mason G. R., Sietsema K., Hukkanen J., Silverman P. Pulmonary epithelial sieving of small solutes in rat lungs. J Appl Physiol (1985) 1988 Aug;65(2):640–648. doi: 10.1152/jappl.1988.65.2.640. [DOI] [PubMed] [Google Scholar]
  8. Effros R. M., Mason G. R., Silverman P., Reid E., Hukkanen J. Movement of ions and small solutes across endothelium and epithelium of perfused rabbit lungs. J Appl Physiol (1985) 1986 Jan;60(1):100–107. doi: 10.1152/jappl.1986.60.1.100. [DOI] [PubMed] [Google Scholar]
  9. Fabre J., Rudhardt M., Blanchard P., Regamey C. Persistence of sisomicin and gentamicin in renal cortex and medulla compared with other organs and serum of rats. Kidney Int. 1976 Dec;10(6):444–449. doi: 10.1038/ki.1976.131. [DOI] [PubMed] [Google Scholar]
  10. Forestier F., Gerrier P., Chaumard C., Quero A. M., Couvreur P., Labarre C. Effect of nanoparticle-bound ampicillin on the survival of Listeria monocytogenes in mouse peritoneal macrophages. J Antimicrob Chemother. 1992 Aug;30(2):173–179. doi: 10.1093/jac/30.2.173. [DOI] [PubMed] [Google Scholar]
  11. Foulstone M., Reading C. Assay of amoxicillin and clavulanic acid, the components of Augmentin, in biological fluids with high-performance liquid chromatography. Antimicrob Agents Chemother. 1982 Nov;22(5):753–762. doi: 10.1128/aac.22.5.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Glauser M. P., Lyons J. M., Braude A. I. Prevention of pyelonephritis due to Escherichia coli in rats with gentamicin stored in kidney tissue. J Infect Dis. 1979 Feb;139(2):172–177. doi: 10.1093/infdis/139.2.172. [DOI] [PubMed] [Google Scholar]
  13. Gould I. M., Legge J. S., Reid T. M. Amoxycillin/clavulanic acid levels in lower respiratory secretions. J Antimicrob Chemother. 1988 Jul;22(1):88–90. doi: 10.1093/jac/22.1.88. [DOI] [PubMed] [Google Scholar]
  14. HERS J. F., MULDER J. The mucosal epithelium of the respiratory tract in muco-purulent bronchitis caused by Haemophilus influenzae. J Pathol Bacteriol. 1953 Jul;66(1):103–108. doi: 10.1002/path.1700660114. [DOI] [PubMed] [Google Scholar]
  15. Honeybourne D., Andrews J. M., Ashby J. P., Lodwick R., Wise R. Evaluation of the penetration of ciprofloxacin and amoxycillin into the bronchial mucosa. Thorax. 1988 Sep;43(9):715–719. doi: 10.1136/thx.43.9.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Johnson J. D., Hand W. L., Francis J. B., King-Thompson N., Corwin R. W. Antibiotic uptake by alveolar macrophages. J Lab Clin Med. 1980 Mar;95(3):429–439. [PubMed] [Google Scholar]
  17. Kaibara M., Kikkawa Y. Osmiophilia of the saturated phospholipid, dipalmitoyl lecithin, and its relationship to the alveolar lining layer of the mammalian lung. Am J Anat. 1971 Sep;132(1):61–78. doi: 10.1002/aja.1001320108. [DOI] [PubMed] [Google Scholar]
  18. Legnani D., Lombardo V. M., Negretto G. G., Beghi G., Caratozzolo O. Comparative clinical and microbiological study of amoxycillin-clavulanic acid and ciprofloxacin in acute purulent exacerbations of chronic bronchitis. J Hosp Infect. 1992 Nov;22 (Suppl A):69–74. doi: 10.1016/s0195-6701(05)80009-x. [DOI] [PubMed] [Google Scholar]
  19. Legnani D., Lombardo V. M., Negretto G. G., Beghi G., Caratozzolo O. Comparative clinical and microbiological study of amoxycillin-clavulanic acid and ciprofloxacin in acute purulent exacerbations of chronic bronchitis. J Hosp Infect. 1992 Nov;22 (Suppl A):69–74. doi: 10.1016/s0195-6701(05)80009-x. [DOI] [PubMed] [Google Scholar]
  20. Low A. S., Taylor R. B., Gould I. M. Determination of clavulanic acid by a sensitive HPLC method. J Antimicrob Chemother. 1989 Nov;24 (Suppl B):83–86. doi: 10.1093/jac/24.suppl_b.83. [DOI] [PubMed] [Google Scholar]
  21. Marlin G. E., Braude P. D., Whelan A. J., Somogyi A. A. Penetration of enoxacin into human bronchial mucosa. Am Rev Respir Dis. 1986 Dec;134(6):1209–1212. doi: 10.1164/arrd.1986.134.5.1209. [DOI] [PubMed] [Google Scholar]
  22. Marlin G. E., Burgess K. R., Burgoyne J., Funnell G. R., Guinness M. D. Penetration of piperacillin into bronchial mucosa and sputum. Thorax. 1981 Oct;36(10):774–780. doi: 10.1136/thx.36.10.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Neu H. C., Wilson A. P., Grüneberg R. N. Amoxycillin/clavulanic acid: a review of its efficacy in over 38,500 patients from 1979 to 1992. J Chemother. 1993 Apr;5(2):67–93. doi: 10.1080/1120009x.1993.11739213. [DOI] [PubMed] [Google Scholar]
  24. Neu H. C., Wilson A. P., Grüneberg R. N. Amoxycillin/clavulanic acid: a review of its efficacy in over 38,500 patients from 1979 to 1992. J Chemother. 1993 Apr;5(2):67–93. doi: 10.1080/1120009x.1993.11739213. [DOI] [PubMed] [Google Scholar]
  25. Pfaller M., Barry A., Fuchs P., Gerlach E., Hardy D., McLaughlin J. Relative efficacy of tazobactam, sulbactam and clavulanic acid in enhancing the potency of ampicillin against clinical isolates of Enterobacteriaceae. Eur J Clin Microbiol Infect Dis. 1993 Mar;12(3):200–205. doi: 10.1007/BF01967112. [DOI] [PubMed] [Google Scholar]
  26. Rennard S. I., Basset G., Lecossier D., O'Donnell K. M., Pinkston P., Martin P. G., Crystal R. G. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol (1985) 1986 Feb;60(2):532–538. doi: 10.1152/jappl.1986.60.2.532. [DOI] [PubMed] [Google Scholar]
  27. Smith G. M., Abbott K. H., Wilkinson M. J., Beale A. S., Sutherland R. Bactericidal effects of ticarcillin-clavulanic acid against Legionella pneumophila pneumonia in immunocompromised weanling rats. Antimicrob Agents Chemother. 1991 Jul;35(7):1423–1429. doi: 10.1128/aac.35.7.1423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith G. M., Sutherland R. Activity of amoxycillin-clavulanic acid against Legionella pneumophila in vitro and in an experimental respiratory infection model. J Hosp Infect. 1992 Nov;22 (Suppl A):61–67. doi: 10.1016/s0195-6701(05)80008-8. [DOI] [PubMed] [Google Scholar]
  29. Staehelin L. A. Structure and function of intercellular junctions. Int Rev Cytol. 1974;39:191–283. doi: 10.1016/s0074-7696(08)60940-7. [DOI] [PubMed] [Google Scholar]
  30. Stamey T. A., Fair W. R., Timothy M. M., Millar M. A., Mihara G., Lowery Y. C. Serum versus urinary antimicrobial concentrations in cure of urinary-tract infections. N Engl J Med. 1974 Nov 28;291(22):1159–1163. doi: 10.1056/NEJM197411282912204. [DOI] [PubMed] [Google Scholar]
  31. Stockley R. A., Dragicevic P., Burnett D., Hill S. L. Role of beta-lactamases in the response of pulmonary infections to amoxycillin/clavulanate. J Antimicrob Chemother. 1989 Nov;24 (Suppl B):73–81. doi: 10.1093/jac/24.suppl_b.73. [DOI] [PubMed] [Google Scholar]
  32. Stokes D. H., Slocombe B., Sutherland R. Bactericidal effects of amoxycillin/clavulanic acid against Legionella pneumophila. J Antimicrob Chemother. 1989 Jan;23(1):43–51. doi: 10.1093/jac/23.1.43. [DOI] [PubMed] [Google Scholar]
  33. TAYLOR A. E., GUYTON A. C., BISHOP V. S. PERMEABILITY OF THE ALVEOLAR MEMBRANE TO SOLUTES. Circ Res. 1965 Apr;16:353–362. doi: 10.1161/01.res.16.4.353. [DOI] [PubMed] [Google Scholar]
  34. Valcke Y., Pauwels R., Van der Straeten M. Pharmacokinetics of antibiotics in the lungs. Eur Respir J. 1990 Jun;3(6):715–722. [PubMed] [Google Scholar]
  35. Walters E. H., Gardiner P. V. Bronchoalveolar lavage as a research tool. Thorax. 1991 Sep;46(9):613–618. doi: 10.1136/thx.46.9.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wenger J. D., Hightower A. W., Facklam R. R., Gaventa S., Broome C. V. Bacterial meningitis in the United States, 1986: report of a multistate surveillance study. The Bacterial Meningitis Study Group. J Infect Dis. 1990 Dec;162(6):1316–1323. doi: 10.1093/infdis/162.6.1316. [DOI] [PubMed] [Google Scholar]
  37. Zhang Y., Steingrube V. A., Wallace R. J., Jr beta-Lactamase inhibitors and the inducibility of the beta-lactamase of Mycobacterium tuberculosis. Am Rev Respir Dis. 1992 Mar;145(3):657–660. doi: 10.1164/ajrccm/145.3.657. [DOI] [PubMed] [Google Scholar]

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