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. 1979 Dec;16(6):743–749. doi: 10.1128/aac.16.6.743

Gentamicin antibacterial activity in the presence of human polymorphonuclear leukocytes.

P Vaudaux, F A Waldvogel
PMCID: PMC352946  PMID: 533256

Abstract

Complete protection of Staphylococcus aureus Wood 46 from gentamicin bactericidal activity was documented for microorganisms located within polymorphonuclear leukocytes. The highest, still ineffective gentamicin concentration tested in the phagocytic assay was 80 times higher than the minimal concentration required to kill uningested organisms. Extracellular gentamicin activity was unaffected by the phagocytic process as demonstrated by microbiological and enzymatic assays, and liberation of intracellular S. aureus by lysis of neutrophils showed the bacteria to be fully susceptible to the antibiotic. These results were corroborated by studies performed with [14C]gentamicin; binding of the labeled antibiotic by resting neutrophils, or by neutrophils ingesting live, killed S. aureus or endotoxin-coated paraffin particles, showed no statistical differences and never exceeded 20% of the extracellular concentration. These results show that intraleukocytic S. aureus are protected from the bactericidal action of gentamicin and suggest that this protection can be explained by poor intracellular penetration of the antibiotic.

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Selected References

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

  1. Alexander J. W., Good R. A. Effect of antibiotics on the bactericidal activity of human leukocytes. J Lab Clin Med. 1968 Jun;71(6):971–983. [PubMed] [Google Scholar]
  2. Barber M., Waterworth P. M. Activity of gentamicin against Pseudomonas and hospital Staphylococci. Br Med J. 1966 Jan 22;1(5481):203–205. doi: 10.1136/bmj.1.5481.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baron D. N., Ahmed S. A. Intracellular concentrations of water and of the principal electrolytes determined by analysis of isolated human leucocytes. Clin Sci. 1969 Aug;37(1):205–219. [PubMed] [Google Scholar]
  4. Bennett J. V., Brodie J. L., Benner E. J., Kirby W. M. Simplified, accurate method for antibiotic assay of clinical specimens. Appl Microbiol. 1966 Mar;14(2):170–177. doi: 10.1128/am.14.2.170-177.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Björkstén B., Peterson P. K., Verhoef J., Quie P. G. Limiting factors in bacterial phagocytosis by human polymorphonuclear leukocytes. Acta Pathol Microbiol Scand C. 1977 Oct;85(5):345–349. doi: 10.1111/j.1699-0463.1977.tb03652.x. [DOI] [PubMed] [Google Scholar]
  6. Bryan L. E., Van Den Elzen H. M. Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria. Antimicrob Agents Chemother. 1977 Aug;12(2):163–177. doi: 10.1128/aac.12.2.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bryant R. E., Hammond D. Interaction of purulent material with antibiotics used to treat Pseudomonas infections. Antimicrob Agents Chemother. 1974 Dec;6(6):702–707. doi: 10.1128/aac.6.6.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  9. Holmes B., Quie P. G., Windhorst D. B., Pollara B., Good R. A. Protection of phagocytized bacteria from the killing action of antibiotics. Nature. 1966 Jun 11;210(5041):1131–1132. doi: 10.1038/2101131a0. [DOI] [PubMed] [Google Scholar]
  10. Lew P. D., Zubler R., Vaudaux P., Farquet J. J., Waldvogel F. A., Lambert P. H. Decreased heat-labile opsonic activity and complement levels associated with evidence of C3 breakdown products in infected pleural effusions. J Clin Invest. 1979 Feb;63(2):326–334. doi: 10.1172/JCI109306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mandell G. L. Interaction of intraleukocytic bacteria and antibiotics. J Clin Invest. 1973 Jul;52(7):1673–1679. doi: 10.1172/JCI107348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mandell G. L., Vest T. K. Killing of intraleukocytic Staphylococcus aureus by rifampin: in-vitro and in-vivo studies. J Infect Dis. 1972 May;125(5):486–490. doi: 10.1093/infdis/125.5.486. [DOI] [PubMed] [Google Scholar]
  13. Musher D. M., Baughn R. E., Templeton G. B., Minuth J. N. Emergence of variant forms of Staphylococcus aureus after exposure to gentamicin and infectivity of the variants in experimental animals. J Infect Dis. 1977 Sep;136(3):360–369. doi: 10.1093/infdis/136.3.360. [DOI] [PubMed] [Google Scholar]
  14. ROGERS D. E., TOMPSETT R. The survival of staphylococci within human leukocytes. J Exp Med. 1952 Feb;95(2):209–230. doi: 10.1084/jem.95.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. SHAFFER J. M., KUCERA C. J., SPINK W. W. The protection of intracellular brucella against therapeutic agents and the bactericidal action of serum. J Exp Med. 1953 Jan;97(1):77–90. doi: 10.1084/jem.97.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schaffner W., Melly M. A., Hash J. H., Koenig M. G. Lysostaphin: an enzymatic approach to staphylococcal disease. I. In vitro studies. Yale J Biol Med. 1967 Feb;39(4):215–229. [PMC free article] [PubMed] [Google Scholar]
  17. Smith A. L., Smith D. H. Gentamicin:adenine mononucleotide transferase: partial purification, characterization, and use in the clinical quantitation of gentamicin. J Infect Dis. 1974 Apr;129(4):391–401. doi: 10.1093/infdis/129.4.391. [DOI] [PubMed] [Google Scholar]
  18. Solberg C. O., Hellum K. B. Protection of phagocytosed bacteria against antimicrobial agents. Scand J Infect Dis Suppl. 1978;(14):246–250. [PubMed] [Google Scholar]
  19. Solberg C. O. Protection of phagocytized bacteria against antibiotics. A new method for the evaluation of neutrophil granulocyte functions. Acta Med Scand. 1972 May;191(5):383–387. [PubMed] [Google Scholar]
  20. Stossel T. P. Evaluation of opsonic and leukocyte function with a spectrophotometric test in patients with infection and with phagocytic disorders. Blood. 1973 Jul;42(1):121–130. [PubMed] [Google Scholar]
  21. Stossel T. P. Phagocytosis (third of three parts). N Engl J Med. 1974 Apr 11;290(15):833–839. doi: 10.1056/NEJM197404112901506. [DOI] [PubMed] [Google Scholar]
  22. Tan J. S., Watanakunakorn C., Phair J. P. A modified assay of neutrophil function: use of lysostaphin to differentiate defective phagocytosis from impaired intracellular killing. J Lab Clin Med. 1971 Aug;78(2):316–322. [PubMed] [Google Scholar]
  23. Vaudaux P., Waldvogel F. A. Methicillin-resistant strains of Staphylococcus aureus: relation between expression of resistance and phagocytosis by polymorphonuclear leukocytes. J Infect Dis. 1979 May;139(5):547–552. doi: 10.1093/infdis/139.5.547. [DOI] [PubMed] [Google Scholar]

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