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. 1993 Sep;37(9):1882–1889. doi: 10.1128/aac.37.9.1882

Adverse effects of pefloxacin in irradiated C3H/HeN mice: correction with glucan therapy.

M L Patchen 1, I Brook 1, T B Elliott 1, W E Jackson 1
PMCID: PMC188087  PMID: 8239601

Abstract

Opportunistic bacterial infections are the predominant cause of death following myelosuppressive radiation exposure. When used alone, a variety of immunomodulators and antibiotics have been reported to reduce radiation-induced death. In these studies, the combined therapeutic effects of the immunomodulator glucan and the quinolone antibiotic pefloxacin were evaluated for survival-enhancing effects in myelosuppressed C3H/HeN mice. Mice were exposed to 7.9 Gy of whole-body 60Co radiation and treated with saline, glucan (250 mg/kg of body weight intravenously, 1 h after irradiation), pefloxacin (64 mg/kg/day orally, days 3 to 24 after irradiation), or glucan plus pefloxacin. Survival 30 days after irradiation in mice receiving these respective treatments was 25, 48, 7, and 85%. Evaluation of granulocyte-macrophage progenitor cell (GM-CFC) recovery in mice receiving these treatments revealed that, compared with recovery in saline-treated mice, glucan stimulated GM-CFC recovery, pefloxacin suppressed GM-CFC recovery, and glucan administered in combination with pefloxacin could override pefloxacin's hemopoietic suppressive effect.

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Selected References

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  1. A protocol for the determination of absorbed dose from high-energy photon and electron beams. Med Phys. 1983 Nov-Dec;10(6):741–771. doi: 10.1118/1.595446. [DOI] [PubMed] [Google Scholar]
  2. BENACERRAF B. Influence of irradiation on resistance to infection. Bacteriol Rev. 1960 Mar;24(1):35–40. doi: 10.1128/br.24.1.35-40.1960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brook I., Elliott T. B., Ledney G. D. Quinolone therapy of Klebsiella pneumoniae sepsis following irradiation: comparison of pefloxacin, ciprofloxacin, and ofloxacin. Radiat Res. 1990 May;122(2):215–217. [PubMed] [Google Scholar]
  4. Brook I., Elliott T. B. Quinolone therapy in the prevention of mortality after irradiation. Radiat Res. 1991 Oct;128(1):100–103. [PubMed] [Google Scholar]
  5. Di Luzio N. R., Williams D. L., McNamee R. B., Edwards B. F., Kitahama A. Comparative tumor-inhibitory and anti-bacterial activity of soluble and particulate glucan. Int J Cancer. 1979 Dec 15;24(6):773–779. doi: 10.1002/ijc.2910240613. [DOI] [PubMed] [Google Scholar]
  6. Easmon C. S., Crane J. P. Uptake of ciprofloxacin by macrophages. J Clin Pathol. 1985 Apr;38(4):442–444. doi: 10.1136/jcp.38.4.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fantoni M., Tamburrini E., Pallavicini F., Antinori A., Nervo P. Influence of ofloxacin and pefloxacin on human lymphocyte immunoglobulin secretion and on polymorphonuclear leucocyte superoxide anion production. J Antimicrob Chemother. 1988 Aug;22(2):193–196. doi: 10.1093/jac/22.2.193. [DOI] [PubMed] [Google Scholar]
  8. Forsgren A., Bredberg A., Riesbeck K. New quinolones: in vitro effects as a potential source of clinical toxicity. Rev Infect Dis. 1989 Jul-Aug;11 (Suppl 5):S1382–S1389. doi: 10.1093/clinids/11.supplement_5.s1382. [DOI] [PubMed] [Google Scholar]
  9. Forsgren A., Schlossman S. F., Tedder T. F. 4-Quinolone drugs affect cell cycle progression and function of human lymphocytes in vitro. Antimicrob Agents Chemother. 1987 May;31(5):768–773. doi: 10.1128/aac.31.5.768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gonzalez J. P., Henwood J. M. Pefloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1989 May;37(5):628–668. doi: 10.2165/00003495-198937050-00003. [DOI] [PubMed] [Google Scholar]
  11. Gootz T. D., Barrett J. F., Sutcliffe J. A. Inhibitory effects of quinolone antibacterial agents on eucaryotic topoisomerases and related test systems. Antimicrob Agents Chemother. 1990 Jan;34(1):8–12. doi: 10.1128/aac.34.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Halkin H. Adverse effects of the fluoroquinolones. Rev Infect Dis. 1988 Jan-Feb;10 (Suppl 1):S258–S261. doi: 10.1093/clinids/10.supplement_1.s258. [DOI] [PubMed] [Google Scholar]
  13. Hathorn J. W., Rubin M., Pizzo P. A. Empirical antibiotic therapy in the febrile neutropenic cancer patient: clinical efficacy and impact of monotherapy. Antimicrob Agents Chemother. 1987 Jul;31(7):971–977. doi: 10.1128/aac.31.7.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hussy P., Maass G., Tümmler B., Grosse F., Schomburg U. Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase alpha primase complex, topoisomerases I and II, and growth of mammalian lymphoblasts. Antimicrob Agents Chemother. 1986 Jun;29(6):1073–1078. doi: 10.1128/aac.29.6.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. King A., Phillips I. The comparative in-vitro activity of pefloxacin. J Antimicrob Chemother. 1986 Apr;17 (Suppl B):1–10. doi: 10.1093/jac/17.suppl_b.1. [DOI] [PubMed] [Google Scholar]
  16. Meijne E. I., van der Winden-van Groenewegen R. J., Ploemacher R. E., Vos O., David J. A., Huiskamp R. The effects of x-irradiation on hematopoietic stem cell compartments in the mouse. Exp Hematol. 1991 Aug;19(7):617–623. [PubMed] [Google Scholar]
  17. Montay G., Goueffon Y., Roquet F. Absorption, distribution, metabolic fate, and elimination of pefloxacin mesylate in mice, rats, dogs, monkeys, and humans. Antimicrob Agents Chemother. 1984 Apr;25(4):463–472. doi: 10.1128/aac.25.4.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Patchen M. L., D'Alesandro M. M., Brook I., Blakely W. F., MacVittie T. J. Glucan: mechanisms involved in its "radioprotective" effect. J Leukoc Biol. 1987 Aug;42(2):95–105. doi: 10.1002/jlb.42.2.95. [DOI] [PubMed] [Google Scholar]
  19. Patchen M. L., D'Alesandro M. M., Chirigos M. A., Weiss J. F. Radioprotection by biological response modifiers alone and in combination with WR-2721. Pharmacol Ther. 1988;39(1-3):247–254. doi: 10.1016/0163-7258(88)90068-x. [DOI] [PubMed] [Google Scholar]
  20. Patchen M. L., Fischer R., MacVittie T. J. Effects of combined administration of interleukin-6 and granulocyte colony-stimulating factor on recovery from radiation-induced hemopoietic aplasia. Exp Hematol. 1993 Feb;21(2):338–344. [PubMed] [Google Scholar]
  21. Patchen M. L., Lotzová E. The role of macrophages and T-lymphocytes in glucan-mediated alteration of murine hemopoiesis. Biomedicine. 1981 Sep;34(2):71–77. [PubMed] [Google Scholar]
  22. Patchen M. L., MacVittie T. J. Hemopoietic effects of intravenous soluble glucan administration. J Immunopharmacol. 1986;8(3):407–425. [PubMed] [Google Scholar]
  23. Patchen M. L., MacVittie T. J., Jackson W. E. Postirradiation glucan administration enhances the radioprotective effects of WR-2721. Radiat Res. 1989 Jan;117(1):59–69. [PubMed] [Google Scholar]
  24. Patchen M. L., MacVittie T. J., Solberg B. D., D'Alesandro M. M., Brook I. Radioprotection by polysaccharides alone and in combination with aminothiols. Adv Space Res. 1992;12(2-3):233–248. doi: 10.1016/0273-1177(92)90113-c. [DOI] [PubMed] [Google Scholar]
  25. Patchen M. L., MacVittie T. J. Stimulated hemopoiesis and enhanced survival following glucan treatment in sublethally and lethally irradiated mice. Int J Immunopharmacol. 1985;7(6):923–932. doi: 10.1016/0192-0561(85)90056-6. [DOI] [PubMed] [Google Scholar]
  26. Patchen M. L., MacVittie T. J., Wathen L. M. Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells. Experientia. 1984 Nov 15;40(11):1240–1244. doi: 10.1007/BF01946654. [DOI] [PubMed] [Google Scholar]
  27. Patchen M. L., MacVittie T. J., Williams J. L., Schwartz G. N., Souza L. M. Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression. Blood. 1991 Feb 1;77(3):472–480. [PubMed] [Google Scholar]
  28. Roche Y., Gougerot-Pocidalo M. A., Fay M., Etienne D., Forest N., Pocidalo J. J. Comparative effects of quinolones on human mononuclear leucocyte functions. J Antimicrob Chemother. 1987 Jun;19(6):781–790. doi: 10.1093/jac/19.6.781. [DOI] [PubMed] [Google Scholar]
  29. Schmidtke J. R., Dixon F. J. The functional capacity of x-irradiated macrophages. J Immunol. 1972 Jun;108(6):1624–1630. [PubMed] [Google Scholar]
  30. TILL J. E., McCULLOCH E. A. Early repair processes in marrow cells irradiated and proliferating in vivo. Radiat Res. 1963 Jan;18:96–105. [PubMed] [Google Scholar]

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