Abstract
The effects of cefodizime and cefuroxime on neutrophil phagocytosis and reactive oxygen production in 54 patients undergoing elective coronary artery bypass grafting were studied. Both drugs were administered twice at a dosage of 40 mg/kg of body weight (pre- and intraoperative). Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled Escherichia coli and Staphylococcus aureus by flow cytometry. Reactive oxygen generation after phagocytosis was estimated by determining the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. In both groups the mean phagocytic ability for E. coli and S. aureus decreased during surgery (-21 and -8%, respectively, for the cefodizime group and -39 and -38%, respectively, for the cefuroxime group; P < 0.05 for all). In the cefodizime group a normalization of mean E. coli and S. aureus neutrophil phagocytosis was seen on day 5 (+9 and -4% compared to preoperative values; P > 0.35 for both), whereas in cefuroxime-treated patients phagocytic ability remained depressed (-37 and -31%; P < 0.04 for both). In both groups mean neutrophil reactive oxygen intermediate (ROI) production after E. coli and S. aureus phagocytosis increased during cardiopulmonary bypass (+44 and +83%, respectively, in the cefodizime group and +58 and +73%, respectively, in the cefuroxime group; P < 0.05 for all). One day after surgery E. coli- and S. aureus-driven neutrophil ROI production was not different from the preoperative values (-2 and +12%, respectively, for the cefodizime group and +7 and +15%, respectively, for the cefuroxime group; P > 0.15 for all). Postoperative serum levels of the C-reactive protein on days 2 and 7 were lower in cefodizime-treated patients (19 +/- 6 and 4 +/- 2 mg/liter versus 23 +/- 6 and 11 +/- 5 mg/liter; P < 0.05 for both). In addition to cefodizime's antimicrobial activity during perioperative prophylaxis, its use in coronary artery bypass grafting can prevent procedure-related prolonged postoperative neutrophil phagocytosis impairment.
Full Text
The Full Text of this article is available as a PDF (139.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Auteri A., Pasqui A. L., Bruni F., Saletti M., Mazza S., Di Renzo M., Maggiore D., Di Perri T. Effect of cefodizime (HR 221) on immunological defects induced by surgical stress. Drugs Exp Clin Res. 1991;17(12):555–561. [PubMed] [Google Scholar]
- Bardosi L., Tekeres M. Impaired metabolic activity of phagocytic cells after anaesthesia and surgery. Br J Anaesth. 1985 May;57(5):520–523. doi: 10.1093/bja/57.5.520. [DOI] [PubMed] [Google Scholar]
- Bass D. A., Parce J. W., Dechatelet L. R., Szejda P., Seeds M. C., Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol. 1983 Apr;130(4):1910–1917. [PubMed] [Google Scholar]
- Bassøe C. F., Laerum O. D., Solberg C. O., Haneberg B. Phagocytosis of bacteria by human leukocytes measured by flow cytometry. Proc Soc Exp Biol Med. 1983 Nov;174(2):182–186. doi: 10.3181/00379727-174-41722. [DOI] [PubMed] [Google Scholar]
- Bassøe C. F., Solberg C. O. Phagocytosis of Staphylococcus aureus by human leukocytes: quantitation by a flow cytometric and a microbiological method. Acta Pathol Microbiol Immunol Scand C. 1984 Feb;92(1):43–50. doi: 10.1111/j.1699-0463.1984.tb00050.x. [DOI] [PubMed] [Google Scholar]
- Bjerknes R., Bassøe C. F. Human leukocyte phagocytosis of zymosan particles measured by flow cytometry. Acta Pathol Microbiol Immunol Scand C. 1983 Oct;91(5):341–348. [PubMed] [Google Scholar]
- Brody J. I., Pickering N. J., Fink G. B., Behr E. D. Altered lymphocyte subsets during cardiopulmonary bypass. Am J Clin Pathol. 1987 May;87(5):626–628. doi: 10.1093/ajcp/87.5.626. [DOI] [PubMed] [Google Scholar]
- Bruce D. L., Wingard D. W. Anesthesia and the immune response. Anesthesiology. 1971 Mar;34(3):271–282. doi: 10.1097/00000542-197103000-00017. [DOI] [PubMed] [Google Scholar]
- Böhmer R. H., Trinkle L. S., Staneck J. L. Dose effects of LPS on neutrophils in a whole blood flow cytometric assay of phagocytosis and oxidative burst. Cytometry. 1992;13(5):525–531. doi: 10.1002/cyto.990130512. [DOI] [PubMed] [Google Scholar]
- Chenoweth D. E., Cooper S. W., Hugli T. E., Stewart R. W., Blackstone E. H., Kirklin J. W. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med. 1981 Feb 26;304(9):497–503. doi: 10.1056/NEJM198102263040901. [DOI] [PubMed] [Google Scholar]
- Donovan A. J. The effect of surgery on reticuloendothelial function. Arch Surg. 1967 Feb;94(2):247–250. doi: 10.1001/archsurg.1967.01330080085022. [DOI] [PubMed] [Google Scholar]
- Dunn P. A., Tyrer H. W. Quantitation of neutrophil phagocytosis, using fluorescent latex beads. Correlation of microscopy and flow cytometry. J Lab Clin Med. 1981 Sep;98(3):374–381. [PubMed] [Google Scholar]
- Hairston P., Manos J. P., Graber C. D., Lee W. H., Jr Depression of immunologic surveillance by pump-oxygenation perfusion. J Surg Res. 1969 Oct;9(10):587–593. doi: 10.1016/0022-4804(69)90015-8. [DOI] [PubMed] [Google Scholar]
- Hammerschmidt D. E., Stroncek D. F., Bowers T. K., Lammi-Keefe C. J., Kurth D. M., Ozalins A., Nicoloff D. M., Lillehei R. C., Craddock P. R., Jacob H. S. Complement activation and neutropenia occurring during cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1981 Mar;81(3):370–377. [PubMed] [Google Scholar]
- Hansen B. G. The occurrence of Staphylococcus epidermidis in a department of thoracic and cardiovascular surgery. A clinical and epidemiological investigation. Scand J Thorac Cardiovasc Surg. 1982;16(3):269–274. doi: 10.3109/14017438209101061. [DOI] [PubMed] [Google Scholar]
- Hisatomi K., Isomura T., Kawara T., Yamashita M., Hirano A., Yoshida H., Eriguchi N., Kosuga K., Ohishi K. Changes in lymphocyte subsets, mitogen responsiveness, and interleukin-2 production after cardiac operations. J Thorac Cardiovasc Surg. 1989 Oct;98(4):580–591. [PubMed] [Google Scholar]
- Jay S. J. Nosocomial infections. Med Clin North Am. 1983 Nov;67(6):1251–1277. doi: 10.1016/s0025-7125(16)31152-x. [DOI] [PubMed] [Google Scholar]
- Kirklin J. K., Westaby S., Blackstone E. H., Kirklin J. W., Chenoweth D. E., Pacifico A. D. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1983 Dec;86(6):845–857. [PubMed] [Google Scholar]
- Labro M. T., Amit N., Babin-Chevaye C., Hakim J. Cefodizime (HR 221) potentiation of human neutrophil oxygen-independent bactericidal activity. J Antimicrob Chemother. 1987 Mar;19(3):331–341. doi: 10.1093/jac/19.3.331. [DOI] [PubMed] [Google Scholar]
- Labro M. T. Cefodizime as a biological response modifier: a review of its in-vivo, ex-vivo and in-vitro immunomodulatory properties. J Antimicrob Chemother. 1990 Nov;26 (Suppl 100):37–47. doi: 10.1093/jac/26.suppl_c.37. [DOI] [PubMed] [Google Scholar]
- Labro M. T. Immunomodulation by antibacterial agents. Is it clinically relevant? Drugs. 1993 Mar;45(3):319–328. doi: 10.2165/00003495-199345030-00001. [DOI] [PubMed] [Google Scholar]
- Markewitz A., Faist E., Niesel T., Lang S., Weinhold C., Reichart B. Changes in lymphocyte subsets and mitogen responsiveness following open-heart surgery and possible therapeutic approaches. Thorac Cardiovasc Surg. 1992 Feb;40(1):14–18. doi: 10.1055/s-2007-1020104. [DOI] [PubMed] [Google Scholar]
- Markewitz A., Faist E., Weinhold C., Lang S., Endres S., Hültner L., Reichart B. Alterations of cell-mediated immune response following cardiac surgery. Eur J Cardiothorac Surg. 1993;7(4):193–199. doi: 10.1016/1010-7940(93)90158-8. [DOI] [PubMed] [Google Scholar]
- Miholic J., Hudec M., Domanig E., Hiertz H., Klepetko W., Lackner F., Wolner E. Risk factors for severe bacterial infections after valve replacement and aortocoronary bypass operations: analysis of 246 cases by logistic regression. Ann Thorac Surg. 1985 Sep;40(3):224–228. doi: 10.1016/s0003-4975(10)60032-x. [DOI] [PubMed] [Google Scholar]
- Nguyen D. M., Mulder D. S., Shennib H. Effect of cardiopulmonary bypass on circulating lymphocyte function. Ann Thorac Surg. 1992 Apr;53(4):611–616. doi: 10.1016/0003-4975(92)90319-y. [DOI] [PubMed] [Google Scholar]
- Norenberg R. G., Sethi G. K., Scott S. M., Takaro T. Opportunistic endocarditis following open-heart surgery. Ann Thorac Surg. 1975 May;19(5):592–604. doi: 10.1016/s0003-4975(10)64440-2. [DOI] [PubMed] [Google Scholar]
- Pacheco Y., Hosni R., Dagrosa E. E., Gormand F., Guibert B., Chabannes B., Lagarde M., Perrin-Fayolle M. Antibiotics and production of granulocyte-macrophage colony-stimulating factor by human bronchial epithelial cells in vitro. A comparison of cefodizime and ceftriaxone. Arzneimittelforschung. 1994 Apr;44(4):559–563. [PubMed] [Google Scholar]
- Perticarari S., Presani G., Mangiarotti M. A., Banfi E. Simultaneous flow cytometric method to measure phagocytosis and oxidative products by neutrophils. Cytometry. 1991;12(7):687–693. doi: 10.1002/cyto.990120713. [DOI] [PubMed] [Google Scholar]
- Riddle P. R., Berenbaum M. C. Postoperative depression of the lymphocyte response to phytohaemagglutinin. Lancet. 1967 Apr 8;1(7493):746–748. doi: 10.1016/s0140-6736(67)91364-5. [DOI] [PubMed] [Google Scholar]
- Roilides E., Walsh T. J., Pizzo P. A., Rubin M. Granulocyte colony-stimulating factor enhances the phagocytic and bactericidal activity of normal and defective human neutrophils. J Infect Dis. 1991 Mar;163(3):579–583. doi: 10.1093/infdis/163.3.579. [DOI] [PubMed] [Google Scholar]
- Roth J. A., Golub S. H., Cukingnan R. A., Brazier J., Morton D. L. Cell-mediated immunity is depressed following cardiopulmonary bypass. Ann Thorac Surg. 1981 Apr;31(4):350–356. doi: 10.1016/s0003-4975(10)60965-4. [DOI] [PubMed] [Google Scholar]
- Slade M. S., Simmons R. L., Yunis E., Greenberg L. J. Immunodepression after major surgery in normal patients. Surgery. 1975 Sep;78(3):363–372. [PubMed] [Google Scholar]
- Szejda P., Parce J. W., Seeds M. S., Bass D. A. Flow cytometric quantitation of oxidative product formation by polymorphonuclear leukocytes during phagocytosis. J Immunol. 1984 Dec;133(6):3303–3307. [PubMed] [Google Scholar]
- Vanholder R., Dagrosa E. E., Van Landschoot N., Waterloos M. A., Ringoir S. M. Antibiotics and energy delivery to the phagocytosis-associated respiratory burst in chronic hemodialysis patients: a comparison of cefodizime and cotrimoxazole. Nephron. 1993;63(1):65–72. doi: 10.1159/000187145. [DOI] [PubMed] [Google Scholar]
- Wenisch C., Parschalk B., Hasenhündl M., Wiesinger E., Graninger W. Effect of cefodizime and ceftriaxone on phagocytic function in patients with severe infections. Antimicrob Agents Chemother. 1995 Mar;39(3):672–676. doi: 10.1128/AAC.39.3.672. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Young L. S. Nosocomial infections in the immunocompromised adult. Am J Med. 1981 Feb;70(2):398–404. doi: 10.1016/0002-9343(81)90779-8. [DOI] [PubMed] [Google Scholar]
- Zimmerman J. J., Millard J. R., Farrin-Rusk C. Septic plasma suppresses superoxide anion synthesis by normal homologous polymorphonuclear leukocytes. Crit Care Med. 1989 Dec;17(12):1241–1246. doi: 10.1097/00003246-198912000-00001. [DOI] [PubMed] [Google Scholar]
- van Velzen-Blad H., Dijkstra Y. J., Schurink G. A., Verbrugh H. A., Verhoef J., Zegers B. J., Ballieux R. E. Cardiopulmonary bypass and host defense functions in human beings: I. Serum levels and role of immunoglobulins and complement in phagocytosis. Ann Thorac Surg. 1985 Mar;39(3):207–211. doi: 10.1016/s0003-4975(10)62578-7. [DOI] [PubMed] [Google Scholar]
- van den Broek P. J. Antimicrobial drugs, microorganisms, and phagocytes. Rev Infect Dis. 1989 Mar-Apr;11(2):213–245. doi: 10.1093/clinids/11.2.213. [DOI] [PubMed] [Google Scholar]