Summary
Sepsis and peritonitis remain a serious challenge for surgical patients, despite improvement in surgical therapy and intensive care and the introduction of new powerful antibiotics. Recentin vitro studies revealed the potential of certain antibiotics, e.g. penicillin-binding protein (PBP) 3-specific antibiotics, to cause antibiotic-induced endotoxin release. Other types of antibiotics, e.g., PBP 2-specific antibiotics, were associated with no or less endotoxin release. Furtherin vitro experiments and investigations in animals support the hypothesis of antibiotic-induced endotoxin release, but there is little clinical evidence. The clinical significance of endotoxin is subject of open dispute with many pro's and contra's. Endotoxin, although and important trigger, may not be the only factor to induce cytokine release, e.g., peptidoglycans were able to stimulate cells to release cytokines. Gram-positive pathogens have gained more importance in clinical sepsis and may not be sufficiently reflected in current clinical studies. The hypothesis that neutralization of endotoxin and proinflammatory cytokines is beneficial in sepsis was seriously challenged by the results of recent clinical and experimental studies. The better understanding of mechanisms in endotoxin-induced cell activation and cell, cell-receptor and soluble receptor interactions led to new treatment options. Recent reports on the complex pathogenesis of peritonitis and the detection of pathogen-related factors with intraperitoneal immune response may have implications on clinical studies investigating the potential of new compounds and the effect of antibiotics on endotoxin release. However, only few reports are available on the clinical significance of antibiotic-induced endotoxin release, and association of endotoxin release with pathogens, mortality or alteration of physiological parameters were not observed. With regard to the particulars of these studies, e.g., a small study population or low mortality rate, mortality may not be an ideal outcome parameter for these studies. There is clinical evidence for antibiotic-induced endotoxin release. However, the need for well-designed and performed studies using newly developed monitoring devices in intensive care therapy is obvious.
Similar content being viewed by others
References
Stone, R.: Search for sepsis drugs goes on despite past failures. Science 264 (1994) 365–367.
Wittmann, D. H., Bansal, N., Bergstein, J. M., Wallance J. R., Wittmann, M. M., Aprahamian, C.: Staged abdominal repair compares favourably with conventional operative therapy for intraabdominal infections when adjusting for prognostic factors with a logistic model. Theor. Surg. 9 (1994) 201–207.
Wittmann, D. H., Schein, M., Condon, R. E.: Management of secondary peritonitis. Ann. Surg. 224 (1996) 10–18.
Kirschner, M.: Die Behandlung der akuten Bauchfellentzündung. Langenbecks. Arch. Klin. Chir. 142 (1926) 253–311.
Holzheimer, R. G., Cavaillon, J. M., Mosca, F., Haupt, W., Stefani, A., DiStefano, R., Torres, A., Capel, P., Aasen, A., Anderson, I., Schöffel, U.: Clinical and basic science aspects of immune pathogenesis of sepsis and peritonitis. Med. Microbiol. Letters 5 (1996) 386–393.
Michie, H. R., Wilmore, D. W.: Sepsis, signals and surgical sequelae (a hypothesis). Arch. Surg. 125 (1990) 531–536.
Holzheimer, R. G., Steinmetz, W. G., Ebentreich, U., Kauffmann, T., Jendrissek, A., Franke, S., Engermann, R., Thiede, A.: Aortic aneurysm repair may cause bacterial translocation with concominant endotoxin release into the systemic circulation and activation of the inflammatory cascade. J. Endotoxin Research 1 (1994) 31.
Jackson, J. J., Kropp, H.: Beta-lactam antibiotic induced release of endotoxin:in vitro comparison of penicillin-binding protein (PBP) 2-specific imipenem and PBP 3-specific ceftazidime. J. Infect. Dis. 165 (1992) 1033–1041.
Seelen, M. A., Athanassion, P., Lynn, W. A., Norsworth, P., Walport, M. J., Cohen, J., Davies, K. A.: The anti-lipid A monoclonal antibody E5 binds to rough gram-negative bacteria, fixes C3, and facilitates binding of bacterial immune complexes to both erythrocytes and monocytes. Immunology 84: (1995) 653–661.
Levy, O., Oos, E., Elsbach, P., Doerfler, M. E., Lehrer, R. I., Weiss, J.: Antibacterial proteins of granulocytes differ in interaction with endotoxin. Comparison of bactericidal/permeability increasing protein, p15s, and defensins. J. Immunol. 154 (1995) 5403–5410.
Crosby, H. A., Bion, J. F., Penn, C. W., Elliott, T. S.: Antibiotic-induced release of endotoxin from bacteriain vitro. J. Med Microbiol. 40 (1994) 23–30.
Bucklin, S. E., Fujihara, Y., Leeson, M. C., Morrison, D. C.: Differential antibiotic-induced endotoxin release from gram-negative bacteria. Eur. J. Clin. Microbiol. Infect. Dis. 13 (Suppl. 1) (1994) 43–51.
Foca, A., Matera, G., Berlinghieri, M. C.: Inhibition of endotoxin-induced interleukin 8 release by teicoplanin in human whole blood. Eur. J. Clin. Microbiol. Infect. Dis. 12 (1993) 940–944.
Burd, R. S., Battafarano, R. J., Cody, C. S., Farber, M. S., Ratz, C. A., Dunn, D. L.: Anti-endotoxin monoclonal antibodies inhibit secretion of tumor necrosis factor-alpha by two different mechanisms. Ann. Surg. 218 (3) (1993) 250–259.
Dofferhoff, A. S., Esselink, M. T., de Vries Hospers, H. G., van Zanten, A., Bom, V. J., Weits, J., Vellenga, E.: The release of endotoxin from antibiotic-treatedEscherichia coli and the production of tumor necrosis factor by human monocytes. J. Antimicrob. Chemother. 31 (1993) 373–384.
Eng, R. H., Smith, S. M., Fan Harvard, P., Ogbara, T.: Effect of antibiotics on endotoxin release from gram-negative bacteria. Diagn. Microbiol. Infect. Dis. 16 (3) (1993) 185–189.
Arditi, M., Kabat, W., Yogev, R.: Antibiotic-induced bacterial killing stimulates tumor necrosis factor-alpha release in whole blood. J. Infect. Dis. 167 (1993) 240–244.
Van den Berg, C., de Neeling, A. J., Schot, C. S., Hustinx, W. N., Wemer, J., de Wildt, D. J.: Delayed antibiotic-induced lysis ofEscherichia coli in vitro is correlated with enhancement of LPS release. Scand. J. Infect. Dis. 24 (1992) 619–627.
Bingen, E., Goury, V., Bennani, H., Lambert Zechovsky, N., Aujard, Y., Darbord, J. C.: Bactericidal activity of beta-lactams and amikacin againstHaemophilus influenzae: effect on endotoxin release. J. Antimicrob. Chemother. 30 (1992) 165–172.
Dofferhoff, A. S., Nijland, J. H., de Vries Hospers, H. G., Mulder, P. O., Weits, J., Bom, V. J.: Effects of different types and combinations of antimicrobial agents on endotoxin release from gram-negative bacteria: anin-vitro andin-vivo study. Scan. J. Infect. Dis. 23 (1991) 745–754.
Simon, D. M., Koenig, G., Trenholme, G. M.: Differences in release of tumour necrosis factor from THP-1 cells stimulated by filtrates of antibiotic-killedEscherichia coli. J. Infect. Dis. 164 (1991) 800–802.
Morrison, D. C., Bucklin, S. E., Leeson, M. C., Norimatsu, M.: Contribution of soluble endotoxin release from gram-negative bacteria by antibiotics to the pathogenesis of experimental sepsis in mice. J. Endotoxin Research 3 (1996) 237–243.
Bucklin, S. E., Morrison, D. C.: Differences in therapeutic efficacy among cell wall active antibiotics in a mouse model of gram-negative sepsis. J. Infect. Dis. 172 (1995) 1519–1527.
Opal, S. M., Horn, D. L., Palardy, J. E., Parejo, N., Jhung, J., Battacharjee, A., Young, L. D.: Thein vivo significance of antibiotic-induced endotoxin release in experimental gram-negative sepsis. J. Endotoxin Research 3 (1996) 245–252.
Cohen, J., McConnell, J. S.: Release of, endotoxin from bacteria exposed to ciprofloxacin and its prevention with polymyxin B. Eur. J. Clin. Microbiol. 5 (1986) 13–17.
Artenstein, A. W., Cross, A. S.: Inhibition of endotoxin reactivity by aminoglycosides. J. Antimicrob. Chemother. 24 (1989) 826–828.
Healy, D. P., Verst-Brasch, C. L., Clendening, C. E., Neely, A. N., Holder, I. A.: Influence of drug class and dose size on antibiotic induced endotoxin/IL-6 release and impact on efficacy of anti-endotoxin antibody. J. Endotoxin Research 3 (1996) 219–227.
Lamp, K. C., Rybak, M. J., McGrath, B. J., Summers, K. K.: Influence of antibiotic and E5 monoclonal immunoglobulin M interactions on endotoxin release fromEscherichia coli andPseudomonas aeruginosa. Antimicrob. Agents Chemother. 40 (1996) 247–252.
Morrison, D. C., Bucklin, S. E.: Evidence for antibiotic-mediated endotoxin release as a contributing factor to lethality in experimental gram-negative sepsis. Scand. J. Infect. Dis. Suppl. 101 (1996) 3–8.
Nitsche, D., Schulze, C., Oesser, S., Dalhoff, A., Sack, M.: Impact of different classes antimicrobial agents on plasma endotoxin activity. Arch. Surg. 131 (1996) 192–199.
Arditi, M., Zhou, J.: Differential antibiotic-induced endotoxin release and interleukin-6 production by human umbilical vein endothelial cells (HUVECs): amplification of the response by coincubation of HUVECs and blood cells. J. Infect. Dis. 175 (1997) 1255–1258.
Hurley, J. C.: Antibiotic-induced release of endotoxin: a reppraisal.Clin. Infect. Dis. 15 (1992) 840–854.
Casey, L. C., Balk, R. A., Bone, R. C.: Plasma cytokine, and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann. Intern. Med. 119 (1993) 771–778.
Bellomo, R.: The cytokine network in the critically ill. Anaesth. Intensive Care 20 (1992) 288–302.
Goris, R. J.: Mediators of multiple organ failure. Intensive Care Med. 16 (Suppl. 3) (1990) S192-S196.
van der Poll, T., Van Deventer, S. J., ten Cate, H., Levi, M., ten Cate, J. W.: Tumor necrosis factor is involved in the appearance of interleukin-1 receptor antagonist in endotoxemia. J. Infect. Dis. 169 (1994) 665–667.
Leeson, M. C., Fujihara, Y., Morrison, D. C.: Evidence for lipopolysaccharide as the predominant proinflammatory mediator in supernatants of antibiotic-treated bacteria. Infect. Immun. 62 (1994) 4975–4980.
Bone, R. C., Balk, R. A., Cerra, F. B., Dellinger, R. P., Fein, A. M., Knaus, W. A., Schein, R. M. H., Sibbald, W. J.: Definition for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 101 (1992) 1644–1655.
Wewers, M. D., Rinehart, J. J., She, Z. W., Herzyk, D. J., Hummel, M. M., Kinney, P. A., Davis, W. B.: Tumor necrosis factor infusions in humans prime neutrophils for hypochlorous acid production. Am. J. Physiol. 259 (1990) L276–282.
Cohen, J., Carlet, J. andthe Intersept Study Group: Intersept: an international multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-α in patients with sepsis. Crit. Care. Med. 24 (1996) 1431–1440.
Morrison, D. C.: Assessment of antibiotic-mediated endotoxin release. J. Endotoxin Research 3 (1996) 275–279.
Kelly, J. L., O'Sullivan, C., O'Riordain, M., O'Riordain, D., Lyons, A., Doherty, J., Mannick, J. A., Rodrick, M. L.: Is circulating endotoxin the trigger for the systemic inflammatory response syndrome seen after injury? Ann. Surg. 225 (1997) 530–541.
Willatts, S. M., Speller, D. C., Winter, R. J.: Incidence of gram-negative bacteremia in sepsis syndrome. Implications for immunotherapy. Anaesthesia 49 (1994) 751–754.
Schöffel, U., Jacobs, E., Ruf, G., Mierswa, F., von Specht, B. U., Farthmann, E. H.: Intraperitoneal microorganisms and the severity of peritonitis. Eur. J. Surg. 161 (1995) 501–508.
Berger, D., Schmidt, U. M., Ott, S., Seidelmann, M., Martin, R., Beger, H. G.: Incidence and pathophysiological relevance of postoperative endotoxemia. FEMS Immunol. Med. Microbiol. 11 (1995) 285–290.
Berger, D., Boelke, E., Seidelmann, M., Berger, H. G.: Evaluation of endotoxemia for diagnosis of urinary tract infection after major surgical procedures. Clin. Chim. Acta 244 (1996) 155–190.
Michie, H. R., Manogue, K. R., Spriggs, D. R.: Detection of circulating tumor necrosis factor after endotoxin administration. N. Engl. J. Med. 318 (1988) 1481–1486.
Rintala, E., Pulkki, K., Mertsola, J., Nevalainen, T., Nikoskelainen, J.: Endotoxin, interleukin-6 and phospholipase A2 as markers of sepsis with hematological maligancies. Scand. J. Infect. Dis. 27 (1995) 39–43.
Weidemann, B., Schletter, J., Dziarski, R., Kusumoto, S., Stelter, F., Rietschel, E. T., Flad, H. D., Ulmer, A. J.: Specific binding of soluble peptidoglycan and muramyldipeptide to CD14 on human monocytes. Infect. Immun. 65 (1997) 858–864.
Schromm, A. B., Brandenburg, K., Rietschel, E. T., Flad, H. D., Carroll, S. F., Seydel, U.: Lipopolysaccharide-binding protein mediates CD14-independent intercalation of lipopolysaccharide into phospholipid membranes. FEBS Lett. 399 (1996) 267–271.
Schletter, J., Brade, H., Brade, L., Kruger, C., Lopponow, H., Kusumoto, S., Rietschel, E. T., Flad, H. D., Ulmer, A. J.: Binding of lipopolysaccharide (LPS) to an 80-kilodalton membrane protein of human cells is mediated by soluble CD14 and LPS-binding protein. Infect. Immun. 63 (1995) 2576–2580.
Seydel, U., Brandenburg, K., Rietschel, E. T.: A case for an endotoxic conformation. Prog. Clin. Biol. Res. 388 (1994) 17–30.
Flad, H. D., Lopponow, H., Rietschel, E. T., Ulmer, A. J.: Agonists and antagonists for lipolysaccharide-induced cytokines. Immunobiology 187 (1993) 303–316.
Mattern, T., Thanhauser, A., Reilling, N., Toellner, K. M., Duchrow, M., Kusumoto, S., Rietschel, E. T., Ernst, M., Brade, H., Flad, H. D.: Endotoxin and lipid A stimulate proliferation of human T cells in the presence of autologous monocytes. J Immunol. 153 (1994) 2996–3004.
Bone, R. C., Balk, R. A., Fein, A. M., Perl, T. M., Wenzel, R. P., Reines, H. D., Quener, R. W., Iberti, T. J., Macintyre, N., Schein, R. M.: A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized controlled trial. The E5 sepsis study group. Crit. Care Med. 23 (1995) 994–1006.
Marra, M. N., Thornton, M. B., Snable, J. L., Wilde, C. G., Scott, R. W.: Endotoxin-binding and-neutralizing properties of recombinant bacteridal/permeability increasing protein and monoclonal antibodies HA-1A and E5. Crit. Care Med. 22 (1994) 559–565.
Christ, W. J., Asano, O., Robidoux, A. L., Perez, M., Wang, Y., Dubuc, G. R., Gavin, W. E., Hawkins, L. D., McGuiness, P. D., Mullarkey, M. A.: E5531, a pure endotoxin antagonist of high potency. Science 268 (1995) 80–83.
DiPadova, F. E., Brade, H., Barclay, G. R., Poxton, I. R., Liehl, E., Schuetze, E., Kocher, H. P., Ramsay, G., Schreier, M. H., McClelland, D. B.: Abroadly cross-protective monoclonal antibody binding toE. coli andSalmonella lipopolysaccharides. Infect. Immun. 61 (1993) 3863–3872.
Kuhn, H. M., Brade, L., Appelmelk, B. J., Kusumoto, S., Rietschel, E. T., Brade, H.: The antibody reactivity of monoclonal lipid A antibodies is influenced by the acylation pattern of lipid A and the assay system employed. Immunobiology 189 (1993) 457–471.
Goldie, A. S., Fearon, K. C., Ross, J. A., Barclay, G. R., Jackson, R. E., Grant, I. S., Ramsay, G., Blyth, A. S., Howie, J. C.: Natural cytokine antagonist and endogenous antiendotoxin core antibodies in sepsis syndrome. The Sepsis Intervention Group. JAMA 274 (1995) 172–177.
Bennett Guerrero, E., Ayuso, L., Hamilton Davis, C., White, W. D., Barclay, G. R., Smith, P. K., King, S. A., Muhlbaier, L. H., Newman, M. F., Mythen, M. G.: Relationship of preoperative antiendotoxin core antibodies and adverse outcomes following cardiac surgery. JAMA 277 (1997) 646–650.
Urbaschek, B., Ditter, B., Becker, K. P., Urbaschek, R. Protective effects and role of endotoxin in experimental septicemia. Circ. Shock 14 (2984) 209–222.
Urbaschek, R., Becker, K. P.: Endotoxinnachweis im Plasma: Spezifität und Aussagekraft für Entwicklung und Prognose einer Sepsis. Infusionsther. Transfusionsmed. 20 (Suppl. 1) (1993) 16–20.
Nishida, J., Ekataksin, W., McDonnell, D., Urbaschek, R., Urbaschek, B., McCuskey, R. S.: Ethanol exacerbates hepatic microvascular endotoxemia and lethality in septic mice. Schock 1 (1994) 413–418.
Prins, J. M., Kuijper, E. J., Mevissen, M. L. C. M., Speelman, P., van Deventer, S. J. H.: Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing ofEscherichia coli in whole blood: of antibiotic class, antibiotic concentration and presence of septic serum. Infect. Immun. 63 (1995) 2235–2242.
Patel, R. T., Deen, K. L., Youngs, D., Warwick, J., Keighley, M. R.: Interleukin 6 is a prognostic indicator of outcome in severe intraabdominal sepsis. Br. J. Surg. 81 (1994) 1306–1308.
de Bont, E. S., Martens, A., van Raan, J., Samson, G., Fetter, W. P., Okken, A., de Leij, L. H., Kimpen, J. L.: Diagnostic value of plasma levels of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in newborns with sepsis. Acta Paediatr. 83 (1994) 696–699.
Fugger, R., Zadrobilek, E., Gotzinger, P., Klimann, S., Rogy, M., Winkler, S., Andel, H., Mittelbrock, M., Roth, E., Schulz, F.: Perioperative TNF alpha and IL-6 concentrations correlate with septic state, organ function, and Apache II scores in intraabdominal infection. Eur. J. Surg. 159 (1993) 525–529.
Holzheiner, R. G., Schein, M., Wittmann, D. H.: Inflammatory response in peritoneal exudate and plasma of patients undergoing planned relaparotomy for severe, pertonitis. Arch. Surg. 130 (1995) 1314–1320.
Holzheimer, R. G., Cavaillon, J. M., Aasen, A. O., Cainzos, M., Schöffel, U.: Clinical routine determination as part of a European Research Network. Shock 7 (1997) 121.
Echtenacher, B., Falk, W., Männel, D. N., Krammer, P. H.: Requirements of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. J. Immunol. 145 (1990) 3762–3766.
Bagby, G. J., Plessala, K. J., Wilson, L. A., Thompson, J. J., Nelson, S.: Divergent efficacy of antibody to tumor necrosis factor alpha in intravascular and peritonitis models of sepsis. J. Infect. Dis. 163 (1991) 83–88.
Villa, P., Sartor, G., Angelini, M., Sironi, M., Conni, M., Gnocchi, P., Isetta, A. M., Grau, G., Buurman, W., van Tits, L. J.: Pattern of cytokines and pharmacomodulation in sepsis induced by cecal ligation and puncture compared with that induced by endotoxin. Clin. Diagn. Lab. Immunol. 2 (1995) 549–553.
Schein, M., Wittmann, D. H., Holzheimer, R., Condon, R. E.: Hypothesis: compartmentalization of cytokines in intraabdominal infection. Surgery 119 (1996) 694–700.
Holzheimer, R. G., Molloy, R., Mendez, M. V., O'Riordain, D., Curley, P., Nestor, M., Collins, K., Saporoschetz, I., Mannick, J. A., Rodrick, M. L.: Multiple system organ failure may be influenced by macrophage hypoactivation as well as hyperactivation—importance of the double challenge. Eur. J. Surg. 161 (1995) 795–803.
Hau, T., Ahrenholz, D. H., Simmons, R. L.: Secondary bacterial peritonitis: the biological basis of treatment. Curr. Probl. Surg. 16 (1979) 1.
Hau, T., Mozes, M. F., Jonasson, O.: Peritonitis nach Nierentransplantation. Langenbecks Arch. Chir. 353 (1981) 269.
Holzheimer, R. G., Quoika, P., Pätzmann, D., Füssle, R.: Nosocomial infections in general surgery: surveillance report from a German university clinic. Infection 18 (1990) 219–225.
Christou, N. V., Turgeon, P., Wassef, R., Rotstein, O., Bohnen, J., Potvin, M.: Management of intraabdominal infections. The case for intraoperative cultures and comprehensive broad-spectrum antibiotic coverage. The Canadian Intraabdominal Infection Study Group. Arch. Surg. 131 (1996) 1193–1201.
Cross, A., Asher, L., Seguin, M., Yuan, L., Kelly, N., Hammack, C., Sadoff, J., Gemski, P.: The importance of lipopolysaccharide-initiated, cytokine-mediated host defense mechanism in mice against extraintestinally invasiveEschierichia coli. J. Clin. Invest. 96 (1995) 676–686.
Prins, J. M., Kuijpers, E. J., Mevissen, M. L., Speelman, P., van Deventer, S. J.: Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing ofEscherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum. Infect. Immun. 63 (1995) 2236–2242.
Rosman, C., Westerveld, G. J., van Oeveren, W., Kooi, K., Bleichrodt, R. P.: Effect of intraperitoneal microbials on the concentration of bacteria, endotoxin, and tumor necrosis factor in abdominal fluid and plasma in rats. Eur. Surg. Res. 28 (1996) 351–360.
Hurley, J. C.: Antibiotic-induced release of endotoxin. A therapeutic paradox. Drug Saf. 12 (1995) 183–195.
Stone, H. H., Kolb, L. D., Geheber, C. E.: Incidence and significance of intraabdominal infections. Ann. Surg. 181 (1975) 705–715.
Lorber, H. H., Swenson, R. M.: The bacteriology of intraabdominal infection. Surg. Clin. North Am. 55 (1975) 1349–1354.
Rotstein, O.: Pentonitis and intraabdominal abscesses. In:Meakins, J. L. (ed.): Surgical infections—diagnosis and treatment. Scientific American Medicine Inc., New York 1994, pp. 329–351.
Prins, J. M., van Agtmael, M. A., Kuijper, E. J., van Deventer, S. J., Speelman, P.: Antibiotic-induced endotoxin releaase in patients with gram-negative urosepsis: a double-blind study comparing imipenem and ceftazidime. J. Infect. Dis. 172 (1995) 886–891.
Arditi, M., Ables, L., Yoger, R.: Cerebrospinal fluid endotoxin levels in children withH. influenzae meningitis before and after iv ceftriaxone. Infect. Dis. 160 (1990) 1005–1011.
Hurley, L. C., Louis, W. J., Tosolini, F. A., Carlin, J. B.: Antibiotic-induced release of endotoxin in chronically bacteriuric patients. Antimicrob. Agents Chemother. 35 (1991) 2388–2394.
Prins, J. M.: Antibiotic induced release of endotoxin—clinical data and human studies. J. Endotoxin Research 3 (1996) 269–273.
Mock, C. N., Jurkovich, G. J., Dries, D. J., Maier, R. V.: Clinical significance of antibiotic endotoxin releasing properties in trauma patients. Arch. Surg. 130 (1995) 1234–1240.
Holzheimer, R. G., Hirte, J. F., Reith, B., Engelhardt, W., Horak, K. H., Leppert, R., Aasen, A., Capel, P., Urbaschek, R., Karch, H., Thiede, A.: Different endotoxin release and IL-6 plasma levels after antibiotic administration in surgical intensive care patients. J. Endotoxin Research 3 (1996) 261–267.
Morrison, D. C.: Assessment of antibiotic mediated endotoxin release. J. Endotoxin Research 3 (1996) 173–178.
Brandenburg, K., Seydel, U., Schromm, A. B., Loppnow, H., Koch, M. H. J., Rietschel, E. T.: Conformation of lipid A, the endotoxic center of bacterial lipopolysaccharide. J. Endotoxin Research 3 (1996) 173–178.
Opal, S. M., Horn, J. E., Palardy, J. E., Parejo, N., Jhung, J., Battacharjee, A., Young, L. D.: Thein vivo significance of antibiotic-induced endotoxin release in experimental gram-negative sepsis. J. Endotoxin Research 3 (1996) 245–252.
Biffl, W. L., Moore, E. E., Moore, F. A., Peterson, V. M.: Interleukin 6 in the injured patient—marker of injury or mediator of inflammation? Ann. Surg. 224 (1996) 647–664.
Tang, G. J., Kuo, C. D., Yen, T. C., Kuo, H. S., Chan, K. H., Yien, H. W., Lee, T. Y.: Perioperative plasma concentrations of tumor necrosis factor-alpha and interleukin-6 in infected patients. Crit. Care Med. 24 (1996) 423–428.
Wittmann, D. H.: Immunological consequences of antibiotic therapy. In:Engemann, R., Holzheimer, R. G., Thiede, A. (eds): Immunology and its impact on infections in surgery. Springer Verlag, Heidelberg Berlin New York 1995, pp. 217–223.
Astiz, M. E., Rackow, E. C., Still, J. G., Howell, S. T., Cato, A., Von Eschen, K. B., Ulrich, J. T., Rudbach, J. A., McMahon, G., Vargas, R.: Pretreatment of normal humans with monophosphoryl lipid A induces tolerance to endotoxin: a prospective, double-blind, randomized, controlled trial. Crit. Care Med. 23 (1995) 9–17.
Bone, R. C., Balk, R. A., Fein, A. M., Perl, T. M., Wenzel, R. P., Reines, H. D., Quenzer, R. W., Iberti, T. J., MacIntyre, N., Schein, R. M.: A second large clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter randomized, controlled trial. The E5 Sepsis Study Group. Crit. Care Med. 23 (1995) 994–1006.
Greenman, R. L., Schein, R. M., Martin, M. A., Wenzel, R. P., MacIntyre, N. R., Emmanuel, G., Chmel, H., Kohler, R. B., McCarty, M., Plouffe, J.: A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group. JAMA 266 (1991) 1097–1102.
Rogy, M. A., Oldenburg, H. S. A., Coyle, S., Trousdale, R., Moldawer, L. L., Lowry, S. F.: Correlation between acute physiology and chronic health evaluation (Apache) III score and immunological parameters in critically ill patients with sepsis. Br. J. Surg. 83 (1996) 396–400.
Holzheimer, R. G., Haupt, W., Thiede, A., Schwarzkopf, A.: The challenge of postoperative infections: does the surgeon make a difference? Infect. Control Hosp. Epidemiol 18 (1997) 449–456.
Imhof, M., Bauer, M.: Time series analysis in critical care monitoring. New Horizons 4 (1996) 519–531.
Aasen, A. O., Soiberg, R., Sveen, O., Gallimore, M. J., Holzheimer, R. G.: Consequences of trauma on circulating cells and the plasma cascade systems. In:Risberg, B.: Trauma care—an update. Pharmacia & Upjohn, Stockholm, Sweden 1996, 118–128.
Hesselvik, J. F., Blombäck, M., Brodin, B., Maller, R.: Coagulation. fibrinolysis, and kallikrein systems in sepsis: relation to outcome. Crit. Care Med. 17 (1989) 724–733.
Aasen, A. O.: The proenzyme functional inhibition index. A new parameter for the evaluation of severely injured and septic patients. Acta Chir. Scand. Suppl. 522 (1985) 211–233.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Holzheimer, R.G. The significance of endotoxin release in experimental and clinical sepsis in surgical patients — Evidence for antibiotic-induced endotoxin release?. Infection 26, 77–84 (1998). https://doi.org/10.1007/BF02767765
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02767765