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Clinical Significance of Antibiotic Endotoxin-Releasing Properties in Trauma Patients

Clinical Significance of Antibiotic Endotoxin-Releasing Properties in Trauma Patients Abstract Objective: To test the hypothesis that antibiotics leading to greater endotoxin release are associated with greater mortality in septic trauma patients. Design: Post hoc analysis of data from a previously conducted prospective, randomized, multicenter study designed to evaluate the efficacy of interferon gamma in preventing infection and death in trauma patients. Setting: Nine level I trauma centers. Patients: Severely injured trauma patients at high risk for sepsis. Eighty percent (N=334) of the enrolled patients developed some manifestation of gram-negative sepsis, defined by the administration of gram-negative specific antibiotics. Main Outcome Measures: The in-hospital mortality rate of patients who received penicillin-binding protein 3/tumor necrosis factor (PBP3/TNF)–specific antibiotics associated with the greatest degree of endotoxin release and TNF production (PBP3/TNF group, n=78: aztreonam. ceftazidime, and cefotaxime sodium) was compared with that of patients not receiving these agents (non-PBP3/TNF group, n=256). Results: Mortality in the PBP3/TNF group (17%) was higher than in the non-PBP3/TNF group (8%, P=.02). The two groups were similar in their mean (±SD) Injury Severity Scores (34±9), ages (31 ± 12 years), and initial degree of bacterial contamination. Conclusions: Antibiotics that are associated with greater release of endotoxin and production of TNF are also associated with greater mortality in septic trauma patients. Decisions regarding antibiotic administration may need to consider the endotoxin-releasing properties of antibiotics in addition to their antibacterial sensitivity spectrum. Prospective studies of the effect of endotoxin-releasing properties of antibiotics on mortality are warranted.(Arch Surg. 1995;130:1234-1241) References 1. Dofferhoff ASM, Nijland JH, deVries-Hospers HG, et al. Effects of different types and combinations of antimicrobial agents on endotoxin release from gram-negative bacteria: an in-vitro and in-vivo study . Scand J Infect Dis . 1991;23: 745-754.Crossref 2. Eng RHK, Smith SM, Fan-Havard P, et al. Effect of antibiotics on endotoxin release from gram-negative bacteria . Diagn Microbiol Infect Dis . 1993;16:185-189.Crossref 3. Jackson JJ, Kropp H. β-lactam antibiotic-induced release of free endotoxin: in vitro comparison of penicillin-binding protein (PBP) 2-specific imipenem and PBP 3-specific ceftazidime . J Infect Dis . 1992;165:1033-1041.Crossref 4. Friedland IR, Jafari H, Ehret S, et al. Comparison of endotoxin release by different antimicrobial agents and the effect on inflammation in experimental Escherichia coli meningitis . J Infect Dis . 1993:168:657-662.Crossref 5. Shenep JL, Barton RP, Morgan KA. Role of antibiotic class in the rate of liberation of endotoxin during therapy for experimental gram-negative bacterial sepsis . J Infect Dis . 1985:151:1012-1018.Crossref 6. Hurley JC. Antibiotic-induced release of endotoxin: a reappraisal . Clin Infect Dis . 1992:15:840-854.Crossref 7. Prins JM, van Deventer SJH, Kuijper EJ, et al. Clinical relevance of antibiotic-induced endotoxin release . Antimicrob Agents Chemother . 1994;38:1211-1218.Crossref 8. Neu HC. Relation of structural properties of beta-lactam antibiotics to antibacterial activity . Am J Med . 1985;79( (suppl 2A) ):2-13.Crossref 9. Tuomanen E, Gilbert K, Tomasz A. Modulation of bacteriolysis by cooperative effects of penicillin-binding proteins 1a and 3 in Escherichia coli . Antimicrob Agents Chemother . 1986:30:659-663.Crossref 10. Arditi M, Ables L, Yogev R. Cerebrospinal fluid endotoxin levels in children with H influenzae meningitis before and after administration of intravenous ceftriaxone . J Infect Dis . 1989;160:1005-1011.Crossref 11. Brandtzaeg P, Kierulf P, Gaustad P, et al. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease . J Infect Dis . 1989;159:195-204.Crossref 12. Hurley JC, Louis WJ, Tosolini FA, et al. Antibiotic-induced release of endotoxin in chronically bacteriuric patients . Antimicrob Agents Chemother . 1991; 35:2388-2394.Crossref 13. Shenep JL, Flynn PM, Barret FF, et al. Serial quantitaion of endotoxemia and bacteremia during therapy for gram-negative bacterial sepsis . J Infect Dis . 1988; 157:565-568.Crossref 14. Dries DJ, Jurkovich GJ, Maier RV, et al. Effect of interferon gamma on infection-related death in patients with severe injuries: a randomized, double-blind, placebo-controlled trial . Arch Surg . 1994;129:1031-1041.Crossref 15. Simon DM, Koenig G, Trenholme GM. Differences in release of tumor necrosis factor from THP-1 cells stimulated by filtrates of antibiotic-killed Escherichia coli . J Infect Dis . 1991;164:800-802.Crossref 16. Altman DG. Practical Statistics for Medical Research . London, England: Chapman & Hall; 1991. 17. Breslow NE, Day NE. Statistical Methods in Cancer Research . Lyon, France: International Agency for Research on Cancer; 1980;1. 18. Jarisch A. Therapeutische Veruche bei Syphilis . Wien Med Wochenschr . 1895; 45:721-724. 19. Gelfand JA, Elin RJ, Berry FW, et al. Endotoxemia associated with the Jarisch-Herxheimer . N Engl J Med . 1976;295:211-213.Crossref 20. Patel JC, Banker DD, Modi CJ. Chloramphenicol in typhoid fever . BMJ . 1949; 2:908-909.Crossref 21. Hopkin DAB. Frapper fort ou frapper doucement: a gram-negative dilemma . Lancet . 1978;2:1193-1194. 22. Georgopapadakou NH. Penicillin-binding proteins and bacterial resistance to β-lactams . Antimicrob Agents Chemother . 1993;37:2045-2053.Crossref 23. Vanden Berg CA, DeNeeling AJ, Schot CS, et al. Delayed antibiotic-induced lysis of Escherichia coli in vitro is correlated with enhancement of LPS release . Scand J Infect Dis . 1992;24:619-627.Crossref 24. Mellado MC, Rodriguez-Contreras A, Mariscal A, et al. Effect of penicillin and chloramphenicol on the growth and endotoxin release by N meningitidis . Epidemiol Infect . 1991;106:283-288.Crossref 25. Arditi M, Kabat W, Yogev R. Antibiotic-induced bacterial killing stimulates tumor necrosis factor-alpha release in whole blood . J Infect Dis . 1993;167:240-244.Crossref 26. Sawyer RG, Adams RB, May AK, et al. Anti-tumor necrosis factor antibody reduces mortality in the presence of antibiotic-induced tumor necrosis factor release . Arch Surg . 1993;128:73-78.Crossref 27. Engebretsen LF, Kierulf P, Brandtzaeg P. Extreme plasminogen activator inhibitor and endotoxin values in patients with meningococcal disease . Thromb Res . 1986;42:713-716.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Clinical Significance of Antibiotic Endotoxin-Releasing Properties in Trauma Patients

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Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1995.01430110092017
Publisher site
See Article on Publisher Site

Abstract

Abstract Objective: To test the hypothesis that antibiotics leading to greater endotoxin release are associated with greater mortality in septic trauma patients. Design: Post hoc analysis of data from a previously conducted prospective, randomized, multicenter study designed to evaluate the efficacy of interferon gamma in preventing infection and death in trauma patients. Setting: Nine level I trauma centers. Patients: Severely injured trauma patients at high risk for sepsis. Eighty percent (N=334) of the enrolled patients developed some manifestation of gram-negative sepsis, defined by the administration of gram-negative specific antibiotics. Main Outcome Measures: The in-hospital mortality rate of patients who received penicillin-binding protein 3/tumor necrosis factor (PBP3/TNF)–specific antibiotics associated with the greatest degree of endotoxin release and TNF production (PBP3/TNF group, n=78: aztreonam. ceftazidime, and cefotaxime sodium) was compared with that of patients not receiving these agents (non-PBP3/TNF group, n=256). Results: Mortality in the PBP3/TNF group (17%) was higher than in the non-PBP3/TNF group (8%, P=.02). The two groups were similar in their mean (±SD) Injury Severity Scores (34±9), ages (31 ± 12 years), and initial degree of bacterial contamination. Conclusions: Antibiotics that are associated with greater release of endotoxin and production of TNF are also associated with greater mortality in septic trauma patients. Decisions regarding antibiotic administration may need to consider the endotoxin-releasing properties of antibiotics in addition to their antibacterial sensitivity spectrum. Prospective studies of the effect of endotoxin-releasing properties of antibiotics on mortality are warranted.(Arch Surg. 1995;130:1234-1241) References 1. Dofferhoff ASM, Nijland JH, deVries-Hospers HG, et al. Effects of different types and combinations of antimicrobial agents on endotoxin release from gram-negative bacteria: an in-vitro and in-vivo study . Scand J Infect Dis . 1991;23: 745-754.Crossref 2. Eng RHK, Smith SM, Fan-Havard P, et al. Effect of antibiotics on endotoxin release from gram-negative bacteria . Diagn Microbiol Infect Dis . 1993;16:185-189.Crossref 3. Jackson JJ, Kropp H. β-lactam antibiotic-induced release of free endotoxin: in vitro comparison of penicillin-binding protein (PBP) 2-specific imipenem and PBP 3-specific ceftazidime . J Infect Dis . 1992;165:1033-1041.Crossref 4. Friedland IR, Jafari H, Ehret S, et al. Comparison of endotoxin release by different antimicrobial agents and the effect on inflammation in experimental Escherichia coli meningitis . J Infect Dis . 1993:168:657-662.Crossref 5. Shenep JL, Barton RP, Morgan KA. Role of antibiotic class in the rate of liberation of endotoxin during therapy for experimental gram-negative bacterial sepsis . J Infect Dis . 1985:151:1012-1018.Crossref 6. Hurley JC. Antibiotic-induced release of endotoxin: a reappraisal . Clin Infect Dis . 1992:15:840-854.Crossref 7. Prins JM, van Deventer SJH, Kuijper EJ, et al. Clinical relevance of antibiotic-induced endotoxin release . Antimicrob Agents Chemother . 1994;38:1211-1218.Crossref 8. Neu HC. Relation of structural properties of beta-lactam antibiotics to antibacterial activity . Am J Med . 1985;79( (suppl 2A) ):2-13.Crossref 9. Tuomanen E, Gilbert K, Tomasz A. Modulation of bacteriolysis by cooperative effects of penicillin-binding proteins 1a and 3 in Escherichia coli . Antimicrob Agents Chemother . 1986:30:659-663.Crossref 10. Arditi M, Ables L, Yogev R. Cerebrospinal fluid endotoxin levels in children with H influenzae meningitis before and after administration of intravenous ceftriaxone . J Infect Dis . 1989;160:1005-1011.Crossref 11. Brandtzaeg P, Kierulf P, Gaustad P, et al. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease . J Infect Dis . 1989;159:195-204.Crossref 12. Hurley JC, Louis WJ, Tosolini FA, et al. Antibiotic-induced release of endotoxin in chronically bacteriuric patients . Antimicrob Agents Chemother . 1991; 35:2388-2394.Crossref 13. Shenep JL, Flynn PM, Barret FF, et al. Serial quantitaion of endotoxemia and bacteremia during therapy for gram-negative bacterial sepsis . J Infect Dis . 1988; 157:565-568.Crossref 14. Dries DJ, Jurkovich GJ, Maier RV, et al. Effect of interferon gamma on infection-related death in patients with severe injuries: a randomized, double-blind, placebo-controlled trial . Arch Surg . 1994;129:1031-1041.Crossref 15. Simon DM, Koenig G, Trenholme GM. Differences in release of tumor necrosis factor from THP-1 cells stimulated by filtrates of antibiotic-killed Escherichia coli . J Infect Dis . 1991;164:800-802.Crossref 16. Altman DG. Practical Statistics for Medical Research . London, England: Chapman & Hall; 1991. 17. Breslow NE, Day NE. Statistical Methods in Cancer Research . Lyon, France: International Agency for Research on Cancer; 1980;1. 18. Jarisch A. Therapeutische Veruche bei Syphilis . Wien Med Wochenschr . 1895; 45:721-724. 19. Gelfand JA, Elin RJ, Berry FW, et al. Endotoxemia associated with the Jarisch-Herxheimer . N Engl J Med . 1976;295:211-213.Crossref 20. Patel JC, Banker DD, Modi CJ. Chloramphenicol in typhoid fever . BMJ . 1949; 2:908-909.Crossref 21. Hopkin DAB. Frapper fort ou frapper doucement: a gram-negative dilemma . Lancet . 1978;2:1193-1194. 22. Georgopapadakou NH. Penicillin-binding proteins and bacterial resistance to β-lactams . Antimicrob Agents Chemother . 1993;37:2045-2053.Crossref 23. Vanden Berg CA, DeNeeling AJ, Schot CS, et al. Delayed antibiotic-induced lysis of Escherichia coli in vitro is correlated with enhancement of LPS release . Scand J Infect Dis . 1992;24:619-627.Crossref 24. Mellado MC, Rodriguez-Contreras A, Mariscal A, et al. Effect of penicillin and chloramphenicol on the growth and endotoxin release by N meningitidis . Epidemiol Infect . 1991;106:283-288.Crossref 25. Arditi M, Kabat W, Yogev R. Antibiotic-induced bacterial killing stimulates tumor necrosis factor-alpha release in whole blood . J Infect Dis . 1993;167:240-244.Crossref 26. Sawyer RG, Adams RB, May AK, et al. Anti-tumor necrosis factor antibody reduces mortality in the presence of antibiotic-induced tumor necrosis factor release . Arch Surg . 1993;128:73-78.Crossref 27. Engebretsen LF, Kierulf P, Brandtzaeg P. Extreme plasminogen activator inhibitor and endotoxin values in patients with meningococcal disease . Thromb Res . 1986;42:713-716.Crossref

Journal

Archives of SurgeryAmerican Medical Association

Published: Nov 1, 1995

References