In vitro and animal studies, but also clinical data, indicate that treatment with antibiotics may cause systemic or local endotoxin liberation. In several studies this so-called 'endotoxin release' was accompanied by a deterioration of parameters of illness. In addition, in vitro studies have clearly demonstrated that equally effective antibiotics can differ in the amount of endotoxin they release. These differences between antibiotics can be related to different modes of anti-bacterial activities. In a number of animal studies these differences in endotoxin-releasing potential resulted in differences in morbidity and/or mortality. In only one study, antibiotics were compared in this respect in septic patients. The results of that study suggested that differences between antibiotics in endotoxin release may indeed affect the inflammatory response during treatment.
Get full access to this article
View all access options for this article.
References
1.
Patel J.C., Banker D.D., Modi C.J.Chloramphenicol in typhoid fever. A preliminary report of clinical trial in 6 cases. BMJ1949; ii: 908-909.
2.
Buxton Hopkin D.A.Frapper fort ou frapper doucement: a Gram-negative dilemma. Lancet1978; ii: 1193-1194.
3.
Prins J.M., van Deventer S.J.H., Kuijper E.J., Speelman P.Clinical relevance of antibiotic-induced endotoxin release. Antimicrob Agents Chemother1994; 38: 1211-1218.
4.
Shenep J.L., Flynn P.M., Barrett F.F., Stidham G.L., Westenkirchner D.F.Serial quantitation of endotoxemia and bacteremia during therapy for Gram-negative bacterial sepsis. J Infect Dis1988; 157: 565-568.
5.
Dofferhoff A.S.M. , Nijland J.H., de Vries-Hospers H.G., Mulder P.O.M., Weits J., Bom V.J.J.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 Dis1991; 23: 745-754.
6.
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 Dis1989; 159: 195-204.
7.
Mustafa M.M., Mertsola J., Ramilo O., Sáez-Llorens X., Risser R.C., McCracken Jr G.H.Increased endotoxin and interleukin-1β concentrations in cerebrospinal fluid of infants with coliform meningitis and ventriculitis associated with intraventricular gentamicin therapy. J Infect Dis1989; 160: 891-895.
8.
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 Dis1989; 160:1005-1011.
9.
Hurley J.C., Louis W.J., Tosolini F.A., Carlin J.B.Antibiotic-induced release of endotoxin in chronically bacteriuric patients . Antimicrob Agents Chemother1991; 35: 2388-2394.
10.
Eng R.H.K., Smith S.M., Fan-Havard P., Ogbara T.Effect of antibiotics on endotoxin release from Gram-negative bacteria. Diagn Microbiol Infect Dis1993: 16: 185-189.
11.
Lamp K.C., Rybak M.J., McGrath B.J., Summers K.K.Influence of antibiotic and E5 monoclonal immunoglobulin M interactions on endotoxin release from Escherichia coli and Pseudomonas aeruginosa. Antimicrob Agents Chemother1996; 40: 247-252.
12.
Shenep J.L. , Barton R.P., Mogan K.A.Role of antibiotic class in the rate of liberation of endotoxin during therapy for experimental gram-negative bacterial sepsis. J Infect Dis1985; 151: 1012-1018.
13.
Friedland I.R. , Jafari H., Ehrett S. et al. Comparison of endotoxin release by different antimicrobial agents and the effect on inflammation in experimental Escherichia coli meningitis. J Infect Dis1993; 168: 657-662.
14.
Täuber M.G. , Shibl A.M., Hackbarth C.J., Larrick J.W., Sande M.A.Antibiotic therapy, endotoxin concentration in cerebrospinal fluid, and brain edema in experimental Escherichia coli meningitis in rabbits. J Infect Dis1987; 156: 456-462.
15.
Mohler J., Fantin B., Mainardi J.L., Carbon C.Influence of antimicrobial therapy on kinetics of tumor necrosis factor levels in experimental endocarditis caused by Klebsiella pneumoniae. Antimicrob Agents Chemother1994; 38: 1017-1022.
16.
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 Dis1995; 172: 1519-1527.
17.
Prins J.M., van Agtmael M.A., Kuijper E.J., van Deventer S.J.H., Speelman P.Antibiotic-induced endotoxin release in patients with gram-negative urosepsis: a double-blind study comparing imipenem and ceftazidime. J Infect Dis1995; 172: 886-891.
18.
Neu H.C.Relation of structural properties of beta-lactam antibiotics to antibacterial activity. Am J Med1985; 79 (Suppl. 2A): 2-13.
19.
Kucers A., Bennett N.McK. The Use of Antibiotics. 4th edn. London: Heinemann, 1987; 525-542.
20.
Bruin K.F., von der Möhlen M.A.M., Derkx B.H.F., Jansen J., ten Cate J.W., van Deventer S.J.H.Characterization of the endotoxin-induced TNF release in whole blood and peripheral blood mononuclear cells. In: Bruin K.F., Endotoxin Responsiveness in Humans. PhD thesis, University of Amsterdam, 1994; 31-42.
21.
Munoz C., Carlet J., Fitting C., Misset B., Bleriot J.P., Cavaillon J.M.Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest1991; 88: 1747-1754.
22.
Mengozzi M. , Ghezzi P.Cytokine down-regulation in endotoxin tolerance . Eur Cytokine Netw1993; 4:89-98.
