Antibiotic-Induced Release of Endotoxin A therapeutic Paradox

Abstract

There is clear experimental evidence that antibiotics increase the bioavailability of endotoxin from Gram-negative bacteria. In this review, data for 2 variables, level of endotoxin and level of bacteria, at the time point closest to 2 hours post-antibiotic exposure were abstracted as a change from baseline readings from each available study, to enable presentation in a graphical overview. This overview indicates that the phenomenon is not limited to beta-lactam agents nor is it apparent only for the more rapidly bactericidal agents. However, evidence that this phenomenon is of clinical importance is scant. With the Jarisch-Herxheimer reaction (JHR), there is clear evidence for an acute deterioration with the initiation of antibiotic therapy and yet uncertainty as to the nature of the bacterial mediator(s) of this reaction. There is no evidence to support the commonly stated concern that therapy with antibiotics with a more rapid bactericidal action may result in the sudden lysis of bacteria with the release of cell wall components and cause a deterioration that might be avoidable through the use of antibiotics with a slower time course of action.

Effects of cytokine-suppressive anti-inflammatory drugs on inflammatory activation in ex vivo human and ovine fetal membranes

“…The reasons for this are several fold and include issues related to participant selection and antibiotic efficacy, tissue biodistribution and microbial resistance (Keelan 2011). In addition, bactericidal antibiotics cause bacterial lysis and release of endotoxins, further activating the innate immune system and promoting the release of prostaglandins that may actually stimulate the onset of labour (Dofferhoff et al 1991, Hurley 1995, Holzheimer 2001). …”

Immunostimulation in the era of the metagenome

“…[137][138][139][140][141] Yet symptom exacerbation resulting from an immunostimulative approach towards pathogens is paradoxical only because it defies previously held intuition.…”

Is Histone a Solitary Vile Sepsis-Inducing Agent or Just "a Member of the Gang"?

“…These agents are expected to be delivered at the inflammatory sites in addition to the PAMPs derived from the bacteria themselves following bacteriolysis (such as lipoteichoic acid [LTA] and peptidoglycan [PPG]) [16,17]. Thus, these mediators (immune derived and bacteria derived) always appear together in the context of sepsis, all of them capable of causing cell injury [18][19][20]. Therefore, the claim that histones are unique, toxic alarmins causing septic shock is questionable [2,3].…”

“…These may be anti-oxidants, proteinase, elastase and PLA2 inhibitors, and anticytokines and perhaps even IV-IgG. Also, since microbial agents undergoing bacteriolysis release a variety of PAMPs [16][17][18][19][20], it could also be considered that the antibiotics used for septic patients should perhaps be bacteriostatic but not bactericidal, thus avoiding a JarischHerxheimer-like phenomenon [25].…”