Enhancement of leukocyte activity against Escherichia coli after brief exposure to chloramphenicol

Abstract

The effect of brief exposure of Escherichia coli to chloramphenicol on the antibacterial activity of normal human leukocytes was studied by following changes in viability of the bacteria in the presence of leukocytes and serum. Growth was suppressed, and the extent of suppression was directly related to the period of exposure and the concentration of chloramphenicol. When exposed to clinically achievable levels of the drug for 10 min, E. coli failed to resume normal growth for 1 to 4 h in the presence of leukocytes and serum after removal of the drug. The post-antibiotic leukocyte enhancement effect required the presence of antibody and complement. This effect demonstrates the importance of early events in the encounter between antibiotic and microorganism in determining the subsequent activity of host defense components.

Intermittent or Continuous Therapy of Experimental Meningitis Due to Streptococcus pneumoniae in Rabbits: Preliminary Observations on the Postantibiotic Effect in Vivo

“…The persistent effect of antibiotics on bacteria has been demonstrated in vitro for a number of different species: S. aureus [11][12][13], S. pneumoniae, Streptococcus [29], and E. coli [12]. The results are qualitatively similar for each of these organisms.…”

“…The results are qualitatively similar for each of these organisms. A postantibiotic effect was observed with several antibiotics including penicillins, cephalosporins, macrolides, chloramphenicol, and vancomycin [11,12]. However, the duration of the effect varies (generally 1.5 to 5 hr after a 2-hr exposure) and is not demonstrable for some agents (e.g., gentamicin).…”

“…Eagle et al [1,2,8] eradicated experi-mental streptococcal infections, despite antibiotic levels in tissue below the MIC during each treatment interval; they ascribed this result to a persistent effect of the drug on the organism, a phenomenon described by Parker et al more than 30 years ago [9,10]. The postantibiotic effect has been clarified further by in vitro studies [11,12], in which short-term exposure of Staphylococcus aureus or Escherichia coli to various antibiotics at or above the MIC produced a continued postantibiotic effect (decreased or stable bacterial counts) for various periods of time after removal of the antibiotic. Even subinhibitory levels of antibiotics can alter the growth rate and morphology of bacteria [13] and may modify important host defense mechanisms [14,15].…”

“…The duration of the initial decline in bacterial titer was variable (1)(2)(3)(4)(5)(6) hr) and did not correlate with peak concentrations of ampicillin in CSF. The second, static phase also varied so that the total duration of the postantibiotic effect was [6][7][8][9][10][11][12] hr. Two of three animals that received the highest dose of ampicillin (62.5 mg/kg) had sterile CSF after 4-6 hr and were presumed "cured".…”

“…Even subinhibitory levels of antibiotics can alter the growth rate and morphology of bacteria [13] and may modify important host defense mechanisms [14,15]. Previous exposure of E. coli to sub-MIC levels of chloramphenicol resulted in a prolonged decline in bacterial concentrations after exposure of the culture to leukocytes, antibody, and complement in vitro [12]. Thus, in vivo, contact of the organism with subtherapeutic concentrations of drug may potentiate host defenses and playa role in outcome of therapy.…”