Clindamycin suppresses endotoxin released by ceftazidime-treated Escherichia coli O55:B5 and subsequent production of tumor necrosis factor alpha and interleukin-1 beta.
Treatment of septicemia caused by Escherichia coli with ceftazidime (CAZ) may be associated with the development of septic shock due to the release of bacterial lipopolysaccharide. We examined the suppressive effect of clindamycin (CLDM) on CAZ-induced release of endotoxin by cultured E. coli and the subsequent production of inflammatory cytokines (tumor necrosis factor alpha [TNF-alpha] and interleukin-1 beta [IL-1 beta]). E. coli ATCC 12014 was incubated in inactivated horse serum with or without CLDM for 1, 4, or 18 h, followed by the addition of CAZ and collection of the culture supernatant at 0, 1, and 2 h. The concentration of endotoxin in each sample was measured by a chromogenic Limulus test. Another portion of the culture supernatant was added to THP-1 cell culture and incubated for 4 h, and the concentrations of TNF-alpha and IL-1 beta in the supernatant were measured by an enzyme-linked immunosorbent assay. In the control group (no CLDM), CAZ administration resulted in significant increases in endotoxin, TNF-alpha, and IL-1 beta concentrations. Pretreatment of E. coli with CLDM for 4 or 18 h before the addition of CAZ significantly suppressed the concentrations of endotoxin, TNF-alpha, and IL-1 beta in a time-dependent manner. In addition, CAZ treatment transformed E. coli from rodshaped bacteria to filament-like structures, as determined by electron microscopy, while pretreatment with CLDM prevented these morphological changes. Our in vitro studies showed that CAZ-induced release of large quantities of endotoxin by E. coli could be suppressed by prior administration of CLDM.
Second Department of Internal Medicine, Oita Medical University, Japan.
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Kishi
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Hirai
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Hiramatsu
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Yamasaki
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Nasu
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D002648:Child; D002981:Clindamycin / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002981:Clindamycin; C044101:endotoxin, Escherichia coli; D002442:Ceftazidime