IN-VIVO TNF INDUCTION BY CULTURE SUPERNATANTS OF ANTIBIOTIC-TREATED ESCHERICHIA-COLI 07-K1 - ROLE OF ANTIBIOTIC CLASS AND CONCENTRATION

Antibiotics may cause an excess release of lipopolysaccharide (LPS) fr om bacteria and thereby promote the production of tumour necrosis fact or (TNF). TNF was measured in the serum of Swiss mice challenged with filtered supernatant of Escherichia coli O7:K1 that had been exposed t o various antibiotics in vitro. Expressed as a function of a standardi zed number of cells remaining after 6 h of exposure to gentamicin, cef tazidime, ciprofloxacin or imipenem, TNF levels associated with antibi otic exposure always exceeded those of controls. However, if differenc es in the remaining number of bacteria were not taken into account, TN F induction by supernatant of control untreated cultures was greater t han that elicited by supernatant from any of the antibiotic-treated cu ltures. With the exception of imipenem, low-dose antibiotic exposure ( 0.5 x MIC) invariably induced higher TNF levels than did high-dose exp osure (10 x MIC), Considerable antibiotic class- and concentration-rel ated differences were noted, LAL equivalent amounts of LPS released by different antibiotics may diverge in their capacity to induce TNF. Ou r results do not support the notion that the use of rapidly bactericid al and lytic antibiotics should be avoided.