INFLUENCE OF ANTIBIOTIC AND E5 MONOCLONAL IMMUNOGLOBULIN-M INTERACTIONS ON ENDOTOXIN RELEASE FROM ESCHERICHIA-COLI AND PSEUDOMONAS-AERUGINOSA

Recent controversy surrounding the activity of monoclonal antibodies a gainst endotoxin highlights the necessity of identifying all factors a ssociated with increased mortality, one of which is endotoxin concentr ations. Antibiotics may induce different patterns of endotoxin release , We compared the release of free endotoxin (in endotoxin units per mi lliliter) over 6 h and changes in numbers of CFU of exponentially grow ing Escherichia coli and Pseudomonas aeruginosa (10(6) to 10(7) CFU/ml ) cultured in chemically defined endotoxin-free. broth combined with p ooled human serum and/or 10 mu g of E5 immunoglobulin M monoclonal ant ibody per ml. MICs and MBCs were tested in each medium at the same ino culum, The inoculum was exposed to antibiotics at a single fixed multi ple of the MIC for each medium (range, two to eight times the MIG), E5 antibody had no effect an MICs, MBCs, bactericidal activity, or endot oxin release, In the presence of 50% serum, amikacin, ceftazidime, imi penem, and ofloxacin each killed equivalent amounts off, coli over 6 h ; however, ceftazidime induced the highest release of endotoxin, Amika cin and ofloxacin produced the most favorable ratio of endotoxin relea se to amount of bacterial killing, In the presence of 50% serum, cefta zidime and imipenem reduced the P. aeruginosa inoculum to the greatest extent over 6 h, Although its bactericidal activity was diminished, o floxacin caused the lowest release of free endotoxin, Imipenem and ofl oxacin showed similar low ratios of endotoxin release to bacterial kil ling, In summary, antibiotic class, presence of serum, and type of org anism influenced bactericidal activity and endotoxin release.