Human Bile Reduces Antimicrobial Activity of Selected Antibiotics Against Enterococcus faecalis and Escherichia coli in vitro [PublishAheadOfPrint]

It has been known from previous studies that body fluids, such as cerebrospinal fluid, lung surfactant and urine, have a strong impact on the bacterial killing of many anti-infective agents. However, the influence of human bile on the antimicrobial activity of antibiotics is widely unknown. Human bile was obtained and pooled from 11 patients undergoing cholecystectomy. After sterilisation of the bile fluid by gamma irradiation its effect on bacterial killing was investigated for linezolid (LZD) and tigecycline (TGC) against Enterococcus faecalis ATCC 29212. Further, ciprofloxacin (CIP), meropenem (MEM) and TGC were tested against Escherichia coli ATCC 25922. Time-kill curves were performed in pooled human bile and Mueller Hinton Broth (MHB) over 24 hours. Bacterial counts (in cfu/ml after 24 hours) of bile growth controls were approximately equal to MHB growth controls for E. coli and approximately 2-fold greater for E. faecalis indicating a promotion of bacterial growth by bile for the latter strain. Bile reduced the antimicrobial activity of CIP, MEM and TGC against E. coli as well as the activity of LZD and TGC against E. faecalis. This effect was strongest for TGC against both strains. Degradation of TGC in bile was identified as the most likely explanation. These findings may have important implications for the treatment of bacterial infections of the gallbladder and biliary tract and should be explored in more detail.

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