Personalized CZA-ATM dosing against an XDR E. coli in liver transplant patients; the application of the in vitro hollow fibre infection model (HFIM)

Background & aimsAn extensively-drug resistant (XDR) NDM and OXA-48 producing E. coli contributing to repeat episodes of biliary sepsis was isolated from the blood stream of a 45-55 year-old male with a background of IgG4 related sclerosing cholangitis. The patient was awaiting orthotopic liver transplant (OLT). There is no standardized antibiotic prophylaxis regimen however in line with the Infectious Diseases Society of America (IDSA) guidance an antibiotic prophylactic regimen of Ceftazidime-Avibactam (CZA) 2.5g TDS with Aztreonam (ATM) 2g TDS IV was proposed. MethodsTo inform the individualised pharmacodynamic outcome likelihood prior to prophylaxis dosing the hollow fibre infection model (HFIM) was applied to simulate the in vivo antibiotic exposures of the CZA-ATM regimen. The HFIM was inoculated with [~]10 x 105 bacterial CFU/mL of the XDR E. coli strain and CFUs/mL were measured for a total of 120 hours to determine the in vitro PK/PD killing dynamics. ResultsA 4-log reduction in CFU/mL in the first ten hours of the regimen exposure was observed however the killing dynamics were slow and six eight-hourly infusions were required to reduce bacterial cells to below the limit of quantification. Thus, the HFIM supported the use of the regimen for infection clearance however highlighted the need for several infusions. Standard local practise is to administer prophylaxis antibiotics at induction of OLT however the HFIM provided data to rationalise earlier dosing therefore the patient was dosed at 24 hours prior to their OLT induction. The patient was subsequently discharged 8 days after surgery. ConclusionsThe HFIM provides a dynamic culture solution for informing individualised medicine by testing antibiotic combinations and exposures against the bacterial isolates cultured from the patients infection.