Personalized CZA-ATM dosing against an XDR E. coli in liver transplant patients; the application of the in vitro hollow fiber system

Abstract

Background: A patient with an extensively drug-resistant (XDR) New Delhi metallo-β-lactamase (NDM) and oxacillinase (OXA-48) producing Escherichia coli (E. coli) infection was awaiting orthotopic liver transplant. There is no standardized antibiotic prophylaxis regimen; however, in line with the Infectious Diseases Society of America guidance, an antibiotic prophylactic regimen of ceftazidime-avibactam 2.5 g TDS with aztreonam 2 g three times a day (TDS) IV was proposed. Methods: The hollow fiber system (HFS) was applied to inform the individualized pharmacodynamic outcome likelihood prior to prophylaxis. Results: A 4-log reduction in CFU/mL in the first 10 h of the regimen exposure was observed; however, the killing dynamics were slow and six 8-hourly infusions were required to reduce bacterial cells to below the limit of quantification. Thus, the HFS supported the use of the regimen for infection clearance; however, it highlighted the need for several infusions. Standard local practice is to administer prophylaxis antibiotics at induction of orthotopic liver transplantation (OLT); however, the HFS provided data to rationalize earlier dosing. Therefore, the patient was dosed at 24 h prior to their OLT induction and subsequently discharged 8 days after surgery. Conclusion: The HFS provides a dynamic culture solution for informing individualized medicine by testing antibiotic combinations and exposures against the bacterial isolates cultured from the patient's infection. (Figure presented.).