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

## TL;DR

A patient with a drug-resistant E. coli infection was treated with a personalized antibiotic regimen guided by a lab system that simulated drug effects before surgery.

## Contribution

The study demonstrates the use of a hollow fiber system to personalize antibiotic dosing for XDR E. coli in a liver transplant patient.

## Key findings

- A 4-log reduction in bacterial count was observed within 10 hours of treatment.
- Six infusions were needed to reduce bacteria below detection limits.
- The HFS supported earlier antibiotic dosing before liver transplant.

## Abstract

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.

The hollow fiber system (HFS) was applied to inform the individualized pharmacodynamic outcome likelihood prior to prophylaxis.

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.

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.
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The HFS‐E. coli informed the prophylactic antimicrobial treatment of an XDR‐E. coli‐infected patient awaiting orthotopic liver transplant. The patient was dosed 24 h prior to their surgery and subsequently discharged 8 days after surgery
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