Prometheus, a titan of ancient Greece mostly known for giving humans fire, is also credited as the creator of human arts and sciences. That balance is on display with antimicrobial stewardship – where we hope to use antibiotics to treat infection but not so much as to create multidrug-resistant organisms or cause infections with Clostridioides difficile. Recently, Australian researchers wanted to look further at whether antibiotics in liver transplant patients influenced the rates of rejection or survival post-transplant.
Adult patients who underwent liver transplantation between January 2015 and June 2022 were included. Tacrolimus levels were followed to ensure that morbidity and mortality were not due to insufficient immunosuppression. All inpatient and outpatient antibiotic usage from 30 days before transplantation to one year after was tallied, excluding the peri-transplant antibiotic therapy that all patients get – three doses of piperacillin/tazobactam 4.5 g IV – and Pneumocystis prophylaxis with trimethoprim/sulfamethoxazole. Days of exposure were tracked, with at least one dose given on a calendar day being one day of exposure. In addition, if two antibiotics were given in one day, that was counted as two days of exposure.
A total of 462 transplant recipients were identified. There was no association with post-transplant surgical complications and rejection or overall survival. There was reduced one-year overall survival with post-transplant bloodstream infections but no association with rejection.
Pre-transplant, 41.6% (192/462) of patients got at least one antibiotic, and they were more likely to be hospitalized and have higher Model for End-Stage Liver Disease scores. Post-transplant, 82.9% (383/462) received at least one antibiotic. In both groups of patients, those who received anaerobe-targeting antibiotics for > 14 days had significantly lower rates of overall one-year survival. Patients who received any antibiotic or anaerobe-targeting antibiotics had significantly higher rates of rejection, while those who received anaerobe-sparing regimens did not have a higher risk of rejection.
The authors hypothesize, using literature showing poor outcomes in other immunosuppressed populations, that anaerobe-targeting antibiotics disrupt the delicate balance of microbiome homeostasis in these patients: In liver physiology, “there is a unique bidirectional relationship between the gut microbiota and the liver, established by the portal vein, which facilitates the passage of microbiota and microbiota-derived products directly to the liver.” Altering that delicate balance might explain the higher rates of rejection and lower rates of survival among liver transplant patients.
Unlike Prometheus, who was granted a new liver nightly, our patients are fortunate to receive one chance at a new life. Further study into how antibiotics, anaerobes and the immune system interact is warranted.