22 Acute Kidney Injury in Burn Patients Following Combination Antibiotic Therapy: A Large Database Analysis

Abstract

Abstract Introduction Burn patients are prone to infections, which often warrants broad-spectrum antibiotic coverage. Vancomycin is a common antibiotic used at burn centers and is administered alone, or in combination with other agents such as piperacillin-tazobactam (Pip/Tazo). A recent study showed that this combination therapy was associated with increased rates of acute kidney injury (AKI) in adult and pediatric burn patients when compared to vancomycin in combination with other antibiotics. However, other studies failed to demonstrate these findings. The degree of nephrotoxic effect of the combination therapy relative to its drug components has not been demonstrated in burn patients. Using a large national database encompassing 41 health care organizations, we sought to determine whether a combination of vancomycin and Pip/Tazo exacerbates AKI in burn patients. Methods Using the TriNetX Global Health Research Network, we identified the population of burn patients with ICD-10 codes T20-T25 and T30-T32 between 2000–2020. We then grouped this population into 4 cohorts based on the administration of broad-spectrum antibiotics they received after the burn incident: vancomycin, Pip/Tazo alone, combination, and neither vancomycin nor Pip/Tazo. All cohorts were balanced for age, gender, and race. We explored the distribution of these cohorts and conducted comparative outcome analysis to determine the relative risk of developing AKI using the ICD10 code N17. Results Comparative analysis showed burn patients who received vancomycin had a 4.81% increased associated risk with AKI compared to those who did not receive either vancomycin or Pip/Tazo (p< 0.0001, RR =3.35, 95%CI= 2.63–4.26). Patients who received Pip/Tazo monotherapy had a 5.1% increased association with AKI compared to those who did not receive either drug (p< 0.0001, RR =3.57, 95%CI: 2.33–5.45). The combination of vancomycin with Pip/Tazo increased the association with AKI by 9.49% compared to patients who did not receive either drug (p< 0.00001, RR=5.65, 95%CI: 4.40–7.26). Combination therapy also increased the risk of AKI when compared to the vancomycin monotherapy (5.01%, p< 0.00001, RR= 1.69, 95%CI: 1.42–2.00) and Pip/Tazo monotherapy (4.85%, p< 0.00002, RR= 1.62, 95%CI: 4.40–7.26). Conclusions The use of broad-spectrum antibiotics in burn patients is associated with a higher risk of AKI. The combination of these drugs affords an increased relative risk of AKI when compared to monotherapy with the respective component drugs. Whether this is associated with selection bias or drug-effect warrants further investigation.