Paediatric acute kidney injury induced by vancomycin monotherapy versus combined vancomycin and meropenem

What is known and objective: Increasing reports of the combined use of vancomycin (VAN) and piperacillin/tazobactam leading to higher nephrotoxicity have led to carbapenems being recommended as an alternative option to combine with VAN when nephrotoxicity is a major concern. However, whether carbapenems also increase the nephrotoxicity of VAN is unclear. This study aimed to determine whether meropenem is a suitable drug to combine with VAN based on whether meropenem enhances the nephrotoxicity of VAN. Methods: This retrospective cohort study enrolled hospitalized children ranging in age from 1 month to 18 years at two tertiary hospitals from 1 February 2017 to 1 February 2018. Patients treated with either VAN or combined VAN and meropenem (VM) for more than 48 hours were eligible for inclusion. Those with underlying kidney diseases or abnormal age-adjusted baseline serum creatinine (SCr) at admission were excluded. Propensity score matching (PSM) was applied to the patients to balance factors associated with acute kidney injury (AKI). In addition, VAN trough concentrations were also compared. AKI was defined as an increase in SCr by ≥50% from baseline or by ≥0.3 mg/dL sustained over at least two consecutive measurements ranging from the time of initiation until 72 hours after the completion of VAN therapy. Results and discussion: The eligibility criteria were met by 183 of 243 identified patients: 101 patients received VAN alone and 82 received VM. PSM resulted in 154 hospitalized children being included (77 patients in each group). The incidence of AKI was 10.7% (8/77) in both of the compared groups, while the VAN trough concentration was significantly higher in the VM group (9.0 mg/L) than in the VAN group (6.6 mg/L, P = 0.007) after controlling for confounders. What is new and conclusion: Despite the elevated VAN trough concentration, meropenem did not increase the nephrotoxicity of VAN and might therefore be an acceptable antibiotic to combine with VAN when necessary.