This prospective comparative observational study will compare the incidence of true nephrotoxicity in adult patients receiving vancomycin in combination with either piperacillin-tazobactam or meropenem.
Vancomycin plus piperacillin-tazobactam has been associated with a higher incidence of kidney injury based mainly on increases in serum creatinine. However, it remains uncertain whether these increases represent true kidney injury or pseudo-nephrotoxicity, in which serum creatinine increases without a corresponding decline in kidney function.
To address this uncertainty, the study will prospectively assess kidney function using both serum creatinine and cystatin C. True nephrotoxicity will be identified when changes in both biomarkers meet the study criteria for acute kidney injury, while an increase in serum creatinine without a corresponding cystatin C increase will be considered pseudo-nephrotoxicity.
The study will compare true nephrotoxicity between patients receiving vancomycin plus piperacillin-tazobactam and those receiving vancomycin plus meropenem. It will also evaluate the timing, persistence, severity, and recovery of kidney injury. The results may help clarify whether the higher rates of nephrotoxicity reported with vancomycin plus piperacillin-tazobactam represent true renal injury and may help guide antibiotic selection when balancing antimicrobial coverage and kidney safety.
Age ≥18 years.
Receipt of vancomycin in combination with either piperacillin-tazobactam or meropenem, with both antimicrobial agents prescribed by the treating physician and expected to be administered concomitantly for >48 hours.
Known advanced chronic kidney disease (CKD), defined as a baseline estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m², or dialysis dependence..
Pregnancy.
Receipt of renal replacement therapy prior to enrollment.
Obstructive uropathy causing AKI.
Patients admitted to King Faisal Specialist Hospital and Research Center, and received vancomycin combined with either piperacillin-tazobactam or meropenem from August 2026 until achieving the pre-specified sample size will be screened for the inclusion and exclusion criteria
Other
Prospective
Not listed
To assess the incidence of developing true nephrotoxicity in patients receiving vancomycin + piperacillin-tazobactam versus vancomycin + meropenem.
True nephrotoxicity is defined as both serum creatinine and cystatin-C meet the AKI criteria on 2026 KDIGO criteria. Serum creatinine-based AKI: defined as any of the following: Change in SCr≥0.3 mg/dL within 48 hours OR SCr≥1.5×baseline within 7 days. Cystatin-C-Based AKI is defined as any of the following: ≥50% increase from baseline cystatin-C OR absolute increase ≥0.3 mg/L from baseline
Difference in time to AKI onset based on serum creatinine and cystatin C between the two groups
Time to AKI onset will be determined independently according to serum creatinine-based and cystatin C-based AKI criteria. Time to AKI onset will be calculated from initiation of the study antibiotic regimen to the first time the participant meets the respective AKI criterion. The difference in time to AKI onset between serum creatinine-based and cystatin C-based assessments will be evaluated and compared between patients receiving vancomycin plus piperacillin-tazobactam and those receiving vancomycin plus meropenem.
Incidence of Transient and Persistent Acute Kidney Injury According to the 2026 KDIGO Criteria between the two study groups
AKI will be classified as transient or persistent according to the 2026 KDIGO AKI/AKD criteria based on the duration of increased serum creatinine or cystatin C, or reduced urine output. The incidence of transient and persistent AKI will be compared between patients receiving vancomycin plus piperacillin-tazobactam and those receiving vancomycin plus meropenem.
Recovery from AKI according to the 2026 KDIGO Criteria
Recovery from AKI will be assessed according to the 2026 KDIGO AKI/AKD criteria using serum creatinine-based and cystatin C-based assessments. The proportion of participants achieving recovery from AKI will be determined and compared between patients receiving vancomycin plus piperacillin-tazobactam and those receiving vancomycin plus meropenem.
Severity of AKI staged according to the 2026 KDIGO criteria between the two groups
The severity of acute kidney injury (AKI) will be assessed according to the 2026 Kidney Disease: Improving Global Outcomes (KDIGO) AKI/AKD criteria. Participants who develop AKI will be classified according to AKI severity (Stage 1, Stage 2, or Stage 3) based on serum creatinine and urine output criteria. The distribution of AKI severity stages will be compared between patients receiving vancomycin plus piperacillin-tazobactam and those receiving vancomycin plus meropenem.
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