An observational study in Nephrotoxicity, Bacterial Infections and Acute Kidney Injury, sponsored by King Faisal Specialist Hospital & Research Center. Not yet recruiting at 1 site in Saudi Arabia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-14.
Sponsored by King Faisal Specialist Hospital & Research Center · Observational
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.
Vancomycin is commonly administered in combination with broad-spectrum beta-lactam antibiotics for empiric treatment of serious infections. Several studies have reported a higher incidence of nephrotoxicity in patients receiving vancomycin plus piperacillin-tazobactam compared with vancomycin combined with other antipseudomonal beta-lactams. However, most of these studies have defined kidney injury using serum creatinine alone. This has raised concern that the observed increase in nephrotoxicity may, at least in part, represent pseudo-nephrotoxicity caused by an increase in serum creatinine without a corresponding reduction in true kidney function.
This prospective, non-interventional, comparative two-arm cohort study will evaluate adult patients receiving vancomycin in combination with either piperacillin-tazobactam or meropenem. Treatment selection, antimicrobial dosing, vancomycin therapeutic drug monitoring, fluid management, hemodynamic management, and other clinical decisions will remain under the responsibility of the treating clinical team and will not be determined by the study investigators.
The primary objective is to compare the incidence of true nephrotoxicity between the two treatment groups. Kidney function will be assessed prospectively using both serum creatinine and cystatin C. True nephrotoxicity will be defined as fulfillment of the study criteria for acute kidney injury using both serum creatinine and cystatin C, whereas pseudo-nephrotoxicity will be defined as serum creatinine-based acute kidney injury without a corresponding increase in cystatin C.
Serum creatinine and cystatin C will be assessed at baseline and serially during combination antimicrobial therapy, with additional follow-up measurements after discontinuation when available according to the study protocol. This simultaneous biomarker assessment is intended to help distinguish functional changes in serum creatinine from kidney injury supported by a parallel change in cystatin C.
Secondary assessments will include the time to onset of acute kidney injury based separately on serum creatinine and cystatin C, the incidence of transient and persistent acute kidney injury, kidney recovery, and the severity of acute kidney injury. Kidney recovery and progression to acute kidney disease will also be assessed during follow-up when applicable.
Patients will be categorized into two observational exposure groups according to the beta-lactam prescribed by the treating team: vancomycin plus piperacillin-tazobactam or vancomycin plus meropenem. Relevant demographic, clinical, laboratory, antimicrobial exposure, and potential nephrotoxic risk factors will be prospectively collected.
The study is designed to clarify whether the higher incidence of nephrotoxicity reported with vancomycin plus piperacillin-tazobactam represents true renal injury or predominantly a serum creatinine-based phenomenon. The findings may improve interpretation of kidney function during antibiotic therapy and may help clinicians balance antimicrobial coverage with the risk of nephrotoxicity when selecting empiric antibiotic regimens.
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
Exclusion Criteria:
Amphotericin B Aminoglycosides Calcineurin inhibitors
Patients who will be receiving a combination of vancomycin and piperacillin-tazobactam for treating various types of infections
Patients who will be receiving a combination of vancomycin and meropenem for treating various types of infections
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
Time frame: From enrollment until 72 hours from stopping vancomycin therapy
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.
Time frame: From enrollment until 72 hours from stopping vancomycin
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.
Time frame: From enrollment until 72 hours from vancomycin therapy cessation
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.
Time frame: From AKI onset through 90 days after AKI onset.
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.
Time frame: From AKI onset through 7 days after AKI onset.
Plan to share: No
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King Faisal Specialist Hospital & Research Center