Differentiating True Nephrotoxicity From Pseudo-nephrotoxicity: A Prospective Comparative Study of Vancomycin Plus Piperacillin-Tazobactam vs. Meropenem Using Serum Creatinine and Cystatin-C

NCT07818265 | Not Yet Recruiting

• 1 other identifier: IRB#2261314
• Study Type: observational
• Target: 304
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nephrotoxicity; Bacterial Infections; Renal Impairment; Acute Kidney Injury

Keywords

Piperacillin tazobactam; Nephrotoxicity; Vancomycin; Meropenem; Cystatin-c; serum creatinine

Outcome Measures

Primary Outcomes (1)

• 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

  From enrollment until 72 hours from stopping vancomycin therapy

Secondary Outcomes (4)

• Difference in time to AKI onset based on serum creatinine and cystatin C between the two groups

  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

  From enrollment until 72 hours from vancomycin therapy cessation

• Recovery from AKI according to the 2026 KDIGO Criteria

  From AKI onset through 90 days after AKI onset.

• Severity of AKI staged according to the 2026 KDIGO criteria between the two groups

  From AKI onset through 7 days after AKI onset.

Study Arms (2)

Vancomycin - Piperacillin Tazobactam

Patients who will be receiving a combination of vancomycin and piperacillin-tazobactam for treating various types of infections

Vancomycin - Meropenem

Patients who will be receiving a combination of vancomycin and meropenem for treating various types of infections

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Recipients of solid organ transplant or hematopoietic stem cell transplantation within one year of presentation
• Concomitant receive of agents known to be nephrotoxins:
• Amphotericin B Aminoglycosides Calcineurin inhibitors
• Patients with AKI 30 days prior to vancomycin initiation
• Admission to the ICU for indication other than postoperative care for \> 72 hours
• Receiving vancomycin therapy within 30 days before the index combination

Sponsors & Collaborators

• King Faisal Specialist Hospital & Research Center: lead

Study Sites (1)

King Faisal Specialist Hospital and Research Center-Riyadh

Riyadh, 11211, Saudi Arabia

Location

Related Publications (1)

• 1. Lewington AJ, Cerda J, Mehta RL. Raising awareness of acute kidney injury: a global perspective of a silent killer. Kidney Int. 2013;84:457-467. 2. Perazella MA, Rosner MH. Drug-Induced Acute Kidney Injury. Clin J Am Soc Nephrol. 2022;17:1220-1233. 3. Fresilli S, Labanca R, Losiggio R, et al. Long-Term Outcomes After Acute Kidney Injury During Hospitalization: A Systematic Review and Meta-Analysis of Matched Controls Studies. Crit Care Med. 2026;54:335-342. 4. Pan K, Li R, Li Y, Ding X, Li X, Lv Q. Vancomycin combined with piperacillin/tazobactam increases the risk of acute kidney injury compared with vancomycin plus other anti-pseudomonal beta-lactams: a systematic review and network meta-analysis. J Antimicrob Chemother. 2025;80:47-58. 5. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Crit Care Med. 2026;54:725-812. 6. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63:e61-e111. 7. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59:e10-52. 8. Chiu CY, Sarwal A. Evaluating the Nephrotoxicity of Area-under-the-Curve-Based Dosing of Vancomycin with Concomitant Antipseudomonal Beta-Lactam Antibiotics: A Systematic Review and Meta-Analysis. Medicina (Kaunas). 2023;59. 9. Rutter WC, Cox JN, Martin CA, Burgess DR, Burgess DS. Nephrotoxicity during Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime. Antimicrob Agents Chemother. 2017;61. 10. Miano TA, Hennessy S, Yang W, et al. Association of vancomycin plus piperacillin-tazobactam

  BACKGROUND

MeSH Terms

Conditions

Bacterial Infections; Acute Kidney Injury; Renal Insufficiency

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Hakeam A Hakeam, MS Pharm., BCPS

CONTACT

+966505494897; hakeam@kfshrc.edu.sa

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Pharmacy Consultant

Study Record Dates

• First Submitted: September 7, 2026
• First Posted: September 14, 2026
• Study Start: September 15, 2026
• Primary Completion (Estimated): June 5, 2027
• Study Completion (Estimated): July 9, 2027
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

SA (1)