Safety and Efficacy of Vancomycin Plus Beta-lactams (SEVPB)

Comparison of the Nephrotoxicity of Vancomycin in Combination With Piperacillin/Tazobactam or Other Beta-lactams in Critically Ill Patients: A Retrospective, Multicenter Study in China

The combination of vancomycin and piperacillin-tazobactam has been associated with an increased risk of acute kidney injury (AKI) in non-critically ill patient populations, but it is still unknown if this association exists in critically ill patients. The objective of this study is to compare AKI and efficacy of vancomycin plus piperacillin-tazobactam or beta-lactams.

Study Overview

• Status: Completed
• Conditions: Critical Illness
• Intervention / Treatment: Drug: vancomycin plus piperacillin/tazobactam; Drug: vancomycin plus other beta-lactams

Detailed Description

The combination of vancomycin and piperacillin-tazobactam has been associated with an increased risk of acute kidney injury (AKI) in non-critically ill patient populations, but limited data regarding this association exists in critically ill patients. The objective of this study is to compare AKI and efficacy of vancomycin plus piperacillin-tazobactam or beta-lactams.

This is a multicenter, retrospective cohort study. Patients from the retrospective cohort will be divided into 2 groups based on the combination regimen received . Patients who meet the inclusion and exclusion criteria will be included in our registry. As a non-intervention study, these information as below will be collected: basic demographics, diagnosis, concomitant nephrotoxic and other antibiotic medications, serum creatine levels, vancomycin concentrations, and indication for antibiotics.

• Study Type: Observational
• Enrollment (Actual): 700

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • First Affiliated Hospital of Xian Jiaotong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

critically ill patients

Description

Inclusion Criteria:

• 18 years or older,
• admitted to intensive care unit
• received the combination of vancomycin and beta-lactams for at least 48 hours
• had a serum creatinine level measured within 24-hour hospital admission
• had at least one VAN level drawn while receiving a combination of study antibiotics

Exclusion Criteria:

• pregnancy or lactating patients
• admission to the intensive care unit during administration or within 72 hours of completing the antibiotics
• had end-stage renal disease
• died within 48 hours of combination antibiotic therapy initiation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
vancomycin plus piperacillin/tazobactam; Critically ill patients who received the combination of VAN (vancomycin) and PTZ (piperacillin/tazobactam) for at least 48 hours during an ICU (intensive care unit) admission, had a baseline serum creatinine (Scr) concentration value within 24 hours of hospital admission.The dosage and frequency of VAN and PTZ were adjusted based on clinical practice and patient characteristics. This is an observational study without any intervention.	Drug: vancomycin plus piperacillin/tazobactam; Patients in intensive care unit who received the combination of VAN(vancomycin) and PTZ (piperacillin/tazobactam) for at least 48 hours, had a serum creatinine level measured in the 24-hour of hospital admission.The dosage and frequency of VAN and PTZ was adjusted based on clinical practice and patient characteristics.
vancomycin plus other beta-lactams; Critically ill patients who received the combination of VAN (vancomycin) and other beta-lactams (cefoperazone/sulbactam, meropenem, imipenem/siastatin, ceftriaxone, ceftazidime, et al) for at least 48 hours during an ICU (intensive care unit) admission, had a baseline serum creatinine (Scr) concentration value within 24 hours of hospital admission.The dosage and frequency of VAN and other beta-lactams were adjusted based on clinical practice and patient characteristics. This is an observational study without any intervention.	Drug: vancomycin plus other beta-lactams; Patients in intensive care unit who received the combination of VAN (vancomycin) and other beta-lactams (cefoperazone/sulbactam, meropenem, imipenem/siastatin, ceftriaxone, ceftazidime, et al) for at least 48 hours, had a baseline serum creatinine (Scr) concentration value within 24 hours of hospital admission.The dosage and frequency of VAN and other beta-lactams were adjusted based on clinical practice and patient characteristics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AKI(acute kidney injury)	the incidence of acute kidney injury	from 24 hours after the start of the combination until discharge up to one month
clinical efficacy	microbial eradication	from 24 hours after the start of the combination until discharge up to one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the length of hospital stay		from hospital admission to discharge up to one month
duration of AKI		the time from AKI onset to resolution of AKI up to one month
onset of AKI		the first occurence of AKI after starting concomitant antimicrobial use up to one month
whether renal function return to baseline or not	whether defined AKI was resoluted or not	from AKI onset to resolution of defined AKI up to one month
major acute kidney events at 30 days (MAKE30)	MAKE30 is assessed 30 days following AKI diagnosis, which is a composite outcome of death, new dialysis, and worsened renal function.	MAKE30 is assessed 30 days following AKI diagnosis
vancomycin trough value assessment	assess the impact of vancomycin exposures on development of AKI	from hospital admission to discharge up to one month

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborators: Second Affiliated Hospital of Xi'an Jiaotong University
• Investigators: Principal Investigator: Yalin Dong, Ph.D, First Affiliated Hospital of Xian Jiaotong University

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): May 30, 2020
• Study Completion (Actual): May 30, 2020

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 12, 2018
• First Posted (Actual): December 14, 2018

Study Record Updates

• Last Update Posted (Actual): June 23, 2020
• Last Update Submitted That Met QC Criteria: June 21, 2020
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Vancomycin; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination; Lactams; beta-Lactams
• Other Study ID Numbers: XJTU1AF2018LSK-169

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No