Pharmacokinetics/ Pharmacodynamics (PK/PD) Study of Vancomycin

Summary

1. Drug resistance of G+ cocci is a severe healthcare problem. According to the Ministry of Health National Antimicrobial Resistant Investigation Net (mohnarin) surveillance report, the isolation rate of MRSA is some 60% in China. MRSA infection has become a serious clinical problem;
2. Vancomycin is a bactericidal glycopeptide antibiotic which inhibits bacterial growth by hindering the synthesis of cell wall in bacteria. It exerts strong antibiotic effect to Gram+ bacteria. It is indicated for serious staphylococcus infections especially MRSA infection and has become the gold standard agent in MRSA treatment;
3. Vancomycin is a time-dependent antibiotic, its clinical and microbiological efficacy is related to area under curve（ AUC）/minimum inhibitory concentration （MIC ）(AUIC). Cmin at steady state is an surrogate parameter of AUIC, which is closely associated to the efficacy;
4. AUIC \>400 and Cmin between 15\~20 mg/L are recommended for effective vancomycin treatment by Infectious Diseases Society of America （IDSA） although it is still disputable;
5. Due to the absence of PK/PD study on vancomycin in China, administration of vancomycin is performed in reference to the recommendation of IDSA. Its suitability to Chinese patients is still to be clarified;
6. Plasma concentrations of vancomycin vary significantly between population and individuals. Factors such as large-volume fluid infusion, hypoproteinemia and renal clearance, etc. will influence the distribution and excretion of vancomycin, resulting in different plasma concentrations between individuals. Results of PK studies differ greatly between China and abroad. Administration based on the AUIC or Cmin recommended by IDSA would not be suitable to Chinese patients. Given the definite long-term benefit of vancomycin treatment, the AUIC or Cmin suitable to Chinese patients must be identified by clinical study.
7. The PK/PD study on vancomycin in the treatment to MRSA septicemia and endocarditis is of great significance for more reasonable use and improved therapeutic efficacy of MRSA infection.

Conditions

• Blood Stream Infections
• Endocarditis
• MRSA

Interventions

DRUG

Vancomycin

Vancomycin was administered for Chinese patients with MRSA blood stream infection and endocarditis Pharmacokinetics: 5 blood samples collected at steady state for the determination of plasma concentrations for population pharmacokinetics (PPK) analysis. Microbiology: blood cultures for MRSA isolation, MIC of vancomycin against MRSA; molecular typing will be analyzed on bacterial strains including heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate Staphylococcus aureus （VISA); Safety evaluation: hepatic and renal function, blood routine test, and so on.

Sponsors & Collaborators

• Shengjing Hospital

  collaborator OTHER

• Tianjin Medical University Cancer Institute and Hospital

  collaborator OTHER

• Qilu Hospital of Shandong University

  collaborator OTHER

• First Affiliated Hospital, Sun Yat-Sen University

  collaborator OTHER

• Guangzhou General Hospital of Guangzhou Military Command

  collaborator OTHER

• The First Affiliated Hospital of Soochow University

  collaborator OTHER

• The First Affiliated Hospital with Nanjing Medical University

  collaborator OTHER

• Zhejiang Provincial Hospital of TCM

  collaborator OTHER

• Second Affiliated Hospital, School of Medicine, Zhejiang University

  collaborator OTHER

• Zhejiang University

  lead OTHER

Principal Investigators

• Yong-hong Xiao, MD · The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-01-31

Primary Completion

2016-01-31

Completion

2016-06-30

Countries

• China

Study Locations