Pharmacokinetics/ Pharmacodynamics (PK/PD) Study of Vancomycin

Study Overview
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Brief Summary
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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; 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; 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; 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; 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; 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. 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.

Detailed Description
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Study design: A multi-center, non-controlled, open-labeled observational study Research objectives Primary objective: To explore the PK/PD target value (AUIC) of vancomycin in the treatment of MRSA septicemia and endocarditis in Chinese patients. Secondary objective: To detect the therapeutic efficacy and safety of vancomycin in the treatment of MRSA septicemia and endocarditis in Chinese patients. To exam the relationship between the Cmin of vancomycin and its efficacy in the treatment to MRSA septicemia and endocarditis. To explore the relationship between MRSA molecular type and vancomycin therapeutic efficacy Medicine and administration Drug: Vancomycin Dosing: 15 20 mg/kg, IV, q 12 8h (or 1 g, IV, q12 8h) for adult patient with normal renal function; Dosage should be adjusted by blood creatinine clearance in patients with impaired renal function; Administration route： 1 2 h/ dosing, IV Drug combination: Drug combination is not recommended for patients with simple MRSA infection; Rifampicin can be combined in case of MRSA artificial valve endocarditis; Anti-G- antibacterial agents can be combined in case of concurrent G- bacterial infections. Duration: Septicemia: 2 4 weeks Endocarditis: 6 8 weeks

Official Title
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Pharmacokinetics/ Pharmacodynamics (PK/PD) Study of Vancomycin in the Treatment of Methicillin-resistant Staphylococcus Aureus（MRSA） Blood Stream Infection (Septicemia) and Endocarditis in Chinese Patients

Conditions
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MRSA, Blood Stream Infections, Endocarditis

Intervention / Treatment
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* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years, male or female; diagnosed as MRSA septicemia or endocarditis; Septicemia clinical manifestations of infection; MRSA infection confirmed by blood culture; Endocarditis: diagnosed according to modified Duke Criteria no therapy with effective anti-MRSA drugs 72 hours prior to the study; Effective anti-MRSA drugs used in China include: vancomycin, norvancomycin, teicoplanin, linezolid, daptomycin, tigecycline, and fusidic acid. Exclusion Criteria: those being allergic to glycopeptides antibiotics; those with osteomyelitis, central nervous system infection or other septic migrations (except for endocarditis); patients with catheter-related bloodstream infection who cannot withdraw catheter; those during chemotherapy for cancer or leukemia; those with agranulocytosis; those with HIV infection; women in pregnancy or lactation; patients receiving vancomycin for less than 72 hours; patients participating in any other clinical trial in 3 months prior to the study (not limited to trials for antibiotics)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRSA blood stream infection patient<br>Intervention:Vancomycin Dosing: 15-20mg/kg, IV,q 12 8h (or 1 g, IV, q12 8h) for adult patient with normal renal function; Dosage should be adjusted by blood creatinine clearance in patients with impaired renal function; Administration route： 1 2 h/ dosing, IV Drug combination: Drug combination is not recommended for patients with simple MRSA infection; Rifampicin can be combined in case of MRSA artificial valve endocarditis; Anti-G- antibacterial agents can be combined in case of concurrent G- bacterial infections. Duration: Septicemia: 2 4 weeks Endocarditis: 6 8 weeks | Drug: Vancomycin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC/MIC of vancomycin in each patient |  | Participants will be followed for the duration of hospital stay, an expected average of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with negative blood culture at the end of treatment |  | Participants will be followed during vancomycin treatment and in average of 4 weeks after vancomycin treatment | 
| Number of participants with adverse events |  | Participants will be followed during vancomycin treatment and in average of 4 weeks after vancomycin treatment | 
| Number of participants survival |  | Participants will be followed during vancomycin treatment and in average of 4 weeks after vancomycin treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics/pharmacodynamics, vancomycin, blood stream infections, Chinese patients, MRSA