A Pharmacokinetics Study of Daptomycin in Critically Ill Patients and Effects of Daptomycin on Kidney

Study Overview
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Brief Summary
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Daptomycin ，is the ﬁrst approved member of a new class of antimicrobials, the cyclic lipopeptides, and presents selective action against gram-positive bacteria, including methicillin- and vancomycin-resistant strains，disrupting the transfer of amino acids in the cell membrane, thus hindering the biosynthesis of bacterial cell cell wall peptide polysaccharide, changing the properties of cytoplasm membrane, can destroy bacterial cell membrane function in many ways, and quickly kill gram-positive bacteria. Because of its unique chemical structure and sterilization mechanism, bacteria rarely develop resistance to daptomycin. Daptomycin can be reversibility combined with human plasma protein (mainly serum albumin) and metabolized mainly through the kidneys. There is still a lot of controversy about the application of daptomycin in patients with severe illness. Although studies suggest that daptomycin has less damage to kidney function than vancomycin, the effect of daptomycin on kidney function in severely ill patients is not yet clear, and more clinical studies are needed to explore their relationship. In addition, it is not clear whether the physiological pathology of specific populations such as sepsis/infectious shock, acute kidney injury, (AKI), hypoproteinemia, and renal replacement treatment affects the pharmacokinetics/pharmacodynamics of Daptomycin. By exploring the application of daptomycin in patients with severe illness, this study explores the effects of special pathological physiological states such as sepsis/infectious shock and hypoproteinemia on daptomycin PK/PD, as well as the effects of different hemoglobin concentrations of daptomycin on the outcome of kidney function.

Official Title
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The Influence Factors of Pharmacokinetics/Pharmacodynamics of Daptomycin in Severe Patients and the the Effect of Different Blood Concentration of Daptomycin on the Outcomes of Renal Function

Conditions
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Infection, Outcome, Fatal

Intervention / Treatment
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* Drug: Daptomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with severe bloodstream infections eligible for daptomycin indications Treatment in the ICU Patients aged 18 to 65 Exclusion Criteria: Pregnant and lactating women The patient or his agent refused to participate in the trial Incomplete clinical medical information Patient participates in another clinical trial at the same time Previous history of myopathy or current CPK increase more than 2 times than normal Patients need to use warfarin anticoagulation Patients use tobramycin for anti-infection Patients use drugs such as cyclosporine and fibrates that can cause adverse reactions to muscle disease Patients with Gram-negative bacterial infections caused by abdominal and respiratory infections Patients with heart failure, respiratory failure, Glasgow coma index (GCS) ≤ 8 points, liver function CHILD PUGH score C that are not related to the infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| critical ill patient with bloodstream infections<br>Severe patients with bloodstream infections often have sepsis / septic shock, acute kidney injury (AKI), hypoproteinemia, and renal replacement treatment. | Drug: Daptomycin<br>* Adult patients are given the recommended dose of daptomycin for injection. Patients with creatinine clearance (CLCR) ≥ 30 mL / min: 6 mg / kg every 24 hours. Patients with creatinine clearance (CLCR) <30mL / min (including hemodialysis or peritoneal dialysis): 6mg / kg every 48 hours. Dissolve 6mg / kg of this drug in 0.9% sodium chloride injection and instill it over a 30-minute time course once every 24 or 48 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent volume of distribution | Apparent volume of distribution of daptomycin in the patient's blood | 1 week | 
| Peak plasma concentration | Peak plasma concentration of daptomycin | 1 week | 
| Plasma trough concentration | Plasma trough concentration of daptomycin | 1 week | 
| Area under the plasma concentration versus time curve (AUC) | Area under the plasma concentration versus time curve (AUC) of daptomycin | 1 week | 
| Clearance of daptomycin | Daptomycin is metabolized mainly by the kidneys | 1 week | 
| Half-life | Half-life of plasma daptomycin | 1 week | 
| Protein binding rate | Reversible binding of daptomycin to plasma proteins (mainly serum albumin) | 1 week | 
| Serum creatinine | Serum creatinine can reflect kidney function | 1 week | 
| Urine output | Urine volume can reflect kidney function | 1 week | 
| Blood Urea Nitrogen | It can reflect kidney function | 1 week | 
| Urine protein | Reflect kidney function | 1 week | 
| Cystatin C | Reflect kidney function | 1 week | 
| β2-microglobulin(β2-MG) | Reflect kidney function | 1 week | 
| Major Adverse kidney Event（MAKE） | Major Adverse kidney Event（MAKE）Refers to death, need for renal replacement therapy, and creatinine levels that are twice or more the baseline value；It can reflects the outcome of renal function. | 28days | 
| ICU mortality | Reflect patient prognosis | 28days | 
| In-hospital mortality | Reflect patient prognosis | 28days | 
| ICU hospital stay length | Reflect patient prognosis | 28 days | 
| Total hospital stay length | Reflect patient prognosis | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| White blood cell count | Reflect the severity of the patient's infection | 1 week | 
| Neutrophil ratio | Reflect the severity of the patient's infection | 1 week | 
| C-Reactive Protein | Reflect the severity of the patient's infection | 1 week | 
| Procalcitonin | Reflect the severity of the patient's infection | 1 week | 
| Interleukin-6 | Reflect the severity of the patient's infection | 1 week | 
| Bacterial culture results | Reflect the severity of the patient's infection | 1 week | 
| Body temperature | Reflect the severity of the patient's infection | 1 week | 
| Vascular drug use days | Assess patients' systemic circulation | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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daptomycin, pharmacokinetics, pharmacodynamics, critical ill patients, outcome