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

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

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.

Inclusion Criteria:

1. Patients with severe bloodstream infections eligible for daptomycin indications
2. Treatment in the ICU
3. Patients aged 18 to 65

Exclusion Criteria:

1. Pregnant and lactating women
2. The patient or his agent refused to participate in the trial
3. Incomplete clinical medical information
4. Patient participates in another clinical trial at the same time
5. Previous history of myopathy or current CPK increase more than 2 times than normal
6. Patients need to use warfarin anticoagulation
7. Patients use tobramycin for anti-infection
8. Patients use drugs such as cyclosporine and fibrates that can cause adverse reactions to muscle disease
9. Patients with Gram-negative bacterial infections caused by abdominal and respiratory infections
10. 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