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Published on: August 30, 2018
Protein Binding of Cefazolin is Not Saturated in Human Synovial Fluid After Single-Dose Perioperative Antibiotic
Steffen T Ubl1, Luc M Arnold1, Sophia Krombholz2
1Department of Orthopedic Surgery, Trauma Surgery and Sports Medicine, Cologne Merheim Medical Center, Witten/Herdecke University, Ostmerheimer Straße 200, 51109, Cologne, Germany.
Insights
Cefazolin protein binding in synovial fluid is concentration-dependent, not saturated, after prophylaxis. Understanding unbound cefazolin levels is key for effective antibiotic activity in joint infections.
Area of Science:
- Pharmacology
- Orthopedic Surgery
- Infectious Disease
Background:
- Cefazolin is a common antibiotic for surgical prophylaxis.
- High protein binding can limit active drug concentration.
- Understanding cefazolin binding in synovial fluid is crucial for efficacy.
Purpose of the Study:
- To characterize cefazolin protein binding in human knee and shoulder synovial fluid.
- To determine if cefazolin binding is concentration-dependent or saturated.
Main Methods:
- Prospective study of 201 patients receiving cefazolin prophylaxis.
- Synovial fluid collected during knee or shoulder surgery.
- Ultra-high-performance liquid chromatography-mass spectrometry used to quantify total and unbound cefazolin.
Main Results:
- Median unbound cefazolin fraction was 24.6% in synovial fluid.
- Unbound fraction increased with unbound concentration (r = 0.38, p < .001).
- No plateau indicating saturation was observed.
Conclusions:
- Cefazolin protein binding in synovial fluid is concentration-dependent.
- Binding does not appear to reach saturation after a single prophylactic dose.
- These findings impact understanding of cefazolin's antimicrobial activity in joint tissues.
Background And Objective:
Cefazolin is widely used for perioperative antibiotic prophylaxis and exhibits high protein binding. As only the unbound fraction exerts antimicrobial activity, understanding protein binding at the target site is essential. This study aimed to characterize the protein binding pattern of cefazolin in human knee and shoulder synovial fluid.
Methods:
This prospective study included adult patients undergoing arthroscopic or open knee or shoulder surgery who received 2 g of intravenous cefazolin as part of routine perioperative antibiotic prophylaxis. Synovial fluid was aspirated immediately before arthroscope insertion or after joint capsule exposure. Total and unbound cefazolin were quantified using an ultra-high-performance liquid chromatography system coupled to mass spectrometry. Protein binding was calculated from paired total and unbound measurements. Concentration dependence was assessed by examining the relationship between the unbound fraction and the unbound concentration, with protein binding saturation defined by the presence of a plateau in this relationship. Statistical significance was defined as p < .05.
Results:
A total of 201 patients were included. Median total and unbound cefazolin concentrations in synovial fluid were 40.4 mg/L and 13.7 mg/L, respectively, corresponding to a median unbound fraction of 24.6%. The unbound fraction increased with rising unbound concentration (r = 0.38; p < .001) without evidence of plateau formation within the observed range.
Conclusions:
Cefazolin exhibits concentration-dependent, but not saturated, protein binding in human synovial fluid after single-dose perioperative antibiotic prophylaxis.
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