Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip

Pharmacokinetics Clinical Trial

— CONCENTRATE  

Official title:

Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05421312
• Other study ID #: 2022-13583
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 2022
• Est. completion date: December 2023

Study information

• Verified date: June 2022
• Source: Radboud University Medical Center
• Contact: Karin Veerman, MD
• Phone: +31683845606
• Email: karin.veerman[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To prevent periprosthetic joint infection (PJI), optimal penetration of antibiotics into the joint-space is needed. In revision arthroplasty, the incidence of PJI is increased compared to primary arthroplasty. In this study, the penetration of antibiotic agents into the synovial fluid and bone will be analyzed. The concentration of antibiotics will be related tot the to the susceptibility (minimal inhibitory concentration; MIC-90) of microorganisms that frequently cause PJI.

Description:

Periprosthetic joint infection (PJI) is a feared complication of joint replacement, with an incidence of 0.5-1% after primary joint replacement and 3-5% after revision arthroplasty. For orthopaedic surgery involving a prosthesis, the administration of systemic antibiotic prophylaxis is strongly recommended to prevent PJI. Cefazolin is widely used as agent of choice in surgical antibiotic prophylaxis. Previous studies, all performed in patients undergoing primary joint replacement, demonstrated that the concentration of cefazolin in bone and synovial fluid was dose-dependent and exceeds the MIC90 for methicillin susceptible Staphylococcus aureus (MSSA), when given as 1 to 4 gram single dose shortly before incision. When a PJI is already present, clindamycin is used as treatment option in PJI caused by staphylococci (when combined with rifampicin) or cutibacteria. A limited number of studies have been performed to analyse the penetration of clindamycin into bone. These studies showed that clindamycin penetrates well into the bone and concentrations exceeded the MIC90 for MSSA. No studies have been performed to analyse the penetration of antibiotic agents into the periarticular tissue in patients who will undergo revision arthroplasty. In revision arthroplasty a foreign body (prosthesis) is in situ and periarticular tissue condition can be compromised due to previous surgical procedures and the presence of bone reaction to the prosthesis. It is not known whether the difference in PJI incidence after primary and revision arthroplasty may be explained by different penetration of the surgical antibiotic prophylaxis. The aim of this explorative study is to analyse the penetration of cefazolin and clindamycin into synovial fluid and bone and whether the concentration of the agents exceeds the MIC90 for micro-organisms frequently causing PJI.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

1. Age 16 years or older.

2. Scheduled second stage revision arthroplasty (reimplantation) of the hip prosthesis during clindamycin 600mg three times a day orally for PJI, started at least 3 days before reimplantation (steady state).

Exclusion Criteria:

1. Antibiotic prophylaxis other than cefazolin 2000mg i.v.

2. Cefazolin use within 4 days previous to the reimplantation, other than the single dose administration of surgical prophylaxis just before incision.

3. Clindamycin loaded bone cement in situ.

4. BMI more than 35 kg/m2.

Related Conditions & MeSH terms

• Bone and Joint Infection
• Pharmacokinetics

Intervention

Drug:
• sampling blood
During the reimplantation, 3 serum samples will be taken at different timepoint during the procedure.
• Sampling synovial fluid
During the reimplantation 1 synovial fluid sample will be taken prior to incision.
• Sampling bone tissue
During the reimplantation 2 cortical bone samples will be taken at different timepoints during the procedure.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University Medical Center	Sint Maartenskliniek

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	penetration cefazolin into synovial fluid	The ratio (%) of the concentration of cefazolin in synovial fluid to serum.	during surgical procedure prior to incision the synovial fluid sample will be taken
Primary	penetration cefazolin into bone tissue	The ratio (%) of the concentration of cefazolin in synovial fluid to serum.	during surgical procedure prior to incision the synovial fluid sample will be taken
Primary	penetration clindamycin into bone tissue	The ratio (%) of the concentration of cefazolin in bone tissue to serum.	during surgical procedure, directly after opening the joint and before reimplantation of the prosthesis the bone samples will be taken
Secondary	AUC/MIC90 of cefazolin	The ratio of area under the curve of cefazolin to the minimal inhibitory concentration-90 of microorganisms	sampling during procedure
Secondary	AUC/MIC90 of clindamycin	The ratio of area under the curve of cefazolin to the minimal inhibitory concentration-90 of microorganisms	sampling during procedure
Secondary	factors associated with reduced cefazolin concentration	univariable and multivariable (if possible) analysis for factors that are associated with reduced concentration of cefazolin (i.e., BMI, age, ..)	sampling during procedure
Secondary	factors associated with reduced clindamycin concentration	univariable and multivariable (if possible) analysis for factors that are associated with reduced concentration of cefazolin (i.e., BMI, age, ..)	sampling during procedure