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

Radboud University Medical Center

Status and phase: Not yet enrolling; Phase 4

Conditions: PJI; Bone and Joint Infection; Pharmacokinetics

Treatments: Drug: Sampling bone tissue; Drug: sampling blood; Drug: Sampling synovial fluid

Study type: Interventional

Funder types: Other

Identifiers

NCT05421312

2022-13583

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

cefazolin

Other group

Description:

The cefazolin antimicrobial prophylaxis (2000mg single dose intravenously 15-60 minutes before incision) is part of standard of care.

Treatment:

Drug: Sampling synovial fluid

Drug: Sampling bone tissue

Drug: sampling blood

Clindamycin

Other group

Description:

The clindamycin (600mg three times daily orally) PJI therapy is part of standard care.

Treatment:

Drug: Sampling synovial fluid

Drug: Sampling bone tissue

Drug: sampling blood