Abstract
Aim
Treatment of chronic prosthetic joint infection (PJI) combines exchange arthroplasty and effective antibiotic therapy. Staphylococci are the most frequent microorganism isolated in PJIs, with resistance to methicillin found in 15–50% of the cases. Data from randomized trials on treatment of methicillin-resistant staphylococci are lacking and the choice of antibiotic(s) and recommendations vary according to authors. To date, combination therapy including vancomycin is the treatment of choice.
Minocycline, a cyclin antibiotic, is naturally effective against methicillin-resistant staphylococci. We use this antibiotic since many years in combination with vancomycin for the treatment of multi-drug resistant staphylococcal bone and joint infections.
The aim of this study is to analyze the outcome of patients treated with combination antibiotic therapy including minocycline for the treatment of chronic methicillin-resistant staphylococcal PJI.
Method
We conducted a cohort study between 2004 and 2014 in our referral center for bone and joint infections. Data were extracted from the prospective database. All the patients receiving an initial combination therapy including at least 4 weeks of minocycline, given orally, and another IV antibiotic, usually high-dose continuous IV vancomycin, for chronic MR staphylococcal PJI and who underwent one or two stage exchange arthroplasty, were included. They were followed prospectively for at least 2 years.
Results
We included 42 patients: 26 patients (62%) had one-stage, 16 patients (38%) had two stage exchange arthroplasty. Median duration of IV and total antibiotic therapy was 42 [40–44] days and 84 [84–88] days, respectively. 41 patients (98%) received vancomycin as associated initial therapy. Thirty-six patients received 100mgx3 per day of minocycline. Six received >300mg per day because of low serum concentrations. Median follow-up was 48 months (IQR 27–58).
Survival rate without infection was 84,5% at 2 years, 70.2% at 6 years.
Four patients reported adverse events due to minocycline: one had grade 4 thrombopenia leading to minocycline withdrawal, two had grade 2 liver toxicity. One patient had grade 1 nauseas.
Two patients with MR Staphylococcus epidermidis knee arthroplasty experienced relapse. Three patients with hip arthroplasty infection developed a new infection within 2 year due to MSSA, Pseudomonas aeruginosa, and plurimicrobial for the last one.
Three further patients developed a new infection 3 (n=2) and 4 years later. They were all acute haematogenous infections.
Conclusions
Our data support the use of minocycline combination therapy with high-dose IV vancomycin for the treatment of chronic PJI due to methicillin-resistant Staphylococci.
