The treatment of prosthetic joint infection with debridement, prosthesis retention and biofilm-active antibiotics

Abstract

Background: Prosthetic joint infection (PJI) is a serious infection that is difficult to cure and is associated with significant morbidity. The pathogenesis of PJI involves bacteria growing in biofilm adherent to the prosthesis surface, making them resistant to eradication with standard antibiotics. Recent evidence demonstrates successful treatment of early PJI with surgical debridement and retention of the prosthesis (DAR) and the biofilm-active antibiotic combination of rifampicin and a fluoroquinolone for staphylococcal infections. However, there are few studies investigating appropriate antibiotics to use in combination with rifampicin for PJI caused by staphylococci resistant to fluoroquinolones or which antibiotics to use for organisms other than staphylococci. Little is known about functional outcomes, quality of life (QOL) or complications after treatment of PJI. The aim of this thesis is to provide further evidence to help guide management in these areas.

Methods: This thesis synthesizes three of my recent studies published in peer-reviewed journals and one study presented at a national scientific meeting. In the first study, outcomes were analysed for consecutive patients with staphylococcal PJI treated with DAR and a combination of rifampicin and fusidic acid. The second examined consecutive patients with a Gram-negative bacillus PJI treated with DAR and ciprofloxacin-based regimens. In the third study, consecutive patients treated for hip PJI with DAR and biofilm-active antibiotics were matched to controls that had hip arthroplasty with no infection, and their function, QOL and complications compared. In the fourth study, a large prospective hip and knee arthroplasty cohort was analysed to determine if PJI treated with DAR and biofilm-active antibiotics was predictive of adverse QOL outcomes.

Results: Of 20 patients with staphylococcal PJI, treatment failure occurred in two patients. The cumulative risk of treatment failure after 1 year was 11.76% (95% CI 3.08–39.40%). Ten of 11 patients with infections involving methicillin-resistant Staphylococcus aureus had successful outcomes.

Of 17 patients with Gram-negative bacillus PJI, treatment failure occurred in two patients. In only one patient was a relapsed Gram-negative infection responsible for the failure and this patient had not been treated with ciprofloxacin. The 2-year survival rate free of treatment failure was 94% (95% CI, 63–99%). In 19 hip PJI cases there was significant improvement 12-months post-arthroplasty in function according to Harris Hip Score and QOL according to the 12-item Short Form Health Survey Physical Component Summary. There was no significant difference in the improvement between 76 controls and the 19 cases. Medical complications occurred more frequently in cases than controls but the rate of surgical complications was the same.

Of 2134 patients in a hip and knee arthroplasty cohort there were 37 patients with PJI treated with DAR and biofilm-active antibiotics. On multivariate logistic analysis, PJI treated this way was not predictive of adverse QOL outcomes according to SF-12 scores, however pre-arthroplasty SF-12, female gender, knee arthroplasty and a comorbidity index were.

Conclusions: DAR in combination with rifampicin and fusidic acid is effective and should be considered for patients with early staphylococcal PJI, including those with infections involving fluoroquinolone-resistant organisms. DAR in combination with ciprofloxacin is effective for patients with early Gram-negative bacillus prosthetic joint infection. Treatment of PJI with DAR and biofilm-active antibiotics was well tolerated and results in good improvements in function and QOL.