Efficacy of doxycycline in treatment of Staphylococcus spp. prosthetic joint infections: a CRIOGO multicentre case–control study

BACKGROUND: Prosthetic joint infections (PJI) of the hip and knee are most often caused by Staphylococcus spp. and require long-term treatment with rifampicin and fluoroquinolone as first-line treatment. However, resistance, contraindications or intolerance highlight the need for effective oral alternatives. Tetracyclines, with favourable bioavailability and bone penetration, represent a potential option. METHODS: CYCLIOS, a multicentre retrospective matched case-control study, included adult patients with staphylococcal hip or knee PJI treated with curative intent. Cases received doxycycline as part of their antibiotic regimen, and controls were matched 1:2 on infection site, age, pathogen and date of multidisciplinary meeting. The primary endpoint was a composite of death or treatment failure at 2 years. RESULTS: Sixty-seven patients were analysed (23 doxycycline group, 44 control). The two groups were comparable except for immunosuppression (17% (4/23) versus 2% (1/44); P = 0.04). The median duration of doxycycline was 75 days (interquartile range [IQR]: 47-83). The primary endpoint occurred in 43% (10/23 and 19/44) of both groups (odds ratio [OR] 1.01, 95% confidence interval [CI] [0.36-2.84]; P = 0.98). Treatment-related adverse events were reported in 35% (8/23) versus 20% (9/44); P = 0.24, but premature discontinuation remained rare (4% (1/23) versus 5% (2/44); P = 1.00). In the conditional logistic regression model, doxycycline exposure was not associated with an increased risk of unfavourable outcome (univariate OR 1.06, 95% CI [0.40-2.81]; P = 0.91 and multivariate OR 0.97, 95% CI [0.23-4.25]; P = 0.97). CONCLUSION: In this multicentre real-life study, doxycycline-based regimen, no significant difference was observed between doxycycline-based regimens and comparator strategies, with acceptable tolerability. Given the observational design and limited sample size, these findings should be considered exploratory. Tetracyclines may represent a pragmatic therapeutic alternative when first-line options are not feasible.