Background Periprosthetic joint infections (PJI) caused by pathogens, for which no biofilm-active antibiotics are available, are often referred to as difficult-to-treat (DTT). However, it is unclear whether the outcome of DTT PJI is worse than those of non-DTT PJI. We evaluated the outcome of DTT and non-DTT PJI in a prospective cohort treated with a two-stage exchange according to a standardized algorithm. Methods Patients with hip and knee PJI from 2013 to 2015 were prospectively included and followed up for ≥ 2 years. DTT PJI was defined as growth of microorganism(s) resistant to all available biofilm-active antibiotics. The Kaplan–Meier survival analysis was used to compare the probability of infection-free survival between DTT and non-DTT PJI and the 95% confidence interval (95% CI) was calculated. Results Among 163 PJI, 30 (18.4%) were classified as DTT and 133 (81.6%) as non-DTT. At a mean follow-up of 33 months (range 24–48 months), the overall treatment success was 82.8%. The infection-free survival rate at 2 years was 80% (95% CI 61–90%) for DTT PJI and 84% (95% CI 76–89%) for non-DTT PJI (p = 0.61). The following mean values were longer in DTT PJI than in non-DTT PJI: hospital stay (45 vs. 28 days; p < 0.001), prosthesis-free interval (89 vs. 58 days; p < 0.001) and duration of antimicrobial treatment (151 vs. 117 days; p = 0.003). Conclusions The outcome of DTT and non-DTT PJI was similar (80–84%), however, at the cost of longer hospital stay, longer prosthesis-free interval and longer antimicrobial treatment. It remains unclear whether patients undergoing two-stage exchange with a long interval need biofilm-active antibiotics. Further studies need to evaluate the outcome in patients treated with biofilm-active antibiotics undergoing short vs. long interval.

Background: There are currently no recommendations to direct the optimal diagnosis and treatment of fungal osteoarticular infections, including prosthetic joint infections and osteomyelitis. Active agents (fluconazole; amphotericin B) are regularly applied per os or intravenously. Other drugs such as voriconazole are used less frequently, especially locally. Voriconazole is less toxic and has promising results. Local antifungal medication during primary surgical treatment has been investigated by implanting an impregnated PMMA cement spacer using intra-articular powder or by daily intra-articular lavage. The admixed dosages are rarely based on characteristic values and microbiological and mechanical data. The purpose of this in vitro study is to investigate the mechanical stability and efficacy of antifungal-admixed PMMA with admixed voriconazole at low and high concentrations. Methods: Mechanical properties (ISO 5833 and DIN 53435) as well as efficacy with inhibition zone tests with two Candida spp. were investigated. We tested three separate cement bodies at each measuring time (n = 3) Results: Mixing high dosages of voriconazole causes white specks on inhomogeneous cement surfaces. ISO compression, ISO bending, and DIN impact were significantly reduced, and ISO bending modulus increased. There was a high efficacy against C. albicans with low and high voriconazole concentrations. Against C. glabrata, a high concentration of voriconazole was significantly more efficient than a dose at a low concentration. Conclusions: Mixing voriconazole powder with PMMA (Polymethylmethacrylate) powder homogeneously is not easy because of the high amount of dry voriconazole in the powder formulation. Adding voriconazole (a powder for infusion solutions) has a high impact on its mechanical properties. Efficacy is already good at low concentrations.

Amphotericin B is used for local delivery from polymethylmethacrylate to treat fungal prosthetic joint infections. The optimal amphotericin B formulation and the influence of different poragens in the bone cements are unknown. To investigate the necessary amount of amphotericin B in the bone cement to prevent Candida biofilm several amphotericin B formulations were studied: non-liposomal and liposomal with or without poragen gentamicin. For the non-liposomal formulation, standard bile salt, the sodium deoxycholate, was used and additionally N-methyl-D-glucamine/palmitate was applied. The activity of the released amphotericin B was tested against C. albicans, C. glabrata, C. parapsilosis and C. krusei biofilms with application of the isothermal calorimeter and standard microbiological methods. Compressive strength was measured before and after antifungal elution from the cements. There is less aggregated N-methyl-D-glucamine/palmitate amphotericin B released but its antifungal activity is equivalent with the deoxycholate amphotericin B. The minimum quantity of antifungal preventing the Candida biofilm formation is 12.5 mg in gram of polymer powder for both non-liposomal formulations. The addition of gentamicin reduced the release of sodium deoxycholate amphotericin B. Gentamicin can be added to N-methyl-D-glucamine/palmitate amphotericin B in order to boost the antifungal release. When using liposomal amphotericin B more drug is released. All amphotericin B formulations were active against Candida biofilms. Although compressive strength slightly decreased, the obtained values were above the level of strength recommended for the implant fixation. The finding of this work might be beneficial for the treatment of the prosthetic joint infections caused by Candida spp.

Biofilm-active antibiotics are suggested to improve the outcome in periprosthetic joint infection (PJI). However, the type, dose and duration of antibiotic treatment is rarely specified and their impact on outcomes is unknown. In this prospective cohort study, the infection and functional outcome were compared in 131 patients with knee PJI treated with or without biofilm-active antibiotics. The infection and functional outcome were evaluated by the Kaplan–Meier survival method to estimate the probability of infection-free survival; comparison between subgroups was performed by log-rank test. The influence of variables on the survival probability was analysed using univariate and multivariate Cox proportional-hazards regression models. Functional outcome was evaluated by pain intensity and the Knee injury and Osteoarthritis Outcome Score (KOOS). Among the 131 patients, 55 (42%) were treated with biofilm-active antibiotics and 76 (58%) were treated with non-biofilm-active antibiotics. The median follow-up period was 3.7 years (range, 2.0–7.6 years), and the infection-free survival probability was 74% (95% CI 61–85%) after 1 year and 56% (95% CI 47–66%) after 2 years. Infection-free survival after 1 year was better for patients who received biofilm-active antibiotics compared with those who did not (83% vs. 70%; P = 0.040) and remained superior after 2 years (67% vs. 48%; P = 0.038). In addition, biofilm-active antibiotic treatment was associated with lower pain intensity (P = 0.006) and higher KOOS on all five subscales. In patients with knee PJI, biofilm-active antibiotic therapy was associated with better infection outcome, lower pain intensity and better joint function.

Abstract Purpose Biofilm-active antibiotics are suggested to improve the outcome of implant-associated infections; however, their role in infections after spinal instrumentation is unclear. Therefore, we evaluated the outcome of patients with spinal implant-associated infections treated with and without biofilm-active antibiotics. Methods The probability of infection-free survival was estimated for treatment of spinal implant-associated infections with and without biofilm-active antibiotics using the Kaplan–Meier method; Cox proportional-hazards regression model was used to identify factors associated with treatment failure. Results Among 93 included patients, early-onset infection was diagnosed in 61 (66%) and late-onset in 32 infections (34%). Thirty patients (32%) were treated with biofilm-active antibiotic therapy and 63 (68%) without it. The infection-free survival after a median follow-up of 53.7 months (range, 8 days-9.4 years) was 67% (95% confidence interval [CI], 55–82%) after 1 year and 58% (95% CI 43–71%) after 2 years. The infection-free survival after 1 and 2 years was 94% (95% CI 85–99%) and 84% (95% CI 71–93%) for patients treated with biofilm-active antibiotics, respectively, and 57% (95% CI 39–80%) and 49% (95% CI 28–61%) for those treated without biofilm-active antibiotics, respectively (p = 0.009). Treatment with biofilm-active antibiotics (hazard ratio [HR], 0.23, 95% CI 0.07–0.77), infection with Staphylococcus auras (HR, 2.19, 95% CI 1.04–4.62) and polymicrobial infection (HR, 2.44, 95% CI 1.09–6.04) were significantly associated with treatment outcome. Severe pain was observed more often in patients without biofilm-active antibiotic therapy (49% vs. 18%, p  = 0.027). Conclusion Treatment with biofilm-active antibiotics was associated with better treatment outcome and less postoperative pain intensity.

Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Thereafter, this needs to be adapted according to culture results as soon as possible. Finally, a minimum follow-up of 12 months after cessation of therapy is recommended. Standardized patient outcome measures purely focusing on FRI are currently not available but the patient-reported outcomes measurement information system (PROMIS) seems to be the preferred tool to assess the patients’ short and long-term outcome. This review summarizes the current general principles which should be considered during the whole treatment process of patients with FRI based on recommendations from the FRI Consensus Group.