Aim. Debridement, Antibiotics, Irrigation, and implant Retention (DAIR) is a surgical treatment protocol suitable for some patients with fracture related infection (FRI). Clinically relevant pre-clinical models of DAIR are scarce and none have been developed in large animals. Therefore, this project aimed to develop a large animal model for FRI including a DAIR approach and compare outcomes after 2 or 5 weeks of infection. Method. Swiss Alpine sheep (n=8), (2–6 years, 50–80 kg) were included in this study. This study was approved by cantonal Ethical authorities in Chur, Switzerland. A 2 mm osteotomy was created in the tibia and fixed with a 10-hole 5.5 mm steel plate. Subsequently, 2.5 mL of saline solution containing 10. 6. CFU/mL of Staphylococcus aureus MSSA (ATCC 25923) was added over the plate. Sheep were observed for 2 (n=3) or 5 weeks (n=5) until revision surgery, during which visibly infected or necrotic tissues were removed, and the wound flushed with saline. All samples were collected for bacterial quantification. After revision surgery, the sheep were treated systemically for 2 weeks with flucloxacillin and for 4 weeks with rifampicin and cotrimoxazole. After 2 further weeks off antibiotics, the animals were euthanized. Bacteriological culture was performed at the end of the study. Bone cores were isolated from the osteotomy site and processed for Giemsa & Eosin and Brown and Brenn staining. A radiographical examination was performed every second week. Results. Bacteriological evaluation of the retrieved samples during revision surgery showed no significant difference between the 2 vs 5 weeks infection periods in term of total CFU counts. At the end of the study, radiographical examination showed callus formation over the osteotomy site in both groups, although the osteotomy was not completely healed in either group. At euthanasia, the 2 weeks infection group showed a higher soft tissue burden compared to the 5 weeks group, whereby the infection in the 5 weeks group was primarily located in the bone and bone marrow. Conclusions. The large animal model of FRI and DAIR was successfully established. Bacteriological outcomes highlight that the increasing duration of the infection does not change the outcome but the location of the infection from a predominantly soft tissue infection to a deeper bone and intramedullary (IM) channel infection. The debridement of the IM channel could potentially reduce the infection burden by eliminating those bacteria not easily reached by systemic antibiotics, though is not practical using conventional techniques

Aims. Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods. For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results. Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion. Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151

Aim. Prosthetic joint infection (PJI) concerns up to 20% of all prosthesis revision procedures. The IDSA recommends at least 2 weeks of intravenous antimicrobial therapy while most of the appropriate antibiotics in these settings have very high oral bioavailability (e.g., rifampicin, cotrimoxazole, fluoroquinolone, clindamycin, fusidic acid, linezolid and doxycycline). Method. AVAPOM is a monocentric retrospective non-inferiority study which included patients who received at least one of the highly bioavailable antibiotics listed above as a documented treatment (i.e., following the intravenous empirical post-operative antibiotic treatment) for PJIs in order to compare the remission rate of infection and the length of hospital stay (LOS). Patients were split between intravenous group (IV, from 1st January 2013 to 31st December 2014) and complete oral group (PO; since 1st January 2015) and were compared on both the PJI outcome regarding the last news available and the length of stay (LOS). Results. Out of a total of 216 patients, our intermediary analysis included 141 patients, with 73 receiving IV treatment (IV) and 68 oral treatment (PO). Remission was recorded in 21.9% IV patients and in 25.0% PO patients after a mean follow-up of 410.4 days ± 36.3 days (p=0.26). The global mortality reached 6.41% in IV group versus 1.25% in PO group (p=0.15). The medium LOS was 16.9 and 12.5 days for respectively IV and PO groups (p=0.0001). Conclusions. Our preliminary results suggest that complete oral and intravenous documented antibiotic treatment for patients with PJIs are comparable with regards to the patients' outcome but oral treatment is associated with a significant reduction of LOS

Early prosthetic joint infections (PJI) are managed with debridement, implant retention and antibiotics (DAIR). Our aim was to evaluate risk factors for failure after stopping antibiotic treatment. From 1999 to 2013 early PJIs managed with DAIR were prospectively collected and retrospectively reviewed. The main variables potentially associated with outcome were gathered and the minimum follow-up was 2 years. Primary endpoint was implant removal or the need of reintroducing antibiotic treatment due to failure. A total of 143 patients met the inclusion criteria. The failure rate after a median (IQR) duration of oral antibiotic treatment of 69 (45–95) days was 11.8%. In 92 cases PJI was due to gram-positive (GP) microorganisms, in 21 due to gram-negatives (GN) and 30 had a polymicrobial infection. In GP infections, combination of rifampin with linezolid, cotrimoxazole or clindamycin was associated with a higher failure rate (27.8%, P=0.026) in comparison to patients receiving a combination of rifampin with levofloxacin, ciprofloxacin or amoxicillin (8.3%) or monotherapy with linezolid or cotrimoxazole (0%) (Figure 1). Among patients with a GN infection, the use of fluoroquinolones was associated with a lower failure rate (7.1% vs 37.5%, P=0.044). Duration of antibiotic treatment was not associated with failure. The only factor associated with failure was the oral antibiotic selection, but not the duration of treatment. Linezolid, cotrimoxazole and clindamycin but not levofloxacin serum concentrations are reduced by rifampin; a fact that could explain our findings. Further studies monitoring serum concentration could help to improve the efficacy of these antibiotics when combining with rifampin

INTRODUCTION. Prosthetic joint related-infections (PJRI) are severe complications in orthopaedic surgery. Staphylococcus aureus and Staphylococcus epidermidis are the most commonly isolated pathogens from implants (1). The variable antimicrobial susceptibility found in these microorganisms, makes it necessary to perform individual susceptibility studies in order to select the best antibiotic combination for clinical management (2). MATERIAL AND METHODS. 35 staphylococcal strains (17 S. aureus, 18 S. epidermidis) were isolated from PJRI using a previously described sonication protocol (3). Biofilm-producing collection strains S. aureus 15981 (4) and S. epidermidis ATCC 35984 were also included in the study. In vitro susceptibility was evaluated against 7 antimicrobial agents: rifampin, vancomycin, ciprofloxacin, cotrimoxazole, cloxacillin, clindamycin, and daptomycin. Minimal Inhibitory Concentration (MIC) assays were determined according to EUCAST recommendations and breakpoints (5). Minimal Bactericidal Concentration (MBC) was also calculated by colony counting after plating the well contents. RESULTS. Antibiotic susceptibility assay results are shown in tables 1 and 2. It is especially remarkable the high number of meticillin-resistant S. aureus (MRSA) strains. Cotrimoxazole and clindamycin showed better results for S. aureus. Rifampin, vancomycin, and daptomycin showed a very good activity, although some resistant strains were detected for the first two. MBC values showed a strain-dependant activity of rifampin and vancomycin. Only daptomycin showed bactericidal activity against all the tested strains. DISCUSSION & CONCLUSIONS. The treatment of PJRI is still a challenge due to the variable antibiotic susceptibility and the growing number of multidrug-resistant strains. The high number of MRSA detected in our study, makes it necessary to search other antibiotics as an alternative to vancomycin, the traditional elective treatment. The high in vitro activity of daptomycin against the tested strains suggests that it could be an important alternative according to other promising results (6). Rifampin associated with other antimicrobials and cotrimoxazole, with a good in vitro activity against most MRSA strains, could be other potential strategies (7, 8)