Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics?A systematic review and narrative synthesis

Approximately 40%of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence.Staphylococcus aureus,the predominant pathogen in human osteomyelitis,is known to persist by phenotypic adaptation as small-colony variants(SCVs)and by formation of intracellular reservoirs,including those in major bone cell types,reducing susceptibility to antibiotics.Intracellular infections with S.aureus are difficult to treat;however,there are no evidence-based clinical guidelines addressing these infections in osteomyelitis.We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S.aureus relevant to osteomyelitis,including protein biosynthesis inhibitors(lincosamides,streptogramins,macrolides,oxazolidines,tetracyclines,fusidic acid,and aminoglycosides),enzyme inhibitors(fluoroquinolones and ansamycines),and cell wall inhibitors(beta-lactam inhibitors,glycopeptides,fosfomycin,and lipopeptides).The PubMed and Embase databases were screened for articles related to intracellular S.aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment,which resulted in 34 full-text articles fitting the inclusion criteria.The combined findings of these studies were largely inconclusive,most likely due to the plethora of methodologies utilized.Therefore,the reported findings in the context of the models employed and possible solutions for improved understanding are explored here.While rifampicin,oritavancin,linezolid,moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments,the scientific evidence for these is still relatively weak.We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S.aureus osteomyelitis to improve treatments and patient outcomes.

Collecting a comprehensive evidence base to monitor fracture rehabilitation: A case study

AIM: To determine the feasibility and potential role of combining radiostereometric analysis(RSA), gait analysis and activity monitoring in the follow-up of fracture patients.METHODS: Two patients with similar 41B3 tibial plateau fractures were treated by open reduction internal fixation augmented with impaction bone grafting and were instructed to partial weight bear to 10 kg for the first six postoperative weeks. Fracture reduction and fixation were assessed by postoperative computer tomographic(CT) scanning. Both patients had tantalum markers inserted intra-operatively to monitor their fracture stability during healing using RSA and differentially loaded RSA(DLRSA) at 6 and 12 wk postoperatively. Gait analyses were performed at 1, 2, 6, and 12 wk postoperatively. Activity monitors were worn for 4 wk between the 2 and 6 wk appointments. In addition to gait analysis, knee function was assessed using the patient reported Lysholm scores, and doctor reported knee range of motion and stability, at 6 and 12 wk postoperatively.RESULTS: There were no complications. CT demonstrated that both fractures were reduced anatomically. Gait analysis indicated that Patient 1 bore weight to 60% of body weight at 2 wk postoperative and 100% at 6 wk. Patient 2 bore weight at 10% of body weight to 6 wk and had very low joint contact forces to that time. At 12 wk however, there was no difference between the gait patterns in the two patients. Patient 1 increased activities of moderate-vigorous intensity from 20 to 60 min/d between 2 and 6 postoperative weeks, whereas Patient 2 remained more stable at 20-30 min/d. The Lysholm scores were similar for both patients and did not improve between 6 and 12 wk postoperatively. DLRSA examination at 12 wk showed that both patients were comfortable to weight bear to 80 kg and under this weight the fractures displaced less than 0.4 mm. RSA measurements demonstrated over time fracture migrations of less than 2 mm in both cases. However, Patient 2, who followed the postoperative weight bearing instructions most closely, displaced less(0.3 mm vs 1.6 mm). CONCLUSION: This study demonstrates the potential of using a combination of RSA, gait analysis and activity monitoring to obtain a comprehensive evidence base for postoperative weight bearing schedules during fracture healing.