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Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve “target-and-release” drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (hydroxybisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.

This work gives an overview of research and development carried out at IIT Madras, using glass fibre reinforced gypsum (GFRG) panels, to provide an innovative solution for rapid and affordable mass housing. The GFRG panels (124 mm thick), made from recycled industrial waste gypsum (from the fertilizer industry), are prefabricated in 3 m × 12 m sizes with cellular cavities inside, which can be filled with reinforced concrete wherever required and can be used as walls as well as floor slabs. The tests carried out (over the past 12 years) establish the performance of GFRG building systems to resist gravity and lateral loads as a load-bearing system (without beams and columns) in multi-storeyed buildings up to 8–10 storeys, with adequate strength, serviceability, durability and ductility. A two-storeyed four-apartment demonstration building has also been successfully constructed in the IIT Madras campus and presently a mass housing scheme (40 apartment units) using this technology is being demonstrated at Nellore. A structural design code has also been approved by the Bureau of Indian Standards, based on the extensive studies carried out on GFRG building systems.