Next-generation treatment strategies to treat osteomyelitis with complete eradication of pathogen at the bone nidus and prevention of emergence of drug resistance is a real challenge in orthopedics. Conventional treatment strategies including long-term adherence of patients to systemic antibiotic delivery, local delivery using nondegradable vehicles, and surgical debridement are not completely effective in achieving successful results. In this study, a broad-spectrum antibiotic, rifampicin (RFP), was incorporated into a biphasic nanohydroxyapatite (nHAP)/calcium sulfate ceramic carrier (NC) system. In vivo release and distribution of rifampicin was evaluated for a period of one month by implanting NC and NC + RFP in a subcutaneous pouch in a rat model. We detected the RFP in bone and implanted NC scaffolds even after day 28 and the concentration was still higher than the minimal inhibitory concentration of RFP when it was implanted with NC in an abdominal subcutaneous pouch. Moreover, we also observed the accumulation of RFP in bone and NC when administered orally, showing strong binding between RFP and nHAP. Additionally, we generated an osteomyelitis bone infection model in the rat tibia using Staphylococcus aureus as an infective agent to evaluate the antibacterial and osteogenic efficiency of RFP containing NC as a delivery system. S. aureus mediated implant infection is a major problem in orthopedics. The results suggested that NC loaded with RFP could eradicate the pathogen completely in the bone nidus. Further, defect healing and bone formation were also evaluated by micro-CT and histological analysis demonstrating proper trabecular-type bone formation at the debridement site and complete healing of the defect when NC + RFP was implanted. Our findings provide an insight into the use of an nHAP based ceramic matrix as a carrier of rifampicin to eradicate the bone infection and simultaneously promote bone healing at the bone nidus.

Antimicrobial resistance (AMR) has been increasing unrelentingly worldwide, thus negatively impacting human health. The discovery and development of novel antibiotics is an urgent unmet need of the hour. However, it has become more challenging, requiring increasingly time-consuming efforts with increased commercial risks. Hence, alternative strategies are urgently needed to potentiate the existing antibiotics. In this context, short cationic peptides or peptidebased antimicrobials that mimic the activity of naturally occurring antimicrobial peptides (AMPs) could overcome the disadvantages of AMPs having evolved as potent antibacterial agents. Besides their potent antibacterial efficacy, short peptide conjugates have also gained attention as potent adjuvants to conventional antibiotics. Such peptide antibiotic combinations have become an increasingly cost-effective therapeutic option to tackle AMR. This Review summarizes the recent progress for peptide-based small molecules as promising antimicrobials and as adjuvants for conventional antibiotics to counter multidrug resistant (MDR) pathogens.

A novel strategy for modulating the self-assembled morphology of diphenylalanine peptides based on centrifugal force mediated spin coating and spin dewetting triggered by disjoining pressure in ultra-thin films during rotation.

A peptide-based molecule offers synergism with fluoroquinolones and their combination “resensitizes” fluoroquinolone-resistant strains of S. aureus, thus presenting a strategy for antibiotic potentiation against nosocomial infections.