Efficacy of NEMO-binding domain peptide used to treat experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus: an in-vivo study

Abstract

PurposeTreatment of chronic osteomyelitis (bone infection) remains a clinical challenge. Our previous study had demonstrated that NEMO-binding domain (NBD) peptide effectively ameliorates the inhibition of osteoblast differentiation by TNF-α in vitro. In this work, NBD peptide was evaluated in vivo for treating chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA) in a rabbit model.MethodsTibial osteomyelitis was induced in 50 New Zealand white rabbits by tibial canal inoculation of MRSA strain. After 3 weeks, 45 rabbits with osteomyelitis were randomly divided into four groups that correspondingly received the following interventions: 1) Control group (9 rabbits, no treatment); 2) Van group (12 rabbits, debridement and parenteral treatment with vancomycin); 3) NBD + Van group (12 rabbits, debridement and local NBD peptide injection, plus parenteral treatment with vancomycin); 4) NBD group (12 rabbits, debridement and local NBD peptide injection). Blood samples were collected weekly for the measurement of leucocyte count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. The rabbits in all four groups were sacrificed 6 weeks after debridement; the anti-infective efficacy was evaluated by radiological, histological, and microbiological examination, and promotion of bone remodeling was quantified by micro-CT using the newly formed bone.ResultsExcept two rabbits in the Control group and one in the NBD group that died from severe infection before the end point, the remaining 42 animals (7, 12, 12, 11 in the Control, Van, NBD + Van, and NBD group respectively) were sacrificed 6 weeks after debridement. In general, there was no significant difference in the leucocyte count, and ESR and CRP levels, although there were fluctuations throughout the follow-up period after debridement. MRSA was still detectable in bone tissue samples of all animals. Interestingly, treatment with NBD peptide plus vancomycin significantly reduced radiological and histological severity scores compared to that in other groups. The best therapeutic efficacy in bone defect repair was observed in the NBD peptide + Van group.ConclusionsIn a model of osteomyelitis induced by MRSA, despite the failure in demonstrating antibacterial effectiveness of NBD peptide in vivo, the results suggest antibiotics in conjunction with NBD peptide to possibly have promising therapeutic potential in osteomyelitis.

High Mycoplasma pneumoniae loads and persistent long-term Mycoplasma pneumoniae DNA in lower airway associated with severity of pediatric Mycoplasma pneumoniae pneumonia

“…In our present study, type 1 was the main genotype and the total MR-MP rate was high up to 97.6% (40/41). In addition, the MR-MP rate of genotype 1 and genotype 2 was 100% (37/37) and 75% (3/4) respectively, which was consistent with our previous report [22]. Macrolides are still used as first-line agents at high frequencies in countries with a high burden of MR-MP strains, such as China and Japan, mainly because of their low minimum inhibitory concentrations against the bacteria, anti-inflammatory effect and low toxicity in young children.…”

Plate-associated localized osteitis in mini-pig by biofilm-forming Methicillin-resistant Staphylococcus aureus (MRSA): establishment of a novel experimental model

“…As we already explain in the introduction, there are numerous studies that aim to prevent the colonization of SA in bone from the outset [28][29][30][31][32]. Despite this large spectrum of studies, almost all were only conducted with Methicillin-sensible SA (MSSA) in small animal models.…”

Prophylactic Effects of NFκB Essential Modulator–Binding Domain Peptides on Bone Infection: An Experimental Study in a Rabbit Model

“…Extensive chronic osteomyelitis was achieved within 3 weeks of S. aureus infection based on the well-established animal models. 27 , 35 S. aureus is the major pathogen among staphylococci, the most common cause of bone infection, and also activates the NFκB pathway. 32 , 33 Our in vivo study of S. aureus infection showed that NBD peptides exhibited infection-prevention efficacy, with lower infection rate and bacterial quantity, as well as radiological and histological scores for osteomyelitis, comparable to cefazolin, providing an opportunity to selectively abrogate the S. aureus –induced activation of NFκB.…”