ABSTRACT
BACKGROUND: The risk of osteomyelitis after open bone fracture may be reduced by locally applied antibiotics. ENC-41-HP (E41), which comprises ciprofloxacin linked to a 'bone seeking' bisphosphonate, loaded on to carrier Skelite calcium phosphate granules (E41-Skelite) has favourable in vitro characteristics for application to wounded bone. This study assessed E41-Skelite in a rat model of acute tibial osteomyelitis. METHODS: Mechanically induced tibial troughs were contaminated with approximately log10 4 colony forming units (c.f.u.) of Staphylococcus aureus (Cowan 1 strain) 'resistant' to E41 (minimum inhibitory concentration 8-16 microg/ml), lavaged and packed with Skelite alone, or with E41-Skelite slurry. Animals were killed at 24 h (n = 62), 72 h (n = 46) or 14 days (n = 12), and each tibia was assessed for S. aureus load (c.f.u./g tibia) and histological appearance (14 days only). RESULTS: At 24 and 72 h, the tibias of rats treated with E41-Skelite (n = 54) had a significantly lower mean (s.e.m.) load of S. aureus than animals that received Skelite alone (n = 54): log10 3.6(0.2) versus 6.4(0.1) c.f.u./g respectively at 24 h (P < 0.001, Mann-Whitney rank sum test) and log10 4.4(0.2) versus 6.6(0.1) c.f.u./g at 72 h (P < 0.001). At 14 days, E41-Skelite-treated tibias had fewer bacteria, no signs of osteomyelitis and histological signs of healing. CONCLUSION: E41-Skelite, a prototype granulated topical antibiotic delivery system, reduced the development of infection in experimental bone wounds.
Subject(s)
Anti-Infective Agents/administration & dosage , Ciprofloxacin/administration & dosage , Diphosphonates/administration & dosage , Osteomyelitis/drug therapy , Surgical Wound Infection/drug therapy , Animals , Calcium Phosphates , Drug Carriers , Drug Combinations , Rats , Staphylococcal Infections/drug therapy , Staphylococcus aureus , Tibial FracturesABSTRACT
A dramatic improvement in full skin thickness burn wounds in rats treated intravenously with the non-ionic surfactant Pluronic F-127 (F-127) has been demonstrated. In this study the F-127 was given 30 min postburn to simulate conditions encountered in a clinical setting. Anaesthetized male rats (300-320 g) received full skin thickness burns by immersion of the anterior chest wall (8 per cent body surface area in a 70 degrees C water-bath for 12 s). Burn wound area was measured immediately and after 48 h. Thirty minutes after the burn, half the animals received equal volumes (8 ml/kg body wt) of either saline or F-127 (12 mM/l concentration) via the tail vein. The animals autopsied at 48 h showed a significant (P < 0.05) reduction in the degree of wound contraction and the wound appeared grossly less damaged in the F-127-treated animals. Histologically, skin biopsies showed less of the microscopic damage usually associated with full skin thickness burns in the F-127-treated animals than in the saline controls. We also used thermography to measure skin temperature of the burn area at 90 min and 48 h postinjury demonstrating alterations in the F-127-treated animals (P < 0.05). In animals followed for 30 days postinjury, there was a significant (P < 0.01) improvement in the wound closure rates in the F-127-treated animals. These observations show a positive therapeutic effect of F-127 on the inflammatory process in the area of a burn that may improve wound healing.
Subject(s)
Burns/therapy , Poloxalene/administration & dosage , Animals , Burns/pathology , Burns/physiopathology , Infusions, Intravenous , Male , Rats , Skin Temperature , Thermography , Time Factors , Wound HealingABSTRACT
We contrasted the collagen-binding potential of the experimental osteomyelitis pathogen, Staphylococcus aureus strain SMH, to several other strains. These included Cowan 1 (binder), Wood 46 (non-binder) and six capsular variants. These measurements were made using an 125I-collagen binding assay. Formalin-killed S. aureus SMH strongly bound commercial type I iodinated collagen (dissociation constant, Kd = 2 x 10(-9) M). The extent of binding was similar to Cowan 1. Binding was saturable and not inhibited by 100 mM solutions of D-glucose, D-galactose, D-mannose, methyl-alpha-L-fucopyranoside, L-hydroxyproline or L-glycine. D-lactose gave moderate inhibition of binding to collagen, and L-fucose was strongly inhibitory. Trypsinized SMH did not bind collagen. None of four Ruthenium-red-staining staphylococci (encapsulated) avidly bound type I collagen. The encapsulated Smith strain, for example, did not bind to collagen but its capsule-negative variant, Smith compact, showed extensive binding. Three of five non-encapsulated S. aureus were strong collagen binders. These data suggest that the prototype bone pathogen binds to the major protein component of bone's extracellular matrix. Collagen-binding is promoted by protein adhesin(s), not capsule. The latter, in fact, appeared to interfere with this interaction. Binding was inhibited by solutions containing the simple monosaccharide, L-fucose.
