Efficacy of Ciprofloxacin-Releasing Bioabsorbable Osteoconductive Bone Defect Filler for Treatment of Experimental Osteomyelitis Due to
            <i>Staphylococcus aureus</i>

Koort, Jyri K.; Mäkinen, Tuula; Suokas, Esa; Veiranto, Minna; Jalava, Jari; Knuuti, Juhani; Törmälä, Pertti; Aro, Hannu T.

doi:10.1128/aac.49.4.1502-1508.2005

Cited by 58 publications

(53 citation statements)

References 39 publications

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“…Since biodegradable polymers are not osteoconductive, osteoconductive ceramics have been combined with biodegradable polymers for use as bone substitutes [20][21][22][23] . Recently, cyprofloxacin (CFLX)-loaded poly(D,L)-lactide matrix containing bioglass microspheres of 90-125 µm diameter showed in vivo efficacy in controlling osteomyelitis and osteoconduction 24,25) . In a previous study, we developed a composite that consists of porousβ-tricalcium phosphate (βTCP) ceramic matrix with gatifloxacine (GFLX)-loaded poly--caprolactone (PCL) in the pores and on the surfaces of βTCP 26) .…”

Section: Introductionmentioning

confidence: 99%

Gatifloxacine-loaded PLGA and β-tricalcium phosphate composite for treating osteomyelitis

et al. 2011

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Gatifloxacine (GFLX)-containing poly(lactide-co-glycolide) (PLGA) was introduced to the pores and surfaces of porous β-tricalcium phosphate (βTCP) granules by melt compounding whereby no toxic solvent was used. The granular composite of GFLX-loaded PLGA and βTCP released GFLX for 42 days in Hanks' balanced solution and exhibited sufficient in vitro bactericidal activity against Streptococcus milleri and Bacteroides fragilis for at least 21 days. For in vivo evaluation, the granular composite was implanted in the dead space created by the debridement of osteomyelitis lesion induced by S. milleri and B. fragilis in rabbit mandible. After a 4-week implantation, the inflammation area within the debrided area was markedly reduced accompanied with osteoconduction and vascularization in half of the rabbits, and even disappeared in one of the six rabbits without any systemic administration of antibiotics. Outside the debrided area, inflammation and sequestrum were observed but the largest of such affected areas amounted to only 0.125 times of the originally infected and debrided area. These findings showed that the granular composite was effective for the local treatment of osteomyelitis as well as an osteoconductive scaffold which supported and encouraged vascularization.

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Section: Introductionmentioning

confidence: 99%

Gatifloxacine-loaded PLGA and β-tricalcium phosphate composite for treating osteomyelitis

et al. 2011

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“…15,16,22,23 In particular, the use of biodegradable implants could provide both high local bactericidal concentrations in tissue for the prolonged time, needed to completely eradicate the infection, and the possibility to match the rate of implant biodegradability, according to the type of infection treated, making surgical removal of the implant unnecessary. 7 However, most of the biodegradable implants evaluated have not given sufficient guarantees of mechanical loading seal and, until now, the FDA has approved only the use of bone cement with gentamicin or tobramycin for the second surgery in a two stage revision procedure.…”

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confidence: 99%

Preliminary investigations on a new gentamicin and vancomycin‐coated PMMA nail for the treatment of bone and intramedullary infections: An experimental study in the rabbit

Giavaresi¹,

Borsari²,

Fini³

et al. 2008

Journal Orthopaedic Research

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To evaluate a new gentamicin-vancomycin-impregnated (2:1) PMMA coating nail as a drug delivery device to treat bone and intramedullary infections, methicillin-resistant Staphylococcus aureus (MRSA) was used to induce femoral osteomyelitis in 20 New Zealand male rabbits. Four weeks after inoculum, the animals were submitted to debridement of infected femur canal, divided into four groups of five animals each and treated according to the following protocols: Group 1, insertion of a steel AISI316 intramedullary nail; Group 2, insertion of a gentamicin-vancomycin-impregnated PMMA nail; Group 3, no therapy; and Group 4 no fixation device and 1-week systemic antibiotic therapy with teicoplanin i.m. At 7 weeks after inoculum, the femurs were explanted sterilely. The radiological score showed that the lowest and best radiological score was observed in Group 2 that was significantly different from the other groups. The highest bacterial load in the femoral canal was found in Group 1, which was significantly different from Group 2 and Group 4 (p < 0.05). Histology showed that Group 2 produced a marked improvement (p < 0.005) of the bone injuries induced by the osteomyelitis in comparison with the other groups (Smeltzer score). The current findings showed that tested device might effectively lead to MRSA infection healing after surgical debridement and immediate implantation. Keywords: PMMA nail; gentamicin-vancomycin coating; intramedullary infections Bone and intramedullary infections are severe complications of fracture management (0-1% for closed fractures and 0-11% for open fractures) 1 and surgical repair (intramedullary nailing 2,3 and lengthening over nails with external fixation 4,5 ) of long bones. A prevalence of methicillin-resistant or gentamicin-resistant Staphyloccous aureus (SA) has been observed, and bone infection with methicillin-resistant SA (MRSA) has increased among patients with implanted orthopedic devices. The current management of these forms of osteomyelitis has two main aims: (a) to limit and resolve the infective process, by removing all foreign material (fixation device), followed by a meticulous debridement of the necrotic and infected area, and by administering systemically prolonged (4-6 weeks) high doses of antibiotics; 6-8 (b) to stabilize the fracture with alternative treatments, mainly external fixators, which are also not without complications. 1,9 The rationale for the long treatment time is based on the observation that revascularization of bone after debridement takes about 4 weeks. 10

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“…PLGA and PLA have been used in several studies that have been successful in treating infection (Garvin et al, 1994;Kanellakopoulou et al, 2000;Liu et al, 2002;Koort et al, 2005;Peng et al, 2010;Ambrose et al, 2014), but only a single antibiotic has been tested. The use of hydroxyapatite (Korkusuz et al, 1993;Shinto et al, 1992;Itokazu et al, 1997), calcium phosphate (Nandi et al, 2008) and calcium sulphate (Turner et al, 2005;Parker et al, 2011) in combination with one antibiotic have also been shown to treat infection.…”

Section: Discussionmentioning

confidence: 99%

A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a contaminated in vivo bone defect model

McLaren

White²,

Cox³

et al. 2014

eCM

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Open fractures are at risk of serious infection and, if infected, require several surgical interventions and courses of systemic antibiotics. We investigated a new injectable formulation that simultaneously hardens in vivo to form a porous scaffold for bone repair and delivers antibiotics at high concentrations to the local site of infection. Duration of antimicrobial activity against Staphylococcus aureus was determined using the serial plate transfer test. Ultimate compressive strength and porosity of the material was measured with and without antibiotics. The material was evaluated in vivo in an ovine medial femoral condyle defect model contaminated with S. aureus. Sheep were sacrificed at either 2 or 13 weeks and the defect and surrounding bone assessed using micro-computed tomography and histology. Antimicrobial activity in vitro persisted for 19-21 days. Sheep with antibiotic-free material and bacteria became infected, while those with antibiotic-containing material and bacteria did not. Similarly, new bone growth was seen in uninoculated animals with plain polymer, and in those with antibiotic polymer with bacteria, but not in sheep with plain polymer and bacteria. The antibiotic-impregnated scaffolds were effective in preventing S. aureus infections whilst supporting bone growth and repair. If translated into clinical practice, this approach might reduce the need for systemic antibiotics.

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Efficacy of Ciprofloxacin-Releasing Bioabsorbable Osteoconductive Bone Defect Filler for Treatment of Experimental Osteomyelitis Due to Staphylococcus aureus

Cited by 58 publications

References 39 publications

Gatifloxacine-loaded PLGA and β-tricalcium phosphate composite for treating osteomyelitis

Gatifloxacine-loaded PLGA and β-tricalcium phosphate composite for treating osteomyelitis

Preliminary investigations on a new gentamicin and vancomycin‐coated PMMA nail for the treatment of bone and intramedullary infections: An experimental study in the rabbit

A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a contaminated in vivo bone defect model

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