Eradication of Staphylococcus aureus in Implant-Associated Osteomyelitis by an Injectable in situ-Forming Depot Antibiotics Delivery System
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Eradication of Staphylococcus aureus in Implant-Associated Osteomyelitis by an Injectable in situ-Forming Depot Antibiotics Delivery System. / Fuglsang-Madsen, Albert Juan; Henriksen, Nicole Lind; Chávez, Elizabeth Serrano; Kvich, Lasse Andersson; Birch, Julie Knippel Melsted; Hartmann, Katrine Top; Eriksen, Thomas; Bjarnsholt, Thomas; Gottlieb, Hans; Andresen, Thomas Lars; Jensen, Louise Kruse; Henriksen, Jonas Rosager; Hansen, Anders Elias.
I: The Journal of Infectious Diseases, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Eradication of Staphylococcus aureus in Implant-Associated Osteomyelitis by an Injectable in situ-Forming Depot Antibiotics Delivery System
AU - Fuglsang-Madsen, Albert Juan
AU - Henriksen, Nicole Lind
AU - Chávez, Elizabeth Serrano
AU - Kvich, Lasse Andersson
AU - Birch, Julie Knippel Melsted
AU - Hartmann, Katrine Top
AU - Eriksen, Thomas
AU - Bjarnsholt, Thomas
AU - Gottlieb, Hans
AU - Andresen, Thomas Lars
AU - Jensen, Louise Kruse
AU - Henriksen, Jonas Rosager
AU - Hansen, Anders Elias
PY - 2024
Y1 - 2024
N2 - BackgroundBone infections with Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics.MethodsCarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology.ResultsCarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9 of 12 and full eradication in 5 of 12 pigs.ConclusionsSustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care.
AB - BackgroundBone infections with Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics.MethodsCarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology.ResultsCarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9 of 12 and full eradication in 5 of 12 pigs.ConclusionsSustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care.
U2 - 10.1093/infdis/jiae139
DO - 10.1093/infdis/jiae139
M3 - Journal article
C2 - 38537273
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
ER -
ID: 389898562