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. Author manuscript; available in PMC: 2022 Nov 28.
Published in final edited form as: ACS Infect Dis. 2021 Nov 11;7(12):3125–3160. doi: 10.1021/acsinfecdis.1c00465

Table 8.

Summary of Preclinical In Vivo Models from the Past Decade Used to Evaluate the Treatment of Orthopedic Implant-Associated Infections with Antimicrobial Agents and Biomaterials

models to evaluate treatment of implant-associated infections
animal model implant/location pathogen antimicrobial agent study duration key evaluation summary ref
mice – BALB/C titanium in femur S. aureusATCC gentamicin, vancomycin (local, sustained) 6 weeks (1) CFU counts antibiotic calcium sulfate/hydroxyapatite spacer for infection treatment 247
292131.35 × 105 CFU (2) collect blood
(3) X-rays
mice – BALB/C poly(ether ether ketone) and titanium in femur S. aureus Xen 36 vancomycin, rifampin (local, sustained) 1 week infection (1) CFU count 3D printed calcium phosphate and PMMA antibiotic spacers for infection treatment 118
8 × 104 CFU 3 weeks antibiotics (2) in vivo BLI
(3) X-rays
(4) micro-CT
(5) SEM biofilm
mice – BALB/C poly(ether ether ketone) and titanium in femur S. aureus Xen 36 vancomycin (local, sustained) 1 week infection (1) CFU count antibiotic PMMA spacers for infection treatment 119
8 × 104 CFU 3 weeks antibiotics (2) in vivo BLI
(3) micro-CT
mice – BALB/C titanium in femur S. aureus Xen 36 gentamicin (local, sustained) 1 week infection (1) CFU count antibiotic PMMA spacers for infection treatment 126
2.5 × 106 CFU 2 weeks antibiotics (2) X-rays
(3) in vivo BLI
mice – BALB/C stainless steel in tibia S. aureus UAMS-1 cefazoline, gentamicin, vancomycin, rifampin (systemic) 1 week infection (1) CFU count evaluation of combination antibiotics for treatment of implant biofilms 248
2.5 × 105 CFU 2 weeks antibiotics (2) SEM biofilm
(3) histology
mice – C57Bl/6 titanium in femur MRSA USA 300 linezolid, rifampin, vancomycin, daptomycin (systemic) 2 weeks infection (1) CFU count evaluation of combination antibiotics for treatment of implant infection 249
1 × 103 CFU 6 weeks antibiotics (2) in vivo BLI
(3) X-rays
(4) micro-CT
mice – C57Bl/6 titanium in tibia S. aureus Xen 36 vancomycin (local, sustained) 2 weeks infection (1) CFU count antibiotic PMMA spacers for infection treatment, need for intravenous antibiotics 127
3 × 105 CFU 4 weeks antibiotics (2) collect blood
(3) X-rays
rats – Sprague–Dawley Kirschner wire in tibia MRSA 40496/08 dalbavancin, vancomycin (systemic) 4 weeks (1) CFU count antibiotics for implant MRSA infection treatment 250
1–5 × 106 CFU (2) X-rays
rats – Sprague–Dawley intramedullary implant in tibia S. aureus EDCC 5055 none 6 weeks (1) CFU count use of CpG oligodeoxynucleotide to treat implant infections 251
1 × 103 CFU (2) histology
rats – Sprague–Dawley Kirschner wire in tibia MRSA N315 vancomycin (local, sustained) 2 weeks infection (1) CFU count antibiotic silicone cement for treatment of implant infection 260
1 × 108 CFU 4 weeks antibiotics (2) X-rays
(3) histology
rats – Sprague–Dawley PMMA in tibia MRSA ATCC 25923 fusidic acid (local, sustained), teicoplanin (systemic) 3 weeks infection (1) CFU count antibiotic cement with systemic antibiotics for treatment of implant infection 131
5 × 105 CFU 2 weeks antibiotics (2) histology
rats – Sprague–Dawley alginate-hyaluronic acid in femur S. aureus KCTC1621 vancomycin (local, sustained) 2 weeks infection (1) CFU count in situ gelling hydrogel for treatment of implant infections 85
1 × 104 CFU 3 and 6 weeks antibiotics (2) micro-CT
(3) collect blood
(4) X-rays
rats – Sprague–Dawley injectable alginate hydrogel in femur S. aureus ATCC 6538 fosfomycin (local, sustained) 1 week infection (1) CFU count injectable antibiotic hydrogel and bacteriophage for treatment of implant infections 105
5 × 104 CFU 1 week antibiotics (2) SEM
(3) histology
rats – Sprague–Dawley silver nanoparticles in gelatin sponge in tibia MRSA ATCC 43300 teicoplanin (local sustained) 3 weeks infection (1) X-ray silver nanoparticles for treatment of implant infections 252
1 × 107 CFU 3 weeks antibiotics (2) collect blood
rats – Wistar stainless steel in femur S. aureus ATCC 29213 moxifloxacin, flucloxacillin, rifampin, vancomycin (systemic) 1 week infection (1) CFU count evaluation of combination antibiotics for treatment of implant infection 253, 254
1 × 108 CFU 2 weeks antibiotics
rats – Wistar collagen sponge and PMMA beads in tibia S. aureus ATCC 292113 gentamicin, cefazolin (local, sustained) 3 weeks infection (1) CFU count comparison of antibiotic carrier for treatment of implant infections 86
5 × 106 CFU 2 or 4 weeks antibiotics
rats – Wistar poly(d-l-lactide-co-glycolide-co-ε-capro-lactone) in tibia S. aureus ciprofloxacin (local, sustained) 4 weeks infection (1) CFU count antibiotic poly(d-l-lactide-co-glycolide-co-ε-caprolactone) implant coating to treat infections 255
1 × 108 CFU 4 weeks antibiotics (2) collect blood
rats – Wistar magnetite encapsulated gelatin particles in tail vein S. aureus gentamicin (local, sustained) 2 weeks infection (1) X-rays magnetite antibiotic particles for treatment of implant infection 25
1 × 109 CFU 2 weeks antibiotic (2) collect blood
(3) histology
rats – Long-Evans titanium in humerus MRSA NR0 vancomycin (systemic) 6 day infection (1) CFU count electrical stimulation with antibiotics to treat implant infection 27
1 × 105 CFU 5 weeks antibiotics (2) X-rays
(3) histology
rabbits – New Zealand White silicone elastomer in tibia MRSA S271 ST20121238 daptomycin, rifampin, ceftaroline (systemic) 1 week infection (1) CFU count evaluation of combination antibiotics for treatment of MRSA implant infection 256, 257
5 × 107 CFU 10 days antibiotics
rabbits – New Zealand White stainless steel in tibia MRSA EDCC 5443 EDCC 5398 vancomycin (local, sustained) 4 weeks infection (1) CFU count antibiotic PMMA spacer for two-stage implant infection revision 132
1 × 105–1 × 107 CFU 4 weeks antibiotics (2) X-rays
(3) histology
rabbits – New Zealand White Ti6Al4 V in femur S. aureus ATCC 29213 gentamicin (local, sustained) 1 week infection (1) CFU count antibiotic PMMA chain for treatment of implant infection (copper and titanium oxide coated) 133
1 × 105 CFU 2 weeks antibiotics (2) collect blood
rabbits – New Zealand White borate bioactive glass in tibia MRSA ATCC 43300 vancomycin (local, sustained) 8 weeks (1) CFU count injectable borate bioactive glass for treating implant infection 30
1 × 108 CFU (2) collect blood
(3) X-rays
(4) histology
rabbits – New Zealand White calcium sulfate in tibia S. aureus ATCC 29213 gentamicin (local, sustained) 2 weeks infection (1) CFU count antibiotic calcium sulfate to treat implant infection 28
2 × 106 CFU 2 weeks antibiotics (2) X-rays
(3) collect blood
rabbits – New Zealand White PLGA in femur S. aureus ATCC 65389 vancomycin (local, sustained) 2 weeks infection (1) CFU count monitor treatment of implant infections with 18F-FDG-PET imaging 35
1 × 105 CFU 2 weeks antibiotics (2) 18F-FDG-PET imaging
rabbits – New Zealand White Hydroxyapatite–polyamino acid in tibia S. aureus vancomycin (local, sustained) 2 weeks infection (1) CFU counts antibiotic hydroxyapatite/polyamino acid for treatment of implant infection and osteogenesis 235
1 × 108 CFU 6 weeks antibiotics (2) X-ray
(3) collect blood
(4) histology
rabbits – New Zealand White stainless steel with silver particles in femur S. aureus ATCC 29213 none 3 weeks infection (1) CFU count silver nanoparticle implant coating to treat infections 258
3 × 106 CFU 3 weeks treatment (2) X-rays
(3) histology
(4) SEM
rabbits – New Zealand White Hydroxyapatite–polyamino acid PLGA in tibia S. aureus ATCC 25923 rifapentine (local, sustained) 4 weeks infection (1) CFU count antibiotic composite material for treatment of implant infection 106
3 × 108 CFU 4 weeks antibiotics (2) collect blood
(3) X-rays
(4) histology
(5) gait analysis
rabbits – New Zealand White chitosan thermosensitive hydrogel in tibia S. aureus Kanin vancomycin (local, sustained) 4 weeks infection (1) collect blood injectable thermosensitive hydrogel with quaternary ammonium chitosan for treatment of implant infections 24
1 × 108 CFU 4–8 weeks antibiotics (2) micro-CT
(3) histology
dogs – Beagle stainless steel in femur S. aureus ATCC 29213 ciprofloxacin (local, sustained) 4 weeks infection (1) CFU count amylose starch antibiotic coated implants to treat infection 259
3 × 108 CFU 6 weeks antibiotics (2) X-rays
(3) histology