Table II.
Key findings of each study.
| Study | Key findings | Other assessments conducted |
|---|---|---|
| Li et al 39 | 1) Mg was highly effective against MRSA-induced osteomyelitis and improved the peri-implant bone formation. 2) The antibiofilm effects of Mg were achieved by reducing bacterial icaA and agr RNAIII transcription levels. |
|
| Hazer et al 53 | 1) PP-g-PEG-A g grafted pedicle screw showed antimicrobial effect and inhibit biofilm formation. 2) Complications: 4 of 14 rats had pus formation localized in the fascia plane. |
|
| Yao et al 67 | The current study provides a novel biomaterial in preventing Staphylococcus aureus related implantation infections and bone loss. |
|
| Li et al 54 | The Mg-Cu alloy showed antibacterial ability demonstrated by microbiological and biofilm formation assays with reduced expression of biofilm, virulence, and antibiotic-resistant genes. |
|
| Min et al 40 | The rapid release of antibiotics and sustained release of BMP-2 successfully eradicated the biofilm and accelerated bone tissue formation. |
|
| Gracia et al 66 | Cefuroxime significantly reduced the bacteria load on bone and K-wire, which was consistent with the antimicrobial effects of 48 hours biofilm in vitro. | Serum antibodies against S. aureus |
| Tran et al 41 | The nanoparticles coating strongly inhibited biofilm formation on the implant and reduced the number of CFU in the surrounding tissue. |
|
| Ashbaugh et al 26 | The polymeric coating can be applied to deliver various antibiotics to prevent biofilm-associated orthopaedic infection by varying the PLGA versus PCL ratios. |
|
| Carli et al 27 | The antimicrobial effects of PMMA spacers fail to eradicate periprosthetic joint infection in the clinically representative mouse model. |
|
| Inzana et al 2015 33 | Co-delivery of rifamycin and vancomycin from 3D-printed CPS significantly reduced the bacteria burden but cannot fully eradicate the biofilm on implant. |
|
| van der Horst et al 42 | 1) 5 days daily injection significantly reduced CFU but cannot eradicate. 2) 10 days of systemic ceftriaxone and local gentamicin showed complete clearance. |
None |
| Greimel et al 48 | 1) Only mono rifampin can significantly reduce the biofilm on the implant but not the bone and soft tissue. 2) Mox plus rif or Flu plus rifamycin showed significant reduction in CFU in bone, soft-tissue and biofilm, and Mox + rif showed eradication of biofilm on implant, but not on bone tissue. |
None |
| Zhu et al 43 | β-defensin 3 inhibits the bacterial growth by regulating inflammatory and immune response in the MRSA-induced implant biofilm infection. Complications: 3 rats died with swelling and white purulent secretion on the wound. |
|
| Jensen et al 59 | 1,600 times of MIC is required to prevent the bacteria attachment, indicating that susceptibility in intro may not reflect in vivo susceptibility. |
|
| Boles et al 28 | Chitosan loaded vancomycin and amikacin (5 mg/ ml) showed higher percentage of clearance rate, which can be further augmented by double the serum concentration. | None |
| Singh et al 60 | NPWTi therapy is associated with decreased bacterial load and biofilm formation compared to wet-to-dry wound dressing. | None |
| Kandemir et al 52 | Clarithromycin enhanced the activity of concomitantly used bactericidal agents by destroying the biofilm formation. | None |
| Inzana et al 2015 34 | PMMA-loaded vancomycin only showed significant effect of decreasing the bacterial burden and osteolysis when combined with systemic antibiotics in a revision model. |
|
| Fang et al 49 | 1) Systemic application of vancomycin did not eradicate the biofilm infection. 2) Magnet nanoparticles combined with local administration of vancomycin enhance the eradication of bacteria in the biofilm-based colony. |
|
| Tomizawa et al 35 | Combination with rifampin is recommended to inhibit implant associated osteomyelitis, due to the limited effects of monotherapy, especially cefazolin. | None |
| Lindsay et al 29 | The S. aureus biofilm is redox-sensitive and ROS scavenger treatment improved the efficacy of antibiotic treatment on bacteria clearance. |
|
| Jørgensen et al 30 | 1) This model is suitable for testing antimicrobial agent treatment as both biofilm and CFU can be assessed. 2) 14 days vancomycin injection was unable to eradicate biofilm infection. 3) Key research gap: despite clear dosage, the serum vancomycin levels cannot be monitored. |
None |
| Shiono et al 65 | The presence of an implant is essential for the development of delayed surgical site infection model. |
|
| Thompson et al 31 | 1) In vitro biofilm-producing activity was associated with the in vivo gram-negative bone infection characterized by bacteria infection, biofilm formation reactive bone changes and inflammatory cells infiltration. 2) Biospecific antibody-targeting Pseudomonas aeruginosa virulence factors reduced the bacteria burden in vivo. |
|
| Nishitani et al 11 | 1) This study showed the S. aureus attachment, proliferation and maturation from day 0 to day 7. 2) Biofilm dispersal was achieved by S. aureus migration in an agrin-dependent way, as presented with empty lacunae and retention of few culture-negative, RNA-positive residual bacteria. |
None |
| Gahukamble et al 55 | 1) C. acnes and S. lugdunensis infection model caused different clinical presentations, including low-grade infection in C. acnes and acute infection in S. lugdunensis. 2) This model is relevant to the periprosthetic joint infection and nonunion fracture fixation, which may be reported as aseptic failure. |
|
| Lovati et al 50 | 1) The severity of osteomyelitis signs and nonunion rate was dosage-dependent. 2) This study provides a relevant preclinical model for subclinical infections in orthopaedic trauma. |
|
| Johansen et al 61 | Bacteria embedded in the opaque biofilm matrix was demonstrated by FISH in a haematogenously spread osteomyelitis model. |
|
| Zhang et al 56 | This study provides a novel rabbit model of infection following internal fixation with biofilm formation. |
|
| Cahill et al 32 | Local application of high-dosage rifampin-loaded hydrogel reduced the bacteria load, which was further enhanced when combined with systemic rifampin application. Complications: two rats died within 24 hours postoperatively with no specified course. |
|
| Marston et al 44 | Local tobramycin showed more significant CFU reduction than doxycycline in the synovium, supporting the current evidence of local application of antibiotics |
|
| Wei et al 51 | IA injection is superior to systemic injection, whereas the combined treatment can eradicate the infection in the two-week course after revision surgery. |
|
| Lovati et al 38 | Diabetic mice challenged with a single inoculum of S. aureus displayed severe osteomyelitis changes and biofilm formation on implant. Complications: two mice had severe signs of infection including joint abscess and fistulae. |
|
| Hu et al 47 | TaON-Ag nanocomposite coated titanium inhibited pathogen adhesion and biofilm formation in both S. aureus and Escherichia coli in vivo. |
|
| Stewart et al 64 | Vancomycin-derivatized plate surfaces inhibited implant colonization with S. aureus and supported bone healing in an infected large animal model. |
|
| Tomizawa et al 37 | Biofilm‐producing S. epidermidis RP62A does not cause prominent osteolysis, reactive bone formation, but persists in biofilm, stimulates a low-grade proinflammatory environment, and inhibits osseous integration. |
|
| Schaer et al 63 | The presence of a N, Ndodecyl,methyl PEI coating on the surface of a metal implant was effective in eliminating the clinical signs of infection, preventing biofilm formation and support bone healing. |
|
| Gordon et al 57 | This rabbit model could serve a valuable preclinical model of IASI to study the pathogenesis and novel diagnostic and therapeutic methods, which allows for real-time monitoring of bacteria burden and inflammation. |
|
| Hadden et al 46 | The study showed a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Complications: One rat with prosthesis dislocation and one with implant loosening. |
|
| Windolf et al 36 | Implant-associated localized osteitis in murine femur fracture by biofilm-forming S. aureus was established, with increased leucocyte count and IL-6 levels |
|
| Wu et al 45 | The overexpression of ASyycG leads to a reduction in biofilm formation and bacterial pathogenicity in vivo. |
|
| Hovis et al 58 | Vancomycin spreading at the infection site successfully prevents infection of the bone and implant in all cases. |
|
| Blirup-Plum et al 62 | The injectable ceramic bone graft substitute loaded with gentamycin cannot be used as a standalone alternative to extensive debridement or be used without the addition of systemic antibiotics. |
|
ABH, alcian blue/haematoxylin; BMP-2, bone morphogenetic protein 2; CFU, colony-forming unit; CPS, calcium phosphate scaffold; CV, crystal violet; ELISA, enzyme-linked immunosorbent assay; FDG, fluorodeoxyglucose; FISH, fluorescence in situ hybridization; H&E, haematoxylin and eosin; IA, intra-articular; IASI, implant-associated spinal infection; IHC, immunohistochemistry; IL, interleukin; K-wire, Kirschner-wire; LC/MS, liquid chromatography-mass spectrometry; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; NF-κB, nuclear factor kappa B; NPWTi, negative pressure wound therapy with instillation; PCL, poly-є-caprolactone; PCR, polymerase chain reaction; PEI, polyethyleneimine; PET, positron emission tomography; PJI, periprosthetic joint infection; PLGA, poly(lactic-co-glycolic acid); PMMA, polymethyl methacrylate; ROS, reactive oxygen species; TLR-4, toll-like receptor 4; TNF-α, tumour necrosis factor-alpha; TRAP, tartrate-resistant acid phosphatase.