Can Stimulan be used as a carrier for local antibiotic delivery in orthopedic infections?

Stimulan as a Local Antibiotic Carrier in Orthopedic Infections

Yes, Stimulan (calcium sulfate) can be effectively used as a carrier for local antibiotic delivery in orthopedic infections, and it functions as a biodegradable bone void filler rather than a traditional bone cement. 1

Key Distinction: Stimulan vs. Bone Cement

• Stimulan is a porous calcium sulfate ceramic bone void filler, not PMMA bone cement 1
• Unlike PMMA cement which remains permanently in situ, calcium sulfate is biodegradable and resorbs over time 1
• Both materials are clinically recognized carriers for local antibiotic delivery in fracture-related infections (FRI) and osteomyelitis 1

Clinical Evidence Supporting Stimulan Use

A multicenter study of 106 patients demonstrated 95% infection control rates when Stimulan beads were used for local antibiotic delivery following surgical debridement 2

• Mean follow-up was 20 months with only 5% persistence of infection 2
• Primary wound closure was achieved in 99% of cases 2
• No significant side effects or complications were reported 2

Comparative Antimicrobial Efficacy

In vitro studies show calcium sulfate (Stimulan) demonstrates superior antibiotic elution characteristics compared to PMMA cement 3, 4

• Calcium sulfate loaded with vancomycin exhibited bacteriostatic properties across the entire concentration range starting from 1 mg/mL 3
• Stimulan produced higher zones of inhibition, more stable antibiotic elution rates, and greater biofilm bacterial killing compared to PMMA 4
• Both carriers showed potency for up to 14 days against Staphylococcus aureus and Staphylococcus epidermidis 4

Clinical Application Guidelines

Local antibiotic carriers should be used for dead-space management after extensive debridement, particularly when blood flow to the infection site is impaired 1

Antibiotic Selection for Calcium Sulfate Carriers:

• Vancomycin combined with a culture-sensitive heat-stable antibiotic is the most commonly used combination 2
• Gentamicin, tobramycin, vancomycin, and clindamycin are the most commonly available commercial formulations 1
• Aminoglycosides, glycopeptides, and fluoroquinolones demonstrate excellent long-term stability at body temperature 1
• Beta-lactam antibiotics degrade rapidly at 37°C and should be avoided 1

Surgical Protocol:

• Thorough surgical debridement must precede carrier insertion 1, 2
• Antibiotic choice should be tailored based on culture results and sensitivity patterns in consultation with microbiology 2
• Primary wound closure should be achieved when possible 2

Advantages Over PMMA Cement

Calcium sulfate offers several theoretical and demonstrated advantages as an antibiotic carrier 1, 4

• Biodegradable nature eliminates need for second surgery to remove carrier 1
• Higher and more sustained antibiotic elution rates 4
• Better biofilm penetration and bacterial killing 4
• No exothermic polymerization process that can denature heat-sensitive antibiotics 1
• Provides osteoconductive scaffold for bone regeneration 1

Important Caveats

While both carriers prevent bacterial growth (bacteriostatic effect), they may not achieve 100% bacterial elimination (bactericidal effect) 3

• The bactericidal efficacy correlates with homogeneity of antibiotic dispersion in the carrier 3
• Local antibiotic carriers should always be used as adjuncts to systemic antibiotic therapy, not as monotherapy 1
• Duration of systemic antibiotics: 12 weeks if implant retained, 6 weeks if implant removed 1

Concerns with Current Practice

There is substantial lack of Level 1 evidence demonstrating efficacy of antibiotic-loaded carriers, and concerns exist about subtherapeutic antibiotic levels following early release 5

• Nonstandardized, surgeon-directed formulations have unknown release kinetics 5
• Subtherapeutic concentrations risk inducing antibiotic resistance 5
• No validated assay exists to determine minimum biofilm eradication concentration for patient-specific organisms 5

Guideline Recommendation Context

Current guidelines suggest against routine use of topical antibiotics as sole adjunctive treatment, but support their use for dead-space management after debridement 1

• The IWGDF/IDSA 2023 guidelines conditionally recommend against topical antibiotics in combination with systemic antibiotics for diabetic foot infections due to low-quality evidence 1
• However, this recommendation applies to soft tissue infections and does not specifically address post-debridement dead-space management in orthopedic infections 1
• The fracture-related infection guidelines explicitly support local antibiotic carriers for dead-space management after extensive debridement 1