Use of Ceftazidime-Avibactam and Aztreonam in Cement Beads for Bone Infections
Direct Answer
There is no published evidence supporting the use of ceftazidime-avibactam or aztreonam in antibiotic-loaded bone cement beads, and these agents should not be used in cement spacers for bone infections. The available guidelines and research address only systemic intravenous administration of these antibiotics for osteomyelitis, not local delivery via polymethylmethacrylate (PMMA) cement 1, 2, 3.
Why These Antibiotics Are Not Suitable for Cement Beads
Lack of Elution Data
- No studies have characterized the elution profiles, thermal stability, or antimicrobial activity of ceftazidime-avibactam or aztreonam when mixed with bone cement 4, 5.
- The high temperatures generated during PMMA polymerization (reaching 80-100°C) may denature these beta-lactam antibiotics, rendering them inactive 4.
- Without validated elution data, there is no way to predict whether therapeutic local concentrations would be achieved or maintained 5.
Established Alternatives with Proven Elution
- Vancomycin and tobramycin are the standard antibiotics for cement beads because their elution profiles, thermal stability, and antimicrobial activity in PMMA have been extensively studied 4, 5.
- Palacos LV cement exhibits the highest vancomycin elution profile among tested formulations, while Stryker Surgical Simplex P shows significantly lower elution for all antibiotics 4.
- High-dose combinations (3g tobramycin + 2g vancomycin per 40g cement) demonstrate optimal cumulative antibiotic release over 28 days 5.
Recommended Approach for MDR Gram-Negative Bone Infections
Systemic Therapy Strategy
- For KPC-producing or OXA-48-producing Klebsiella osteomyelitis: Use ceftazidime-avibactam 2.5g IV every 8 hours as a prolonged 3-hour infusion for 4-6 weeks 1, 6.
- For MBL-producing (NDM, VIM, IMP) Klebsiella osteomyelitis: Use ceftazidime-avibactam 2.5g IV every 8 hours PLUS aztreonam 2g IV every 6 hours for 4-6 weeks 1, 7.
- For difficult-to-treat resistant Pseudomonas aeruginosa osteomyelitis: Ceftazidime-avibactam 2.5g IV every 8 hours for 42 days has demonstrated efficacy 2.
Local Antibiotic Delivery
- Use vancomycin and tobramycin in cement beads or spacers for local delivery, as these have established efficacy and safety profiles 4, 5.
- Combine local antibiotic delivery with systemic ceftazidime-avibactam or ceftazidime-avibactam plus aztreonam based on the carbapenemase type 1, 3.
Critical Pitfalls to Avoid
- Do not attempt to mix ceftazidime-avibactam or aztreonam into bone cement without validated elution data and thermal stability studies, as this may result in antibiotic inactivation and treatment failure 4, 5.
- Do not add colistin to the ceftazidime-avibactam plus aztreonam regimen for MBL-producers, as this combination demonstrates superior outcomes without colistin (30-day mortality 19.2% vs 44% with colistin-containing regimens) 7.
- Do not use standard infusions of ceftazidime-avibactam; prolonged 3-hour infusions are associated with improved 30-day survival 1.