Can ceftazidime-avibactam and aztreonam be mixed with Stimulan (antibiotic-loaded bone cement)?

Compatibility of Ceftazidime-Avibactam and Aztreonam with Stimulan

Yes, ceftazidime-avibactam and aztreonam can be safely used alongside Stimulan antibiotic-loaded bone cement, as there is no pharmacological interaction between systemically administered antibiotics and locally delivered antibiotics from bone cement—they work through different mechanisms. 1

Key Clinical Principle

• Systemically administered ceftazidime-avibactam and aztreonam do not interact with antibiotics delivered locally from calcium sulfate-based bone cement systems like Stimulan 1
• The systemic antibiotics circulate through the bloodstream while Stimulan releases antibiotics directly into the local tissue space, making pharmacological interference impossible 1

When to Use This Combination for Bone Infections

For multidrug-resistant Klebsiella bone infections, the treatment algorithm depends entirely on the carbapenemase type: 2

• KPC-producing or OXA-48-producing strains: Use ceftazidime-avibactam monotherapy at 2.5 g IV every 8 hours as a prolonged 3-hour infusion 2

• MBL-producing strains (NDM, VIM, IMP): Use ceftazidime-avibactam 2.5 g IV every 8 hours PLUS aztreonam 2 g IV every 6 hours 2

• The combination for MBL-producers demonstrates significantly lower 30-day mortality (19.2% vs 44%) compared to alternative therapies 1, 3

• This combination achieves synergistic activity in 90% of MBL-producing strains 2

Critical Diagnostic Step

• Always ascertain the carbapenemase type before initiating treatment through phenotypic testing or genotypic PCR testing for MBL genes 2
• This combination is ineffective against non-MBL resistance mechanisms, making identification essential 3

Treatment Duration for Bone Infections

• Treat bone and musculoskeletal infections for a minimum of 4-6 weeks 2

Important Caveats

• Ceftazidime-avibactam resistance can emerge in 3.8-10.4% of cases during treatment 2, 1
• Do NOT add polymyxin or fosfomycin routinely for MBL-producers, as the ceftazidime-avibactam plus aztreonam combination alone demonstrates superior outcomes 2
• Monitor for clinical improvement within 48-72 hours and obtain repeat cultures if clinical deterioration occurs 2

Intravenous Compatibility Confirmation

• Ceftazidime-avibactam (at concentrations of 8,25, and 50 mg/mL) is fully compatible with aztreonam (at concentrations of 10 and 20 mg/mL) when administered via Y-site infusion 4
• No particulate matter, color changes, turbidity, or pH changes occur when these agents are mixed 4