Compatibility of Ceftazidime-Avibactam and Aztreonam with Stimulan for Local Therapy
There is no pharmacological interaction between systemically administered ceftazidime-avibactam/aztreonam and locally delivered antibiotics from Stimulan (calcium sulfate bone cement), as they work through different mechanisms—systemic antibiotics circulate through the bloodstream while Stimulan provides local antibiotic delivery at the surgical site. 1
Key Clinical Considerations
Mechanism and Safety Profile
Stimulan is a calcium sulfate-based antibiotic delivery system used for local antibiotic delivery in orthopedic infections, and the systemic administration of ceftazidime-avibactam plus aztreonam does not interfere with locally delivered antibiotics from bone cement. 1
The two delivery systems operate independently: systemic antibiotics achieve therapeutic concentrations through intravenous administration, while Stimulan releases antibiotics directly at the infection site through gradual dissolution of the calcium sulfate matrix. 1
Intravenous Compatibility Confirmed
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, with no evidence of particulate matter, color changes, turbidity, or pH alterations over 12 hours. 2
Ceftazidime does not affect the in vitro activity of aztreonam/avibactam, with MICs remaining within one 2-fold dilution regardless of ceftazidime concentration. 3
Clinical Efficacy for Target Pathogens
Metallo-β-Lactamase Producing Organisms
The ESCMID guidelines suggest aztreonam and ceftazidime-avibactam combination therapy for patients with severe infections caused by CRE carrying metallo-β-lactamases (conditional recommendation, moderate evidence). 4
This combination demonstrates significantly lower 30-day mortality (19.2% vs 44%) compared to other treatment options including colistin, tigecycline, and fosfomycin for MBL-producing Enterobacterales infections. 4
Critical Caveats
Ensure the causative organism is an MBL-producer (NDM, VIM, IMP) before using this combination, as it is ineffective against non-MBL resistance mechanisms. 1
Pseudomonas aeruginosa producing NDM or VIM may remain resistant to the aztreonam-ceftazidime/avibactam combination due to non-β-lactamase resistance mechanisms. 5
Monitor for ceftazidime-avibactam resistance development during treatment, though this occurs in only 3.8-10.4% of cases. 1
Practical Implementation
Administer ceftazidime-avibactam and aztreonam systemically via intravenous infusion while using Stimulan for local antibiotic delivery at the surgical site—these can be used concurrently without concern for drug-drug interactions. 1
For VIM-type-producing Gram-negative bacteria, the combination showed synergistic activity in 16 out of 19 isolates with 30-day mortality of 17%. 6