Can Colistin Be Combined with Aztreonam?
Yes, colistin can be combined with aztreonam, but this combination is NOT the preferred regimen for most multidrug-resistant Gram-negative infections. The combination you should actually be using depends entirely on the specific pathogen and its resistance mechanism.
The Critical Distinction: What Pathogen Are You Treating?
For Metallo-β-lactamase-producing CRE (e.g., NDM producers):
Use ceftazidime-avibactam PLUS aztreonam instead 1, 2. This combination is specifically recommended because:
- Aztreonam is not hydrolyzed by metallo-β-lactamases
- Ceftazidime-avibactam protects aztreonam from other β-lactamases
- Clinical data shows 30-day mortality of 19.2% with ceftazidime-avibactam/aztreonam versus 44% with other regimens (p=0.007) 2
For CRE susceptible ONLY to polymyxins (colistin):
Combination therapy with colistin plus another active agent is suggested 1. However:
- No specific combination (including colistin + aztreonam) has proven superiority
- The guidelines state: "treatment with more than one drug active in vitro" but provide "no recommendation for or against specific combinations" 1
For Carbapenem-resistant Pseudomonas aeruginosa (CRPA):
When using colistin, combine it with another active agent 1, but again, no specific combination is recommended over others.
For Carbapenem-resistant Acinetobacter baumannii:
Colistin monotherapy versus colistin-carbapenem combination showed NO significant difference in the largest randomized trial (406 patients): clinical failure was 79% with monotherapy versus 73% with combination (RR 0.93,95% CI 0.83-1.03, p=NS) 3.
Why NOT Colistin + Aztreonam as First Choice?
The FDA label for aztreonam explicitly warns: "Certain antibiotics may induce high levels of beta-lactamase in vitro in some Gram-negative aerobes such as Enterobacter and Pseudomonas species, resulting in antagonism to many beta-lactam antibiotics including aztreonam" 4. This suggests potential antagonism when combining aztreonam with beta-lactamase inducers, though colistin itself is not a beta-lactamase inducer.
More importantly, there is no high-quality evidence supporting colistin + aztreonam specifically. The guidelines recommend:
- Ceftazidime-avibactam + aztreonam for MBL-producers (NOT colistin + aztreonam) 1, 2
- For infections susceptible only to older agents like colistin, combination therapy is suggested but without preference for specific partners 1
Practical Algorithm for Decision-Making:
Step 1: Identify the carbapenemase type
- If MBL-producer (NDM, VIM, IMP) → Use ceftazidime-avibactam + aztreonam 1, 2
- If KPC or OXA-48 → Use ceftazidime-avibactam or meropenem-vaborbactam monotherapy 1
Step 2: If new agents unavailable or organism resistant to them
- Severe infection → Use colistin + another active agent (could include aztreonam if susceptible, but no specific advantage) 1
- Non-severe infection → Consider monotherapy with active agent 1
Step 3: For Acinetobacter baumannii specifically
- Colistin monotherapy is reasonable based on the AIDA trial showing no benefit of combination 3
Critical Caveats:
- Colistin has significant nephrotoxicity risk (8-48% in various studies) 5, 6, 7, though recent data suggests rates may be lower with modern dosing
- Colistin pharmacokinetics are highly variable and influenced by renal function 8, 7, 9
- Loading dose of colistin (9 million units) is generally recommended for systemic infections to rapidly achieve therapeutic levels, though evidence for UTIs specifically is mixed 6
- Aztreonam requires concurrent therapy for Gram-positive coverage and anaerobes per FDA labeling 4
Bottom Line:
Do NOT default to colistin + aztreonam. Instead, use ceftazidime-avibactam + aztreonam for MBL-producers, or use newer agents as monotherapy when possible. Reserve colistin combinations (with any partner, including aztreonam) only when organisms are resistant to all newer agents and susceptible to both drugs in vitro.