Ceftazidime-Avibactam Plus Aztreonam Is the Preferred Combination
For serious infections caused by organisms co-producing metallo-β-lactamases (MBLs) and serine β-lactamases, you should use ceftazidime-avibactam (2.5g IV q8h) combined with aztreonam (2g IV q8h) rather than aztreonam-avibactam alone. This triple-agent approach (ceftazidime + avibactam + aztreonam) is strongly recommended by multiple international guidelines and demonstrates superior mortality outcomes. 1, 2, 3
Why the Three-Drug Combination Is Superior
Mechanistic Rationale
- Aztreonam is not hydrolyzed by metallo-β-lactamases but remains vulnerable to the serine β-lactamases (ESBLs, AmpC, KPC) that these organisms commonly co-produce. 1, 3
- Avibactam protects aztreonam from degradation by serine β-lactamases, restoring aztreonam's activity against the MBL-producing pathogen. 2, 4
- Ceftazidime serves as the carrier molecule for avibactam delivery and provides additional β-lactam coverage, though ceftazidime itself is hydrolyzed by MBLs. 1
Clinical Outcomes Strongly Favor This Combination
- The American Thoracic Society and IDSA report 30-day mortality of 19.2% with ceftazidime-avibactam plus aztreonam versus 44% with alternative regimens (including colistin-based therapy) for MBL-producing carbapenem-resistant Enterobacteriaceae. 1, 2, 3
- The Italian Society of Infection and Tropical Diseases issues a STRONG recommendation with MODERATE certainty for this triple combination in MBL-producing CRE infections. 2
- Clinical cure rates reach 77.5% in NDM-positive isolates when treated with ceftazidime-avibactam plus aztreonam. 2
Why Aztreonam-Avibactam Alone Is Not Currently Recommended
Lack of Guideline Support
- No major guideline recommends aztreonam-avibactam as a standalone formulation for MBL-producing infections. All guideline recommendations specify the three-component regimen: ceftazidime-avibactam PLUS aztreonam. 1, 2, 3
- The European Society of Clinical Microbiology and Infectious Diseases provides a conditional recommendation with moderate-quality evidence specifically for ceftazidime-avibactam 2.5g IV q8h PLUS aztreonam—not aztreonam-avibactam alone. 1
Practical Availability Issues
- Aztreonam-avibactam as a fixed-dose combination product is not yet commercially available in most settings, though it is mentioned as a future option. 2
- The established regimen uses separately administered ceftazidime-avibactam and aztreonam, which are both FDA-approved and readily available. 2
Critical Implementation Details
Dosing Regimen
- Ceftazidime-avibactam: 2.5g IV every 8 hours (infused over 2 hours). 1, 2
- Aztreonam: 2g IV every 8 hours. 2
When to Use This Combination
- MBL production (NDM, VIM, IMP) is confirmed or strongly suspected based on carbapenemase typing or local epidemiology. 1, 2
- The organism demonstrates co-production of serine β-lactamases (ESBLs, AmpC, KPC) alongside the MBL. 1, 2
- Obtain carbapenemase genotyping or phenotypic testing immediately to confirm MBL production before or concurrent with empiric therapy initiation. 1, 2
Important Caveats and Pitfalls
- Never use aztreonam monotherapy for MBL-producing organisms—co-produced serine β-lactamases will render it ineffective. 2
- In vitro synergy testing should be performed when possible, as 18.3% of isolates may demonstrate aztreonam MICs ≥4 μg/mL even in combination with avibactam. 5
- Resistance emergence occurs in 3.8–10.4% of patients receiving ceftazidime-avibactam; obtain repeat cultures if clinical deterioration occurs within 48–72 hours. 2
- This combination is ineffective against non-MBL resistance mechanisms in Pseudomonas aeruginosa—carbapenemase typing is essential. 1