Aztreonam Plus Avibactam for Aztreonam-Resistant Klebsiella Infections
Yes, aztreonam plus avibactam (or ceftazidime-avibactam) should be used for aztreonam-resistant Klebsiella species, particularly when metallo-β-lactamase (MBL) production is confirmed or suspected. This combination restores aztreonam activity even when the organism shows resistance to aztreonam alone.
Mechanism Explaining Why This Works Despite Aztreonam Resistance
Aztreonam-resistant Klebsiella species typically harbor both metallo-β-lactamases (which don't hydrolyze aztreonam) AND serine β-lactamases like ESBLs or AmpC enzymes (which DO hydrolyze aztreonam), creating the resistance phenotype 1, 2.
Avibactam inhibits the serine β-lactamases (ESBLs, AmpC, KPC) that would otherwise destroy aztreonam, while aztreonam remains stable against the MBLs, creating synergistic activity 1, 2.
In vitro studies demonstrate that 99.9% of Enterobacterales isolates producing multiple β-lactamase classes—including those with aztreonam MICs ≥128 mg/L—become susceptible (MIC ≤4 mg/L) when aztreonam is combined with avibactam at 4 mg/L 2.
The combination protects aztreonam from hydrolysis and provides dramatic MIC reductions: strains with aztreonam MICs of ≥128 mg/L show dramatically increasing susceptibility with increasing avibactam concentrations 1.
Guideline-Based Recommendations
The Italian Society of Infection and Tropical Diseases (SIMIT) provides a STRONG recommendation with MODERATE certainty of evidence for ceftazidime-avibactam plus aztreonam in MBL-producing carbapenem-resistant Enterobacterales (CRE) infections 3.
The combination demonstrated 30-day mortality of 19.2% versus 44% (P=0.007) compared to other active antibiotics in patients with bloodstream infections caused by MBL-producing CRE, predominantly NDM-producing Klebsiella pneumoniae 3, 4.
This combination also showed lower clinical treatment failure rates (HR: 0.30,95% CI 0.14-0.65) and shorter hospital length of stay (HR: 0.49,95% CI -0.82) 3.
Clinical Application for Your Wound Infection
For wound infections caused by aztreonam-resistant Klebsiella, use ceftazidime-avibactam 2.5g IV every 8 hours PLUS aztreonam 2g IV every 8 hours (or aztreonam-avibactam when commercially available) 4.
The combination is particularly indicated when MBL production (NDM, VIM, IMP) is confirmed or suspected based on local epidemiology 3, 4.
In a study of 57 CRE infections (57.9% intra-abdominal and hospital-acquired pneumonia), the cure rate was 77.5% in patients receiving ceftazidime-avibactam plus aztreonam for NDM-positive infections 3.
Critical Pitfalls to Avoid
Never use aztreonam monotherapy for MBL-producing organisms—it will fail due to co-produced serine β-lactamases that hydrolyze aztreonam 4, 5.
Obtain carbapenemase typing (PCR or phenotypic testing) whenever possible before treatment initiation, as the combination is specifically designed for MBL producers 3.
Monitor for resistance emergence: 3.8-10.4% of patients develop ceftazidime-avibactam resistance during treatment; obtain repeat cultures if clinical deterioration occurs within 48-72 hours 4.
The highest mortality rates in comparative studies were observed with colistin-containing regimens (44% mortality), making aztreonam-avibactam combinations clearly superior 3.
Alternative Considerations
Cefiderocol may be considered as an alternative with a CONDITIONAL recommendation and LOW certainty of evidence, showing 75% clinical cure in MBL-producing CRE subgroup analysis 3.
However, cefiderocol has concerns regarding high MIC values and risk of treatment-emergent resistance that require further investigation 3.