Aztreonam in NDM-Producing UTI
For urinary tract infections caused by NDM-producing organisms, aztreonam combined with ceftazidime-avibactam is the preferred treatment, with a STRONG recommendation and MODERATE certainty of evidence. 1, 2
Why This Combination Works
Aztreonam is uniquely stable against NDM and other metallo-β-lactamases because these enzymes cannot hydrolyze monobactam antibiotics. 1, 2 However, aztreonam cannot be used alone because NDM-producing organisms co-produce other β-lactamases (ESBLs and cephalosporinases) that will inactivate aztreonam monotherapy. 1, 2
Ceftazidime-avibactam protects aztreonam from these co-produced enzymes, creating synergistic activity that restores full antimicrobial efficacy. 3 In vitro testing demonstrates that aztreonam susceptibility is fully restored in 86% of MBL-producing Enterobacterales when combined with ceftazidime-avibactam. 3
Clinical Evidence Supporting This Recommendation
In bloodstream infections caused by NDM-producing Klebsiella pneumoniae, patients receiving ceftazidime-avibactam plus aztreonam had 30-day mortality of 19.2% versus 44% in those receiving other active antibiotics (P = 0.007). 1, 2 This represents a 56% relative risk reduction in mortality. 1
The highest mortality rates were observed in patients who received colistin-containing regimens, making older alternatives significantly inferior. 1
A recent Polish single-center study of 23 patients with KP-NDM infections (including urinary tract infections) treated with ceftazidime-avibactam plus aztreonam achieved microbiological eradication in 100% of cases. 4
Dosing for UTI
Administer ceftazidime-avibactam 2.5 g IV every 8 hours plus aztreonam 2 g IV every 8 hours in patients with normal renal function. 4
Adjust both agents for reduced renal function according to creatinine clearance. 4 For uncomplicated UTI with normal renal function, aztreonam 0.5 g twice daily may be sufficient when combined with ceftazidime-avibactam, though this lower dose is based on older monotherapy data. 5
Alternative Option (Less Preferred)
Cefiderocol may be considered as an alternative with CONDITIONAL recommendation and LOW certainty of evidence, achieving 75% clinical cure in MBL-producing CRE infections. 1, 2 However, concerns exist regarding high MIC values and risk of treatment-emergent resistance with cefiderocol. 1
Critical Pitfalls to Avoid
Never use aztreonam monotherapy for NDM infections—it will fail due to co-produced β-lactamases that inactivate aztreonam. 1, 2
Do not delay treatment waiting for carbapenemase typing—if NDM is suspected based on epidemiology or rapid testing, initiate ceftazidime-avibactam plus aztreonam immediately. 1
Monitor for clinical deterioration within 48-72 hours and obtain repeat cultures, as 3.8-10.4% of patients develop resistance during treatment. 2
Avoid colistin-based regimens as first-line therapy—they are associated with significantly higher mortality compared to the aztreonam combination. 1
Treatment Duration
For complicated UTI, treat for a median of 8-9 days based on clinical response. 5 Patients with major underlying structural abnormalities of the urinary tract may experience early relapses and require longer courses or source control. 6