Treatment of NDM-Producing Bacterial Infections

Introduction to Aztreonam Combination Therapy

The Italian Society of Infection and Tropical Diseases (SIMIT) provides a STRONG recommendation with MODERATE certainty of evidence for the use of aztreonam combined with ceftazidime-avibactam in MBL-producing CRE infections, demonstrating significantly lower 30-day mortality (19.2% vs 44%) compared to alternative regimens including colistin-based therapies, in patients with NDM-producing bacterial infections 1
Aztreonam is uniquely stable against metallo-β-lactamases (including NDM) because MBLs cannot hydrolyze this monobactam antibiotic, but it cannot be used as monotherapy because NDM-producing organisms co-produce other β-lactamases (ESBLs and cephalosporinases) that inactivate aztreonam, in the treatment of NDM-producing bacterial infections 1

The Infectious Diseases Society of America endorses the combination of ceftazidime-avibactam and aztreonam as preferred therapy for metallo-β-lactamase-producing carbapenem-resistant Enterobacterales, with a STRONG recommendation and MODERATE certainty of evidence, in patients with NDM-producing bacterial infections 1
An observational study of bloodstream infections caused by MBL-producing CRE (predominantly NDM-producing Klebsiella pneumoniae) demonstrated that patients receiving ceftazidime-avibactam plus aztreonam had 30-day mortality of 19.2% versus 44% in those receiving other active antibiotics, in the treatment of NDM-producing bacterial infections 1

Cefiderocol may be considered as an alternative with CONDITIONAL recommendation and LOW certainty of evidence, in the treatment of NDM-producing bacterial infections, with clinical cure rates of 75% (12/16) in the CREDIBLE-CR trial subgroup with MBL-producing CRE 1
The combination of aztreonam and ceftazidime-avibactam is not recommended for use with polymyxin or fosfomycin, as this dual regimen alone demonstrates superior outcomes compared to colistin-containing regimens, in patients with NDM-producing bacterial infections 2

Do NOT use aztreonam monotherapy for NDM infections—it will fail due to co-produced β-lactamases, in the treatment of NDM-producing bacterial infections 1
Monitor for resistance emergence: 3.8-10.4% of patients develop ceftazidime-avibactam resistance during treatment of KPC-producing CRE; obtain repeat cultures if clinical deterioration occurs within 48-72 hours, in patients with NDM-producing bacterial infections 2