Treatment of Resistant Gram-Negative Infections

Introduction to Aztreonam Combination Therapies

The combination of ceftazidime-avibactam and aztreonam demonstrates significantly lower 30-day mortality (19.2% vs 44%) compared to alternative therapies for metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) 1, 2, 3
The Infectious Diseases Society of America provides a STRONG recommendation with MODERATE certainty of evidence for this combination in MBL-producing CRE 4
The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) provides moderate-certainty evidence for this combination against bloodstream infections caused by MBL-producing CRE 9, 10

For MBL-producing CRE, use ceftazidime-avibactam 2.5 g IV every 8 hours (as 3-hour infusion) PLUS aztreonam 2 g IV every 6 hours 1, 7, 2, 3, 4, 8
This combination demonstrates synergistic activity in 90% of MBL-producing strains 8
Clinical outcomes from prospective study (N=102 patients with MBL-producing CRE bacteremia): 30-day mortality 19.2% with ceftazidime-avibactam plus aztreonam versus 44% with other active antimicrobials (HR 0.37, 95% CI 0.13-0.74) 1, 7, 2, 3
For non-MBL CRE (KPC, OXA-48), use ceftazidime-avibactam monotherapy at 2.5 g IV every 8 hours as a 3-hour prolonged infusion 10, 8
Five retrospective cohorts (N=824 patients) showed no mortality benefit from adding other antibiotics to ceftazidime-avibactam for KPC and OXA-48 producers 9, 10

Do NOT use aztreonam monotherapy for MBL-producing organisms, as co-produced β-lactamases (ESBLs, cephalosporinases) inactivate it 4, 5
The ceftazidime-avibactam component protects aztreonam from these co-produced enzymes 1, 7, 2
Do NOT add polymyxin or fosfomycin routinely, as the ceftazidime-avibactam plus aztreonam dual regimen alone demonstrates superior outcomes compared to colistin-containing regimens 4, 8
Additional agents are not needed unless specifically indicated by susceptibility testing 1, 2, 3

Minocycline (or its derivative tigecycline) is used in combination regimens for CRAB pulmonary infections, not with aztreonam but rather with carbapenems, sulbactam, aminoglycosides, rifampicin, or fosfomycin 6, 1, 2
Both tigecycline-based and polymyxin-based combination therapies are equally preferable for CRAB pulmonary infections (weak recommendation, very low-quality evidence) 6, 1, 7, 2