Aztreonam Sensitivity to NDM-Producing Klebsiella
Aztreonam alone is NOT effective against NDM-producing Klebsiella because these organisms co-produce other β-lactamases (ESBLs and cephalosporinases) that inactivate aztreonam, but aztreonam COMBINED with ceftazidime-avibactam is highly effective because aztreonam remains stable against the NDM enzyme while avibactam protects it from the co-produced β-lactamases. 1
Understanding the Resistance Mechanism
NDM (New Delhi metallo-β-lactamase) cannot hydrolyze aztreonam, making aztreonam uniquely stable against this specific carbapenemase. 1
However, NDM-producing Klebsiella simultaneously produce additional β-lactamases including ESBLs (like CTX-M) and cephalosporinases that rapidly destroy aztreonam when used alone. 1
This explains why aztreonam monotherapy will fail clinically despite the NDM enzyme's inability to degrade it—the co-produced enzymes render it ineffective. 1
Recommended Treatment Strategy
The Infectious Diseases Society of America provides a STRONG recommendation with MODERATE certainty of evidence for using ceftazidime-avibactam (2.5 g IV every 8 hours) PLUS aztreonam (2 g IV every 6 hours) as preferred therapy for NDM-producing Klebsiella. 1, 2
This combination demonstrates synergistic activity in 90% of MBL-producing strains. 2
Clinical outcomes show 30-day mortality of 19.2% with this combination versus 44% with alternative regimens including colistin-based therapies. 1, 2
The Italian Society of Infection and Tropical Diseases (SIMIT) endorses this approach with a STRONG recommendation. 1
Mechanism of the Combination
Ceftazidime-avibactam protects aztreonam from degradation by the co-produced ESBLs and cephalosporinases. 1
Aztreonam then effectively targets the bacterial cell wall synthesis without being affected by the NDM enzyme. 1
This dual mechanism achieves bacterial killing that neither agent can accomplish alone against NDM-producers. 3
Critical Pitfalls to Avoid
DO NOT use aztreonam monotherapy—it will fail due to co-produced β-lactamases despite NDM's inability to hydrolyze it. 1
DO NOT add polymyxin or fosfomycin routinely to the ceftazidime-avibactam plus aztreonam combination, as the dual regimen alone demonstrates superior outcomes compared to colistin-containing regimens. 1, 2
Confirm the organism is truly an MBL-producer (NDM, VIM, or IMP) through phenotypic or genotypic PCR testing before using this combination, as it is ineffective against non-MBL resistance mechanisms like KPC or OXA-48. 2, 4
Monitoring for Treatment Failure
Monitor for clinical improvement within 48-72 hours of initiating therapy. 2
Obtain repeat cultures if clinical deterioration occurs to assess for resistance development, which occurs in 3.8-10.4% of cases. 1, 2
There are currently no standardized antimicrobial susceptibility testing methods or clinical breakpoints approved for the ceftazidime-avibactam plus aztreonam combination. 2