Are Klebsiella species and Escherichia coli susceptible to aztreonam?

Aztreonam Susceptibility in Klebsiella and E. coli

Yes, both Klebsiella species and E. coli are generally susceptible to aztreonam, but resistance can develop through extended-spectrum β-lactamase (ESBL) production, making susceptibility testing essential before use.

Baseline Susceptibility

Aztreonam demonstrates excellent activity against wild-type strains of both organisms:

• E. coli: Over 99% of isolates show susceptibility to aztreonam 1
• Klebsiella species: All 118 tested Klebsiella strains (including K. pneumoniae and K. oxytoca) demonstrated susceptibility 1
• FDA-approved indications: Aztreonam is specifically indicated for urinary tract infections, lower respiratory tract infections, septicemia, skin infections, intra-abdominal infections, and gynecologic infections caused by E. coli and Klebsiella pneumoniae 2

Critical Resistance Mechanisms

ESBL Production

Klebsiella species can acquire resistance to aztreonam through ESBL production 3. This is the most clinically significant resistance mechanism:

• ESBLs confer resistance to cephalosporins AND aztreonam simultaneously 3
• When revised CLSI breakpoints are applied, 89.2% of ESBL-producing E. coli and 67.7% of ESBL-producing K. pneumoniae may still test as susceptible or intermediate to aztreonam, creating a false sense of susceptibility 4
• ESBL-producing strains remain susceptible to carbapenems, which should be the preferred treatment 3

AmpC β-Lactamases

• Plasmid-mediated AmpC enzymes can cause resistance to aztreonam in both species 3
• The pooled prevalence of AmpC-producing E. coli in Africa is 15.32% and K. pneumoniae is 17.25%, with increasing trends after 2020 5
• AmpC confers resistance to narrow- and broad-spectrum cephalosporins, β-lactam/β-lactamase inhibitor combinations, and aztreonam 5

Clinical Decision Algorithm

For empiric therapy:

1. If local ESBL prevalence is <10% and no recent antibiotic exposure: aztreonam is appropriate 2
2. If ESBL risk factors present (prior cephalosporin/fluoroquinolone use within 3 months, hospitalization within 12 months, nursing facility residence): avoid aztreonam, use carbapenems 6
3. If carbapenem-resistant Enterobacterales (CRE) suspected: aztreonam is NOT appropriate as monotherapy 7

For directed therapy:

• Always obtain susceptibility testing before using aztreonam for serious infections 2
• If ESBL-positive by testing: use carbapenems instead, even if aztreonam MIC appears susceptible 4
• For metallo-β-lactamase producers: ceftazidime-avibactam plus aztreonam combination shows 95-98.8% synergy 8

Important Caveats

Do not rely on susceptibility testing alone for ESBL producers: The revised CLSI breakpoints fail to identify many ESBL-producing organisms, with nearly 90% of ESBL-producing E. coli testing falsely susceptible to aztreonam 4. This represents a critical pitfall in clinical practice.

Combination therapy considerations: For difficult-to-treat resistant P. aeruginosa (DTR-PA), aztreonam is included in the definition of resistance (non-susceptibility to aztreonam plus other agents) 7. However, aztreonam combined with ceftazidime-avibactam demonstrates excellent activity against metallo-β-lactamase-producing CRE 9.

Geographic variation matters: In Taiwan, routine ESBL screening is performed, and clinicians are trained to use carbapenems for ESBL infections rather than relying on aztreonam susceptibility results 10.