What is the antibacterial coverage of Aztreonam (Aztreonam)?

Aztreonam Antibacterial Coverage

Aztreonam provides selective coverage exclusively against aerobic Gram-negative bacteria, with no activity against Gram-positive organisms or anaerobes, making it essential to combine with other agents when treating mixed infections. 1

Spectrum of Activity

Gram-Negative Coverage (Active)

Enterobacteriaceae (Excellent Activity):

• Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca - MIC typically <1 mcg/mL 1, 2
• Proteus mirabilis, Enterobacter species, Citrobacter species 1
• Serratia marcescens, Morganella morganii, Providencia species 1

Non-Fermenters (Moderate Activity):

• Pseudomonas aeruginosa - MIC90 of 8-16 mcg/mL, comparable to other antipseudomonal beta-lactams 2, 3
• Haemophilus influenzae (including ampicillin-resistant and beta-lactamase-producing strains) 1
• Neisseria gonorrhoeae (including penicillinase-producing strains) 1

Other Susceptible Organisms:

• Aeromonas hydrophila, Pasteurella multocida, Yersinia enterocolitica 1

No Coverage (Inactive)

Gram-Positive Bacteria:

• Aztreonam has no activity against any Gram-positive organisms including Staphylococcus aureus (MSSA or MRSA), Streptococcus species, and Enterococcus species 1, 2, 4
• This is due to poor binding to penicillin-binding proteins (PBPs) of Gram-positive bacteria 2

Anaerobic Bacteria:

• Aztreonam has no activity against anaerobes including Bacteroides fragilis and Clostridium species 1, 4, 3
• Minimal effect on indigenous fecal anaerobic flora 1, 3

Mechanism and Resistance

Mechanism of Action:

• Aztreonam binds with high affinity to penicillin-binding protein 3 (PBP-3) of aerobic Gram-negative bacteria, inhibiting cell wall synthesis 2
• Demonstrates stability against many beta-lactamases (both penicillinases and cephalosporinases) 1, 2

Unique Property for Metallo-β-Lactamase Producers:

• Aztreonam is uniquely stable against metallo-β-lactamases (MBLs), making it valuable for MBL-producing carbapenem-resistant Enterobacteriaceae (CRE) 5, 6
• When combined with ceftazidime-avibactam, this regimen shows significantly lower 30-day mortality (19.2% vs 44%) for MBL-producing CRE infections 5, 6

Clinical Application Guidelines

When Aztreonam Requires Additional Coverage:

According to the Infectious Diseases Society of America, if aztreonam is used for hospital-acquired pneumonia in patients with severe penicillin allergy, additional coverage for methicillin-sensitive Staphylococcus aureus (MSSA) must be included because aztreonam lacks Gram-positive activity 7, 5

Combination Therapy Recommendations:

• For high-risk hospital-acquired pneumonia with dual antipseudomonal coverage needed: aztreonam can be combined with aminoglycosides or fluoroquinolones 7
• Aztreonam can be used as an adjunctive agent with another beta-lactam because it has different targets within the bacterial cell wall 7
• For mixed infections or unknown etiology, combine aztreonam with agents covering Gram-positive and anaerobic bacteria 4, 8

Synergy:

• Aztreonam demonstrates synergy with aminoglycosides against most strains of P. aeruginosa, many Enterobacteriaceae, and other Gram-negative aerobic bacilli 1, 2

Critical Caveats

Major Limitation:

• The European Respiratory Society notes that aztreonam has no Gram-positive activity and should have another agent added to cover MSSA when used for empiric pneumonia therapy 7

Pseudomonas Considerations:

• While active against P. aeruginosa, bacteriologic cure rates may be lower in patients with structural lung disease (cystic fibrosis, bronchiectasis) or chronic colonization 8, 3

Resistance Mechanisms:

• Resistance occurs through beta-lactamase hydrolysis (except MBLs), PBP alterations, and decreased permeability 1
• Some beta-lactamase-inducing antibiotics (cefoxitin, imipenem) may cause antagonism when used concurrently 1