Aztreonam: Clinical Applications and Therapeutic Uses
Aztreonam is primarily used for treating infections caused by aerobic gram-negative bacteria, particularly in patients with beta-lactam allergies, as it has minimal cross-reactivity with other beta-lactam antibiotics. It is especially valuable for treating susceptible multidrug-resistant gram-negative infections and as part of combination therapy for metallo-beta-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE).
Spectrum of Activity
Aztreonam has a unique and targeted spectrum of activity:
Highly effective against:
- Most Enterobacteriaceae (E. coli, Klebsiella pneumoniae, Proteus mirabilis)
- Pseudomonas aeruginosa
- Haemophilus influenzae
- Serratia marcescens
No activity against:
- Gram-positive bacteria
- Anaerobic bacteria (including Bacteroides fragilis)
This selective spectrum makes aztreonam particularly valuable when targeting gram-negative infections while preserving the anaerobic gut flora 1.
FDA-Approved Indications
Aztreonam is FDA-approved for treating the following infections caused by susceptible gram-negative microorganisms 1:
- Urinary tract infections (complicated and uncomplicated), including pyelonephritis and cystitis
- Lower respiratory tract infections, including pneumonia and bronchitis
- Septicemia
- Skin and skin-structure infections, including postoperative wounds, ulcers, and burns
- Intra-abdominal infections, including peritonitis
- Gynecologic infections, including endometritis and pelvic cellulitis
Special Clinical Applications
1. Alternative to Aminoglycosides
Aztreonam serves as an effective alternative to aminoglycosides or third-generation cephalosporins in patients with serious gram-negative infections, particularly when there are concerns about nephrotoxicity or ototoxicity 2.
2. Beta-Lactam Allergic Patients
Due to its unique monobactam structure, aztreonam has minimal cross-reactivity with other beta-lactams, making it suitable for patients with documented allergies to penicillins or cephalosporins 3.
3. Role in Multidrug-Resistant Infections
Aztreonam has a special role in treating infections caused by multidrug-resistant gram-negative pathogens:
MBL-producing CRE infections: Aztreonam is uniquely active against metallo-beta-lactamase-producing CRE, but as monotherapy does not cover other broad-spectrum beta-lactamases or carbapenemases frequently co-produced by such strains 4.
Combination with ceftazidime-avibactam: This combination shows significant synergy against NDM-producing and KPC-producing CRE isolates, as aztreonam is not hydrolyzed by metallo-beta-lactamases 4. Studies show this combination is associated with lower 30-day mortality (HR: 0.37,95% CI 0.13-0.74) and lower clinical treatment failure rates compared to other antimicrobial therapies for MBL-producing CRE infections 4.
Important Considerations for Use
Combination Therapy Requirements
For mixed infections: When used empirically or for suspected mixed infections, aztreonam should be combined with agents active against gram-positive and/or anaerobic bacteria 1, 5.
For MBL-producing CRE: Aztreonam should not be used as monotherapy but rather in combination with ceftazidime-avibactam for optimal efficacy 4.
Administration and Dosing
- Standard dosing is 1-2 grams IV every 8-12 hours for moderate to severe infections 3.
- Must be administered parenterally (IV or IM) as oral bioavailability is very low (approximately 1%) 2.
Clinical Efficacy
Aztreonam has demonstrated high clinical response rates across various infection types:
- 82% for urinary tract infections
- 79% for lower respiratory tract infections
- 98% for septicemia
- 88% for skin/skin structure infections
- 85% for intra-abdominal infections
- 100% for gynecologic infections 6
Pitfalls and Caveats
Not for monotherapy in mixed infections: Due to lack of activity against gram-positive and anaerobic bacteria, aztreonam should not be used alone when these pathogens are suspected 5.
Limited efficacy in structural abnormalities: Patients with major underlying structural abnormalities of the urinary tract may experience early relapses of bacteriuria despite treatment 7.
Pseudomonas in cystic fibrosis: While generally effective against Pseudomonas aeruginosa, aztreonam has shown limited efficacy in eradicating these infections in patients with cystic fibrosis 7.
Beta-lactamase induction: Certain antibiotics (e.g., cefoxitin, imipenem) may induce high levels of beta-lactamase in some gram-negative bacteria, potentially resulting in antagonism to aztreonam. These beta-lactamase-inducing antibiotics should not be used concurrently with aztreonam 1.
By understanding these specific applications and limitations, clinicians can optimize the use of aztreonam in their antimicrobial armamentarium, particularly for targeted gram-negative infections and in patients with limited antibiotic options.