Side Effects of Aztreonam
Aztreonam is generally well-tolerated with a favorable safety profile, particularly notable for its lack of nephrotoxicity and ototoxicity, making it safer than aminoglycosides for patients with renal impairment or seizure disorders. 1, 2
General Side Effects Profile
Common Adverse Reactions
- Gastrointestinal effects: Nausea, vomiting, and diarrhea occur but at lower rates than broad-spectrum cephalosporins due to less disruption of normal GI flora 2
- Local reactions: Phlebitis or discomfort at injection sites 3
- Hepatic: Transient elevations in liver function tests may occur 2
- Hematologic: Biochemical and hematologic abnormalities are rarely clinically significant 2
Serious but Rare Adverse Effects
- Hypersensitivity reactions: Aztreonam is weakly immunogenic and has negligible immunologic cross-reactivity with other beta-lactams, making it safe for patients with IgE-mediated penicillin hypersensitivity 4, 2
- Exception: Cross-reactivity exists only with ceftazidime due to shared R1 side chain; avoid aztreonam in patients with confirmed ceftazidime allergy 4
Special Considerations for High-Risk Populations
Patients with Impaired Renal Function
Aztreonam requires dose adjustment in renal impairment but does NOT cause nephrotoxicity, unlike aminoglycosides. 1, 5, 6
Dosing Adjustments Required:
- Creatinine clearance 10-30 mL/min/1.73m²: Reduce dose to half the usual amount after initial loading dose of 1-2g 1
- Creatinine clearance <10 mL/min/1.73m² (including hemodialysis): Give usual initial dose (500mg, 1g, or 2g), then maintenance dose should be one-fourth of usual initial dose at standard intervals (6,8, or 12 hours) 1
- Post-hemodialysis supplementation: Give one-eighth of the initial dose after each hemodialysis session for serious/life-threatening infections 1
Why Renal Dosing Matters:
- Aztreonam is primarily excreted unchanged in urine by glomerular filtration and tubular secretion 3, 6
- Serum half-life increases from 1.5-2.1 hours in normal renal function to prolonged levels in renal impairment 6, 7
- Creatinine clearance is the most significant variable explaining patient variability in aztreonam clearance 7
Critical distinction: Unlike cefepime (another beta-lactam), aztreonam does not cause neurotoxicity even with accumulation in renal failure 8, 2
Patients with Seizure Disorders
Aztreonam does NOT increase seizure risk and is safe in patients with seizure disorders, unlike other antibiotics used for similar indications. 2
Comparative Safety:
- Amantadine: Increased incidence of seizures reported in patients with seizure history; requires close observation 4
- Rimantadine: Seizures or seizure-like activity reported in patients with seizure history not on anticonvulsants 4
- Cefepime: High pro-convulsive activity (relative activity 160 vs penicillin G at 100); causes neurotoxicity including seizures, especially in renal impairment 8
- Aztreonam: No evidence of CNS toxicity or seizure induction 2
Key Safety Advantages
What Aztreonam Does NOT Cause (Unlike Alternatives):
- No nephrotoxicity: Unlike aminoglycosides (gentamicin, tobramycin, amikacin) which cause renal impairment in 3.4-8.7% of patients 4, 5, 6, 2
- No ototoxicity: Unlike aminoglycosides which cause hearing loss and vestibular dysfunction 4, 5, 6, 2
- No coagulation disorders: Unlike some other beta-lactams 5, 6
- No CNS effects: Unlike amantadine/rimantadine (nervousness, anxiety, insomnia, confusion, hallucinations, seizures) 4
- No neurotoxicity: Unlike cefepime which causes encephalopathy and seizures in renal impairment 8
Minimal Drug Disruption:
- Does not displace bilirubin from albumin, making it safe in neonates 2
- Penetrates readily into cerebrospinal fluid 2
- Less GI flora disruption compared to broad-spectrum cephalosporins 2
Clinical Monitoring Recommendations
Essential Monitoring:
- Renal function: Monitor creatinine clearance, especially in elderly patients who may have diminished renal function despite normal serum creatinine 1
- Hypersensitivity: Watch for allergic reactions, though incidence is low 2
- Hepatic function: Periodic LFT monitoring during prolonged therapy 2
No Routine Monitoring Required For:
- Serum drug levels (unlike aminoglycosides) 3
- Audiometry or vestibular testing (no ototoxicity) 2
- Neurological assessment for drug-induced effects (no CNS toxicity) 2
Special Populations
Pregnancy and Lactation:
- Crosses placenta and enters fetal circulation 1
- Should be used during pregnancy only if clearly needed 1
- Excreted in breast milk at <1% of maternal serum concentrations; consider temporary discontinuation of nursing 1