What are the potential side effects of Aztreonam (Aztreonam) in patients, particularly those with impaired renal function?

Aztreonam Side Effects

Aztreonam has an excellent safety profile with minimal nephrotoxicity or ototoxicity, making it significantly safer than aminoglycosides for treating gram-negative infections, though dose adjustment is required in renal impairment. 1, 2

Common Side Effects

The most frequently reported adverse effects occur at low rates:

• Local injection site reactions are the most common adverse effect, occurring in approximately 6.8% of patients receiving multiple doses 3
• Gastrointestinal symptoms including diarrhea, nausea, and vomiting occur less frequently than with broad-spectrum cephalosporins due to minimal disruption of normal intestinal flora 2, 3
• Rash occurs occasionally but is generally mild and self-limited 3
• Transient elevation of liver enzymes (AST/ALT) occurs at low frequency, with three-fold increases comparable to control antibiotics 3

Serious Adverse Effects (Rare)

• Hypersensitivity reactions can occur but are rare; importantly, aztreonam has negligible immunologic cross-reactivity with other beta-lactams and can be safely administered to patients with IgE-mediated penicillin hypersensitivity 2
• Treatment discontinuation due to adverse effects occurs in only 2.1% of patients 3
• Superinfections occur in 2-6% of patients, similar to other beta-lactam antibiotics 3

Key Safety Advantages

Aztreonam does NOT cause the following toxicities commonly seen with aminoglycosides:

• No nephrotoxicity: Unlike aminoglycosides, aztreonam does not cause kidney damage and is considered a useful nonnephrotoxic drug 4, 5
• No ototoxicity: There is no evidence of hearing loss or vestibular dysfunction 2, 5
• No routine serum level monitoring required, unlike aminoglycosides 5
• Does not displace bilirubin from albumin, making it safe in neonates 2

Special Populations

Patients with Renal Impairment

Dosage must be adjusted in renal dysfunction because 60-70% of aztreonam is excreted unchanged in the urine:

• Creatinine clearance 10-30 mL/min/1.73 m²: Reduce dose by half after an initial loading dose of 1-2 g 1
• Creatinine clearance <10 mL/min/1.73 m² (including hemodialysis): Give usual initial dose, then maintenance dose should be one-fourth of the usual dose at standard intervals; give one-eighth of initial dose after each hemodialysis session 1
• Serum clearance is directly proportional to creatinine clearance, requiring careful dose adjustment 4

Elderly Patients

• Renal function is a major determinant of dosage in elderly patients who may have diminished renal function 1
• Serum creatinine may not accurately reflect renal status; creatinine clearance estimates should be obtained 1
• Mean serum half-life increases and renal clearance decreases with age, consistent with age-related decline in renal function 1

Pediatric Patients

• Safety and effectiveness established for ages 9 months to 16 years for intravenous administration 1
• Insufficient data for infants under 9 months or for intramuscular administration in pediatric patients 1
• Aztreonam penetrates readily into cerebrospinal fluid and does not displace bilirubin from albumin, making it potentially safer than some alternatives in this population 2

Pregnancy and Lactation

• Aztreonam crosses the placenta and enters fetal circulation 1
• Animal studies at doses 2.2-2.9 times the maximum human dose showed no evidence of embryotoxicity, fetotoxicity, or teratogenicity 1
• Should be used during pregnancy only if clearly needed as adequate human studies are lacking 1
• Excreted in breast milk at concentrations <1% of maternal serum levels; consider temporary discontinuation of nursing 1

Clinical Monitoring

No routine monitoring is required for most patients, which is a major advantage over aminoglycosides. 5

However, monitor the following in specific situations:

• Liver function tests if baseline hepatic disease is present 3
• Renal function in elderly patients and those with baseline renal impairment 1
• Signs of superinfection during prolonged therapy 3

Common Pitfalls to Avoid

• Do not assume standard dosing is safe in renal impairment: Failure to adjust doses in patients with creatinine clearance <30 mL/min can lead to drug accumulation 1, 4
• Do not rely solely on serum creatinine in elderly patients: Use calculated creatinine clearance for accurate dosing 1
• Do not withhold aztreonam from penicillin-allergic patients: Aztreonam has negligible cross-reactivity and can be safely used in IgE-mediated penicillin hypersensitivity 2
• Do not use doses smaller than indicated: Inadequate dosing may lead to treatment failure, particularly with Pseudomonas aeruginosa infections 1