What is the recommended pediatric dose of aztreonam (Intramuscular (IM) or Intravenous (IV)) for a child with normal or impaired renal function?

Pediatric Dosing of Aztreonam (IM/IV)

Standard Dosing for Pediatric Patients with Normal Renal Function

For pediatric patients with normal renal function, aztreonam should be administered intravenously at 30 mg/kg every 8 hours for mild to moderate infections, or 30 mg/kg every 6-8 hours for moderate to severe infections, with a maximum daily dose of 120 mg/kg/day. 1, 2

Dosing by Infection Severity

• Mild to moderate infections: 30 mg/kg IV every 8 hours 1, 2
• Moderate to severe infections: 30 mg/kg IV every 6-8 hours 1, 2
• Maximum daily dose: 120 mg/kg/day 1, 2

Route of Administration

• Intravenous administration is strongly recommended for pediatric patients, as there are insufficient data regarding intramuscular administration in this population 1, 2
• The IV route is particularly important for patients requiring single doses greater than 1 g or those with bacterial septicemia, localized parenchymal abscess, peritonitis, or other severe systemic or life-threatening infections 2

Special Populations and Considerations

Complicated Intra-Abdominal Infections

• For pediatric patients with complicated intra-abdominal infection, aztreonam 90-120 mg/kg/day divided every 6-8 hours is an acceptable regimen 1
• β-lactam antibiotic dosages (including aztreonam) should be maximized if undrained intra-abdominal abscesses may be present 1

Cystic Fibrosis Patients

• For children with cystic fibrosis infected with Pseudomonas aeruginosa, a higher dose of 200 mg/kg/day divided every 6 hours would be predicted to maintain serum concentrations above the MIC for these organisms for the majority of the dosing interval 3
• This recommendation is based on pharmacokinetic data showing mean half-life of 1.3 hours, steady-state volume of distribution of 0.25 L/kg, and body clearance of 127.2 ml/min/1.73m² in children with cystic fibrosis 3

Multidrug-Resistant Infections

• For multidrug-resistant tuberculosis in children, aztreonam (combined with clavulanate) should be dosed at 20-40 mg/kg per dose three times daily, with frequency reduction required in renal dysfunction 4
• For carbapenem-resistant Enterobacterales or extensively drug-resistant organisms, standard dosing recommendations apply, though combination therapy is often required 4

Renal Impairment Dosing

There are insufficient data regarding dosing in pediatric patients with renal impairment. 1, 2

• In adult patients with renal impairment, dosage adjustments are made based on creatinine clearance, but specific pediatric guidelines are not established 2
• Serum clearance of aztreonam is directly proportional to creatinine clearance, so dosage adjustment must be made in the presence of reduced clearance 5

Pharmacokinetic Considerations

Distribution and Elimination

• Aztreonam is widely distributed in body tissues and fluids with a steady-state volume of distribution of approximately 0.18 L/kg 5
• The average elimination half-life is 1.7 hours in adults and children, but approximately 1.3 hours in children with cystic fibrosis 5, 3
• Between 60-70% of the drug is excreted unchanged in the urine 5

Peak Concentrations

• After a 2 gram IV dose in adults, MIC90 values for most Enterobacteriaceae are exceeded for 8 hours, and for P. aeruginosa for almost 6 hours 5
• Intramuscular dosing results in peak serum levels in approximately one hour, while intravenous dosing results in peak levels within five minutes 5

Duration of Therapy

• Aztreonam should generally be continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained 2
• Persistent infections may require treatment for several weeks 2
• Doses smaller than those indicated should not be used 2

Administration Guidelines

IV Preparation

• For bolus injection: Reconstitute vial contents with 6-10 mL Sterile Water for Injection 2
• For infusion: Each gram should be initially reconstituted with at least 3 mL Sterile Water for Injection, then further diluted in appropriate IV solution 2
• Use reconstituted solution immediately and discard any remaining unused solution 2

Compatibility

• Aztreonam IV solutions (≤2% w/v) are stable for up to 48 hours at room temperature or 7 days refrigerated when mixed with clindamycin, gentamicin, tobramycin, or cefazolin 2
• Aztreonam is incompatible with nafcillin sodium, cephradine, and metronidazole 2

Important Clinical Caveats

When to Use Aztreonam

• Aztreonam is particularly useful as a nonnephrotoxic alternative to aminoglycosides for aerobic gram-negative infections 5, 6
• It can replace the aminoglycoside component in mixed infections involving both gram-positive and gram-negative bacteria 6
• For children with severe β-lactam allergies, ciprofloxacin plus metronidazole or an aminoglycoside-based regimen (which could include aztreonam) are recommended 1

Limitations

• Aztreonam has no activity against gram-positive bacteria or anaerobes, so concurrent therapy with other antimicrobial agents is recommended before the causative organism is determined, particularly in seriously ill or immunocompromised patients 7, 6
• Resistance may emerge during treatment of P. aeruginosa infections 7
• Stenotrophomonas maltophilia is typically resistant to aztreonam 7

Monitoring

• No specific therapeutic drug monitoring is routinely required for aztreonam 5
• Clinical response should be assessed at 48 hours to determine continuation of therapy 2