What is the dosage and administration of Aztreonam (Aztreonam) for treating infections caused by susceptible gram-negative bacteria?

Aztreonam Dosing and Administration for Gram-Negative Infections

Standard Dosing Regimen

For moderately severe systemic infections, administer aztreonam 1-2 g IV every 8 hours; for severe or life-threatening infections, use 2 g IV every 6-8 hours, with the intravenous route mandatory for doses exceeding 1 g or in patients with septicemia, abscess, or peritonitis. 1

Dosing by Infection Severity

• Urinary tract infections: 500 mg to 1 g every 8-12 hours 1
• Moderately severe systemic infections: 1-2 g every 8-12 hours 1
• Severe systemic or life-threatening infections: 2 g every 6-8 hours 1
• Pseudomonas aeruginosa infections: 2 g every 6-8 hours is recommended at least initially, given the serious nature of these infections 1

Route Selection

• Intramuscular administration is appropriate for doses ≤1 g in less severe infections 1
• Intravenous administration is required for single doses >1 g, bacterial septicemia, localized parenchymal abscess, peritonitis, or other severe systemic infections 1

Renal Dose Adjustments

Halve the standard dose for patients with creatinine clearance 10-30 mL/min/1.73 m² after an initial loading dose, and reduce to one-fourth the usual dose for creatinine clearance <10 mL/min/1.73 m². 1

Specific Renal Dosing Algorithm

• CrCl 10-30 mL/min/1.73 m²: Give full loading dose (1-2 g), then reduce maintenance dose by 50% at usual intervals 1
• CrCl <10 mL/min/1.73 m² (including hemodialysis): Give full initial dose (500 mg, 1 g, or 2 g), then one-fourth of initial dose at usual intervals (every 6,8, or 12 hours) 1
• Post-hemodialysis supplementation: Give one-eighth of the initial dose after each hemodialysis session 1

Pediatric Dosing

For pediatric patients aged 1 month to 12 years with normal renal function, administer 30 mg/kg IV every 6-8 hours for moderate-to-severe infections (maximum 120 mg/kg/day), with intravenous administration required. 1

• Mild to moderate infections: 30 mg/kg every 8 hours 1
• Moderate to severe infections: 30 mg/kg every 6-8 hours 1
• Insufficient data exist for intramuscular administration or dosing in pediatric patients with renal impairment 1

Duration of Therapy

Continue aztreonam for at least 48 hours after the patient becomes asymptomatic or bacterial eradication is documented; persistent infections may require several weeks of treatment. 1

Combination Therapy for Metallo-β-Lactamase Producers

When treating infections caused by metallo-β-lactamase-producing carbapenem-resistant Enterobacteriaceae (particularly NDM producers), combine aztreonam 2 g IV every 6 hours with ceftazidime-avibactam 2.5 g IV every 8 hours (infused over 2 hours), which demonstrates significantly lower 30-day mortality (19.2% vs 44%) compared to alternative regimens. 2, 3

Critical Mechanistic Rationale

• Aztreonam is stable against metallo-β-lactamases (including NDM, VIM, IMP) but is hydrolyzed by ESBLs and AmpC enzymes commonly co-produced by these organisms 2, 3
• Never use aztreonam monotherapy for MBL-producing infections—it will fail due to co-produced β-lactamases 3
• The combination achieves synergistic activity in 90% of MBL-producing strains 4

Carbapenemase-Specific Algorithm

• KPC or OXA-48 producers: Use ceftazidime-avibactam 2.5 g IV every 8 hours as monotherapy (nearly 100% susceptibility) 2, 4
• MBL producers (NDM, VIM, IMP): Use ceftazidime-avibactam 2.5 g IV every 8 hours PLUS aztreonam 2 g IV every 6 hours 2, 3, 4
• Obtain carbapenemase genotyping or phenotypic testing immediately to guide therapy 2, 4

Preparation and Compatibility

• For IV bolus: Reconstitute with 6-10 mL Sterile Water for Injection 1
• For IV infusion: Reconstitute each gram with at least 3 mL Sterile Water for Injection, then further dilute in compatible solutions (0.9% NaCl, D5W, Lactated Ringer's) 1
• For IM injection: Reconstitute with at least 3 mL appropriate diluent per gram 1

Stability and Incompatibilities

• Aztreonam admixtures with clindamycin, gentamicin, tobramycin, or cefazolin are stable for 48 hours at room temperature or 7 days refrigerated 1
• Aztreonam is incompatible with nafcillin, cephradine, and metronidazole—do not mix 1

Important Clinical Caveats

• Aztreonam has exceptional activity against aerobic gram-negative bacteria but no activity against gram-positive bacteria or anaerobes, requiring combination therapy for mixed infections 5, 6, 7
• Peak serum levels occur within 5 minutes after IV dosing and approximately 1 hour after IM dosing 5
• Urinary concentrations reach approximately 3,000 mcg/mL two hours after a 1 g IV dose 5
• Monitor for resistance emergence (3.8-10.4% in KPC-producing CRE); obtain repeat cultures if clinical deterioration occurs within 48-72 hours 3, 4