What is the recommended dosage and treatment duration for Aztreonam (Aztreonam) in treating infections caused by susceptible gram-negative bacteria?

Aztreonam Dosing and Treatment Duration for Gram-Negative Infections

Standard Dosing Regimens

For susceptible gram-negative infections, aztreonam should be dosed at 500 mg to 2 g every 6-12 hours intravenously or intramuscularly depending on infection severity, with treatment continued for at least 48 hours after clinical improvement or bacterial eradication is documented. 1

Dosing by Infection Severity

Adults:

• 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/life-threatening infections: 2 g every 6-8 hours 1
• Pseudomonas aeruginosa infections: 2 g every 6-8 hours at initiation (due to higher MICs of 8-16 mcg/mL) 1, 2
• Maximum daily dose: 8 g per day 1

Pediatric patients (1 month to 12 years):

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

Route of Administration

Use intravenous route for:

• Single doses >1 g 1
• Bacterial septicemia 1
• Localized parenchymal abscesses (intra-abdominal) 1
• Peritonitis 1
• Any severe systemic or life-threatening infection 1

Renal Dose Adjustments

Creatinine clearance 10-30 mL/min/1.73m²:

• Give standard loading dose (1-2 g), then reduce maintenance dose by 50% at usual intervals 1

Creatinine clearance <10 mL/min/1.73m² (including hemodialysis):

• Give standard initial dose (500 mg, 1 g, or 2 g) 1
• Maintenance: one-fourth of initial dose at usual intervals (every 6,8, or 12 hours) 1
• Supplemental dosing: Give one-eighth of initial dose after each hemodialysis session 1

Treatment Duration

Continue aztreonam for at least 48 hours after the patient becomes asymptomatic OR evidence of bacterial eradication is obtained. 1

• Persistent infections: May require several weeks of treatment 1
• Osteomyelitis: Typically 7-42 days based on clinical response 3
• Pseudomonas aeruginosa pulmonary infections in cystic fibrosis: Clinical improvement occurs but bacteriologic cure is rarely achieved (similar to other agents) 4

Combination Therapy for Resistant Organisms

Metallo-β-lactamase-producing CRE (NDM, VIM)

Aztreonam combined with ceftazidime-avibactam is the preferred treatment for metallo-β-lactamase-producing carbapenem-resistant Enterobacterales, demonstrating 30-day mortality of 19.2% versus 44% with alternative therapies. 5, 6, 7

Mechanistic rationale:

• Aztreonam is not hydrolyzed by metallo-β-lactamases but IS susceptible to ESBLs and AmpC enzymes co-produced by these organisms 7, 8
• Ceftazidime-avibactam inhibits the co-produced ESBLs/AmpC, protecting aztreonam 5
• Never use aztreonam monotherapy for MBL-producing organisms—it will fail 7

Dosing for combination therapy:

• Standard aztreonam dosing (2 g every 6-8 hours IV) plus ceftazidime-avibactam per its labeling 5
• Identify carbapenemase type before treatment when possible 5, 8

Synergy with Aminoglycosides

Aztreonam demonstrates synergy when combined with aminoglycosides against P. aeruginosa, Acinetobacter, and gentamicin-resistant gram-negative rods 2

Pharmacokinetic Considerations

Peak levels:

• Intramuscular: Peak at ~1 hour 2
• Intravenous: Peak within 5 minutes 2
• Elimination half-life: 1.6-2 hours 2, 9

After 2 g IV dose:

• MIC90 exceeded for 8 hours against most Enterobacteriaceae 2
• MIC90 exceeded for ~6 hours against P. aeruginosa 2
• Urinary concentrations reach ~3,000 mcg/mL at 2 hours after 1 g IV dose 2

Critical Pitfalls to Avoid

• Do not use doses smaller than indicated—inadequate dosing promotes resistance 1
• Do not use aztreonam monotherapy for polymicrobial infections—it lacks activity against gram-positive cocci and anaerobes; combine with appropriate coverage 4, 9
• Monitor for resistance emergence: 3.8-10.4% of patients develop resistance during treatment of carbapenem-resistant organisms 5, 7
• Adjust for renal function in elderly patients—serum creatinine alone may underestimate renal impairment; calculate creatinine clearance 1
• Structural urinary tract abnormalities: Early bacteriuria relapses are common; may require prolonged therapy or surgical correction 4

Spectrum of Activity

Active against (MIC90 ≤1.6 mg/L):

• Most Enterobacteriaceae (except Enterobacter species which require higher concentrations) 10
• Neisseria and Haemophilus species 2
• Pseudomonas aeruginosa (MIC90: 8-32 mg/L) 2, 10

Inactive against:

• Gram-positive aerobic bacteria 2, 10
• Anaerobes including Bacteroides fragilis 10
• Minimal effect on indigenous fecal anaerobes 10