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 for Adults

For susceptible gram-negative infections, aztreonam should be dosed at 500 mg to 2 g IV/IM every 6-12 hours depending on infection severity, with treatment continued for at least 48 hours after clinical improvement or bacterial eradication, though persistent infections may require several weeks of therapy. 1

Dosing by Infection Severity

• Urinary tract infections: 500 mg or 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 of Administration

• Use IV route for patients requiring single doses >1 g or those with bacterial septicemia, localized parenchymal abscess, peritonitis, or other severe systemic/life-threatening infections 1
• IM administration is acceptable for less severe infections with doses ≤1 g 1

Renal Dose Adjustments

Aztreonam requires dose reduction in renal impairment since 60-70% is excreted unchanged in urine. 1, 2

• CrCl 10-30 mL/min: Give usual loading dose (1-2 g), then halve the maintenance dose 1
• CrCl <10 mL/min or hemodialysis: Give usual initial dose (500 mg, 1 g, or 2 g), then maintenance dose is one-fourth of initial dose at usual intervals (6,8, or 12 hours); give one-eighth of initial dose after each hemodialysis session for serious infections 1

Pediatric Dosing

For pediatric patients (1 month to 12 years), administer aztreonam IV only, as insufficient data exist for IM dosing or dosing in pediatric renal impairment. 1

• Mild to moderate infections: 30 mg/kg every 8 hours 1
• Moderate to severe infections: 30 mg/kg every 6-8 hours 1
• Maximum daily dose: 120 mg/kg/day 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 treatment for several weeks 1
• Bone and musculoskeletal infections: Minimum 4-6 weeks when used as part of combination therapy for multidrug-resistant organisms 3

Special Considerations for Carbapenem-Resistant Enterobacterales (CRE)

For metallo-β-lactamase (MBL)-producing CRE causing severe infections, aztreonam must be combined with ceftazidime-avibactam rather than used as monotherapy. 4, 5, 6

Combination Therapy Dosing for MBL-Producing CRE

• Aztreonam: 2 g IV every 6 hours 3
• Plus ceftazidime-avibactam: 2.5 g IV every 8 hours as a prolonged 3-hour infusion 3
• This combination demonstrates significantly lower 30-day mortality (19.2% vs 44%) compared to alternative therapies 5, 6

Mechanistic Rationale

• Aztreonam is not hydrolyzed by metallo-β-lactamases but is susceptible to ESBLs and AmpC enzymes commonly co-produced by MBL-producing organisms 6
• Ceftazidime-avibactam protects aztreonam from these co-produced beta-lactamases, creating synergistic activity in 90% of MBL-producing strains 3
• Do NOT use aztreonam monotherapy for CRE, as it does not cover other beta-lactamases often co-produced by such strains 5

Clinical Caveats and Pitfalls

• Never use doses smaller than indicated, as this promotes resistance 1
• Elderly patients: Renal status is a major determinant of dosage; obtain creatinine clearance estimates rather than relying solely on serum creatinine 1
• Pseudomonas aeruginosa in cystic fibrosis: Aztreonam shows clinical improvement but often fails to achieve bacteriologic cure 7
• Structural urinary tract abnormalities: Expect early relapses of bacteriuria despite initial clinical response 7
• Resistance emergence: Monitor for clinical deterioration and obtain repeat cultures, as resistance can develop during therapy, particularly with P. aeruginosa 8
• Gram-positive and anaerobic coverage: Aztreonam has NO activity against gram-positive bacteria or anaerobes; combination therapy is mandatory for mixed infections 9, 10, 8