What is the dosage and treatment duration of Azactam (aztreonam) for infections caused by gram-negative bacteria?

Aztreonam Dosage and Treatment Duration for Gram-Negative Infections

For infections caused by gram-negative bacteria, aztreonam should be dosed at 1-2 grams IV every 6-8 hours for severe infections and 500 mg-1 gram IV every 8-12 hours for less severe infections, with treatment duration generally continuing for at least 48 hours after clinical improvement or until evidence of bacterial eradication, typically 7-14 days total. 1

Standard Dosing Recommendations

Adult Dosing

• Urinary tract infections: 500 mg or 1 g IV/IM every 8-12 hours
• Moderately severe systemic infections: 1 g or 2 g IV/IM every 8-12 hours
• Severe systemic or life-threatening infections: 2 g IV every 6-8 hours
• Pseudomonas aeruginosa infections: 2 g IV every 6-8 hours is recommended due to the serious nature of these infections 1

Pediatric Dosing

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

Duration of Treatment

Treatment duration depends on the severity and site of infection:

• Generally, aztreonam should be continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained
• Persistent infections may require treatment for several weeks
• For complicated urinary tract infections, typical duration is 7-14 days (14 days for men when prostatitis cannot be excluded) 2, 1

Dosage Adjustments

Renal Impairment

• Creatinine clearance 10-30 mL/min: Half the usual dose after an initial loading dose of 1-2 g
• Creatinine clearance <10 mL/min: Initial dose of 500 mg, 1 g, or 2 g, followed by maintenance dose of one-fourth the usual initial dose at the usual fixed interval
• Hemodialysis patients: For serious infections, add one-eighth of the initial dose after each hemodialysis session 1

Elderly Patients

• Dosage should be adjusted based on creatinine clearance estimates, as elderly patients often have diminished renal function 1

Special Clinical Scenarios

Carbapenem-Resistant Gram-Negative Infections

• For metallo-β-lactamases-producing CRE infections, aztreonam combined with ceftazidime-avibactam is suggested as a preferential choice over other antimicrobial therapies 3
• This combination shows good in-vitro synergy against NDM-producing and KPC-producing CRE isolates 3, 2
• The combination is associated with lower 30-day mortality (19.2% vs 44%) and lower clinical treatment failure rates compared to other active antimicrobial agents 3

Hospital-Acquired Pneumonia (HAP)

• For HAP patients with severe penicillin allergy, aztreonam at 2 g IV every 8 hours can be used as an alternative to β-lactam-based antibiotics 3
• When aztreonam is used for HAP, coverage for gram-positive organisms should be included since aztreonam has no activity against gram-positive bacteria 3, 2

Administration Routes

• The intravenous route is recommended for:
  • Patients requiring single doses greater than 1 g
  • Patients with bacterial septicemia
  • Patients with localized parenchymal abscess
  • Patients with peritonitis
  • Patients with other severe systemic or life-threatening infections 1

Important Clinical Considerations

• Aztreonam has a unique spectrum of activity against aerobic gram-negative bacteria but has no activity against gram-positive bacteria and anaerobes 2, 4
• It is particularly valuable for patients with β-lactam allergies due to minimal cross-reactivity with other β-lactam antibiotics 2
• For mixed infections or those of unknown etiology, combination therapy is recommended to ensure coverage of gram-positive and anaerobic bacteria 5
• Aztreonam can be safely combined with antibiotics targeting gram-positive organisms (e.g., vancomycin, linezolid) or anaerobes 1

Monitoring

• Regular assessment of clinical response and bacterial eradication
• Monitor renal function, especially in elderly patients or those with pre-existing renal impairment
• Common adverse effects include diarrhea, abdominal discomfort, transaminase elevations, and eosinophilia 2

By following these dosing guidelines and treatment durations, aztreonam can effectively treat gram-negative infections while minimizing the risk of adverse effects and antimicrobial resistance.