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 bacterial 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 g or 2 g every 8-12 hours 1

Severe systemic or life-threatening infections:

• 2 g every 6-8 hours 1
• The IV route is mandatory for single doses >1 g or in patients with septicemia, parenchymal abscesses, peritonitis, or other severe infections 1

Pseudomonas aeruginosa infections:

• 2 g every 6-8 hours is recommended at least initially, given the serious nature of these infections 1

Special Populations

Renal Impairment

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

• Give standard loading dose (1-2 g), then halve all subsequent doses 1

Severe renal failure (CrCl <10 mL/min/1.73 m²) or hemodialysis:

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

Pediatric Patients (1 month to 12 years)

Mild to moderate infections:

• 30 mg/kg IV every 8 hours 1

Moderate to severe infections:

• 30 mg/kg IV every 6-8 hours 1
• Maximum daily dose: 120 mg/kg/day 1
• IV administration only; insufficient data for IM dosing in children 1

Elderly Patients

• Estimate creatinine clearance (serum creatinine alone is unreliable) and adjust dosing accordingly, as renal function is the major determinant 1

Treatment Duration

General principle: Continue aztreonam for at least 48 hours after the patient becomes asymptomatic or bacterial eradication is documented 1

Persistent infections: May require several weeks of treatment 1

Bone and musculoskeletal infections: Minimum 4-6 weeks when used in combination regimens for multidrug-resistant organisms 2

Combination Therapy for Carbapenem-Resistant Enterobacterales

For metallo-β-lactamase (MBL)-producing CRE with severe infections, aztreonam 2 g IV every 6 hours should be combined with ceftazidime-avibactam 2.5 g IV every 8 hours as a 3-hour infusion, demonstrating significantly lower 30-day mortality (19.2% vs 44%) compared to alternative therapies. 3, 4, 2

Mechanistic Rationale

• Aztreonam is not hydrolyzed by metallo-β-lactamases (NDM, VIM, IMP) but remains susceptible to ESBLs and AmpC enzymes commonly co-produced by these organisms 3, 4
• Ceftazidime-avibactam protects aztreonam from these co-produced beta-lactamases, creating synergistic activity in 90% of MBL-producing strains 2
• This combination is specifically recommended by ESCMID guidelines for severe CRE infections carrying MBLs and/or resistant to newer antibiotic monotherapies (conditional recommendation, moderate certainty of evidence) 5, 4

Critical Caveat

• Identify the carbapenemase type before treatment whenever possible through phenotypic or genotypic PCR testing 2
• This combination is ineffective against non-MBL resistance mechanisms in Pseudomonas aeruginosa 4
• For KPC-producing or OXA-48-producing CRE, use ceftazidime-avibactam monotherapy instead 2

Pharmacokinetic Considerations

• Peak serum levels occur within 5 minutes after IV dosing and approximately 1 hour after IM dosing 6
• Elimination half-life: 1.7 hours, necessitating frequent dosing 6
• After 2 g IV, MIC90 values for most Enterobacteriaceae are exceeded for 8 hours and for P. aeruginosa for almost 6 hours 6
• 60-70% excreted unchanged in urine, achieving concentrations approximating 3,000 mcg/mL two hours after 1 g IV 6
• Widely distributed to bone, prostate, and cerebrospinal fluid at concentrations above MIC90 for most gram-negative bacteria 6

Important Clinical Pitfalls

Do not use doses smaller than indicated in the FDA labeling, as this may lead to treatment failure 1

Aztreonam has no activity against gram-positive bacteria or anaerobes, so combination therapy is required for polymicrobial infections or empiric therapy when the pathogen is unknown 7, 8, 9

For Pseudomonas aeruginosa in cystic fibrosis patients, bacteriologic cure is rarely achieved despite clinical improvement, similar to other antipseudomonal agents 10

Resistance emergence occurs in 3.8-10.4% of KPC-producing CRE infections treated with ceftazidime-avibactam; the addition of aztreonam for MBL-producers provides resistance suppression 2