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

Aztreonam: Recommended Use and Dosage for Gram-Negative Bacterial Infections

Aztreonam is indicated for the treatment of infections caused by susceptible gram-negative bacteria, with dosing ranging from 500 mg to 2 g every 6-12 hours depending on infection severity, with specific dosage adjustments required for renal impairment. 1

Spectrum of Activity

• Aztreonam is a monobactam antibiotic with selective activity against gram-negative aerobic bacteria and is inactive against gram-positive bacteria and anaerobes 2
• Particularly effective against Enterobacteriaceae (including E. coli, Klebsiella pneumoniae, Proteus mirabilis), Pseudomonas aeruginosa, Haemophilus influenzae, and other gram-negative pathogens 1
• Demonstrates stability against many beta-lactamases, making it valuable for treating certain resistant gram-negative infections 2

FDA-Approved Indications

Aztreonam is indicated for the treatment of the following infections caused by susceptible gram-negative microorganisms:

• Urinary tract infections (complicated and uncomplicated) 1
• Lower respiratory tract infections (pneumonia and bronchitis) 1
• Septicemia 1
• Skin and skin-structure infections 1
• Intra-abdominal infections (including peritonitis) 1
• Gynecologic infections 1

Dosage Recommendations

Adult Dosing

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

Pediatric Dosing

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

Renal Impairment Dosing

• For patients with creatinine clearance between 10-30 mL/min/1.73 m², the dosage should be halved after an initial loading dose of 1 g or 2 g 1
• For severe renal failure (creatinine clearance <10 mL/min/1.73 m²), maintenance dose should be one-fourth of the usual initial dose given at the usual fixed interval 1
• For hemodialysis patients with serious infections, one-eighth of the initial dose should be given after each hemodialysis session in addition to maintenance doses 1

Special Use in Resistant Infections

• Metallo-β-lactamase-producing Carbapenem-Resistant Enterobacterales: Aztreonam combined with ceftazidime-avibactam is strongly recommended as the preferred treatment 3, 4
• This combination has shown significantly lower 30-day mortality (19.2% vs 44%) compared to other treatment options for these highly resistant infections 3, 4
• Aztreonam is uniquely active against metallo-β-lactamase-producing CRE as it is not hydrolyzed by these enzymes, though as monotherapy it does not cover other beta-lactamases often co-produced by such strains 3

Administration Routes

• Intravenous route is recommended for patients requiring single doses greater than 1 g or those with bacterial septicemia, localized parenchymal abscess, peritonitis, or other severe systemic or life-threatening infections 1
• Intramuscular administration is an alternative for less severe infections 1
• Oral administration is not effective due to poor bioavailability (approximately 1%) 5

Duration of Therapy

• Generally, aztreonam should be continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained 1
• Persistent infections may require treatment for several weeks 1

Clinical Considerations and Caveats

• When treating infections of unknown etiology, concurrent therapy with other antimicrobial agents is recommended to cover gram-positive and anaerobic pathogens 1, 6
• Certain antibiotics (e.g., cefoxitin, imipenem) may induce high levels of beta-lactamase in some gram-negative bacteria, potentially resulting in antagonism to aztreonam; these should not be used concurrently 1
• Aztreonam is incompatible with nafcillin sodium, cephradine, and metronidazole 1
• In the absence of anaerobes, aztreonam has minimal effect on indigenous fecal flora, which may be advantageous in preventing C. difficile infections 5

Pharmacokinetics

• Peak serum levels occur within 5 minutes after IV injection and about 1 hour after IM injection 1
• Serum half-life averages 1.7 hours in patients with normal renal function 1
• Approximately 60-70% of a dose is excreted unchanged in the urine within 8 hours 1
• Serum protein binding averages 56% 1

Aztreonam represents a valuable option for treating gram-negative infections, particularly in patients with allergies to other beta-lactams or when aminoglycoside toxicity is a concern 5, 7.