Aztreonam (Systemic)

Name: Aztreonam (Systemic)

Uses of Aztreonam

  • It is used to treat or prevent bacterial infections.

Pronunciation

(AZ tree oh nam)

Pharmacologic Category

  • Antibiotic, Monobactam

Pharmacology

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Monobactam structure makes cross-allergenicity with beta-lactams unlikely.

Absorption

IM: Well absorbed; IM and IV doses produce comparable serum concentrations

Distribution

Injection: Widely into body tissues, cerebrospinal fluid, bronchial secretions, peritoneal fluid, bile, and bone

Vd: Neonates: 0.26 to 0.36 L/kg; Children: 0.2 to 0.29 L/kg; Adults: 0.2 L/kg

Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)

CSF:blood level ratio: Meninges: Inflamed: 8% to 40%; Normal: ~1%

Metabolism

Injection: Hepatic (minor %)

Excretion

Injection: Urine (60% to 70% as unchanged drug); feces (~13% to 15%)

Time to Peak

IM, IV push: Within 60 minutes; IV infusion: 1.5 hours

Half-Life Elimination

Injection:

Neonates: <7 days, ≤2.5 kg: 5.5 to 9.9 hours; <7 days, >2.5 kg: 2.6 hours; 1 week to 1 month: 2.4 hours

Children 2 months to 12 years: 1.7 hours

Children with cystic fibrosis: 1.3 hours

Adults: Normal renal function: 1.7 to 2.9 hours

End-stage renal disease: 6 to 8 hours

Protein Binding

56%

Off Label Uses

Osteomyelitis, native vertebral

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, aztreonam is an effective and recommended alternative treatment option for the treatment of native vertebral osteomyelitis due to Pseudomonas aeruginosa in patients with severe penicillin allergy and quinolone-resistant strains.

Surgical prophylaxis (perioperative)

Based on the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Surgical Infection Society (SIS), and the Society of Healthcare Epidemiology of America (SHEA) guidelines for antimicrobial prophylaxis in surgery, aztreonam is an effective and recommended alternative agent (in combination with other antibiotics) for patients with beta-lactam allergy for a number of surgical procedures (eg, gastroduodenal, biliary tract, appendectomy, hysterectomy, urologic involving implanted prosthesis, liver transplantation, or pancreas and pancreas-kidney transplantation) and may be used first-line in combination with cefazolin for procedures involving implanted prosthetic material (eg, penile prosthesis).

Dosing Adult

Urinary tract infection: IM, IV: 500 mg to 1 g every 8 to 12 hours

Moderately severe systemic infections: 1 g IV or IM or 2 g IV every 8 to 12 hours. Note: IV route preferred for septicemia, intra-abdominal abscess, or peritonitis; higher doses (8 to 12 g daily) may be needed for patients with cystic fibrosis (Zobell 2013) or other infections (Solomkin 2010).

Osteomyelitis, native vertebral due to P. aeruginosa (off-label use): IV: 2 g every 8 hours for 6 weeks Note: Double coverage may be considered (ie, aztreonam plus an aminoglycoside) (IDSA [Berbari 2015])

Severe systemic or life-threatening infections (eg, Pseudomonas aeruginosa): IV: 2 g every 6 to 8 hours; maximum: 8 g daily. Note: Higher doses (8 to 12 g daily) may be needed for patients with cystic fibrosis (Zobell 2013) or other infections (Solomkin 2010).

Pneumonia, hospital-acquired or ventilator-associated (alternative therapy) (off-label dose): IV: 2 g every 8 hours for 7 days; may consider shorter or longer durations depending on rate of clinical improvement. When used as empiric therapy, use in combination with an agent active against Staphylococcus aureus with or without an additional antipseudomonal agent (dependent on patient and institution-specific risk factors) (Kalil 2016).

Surgical (perioperative) prophylaxis (off-label use): IV: 2 g within 60 minutes prior to surgery. Doses may be repeated in 4 hours if procedure is lengthy or if there is excessive blood loss (Bratzler 2013).

Reconstitution

IM: Reconstitute vial with at least 3 mL SWFI, sterile bacteriostatic water for injection, NS, or bacteriostatic sodium chloride per gram of aztreonam; immediately shake vigorously.

IV:

Bolus injection: Reconstitute vial with 6 mL to 10 mL SWFI; immediately shake vigorously.

Infusion: Reconstitute vial with at least 3 mL SWFI per gram of aztreonam; immediately shake vigorously. Reconstituted solutions are colorless to light yellow straw and may turn pink upon standing without affecting potency. Further dilute in an appropriate solution for infusion (eg, D5W, NS) to a final concentration ≤2% (ie, final concentration should not exceed 20 mg/mL).

Warnings/Precautions

Concerns related to adverse effects:

• Beta-lactam allergy: Rare cross-allergenicity to penicillins, cephalosporins, or carbapenems may occur; use with caution in patients with a history of hypersensitivity to beta-lactams.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use the injectable formulation with caution in patients with renal impairment; dosing adjustment required.

• Toxic epidermal necrolysis: Use with caution in bone marrow transplant patients with multiple risk factors for toxic epidermal necrolysis (TEN) (eg, sepsis, radiation therapy, drugs known to cause TEN); rare cases of TEN in this population have been reported.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Injection: Periodic liver function test; monitor for signs of anaphylaxis during first dose

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