Aztreonam

• Approved Indications:
• Moderate to severe infections caused by susceptible aerobic gram-negative bacteria.
• Urinary tract infections (cystitis, pyelonephritis).
• Lower respiratory tract infections, including pneumonia.
• Intra-abdominal infections, including peritonitis.
• Skin and soft tissue infections.
• Gynecological infections such as pelvic inflammatory disease.
• Septicemia due to susceptible gram-negative bacteria.
• Bone and joint infections.
• Meningitis caused by susceptible organisms.
• Off-label and Clinically Accepted Uses:
• Pulmonary infections in cystic fibrosis patients caused by Pseudomonas aeruginosa.
• Surgical prophylaxis in high-risk procedures.
• Treatment of infections in penicillin-allergic patients due to minimal cross-reactivity.

Route: Intravenous (IV) or intramuscular (IM) injection.

Adults:

• Typical dosing ranges from 1 to 2 grams every 8 to 12 hours, adjusted according to infection severity and clinical response.
• For severe infections, 2 grams IV every 8 hours may be used.

Pediatrics:

• Dosage based on body weight: generally 30 to 50 mg/kg every 8 hours, maximum daily dose not to exceed adult doses.
• Neonates and infants require careful dosing adjustments and close monitoring.

Elderly:

• Use standard adult doses; monitor renal function closely.

Renal Impairment:

• Dosage adjustments necessary for creatinine clearance <30 mL/min.
• Increased dosing intervals or reduced doses advised to avoid accumulation.

Administration Notes:

• IV infusion is typically diluted in compatible fluids and administered over approximately 30 minutes.
• IM injections should be given deep into large muscles.
• Reconstituted solutions should be used promptly to maintain potency and sterility.

Aztreonam is a monobactam beta-lactam antibiotic that inhibits bacterial cell wall synthesis. It binds selectively to penicillin-binding protein 3 (PBP-3) of susceptible aerobic gram-negative bacteria, disrupting peptidoglycan cross-linking essential for cell wall structural integrity. This results in cell wall weakening, bacterial lysis, and cell death. Aztreonam is active predominantly against aerobic gram-negative bacilli, including Pseudomonas aeruginosa, but lacks significant activity against gram-positive or anaerobic bacteria.

• Absorption:
  Not absorbed orally; administered parenterally (IV or IM).
• Distribution:
  Widely distributed throughout body tissues and fluids, including bile, sputum, urine, and cerebrospinal fluid (when meninges are inflamed).
  Volume of distribution approximates extracellular fluid volume.
• Metabolism:
  Minimal hepatic metabolism; largely excreted unchanged.
• Elimination Half-life:
  Approximately 1.7 hours in patients with normal renal function.
• Excretion:
  Primarily eliminated unchanged via renal glomerular filtration.

• Pregnancy:
  FDA Category B — animal studies have not demonstrated fetal risk; however, adequate and well-controlled studies in pregnant women are lacking. Use only if clearly needed.
• Lactation:
  Excreted in breast milk in small amounts; use with caution during breastfeeding.

• Primary Therapeutic Class: Antibiotic
• Subclass: Monobactam beta-lactam antibiotic

• Known hypersensitivity to aztreonam or any component of the formulation.
• Use with caution in patients with known hypersensitivity to other beta-lactam antibiotics due to rare potential cross-reactivity.

• Hypersensitivity reactions, including anaphylaxis and angioedema, may occur; discontinue immediately if such reactions develop.
• Prolonged use may lead to superinfection, including fungal infections.
• Renal function should be monitored during therapy, with dose adjustments as necessary.
• Caution advised in neonates and infants due to immature renal clearance.

Common:

• Injection site reactions (pain, inflammation).
• Rash.
• Diarrhea.
• Nausea, vomiting.

Serious but Rare:

• Severe allergic reactions (anaphylaxis).
• Clostridioides difficile-associated diarrhea.
• Transient elevations in liver enzymes.
• Hematologic abnormalities such as neutropenia or thrombocytopenia.

• No significant direct interactions reported.
• Concurrent nephrotoxic drugs (e.g., aminoglycosides, vancomycin) may increase risk of kidney damage; monitor renal function closely.
• Probenecid may reduce renal clearance of aztreonam, increasing plasma concentrations.

• Remains a preferred antibiotic for gram-negative infections in penicillin-allergic patients.
• Increasing bacterial resistance requires susceptibility testing prior to therapy.
• Combination therapy may be recommended for multi-drug resistant infections.

• Store powder and reconstituted solutions at 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• After reconstitution, use within recommended timeframe (typically 24 hours refrigerated).
• Do not freeze.