Aztreonam

Aztreonam is a monobactam active only against aerobic Gram-negative bacilli, including Pseudomonas aeruginosa. It is used when beta-lactam allergy limits other options and, in combination with ceftazidime avibactam, for metallo-beta-lactamase producing Enterobacterales.

Classification. Beta-lactam, monobactam.

Mechanism. Binds penicillin-binding protein 3 of Gram-negative bacilli; stable to metallo-beta-lactamases but hydrolysed by ESBL, AmpC and KPC enzymes.

Spectrum. Enterobacterales without ESBL or AmpC, Pseudomonas aeruginosa, Haemophilus, Neisseria. No activity against Gram-positive organisms or anaerobes.

Pharmacokinetics. IV or IM. Half-life 1.5 to 2 hours. Protein binding about 56%. About 60 to 70% excreted unchanged in urine. Reasonable CSF penetration in meningitis.

No loading dose. Maximum 8 g daily.

Adults. - Urinary tract infection: 500 mg to 1 g IV or IM every 8 to 12 hours. - Moderate to severe infection (pneumonia, sepsis, intra-abdominal, pelvic, skin): 1 to 2 g IV every 8 hours. - Severe infection, Pseudomonas: 2 g IV every 6 to 8 hours. - Metallo-beta-lactamase producing Enterobacterales (specialist use): aztreonam 2 g every 8 hours together with ceftazidime avibactam 2.5 g every 8 hours. - Inhaled aztreonam lysine in cystic fibrosis (Pseudomonas suppression): 75 mg three times daily for 28 days, then 28 days off, under specialist direction.

Children 1 month and over. 30 mg/kg every 6 to 8 hours; severe infection 50 mg/kg every 6 to 8 hours (maximum 8 g daily). Neonates: 30 mg/kg every 8 to 12 hours.

Alternatives. Ciprofloxacin, aminoglycosides, ceftazidime or cefepime (allergy permitting), meropenem.

Contraindications. Hypersensitivity to aztreonam. Aztreonam shares an identical side chain with ceftazidime, so patients with ceftazidime allergy may react.

Beta-lactam allergy. Cross-reactivity with penicillins and most cephalosporins is negligible, so it can be given to patients with those allergies.

Adverse effects. Rash, diarrhoea, nausea, injection-site reactions, raised liver enzymes, eosinophilia. Serious: anaphylaxis, Clostridioides difficile infection, severe skin reactions, hepatitis, thrombocytopenia.

Interactions. Warfarin (INR rise), probenecid, aminoglycosides (synergy and additive nephrotoxicity).

Common prescribing errors. Using it as monotherapy when Gram-positive or anaerobic organisms may be involved, not reducing dose in renal failure, and using it in ceftazidime allergy.

Special groups.

• Pregnancy and breastfeeding: acceptable.
• Older adults: adjust by kidney function.
• Kidney impairment: after the first full dose, creatinine clearance 10 to 30 mL/min give 50% of the usual dose; under 10 mL/min give 25%. Haemodialysis: initial dose 500 mg to 2 g, then 25% of the usual dose every 6 to 12 hours, with one eighth of the initial dose added after each session.
• Liver impairment: in chronic liver disease such as alcoholic cirrhosis reduce the dose by 20 to 25% for long courses.
• Region: availability in East Africa is limited.

Preparation. IV bolus: dissolve in 6 to 10 mL water for injection and inject over 3 to 5 minutes. Infusion: dilute to 50 to 100 mL of 0.9% sodium chloride or 5% glucose and infuse over 20 to 60 minutes. IM: reconstitute 1 g with 3 mL of water or 0.9% sodium chloride.

Baseline and monitoring. - Baseline: allergy history (including ceftazidime), cultures, creatinine, liver tests. - During treatment: creatinine, full blood count and liver tests twice weekly. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, severe skin reaction, hepatitis or severe diarrhoea.

Referral and escalation. Infectious diseases consultation for metallo-beta-lactamase producers, resistant Pseudomonas and combination therapy.