Monobactams

Monobactams are monocyclic beta-lactams, of which aztreonam is the only systemic agent. Aztreonam is active only against aerobic Gram-negative bacilli including Pseudomonas aeruginosa, has no Gram-positive or anaerobic activity, and is stable to metallo-beta-lactamases. This makes it useful in penicillin allergy and, with an inhibitor, in metallo-beta-lactamase infection.

Mechanism. Selective binding to PBP3 of Gram-negatives leading to filamentation and lysis. Hydrolysed by ESBLs, AmpC enzymes and serine carbapenemases (KPC, OXA-48) but not by metallo-enzymes (NDM, VIM, IMP).

Pharmacokinetics. Given IV or IM; half-life about 2 hours; eliminated mainly unchanged by the kidney; penetrates tissues and inflamed meninges moderately. An inhaled lysine formulation delivers high airway concentrations with minimal absorption.

Spectrum. Enterobacterales, P. aeruginosa, H. influenzae, Neisseria. Inactive against Gram-positives, anaerobes, Acinetobacter (variable) and Stenotrophomonas.

• Aztreonam (IV or IM): systemic therapy, always combined with an agent covering Gram-positives and anaerobes when mixed infection is possible.
• Aztreonam lysine (inhaled): suppressive treatment of chronic Pseudomonas infection in cystic fibrosis.
• Aztreonam-avibactam: a combination for resistant Gram-negative infections including metallo-beta-lactamase producers; recently licensed in some regions.

Adult regimens (normal renal function).

• Aztreonam 1 to 2 g IV every 8 hours; severe infection or Pseudomonas 2 g every 6 to 8 hours (maximum 8 g daily).
• Inhaled aztreonam lysine 75 mg three times daily for 28 days, alternating with 28 days off.
• Metallo-beta-lactamase producers: aztreonam 2 g IV every 6 to 8 hours given together with ceftazidime-avibactam (so the avibactam protects aztreonam from co-produced serine enzymes), under specialist direction.
• Children: 30 mg/kg IV every 6 to 8 hours (maximum 8 g daily).

Selection. Use for Gram-negative infection in patients with severe immediate penicillin or cephalosporin allergy, together with vancomycin or metronidazole where Gram-positive or anaerobic cover is needed. Cross-reactivity with penicillins and most cephalosporins is negligible; ceftazidime shares an identical side chain with aztreonam, and cefiderocol also shares it, so ceftazidime allergy is the key exception.

Contraindications. Hypersensitivity to aztreonam or ceftazidime (shared side chain).

Serious and common effects. Rash; diarrhoea; nausea; transaminase elevation; phlebitis and injection-site reaction; rarely C. difficile infection, toxic epidermal necrolysis and neutropenia.

Interactions. Few. Probenecid raises levels modestly; additive nephrotoxicity if combined with aminoglycosides.

Monitoring. Renal function and liver tests in prolonged courses; full blood count weekly.

Special groups.

• Pregnancy and breastfeeding: acceptable when needed.
• Renal impairment: for creatinine clearance 10 to 30 mL/min, give the usual loading dose then half the dose at the usual interval; under 10 mL/min, a quarter of the dose; dose after haemodialysis.
• Older adults: adjust for renal function.
• Hepatic impairment: reduce dose in severe cirrhosis.