Can aztreonam (Azactam) cause confusion?

Can Aztreonam Cause Confusion?

Yes, aztreonam can cause confusion, though it occurs at a low incidence of less than 1% and is significantly less neurotoxic than many other beta-lactam antibiotics. 1

Neurotoxicity Profile of Aztreonam

Relative Risk Compared to Other Beta-Lactams

• Aztreonam has a relatively low pro-convulsive activity (42) compared to penicillin G (100), making it substantially less neurotoxic than cefazolin (294) or cefepime (160). 2
• This lower neurotoxicity threshold means aztreonam is among the safer beta-lactam options when neurological adverse effects are a concern. 2

Documented Neurological Side Effects

• The FDA label for aztreonam lists confusion as a documented adverse reaction occurring at less than 1% incidence, along with other neurological manifestations including seizure, encephalopathy, vertigo, paresthesia, insomnia, and dizziness. 1
• These neurological symptoms are part of the broader spectrum of beta-lactam neurotoxicity that can manifest as acute confusional state, encephalopathy, myoclonus, seizures, and status epilepticus. 2

Key Risk Factors for Beta-Lactam Neurotoxicity

Renal Impairment as Primary Risk Factor

• The main risk factor for beta-lactam-associated neurological toxicity, including confusion, is renal failure, which causes rapid drug accumulation. 2
• Between 60-70% of aztreonam is excreted unchanged in the urine, and serum clearance is directly proportional to creatinine clearance, necessitating dosage adjustment in reduced renal function. 3
• Dosage must be adjusted in patients with renal impairment to prevent accumulation and potential neurotoxicity. 4, 5

Critical Care Setting Considerations

• In critically ill patients with unexplained neurological manifestations, antibiotic toxicity should be considered, with therapeutic drug monitoring and temporary suspension of beta-lactam administration discussed. 2
• The benefit-risk balance likely decreases when drug concentrations exceed eight times the minimum inhibitory concentration (MIC). 2

Clinical Implications

When to Suspect Aztreonam-Related Confusion

• Consider aztreonam as a potential cause when confusion develops in patients with:
  • Renal impairment (even if dosing was adjusted) 2
  • Critically ill status requiring ICU care 2
  • Unexplained neurological deterioration during treatment 2

Comparative Safety Advantage

• Aztreonam's low neurotoxicity profile makes it preferable to cefepime or cefazolin when treating gram-negative infections in patients at risk for neurological complications. 2
• Unlike aminoglycosides, aztreonam is not nephrotoxic and has a low incidence of serious adverse effects overall. 6, 5

Management Approach

• If confusion develops during aztreonam therapy, temporarily discontinue the drug and consider therapeutic drug monitoring if available. 2
• Ensure appropriate dose reduction in patients with any degree of renal dysfunction. 3, 4
• Monitor for resolution of confusion after drug discontinuation to confirm causality. 2

Important Caveats

• The overall incidence of confusion with aztreonam remains low (less than 1%), making it a relatively safe option compared to other beta-lactams. 1
• Most patients tolerate aztreonam well, with the majority of adverse effects being local reactions at injection sites rather than systemic neurological effects. 1
• Aztreonam's selective activity against gram-negative bacteria means it must be combined with other agents for mixed infections, but this does not increase its neurotoxicity risk. 4, 7