Drug-Induced Fever Risk with Ceftazidime/Avibactam (Zavicefta) Plus Aztreonam
The combination of ceftazidime/avibactam (Zavicefta) plus aztreonam can potentially cause drug-induced fever, though this adverse effect is not commonly reported in clinical studies and guidelines addressing this combination.
Evidence from Clinical Use
The available evidence does not specifically highlight drug-induced fever as a prominent adverse effect of the ceftazidime/avibactam plus aztreonam combination:
Multiple international guidelines recommend ceftazidime/avibactam plus aztreonam as preferred therapy for metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales infections, with no specific warnings about drug fever 1.
Clinical studies evaluating this combination reported low incidence of adverse events overall, with no specific mention of drug-induced fever as a notable complication 1.
A recent 2025 study of 23 patients treated with ceftazidime/avibactam plus aztreonam for resistant Klebsiella pneumoniae bloodstream infections reported no adverse events related to antibiotic therapy 2.
Another 2025 study of eight patients with VIM-producing Pseudomonas aeruginosa infections treated with this combination reported no adverse events related to antibiotic therapy 3.
Individual Component Considerations
Aztreonam-Specific Data
Historical data from 1989 showed that β-lactam antibiotics can induce drug fever, with newer derivatives having higher incidence rates 4.
In that older study, piperacillin induced drug fever in 17% of patients, cefotaxime in 15%, and ceftizoxime in 14%, while older agents like ampicillin (3%) and cefazolin (0%) had lower rates 4.
The FDA label for aztreonam warns about hypersensitivity reactions but does not specifically list drug fever as a common adverse effect 5.
Aztreonam can cause hypersensitivity reactions in patients with or without prior exposure, requiring discontinuation if allergic reactions occur 5.
Ceftazidime/Avibactam Component
- No specific data on drug-induced fever from ceftazidime/avibactam is provided in the available guidelines or recent clinical studies 1.
Clinical Implications
If fever develops or persists during treatment with ceftazidime/avibactam plus aztreonam, consider the following diagnostic approach:
First, rule out inadequate source control, treatment failure, or new infection as causes of persistent fever 1.
Evaluate for other common causes of fever in critically ill patients, including catheter-related infections, Clostridioides difficile infection, and non-infectious causes 5.
Consider drug-induced fever if fever pattern shows gradual rise to high remittent fever with no other identifiable cause, particularly if accompanied by transient elevation of lactate dehydrogenase or mild neutropenia/thrombocytopenia 4.
Drug fever typically resolves promptly (within 48-72 hours) after discontinuation of the causative antibiotic 4.
Common Pitfalls
Do not automatically attribute persistent fever to drug reaction without first ensuring adequate infection control and ruling out treatment failure 1.
Be aware that the combination is generally well-tolerated based on recent clinical experience, so drug fever should not be the first consideration 2, 3.
Remember that hypersensitivity reactions to aztreonam are rare and typically manifest as skin reactions rather than isolated fever 5, 6.