Aztreonam: monobactam antibiotic with gram-negative activity
Aztreonam (brand names Azactam, Cayston) is the only clinically used antibiotic from the monobactam class. Characteristic is the monocyclic beta lactam ring without a further ring, which results in pure gram-negative activity. First approved in 1986, aztreonam is mainly used for infections with aerobic gram-negative pathogens, including Pseudomonas aeruginosa, enterobacteria and Haemophilus influenzae.
Aztreonam is a valuable option for patients with penicillin or cephalosporin allergy, since cross-reactions are very rare. The only known exception is partial cross-reactivity with ceftazidime due to a similar side chain. Aztreonam is not active against gram-positive pathogens or anaerobes.
Mechanism of action
Aztreonam, like all beta lactam antibiotics, inhibits the penicillin-binding protein PBP 3, an enzyme of bacterial cell wall synthesis. PBP 3 is essential for cross-linking peptidoglycan in the growing bacterial cell wall. Disrupted cross-linking destabilises the wall and the bacterial cell lyses.
The selective activity against gram-negative pathogens is based on the fact that aztreonam binds with high affinity only to PBP 3 of gram-negative bacteria. Gram-negative PBP 3 differs structurally from the corresponding proteins of gram-positive pathogens, which is why staphylococci, streptococci and enterococci are not covered.
Aztreonam is stable against many beta lactamases including AmpC, but not against ESBL and carbapenemases. In some regimens, aztreonam is combined with beta lactamase inhibitors such as avibactam to extend the spectrum to ESBL and some carbapenemase producers.
Indications
- Complicated urinary tract infections: including acute pyelonephritis from gram-negative pathogens
- Lower respiratory tract infections: pneumonia from Pseudomonas, Haemophilus, Klebsiella
- Complicated skin and soft tissue infections: with gram-negative involvement
- Septic conditions: in combination with substances active against gram-positive pathogens and anaerobes
- Gynaecological infections: with proven gram-negative pathogen
- Cystic fibrosis: aztreonam for inhalation (Cayston) for chronic Pseudomonas colonisation
- Penicillin or cephalosporin allergy: as alternative with documented allergy
Dosing and administration
Adults parenterally: 1 to 2 g intravenously or intramuscularly every 8 to 12 hours, in severe infections up to 8 g per day.
Inhaled use in cystic fibrosis (Cayston): 75 mg three times daily via a special nebuliser, in 28-day cycles of treatment and 28-day pauses.
Renal impairment: dose adjustment required; with creatinine clearance below 30 ml/min reduce to 50 % of normal dose, on dialysis additional dose after dialysis.
Intravenous administration is given as a short infusion over 20 to 60 minutes or as a bolus over 3 to 5 minutes.
Treatment duration: usually 7 to 14 days depending on indication and clinical course. For chronic inhalation therapy, individual adjustment.
Side effects
Common: pain or irritation at the injection site, rash, gastrointestinal complaints (nausea, vomiting, diarrhoea), raised liver transaminases, eosinophilia.
Uncommon: thrombophlebitis, allergic skin reactions, pruritus, vaginal candidiasis, dizziness, headache.
Rare and very rare: anaphylaxis, Stevens Johnson syndrome, antibiotic-associated colitis from Clostridioides difficile, hepatitis, acute interstitial nephritis, seizures with very high doses.
Inhaled therapy: cough, wheezing, nasal congestion, throat irritation, bronchospasm. A bronchial provocation test is recommended before first use.
Important points:
- In contrast to penicillins and cephalosporins, cross-allergy is very rare
- Patients with documented ceftazidime allergy should receive aztreonam with caution due to possible partial cross-reactivity
- With prolonged therapy, selection of resistant pathogens or fungal infections is possible
Interactions
- Probenecid and furosemide: reduced renal excretion of aztreonam, levels can rise
- Anticoagulants (warfarin, phenprocoumon): increased effect through influence on gut flora and vitamin K synthesis, monitor INR
- Aminoglycosides: often combined synergistically against Pseudomonas; note incompatibility in the same infusion solution
- Clavulanic acid: can have an inducing effect on beta lactamases, undesirable in combination with aztreonam
- Chemotherapy: in febrile neutropenia often combined
Special considerations
Pregnancy: data on use in pregnancy are limited, animal data show no teratogenicity. If clinically required, acceptable.
Breastfeeding: small amounts pass into milk; breastfeeding under therapy is usually possible, monitor the infant for diarrhoea or fungal infection.
Allergic reactions: despite rare cross-reactivity, the allergy history should be carefully taken before use. With any acute allergic reaction, immediate stop of therapy and emergency measures.
Duration of use: as with all antibiotics, as short as possible, as long as needed. Too short treatment promotes recurrence and resistance, too long treatment side effects and selection.
Patients with cystic fibrosis: the inhaled use requires a special nebuliser system (Altera). Correct use is a prerequisite for efficacy.
Resistance: ESBL and carbapenemases can degrade aztreonam. Susceptibility testing is therefore routine in hospitals, especially for nosocomial and severely ill patients.
Related substances
- Imipenem, broad-spectrum carbapenem
- Meropenem, central carbapenem
- Tazobactam, beta lactamase inhibitor
- Sulbactam, another beta lactamase inhibitor
- Tigecyclin, reserve antibiotic for multi-resistant pathogens
Frequently asked questions
Can I receive aztreonam with penicillin allergy?
In most cases yes. Aztreonam shows only very rare cross-reactions with penicillins or cephalosporins because the side chain and the monocyclic structure differ. The exception is ceftazidime, which has a similar side chain. Allergy history should still be carefully taken and clarified by an allergist if uncertain.
Why is aztreonam used by inhalation?
For cystic fibrosis with chronic Pseudomonas aeruginosa colonisation. Inhaled use achieves high drug levels directly at the infection site in the bronchi and reduces systemic side effects. In 28-day cycles alternating with tobramycin or colistin, Pseudomonas burden can be effectively reduced.
Does aztreonam work against all gram-negative bacteria?
No. It works well against aerobic gram-negative pathogens such as E. coli, Klebsiella, Enterobacter, Pseudomonas, Haemophilus. Anaerobes like Bacteroides are not covered, nor are gram-positive pathogens or atypical bacteria. ESBL and carbapenemase producers may be resistant.
How is therapy adjusted in renal impairment?
Aztreonam is mainly excreted renally. With reduced function the dose is reduced; with GFR under 30 ml/min by about half. In dialysis patients an additional dose is given after dialysis since aztreonam is dialysed.
Sources
- EMA Cayston (aztreonam) EPAR
- BfArM Federal Institute for Drugs and Medical Devices
- AWMF guidelines CF and sepsis
- Gelbe Liste aztreonam monograph
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