Azonam1 gm

Azonam is a monobactam antibiotic indicated for the treatment of infections caused by susceptible aerobic gram-negative microorganisms.

Established / FDA-Approved Uses

• Urinary tract infections (complicated and uncomplicated, including pyelonephritis and cystitis)
• Lower respiratory tract infections, including pneumonia and bronchitis
• Septicemia
• Skin and skin-structure infections, including infected postoperative wounds, ulcers, and burns
• Intra-abdominal infections, including peritonitis
• Gynecologic infections, including endometritis and pelvic cellulitis

Adjunct / Combination Use

Azonam may be used as adjunctive therapy to surgery for the management of overt or subclinical infections resulting from abscesses and hollow viscus perforations. Because Azonam has activity only against aerobic gram-negative bacteria, it is frequently combined with an agent active against gram-positive and/or anaerobic organisms when the infection may be mixed.

Guideline-Supported / Specialized Use

An inhaled formulation of Azonam is used as maintenance therapy to improve respiratory symptoms in patients with cystic fibrosis colonized with Pseudomonas aeruginosa; this inhaled form has distinct dosing and administration and is not interchangeable with the injectable form discussed here.

Azonam is particularly useful in patients with a history of severe (immediate-type) hypersensitivity to penicillins or cephalosporins, since it shows minimal cross-reactivity with other beta-lactam classes (see Precautions for an important exception involving ceftazidime).

Azonam should be used only for infections that are proven or strongly suspected to be caused by susceptible bacteria; it should not be used as broad empiric therapy without evidence or strong suspicion of a susceptible gram-negative infection, in order to reduce the development of drug-resistant bacteria.

Each vial for injection contains Aztreonam as the active ingredient, formulated with L-arginine to improve solubility. The formulation is sodium-free. Aztreonam is available in strengths of 1 g and 2 g per vial for reconstitution as an intravenous or intramuscular injection.

Azonam is a synthetic, bactericidal monobactam antibiotic — a class distinct from penicillins, cephalosporins, and carbapenems, all of which share a bicyclic beta-lactam ring structure. Azonam has a unique monocyclic beta-lactam ring, which accounts for its narrow, gram-negative-only spectrum of activity and its low potential for cross-allergenicity with other beta-lactam antibiotics.

Azonam is administered parenterally (intravenously or intramuscularly) for systemic infections; a separate inhaled formulation exists for specific pulmonary indications.

Azonam belongs to the monobactam class of antibiotics, a subgroup of beta-lactam antimicrobials with a monocyclic (single-ring) beta-lactam structure and activity limited to aerobic gram-negative bacteria.

Mechanism of Action

Aztreonam is a bactericidal agent that acts by binding to penicillin-binding protein 3 (PBP-3) on the outer membrane of susceptible gram-negative bacteria. This binding inhibits bacterial cell wall synthesis, leading to filamentation and subsequent bacterial cell lysis and death.

Spectrum of Activity

Aztreonam has activity limited to aerobic gram-negative bacteria, including many strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, Serratia species, and Haemophilus influenzae. It has no clinically useful activity against gram-positive bacteria or anaerobic organisms, so it is often combined with other agents when mixed infections are suspected.

Pharmacokinetics

Aztreonam is well absorbed after intramuscular injection and achieves therapeutic serum concentrations rapidly after intravenous administration. It is widely distributed into body tissues and fluids, undergoes limited hepatic metabolism, and is eliminated primarily by the kidneys via glomerular filtration and tubular secretion, with an elimination half-life of approximately 1.5–2 hours in patients with normal renal function.

Azonam is administered parenterally by a healthcare professional — via slow intravenous push, intravenous infusion, or deep intramuscular injection — and must not be self-administered at home without medical supervision. Each dose should be reconstituted immediately before use according to the recommended diluent and volume, and administration sites should be rotated for intramuscular injections. Intramuscular injection should not be used for severe or life-threatening infections; the intravenous route is preferred in those cases.

The following drug interactions with Azonam are clinically relevant:

• Beta-lactamase-inducing antibiotics (e.g., cefoxitin, imipenem): May induce beta-lactamase production that can antagonize the activity of Azonam; concurrent use is generally not recommended.
• Aminoglycosides (e.g., gentamicin, tobramycin): Azonam shows synergistic activity against certain gram-negative organisms, including Pseudomonas aeruginosa and Enterobacteriaceae, when combined with an aminoglycoside; renal function should be monitored during concurrent use because aminoglycosides carry independent nephrotoxicity risk.
• Probenecid and furosemide: May produce small, clinically insignificant increases in serum concentrations of Azonam by affecting renal tubular secretion; no dose adjustment is generally required.

Azonam does not produce a disulfiram-like reaction with alcohol, unlike some other beta-lactam antibiotics.

Common Side Effects (≥1%)

• Gastrointestinal: diarrhea, nausea, vomiting
• Skin: rash
• Local reactions: phlebitis/thrombophlebitis at the intravenous site, discomfort or swelling at the intramuscular injection site

Less Common but Serious Side Effects (<1%)

• Hypersensitivity reactions, including anaphylaxis, angioedema, and bronchospasm (see Precautions)
• Clostridioides difficile-associated diarrhea and pseudomembranous colitis (see Precautions)
• Severe skin reactions, including toxic epidermal necrolysis and exfoliative dermatitis
• Blood disorders, including pancytopenia, neutropenia, and thrombocytopenia
• Transient elevation of liver enzymes (AST, ALT, alkaline phosphatase)
• Low blood pressure, transient ECG changes, or flushing
• Neurological effects, including seizure, confusion, vertigo, and paresthesia

Patients should seek prompt medical attention for signs of a serious allergic reaction, severe or persistent diarrhea, unusual bleeding or bruising, or yellowing of the skin or eyes.

Pregnancy: Animal reproduction studies with Azonam have not shown evidence of embryotoxicity or teratogenicity at doses several times the maximum recommended human dose. However, adequate and well-controlled studies in pregnant women are not available. Azonam should be used during pregnancy only if clearly needed, and only if the potential benefit to the mother justifies the potential risk to the fetus; a physician should always be consulted before use during pregnancy.

Lactation: Azonam is excreted into human breast milk, but at concentrations less than 1% of those found in maternal serum. Caution is advised when Azonam is administered to a nursing mother, and a physician should be consulted to weigh the benefits of treatment against any potential effect on the breastfed infant; temporary discontinuation of nursing may be considered in some cases.

Hypersensitivity Reactions

Although cross-reactivity of Azonam with penicillins and cephalosporins is rare because of its unique monobactam structure, serious hypersensitivity reactions, including anaphylaxis, have been reported. Azonam should be used with appropriate caution and monitoring in patients with a history of severe beta-lactam allergy. Notably, Azonam shares a similar side chain with ceftazidime, and cross-reactivity specifically with ceftazidime has been reported; extra caution is warranted in patients with a known ceftazidime allergy. Azonam should be discontinued immediately if an allergic reaction occurs, and appropriate emergency treatment instituted.

Clostridioides difficile-Associated Diarrhea

As with virtually all antibiotics, Azonam use has been associated with Clostridioides difficile-associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis. CDAD should be considered in any patient who develops diarrhea during or after treatment with Azonam.

Superinfection

Because Azonam is active only against aerobic gram-negative organisms, prolonged use may result in overgrowth of non-susceptible organisms, including gram-positive bacteria and fungi. Patients should be monitored for signs of superinfection during prolonged therapy.

Hepatic Effects

Transient elevations in liver enzymes have been reported with Azonam; periodic monitoring of hepatic function is advisable during prolonged treatment.

Renal Impairment

Azonam is eliminated primarily by the kidneys, and dose adjustment is required in patients with reduced renal function (see Dosage and Administration).

Appropriate Use / Antibiotic Stewardship

Azonam should be reserved for infections that are proven or strongly suspected to be caused by susceptible gram-negative bacteria, and should not be used for broad empiric therapy without such evidence, to help limit the emergence of drug-resistant bacteria. Take Azonam exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice.

Inhaled Formulation

A separate inhaled formulation of Azonam is available for specific chronic pulmonary indications, such as in cystic fibrosis patients colonized with Pseudomonas aeruginosa. The inhaled formulation has distinct administration technique, dosing schedule, and monitoring requirements, and is not interchangeable with the intravenous/intramuscular formulation described in this document.

There is limited clinical experience with Azonam overdosage. In the event of a suspected overdose, seek immediate medical attention or contact your local emergency services or a poison control center. Azonam can be removed from the blood by hemodialysis and, to a lesser extent, by peritoneal dialysis, which may be considered by a physician as part of the management of significant overdose, particularly in patients with renal impairment. Management is otherwise supportive and symptomatic, under medical supervision.

Store at room temperature (20°C to 25°C / 68°F to 77°F), away from excessive heat, light, and moisture, in the original package. Keep out of reach of children. Once reconstituted, use according to the timelines specified by the manufacturer or dispensing pharmacist.

Pediatric Use

Safety and efficacy of Azonam have been established in pediatric patients aged 9 months to 16 years for the approved indications, using the weight-based dosing described above. Safety and efficacy have not been established in infants younger than 9 months, or for septicemia and skin/skin-structure infections caused by Haemophilus influenzae type b in the pediatric population; use in these situations should be at the physician's discretion.

Geriatric Use

Elderly patients may have reduced renal, hepatic, or cardiac function, and serum creatinine may not accurately reflect true renal status in this population. Dose selection for elderly patients should be individualized, generally starting at the lower end of the dosing range, with renal function assessed via creatinine clearance estimation and doses adjusted accordingly.

Renal Impairment

Dose reduction is required in patients with creatinine clearance below 30 mL/min/1.73 m² (see Dosage and Administration).

Hepatic Impairment

Azonam undergoes limited hepatic metabolism; hepatic function should be monitored in patients with pre-existing liver disease, though formal dose-adjustment guidelines are not well established.

The duration of treatment with Azonam depends on the type and severity of the infection and the patient's clinical response, and should be determined by the treating physician. As a general principle, therapy is continued for at least 48 hours after the patient becomes afebrile and asymptomatic, or until there is evidence that the infecting organism has been eradicated. Patients should complete the full course of Azonam exactly as prescribed, even if they feel better before the course is finished, to reduce the risk of relapse and antibiotic resistance.

Azonam for injection is supplied as a sterile powder that must be reconstituted before use.

• For intramuscular injection: reconstitute each 1 g vial with at least 3 mL of an appropriate diluent (such as Sterile Water for Injection) to form a solution suitable for deep intramuscular injection.
• For intravenous injection (bolus): reconstitute with Sterile Water for Injection to a concentration not exceeding 20 mg/mL, and inject slowly over 3–5 minutes directly into a vein or into the tubing of a compatible, freely flowing intravenous infusion.
• For intravenous infusion: initially reconstitute each vial with at least 3 mL of diluent per gram, then further dilute with a compatible intravenous fluid to a concentration not exceeding 20 mg/mL for infusion over 20–60 minutes.

The reconstituted solution should be inspected visually for particulate matter and discoloration prior to administration, and should not be mixed in the same container with other antibiotics. Follow the specific manufacturer's instructions for reconstitution volumes, compatible diluents, and stability once reconstituted.

Aztreonam belongs to the monobactam class of beta-lactam antibiotics.

Aztreonam exerts a bactericidal effect by binding preferentially to penicillin-binding protein 3 (PBP-3) in the outer membrane of susceptible aerobic gram-negative bacteria, disrupting bacterial cell wall synthesis and causing cell lysis and death.

B

Azonam is approved for use in pediatric patients aged 9 months to 16 years, administered intravenously at a dose of 30 mg/kg every 6–8 hours depending on infection severity, up to a maximum of 120 mg/kg/day. Safety and efficacy have not been established in infants below 9 months of age. Common adverse effects reported in pediatric clinical trials include rash, diarrhea, and fever; laboratory monitoring may show transient increases in eosinophils or liver enzymes. Azonam should be used in children only under close medical supervision, with the full course completed exactly as prescribed.