Aztreonam

Aztreonam belongs to the pharmacological class of monocyclic beta-lactam antibiotic.

Aztreonam has been approved to relieve symptoms and also for the treatment and maintenance of Intra-abdominal infection, health care–associated or high-risk community-acquired infection, Meningitis, bacterial, Osteomyelitis, native vertebral due to P. aeruginosa, Pneumonia, Severe systemic or life-threatening infections, S. maltophilia infection, multidrug-resistant, Surgical prophylaxis, Urinary tract infection.

Aztreonam is a beta-lactam antibiotic that exhibits bactericidal activity by inhibiting bacterial cell wall synthesis. After intravenous administration, Aztreonam is rapidly distributed into tissues and fluids, with peak plasma concentrations achieved within 30 minutes to 2 hours. The drug is eliminated primarily by the kidneys via glomerular filtration and tubular secretion. The elimination half-life in patients with normal renal function is approximately 2 hours, but this may be prolonged in patients with impaired renal function. Aztreonam is not metabolized in the liver and does not accumulate in the body with repeated dosing. No significant drug interactions have been reported with Aztreonam.

The common side effects involved in using Aztreonam are Diarrhea, Nausea, Vomiting, Abdominal pain, Headache, Dizziness, Rash, Itching,.

Aztreonam is available in the form of Inhalation Solution, Powder for Injection.

Aztreonam is approved in Germany, Japan, Malaysia, India, the U.K.,U.S, and China.

Aztreonam belongs to the pharmacological class of monocyclic beta-lactam antibiotic.

Aztreonam works by interfering with bacterial cell wall synthesis, which leads to the death of susceptible gram-negative and gram-positive bacteria. 

Aztreonam has been approved to relieve symptoms and also for the treatment and maintenance of Intra-abdominal infection, health care–associated or high-risk community-acquired infection, Meningitis, bacterial, Osteomyelitis, native vertebral due to P. aeruginosa, Pneumonia, Severe systemic or life-threatening infections, S. maltophilia infection, multidrug-resistant, Surgical prophylaxis, Urinary tract infection.

The onset of action for Aztreonam is usually rapid, with clinical improvement observed within 24-48 hours of initiating therapy.

The duration of action for Aztreonam is dependent on factors such as the dose administered, the severity of the infection, and the patient's renal function. In patients with normal renal function, the elimination half-life of Aztreonam is approximately 2 hours. In patients with impaired renal function, the half-life may be prolonged, leading to an increased duration of action.

Aztreonam is found to be available in the form of Inhalation Solution, Powder for Injection.

Aztreonam can be used in the following treatment:

• Intra-abdominal infection, health care-associated or high-risk community-acquired infection
• Meningitis, bacterial
• Osteomyelitis, native vertebral due to P. aeruginosa
• Pneumonia
• Severe systemic or life-threatening infections
• S. maltophilia infection, multidrug-resistant
• Surgical prophylaxis
• Urinary tract infection

Aztreonam can help to relieve symptoms and also for the treatment and maintenance of Intra-abdominal infection, health care–associated or high-risk community-acquired infection, Meningitis, bacterial, Osteomyelitis, native vertebral due to P. aeruginosa, Pneumonia, Severe systemic or life-threatening infections, S. maltophilia infection, multidrug-resistant, Surgical prophylaxis, Urinary tract infection.

Aztreonam is approved for use in the following clinical indications:

• Intra-abdominal infection, health care-associated or high-risk community-acquired infection
• Meningitis, bacterial
• Osteomyelitis, native vertebral due to P. aeruginosa
• Pneumonia
• Severe systemic or life-threatening infections
• S. maltophilia infection, multidrug-resistant
• Surgical prophylaxis
• Urinary tract infection

Intra-abdominal infection, healthcare-associated or high-risk community-acquired infection:

Adult dose: 1-2 grams every 8-12 hours via intravenous (IV) infusion over 30 minutes

Pediatric dose: 30 mg/kg every 6-8 hours via IV infusion over 30 minutes

Meningitis, bacterial:

Adult dose: 2 grams every 8 hours via IV infusion over 30 minutes

Pediatric dose: 30 mg/kg every 6 hours via IV infusion over 30 minutes

Osteomyelitis, native vertebral due to P. aeruginosa:

Adult dose: 2 grams every 8 hours via IV infusion over 30 minutes

Pediatric dose: 30 mg/kg every 6-8 hours via IV infusion over 30 minutes

Pneumonia:

Adult dose: 1-2 grams every 8-12 hours via IV infusion over 30 minutes

Pediatric dose: 30 mg/kg every 6-8 hours via IV infusion over 30 minutes

Severe systemic or life-threatening infections:

Adult dose: 2 grams every 6-8 hours via IV infusion over 30 minutes

Pediatric dose: 30 mg/kg every 6 hours via IV infusion over 30 minutes

S. maltophilia infection, multidrug-resistant:

Adult dose: 2 grams every 6-8 hours via IV infusion over 30 minutes

Pediatric dose: 30 mg/kg every 6 hours via IV infusion over 30 minutes

Surgical prophylaxis:

Adult dose: 1 gram 30 minutes before surgery via IV infusion over 30 minutes

Pediatric dose: 30 mg/kg 30 minutes before surgery via IV infusion over 30 minutes

Urinary tract infection:

Adult dose: 1-2 grams every 8-12 hours via IV infusion over 30 minutes

Pediatric dose: 30 mg/kg every 6-8 hours via IV infusion over 30 minutes

Injection: Aztreonam powder for solution for infusion in vials or pre-filled syringes with various strengths, including 1.5 g, 3 g, and 4.5 g.

Inhalation Solution, Powder for Injection.

• Dosage Adjustments in Kidney Patients:

CrCl 10-30 mL/min: A loading dose of 1-2 g is given, followed by 50% of the usual dosage.

CrCl <10 mL/min: A loading dose of 1-2 g is given, followed by 25% of the usual dosage.

• Dosage Adjustments in Pediatric Patients:

Cystic Fibrosis (Pseudomonas aeruginosa), Acute Pulmonary Exacerbation

Limited data is available for infants, children, and adolescents. The recommended intravenous (IV) dosage is 200 to 300 mg/kg/day divided every 6 hours, with a maximum daily dose of 12 g/day. Administration of the total daily dose by continuous infusion has been reported.

Intra-abdominal Infections, Complicated

For infants, children, and adolescents aged less than 9 months, limited data is available. The recommended IV dosage is 90 to 120 mg/kg/day in divided doses every 6 to 8 hours, as part of an appropriate combination regimen. The maximum dose is 2,000 mg/dose, and the treatment duration varies based on the specific source of infection, success of source control procedures, and clinical response. A total duration of 5 days is typically recommended in patients with adequate source control.

Meningitis or Ventriculitis, Healthcare-Associated

Limited data is available for infants, children, and adolescents. The recommended IV dosage is 120 mg/kg/day in divided doses every 6 to 8 hours. Doses up to 200 mg/kg/day divided every 6 hours have been reported in patients aged 2 to 18 years. The maximum daily dose is 8 g/day, and the duration of treatment varies based on the isolated pathogen, cerebrospinal fluid studies, and clinical presentation. Gram-negative pathogens should be treated for at least 10 to 14 days.

Peritonitis (Peritoneal Dialysis), Treatment

For infants, children, and adolescents, the recommended intraperitoneal dosage is continuous. The loading dose is 1,000 mg per liter of dialysate, and the maintenance dose is 250 mg per liter.

Surgical Prophylaxis

For children and adolescents, the recommended IV dosage is 30 mg/kg within 60 minutes before incision. It may be repeated in 4 hours for prolonged procedures or excessive blood loss. The maximum dose is 2,000 mg/dose.

Urinary Tract Infection

Limited data is available for infants, children, and adolescents aged less than 9 months. The recommended IV dosage is 90 to 120 mg/kg/day in divided doses every 6 to 8 hours. The treatment duration depends on the age of the patient, response to therapy, and extent of involvement. In patients aged 2 years and older, treatment duration may be as short as 3 to 5 days for uncomplicated cystitis or 6 to 10 days for pyelonephritis. Patients aged less than 2 years may require a longer course, such as 7 to 14 days.

There are no specific dietary restrictions related to the use of Aztreonam.

Aztreonam may be contraindicated under the following conditions:

• In patients with known hypersensitivity to Aztreonam, cephalosporin, penicillin, or any component of the formulation.

The physician should closely monitor the patients and keep pharmacovigilance as follows:

Aztreonam (aztreonam for injection, USP) and Cross-Reactivity with Beta-Lactam Antibiotics

Cross-Reactivity and Hypersensitivity

Animal and human data suggest that Aztreonam is rarely cross-reactive with other beta-lactam antibiotics and is weakly immunogenic. However, patients with or without prior exposure to Aztreonam may experience hypersensitivity reactions. Thus, careful inquiry should be made to determine whether the patient has any history of hypersensitivity reactions to any allergens.

Although rare, patients with a history of hypersensitivity to beta-lactams, such as penicillins, cephalosporins, and/or carbapenems, should receive Aztreonam with caution. In case of an allergic reaction, the drug should be discontinued, and supportive treatment initiated, including pressor amines, antihistamines, and corticosteroids. Serious hypersensitivity reactions may require epinephrine and other emergency measures.

Clostridium difficile-Associated Diarrhea (CDAD)

Clostridium difficile-associated diarrhea (CDAD) is a possible consequence of using antibacterial agents like Aztreonam. CDAD ranges from mild diarrhea to fatal colitis, and occurs when the use of antibacterial agents disrupts the normal flora of the colon leading to C. difficile overgrowth. Hypertoxin-producing strains of C. difficile can cause increased morbidity and mortality, as these infections can be resistant to antimicrobial therapy and may require colectomy.

If CDAD is suspected or confirmed, the use of antibiotics not directed against C. difficile may need to be discontinued. Clinically indicated management, including fluid and electrolyte replacement, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation, should be initiated.

Rare Adverse Effects

In rare cases, Aztreonam has been associated with toxic epidermal necrolysis in patients undergoing bone marrow transplant with multiple risk factors, such as sepsis, radiation therapy, and other concurrently administered drugs associated with toxic epidermal necrolysis.

Precautions

Aztreonam should be prescribed only for proven or strongly suspected bacterial infections or prophylactic indications. Inappropriate use of Aztreonam increases the risk of developing drug-resistant bacteria.

In patients with impaired hepatic or renal function, appropriate monitoring is recommended during therapy.

Concurrent use of an aminoglycoside with Aztreonam, especially at high dosages or for prolonged periods, may result in renal toxicity or ototoxicity. Therefore, renal function should be monitored.

The use of antibiotics might promote the overgrowth of nonsusceptible organisms, which including Gram-positive organisms (Staphylococcus aureus and Streptococcus faecalis) and also fungi. Appropriate measures should be taken in case of superinfection during therapy.

There is no specific alcohol warning related to the use of Aztreonam according to the USFDA.

Aztreonam is present in human milk, but in concentrations less than 1% of those in maternal serum. However, it is recommended to temporarily discontinue nursing and consider formula feedings when taking aztreonam.

Pregnancy Category B: Aztreonam Use During Pregnancy

Aztreonam is a medication that is sometimes used during pregnancy to treat bacterial infections. However, it is important to understand how the drug may affect a developing fetus.

Placental Crossing and Animal Studies

According to animal studies, Aztreonam is capable of crossing the placenta and entering the fetal circulation. However, daily doses of aztreonam in pregnant rats and rabbits, up to 1800 mg/kg and 1200 mg/kg respectively, did not demonstrate any embryotoxicity, fetotoxicity, or teratogenicity. These doses were 2.2- and 2.9-fold greater than that of the maximum recommended human dose (MRHD) for adults of 8 g per day based on body surface area.

Human Studies and Recommendations

There are currently no adequate and well-controlled studies on the effect of aztreonam on human pregnancy outcomes. As animal reproduction studies do not always predict human response, aztreonam should only be used during pregnancy if it is clearly needed.

There are no known food warnings related to the use of aztreonam.

The adverse reactions related to Aztreonam can be categorized as follows:

Common:

• Diarrhea
• Nausea and vomiting
• Skin rash or itching
• Pain or inflammation at the injection site
• Headache

Less Common:

• Fever or chills
• Dizziness
• Stomach cramps or pain
• Joint pain
• Abnormal liver function tests

Rare:

• Seizures
• Stevens-Johnson Syndrome (a severe skin reaction)
• Anaphylaxis (a severe allergic reaction)
• Blood disorders such as leukopenia, neutropenia, and thrombocytopenia
• Pseudomembranous colitis (a severe intestinal infection caused by the bacterium Clostridium difficile)

The clinically relevant drug interactions of Aztreonam is briefly summarized here:

There are no known significant drug interactions with aztreonam. However, caution should be exercised when administering aztreonam with other drugs that have the potential to cause nephrotoxicity or ototoxicity, as these effects may be additive. Additionally, concomitant use of aztreonam with other drugs that affect renal function, such as diuretics or nonsteroidal anti-inflammatory drugs (NSAIDs), may increase the risk of renal toxicity. Monitoring of renal function and electrolyte levels is recommended when these drugs are co-administered with aztreonam.

The following are the side effects involving Aztreonam:

• Nausea
• Vomiting
• Diarrhea
• Headache
• Rash
• Localized skin reactions at the injection site
• Pain or swelling at the injection site
• Increased liver enzymes (transaminases)
• Increased blood urea nitrogen (BUN)
• Increased serum creatinine

Pregnancy Category B: Aztreonam Use During Pregnancy

Aztreonam is a medication that is sometimes used during pregnancy to treat bacterial infections. However, it is important to understand how the drug may affect a developing fetus.

Placental Crossing and Animal Studies

According to animal studies, Aztreonam is capable of crossing the placenta and entering the fetal circulation. However, daily doses of aztreonam in pregnant rats and rabbits, up to 1800 mg/kg and 1200 mg/kg respectively, did not demonstrate any embryotoxicity, fetotoxicity, or teratogenicity. These doses were 2.2- and 2.9-fold greater than the maximum recommended human dose (MRHD) for adults of 8 g per day based on body surface area.

Human Studies and Recommendations

There are currently no adequate and well-controlled studies on the effect of aztreonam on human pregnancy outcomes. As animal reproduction studies do not always predict human response, aztreonam should only be used during pregnancy if it is clearly needed.

Nursing Mothers

Aztreonam is present in human milk, but in concentrations less than 1% of those in maternal serum. However, it is recommended to temporarily discontinue nursing and consider formula feedings when taking aztreonam.

Pediatric Use

The safety and effectiveness of intravenous Aztreonam have been established in the age groups 9 months to 16 years. However, data is insufficient for pediatric patients under 9 months of age or for certain treatment indications/pathogens. In pediatric patients with cystic fibrosis, higher doses of Aztreonam may be necessary.

Geriatric Use

Clinical studies of Aztreonam did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. However, elderly patients may experience an age-related decrease in creatinine clearance, which could increase the risk of toxic reactions to aztreonam. Therefore, renal function should be monitored, and dosage adjustments made accordingly in elderly patients.

Physicians should be knowledgeable and vigilant about the treatment and identification of overdosage of Aztreonam.

Overdose of Aztreonam can lead to potential adverse effects such as seizures, encephalopathy, and neuromuscular excitability. There is no specific antidote for an overdose of Aztreonam. In case of overdose, supportive care and treatment of symptoms should be provided. Hemodialysis may be considered as a means of removing Aztreonam from the body since it is not significantly bound to plasma proteins.

If an overdose of Aztreonam is suspected, medical attention should be sought immediately. The patient should be monitored closely for any signs of toxicity and vital signs should be carefully evaluated. Treatment may include symptomatic and supportive measures such as airway management, oxygenation, and hydration.

In case of seizures, benzodiazepines may be administered to control them. In case of neuromuscular excitability, calcium channel blockers such as diltiazem or verapamil may be administered. If necessary, anticonvulsants or other medications to manage symptoms may also be given. Close monitoring of the patient's renal and hepatic function is also recommended.

Pharmacodynamics

Aztreonam is an effective beta-lactam antibiotic that is utilized in the treatment of infections caused by certain gram-negative bacteria. This monocyclic beta-lactam antibiotic was first derived from Chromobacterium violaceum and is resistant to the effects of beta-lactamases, making it particularly effective against resistant bacterial strains. Aztreonam is commonly prescribed for infections of the meninges, bladder, and kidneys caused by gram-negative bacteria.

Pharmacokinetics

Pharmacokinetic Parameters:

• Absorption

Aztreonam is poorly absorbed from the gastrointestinal tract following oral administration, with less than 1% of the dose being absorbed. However, it is completely absorbed following intramuscular administration.

• Volume of distribution

The steady-state volume of distribution of aztreonam in healthy adults is 12.6 L.

• Protein binding

Aztreonam binds to serum proteins to a moderate extent, with an average protein binding of 56%. Protein binding is independent of dose. However, impaired renal function has been shown to decrease protein binding to 36-43%.

• Metabolism

Aztreonam is minimally metabolized, with approximately 6 to 16% of the dose being metabolized to inactive compounds by hydrolysis of the beta-lactam bond, resulting in an open-ring compound.

• Route of elimination

Aztreonam is primarily eliminated unchanged in the urine in healthy individuals, with urinary excretion of a single parenteral dose being essentially complete by 12 hours after injection. In healthy subjects, aztreonam is excreted in the urine about equally by active tubular secretion and glomerular filtration.

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