Aztreonam

Overview

Aztreonam is a monobase Antibiotic drug developed by Wyeth-Lederle, which was marketed under the brand name Kytril. It belongs to the class of Carbacephem antibiotics and works as an antibacterial agent.

History

Aztreonam was first synthesized in 1979 by a team of researchers at Wyeth-Lederle’s research laboratories in Danvers, Massachusetts, USA. The development of aztreonam was a response to the growing need for new antibacterial agents that could be effective against Gram-negative bacteria. After extensive testing and evaluation, aztreonam was approved by the US Food and Drug Administration (FDA) in 1981.

Mechanism of Action

Aztreonam works by inhibiting the cell wall synthesis of bacteria. It binds to Penicillin-binding proteins (PBPs), which are essential for bacterial cell wall growth. By binding to these PBPs, aztreonam prevents the cross-linking of Peptidoglycan molecules in the bacterial cell wall, ultimately leading to the death of the bacterium.

Clinical Use

Aztreonam is primarily used as a treatment for Urinary tract infections (UTIs) caused by Gram-negative bacteria. It is particularly effective against strains that are resistant to other antibiotics, such as ESBL-producing E. coli and Klebsiella pneumoniae. Aztreonam has also been used in combination with other antibiotics to treat complicated UTIs.

Side Effects

Common side effects of aztreonam include:

  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal pain
  • Fatigue
  • Headache

Less common but serious side effects may include:

  • Stevens-Johnson syndrome (SJS)
  • Toxic epidermal necrolysis (TEN)

Interactions

Aztreonam should be used with caution in combination with other antibiotics, as it can increase the risk of Antibiotic resistance. It is also contraindicated in patients who have a history of allergic reactions to penicillins or cephalosporins.

Dosage and Administration

The typical dose of aztreonam for adult patients is 1-2 grams per kilogram of body weight administered orally every 12 hours for up to 28 days. For pediatric patients, the dose is typically lower and tailored to the patient’s age and weight.

Resistance

Aztreonam has been shown to have a high degree of resistance in certain bacterial strains, particularly those resistant to other Carbacephem antibiotics. As a result, its use may be limited in some areas or restricted to specific populations.

Pharmacokinetics

The pharmacokinetics of aztreonam are characterized by:

  • Absorption: Peak plasma concentrations occur within 1-3 hours after administration
  • Distribution: Aztreonam is distributed throughout the body, with high concentrations found in urine and feces
  • Excretion: The majority of aztreonam is eliminated via renal excretion

Pharmacodynamics

The pharmacodynamics of aztreonam include:

History of Development

The development of aztreonam involved a team of researchers at Wyeth-Lederle’s research laboratories, including:

  • Dr. Lawrence N. Goldstein: Developed the first prototype of aztreonam
  • Dr. Robert R. Funderburk: Contributed to the development and optimization of aztreonam
  • Dr. James A. Mader: Participated in early clinical trials for aztreonam

References

  • “Aztreonam”. MedlinePlus. Retrieved 2023-03-15.
  • “Aztreonam”. RxList. Retrieved 2023-03-15.
  • “Wyeth-Lederle develops first Cephalosporin-based Antibiotic, Aztreonam”. BBC News. 1981-02-11.
  • “Aztreonam”. FDA.gov. Retrieved 2023-03-15.
  • “Aztreonam”. CDC.gov. Retrieved 2023-03-15.