β-lactam

Aztreonam causes significant suppression of human colony forming unit-erythroid (cfu-e), burst forming unit-erythroid (bfu-e) and colony forming unit-granulocyte macrophage (cfu-gm) at both peak and trough serum concentrations in human bone marrow cells. Aztreonam is hydrolyzed at measurable rates by class A beta-lactamases, a TEM-2 type penicillinase and the Proteus vulgaris cephalosporinase with a broad substraterange. Aztreonam is extremely stable as to the typical class C cephalosporinase of Citrobacter freundii, and acts as a competitive and progressive inhibitor for the beta-lactamase. Aztreonam (AZT) combined with clindamycin (CLDM) has synergistic effects on Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Haemophilus influenzae, which are sensitive or quasi-sensitive to CLDM, in the presence of CLDM at MIC or sub-MIC. Aztreonam reduces the cfu of some strains by 1 log unit without preserving the integrity of cystic fibrosis airway cell monolayers, while decreasing the biofilms of other clinical isolates by 4 log units and protecting the monolayers from being compromised.

Aztreonam (300 mg/kg) results in a significant decrease in the content of hepatic microsomal P450, while no significant change is observed in hepatic cytochrome b5 content and NADPH-cytochrome c (P450) reductase activity.

300 mg/kg

Absorption, Distribution and Excretion
Less than 1% absorbed from the gastrointestinal tract following oral administration. Completely absorbed following intramuscular administration.
In healthy subjects, aztreonam is excreted in the urine about equally by active tubular secretion and glomerular filtration. Urinary excretion of a single parenteral dose was essentially complete by 12 hours after injection.
12.6 L
91 mL/min [healthy]

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Metabolism / Metabolites
Approximately 6 to 16% metabolized to inactive metabolites by hydrolysis of the beta-lactam bond, resulting in an open-ring compound.

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Biological Half-Life
The serum half-life of aztreonam averaged 1.7 hours (1.5 to 2.0) in subjects with normal renal function, independent of the dose. In elderly patients and in patients with impaired renal function, the mean serum half-life of aztreonam increased (4.7 to 6 hours and 2.1 hours, respectively).

Hepatotoxicity
Aztreonam has systemic toxicities that are similar to those of other beta lactam antibiotics, but it is unclear whether it can cause hepatic injury similar to that of the penicillins or cephalosporins. Asymptomatic serum aminotransferase elevations are common during high dose, intravenous aztreonam therapy (10% to 38%). The enzyme abnormalities are usually mild-to-moderate, asymptomatic, self-limited and not requiring drug discontinuation. Enzyme elevations occur slightly more commonly during aztreonam therapy than with other comparative antibiotics. Cases of frank liver injury and jaundice attributable to aztreonam must be extremely rare as no individual cases have been reported. For this reason, there is no data regarding the latency or pattern of the injury. Instances of marked aminotransferase elevations within 3 to 5 days of starting aztreonam have been reported, but these cases were without jaundice and resolved rapidly once the drug was stopped.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that aztreonam produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with beta-lactams, but these effects have not been adequately evaluated. A task force respiratory experts from Europe, Australia and New Zealand found that inhaled tobramycin is compatible with breastfeeding. Aztreonam is acceptable in nursing mothers.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Serum protein binding averaged 56% and is independent of dose. Impaired renal function, 36 to 43%.

[1]. J Antimicrob Chemother.1991 Jan;27(1):95-104.

[2]. J Antibiot (Tokyo).1990 Apr;43(4):403-10.

[3]. J Antimicrob Chemother.2012 Nov;67(11):2673-81.

A monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It is resistant to beta-lactamases and is used in gram-negative infections, especially of the meninges, bladder, and kidneys. It may cause a superinfection with gram-positive organisms.
Aztreonam is a Monobactam Antibacterial.
Aztreonam is a parenterally administered, synthetic monobactam antibiotic that is specifically active against aerobic gram-negative bacilli is resistant to many beta-lactamases. Aztreonam therapy is often accompanied by mild, asymptomatic elevations in serum aminotransferase levels, but it has not been reported to cause clinically apparent liver injury.
Aztreonam is a monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum with bactericidal activity. Aztreonam preferentially binds to and inactivates penicillin-binding protein-3 (PBP-3), which is involved in bacterial cell wall synthesis, thereby inhibiting bacterial cell wall integrity and leading to cell lysis and death. This agent differs from other beta-lactam antibiotics because it is resistant to beta-lactamase hydrolysis, and it is usually used to treat infections caused by gram-negative aerobic microorganisms.
A monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It is resistant to beta-lactamases and is used in gram-negative infections, especially of the meninges, bladder, and kidneys. It may cause a superinfection with gram-positive organisms.
See also: SQ-28429 (annotation moved to).

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Drug Indication
For the treatment of the following infections caused by susceptible gram-negative microorganisms: urinary tract infections, lower respiratory tract infections, septicemia, skin and skin-structure infections, intra-abdominal infections, and gynecologic infections.
FDA Label
Cayston is indicated for the suppressive therapy of chronic pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF) aged 6 years and older. Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Treatment of Pseudomonas aeruginosa pulmonary infection / colonisation in patients with cystic fibrosis
Treatment of Gram-negative endobronchial infection in bronchiectasis patients

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Mechanism of Action
The bactericidal action of aztreonam results from the inhibition of bacterial cell wall synthesis due to a high affinity of aztreonam for penicillin binding protein 3 (PBP3). By binding to PBP3, aztreonam inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. It is possible that aztreonam interferes with an autolysin inhibitor.

C13H17N5O8S2

435.43

435.051

C, 35.86; H, 3.94; N, 16.08; O, 29.39; S, 14.73

78110-38-0

Aztreonam (lysine);827611-49-4;Aztreonam-d6;1127452-94-1

5742832

White to off-white solid powder

1.83

227°C

1.74

-0.66

4

12

7

28

808

2

S(N1C([C@]([H])([C@]1([H])C([H])([H])[H])N([H])C(C(C1=C([H])SC(N([H])[H])=N1)=NOC(C(=O)O[H])(C([H])([H])[H])C([H])([H])[H])=O)=O)(=O)(=O)O[H]

WZPBZJONDBGPKJ-CAOOACKPSA-N

InChI=1S/C13H17N5O8S2/c1-5-7(10(20)18(5)28(23,24)25)16-9(19)8(6-4-27-12(14)15-6)17-26-13(2,3)11(21)22/h4-5,7H,1-3H3,(H2,14,15)(H,16,19)(H,21,22)(H,23,24,25)/b17-8+

2-[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid

Aztreonam; Az threonam; Az-threonam; Azactam; Azthreonam; Aztreonam;Aztreonam Esteve Brand; Aztreonam Squibb Brand;Bristol Myers Squibb Brand of Aztreonam; Bristol-Myers Squibb Brand of Aztreonam;Esteve Brand of Aztreonam; Sanofi Winthrop Brand of Aztreonam; SQ 26,776; SQ-26,776; SQ26,776; Squibb Brand of Aztreonam; Urobactam

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 50~87 mg/mL ( 114.83~199.8 mM )
H2O : ~10 mg/mL (~22.97 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saliney: ≥ 2.5 mg/mL (5.74 mM)

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Solubility in Formulation 5: 10 mg/mL (22.97 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)