β-lactam
Bacterial Penicillin-Binding Protein 3 (PBP3) (MIC values: Escherichia coli = 0.03-0.25 μg/mL; Klebsiella pneumoniae = 0.06-0.5 μg/mL; Pseudomonas aeruginosa = 1-4 μg/mL) [1][2][3]
- Other Gram-negative bacterial PBPs (PBP1a, PBP2) [1][2]

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.

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Aztreonam (SQ-26776) exhibits potent and selective antibacterial activity against Gram-negative bacteria. For Enterobacteriaceae: it inhibited Escherichia coli (including ESBL-producing strains) with MIC50 = 0.06 μg/mL, MIC90 = 0.12 μg/mL; Klebsiella pneumoniae with MIC50 = 0.12 μg/mL, MIC90 = 0.25 μg/mL; Salmonella typhi with MIC50 = 0.03 μg/mL, MIC90 = 0.06 μg/mL [1][2][3]
- For non-fermenting Gram-negative bacteria: it suppressed Pseudomonas aeruginosa with MIC50 = 2 μg/mL, MIC90 = 4 μg/mL; Acinetobacter baumannii with MIC50 = 1 μg/mL, MIC90 = 2 μg/mL [1][3]
- It showed bactericidal activity: time-kill curve assays demonstrated that at 2×MIC, it reduced viable counts of Escherichia coli by ≥3 log10 CFU/mL within 6 hours and Pseudomonas aeruginosa by ≥3 log10 CFU/mL within 8 hours [1][2]
- It is stable to most β-lactamases (ESBLs, AmpC β-lactamases, penicillinases) but susceptible to metallo-β-lactamases (MBLs) [3]
- It has no antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) or anaerobic bacteria (Bacteroides fragilis) at concentrations up to 64 μg/mL [1][2]
- No cytotoxicity to human epithelial cells (HEp-2) or fibroblasts (NHF) at concentrations up to 200 μg/mL [1]

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.

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In mice with Escherichia coli-induced intra-abdominal sepsis, intravenous administration of Aztreonam (SQ-26776) (10 mg/kg, 20 mg/kg, 40 mg/kg, every 8 hours for 3 days) dose-dependently improved survival. Survival rates were 50% (10 mg/kg), 80% (20 mg/kg), and 95% (40 mg/kg), compared to 15% in the vehicle control group. It reduced bacterial load in peritoneal fluid by ~5 log10 CFU/mL at 40 mg/kg [1]
- In rats with Pseudomonas aeruginosa-induced pneumonia, intratracheal administration of Aztreonam (SQ-26776) (15 mg/kg, 30 mg/kg, once daily for 5 days) alleviated lung infection: lung bacterial counts decreased by ~4 log10 CFU/g (15 mg/kg) and ~6 log10 CFU/g (30 mg/kg); histological analysis showed reduced pulmonary inflammation and edema [2]
- In a clinical study of patients with Gram-negative bacterial infections , intravenous Aztreonam (SQ-26776) (1 g every 8 hours for 7-14 days) achieved a clinical cure rate of 83% for urinary tract infections, 79% for respiratory tract infections, and 75% for skin/soft tissue infections [3]

Bacterial PBP binding assay: Purified PBPs (PBP3, PBP1a, PBP2) from Escherichia coli and Pseudomonas aeruginosa were incubated with Aztreonam (SQ-26776) (0.01-20 μg/mL) and radiolabeled penicillin G at 37°C for 30 minutes. SDS-PAGE electrophoresis and autoradiography were performed to quantify PBP binding inhibition, confirming high affinity for PBP3 [1][2]
- MIC determination assay: Clinical Gram-negative bacterial isolates were inoculated into Mueller-Hinton broth containing serial dilutions of Aztreonam (SQ-26776) (0.001-128 μg/mL) and incubated at 37°C for 18-24 hours. The lowest concentration inhibiting visible bacterial growth was defined as MIC [1][2][3]
- β-lactamase stability assay: Aztreonam (SQ-26776) (10 μg/mL) was incubated with purified β-lactamases (ESBLs, AmpC, MBLs) at 37°C for 1 hour. Residual antibacterial activity was measured by agar diffusion assay, with inhibition zone diameter used to evaluate stability [3]

Time-kill curve assay: Bacterial suspensions (10⁶ CFU/mL) were incubated with Aztreonam (SQ-26776) at 0.5×MIC, 1×MIC, 2×MIC, and 4×MIC at 37°C. Aliquots were sampled at 0, 2, 4, 6, 8, and 24 hours, serially diluted, and plated on agar plates. Colonies were counted after 24 hours to determine viable bacterial counts [1][2]
- Cytotoxicity assay: Human HEp-2 cells and NHF cells were seeded in 96-well plates and treated with Aztreonam (SQ-26776) (0.1-200 μg/mL) for 24 hours. MTT reagent was added, and absorbance at 570 nm was measured to evaluate cell viability [1]

300 mg/kg

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Mouse intra-abdominal sepsis model: CD-1 mice were intraperitoneally inoculated with Escherichia coli (10⁸ CFU/mouse) mixed with 5% mucin. Aztreonam (SQ-26776) was dissolved in normal saline and administered via intravenous injection at 10 mg/kg, 20 mg/kg, or 40 mg/kg every 8 hours for 3 days. Survival was monitored for 7 days; peritoneal fluid was collected for bacterial load quantification [1]
- Rat pneumonia model: Sprague-Dawley rats were intratracheally inoculated with Pseudomonas aeruginosa (10⁷ CFU/rat). Aztreonam (SQ-26776) was dissolved in normal saline and administered via intratracheal injection at 15 mg/kg or 30 mg/kg once daily for 5 days. Rats were sacrificed, and lung tissues were collected for bacterial count and histological analysis [2]

Absorption, Distribution and Excretion
After oral administration, less than 1% is absorbed via the gastrointestinal tract. It is completely absorbed after intramuscular injection. In healthy subjects, aztreonam is primarily excreted in the urine via active tubular secretion and glomerular filtration, in roughly equal proportions. Following a single parenteral administration, the drug is almost completely excreted in the urine within 12 hours. 12.6 L 91 mL/min [Health] Metabolism/Metabolites Approximately 6% to 16% of the drug is metabolized to inactive metabolites via β-lactam bond hydrolysis, forming open-ring compounds. Biological Half-Life In subjects with normal renal function, the mean serum half-life of aztreonam is 1.7 hours (1.5 to 2.0 hours), regardless of dose. In elderly patients and patients with impaired renal function, the mean serum half-life of aztreonam was prolonged (4.7 to 6 hours and 2.1 hours, respectively).

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In healthy volunteers, after intravenous administration of aztreonam (SQ-26776) (1 g, 2 g), the peak plasma concentration (Cmax) at the end of infusion was 125 μg/mL (1 g) and 242 μg/mL (2 g), respectively [3]
- The plasma elimination half-life (t1/2) in adults was 1.5-2.0 hours, and in elderly patients (≥65 years) it was 2.5-3.0 hours [3]
- The urinary excretion rate within 24 hours was approximately 70-80%, of which approximately 95% was the unchanged drug [1][3]
- Good tissue distribution: renal tissue/plasma concentration ratio = 6.2, lung = 1.5, peritoneal fluid = 1.1, cerebrospinal fluid (CSF) = 0.3 (meningitis patients) [3]
- The plasma protein binding rate was approximately 15-20% [1][3]

Hepatotoxicity
The systemic toxicity of aztreonam is similar to other β-lactam antibiotics, but it is unclear whether it will cause liver injury like penicillins or cephalosporins. Asymptomatic elevations of serum transaminases are common (10% to 38%) during high-dose intravenous aztreonam treatment. These enzyme abnormalities are usually mild to moderate, asymptomatic, and resolve spontaneously without discontinuation of the drug. The incidence of enzyme elevations during aztreonam treatment is slightly higher than with other antibiotics in the same class. Such cases are extremely rare because there are no reported cases of significant liver injury and jaundice caused by aztreonam. Therefore, there is currently no data on the latency period or pattern of liver injury. There have been reports of significant transaminase elevations within 3 to 5 days after starting aztreonam, but these cases were without jaundice and returned to normal rapidly after discontinuation of the drug. Probability Score: E (Unlikely to cause clinically significant liver injury).

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Use during pregnancy and lactation>
◉ Overview of use during lactation
Limited information suggests that aztreonam concentrations in breast milk are low and are not expected to have adverse effects on breastfed infants. There have been reports that β-lactam antibiotics occasionally disrupt the infant gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. A working group of respiratory experts from Europe, Australia, and New Zealand found that inhaled tobramycin is compatible with breastfeeding. Aztreonam can be used in breastfeeding women.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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Protein binding
The average serum protein binding rate is 56%, and is dose-independent. Renal impairment, 36% to 43%.

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In vitro experiments showed that aztreonam (SQ-26776) at concentrations up to 200 μg/mL was non-cytotoxic to human cells[1]
-In vivo experiments showed that intravenous injection of aztreonam (SQ-26776) at doses up to 200 mg/kg for 14 days (rats) did not cause significant changes in body weight, organ index, or serum ALT/AST/creatinine levels[1]
-Clinical trial data showed that adverse events were mild to moderate: gastrointestinal reactions (nausea, diarrhea, 4-6%), rash (2-3%), and elevated liver enzymes (1-2%); no serious nephrotoxicity, neurotoxicity, or hematologic toxicity was reported[3]
-Acute intravenous LD50 in mice >5000 mg/kg[1]

[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.

Aztreonam is a monocyclic β-lactam antibiotic, originally isolated from Chromobacterium violaceum. It is resistant to β-lactamases and is used to treat Gram-negative bacterial infections, particularly those of the meninges, bladder, and kidneys. It may cause superinfection with Gram-positive bacteria. Aztreonam is a monocyclic β-lactam antibiotic. Aztreonam is a synthetic monocyclic β-lactam antibiotic administered parenterally. It has specific activity against aerobic Gram-negative bacilli and is resistant to multiple β-lactamases. Aztreonam treatment is usually accompanied by a mild elevation of serum transaminase levels, but is asymptomatic, and there have been no reports of clinically significant liver damage. Aztreonam is a monocyclic β-lactam antibiotic, originally isolated from Chromobacterium violaceum, and has 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, leading to cell lysis and death. Unlike other β-lactam antibiotics, this drug is resistant to β-lactamase hydrolysis and is commonly used to treat infections caused by Gram-negative aerobic microorganisms. Aztreonam is a monocyclic β-lactam antibiotic, originally isolated from Chlorella vulgaris. It is resistant to β-lactamases and is used to treat Gram-negative bacterial infections, particularly those of the meninges, bladder, and kidneys. It may cause superinfection with Gram-positive bacteria. See also: SQ-28429 (note moved to). Drug Indications For the treatment of the following infections caused by susceptible Gram-negative bacteria: urinary tract infections, lower respiratory tract infections, sepsis, skin and soft tissue infections, intra-abdominal infections, and gynecological infections.
FDA Label
Cayston is indicated for the treatment of chronic lung infections caused by Pseudomonas aeruginosa in patients aged 6 years and older with cystic fibrosis (CF). Official guidelines for the rational use of antimicrobial agents should be considered.
Treatment of Pseudomonas aeruginosa lung infections/colonization in patients with cystic fibrosis
Treatment of Gram-negative intrabronchial infections in patients with bronchiectasis

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Mechanism of Action>
The bactericidal effect of aztreonam stems from its high affinity for penicillin-binding protein 3 (PBP3), thereby inhibiting bacterial cell wall synthesis. Aztreonam inhibits the third (and final) stage of bacterial cell wall synthesis by binding to PBP3. Subsequently, bacterial cell wall autolysins (such as autolysins) mediate cell lysis. Aztreonam may interfere with the action of autolysin inhibitors.

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Aztreonan (SQ-26776) is a synthetic monocyclic β-lactam antibiotic with selective activity against Gram-negative bacteria[1][2][3]
- Its antimicrobial mechanism involves specific binding to bacterial PBP3, inhibiting bacterial cell wall synthesis, and ultimately leading to bacterial cell lysis[1][2]
- It is stable against most β-lactamases and is therefore effective against β-lactam antibiotic-resistant Gram-negative bacteria (except for metallo-β-lactamase-producing strains)[3]
- Approved indications include urinary tract infections, respiratory tract infections, skin/soft tissue infections, intra-abdominal infections, and sepsis caused by susceptible Gram-negative bacteria[3]
- It is administered intravenously or intramuscularly (there is no oral formulation due to low oral bioavailability, <1%).[1][3]
- It has no cross-sensitization with penicillin or cephalosporins and is therefore a safe option for patients allergic to penicillin.[3]

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.)