β-lactam

Against strains of P. aeruginosa, ceftazidime (0–8 μg/mL, approximately, 24 h) exhibits antibacterial and anti-biofilm properties[2].
Ceftazidime exhibits inhibitory effects on isolates of S. maltophilia at concentrations of 0–40 μg/mL, roughly 18–20 hours[3].

In a murine thigh infection model, ceftazidime (2 h infusion of injection, 2 000 mg every 8 h for 24 h) moderately reduces bacterial density[4].

Cell Line: P. aeruginosa strains (PAO1, PA1, PA2)
Concentration: 0-8 µg/mL approximately
Incubation Time: 24 h
Result: showed MIC values of 2-4 µg/mL for antibacterial and anti-biofilm activities.

Animal Model: Murine thigh infection model[4]
Dosage: 2000 mg
Administration: 2 h infusion of injection, every 8 h for 24 h.
Result: decreased bacterial density when compared to the isogenic strain of NDM (New Delhi metallo-β-lactamase).

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Murine Neutropenic Thigh Infection Model:** Pathogen-free female ICR mice (20-22 g) were rendered neutropenic with intraperitoneal injections of cyclophosphamide (100 mg/kg and 150 mg/kg) given 4 and 1 day prior to inoculation. Three days prior to inoculation, mice received a single intraperitoneal injection of uranyl nitrate (5 mg/kg) to induce a controlled renal impairment to slow drug clearance. Thighs were inoculated intramuscularly with approximately 10⁷ CFU/mL of the test isolate. Two hours post-inoculation, groups of three mice were administered human simulated regimens of Ceftazidime (2,000 mg every 8h as a 2-h infusion) or ceftazidime-avibactam (2,000/500 mg every 8h as a 2-h infusion) for 24 hours. Control animals received normal saline. Untreated control mice were sacrificed at 0h (start of therapy), and treatment and 24h control mice were sacrificed after 24 hours. Thighs were harvested, homogenized, and plated for bacterial density determination. Efficacy was calculated as the change in log₁₀ CFU/mL compared to 0h controls. [4]

Absorption, Distribution and Excretion
In healthy men, the mean Cmax value for intravenous ceftazidime at doses between 500 mg and 2 g ranged from 42 to 170 μg/mL and was reached immediately after the infusion. Following intramuscular injection of 1 g ceftazidime, the Cmax value was reached approximately 1 hour after injection, ranging from 37 to 43 mg/L. After intramuscular injections of 500 mg and 1 g ceftazidime, serum concentrations remained above 4 μg/mL for 6 and 8 hours, respectively. Within the therapeutic range, the Cmax and AUC of ceftazidime showed a linear relationship with the dose. In individuals with normal renal function, no accumulation was observed with intravenous ceftazidime every eight hours for 10 days at doses of 1 g or 2 g. Approximately 80% to 90% of the dose of ceftazidime administered intramuscularly or intravenously is excreted unchanged via the kidneys within 24 hours. Following intravenous administration, 50% of the dose appears in the urine within two hours, and another 32% appears within eight hours. The volume of distribution of ceftazidime is 15–20 liters. The mean renal clearance of ceftazidime in healthy subjects ranges from 72 to 141 mL/min, while the calculated plasma clearance is approximately 115 mL/min. Metabolites/Metabolites: Ceftazidime is hardly metabolized. Biological Half-Life: The elimination half-life of ceftazidime in healthy subjects is 1.5–2.8 hours. Because ceftazidime is primarily excreted by the kidneys, its half-life is significantly prolonged in patients with renal impairment. In patients with creatinine clearance < 12 mL/min, the half-life is prolonged to 14–30 hours.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Limited information suggests that ceftazidime is present in low concentrations in breast milk and is not expected to have adverse effects on breastfed infants. Avibactam has not been studied in breastfeeding women. There are reports that cephalosporins occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Ceftazidime-avibactam 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.
◉ Summary of Use During Lactation
Limited information suggests that ceftazidime is present in low concentrations in breast milk and is not expected to have adverse effects on breastfed infants. There are reports that cephalosporins occasionally disrupt the gut microbiota of infants, leading to diarrhea or thrush, but these effects have not been fully assessed. Ceftazidime can be used by 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 plasma protein binding rate of ceftazidime ranges from 5-22.8% (usually less than 10%) and is concentration-independent. Studies have shown that ceftazidime can bind to human serum albumin.

[1]. Ceftazidime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1985 Feb;29(2):105-61.

[2]. In vitro activities of cellulase and ceftazidime, alone and in combination against Pseudomonas aeruginosa biofilms. BMC Microbiol. 2021 Dec 16;21(1):347.

[3]. Avibactam potentiated the activity of both ceftazidime and aztreonam against S. maltophilia clinical isolates in vitro. BMC Microbiol. 2021 Feb 22;21(1):60.

[4]. Unexpected in vivo activity of ceftazidime alone and in combination with avibactam against New Delhi metallo-β-lactamase-producing Enterobacteriaceae in a murine thigh infection model. Antimicrob Agents Chemother. 2014 Nov;58(11):7007-9.

Ceftazidime is a third-generation cephalosporin antibiotic with a pyridin-1-ylmethyl group and a {[(2Z)-2-(2-amino-1,3-thiazolyl-4-yl)-2-{[(2-carboxypropyl-2-yl)oxy]imino}acetamide group attached to the cephalosporin skeleton at positions 3 and 7, respectively. It has antibacterial, EC 2.4.1.129 (peptidoglycan glycosyltransferase) inhibitor, and drug allergen effects. It is a cephalosporin compound and also an oxime ether compound. It is the conjugate acid of ceftazidime (1-). Bacterial cell walls are composed of a glycopeptide polymer commonly called peptidoglycan, whose synthesis and remodeling are achieved through the action of an enzyme called penicillin-binding proteins (PBPs). β-lactam antibiotics, including cephalosporins, are penicillin-binding protein (PBP) inhibitors; they inhibit essential PBPs, leading to impaired cell wall homeostasis, loss of cell integrity, and ultimately bacterial death. Ceftazidime is a third-generation cephalosporin with broad-spectrum antibacterial activity, including effectiveness against certain drug-resistant bacteria such as Pseudomonas aeruginosa. Ceftazidime was approved by the U.S. Food and Drug Administration (FDA) on July 19, 1985, and is currently used alone or in combination with a non-β-lactamase inhibitor [avibactam] to treat a variety of bacterial infections. The effects of ceftazidime in the Chinese honeybee (Apis cerana) have been reported, and relevant data are available. Ceftazidime is a bactericidal third-generation β-lactam cephalosporin antibiotic. Ceftazidime binds to and inactivates penicillin-binding protein (PBP) located on the inner membrane of the bacterial cell wall. PBP is involved in the final stages of bacterial cell wall assembly and cell wall remodeling during cell division. Inactivation of PBP interferes with the cross-linking of peptidoglycan chains, which is crucial for maintaining the strength and rigidity of the bacterial cell wall. This leads to weakening of the bacterial cell wall, ultimately resulting in cell lysis. Compared to second- and first-generation cephalosporins, ceftazidime exhibits higher activity against Gram-negative bacteria but lower activity against Gram-positive bacteria. Ceftazidime can also cross the blood-brain barrier and reach therapeutic concentrations in the central nervous system (CNS). Anhydrous ceftazidime is the anhydrous form of ceftazidime, a third-generation β-lactam cephalosporin antibiotic with bactericidal activity. Ceftazidime is a semi-synthetic broad-spectrum antibacterial drug derived from cefuroxime, particularly suitable for treating Pseudomonas aeruginosa and other Gram-negative bacterial infections in debilitated patients. Indications: Ceftazidime is indicated for the treatment of lower respiratory tract infections, skin and soft tissue infections, urinary tract infections, bacterial sepsis, bone and joint infections, gynecological infections, intra-abdominal infections (including peritonitis), and central nervous system infections (including meningitis) caused by susceptible bacteria. Ceftazidime in combination with avibactam is used to treat infections caused by susceptible Gram-negative bacteria, including complicated intra-abdominal infections (cIAI, requiring metronidazole) and complicated urinary tract infections (cUTI, including pyelonephritis), in patients three months of age or older. This combination therapy is also indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years of age or older. In all cases, to reduce the risk of bacterial resistance and maintain clinical efficacy, ceftazidime should only be used for infections confirmed or highly suspected to be caused by susceptible strains.
FDA Label

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Mechanism of Action
The bacterial cell wall, located in the pericellular space of Gram-positive bacteria and the periplasmic space of Gram-negative bacteria, is composed of glycopeptide polymers synthesized by cross-linking glycans on alternating sugar chains with peptide chains, commonly referred to as peptidoglycans. Cell wall formation, recycling, and remodeling require a variety of enzymes, including a class of enzymes with similar active site characteristics, although their functions differ and sometimes overlap. These include carboxypeptidase, endopeptidase, transpeptidase, and transglycosylase, collectively known as penicillin-binding proteins (PBPs). Different bacteria have varying numbers of PBPs; some are considered essential, while others are redundant. Typically, inhibition of one or more essential penicillin-binding proteins (PBPs) leads to impaired cell wall homeostasis, loss of cell integrity, and ultimately, bactericidal activity. Ceftazidime is a semi-synthetic third-generation cephalosporin with broad-spectrum antibacterial activity against a wide range of Gram-negative bacteria and some Gram-positive bacteria. Like other β-lactam antibiotics, ceftazidime exerts its bactericidal effect primarily by directly inhibiting specific PBPs in susceptible bacteria. In vitro studies have shown that ceftazidime primarily binds to PBP3, with weaker binding to PBP1a/1b and PBP2, exhibiting inhibitory effects against Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Although binding to other PBPs (e.g., PBP4) can be detected, the required concentrations are far higher than clinically observed. Similarly, ceftazidime binds to PBP1, 2, and 3 of Staphylococcus aureus, but its affinity for PBP4 is much lower. Recent data on Mycobacterium abscessus indicate that ceftazidime inhibits PonA1, PonA2, and PbpA at moderate concentrations.

546.099

C, 48.34; H, 4.06; N, 15.38; O, 20.49; S, 11.73

72558-82-8

Ceftazidime pentahydrate;78439-06-2

5481173

White to off-white solid powder

103-113

-2.84

3

12

8

37

1020

2

S1C([H])([H])C(C([H])([H])[N+]2C([H])=C([H])C([H])=C([H])C=2[H])=C(C(=O)[O-])N2C([C@@]([H])([C@]12[H])N([H])C(/C(/C1=C([H])SC(N([H])[H])=N1)=N\OC(C(=O)O[H])(C([H])([H])[H])C([H])([H])[H])=O)=O

ORFOPKXBNMVMKC-LGJNPRDNSA-N

InChI=1S/C22H22N6O7S2/c1-22(2,20(33)34)35-26-13(12-10-37-21(23)24-12)16(29)25-14-17(30)28-15(19(31)32)11(9-36-18(14)28)8-27-6-4-3-5-7-27/h3-7,10,14,18H,8-9H2,1-2H3,(H4-,23,24,25,29,31,32,33,34)/b26-13+

(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Fortaz; Fortum; GR 20263; GR-20263; GR20263; LY 139381; LY-139381; LY139381; Tazidime; Ceftazidime anhydrous; Ceftazidime Pentahydrate;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

H2O : 25 ~100 mg/mL (~182.96 mM)
DMSO : ~2 mg/mL ( ~3.65 mM )

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.81 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 20.8 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: ≥ 2.08 mg/mL (3.81 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 20.8 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: ≥ 2.08 mg/mL (3.81 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 20.8 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% Saline: ≥ 2.08 mg/mL (3.81 mM)

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Solubility in Formulation 5: 100 mg/mL (182.96 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.)