 Chemical Structure.png)
Ceftazidime (GR-20263; GR20263; LY-139381; Tazidime; Fortaz, Tazicef; Avycaz) is a potent, third generation, and broad-spectrum β-lactam antibiotic approved for use as an antimicrobial agent for treating febrile neutropenia in patients with cancer. It is administered intravenously or intramuscularly. As a class, cephalosporins have activity against Gram-positive and Gram-negative bacteria. The balance of activity tips toward Gram-positive organisms for earlier generations; later generations of cephalosporins have more Gram-negative coverage. Ceftazidime is one of the few in this class with activity against Pseudomonas.
Physicochemical Properties
| Exact Mass | 546.099 |
| Elemental Analysis | C, 48.34; H, 4.06; N, 15.38; O, 20.49; S, 11.73 |
| CAS # | 72558-82-8 |
| Related CAS # | Ceftazidime pentahydrate;78439-06-2 |
| PubChem CID | 5481173 |
| Appearance | White to off-white solid powder |
| Melting Point | 103-113 |
| LogP | -2.84 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 37 |
| Complexity | 1020 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | 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 |
| InChi Key | ORFOPKXBNMVMKC-LGJNPRDNSA-N |
| InChi Code | 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+ |
| Chemical Name | (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 |
| Synonyms | Fortaz; Fortum; GR 20263; GR-20263; GR20263; LY 139381; LY-139381; LY139381; Tazidime; Ceftazidime anhydrous; Ceftazidime Pentahydrate; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
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. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | β-lactam |
| ln Vitro |
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]. |
| ln Vivo | 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 Assay |
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 Protocol |
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). |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Ceftazidime administered intravenously in healthy males produced mean Cmax values of between 42 and 170 μg/mL for doses between 500 mg and 2 g, and are reached immediately following the end of the infusion period. The Cmax for 1 g of ceftazidime administered intramuscularly is attained approximately one hour following injection and is between 37 and 43 mg/L. Following intramuscular administration of 500 mg and 1 g of ceftazidime, the serum concentration remained above 4 μg/mL for six and eight hours, respectively. Ceftazidime Cmax and AUC show linear proportionality to the dose over the therapeutic range. In individuals with normal renal function, ceftazidime given intravenously every eight hours for 10 days as either 1 or 2 g doses showed no accumulation. Approximately 80% to 90% of an intramuscular or intravenous dose of ceftazidime is excreted unchanged by the kidneys over a 24-hour period. When administered intravenously, 50% of the dose appears in the urine within two hours, with another 32% of the dose appearing by eight hours post-administration. Ceftazidime has a volume of distribution of 15-20 L. 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. Metabolism / Metabolites Ceftazidime is not appreciably metabolized. Biological Half-Life Ceftazidime has an elimination half-life of 1.5-2.8 hours in healthy subjects. As ceftazidime is primarily renally excreted, 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 between 14 and 30 hours. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Limited information indicates that ceftazidime produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Avibactam has not been studied in nursing mothers. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with cephalosporins, but these effects have not been adequately evaluated. Ceftazidime-avibactam 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. ◉ Summary of Use during Lactation Limited information indicates that ceftazidime 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 cephalosporins, but these effects have not been adequately evaluated. Ceftazidime and 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. Protein Binding Ceftazidime plasma protein binding ranges from 5-22.8% (typically less than 10%) and is independent of concentration. Ceftazidime has been shown to bind human serum albumin. |
| References |
[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. |
| Additional Infomation |
Ceftazidime is a third-generation cephalosporin antibiotic bearing pyridinium-1-ylmethyl and {[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-{[(2-carboxypropan-2-yl)oxy]imino}acetamido groups at positions 3 and 7, respectively, of the cephem skeleton. It has a role as an antibacterial drug, an EC 2.4.1.129 (peptidoglycan glycosyltransferase) inhibitor and a drug allergen. It is a cephalosporin and an oxime O-ether. It is a conjugate acid of a ceftazidime(1-). Bacteria possess a cell wall comprising a glycopeptide polymer commonly known as peptidoglycan, which is synthesized and remodelled through the action of a family of enzymes known as "penicillin-binding proteins" (PBPs). β-lactam antibiotics, including cephalosporins, are PBP inhibitors that, through inhibition of essential PBPs, result in impaired cell wall homeostasis, loss of cell integrity, and ultimately bacterial cell death. Ceftazidime is a third-generation cephalosporin with broad-spectrum antibacterial activity, including against some treatment-resistant bacteria such as Pseudomonas aeruginosa. Ceftazidime was approved by the FDA on July 19, 1985, and is currently available either alone or in combination with the non-β-lactam β-lactamase inhibitor [avibactam] to treat a variety of bacterial infections. Ceftazidime has been reported in Apis cerana with data available. Ceftazidime is a beta-lactam, third-generation cephalosporin antibiotic with bactericidal activity. Ceftazidime binds to and inactivates penicillin-binding proteins (PBP) located on the inner membrane of the bacterial cell wall. PBPs participate in the terminal stages of assembling the bacterial cell wall, and in reshaping the cell wall during cell division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis. Compared to the second and first generation cephalosporins, ceftazidime is more active against gram-negative bacteria and less active against gram-positive bacteria. Ceftazidine also crosses the blood-brain barrier and reaches therapeutic concentrations in the central nervous system (CNS). Ceftazidime Anhydrous is an anhydrous form of ceftazidime, a third-generation, beta-lactam, cephalosporin antibiotic with bactericidal activity. Semisynthetic, broad-spectrum antibacterial derived from CEPHALORIDINE and used especially for Pseudomonas and other gram-negative infections in debilitated patients. Drug Indication Ceftazidime is indicated for the treatment of lower respiratory tract infections, skin and skin structure infections, urinary tract infections, bacterial septicemia, bone and joint infections, gynecologic infections, intra-abdominal infections (including peritonitis), and central nervous system infections (including meningitis) caused by susceptible bacteria. Ceftazidime is indicated in combination with [avibactam] to treat infections caused by susceptible Gram-negative organisms, including complicated intra-abdominal infections (cIAI), in conjunction with [metronidazole], and complicated urinary tract infections (cUTI), including pyelonephritis, in patients aged three months and older. This combination is also indicated to treat hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients aged 18 years and older. In all cases, to mitigate the risk of bacterial resistance and preserve clinical efficacy, ceftazidime should only be used for infections that are confirmed or strongly suspected to be caused by susceptible bacterial strains. FDA Label Mechanism of Action The bacterial cell wall, which is located at the periphery of Gram-positive bacteria and within the periplasm of Gram-negative bacteria, comprises a glycopeptide polymer synthesized through cross-linking of glycans to peptide stems on alternating saccharides, which is known commonly as peptidoglycan. Cell wall formation, recycling, and remodelling require numerous enzymes, including a family of enzymes with similar active site character despite distinct and sometimes overlapping roles as carboxypeptidases, endopeptidases, transpeptidases, and transglycosylases, known as "penicillin-binding proteins" (PBPs). The number of PBPs differs between bacteria, in which some are considered essential and others redundant. In general, inhibition of one or more essential PBPs results in impaired cell wall homeostasis, loss of cell integrity, and is ultimately bactericidal. Ceftazidime is a semisynthetic third-generation cephalosporin with broad activity against numerous Gram-negative and some Gram-positive bacteria. Like other β-lactam antibiotics, ceftazidime exhibits its bactericidal effect primarily through direct inhibition of specific PBPs in susceptible bacteria. _In vitro_ experiments in Gram-negative bacteria such as _Escherichia coli_, _Pseudomonas aeruginosa_, _Acinetobacter baumannii_, and _Klebsiella pneumoniae_ suggest that ceftazidime primarily binds to PBP3, with weaker binding to PBP1a/1b and PBP2 as well; although binding to other PBPs, such as PBP4, is detectable, the concentrations required are much greater than those achieved clinically. Similarly, ceftazidime showed binding to _Staphylococcus aureus_ PBP 1, 2, and 3 with a much lower affinity for PBP4. Recent data for _Mycobacterium abcessus_ suggest that ceftazidime can inhibit PonA1, PonA2, and PbpA at intermediate concentrations. |
Solubility Data
| Solubility (In Vitro) |
H2O : 25 ~100 mg/mL (~182.96 mM) DMSO : ~2 mg/mL ( ~3.65 mM ) |
| Solubility (In Vivo) |
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. 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. 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. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.08 mg/mL (3.81 mM) 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. (Please use freshly prepared in vivo formulations for optimal results.) |