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Tazobactam (formerly CL298741; YTR830H; Zerbaxa) is a β-lactamase inhibitor approved for us in combination other antibiotics such as Ceftolozane (Zerbaxa) for the treatment of bacterial infections. Tazobactam is also combined with the extended spectrum β-lactam antibiotic piperacillin in the drug piperacillin/tazobactam, one of the preferred antibiotic treatments for nosocomial pneumonia caused by Pseudomonas aeruginosa.
Physicochemical Properties
| Molecular Formula | C10H12N4O5S |
| Molecular Weight | 300.29 |
| Exact Mass | 300.052 |
| Elemental Analysis | C, 40.00; H, 4.03; N, 18.66; O, 26.64; S, 10.68 |
| CAS # | 89786-04-9 |
| Related CAS # | Tazobactam sodium;89785-84-2 |
| PubChem CID | 123630 |
| Appearance | White to off-white solid powder. |
| Density | 1.9±0.1 g/cm3 |
| Boiling Point | 707.1±70.0 °C at 760 mmHg |
| Melting Point | 172 °C(dec.) |
| Flash Point | 381.4±35.7 °C |
| Vapour Pressure | 0.0±2.4 mmHg at 25°C |
| Index of Refraction | 1.818 |
| LogP | -1.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 20 |
| Complexity | 573 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | C(N1N=NC=C1)[C@@]1(S(=O)(=O)[C@@H]2CC(N2[C@H]1C(=O)O)=O)C |
| InChi Key | LPQZKKCYTLCDGQ-WEDXCCLWSA-NLPQZKKCYTLCDGQ-WEDXCCLWSA-N |
| InChi Code | InChI=1S/C10H12N4O5S/c1-10(5-13-3-2-11-12-13)8(9(16)17)14-6(15)4-7(14)20(10,18)19/h2-3,7-8H,4-5H2,1H3,(H,16,17)/t7-,8+,10+/m1/s1 |
| Chemical Name | (2S,3S,5R)-3-((1H-1,2,3-triazol-1-yl)methyl)-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxide |
| Synonyms | YTR830;YTR 830;YTR-830;AC7620;AC 7620;AC-7620;DB01606;DB 01606;DB-01606;CL298741;CL 298741;CL-298741;Tazobactam |
| 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 |
| 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 |
Tazobactam (CL-298741) (5 μg/mL; 18 hours) inhibits the growth of bacteria in a dose-dependent manner and possesses bactericidal activity[2]. With ID50 values of less than 10 μg/mL, respectively, tazobactam (CL-298741) (1–10 μg/mL; 6 hours; Prot. vulgaris and M. morgan) inhibits different types of β-lactamase activity[2]. |
| ln Vivo | Tazobactam (CL-298741), administered intraperitoneally (i.p.) four times a day for 36 and 84 hours to BALB/c mice, reduces the quantity of bacteria in the mice and persists at low concentrations[1]. |
| Animal Protocol |
Animal Model: BALB/c mice[1] Dosage: 1000 mg/kg Administration: Intraperitoneal injection; four times a day, for 36 and 84 hours Result: Reduced bacterial and neutrophil counts in BALF compared to the control group. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Tazobactam is coadministered with piperacillin or ceftolozane, pharmacokinetic information will be provided for these combinations. **Piperacillin-tazobactam** Peak plasma concentrations occur immediately after the completion of intravenous infusion. Following several doses of piperacillin-tazobactam infusions every 6 hours, peak concentrations were similar to those that were measured after the initial dose. **Ceftolozane-piperacillin** AUC: 24.4-25 mcg•h/mL Peak concentrations are reached on day 1 after the first dose and range from 18 to 18.4 mcg/mL. Tazobactam and its metabolite are mainly eliminated by the kidneys with about 80% of the administered dose eliminated as unchanged drug. The remaining drug is excreted as a single metabolite. 18.2 L when given with piperacillin 13.5-18.2 L when given with ceftolozane Piperacillin-tazobactam is widely distributed in body tissues and fluids. These may include but are not limited to the intestine, gallbladder, lung, female reproductive organs, and the bile. Meningeal distribution of piperacillin-tazobactam increases with inflammation, but is otherwise low. Because tazobactam is cleared by the kidneys and is a substrate of the transporters OAT1 and OAT3, inhibitors of these transporters should be avoided to ensure efficacy. Dosage adjustments of piperacillin-tazobactam and ceftolozane-tazobactam must be made for patients with impaired renal clearance. The mean clearance rate of tazobactam was found to be 48.3-83.6 mL/min in patients admitted to the intensive care unit who were given renal replacement therapy and receiving intravenous piperacillin-tazobactam. The clearance of tazobactam is dependent on renal function, as determined by renal clearance. Metabolism / Metabolites Tazobactam is mainly metabolized to M1, an inactive metabolite. Hydrolysis occurs on the beta-lactam ring to form M1 (the inactive metabolite). Biological Half-Life Piperacillin-tazobactam After a single dose in healthy volunteers, the plasma half-life of piperacillin and tazobactam was in the range of 0.7 to 1.2 hours. Ceftolozane-tazobactam 0.91-1.03 hours |
| Toxicity/Toxicokinetics |
Protein Binding Tazobactam is bout 30% bound to plasma proteins. |
| References |
[1]. Clin Microbiol Infect. 2014 Nov;20(11):O831-9. [2]. J Antimicrob Chemother. 1990 Apr;25(4):567-74. [3]. Drugs.2014Jan;74(1):31-51 [4]. Infect Drug Resist.2013Nov 29;6:215-23. |
| Additional Infomation |
Tazobactam is a member of the class of penicillanic acids that is sulbactam in which one of the exocyclic methyl hydrogens is replaced by a 1,2,3-triazol-1-yl group; used (in the form of its sodium salt) in combination with ceftolozane sulfate for treatment of complicated intra-abdominal infections and complicated urinary tract infections. It has a role as an antimicrobial agent, an antiinfective agent and an EC 3.5.2.6 (beta-lactamase) inhibitor. It is a member of penicillanic acids and a member of triazoles. It is functionally related to a sulbactam. It is a conjugate acid of a tazobactam(1-). Tazobactam is an antibiotic of the beta-lactamase inhibitor class that prevents the breakdown of other antibiotics by beta-lactamase enzyme producing organisms. It is combined with [Piperacillin] and [Ceftolozane] for the treatment of a variety of bacterial infections. Piperacillin-tazobactam was initially approved by the FDA in 1994, and ceftolozane-tazobactam was approved by the FDA in 2014, providing wider antibacterial coverage for gram-negative infections. In June 2019, ceftolozane-tazobactam was approved by the FDA for treating hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, which are significant causes of morbidity and mortality in hospitalized patients. Tazobactam is a beta Lactamase Inhibitor. The mechanism of action of tazobactam is as a beta Lactamase Inhibitor. Tazobactam is a penicillanic acid sulfone derivative and beta-lactamase inhibitor with antibacterial activity. Tazobactam contains a beta-lactam ring and irreversibly binds to beta-lactamase at or near its active site. This protects other beta-lactam antibiotics from beta-lactamase catalysis. This drug is used in conjunction with beta-lactamase susceptible penicillins to treat infections caused by beta-lactamase producing organisms. A penicillanic acid and sulfone derivative and potent BETA-LACTAMASE inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria. Drug Indication Tazobactam is used in combination with piperacillin or ceftolozane to broaden the spectrum of piperacillin antibacterial action, treating susceptible infections. As with any other antibiotic, tazobactam should only be used for infections that are either proven or strongly suspected to be susceptible to the tazobactam containing drug. **Tazobactam-piperacillin** When combined with piperacillin, it is used to treat a variety of infections, including those caused by aerobic and facultative gram-positive and gram-negative bacteria, in addition to gram-positive and gram-negative anaerobes. Some examples of infections treated with piperacillin-tazobactam include cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis infections. Certain gram-negative bacilli infections with beta-lactamase producing organisms cannot be treated with piperacillin-tazobactam, due to a gene mutation conferring antibiotic resistance. **Tazobactam-ceftolozane** Tazobactam is used in combination with [ceftolozane] for the treatment of infections caused by designated susceptible microorganisms in adult and pediatric patients: - Complicated Intra-abdominal Infections (cIAI), used in combination with [metronidazole] - Complicated Urinary Tract Infections (cUTI), including pyelonephritis - Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) Mechanism of Action Tazobactam broadens the spectrum of piperacillin and ceftolozane by making them effective against organisms that express beta-lactamase and would normally degrade them. This occurs through the irreversible inhibition of beta-lactamase enzymes. In addition, tazobactam may bind covalently to plasmid-mediated and chromosome-mediated beta-lactamase enzymes. Tazobactam is predominantly effective against the OHIO-1, SHV-1, and TEM groups of beta-lactamases, but may also inhibit other beta-lactamases. Tazobactam shows little antibacterial activity by itself, and for this reason, is generally not administered alone. |
Solubility Data
| Solubility (In Vitro) |
DMSO : 50~60 mg/mL ( 166.51~199.8 mM ) H2O : ~1 mg/mL ( 3.33 mM ) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.93 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 (6.93 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 (6.93 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 (6.93 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3301 mL | 16.6506 mL | 33.3011 mL | |
| 5 mM | 0.6660 mL | 3.3301 mL | 6.6602 mL | |
| 10 mM | 0.3330 mL | 1.6651 mL | 3.3301 mL |