β-lactam
Tazobactam (CL-298741; YTR-830H) targets bacterial β-lactamases (including TEM-1, TEM-2, SHV-1, OXA-1, PSE-1) with Ki values ranging from 0.01–0.1 μM for class A β-lactamases [2]
Tazobactam (CL-298741; YTR-830H) irreversibly inhibits plasmid-mediated and chromosomally encoded β-lactamases [3]

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].

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In clinical isolates of Escherichia coli producing TEM-1 β-lactamase, Tazobactam (CL-298741; YTR-830H) (4 μg/mL) in combination with piperacillin reduced the MIC of piperacillin from >256 μg/mL to 8 μg/mL [2]
Against β-lactamase-producing Staphylococcus aureus (methicillin-susceptible), Tazobactam (CL-298741; YTR-830H) (2 μg/mL) combined with ampicillin decreased the ampicillin MIC from 64 μg/mL to 2 μg/mL [1]
For Pseudomonas aeruginosa strains producing PSE-1 β-lactamase, Tazobactam (CL-298741; YTR-830H) (8 μg/mL) in combination with ticarcillin reduced the ticarcillin MIC by 16–32 fold (from 128 μg/mL to 4–8 μg/mL) [4]
Tazobactam (CL-298741; YTR-830H) alone exhibited no significant antibacterial activity (MIC >256 μg/mL) against most Gram-positive and Gram-negative bacteria, but potentiated the activity of β-lactam antibiotics by inhibiting β-lactamase-mediated hydrolysis [3]

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].

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In a murine model of Escherichia coli (TEM-1-producing) sepsis, intraperitoneal administration of Tazobactam (CL-298741; YTR-830H) (20 mg/kg) combined with piperacillin (100 mg/kg) every 8 hours for 3 days resulted in 90% survival rate, compared to 20% survival in the piperacillin monotherapy group [2]
In a rat model of Klebsiella pneumoniae (SHV-1-producing) pneumonia, intravenous Tazobactam (CL-298741; YTR-830H) (15 mg/kg) plus ceftazidime (60 mg/kg) twice daily for 5 days reduced lung bacterial load by 3.2 log10 CFU/g, whereas ceftazidime alone reduced it by only 0.8 log10 CFU/g [4]
In a rabbit model of Staphylococcus aureus (β-lactamase-producing) skin infection, subcutaneous Tazobactam (CL-298741; YTR-830H) (10 mg/kg) combined with ampicillin (50 mg/kg) three times daily for 4 days resolved skin lesions in 85% of animals, compared to 30% in the ampicillin alone group [1]

Purify class A β-lactamases (TEM-1, SHV-1) from recombinant E. coli cultures. Dilute the enzyme to a final concentration of 0.1 μM in assay buffer (pH 7.0). Incubate the enzyme with serial dilutions of Tazobactam (CL-298741; YTR-830H) (0.001–1 μM) at 37°C for 30 minutes. Add the β-lactam substrate (nitrocefin) at a concentration of 100 μM, and measure the absorbance change at 486 nm over 10 minutes to determine enzyme activity. Calculate the Ki value based on the inhibition curve [2]
For class C β-lactamase inhibition assay, isolate chromosomally encoded AmpC β-lactamase from Enterobacter cloacae. Incubate the enzyme (0.2 μM) with Tazobactam (CL-298741; YTR-830H) (0.1–5 μM) for 60 minutes at 37°C. Use cephalosporin as the substrate, and monitor substrate hydrolysis by HPLC to quantify inhibition efficiency [3]

Prepare bacterial suspensions of β-lactamase-producing strains (E. coli, S. aureus) at a concentration of 5×105 CFU/mL in Mueller-Hinton broth. Dispense 100 μL of the suspension into 96-well plates, and add serial dilutions of Tazobactam (CL-298741; YTR-830H) (0.125–32 μg/mL) combined with a fixed concentration of β-lactam antibiotic (piperacillin, ampicillin) at 1× MIC of the antibiotic alone. Incubate the plates at 37°C for 18–24 hours. Determine the MIC as the lowest concentration of the combination that inhibits visible bacterial growth [1]
For time-kill curve analysis, inoculate E. coli (TEM-1-producing) into broth containing Tazobactam (CL-298741; YTR-830H) (4 μg/mL) plus piperacillin (16 μg/mL). Incubate at 37°C with shaking, and sample at 0, 2, 4, 6, 8, and 24 hours. Dilute samples and plate on agar plates to count viable colonies (CFU/mL) and generate time-kill curves [2]

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.

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Murine sepsis model: 6–8 week-old BALB/c mice (n=10/group) were intraperitoneally infected with 1×108 CFU of TEM-1-producing E. coli. One hour post-infection, mice were treated with Tazobactam (CL-298741; YTR-830H) (20 mg/kg) combined with piperacillin (100 mg/kg) via intraperitoneal injection. Dosing was repeated every 8 hours for 3 days. Survival was monitored for 7 days, and blood samples were collected on day 3 to quantify bacterial load [2]
Rat pneumonia model: 10–12 week-old Sprague-Dawley rats (n=8/group) were intratracheally inoculated with 5×107 CFU of SHV-1-producing K. pneumoniae. Two hours post-infection, Tazobactam (CL-298741; YTR-830H) (15 mg/kg) and ceftazidime (60 mg/kg) were administered via intravenous injection. Dosing was repeated twice daily for 5 days. Rats were euthanized on day 5, and lung tissues were homogenized to measure bacterial load [4]
Rabbit skin infection model: New Zealand white rabbits (n=6/group) were inoculated subcutaneously with 2×106 CFU of β-lactamase-producing S. aureus on the dorsal skin. Four hours post-infection, Tazobactam (CL-298741; YTR-830H) (10 mg/kg) plus ampicillin (50 mg/kg) was administered via subcutaneous injection. Dosing was repeated three times daily for 4 days. Skin lesion size was measured daily, and lesion tissues were collected on day 4 for bacterial counting [1]

Absorption, Distribution and Excretion
Tazobactam can be used in combination with piperacillin or cefoloza. Pharmacokinetic information for these combinations is provided below. Piperacillin-Tazobactam: Peak plasma concentrations are reached immediately after intravenous infusion. After every 6 hours of piperacillin-tazobactam infusion, peak concentrations are similar to those measured after the first dose. Cefoloza-Piperacillin: AUC: 24.4–25 mcg•h/mL. Peak concentrations are reached on day 1 after the first dose, ranging from 18 to 18.4 mcg/mL. Tazobactam and its metabolites are primarily excreted by the kidneys; approximately 80% of the administered dose is excreted unchanged. The remaining drug is excreted as a single metabolite. When used in combination with piperacillin, plasma concentrations are 18.2 L; when used in combination with cefoloza, plasma concentrations are 13.5–18.2 L. Piperacillin-tazobactam is widely distributed in tissues and fluids throughout the body, including but not limited to the intestines, gallbladder, lungs, female reproductive organs, and bile. Inflammation may increase the distribution of piperacillin-tazobactam in the meninges; otherwise, distribution is lower. Because tazobactam is cleared by the kidneys and is a substrate of the OAT1 and OAT3 transporters, inhibitors of these transporters should be avoided to ensure efficacy. The dosage of piperacillin-tazobactam and cefoloza-tazobactam must be adjusted in patients with impaired renal function. In intensive care unit patients receiving renal replacement therapy and intravenous piperacillin-tazobactam, the mean clearance of tazobactam was 48.3–83.6 mL/min. Tazobactam clearance depends on renal function, which is determined by renal clearance. Metabolism/Metabolites: Tazobactam is primarily metabolized to the inactive metabolite M1. M1 (the inactive metabolite) is generated by hydrolysis of the β-lactam ring.

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Biological Half-Life
In healthy volunteers, the plasma half-life of piperacillin and tazobactam is 0.7 to 1.2 hours after a single dose. Cefolozani-Tazobactam 0.91–1.03 h

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In healthy volunteers, after intravenous injection of tazobactam (CL-298741; YTR-830H) (1 g), the peak plasma concentration (Cmax) was 42 μg/mL, the terminal half-life (t1/2) was 1.0–1.2 h, and the area under the curve (AUC0–∞) was 58 μg·h/mL [3]
Tazobactam (CL-298741; YTR-830H) is widely distributed in systemic tissues and fluids, including the lungs, skin, and peritoneal fluid, with an adult volume of distribution (Vd) of 18–22 L [4]
approximately 80–85% Tazobactam (CL-298741; tazobactam (YTR-830H) is excreted unchanged in the urine via glomerular filtration and tubular secretion. Renal clearance is 150–180 mL/min [3]. Tazobactam (CL-298741; YTR-830H) has an oral bioavailability of less than 10%, and therefore can only be administered intravenously or intramuscularly [2].

Protein Binding
Tazobactam binds to plasma proteins at a rate of approximately 30%. In clinical trials, tazobactam (CL-298741; YTR-830H) (up to 4 g daily for 14 days) was well tolerated. Common adverse events included diarrhea (8%), nausea (5%), and rash (3%), ranging from mild to moderate severity.[3] The plasma protein binding rate of tazobactam (CL-298741; YTR-830H) was 20-25%.[4] In 4-week subchronic toxicity studies in rats and dogs, doses up to 300 mg/kg/day (equivalent to 10 times the human therapeutic dose) did not show significant hepatotoxicity or nephrotoxicity, and ALT, AST, creatinine, or BUN levels remained unchanged.[2]

[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.

Tazobactam belongs to the penicillinic acid class of antibiotics. Its structure is similar to sulbactam, except that the outer ring methyl hydrogen is replaced by a 1,2,3-triazol-1-yl group. Tazobactam (in sodium form) is used in combination with cefoloza sulfate to treat complicated intra-abdominal infections and complicated urinary tract infections. Tazobactam has antibacterial, anti-infective, and β-lactamase inhibitory (EC 3.5.2.6) effects. Tazobactam belongs to the penicillinic acid and triazole class of antibiotics, and its function is similar to sulbactam; it is the conjugate acid of tazobactam (1-). Tazobactam is a β-lactamase inhibitor antibiotic that prevents β-lactamase-producing microorganisms from breaking down other antibiotics. It is used in combination with piperacillin and cefoloza to treat a variety of bacterial infections. Piperacillin-tazobactam was initially approved by the FDA in 1994, and cefoloza-tazobactam was approved by the FDA in 2014, thus expanding the antibacterial spectrum against Gram-negative bacterial infections. In June 2019, cefoloza-tazobactam received FDA approval for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, both of which are major causes of morbidity and mortality in hospitalized patients. Tazobactam is a β-lactamase inhibitor. Its mechanism of action is as a β-lactamase inhibitor. Tazobactam is a penicillin sulfone derivative and also a β-lactamase inhibitor with antibacterial activity. Tazobactam contains a β-lactam ring that irreversibly binds to β-lactamases at or near their active site. This protects other β-lactam antibiotics from β-lactamase catalysis. It is used in combination with β-lactamase-sensitive penicillins to treat infections caused by β-lactamase-producing bacteria. Tazobactam is a penicillinic acid and sulfone derivative and a potent β-lactamase inhibitor that enhances the activity of other antibacterial drugs against β-lactamase-producing bacteria.

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Drug Indications
Tazobactam is used in combination with piperacillin or cefoloza to broaden the antibacterial spectrum of piperacillin for the treatment of infections caused by susceptible bacteria. As with any other antibiotic, tazobactam is only indicated for infections that are confirmed or highly suspected to be susceptible to drugs containing tazobactam. Tazobactam-piperacillin, used in combination with piperacillin, is used to treat a variety of infections, including those caused by aerobic and facultative anaerobic Gram-positive and Gram-negative bacteria, as well as those caused by Gram-positive and Gram-negative anaerobic bacteria. Piperacillin-tazobactam can be used to treat infections such as cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis. Some infections caused by β-lactamase-producing Gram-negative bacilli cannot be treated with piperacillin-tazobactam due to resistance caused by gene mutations.
Tazobactam-Cefolozanil: Tazobactam, in combination with cefolozanil, is used to treat infections in adults and children caused by specific susceptible microorganisms: - Complicated intra-abdominal infections (cIAI), in combination with metronidazole - Complicated urinary tract infections (cUTI), including pyelonephritis - Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP)

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Mechanism of Action
Tazobactam broadens the antibacterial spectrum of piperacillin and cefolozanil by irreversibly inhibiting β-lactamases, making piperacillin and cefolozanil effective against microorganisms that express β-lactamases and typically degrade them. Furthermore, tazobactam may covalently bind to plasmid-mediated and chromosome-mediated β-lactamases. Tazobactam is primarily effective against β-lactamases in the OHIO-1, SHV-1, and TEM groups, but may also inhibit other β-lactamases. Tazobactam itself has weak antibacterial activity and is therefore usually not used alone.

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Tazobactam (CL-298741; YTR-830H) is a β-lactamase inhibitor whose mechanism of action is to irreversibly bind to the active site of β-lactamase, preventing it from hydrolyzing β-lactam antibiotics[2].
Clinically, tazobactam is often used in combination with β-lactam antibiotics (piperacillin, ceftazidime, ampicillin) to treat infections caused by β-lactamase-producing Gram-positive and Gram-negative bacteria, including pneumonia, sepsis, skin and soft tissue infections, and urinary tract infections[3].
Tazobactam (CL-298741; YTR-830H) has a stronger inhibitory effect on TEM and SHV type β-lactamases than clavulanic acid. At high concentrations, it is active against certain class C β-lactamases (AmpC) [4]
In patients with renal insufficiency (creatinine clearance <30 mL/min), the dose of tazobactam (CL-298741; YTR-830H) needs to be reduced by 50% due to decreased renal excretion [3]

C10H12N4O5S

300.29

300.052

C, 40.00; H, 4.03; N, 18.66; O, 26.64; S, 10.68

89786-04-9

Tazobactam sodium;89785-84-2

123630

White to off-white solid powder.

1.9±0.1 g/cm3

707.1±70.0 °C at 760 mmHg

172 °C(dec.)

381.4±35.7 °C

0.0±2.4 mmHg at 25°C

1.818

-1.7

1

7

3

20

573

3

C(N1N=NC=C1)[C@@]1(S(=O)(=O)[C@@H]2CC(N2[C@H]1C(=O)O)=O)C

LPQZKKCYTLCDGQ-WEDXCCLWSA-NLPQZKKCYTLCDGQ-WEDXCCLWSA-N

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

(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

YTR830;YTR 830;YTR-830;AC7620;AC 7620;AC-7620;DB01606;DB 01606;DB-01606;CL298741;CL 298741;CL-298741;Tazobactam

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 : 50~60 mg/mL ( 166.51~199.8 mM )
H2O : ~1 mg/mL ( 3.33 mM )

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.

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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.

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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.

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.08 mg/mL (6.93 mM)

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