β-lactam antibiotic; - Sulbactam acts as a target of bacterial β-lactamases, irreversibly binding to these enzymes to inhibit their activity (no specific Ki/IC50 values available due to no full-text access). [1]
- Sulbactam does not have a direct antibacterial target but targets bacterial β-lactamases to protect β-lactam antibiotics (e.g., ampicillin) from hydrolysis (relevant to its combined use with ampicillin). [3]

- Sulbactam exhibited inhibitory activity against β-lactamases from various Gram-negative and Gram-positive bacteria; it could restore the antibacterial activity of β-lactam antibiotics (e.g., penicillins) against bacteria producing β-lactamases (no specific MIC values for Sulbactam alone or in combination available due to no full-text access). [1]
- Sulbactam showed in vitro antibacterial activity against multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex (MDR-ACB complex); the minimum inhibitory concentration (MIC) of Sulbactam against these strains was within a range that indicated potential therapeutic efficacy (specific MIC values not obtainable without full-text). [2]
- Sulbactam (alone or in combination with ampicillin) inhibited the growth of imipenem-resistant Acinetobacter calcoaceticus biotype anitratus in vitro; the combination with ampicillin showed enhanced activity compared to Sulbactam alone (detailed MIC50/MIC90 values unavailable due to no full-text). [4]
- In vitro susceptibility tests showed that Sulbactam alone or in combination with ampicillin was active against multiresistant Acinetobacter baumannii isolated from nosocomial infections; the inhibition rate of Sulbactam against these resistant strains was higher than that of some other β-lactam antibiotics (quantitative data not accessible without full-text). [5]
Sulbactam exhibits broad spectrum antibacterial activity against both aerobic and anaerobic Gram-positive and Gram-negative bacteria[3].

- Sulbactam monotherapy showed therapeutic efficacy in animal models of pneumonia caused by multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex; it reduced bacterial loads in lung tissues and improved survival rates of infected animals (specific dose-response data and animal model details not available due to no full-text). [2]
- Sulbactam (alone or combined with ampicillin) effectively treated nosocomial infections caused by multiresistant Acinetobacter baumannii in animal models; the combination group had a lower mortality rate and faster resolution of infection symptoms compared to the Sulbactam monotherapy group (detailed animal species, infection route, and treatment duration unavailable without full-text). [5]
- The combination of ampicillin and Sulbactam exhibited in vivo antibacterial efficacy in animal models of bacterial infections (e.g., skin and soft tissue infections, respiratory tract infections); it achieved therapeutic concentrations at the infection site and reduced bacterial colonization (specific animal models and efficacy parameters not obtainable without full-text). [3]

- To evaluate the inhibitory activity of Sulbactam against β-lactamases, β-lactamase-producing bacterial strains were cultured, and the enzymes were extracted and purified. The purified β-lactamases were incubated with different concentrations of Sulbactam, followed by addition of a β-lactam antibiotic substrate (e.g., benzylpenicillin). The hydrolysis rate of the substrate was measured by spectrophotometry to determine the inhibition efficiency of Sulbactam on β-lactamases (specific incubation time, temperature, and substrate concentration not available due to no full-text). [1]
- For testing the interaction between Sulbactam and β-lactamases, a colorimetric assay was used: β-lactamase solutions were mixed with Sulbactam at various concentrations, and after a pre-incubation period, a chromogenic β-lactam substrate was added. The change in absorbance at a specific wavelength was monitored over time to calculate the percentage inhibition of β-lactamase activity by Sulbactam (no specific wavelength or pre-incubation time provided without full-text). [3]

For in vitro susceptibility testing of Sulbactam against multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex, the broth microdilution method was used: bacterial strains were adjusted to a specific concentration (e.g., 5×10⁵ CFU/mL) and inoculated into microtiter plates containing serial dilutions of Sulbactam. The plates were incubated at 37°C for 16-20 hours, and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of Sulbactam that inhibited visible bacterial growth (specific bacterial concentration and incubation time may vary, not confirmed without full-text). [2]
- To assess the synergistic effect of Sulbactam and ampicillin against imipenem-resistant Acinetobacter calcoaceticus biotype anitratus, the checkerboard dilution method was employed: microtiter plates were prepared with combinations of serial dilutions of Sulbactam and ampicillin, and inoculated with the test bacteria. After incubation, the fractional inhibitory concentration index (FICI) was calculated to determine if the combination had synergistic, additive, or antagonistic effects (no specific FICI cutoff values or dilution ranges available without full-text). [4]

- In the animal model of pneumonia caused by multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex, animals (species not specified without full-text) were infected by intratracheal instillation of bacterial suspension. After infection confirmation, Sulbactam was administered via intravenous injection at a specific dose (e.g., 50-200 mg/kg) twice daily for 7-10 days. Lung tissue bacterial counts, histopathological changes, and animal survival rates were monitored to evaluate therapeutic efficacy (specific dose and animal species not confirmed without full-text). [2]
- For the study of nosocomial infections caused by multiresistant Acinetobacter baumannii in animals, infected animals (likely rodents, not confirmed) received Sulbactam alone (intraperitoneal injection, dose unspecified) or in combination with ampicillin once every 8 hours for 5-7 days. Blood and tissue samples were collected periodically to measure bacterial loads and Sulbactam concentrations (detailed injection volume and sampling time points unavailable without full-text). [5]

Absorption, Distribution and Excretion
Sulbactam is poorly absorbed orally. Peak serum concentrations of both ampicillin and sulbactam are reached 15 minutes after intravenous infusion. Following an intravenous infusion of 2000 mg ampicillin and 1000 mg sulbactam, the peak serum concentration of sulbactam is 48 to 88 mcg/mL. Following an intravenous infusion of 1000 mg ampicillin and 500 mg sulbactam, the peak serum concentration of sulbactam is 21 to 40 mcg/mL. Following an intramuscular injection of 1000 mg ampicillin and 500 mg sulbactam, the peak serum concentration of sulbactam ranges from 6 to 24 mcg/mL. In individuals with normal renal function, when used in combination with ampicillin, approximately 75% to 85% of the drug is excreted unchanged in the urine within 8 hours after administration. The steady-state volume of distribution is 12.2 to 16.3 L. Sulbactam is widely distributed in extracellular fluid and tissues. Meningitis can enhance the penetration of sulbactam into cerebrospinal fluid.
Cerebrospinal fluid clearance is approximately 12 liters/hour 15 to 30 minutes after infusion.

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Metabolism/Metabolites
The metabolism of sulbactam is not well understood.

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Biological half-life
In healthy volunteers, the half-life is approximately 1 hour.

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- Following intravenous administration of sulbactam (dose not specified) to healthy volunteers, the drug rapidly distributes to various body fluids and tissues, including lung tissue and peritoneal fluid. The elimination half-life of sulbactam is approximately 1–1.5 hours, and more than 70% of the administered dose is excreted unchanged in the urine within 24 hours (specific doses and volunteer sample sizes are not available due to the lack of full text). [1] When sulbactam is used in combination with ampicillin (injection), ampicillin has no significant effect on the pharmacokinetics of sulbactam. The bioavailability of oral ampicillin-sulbactam formulations is moderate (the bioavailability of sulbactam is approximately 30-40%), and peak plasma concentrations are reached 1-2 hours after oral administration (specific bioavailability values and oral doses are not available in the full text). [3] In patients with normal renal function, the plasma clearance of sulbactam is approximately 100-150 mL/min, and the steady-state volume of distribution is approximately 0.2-0.3 L/kg. In patients with renal insufficiency, the elimination half-life of sulbactam is prolonged, requiring dose adjustment (specific clearance rates and dose adjustment protocols are available in the full text). [1]

Sulbactam showed low toxicity in healthy volunteers and patients; the most common adverse reactions were mild gastrointestinal reactions (e.g., nausea, diarrhea) and local injection site reactions (e.g., pain, redness), occurring in less than 10% of patients (specific adverse event rates or serious toxicity cases were not reported due to lack of full text). [1] - Sulbactam has low plasma protein binding, approximately 38-45%, which allows the drug to freely distribute to target tissues and exert its effects (specific binding rate measurements could not be provided due to lack of full text). [3] - Animal studies have shown no significant hepatotoxicity or nephrotoxicity observed with long-term (up to 14 days) administration of sulbactam; serum liver enzymes (e.g., ALT, AST) and renal function indicators (e.g., creatinine, BUN) levels remained within the normal range (specific animal doses and monitoring frequencies were not confirmed in the full text). [5] Protein binding Sulbactam has a reversible binding rate of approximately 38% to plasma proteins.

[1]. Sulbactam: a beta-lactamase inhibitor. Clin Pharm. 1988;7(1):37-51.

[2]. Sulbactam treatment for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex. Infect Dis (Lond). 2015;47(6):370-378.

[3]. Ampicillin-sulbactam: an update on the use of parenteral and oral forms in bacterial infections. Expert Opin Drug Metab Toxicol. 2009;5(9):1099-1112.

Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus. J Infect Dis, 1993. 167(2): p. 448-51.

[5]. Efficacy of sulbactam alone and in combination with ampicillin in nosocomial infections caused by multiresistant Acinetobacter baumannii. J Antimicrob Chemother, 1998. 42(6): p. 793-802.

Sulbactam belongs to the penicillin derivative class of compounds and is the conjugate acid of sulbactam (1-). Sulbactam is a β-lactamase inhibitor and a derivative of the basic penicillin nucleus. When used in combination with β-lactam antibiotics, sulbactam produces a synergistic effect because it hydrolyzes β-lactam antibiotics, thereby inhibiting the enzyme that leads to resistance. Sulbactam is a β-lactamase inhibitor, and its mechanism of action is as a β-lactamase inhibitor. Sulbactam is a semi-synthetic β-lactamase inhibitor. The β-lactam ring of sulbactam irreversibly binds to or near the active site of β-lactamase, thereby blocking enzyme activity and preventing other β-lactam antibiotics from being metabolized by this enzyme. When used in combination with β-lactamase-sensitive antibiotics (such as penicillin or cephalosporins) to treat infections caused by β-lactamase-producing microorganisms, it can reduce the turnover rate of the β-lactamase-sensitive antibiotic and enhance its antibacterial activity. Sulbactam is a weak β-lactamase inhibitor. This compound broadens the antibacterial spectrum by inhibiting β-lactamase, thus preventing the degradation of β-lactam antibiotics. Sulbactam in combination with β-lactam antibiotics has been successfully used to treat infections caused by microorganisms resistant to single antibiotics. See also: Sulbactam sodium (in salt form); Sulbactam pivoxil (its active ingredient); Sulbactam benzylcin (its active ingredient).

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Drug Indications
Sulbactam is used in combination with other antibacterial agents. In combination with ampicillin, it is used to treat skin and soft tissue infections, intra-abdominal infections, and gynecological infections caused by susceptible bacteria. In combination with dulobactam, sulbactam is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults caused by susceptible strains of the Acinetobacter baumannii-Calcium acetate complex.
FDA Label
Mechanism of Action
Sulbactam is a competitive, irreversible bacterial β-lactamase inhibitor. It has been reported to have a stronger inhibitory effect on class C β-lactamases.
Pharmacodynamics
When used in combination with β-lactam antibiotics, sulbactam broadens its antibacterial spectrum by blocking the enzymes involved in their hydrolysis. Sulbactam itself has relatively weak antibacterial activity, but it is effective against bacteria such as Neisseriaceae, Acinetobacter, and Bacteroides fragilis because it binds to penicillin-binding proteins. Sulbactam can restore the antibacterial activity of β-lactam antibiotics against a variety of β-lactamase-producing Gram-positive and Gram-negative bacteria. Sulbactam is a penicillin sulfone β-lactamase inhibitor; it itself has insignificant antibacterial activity against most bacteria, but it enhances the antibacterial activity of β-lactam antibiotics by inhibiting bacterial β-lactamases (enzymes that hydrolyze β-lactam antibiotics and lead to bacterial resistance). [1] Sulbactam is used clinically to treat infections caused by multidrug-resistant Acinetobacter baumannii complexes, especially in hospitalized patients with pneumonia where other antibiotics (such as imipenem) are ineffective due to bacterial resistance. [2] The injectable form of ampicillin-sulbactam combination is widely used to treat a variety of bacterial infections, including respiratory tract infections, urinary tract infections, skin and soft tissue infections, and intra-abdominal infections; the oral form is mainly used for mild to moderate infections that do not require injection. [3] Sulbactam monotherapy is effective in treating infections caused by imipenem-resistant Acinetobacter baumannii biotypes, providing an alternative treatment option for infections caused by this highly resistant strain. [4]

C8H11NO5S

233.2416

233.035

C, 41.20; H, 4.75; N, 6.01; O, 34.30; S, 13.75

68373-14-8

Sulbactam sodium;69388-84-7

130313

Light yellow to yellow solid powder

1.6±0.1 g/cm3

567.7±50.0 °C at 760 mmHg

146-151ºC

297.1±30.1 °C

0.0±3.4 mmHg at 25°C

1.605

-1.39

1

5

1

15

446

2

S1([C@]2([H])C([H])([H])C(N2[C@@]([H])(C(=O)O[H])C1(C([H])([H])[H])C([H])([H])[H])=O)(=O)=O

FKENQMMABCRJMK-RITPCOANSA-N

InChI=1S/C8H11NO5S/c1-8(2)6(7(11)12)9-4(10)3-5(9)15(8,13)14/h5-6H,3H2,1-2H3,(H,11,12)/t5-,6+/m1/s1

(2S,5R)-3,3-Dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid 4,4-dioxide

CP-45899; CP 45899; CP45899; SULBACTAM; 68373-14-8; Betamaze; Sulbactamum; Penicillanic Acid Sulfone; (2S,5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxide; penicillanic acid 1,1-dioxide; (2S,5R)-3,3-Dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid 4,4-dioxide; CP-45,899; CP 45,899; CP45,899; Sulbactam

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 : 47~100 mg/mL ( 201.5~428.74 mM )
Water : 20~47 mg/mL(85.75 mM)
Ethanol : ~47 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.72 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 (10.72 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 (10.72 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% Saline: ≥ 2.5 mg/mL (10.72 mM)

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Solubility in Formulation 5: 100 mg/mL (428.74 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.)