Sulbactam

Chemical compound

J01CG01 (WHO)

UK: POM (Prescription only)

Pharmacokinetic dataProtein binding29%Elimination half-life0.65–1.20 hrsExcretionMainly kidneys (41–66% within 8 hrs)Identifiers

IUPAC name

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

CAS Number

68373-14-8^Y

PubChem CID

130313

ChemSpider

115306^Y

UNII

S4TF6I2330

KEGG

D08533^Y

ChEBI

CHEBI:9321^Y

ChEMBL

ChEMBL403^Y

CompTox Dashboard (EPA)

DTXSID1023605

ECHA InfoCard100.063.506

Chemical and physical dataFormulaC₈H₁₁NO₅SMolar mass233.24 g·mol⁻¹3D model (JSmol)

Interactive image

Melting point148 to 151 °C (298 to 304 °F)

SMILES

O=S2(=O)C([C@@H](N1C(=O)C[C@H]12)C(=O)O)(C)C

InChI

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^Y
Key:FKENQMMABCRJMK-RITPCOANSA-N^Y

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Sulbactam is a β-lactamase inhibitor. This drug is given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys the antibiotics.^[1]

It was patented in 1977 and approved for medical use in 1986.^[2]

Medical uses

The combination ampicillin/sulbactam (Unasyn) is available in the United States.^[3]

The combination cefoperazone/sulbactam (Sulperazon) is available in many countries.^[4]

The co-packaged combination sulbactam/durlobactam was approved for medical use in the United States in May 2023.^[5]

Mechanism

Sulbactam is primarily used as a suicide inhibitor of β-lactamase, shielding more potent beta-lactams such as ampicillin.^[6] Sulbactam itself contains a beta-lactam ring, and has weak antibacterial activity by inhibiting penicillin binding proteins (PBP) 1 and 3, but not 2.^[7]

References

^ Totir MA, Helfand MS, Carey MP, Sheri A, Buynak JD, Bonomo RA, Carey PR (August 2007). "Sulbactam forms only minimal amounts of irreversible acrylate-enzyme with SHV-1 beta-lactamase". Biochemistry. 46 (31): 8980–8987. doi:10.1021/bi7006146. PMC 2596720. PMID 17630699.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 492. ISBN 9783527607495.
^ "Unasyn- ampicillin sodium and sulbactam sodium injection, powder, for solution". DailyMed. U.S. National Library of Medicine. 29 March 2023. Retrieved 25 May 2023.
^ "Sulperazon". drugs.com.
^ "FDA Approves New Treatment for Pneumonia Caused by Certain Difficult-to-Treat Bacteria". U.S. Food and Drug Administration (Press release). 24 May 2023. Retrieved 24 May 2023.
^ Crass RL, Pai MP (February 2019). "Pharmacokinetics and Pharmacodynamics of β-Lactamase Inhibitors". Pharmacotherapy. 39 (2): 182–195. doi:10.1002/phar.2210. PMID 30589457. S2CID 58567725.
^ Penwell WF, Shapiro AB, Giacobbe RA, Gu RF, Gao N, Thresher J, et al. (March 2015). "Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii". Antimicrobial Agents and Chemotherapy. 59 (3): 1680–1689. doi:10.1128/AAC.04808-14. PMC 4325763. PMID 25561334.

β-lactamase sensitive (1st generation)	Benzylpenicillin (G)^# Benzathine benzylpenicillin^# Procaine benzylpenicillin^# Phenoxymethylpenicillin (V)^# Propicillin^‡ Pheneticillin^‡ Azidocillin^‡ Clometocillin^‡ Penamecillin^‡
β-lactamase resistant (2nd generation)	Cloxacillin^# (Dicloxacillin Flucloxacillin) Oxacillin Nafcillin Methicillin^‡

Extended
spectrum

Aminopenicillins (3rd generation)	Amoxicillin^# Ampicillin^# (Pivampicillin Hetacillin^‡ Bacampicillin^‡ Lenampicillin Metampicillin^‡ Talampicillin^‡) Epicillin^‡
Carboxypenicillins (4th generation)	Ticarcillin Carbenicillin^‡ / Carindacillin^‡ Temocillin^‡
Ureidopenicillins (4th generation)	Piperacillin Azlocillin^‡ Mezlocillin^‡
Other	Mecillinam (Pivmecillinam) Sulbenicillin^‡

Carbapenems / Penems

Cephems
Cephalosporins
Cephamycins
Carbacephems

1st generation	Cefazolin^# Cefalexin ^# Cefadroxil Cefapirin Cefazedone^‡ Cefazaflur^‡ Cefradine^‡ Cefroxadine^‡ Ceftezole^‡ Cefaloglycin^‡ Cefacetrile^‡ Cefalonium^‡ Cefaloridine^‡ Cefalotin Cefatrizine^‡
2nd generation	Cefaclor Cefprozil Cefuroxime Cefuroxime axetil Cefamandole^‡ Cefonicid^‡ Ceforanide^‡ Cefuzonam^‡ Cephamycin (Cefoxitin Cefotetan Cefminox^‡ Cefbuperazone^‡ Cefmetazole^‡) Carbacephem (Loracarbef^‡)
3rd generation	Cefixime^# Ceftriaxone^# Cefotaxime^# Antipseudomonal (Ceftazidime^# Cefoperazone) Cefdinir Cefcapene Cefdaloxime Ceftizoxime Cefmenoxime Cefpiramide Cefpodoxime Ceftibuten Cefditoren Cefotiam^‡ Cefetamet^‡ Cefodizime^‡ Cefpimizole^‡ Cefsulodin^‡ Cefteram^‡ Ceftiolene^‡ Oxacephem (Flomoxef Latamoxef^‡)
4th generation	Cefepime Cefozopran^‡ Cefpirome Cefquinome^‡
5th generation	Ceftaroline fosamil Ceftolozane Ceftobiprole
Siderophore	Cefiderocol^#
Veterinary	Ceftiofur Cefquinome Cefovecin

Monobactams

β-lactamase inhibitors

Combinations

Polypeptides

Glycopeptides Lipoglycopeptides	Inhibit PG chain elongation: Vancomycin^# (Oritavancin Telavancin) Teicoplanin (Dalbavancin) Ristocetin^‡ Avoparcin Inhibit autolysin: Corbomycin (not approved)
Lipopeptides	Insert into bacterial cell wall causing perforation and depolarization: Daptomycin Surfactin
Polymyxins	Bind to LPS in the outer bacterial membrane, acting in detergent-like fashion: Colistin Polymyxin B
Other	Inhibits PG elongation and crosslinking: Ramoplanin^§