Identification

Name
Sulbactam
Accession Number
DB09324
Type
Small Molecule
Groups
Approved
Description

Sulbactam is a β-lactamase inhibitor given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys antibiotic activity.

Structure
Thumb
Synonyms
  • (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
  • penicillanic acid sulfone
  • Sulbactam Benzathine
External IDs
CP 45899 / CP 458992 / CP-45899 / CP-45899-2 / CP-45899-99 / CP-458992 / CP45899 / CP458992
Product Ingredients
IngredientUNIICASInChI Key
Sulbactam sodiumDKQ4T82YE669388-84-7NKZMPZCWBSWAOX-IBTYICNHSA-M
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Ampicillin and SulbactamSulbactam sodium (0.5 g/1) + Ampicillin sodium (1 g/1)Injection, powder, for solutionIntravenousAurobindo Pharma2010-09-202012-09-12Us
Ampicillin and SulbactamSulbactam sodium (0.5 g/1) + Ampicillin sodium (1 g/1)Injection, powder, for solutionIntravenousHospira, Inc.2012-03-192012-03-19Us
Ampicillin and SulbactamSulbactam sodium (1 g/1) + Ampicillin sodium (2 g/1)Injection, powder, for solutionIntramuscular; IntravenousFresenius Kabi USA, LLC2005-11-29Not applicableUs
Ampicillin and SulbactamSulbactam sodium (1 g/1) + Ampicillin sodium (2 g/1)Injection, powder, for solutionIntramuscular; IntravenousSandoz Inc2006-07-25Not applicableUs
Ampicillin and SulbactamSulbactam sodium (1 g/1) + Ampicillin sodium (2 g/1)Injection, powder, for solutionIntravenousHospira, Inc.2006-07-25Not applicableUs
Ampicillin and SulbactamSulbactam sodium (125 mg/1mL) + Ampicillin sodium (250 mg/1mL)Injection, powder, for solutionIntravenousWest Ward Pharmaceutical2009-12-22Not applicableUs
Ampicillin and SulbactamSulbactam sodium (0.5 g/20mL) + Ampicillin sodium (1 g/20mL)Injection, powder, for solutionIntramuscular; IntravenousWG Critical Care, LLC2005-11-30Not applicableUs
Ampicillin and SulbactamSulbactam sodium (1 g/1) + Ampicillin sodium (2 g/1)Injection, powder, for solutionIntramuscular; IntravenousClaris Lifesciences, Inc.2015-12-14Not applicableUs
Ampicillin and SulbactamSulbactam sodium (5 g/100mL) + Ampicillin sodium (10 g/100mL)Injection, powder, for solutionIntravenousWG Critical Care, LLC2005-11-25Not applicableUs
Ampicillin and SulbactamSulbactam sodium (125 mg/1mL) + Ampicillin sodium (250 mg/1mL)Injection, powder, for suspensionIntramuscular; IntravenousMylan Institutional2012-11-272014-05-31Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Ampicillin and SulbactamSulbactam sodium (1 g/1) + Ampicillin sodium (2 g/1)Injection, powder, for suspensionIntramuscular; IntravenousCardinal Health2011-05-202014-02-28Us
Categories
UNII
S4TF6I2330
CAS number
68373-14-8
Weight
Average: 233.242
Monoisotopic: 233.035793157
Chemical Formula
C8H11NO5S
InChI Key
FKENQMMABCRJMK-RITPCOANSA-N
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
IUPAC Name
(2S,5R)-3,3-dimethyl-4,4,7-trioxo-4λ⁶-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
SMILES
[H][C@@]12CC(=O)N1[C@@]([H])(C(O)=O)C(C)(C)S2(=O)=O

Pharmacology

Indication

Sulbactam is currently available in combination products with ampicillin. Within this formulation it is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below. Skin and Skin Structure Infections caused by beta-lactamase producing strains of Staphylococcus aureus, Escherichia coli, Klebsiella spp. (including K. pneumoniae), Proteus mirabilis, Bacteroides fragilis, Enterobacter spp., and Acinetobacter calcoaceticus. Intra-Abdominal Infections caused by beta-lactamase producing strains of Escherichia coli, Klebsiella spp. (including K. pneumoniae), Bacteroides spp. (including B. fragilis), and Enterobacter spp. Gynecological Infections caused by beta-lactamase producing strains of Escherichia coli, and Bacteroides spp. (including B. fragilis).

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Sulbactam is an irreversible inhibitor of β-lactamase; by binding and inhibiting β-lactamase produced by bacterial cells, sulbactam is thereby able to prevent it from reducing antibiotic activity. Although sulbactam alone possesses little useful antibacterial activity, except against the Neisseriaceae, whole organism studies have shown that sulbactam restores ampicillin activity against beta-lactamase producing strains. In particular, sulbactam has good inhibitory activity against the clinically important plasmid mediated beta-lactamases most frequently responsible for transferred drug resistance. The presence of sulbactam in formulations with ampicillin effectively extends the antibacterial spectrum of ampicillin to include many bacteria normally resistant to it and to other beta-lactam antibacterials. Thus, products with ampicillin + sulbactam possess the properties of a broad-spectrum antibacterial and a beta-lactamase inhibitor.

TargetActionsOrganism
ABeta-lactamase
inhibitor
Staphylococcus aureus
Absorption

Peak serum concentrations are reached almost immediately following a 15-minute intravenous infusion of sulbactam + ampicillin. Mean peak serum levels for sulbactam range from 48 to 88 mcg/mL following intravenous administration of 2000 mg of ampicillin plus 1000 mg sulbactam. After an intramuscular injection of 1000 mg ampicillin plus 500 mg sulbactam, peak sulbactam serum levels ranging from 6 to 24 mcg/mL are attained.

Volume of distribution

Penetration of both ampicillin and sulbactam into cerebrospinal fluid in the presence of inflamed meninges has been demonstrated after IV administration.

Protein binding

Approximately 38% reversibly bound to human serum protein.

Metabolism
Not Available
Route of elimination

Approximately 75 to 85% of both ampicillin and sulbactam are excreted unchanged in the urine during the first 8 hours after administration.

Half life

~1 hr

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Streptococcus pyogenes
  • Streptococcus pneumoniae
  • Staphylococcus saprophyticus
  • Haemophilus influenzae
  • Neisseria gonorrhoeae
  • Escherichia coli
  • Staphylococcus aureus
  • Enterococcus faecalis
  • Moraxella catarrhalis
  • Staphylococcus epidermidis
  • Proteus vulgaris
  • Klebsiella
  • Proteus mirabilis
  • Providencia stuartii
  • Streptococcus viridans
  • Providencia rettgeri
  • Morganella morganii
  • Bacteroides
  • Bacteroides fragilis
  • Peptococcus
  • Peptostreptococcus
  • Clostridium
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Sulbactam is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Sulbactam is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Sulbactam is combined with 4-hydroxycoumarin.
AbacavirAbacavir may decrease the excretion rate of Sulbactam which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Sulbactam which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Sulbactam which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Sulbactam which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Sulbactam is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Sulbactam which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Sulbactam which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Totir MA, Helfand MS, Carey MP, Sheri A, Buynak JD, Bonomo RA, Carey PR: Sulbactam forms only minimal amounts of irreversible acrylate-enzyme with SHV-1 beta-lactamase. Biochemistry. 2007 Aug 7;46(31):8980-7. Epub 2007 Jul 13. [PubMed:17630699]
  2. Helfand MS, Totir MA, Carey MP, Hujer AM, Bonomo RA, Carey PR: Following the reactions of mechanism-based inhibitors with beta-lactamase by Raman crystallography. Biochemistry. 2003 Nov 25;42(46):13386-92. [PubMed:14621983]
External Links
KEGG Drug
D08533
KEGG Compound
C07770
PubChem Compound
130313
PubChem Substance
310265206
ChemSpider
115306
BindingDB
50021954
ChEBI
9321
ChEMBL
CHEMBL403
HET
0RN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sulbactam
ATC Codes
J01CG01 — Sulbactam
PDB Entries
4fh2
FDA label
Download (8.76 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1CompletedBasic ScienceHealthy Volunteers1
1RecruitingTreatmentAcinetobacter Baumannii Infection1
2CompletedTreatmentCleft Palates1
2Unknown StatusTreatmentRespiratory Tract Infections (RTI) / Urinary Tract Infections (UTIs)1
2, 3CompletedTreatmentChorioamnionitis1
3CompletedTreatmentInfection During Hemodialysis1
3CompletedTreatmentLung Abscess / Pneumonia, Aspiration1
3RecruitingOtherRenal Stones1
4Active Not RecruitingNot AvailableAcinetobacter Infections1
4CompletedPreventionCancer, Breast1
4CompletedTreatmentIntra-Abdominal Infections1
4CompletedTreatmentPneumonia1
4RecruitingPreventionFractures, Open / Post-Op Wound Infection1
4Unknown StatusTreatmentRespiratory Tract Infections (RTI) / Urinary Tract Infections (UTIs)1
4WithdrawnPreventionVentilator-associated Bacterial Pneumonia1
Not AvailableCompletedNot AvailableLung Abscess / Peritonitis / Pneumonia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntramuscular; Intravenous
Injection, powder, for solutionIntravenous
Injection, powder, for suspensionIntramuscular; Intravenous
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility48.5 mg/mLALOGPS
logP-0.92ALOGPS
logP-0.89ChemAxon
logS-0.68ALOGPS
pKa (Strongest Acidic)3.09ChemAxon
pKa (Strongest Basic)-3.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area91.75 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity48.21 m3·mol-1ChemAxon
Polarizability20.63 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acids and derivatives
Alternative Parents
Penams / Thiazolidines / Tertiary carboxylic acid amides / Sulfones / Azetidines / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 3 more
Substituents
Alpha-amino acid or derivatives / Penam / Beta-lactam / Sulfone / Tertiary carboxylic acid amide / Thiazolidine / Azetidine / Carboxamide group / Lactam / Monocarboxylic acid or derivatives
show 12 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
penicillanic acids (CHEBI:9321)

Targets

Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Beta-lactamase activity
Specific Function
Not Available
Gene Name
blaZ
Uniprot ID
P00807
Uniprot Name
Beta-lactamase
Molecular Weight
31348.98 Da
References
  1. Totir MA, Helfand MS, Carey MP, Sheri A, Buynak JD, Bonomo RA, Carey PR: Sulbactam forms only minimal amounts of irreversible acrylate-enzyme with SHV-1 beta-lactamase. Biochemistry. 2007 Aug 7;46(31):8980-7. Epub 2007 Jul 13. [PubMed:17630699]
  2. Helfand MS, Totir MA, Carey MP, Hujer AM, Bonomo RA, Carey PR: Following the reactions of mechanism-based inhibitors with beta-lactamase by Raman crystallography. Biochemistry. 2003 Nov 25;42(46):13386-92. [PubMed:14621983]

Drug created on November 17, 2015 10:59 / Updated on November 02, 2018 08:49