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 sodiumDKQ4T82YE6 69388-84-7NKZMPZCWBSWAOX-IBTYICNHSA-M
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Ampicillin and SulbactamSulbactam (5 g/100mL) + Ampicillin (10 g/100mL)Injection, powder, for solutionIntravenousWG Critical Care, LLC2005-11-25Not applicableUs
Ampicillin and SulbactamSulbactam (.5 g/1) + Ampicillin (1 g/1)Injection, powder, for solutionIntramuscular; IntravenousSagent Pharmaceuticals2017-08-15Not applicableUs
Ampicillin and SulbactamSulbactam (1 g/1) + Ampicillin (2 g/1)Injection, powder, for solutionIntramuscular; IntravenousAuro Medics Pharma Llc2012-02-10Not applicableUs
Ampicillin and SulbactamSulbactam (125 mg/mL) + Ampicillin (250 mg/mL)Injection, powder, for suspensionIntramuscular; IntravenousMylan Institutional2012-11-272017-02-18Us
Ampicillin and SulbactamSulbactam (1 g/1) + Ampicillin (2 g/1)Injection, powder, for solutionIntravenousHospira, Inc.2006-07-25Not applicableUs
Ampicillin and SulbactamSulbactam (.5 g/4mL) + Ampicillin (1 g/4mL)Injection, powder, for solutionIntramuscular; IntravenousHospira, Inc.2006-07-25Not applicableUs
Ampicillin and SulbactamSulbactam (50 mg/mL) + Ampicillin (100 mg/mL)Injection, powder, for solutionIntravenousHospira, Inc.2006-07-25Not applicableUs
Ampicillin and SulbactamSulbactam (.5 g/1) + Ampicillin (1 g/1)Injection, powder, for solutionIntramuscular; IntravenousClaris Lifesciences, Inc.2015-12-14Not applicableUs
Ampicillin and SulbactamSulbactam (5 g/1) + Ampicillin (10 g/1)Injection, powder, for solutionIntravenousSandoz2006-07-25Not applicableUs
Ampicillin and SulbactamSulbactam (1 g/3g) + Ampicillin (2 g/3g)Injection, powder, for solutionIntravenousWest Ward Pharmaceutical2009-12-22Not applicableUs
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][[email protected]@]12CC(=O)N1[[email protected]@]([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).

Structured Indications
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
DrugInteractionDrug group
AcenocoumarolSulbactam may increase the anticoagulant activities of Acenocoumarol.Approved
AclarubicinThe serum concentration of Aclarubicin can be decreased when it is combined with Sulbactam.Investigational
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Sulbactam.Approved, Vet Approved
AmrubicinThe serum concentration of Amrubicin can be decreased when it is combined with Sulbactam.Approved, Investigational
annamycinThe serum concentration of annamycin can be decreased when it is combined with Sulbactam.Investigational
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Sulbactam.Experimental, Vet Approved
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Sulbactam.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Sulbactam.Investigational
BekanamycinThe serum concentration of Bekanamycin can be decreased when it is combined with Sulbactam.Experimental
ChlortetracyclineThe therapeutic efficacy of Sulbactam can be decreased when used in combination with Chlortetracycline.Approved, Vet Approved
ClorindioneSulbactam may increase the anticoagulant activities of Clorindione.Experimental
DaunorubicinThe serum concentration of Daunorubicin can be decreased when it is combined with Sulbactam.Approved
DemeclocyclineThe therapeutic efficacy of Sulbactam can be decreased when used in combination with Demeclocycline.Approved
DibekacinThe serum concentration of Dibekacin can be decreased when it is combined with Sulbactam.Experimental
DicoumarolSulbactam may increase the anticoagulant activities of Dicoumarol.Approved
DihydrostreptomycinThe serum concentration of Dihydrostreptomycin can be decreased when it is combined with Sulbactam.Vet Approved
DiphenadioneSulbactam may increase the anticoagulant activities of Diphenadione.Experimental
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Sulbactam.Approved, Investigational
DoxycyclineThe therapeutic efficacy of Sulbactam can be decreased when used in combination with Doxycycline.Approved, Investigational, Vet Approved
EpirubicinThe serum concentration of Epirubicin can be decreased when it is combined with Sulbactam.Approved
Ethyl biscoumacetateSulbactam may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneSulbactam may increase the anticoagulant activities of Fluindione.Investigational
FramycetinThe serum concentration of Framycetin can be decreased when it is combined with Sulbactam.Approved
GeneticinThe serum concentration of Geneticin can be decreased when it is combined with Sulbactam.Experimental
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Sulbactam.Approved, Vet Approved
GENTAMICIN C1AThe serum concentration of GENTAMICIN C1A can be decreased when it is combined with Sulbactam.Experimental
GPX-150The serum concentration of GPX-150 can be decreased when it is combined with Sulbactam.Investigational
Hygromycin BThe serum concentration of Hygromycin B can be decreased when it is combined with Sulbactam.Vet Approved
IdarubicinThe serum concentration of Idarubicin can be decreased when it is combined with Sulbactam.Approved
INNO-206The serum concentration of INNO-206 can be decreased when it is combined with Sulbactam.Investigational
IsepamicinThe serum concentration of Isepamicin can be decreased when it is combined with Sulbactam.Experimental
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Sulbactam.Approved, Vet Approved
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Sulbactam.Approved
MetrizamideThe serum concentration of Metrizamide can be decreased when it is combined with Sulbactam.Approved
MicronomicinThe serum concentration of Micronomicin can be decreased when it is combined with Sulbactam.Experimental
MinocyclineThe therapeutic efficacy of Sulbactam can be decreased when used in combination with Minocycline.Approved, Investigational
Mycophenolic acidThe serum concentration of the active metabolites of Mycophenolic acid can be reduced when Mycophenolic acid is used in combination with Sulbactam resulting in a loss in efficacy.Approved
NeamineThe serum concentration of Neamine can be decreased when it is combined with Sulbactam.Experimental
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Sulbactam.Approved, Vet Approved
NetilmicinThe serum concentration of Netilmicin can be decreased when it is combined with Sulbactam.Approved
ParomomycinThe serum concentration of Paromomycin can be decreased when it is combined with Sulbactam.Approved, Investigational
PhenindioneSulbactam may increase the anticoagulant activities of Phenindione.Approved
PhenprocoumonSulbactam may increase the anticoagulant activities of Phenprocoumon.Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Sulbactam.Approved
PirarubicinThe serum concentration of Pirarubicin can be decreased when it is combined with Sulbactam.Investigational
PlazomicinThe serum concentration of Plazomicin can be decreased when it is combined with Sulbactam.Investigational
PlicamycinThe serum concentration of Plicamycin can be decreased when it is combined with Sulbactam.Approved, Withdrawn
ProbenecidThe serum concentration of Sulbactam can be increased when it is combined with Probenecid.Approved
PuromycinThe serum concentration of Puromycin can be decreased when it is combined with Sulbactam.Experimental
RibostamycinThe serum concentration of Ribostamycin can be decreased when it is combined with Sulbactam.Approved
SabarubicinThe serum concentration of Sabarubicin can be decreased when it is combined with Sulbactam.Investigational
SisomicinThe serum concentration of Sisomicin can be decreased when it is combined with Sulbactam.Investigational
SP1049CThe serum concentration of SP1049C can be decreased when it is combined with Sulbactam.Investigational
SpectinomycinThe serum concentration of Spectinomycin can be decreased when it is combined with Sulbactam.Approved, Vet Approved
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Sulbactam.Approved, Vet Approved
StreptozocinThe serum concentration of Streptozocin can be decreased when it is combined with Sulbactam.Approved
TioclomarolSulbactam may increase the anticoagulant activities of Tioclomarol.Experimental
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Sulbactam.Approved, Investigational
ValrubicinThe serum concentration of Valrubicin can be decreased when it is combined with Sulbactam.Approved
WarfarinSulbactam may increase the anticoagulant activities of Warfarin.Approved
Zoptarelin doxorubicinThe serum concentration of Zoptarelin doxorubicin can be decreased when it is combined with Sulbactam.Investigational
ZorubicinThe serum concentration of Zorubicin can be decreased when it is combined with Sulbactam.Experimental
Food Interactions
Not Available

References

Synthesis Reference
Not Available
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
J01CR50 — Combinations of penicillinsJ01CG01 — Sulbactam
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Download (8.76 MB)
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1RecruitingTreatmentAcinetobacter Baumannii Infection1
2CompletedTreatmentCleft Palates1
2Unknown StatusTreatmentRespiratory Tract Infections (RTI) / Urinary Tract Infections (UTIs)1
2, 3Active Not RecruitingTreatmentChorioamnionitis1
3CompletedTreatmentInfection During Hemodialysis1
3CompletedTreatmentLung Abscess / Pneumonia, Aspiration1
3RecruitingOtherRenal Stones1
4Active Not RecruitingNot AvailableAcinetobacter Infections1
4CompletedPreventionCancer, Breast1
4CompletedTreatmentIntra-Abdominal Infections1
4CompletedTreatmentPneumonia1
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 chemical entities 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
Chemical entities
Super Class
Organic compounds
Class
Organic acids and derivatives
Sub Class
Carboxylic acids and derivatives
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 October 02, 2017 06:15