Sulbactam

Identification

Summary

Sulbactam is an beta-lactamase inhibitor antibiotic combined with other antibiotics to treat a variety of susceptible bacterial infections.

Brand Names
Unasyn, Xacduro
Generic Name
Sulbactam
DrugBank Accession Number
DB09324
Background

Sulbactam is a beta (β)-lactamase inhibitor and a derivative of the basic penicillin nucleus.6 When given in combination with β-lactam antibiotics, sulbactam produces a synergistic effect as it blocks the enzyme responsible for drug resistance by hydrolyzing β-lactams.2

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 233.242
Monoisotopic: 233.035793157
Chemical Formula
C8H11NO5S
Synonyms
  • (2S,5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid 4,4-dioxide
  • (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
  • Sulbactamum
External IDs
  • CP 45899
  • CP-45899
  • CP45899

Pharmacology

Indication

Sulbactam is used in combination with other antibacterial agents. With ampicillin, it is used to treat skin and skin structure infections, intra-abdominal infections, and gynecological infections caused by susceptible bacteria.6

In combination with durlobactam, sulbactam is indicated in adults for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.5

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatAcute bacterial rhinosinusitisCombination Product in combination with: Ampicillin (DB00415)••• •••••
Used in combination to treatAnimal biteCombination Product in combination with: Ampicillin (DB00415)••• •••••
Used in combination to treatBacterial infectionsCombination Product in combination with: Ampicillin (DB00415)••••••••••••
Used in combination to treatBacterial infections caused by beta lactamase producing bacteriaCombination Product in combination with: Amoxicillin (DB01060)•••••••••••••••••••••• ••••••
Used in combination to treatCatheter related infectionCombination Product in combination with: Ampicillin (DB00415)••• •••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

When given together with beta-lactam antibiotics, sulbactam broadens their antibacterial spectrum by blocking the enzyme involved in their hydrolysis.2

Sulbactam alone possesses weak intrinsic antibacterial activity except against the Neisseriaceae,6 Acinetobacter spp., and Bacteroides fragilis as it can bind to the penicillin-binding proteins.3,4 Sulbactam restores the activity of beta-lactam antibiotics against a range of beta-lactamase-producing gram-positive and gram-negative bacteria.6

Mechanism of action

Sulbactam is a competitive, irreversible bacterial beta (β)-lactamase inhibitor.4 It is reported to be more potent against class C beta-lactamases.3

TargetActionsOrganism
ABeta-lactamase
inhibitor
Staphylococcus aureus
Absorption

Sulbactam is poorly absorbed after oral administration.1 Peak serum concentrations of ampicillin and sulbactam are reached following a 15-minute intravenous infusion. After the intravenous administration of 2000 mg of ampicillin plus 1000 mg sulbactam, peak sulbactam serum levels corresponded to 48 to 88 mcg/mL. After the intravenous administration of 1000 mg ampicillin plus 500 mg sulbactam, peak sulbactam serum levels corresponded to 21 to 40 mcg/mL. After an intramuscular injection of 1000 mg ampicillin plus 500 mg sulbactam, peak sulbactam serum levels ranged from 6 to 24 mcg/mL.6

Volume of distribution

The steady-state volumes of distribution range from 12.2 to 16.3 L. Sulbactam exhibits extensive distribution in extracellular fluids and tissues.2 Penetration of sulbactam into cerebrospinal fluid is enhanced in the presence of inflamed meninges.6

Protein binding

Sulbactam is approximately 38% reversibly bound to plasma proteins.6

Metabolism

Metabolism of sulbactam has not been characterized.1

Route of elimination

When given in combination with ampicillin in individuals with normal renal function, approximately 75 to 85% of the drug is excreted unchanged in the urine during the first eight hours after administration.6

Half-life

In healthy volunteers, the half-life is approximately one hour.6

Clearance

Eenal clearance is approximately 12 L/h following infusion over 15 to 30 minutes.1

Adverse Effects
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Toxicity

The oral LD50 of sulbactam sodium is >4000 mg/kg in rats and >10,000 mg/kg in mice. The intravenous LD50 of sulbactam sodium is 4582 mg/kg in rats and 3604 mg/kg in mice.7

There is no information on the clinical signs and symptoms associated with a sulbactam overdose. Neurological adverse reactions, including convulsions, may occur. While sulbactam is removable by hemodialysis, there is limited clinical information regarding the use of hemodialysis to treat overdosage.5

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir 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.
AcetaminophenAcetaminophen may decrease the excretion rate of Sulbactam which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Sulbactam which could result in a lower serum level and potentially a reduction in efficacy.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Sulbactam benzathine49MU89FVBV83031-43-0YSEPFTSCLHUBNH-HFKSPEPWSA-N
Sulbactam sodiumDKQ4T82YE669388-84-7NKZMPZCWBSWAOX-IBTYICNHSA-M
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ALFASID 1 G IM/IV ENJEKSIYON ICIN TOZ ICEREN FLAKON, 1 ADETSulbactam (500 mg) + Ampicillin (1000 mg)Injection, powder, for solutionIntramuscular; IntravenousYAVUZ İLAÇ ECZA DEPOSU MEDİKAL ÜRÜNLER SAN.VE TİC. A.Ş.2011-06-08Not applicableTurkey flag
ALFASID 1 GR IM ENJ. ICIN TOZ ICEREN FLAKON, 1 ADETSulbactam (500 mg) + Ampicillin (1000 mg)Injection, powder, for solutionIntramuscular; IntravenousYAVUZ İLAÇ ECZA DEPOSU MEDİKAL ÜRÜNLER SAN.VE TİC. A.Ş.2011-01-20Not applicableTurkey flag
ALFASID 250 MG IM ENJ.ICIN TOZ ICEREN FLAKON, 1 ADETSulbactam (125 mg) + Ampicillin sodium (250 mg)Injection, powder, for solutionIntramuscular; IntravenousYAVUZ İLAÇ ECZA DEPOSU MEDİKAL ÜRÜNLER SAN.VE TİC. A.Ş.2009-07-03Not applicableTurkey flag
ALFASID 250 MG IM/IV ENJ.ICIN TOZ ICEREN FLAKON, 1 ADETSulbactam (125 mg) + Ampicillin sodium (250 mg)Injection, powder, for solutionIntramuscular; IntravenousYAVUZ İLAÇ ECZA DEPOSU MEDİKAL ÜRÜNLER SAN.VE TİC. A.Ş.2009-07-03Not applicableTurkey flag
ALFASID 500 MG IM ENJ.ICIN TOZ ICEREN FLAKONSulbactam (500 mg) + Ampicillin (1000 mg)Injection, powder, for solutionIntramuscularYAVUZ İLAÇ ECZA DEPOSU MEDİKAL ÜRÜNLER SAN.VE TİC. A.Ş.2008-05-14Not applicableTurkey flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Ampicillin and SulbactamSulbactam sodium (1 g/1) + Ampicillin sodium (2 g/1)Injection, powder, for suspensionIntramuscular; IntravenousCardinal Health2011-05-202014-02-28US flag

Categories

ATC Codes
J01CG01 — Sulbactam
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aliphatic heteropolycyclic compound / Alpha-amino acid or derivatives / Azacycle / Azetidine / Beta-lactam / Carbonyl group / Carboxamide group / Carboxylic acid / Hydrocarbon derivative / Lactam
show 12 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
penicillanic acids (CHEBI:9321)
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

Chemical Identifiers

UNII
S4TF6I2330
CAS number
68373-14-8
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-4lambda6-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

References

General References
  1. Campoli-Richards DM, Brogden RN: Sulbactam/ampicillin. A review of its antibacterial activity, pharmacokinetic properties, and therapeutic use. Drugs. 1987 Jun;33(6):577-609. doi: 10.2165/00003495-198733060-00003. [Article]
  2. Peechakara BV, Gupta M: Ampicillin/Sulbactam. . [Article]
  3. Stover KR, Barber KE, Wagner JL: Allergic Reactions and Cross-Reactivity Potential with Beta-Lactamase Inhibitors. Pharmacy (Basel). 2019 Jun 28;7(3). pii: pharmacy7030077. doi: 10.3390/pharmacy7030077. [Article]
  4. Noguchi JK, Gill MA: Sulbactam: a beta-lactamase inhibitor. Clin Pharm. 1988 Jan;7(1):37-51. [Article]
  5. FDA Approved Drug Products: XACDURO (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use [Link]
  6. DailyMed Label: UNASYN (ampicillin sodium and sulbactam sodium) intravenous and intramuscular injection, powder, for solution [Link]
  7. Pfizer: Unasyn (Ampicillin and Sulbactam) MSDS [Link]
KEGG Drug
D02223
KEGG Compound
C07770
PubChem Compound
130313
PubChem Substance
310265206
ChemSpider
115306
BindingDB
50021954
RxNav
10167
ChEBI
9321
ChEMBL
CHEMBL403
ZINC
ZINC000000897244
PDBe Ligand
0RN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sulbactam
PDB Entries
4fh2 / 7k8k / 8ebr
FDA label
Download (8.76 MB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableLung Abscess / Peritonitis / Pneumonia1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableRisk Factors1somestatusstop reasonjust information to hide
Not AvailableRecruitingPreventionAntibacterial therapy / Biliary Atresia / Cholangitis1somestatusstop reasonjust information to hide
Not AvailableRecruitingPreventionAntibiotics / Lactate / Postoperative Infections1somestatusstop reasonjust information to hide
Not AvailableRecruitingPreventionAortic Aneurysm and Dissection / Cardiac Valve Disease / Thoracic Aortic Aneurysm (TAA) / Thoracic Aortic Dissections1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntramuscular; Intravenous
Injection, powder, for solutionIntravenous
Injection, powder, for suspensionIntramuscular; Intravenous
Injection, powder, for solutionParenteral
Injection, powder, for solutionIntramuscular
InjectionIntramuscular; Intravenous1 gr
InjectionIntramuscular
Injection, solutionIntramuscular; Intravenous1 g
Injection, powder, for solutionParenteral
SolutionConjunctival; Ophthalmic150 mg
SuspensionConjunctival; Ophthalmic
Injection, powder, for solutionParenteral547.12 MG/1062.91MG
Powder500 mg/1vial
SolutionConjunctival; Ophthalmic300 mg
SuspensionOral3.000 g
Tablet, coatedOral
Injection, powder, for solutionParenteral1 g
Injection, solutionIntramuscular; Intravenous
InjectionIntramuscular; Intravenous
SolutionConjunctival; Ophthalmic; Topical300 mg
Injection, solutionIntramuscular
SolutionConjunctival; Ophthalmic100 mg
SolutionOral
SolutionParenteral1000.000 mg
TabletOral
Powder
Injection, powder, for solutionIntramuscular; Intravenous1 g
Injection, powder, for solutionIntramuscular; Intravenous2 g
Injection, powder, for solutionIntramuscular; Intravenous500 mg
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous
Injection, powder, for solution; injection, powder, lyophilized, for solution; kitIntravenous
Injection, powder, for solution
Powder, for suspensionOral
Tablet, film coated
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9309245No2016-04-122033-04-02US flag
US9623014No2017-04-182033-04-02US flag
US9968593No2018-05-152035-11-17US flag
US10376499No2019-08-132035-11-17US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)156https://www.fishersci.com/store/msds?partNumber=AC455350250&productDescription=SULBACTAM+25GR&vendorId=VN00032119&countryCode=US&language=en
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/MSsplash10-001i-0090000000-294fa7fe6b712f884149
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0590000000-de34b52fc1a9def9e8d3
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-053r-4590000000-1458fe4517fd392c8c49
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-6190000000-0668e5c19dcb76f50b86
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-01b9-9100000000-bcad6db573484195483e
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-08nc-9640000000-6ded84944c6fcafe64ae
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-148.112336
predicted
DarkChem Lite v0.1.0
[M-H]-148.9225
predicted
DeepCCS 1.0 (2019)
[M+H]+148.819036
predicted
DarkChem Lite v0.1.0
[M+H]+151.31862
predicted
DeepCCS 1.0 (2019)
[M+Na]+148.541536
predicted
DarkChem Lite v0.1.0
[M+Na]+157.23123
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Not Available
Specific Function
beta-lactamase activity
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. [Article]
  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. [Article]
  3. DailyMed Label: UNASYN (ampicillin sodium and sulbactam sodium) intravenous and intramuscular injection, powder, for solution [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
Specific Function
alpha-ketoglutarate transmembrane transporter activity
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. FDA Approved Drug Products: XACDURO (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use [Link]

Drug created at November 17, 2015 17:59 / Updated at June 02, 2024 21:55