Carbenicillin: Difference between revisions

Carbenicillin
INN
Drug class
Routes of administration	Oral, parenteral
Pregnancy category	Passes into breast milk
Bioavailability	30 to 40%
Metabolism	Minimal
Elimination half-life	1 hour
Excretion	Renal (30 to 40%)
Legal status	Rx-only
CAS Number	4697-36-3
PubChem	20824
DrugBank	DB00578
ChemSpider	19599
KEGG	D07614

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Revision as of 18:39, 26 April 2024

Chemical compound

Carbenicillin is a bactericidal antibiotic belonging to the carboxypenicillin subgroup of the penicillins.<ref>,

 Carfecillin: antibacterial activity in vitro and in vivo, 
 Chemotherapy, 
 1977,
 Vol. 23(Issue: 6),
 pp. 424–35,
 DOI: 10.1159/000222012,
 PMID: 21771,</ref> It was discovered  by scientists at Beecham and marketed as Pyopen. It has Gram-negative coverage which includes Pseudomonas aeruginosa but limited Gram-positive coverage. The carboxypenicillins are susceptible to degradation by beta-lactamase enzymes, although they are more resistant than ampicillin to degradation. Carbenicillin is also more stable at lower pH than ampicillin.

Pharmacology

The antibiotic is highly soluble in water and is acid-labile. A typical lab working concentration is 50 to 100 μg per mL. citation needed ^{(March 2023)}

It is a semi-synthetic analogue of the naturally occurring benzylpenicillin. Carbenicillin at high doses can cause bleeding. Use of carbenicillin can cause hypokalemia by promoting potassium loss at the distal convoluted tubule of the kidney. citation needed ^{(March 2023)}

In molecular biology, carbenicillin may be preferred as a selecting agent (see plasmid stabilisation technology) because its breakdown results in byproducts with a lower toxicity than analogous antibiotics like ampicillin. Carbenicillin is more stable than ampicillin and results in fewer satellite colonies on selection plates. However, in most situations this is not a significant problem so ampicillin is sometimes used due to its lower cost. citation needed ^{(March 2023)}

Spectrum of bacterial susceptibility and resistance

Carbenicillin has been shown to be effective against bacteria responsible for causing urinary tract infections including Pseudomonas aeruginosa, Escherichia coli, and some Proteus species. The following represents carbenicillin susceptibility data for a few medically significant organisms.<ref>

Carbenicillin Disodium, USP Susceptibility and Minimum Inhibitory Concentration (MIC) Data(link). {{{website}}}.

January 6, 2020.

</ref> This is not representative of all species of bacteria susceptible to carbenicillin exposure.

Escherichia coli 1.56 μg/ml - 64 μg/ml
Proteus mirabilis 1.56 μg/ml - 3.13 μg/ml
Pseudomonas aeruginosa 3.13 μg/ml - >1024 μg/ml

References

@@ Line 1: / Line 1: @@
-[[File:Carbenicillin.svg|Carbenicillin|thumb]] '''Carbenicillin''' is a broad-spectrum, beta-lactam [[antibiotic]] that belongs to the [[carboxypenicillin]] subgroup of [[penicillins]]. It was discovered as a natural product of the fungus ''Penicillium'' and later synthesized for medical use. Carbenicillin is primarily effective against [[Gram-negative bacteria]], including [[Pseudomonas aeruginosa]], a pathogen known for its resistance to many antibiotics. This makes carbenicillin particularly valuable in treating infections caused by this bacterium, such as [[pneumonia]], [[urinary tract infections]] (UTIs), and [[septicemia]].
+{{short description|Chemical compound}}
+{{Drugbox
+| Verifiedfields = changed
+| verifiedrevid = 460017669
+| IUPAC_name = (2''S'',5''R'',6''R'')-6-{[carboxy(phenyl)acetyl]amino}-<br />3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]<br />heptane-2-carboxylic acid
+| image = Carbenicillin.svg
+| synonyms = CB<ref>{{cite web |title=Antibiotic abbreviations list |url=https://microbiologie-clinique.com/antibiotic-family-abbreviation.html |access-date=22 June 2023}}</ref>
+<!--Clinical data-->
+| tradename = Geocillin; Pyopen
+| Drugs.com = {{drugs.com|monograph|geocillin}}
+| pregnancy_US = B
+| pregnancy_category = Passes into [[breast milk]]
+| legal_status= Rx-only
+| routes_of_administration = Oral, parenteral
+<!--Pharmacokinetic data-->
+| bioavailability = 30 to 40%
+| protein_bound = 30 to 60%
+| metabolism = Minimal
+| elimination_half-life = 1 hour
+| excretion = [[Kidney|Renal]] (30 to 40%)
+<!--Identifiers-->
+| CAS_number_Ref = {{cascite|correct|??}}
+| CAS_number = 4697-36-3
+| ATC_prefix = J01
+| ATC_suffix = CA03
+| ATC_supplemental =
+| PubChem = 20824
+| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
+| DrugBank = DB00578
+| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
+| ChemSpiderID = 19599
+| UNII_Ref = {{fdacite|correct|FDA}}
+| UNII = G42ZU72N5G
+| ChEBI_Ref = {{ebicite|correct|EBI}}
+| ChEBI = 3393
+| ChEMBL_Ref = {{ebicite|correct|EBI}}
+| ChEMBL = 1214
+| KEGG_Ref = {{keggcite|changed|kegg}}
+| KEGG = D07614
+<!--Chemical data-->
+| C=17 | H=18 | N=2 | O=6 | S=1
+| smiles = O=C(O)[C@@H]2N3C(=O)[C@@H](NC(=O)C(c1ccccc1)C(=O)O)[C@H]3SC2(C)C
+| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
+| StdInChI = 1S/C17H18N2O6S/c1-17(2)11(16(24)25)19-13(21)10(14(19)26-17)18-12(20)9(15(22)23)8-6-4-3-5-7-8/h3-7,9-11,14H,1-2H3,(H,18,20)(H,22,23)(H,24,25)/t9?,10-,11+,14-/m1/s1
+| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
+| StdInChIKey = FPPNZSSZRUTDAP-UWFZAAFLSA-N
+}}
-==Mechanism of Action==
+'''Carbenicillin''' is a [[bactericidal]] [[antibiotic]] belonging to the [[carboxypenicillin]] subgroup of the [[penicillin]]s.<ref>{{cite journal |vauthors=Basker MJ, Comber KR, Sutherland R, Valler GH |title=Carfecillin: antibacterial activity in vitro and in vivo |journal=Chemotherapy |volume=23 |issue=6 |pages=424–35 |year=1977 |pmid=21771 |doi= 10.1159/000222012}}</ref> It was discovered  by scientists at [[Beecham (pharmaceutical company)|Beecham]] and marketed as Pyopen. It has [[Gram-negative]] coverage which includes ''[[Pseudomonas aeruginosa]]'' but limited [[Gram-positive]] coverage. The carboxypenicillins are susceptible to degradation by [[beta-lactamase]] enzymes, although they are more resistant than [[ampicillin]] to degradation. Carbenicillin is also more stable at lower pH than ampicillin.
-Carbenicillin works by inhibiting the synthesis of the bacterial [[cell wall]], leading to cell lysis and death. It targets the penicillin-binding proteins (PBPs) located inside the bacterial cell wall, which are essential for the cross-linking process that gives the cell wall its strength. By inhibiting these proteins, carbenicillin disrupts the cell wall's integrity, causing the bacteria to burst and die due to osmotic pressure differences.
-==Pharmacokinetics==
+== Pharmacology ==
-After administration, carbenicillin is absorbed and distributed throughout the body. However, its bioavailability can be limited when taken orally, leading to its predominant administration via intravenous or intramuscular injections for systemic infections. Carbenicillin is excreted primarily through the kidneys, making renal function an important consideration in dosing.
+The antibiotic is highly soluble in water and is acid-labile. A typical lab working concentration is 50 to 100&nbsp;μg per mL.{{cn|date=March 2023}}
-==Clinical Use==
+It is a semi-synthetic analogue of the naturally occurring [[benzylpenicillin]]. Carbenicillin at high doses can cause bleeding. Use of carbenicillin can cause [[hypokalemia]] by promoting [[potassium]] loss at the [[distal convoluted tubule]] of the kidney.{{cn|date=March 2023}}
-Carbenicillin is used to treat a variety of infections caused by susceptible Gram-negative organisms. Its efficacy against ''Pseudomonas aeruginosa'' makes it a critical antibiotic for managing severe infections in hospital settings, including respiratory infections, UTIs, and septicemia. However, the emergence of antibiotic resistance has limited its use, and it is often reserved for cases where the pathogen is known to be susceptible or other treatments have failed.
-==Resistance==
+In [[molecular biology]], carbenicillin may be preferred as a selecting agent (see [[plasmid stabilisation technology]]) because its breakdown results in byproducts with a lower toxicity than analogous antibiotics like [[ampicillin]]. Carbenicillin is more stable than ampicillin and results in fewer satellite colonies on selection plates.<!-- citation: <ref>{{cite web|last=Promega|title=Can carbenicillin be substituted for ampicillin when selecting for the pGEM Vectors?|url=http://www.promega.com/resources/articles/pubhub/enotes/can-carbenicillin-be-substituted-for-ampicillin-when-selecting-for-the-pgem-vectors/|access-date=23 August 2011}}</ref> --> However, in most situations this is not a significant problem so [[ampicillin]] is sometimes used due to its lower cost.{{cn|date=March 2023}}
-The widespread use of beta-lactam antibiotics, including carbenicillin, has led to the development of resistance among some bacterial strains. Mechanisms of resistance include the production of beta-lactamases, enzymes that break down the antibiotic molecule, and alterations in the target PBPs, reducing the drug's affinity for its target. To combat resistance, carbenicillin is sometimes used in combination with beta-lactamase inhibitors, which protect the antibiotic from enzymatic degradation.
-==Side Effects==
+==Spectrum of bacterial susceptibility and resistance==
-Like other penicillins, carbenicillin can cause allergic reactions in some individuals, ranging from mild rashes to severe anaphylaxis. Other common side effects include gastrointestinal disturbances, such as nausea, vomiting, and diarrhea. Due to its mode of excretion, carbenicillin can also impact kidney function, necessitating monitoring in patients with renal impairment.
+Carbenicillin has been shown to be effective against bacteria responsible for causing urinary tract infections including ''Pseudomonas aeruginosa, Escherichia coli'', and some ''Proteus'' species. The following represents carbenicillin susceptibility data for a few medically significant organisms.<ref>{{cite web | title = Carbenicillin Disodium, USP Susceptibility and Minimum Inhibitory Concentration (MIC) Data | date = January 6, 2020 | url = http://www.toku-e.com/Assets/MIC/Carbenicillin%20disodium%20USP.pdf }}</ref> This is not representative of all species of bacteria susceptible to carbenicillin exposure.
+* ''Escherichia coli'' 1.56 μg/ml - 64 μg/ml
+* ''Proteus mirabilis'' 1.56 μg/ml - 3.13 μg/ml
+* ''Pseudomonas aeruginosa'' 3.13 μg/ml - >1024 μg/ml
-==Conclusion==
+==References==
-Carbenicillin remains an important tool in the treatment of infections caused by ''Pseudomonas aeruginosa'' and other Gram-negative bacteria. Despite challenges posed by antibiotic resistance, its role in managing severe infections underscores the need for ongoing research into new antibiotics and resistance mechanisms.
+{{reflist}}
+==Further reading==
+* {{cite journal |vauthors=Pawełczyk E, Zajac M, Knitter B, Mikołajczak P |title=Kinetics of drug decomposition. Part 66. Kinetics of the hydrolysis of carphecillin in aqueous solution |journal=Polish Journal of Pharmacology and Pharmacy |volume=33 |issue=3 |pages=373–86 |date=October 1981 |pmid=7322950 }}
+{{PenicillinAntiBiotics}}
-[[Category:Antibiotics]]
 [[Category:Penicillins]]
+[[Category:Phenyl compounds]]
-{{medicine-stub}}