Oxacillin: Difference between revisions

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			{{short description\|Chemical compound}}
	{{Drugbox		{{Drugbox
			\| Verifiedfields = changed
	\| verifiedrevid = 408782041
			\| Watchedfields = changed
	\|IUPAC_name=(2''S'',5''R'',6''R'')-3,3-dimethyl-6--7-oxo-4-thia-1-<br>azabicycloheptane-2-carboxylic acid
			\| verifiedrevid = 408783354
	\|image=Oxacillin skeletal.svg
			\| IUPAC_name = (2''S'',5''R'',6''R'')-3,3-dimethyl-6--7-oxo-4-thia-1-<br>azabicycloheptane-2-carboxylic acid
	\|StdUNII_Ref = {{fdacite\|correct\|FDA}}= {{fdacite\|correct\|FDA}}= {{fdacite\|correct\|FDA}}
			\| image = Oxacillin skeletal.svg
			\| image2 = Oxacillin-based-on-xtal-3D-bs-17.png
			<!--Clinical data-->
			\| tradename = Bactocill
			\| Drugs.com = {{drugs.com\|monograph\|bactocill}}
			\| MedlinePlus = a685020
			\| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
			\| pregnancy_US = <!-- A / B / C / D / X -->
			\| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
			\| legal_UK = <!-- GSL / P / POM / CD -->
			\| legal_US = <!-- OTC / Rx-only -->
			<!--Identifiers-->
			\| CAS_number_Ref = {{cascite\|correct\|??}}
			\| CAS_number = 66-79-5
			\| ATC_prefix = J01
			\| ATC_suffix = CF04
			\| ATC_supplemental = {{ATCvet\|J51\|CF04}}
			\| PubChem = 6196
			\| DrugBank_Ref = {{drugbankcite\|changed\|drugbank}}
			\| DrugBank = DB00713
			\| ChemSpiderID_Ref = {{chemspidercite\|changed\|chemspider}}
			\| ChemSpiderID = 5961
			\| UNII_Ref = {{fdacite\|correct\|FDA}}
	\| UNII = UH95VD7V76		\| UNII = UH95VD7V76
	\| ChEMBL_Ref = {{ebicite\|correct\|EBI}}
	\| ChEMBL = 891
	\| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}}
	\| StdInChI = 1S/C19H18ClN3O5S/c1-8-11(12(22-28-8)9-6-4-5-7-10(9)20)15(24)21-13-16(25)23-14(18(26)27)19(2,3)29-17(13)23/h4-7,13-14,17H,1-3H3,(H,21,24)(H,26,27)/t13-,14+,17-/m1/s1
	\| StdInChIKey_Ref = {{stdinchicite\|correct\|chemspider}}
	\| StdInChIKey = LQOLIRLGBULYKD-JKIFEVAISA-N
	\| CAS_number=66-79-5
	\| CASNo_Ref = {{cascite\|correct\|CAS}}
	\|ATC_prefix=J01
	\|ATC_suffix=CF04
	\|ATC_supplemental={{ATCvet\|J51\|CF04}}
	\|PubChem = 6098
	\| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}}
	\| ChemSpiderID=5873
	\|DrugBank=
	\| KEGG_Ref = {{keggcite\|correct\|kegg}}		\| KEGG_Ref = {{keggcite\|correct\|kegg}}
	\| KEGG = D08307		\| KEGG = D08307
			\| ChEBI_Ref = {{ebicite\|changed\|EBI}}
	\|C=19\|H=19\|N=3\|O=5\|S=1
			\| ChEBI = 7809
	\|molecular_weight=401.436 g/mol
			\| ChEMBL_Ref = {{ebicite\|changed\|EBI}}
	\|boiling_point = 686.8
			\| ChEMBL = 819
	\|bioavailability=
			<!--Chemical data-->
	\|density = 1.49
			\| C=19 \| H=19 \| N=3 \| O=5 \| S=1
	\|protein_bound=
			\| smiles = 12SC(C)(C)(N1C(=O)2NC(=O)C1=C(C)ON=C1C1=CC=CC=C1)C(O)=O
	\|metabolism=
			\| StdInChI_Ref = {{stdinchicite\|changed\|chemspider}}
	\|elimination_half-life=
			\| StdInChI = 1S/C19H19N3O5S/c1-9-11(12(21-27-9)10-7-5-4-6-8-10)15(23)20-13-16(24)22-14(18(25)26)19(2,3)28-17(13)22/h4-8,13-14,17H,1-3H3,(H,20,23)(H,25,26)/t13-,14+,17-/m1/s1
	\|excretion=
			\| StdInChIKey_Ref = {{stdinchicite\|changed\|chemspider}}
	\|pregnancy_AU=<!-- A / B1 / B2 / B3 / C / D / X -->
			\| StdInChIKey = UWYHMGVUTGAWSP-JKIFEVAISA-N
	\|pregnancy_US=<!-- A / B / C / D / X -->
			\| density = 1.49
	\|pregnancy_category=
			\| boiling_point = 686.8
	\|legal_AU=<!-- Unscheduled / S2 / S4 / S8 -->
	\|legal_UK=<!-- GSL / P / POM / CD -->
	\|legal_US=<!-- OTC / Rx-only -->
	\|legal_status=
	\|routes_of_administration=
	\|smiles = O=C(O)3N4C(=O)(NC(=O)c2c(onc2c1ccccc1Cl)C)4SC3(C)C
	}}		}}

	'''Oxacillin ~~sodium~~''' (trade name '''Bactocill''') is a ] ] of the ] class.		'''Oxacillin''' (trade name '''Bactocill''') is a ] ] of the ] class developed by ].<ref name="Greenwood2008">{{cite book\| vauthors = Greenwood D \|title=Antimicrobial drugs: chronicle of a twentieth century medical triumph\|url=https://books.google.com/books?id=i4_FZHmzjzwC&pg=PA124\|access-date=18 November 2010\|year=2008\|publisher=Oxford University Press US\|isbn=978-0-19-953484-5\|pages=124–}}</ref>

			<!-- Society and culture -->
	It was developed by ].<ref name="Greenwood2008">{{cite book\|author=David Greenwood\|title=Antimicrobial drugs: chronicle of a twentieth century medical triumph\|url=http://books.google.com/books?id=i4_FZHmzjzwC&pg=PA124\|accessdate=18 November 2010\|year=2008\|publisher=Oxford University Press US\|isbn=9780199534845\|pages=124–}}</ref>
			It was patented in 1960 and approved for medical use in 1962.<ref name=Fis2006>{{cite book \| vauthors = Fischer J, Ganellin CR \|title=Analogue-based Drug Discovery \|date=2006 \|publisher=John Wiley & Sons \|isbn=9783527607495 \|page=490 \|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA490 \|language=en}}</ref>

	==~~Uses~~==		==Medical uses==

	Oxacillin is a penicillinase-resistant β-lactam. It is similar to methicillin, and has replaced methicillin in clinical use. Another related compound is nafcillin. Since it is resistant to penicillinase enzymes, such as that produced by '']'', it is widely used clinically in the US to treat penicillin-resistant '']''. However, resistant strains called ] (MRSA/ORSA) are highly prevalent in the U.S. and the U.K.

			Oxacillin is a penicillinase-resistant ]. It is similar to ], and has replaced methicillin in clinical use. Other related compounds are ], ], ], and ]. Since it is resistant to penicillinase enzymes, such as that produced by '']'', it is widely used clinically in the US to treat penicillin-resistant '']''. However, with the introduction and widespread use of both oxacillin and methicillin, ] strains called ] and oxacillin-resistant ''Staphylococcus aureus'' (MRSA/ORSA) have become increasingly prevalent worldwide. MRSA/ORSA can be treated with ] or other new antibiotics.{{cn\|date=March 2023}}
	==References==
	{{Reflist}}

			==Contraindications==
	{{Cell wall disruptive antibiotics}}
			The use of oxacillin is contraindicated in individuals that have experienced a hypersensitivity reaction to any medication in the penicillin family of antibiotics.<ref name="Bactocill">Drugs.com: </ref> Cross-allergenicity has been documented in individuals taking oxacillin that experienced a previous hypersensitivity reaction when given ] and ].<ref>Apothecon. Oxacillin sodium for injection for intramuscular or intravenous injection prescribing information. Princeton, NJ; 2001 Jan.</ref><ref>{{cite journal \| vauthors = Erffmeyer JE \| title = Adverse reactions to penicillin. Part I \| journal = Annals of Allergy \| volume = 47 \| issue = 4 \| pages = 288–93 \| date = October 1981 \| pmid = 6171185 }}</ref>

			==Adverse effects==
	]
			{{further\|Penicillin drug reaction}}
	]
			Commonly reported adverse effects associated with the use of oxacillin include skin rash, diarrhea, nausea, vomiting, hematuria, agranulocytosis, eosinophilia, leukopenia, neutropenia, thrombocytopenia, hepatotoxicity, acute interstitial nephritis, and fever. High doses of oxacillin have been reported to cause renal, hepatic, and nervous system toxicity. Common to all members of the penicillin class of drugs, oxacillin may cause acute or delayed hypersensitivity reactions. As an injection, oxacillin may cause injection site reactions, which may be characterized by redness, swelling, and itching.<ref name="Bactocill"/>

			==Pharmacology==

			===Mechanism of Action===
	{{Antibiotic-stub}}
			Oxacillin, through its β-lactam ring, covalently binds to penicillin-binding proteins, which are enzymes involved in the synthesis of the bacterial cell wall. This binding interaction interferes with the transpeptidation reaction and inhibits the synthesis of peptidoglycan, a prominent component of the cell wall. By decreasing the integrity of the bacterial cell wall, it is thought that oxacillin and other penicillins kill actively growing bacteria through cell autolysis.<ref name="Basic and Clinical Pharmacology">{{cite book\| vauthors = Katzung B, Trevor A \|title=Basic and Clinical Pharmacology\|date=2014\|publisher=Mcgraw-Hill\|location=New York\|isbn=978-0071825054\|edition=13TH\|url=http://accesspharmacy.mhmedical.com/book.aspx?bookid=1193\|access-date=3 November 2017}}</ref>

			==Chemistry==
	]
			As with other members of the penicillin family, the chemical structure of oxacillin features a 6-aminopenicillanic acid nucleus with a substituent attached to the amino group. The 6-aminopenicillanic acid nucleus consists of a thiazolidine ring attached to a β-lactam ring, which is the active moiety responsible for the antibacterial activity of the penicillin family. The substituent present on oxacillin is thought to impart resistance to degradation via bacterial β-lactamases.<ref name="Basic and Clinical Pharmacology"/>
	]

	]
			==History==
	]
			Oxacillin, a derivative of ], was first synthesized in the early 1960s as part of a research initiative led by ] and John Naylor of ], in consort with ]. Members of the ] penicillin family, which includes ], ], and oxacillin, were synthesized to counter the increasing prevalence of infections caused by penicillin-resistant '']''. While methicillin could only be administered via injection, the isoxazolyl penicillins, including oxacillin, could be given orally or by injection. Following the synthesis of cloxacillin and oxacillin, Beecham retained the right to commercially develop cloxacillin in the United Kingdom while Bristol-Myers was given the marketing rights for oxacillin in the United States.<ref name="Greenwood2008"/>
	]

	]
			==Society and Culture==
	]
			===FDA Approval History<ref name="Bactocill"/>===
	]
			*April 8, 1971: Oxacillin Sodium Injectable
	]
			**Applicant: Sandoz
			*July 27, 1973: Bactocill Capsule
			**Applicant: GlaxoSmithKline
			*March 10, 1980: Oxacillin Sodium Capsule
			**Applicant: Ani Pharms Inc
			*May 15, 1980: Oxacillin Sodium for Solution
			**Applicant: TEVA
			*June 2, 1981: Bactocill for Solution
			**Applicant: GlaxoSmithKline
			*December 23, 1986: Oxacillin Sodium Powder
			**Applicant: Sandoz
			*September 29, 1988: Oxacillin Sodium Injectable
			**Applicant: Watson Labs Inc
			*October 26, 1988: Oxacillin Sodium Injectable
			**Applicant: Watson Labs Inc
			*October 26, 1989: Bactocill in Plastic Container Injectable
			**Applicant: Baxter Healthcare
			*March 30, 2012: Oxacillin Sodium Injectable
			**Applicant: Sagent Pharms
			*January 18, 2013: Oxacillin Sodium Injectable
			**Applicant: Aurobindo Pharma LTD
			*August 25, 2014: Oxacillin Sodium Injectable
			**Applicant: Mylan Labs LTD
			*December 11, 2015: Oxacillin Sodium Injectable
			**Applicant: Hospira Inc
			*July 31, 2017: Oxacillin Sodium Injectable
			**Applicant: Wockhardt Bio/Ag

			===Pricing===
			The ] (AWP) for oxacillin products are provided as follows. The prices listed below are intended to serve as reference values and do not represent the pricing determined by any single manufacturer or entity.<ref name="Bactocill"/>
			*Bactocill in Dextrose Intravenous
			**1 g/50 mL: $20.37
			**2 g/50 mL: $32.48
			*Oxacillin Sodium Injection
			**1 g: $17.52
			**2 g: $33.99
			**10 g: $138.77

			== References ==

			*

			{{Reflist}}

			{{Cell wall disruptive antibiotics}}

			]
			]
			]

Latest revision as of 12:14, 9 August 2023

Chemical compound Pharmaceutical compound

Oxacillin
Clinical data


Trade names	Bactocill
AHFS/Drugs.com	Monograph
MedlinePlus	a685020
ATC code	J01CF04 (WHO) QJ51CF04 (WHO)
Identifiers
IUPAC name (2S,5R,6R)-3,3-dimethyl-6--7-oxo-4-thia-1- azabicycloheptane-2-carboxylic acid
CAS Number	66-79-5
PubChem CID	6196
DrugBank	DB00713
ChemSpider	5961
UNII	UH95VD7V76
KEGG	D08307
ChEBI	CHEBI:7809
ChEMBL	ChEMBL819
CompTox Dashboard (EPA)	DTXSID8023397
ECHA InfoCard	100.000.577
Chemical and physical data
Formula	C₁₉H₁₉N₃O₅S
Molar mass	401.44 g·mol
3D model (JSmol)	Interactive image
Density	1.49 g/cm
Boiling point	686.8 °C (1,268.2 °F)
SMILES 12SC(C)(C)(N1C(=O)2NC(=O)C1=C(C)ON=C1C1=CC=CC=C1)C(O)=O
InChI InChI=1S/C19H19N3O5S/c1-9-11(12(21-27-9)10-7-5-4-6-8-10)15(23)20-13-16(24)22-14(18(25)26)19(2,3)28-17(13)22/h4-8,13-14,17H,1-3H3,(H,20,23)(H,25,26)/t13-,14+,17-/m1/s1 Key:UWYHMGVUTGAWSP-JKIFEVAISA-N
(what is this?) (verify)

Oxacillin (trade name Bactocill) is a narrow-spectrum beta-lactam antibiotic of the penicillin class developed by Beecham.

It was patented in 1960 and approved for medical use in 1962.

Medical uses

Oxacillin is a penicillinase-resistant β-lactam. It is similar to methicillin, and has replaced methicillin in clinical use. Other related compounds are nafcillin, cloxacillin, dicloxacillin, and flucloxacillin. Since it is resistant to penicillinase enzymes, such as that produced by Staphylococcus aureus, it is widely used clinically in the US to treat penicillin-resistant Staphylococcus aureus. However, with the introduction and widespread use of both oxacillin and methicillin, antibiotic-resistant strains called methicillin-resistant and oxacillin-resistant Staphylococcus aureus (MRSA/ORSA) have become increasingly prevalent worldwide. MRSA/ORSA can be treated with vancomycin or other new antibiotics.

Contraindications

The use of oxacillin is contraindicated in individuals that have experienced a hypersensitivity reaction to any medication in the penicillin family of antibiotics. Cross-allergenicity has been documented in individuals taking oxacillin that experienced a previous hypersensitivity reaction when given cephalosporins and cephamycins.

Adverse effects

Further information: Penicillin drug reaction

Commonly reported adverse effects associated with the use of oxacillin include skin rash, diarrhea, nausea, vomiting, hematuria, agranulocytosis, eosinophilia, leukopenia, neutropenia, thrombocytopenia, hepatotoxicity, acute interstitial nephritis, and fever. High doses of oxacillin have been reported to cause renal, hepatic, and nervous system toxicity. Common to all members of the penicillin class of drugs, oxacillin may cause acute or delayed hypersensitivity reactions. As an injection, oxacillin may cause injection site reactions, which may be characterized by redness, swelling, and itching.

Pharmacology

Mechanism of Action

Oxacillin, through its β-lactam ring, covalently binds to penicillin-binding proteins, which are enzymes involved in the synthesis of the bacterial cell wall. This binding interaction interferes with the transpeptidation reaction and inhibits the synthesis of peptidoglycan, a prominent component of the cell wall. By decreasing the integrity of the bacterial cell wall, it is thought that oxacillin and other penicillins kill actively growing bacteria through cell autolysis.

Chemistry

As with other members of the penicillin family, the chemical structure of oxacillin features a 6-aminopenicillanic acid nucleus with a substituent attached to the amino group. The 6-aminopenicillanic acid nucleus consists of a thiazolidine ring attached to a β-lactam ring, which is the active moiety responsible for the antibacterial activity of the penicillin family. The substituent present on oxacillin is thought to impart resistance to degradation via bacterial β-lactamases.

History

Oxacillin, a derivative of methicillin, was first synthesized in the early 1960s as part of a research initiative led by Peter Doyle and John Naylor of Beecham, in consort with Bristol-Myers. Members of the isoxazolyl penicillin family, which includes cloxacillin, dicloxacillin, and oxacillin, were synthesized to counter the increasing prevalence of infections caused by penicillin-resistant Staphylococcus aureus. While methicillin could only be administered via injection, the isoxazolyl penicillins, including oxacillin, could be given orally or by injection. Following the synthesis of cloxacillin and oxacillin, Beecham retained the right to commercially develop cloxacillin in the United Kingdom while Bristol-Myers was given the marketing rights for oxacillin in the United States.

Society and Culture

FDA Approval History

April 8, 1971: Oxacillin Sodium Injectable
- Applicant: Sandoz
July 27, 1973: Bactocill Capsule
- Applicant: GlaxoSmithKline
March 10, 1980: Oxacillin Sodium Capsule
- Applicant: Ani Pharms Inc
May 15, 1980: Oxacillin Sodium for Solution
- Applicant: TEVA
June 2, 1981: Bactocill for Solution
- Applicant: GlaxoSmithKline
December 23, 1986: Oxacillin Sodium Powder
- Applicant: Sandoz
September 29, 1988: Oxacillin Sodium Injectable
- Applicant: Watson Labs Inc
October 26, 1988: Oxacillin Sodium Injectable
- Applicant: Watson Labs Inc
October 26, 1989: Bactocill in Plastic Container Injectable
- Applicant: Baxter Healthcare
March 30, 2012: Oxacillin Sodium Injectable
- Applicant: Sagent Pharms
January 18, 2013: Oxacillin Sodium Injectable
- Applicant: Aurobindo Pharma LTD
August 25, 2014: Oxacillin Sodium Injectable
- Applicant: Mylan Labs LTD
December 11, 2015: Oxacillin Sodium Injectable
- Applicant: Hospira Inc
July 31, 2017: Oxacillin Sodium Injectable
- Applicant: Wockhardt Bio/Ag

Pricing

The average wholesale price (AWP) for oxacillin products are provided as follows. The prices listed below are intended to serve as reference values and do not represent the pricing determined by any single manufacturer or entity.

Bactocill in Dextrose Intravenous
- 1 g/50 mL: $20.37
- 2 g/50 mL: $32.48
Oxacillin Sodium Injection
- 1 g: $17.52
- 2 g: $33.99
- 10 g: $138.77

References

ChemBank

^ Greenwood D (2008). Antimicrobial drugs: chronicle of a twentieth century medical triumph. Oxford University Press US. pp. 124–. ISBN 978-0-19-953484-5. Retrieved 18 November 2010.
Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 490. ISBN 9783527607495.
^ Drugs.com: Bactocill
Apothecon. Oxacillin sodium for injection for intramuscular or intravenous injection prescribing information. Princeton, NJ; 2001 Jan.
Erffmeyer JE (October 1981). "Adverse reactions to penicillin. Part I". Annals of Allergy. 47 (4): 288–93. PMID 6171185.
^ Katzung B, Trevor A (2014). Basic and Clinical Pharmacology (13TH ed.). New York: Mcgraw-Hill. ISBN 978-0071825054. Retrieved 3 November 2017.

Antibacterials active on the cell wall and envelope (J01C-J01D)

β-lactams
(inhibit synthesis
of peptidoglycan
layer of bacterial
cell wall by binding
to and inhibiting
PBPs, a group of
D-alanyl-D-alanine
transpeptidases)

Penicillins (Penams)

Narrow
spectrum

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

Lipopeptides	Insert into bacterial cell wall causing perforation and depolarization: Daptomycin Surfactin
Other	Inhibits PG elongation and crosslinking: Ramoplanin

Intracellular

Inhibit PG subunit synthesis and transport: NAM synthesis inhibition (Fosfomycin)
DADAL/AR inhibitors (Cycloserine)
bactoprenol inhibitors (Bacitracin)

Other

WHO-EM
Withdrawn from market
Clinical trials:
- Phase III
- Never to phase III

Categories: