Sultamicillin: Difference between revisions

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			{{Short description\|Chemical compound}}
	{{Drugbox		{{Drugbox
			\| Verifiedfields = changed
⚫	\| verifiedrevid = ~~447429128~~
			\| Watchedfields = changed
⚫	\| IUPAC_name = heptane-2-carbonyl]oxymethyl(2''R'')-6-{amino}-3,3-dimethyl-7-oxo-~~<br>~~4-thia-1-azabicycloheptane-2-carboxylate
		⚫	\| verifiedrevid = 470474605
		⚫	\| IUPAC_name = heptane-2-carbonyl]oxymethyl(2''R'')-6-{amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicycloheptane-2-carboxylate
	\| image = Sultamicillin.svg		\| image = Sultamicillin.svg

	<!--Clinical data-->		<!--Clinical data-->
	\| tradename =		\| tradename = Unasyn, Unacid PD oral
	\| Drugs.com = {{drugs.com\|international\|sultamicillin}}		\| Drugs.com = {{drugs.com\|international\|sultamicillin}}
	\| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->		\| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
	\| pregnancy_US = <!-- A / B / C / D / X -->		\| pregnancy_US = <!-- A / B / C / D / X -->
	\| pregnancy_category =		\| pregnancy_category =
	\| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->		\| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
	\| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->		\| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
	\| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->		\| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
	\| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->		\| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
	\| legal_status =		\| legal_status =
	\| routes_of_administration = Oral		\| routes_of_administration = ]

	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	\| bioavailability =		\| bioavailability = 80%
	\| protein_bound =		\| protein_bound =
	\| metabolism =		\| metabolism =
	\| elimination_half-life =		\| elimination_half-life =
	\| excretion =		\| excretion = Mainly via kidney

	<!--Identifiers-->		<!--Identifiers-->
			\| CAS_number_Ref = {{cascite\|changed\|??}}
	\| CAS_number = 76497-13-7		\| CAS_number = 76497-13-7
	\| ATC_prefix = J01		\| ATC_prefix = J01
	\| ATC_suffix = CR04		\| ATC_suffix = CR04
			\| ChEMBL_Ref = {{ebicite\|correct\|EBI}}
			\| ChEMBL = 506110
	\| PubChem = 444022		\| PubChem = 444022
	\| DrugBank_Ref = {{drugbankcite\|correct\|drugbank}}		\| DrugBank_Ref = {{drugbankcite\|correct\|drugbank}}
	\| DrugBank =		\| DrugBank =
	\| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}}		\| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}}
	\| ChemSpiderID = 392048		\| ChemSpiderID = 392048
Line 39:		Line 42:
	\| ChEBI_Ref = {{ebicite\|correct\|EBI}}		\| ChEBI_Ref = {{ebicite\|correct\|EBI}}
	\| ChEBI = 51770		\| ChEBI = 51770

	<!--Chemical data-->		<!--Chemical data-->
	\| C=25 \| H=30 \| N=4 \| O=9 \| S=2		\| C=25 \| H=30 \| N=4 \| O=9 \| S=2
	\| molecular_weight = 594.659 g/mol
	\| smiles = O=C(OCOC(=O)2N1C(=O)C1S(=O)(=O)C2(C)C)4N5C(=O)(NC(=O)(c3ccccc3)N)5SC4(C)C		\| smiles = O=C(OCOC(=O)2N1C(=O)C1S(=O)(=O)C2(C)C)4N5C(=O)(NC(=O)(c3ccccc3)N)5SC4(C)C
	\| InChI = 1/C25H30N4O9S2/c1-24(2)17(29-20(32)16(21(29)39-24)27-19(31)15(26)12-8-6-5-7-9-12)22(33)37-11-38-23(34)18-25(3,4)40(35,36)14-10-13(30)28(14)18/h5-9,14-18,21H,10-11,26H2,1-4H3,(H,27,31)/t14-,15-,16-,17+,18+,21-/m1/s1
	\| InChIKey = OPYGFNJSCUDTBT-PMLPCWDUBA
	\| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}}		\| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}}
	\| StdInChI = 1S/C25H30N4O9S2/c1-24(2)17(29-20(32)16(21(29)39-24)27-19(31)15(26)12-8-6-5-7-9-12)22(33)37-11-38-23(34)18-25(3,4)40(35,36)14-10-13(30)28(14)18/h5-9,14-18,21H,10-11,26H2,1-4H3,(H,27,31)/t14-,15-,16-,17+,18+,21-/m1/s1		\| StdInChI = 1S/C25H30N4O9S2/c1-24(2)17(29-20(32)16(21(29)39-24)27-19(31)15(26)12-8-6-5-7-9-12)22(33)37-11-38-23(34)18-25(3,4)40(35,36)14-10-13(30)28(14)18/h5-9,14-18,21H,10-11,26H2,1-4H3,(H,27,31)/t14-,15-,16-,17+,18+,21-/m1/s1
Line 51:		Line 50:
	\| StdInChIKey = OPYGFNJSCUDTBT-PMLPCWDUSA-N		\| StdInChIKey = OPYGFNJSCUDTBT-PMLPCWDUSA-N
	}}		}}
			<!-- Definition and medical uses -->
	'''Sultamicillin''' is an oral form of the antibiotic combination (] or mutual ]) ]. It contains ] ] and ] and is marketed under a number of trade names, including '''Saltum''' and '''Unasyn'''
			'''Sultamicillin''', sold under the brand name '''Unasyn''' among others, is an oral form of the ] antibiotic combination ]. It is used for the treatment of bacterial infections of the upper and lower ], the kidneys and ], skin and ], among other organs. It contains ]ified ] and ].<ref name="AC">{{cite book\|title=Austria-Codex\| veditors = Haberfeld H \|at=Unasyn-Filmtabletten \|publisher=Österreichischer Apothekerverlag\|location=Vienna\|year=2020\|language=de}}</ref>

			Sultamicillin is better absorbed from the gut than ampicillin/sulbactam, decreasing the chances of ] and ]. The inclusion of sulbactam extends ampicillin's spectrum of action to ] producing strains of bacteria.<ref name="Mutschler">{{cite book\| vauthors = Mutschler E \|title=Arzneimittelwirkungen\|language=German\|location=Stuttgart\|publisher=Wissenschaftliche Verlagsgesellschaft\|year=2013\|edition=10\|pages=745, 748\|isbn=978-3-8047-2898-1}}</ref> Oral sulbactam with the ] form provides a regimen of continuous sulbactam therapy throughout the treatment, resulting in better clinical results.{{fact\|date=February 2021}}
⚫	== References ==
	*Singh GS. ''Beta-lactams in the new millennium. Part-II: cephems, oxacephems, penams and sulbactam.''
	Mini Rev Med Chem. 2004 Jan;4(1):93-109. Review.
	{{DOI\|10.2174/1389557043487547}} PMID 14754446

			<!-- Society and culture -->
	{{PenicillinAntiBiotics}}
			It was patented in 1979 and approved for medical use in 1987.<ref name=Fis2006>{{cite book \| vauthors = Fischer J, Ganellin CR \|title=Analogue-based Drug Discovery \|date=2006 \|publisher=John Wiley & Sons \|isbn=978-3-527-60749-5 \|page=491 \|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA491 \|language=en}}</ref>

			== Medical uses ==
	{{antibiotic-stub}}
			{{medref\|section\|date=September 2014}}
			Medical uses for sultamicillin include:

			* Skin and soft tissue infections<ref name="AC" /> - ]s, ]s, ], ], ], ]s and abscesses caused by '']'' and '']''.
			* ]s<ref name="AC" /> - ] and ] caused by '']'' and ''S. aureus''. Acute and chronic sinusitis caused by ''S. aureus'', '']'', '']'' and ''S. progenies''. {{clarify\|date=February 2021}} ], particularly suppurative otitis media, with or without ] antrum.
			* ]s<ref name="AC" /> - ]s,<ref name="Mutschler_therapy">{{cite book\| vauthors = Mutschler E \|title=Arzneimittelwirkungen\|language=German\|location=Stuttgart\|publisher=Wissenschaftliche Verlagsgesellschaft\|year=2013\|edition=10\|page=790\|isbn=978-3-8047-2898-1}}</ref> ], ] caused by ''S. pneumoniae'', ''H. influenzae'', ''Staphylococcus aureus'' and ''S. progenies''. Acute exacerbations of ].
			* ]s<ref name="AC" /> - ], ] caused by '']'', '']'', '']'' and ''Staphylococcus aureus''.
			* Surgical infections - prophylaxis and treatment of surgical site infections, peri-operative prophylaxis in orthopaedic and cardiovascular surgery.
			* Gynecological infections - Caused by beta-lactamase producing strains of ''E. coli'' and '']'' sp. (including '']'').
			* Infections of the ] - Bacterial ], treatment of '']'' infections as a part of MDT{{clarify\|date=February 2021}} in ulcer management.

			== Contraindications ==
			Sultamicillin is contraindicated in people with penicillin allergy and those with ], as these have an increased risk of developing severe rashes.<ref name="AC" /><ref name=="Friedel" />

			== Adverse effects ==
			The most common side effect, as with many other antibiotics, is ] and soft stool. In Japanese clinical trials, these occurred with a frequency of 3.7% and 1.1%, respectively; however, in studies outside Japan, diarrhoea was much more common at 10% to over 50% in patients taking sultamicillin. Other adverse effects occurring in the range of 1 to 10% of people include nausea, vomiting, stomach ache, headache, rashes, and ]. ] caused by ]s is a rare complication.<ref name="AC" /><ref name=="Friedel" />

			== Interactions ==
			Interactions with other drugs are similar to other penicillins: ] increases the risk for patients to develop rashes. Penicillins slow down the elimination of ], potentially increasing its adverse effects. Conversely, the elimination of sultamicillin's active constituents (ampicillin and sulbactam) is reduced by ] and probably by the ]s (NSAIDs) ], ] and ].<ref name="AC" />

			== Pharmacology ==
			=== Pharmacokinetics ===
			] (blue), ] (red), and the ] link (black).]]
			Sultamicillin is a ] or (mutual ]) of ampicillin and sulbactam. After oral intake, it is absorbed and ] cleaved to ampicillin and sulbactam by ]s in the gut wall. These two substances are then released into the system in a 1:1 ] ratio. Their pharmacokinetic behaviour is similar (and practically independent of food intake): they reach peak concentrations after about one hour; their ] is 26% (ampicillin) and 29% (sulbactam); and their ] are 45–80 minutes and 40–70 minutes, respectively. Both drugs are mainly eliminated via the kidneys: within eight hours after intake, 46 to 80% of the ampicillin and 41 to 66% of the sulbactam are found in the urine.<ref name="Mutschler" /><ref name=="Friedel" />

			=== Mechanism of action ===
			{{see\|Ampicillin#Mechanism of action\|β-Lactamase inhibitor#Mechanism of action}}
			Ampicillin, a ] orally active ] ] antibiotic, exerts antibacterial activity against sensitive organisms by inhibiting biosynthesis of cell wall mucopeptide. Sulbactam, a ], irreversibly inhibits many ]s that occur in resistant bacteria strains.<ref name="AC" />

			== Chemistry ==
			Ampicillin and sulbactam are linked via a ], forming two ] bonds (or more accurately ] bonds). Sultamicillin is used in form of the ] salt.<ref name="Mutschler" /><ref name=="Friedel">{{cite journal \| vauthors = Friedel HA, Campoli-Richards DM, Goa KL \| title = Sultamicillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use \| journal = Drugs \| volume = 37 \| issue = 4 \| pages = 491–522 \| date = April 1989 \| pmid = 2661196 \| doi = 10.2165/00003495-198937040-00005 \| s2cid = 195693347 }}</ref>

		⚫	== References ==
			{{Reflist}}

	]		{{Cell wall disruptive antibiotics}}

			]
	]
			]
	]
			]
			]

Latest revision as of 21:17, 20 October 2024

Chemical compound Pharmaceutical compound

Sultamicillin
Clinical data

Trade names	Unasyn, Unacid PD oral
AHFS/Drugs.com	International Drug Names
Routes of administration	By mouth
ATC code	J01CR04 (WHO)
Pharmacokinetic data
Bioavailability	80%
Excretion	Mainly via kidney
Identifiers
IUPAC name heptane-2-carbonyl]oxymethyl(2R)-6-{amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicycloheptane-2-carboxylate
CAS Number	76497-13-7
PubChem CID	444022
ChemSpider	392048
UNII	65DT0ML581
KEGG	D05972
ChEBI	CHEBI:51770
ChEMBL	ChEMBL506110
CompTox Dashboard (EPA)	DTXSID501010077
Chemical and physical data
Formula	C₂₅H₃₀N₄O₉S₂
Molar mass	594.65 g·mol
3D model (JSmol)	Interactive image
SMILES O=C(OCOC(=O)2N1C(=O)C1S(=O)(=O)C2(C)C)4N5C(=O)(NC(=O)(c3ccccc3)N)5SC4(C)C
InChI InChI=1S/C25H30N4O9S2/c1-24(2)17(29-20(32)16(21(29)39-24)27-19(31)15(26)12-8-6-5-7-9-12)22(33)37-11-38-23(34)18-25(3,4)40(35,36)14-10-13(30)28(14)18/h5-9,14-18,21H,10-11,26H2,1-4H3,(H,27,31)/t14-,15-,16-,17+,18+,21-/m1/s1 Key:OPYGFNJSCUDTBT-PMLPCWDUSA-N
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Sultamicillin, sold under the brand name Unasyn among others, is an oral form of the penicillin antibiotic combination ampicillin/sulbactam. It is used for the treatment of bacterial infections of the upper and lower respiratory tract, the kidneys and urinary tract, skin and soft tissues, among other organs. It contains esterified ampicillin and sulbactam.

Sultamicillin is better absorbed from the gut than ampicillin/sulbactam, decreasing the chances of diarrhea and dysentery. The inclusion of sulbactam extends ampicillin's spectrum of action to beta-lactamase producing strains of bacteria. Oral sulbactam with the intravenous form provides a regimen of continuous sulbactam therapy throughout the treatment, resulting in better clinical results.

It was patented in 1979 and approved for medical use in 1987.

Medical uses

This section needs more reliable medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Sultamicillin" – news · newspapers · books · scholar · JSTOR (September 2014)

Medical uses for sultamicillin include:

Skin and soft tissue infections - furuncles, carbuncles, cellulitis, paronychia, impetigo contagiosa, diabetic foot ulcers and abscesses caused by Staphylococcus aureus and Streptococcus pyogenes.
Upper respiratory tract infections - pharyngitis and tonsillitis caused by S. pyogenes and S. aureus. Acute and chronic sinusitis caused by S. aureus, S. pneumoniae, H. influenzae and S. progenies. Otitis media, particularly suppurative otitis media, with or without mastoiditis antrum.
Lower respiratory tract infections - bacterial pneumonias, bronchitis, bronchiectasis caused by S. pneumoniae, H. influenzae, Staphylococcus aureus and S. progenies. Acute exacerbations of COPD.
Urinary tract infections - pyelonephritis, cystitis caused by Escherichia coli, Proteus mirabilis, Klebsiella and Staphylococcus aureus.
Surgical infections - prophylaxis and treatment of surgical site infections, peri-operative prophylaxis in orthopaedic and cardiovascular surgery.
Gynecological infections - Caused by beta-lactamase producing strains of E. coli and Bacteroides sp. (including B. fragilis).
Infections of the gastrointestinal tract - Bacterial esophagitis, treatment of H. pylori infections as a part of MDT in ulcer management.

Contraindications

Sultamicillin is contraindicated in people with penicillin allergy and those with mononucleosis, as these have an increased risk of developing severe rashes.

Adverse effects

The most common side effect, as with many other antibiotics, is diarrhoea and soft stool. In Japanese clinical trials, these occurred with a frequency of 3.7% and 1.1%, respectively; however, in studies outside Japan, diarrhoea was much more common at 10% to over 50% in patients taking sultamicillin. Other adverse effects occurring in the range of 1 to 10% of people include nausea, vomiting, stomach ache, headache, rashes, and infections with Candida albicans. Haemorrhagic colitis caused by Clostridioides difficile infections is a rare complication.

Interactions

Interactions with other drugs are similar to other penicillins: allopurinol increases the risk for patients to develop rashes. Penicillins slow down the elimination of methotrexate, potentially increasing its adverse effects. Conversely, the elimination of sultamicillin's active constituents (ampicillin and sulbactam) is reduced by probenecid and probably by the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin, indometacin and phenylbutazone.

Pharmacology

Pharmacokinetics

Sultamicillin is a codrug or (mutual prodrug) of ampicillin and sulbactam. After oral intake, it is absorbed and hydrolytically cleaved to ampicillin and sulbactam by enzymes in the gut wall. These two substances are then released into the system in a 1:1 molar ratio. Their pharmacokinetic behaviour is similar (and practically independent of food intake): they reach peak concentrations after about one hour; their plasma protein binding is 26% (ampicillin) and 29% (sulbactam); and their elimination half-lives are 45–80 minutes and 40–70 minutes, respectively. Both drugs are mainly eliminated via the kidneys: within eight hours after intake, 46 to 80% of the ampicillin and 41 to 66% of the sulbactam are found in the urine.

Mechanism of action

Further information: Ampicillin § Mechanism of action, and β-Lactamase inhibitor § Mechanism of action

Ampicillin, a semi-synthetic orally active broad-spectrum penicillin antibiotic, exerts antibacterial activity against sensitive organisms by inhibiting biosynthesis of cell wall mucopeptide. Sulbactam, a beta-lactamase inhibitor, irreversibly inhibits many beta-lactamases that occur in resistant bacteria strains.

Chemistry

Ampicillin and sulbactam are linked via a methylene group, forming two ester bonds (or more accurately acylal bonds). Sultamicillin is used in form of the tosylate salt.

References

^ Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Unasyn-Filmtabletten.
^ Mutschler E (2013). Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 745, 748. ISBN 978-3-8047-2898-1.
Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 491. ISBN 978-3-527-60749-5.
Mutschler E (2013). Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 790. ISBN 978-3-8047-2898-1.
^ Friedel HA, Campoli-Richards DM, Goa KL (April 1989). "Sultamicillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use". Drugs. 37 (4): 491–522. doi:10.2165/00003495-198937040-00005. PMID 2661196. S2CID 195693347.

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: