Ampicillin: Difference between revisions

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{{Short description|Antibiotic}}

Ampicillin (C₁₆H₁₈N₃O₄S ; [[CAS]] No.: 69-53-4) is an [[aminopenicillin]] and, as such, is a broad-spectrum [[antibiotic]] and has been used extensively to treat [[bacterium|bacterial]] [[infection]]s since 1961. It is suspected to cause certain types of [[cancer]] in [[human]]s and animals. Belonging to the group of [[beta-lactam antibiotic]]s, ampicillin is able to penetrate [[gram-negative]] bacteria. It inhibits the third and final stage of bacterial [[cell wall]] synthesis, which ultimately leads to cell [[lysis]].

{{Distinguish|Amoxicillin}}

{{Use dmy dates|date=June 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 443387440

| image = Ampicillin structure.svg

| image_class = skin-invert-image

| caption = [[Skeletal formula]] of ampicillin

| width = 200

| alt =

| image2 = Ampicillin-from-xtal-3D-bs-17.png

| image_class2 = bg-transparent

| caption2 = [[Ball-and-stick model]] of the [[zwitterion]]ic form of ampicillin found in the [[crystal structure]] of the trihydrate<ref>{{ cite journal | url = https://dx.doi.org/10.5517/ccb0nkj | title = CSD Entry: AMPCIH01 | website = [[Cambridge Structural Database]]: Access Structures | year = 2006 | publisher = [[Cambridge Crystallographic Data Centre]] | doi = 10.5517/ccb0nkj | access-date = 28 June 2022 | vauthors = Burley JC, Van De Streek J, Stephens PW }}</ref><ref>{{ cite journal | title = Ampicillin trihydrate from synchrotron powder diffraction data | vauthors = Burley JC, van de Streek J, Stephens PW | journal = [[Acta Crystallographica Section E]] | volume = 62 | pages = o797–o799 | year = 2006 | issue = 2 | doi = 10.1107/S1600536806001371 | bibcode = 2006AcCrE..62O.797B | doi-access = free }}</ref>

| width2 = 180

| alt2 =

<!-- Clinical data -->

Ampicillin is often used in [[molecular biology]] as a test for the uptake of genes (e.g., by [[plasmid]]s) by bacteria (e.g., <i>[[E. coli]]</i>). A gene that is to be inserted into a bacterium is coupled to a gene [[code for|coding for]] an ampicillin resistance. The treated bacteria are then grown on a medium containing ampicillin. Only those bacteria that carry the ampicillin resistance and, therefore, the gene can survive.

| pronounce =

<center> [[image:ampicillin.png]] <br><i>Image in the PD.</i></center>

| tradename = Principen, others<ref name="drugs.comINT">{{cite web | title=Ampicillin - international drug names | website=Drugs.com | date=30 November 2019 | url=https://www.drugs.com/international/ampicillin.html | archive-url=https://web.archive.org/web/20191130211432/https://www.drugs.com/international/ampicillin.html | archive-date=30 November 2019 | url-status=live | access-date=26 January 2020 }}</ref>

| Drugs.com = {{drugs.com|monograph|ampicillin}}

| MedlinePlus = a685002

| DailyMedID = Ampicillin

| pregnancy_AU = A

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Ampicillin Use During Pregnancy | website=Drugs.com | date=2 May 2019 | url=https://www.drugs.com/pregnancy/ampicillin.html | access-date=26 January 2020 | archive-url=https://web.archive.org/web/20190822052019/https://www.drugs.com/pregnancy/ampicillin.html | archive-date=22 August 2019 | url-status=live }}</ref>

| pregnancy_category =

| routes_of_administration = [[By mouth]], [[Intravenous therapy|intravenous]], [[intramuscular]]

| class = [[Aminopenicillin]]s

| ATC_prefix = J01

| ATC_suffix = CA01

| ATC_supplemental = {{ATC|S01|AA19}} {{ATCvet|J51|CA01}} {{ATC|J01|CR50}} {{ATC|J01|CA51}}

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled-->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = POM

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = <ref name=AHFS2015 />

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->

| legal_UN_comment =

| legal_status = <!--For countries not listed above-->

<!-- Pharmacokinetic data -->

| bioavailability = 62% ±17% (parenteral)<br /><!--<ref name=eghianruwa/>-->< 30–55% (oral)<!--<ref name=AHFS2015 />-->

| protein_bound = 15 to 25%<!--<ref name=eghianruwa/>-->

| metabolism = 12 to 50%

| metabolites = [[Penicilloic acid]]<!--<ref name=eghianruwa/>-->

| onset =

| elimination_half-life = Approx. 1 hour<!--<ref name=eghianruwa/>-->

| duration_of_action =

| excretion = 75 to 85% [[kidney]]

<!-- Identifiers -->

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 69-53-4

| CAS_supplemental =

| PubChem = 6249

| IUPHAR_ligand =

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00415

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 6013

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 7C782967RD

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D00204

| KEGG2_Ref = {{keggcite|correct|kegg}}

| KEGG2 = C06574

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 28971

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 174

| NIAID_ChemDB =

| PDB_ligand = AIC

| synonyms = AM/AMP<ref>{{cite web |title=Antibiotic abbreviations list |url=https://microbiologie-clinique.com/antibiotic-family-abbreviation.html |access-date=22 June 2023}}</ref>

<!-- Chemical and physical data -->

| IUPAC_name = (2''S'',5''R'',6''R'')-6-([(2''R'')-2-Amino-2-phenylacetyl]amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

| C = 16

| H = 19

| N = 3

| O = 4

| S = 1

| SMILES = CC1(C(N2C(S1)C(C2=O)NC(=O)C(C3=CC=CC=C3)N)C(=O)O)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C16H19N3O4S/c1-16(2)11(15(22)23)19-13(21)10(14(19)24-16)18-12(20)9(17)8-6-4-3-5-7-8/h3-7,9-11,14H,17H2,1-2H3,(H,18,20)(H,22,23)/t9-,10-,11+,14-/m1/s1

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = AVKUERGKIZMTKX-NJBDSQKTSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

}}

<!-- Definition and uses -->

'''Ampicillin''' is an [[antibiotic]] belonging to the [[aminopenicillin]] class of the [[penicillin]] family. The drug is used to prevent and treat several [[bacterial infection]]s, such as [[respiratory tract infection]]s, [[urinary tract infections]], [[meningitis]], [[salmonellosis]], and [[endocarditis]].<ref name=AHFS2015/> It may also be used to prevent [[group B streptococcal infection]] in newborns.<ref name=AHFS2015/> It is used by mouth, by [[intramuscular injection|injection into a muscle]], or intravenously.<ref name=AHFS2015>{{cite web|title=Ampicillin|url=https://www.drugs.com/monograph/ampicillin.html|publisher=The American Society of Health-System Pharmacists|access-date=1 August 2015|url-status=live|archive-url=https://web.archive.org/web/20150712001731/http://www.drugs.com/monograph/ampicillin.html|archive-date=12 July 2015}}</ref>

<!-- Adverse effects -->

Common side effects include rash, nausea, and diarrhea.<ref name=AHFS2015/> It should not be used in people who are [[allergic to penicillin]].<ref name=AHFS2015/> Serious side effects may include [[Clostridioides difficile infection|''Clostridioides difficile'' colitis]] or [[anaphylaxis]].<ref name=AHFS2015/> While usable in those with [[kidney problem]]s, the dose may need to be decreased.<ref name=AHFS2015/> Its use during [[pregnancy]] and [[breastfeeding]] appears to be generally safe.<ref name=AHFS2015/><ref>{{cite web|title=Ampicillin use while Breastfeeding|url=https://www.drugs.com/breastfeeding/ampicillin.html|access-date=1 August 2015|date=March 2015|url-status=live|archive-url=https://web.archive.org/web/20150923220701/http://www.drugs.com/breastfeeding/ampicillin.html|archive-date=23 September 2015}}</ref>

<!-- Society and culture -->

Ampicillin was discovered in 1958 and came into commercial use in 1961.<ref>{{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|url-status=live|archive-url=https://web.archive.org/web/20161220081307/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA490|archive-date=20 December 2016}}</ref><ref>{{cite book| vauthors = Ravina E |title=The evolution of drug discovery : from traditional medicines to modern drugs|date=2011|publisher=Wiley-VCH|___location=Weinheim|isbn=9783527326693|page=262|edition=1|url=https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA262|url-status=live|archive-url=https://web.archive.org/web/20160809201757/https://books.google.ca/books?id=iDNy0XxGqT8C&pg=PA262|archive-date=9 August 2016}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | ___location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> The World Health Organization classifies ampicillin as critically important for human medicine.<ref>{{cite book | vauthors=((World Health Organization)) | year=2019 | title=Critically important antimicrobials for human medicine | edition=6th revision | author-link = World Health Organization | publisher = World Health Organization | ___location = Geneva | hdl=10665/312266 | isbn=9789241515528 | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2015/>

==Medical uses==

=== Diseases ===

*[[Bacterial meningitis]]; an aminoglycoside can be added to increase efficacy against gram-negative meningitis bacteria<ref name="dailymed">{{cite web | title=Ampicillin- ampicillin sodium injection, powder, for solution | website=DailyMed | date=11 September 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0642ef5e-7eff-4117-a0df-4bd15d7b7d63 | access-date=25 January 2020 | archive-url=https://web.archive.org/web/20180222104913/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0642ef5e-7eff-4117-a0df-4bd15d7b7d63 | archive-date=22 February 2018 | url-status=live }}</ref>

*[[Endocarditis]] by [[Enterococcus|enterococcal]] strains (off-label use); often given with an aminoglycoside<ref name="medscape">{{cite web|url=http://reference.medscape.com/drug/ampi-omnipen-ampicillin-342475|title=ampicillin (Rx)|last=WebMD|work=Medscape|access-date=22 August 2017|archive-url=https://web.archive.org/web/20170815211547/http://reference.medscape.com/drug/ampi-omnipen-ampicillin-342475|archive-date=15 August 2017|url-status=live}}</ref>

*[[Gastrointestinal]] infections caused by contaminated water or food (for example, by ''[[Salmonella]]'')<ref name="dailymed" />

*[[Genito-urinary tract]] infections<ref name="dailymed" />

*[[Healthcare-associated infections]] that are related to infections from using [[catheter|urinary catheters]] and that are unresponsive to other medications<ref name="Harrison">{{cite book|title=Harrison's Principles of Internal Medicine | volume = 1 | vauthors = Finberg R, Fingeroth J | name-list-style = vanc |publisher=McGraw-Hill Medical|year=2012|isbn=978-0-07-174887-2| veditors = Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J |edition = 18th|chapter=Chapter 132: Infections in Transplant Recipients }}</ref>

*[[Otitis media]] (middle ear infection)

*Prophylaxis (i.e. to prevent infection) in those who previously had [[rheumatic heart disease]] or are undergoing dental procedures, vaginal [[Hysterectomy|hysterectomies]], or [[C-sections]].<ref name="AHFS2015" /> It is also used in pregnant woman who are carriers of [[group B streptococci]] to prevent early-onset neonatal infections.<ref name="AHFS2015" />

*[[Respiratory infections]], including [[bronchitis]], [[pharyngitis]]<ref name="dailymed" />

*[[Sinusitis]]

*[[Sepsis]]<ref name=dailymed-vet>{{cite web | title=Ampicillin injection, powder, for suspension | website=DailyMed | date=26 October 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=af6eb56d-698f-43aa-bb3b-a0a69732a7ae | access-date=26 January 2020 | archive-url=https://web.archive.org/web/20180222165046/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=af6eb56d-698f-43aa-bb3b-a0a69732a7ae | archive-date=22 February 2018 | url-status=live }}</ref>

*[[Whooping cough]], to prevent and treat [[secondary infection]]s<ref name="AHFS2015" />

Ampicillin used to also be used to treat [[gonorrhea]], but there are now too many strains resistant to penicillins.<ref name="AHFS2015" />

===Bacteria===

Ampicillin is used to treat infections by many [[gram-positive bacteria|gram-positive]] and [[gram-negative bacteria]]. It was the first "broad spectrum" penicillin with activity against gram-positive bacteria, including ''[[Streptococcus pneumoniae]]'', ''[[Streptococcus pyogenes]]'', some isolates of ''[[Staphylococcus aureus]]'' (but not penicillin-resistant or [[Methicillin-resistant Staphylococcus aureus|methicillin-resistant strains]]), ''[[Trueperella pyogenes|Trueperella]]'', and some ''[[Enterococcus]]''. It is one of the few antibiotics that works against multidrug resistant ''[[Enterococcus faecalis]]'' and ''[[E. faecium]]''.<ref name="magdesian">{{cite book|url=https://books.google.com/books?id=AiV4DgAAQBAJ&pg=PT59|title=Equine Pharmacology, an Issue of Veterinary Clinics of North America: Equine Practice, E-Book| vauthors = Magdesian KG |publisher=Elsevier Health Sciences|year=2017|isbn=978-0-323-52438-4|pages=59}}</ref> Activity against gram-negative bacteria includes ''[[Neisseria meningitidis]]'', some ''[[Haemophilus influenzae]]'', and some of the [[Enterobacteriaceae]] (though most Enterobacteriaceae and ''[[Pseudomonas]]'' are resistant).<ref name="magdesian" /><ref name=papich>{{cite book|url=https://books.google.com/books?id=ip8_CwAAQBAJ&pg=PA43|title=Saunders Handbook of Veterinary Drugs: Small and Large Animal| vauthors = Papich MG |publisher=Elsevier Health Sciences|year=2015|isbn=978-0-323-24485-5|pages=43–47}}</ref> Its spectrum of activity is enhanced by co-administration of [[sulbactam]], a drug that inhibits [[beta lactamase]], an enzyme produced by bacteria to inactivate ampicillin and related antibiotics.<ref name="Hauser">{{cite book|url=https://books.google.com/books?id=17pMk0v3_bYC&pg=PA25|title=Antibiotic Basics for Clinicians: The ABCs of Choosing the Right Antibacterial Agent| vauthors = Hauser AR |publisher=Lippincott Williams & Wilkins|year=2012|isbn=978-1-4511-1221-4|pages=25–28}}</ref><ref>{{cite journal | vauthors = Akova M | title = Sulbactam-containing beta-lactamase inhibitor combinations | journal = Clinical Microbiology and Infection | volume = 14 | pages = 185–188 | date = January 2008 | issue = Suppl 1 | pmid = 18154545 | doi = 10.1111/j.1469-0691.2007.01847.x | doi-access = free }}</ref> It is sometimes used in combination with other antibiotics that have different mechanisms of action, like [[vancomycin]], [[linezolid]], [[daptomycin]], and [[tigecycline]].<ref name="Suleyman2016rev">{{cite journal | vauthors = Suleyman G, Zervos MJ | title = Safety and efficacy of commonly used antimicrobial agents in the treatment of enterococcal infections: a review | journal = Expert Opinion on Drug Safety | volume = 15 | issue = 2 | pages = 153–167 | date = 2016 | pmid = 26629598 | doi = 10.1517/14740338.2016.1127349 | s2cid = 25488987 }}</ref><ref>{{cite book| vauthors = Torok ME, Moran E, Cooke F |title=Oxford Handbook of Infectious Diseases and Microbiology|publisher=Oxford University Press|isbn=9780191503108|page=721|url=https://books.google.com/books?id=G4KuDQAAQBAJ&pg=PA721|language=en|url-status=live|archive-url=https://web.archive.org/web/20170323064830/https://books.google.com/books?id=G4KuDQAAQBAJ&pg=PA721|archive-date=23 March 2017|date=December 2016}}</ref>

===Available forms===

Ampicillin can be administered by [[oral administration|mouth]], an [[intramuscular injection]] (shot) or by [[intravenous infusion]].<ref name=AHFS2015/> The oral form, available as [[Capsule (pharmacy)|capsules]] or oral suspensions, is not given as an initial treatment for severe infections, but rather as a follow-up to an IM or IV injection.<ref name="AHFS2015" /> For IV and IM injections, ampicillin is kept as a powder that must be reconstituted.<ref name="wanamaker">{{cite book|url=https://books.google.com/books?id=7s3sAwAAQBAJ&pg=PA243|title=Applied Pharmacology for Veterinary Technicians - E-Book| vauthors = Wanamaker BP, Massey K |publisher=Elsevier Health Sciences|year=2014|isbn=978-0-323-29170-5|pages=244}}</ref>

IV injections must be given slowly, as rapid IV injections can lead to convulsive [[seizures]].<ref name="AHFS2015" /><ref>{{cite web | last=WebMD | title=Ampicillin Intravenous: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing | work=WebMD | access-date=23 February 2018 | url=https://www.webmd.com/drugs/2/drug-18412/ampicillin-intravenous/details | archive-url=https://web.archive.org/web/20180223171300/https://www.webmd.com/drugs/2/drug-18412/ampicillin-intravenous/details | archive-date=23 February 2018 | url-status=live }}</ref>

=== Specific populations===

Ampicillin is one of the most used drugs in pregnancy,<ref name="weiner">{{cite book|url=https://archive.org/details/completeguidetom0000wein_t9k5|url-access=registration|quote=ampicillin pregnancy.|title=The Complete Guide to Medications During Pregnancy and Breastfeeding: Everything You Need to Know to Make the Best Choices for You and Your Baby| vauthors = Weiner CP, Rope K |publisher=St. Martin's Press|year=2013|isbn=978-1-250-03720-6|pages=[https://archive.org/details/completeguidetom0000wein_t9k5/page/47 47]–49}}</ref> and has been found to be generally harmless both by the [[Food and Drug Administration]] in the U.S. (which classified it as [[Pregnancy category#United States|category B]]) and the [[Therapeutic Goods Administration]] in Australia (which classified it as [[Pregnancy category#Australia|category A]]).<ref name="AHFS2015" /><ref>{{cite web|url=https://www.tga.gov.au/prescribing-medicines-pregnancy-database|title=Prescribing medicines in pregnancy database | author = Australian Government Department of Health Therapeutic Goods Administration|date=25 October 2017|work=Therapeutic Goods Administration (TGA)|publisher=Australian Government Department of Health|access-date=23 February 2018|archive-url=https://web.archive.org/web/20161220210434/https://www.tga.gov.au/prescribing-medicines-pregnancy-database|archive-date=20 December 2016|url-status=live}} {{Small|Note: scroll down to "Search by name" and type "ampicillin" into the search bar. Requires JavaScript to be enabled.}} <!-- If you can find a way to link directly to the "ampicillin" entry, please replace the URL (and title, if needed) and remove the appended note. --></ref> It is the drug of choice for treating ''[[Listeria monocytogenes]]'' in pregnant women, either alone or combined with an aminoglycoside.<ref name="AHFS2015" /> Pregnancy increases the [[Clearance (pharmacology)|clearance]] of ampicillin by up to 50%, and a higher dose is thus needed to reach therapeutic levels.<ref name="weiner" /><ref name="rello">{{cite book|url=https://books.google.com/books?id=wysQmU5bYAAC&pg=PA172|title=Infectious Diseases in Critical Care| vauthors = Rello J, Kollef MH, Díaz E, Rodríguez A |publisher=Springer Science & Business Media|year=2010|isbn=978-3-540-34406-3|pages=172}}</ref>

Ampicillin crosses the [[placenta]] and remains in the [[amniotic fluid]] at 50–100% of the concentration in maternal [[Plasma (blood)|plasma]]; this can lead to high concentrations of ampicillin in the newborn.<ref name="rello" />

While lactating mothers secrete some ampicillin into their breast milk, the amount is minimal.<ref name="AHFS2015" /><ref name="weiner" />

In newborns, ampicillin has a longer half-life and lower plasma protein binding.<ref name=eghianruwa>{{cite book|url=https://books.google.com/books?id=CtfIAgAAQBAJ&pg=PA26|title=Essential Drug Data for Rational Therapy in Veterinary Practice| vauthors = Eghianruwa K |publisher=AuthorHouse|year=2014|isbn=978-1-4918-0010-2|pages=26}}</ref> The clearance by the kidneys is lower, as kidney function has not fully developed.<ref name="AHFS2015" />

== Contraindications ==

Ampicillin is contraindicated in those with a [[Penicillin allergy|hypersensitivity to penicillins]], as they can cause fatal [[anaphylactic]] reactions. Hypersensitivity reactions can include frequent skin [[rash]]es and [[hives]], [[exfoliative dermatitis]], [[erythema multiforme]], and a temporary decrease in both [[Red blood cell|red]] and [[white blood cells]].<ref name="dailymed" />

Ampicillin is not recommended in people with concurrent mononucleosis, as over 40% of patients develop a skin rash.<ref name="dailymed" />

==Side effects==

Ampicillin is comparatively less toxic than other antibiotics, and side effects are more likely in those who are sensitive to penicillins and those with a history of [[asthma]] or [[allergies]].<ref name="dailymed" /> In very rare cases, it causes severe side effects such as [[angioedema]], anaphylaxis, and ''[[C. difficile]]'' infection (that can range from mild [[diarrhea]] to serious [[pseudomembranous colitis]]).<ref name="dailymed" /> Some develop [[Black hairy tongue|black "furry" tongue]]. Serious adverse effects also include [[seizure]]s and [[serum sickness]]. The most common side effects, experienced by about 10% of users are diarrhea and rash. Less common side effects can be [[nausea]], [[vomiting]], [[itching]], and blood [[dyscrasia#Modern use|dyscrasia]]s. The gastrointestinal effects, such as hairy tongue, nausea, vomiting, diarrhea, and colitis, are more common with the oral form of penicillin.<ref name="dailymed" /> Other conditions may develop up several weeks after treatment.<ref name=AHFS2015/>

=== Overdose ===

Ampicillin overdose can cause behavioral changes, [[confusion]], blackouts, and convulsions, as well as neuromuscular hypersensitivity, [[electrolyte imbalance]], and [[kidney failure]].<ref name="dailymed" />

== Interactions ==

Ampicillin reacts with [[probenecid]] and [[methotrexate]] to decrease [[renal excretion]]. Large doses of ampicillin can increase the risk of bleeding with concurrent use of [[warfarin]] and other oral anticoagulants, possibly by inhibiting platelet aggregation.<ref>{{cite web|url=https://www.drugs.com/drug-interactions/ampicillin-with-anisindione-196-0-210-0.html?professional=1|title=Drug interactions between ampicillin and anisindione|work=Drugs.com|access-date=22 February 2018|archive-url=https://web.archive.org/web/20180223171235/https://www.drugs.com/drug-interactions/ampicillin-with-anisindione-196-0-210-0.html?professional=1|archive-date=23 February 2018|url-status=live}}</ref> Ampicillin has been said to make [[oral contraceptives]] less effective,<ref name=AHFS2015/> but this has been disputed.<ref>{{cite book|url=https://books.google.com/books?id=94x8C5pbhqoC&pg=PA213|title=Drug Interactions in Infectious Diseases| vauthors = Piscitelli SC, Rodvold KA, Pai MP |publisher=Springer Science & Business Media|year=2011|isbn=978-1-61779-213-7|pages=213–214}}</ref> It can be made less effective by other antibiotic, such as [[chloramphenicol]], [[erythromycin]], [[cephalosporins]], and [[tetracyclines]].<ref name="wanamaker" /> For example, tetracyclines inhibit protein synthesis in bacteria, reducing the target against which ampicillin acts.<ref>{{cite web|url=https://www.drugs.com/drug-interactions/ampicillin-with-bismuth-subcitrate-potassium-metronidazole-tetracycline-196-0-388-0.html?professional=1|title=Drug interactions between ampicillin and bismuth subcitrate potassium / metronidazole / tetracycline|work=Drugs.com|access-date=22 February 2018|archive-url=https://web.archive.org/web/20180223171253/https://www.drugs.com/drug-interactions/ampicillin-with-bismuth-subcitrate-potassium-metronidazole-tetracycline-196-0-388-0.html?professional=1|archive-date=23 February 2018|url-status=live}}</ref> If given at the same time as aminoglycosides, it can bind to it and inactivate it. When administered separately, aminoglycosides and ampicillin can potentiate each other instead.<ref name="AHFS2015" /><ref>{{cite web|url=https://www.drugs.com/drug-interactions/amikacin-with-ampicillin-153-0-196-0.html?professional=1|title=Drug interactions between amikacin and ampicillin|work=Drugs.com|access-date=22 February 2018|archive-url=https://web.archive.org/web/20180223171312/https://www.drugs.com/drug-interactions/amikacin-with-ampicillin-153-0-196-0.html?professional=1|archive-date=23 February 2018|url-status=live}}</ref>

Ampicillin causes skin rashes more often when given with [[allopurinol]].<ref name="dailymed" />

Both the live cholera vaccine and live typhoid vaccine can be made ineffective if given with ampicillin. Ampicillin is normally used to treat cholera and typhoid fever, lowering the immunological response that the body has to mount.<ref>{{cite web|url=https://www.drugs.com/drug-interactions/ampicillin-with-cholera-vaccine-live-196-0-3772-0.html?professional=1|title=Drug interactions between ampicillin and cholera vaccine, live|work=Drugs.com|access-date=22 February 2018|archive-url=https://web.archive.org/web/20180223171311/https://www.drugs.com/drug-interactions/ampicillin-with-cholera-vaccine-live-196-0-3772-0.html?professional=1|archive-date=23 February 2018|url-status=live}}</ref><ref>{{cite web|url=https://www.drugs.com/drug-interactions/ampicillin-with-typhoid-vaccine-live-196-0-2271-0.html?professional=1|title=Drug interactions between ampicillin and typhoid vaccine, live|work=Drugs.com|access-date=22 February 2018|archive-url=https://web.archive.org/web/20180223110946/https://www.drugs.com/drug-interactions/ampicillin-with-typhoid-vaccine-live-196-0-2271-0.html?professional=1|archive-date=23 February 2018|url-status=live}}</ref><ref>{{cite web|url=https://emedicine.medscape.com/article/962643-medication|title=Cholera Medication| vauthors = Handa S |date=22 June 2017|work=Medscape|access-date=23 February 2018|archive-url=https://web.archive.org/web/20180223110950/https://emedicine.medscape.com/article/962643-medication|archive-date=23 February 2018|url-status=live}}</ref>

==Pharmacology==

===Mechanism of action===

[[File:Ampicillin with amine highlighted.svg|class=skin-invert-image|thumb|The amino group (highlighted in magenta) is present on ampicillin but not [[penicillin G]].]]

Ampicillin is in the [[penicillin]] group of [[β-Lactam antibiotic|beta-lactam antibiotic]]s and is part of the [[aminopenicillin]] family. It is roughly equivalent to [[amoxicillin]] in terms of activity.<ref name=AHFS2015/> Ampicillin is able to penetrate gram-positive and some gram-negative bacteria. It differs from [[Benzylpenicillin|penicillin G]], or benzylpenicillin, only by the presence of an [[amino]] group. This amino group, present on both ampicillin and amoxicillin, helps these antibiotics pass through the pores of the outer membrane of gram-negative bacteria, such as ''[[Escherichia coli]]'', ''[[Proteus mirabilis]]'', ''[[Salmonella enterica]]'', and ''[[Shigella]]''.<ref name="Hauser" /><ref>{{cite journal | vauthors = Delcour AH | title = Outer membrane permeability and antibiotic resistance | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1794 | issue = 5 | pages = 808–816 | date = May 2009 | pmid = 19100346 | pmc = 2696358 | doi = 10.1016/j.bbapap.2008.11.005 }}</ref>

Ampicillin acts as an irreversible inhibitor of the enzyme [[DD-Transpeptidase|transpeptidase]], which is needed by bacteria to make the cell wall.<ref name="AHFS2015" /> It inhibits the third and final stage of bacterial cell wall synthesis in [[binary fission]], which ultimately leads to cell [[lysis]]; therefore, ampicillin is usually [[bacteriolytic]].<ref name="AHFS2015" /><ref name="Goodman">{{cite book | veditors = Brunton L, Chabner B, Knollman B | vauthors = Petri WA | title=Goodman and Gilman's the Pharmacological Basis of Therapeutics | edition = Twelfth | chapter=Penicillins, Cephalosporins, and Other Beta-Lactam Antibiotics | ___location=New York | year=2011 | pages=1477–1504 | publisher=McGraw Hill Professional | isbn=978-0-07-176939-6 }}</ref>

===Pharmacokinetics===

Ampicillin is well-absorbed from the [[GI tract]] (though food reduces its absorption), and reaches peak concentrations in one to two hours. The [[bioavailability]] is around 62% for parenteral routes. Unlike other penicillins, which usually bind 60–90% to [[plasma proteins]], ampicillin binds to only 15–20%.<ref name="AHFS2015" /><ref name="eghianruwa" />

Ampicillin is distributed through most tissues, though it is concentrated in the liver and kidneys. It can also be found in the [[cerebrospinal fluid]] when the meninges become inflamed (such as, for example, meningitis).<ref name="eghianruwa" /> Some ampicillin is metabolized by hydrolyzing the beta-lactam ring to [[penicilloic acid]],<ref name="AHFS2015" /> though most of it is excreted unchanged.<ref name="dailymed" /> In the kidneys, it is filtered out mostly by [[tubular secretion]]; some also undergoes [[glomerular filtration]], and the rest is excreted in the [[feces]] and [[bile]].

[[Hetacillin]] and [[pivampicillin]] are ampicillin [[esters]] that have been developed to increase bioavailability.<ref name=giguere>{{cite book|url=https://books.google.com/books?id=ybA2AAAAQBAJ&pg=RA2-PT166|title=Antimicrobial Therapy in Veterinary Medicine| vauthors = Giguère S, Prescott JF, Dowling PM |publisher=John Wiley & Sons|year=2013|isbn=978-1-118-67507-6|pages=167–170}}</ref>

==History==

Ampicillin has been used extensively to treat bacterial infections since 1961.<ref name = acred>{{cite journal | vauthors = Acred P, Brown DM, Turner DH, Wilson MJ | title = Pharmacology and chemotherapy of ampicillin--a new broad-spectrum penicillin | journal = British Journal of Pharmacology and Chemotherapy | volume = 18 | issue = 2 | pages = 356–369 | date = April 1962 | pmid = 13859205 | pmc = 1482127 | doi = 10.1111/j.1476-5381.1962.tb01416.x }}</ref> Until the introduction of ampicillin by the British company [[Beecham (pharmaceutical company)|Beecham]], penicillin therapies had only been effective against gram-positive organisms such as [[Staphylococcus|staphylococci]] and [[Streptococcus|streptococci]].<ref name=Goodman/> Ampicillin (originally branded as "Penbritin") also demonstrated activity against gram-negative organisms such as ''H. influenzae'', [[coliform]]s, and ''[[Proteus (bacterium)|Proteus]]'' spp.<ref name = acred/>

== Society and culture ==

=== Economics ===

Ampicillin is relatively inexpensive.<ref>{{cite book | vauthors = Hanno PM, Guzzo TJ, Malkowicz SB, Wein AJ |title=Penn Clinical Manual of Urology E-Book |date=2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-24466-4 |page=122 |url=https://books.google.com/books?id=OQTbAgAAQBAJ&pg=PA122 |language=en}}</ref> In the United States, it is available as a [[generic medication]].<ref name=AHFS2015/>

==Veterinary use==

In veterinary medicine, ampicillin is used in cats, dogs, and farm animals to treat:<ref name="dailymed-vet" /><!-- If ref is not specified for bullet point, info is from this ref -->

* [[Anal gland]] infections

* Cutaneous infections, such as [[abscesses]], [[cellulitis]], and pustular [[dermatitis]]

* ''[[E. coli]]'' and ''Salmonella'' infections in [[cattle]], [[sheep]], and [[goats]] (oral form). Ampicillin use for this purpose had declined as bacterial resistance has increased.<ref name="giguere" />

* [[Mastitis]] in [[Pig|sows]]<ref>{{cite web|url=http://www.merckvetmanual.com/reproductive-system/mastitis-in-large-animals/mastitis-in-sows|title=Mastitis in Sows| vauthors = Erskine R |work=Merck Veterinary Manual|access-date=22 August 2017|archive-url=https://web.archive.org/web/20170704115129/http://www.merckvetmanual.com/reproductive-system/mastitis-in-large-animals/mastitis-in-sows|archive-date=4 July 2017|url-status=live}}</ref>

* Mixed aerobic–anaerobic infections, such as from cat bites<ref name="giguere" />

* Multidrug-resistant ''Enterococcus faecalis'' and ''E. faecium''<ref name="magdesian" />

* Prophylactic use in [[poultry]] against ''Salmonella'' and sepsis from ''E. coli'' or ''Staphylococcus aureus''<ref name="giguere" />

* [[Respiratory tract infections]], including [[tonsilitis]], [[bovine respiratory disease]], [[shipping fever]], [[bronchopneumonia]], and calf and bovine pneumonia

* Urinary tract infections in dogs

Horses are generally not treated with oral ampicillin, as they have low bioavailability of beta-lactams.<ref name="magdesian" />

The half-life in animals is around that same of that in humans (just over an hour). Oral absorption is less than 50% in cats and dogs, and less than 4% in horses.<ref name="papich" />

== References ==

{{Reflist}}

== External links ==

* {{cite patent |country=GB |number=902703 |status=patent |title=Penicillins |pubdate=1962-08-09 |fdate=1960-08-25 |pridate=1960-08-25 |inventor=Frank Peter Doyle, John Herbert Charles Nayler, Harry Smith |assign1=Beecham Research Laboratories Ltd |url=https://worldwide.espacenet.com/publicationDetails/biblio?CC=GB&NR=902703&KC=&FT=E&locale=en_EP}}

* {{cite patent |country=US |number=2985648 |status=patent |title=Alpha-aminobenzylpenicillins |pubdate=1961-05-23 |gdate=1961-05-23 |fdate=1961-02-02 |pridate=1958-10-06 |inventor=Frank Peter Doyle, John Herbert Charles Nayler, Harry Smith |url=https://worldwide.espacenet.com/publicationDetails/biblio?CC=US&NR=2985648&KC=&FT=E&locale=en_EP}}

* {{cite patent |country=US |number=3157640 |status=patent |title=D-(-)-alpha-aminobenzylpenicillin trihydrate |pubdate=1964-11-17 |gdate=1964-11-17 |fdate=1963-03-21 |pridate=1963-03-21 |invent1=David A Johnson |invent2=Glenn A Hardcastle Jr |assign1=Bristol Myers Co |url=https://worldwide.espacenet.com/publicationDetails/biblio?CC=US&NR=3157640&KC=&FT=E&locale=en_EP}}

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