Amoxicillin/clavulanic acid

Overview

Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand names Augmentin, and Ranclav among others, is an antibiotic medication used for the treatment of a number of bacterial infections. It is a combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. It is specifically used for otitis media, streptococcal pharyngitis, pneumonia, cellulitis, urinary tract infections, and animal bites. It can be administered orally or intravenously.[1][2] WP

Common side effects include diarrhea, vomiting, and allergic reactions. It also increases the risk of yeast infections, headaches, and blood clotting problems. It is not recommended in people with a history of a penicillin allergy. It is relatively safe for use during pregnancy.[1][2][3] WP

Amoxicillin/clavulanic acid was approved for medical use in the United States in 1984. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies amoxicillin/clavulanic-acid as critically important for human medicine. It is available as a generic medication. In 2023, it was the 66th most commonly prescribed medication in the United States, with more than 9 million prescriptions.[1][4–8] WP

Uses, dosage and effects

Overview

As of 2010, when susceptible bacteria are implicated, moxicillin/clavulanic acid has been widely used to prevent infections, e.g., in[9] WP

• surgical chemoprophylaxis;[9] WP

or to treat ongoing infections, including: WP

• urinary tract infections;[9] WP
• respiratory tract infections;[9] WP
• skin and soft tissue infections (SSTIs);[9] WP
• mixed Gram-negative, Gram-positive, and anaerobic infections: WP
• of the foot, associated with diabetes;[9] WP
• in lung abscesses;[9] WP
• in empyema;[9] WP
• in peritonitis;[9] WP
• in post-operative obstetric/gynocologic cases;[9] WP
• in "intra-abdominal collections";[9] WP
• infections caused by animal and human bites (including human "fight bite" wounds),[9][10] WP⚠ Wikipedia itself has flagged this text: failed verification.
• in cases of chemotherapy-related fever and neutropenia (at low risk);[9] WP
• Burkholderia pseudomallei melioidosis (first-line pediatric/pregnancy, second-line adult);[9] WP
• as an anti-mycobacterial component option in multi-resistant tuberculosis;[9] WP
• as a second-line for nocardiosis assigned to Nocardia brasiliensis, and as possible option for other cases;[9] WP
• after ceftriaxone/cefixime, as an alternative, as a co-therapy against penicillin-sensitive or beta-lactamase positive gonorrhoea;[9] WP
• in chancroid due to multi-resistant Haemophilus ducreyi;[9] WP
• after metronidazole and clindamycin, as an option against bacterial vaginosis;[9] WP
• dental infections associated with oral bacteria, WP⚠ Wikipedia itself has flagged this text: citation needed.
• Sinus infections; WP⚠ Wikipedia itself has flagged this text: citation needed.
• Tonsillitis; WP⚠ Wikipedia itself has flagged this text: citation needed.
• cat scratches; and WP⚠ Wikipedia itself has flagged this text: citation needed.
• Diverticulitis. WP⚠ Wikipedia itself has flagged this text: citation needed.

Urinary tract infections

Amoxicillin/clavulanic acid is a second-line therapy in the treatment of uncomplicated urinary tract infections (UTIs). It is active against UTIs caused by Staphylococcus saprophyticus, Enterococci (e.g., Enterococcus faecalis), Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. It is a definitive treatment against susceptible extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria. The drug is not effective against Pseudomonas aeruginosa, Morganella morganii, or Providencia stuartii, nor against AmpC β-lactamase- and ESBL-producing Gram-negative bacteria or carbapenem-resistant Enterobacteriaceae (CRE). It is not recommended in the empiric treatment of acute pyelonephritis or hospital-acquired UTIs.[11][12] WP

As determined by a 2014 literature review of antibiotics for UTIs, respective early clinical cure and early bacterial cure rates were 91% and 91% for trimethoprim/sulfamethoxazole, 92% and 87% for nitrofurantoin, 91% and 83% for fosfomycin, 90% and 91% for fluoroquinolones (ciprofloxacin and norfloxacin), and 86% and 81% for β-lactams (amoxicillin/clavulanic acid and cefpodoxime). In a large high-quality randomized controlled trial of amoxicillin/clavulanic acid for UTI in 370 women, early and late clinical cure rates were 79% and 58%, respectively. Amoxicillin/clavulanic acid reaches a relatively low urine concentration, which might be involved in its lower effectiveness than other antibiotics.[11][12] WP

Amoxicillin/clavulanic acid is less effective in the treatment of UTI than first-line therapies used to treat UTIs. A 2012 network meta-analysis of antibiotics for uncomplicated UTIs found that it was less effective than all other assessed agents, including trimethoprim/sulfamethoxazole, nitrofurantoin, fosfomycin, fluoroquinolones (ciprofloxacin, norfloxacin, and gatifloxacin), and pivmecillinam. However, selection of an empirical antibiotic should be based on local or regional susceptibility data. Additionally, selection of the most appropriate and narrowest effective antibiotic is recommended to help limit increased antibiotic resistance to broad-spectrum antibiotics.[11][12][13] WP

Combining amoxicillin/clavulanic acid with aztreonam can further enhance its activity against certain resistant UTI-causing bacteria.[12] WP

Tuberculosis

It is also used for tuberculosis that is resistant to other treatments. The World Health Organization recommends giving amoxicillin-clavulanate along with meropenem as one of the therapeutic options in drug-resistant tuberculosis. However, across the spectrum of dosage of amoxicillin-clavulanate combination, the dose of clavulanate is constant at 125 mg, whereas the dose of amoxicillin varies at 250 mg, 500 mg and 875 mg. Thus the use of low-dose amoxicillin-clavulanate in combination with meropenem may be used in part of a treatment regimen for drug-resistant TB and this has been demonstrated in a clinical setting also. Its efficacy is attributed not to the amoxicillin component, but to the protective action of clavulanic acid over meropenem against beta-lactamase produced by the mycobacteria. Therefore, the minimum dosage of amoxicillin (250 mg) is recommended.[1][14][15] WP

Veterinary use

As stated by the FDA in its update tables to its "Approved Animal Drug Products" (Green Book), amoxicillin/clavulanic acid was, as of April 2024, being used in veterinary practice for a variety of conditions, including, for instance, in dogs, for [s]kin and soft tissue infections such as wounds, abscesses, cellulitis, superficial/juvenile and deep pyoderma due to susceptible strains of the following organisms: β-lactamase-producing Staphylococcus aureus, non-β-lactamase-producing Staphylococcus aureus, Staphylococcus spp., Streptococcus spp., and E. coli; and periodontal infections due to susceptible strains of both aerobic and anaerobic bacteria [emphasis added], and in cats, for [s]kin and soft tissue infections such as wounds, abscesses, and cellulitis/dermatitis due to susceptible strains of the following organisms: β-lactamase-producing Staphylococcus aureus, non-β-lactamase-producing Staphylococcus aureus, Staphylococcus spp., Streptococcus spp., E. coli, and Pasteurella spp; urinary tract infections (cystitis) due to susceptible strains of E. coli [emphasis added].[16] WP

Risks and side effects

Adverse effects

Possible side effects include diarrhea, vomiting, nausea, thrush, and skin rash. These do not usually require medical attention. As with all antimicrobial agents, antibiotic-associated diarrhea due to Clostridioides difficile infection—sometimes leading to pseudomembranous colitis—may occur during or after treatment with amoxicillin/clavulanic acid.[9] WP

Rarely, cholestatic jaundice (also referred to as cholestatic hepatitis, a form of liver toxicity) has been associated with amoxicillin/clavulanic acid. The reaction may occur up to several weeks after treatment has stopped and usually takes weeks to resolve. It is more frequent in men, older people, and those who have taken long courses of treatment; the estimated overall incidence is one in 100,000 exposures. In the United Kingdom, co-amoxiclav carries a warning from the Committee on Safety of Medicines to this effect.[9][10] WP

As all aminopenicillins, amoxicillin has been associated with Stevens–Johnson syndrome / toxic epidermal necrolysis, although these reactions are very rare.[9][17] WP

Pharmacology

Pharmacology

Amoxicillin is an antibiotic of the penicillin family, while clavulanic acid is a non-antibiotic β-lactamase inhibitor that prevents inactivation of penicillins by certain resistant bacteria.[18] WP

History

History

Amoxicillin/clavulanic acid is the International Nonproprietary Name (INN) for this two-drug combination; "co-amoxiclav" is the British Approved Name (BAN). British scientists working at Beecham (now part of GlaxoSmithKline) filed for U.K. patent protection for amoxicillin/clavulanic acid in 1977, which was granted in 1982. It was originally sold under the brand name Augmentin.[10][19][20] WP⚠ Wikipedia itself has flagged this text: citation needed.⚠ Wikipedia itself has flagged this text: failed verification.

Chemistry

Formula

C24H28N4O10S PC

Formula (Wikipedia infobox)

C24H27KN4O10S WP⚠ Wikipedia and PubChem give different formulas. Both are shown as each source has it.

CAS number

79198-29-1 PC

Molar mass (g/mol)

564.6 PC

IUPAC name (computed by PubChem)

(2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2R,3Z,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid PC

SMILES

CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)[C@@H](C3=CC=C(C=C3)O)N)C(=O)O)C.C1[C@@H]2N(C1=O)[C@H](/C(=C/CO)/O2)C(=O)O PC

InChIKey

QJVHTELASVOWBE-AGNWQMPPSA-N PC

PubChem CID

6435924

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Amoxicillin and Clavulanate Potassium
2. Other WHO Model Formulary 2008. 2009
3. Journal / agency Gillies M, Ranakusuma A, Hoffmann T, Thorning S, McGuire T, Glasziou P, Del Mar C. Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication. CMAJ. January 2015. doi:10.1503/cmaj.140848 · PMID 25404399 · PMC4284189
4. Other World Health Organization model list of essential medicines: 21st list 2019. 2019
5. Other World Health Organization model list of essential medicines: 22nd list (2021). 2021
6. Other Critically important antimicrobials for human medicine. 2019
7. Other Top 300 of 2023
8. Other Amoxicillin; Clavulanate Drug Usage Statistics, United States, 2014 - 2023
9. Other Gordon D. Kucers' the Use of Antibiotics: a Clinical Review of Antibacterial, Antifungal, Antiparasitic and Antiviral Drugs. 2010
10. Other Pharm. Press Joint Formulary Committee (JFC). British National Formulary (BNF). 2009
11. Journal / agency Grigoryan L, Trautner BW, Gupta K. Diagnosis and management of urinary tract infections in the outpatient setting: a review. JAMA. 2014. doi:10.1001/jama.2014.12842 · PMID 25335150
12. Journal / agency Bader MS, Loeb M, Leto D, Brooks AA. Treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents. Postgrad Med. April 2020. doi:10.1080/00325481.2019.1680052 · PMID 31608743
13. Journal / agency Knottnerus BJ, Grigoryan L, Geerlings SE, Moll van Charante EP, Verheij TJ, Kessels AG, ter Riet G. Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: network meta-analysis of randomized trials. Fam Pract. December 2012. doi:10.1093/fampra/cms029 · PMID 22516128
14. Other WHO treatment guidelines for drug-resistant tuberculosis, 2016 update. 2016
15. Journal / agency Mishra G, Caminero J. First Successful Use of Low Dose Amoxicillin-Clavulanic Acid in Management of Drug Resistant Tuberculosis. Journal of Clinical and Diagnostic Research. 2018. doi:10.7860/JCDR/2018/37279.12145
16. Journal / agency FDA Staff. Recent Animal Drug Approvals. 5 April 2024
17. Journal / agency Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet Journal of Rare Diseases. December 2010. doi:10.1186/1750-1172-5-39 · PMID 21162721 · PMC3018455
18. Journal / agency Sutherland R. Beta-lactamase inhibitors and reversal of antibiotic resistance. Trends in Pharmacological Sciences. June 1991. doi:10.1016/0165-6147(91)90557-9 · PMID 2048218
19. Other Pharmaceutical compositions
20. Journal / agency Bryan J. Still going strong at 30: co-amoxiclav. The Pharmaceutical Journal. 23 June 2011

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.