Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand name Augmentin, among others, is an

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

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 Otitis media is a group of Inflammation, inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pullin ...

, streptococcal pharyngitis,

pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...

, urinary tract infections, and animal bites. It can be administered orally or intravenously. Common

side effects In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually used ...

include

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

, vomiting, and

allergic reactions Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...

. It also increases the risk of

yeast infections Candidiasis is a fungal infection due to any species of the genus '' Candida'' (a yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the ...

, 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. 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 2022, it was the 96th most commonly prescribed medication in the United States, with more than 6million prescriptions.

Medical uses

Amoxicillin/clavulanic acid is widely used to treat or prevent many infections caused by susceptible bacteria, such as: *

Urinary tract infection A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyel ...

s * Respiratory tract infections *

Skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

and soft tissue infections * Sinus infections *

Tonsillitis Tonsillitis is inflammation of the tonsils in the upper part of the throat. It can be acute or chronic. Acute tonsillitis typically has a rapid onset. Symptoms may include sore throat, fever, enlargement of the tonsils, trouble swallowing, and en ...

* Cat scratches * Infections caused by the bacterial flora of the mouth, such as: ** Dental infections ** Infected animal bites ** Infected human bites (including uncomplicated "clenched-fist" or "reverse-bite" injuries) * Treatment-resistant

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

(see below)

Urinary tract infections

Amoxicillin/clavulanic acid is a second-line therapy in the treatment of uncomplicated

urinary tract infection A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyel ...

s (UTIs). It is active against UTIs caused by '' Staphylococcus saprophyticus'', '' Enterococci'' (e.g., '' Enterococcus faecalis''), ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'', '' Klebsiella pneumoniae'', and ''

Proteus mirabilis ''Proteus mirabilis'' is a Gram-negative, facultatively Anaerobic organism, anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus (bacterium), Proteus'' infections in human ...

''. It is a definitive treatment against susceptible extended-spectrum β-lactamase (ESBL)-producing

Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

. The drug is not effective against ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

'', '' 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 Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications ...

or hospital-acquired UTIs. As determined by a 2014

literature review A literature review is an overview of previously published works on a particular topic. The term can refer to a full scholarly paper or a section of a scholarly work such as books or articles. Either way, a literature review provides the rese ...

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 Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin ...

and

norfloxacin Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteri ...

), and 86% and 81% for β-lactams (amoxicillin/clavulanic acid and cefpodoxime). In a large high-quality

randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical ...

of amoxicillin/clavulanic acid for UTI in 370women, early and late clinical cure rates were 79% and 58%, respectively. Amoxicillin/clavulanic acid reaches a relatively low

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

concentration, which might be involved in its lower effectiveness than other antibiotics. 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 Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...

broad-spectrum antibiotic A broad-antimicrobial spectrum, spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are ...

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

Tuberculosis

It is also used for

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 Beta-lactamases (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapene ...

produced by the

mycobacteria ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') a ...

. Therefore, the minimum dosage of amoxicillin (250 mg) is recommended.

Adverse effects

Possible side effects include

, vomiting,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

, thrush, and skin

rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracke ...

. 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. 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. As all aminopenicillins, amoxicillin has been associated with

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and #Classification, Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN) overlap, they are considered febrile mucocutaneous d ...

toxic epidermal necrolysis Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and f ...

, although these reactions are very rare.

Pharmacology

Amoxicillin is an

while clavulanic acid is a non-antibiotic β-lactamase inhibitor which prevents

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

of amoxicillin by certain

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

. In addition to its β-lactamase inhibition, clavulanic acid shows

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

actions and effects and has been studied in the potential treatment of various psychiatric and

neurological disorder Neurological disorders represent a complex array of medical conditions that fundamentally disrupt the functioning of the nervous system. These disorders affect the brain, spinal cord, and nerve networks, presenting unique diagnosis, treatment, and ...

History

British scientists working at Beecham (now part of

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

), filed for patent protection for the drug combination in 1977, which was granted in 1982. It was sold under the brand name Augmentin.

Preparations

Amoxicillin/clavulanic acid is the International Nonproprietary Name (INN) and co-amoxiclav is the

British Approved Name A British Approved Name (BAN) is the official, non-proprietary, or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia (BP). The BAN is also the official name used in some countries around the world, because ...

(BAN). Many branded products indicate their strengths as the quantity of amoxicillin. Augmentin 250, for example, contains 250 mg of amoxicillin and 125 mg of clavulanic acid. An intravenous preparation has been available in the UK since 1985, but no parenteral preparation is available in the US; the nearest equivalent is ampicillin/sulbactam. Suspensions of amoxicillin/clavulanic acid are available for use in children. They must be refrigerated to maintain effectiveness.

Veterinary use

Amoxicillin/clavulanic acid is used in numerous animals for a variety of conditions: * Dogs: Skin 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. * Cats: Skin 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.''

Bacterial resistance

Bacterial

is a growing problem in

veterinary medicine Veterinary medicine is the branch of medicine that deals with the prevention, management, medical diagnosis, diagnosis, and treatment of disease, disorder, and injury in non-human animals. The scope of veterinary medicine is wide, covering all a ...

. Amoxicillin/clavulanic acid is reported to be effective against clinical ''

Klebsiella ''Klebsiella'' is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. ''Klebsiella'' is named after German-Swiss microbiologist Edwin Klebs (1834–1913). Carl Friedlander described ' ...

'' infections, but is not efficacious against ''

Pseudomonas ''Pseudomonas'' is a genus of Gram-negative bacteria belonging to the family Pseudomonadaceae in the class Gammaproteobacteria. The 348 members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a ...

'' infections.Federation of Veterinarians in Europe Position Paper: "Antibiotic Resistance & Prudent Use of Antibiotics in Veterinary Medicine"

References

{{DEFAULTSORT:Amoxicillin Clavulanic Acid Cat medications Combination antibiotics Dog medications Drugs developed by GSK plc Hepatotoxins Penicillins Veterinary drugs World Health Organization essential medicines Wikipedia medicine articles ready to translate