Amoxicillin and Clavulanate Potassium: Comprehensive Guide

Antibiotic resistance has become a growing global health concern in recent years. With more bacteria evolving resistance to commonly used antibiotics, researchers and healthcare professionals are turning to combination therapies, among other strategies, to combat resistant infections. One such combination is amoxicillin and clavulanate potassium, a pairing that has been shown to be effective in treating various bacterial infections in clinical settings.

[signup]

What Is Amoxicillin and Clavulanate Potassium?

Amoxicillin-clavulanate, commonly sold under the trade name Augmentin, is a combination antibiotic medication used to treat bacterial infections. 

Chemical Composition and Mechanism

Amoxicillin is a beta-lactam antibiotic belonging to the penicillin family. Beta-lactams work by inhibiting bacterial cell wall synthesis. Bacteria have a cell wall made up of a material called peptidoglycan. They use penicillin-binding proteins (PBPs) to link peptidoglycans together and form a strong wall. Amoxicillin attaches itself to PBPs, preventing them from doing their job. As a result, the bacterial cell wall becomes weak and unstable, causing bacteria to die.

Some bacterial species have evolved to produce enzymes called beta-lactamases that break down the beta-lactam ring that makes up part of the chemical structure of beta-lactam antibiotics. This protective mechanism contributes to the problem of antibiotic resistance. 

Clavulanate potassium, or clavulanic acid, is a beta-lactamase inhibitor. It binds to and deactivates beta-lactamases to prevent the bacterial degradation of beta-lactam rings of beta-lactam antibiotics.

How the Combination Works

Although amoxicillin is a broad-spectrum antibiotic, meaning it can target a wide range of bacteria, it is vulnerable to inactivation by beta-lactamases. Combining amoxicillin with clavulanic acid protects it from being degraded, allowing it to remain effective against bacteria that produce beta-lactamases, which would otherwise be resistant to amoxicillin on its own.

Approved Uses and Indications

To prevent the further development of antimicrobial drug resistance, amoxicillin-clavulanate should only be used to treat infections caused by susceptible beta-lactamase-producing bacteria, including:

• Staphylococcus aureus
• Enterobacter species 
• Escherichia coli 
• Haemophilus influenzae 
• Klebsiella species 
• Moraxella catarrhalis 

Common Infections Treated

The U.S. Food and Drug Administration (FDA) has approved amoxicillin-clavulanate to treat the following types of bacterial infections caused by susceptible bacteria:

• Lower respiratory tract infections, such as community-acquired pneumonia (CAP)
• Acute bacterial otitis media (AOM)
• Sinusitis
• Skin and soft tissue infections, such as impetigo
• Urinary tract infections (UTI) 

Off-Label Uses

Doctors may prescribe amoxicillin-clavulanate off-label to treat other bacterial infections, such as: 

• Bite wounds
• Strep throat
• Acute exacerbations of chronic obstructive pulmonary disease (COPD)
• Diabetic foot infections
• Tooth infections
• Peritonsillar abscess

‍Off-label use should be done only under the supervision of a healthcare professional.

Dosage and Administration

Amoxicillin comes in different dosage forms and strengths. The strength is listed as the amount of amoxicillin followed by the amount of clavulanic acid.

• Tablets: 250 mg/125 mg, 500 mg/125 mg, 875 mg/125 mg
• Liquid Suspension: 125 mg/31.25 mg per 5 mL, 200 mg/28.5 mg per 5 mL, 250 mg/62.5 mg per 5 mL, 400 mg/57 mg per 5 mL
• Chewable Tablets: 125 mg/31.25 mg, 200 mg/28.5 mg, 250 mg/62.5 mg, 400 mg/57 mg

Recommended Dosages

Your doctor will prescribe a dosage based on age, body weight, the type of severity of infection being treated, and kidney function. The dosing guidelines below are general and should not replace a healthcare provider's recommendations.

Adults

• Most Infections: one 500-mg or 875-mg oral tablet every 12 hours
• Respiratory Tract and Other Severe Infections: one 875-mg oral tablet every 12 hours or one 500-mg tablet every 8 hours

Dose adjustments should be made for those with impaired kidney function based on glomerular filtration rate (GFR):

• GFR 10-30 mL/min: one 250-mg or 500-mg or oral tablet every 12 hours, depending on the severity of the infection
• GFR less than 10 mL/min: one 250-mg or 500-mg oral tablet every 24 hours, depending on the severity of the infection

Pediatrics

• Children Weighing at Least 40 Kg: follow adult dosing recommendations
• Younger Than 3 Months: 30 mg/kg/day, divided into two equal doses taken every 12 hours (use of the 125-mg/5-mL oral suspension is recommended)
• Ages 3 Months and Older: 25 to 45 mg/kg/day, divided into two equal doses taken every 12 hours (use of the 200-mg/5-mL or 400-mg/5-mL oral suspension is recommended)

Administration Instructions

• The absorption of clavulanate potassium is reduced on an empty stomach. To enhance absorption, take amoxicillin-clavulanate with food at the beginning of a meal.
• Adults who have trouble swallowing tablets can use the 125 mg/5 mL or 250 mg/5 mL oral suspension instead of the 500-mg tablet. The 200 mg/5 mL or 400 mg/5 mL suspension can be used as an alternative to the 875-mg tablet.
• Two 250-mg tablets can not be substituted for one 500-mg tablet.
• One 250-mg tablet should not be substituted for one 250-mg chewable tablet.
• Children should not take the 250-mg tablet until they weigh at least 40 kg. 
• If you miss a dose, take it as soon as you remember. If it's almost time for your next dose, skip the missed dose and take the next one at the regular time. Do not take two doses at once to make up for a missed dose. 
• Complete the full course of antibiotics as prescribed, even if you start feeling better before finishing the medication. Stopping early can allow the infection to return and contribute to antibiotic resistance.

Potential Side Effects and Risks

While amoxicillin-clavulanate is generally safe and well tolerated, it may cause adverse effects in some people, some of which may be more serious than others.

Common Side Effects

According to clinical trials, the more common side effects of amoxicillin-clavulanate include:

• Diarrhea
• Nausea
• Skin rash and hives
• Vaginitis
• Vomiting
• Abdominal discomfort
• Gas
• Headache

Serious Adverse Effects

Serious side effects are not common but can happen when taking amoxicillin-clavulanate. Contact your doctor immediately if you begin to experience any of the following: 

• Liver Problems: jaundice, abdominal swelling, abdominal pain, fatigue
• Severe Allergic or Skin Reactions: red skin rash, blistering, skin peeling, swelling of the lips or tongue, difficulty breathing
• Clostridioides difficile Colitis: watery diarrhea, bloody stools, abdominal pain, fever
• Drug-Induced Enterocolitis Syndrome (DIES): vomiting, abdominal pain, diarrhea, pale skin, dehydration

Managing Side Effects

Some side effects may improve as your body adjusts to the medication. Mild side effects can often be managed at home with simple remedies. Examples include: 

• Diarrhea: Taking Saccharomyces boulardii has been associated with a reduction in antibiotic-associated diarrhea in adults and children.
• Nausea: Take your medication with food, drink ginger tea, or use peppermint aromatherapy
• Headache: Head pain can be managed with over-the-counter pain medications (e.g., ibuprofen and acetaminophen), cold packs, meditation, and peppermint aromatherapy.

If you ever have any questions, never hesitate to reach out to your doctor for medical support, especially if side effects persist or worsen over time. 

Drug Interactions and Contraindications

Precautions should be taken in certain situations to ensure drug safety. 

Drug-Drug Interactions

Taking amoxicillin-clavulanate with certain medications can change how the drugs work and increase the risk of side effects. Always let your doctor know about any other medications or supplements you are taking to prevent drug interactions. 

Major interactions to be aware of include:

• Probenecid decreases the elimination of amoxicillin from the body, increasing its blood concentrations. Co-administration is not recommended.
• Taking oral anticoagulants with amoxicillin has been shown to increase the risk of excessive bleeding. Patients on anticoagulants should be closely monitored, and the dose of the oral anticoagulant may need to be temporarily adjusted when taking amoxicillin-clavulanate.
• Allopurinol may increase the incidence of amoxicillin-associated allergic reactions.  
• Amoxicillin-clavulanate may reduce the efficacy of combined oral contraceptive pills (OCPs). Patients should be advised to abstain from sexual intercourse or use an additional form of contraception during treatment and for a short period afterward to prevent unintended pregnancy.

Contraindications

Amoxicillin-clavulanate should not be taken in the following circumstances: 

• History of serious allergic reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin-clavulanate or other beta-lactam antibiotics
• History of amoxicillin-clavulanate-associated liver dysfunction
• Patients with phenylketonuria (PKU) should not be given aspartame-containing formulations of amoxicillin-clavulanate (i.e., 200 mg/5 mL and 400 mg/5 mL oral suspensions and 200-mg and 400-mg chewable tablets). Aspartame can increase phenylalanine levels in individuals with PKU and cause neurological complications.

Comparisons with Other Antibiotics

Amoxicillin provides broad-spectrum coverage against many gram-positive and some gram-negative bacteria but lacks activity against beta-lactamase producers. Adding clavulanate to amoxicillin extends its coverage to include beta-lactamase-producing strains of bacteria.

Clavulanic acid increases the rate of gastrointestinal side effects, including Clostridium difficile infection, which may limit the maximum daily dosage of amoxicillin-clavulanate that patients can tolerate.

Alternative Antibiotic Options

If amoxicillin-clavulanate is not well suited for you, other antibiotics are available to treat the same conditions. The best choice of antibiotic will depend on your age, the type of infection being treated, allergies, and local antibiotic resistance patterns. 

Examples of alternative antibiotics to amoxicillin-clavulanate include: 

• Lower Respiratory Tract Infections: azithromycin, doxycycline, levofloxacin, and moxifloxacin
• Otitis Media: cefdinir, cefuroxime, cefpodoxime, and ceftriaxone 
• Sinusitis: doxycycline and levofloxacin
• Skin Infections: cephalexin and ciprofloxacin 
• UTIs: nitrofurantoin and trimethoprim/sulfamethoxazole

[signup]

Key Takeaways

• Amoxicillin is a broad-spectrum antibiotic that targets and kills a wide range of gram-positive and gram-negative bacteria.
• Combining clavulanate with amoxicillin helps combat antibiotic resistance by inhibiting beta-lactamase enzymes, which some bacteria produce to inactivate amoxicillin.
• Amoxicillin-clavulanate is FDA-approved to treat respiratory tract, ear, sinus, skin, and urinary tract infections caused by susceptible bacteria.
• Amoxicillin-clavulanate may not be appropriate for patients with a known allergy to penicillin or beta-lactam antibiotics, or those with certain liver conditions.
• Use this medication responsibly by following the prescribed dosage and completing the entire course of treatment. Always consult a healthcare provider for personalized advice before taking amoxicillin-clavulanate or during treatment if you experience side effects.