Azithromycin (Zithromax) vs amoxicillin-clavulanate (Augmentin): antibiotics compared

At a glance

• Antibiotic family

  Azithromycin

  Macrolide

  Amoxicillin-clavulanate

  Penicillin plus a beta-lactamase inhibitor

• Labeled uses

  Azithromycin

  Sinusitis, chronic bronchitis flares, some pneumonias, skin infections, chlamydia; second choice for strep throat

  Amoxicillin-clavulanate

  Ear, sinus, lower respiratory, skin and urinary tract infections caused by beta-lactamase-producing bacteria

• Course

  Azithromycin

  Once a day for 3 to 5 days, or a single dose for chlamydia

  Amoxicillin-clavulanate

  Every 8 or 12 hours, at the start of a meal

• Main cautions

  Azithromycin

  Heart rhythm (QT), liver injury, myasthenia gravis

  Amoxicillin-clavulanate

  Penicillin allergy, liver problems, rash in mononucleosis

• Generic

  Azithromycin

  Yes, tablets and suspension

  Amoxicillin-clavulanate

  Yes

What clavulanate adds

Amoxicillin is a penicillin-type antibiotic. Some bacteria make beta-lactamase enzymes that break it down; clavulanate blocks those enzymes so the amoxicillin keeps working. The Augmentin label covers lower respiratory tract infections, ear infections, sinusitis, skin infections and urinary tract infections caused by beta-lactamase-producing bacteria, and it says the combination is not the choice when testing shows the bacteria do not make that enzyme. Its strengths are not interchangeable either: two 250 mg tablets must not be substituted for one 500 mg tablet, because each tablet carries the same 125 mg of clavulanate.

Where azithromycin fits

Azithromycin is a macrolide, a different family that does not depend on blocking beta-lactamase. Its label covers acute bacterial sinusitis, flares of chronic bronchitis, community-acquired pneumonia in people well enough for tablets, uncomplicated skin infections, urethritis and cervicitis (chlamydia), chancroid, and ear infections and pneumonia in children six months and older. For strep throat it is labeled only as an alternative for people who cannot take first-line treatment, so a penicillin allergy is one reason it is chosen; it must not be used by anyone allergic to azithromycin, erythromycin or another macrolide.

Course length

The usual adult azithromycin course is 500 mg on the first day then 250 mg once a day for four more days, 500 mg a day for three days for sinusitis or a bronchitis flare, or a single 1 g dose for chlamydia, with or without food. Augmentin is taken every 12 hours (500 mg or 875 mg) or every 8 hours, at the start of a meal to improve absorption of the clavulanate and reduce stomach upset; the label does not fix a course length for adults, so the prescriber sets it. With either, finish the prescription even when you feel better.

Side effects and cautions

Diarrhea, nausea and vomiting are common with both; azithromycin also commonly causes stomach pain, and the Augmentin label also lists rash and vaginal irritation or yeast infection. Both labels warn that severe or watery diarrhea during or in the weeks after treatment can be Clostridioides difficile infection and needs prompt care. Azithromycin can prolong the QT interval and cause dangerous heart rhythms, so it is used with care in people with heart rhythm problems or on other medicines that affect rhythm; it can worsen myasthenia gravis, and serious liver injury, including fatal cases, has been reported. Augmentin must not be used by anyone who has had a serious allergic reaction to a penicillin or cephalosporin, or who had liver problems or jaundice with it before; it is avoided in people with mononucleosis, who often develop a rash with amoxicillin, and MedlinePlus notes it can make combined birth control pills less effective.

Interactions

Azithromycin can increase the effect of warfarin, so clotting tests are checked, and aluminum or magnesium antacids are taken at a different time from it. Augmentin raises the chance of a rash when taken with allopurinol, is not recommended with probenecid, and can prolong clotting times in people on warfarin.

Cost

Both are available as generics: azithromycin as 250 mg and 500 mg tablets and as a suspension for children, and amoxicillin-clavulanate as tablets, chewable tablets and a suspension. Each pharmacy sets its own cash price for each form and strength, and a short azithromycin course is a handful of tablets while an Augmentin course is a longer run at two or three tablets a day, so ask for a quote on the exact product, strength and quantity prescribed.

Read more

• Azithromycin guide
• Amoxicillin-clavulanate guide
• Azithromycin guide
• Amoxicillin-clavulanate guide
• Azithromycin vs amoxicillin