Keflex vs. Zithromax

See how Keflex and Zithromax compare on approved uses, dosing, side effects, and cost.

Key Takeaways

  • Keflex is a first-generation cephalosporin usually taken multiple times a day for one to two weeks, while Zithromax is a macrolide often given as a short five-day or single-dose course.

  • Both drugs can cause stomach upset, but Zithromax carries specific FDA warnings about heart rhythm changes and liver damage that Keflex does not share.

  • Keflex is commonly used for skin, bone, and urinary infections, while Zithromax is often chosen for respiratory infections and certain sexually transmitted infections.

Keflex vs. Zithromax Drug Summary

Keflex

Keflex (cephalexin) is a first-generation cephalosporin antibiotic used for infections like strep throat, ear infections, skin infections, and urinary tract infections. It works by weakening bacterial cell walls and is usually taken as a capsule, tablet, or liquid several times a day for one to two weeks.

Zithromax

Zithromax (azithromycin) is a macrolide antibiotic used for infections like pneumonia, sinusitis, skin infections, and certain sexually transmitted infections. It works by blocking bacterial protein production and is often taken as a short five-day course or a single dose because it stays in tissue longer than most antibiotics.

Keflex vs. Zithromax Side Effects

Keflex

Most common
Abdominal pain (not specified)
Vomiting (not specified)
Nausea (not specified)
Diarrhea (not specified)

Zithromax

Most common
Abdominal pain (up to 7%)
Vomiting (up to 7%)
Nausea (up to 18%)
Diarrhea (up to 14%)

Keflex vs. Zithromax Dosage

Keflex

Dosage
Dosage Table
STAGE DOSE WHEN
Starting dose 25-50 mg/kg/day divided At the start
Maximum dose up to 4 g/day divided If needed
Dose changes 3 increases As tolerated

Zithromax

Dosage
Dosage Table
STAGE DOSE WHEN
Starting dose 500 mg once daily Day 1
Maximum dose 30 mg/kg single dose If needed
Dose changes 5 increases As tolerated

Keflex vs. Zithromax Indications

Keflex

Keflex is FDA-approved for common bacterial infections including respiratory tract infections, ear infections, skin infections, bone infections, and urinary tract infections. It is not effective against Pseudomonas or Acinetobacter bacteria, so doctors reserve it for infections caused by susceptible organisms.

  • Respiratory tract infections

  • Otitis media (ear infections)

  • Skin and skin structure infections

  • Bone infections

  • Genitourinary tract infections

Zithromax

Zithromax is FDA-approved for infections such as pneumonia, bronchitis flare-ups, sinusitis, skin infections, and certain sexually transmitted infections like chlamydia and gonorrhea. It is also used to prevent and treat MAC infections in people with advanced HIV, but it is not effective against viral illnesses.

  • Community-acquired pneumonia

  • Acute bacterial sinusitis

  • Skin and skin structure infections

  • Chlamydia and gonorrhea infections

  • MAC disease prevention and treatment

Keflex vs. Zithromax Pros and Cons

Keflex

Keflex has a long track record of safety and predictable dosing, and it does not carry the heart rhythm warnings seen with macrolides. It does require more frequent daily dosing and a longer overall course, and it isn't effective against certain resistant or atypical bacteria.

Pros

  • Long-established safety record since 1971

  • No FDA warning for heart rhythm effects

  • Effective against common skin and bone bacteria

  • No black-box-level liver toxicity warning

Cons

  • Requires dosing 2 to 4 times daily

  • Typical course runs 7 to 14 days

  • Not effective against atypical bacteria like chlamydia

  • Not effective against Pseudomonas or Acinetobacter

Zithromax

Zithromax's long tissue half-life allows short five-day or even single-dose treatment courses, which can improve adherence for some infections. It carries FDA warnings for heart rhythm changes and rare but serious liver toxicity that Keflex does not carry.

Pros

  • Short courses, often just 5 days or one dose

  • Covers atypical bacteria like chlamydia and mycoplasma

  • Convenient once-daily dosing

  • Effective for certain sexually transmitted infections

Cons

  • FDA warning for QT prolongation and arrhythmia risk

  • Rare but serious liver toxicity warning

  • Risk factor for cardiovascular death in some patients

  • Not first-line for skin or bone infections

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