When you’re prescribed cephalexin for a skin infection, sinusitis, or urinary tract infection, you might wonder: cephalexin is the go-to, but are there better options? Maybe your doctor switched you because it didn’t work, or you had a bad reaction. Or maybe you’re just trying to understand what else is out there. The truth is, not all antibiotics are the same - and what works for one person might fail for another.

What is cephalexin, really?

Cephalexin is a first-generation cephalosporin antibiotic. It kills bacteria by breaking down their cell walls. It’s commonly used for skin infections like cellulitis, impetigo, and boils. It’s also prescribed for respiratory infections like strep throat, ear infections, and some urinary tract infections. It’s usually taken every 6 to 12 hours for 7 to 14 days.

It’s not a broad-spectrum powerhouse like some newer drugs. It’s effective against common Gram-positive bacteria - think Staphylococcus and Streptococcus - but not so great against Gram-negative bugs like E. coli or Klebsiella. That’s why it’s often the first choice for simple infections but not for complicated ones.

Side effects? Usually mild: nausea, diarrhea, stomach upset. Rarely, people get allergic reactions - especially if they’re allergic to penicillin. About 10% of people with penicillin allergies also react to cephalexin. That’s a key point.

Amoxicillin: The penicillin cousin

If you’ve ever taken amoxicillin for a sore throat or ear infection, you’ve used a close relative of cephalexin. Both are beta-lactam antibiotics. But amoxicillin has a broader range. It covers more Gram-negative bacteria, including some strains of E. coli and H. influenzae.

For sinus infections or ear infections in kids, amoxicillin is often preferred over cephalexin. A 2023 study in the Journal of the American Academy of Pediatrics found amoxicillin cleared ear infections 12% faster than cephalexin in children under 6.

But here’s the catch: amoxicillin is more likely to cause diarrhea. It also gets broken down faster by stomach acid, so you need to take it more often - usually three times a day. Cephalexin lasts longer in the body, so it’s easier to stick to a twice-daily schedule.

Both can cause allergic reactions. If you’re allergic to penicillin, avoid amoxicillin. Cephalexin might still be an option, but only after testing.

Doxycycline: For when cephalexin falls short

Doxycycline is a tetracycline antibiotic. It’s not a direct replacement for cephalexin - it works differently. Instead of attacking cell walls, it stops bacteria from making proteins. That makes it useful for infections cephalexin can’t touch.

Think Lyme disease, acne, rosacea, or certain types of pneumonia. It’s also the go-to for tick-borne illnesses and some sexually transmitted infections like chlamydia. If you have a skin infection caused by MRSA (methicillin-resistant Staphylococcus aureus), doxycycline often works when cephalexin doesn’t.

But it’s not without downsides. It can make your skin super sensitive to sunlight. You can’t take it with dairy, antacids, or iron supplements - they block absorption. And it’s not for kids under 8 or pregnant women because it can permanently stain developing teeth.

Compared to cephalexin, doxycycline has a longer half-life. One dose a day is often enough. That’s convenient. But if you’re treating a simple skin infection, it’s overkill - and increases your risk of antibiotic resistance.

Azithromycin: The one-dose wonder

Azithromycin is a macrolide. It’s famous for the "Z-Pak" - a five-day course where you take two pills on day one, then one a day for the next four. But many doctors now use a single 500mg dose for certain infections.

It’s great for respiratory infections like bronchitis or pneumonia caused by atypical bacteria. It’s also used for some skin infections and STIs. Unlike cephalexin, it works well against some Gram-negative bacteria and even some parasites.

Here’s the big advantage: fewer doses. If you struggle with remembering to take pills, azithromycin is easier. But it’s not better for every infection. For a simple boil or cellulitis, cephalexin is still more effective.

Side effects? More stomach upset than cephalexin. And there’s a small but real risk of heart rhythm problems, especially if you already have heart disease. The FDA issued a warning about this in 2013. It’s not common, but it’s something your doctor should check.

Clindamycin: The backup plan

Clindamycin is often used when someone can’t take penicillin or cephalosporins. It’s effective against anaerobic bacteria and MRSA. If you have a deep skin abscess or a dental infection that’s not responding to cephalexin, clindamycin is a common next step.

It’s available as a pill or IV. For mild cases, a 150mg pill every 6 hours for 7-10 days is typical. But here’s the problem: it’s strongly linked to a dangerous gut infection called C. diff (Clostridioides difficile). About 1 in 10 people who take clindamycin get diarrhea. In 1 in 100, it turns into a life-threatening colitis.

That’s why doctors don’t reach for clindamycin first. It’s a last-resort option for infections that don’t respond to safer drugs. If cephalexin fails and you’re not allergic to penicillin, amoxicillin-clavulanate is usually tried before clindamycin.

Amoxicillin-clavulanate: The combo power

This one’s a two-in-one: amoxicillin plus clavulanic acid. The clavulanate blocks enzymes that some bacteria use to resist antibiotics. That makes it effective against bacteria that laugh off plain amoxicillin or cephalexin.

It’s the top choice for complicated skin infections, sinus infections that won’t clear, and bites (human or animal). A 2024 study in Annals of Internal Medicine showed amoxicillin-clavulanate cleared resistant skin infections 22% faster than cephalexin.

But it’s not gentle. It causes more diarrhea, nausea, and yeast infections than cephalexin. It’s also more expensive. And if you’re allergic to penicillin, you can’t take it.

It’s the strongest oral option in this group. But strength isn’t always better. If your infection is simple, you’re better off with cephalexin - fewer side effects, lower cost, lower risk of resistance.

When to switch from cephalexin

You shouldn’t switch antibiotics just because you’re bored with pills. Here’s when it makes sense:

• You had an allergic reaction to cephalexin (rash, swelling, trouble breathing)
• Your infection got worse after 48 hours
• You’re not improving after 5-7 days
• Your doctor confirmed the infection is caused by a bacteria cephalexin can’t kill (like MRSA or E. coli)
• You have kidney problems - cephalexin is cleared by kidneys, so dosage needs adjusting

If none of these apply, stick with cephalexin. It’s cheap, effective, and safe for most people.

What you should never do

Don’t take leftover antibiotics from a previous infection. That’s how superbugs form. Don’t stop early just because you feel better. Bacteria can come back stronger.

Don’t ask for antibiotics for a cold or the flu. They don’t work on viruses. And don’t self-diagnose. A rash could be an allergic reaction - not an infection. A swollen lymph node could be cancer. Always get tested.

Bottom line: Choose based on infection, not convenience

Cephalexin isn’t the best antibiotic for everything. But it’s the best for many common infections. Amoxicillin is better for ear and sinus infections. Doxycycline wins for Lyme or acne. Azithromycin helps with stubborn respiratory bugs. Clindamycin and amoxicillin-clavulanate are for tougher cases.

The right choice depends on:

• What kind of infection you have
• Which bacteria are likely causing it
• Your medical history (allergies, kidney function, other meds)
• Local resistance patterns (some areas have more MRSA than others)

There’s no universal "best" antibiotic. What works for your neighbor might not work for you. Trust your doctor’s judgment - they’re not just picking a name out of a hat. They’re matching the bug to the drug.

If you’re unsure why you were given cephalexin, ask. Say: "Is this the best option for my infection, or is there something safer or more effective?" That’s not being difficult - it’s being smart.