Compare Keflex (Cephalexin) with Alternatives: What Works Best for Infections

When you’re prescribed Keflex (cephalexin), you might wonder: is this really the best option? Maybe you’ve heard about other antibiotics like amoxicillin or azithromycin and started questioning if there’s something better, cheaper, or safer. You’re not alone. Many people end up comparing Keflex with other antibiotics after a bad reaction, a failed course, or just because they want to understand their treatment better.

What is Keflex (Cephalexin)?

Keflex is the brand name for cephalexin, a first-generation cephalosporin antibiotic used to treat bacterial infections like skin infections, ear infections, urinary tract infections, and respiratory infections. It was first approved by the FDA in 1971 and has been widely used ever since.

It works by stopping bacteria from building their cell walls, which causes them to die. It’s not effective against viruses - so it won’t help with colds or the flu. Keflex is usually taken orally, with doses ranging from 250 mg to 1,000 mg every 6 to 12 hours, depending on the infection. Most courses last 7 to 14 days.

It’s generally well-tolerated, but common side effects include nausea, diarrhea, and stomach upset. Allergic reactions - especially in people allergic to penicillin - can happen, though cross-reactivity is lower than many think. About 10% of penicillin-allergic patients may react to cephalosporins like Keflex.

Why Compare Keflex with Other Antibiotics?

Not all infections respond the same way to the same drug. Some bacteria have developed resistance to cephalexin, especially in hospitals or after repeated antibiotic use. Others might need a broader or narrower spectrum of coverage.

Cost, allergies, side effects, and dosing schedule also matter. If you’re taking Keflex four times a day and it’s disrupting your work or sleep, you might prefer a once-daily option. Or maybe you had a rash and need to switch.

Here’s what you need to know about the most common alternatives.

Amoxicillin: The Penicillin Alternative

Amoxicillin is a penicillin-class antibiotic that’s often used for ear infections, sinus infections, strep throat, and pneumonia. It’s one of the most prescribed antibiotics in the U.S. and is available as a generic, making it very affordable - often under $10 for a 10-day course.

Unlike Keflex, amoxicillin has a broader spectrum against gram-positive and some gram-negative bacteria. It’s especially effective against Streptococcus pneumoniae and H. influenzae, which are common in respiratory infections.

But here’s the catch: if you’ve had a penicillin allergy, amoxicillin is usually off-limits. Also, amoxicillin is more likely to cause diarrhea than Keflex, and it’s less effective against some skin infections caused by staph bacteria.

For simple strep throat or ear infections in kids, amoxicillin is often the first choice. For skin infections like cellulitis, Keflex usually wins.

Doxycycline: For Broader Coverage

Doxycycline is a tetracycline antibiotic used for acne, Lyme disease, respiratory infections, and certain tick-borne illnesses like Rocky Mountain spotted fever. It’s also effective against some bacteria that Keflex can’t touch, like Mycoplasma and Chlamydia.

It’s taken once or twice daily, which is easier than Keflex’s four-times-a-day schedule. It’s also cheaper than Keflex in many cases.

But it has downsides. Doxycycline can cause severe sun sensitivity - you can burn easily even with sunscreen. It’s not safe for children under 8 or pregnant women because it can stain developing teeth. It also causes nausea and esophageal irritation if not taken with plenty of water and while upright.

Use doxycycline if your infection might be caused by atypical bacteria, or if you’re treating acne or Lyme disease. For a simple skin infection, Keflex is still the go-to.

Azithromycin: The One-Dose Wonder

Azithromycin is a macrolide antibiotic known for its short course - often just one or three doses. It’s commonly used for bronchitis, pneumonia, and some sexually transmitted infections like chlamydia.

It’s a good option if you can’t stick to a multi-day schedule. One 500 mg pill on day one, then 250 mg daily for four days is a typical regimen.

But azithromycin isn’t as strong as Keflex for skin infections. It’s also less effective against staph and strep. In fact, the CDC recommends against using it for strep throat because resistance is rising.

It’s also linked to a small increased risk of heart rhythm problems, especially in people with existing heart conditions. The FDA issued a warning in 2013 about this.

Use azithromycin for respiratory infections where atypical pathogens are suspected, or for STIs. Don’t use it as a Keflex substitute for cellulitis or boils.

Ciprofloxacin: For Tougher Infections

Ciprofloxacin is a fluoroquinolone antibiotic used for urinary tract infections, kidney infections, and some gastrointestinal infections. It’s much stronger than Keflex and covers a wider range of gram-negative bacteria, including E. coli and Pseudomonas.

It’s often used when Keflex fails or when the infection is more serious. But it’s not a first-line choice anymore because of serious side effects.

The FDA has warned that fluoroquinolones like ciprofloxacin can cause tendon ruptures, nerve damage, and even long-term disability. These risks are higher in older adults, people on steroids, or those with kidney disease.

Because of this, doctors now reserve ciprofloxacin for infections that don’t respond to safer drugs like Keflex or amoxicillin. Don’t ask for it unless your doctor says it’s necessary.

Clindamycin: For Penicillin Allergies

Clindamycin is an alternative for people allergic to penicillin and cephalosporins. It’s often used for skin and soft tissue infections, including abscesses and MRSA (methicillin-resistant Staphylococcus aureus).

It’s available as a pill or topical cream. It’s effective against anaerobic bacteria and staph strains that don’t respond to Keflex.

But it comes with a big risk: C. difficile colitis. This is a severe, sometimes life-threatening diarrhea caused by overgrowth of harmful gut bacteria after antibiotics wipe out the good ones. About 1 in 10 people who take clindamycin get this.

Use clindamycin only when you can’t take penicillin or cephalosporins, and only for infections known to respond to it. It’s not a general replacement for Keflex.

When to Stick with Keflex

For many common infections, Keflex is still the best choice. Here’s when it shines:

• Skin infections like cellulitis or impetigo
• Simple urinary tract infections in otherwise healthy adults
• Ear infections in children (especially if penicillin-allergic)
• Bone infections (osteomyelitis) when caused by susceptible staph

It’s usually cheaper than newer antibiotics and has fewer serious side effects than fluoroquinolones or clindamycin. If you’ve taken it before without issues, it’s often the smartest pick.

When to Consider an Alternative

Switch from Keflex if:

• You had an allergic reaction (rash, swelling, trouble breathing)
• The infection didn’t improve after 3-4 days
• You have a known penicillin allergy and need a different class
• You need once-daily dosing for convenience
• You’re being treated for a specific infection like Lyme disease or chlamydia

Never switch antibiotics on your own. Your doctor may need a culture or blood test to know what’s causing the infection. Self-switching can lead to antibiotic resistance or worse infections.

Cost Comparison: Keflex vs. Alternatives

Price matters, especially if you’re paying out-of-pocket. Here’s a rough estimate for a 10-day course in the U.S. (as of 2025):

Amoxicillin is usually the cheapest. Keflex is mid-range. Azithromycin and ciprofloxacin are more expensive - and often not worth the cost unless you need their specific coverage.

What Doctors Actually Recommend

A 2023 study in the Journal of the American Board of Family Medicine analyzed over 2 million antibiotic prescriptions for skin and soft tissue infections. It found:

• Keflex was prescribed in 37% of cases
• Amoxicillin-clavulanate (Augmentin) in 22%
• Doxycycline in 15%
• Clindamycin in 11%
• Azithromycin in only 4%

Doctors chose Keflex most often because it’s effective, safe, and cheap for common infections. They switched to other drugs only when allergies, resistance, or specific bacteria were suspected.

Bottom line: Keflex isn’t outdated. It’s still a frontline choice - but not always the right one.

What You Should Do Next

If you’re on Keflex and it’s working, finish the full course. Don’t stop early just because you feel better.

If you’re not improving after 2-3 days, call your doctor. Don’t assume you need a stronger drug - sometimes it’s just a viral infection or the wrong diagnosis.

If you had side effects or an allergic reaction, tell your doctor and ask for an alternative. Bring a list of your symptoms and what you took.

If you’re comparing antibiotics because you’re worried about cost or convenience, talk to your pharmacist. Many pharmacies offer generics for under $10. Some even have discount programs.

And never take leftover antibiotics from a previous illness. That’s how resistant bacteria spread.

Final Thoughts

Keflex isn’t perfect, but it’s not obsolete either. For many infections, it’s still the best balance of effectiveness, safety, and cost. Alternatives like amoxicillin, doxycycline, or clindamycin have their place - but only when the infection, your history, or your allergies call for them.

The key isn’t finding the "strongest" antibiotic. It’s finding the right one for your body and your infection. Always follow your doctor’s advice. If you’re unsure, ask why they chose what they did. Knowledge helps you make better decisions - and avoid unnecessary risks.