Most cellulitis is treated with oral antibiotics that target streptococcal bacteria, the most common cause. A standard course lasts about five days, though more complicated infections may need up to 14 days. The specific antibiotic your doctor chooses depends on whether the infection looks purulent (producing pus), whether MRSA is a concern, and how severe your symptoms are.
First-Line Antibiotics for Standard Cellulitis
Typical cellulitis appears as a spreading area of redness, warmth, and swelling without a drainable pocket of pus. This type is called non-purulent cellulitis, and it’s almost always caused by streptococcal bacteria. The two primary oral antibiotics used to treat it are cephalexin (500 mg four times daily) and penicillin VK (250 to 500 mg four times daily). Cephalexin is prescribed more frequently in practice because it also covers some staphylococcal bacteria, giving slightly broader protection.
These antibiotics work well for mild to moderate cases where you don’t have a high fever, rapid heart rate, or other signs that the infection has become systemic. If your cellulitis is limited to a patch of red, swollen skin and you’re otherwise feeling okay, an oral course of one of these medications is the standard approach.
When MRSA Is a Concern
If your cellulitis has pus, developed after a puncture wound, or you have risk factors for MRSA (a previous MRSA infection, recent hospitalization, IV drug use, or known MRSA nasal colonization), the antibiotic strategy changes. Standard cephalexin and penicillin don’t reliably kill MRSA, so your doctor needs to add or substitute drugs that do.
For oral treatment covering both streptococcus and MRSA, the usual combinations are:
- Clindamycin alone, which covers both bacterial types in a single pill
- Trimethoprim-sulfamethoxazole (Bactrim) plus a penicillin-type drug like cephalexin or amoxicillin, because trimethoprim-sulfamethoxazole handles MRSA well but has unreliable streptococcal coverage on its own
- Doxycycline plus a penicillin-type drug, following the same logic
A common regimen for MRSA-risk cellulitis is trimethoprim-sulfamethoxazole (800 mg/160 mg twice daily) combined with cephalexin (500 mg four times daily) for five days. If you can’t tolerate trimethoprim-sulfamethoxazole, clindamycin (300 to 450 mg four times daily) is the typical substitute.
Options if You’re Allergic to Penicillin
A true severe penicillin allergy rules out the entire penicillin and cephalosporin family, which eliminates the most commonly prescribed cellulitis drugs. The primary alternative in that situation is clindamycin, which covers streptococcus effectively and also has activity against many staphylococcal strains including some MRSA. Other options include erythromycin and roxithromycin, though these are used less frequently.
It’s worth noting that many people who believe they have a penicillin allergy actually don’t. If your “allergy” was documented in childhood based on a mild rash, it may be worth discussing allergy testing with your doctor, since confirming you can safely take penicillin-type drugs opens up the most effective and best-studied treatment options.
Severe Cellulitis and IV Antibiotics
Cellulitis that comes with high fever, rapidly spreading redness, low blood pressure, or signs of a systemic inflammatory response typically requires hospital admission and intravenous antibiotics. For non-purulent severe cellulitis, IV options that target streptococcus and standard staph include first-generation cephalosporins. When MRSA risk factors are present, vancomycin given intravenously is the most common choice.
Once the infection starts improving on IV therapy, doctors typically transition you to oral antibiotics to finish the course at home. If you were started on IV vancomycin for suspected MRSA, the oral switch is usually to trimethoprim-sulfamethoxazole or clindamycin.
How Long Treatment Lasts
The CDC recommends five days of antibiotics for most cellulitis cases. This is shorter than many people expect, but a meta-analysis of eight trials involving nearly 1,500 adults found no difference in cure rates between five-to-six-day courses and longer ones. Finishing a short course is just as effective for uncomplicated infections.
That said, treatment can extend up to 14 days if the infection is severe, you’re immunocompromised, or your symptoms haven’t meaningfully improved by day five. Your doctor will typically reassess around the five-day mark and decide whether to extend based on how the redness and swelling are responding.
What to Expect During Treatment
Cellulitis often looks worse before it looks better. In the first 24 to 48 hours after starting antibiotics, redness can continue to spread slightly as your immune system ramps up its response. This doesn’t necessarily mean the antibiotic isn’t working. A useful trick is to draw a line around the border of the redness with a pen so you can objectively track whether it’s still expanding after two to three days.
Genuine improvement usually means the redness stops spreading, pain decreases, and any fever resolves. If after 48 to 72 hours on antibiotics you’re getting worse, with expanding redness, increasing pain, or new fever, that signals a possible need to switch antibiotics or investigate whether there’s an underlying abscess that needs drainage. An abscess won’t resolve with antibiotics alone and requires a procedure to drain the pus.
Residual redness and mild swelling can linger for days or even a couple of weeks after the infection itself is cleared, especially on the lower legs where circulation is slower. This lingering discoloration is not a sign of treatment failure as long as tenderness, warmth, and fever have resolved.