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It could, and you should apply it to the burn, but in case of a large second degree burn, it's recommended you go immediately to see a doctor.

It's actually not a good idea to apply the triple antibiotic at all on serious burns, not because it won't work as effectively on large and serious burns such as a 2nd degree burn but it's a topical and you don't want those antibiotics to get in your system which applying to the burn will do. The antibiotics are not good to have in the system at all which is why it's also not recommended for large or deep cuts that go into the dermis. You definitely need to go see a doctor so they can prescribe a prescription that won't interfere or react to being in your system. The most commonly prescribed burn cream is called Silvadene and it has a generic on the market so it's relatively cheap.

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Q: Can triple antibiotic prevent a large second degree burn infection?
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