How to Prepare for Allergy Testing for Antibiotic Reactions

If you’ve been told you’re allergic to penicillin or another antibiotic, you’re not alone. About 10% of people in the U.S. say they have an antibiotic allergy. But here’s the surprising part: less than 1% of those people are actually allergic when tested properly. Most of the time, what was once labeled as an allergy turned out to be a side effect, a rash from a virus, or just a misdiagnosis years ago. The problem? That label sticks. And it leads to worse outcomes - not better ones.

Why Getting Tested Matters

When doctors think you’re allergic to penicillin, they avoid it. Instead, they give you stronger, more expensive antibiotics like vancomycin, clindamycin, or daptomycin. These drugs cost up to 150 times more. They also increase your risk of dangerous infections like C. diff, which can land you back in the hospital. Studies show people with unconfirmed penicillin allergies stay in the hospital nearly two days longer on average. They’re also more likely to develop antibiotic-resistant infections.

Getting tested isn’t just about avoiding a rash. It’s about getting the right treatment, saving money, and protecting your long-term health. If you’ve ever had a reaction to an antibiotic - even if it was years ago - you should consider testing. Especially if you’ve been told you’re allergic but never saw an allergist.

What You Need to Do Before Your Appointment

Preparation is everything. If you don’t stop the right medications ahead of time, your test results could be wrong. That means you might be told you’re still allergic when you’re not - or worse, you could miss a real allergy.

Stop antihistamines. This is the most common mistake. Over-the-counter drugs like Benadryl, Zyrtec, Claritin, and Allegra block the body’s allergic response. That means they can hide a true reaction during testing. You need to stop them well in advance:

• First-generation antihistamines (Benadryl, hydroxyzine): Stop at least 72 hours before testing.
• Second-generation antihistamines (Zyrtec, Claritin, Allegra, Xyzal): Stop 7 full days before.
• Tricyclic antidepressants like doxepin: Stop 14 days before. These have strong antihistamine effects and are easy to overlook.

Don’t assume your doctor will remind you. Write down every medication you take - even supplements - and bring the list to your appointment. Some blood pressure medications, like ACE inhibitors, can make an allergic reaction harder to treat. Your allergist needs to know about those too.

What Happens During the Test

Allergy testing for antibiotics follows a clear, safe, step-by-step process. It’s not scary - and it’s not painful.

Step 1: Skin Prick Test
A tiny drop of penicillin solution is placed on your skin, then gently pricked with a small plastic device. It feels like a light scratch. No needles. No blood. If you’re allergic, a small red bump will appear within 15 minutes - like a mosquito bite that itches. If nothing happens, you move to the next step.

Step 2: Intradermal Test
If the skin prick is negative, a small amount of the antibiotic is injected just under the skin. This creates a tiny bubble (a bleb). Again, if you’re allergic, redness or swelling larger than 3mm will form within 15 minutes. This step is more sensitive than the skin prick and catches reactions the first test might miss.

Step 3: Oral Challenge (If Needed)
If both skin tests are negative, you’ll get a small dose of the antibiotic by mouth - usually 10% of a regular pill. You’ll be watched for 30 minutes. Then you’ll take the full dose and be monitored for another 60 minutes. Most people feel nothing. Some get a mild stomach upset or a little itching. That doesn’t mean you’re allergic. Doctors know how to tell the difference.

The risk of a serious reaction during testing is extremely low - about 0.06%. That’s less than 1 in 1,000. The clinic will have epinephrine, oxygen, and other emergency tools ready. You’re safer during the test than you are taking the wrong antibiotic for weeks.

What the Results Mean

A negative test means you’re not allergic. That’s it. No more labels. You can take penicillin safely. You’ll be able to use cheaper, more effective antibiotics in the future. Your doctor can stop avoiding penicillin when you’re sick.

A positive test means you likely have a true allergy. You’ll get a plan to avoid that drug and carry an epinephrine auto-injector if needed. But here’s the hopeful part: most people outgrow their antibiotic allergy. About half of people who had a severe reaction to penicillin lose their allergy within five years. Eighty percent lose it within ten. That means even if you tested positive years ago, you might be safe to test again now.

Some people get delayed reactions - itching or redness at the test site 4 to 8 hours later. That’s common (about 15% of cases) and usually mild. Over-the-counter hydrocortisone cream helps. It doesn’t mean you’re allergic to the drug. It’s just your skin reacting to the test.

What to Expect After Testing

If you’re cleared, your allergist will give you a letter to give your doctor. You’ll be taken off the allergy list in your medical records. That’s huge. It means next time you have an infection - a sinus infection, pneumonia, or even a simple ear infection - your doctor can pick the best, safest, cheapest antibiotic.

One patient in Boston had osteomyelitis. For months, she was on daptomycin - $1,850 per dose. After testing, she switched to penicillin - $12 per dose. Her annual cost dropped from over $67,000 to less than $5,000. That’s not just money. That’s peace of mind.

If you’re still allergic, you’ll get a plan. You’ll learn how to recognize symptoms, when to use epinephrine, and what antibiotics to avoid. You’ll also know that alternatives exist - and that your allergy doesn’t mean you’re out of options.

Why So Few People Get Tested

You’d think this would be routine. But only 17% of primary care doctors follow the guidelines. Why? Access. There aren’t enough allergists. In 63% of rural U.S. counties, there’s not a single allergy specialist. Many clinics don’t have the equipment or training to do the test safely.

But things are changing. New research shows that with proper supervision, low-risk patients can safely do the oral challenge at home. A pilot program at UCSF had a 95% success rate. That could bring testing to places that never had it before.

By 2027, 75% of U.S. hospitals are expected to have formal programs to remove false antibiotic allergy labels. That’s up from just 42% in 2023. Every test done saves money, prevents resistance, and saves lives.

Next Steps: What to Do Now

If you’ve been told you’re allergic to penicillin or another antibiotic:

1. Check your medical records. Is the allergy clearly documented? What was the reaction? (Rash? Swelling? Trouble breathing?)
2. Stop taking antihistamines at least 7 days before your appointment. Write down every medication you take.
3. Ask your primary care doctor for a referral to an allergist. Say: “I’d like to be tested for a possible penicillin allergy.”
4. Bring your list of medications and any past reaction details.
5. After testing, get a written report and ask your doctor to update your records.

You don’t need to live with a label that might be wrong. You don’t need to pay more for antibiotics. You don’t need to risk a worse infection. Testing is safe, accurate, and life-changing. And it’s available - you just have to ask.