How to Prepare for Allergy Testing for Antibiotic Reactions

Many people believe they’re allergic to antibiotics-especially penicillin-because they had a rash, stomach upset, or felt dizzy after taking one years ago. But here’s the truth: penicillin allergy is often misdiagnosed. About 10% of people in the U.S. say they’re allergic, but less than 1% actually are when tested properly. That means millions are avoiding safe, effective, and cheaper antibiotics out of fear, not fact. If you’ve been told you’re allergic to penicillin or another antibiotic, getting tested isn’t just helpful-it could change how you’re treated for every infection from now on.

Why Testing Matters

If you’re labeled allergic to penicillin, doctors often switch you to broader-spectrum antibiotics like vancomycin, clindamycin, or fluoroquinolones. These drugs are more expensive, less targeted, and increase your risk of side effects and antibiotic-resistant infections. Studies show patients with unconfirmed penicillin allergies get these stronger drugs 69% more often. That adds up to nearly $6,000 extra in healthcare costs per person every year. Worse, it fuels the global crisis of antibiotic resistance.

The good news? Allergy testing for beta-lactam antibiotics like penicillin, amoxicillin, and ampicillin is accurate, safe, and widely available. When done right, a negative test result means you’re 95-98% likely not allergic. That opens the door to safer, cheaper, and more effective treatment for everything from ear infections to pneumonia.

What You Need to Do Before Testing

Preparation is the most important step-and the one most people mess up. You can’t just show up and expect accurate results. Your body needs to be free of medications that hide allergic reactions.

• Stop all first-generation antihistamines like diphenhydramine (Benadryl) and hydroxyzine at least 72 hours before your appointment.
• Stop second-generation antihistamines like cetirizine (Zyrtec), loratadine (Claritin), fexofenadine (Allegra), and levocetirizine (Xyzal) for a full 7 days. These are common in cold and allergy meds, so check labels carefully.
• If you take tricyclic antidepressants like doxepin, stop them 14 days before testing. These also block histamine and can interfere with results.
• Don’t stop blood pressure meds like beta-blockers or ACE inhibitors unless your doctor tells you to. But do tell your allergist you’re taking them. Beta-blockers can mask early signs of anaphylaxis, and ACE inhibitors can make reactions harder to treat.
• Bring a full list of every medication, supplement, and herbal product you take. Even over-the-counter stuff matters.

Missing one of these steps can lead to a false negative-meaning you’re told you’re not allergic when you actually are. That’s dangerous. Follow the rules exactly.

What Happens During the Test

Testing is done in three steps, usually over 2-3 hours. It’s done in a clinic or hospital setting where emergency equipment is on hand.

1. Skin prick test: A tiny drop of penicillin solution is placed on your skin, then the surface is lightly pricked with a small plastic device. It feels like a quick mosquito bite. No needles. No pain. If you’re allergic, a red, itchy bump will appear within 15 minutes.
2. Intradermal test: If the skin prick is negative, a small amount of the solution is injected just under the skin with a thin needle. This forms a tiny bubble. Again, redness or swelling over 3mm means a positive reaction.
3. Oral challenge: If both skin tests are negative, you’ll be given a small dose of the antibiotic-usually amoxicillin or penicillin-in pill form. You’ll be watched for 30 minutes. Then you’ll get the full dose and monitored for another 60 minutes. Most people feel nothing. A few get mild itching or a rash. Only about 1 in 1,600 people have a serious reaction.

Throughout the whole process, epinephrine, antihistamines, and breathing treatments are kept ready. But serious reactions are extremely rare. The risk of anaphylaxis during testing is about 0.06%-lower than the risk of being struck by lightning.

What the Results Mean

A positive skin test means you likely have a true IgE-mediated allergy. That means your immune system reacts quickly to the drug. You should avoid it and carry an epinephrine auto-injector if you’re at risk of future exposure.

A negative test means you’re not allergic. You can safely take penicillin and related antibiotics. Your medical records will be updated, and you’ll be able to use cheaper, more effective drugs going forward.

But here’s something many don’t know: allergies can fade. About half of people who had a severe reaction to penicillin as a child lose their allergy within 5 years. By 10 years, 80% no longer react. If you were told you were allergic years ago, retesting is worth it-even if you haven’t taken penicillin since.

What to Expect After Testing

Most people feel fine right after. Some report mild itching or redness at the test site. That’s normal and usually goes away in a few hours. If you get delayed itching or swelling 4-8 hours later, apply hydrocortisone cream. That happens in about 15% of cases.

Don’t be surprised if your doctor asks you to take a full dose of the antibiotic at home the next day. This is called a “home challenge” and is safe for low-risk patients under supervision. A recent study at UCSF showed 95% success with this method.

Real Benefits, Real Savings

One patient in Birmingham had osteomyelitis-a bone infection. She was told she was allergic to penicillin, so she was put on daptomycin, which costs $1,850 per dose. After testing proved she wasn’t allergic, she switched to penicillin at $12 a dose. Her annual antibiotic bill dropped from $67,525 to $4,380.

That’s not rare. Every time someone gets de-labeled as allergic, it saves the healthcare system an average of $5.70 for every $1 spent on testing. That’s because fewer broad-spectrum antibiotics are used, fewer infections become resistant, and hospital stays get shorter by nearly two days on average.

Who Should Get Tested?

You should consider testing if:

• You were told you’re allergic to penicillin or amoxicillin as a child
• You’ve avoided penicillin-based antibiotics for years
• You’ve had a rash after taking an antibiotic but no breathing trouble or swelling
• You’re facing surgery or an infection and need the best antibiotic
• You’re on multiple antibiotics and experiencing side effects

If you’ve had anaphylaxis, hives, or swelling with breathing trouble, you should still get tested-but only under strict supervision. Don’t assume you’re allergic forever.

What If There’s No Allergist Near You?

In rural areas or places without allergy specialists, access is still a problem. Only 17% of primary care providers follow current testing guidelines. But things are changing. Telemedicine programs are now helping patients safely complete oral challenges at home under video supervision. By 2027, 75% of U.S. hospitals are expected to have formal de-labeling programs. You might not need to travel far.

Ask your GP or pharmacist for a referral to an allergist. If they say it’s not necessary, ask them to check the 2022 AAAAI/IDSA guidelines. You have the right to accurate information about your health.

What’s Next for Testing?

Right now, skin testing is the gold standard. Blood tests for penicillin allergy are not reliable and shouldn’t be used. But a new NIH-funded project is developing a point-of-care blood test that could replace skin testing by 2028. That could make testing faster, cheaper, and available in every clinic.

For now, skin testing is your best bet. It’s safe, proven, and life-changing.