“We used to say nine out of 10 people who report a penicillin allergy are skin-test negative. Now it looks more like 19 out of 20,” said Dr. David Lang, president-elect of the American Academy of Allergy, Asthma and Immunology and chairman of allergy and immunology in the respiratory institute at the Cleveland Clinic.

Patients can get mislabeled as allergic to penicillin in a number of different ways. They may experience bad drug reactions like headaches, nausea or diarrhea, which are not true allergic reactions but are misinterpreted. Alternatively, they may develop a symptom like a rash, which is indicative of a real allergic reaction but could be caused by an underlying illness and not by the drug.

And many people who have avoided penicillin for a decade or more after a true, severe allergic reaction will not experience that reaction again. “Even for those with true allergy, it can wane,” said Dr. Kimberly Blumenthal, the review’s senior author, who is an allergist and an assistant professor at Harvard Medical School. “We don’t really understand this, but once you’ve proven you’re tolerant, you go back to having the same risk as someone who never had an allergy” to penicillin.

It’s a good idea to find out if your allergy is real or not because penicillin antibiotics, which are part of a group of drugs called beta-lactam antibiotics, are among the safest and most effective treatments for many infections. Beta-lactams are the treatment of choice for Group A Streptococcus, which can cause pneumonia, toxic shock and other syndromes; Group B Strep, which causes meningitis; Staphylococcus aureus and other pathogens. Beta-lactams are used prophylactically to prevent infections during surgery, and studies have found that patients with penicillin allergies who are given second-line antibiotics before surgery had a substantially greater risk of a surgical site infection. Beta-lactams are also the first line treatment for syphilis and gonorrhea.

Substitutes like fluoroquinolones, clindamycin, vancomycin and third-generation cephalosporins are available, but they are often both less effective and more expensive, and many are broader spectrum antibiotics, which can lead to the development of resistant organisms and other side effects, experts say. Studies have shown that patients with penicillin allergies are at increased risk for developing serious infections like Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococcus.

Don’t challenge yourself to penicillin on your own, experts warn. Patients who have been told they’re allergic to penicillin should talk to their doctors, who should take a careful history and review the symptoms of the reaction.

If the past reaction to penicillin included symptoms like headache, nausea, vomiting and itching, or the diagnosis was made based on a family history of the allergy, the patient is considered low risk and may be able to take a first dose of penicillin or a related antibiotic, such as amoxicillin, under medical observation.

If the past reaction included hives, a rash, swelling or shortness of breath, patients should have penicillin skin testing, which involves a skin prick test using a small amount of penicillin reagent, followed by a second test that places the reagent under the skin if the first test is negative. If both tests are negative, the patient is unlikely to be allergic to penicillin, and an oral dose may be given under observation to confirm.