Dr. Conway McLean, Journal columnist

Joan was a college athlete, playing on her school’s varsity soccer team, a nationally ranked program. She had aspirations of going on in the sport and competing at a higher level. Until, that is, she tore her ACL, that vital knee ligament, which necessitated surgical repair. Because her parents said she was allergic to penicillin, she was given a different antibiotic as part of her peri-operative antibiotic regimen. This drug, a broad spectrum antibiotic, is frequently prescribed for those with an allergy to penicillin-type drugs. Unfortunately for Joan, she developed a C. difficile GI infection as a result of the antibiotic.

Although they are considered relatively benign medications, antibiotics can have dangerous consequences. Joan’s condition was due to an imbalance in her gut bacteria, a critically important part of health. This can be a potentially serious result of various broad spectrum drugs, reducing many different kinds of bugs, some harmful and others beneficial. Joan required prolonged hospitalization, critically delaying the rehabilitation of her knee. This delay knocked her out of the competition for a position with the national team, and she was never able to reach that level of fitness and skill.

An important question here, dear reader, which you may have asked yourself, was Joan actually allergic to penicillin? How often is this claim accurate? And how many are injured or harmed in some fashion due to inaccurate reporting of an allergy to this common and beneficial pharmaceutical agent? These are critical questions to which definitive answers are needed.

Being labeled penicillin-allergic is extremely common, although typically these claims are unsubstantiated. Current estimates claim 8% to 25% of the global population believes they are penicillin allergic. Shockingly, the available evidence indicates 90%-99% of those individuals with a reported penicillin allergy are not truly allergic. Most diagnoses of penicillin allergy are made in childhood and relate to events that are not allergic in nature.

Commonly, a child will be prescribed a penicillin-type medication and sometime thereafter, will suffer some mild medical event, be it a rash, upset stomach, or other completely unrelated condition. Too often, some health care worker, family member, or friend will utter the critical phrase “they must be allergic to penicillin!” The damage is done, the label applied. No testing is typically done, the individual henceforth will believe they are indeed allergic to the drug.

Many assume there is little harm as a result of this misdiagnosis. The solution is simple: give a different antibiotic. But this often results in various negative, dangerous consequences. The dangers of resistant bacteria due to inappropriate use of antibiotics are real and growing. Most surgery patients reporting a penicillin allergy receive second-line antibiotic prophylactically, which raises concerns about antimicrobial effectiveness. Other risks include an increase in healthcare-associated infections, including increased odds of a secondary C. diff infection (aka Clostridium difficile). Also resulting from the use of less than optimal antimicrobials is an increased risk of getting a MRSA or some other drug-resistant infection.

Penicillin allergy labels directly impact antimicrobial stewardship, the responsible and appropriate use of antibiotics. They cause the use of less effective and broader spectrum antimicrobials and are thus associated with the development of resistant bacteria. Patients with a reported penicillin allergy had a 50% increase in the risk of developing a surgical site infection, attributable to the receipt of second-line antibiotics before some surgery.

Some might question how common this phenomenon is. Many studies declare 98% of penicillin-allergy labels are incorrect when tested. Unfortunately, because of the scarcity of trained allergists in American healthcare, only a minority of surgical patients have the opportunity to undergo testing before surgery. Various testing protocols exist, but are rarely utilized in this scenario. One suggestion is to provide appropriate training to various healthcare professionals so that they can, in collaboration with allergists, provide testing for selected patients.

Penicillin belongs to an important class of drugs called the beta-lactam antibiotics. These are generally very effective at eradicating many common bacterial infections and are relatively inexpensive. Thus, they are widely used to treat skin, ear, sinus and upper respiratory tract infections. There are numerous examples of this class of drug including penicillin derivatives such as ampicillin and amoxicillin, as well as cephalosporins, monobactams, and carbapenems. As with nearly all drugs, penicillin-type medications can result in some common side effects. However, a true drug allergy accounts for very few of all the reported adverse drug reactions. Although a myth persists that approximately 10% of patients with a history of penicillin allergy will have an allergic reaction if given a cephalosporin, the overall cross-reactivity rate is approximately 1% when using first-generation cephalosporins.

For those individuals who are truly penicillin-allergic, the potential repercussions can be significant, with the determining factor being the type of allergy. The development of a rash is common, but this type of reaction produces little in the way of a response other than some itching. People reporting thrush, a fungal infection of the mouth, with penicillin use are easily designated as having a low (or indeed no) risk above the general population. The real danger is when an anaphylactic reaction occurs.

Hypersensitivity reactions are a serious problem in the use of these drugs, although the estimated frequency of anaphylaxis is quite low, between 1 and 5 per 10 000 cases of penicillin therapy. This equates to about one-hundredth of one percent chance someone will have this emergent condition. This type of hypersensitivity reaction is clearly the most dangerous adverse event. This can result in various complications including nausea, vomiting, itching, wheezing, swelling of the throat and ultimately, cardiovascular collapse, often a fatal development.

Clarification of penicillin allergies as part of routine preoperative care would go a long way to decrease the risk of post-operative infections. But there is no accepted consensus in the literature on how to group patients into different levels of risk. Patients who give a clear history of anaphylaxis or severe cutaneous reactions are easily categorized as being at high risk. Yet, there are numerous cases where the situation is not so clearly defined, especially the intermediate reaction, which is eminently harder to classify. Far too common, and impossible to define, is the prototypical history of ‘no recollection of the event’.

The identification of patients who truly carry this type of allergy will invariably lead to improved utilization of antibiotics, thus slowing the spread of drug-resistant bacteria. We need to review how patients are assessed and defined as ‘ALLERGIC’. What are the best testing strategies? What should the minimum standards of safe testing be? Once again, our medico-legal system has failed to adequately answer these questions. These are important, both from the perspective of inappropriate antibiotic use, and the rare but potentially-fatal anaphylactic reaction. Better answers are needed; lives hang in the balance.

Editor’s note: Dr. Conway McLean is a physician practicing foot and ankle medicine in the Upper Peninsula, with a move of his Marquette office to the downtown area. McLean has lectured internationally on wound care and surgery, being double board certified in surgery, and also in wound care. He has a sub-specialty in foot-ankle orthotics. Dr. McLean welcomes questions or comments atdrcmclean@outlook.com.