Don’t overlook penicillin to combat antimicrobial resistance

Ninety-one years ago, on Sept. 28, Alexander Fleming, a young bacteriologist, discovered penicillin, forever changing the health-care landscape and dramatically improving our ability to treat common and lesser common infections. 

The introduction of penicillin saved many lives during World War II by combating infections in wound and burn victims more successfully and opened the door for further discovery — encouraging improved outcomes of surgical procedures and fostering innovation leading to our ability to perform organ transplantation. 

This arc of transformation in modern medicine has now given way to an era of uncertainty where antibiotic resistance is rendering increasing numbers of infections difficult or even impossible to treat. These infections lead to longer hospital stays, increased health care costs, greater suffering, and even death. This surge in resistance has been associated with the overuse and misuse of antimicrobial drugs, and it is a complex problem that requires a multi-faceted solution.

Ironically, one of the primary ways to combat antimicrobial resistance begins with penicillin. Penicillin is the most commonly reported drug allergy. Approximately 10 percent of the U.S. population report being allergic to penicillin, yet 9 out of 10 patients reporting a penicillin allergy are not truly allergic when formally evaluated, such that fewer than one percent of the population is truly allergic to penicillin. 

Successful antimicrobial stewardship is undermined when a reported allergy to penicillin leads to the use of broad-spectrum non-penicillin antibiotics that increase the risk of resistance and adverse events. 

The Centers for Disease Control and Prevention (CDC) recently cited the importance of correctly identifying if patients are penicillin-allergic in decreasing the unnecessary use of broad-spectrum antibiotics in its 2018 update of Antibiotic Use in the United States: Progress and Opportunities. 

Over-diagnosis of penicillin allergy adversely impacts medical costs for both patients and health care systems. Antibiotic costs for patients reporting penicillin allergy are up to 63 percent higher than for those who do not report being penicillin-allergic. Additionally, patients labeled penicillin-allergic may have a threefold increased risk of adverse drug events. 

In the hospital setting, having penicillin allergy listed in the medical record translates to approximately 10 percent more hospital days, 30 percent higher incidence of Vancomycin-resistant enterococci (VRE) infections, 23 percent higher incidence of C difficile infections, and 14 percent higher incidence of Methicillin-resistant Staphylococcus aureus (MRSA) infections. 

This increased morbidity can be prevented by appropriate evaluation to “de-label” the overwhelming majority of these patients (greater than 90 percent) and permit administration of penicillins when a member of this group of antibiotics is the most appropriate agent.

Recent studies have confirmed that correctly identifying those who are not actually penicillin allergic improves antibiotic prescribing and helps combat the risk of “super-bugs” by allowing patients access to safer, less toxic penicillin antibiotics. 

By some estimates, up to half of all hospitalized patients in the U.S. receive antibiotics, and up to half of antimicrobial use may be inappropriate. There is a causal relationship between inappropriate antimicrobial use and resistance; changes in antimicrobial use can encourage parallel changes in the prevalence of resistance.

The American Academy of Allergy, Asthma, & Immunology strongly supports more widespread and routine use of penicillin skin testing for patients with a self-reported history of allergy to penicillin. This testing can accurately identify the approximately 9 of 10 patients who, despite reporting a history of penicillin allergy, can safely receive penicillin. 

The growing threat of antimicrobial resistance, combined with the dwindling pipeline of novel antibiotic research, requires policies that prevent inappropriate use of antibiotics, and penicillin allergy testing should be considered an essential component of existing efforts to address this ominous threat to public health. 

The U.S. Department of Health and Human Services must do more to educate the public and health care providers regarding the importance of penicillin allergy testing and protect patient access to the medical advancements made possible by Alexander Fleming’s revolutionary discovery almost a century ago.

David M. Lang, M.D., is president of the American Academy of Allergy, Asthma & Immunology (AAAAI), chairman of the Department of Allergy and Clinical Immunology, co-director of the Asthma Center, and director of the Allergy/Immunology Fellowship Training Program in the Respiratory Institute at the Cleveland Clinic.