Penicillin 'Allergy' History May Be Inaccurate and Costly

Penicillin "allergy" history is often inaccurate. Still, it is linked to more extended hospital stays, significantly more antibiotic use, and increased prevalence of Clostridium Difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) infections, according to a retrospective, matched cohort study published in the March issue of the Journal of Allergy and Clinical Immunology.

"It is important to know if you are allergic to penicillin," lead author Eric Macy, MD, from the Southern California Permanente Medical Group, Department of Allergy, San Diego Medical Center, said in a news release. "This medical history detail impacts not only critical health care decisions, but it greatly impacts cost."

The study's cohort consisted of patients admitted to Kaiser Foundation hospitals in Southern California between 2010 and 2012. The investigators matched two unique control patients to each of 51,582 (99.6% of all possible cases) unique hospitalized subjects with penicillin allergy. Matching was by discharge diagnosis category, sex, age, and admission date. The mean duration of follow-up was 20.1 ± 10.5 months, and 11.2% of patients admitted had a history of penicillin allergy.

"[This study] is a great piece of work regarding drug allergy in the general population and underscores the importance of allergy evaluation for all patients with a label of penicillin allergy," Mariana Castells, MD, PhD, director of the Drug Hypersensitivity and Desensitization Center and the Allergy Immunology Training Program and associate director of the Mastocytosis Center at Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, told Medscape Medical News when asked for independent comment. "Labeling patients as penicillin-allergic is a risk factor for increased antibiotic utilization, resource utilization, and complications."

Compared with control patients, patients with penicillin allergy had an average of 0.59 more total hospital days during follow-up (9.9%; 95% confidence interval [CI], 0.47 - 0.71), and they received significantly more fluoroquinolones, clindamycin, and vancomycin (P < .0001 for each). Compared with control patients, patients with penicillin allergy also had more resistant infections during follow-up: 23.4% more C difficile (95% CI, 15.6% - 31.7%), 14.1% more MRSA (95% CI, 7.1% - 21.6%), and 30.1% more VRE (95% CI, 12.5% - 50.4%).

"In the hospital setting, we found [that history of penicillin allergy] translates to about 10% more hospital days and significantly more [C difficile, MRSA, and VRE] infections," Dr. Macy said in the release. "These adverse events occur because penicillin 'allergic' patients are given more broad-spectrum antibiotics, including ciprofloxacin, vancomycin, clindamycin, and third or greater generation cephalosporins. Previous work by our group has shown [that] less than 5% of individuals with a history of penicillin 'allergy' are truly allergic."

Accurate Diagnosis of Penicillin Allergy

Of 30 million US patients reported to be penicillin-allergic, an estimated 28.5 million are not, according to the news release, meaning that up to 19 of 20 patients who think they are allergic to penicillin are misinformed. Overreporting of penicillin allergy may increase medical costs for patients and healthcare systems, as antibiotic costs for patients reporting penicillin allergies are up to 63% higher than for those who do not report being penicillin-allergic.

How can clinicians distinguish true penicillin allergy from nonspecific or vague allergic symptoms?

"By seeking an allergy consultation and having a skin test done with the appropriate major and minor penicillin reagents and controls (penicillin, Pre-Pen, and [minor determinant mixture])," Dr. Castells said. "In terms of further research, patients presenting with reactions to penicillin and beta-lactams should be evaluated by skin testing with appropriate reagents (penicillin, Pre-Pen, and [minor determinant mixture]) in a prospective fashion, and a decrease in antibiotics utilization, costs, and complications should be evaluated. "

Testing for penicillin allergy may result in cost savings, improved patient care, and fewer drug-resistant bacteria.

According to Dr. Castells, this study's main strength is its access to a large patient population and matching with controls. Limitations include the inability to categorize penicillin allergy by clinical symptoms (anaphylactic or type 1 vs. type 4) or confirm it by skin testing.

"The label of penicillin allergy can include non-life-threatening rashes (type 4 reaction) [and] life-threatening reactions (hives, shortness of breath, throat tightening, anaphylaxis, all type 1, [immunoglobulin E]/mediated reactions), idiosyncratic reactions (kidney failure), or other less severe reactions (gastric upset)," Dr. Castells concluded. "Some patients are labeled as allergic since they were told they had reactions as infants, but the reactions were not recorded."

Potential Cost-Savings

The investigators present calculations regarding potential cost savings. The estimated cost of performing penicillin skin testing on the 51,582 subjects with penicillin allergy would be approximately $6.8 million, according to an accompanying editorial by Roland Solensky, MD, from the Corvallis Clinic in Oregon, but reducing the hospital stay by 0.59 days per patient would save $64.6 million.

"Most importantly, the cost analysis is based on a single patient encounter, whereas the cost throughout a patient's life, with multiple encounters and antibiotic prescriptions, would likely yield much larger cost differences," Dr. Solensky writes.

"An important and underappreciated aspect of penicillin allergy [is] the morbidity, mortality, and economic costs associated with the unnecessary withholding of appropriate therapy in a large number of patients mistakenly labeled as having penicillin allergy.... The public health implications of penicillin allergy are enormous, and it is clearer than ever that penicillin skin testing should play an important role in improving appropriate use of antibiotic therapy."

The Kaiser Permanente Health Care Program and ALK-Abelló supported this study. Dr. Macy reported receiving research support from ALK-Abelló and consultancy fees from Biomarin. His coauthor has reported receiving research support from ALK-Abelló. Dr. Castells has disclosed no relevant financial relationships. Dr. Solensky has received research support from Allerquest and Merck, has received consultant fees from Optimer Pharmaceuticals, is employed by the Corvallis Clinic, and has provided expert testimony.

Laurie Barclay, MD March 13, 2014
J Allergy Clin Immunol. 2014; 133:790-798