Arroliga, M. E., A. Vazquez-Sandoval, J. Dvoracek and A. C. Arroliga (2016). “Penicillin skin testing is a safe method to guide beta-lactam administration in the intensive care unit.” Ann Allergy Asthma Immunol 116(1): 86-87.
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Geng et al. analyzed factors associated with negative histamine control reactions in patients evaluated with a penicillin skin test (PST) for allergy to β-lactams. In a case–control study of 52 patients with a negative response and 125 controls with a normal response, they used histamine dihydrochloride at a concentration of 6 mg/mL for prick or puncture skin testing but did not perform intradermal testing.1 Admission to an intensive care unit (ICU), older age, and treatment with systemic steroids and H2 blockers were associated with negative histamine responses. Geng et al1 cited our work and suggested that it was difficult to assess the precise risk of a negative histamine response during skin testing in the ICU owing to the heterogeneity of conditions, comorbidities, and medications. The response to histamine is influenced by many factors, including but not limited to age, sex, reactivity to allergens, and photoaging of the skin. Histamine response decreases with aging (>65 years), particularly in women. Patients with multiple allergen sensitizations as indicated by multiple positive skin test responses tend to have larger histamine wheals. Medications such as H2 blockers and photoaging are associated with a weaker response to histamine. These factors might be of importance in the study by Geng et al. because there were differences in age between patients with negative histamine responses and controls. Patients with negative histamine responses were older than the patients in our cohorts. There are many differences besides age between our reports and the report of Geng et al. Geng et al. did not use intradermal testing owing to concerns of subjecting patients to a higher risk of exposure to intradermal antibiotics that could lead to anaphylaxis. All our patients underwent intradermal testing as part of our PST protocol. The PST is safe provided that strict protocols are followed. Intradermal testing must be preceded by a negative prick or puncture test reaction to increase safety. Intradermal tests have higher sensitivity than prick or puncture tests when testing for penicillin allergy. Positive responses are those that have a wheal of at least 5 mm in diameter and a flare larger than the wheal with a negative response to the control saline solution and a positive response to histamine. Our studies dealt with the questions of whether patients with a history of penicillin allergy admitted to an ICU could take penicillins safely. In a cohort of 596 patients of whom 300 were admitted to the ward and 145 to the ICU, the PST was safe and helped to guide the administration of β-lactams. The PST response was negative in 88%, positive in 8%, and indeterminate (negative histamine response) in 3.4%. Most of our positive results were with PrePen intradermal injection (36 of 49) and only 0.17% of patients developed an urticarial reaction after an intradermal PST. From 39%4 to 57%9 were challenged safely with a β-lactam (the percentage of patients challenged in the ICU was 70%) with a negative predictive value for an IgE-mediated event of 99.3%. Two of 290 patients had a reaction that included flushing and urticarial and a pruritic rash within 12 hours of administration of a β-lactam. Although we did not do it in our studies, current recommendations include the administration of a single oral dose of amoxicillin to confirm adequate tolerance after a negative PST response. The PST adequately performed in patients labeled allergic to penicillins could have an important impact from the public health point of view. Patients labeled as allergic to penicillins or first-generation cephalosporins without formal evaluation have more hospital use and have increased rates of infections with Clostridium difficile, vancomycin-resistant Enterococcus species, and methicillin-resistant Staphylococcus aureus. In patients with life-threatening infections, such as methicillin-sensitive S aureus, allergy evaluation with a history-appropriate PST is preferred. In summary, the PST is safe and a very useful tool in the management of the ambulatory and hospitalized patient with a history of penicillin allergy, including the critically ill. Allergists and immunologists working together with infectious diseases specialists and critical care physicians are in a unique position to help make the correct diagnosis. Making the correct diagnosis will have financial and epidemiologic consequences for the patient and for the entire health care system.