Invited Commentary <\/p>\n\n\n\n
August 7, 2023<\/p>\n\n\n\n
\nFor the birth of something new, there has to be a happening. Newton saw an apple fall; James Watt watched a kettle boil; Roentgen fogged some photographic plates. And these people knew enough to translate ordinary happenings into something new...<\/p>\n\n\n\n
Alexander Fleming<\/p>\n<\/blockquote>\n\n\n\n
Fleming changed the practice of medicine with his serendipitous discovery of penicillin in 1928. Since that time, different preparations of penicillin-based antibiotics have been developed, microbial threats have morphed, and, unfortunately, penicillin allergy has become ordinary. Upwards of 10% of outpatients and 15% of inpatients report a penicillin allergy.1<\/a><\/sup> With such an ordinary occurrence, the frequent default is use of second-line antibiotics, since this approach is often more accessible than an evaluation for penicillin allergy. Although the use of second-line antibiotics due to penicillin allergy may be an ordinary happening, it should not be mistaken as benign, or even low risk. The use of second-line antibiotics in patients with a penicillin allergy has been associated with poor individual health outcomes, including decreased cure rates, increased recurrence rates, increased adverse effects, and increased mortality.2<\/a><\/sup> It has also been associated with vital public health concerns of increased health care costs and antimicrobial resistance.2<\/a><\/sup> The admirable work by Copaescu et al3<\/a><\/sup> uses the validated Penicillin Allergy Decision Rule (PEN-FAST) tool in a randomized clinical trial comparing traditional penicillin skin testing (PST) with a direct challenge in patients reporting a penicillin allergy. This is a call to end the ordinary happening of accepting a penicillin allergy label and embrace the something new of delabeling low-risk patients with a direct challenge. It also serves as a firm evidence base for health care clinicians outside the allergy\/immunology purview to embrace this change in appropriate settings with the necessary clinical training.<\/a><\/p>\n\n\n\n
In their work, Copaescu et al3<\/a><\/sup> used the PEN-FAST tool to identify patients at low risk for a reaction to penicillin (PEN FAST score of <3) and randomized these patients to undergo PST (control group) or a direct challenge (intervention group). The primary end point of this multicenter, international study was a positive oral challenge to penicillin. A direct challenge to penicillin without previous skin testing was demonstrated to be noninferior to PST, with 1 of 187 (0.5%) of the intervention group and 1 of 190 (0.5%) in the control group experiencing a positive challenge, with a risk difference of 0.0084% (90% CI, \u22121.22% to 1.24%). The analysis also demonstrated that direct challenge took less time and carried a similar safety and efficacy profile compared with PST. Although a previous randomized clinical trial had similar findings,4<\/a><\/sup> the present study is superior based on its larger sample size, use of a validated screening tool, and multicenter and multinational enrollment. As stated by Copaescu et al3<\/a><\/sup> in the Discussion of their article, the recent drug allergy practice parameters recommend considering a direct challenge in adults, but this was a conditional recommendation with low-quality evidence.2<\/a><\/sup> The current study should be practice changing to move to direct challenges in low-risk adults in place of PST, thus allowing more penicillin allergy evaluations to completed by clinicians not specialized in allergy\/immunology.<\/a><\/p>\n\n\n\n
The PEN-FAST tool is a distinct advantage of this study and prime for uptake among health care professionals less experienced with penicillin allergy evaluations. It is known that penicillin allergy knowledge in health care professionals is lacking,5<\/a><\/sup> but with only approximately 3400 practicing allergy\/immunology physicians in the US,6<\/a><\/sup>it is impossible to combat penicillin allergy through allergy\/immunology channels alone. The PEN-FAST has been validated in multiple studies,7<\/a><\/sup>,8<\/a><\/sup> so it has essentially been preapproved by experts in drug allergies, and its accessibility and ease of use obviates concern about lack of knowledge among health care professionals. It is already available in online medical calculators and could be used in clinical decision support in electronic records.<\/a><\/p>\n\n\n\n
The inpatient setting is an optimal area to institute direct challenges guided by PEN-FAST outside of expert supervision. This setting has the best evidence for optimizing antibiotic use, decreasing adverse effects, and containing costs with delabeling of penicillin allergy.2<\/a><\/sup> Further, hospitalized patients have time to undergo challenges and have a baseline level of supervision. Given the reassuring safety data provided in this study,3<\/a><\/sup> a higher level of care or 1:1 nursing is not required to institute this change. In addition to general medical inpatients, other inpatient groups for which penicillin allergy would be beneficial, including transplant, hematology\/oncology, and surgical patients, can be targeted for direct challenges.<\/a><\/p>\n\n\n\n
The data provided in the PALACE study are exciting, but their use may not be feasible in certain settings, such as busy outpatient internal medicine or family practice offices. The infrastructure of shorter office visits for patients with multiple comorbidities may not lend itself to elective challenges. While there are some data for penicillin allergy delabeling in the emergency department, the unpredictable environment with overcrowding is also not optimal to approach penicillin allergy systematically. Further caveats with the PALACE study data were that most patients had a PEN-FAST score of 1 or 2, so it is unknown if a score of 3 confers any additional risk compared with PST, and most of the patients included in the study were White, so generalizability among different racial and ethnic minority groups is also unknown.<\/a><\/p>\n\n\n\n