TY - JOUR
T1 - The Immediate and Delayed Maximal Nonirritating Skin Testing Concentrations of β-Lactam Antibiotics
AU - Gonzalez-Estrada, Alexei
AU - Carrillo-Martin, Ismael
AU - Garzon-Siatoya, W. Tatiana
AU - Joundi, Hajara
AU - Morgenstern-Kaplan, Dan
AU - Renew, J. Ross
AU - Powers, H. Ross
AU - Nelson, Jared D.
AU - Bosch, Wendelyn
AU - Epps, Kevin L.
AU - Gonzalez-Estrada, Aurora
AU - Kinate, Susan
AU - Rank, Matthew A.
AU - Rukasin, Christine R.F.
AU - Volcheck, Gerald W.
AU - Park, Miguel
N1 - Publisher Copyright:
© 2024 American Academy of Allergy, Asthma & Immunology
PY - 2024/11
Y1 - 2024/11
N2 - Background: Maximal skin testing (ST) nonirritant concentrations (NICs) are consistent for penicillin and aminopenicillin among guidelines. However, there is variability among guidelines for maximal ST NICs of cephalosporins. Objective: To determine maximal immediate and delayed ST NICs of 15 β-lactams in β-lactam-tolerant and β-lactam-naïve participants. Methods: We performed a single-center, nonrandomized prospective study between September 2019 and January 2022 in adult participants. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at 6 increasing concentrations of 1 or more β-lactams. A concentration was considered irritant when more than 5% of participants had a positive test. A positive test was defined as a wheal ≥3 mm compared with negative control accompanied by a ≥5 mm flare for SPT/IDT and induration ≥5 mm with associated erythema at 48 hours for delayed readings (dIDT). Sensitivity analyses using 3 alternative IDT positive criteria were conducted. Results: A total of 747 participants with a median age of 64 (interquartile range: 54-72) years (52% male, 85% White, and 92% non-Hispanic) underwent 20,858 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT/dIDT NICs (mg/mL): ampicillin (41.6/125), ampicillin-sulbactam (93.8/187.5), aztreonam (6.3/25), cefazolin (55/165), cefepime (35/140), cefoxitin (45/90), ceftaroline (7.5/15), ceftriaxone (58.3/175), cefuroxime (55/110), ertapenem (16.6/50), imipenem-cilastin (6.3/25), meropenem (8.3/25), nafcillin (31.3/62.5), oxacillin (20.9/83.5), and piperacillin-tazobactam (112.5/225). dIDTs were almost all completely nonirritant close to or at undiluted concentrations. There were no differences when we applied 3 IDT positivity criteria to our raw data. Conclusions: Our results suggest that SPTs with undiluted stock β-lactam antibiotic concentrations are nonirritant. Compared with previously published nonirritant concentrations, we propose a 2- to 50-fold increase to the maximal IDT and dIDT NICs of 15 β-lactam antibiotics. When performing dIDTs, a higher concentration should be used rather than the same IDT concentration.
AB - Background: Maximal skin testing (ST) nonirritant concentrations (NICs) are consistent for penicillin and aminopenicillin among guidelines. However, there is variability among guidelines for maximal ST NICs of cephalosporins. Objective: To determine maximal immediate and delayed ST NICs of 15 β-lactams in β-lactam-tolerant and β-lactam-naïve participants. Methods: We performed a single-center, nonrandomized prospective study between September 2019 and January 2022 in adult participants. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at 6 increasing concentrations of 1 or more β-lactams. A concentration was considered irritant when more than 5% of participants had a positive test. A positive test was defined as a wheal ≥3 mm compared with negative control accompanied by a ≥5 mm flare for SPT/IDT and induration ≥5 mm with associated erythema at 48 hours for delayed readings (dIDT). Sensitivity analyses using 3 alternative IDT positive criteria were conducted. Results: A total of 747 participants with a median age of 64 (interquartile range: 54-72) years (52% male, 85% White, and 92% non-Hispanic) underwent 20,858 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT/dIDT NICs (mg/mL): ampicillin (41.6/125), ampicillin-sulbactam (93.8/187.5), aztreonam (6.3/25), cefazolin (55/165), cefepime (35/140), cefoxitin (45/90), ceftaroline (7.5/15), ceftriaxone (58.3/175), cefuroxime (55/110), ertapenem (16.6/50), imipenem-cilastin (6.3/25), meropenem (8.3/25), nafcillin (31.3/62.5), oxacillin (20.9/83.5), and piperacillin-tazobactam (112.5/225). dIDTs were almost all completely nonirritant close to or at undiluted concentrations. There were no differences when we applied 3 IDT positivity criteria to our raw data. Conclusions: Our results suggest that SPTs with undiluted stock β-lactam antibiotic concentrations are nonirritant. Compared with previously published nonirritant concentrations, we propose a 2- to 50-fold increase to the maximal IDT and dIDT NICs of 15 β-lactam antibiotics. When performing dIDTs, a higher concentration should be used rather than the same IDT concentration.
KW - Ampicillin
KW - Ampicillin-sulbactam
KW - Antibacterial agents
KW - Aztreonam
KW - Cefazolin
KW - Cefepime
KW - Cefoxitin
KW - Ceftaroline
KW - Cefuroxime
KW - Delayed intradermal readings
KW - Drug hypersensitivity
KW - Ertapenem
KW - Imipenem-cilastin
KW - Intradermal testing
KW - Meropenem
KW - Nafcillin
KW - Nonirritant concentrations
KW - Oxacillin
KW - Penicillin hypersensitivity
KW - Piperacillin-tazobactam
KW - Prick testing
KW - Skin testing
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U2 - 10.1016/j.jaip.2024.07.022
DO - 10.1016/j.jaip.2024.07.022
M3 - Article
C2 - 39089437
AN - SCOPUS:85202480003
SN - 2213-2198
VL - 12
SP - 3016-3024.e14
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 11
ER -