Outcome of a de-labelling algorithm compared with results of penicillin (ß-lactam) allergy testing.

BACKGROUND: Penicillin allergy labels frequently impede guideline-directed treatment with a penicillin or other ß-lactam antibiotics. Despite presumed allergy, targeted questioning may indicate a low probability of sensitization and permit reasonably safe administration of the antibiotic in question. In this study, we evaluated a standardized algorithm aiming to differentiate non-allergic patients from those with true allergic ß-lactam hypersensitivity. METHODS: We retrospectively applied a de-labelling algorithm in 800 consecutive patients with suspected ß-lactam hypersensitivity. All had undergone complete allergy work-up permitting to definitely exclude or diagnose ß-lactam allergy between 2009 and 2019. RESULTS: In 595 (74.4%) out of 800 cases evaluated, ß-lactam allergy could be excluded by negative challenge testing. IgE-mediated anaphylaxis was diagnosed in 70 (8.7%) patients, delayed-type hypersensitivity in 135 (16.9%). In 62 (88.6%) anaphylaxis cases, the algorithm correctly advised to use an alternative antibiotic. Accuracy was higher in patients with moderate to severe anaphylaxis (97.7%) compared to those with a history of mild reactions (73.1%). The algorithm correctly identified 122 (90.4%) patients with proven delayed-type hypersensitivity. It permitted de-labelling in 330 (55.5%) out of 595 patients with diagnostic exclusion of penicillin hypersensitivity, but failed to identify the remaining 265 (44.5%) as low-risk cases. CONCLUSIONS: The algorithm detected 89.8% of cases with penicillin (ß-lactam) allergy, sensitivity was optimal for moderate to severe anaphylaxis. Study data justify the implementation of a standardized de-labelling algorithm under close supervision in order to permit guideline-directed treatment and reduce the use of broad-spectrum antibiotics as part of an antibiotic stewardship program.

Ex vivo-expanded highly pure ABCB5+ mesenchymal stromal cells as Good Manufacturing Practice-compliant autologous advanced therapy medicinal product for clinical use: process validation and first in-human data.

BACKGROUND AIM: Mesenchymal stromal cells (MSCs) hold promise for the treatment of tissue damage and injury. However, MSCs comprise multiple subpopulations with diverse properties, which could explain inconsistent therapeutic outcomes seen among therapeutic attempts. Recently, the adenosine triphosphate-binding cassette transporter ABCB5 has been shown to identify a novel dermal immunomodulatory MSC subpopulation. METHODS: The authors have established a validated Good Manufacturing Practice (GMP)-compliant expansion and manufacturing process by which ABCB5+ MSCs can be isolated from skin tissue and processed to generate a highly functional homogeneous cell population manufactured as an advanced therapy medicinal product (ATMP). This product has been approved by the German competent regulatory authority to be tested in a clinical trial to treat therapy-resistant chronic venous ulcers. RESULTS: As of now, 12 wounds in nine patients have been treated with 5 × 105 autologous ABCB5+ MSCs per cm2 wound area, eliciting a median wound size reduction of 63% (range, 32-100%) at 12 weeks and early relief of pain. CONCLUSIONS: The authors describe here their GMP- and European Pharmacopoeia-compliant production and quality control process, report on a pre-clinical dose selection study and present the first in-human results. Together, these data substantiate the idea that ABCB5+ MSCs manufactured as ATMPs could deliver a clinically relevant wound closure strategy for patients with chronic therapy-resistant wounds.

Predominant patterns of ß-lactam hypersensitivity in a single German Allergy Center: exanthem induced by aminopenicillins, anaphylaxis by cephalosporins.

BACKGROUND: Penicillins and other ß-lactam antibiotics are the most common elicitors of allergic drug reaction. However, data on the pattern of clinical reaction types elicited by specific ß-lactams are scarce and inconsistent. We aimed to determine patterns of ß-latam allergy, i.e. the association of a clinical reaction type with a specific ß-lactam antibiotic. METHODS: We retrospectively evaluated data from 800 consecutive patients with suspected ß-lactam hypersensitivity over a period of 11 years in a single German Allergy Center. RESULTS: ß-lactam hypersensitivity was definitely excluded in 595 patients, immediate-type (presumably IgE-mediated) hypersensitivity was diagnosed in 70 and delayed-type hypersensitivity in 135 cases. Most (59 out of 70, 84.3%) immediate-type anaphylactic reactions were induced by a limited number of cephalosporins. Delayed reactions were regularly caused by an aminopenicillin (127 out of 135, 94.1%) and usually manifested as a measles-like exanthem (117 out of 135, 86.7%). Intradermal testing proved to be the most useful method for diagnosing ß-lactam allergy, but prick testing was already positive in 24 out of 70 patients with immediate-type hypersensitivity (34.3%). Patch testing in addition to intradermal testing did not provide additional information for the diagnosis of delayed-type hypersensitivity. Almost all ß-lactam allergic patients tolerated at least one, usually several alternative substances out of the ß-lactam group. CONCLUSIONS: We identified two patterns of ß-lactam hypersensitivity: aminopenicillin-induced exanthem and anaphylaxis triggered by certain cephalosporins. Intradermal skin testing was the most useful method to detect both IgE-mediated and delayed-type ß-lactam hypersensitivity.