IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of alternative cephalosporins

BACKGROUND: Studies regarding the cross-reactivity and tolerability of alternative cephalosporins in large samples of subjects with an IgE-mediated hypersensitivity to cephalosporins are lacking. OBJECTIVE: We sought to evaluate the possibility of using alternative cephalosporins in subjects with cephalosporin allergy who especially require them. METHODS: One hundred two subjects with immediate reactions to cephalosporins and positive skin test results to the responsible drugs underwent serum specific IgE assays with cefaclor and skin tests with different cephalosporins. Subjects were classified in 4 groups: group A, positive responses to 1 or more of ceftriaxone, cefuroxime, cefotaxime, cefepime, cefodizime, and ceftazidime; group B, positive responses to aminocephalosporins; group C, positive responses to cephalosporins other than those belonging to the aforementioned groups; and group D, positive responses to cephalosporins belonging to 2 different groups. Group A subjects underwent challenges with cefaclor, cefazolin, and ceftibuten; group B participants underwent challenges with cefuroxime axetil, ceftriaxone, cefazolin, and ceftibuten; and group C and D subjects underwent challenges with some of the aforementioned cephalosporins selected on the basis of their patterns of positivity. RESULTS: There were 73 subjects in group A, 13 in group B, 7 in group C, and 9 in group D. Challenges with alternative cephalosporins (ceftibuten in 101, cefazolin in 96, cefaclor in 82, and cefuroxime axetil and ceftriaxone in 22 subjects) were well tolerated. CONCLUSIONS: Cephalosporin hypersensitivity does not seem to be a class hypersensitivity. Subjects with cephalosporin allergy who especially require alternative cephalosporins might be treated with compounds that have side-chain determinants different from those of the responsible cephalosporins and have negative pretreatment skin test responses

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins

BACKGROUND: Studies performed on samples larger than 100 subjects with a documented IgE-mediated hypersensitivity to penicillins have demonstrated a cross-reactivity rate of approximately 1% between penicillins and both imipenem and meropenem, whereas a single study found a cross-reactivity rate of 6.2% with aztreonam in 16 such subjects. OBJECTIVE: To assess the cross-reactivity and tolerability of aztreonam and 3 carbapenems (imipenem-cilastatin, meropenem, and ertapenem) in patients with documented IgE-mediated hypersensitivity to penicillins. METHODS: A total of 212 consecutive subjects with immediate reactions to penicillins and positive results on skin tests to at least 1 penicillin reagent underwent skin tests with aztreonam and carbapenems; subjects with negative results were challenged with escalating doses of aztreonam and carbapenems. RESULTS: All subjects displayed negative skin test results to both aztreonam and carbapenems; 211 accepted challenges and tolerated them. Challenges were not followed by full therapeutic courses. CONCLUSIONS: These data indicate the tolerability of both aztreonam and carbapenems in penicillin-allergic subjects. In those who especially require these alternative β-lactams, however, we recommend pretreatment skin tests, both because rare cases of cross-reactivity have been reported and because negative results indicate tolerability

Natural evolution of skin-test sensitivity in patients with IgE-mediated hypersensitivity to cephalosporins

There are studies demonstrating that skin-test sensitivity to penicillins can decrease over time and that allergic patients may lose sensitivity if the responsible compounds are avoided. With regard to subjects with IgE-mediated hypersensitivity to cephalosporins, however, such studies are lacking. We evaluated prospectively in a 5-year follow-up 72 cephalosporin-allergic patients. After the first evaluation, patients were classified into two groups according to their patterns of allergologic-test positivity: to both penicillins and cephalosporins (group A), or only to cephalosporins (group B). Skin tests and serum-specific IgE assays were repeated 1 year later and, in case of persistent positivity, 3 and 5 years after the first allergologic examination. Seven (43.7%) of the 16 subjects of group A and 38 (67.8%) of the 56 patients of group B became negative; one was lost to follow-up. Patients of group B became negative sooner and more frequently than group A subjects

Reply

To the Editor: We read with great interest Drs. Baldo and Pham’s observations1 concerning our article2 and specifically their final claim that in selecting alternative cephalosporins in cephalosporin allergic subjects, “similarities and differences between R1 groups need to be noted but failure to do likewise for the R2 groups may lead to serious consequences for the occasional patient”

Diagnosing multiple drug hypersensitivity in children

Multiple drug hypersensitivity (MDH) has been defined as a hypersensitivity to two or more chemically different drugs. Two types of MDH have been reported: the first one, which develops to different drugs administered simultaneously and the second type, in which sensitizations develop sequentially. In children, studies which diagnose MDH on the basis of positive allergologic tests to 2 or more chemically different drugs are lacking

Silk fibroin-based hydrogels and scaffolds for osteochondral repair and regeneration

Osteochondral lesions treatment and regeneration demands biomimetic strategies aiming physicochemical and biological properties of both bone and cartilage tissues, with long-term clinical outcomes. Hydrogels and scaffolds, appeared as assertive approaches to guide the development and structure of the new osteochondral engineered tissue. Moreover, these structuresalone or in combination with cells and bioactive molecules, bring the mechanical support after in vitro and in vivo implantation. Moreover, multilayered structures designed with continuous interfaces, furnish appropriate features of the cartilage and subchondral regions, namely microstructure, composition, and mechanical properties. Owing the potential as scaffolding materials, natural and synthetic polymers, bioceramics, and composites, have been employed. Particularly, significance is attributed to the natural-based biopolymer silk ï¬ broin from the Bombyx mori silkworm, considering its unique mechanical and biological properties. The significant studies on silk fibroin-based structures, namely hydrogels and scaffolds, towards bone, cartilage, and osteochondral tissue repair and regeneration are overviewed herein. The developed biomimetic strategies, processing methodologies, and final properties of the structures are summarized and discussed in depth.s The authors thank to the project FROnTHERA (NORTE-01-0145- FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The financial support from the Portuguese Foundation for Science and Technology to Hierarchitech project (M-ERA-NET/0001/2014), for the fellowship grant (SFRH/ BPD/113806/2015) and for the fund provided under the program Investigador for J. M. Oliveira (IF/00423/2012 and IF/01285/2015) are also greatly acknowledged.info:eu-repo/semantics/publishedVersio