Impact of penicillin allergy records on antimicrobial prescribing in hospitalised patients.

BACKGROUND: The overdiagnosis of penicillin allergy and misclassification of non-truly allergic reactions is a growing public health problem, associated with the overuse of broad-spectrum and restricted antimicrobials. We aimed to evaluate the impact of penicillin allergy status on antimicrobial prescribing. METHODS: A retrospective study of inpatients with a documented penicillin allergy receiving antimicrobials was conducted from 1 April to 1 July 2021. Antimicrobial prescribing and clinical characteristics were compared between patients with an active penicillin allergy label and those whose label was removed following antimicrobial stewardship team review. Antimicrobials were classified in two categories: i) 'Access' (recommended), ii) 'Watch and Reserve' (restricted) according to WHO AWaRe classification, a tool to guide appropriate antibiotic use. RESULTS: 437 patients with a documented penicillin allergy receiving antimicrobials were included. 353 patients with an active penicillin allergy label, more frequently received antimicrobials from the 'Watch and Reserve list' (283;80% vs 30;37%; p<0.001). In contrast, 84 patients who were de-labelled received more often antimicrobials from the 'Access list' (53;63% vs 64;18%; p<0.001). CONCLUSIONS: Penicillin allergy reviews and de-labelling strategies may reduce the use of restricted antimicrobials under the 'Watch and Reserve list'. This practice should be encouraged and reinforced in all hospitals.

A Pan-Cancer Review of ALK Mutations: Implications for Carcinogenesis and Therapy.

The anaplastic lymphoma kinase (ALK) is a druggable target for cancer therapy. By and large, the oncogenic activation of ALK in human tumors is known to occur by gene rearrangement (e.g. EML4-ALK, NMP-ALK, etc.). Clinical use of ALK inhibitors for "ALK-rearranged" lung cancers has remarkably improved patient survival. To date, much has been known about ALK gene rearrangement in human carcinogenesis and its drug sensitivity relationship. However, emerging genomic data from the Cancer Genome Atlas (TCGA, USA) are now revealing common ALK point mutations (~3.06%) in various cancer types other than lung cancer. Importantly, several recent studies have demonstrated that ALK point mutations, independent of ALK-gene rearrangement, can be oncogenic. Thus, ALK mutations can be pathogenically and perhaps therapeutically important for various cancer types. Here, we summarized the latest ALK mutation frequencies and mutation patterns across 17 human cancer types stemming from TCGA. Unlike many other oncogenes with high frequency of hotspot mutations, ALK point mutations tend to span along the entire gene. Up till now, several recurrent mutations (G263, R401, R551, P968 and E1242) and mutation-rich cluster regions have been identified, but their functional effects remain unknown. We also conducted a comprehensive review of all ALK-mutated human cancer cell lines (from the Cell Line Encyclopedia (CCLE) and the NCI-60 panel), which can be used as model systems for ALK mutation biology and drug screening studies. Lastly, we summarized both the preclinical and clinical findings of ALK mutations on carcinogenesis and drug sensitivity, which may provide important insight into new treatment strategies and prompt future ALK mutation studies in various cancer types.