Mihai Mara-Mădălina, Anghelescu Iuliana, Holban Alina Maria, Gheorghe-Barbu Irina, Chifiriuc Mariana-Carmen, Dițu Lia-Mara, Ilie Cornelia-Ioana, Anghelescu Dan, Bălăceanu-Gurău Beatrice
Department of Oncologic Dermatology, "Elias" Emergency University Hospital, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.
Research Institute of the University of Bucharest, University of Bucharest, 050663 Bucharest, Romania.
Int J Mol Sci. 2025 Jul 9;26(14):6595. doi: 10.3390/ijms26146595.
Cutaneous adverse reactions (CARs) are common complications of epidermal growth factor receptor (EGFR) inhibitor therapy, with papulopustular eruptions and paronychia being the most frequent. Growing scientific evidence implies that is involved in the pathogenesis of these reactions. This observational prospective study characterized 42 strains isolated from CARs, analyzing antibiotic resistance, biofilm formation, soluble virulence factors, and virulence/resistance genes using multiplex polymerase chain reaction (PCR). was identified in 90% of lesions; in 33% of cases, nasal and skin isolates were genetically identical. High resistance rates were noted for penicillins (85%) and tetracyclines (57%), while all strains remained susceptible to fluoroquinolones, vancomycin, and rifampicin. All isolates formed biofilms, and DNase/esculinase production significantly correlated with CAR severity. An enzymatic score based on these markers was associated with an 18-fold increased risk of severe reactions. Genotypically, and were prevalent (85.7%), while exotoxin genes were less common. These findings support a key role for in exacerbating CARs via antibiotic resistance, biofilm production, and the expression of virulence factor. Additionally, we emphasize the role of routine microbial screening-including nasal swabs-and therapy guided by antibiograms. Furthermore, the enzymatic score may further be validated as a predictive biomarker.
皮肤不良反应（CARs）是表皮生长因子受体（EGFR）抑制剂治疗的常见并发症，丘疹脓疱性皮疹和甲沟炎最为常见。越来越多的科学证据表明，[具体细菌名称未给出]参与了这些反应的发病机制。这项观察性前瞻性研究对从CARs中分离出的42株[具体细菌名称未给出]进行了特征分析，使用多重聚合酶链反应（PCR）分析抗生素耐药性、生物膜形成、可溶性毒力因子以及毒力/耐药基因。在90%的病变中鉴定出了[具体细菌名称未给出]；在33%的病例中，鼻腔和皮肤分离株基因相同。青霉素（85%）和四环素（57%）的耐药率较高，而所有菌株对氟喹诺酮类、万古霉素和利福平仍敏感。所有分离株均形成生物膜，DNase/七叶苷酶产生与CAR严重程度显著相关。基于这些标志物的酶学评分与严重反应风险增加18倍相关。从基因型上看，[具体基因名称未给出]和[具体基因名称未给出]普遍存在（85.7%），而外毒素基因较少见。这些发现支持了[具体细菌名称未给出]通过抗生素耐药性、生物膜产生和毒力因子表达在加重CARs方面的关键作用。此外，我们强调常规微生物筛查（包括鼻拭子）和根据抗菌谱进行治疗的作用。此外，酶学评分可能进一步被验证为预测生物标志物。
