Qiao Yanli, Chen Yechao, Wang Qiaoyun, Liu Jingrui, Guo Xiaohui, Gu Qiaoling, Ding Peng, Zhang Haixia, Mei Hongliang
Department of Pharmacy, Nanjing Drum Tower Hospital, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
Front Pharmacol. 2024 Jul 26;15:1413944. doi: 10.3389/fphar.2024.1413944. eCollection 2024.
Recently, the rise of antibiotic resistance has prompted a reconsideration of tetracyclines. However, existing studies are inadequate in assessing the pediatric safety of this class of antibiotics. To address the gap, our study aims to comprehensively assess the safety of tetracyclines in children.
Adverse event (AE) reports from January 2005 to September 2023 were obtained from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, and reporting odds ratio (ROR) was performed to identify potential risk signals in children under 18 years old who were administered any of the three tetracyclines: doxycycline, minocycline, and tigecycline.
A total of 1903 AE cases were included in our study: 782 for doxycycline, 981 for minocycline, and 140 for tigecycline. Doxycycline and tigecycline were predominantly associated with "general disorders and administration site conditions" and "gastrointestinal disorders," while minocycline was more frequently linked to "skin and subcutaneous tissue disorders" and "gastrointestinal disorders." Psychiatric risks predominantly included depression, suicidal ideation, and suicide attempt. In the category of skin and subcutaneous tissues, 30.88% of the minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) cases resulted in death, alongside a high occurrence of co-occurring AEs such as multiple organ dysfunction syndrome, Type 1 Diabetes Mellitus (T1DM), and autoimmune thyroiditis. As for the endocrine system, both doxycycline and minocycline were found to potentially increase the risk of thyroid dysfunction. For children under the age of 8, doxycycline was associated with tooth discoloration (N = 7, ROR = 20.11%, 95% CI: 9.48-42.67), although it remained unclear whether the discoloration was permanent.
Our findings indicated that for pediatric patients, the majority of results were in line with the prescribing information and previous studies, and minocycline tended to cause more frequent and severe AEs than doxycycline. However, it is noteworthy that exceptions were found for psychiatric disorders and thyroid dysfunction associated with doxycycline, which are not mentioned in its FDA prescribing information. Additionally, further safety studies on tigecycline are still needed for children. When prescribing tetracyclines to pediatric patients, a careful risk-benefit assessment is crucial.
近期，抗生素耐药性的上升促使人们重新审视四环素类药物。然而，现有研究在评估这类抗生素对儿童的安全性方面并不充分。为填补这一空白，我们的研究旨在全面评估四环素类药物在儿童中的安全性。
从美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库获取2005年1月至2023年9月的不良事件（AE）报告，并进行报告比值比（ROR）分析，以确定18岁以下使用三种四环素类药物（多西环素、米诺环素和替加环素）中任何一种的儿童的潜在风险信号。
我们的研究共纳入1903例AE病例：多西环素782例，米诺环素981例，替加环素140例。多西环素和替加环素主要与“全身性疾病和给药部位状况”以及“胃肠道疾病”相关，而米诺环素更常与“皮肤和皮下组织疾病”以及“胃肠道疾病”相关。精神风险主要包括抑郁、自杀意念和自杀未遂。在皮肤和皮下组织类别中，米诺环素引起的药物超敏反应伴嗜酸性粒细胞增多和全身症状（DRESS）病例中有30.88%导致死亡，同时还经常出现多器官功能障碍综合征、1型糖尿病（T1DM）和自身免疫性甲状腺炎等合并发生的AE。至于内分泌系统，发现多西环素和米诺环素都可能增加甲状腺功能障碍的风险。对于8岁以下儿童，多西环素与牙齿变色有关（N = 7，ROR = 20.11%，95%CI：9.48 - 42.67），尽管变色是否为永久性尚不清楚。
我们的研究结果表明，对于儿科患者，大多数结果与处方信息和先前研究一致，米诺环素往往比多西环素更容易引起更频繁、更严重的AE。然而，值得注意的是，发现了与多西环素相关的精神疾病和甲状腺功能障碍的例外情况，这些在其FDA处方信息中未提及。此外，仍需要对替加环素在儿童中的安全性进行进一步研究。在给儿科患者开四环素类药物时，仔细的风险效益评估至关重要。
