The Versiti Blood Research Institute, Versiti Wisconsin Inc, Milwaukee, Wisconsin, USA.
Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Transfusion. 2021 May;61(5):1600-1608. doi: 10.1111/trf.16295. Epub 2021 Feb 13.
Beta-lactam antibiotics are a relatively common cause of immune thrombocytopenia. Because the many beta-lactam drugs now in clinical use have structural similarities, when a patient experiences this complication the question of whether an alternative member of this drug family can safely be used often arises but there are little data available to guide this decision.
Drug-dependent, platelet-reactive antibodies from 32 patients who experienced thrombocytopenia while being treated with a beta-lactam drug of the penam (piperacillin, etc.) or cephem (ceftriaxone etc.) groups were studied for serologic cross-reactivity with other drugs from these families using flow cytometry. Cross-reactions observed were analyzed for correlations with structural features of the drugs tested.
Among 14 antibodies specific for penam drugs, five "strong" cross-reactions with other penam drugs were found. Among 18 antibodies specific for cephem drugs, 8 "strong cross-reactions were identified. Antibodies induced by penam drugs did not cross-react strongly with cephem drugs and vice versa. A strong correlation between cross-reactions and similar or identical R1 side groups of the beta-lactams studied was observed.
The findings suggest that patients who experience immune thrombocytopenia while being treated with a beta-lactam of the penam group can safely be treated with a cephem drug and vice versa. If a patient is to be switched to another beta lactam within the same group, the likelihood of serologic cross-reactivity can be minimized by choosing an agent with a distinctly different R1 side group.
β-内酰胺类抗生素是引起免疫性血小板减少症的一个相对常见的原因。由于目前临床使用的许多β-内酰胺类药物具有结构相似性，当患者出现这种并发症时，经常会出现是否可以安全使用该药物家族的另一种药物的问题，但可用于指导这一决策的数据很少。
使用流式细胞术研究了 32 名因使用青霉素（哌拉西林等）或头孢菌素（头孢曲松等）类β-内酰胺药物而发生血小板减少的患者的药物依赖性、血小板反应性抗体与来自这些家族的其他药物之间的血清学交叉反应性。分析观察到的交叉反应与所测试药物的结构特征之间的相关性。
在 14 种针对青霉素类药物的抗体中，发现了 5 种与其他青霉素类药物的“强”交叉反应。在 18 种针对头孢菌素类药物的抗体中，鉴定出 8 种“强交叉反应”。青霉素类药物诱导的抗体与头孢菌素类药物之间没有强烈的交叉反应，反之亦然。观察到交叉反应与所研究的β-内酰胺类药物的类似或相同的 R1 侧基之间存在很强的相关性。
研究结果表明，因使用青霉素类药物而发生免疫性血小板减少症的患者可以安全地接受头孢菌素类药物治疗，反之亦然。如果要将患者切换到同一组中的另一种β-内酰胺类药物，则通过选择具有明显不同的 R1 侧基的药物，可将血清学交叉反应的可能性降到最低。
