Bassetti Matteo, Righi Elda
a Infectious Diseases Division , Santa Maria Misericordia Hospital , Udine , Italy.
Expert Opin Drug Saf. 2016;15(4):467-81. doi: 10.1517/14740338.2016.1142528. Epub 2016 Feb 6.
Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of severe nosocomial and community-acquired infections. Various adverse effects have been associated with compounds that are commonly used in the treatment of MRSA.
Prolonged use of high-dose vancomycin has been linked with nephrotoxicity. Linezolid use has been associated with lactic acidosis in regimens longer than 14 days and occurrence of thrombocytopenia in patients with renal impairment. Daptomycin use correlates with reversible and often asymptomatic myopathy. Among new compounds, telavancin has shown increased toxicity compared to vancomycin, especially in patients with severe renal impairment, while a low rate of adverse effects was reported others glycolipopeptides such as dalbavancin and oritavancin and for new cephalosporins. Recently studied oxazolidinones (tedizolid and radezolid) also showed mild adverse effects in Phase 2 and 3 clinical trials.
Due to the constant increase in antimicrobial resistance, the use of higher doses and prolonged regimens of antibiotics employed in the treatment of Gram-positive infections has become more common and linked to increased toxicity. Furthermore, new compounds with MRSA activity have been recently approved and will be regularly employed in clinical practice. The knowledge of the adverse effects and risk factors for the development of toxicity associated with anti-MRSA antimicrobials is paramount for the correct use of old and new compounds, especially in the treatment of severe infections.
耐甲氧西林金黄色葡萄球菌(MRSA)是严重医院感染和社区获得性感染的常见病因。常用于治疗MRSA的化合物会产生各种不良反应。
长期大剂量使用万古霉素与肾毒性有关。使用利奈唑胺超过14天的治疗方案会导致乳酸酸中毒,肾功能不全患者会出现血小板减少症。使用达托霉素与可逆且通常无症状的肌病相关。在新化合物中,替加环素与万古霉素相比毒性增加,尤其是在严重肾功能不全的患者中,而其他糖肽类药物(如达巴万星和奥利万星)以及新型头孢菌素的不良反应发生率较低。最近研究的恶唑烷酮类药物(特地唑胺和雷地唑胺)在2期和3期临床试验中也显示出轻微的不良反应。
由于抗菌药物耐药性不断增加,治疗革兰氏阳性感染时使用更高剂量和更长疗程的抗生素变得更加普遍,且与毒性增加有关。此外,最近已批准了具有抗MRSA活性的新化合物,并将在临床实践中经常使用。了解与抗MRSA抗菌药物相关的不良反应和毒性发生的危险因素对于正确使用新旧化合物至关重要,尤其是在治疗严重感染时。