Chan Joshua I, Noor Asif, Clauss Christie, Aggarwal Renu, Nayak Amrita
J Pediatr Pharmacol Ther. 2020 Jan-Feb;25(1):68-74. doi: 10.5863/1551-6776-25.1.68.
We report on a former 28-week gestation neonate with persistent methicillin-resistant Staphylococcus aureus (MRSA) endocarditis, with a heterozygous Factor V Leiden mutation. The neonate became clinically ill after 1 week of life, with positive blood cultures for MRSA. Echocardiography revealed large thrombi in the inferior vena cava and right atrium. Bacteremia persisted despite removal of umbilical arterial and venous catheters and empiric administration of therapeutic doses of vancomycin (minimum inhibitory concentration [MIC] 2 mg/L) and ceftazidime. To narrow therapy, ceftazidime was discontinued, while gentamicin and rifampin were added. Cultures remained positive and, therefore, linezolid was added, and subsequent blood cultures became negative. Since prolonged linezolid use of 2 weeks or longer carries potential adverse effects, antibiotics were changed to daptomycin, which is bactericidal and recommended for treatment of invasive MRSA infections when vancomycin MICs are ≥2 mg/L to minimize vancomycin treatment failure. Enoxaparin was initiated, with anti-Xa assay monitoring. A workup for thrombophilia revealed heterozygous Factor V Leiden mutation. Serial echocardiograms demonstrated decreasing size of the thrombi, which were no longer visualized at 2 months of age. Creatinine kinase remained normal. The infant had no seizures on daptomycin. The management of persistent MRSA bacteremia in neonates associated with a large thrombus poses a unique challenge due to the long duration of treatment. To our knowledge, this is the first case of prolonged and safe daptomycin and enoxaparin use in a preterm neonate. Daptomycin may be considered in cases of clinical failure with vancomycin when a lengthy treatment course is contemplated.
我们报告了一名孕28周出生的新生儿,患有持续性耐甲氧西林金黄色葡萄球菌(MRSA)心内膜炎,并伴有杂合子凝血因子V莱顿突变。该新生儿出生1周后出现临床症状,血培养MRSA呈阳性。超声心动图显示下腔静脉和右心房有大的血栓。尽管拔除了脐动静脉导管并经验性给予治疗剂量的万古霉素(最低抑菌浓度[MIC]为2mg/L)和头孢他啶,但菌血症仍持续存在。为了缩小治疗范围,停用了头孢他啶,同时加用庆大霉素和利福平。血培养仍为阳性,因此加用利奈唑胺,随后血培养转为阴性。由于长期使用利奈唑胺2周或更长时间有潜在不良反应,抗生素改为达托霉素,达托霉素具有杀菌作用,当万古霉素MIC≥2mg/L时,推荐用于治疗侵袭性MRSA感染,以尽量减少万古霉素治疗失败。开始使用依诺肝素,并监测抗Xa活性。血栓形成倾向检查发现杂合子凝血因子V莱顿突变。系列超声心动图显示血栓大小逐渐减小,在2月龄时不再可见。肌酸激酶保持正常。该婴儿使用达托霉素期间未发生惊厥。由于治疗时间长,新生儿持续性MRSA菌血症合并大血栓的管理面临独特挑战。据我们所知,这是首例在早产儿中长时间安全使用达托霉素和依诺肝素的病例。当考虑进行长疗程治疗且万古霉素临床治疗失败时,可考虑使用达托霉素。