Salinas Beatriz, Guembe María, Cussó Lorena, Kestler Martha, Guinea Jesús, Desco Manuel, Muñoz Patricia, Bouza Emilio
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Med Mycol. 2019 Jun 1;57(4):496-503. doi: 10.1093/mmy/myy065.
In cases where catheter-related candidemia (CRC) must be managed without catheter withdrawal, antifungal lock therapy using highly active anti-biofilm (HAAB) agents is combined with systemic treatment. However, the activity of HAAB agents has never been studied in in vivo models using bioluminescence. We assessed the efficacy of micafungin using a bioluminescent Candida albicans SKCA23-ACTgLuc strain in an animal model of CRC. We divided 33 female Wistar rats into five groups: sham (A), infected nontreated (B), treated with lock therapy (0.16 mg/ml) (C), systemically treated only (1 mg/kg) (D), and systemically treated+lock (E). Catheters were colonized 24 h before insertion into the femoral vein (day 0). Treatment started on day 1 and lasted 7 days, followed by 7 days of surveillance. Bioluminescence assays were carried out on days 1, 3, 5, and 14, together with daily monitoring of clinical variables. Postmortem microbiological cultures from the catheter and several tissue samples were also obtained. Overall, 28 rats (84.8%) completed the study. Group B animals showed significant weight loss at days 2, 4, and 5 compared with groups C and D (P < .05). In group B, no animals survived after day 7, 75% had CRC, and bioluminescence remained constant 5 days after catheter implantation. Positive catheter culture rates in groups C, D, and E were, respectively, 83.3%, 62.5%, and 25.0% (P = .15). Micafungin proved to be a HAAB agent when administered both systemically and in lock therapy in an animal model of CRC, although the bioluminescence signal persists after treatment. This persistence should be further analyzed.
在必须在不拔除导管的情况下处理导管相关念珠菌血症（CRC）的病例中，使用高活性抗生物膜（HAAB）药物的抗真菌封管疗法与全身治疗联合使用。然而，HAAB药物的活性从未在使用生物发光的体内模型中进行过研究。我们在CRC动物模型中，使用生物发光的白色念珠菌SKCA23-ACTgLuc菌株评估了米卡芬净的疗效。我们将33只雌性Wistar大鼠分为五组：假手术组（A）、感染未治疗组（B）、封管疗法治疗组（0.16 mg/ml）（C）、仅全身治疗组（1 mg/kg）（D）和全身治疗+封管组（E）。在将导管插入股静脉前24小时（第0天）使其定植。治疗于第1天开始，持续7天，随后进行7天的监测。在第1、3、5和14天进行生物发光测定，并每日监测临床变量。还获取了导管和多个组织样本的死后微生物培养物。总体而言，28只大鼠（84.8%）完成了研究。与C组和D组相比，B组动物在第2、4和5天体重显著减轻（P <.05）。在B组中，第7天后无动物存活，75%患有CRC，导管植入后5天生物发光保持恒定。C组、D组和E组的导管阳性培养率分别为83.3%、62.5%和25.0%（P = 0.15）。在CRC动物模型中，当全身给药和封管治疗时，米卡芬净被证明是一种HAAB药物，尽管治疗后生物发光信号持续存在。这种持续性应进一步分析。
