Khoory B J, Fanos V, Dall'Agnola A, Cataldi L
Clinica Pediatrica, Università di Verona, Italia.
Pediatr Med Chir. 1996 Sep-Oct;18(5):495-9.
Antibiotics are the leading cause of drug-induced kidney disease, and among them the aminoglycosides (AMG) are the main nephrotoxic agents, bringing about kidney damage via a direct dose-dependent mechanism. The combination of an aminoglycoside and a penicillin derivative is still the most commonly recommended and used first-line treatment modality in the empirical therapy of neonatal sepsis, despite the low therapeutic index of AMG. The immaturity of neonatal kidney function, particularly in preterm neonates, makes newborn infants particularly susceptible to AMG-induced kidney damage. Numerous factors intervene in bringing about AMG-induced kidney damage, such as factors related to the antibiotic itself (intrinsic toxicity, administration route, type of monitoring of blood concentrations), those related to the subject treated (neonatal age, constitutional sensitivity), and others related to associated pathology (neonatal anoxia, renal hypoperfusion, respiratory distress/mechanical ventilation, hyperbilirubinaemia/phototherapy, electrolyte disorders, and even the acute sepsis calling for antibiotic therapy), as well as pharmacological factors (concomitant therapies such as diuretics, indomethacin and other antibiotics, particularly glycopeptides and cephalosporins).
抗生素是药物性肾病的主要病因,其中氨基糖苷类药物(AMG)是主要的肾毒性药物,通过直接的剂量依赖性机制导致肾损伤。尽管AMG的治疗指数较低,但在新生儿败血症的经验性治疗中,氨基糖苷类药物与青霉素衍生物的联合用药仍然是最常推荐和使用的一线治疗方式。新生儿肾功能不成熟,尤其是早产儿,使得新生儿特别容易受到AMG引起的肾损伤。导致AMG引起肾损伤的因素众多,例如与抗生素本身相关的因素(内在毒性、给药途径、血药浓度监测类型)、与接受治疗的对象相关的因素(新生儿年龄、体质敏感性)、与相关病理状况相关的其他因素(新生儿缺氧、肾灌注不足、呼吸窘迫/机械通气、高胆红素血症/光疗、电解质紊乱,甚至是需要抗生素治疗的急性败血症),以及药理学因素(如利尿剂、吲哚美辛和其他抗生素,特别是糖肽类和头孢菌素类等联合治疗)。