毒理性
静脉注射头孢曲松与3%至46%的患者发生胆泥形成有关。儿童的发生率可能高于成人，并且与较高剂量和较长的治疗疗程以及可能的禁食或脱水有关。这种综合征被称为“假性结石病”，因为泥沙和结石主要由头孢曲松组成，停药后会自行溶解，这表明可以避免手术。大多数病例发生时几乎没有或没有症状。据报道，多达5%的患者在发展成假性结石病时会出现胆绞痛的明显症状。通常情况下，即使有胆绞痛，血清酶和胆红素水平仍然正常，但在罕见情况下，可能会有胆汁淤积性黄疸或胆石性胰腺炎，这可能会很严重并需要手术治疗。胆泥和胆囊疾病的症状可能在开始治疗后的几天内出现，但通常在停用头孢曲松后会迅速缓解，尽管泥沙和胆结石可能会在超声波检查中持续几个月。
头孢曲松还可能导致一种与其他头孢菌素相似的免疫过敏性胆汁淤积性肝炎。这种反应是特异质性的，非常罕见。在开始治疗后的1到4周内，会出现腹痛、恶心、瘙痒和黄疸的症状，并在停用抗生素后的1到2周内可能恶化。血清酶升高和免疫过敏性特征如发热、皮疹和嗜酸性粒细胞增多的胆汁淤积模式很常见。损伤通常是轻微的和自限性的。
可能性评分：B（头孢曲松是临床上明显肝损伤的非常可能原因，也可能导致胆泥和“假性结石病”，这是由胆汁中头孢曲松的结晶引起的）。
Parenteral administration of ceftriaxone has been associated with development of biliary sludge in 3% to 46% of patients. The incidence may be higher in children than adults and is associated with higher doses and longer courses of treatment and possibly with fasting or dehydration. The syndrome is referred to as “pseudolithiasis” as the sludge and stones consist largely of ceftriaxone and they resolve spontaneously when the drug is stopped, indicating that surgery can be avoided. Most cases occur with minimal or no symptoms. Frank symptoms of cholecystitis are reported in up to 5% of patients who develop pseudo-lithiasis. Typically, serum enzymes and bilirubin levels remain normal even with biliary colic, but in rare instances there is cholestatic jaundice or gallstone pancreatitis that can be severe and require surgical intervention. Sludge and symptoms of gallbladder disease can arise within a few days of starting therapy, but typically resolve rapidly once ceftriaxone is stopped, although sludge and gallstones may be detectable by ultrasound for several months.
Ceftriaxone can also lead to an immunoallergic form of cholestatic hepatitis similar to what has been described with other cephalosporins. This reaction is idiosyncratic and is very rare. Symptoms of abdominal pain, nausea, pruritis and jaundice arise within 1 to 4 weeks of initiation of therapy and may worsen for 1 to 2 weeks after stopping the antibiotic. A cholestatic pattern of serum enzyme elevations and immunoallergic features of fever, rash and eosinophilia are common. The injury is usually mild and self-limited.
Likelihood score: B (ceftriaxone is a very likely cause of clinically apparent liver injury and can also lead to biliary sludge and “pseudolithiasis” caused by crystallization of ceftriaxone in bile present in the gallbladder or biliary tree).
来源:LiverTox
