毒理性
氧哌青霉素与两种形式的中毒性肝损伤有关，首先是与高剂量静脉治疗相关的急性且短暂的血清转氨酶水平升高；其次是一种更持久的、通常是胆汁淤积性的特应性肝损伤，这种损伤与其他第二代青霉素类如双氯青霉素、氟氯青霉素和萘夫西林的中毒性肝损伤相似。
高剂量的静脉氧哌青霉素治疗常常伴随着血清ALT水平的升高，升高幅度为正常上限的2到20倍，通常在治疗1到3周后出现。碱性磷酸酶水平仅略有升高。可能出现发热和非特异性症状如腹痛和恶心，但往往缺席。一些患者会出现嗜酸性粒细胞增多，但皮疹和关节痛不常见。血清转氨酶水平在停用氧哌青霉素或转为较低剂量（尤其是口服制剂）后迅速降至正常范围（1到2周内）。不会出现黄疸。这种反应似乎不会与天然青霉素、克林霉素甚至萘夫西林发生交叉反应。静脉注射羧苄青霉素可引起类似的综合征。这种肝毒性在HIV阳性个体中可能比非感染个体更常见。
除了高剂量静脉治疗期间常见的无症状血清转氨酶升高综合征外，氧哌青霉素还可能但很少导致一种更持久的通常是胆汁淤积性肝炎，这种肝炎在开始治疗后的1到6周出现，可能持续数周到数月。这种特应性肝损伤与双氯青霉素和其他第二代青霉素类描述的损伤相似。可能出现免疫性过敏特征如皮疹、发热和嗜酸性粒细胞增多，但不太明显。未发现自身抗体。肝损伤可能持续较长时间，但通常在发病后1到2个月内缓解。肝活检通常显示胆汁淤积性肝炎伴混合性炎症浸润。
可能性评分：B（可能是临床上明显肝损伤的罕见原因）。
Oxacillin has been linked to two forms of hepatotoxicity, first an acute and transient elevation in serum aminotransferase levels occurring with high doses of intravenous therapy; and second, a more prolonged, usually cholestatic, idiosyncratic liver injury that is similar to the hepatotoxicity of other second-generation penicillins such as dicloxacillin, flucloxacillin, and nafcillin.
High doses of intravenous oxacillin are commonly accompanied by elevations in serum ALT in the range of 2 to 20 times the upper limit of normal arising after 1 to 3 weeks of therapy. Alkaline phosphatase levels are only minimally elevated. Fever and nonspecific symptoms of abdominal pain and nausea can occur, but are often absent. Eosinophilia is present in some patients, but rash and arthralgias are uncommon. Serum aminotransferase levels rapidly fall into the normal range (in 1 to 2 weeks) with discontinuation of oxacillin or switch to lower doses, particularly in oral formulations. Jaundice does not occur. There appears to be no cross reactivity of this response with the natural penicillins, clindamycin or even nafcillin. Intravenous carbenicillin can cause a similar syndrome. This hepatotoxicity may be more common in HIV-positive than noninfected individuals.
In addition to the common syndrome of asymptomatic serum aminotransferase elevations during high dose intravenous therapy, oxacillin can also but rarely lead to a more prolonged usually cholestatic hepatitis that appears 1 to 6 weeks after starting therapy and may persist for weeks to months. This form of idiosyncratic liver injury is similar to that described with dicloxacillin and other second generation penicillins. Immunoallergic features of rash, fever and eosinophilia can occur, but are not prominent. Autoantibodies are not found. The liver injury can be prolonged, but generally resolves within 1 to 2 months of onset. Liver biopsy generally shows a cholestatic hepatitis with mixed inflammatory infiltrates.
Likelihood score: B (likely rare cause of clinically apparent liver injury).
来源:LiverTox
