Department of Respiratory Diseases, Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium.
Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven, Belgium.
BMC Pulm Med. 2022 Mar 27;22(1):110. doi: 10.1186/s12890-022-01904-4.
Variability in triazole plasma concentrations by drug interactions is well known. An interaction between voriconazole and flucloxacillin has already been described. In our case we observed a similar interaction between posaconazole and flucloxacillin, which in our knowledge has not ever been reported in literature.
A 60-year-old male who had a double lung transplantation for end-stage chronic obstructive pulmonary disease was being treated with voriconazole for invasive pulmonary aspergillosis (IPA). During this treatment he presented at the emergency room and was diagnosed with endocarditis for which a combination of amoxicillin, flucloxacillin and gentamicin was initiated. A known interaction between voriconazole and flucloxacillin was observed, with a drop of the voriconazole levels, and treatment for IPA was switched to posaconazole. After ending the treatment for endocarditis, the patient had a catheter infection for which flucloxacillin was reinitiated. Unexpectedly we saw a similar immediate drop in posaconazole levels, recovering after ending treatment with flucloxacillin.
We describe a new interaction between posaconazole and flucloxacillin. Presumably the underlying mechanism is activation of the pregnane X receptor by flucloxacillin, which can induce cytochrome P450, uridine glucuronosyl transferase (UGT1A4) and P-glycoprotein. We advise caution when combining flucloxacillin and triazoles, because interactions may lead to undertreatment of invasive aspergillosis.
药物相互作用导致三唑类药物的血浆浓度存在差异，这是众所周知的。已有报道称伏立康唑与氟氯西林之间存在相互作用。在我们的病例中，我们观察到泊沙康唑与氟氯西林之间也存在类似的相互作用，据我们所知，这在文献中尚未报道过。
一位 60 岁男性，因终末期慢性阻塞性肺疾病行双肺移植，因侵袭性肺曲霉病（IPA）接受伏立康唑治疗。在此期间，他因心内膜炎到急诊就诊，给予阿莫西林、氟氯西林和庆大霉素联合治疗。观察到伏立康唑与氟氯西林之间存在已知的相互作用，伏立康唑水平下降，并将 IPA 的治疗药物转换为泊沙康唑。在心内膜炎治疗结束后，患者发生导管感染，再次开始使用氟氯西林。出乎意料的是，我们发现泊沙康唑水平也出现了类似的立即下降，在结束氟氯西林治疗后恢复。
我们描述了泊沙康唑与氟氯西林之间的一种新的相互作用。推测其潜在机制是氟氯西林激活了孕烷 X 受体，这可能诱导细胞色素 P450、尿苷二磷酸葡萄糖醛酸转移酶（UGT1A4）和 P-糖蛋白。当联合使用氟氯西林和三唑类药物时，我们建议谨慎，因为相互作用可能导致侵袭性曲霉病治疗不足。
