背景:无论可用的抗真菌药,腹内念珠菌病(IAC)死亡率仍然很高,这对临床医生构成了挑战.
方法:本文讨论了治疗IAC的替代抗真菌药物。由于抗真菌药必需渗透到腹膜腔中的特殊性,因此应将该临床实体与念珠菌菌血症分开处理。在病理生理事实改变正常药物分布的危重患者中,腹腔内浓度可能会受到进一步限制。在侵袭性念珠菌病的指南中,推荐棘球白素作为一线治疗。然而,考虑到公布的数据,我们的药效学分析表明需要增加剂量,一些作者假设,在腹膜液中达到足够的药代动力学(PK)水平。鉴于文献中关于基于PK/PD的IAC治疗的证据有限,提出了一种指导抗真菌治疗的算法。对于表现为念珠菌菌血症或眼内炎的脓毒症/脓毒性休克患者,提倡使用脂质体两性霉素B作为一线治疗。或事先接触棘白菌素和/或氟康唑,或光滑念珠菌感染。其他情况和替代方案,如新化合物或联合疗法,也进行了分析。
结论:迫切需要更有力的临床试验,检查患者异质性和抗真菌耐药性监测的研究,以加强患者护理和优化治疗结果。这些证据将有助于完善现有指南,并有助于采取更个性化和有效的方法来治疗这种严重的医疗状况。同时,建议扩大对其他选择的考虑,如两性霉素B脂质体,作为一线治疗,直到获得菌图的结果,并且可以实施抗真菌管理以防止耐药性的发展。
Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians.
This opinion paper discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution.
Echinocandins are recommended as first-line treatment in
guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to
echinocandins and/or fluconazole, or with infections by Candida glabrata. Other situations and alternatives, such as new compounds or combination therapy, are also analysed.
There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing
guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance.