Infectious complications after hematopoietic stem cell transplantation: current status and future perspectives in Korea

Cho, Sung-Yeon; Lee, Hyeon-Jeong; Lee, Dong-Gun

Voriconazole is the drug of choice for treating IA. Voriconazole therapeutic drug monitoring can be used in many centers, and the target trough level is 1 to 5.5 mg/L. The CYP2C19 polymorphism affects the pharmacokinetics of voriconazole. Among Korean hematologic patients, 28% are extensive metabolizers (EMs), 48% are heterozygous EMs, and 14% are poor metabolizers. While subtherapeutic initial trough levels were common in EMs, there was no significant relationship between CYP2C19 genotype and the clinical outcomes of IA or the toxicity of voriconazole [56] . Isavuconazole is non-inferior to voriconazole for the primary treatment of suspected invasive mold disease, with fewer drug-related adverse events [57, 58] . Salvage therapy includes liposomal amphotericin B, caspofungin, posaconazole, and itraconazole, or a combination of them [58] . Treatment duration is at least 6 to 12 weeks, which should be individualized according to the changes in radiologic, microbiologic, and immunologic parameters. IFIs can occur during treatment with anti-mold agents. Patients with GVHD under long-term immunosuppressive therapy should be on antifungal agents to prevent IFIs (Table 3 ). In particular, there is a risk of IFIs other than aspergillosis, such as mucormycosis or other rare molds [48, 59, 60] . A retrospective single-center study reported that the prevalence and incidence of voriconazole-breakthrough IFIs were 2.25% and 0.22 cases per year, respectively. The overall mortality rate was 44.4% [61] . The possible causes of breakthrough IFI during voriconazole treatment were persistent immunodeficiency, neutropenia, low voriconazole concentration, or poor vascular supply (i.e., abscess or necrotic tissue) [61] . In voriconazole-refractory IA, clinicians should consider the following: misdiagnosis or coinfection with another mold, inadequate blood voriconazole concentration, inadequate tissue drug concentration, immune reconstitution inflammatory syndrome, or infection with voriconazole-resistant Aspergillus [62] . Proven/probable IA patients reportedly have a low culture-positive rate (17.7%) [63] . To determine the azole-resistance rate of Aspergillus clinical isolates in Korea, culture-positive cases should undergo susceptibility testing.