Short course of voriconazole therapy as a risk factor for relapse of invasive pulmonary aspergillosis

Abstract

To investigate associations of the duration of voriconazole treatment and radiological response with relapse of invasive pulmonary aspergillosis (IPA) in immunocompromised patients, we explored the risk factors for IPA relapse after successful initial treatment. All patients with proven or probable IPA who had finished voriconazole treatment between 2005 and 2019 in a tertiary-care hospital were reviewed. IPA relapse was defined as re-diagnosis of proven or probable IPA at the same site within 1 year after treatment termination. Short course of voriconazole treatment was defined as a treatment less than 9 weeks, which is a median of the recommended minimum duration of therapy from the Infectious Disease Society of America. The radiological response was defined as a reduction in IPA burden by more than 50% on chest computed tomography. Of 87 patients who had completed voriconazole treatment, 14 (16.1%) experienced IPA relapse. Multivariable Cox regression identified that short voriconazole treatment duration (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.1–12.3; P = 0.033) and radiological non-response (aHR, 4.6; 95% CI, 1.2–17.5; P = 0.026) were independently associated with relapse of IPA after adjusting for several clinical risk factors. Longer duration of therapy should be considered for those at higher risk of relapse.

Antifungals: From Pharmacokinetics to Clinical Practice

“…Mortality rates range from 30% to 90%, varying by patient population as well as by severity and duration of immunosuppression [29][30][31][32]. As with the Candida species, there is a serious concern regarding the emergence of resistance mainly associated with the treatment of Aspergillus species [29][30][31]33,34].…”

“…Guidelines from the Infectious Diseases Society of America (IDSA) also recommended voriconazole as a primary therapy for invasive aspergillosis and as an alternative therapy for candidemia [21,32]. However, in recent years, Aspergillus fumigatus, one of the main entities associated with invasive aspergillosis, developed mech-anisms that showed high resistance to voriconazole and were associated with treatment failure [34,[77][78][79][80].…”