TR34/L98H Mutation in CYP51A Gene in Aspergillus fumigatus Clinical Isolates During Posaconazole Prophylaxis: First Case in Korea

Hyeon-Jeong Lee,Hye-Sun Chun,Sung-Yeon Cho,Dong-Gun Lee,Yeon-Joon Park,Chulmin Park

doi:10.1007/s11046-018-0271-8

Abstract

Azole resistance in Aspergillus fumigatus is an emerging problem, especially in immunocompromised patients. It has been reported worldwide, including in Asia, but has not yet been reported in Korea. Here, we report a case of invasive pulmonary aspergillosis (IPA) caused by azole-resistant A. fumigatus that developed in a hematopoietic stem cell transplantation recipient during posaconazole prophylaxis for immunosuppressive therapy of graft-versus-host diseases. We identified TR34/L98H/S297T/F495L mutation in the CYP51A gene of A. fumigatus clinical isolate obtained from bronchial washing fluid. Minimal inhibitory concentrations for itraconazole, voriconazole, and posaconazole were > 16, 1, and 4 μg/mL, respectively. While IPA improved partially under voriconazole treatment, the patient died from carbapenemase-producing Klebsiella pneumoniae bacteremia. Further epidemiological surveillance studies are warranted.

Highlights

Aspergillus infections including invasive aspergillosis (IA) mainly affect immunocompromised patients, such as hematopoietic stem cell transplantation (HSCT) recipients or patients undergoing immunosuppressive therapy
As triazole drugs have been the mainstay of both treatment and prevention of IA since the 1990s, there were concerns about the increasing possibility of that azole-resistant Aspergillus spp. or azole breakthrough IA by expanding the usage of triazoles [2]
Since the first azole-resistant A. fumigatus was found both in the Netherlands and in Italy in 1998 [3], azole resistance in A. fumigatus isolates has been found in almost every European country, the Middle East, Asia, Africa, Australia, and most recently, North and South America

Summary

Introduction

Aspergillus infections including invasive aspergillosis (IA) mainly affect immunocompromised patients, such as hematopoietic stem cell transplantation (HSCT) recipients or patients undergoing immunosuppressive therapy. Lee Division of Infectious Diseases, Department of Internal Medicine, The Catholic Blood and Marrow Transplantation Center, Vaccine Bio Research Institute, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seochogu, Seoul 06591, Republic of Korea e-mail: cho.sy@catholic.ac.kr F495L mutation in the CYP51A gene of A. fumigatus clinical isolate obtained from bronchial washing fluid.

Results

Conclusion