Prospective multicentre study on azole resistance in Aspergillus isolates from surveillance cultures in haematological patients in Italy

A Prigitano; M C Esposto; A Grancini; M Passera; M Paolucci; M Stanzani; A Sartor; A Candoni; L Pitzurra; P Innocenti; A Micozzi; G Lo Cascio; M Delia; A Mosca; M Mikulska; C Ossi; C Fontana; M Pizzolante; M Gelmi; C Cavanna; F Lallitto; G Amato; A Vella; L Pagano; R Bandettini; G De Lorenzis; M Cogliati; L Romanò; A Tortorano

doi:10.1016/j.jgar.2020.01.016

Prospective multicentre study on azole resistance in Aspergillus isolates from surveillance cultures in haematological patients in Italy

J Glob Antimicrob Resist. 2020 Sep:22:231-237. doi: 10.1016/j.jgar.2020.01.016. Epub 2020 Feb 13.

Authors

A Prigitano¹, M C Esposto², A Grancini³, M Passera⁴, M Paolucci⁵, M Stanzani⁵, A Sartor⁶, A Candoni⁶, L Pitzurra⁷, P Innocenti⁸, A Micozzi⁹, G Lo Cascio¹⁰, M Delia¹¹, A Mosca¹², M Mikulska¹³, C Ossi¹⁴, C Fontana¹⁵, M Pizzolante¹⁶, M Gelmi¹⁷, C Cavanna¹⁸, F Lallitto¹⁸, G Amato¹⁹, A Vella²⁰, L Pagano²¹, R Bandettini²², G De Lorenzis²³, M Cogliati², L Romanò², A Tortorano²

Affiliations

¹ Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy. Electronic address: anna.prigitano@unimi.it.
² Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
³ I.R.C.C.S. Foundation, Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁴ Microbiology and Virology Unit, Asst. Papa Giovanni XXIII, Bergamo, Italy.
⁵ Institute of Hematology, Lorenzo e Ariosto Seràgnoli, Sant'Orsola-Malpighi Hospital Policlinico, University of Bologna, Bologna, Italy.
⁶ Division of Hematology, ASUIUD, University of Udine, Udine, Italy.
⁷ Dipartimento di Medicina, Università degli Studi di Perugia, Perugia, Italy.
⁸ Laboratory of Microbiology and Virology, Comprensorio Sanitario di Bolzano-AS Alto Adige, Bolzano, Italy.
⁹ Department of Translational and Precision Medicine, Sapienza Università di Roma, Rome, Italy.
¹⁰ Microbiology Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
¹¹ Department of Emergency and Organ Transplantation-UO Haematology with transplantation, AO Universitaria Policlinico di Bari, Bari, Italy.
¹² Interdisciplinary Department of Medicine, AO Universitaria Policlinico di Bari, Bari, Italy.
¹³ Università degli Studi di Genova (DISSAL) and Ospedale Policlinico San Martino, Genoa, Italy.
¹⁴ Laboratory of Microbiology and Virology, San Raffaele Scientific Institute, Milan, Italy.
¹⁵ Department of Experimental Medicine, University of Tor Vergata Polyclinic of Tor Vergata, Rome, Italy.
¹⁶ Laboratory of Microbiology, Vito Fazzi Regional Hospital Lecce, Lecce, Italy.
¹⁷ ASST Spedali Civili di Brescia, Brescia, Italy.
¹⁸ Microbiology and Virology Unit, IRCCS Policlinico San Matteo, Pavia, Italy.
¹⁹ UOC. Patologia Clinica, AO A. Cardarelli, Naples, Italy.
²⁰ Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
²¹ Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.
²² Clinical Pathology and Microbiology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
²³ Department of Agricultural and Environmental Sciences-Production, Landscape, Agroenergy, Università degli Studi di Milano, Milan, Italy.

PMID: 32061880
DOI: 10.1016/j.jgar.2020.01.016

Abstract

Objectives: This study was conducted to assess the prevalence of azole resistance in Aspergillus isolates from patients with haematological malignancies or who were undergoing haematopoietic stem cell transplantation and to identify the molecular mechanism of resistance.

Methods: In this 28-month prospective study involving 18 Italian centres, Aspergillus isolates from surveillance cultures were collected and screened for azole resistance, and mutations in the cyp51A gene were identified. Resistant isolates were genotyped by microsatellite analysis, and the allelic profiles were compared with those of resistant environmental and clinical isolates from the same geographical area that had been previously genotyped.

Results: There were 292 Aspergillus isolates collected from 228 patients. The isolates belonged mainly to the section Fumigati (45.9%), Nigri (20.9%), Flavi (16.8%) and Terrei (4.8%). Three isolates showed itraconazole resistance: Aspergillus fumigatus sensu stricto, Aspergillus lentulus (section Fumigati) and Aspergillus awamori (section Nigri). The itraconazole resistance rates were 1% and 1.48% considering all Aspergillus spp. isolates and the Aspergillus section Fumigati, respectively. The prevalence of azole resistance among all the patients was 1.3%. Among patients harbouring A. fumigatus sensu stricto isolates, the resistance rate was 0.79%. The A. fumigatus isolate, with the TR₃₄/L98H mutation, was genotypically distant from the environmental and clinical strains previously genotyped.

Conclusions: In this study, the Aspergillus azole resistance rate was 1% (3/292). In addition to A. fumigatus sensu stricto, A. lentulus and A. awamori azole-resistant isolates were identified. Therefore, it is important have a correct identification at the species level to address a rapid therapy better, quickly understand the shift towards cryptic species and have an updated knowledge of the local epidemiology.

Keywords: Aspergillus spp.; Azole resistance; Haematological; Haematopoietic stem cell transplantation.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Antifungal Agents / pharmacology
Antifungal Agents / therapeutic use
Aspergillus / genetics
Azoles* / pharmacology
Drug Resistance, Fungal*
Humans
Italy / epidemiology
Microbial Sensitivity Tests
Prospective Studies

Substances

Antifungal Agents
Azoles

Supplementary concepts

Aspergillus awamori
Aspergillus lentulus