Editorial

Antifungal susceptibility testing in Australasian clinical laboratories: we must improve our performance

This study aimed to validate the performance of the custom formulated Sensititre YeastOne One (SYO) microdilution plate which includes isavuconazole (AUSNMRC1) to perform susceptibility testing on clinically relevant yeast and mould species across three Australian reference laboratories. The minimum inhibitory concentration (MIC) results were compared with the IVD approved SYO YO10 microdilution plate and isavuconazole gradient strips. A total of 127 isolates were tested on both the YO10 and AUSNMRC1 plates. The overall essential agreement (EA) and categorical agreement (CA) for the eight common drugs was 99.9% and 98.8%, respectively. The EA was 96.9% for the isavuconazole MICs obtained using the AUSNMRC1 plate and gradient strip. The MIC results for all nine antifungals on the AUSNMRC1 panel were highly reproducible for all quality control and reference strains and the overall EA and CA for 45 clinical strains tested across all three participating laboratories were >93% and 94.1%, respectively. These findings demonstrate the SYO AUSNMRC1 plate provides a commercial means to determine isavuconazole MICs by broth microdilution testing.

The objective of this study was to review the antifungal susceptibility of clinical mould isolates performed by the New Zealand Mycology Reference Laboratory.

Isolates were either local or referred for testing from other New Zealand laboratories. All isolates were tested by the broth colorimetric microdilution method, Sensititre YeastOne (SYO). Epidemiological cut-off values (ECVs) derived from either the Clinical and Laboratory Standards Institute (CLSI) method or SYO were used to determine the proportion of non-wild type (non-WT) isolates, i.e., those with an increased likelihood to harbour acquired mechanisms of resistance.

A total of 614 isolates were tested. Most isolates (55%) were from the respiratory tract followed by musculoskeletal tissue (17%), eye (10%) and abdomen (5%). The azoles had similar activity except for voriconazole which was less active against the Mucorales. The echinocandins had good activity against Aspergillus spp., other hyaline moulds and dematiaceous isolates but were inactive against Fusarium spp., Lomentospora prolificans and the Mucorales. Amphotericin B had best activity against the Mucorales. The two least susceptible groups were Fusarium spp. and L. prolificans isolates. Three Aspergillus isolates were non-WT for amphotericin B, and four non-WT for azoles. Non-WT were not encountered for caspofungin.

Non-Aspergillus isolates in New Zealand have susceptibility patterns similar to those reported elsewhere. In contrast to a growing number of other countries, azole resistance was rare in A. fumigatus sensu stricto. Non-WT isolates were uncommon. The results provide a baseline for monitoring emerging antifungal resistance in New Zealand and support current Australasian treatment guidelines for invasive fungal infections.

Las infecciones fúngicas, incluyendo aquellas producidas por hongos que pueden ser resistentes o multirresistentes a los antifúngicos, representan un serio problema de salud pública. La información sobre la sensibilidad de estos microorganismos a los distintos antifúngicos debe ser analizada lo más rápidamente posible para ayudar a los profesionales clínicos a instaurar un tratamiento adecuado. Desafortunadamente, las pruebas de sensibilidad a los antifúngicos no están tan desarrolladas ni implementadas como las de los antibacterianos, que son similares tanto en su diseño como en su precisión y reproducibilidad, pero laboriosas y lentas. En este artículo realizamos una revisión de los métodos de estudio de sensibilidad in vitro, tanto los de referencia (CLSI y EUCAST) como los comerciales y los nuevos métodos basados en la proteó-mica (MALDI-TOF MS) y en la detección de genes de resistencia por técnicas de amplificación de ácidos nucleicos. Además, se comentan los nuevos puntos de corte clínicos establecidos recientemente, así como los puntos de corte epidemiológicos, que se trata de una nueva categoría que puede ayudar a identificar de manera precoz las cepas aisladas que han adquirido mecanismos de resistencia. También se comentan las ventajas y las limitaciones de cada uno de los métodos revisados. Por tanto, puede concluirse que, aunque se ha avanzado mucho en los estudios de sensibilidad in vitro a los antifúngicos, aún existen limitaciones en su aplicación en la práctica diaria de un laboratorio de microbiología aunque parece que el futuro es esperanzador con las nuevas tecnologías basadas en la proteómica y en la amplificación de los ácidos nuclei-cos. Información sobre el suplemento: este artículo forma parte del suplemento titulado «Programa de Control de Calidad Externo SEIMC. Año 2016», que ha sido patrocinado por Roche, Vircell Microbiologists, Abbott Molecular y Francisco Soria Melguizo, S.A.

© 2019 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosasy Microbiología Clínica. Todos los derechos reservados.

Fungal diseases, including those caused by (multi)drug-resistant fungi, still represent a global public health concern. Information on the susceptibility of these microorganisms to antifungal agents must be quickly produced to help clinicians initiate appropriate antifungal therapies. Unfortunately, antifungal susceptibility tests are not as developed or widely implemented as antibacterial tests, being similar in design, accuracy and reproducibility, but also laborious and slow. In this article, we review the methods of in vitro susceptibility testing, both reference (CLSI and EUCAST), commercial and new methods based on proteomics (MALDI-TOF MS) and in the detection of resistance genes by nucleic acid amplification techniques. In addi-tion, we discuss the newly established clinical breakpoints, as well as the epidemiological cut-off points, which constitute a new category that can help in the early identification of isolates that have acquired resistance mechanisms. We also discuss the advantages and limitations of each of the methods studied. Therefore, we can conclude that, although there has been much progress in studies of in vitro susceptibility testing to antifungals, there are still limitations in its application in the daily routine of microbiology labo-ratories, although it seems that the future is promising with the new technologies based on proteomics and nucleic acid amplification. Supplement information: This article is part of a supplement entitled «SEIMC External Quality Control Programme. Year 2016», which is sponsored by Roche, Vircell Microbiologists, Abbott Molecular and Francisco Soria Melguizo, S.A.

© 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosasy Microbiología Clínica. All rights reserved.