Table 2. Single-resistance mutations in triazole-resistant A. fumigatus recovered from azole-naïve patients and environmental samples.
| Origin and year* | Geographic region | Sample | Azole exposure | Cyp51A resistance mechanisms§ (# of isolates) | Resistance phenotype | Comment | Reference |
|---|---|---|---|---|---|---|---|
| Clinical | |||||||
| 2006–2009 | France | Clinical | None | G432S (1) | ITC R, PCZ S, VCZ S | [21] | |
| 2010 | Germany | Pulmonary sample | None | M220L (1) | ITC R, PCZ R, VCZ S | [22] | |
| 2011–2015 | France | Clinical | No systemic antifungal treatment in last 6 months | A284T (1); H285Y (1) | ITC S, PCZ R, VCZ S ITC R, PCZ R, VCZ R |
Also isolates reported with changes at F46Y; M172V; N248T; D255E; E427K; in different combinations giving slightly elevated PCZ MICs | [23] |
| 2013 | Argentina | Cornea surface | None | G54E (1) | ITC R, PCZ S, VCZ S | [24] | |
| 2014 | France | Pulmonary sample | None | F219I (1) | ITC R, PCZ R, VCZ S | [25] | |
| 2014* | Unknown | Pulmonary sample | None | Y121F (1) | ITC s, PCZS, VCZ R, | [26] | |
| 2013–2014 | India | Pulmonary sample | None | P216L (3) G54R (1) Y431C (2) |
ITC R, PCZ S, VCZ S ITC R, PCZ S, VCZ R ITC R, PCZ S/R, VCZ S |
[27] | |
| Environmental | |||||||
| 2005* | Switzerland | Soil | n.a. | Unknown (1), F46Y, M172V, E427K (1) § |
ITC S, VCZ R ITC R, VCZ S |
In addition, several environmental isolates with ITC MIC 2–8 mg/l were reported without sequence information | [28] |
| 2007 | the Netherlands | Soil | n.a. | Unknown (3) F46Y/M172V/E427K§ (2) |
ITC R, PCZ S, VCZ R; ITC R, PCZ S, VCZ S; ITC S, PCZ S, VCZ R; ITC S, PCZ S, VCZ R |
[29] | |
| 2009–2011 | Great Britain | Soil, Air | n.a. | Unknown (2) | ITC R, PCZ R, VCZ S-I | [30] | |
| 2011–2015 | France | Dust, Patients home | n.a. | H285Y (1) | ITC R, PCZ R, VCZ R | Also, isolates reported with SNPs at F46Y; M172V; N248T; D255E; E427K; in different combinations, giving slightly elevated PCZ MICs |
[23] |
| 2011–2012 | Italy | Soil | n.a. | Unknown (1), F46Y/M172V/ N248T/D255E (1) § | ITC R, PCZ R, VCZ S; ITC R, PCZ R, VCZ I |
[31] | |
| 2012–2013 | Germany | Soil | n.a. | G54A (2) M220I (1) |
ITC R, PCZ R, VCZ S; ITC R, PCZ R, VCZ R |
[32] | |
| 2013–2014 | Tanzania, Roemania, India | Soil | n.a. | G54E (21) | ITC R, PCZ R, VCZ S | [33] | |
| 2014–2016 | Taiwan | Soil, Air | n.a. | WT cyp51A or SNPs (5) | ITC S-R, PCZ R, VCZ S-R | [34] | |
| 2014–2017 | Italy | Soil | n.a. | G54E | ITC R, PCZ R, VCZ S | [35] | |
| 2015 | Switzerland | Soil | n.a. | G54R | ITC R, PCZ S, VCZ S | [36] | |
| 2015–2016 | France | Soil | Propiconazole and tebuconazole | Unknown (1), P216L (1) | ITC R, PCZ R, VCZ R; ITC R, PCZ R, VCZ S |
[37] | |
| 2017* | Colombia | Soil | n.a. | Unknown | ITC R, VCZ S | [38] |
*Year of publication, as date of sampling was not provided.
§Amino acid alterations that are reported in azole-susceptible and -resistant isolates.
Abbreviations: I, intermediate; ITC, itraconazole; PCZ, posaconazole; R, resistant; S, susceptible; VCZ, voriconazole.