Table 4.
Global distribution of T. interdigitale/T. mentagrophytes clinical isolates exhibiting reduced susceptibility to terbinafine.
| Country | Type of Study | Sampling Year | Tinea Infection | No of Isolates (Species) |
AST Method (Protocol) | TRB MIC (mg/L); % of Non-WT Isolates |
Other Antifungals Tested against TRB Non-WT Isolates (MIC (mg/L), % of Non-WT Isolates) |
Amino Acid Substitution within the SQLE (Codon Change) |
|---|---|---|---|---|---|---|---|---|
| Belgium [75] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) | 2018 | Tinea capitis | 5 (Tm) |
BMD (EUCAST E.Def 11.0) |
0.016–4; 20% | ITC (0.016, 0%) VRC (0.5, 0%) AMO (0.06, 0%) |
Phe397Leu (NA) |
| Denmark [7] | Case series | ND | Various typesof tinea | 2 (Ti) |
BMD (EUCAST E.Def 11.0) |
>4–>8; 100% | ND | Phe397Leu (n = 1) Leu393Phe (n = 1) (NA) |
| Finland [76] | Case series | 2019 | Tinea cutis glabrae | 4 (Tm VIII) |
BMD (ND) |
4–>8 (data available only for non-WT isolates); 75% | ND | ND |
| Germany [12] | Case series | 2016–2020 (72% during 2019–2020) |
Various types of tinea (mainly tinea corporis and tinea cruris) |
29 (Tm VIII) |
Agar screening (SDA containing TRB 0.2 mg/L) BMD (CLSI M38-A2) |
<0.2–16; 45% | ITC (0.008–0.5, 20%) a VRC (0.008–0.25, 20%) a |
Phe397Leu (n = 10) (TTC→CTC/TTC→TTA) Phe397Leu, Ala448Thr (n = 2) (TTC→CTC, GCT→ACT) Leu393Phe (n = 1) (TTA→TTC) |
| Germany [77] | Case report | 2019 | Tinea corporis, tinea cruris | 1 (Tm VIII) |
ND | ND | ND | Phe397Leu (TTC→CTC) |
| Germany [26] | Case report | ND | Tinea corporis | 1 (Tm VIII) |
Agar screening(SDA containing TRB 0.2 mg/L) | ND | ND | Phe397Leu (TTC→TTA) |
| Greece (present study) | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates) | 2010–2019 | Various types of tinea |
24 (Tm) |
BMD (EUCAST E.Def 11.0) |
0.008–8; 37.5% (all Tm VIII) |
ITC (0.016–0.125, 0%) VRC (0.03–0.5, 0%) AMO (0.125–0.5, 0%) |
Leu393Ser (n = 5) (TTA→TCA) Phe397Leu (n = 4) (TTC→TTA) |
| India [6] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) | 2017–2019 | Various types of tinea (mainly tinea corporis and tinea cruris) |
279 (Tm VIII) |
Agar screening(SDA containing TRB 0.2 mg/L) BMD (CLSI M38-A2) |
0.125–16; 71% | NA d | Phe397Leu (n = 153) (1189T→C/1191C→A/G) Phe397Leu, Ala448Thr (n = 27) (1189T→C/1191C→A/G, 1342G→A) Leu393Ser (n = 7) b (1178T→C) Leu393Phe (n = 6) (1179A→C) His440Tyr (n = 2) c (1318C→T) Gln408Leu, Ala448Thr (n = 2) b (1223A→T, 1342G→A) Ser443Pro (n = 1) c (1327T→C) Ser395Pro, Ala448Thr (n = 1) c (1183T→C, 1342G→A) |
| India [68] | Multicenter laboratory-based (screening of Ti/Tm clinical isolates) | 2014–2018 | Various types of tinea |
498 (Ti/Tm) |
BMD (CLSI M38-A2) |
0.016–32; 11% | NA d | Phe397Leu (n = 43) (NA) WT (n = 14) (-) |
| India [64] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) | 2014–2018 | Various types of tinea (mainly tinea corporis and tinea cruris) |
129 (Ti/Tm) |
BMD (CLSI M38-A2) |
0.125–32; 37% | ITC (0.06–2, 2%) VRC (0.03–0.5, 0%) FLC (0.5–64, 20%) LLC (0.004–0.03, 0%) CLT (1–8, 78%) MCZ (0.5–4, 80%) KTC (0.25–8, 9%) GRS (2–>8, 100%) STC (0.125- > 16, 35%) |
Phe397Leu (n = 39) Leu393Phe (n = 7) (NA) |
| India [33] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates) | 2017 | Various types of tinea (mainly tinea corporis and tinea cruris) |
ND (97 patients with Tm infection) |
BMD (CLSI M38-A2) |
2–16 (data available only for non-WT isolates); 15 isolates obtained from 13 patients (13%) | ND | Phe397Leu (TTC→CTC/TTC→TTA) |
| India [62] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates) | 2016–2017 | Tinea corporis, tinea cruris | 64 (Ti) |
BMD (CLSI M38-A2) |
0.25–>32; 61% | NA d | Phe397Leu (n = 10) a Leu393Phe (n = 3) WT (n = 4) (NA) |
| India [10] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) | 2015–2017 | Various types of tinea (mainly tinea corporis and tinea cruris) |
63 (Ti) |
BMD (CLSI M38-A2) |
0.06–>32; 32% | ITC (0.06–> 16, 25%) VRC (0.06–> 16, 10%) FLC (0.5–> 64, 80%) LLC (≤ 0.004–0.5, 0%) CLT (2–16, 100%) MCZ (1–> 16, 80%) KTC (0.5–> 32, 35%) GRS (2–> 8, 100%) AMB (0.25–1, 0%) STC (0.5–> 16, 75%) |
Phe397Leu (n = 12) Leu393Phe (n = 8) (NA) |
| India [44] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates recovered from recalcitrant/refractory cases) | 2014–2017 | Various types of tinea (mainly tinea corporis and tinea cruris) |
31 (Tm) |
BMD (CLSI M38-A2) |
0.03–16; 74% | NA d | ND |
| India [45] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates recovered from recurrent cases) | 2015 | Various types of tinea (mainly tinea corporis and tinea cruris) |
36 (Tm) 10 (Ti) |
BMD(CLSI M38-A2) |
Tm: 0.016–8; 11% Ti: 0.016–8; 10% |
NA d | ND |
| India [46] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates) | 2014–2015 | Various types of tinea (mainly tinea corporis and tinea cruris) |
37 (Ti) |
BMD (CLSI M38-A2) |
0.03–16; 8% | NA d | ND |
| India [47] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates) | 2014 | Various types of tinea (mainly tinea corporis and tinea cruris) |
88 (Ti) |
BMD (CLSI M38-A2) |
0.016–32; 17% | NA d | Phe397Leu (n = 4) (TTC→CTC) WT (n = 11) (-) |
| India [31] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) [48] | ND | Various types of tinea (mainly tinea corporis and tinea cruris) |
34 (Tm) |
BMD (CLSI M38-A2) |
0.06–4; 24% | NA d | ND |
| Iran [65] | Multicenter laboratory-based (screening of Ti/Tm clinical isolates) | 2016–2018 | Various types of tinea |
45 (28 Tm VIII, 17 Tm) |
BMD (CLSI M38-A2) |
0.008–>32; 11% (all Tm VIII) |
ITC (0.125–2, NA) LLC (0.004–0.008, 0%) GRS (1–4, NA) EFC (0.002–0.008, 0%) CLT (1–8, NA) AMO (0.5–2, NA) |
Phe397Leu, Ala448Thr (n = 4) Leu393Ser, Ala448Thr (n = 4) (NA) |
| Iran [21] | Multicenter laboratory-based (screening of Ti/Tm clinical isolates) | 2016–2018 | Various types of tinea |
140 (45 Tm, 95 Tm) |
BMD (CLSI M38-A2) |
Tm: 0.004–>32; 11% (all Tm VIII) Ti: 0.004–0.25; 0% |
ND | ND |
| Iran [11] | Case series | ND | Various types of tinea |
4 (Tm VIII) |
BMD (CLSI M38-A2) |
>8; 100% | ITC (≥ 4, 100%) FLC (≥ 16, 100%) VRC (0.25–0.5, 0%) POS (0.03–0.06, 0%) |
Phe397Leu (TTC→TTA) |
| Japan [69] | Case report | 2017–2018 | Tinea pedis | 1 (Ti) |
BMD for TRB (CLSI M38-A) E-test for ITC |
2; 100% | ITC (0.5, 0%) | WT (-) |
| Japan [73] | Case report | ND | Tinea corporis | 1 (Ti) |
BMD (CLSI M38-A2) |
32; 100% | ITC (≤ 0.03, 0%) RVC (≤ 0.03, 0%) |
Phe397Leu (NA) |
| Japan [72] | Case report | ND | Tinea corporis, tinea cruris, tinea faciei | 1 (Ti) |
BMD (CLSI M38-A2) |
>32; 100% | ITC (0.03, 0%) RVC (0.5, 0%) LLC (≤ 0.03, 0%) CLT (4, 100%) MCZ (8, 100%) |
Phe397Leu (NA) |
| Poland [78] | Multicenter laboratory-based (screening of Tm isolates) | 2016–2019 | Tinea capitis, tinea unguium | 7 (Tm) |
BMD (CLSI M38-A2) |
0.004–32; 14% | NA d | Leu393Phe (NA) |
| Russian Federation [79] | Multicenter laboratory-based (screening of Tm isolates) | 2015–2018 | Strains isolated from symptomatic animals (cats and dogs) | 10 (Tm) |
BMD (EUCAST E.Def 9.3.1) |
>32 (data available only for non-WT isolates); 40% | ENC (NA, 0%) KTC (NA, 0%) |
ND |
| Switzerland [24] | Multicenter laboratory-based (screening of Ti/Tm clinical isolates) | 2009–2019 | Various types of tinea (mainly tinea corporis and tinea faciei) |
162 (Tm) |
BMD [80] | >4 (data available only for non-WT isolates); 2% (all Tm VIII) | ITC (NA, 0%) FLC (NA, 0%) KTC (NA, 0%) GRS (NA, 0%) |
Phe397Leu (NA) |
| Switzerland [9] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) | 2013–2016 | Tinea unguium | 412 (Ti) |
Agar screening(SDA containing TRB 0.2 mg/L) BMD only for TRB non-WT isolates (CLSI M38-A2) |
32; 0.2% | ND | Phe397Leu (TTC→CTC) |
| Switzerland [80] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates) | ND | ND | 7 (Tm) |
BMD [80] | ≤0.004–>8; 14% | NA d | Phe397Leu(NA) |
| Switzerland [74] | Case report | ND | Tinea corporis | 2 (Tm) |
BMD for TRB (CLSI M38-A) Sensititre YeastOne for azoles |
>1; 100% | ITC (0.016, 0%) POS (0.008, 0%) |
Gln408Leu (CAA→CTA) |
a: data available for a proportion of isolates; b: moderately-resistant isolates (TRB MIC 1 mg/L); c: low-resistant isolates (TRB MIC 0.125–0.25 mg/L); d: several antifungals have been tested, but isolates with a non-WT phenotype to TRB have not been analyzed separately. Abbreviations: NA: not available, ND: not determined, Ti: T. interdigitale, Tm: T. mentagrophytes, Tm VIII: T. mentagrophytes Type VIII (India), TRB: terbinafine, FLC: fluconazole, ITC: itraconazole, POS: posaconazole, VRC: voriconazole, RVC: ravuconazole, LLC: luliconazole, GRS: griseofulvin, KTC: ketoconazole, MCZ: miconazole, CLT: clotrimazole, AMB: Amphotericin B, AMO: amorolfine, STC: sertaconazole, ENC: enilconazole, EFC: efinaconazole, MIC: minimum inhibitory concentration, AST: antifungal susceptibility testing, WT: wild-type, BMD: broth microdilution method, SDA: Sabouraud dextrose agar, SQLE: squalene epoxidase.