Table 3.
Globally reported T. rubrum clinical isolates exhibiting reduced susceptibility to terbinafine.
| Country | Type of Study | Sampling Year | Tinea Infection | No of Isolates | 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) |
|---|---|---|---|---|---|---|---|---|
| Denmark [38] | Case report | ND | Tinea corporis, tinea pedis | 1 | BMD (EUCAST E.Def 9.3) |
4; 100% | FLC (4, 0%) ITC (0.125, 0%) ISA (0.125, 0%) VRC (0.125, 0%) POS (0.03, 0%) |
Phe397Leu [7] (NA) |
| Denmark [39] | Case report | ND | Tinea corporis | 1 | BMD (EUCAST E.Def 9.3) |
>4; 100% | ITC (0.03, 0%) | Phe397Leu [7] (NA) |
| Denmark [7] | Case series | ND | Various typesof tinea | 10 | BMD (EUCAST E.Def 11.0) |
0.125–>8; 100% | ND | Phe397Leu (n = 4) Leu393Ser (n = 2) b Leu393Phe (n = 1) Phe415Ser (n = 1) c His440Tyr, Phe484Tyr (n = 1) c Ile121Met, Val237Ile (n = 1) c (NA) |
| India [6] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) | 2017–2019 | Various typesof tinea (mainly tinea corporis and tinea cruris) | 18 | Agar screening(SDA containing TRB 0.2 mg/L) BMD (CLSI M38-A2) |
0.03–8; 44% | NA d | Phe397Leu (TTC→CTC) |
| India [44] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates recovered from recalcitrant/refractory cases) | 2014–2017 | Various typesof tinea (mainly tinea corporis and tinea cruris) | 13 | BMD (CLSI M38-A2) |
0.125–8; 54% | NA d | ND |
| India [45] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates recovered from recurrent cases) | 2015 | Various typesof tinea (mainly tinea corporis and tinea cruris) | 29 | BMD (CLSI M38-A2) |
0.016–16; 10% | NA d | ND |
| India [46] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates) | 2014–2015 | Tinea corporis, tinea cruris | 5 | BMD (CLSI M38-A2) |
0.03–8; 40% | NA d | ND |
| India [47] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates) | 2014 | Various typesof tinea (mainly tinea corporis and tinea cruris) | 35 | BMD (CLSI M38-A2) |
0.016–16; 14% | NA d | Phe397Leu (n = 1) (TTC→CTC) WT (n = 3) (-) |
| India [31] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) [48] | ND | Various typesof tinea (mainly tinea corporis and tinea cruris) | 18 | BMD (CLSI M38-A2) |
0.03–4; 11% | NAd | ND |
| Iran [8] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) | ND | Tinea corporis, tinea pedis | 20 | BMD (CLSI M38-A2) |
0.004–> 32; 10% | LLC (NA, 0%) d | Leu393Phe (n = 1) (TTA→TTT) WT (n = 1) (-) |
| Japan [32] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) | 2020 | Various typesof tinea (mainly tinea pedis and tinea corporis) | 128 | Agar screening(SDA containing TRB 1 mg/L) BMD (CLSI M38-A2) |
32–>32; 4% | ITC (≤0.03–0.25, 0%) RVC (≤0.03–0.06, 0%) LLC (≤0.03, 0%) |
Leu393Phe (1179A→C/T) |
| Japan [37] | Case report | 2017 2019 |
Tinea unguium (fingernails) |
2 a | BMD (CLSI M38-A2) |
8–16; 100% | ITC (0.06–0.25, 0%) RVC (≤0.03, 0%) |
Phe397Leu (TTC→TTA) |
| Japan [40] | Case report | 2016 | Tinea pedis | 1 | BMD (CLSI M38-A2) |
>128; 100% | ITC (0.03, 0%) | Leu393Phe (TTA→TTC) |
| Malaysia [41] | Single-center laboratory-based (screening of Trichophyton spp. clinical isolates) | 2012–2013 | Various types of tinea |
3 | BMD (CLSI M38-A2) |
2–4; 100% | AMB (0.06–0.125, 0%) ITC (0.5, 0%) CLT (0.06–0.125, 0%) KTC (0.25–0.5, 0%) MCZ (0.5, 0%) |
ND |
| United States of America [36] | Case report | ND | Tinea corporis, tinea unguium (toenails) | 1 | BMD (CLSI M38-A2) |
>0.5; 100% | FLC (≤0.03, 0%) | ND |
| North America [43] | Case report | ND [49] | Tinea unguium (toenails) | 6 a | BMD (CLSI M27-A) |
4; 100% | FLC (0.25–0.5, 0%) ITC (≤0.06, 0%) GRS (0.125–0.5, 0%) |
Leu393Phe [50] (TTA→TTC) |
| Switzerland [9] | Multicenter laboratory-based (screening of Trichophyton spp. clinical isolates) | 2013–2016 | Tinea unguium, tinea pedis |
1644 | Agar screening(SDA containing TRB 0.2 mg/L) BMD only for TRB non-WT isolates (CLSI M38-A2) |
1–>128; 1% | ND | Leu393Phe (n = 4) (TTA→TTT) Leu393Ser (n = 2) (TTA→TCA) Phe397Leu (n = 4) (TTC→TTA/TTC→CTC) Phe397Ile (n = 1) (TTC→ATC) Phe397Val (n = 1) (TTC→GTC) Phe415Ile (n = 1) b (TTC→ATC) Phe415Ser (n = 1) (TTC→TCC) Phe415Val (n = 1) (TTC→GTC) His440Tyr (n = 1) b (CAT→TAT) |
| Switzerland [42] | Case report | ND | ND | 1 | BMD (CLSI M38-A) |
64; 100% | FLC (NA, 0%) ITC (NA, 0%) GRS (NA, 0%) |
Phe397Leu (TTC→TTA) |
a: obtained sequentially from a single patient; 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, TRB: terbinafine, FLC: fluconazole, ITC: itraconazole, ISA: isavuconazole, POS: posaconazole, VRC: voriconazole, RVC: ravuconazole, LLC: luliconazole, GRS: griseofulvin, KTC: ketoconazole, MCZ: miconazole, CLT: clotrimazole, AMB: Amphotericin B, MIC: minimum inhibitory concentration, AST: antifungal susceptibility testing, WT: wild-type, BMD: broth microdilution method, SDA: Sabouraud dextrose agar, SQLE: squalene epoxidase.