Table 2.
Overview of antifungal clinical studies (Chronological order)
| Antifungal | Dose | Route | target | Fungi | n | Design | Duration | benefits/outcome | Refs. |
|---|---|---|---|---|---|---|---|---|---|
| Ketoconazole | 400 mg, qd | oral | ABPA, Aspergiloma | S | 10 | DB | 12 M | Af-IgG, symptom score (↓) | Shale [85] |
| Itraconazole | 50–400 mg, qd | oral |
Aspergillosis Aspergilloma |
S | 137 | Open | 11-780D |
5 ABPA patients: Symptom (4/5↓) Fungus (3/4↓) cure/improved:60% in IA, 66% in chronic necrotising pulmonary aspergillosis |
De Beule [86] |
| Inhaled Natamycin | 5 mg, bid | inhaled | ABPA | S | 25 | DB | 50 W |
17 patient (9 natamycin, 8 placebo) completed No evidence that natamycin conferred benefit on ABPA |
Currie [87] |
| Itraconazole | 200 mg, bid | oral | ABPA (CF, asthma) | S C | 6 | Open | 1-6 M (3.9 M mean) | Symptom, tIgE, steroid use (↓),Af-IgG ( →), sputum culture negative in 2/3 | Denning [88] |
| Itraconazole | 200 mg qd | oral | ABPA | S | 12 | Open | ≥ 6 M | 11/12 improvement, blood eosinophil, tIgE (↓), Af precipitins -ve (7/12) | Germaud [89] |
| Fluconazole | 100 mg qd | oral | Asthma with dermatophytosis | C | 11 | DB | 5 M + 36 M | bronchial sensitivity to Trichophyton, oral steroid use and symptom (↓) PEF(↑) | Ward [68] |
| Itraconazole | 200 mg qd | oral | ABPA | S | 14 | Open | 12 M | Lung function (↑), blood esopinophilia, tIgE and steroid use (↓), Af-IgE ( →), | Salez [90] |
| Itraconazole | 200 mg bid | oral | ABPA | S | 55 | DB | 16 W | Overall improvement (19% Placebo, 46% ITC), %change on tIgE -60% ITC vs. -44% PLB | Stevens [58] |
| Itraconazole | 400 mg qd | oral | ABPA | S | 29 | DB | 16 W | Sputum eosinophil, ECP and serum tIgE/Af-IgG against A. fumigatus (↓), Exacerbation requiring oral steroids (↓),%change on tIgE -20% ITC vs. + 1% PLB | Wark [59] |
|
Itraconazole Fluconazole |
200 mg qd 150 mg qd |
oral | ABPA | S | 44 | RS | 6 M | ITC > FLU: Better control of asthma symptom, less requirement of reliever/steroid, lesser exacerbation, vs. non-treatment | Rai [91] |
| Itraconazole | 200 mg bid | oral | SAFS | S | 58 | DB | 32 W | AQLQ, Rhinitis score, PFT, tIgE (improved vs. Placebo). 60% large improvement. %change on tIgE -27% ITC vs. + 12% PLB | Denning [61] |
| Itraconazole | 100-450 mg qd | oral |
ABPA SAFS |
S | 33 | RS | > 6 M | Lung function (↑), tIgE, Af-RAST, eosinophil, steroid use (↓) | Pasqualotto [92] |
|
Voriconazole Posaconazole |
300-600 mg qd 800 mg qd |
oral |
ABPA, SAFS (Iraconazole-failed) |
S | 25 | Open | ≥ 6 M |
Clinical response VOR (70% in), POS (78%) after 3 M treatment tIgE, RAST-Af (↓) after ≥ 9 M treatment |
Chishimba [13] |
|
Voriconazole (EVITA3) |
200 mg bid | oral | Af associated asthma | S | 56 | DB | 3 M | no difference on severe exacerbation, QOL, lung function, t or Af-IgE/IgG, blood/sputum eosinophil vs. placebo | Agbetile [62] |
| Amphotericin B | 10 mg bid | nebulised |
ABPA, SAFS (Itraconazole/voriconazole failed) |
S | 21 | Open |
30D (median) 0–1825D |
14% (3/21) Clinical benefit 33% (7/21), failed initial dose due to Bronchospasm 52% (11/21), discontinued within 12 M |
Chishimba [11] |
| Amphotericin B | 10 mg bid thrice a week | nebulised | ABPA | S | 21 | DB | 4 M | Frequency of exacerbation (↓ vs. nebulized budesonide), 3 patients, bronchospasm after nebulization of AMB | Ram [12] |
| Itraconazole | 200 mg bid | oral | ABPA (acute stage) | S | 131 | DB | 4 M |
ITC was effective, but overall efficacy: ITC < prednisolone, side effects ITC < prednisolone The time to the first exacerbation: ITC = prednisolone %change on tIgE -66% ITC vs. 67% PDS |
Agarwal [10] |
| Voriconazole | 200 mg bid | oral | ABPA (acute stage) | S | 50 | unblinded, randomised | 4 M |
VRC: Exacerbation, IgE, SGRQ(↓), Lung function (↑) But, VRC appears to be as effective as prednisolone |
Agarwal [93] |
| Amphotericin B | 10 mg bid | nebulised | Pulmonary Aspergillosis | S | 177 | RS | 4 M to 6Y |
Poorly tolerated (66% only) due to increased breathlessness Some patients showed t/Af IgE, Af-IgG(↓) |
Otu [60] |
ABPA, Allergic Bronchopulmonary Aspergillosis; Af, Aspergillus fumigatus; AMB, Amphotericin B; bid, bis in die (twice daily); C, colonised (culture; PCR or any format of fungal detection); D, day; DB, double blind; ITC, itraconazole; M, month; PDS, prednisolone; POS, posaconazole; PLB, placebo; qd, quaque die (once daily); RS, retrospective; S, sensitised (blood IgE or skin); SAFS, Severe Asthma with Fungal Sensitisation; tIgE, total IgE; VOR, voriconazole; W, week; Y, year