Table 3. Characteristics of included animal studies.
| Studies | Types of animals | Sample sizes | Aspergillus | MIC(µg/mL) | Infective doses | Treatments |
Duration of treatment (days) | Findings | |
|---|---|---|---|---|---|---|---|---|---|
| Combination therapy | Monotherapy | ||||||||
| Kirkpatrick WR et al., 2002 (7) | Male guinea pigs | 72 | A. fumigatus | VRC 0.5, CAS 32 | 1×106 conidia | CAS 1 or 2.5 mg/kg/day IP + VRC 5 mg/kg/day PO | CAS 1 or 2.5 mg/kg/day IP or VRC 5 mg/kg/day PO | 5 | Mortality↓ (P<0.0025 compared to CAS); no differences compared to VRC |
| Luque JC et al., 2003 (6) | Female mice | 40 | A. fumigatus | ITZ 1.56, MICA >16 | 8×106 conidia | MICA 3 mg/kg q12h + ICZ 100 mg/kg/day | MICA 3 mg/kg q12h or ICZ 100 mg/kg/day or no drug | 12 | Survival↑ (P<0.05 compared to MICA); no differences compared to ICZ |
| Petraitis V et al., 2003 (5) | Female rabbits | 36 | A. fumigatus | RAV 1.0, MICA 0.25 | 1×108-1.25×108 conidia | MICA 1 mg/kg/day IV + RAV 2.5 mg/kg/day IV | MICA 1 mg/kg IV or RAV 2.5 mg/kg IV or no drug | 12 | Mortality↓ (P≤0.001); residual fungal burden↓ (P≤0.05); galactomannan indexes↓ (P≤0.01) |
| MacCallum DM et al., 2005 (15) | Male Guinea pigs | 90 | A. fumigatus | VRC 0.032 to 0.5, CAS 0.125 | 104 or 103 conidia/g | CAS 1 mg/kg/day IP + VRC 1 mg/kg PO q12h | VRC 1 mg/kg PO q12h or CAS 1 mg/kg/day IP | 7 | Survival↑ (P=0.048 compared to CAS with 103 conidia/g) |
| Clemons KV et al., 2006 (9) | Female mice | 40 | A. fumigatus | NR | 3.96×104 conidia | MICA 1 mg/kg/day + ICZ 100 mg/kg/day | MICA 1 mg/kg/day or ICZ 100 mg/kg/day or no drug | 10 | Survival↓ (P>0.05) |
| van de Sande WW et al., 2009 (8) | Female rats | 58 | A. fumigatus | NR | NR | AFG 20 mg/kg/day on day 1, followed 5 mg/kg/day + VRC 7.5, 10, 12.5, and 15 mg/kg on days 0, 1, 2, and 3 and 17.5 mg/kg on day 4 and beyond, IP q12h | AFG or VRC or no drug | 5-10 | Survival↓ (P=0.3290); galactomannan indexes (P=0.0238 and P=0.0357) |
| Petraitis V et al., 2009 (16) | Female rabbits | 70 | A. fumigatus | VRC 0.5 to 1.0, AFG 0.25 | 1.0×108-1.25×108 conidia | AFG 5 or 10 mg/kg/day IV + VRC 10 mg/kg q8h IV | AFG 5 or 10 mg/kg/day IV or VRC 10 mg/kg q8h IV or no drug | 12 | Survival↑ (P<0.001) (AFG 5 mg/kg/day); survival↓ (P>0.05) (AFG 10 mg/kg/day); residual fungal burden↓ (P<0.05); galactomannan indexes↓ (P<0.05) |
| Calvo E et al., 2012 (17) | Male mice | 240 | A. flavus | VRC 0.5 to 1.0, AFG > 32 | 8×103 CFU | AFG 1 mg/kg/day IP + VRC 12.5 mg/kg PO q12h | AFG 1 mg/kg/day IP or VRC 12.5 mg/kg PO q12h or no drug | 7 | Survival↑ (P<0.05); residual fungal burden↓ (P<0.05); galactomannan indexes↓ (P<0.05) |
| Seyedmousavi S et al., 2013 (18) | Female mice | 882 | VRC-S and VRC-R A. fumigatus | VRC 0.25 and 4, AFG 0.031 | 2.4×107 and 2.5×107 conidia | AFG 20 mg/kg/day + VRC 20 mg/kg | AFG 10 mg/kg/day or VRC 20 mg/kg | 7 | Synergistic in VRC-S; additive in VRC-R |
AFG, anidulafungin; AMB, amphotericin B; CAS, caspofungin; ICZ, itraconazole; L-AMB, liposomal amphotericin B; MICA, micafungin; POC, posaconazole; RAV, ravuconazole; VRC, voriconazole; VRC-S, voriconazole-susceptible; VRC-R, voriconazole-resistant; IP, intraperitoneal; IV, intravenous; PO, peros (oral); q12h, every 12 h; NR, not reported; MIC, minimal inhibitory concentration.