Table 3.
Overview of all influenza-associated pulmonary aspergillosis cases
| IAPA; study arm | Age/sex | Underlying risk factor | Serum GM ODI (first; highest) | BAL GM ODI (first; highest) | BAL Aspergillus PCR | Culture (source; isolate) | Azole suscep-tibilitya | Tracheo-bronchitisb | EORTC/MSGERC [22] | Modified AspICU [2] | ICM2020 case definition [23] | Days between ICU admission and diagnosis IAPA | Days between IAPA and start antifungal therapy | Therapy | Outcome | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Early | 69/F | COPD | 1.13; 1.13 | 2.94; 2.94 | NP | BAL, BA; A. fumigatus, A. terreus | No data | No | NC | IPA | Probable IAPA | 1 | 0 | Vorico (11d) | Died in ICU (12d) |
| 2 | Early | 61/F | COPD | NP; NP | 1.24; 1.24 | Positive | NA | No data | No | NC | IPA | Probable IAPA | 2 | 3 | Vorico (12d) | Died in ICU (18d) |
| 3 | Early | 70/M | / | NP; NP | 6.5; 6.5 | Positive | NA | Susceptible | No | NC | IPA | Probable IAPA | 1 | NA | None | Died in ICU (3d) |
| 4 | Early | 85/M | / | 0.1; 0.1 | 1.3; 1.3 | Negative | NA | No data | No | NC | IPA | Probable IAPA | 1 | 1 | Vorico (43d) | Alive |
| 5 | Early | 50/M | CS before ICU (0.06 mg/kg/day)c | 0; 0.1 | 5.3; 5.6 | Positive | NA | Susceptible | No | NC | IPA | Probable IAPA | 2 | 1 | Vorico and Caspo, Amph B (69d) | Alive |
| 6 | Early | 49/M | / | 0.05; 0.05 | 2.09; 2.09 | Positive | BAL, BA; A. fumigatus | Susceptible | No | NC | IPA | Probable IAPA | 2 | 0 | Vorico (43d) | Alive |
| 7 | Early | 60/F | COPD, CS before ICU (0.22 mg/kg/day)c | 0.7; 0.7 | NP; NP | NP | BAL, BA, sputum; A. fumigatus | Susceptible | No | NC | IPA | Probable IAPA | 1 | 1 | Vorico and Caspo (10d) | Died in ICU (12d) |
| 8 | Early | 51/F | / | 0.3; 0.3 | 2.6; 2.6 | Negative | NA | No data | No | NC | IPA | Probable IAPA | 1 | 0 | POS and Micafun (4d) | Died in ICU (6d) |
| 9 | Early | 63/M | / | 3.5; 3.5 | 8.9; 8.9 | Positive | BAL; A. fumigatus | Susceptible | Yes | NC | IPA | Probable IAPA | 2 | 0 | Vorico and Micafun (2d) | Died in ICU (5d) |
| 10 | Early | 66/F | COPD | 0.6; 0.6 | 0.6; 0.6 | NP | BA, sputum; A. fumigatus | Susceptible | No | NC | IPA | Probable IAPA | 1 | 3 | Vorico and Anidula (10d) | Alive |
| 11 | Early | 60/M | COPD, CS before ICU (dose missing)c | 0.1; 0.2 | 0.2; 0.2 | NP | BAL; A. fumigatus | Susceptible | Yes | NC | IPA | Probable IAPA | 1 | 3 | Vorico and Anidula and nebAmph B (16d) | Alive |
| 12 | Early | 52/M | / | 0.5; 0.5 | 0.1; 0.1 | NP | NA | No data | Yes | NC | IPA | NC | 0 | 2 | Vorico and Anidula, POS and nebAmph B (14d) | Died in hospital (23d) |
| 13 | Early | 60/M | Lung transplant, use of calcineurin inhibitor and CS before ICU (0.14 mg/kg/day)c | 0; 0 | 4.3; 4.3 | Positive | BA; A. fumigatus | Susceptible | Yes | Proven IPA | Proven IPA | Proven IAPA | 2 | 2 | POS (7d) | Died in ICU (12d); autopsy proven |
| 14 | Early | 62/F | / | 0.2; 0.2 | 5.5; 5.5 | NP | NA | No data | No | NC | IPA | Probable IAPA | 0 | 0 | Vorico (97d) | Alive |
| 15 | Early | 39/M | / | 0.04; 0.04 | 1.38; 1.38 | Positive | BAL; A. fumigatus | Susceptible | No | NC | IPA | Probable IAPA | 1 | 4 | Vorico and Caspo (12d) | Died in ICU (17d) |
| 16 | Late POS | 55/F | Undifferentiated autoinflammatory disorder; CS before and during ICU (0.21 and 1.16 mg/kg/day)c | 0.4; 0.4 | 0.4; 1 | Positive | NA | Susceptible | No | NC | IPA | Probable IAPA | 8 | 1 | Vorico, POS (62d) | Alive |
| 17 | Late; POS | 59/M | COPD; CS before and during ICU (0.01 and 0.96 mg/kg/day)c | 0; 0.1 | 0.1; 5.7 | Negative | NA | No data | No | NC | IPA | Probable IAPA | 12 | 1 | Vorico (1d) | Died in ICU (13d) |
| 18 | Late; SOC | 79/M | COPD | 0.32; 0.32 | 0.72; 0.72 | NP | BAL, BA; A. fumigatus | Susceptible | No | NC | IPA | Probable IAPA | 3 | 0 | Vorico (31d) | Died in ICU (37d) |
| 19 | Late; SOC | 51/M | CS during ICU (0.01 mg/kg/day)c | 0.19; 0.19 | 2.14; 2.14 | NP | BAL, sputum; A. fumigatus | Susceptible | No | Proven IPA | Proven IPA | Proven IAPA | 4 | 0 | Vorico, Anidula (28d) | Died in ICU (33d), autopsy proven |
| 20 | Late; SOC | 64/F | Inherited immunodeficiency | 0.1; 0.1 | 0.1; 5.4 | Positive | NA | Susceptible | No | Probable IPA | IPA | Probable IAPA | 6 | 1 | Vorico (23d) | Alive |
| 21 | Late; SOC | 66/M | CS before and during ICU (0.34 and 0.38 mg/kg/day)c | 0.1; 0.1 | 0.2; 0.2 | Positived | NA | Susceptible | No | Proven IPA | Proven IPA | Proven IAPA | 9 | NA | None | Died in ICU (9d), autopsy proven |
All patients presented with at least one clinical sign and radiological criterion according to the modified AspICU algorithm, data not mentioned in table
Amph B amphotericin B, Anidula anidulafungin, BA bronchial aspirate, BAL broncho-alveolar lavage, Caspo caspofungin, COPD chronic obstructive pulmonary disease, CS corticosteroids, d day(s), EORTC/MSGERC European Organisation for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium, F female, GM galactomannan, IAPA influenza-associated pulmonary aspergillosis, IPA invasive pulmonary aspergillosis, M male, Micafun micafungin, NA not applicable, NC not classifiable, nebAmph B nebulized amphotericin B, NP not performed, ODI optical density index, PCR polymerase chain reaction, POS posaconazole, Vorico voriconazole
aAzole susceptibility: based on broth microdilution testing of isolates using EUCAST methodology and clinical breakpoints [24] or on detection of TR34/L98H and TR46/Y121F/T289A resistance mechanisms via PCR
bTracheobronchitis: signs of Aspergillus tracheobronchitis include ulceration(s), nodule(s), pseudomembrane(s), plaque(s) and eschar(s)
cCorticosteroid dose expressed as mean dose in mg/kg/day of prednisone equivalent
dPerformed post-mortem on stored BAL fluid (obtained during ICU admission)