Table 1 Characteristics of patients with IA
Total | Non-neutropenic | Neutropenic (NF < 500) | p-value* (Significance level p < 0.001) | |
|---|---|---|---|---|
Number of patients | 112 | 101 (90.2%) | 11 (9.8%) | |
Demographic data | ||||
Sex: | ||||
Male | 78 (69.6%) | 71/101 (70.3%) | 7/11 (63.6%) | |
Female | 34 (30.4%) | 30/101 (29.7%) | 4/11 (36.4%) | |
Age (median [IQR]) | 64 (58–70.5) | 68 (58–75) | ||
Hematologic malignancy | 22 (19.6%) | 12/101 (11.9%) | 11/11 (100%) | 0.0001 |
HSCT | 7 (6.3%) | 5/101 (4.9%) | 2/11 (18.2%) | 0.140 |
Chronic lung disease | 48 (42.9%) | 46/101 (45.5%) | 2/11 (18.2%) | 0.112 |
COPD | 11 (9.8%) | 10/101 (9.9%) | 1/11 (9.1%) | 0.999 |
Chronic kidney disease | 24 (21.4%) | 23/101 (22.8%) | 1/11 (9.1%) | |
Dialysis | 5 (4.5%) | 5/101 (4.9%) | 0 (0%) | |
Liver disease | 6 (5.4%) | 6/101 (5.9%) | 0 (0%) | |
Cirrhosis | 3 (2.7%) | 2/101 (1.9%) | 1/11 (9.1%) | |
Heart disease | 16 (14.3%) | 16/101 (15.8%) | 0 (0%) | |
Gastrointestinal disease | 7 (6.3%) | 6/101 (5.9%) | 1/11 (9.1%) | |
Neurologic disease | 7 (6.3%) | 6/101 (5.9%) | 1/11 (9.1%) | |
Post-surgical | 1 (0.9%) | 0 (0%) | 1/11 (9.1%) | |
Other | 14 (12.5%) | 12/101 (11.9%) | 2/11 (18.2%) | |
Solid cancer | 9 (8%) | 8/101 (7.9%) | 1/11 (9.1%) | 0.999 |
Lung cancer | 6 (5.4%) | 5/101 (4.9%) | 1/11 (9.1%) | |
Lung methastasis | 2 (1.8%) | 2/101 (1.9%) | 0 (0%) | |
Pulmonary radiotherapy | 4 (3.6%) | 4/101 (3.9%) | 0 (0%) | |
Immunotherapy | 3 (2.7%) | 3/101 (2.9%) | 0 (0%) | |
SARS-CoV2 (last month) | 30 (26.8%) | 30/101 (29.7%) | 0 (0%) | 0.035 |
Influenza (last month) | 4 (3.6%) | 4/101 (3.9%) | 0 (0%) | 0.999 |
CMV reactivation | 29 (25.9%) | 29/101 (28.7%) | 0 (0%) | 0.037 |
Lymphopenia (< 1000) | 49 (43.8%) | 42/101 (41.6%) | 7/11 (63.6%) | 0.206 |
Chemotherapy | 15 (13.4%) | 6/101 (5.9%) | 9/11 (81.8%) | 0.0001 |
Previous steroids | 80 (71.4%) | 78/101 (77.2%) | 2/11 (18.2%) | 0.0001 |
SOT | 48 (42.9%) | 47/101 (46.5%) | 1(2.1%) | 0.023 |
Liver transplant | 3 (2.7%) | 2/101 (1.9%) | 1/11 (9.1%) | |
Kidney transplant | 8 (7.1%) | 7/101 (6.9%) | 1/11 (9.1%) | |
Heart transplant | 3 (2.7%) | 3/101 (2.9%) | 0 (0%) | |
Lung transplant | 35 (31.3%) | 35/101 (34.7%) | 0 (0%) | 0.016 |
Immunosuppressants | 74 (67%) | 65/101 (64.4%) | 10/11 (90.9%) | 0.097 |
Tacrolimus | 47 (42%) | 44/101 (43.6%) | 3/11 (27.3%) | |
Cyclosporin | 4 (3.6%) | 4/101 (3.9%) | 0 (0%) | |
Mycophenolate | 40 (35.7%) | 39/101 (38.6%) | 1/11 (9.1%) | |
Everolimus | 6 (5.4%) | 6/101 (5.9%) | 0 (0%) | |
Sirolimus | 1 (0.9%) | 1/101 (0.9%) | 0 (0%) | |
Others | 3 (2.7%) | 3/101 (2.9%) | 0 (0%) | |
Targeted therapy: | 10 (8.9%) | 8/101 (7.9%) | 2/11 (18.2%) | 0.255 |
Ibrutinib | 1 (0.9%) | 1/101 (0.9%) | 0 (0%) | |
Venetoclax | 2 (1.8%) | 1/101 (0.9%) | 1/11 (9.1%) | |
Rituximab | 2 (1.8%) | 1/101 (0.9%) | 1/11 (9.1%) | |
Other | 6 (5.4%) | 5/101 (4.9%) | 1/11 (9.1%) | |
Tocilizumab | 23 (20.5%) | 23/101 (22.8%) | 0 (0%) | |
HIV/AIDS | 1 (0.9%) | 1/101 (0.9%) | 0 (0%) | 0.999 |
Other causes of immunosuppression | 10 (8.9%) | 10/101 (9.9%) | 0 (0%) | |
IFI data | ||||
IFI category | 0.999 | |||
Proven | 13 (11.6%) | 12/101 (11.9%) | 1/11 (9.1%) | |
Probable/putative | 88 (78.6%) | 79/101 (78.2%) | 9/11 (81.8%) | |
Possible | 11 (9.8%) | 10/101 (9.9%) | 1/11 (9.1%) | |
Presentation of the IFI | 0.999 | |||
Disseminated | 6 (5.4%) | 6/101 (5.9%) | 0 (0%) | |
Localized | 106 (94.6%) | 95/101 (94.1%) | 11/11 (100%) | |
Site of involvement: | ||||
Endocarditis | 1 (0.9%) | 1/101 (0.9%) | 0 (0%) | |
Pulmonary | 100 (89.3%) | 89/101 (88.1%) | 11/11 (100%) | |
Skin-soft tisssue | 4 (3.6%) | 4/101 (3.9%) | 0 (0%) | |
Sinusal | 1 (0.9%) | 1/101 (0.9%) | 0 (0%) | |
Cerebral | 2 (1.8%) | 2/101 (1.9%) | 0 (0%) | |
Osteoarticular | 1 (0.9%) | 1/101 (0.9%) | 0 (0%) | |
Surgical wound | 2 (1.8%) | 2/101 (1.9%) | 0 (0%) | |
Tracheobronchitis | 8 (7.1%) | 8/101 (7.9%) | 0 (0%) | |
Others (suture, empyema, endophthalmitis…) | 10 (8.9%) | 10/101 (9.9%) | 0 (0%) | |
Reason for admission: IFI | 14 (12.5%) | 13/101 (12.9%) | 1/11 (9.1%) | |
Microbiology | ||||
Patients with at least one positive culture | 90 (80.4%) | 84/101 (83.2%) | 6/11 (54.5%) | 0.023 |
Aspergillus section (including cryptic species) | ||||
Fumigati | 61/93 (65.6%) | 56/86 (65.1%) | 5/7 (71.4%) | 0.350 |
Terrei | 9/93 (9.7%) | 9/86 (10.5%) | 0 (0%) | |
Nidulantes | 2/93 (2.2%) | 2/86 (2.3%) | 0 (0%) | |
Flavi | 6/93 (6.5%) | 6/86 (7%) | 0 (0%) | |
Nigri | 4/93 (4.3%) | 3/86 (3.5%) | 1 (14.3%) | |
Mixed | 8/93 (8.6%) | 8/86 (9.3%) | 0/7 (0%) | |
Spp | 3/93 (3.2%) | 2 (2.3%) | 1/7 (14.3%) | |
Cryptic species: A. lentulus, A. hortai, A. spinilosporus, A. fumigatiaffinis, Neosartorya udagawae | 13/93 (14%) | 11/86 (12.8%) | 2/7 (28.6%) | 0.252 |
Beta-D-glucan + serum (total n = 14) | 4/14 (28.6%) | 4/13 (30.8%) | 0/1 (0%) | 0.999 |
Galactomannan + serum (total n = 81) | 23/81 (28.4%) | 18/71 (25.7%) | 5/11 (45.5%) | 0.137 |
Bronchoscopy performed | 78 (71.4%) | 67/101 (66.3%) | 11/11 (100%) | |
Fungal stain BAL | ||||
KOH | 15/78 (19.2%) | 11/13(84.6%) | 4/4 (100%) | |
Calcofluor white | 2/78 (2.6%) | 2/13 (15.4%) | 0 (0%) | |
Not performed | 61/78 (54.5%) | |||
Fungal stain in BAL (total = 17) | ||||
Septate hyphae | 4/17(23.5%) | 4/13(30.8%) | 0 (0%) | |
Negative | 13/17 (76.5%) | 9/13 (69.2%) | 4/4(100%) | |
Galactomanan + BAL (total = 41) | 32/41 (78%) | 26/32 (81.3%) | 6/9 (66.7%) | 0.304 |
PCR Aspergillus BAL (n = 22) | ||||
Positives | 13/22 (59.1%) | 8/13 (61.5%) | 5/9 (55.5%) | 0.999 |
PCR Mucor BAL (n = 4) | ||||
Positives | 0/4 (0%) | 0/2 (0%) | 0/2 (0%) | – |
PCR Fusarium BAL (n = 4) | ||||
Positives | 0/4 (0%) | 0/2 (0%) | 0/2 (0%) | – |
PCR Scedosporium BAL (n = 4) | ||||
Positives | 0/4 (0%) | 0/2 (0%) | 0/2 (0%) | – |
PCR panfungal BAL (n = 17) | ||||
Positives | 5/17 (29.4%) | 4/10 (40%) | 1/7 (14.3%) | 0.304 |
Precipitins (IgG Aspergillus) (n = 13) | ||||
Positive | 1/13 (7.7%) | 1/13 (7.7%) | 0 (0%) | – |
Biopsy performed | 19/112 (17%) | 18/101 (17.8%) | 1/11 (9.1%) | |
Biopsy positive | 9/19 (47.4%) | 8/18 (44.4%) | 1/1 (100%) | |
Imaging tests | ||||
CNS CT scan performed | 15 (13.4%) | 12/101 (11.9%) | 3/11 (27.3%) | |
*Fungal involvement | 3/14 (14.3%) | 3/12 (1.9%) | 0/3 (0%) | |
Chest CT scan performed | 105 (93.8%) | 94/101 (93.1%) | 11/11 (100%) | |
Pulmonary nodules | 49/105 (46.7%) | 41/94 (43.6%) | 8/11 (72.7%) | 0.108 |
Halo sign | 12/105 (11.4%) | 7/94 (7.4%) | 5/11 (45.5%) | 0.003 |
Cavitation- crescent | 23/105 (21.9%) | 20/94 (21.3%) | 3/11 (27.3%) | 0.702 |
Tree in bud | 13/105 (12.4%) | 13/94(13.8%) | 0/11 (0%) | 0.352 |
Ground glass opacities | 53/105 (50.5%) | 44/94 (46.8%) | 9/11 (81.8%) | 0.052 |
Consolidation | 39/105 (37.1%) | 33/94 (35.1%) | 6/11 (54.5%) | |
Interstitial infiltrates | 33/105 (31.4%) | 30/94 (31.9%) | 3/11 (27.3%) | |
Pleural effusion | 35/105 (33.3%) | 31/94 (32.9%) | 4/11 (36.4%) | |
Sinusal CT scan performed | 2 (1.8%) | 1/101 (0.9%) | 1/11 (9.1%) | |
*Fungal involvement | 1 (50%) | 0/1 (0%) | 1/1 (100%) | |
PET-CT performed | 28 (25%) | 22/101 (21.8%) | 6/11 (54.5%) | 0.027 |
Indication PET-CT | ||||
Fever | 9/28 (32.1%) | 6/22 (27.3%) | 3/6 (50%) | |
Staging | 15/28 (53.6%) | 12/22 (54.5%) | 3/6 (50%) | |
Monitoring | 4/28 (14.3%) | 4/22 (18.2%) | 0 | |
Antifungal therapy | ||||
Antifungal prophylaxis: breakthrough IFI | 41 (36.6%) | 34/101 (33.7%) | 7/11 (63.6%) | 0.664 |
Prior AF prophylaxis: | ||||
Fluconazole | 7/41 (17.1%) | 4/34 (11.8%) | 3/7 (42.9%) | |
Posaconazole | 3/41 (7.3%) | 0 (0%) | 3/7 (42.9%) | |
Voriconazole | 1/41 (2.4%) | 1/34 (2.9%) | 0 (0%) | |
Isavuconazole | 1/41 (2.4%) | 1/34 (2.9%) | 0 (0%) | |
Micafungin | 2/41 (4.9%) | 2/34 (5.9%) | 0 (0%) | |
Anidulafungin | 2/41 (4.9%) | 1/34 (2.9%) | 1/7 (14.3%) | |
L-Amphotericin B (nebulized) | 33/41 (80.5%) | 33/34 (97.1%) | 0 (0%) | |
Resistant to prior AF | 21/41 (51.2%) | 17/34 (50%) | 4/7 (57.1%) | 0.686 |
Empirical AF therapy | ||||
Posaconazole | 3 (2.7%) | 2/101 (1.9%) | 1/11 (9.1%) | |
Voriconazole | 37 (33%) | 34/101 (33.7%) | 3/11 (27.3%) | |
Isavuconazole | 60 (53.6%) | 58/101 (57.4%) | 2/11 (18.2%) | |
Caspufungin | 2 (1.8%) | 2/101 (1.9%) | 0 | |
Micafungin | 15 (13.4%) | 15/101 (14.9%) | 0 | |
Anidulafungin | 8 (7.1%) | 8/101 (7.9%) | 0 | |
L-Amphotericin B (intravenous) | 12 (10.7%) | 6/101 (5.9%) | 6/11 (54.5%) | |
Resistant to empiric AF | 11 (9.8%) | 8/101 (7.9%) | 3/11 (27.3%) | 0.070 |
Targeted AF therapy | ||||
Posaconazole | 2 (1.8%) | 1/101 (0.9%) | 1/11 (9.1%) | |
Voriconazole | 25 (22.3%) | 20/101 (19.8%) | 5/11 (45.5%) | |
Isavuconazole | 63 (56.3%) | 60/101 (59.4%) | 3/11 (27.3%) | |
Caspufungin | 2 (1.8%) | 1/101 (0.9%) | 1/11 (9.1%) | |
Micafungin | 11 (9.8%) | 11/101 (10.9%) | 0 (0%) | |
Anidulafungin | 13 (11.6%) | 10/101 (9.9%) | 3/11 (27.3%) | |
L-Amphotericin B (intravenous) | 25 (22.3%) | 18/101 (17.8%) | 7/11 (63.6%) | |
Duration of therapy Median (IQR) | 44 (20–122) | 48 (21–161) | 40 (15–53) | |
Evolution | ||||
Coinfection (global) | 77 (68.8%) | 72/101 (65.5%) | 5/11 (45.5%) | 0.079 |
Virus coinfection | 36/77 (46.8%) | 35/72 (48.6%) | 1/5 (20%) | 0.101 |
Bacterial coinfection | 54/77 (70.1%) | 49/72 (68.1%) | 5/5 (100%) | |
Micobacterial coinfection | 3/77 (3.9%) | 3/72 (4.2%) | 0 (0%) | |
ICU due to IFI | 5 (4.5%) | 3/101 (2.9%) | 2/11 (18.2%) | |
Source Control | 9 (8%) | 9/101 (8.9%) | 0 (0%) | |
Reduction of immunosuppressants | 26 (23.2%) | 24/101 (23.8%) | 2/11 (18.2%) | |
Outcome | ||||
Graft loss if SOT | 5/48 (10.4%) | 4/47 (8.5%) | 1/1 (100%) | 0.104 |
Delay chemotherapy or HSCT | 8 (7.1%) | 3/101 (2.9%) | 5/11 (45.5%) | 0.637 |
Hospital death | 38 (33.9%) | 33/101 (32.7%) | 5/11 (45.5%) | 0.685 |
Discharged under AF | 55 (49.1%) | 51/101 (50.5%) | 4/11 (36.4%) | 0.685 |
Evaluated by ID | 63 (56.3%) | 52/101 (51.5%) | 11/11 (100%) |