By Stan Deresinski, MD, FIDSA
Synopsis: Bloodstream infections due to molds are uncommon, occurring predominantly in association with severe immunocompromise, even in the presence of anti-mold prophylaxis.
Source: Tala-Ighil AT, Garcia-Hermoso D, Dalle F, et al; for the French Mycoses Study Group. Epidemiology and prognostic factors associated with mold-positive blood cultures: 10-year data from a French prospective surveillance program (2012–2022). Clin Infect Dis. 2025;80(3):529-539.
Tala-Ighil and colleagues examined cases of bloodstream infection due to molds reported to a French national surveillance network with 30 participating centers from 2012-2022. Of the 117 cases of non-yeast fungemia, 28 cases were caused by dimorphic fungi and were excluded, as were nine cases deemed to represent “pseudofungemia,” and three with insufficient data. The final cohort consisted of 80 patients with 80 episodes of true mold infection, 54 (68%) of which were due to multiple species of Fusarium spp. Eight (10%) infections were due to Lomentospora prolificans, while Trichoderma, Aspergillus, and Mucorales each accounted for four cases. The remaining cases consisted of one each of species of Scedosporium, Nannizziopsis, Paecilomyces, Phialemeniopsis, Purpureocillium, and Exophiala.
The median age of the 80 patients was 56 years, and 51 (64%) were male; 74 (93%) had an indwelling central venous catheter. Hematological malignancy was present in 56 patients (70%) and 24 of the 56 had undergone allogeneic hematopoietic stem cell transplantation (aHSCT) at a median interval of 49 days (interquartile range [IQR], 20-402 days) prior to fungemia. Antifungal prophylaxis with an echinocandin, posaconazole, or amphotericin B was being received in 33 (41%) at the time of infection.
Of the 54 patients with fusariosis, 39 patients (72%) had a history of hematologic malignancy, and 18 of the 39 patients had undergone aHSCT; 30/54 patients (55.5%) were neutropenic and 25 patients (46%) had received an antifungal within the prior 30 days. Seven (13%) had gastrointestinal conditions (e.g., portal hypertension, pancreatitis, etc.). Seven (88%) of the eight patients with L. prolificans fungemia had a history of hematologic malignancy and four patients had undergone aHSCT; 5/8 patients had received an antifungal agent within the prior 30 days.
Among the 69 patients from the total cohort for whom data were available, 48 (70%) had evidence of organ involvement — pulmonary and cutaneous in 30 patients (63%) each; 15/69 patients (22%) had both. Only three patients (4%) had symptomatic central nervous system involvement. Of the 47 patients with Fusarium infection, 24 (51%) had cutaneous involvement while pulmonary involvement was detected in 19 (40%); both sites were affected in 12 patients (26%). Six of seven patients with L. prolificans infection had pulmonary lesions and half had cutaneous disease.
The median interval from blood draw to detection of fungemia was 72.0 hours (IQR, 52.3-90.0 hours) and was similar across genera, with the exception of Mucorales, for which the median time was 38.4 hours (IQR, 37.6-40.0 hours). Nineteen (29%) of 66 removed central venous catheters were culture positive.
Ninety-day mortality was 53%, with the following being independently associated with this outcome: Lomentospora prolificans (odds ratio [OR], 33.3 [95% confidence interval (CI): 3.52-4456]), Aspergillus spp. fungemia (OR, 14.2 [95% CI: 1.25-2006]), and corticosteroid exposure (OR, 7.85 [95% CI: 1.64-37.6]).
Commentary
Fungemia due to molds is uncommonly encountered. A national surveillance study in Denmark reported that only 9/1,939 fungal isolates over 12 years were molds.1 Data from several hematological units in Italy reported that 17/215 (8%) fungal bloodstream infections were due to molds.2 Among these, 11 (65%) were Fusarium spp., three (17%) were Aspergillus fumigatus, and the remaining isolates were accounted for by one for each of Mucor spp., Trichoderma viridae, and Scedosporium apiospermium (6%). The associated mortality was 70%.
A major feature of these infections is their frequent antifungal resistance, which may account for their frequent occurrence despite antifungal prophylaxis. The Infectious Diseases Society of America (IDSA) recommends prophylaxis targeting Aspergillus in high-risk patients, but breakthrough infections are not rare, as observed here and as recently reviewed.3 Of course, this antifungal resistance also may adversely affect the therapeutic approach once the breakthrough is recognized. As pointed out, that recognition may be delayed by the prolonged incubation required for detection of molds in blood cultures. Molecular methods, if readily available with rapid turnaround times, may overcome this problem.4
Stan Deresinski, MD, FIDSA, is Clinical Professor of Medicine, Stanford University.
References
1. Astvad KMT, Johansen HK, Røder BL, et al. Update from a 12-year nationwide fungemia surveillance: Increasing intrinsic and acquired resistance causes concern. J Clin Microbiol. 2018;56:e01564-17.
2. Criscuolo M, Marchesi F, Candoni A, et al. Fungaemia in haematological malignancies: SEIFEM-2015 survey. Eur J Clin Invest. 2019;49:e13083.
3. Deresinski S. Failure of anti-mold prophylaxis in patients with hematological malignancies — frequency and therapeutic management. In the Literature. Clin Infect Dis. 2025;80. [In press].
4. Lieu A, Zimmet AN, Pozdol J, et al. Concordance of non-invasive plasma cell-free DNA with invasive diagnostics for diagnosis of invasive fungal disease. Clin Infect Dis. 2025; Jan 17:ciaf021. doi: 10.1093/cid/ciaf021. [Online ahead of print].
Bloodstream infections due to molds are uncommon, occurring predominantly in association with severe immunocompromise, even in the presence of anti-mold prophylaxis.
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