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. 2023 Feb 8;10(2):ofad059.
doi: 10.1093/ofid/ofad059. eCollection 2023 Feb.

Invasive Scedosporium and Lomentospora prolificans Infections in Australia: A Multicenter Retrospective Cohort Study

Chin Fen Neoh  1   2   3 , Sharon C A Chen  4   5 , Amy Crowe  6 , Kate Hamilton  4 , Quoc A Nguyen  7   8 , Debbie Marriott  7 , Jason A Trubiano  1   3   9 , Tim Spelman  10 , David C M Kong  11   12   13   14 , Monica A Slavin  1   2   3
Affiliations

Invasive Scedosporium and Lomentospora prolificans Infections in Australia: A Multicenter Retrospective Cohort Study

Chin Fen Neoh et al. Open Forum Infect Dis. .

Abstract

Background: Management of Scedosporium/Lomentospora prolificans infections remains challenging. We described predisposing factors, clinical manifestations, and outcomes of these rare mold infections, including predictors of early (1-month) and late (18-month) all-cause mortality and treatment failure.

Methods: We conducted a retrospective Australian-based observational study of proven/probable Scedosporium/L prolificans infections from 2005 to 2021. Data on patient comorbidities, predisposing factors, clinical manifestations, treatment, and outcomes up to 18 months were collected. Treatment responses and death causality were adjudicated. Subgroup analyses, multivariable Cox regression, and logistic regression were performed.

Results: Of 61 infection episodes, 37 (60.7%) were attributable to L prolificans. Forty-five of 61 (73.8%) were proven invasive fungal diseases (IFDs), and 29 of 61 (47.5%) were disseminated. Prolonged neutropenia and receipt of immunosuppressant agents were documented in 27 of 61 (44.3%) and 49 of 61 (80.3%) episodes, respectively. Voriconazole/terbinafine was administered in 30 of 31 (96.8%) L prolificans infections, and voriconazole alone was prescribed for 15 of 24 (62.5%) Scedosporium spp infections. Adjunctive surgery was performed in 27 of 61 (44.3%) episodes. Median time to death post-IFD diagnosis was 9.0 days, and only 22 of 61 (36.1%) attained treatment success at 18 months. Those who survived beyond 28 days of antifungal therapy were less immunosuppressed with fewer disseminated infections (both P < .001). Disseminated infection and hematopoietic stem cell transplant were associated with increased early and late mortality rates. Adjunctive surgery was associated with lower early and late mortality rates by 84.0% and 72.0%, respectively, and decreased odds of 1-month treatment failure by 87.0%.

Conclusions: Outcomes associated with Scedosporium/L prolificans infections is poor, particularly with L prolificans infections or in the highly immunosuppressed population.

Keywords: lomentosporiosis; outcomes; scedosporiosis; survivors; treatment response.

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Conflict of interest statement

Potential conflicts of interest. C. F. N. has received a fellowship grant from Gilead Sciences Australia. S. C.-A. C. has received educational grants from F2G and Merck Sharp & Dohme Australia. T. S. sat on advisory boards and steering committees for Biogen. M. A. S. has received grants from Gilead Sciences, Merck, F2G, and Pfizer, and participated in data and safety monitoring boards for Cidara and Roche, adjudication committees for Pfizer, and advisory boards for Merck, Gilead Sciences, F2G, Cidara, Pfizer unrelated, to the submitted work. All other authors report no potential conflicts.

Figures

Figure 1.
Figure 1.
Survival curves stratified by causative fungal pathogen (A) and immunosuppression level (B). Abbreviation: IFD, invasive fungal disease.
Figure 2.
Figure 2.
Heat maps depicting overall treatment response up to 18-month follow-up after initiation of antifungal treatment for the nonsurvivor subgroup with Lomentospora prolificans infection (n = 26; A) and the survivor subgroup with L prolificans infection (n = 11; B). Cases 24, 32, and 37 were lost to follow-up. A cutoff of ±1.5 months around each follow-up time point was used to allow for the fact that follow-up visits may not be conducted at exactly each time point given the retrospective study design. Immunosuppression level: high (H; eg, hematological malignancy [HM], hematopoietic stem cell transplant [HSCT]); moderate (M; eg, solid organ transplant [SOT], immunosuppressed for reasons other than HM/HSCT and SOT); or low/no (L; eg, minor/no medical condition).
Figure 3.
Figure 3.
Heat maps depicting overall treatment response up to 18-month follow-up after initiation of antifungal treatment for those with Scedosporium spp infections (n = 24). Case 15 was lost to follow-up. A cutoff of ±1.5 months around each follow-up time point was used to allow for the fact that follow-up visits may not be conducted at exactly each time point given the retrospective study design. Only case 2 did not survive beyond 28 days of antifungal therapy. Immunosuppression level: high (H; eg, hematological malignancy [HM], hematopoietic stem cell transplant [HSCT]); moderate (M; eg, solid organ transplant [SOT], immunosuppressed for reasons other than HM/HSCT and SOT); or low/no (L; eg, minor/no medical condition).
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