Australian Scedosporium Study

Monash Infectious Diseases participated in this study coordinated by the Australian and New Zealand Mycoses Interest Group (ANZMIG), a special interest group (SIG) of the Australasian Society for Infectious Diseases (ASID).

Publications
Population-based surveillance for scedosporiosis in Australia: epidemiology, disease manifestations and emergence of Scedosporium aurantiacum infection.
Heath CH, Slavin MA, Sorrell TC, Handke R, Harun A, Phillips M, Nguyen Q, Delhaes L, Ellis D, Meyer W, Chen SC; Australian Scedosporium Study Group.
Clin Microbiol Infect. 2009 Jul;15(7):689-93. doi: 10.1111/j.1469-0691.2009.02802.x. Epub 2009 Jun 22.
PMID: 19549223 [PubMed – indexed for MEDLINE]
Abstract. Australia-wide population-based surveillance for scedosporiosis identified 180 cases, with 118 (65.6%) cases of colonization and 62 (34.4%) cases of infection. Predisposing factors for isolation of Scedosporium spp. included chronic lung disease in 37.8% and malignancy in 21.7% of cases. Predictors of invasive disease (n=62) included haematological stem cell transplantation (n=7), leukaemia (n=16) and diabetes mellitus (n=8). Of 183 phenotypically-speciated isolates, 75 (41%) were Scedosporium prolificans (risk factors: haematologic cancer (n=17), neutropaenia (n=14)) and 108 (59%) had Scedosporium apiospermum/Pseudallescheria boydii phenotype [risk factor: diabetes (n=15)]. Scedosporium prolificans (p 0.01) and leukaemia (p 0.03) independently predicted death. Epidemiological and antifungal susceptibility profiles of Scedosporium aurantiacum (prevalence>or=15.8%) and S. apiospermum were similar. No patient with S. aurantiacum infection (n=6) died. This is the first description of clinical features associated with S. aurantiacum.

Molecular typing of Australian Scedosporium isolates showing genetic variability and numerous S. aurantiacum.
Delhaes L, Harun A, Chen SC, Nguyen Q, Slavin M, Heath CH, Maszewska K, Halliday C, Robert V, Sorrell TC; Australian Scedosporium (AUSCEDO) Study Group, Meyer W.
Emerg Infect Dis. 2008 Feb;14(2):282-90. doi: 10.3201/eid1402.070920.
PMID: 18258122 [PubMed – indexed for MEDLINE]
Abstract. One hundred clinical isolates from a prospective nationwide study of scedosporiosis in Australia (2003-2005) and 46 additional isolates were genotyped by internal transcribed spacer-restriction fragment length polymorphism (ITS-RFLP) analysis, ITS sequencing, and M13 PCR fingerprinting. ITS-RFLP and PCR fingerprinting identified 3 distinct genetic groups. The first group corresponded to Scedosporium prolificans (n = 83), and the other 2 comprised isolates previously identified as S. apiospermum: one of these corresponded to S. apiospermum (n = 33) and the other to the newly described species S. aurantiacum (n = 30). Intraspecies variation was highest for S. apiospermum (58%), followed by S. prolificans (45%) and S. aurantiacum (28%) as determined by PCR fingerprinting. ITS sequence variation of 2.2% was observed among S. apiospermum isolates. No correlation was found between genotype of strains and their geographic origin, body site from which they were cultured, or colonization versus invasive disease. Twelve S. prolificans isolates from 2 suspected case clusters were examined by amplified fragment length polymorphism analysis. No specific clusters were confirmed.

Hospital costs, length of stay and mortality attributable to invasive scedosporiosis in haematology patients.
Heng SC, Slavin MA, Chen SC, Heath CH, Nguyen Q, Billah B, Nation RL, Kong DC.
J Antimicrob Chemother. 2012 Sep;67(9):2274-82. doi: 10.1093/jac/dks210. Epub 2012 May 29.
PMID: 22643193 [PubMed – indexed for MEDLINE]
BACKGROUND: Scedosporium species are increasingly recognized as a cause of invasive mould disease in haematology patients, but little is known about the hospitalization costs and outcomes attributable to invasive scedosporiosis (SCEDO).
METHODS: A retrospective case-control study was undertaken during 2002-10 to determine the attributable inpatient costs, length of stay (LOS) and mortality associated with SCEDO in haematology patients. Case patients with SCEDO (n = 30) were matched 1 : 2 to controls (n = 60) according to haematological diagnosis, admission year and age. Diagnostics, antifungal drugs, ward and other SCEDO-related costs were estimated using actual cost data. Median regression modelling was used to adjust for variables that were not accounted for in the matched-pairs analysis.
RESULTS: The crude total median cost of treating SCEDO was AU$32 182 per patient versus AU$17 424 per control. In multivariable analysis, SCEDO was associated with median excess costs of AU$23 611 (95% CI = AU$17 992-AU$29 231; P < 0.001), approximating US$15 509 at purchasing power parity, with prolonged LOS of 13 days (95% CI = 8.2-17.8 days; P < 0.001). Exclusion of cases and matched pairs with early death further increased the median excess cost and LOS. The cost differential was driven by ward costs (64%, P = 0.005) and antifungal treatment costs (29%, P < 0.001). The all-cause inpatient mortality was 38 times higher for the SCEDO cases versus the control group (63.3% versus 1.7%; P < 0.001).
CONCLUSIONS: SCEDO has substantial impact on hospital resource consumption, LOS and mortality in haematology patients. Risk factors and preventative measures for SCEDO should be further studied.


Treatment of scedosporiosis with voriconazole: clinical experience with 107 patients.

Troke P, Aguirrebengoa K, Arteaga C, Ellis D, Heath CH, Lutsar I, Rovira M, Nguyen Q, Slavin M, Chen SC; Global Scedosporium Study Group.
Antimicrob Agents Chemother. 2008 May;52(5):1743-50. doi: 10.1128/AAC.01388-07. Epub 2008 Jan 22.
PMID:18212110 [PubMed – indexed for MEDLINE]
Abstract. The efficacy of voriconazole in 107 patients with scedosporiosis was analyzed. Principal infection sites were the lungs/sinuses (24%), central nervous system (CNS) (20%), and bone (18%), while 21% of patients had disseminated infection. Solid organ transplantation (22%), hematological malignancy (21%), and surgery/trauma (15%) were the predominant underlying conditions. A successful therapeutic response was achieved in 57% of patients (median, 103 therapy days), with > 98% of those responding receiving > or = 28 days of therapy. Patients receiving primary therapy showed a 61% response versus 56% for the others. The best therapeutic responses were seen for skin/subcutaneous (91%) or bone (79%) infections, and the lowest for CNS infections (43%). Patients without major immune suppression (72%) or those with solid organ transplantation (63%) or various hematological conditions (60%) showed the best responses by underlying condition. Median known survival time was 133 days (therapy successes, 252 days; failures, 21 days). In all, 43 (40%) patients died, 73% due to scedosporiosis. Patients with Scedosporium prolificans infection had significantly reduced survival times (P = 0.0259) and were more likely to die from fungal infection (P = 0.002) than were Scedosporium apiospermum-infected patients. In a subset of 43 patients where voriconazole baseline MICs were available, response to voriconazole was higher for S. apiospermum-infected patients (54% response; MIC(50), 0.25 microg/ml) than for S. prolificans-infected patients (40% response; MIC(50), 4.0 microg/ml). Voriconazole demonstrated clinically useful activity in the treatment of both S. apiospermum and S. prolificans infections and was well tolerated.

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