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Infections caused by Scedosporium/Lomentospora species: Clinical and microbiological findings in 21 cases

Infections caused by Scedosporium/Lomentospora species: Clinical and microbiological findings in... Abstract The clinical and microbiological characteristics of infections caused by Scedosporium/ Lomentospora species in 21 patients are described. We searched retrospectively the records for Scedosporium/ Lomentospora species seen at the University Hospital Virgen de las Nieves from 2006 to 2017. Out of them, 16 were male; mean age at diagnosis was 57.8 (±SD 15) years; all patients had risk factors for fungal infection such as corticosteroids and/or immunosuppressive treatment in 18 (85.7%) patients, pulmonary diseases in seven (33.3%) cases, hematological malignancies in six (28.5%), and organ transplantation in three (14.2%) patients. Most patients had infection in the lung/pleura (17/80.9%); cough was present in 12 patients and dyspnea in another 12, and the mean interval until diagnosis was 13.6 days. The most frequent species was S. apiospermum/S. boydii in 14 patients (66.6%), followed by L. prolificans in seven. The diagnosis was obtained from sputum in 12 (57.1%) cases, followed by pleural fluid and bronchoalveolar lavage in two of each. The most frequently used antifungals were voriconazole and amphotericin B, but combination of more than one antifungal drug was only used in three patients. Ten patients were cured, and six patients died as a consequence of the infection; three patients had chronic infection. In general, infections caused by Scedosporium/Lomentospora species are rare, serious, and difficult to diagnose and treat, having a high index or mortality especially in those caused by L. prolificans. Scedosporium/Lomentospora species, infection, antifungal drugs, invasive fungal disease, colonization Introduction Scedosporium spp. are fungal opportunistic pathogens causing serious infections difficult to treat. S. prolificans and S. apiospermum are the only recognized species that recently belonged to this genus, although molecular studies have demonstrated that S. apiospermum is a complex composed by five species.1,2 Moreover, S. prolificans is genetically distinct from the other Scedosporium species, and it was reassigned to the genus Lomentospora and is now called L. prolificans.2 Both species may cause invasive fungal disease with similar pathogeny, clinical manifestations, and severity, although they may act as surface or body cavities colonizers such as in patients with cystic fibrosis.3 In the last years, the infections caused by Scedosporium/Lomentospora species have increased, especially in immunossupressed patients, and are characterized by both their virulence and resistance to the majority of antifungals. Recently, we were confronted with a fatal case of pleural infection due to S. apiospermium (case 10). Due to its rarity, we have retrospectively reviewed the records of all cases seen in our hospital in the last 11 years, and we have analysed the most important clinical and microbiologic findings. Methods We describe the clinical and microbiologic characteristics of 21 patients with Scedosporium/Lomentospora infection seen at the University Hospital Virgen de las Nieves (Granada, Spain) during the period 2006–2017. We traced 41 cases caused by Scedosporium/Lomentospora described in sufficient detail through their clinical histories. We defined Scedosporium/Lomentospora infection according previous published guidelines.4,5 Of the 41 patients with positive cultures for Scedosporium/Lomentospora, only 21 met the criteria for “proven” or “probable” infection.4 Data on age and sex, localization of infection, fungal species, risk factors and/or underlying diseases, time until diagnosis, clinical manifestations, laboratory and radiological findings, microbiologic diagnosis, treatment, and outcome were recorded. Inoculation of media was performed according the type of sample following the standardized procedures in our laboratory. Overall, the specimens were inoculated in aerobic and anaerobic blood agar (BD Columbia Agar 5% Sheepblood®, Becton Dickinson, Franklin Lakes, NJ, USA), chocolate agar (BD Choco Agar, Becton Dickinson), and thioglycolate broth (in pleural fluid, bronchoalveolar lavage fluid and abscesses) (BDTM Fluid Thioglycollate Medium, Becton Dickinson), all incubated at 37 °C. Because fungal infection was suspected, Sabouraud agar and Sabouraud agar with cycloheximide (BD SAB, Becton Dickinson) were also used and incubated at 30 °C. Definitive diagnosis was performed by specimen culture and macroscopic appearance (Fig. 1), observation of fungal elements by microscopy (Fig. 2)6 and, in some instances (cases 10 and 13), by molecular methods such as polymerase chain reaction (PCR), performing sequentiation of both the ITS and the β-tubulin with the TUB-F and TUB-R primers7 and proteomic techniques such as Maldi-tof (Bruker Biotyper, Billerica, MA, USA).8 Figure 1. View largeDownload slide Macroscopic colonies of Scedosporium apiospermium in Sabouraud agar (from case 10). It can observe the grayish white colonies aspect. This Figure is reproduced in color in the online version of Medical Mycology. Figure 1. View largeDownload slide Macroscopic colonies of Scedosporium apiospermium in Sabouraud agar (from case 10). It can observe the grayish white colonies aspect. This Figure is reproduced in color in the online version of Medical Mycology. Figure 2. View largeDownload slide Cotton blue lactophenol stain (from case 10) (×400). Long and short hyaline conidiophores as well as oval conidia may be observed. This Figure is reproduced in color in the online version of Medical Mycology. Figure 2. View largeDownload slide Cotton blue lactophenol stain (from case 10) (×400). Long and short hyaline conidiophores as well as oval conidia may be observed. This Figure is reproduced in color in the online version of Medical Mycology. In two cases (10 and 13), the strain was sent to the National Centre of Microbiology (Majadahonda, Madrid, Spain) for susceptibility study, which was performed according to the EUCAST method.9 Results General characteristics Table 1 summarizes the clinical and microbiologic findings for the 21 patients with infection due to Scedosporium/Lomentospora. There were 16 (76.1%) men and the mean age of patients was 57.8 (±SD 15) years (range, 16–87 years). The mean interval from onset of symptoms to infection diagnosis was 13.6 days (range, 3–24 days), although for eight patients this interval was not reported. Table 1. Main findings in 21 patients with infection caused by Scedosporium/Lomentospora species seen at the University Hospital Virgen de las Nieves (2006–2017). Case Age (years)/ sex Localization of infection Species Risk factors and/or underlying diseases Time until diagnosis (days) Clinical manifestations Laboratory findings Radiological findings Microbiologic diagnosis Treatment Outcome 1 46/M Lung S. apiospermum Mieloma multiple CTS and IS treatment BMT Chronic GVHD 14 Fever, cough CRP 5.2 Bilateral interstitial infiltrate BAL culture AmB Cure 2 72/M Lung S. apiospermum COPD CTS treatment NR Fever, cough, dyspnea CRP 9.4 Alveolar condensation Pleural effusion BAL culture AmB Death 3 34/M Periorbital S. apiospermum Previous orbital surgery due to a severe trauma NR Periorbital abscess NR Normal Periorbital abscess culture Vz Surgery Cure 4 87/M Lung S. apiospermum CRD-Dialysis DM LTAT 9 Dyspnea, cough, chest pain CRP 10.4 Small basal condensation Sputum culture Vz Cure 5 68/M Skin S. apiospermum Liver transplantation CTS and IS treatment DM NR Cutaneous lesion, pain, asthenia, Leukopenia Neutropenia Normal Cutaneous biopsy culture Vz Death 6 63/M Lung S. apiospermum Liver transplantation CTS and IS treatment 15 Chest pain, cough CRP 1 Basal condensation Pleural effusion Sputum culture Vz Cure 7 75/M Lung S. apiospermum COPD CTS treatment DM 18 Dyspnea, cough NR Lung multiple nodules Cavitation Sputum culture Vz Cure 8 45/M Lung S. apiospermum COPD Bronchiectasias CTS treatment NR Productive cough, dyspnea NR Bronchiectasias Bullous emphysema Sputum culture Vz Chronic infection 9 16/M Lung S. apiospermum Cystic fibrosis Bronchiectasias LTAT NR Productive cough, fever CRP 11.2 Bilateral interstitial pattern Bronchiectasias Sputum culture Itr Chronic infection 10 34/F Pleural S. apiospermum Hodgkin lymphoma Chronic GVHD CTS and IS treatment 3 Dyspnea CRP 387.7 Pleural effusion Pleural fluid culture PCR Maldi-tof Vz Death 11 71/F Lung S. apiospermum Bronchiectasias Pneumonectomy due to lung polycystoses LTAT CTS treatment 19 Dyspnea, productive cough, hemoptysis CRP 1.43 Bronchiectasias Cysts Sputum culture Vz Cure 12 78/M Lung S. apiospermum Cervical metastasis from a cutaneous epidermoid cancer Radiotherapy CTS and IS treatment 8 Increase of secretions Nodular lesion in lung NR Nodule in lower left lobe Sputum culture NR NR 13 26/M Mediastinum S. apiospermum CGD CTS treatment 10 Cervical pain, mediastinal abscess CRP 44.18 Alveolar condensation Mediastinal and pulmonar abscesses Mediastinal abscess drainage PCR Vz + terb Vz + mic Cure 14 74/F Lung S. apiospermum CRD CTS treatment 7 Cough, dyspnea CRP 4.8 Alveolar condensation Sputum culture Vz Cure 15 53/M Blood L. prolificans Acute myeloid leukemia CTS and IS treatment NR Asthenia, fever abdominal pain Neutropenia Normal Blood cultures Vz + ter Death 16 64/M Lung L. prolificans Lymphoblastic B lymphoma CTS and IS treatment 18 Fever, productive cough, dyspnea NR Multiple alveolar infiltrate Nodules Sputum culture Vz Death 17 80/F Lung L. prolificans Chronic lymphatic leukemia CTS and IS treatment 24 Asthenia, fever, dyspnea NR Alveolar condensation Bronchiectasias Sputum culture Vz Death 18 38/F Pleural L. prolificans Pulmonary sarcoidosis CTS treatment NR Dyspnea, chest pain NR Pleural effusion Pleural fluid culture Vz Cure 19 65/M Lung L. prolificans Pulmonary transplantation CTS and IS treatment NR Productive cough, dyspnea CRP 0.9 Condensation lower right lobe Sputum culture Vz Moved to other hospital 20 72/M Lung L. prolificans COPD Psoriasis CTS and IS treatment 20 Productive cough, dyspnea, chest pain, chills CRP 17.56 Condensation lower right lobe Pleural effusion Bronchial aspirate culture Vz Cure 21 53/M Lung L. prolificans Aplastic anemia BMT Chronic GVHD DM CTS and IS treatment 13 Cough, dyspnea, anorexia, chest pain NR Alveolar infiltration Bronchiectasias Multiple disseminated nodules Sputum culture AmB + Vz Chronic infection Case Age (years)/ sex Localization of infection Species Risk factors and/or underlying diseases Time until diagnosis (days) Clinical manifestations Laboratory findings Radiological findings Microbiologic diagnosis Treatment Outcome 1 46/M Lung S. apiospermum Mieloma multiple CTS and IS treatment BMT Chronic GVHD 14 Fever, cough CRP 5.2 Bilateral interstitial infiltrate BAL culture AmB Cure 2 72/M Lung S. apiospermum COPD CTS treatment NR Fever, cough, dyspnea CRP 9.4 Alveolar condensation Pleural effusion BAL culture AmB Death 3 34/M Periorbital S. apiospermum Previous orbital surgery due to a severe trauma NR Periorbital abscess NR Normal Periorbital abscess culture Vz Surgery Cure 4 87/M Lung S. apiospermum CRD-Dialysis DM LTAT 9 Dyspnea, cough, chest pain CRP 10.4 Small basal condensation Sputum culture Vz Cure 5 68/M Skin S. apiospermum Liver transplantation CTS and IS treatment DM NR Cutaneous lesion, pain, asthenia, Leukopenia Neutropenia Normal Cutaneous biopsy culture Vz Death 6 63/M Lung S. apiospermum Liver transplantation CTS and IS treatment 15 Chest pain, cough CRP 1 Basal condensation Pleural effusion Sputum culture Vz Cure 7 75/M Lung S. apiospermum COPD CTS treatment DM 18 Dyspnea, cough NR Lung multiple nodules Cavitation Sputum culture Vz Cure 8 45/M Lung S. apiospermum COPD Bronchiectasias CTS treatment NR Productive cough, dyspnea NR Bronchiectasias Bullous emphysema Sputum culture Vz Chronic infection 9 16/M Lung S. apiospermum Cystic fibrosis Bronchiectasias LTAT NR Productive cough, fever CRP 11.2 Bilateral interstitial pattern Bronchiectasias Sputum culture Itr Chronic infection 10 34/F Pleural S. apiospermum Hodgkin lymphoma Chronic GVHD CTS and IS treatment 3 Dyspnea CRP 387.7 Pleural effusion Pleural fluid culture PCR Maldi-tof Vz Death 11 71/F Lung S. apiospermum Bronchiectasias Pneumonectomy due to lung polycystoses LTAT CTS treatment 19 Dyspnea, productive cough, hemoptysis CRP 1.43 Bronchiectasias Cysts Sputum culture Vz Cure 12 78/M Lung S. apiospermum Cervical metastasis from a cutaneous epidermoid cancer Radiotherapy CTS and IS treatment 8 Increase of secretions Nodular lesion in lung NR Nodule in lower left lobe Sputum culture NR NR 13 26/M Mediastinum S. apiospermum CGD CTS treatment 10 Cervical pain, mediastinal abscess CRP 44.18 Alveolar condensation Mediastinal and pulmonar abscesses Mediastinal abscess drainage PCR Vz + terb Vz + mic Cure 14 74/F Lung S. apiospermum CRD CTS treatment 7 Cough, dyspnea CRP 4.8 Alveolar condensation Sputum culture Vz Cure 15 53/M Blood L. prolificans Acute myeloid leukemia CTS and IS treatment NR Asthenia, fever abdominal pain Neutropenia Normal Blood cultures Vz + ter Death 16 64/M Lung L. prolificans Lymphoblastic B lymphoma CTS and IS treatment 18 Fever, productive cough, dyspnea NR Multiple alveolar infiltrate Nodules Sputum culture Vz Death 17 80/F Lung L. prolificans Chronic lymphatic leukemia CTS and IS treatment 24 Asthenia, fever, dyspnea NR Alveolar condensation Bronchiectasias Sputum culture Vz Death 18 38/F Pleural L. prolificans Pulmonary sarcoidosis CTS treatment NR Dyspnea, chest pain NR Pleural effusion Pleural fluid culture Vz Cure 19 65/M Lung L. prolificans Pulmonary transplantation CTS and IS treatment NR Productive cough, dyspnea CRP 0.9 Condensation lower right lobe Sputum culture Vz Moved to other hospital 20 72/M Lung L. prolificans COPD Psoriasis CTS and IS treatment 20 Productive cough, dyspnea, chest pain, chills CRP 17.56 Condensation lower right lobe Pleural effusion Bronchial aspirate culture Vz Cure 21 53/M Lung L. prolificans Aplastic anemia BMT Chronic GVHD DM CTS and IS treatment 13 Cough, dyspnea, anorexia, chest pain NR Alveolar infiltration Bronchiectasias Multiple disseminated nodules Sputum culture AmB + Vz Chronic infection AmB, amphotericin B; BAL, bronchoalveolar lavage; BMT, bone marrow transplantation; CGD, chronic granulomatous disease; COPD, chronic obstructive pulmonary disease; CRD, chronic renal disease; CRP, C-reactive protein (acceptable values 0.02–5 mg/l);; CTS, corticosteroids; DM, diabetes mellitus; F, female; GVHD, graft-versus-host-disease; IS, immunosuppressive; Itr, itraconazole; LTAT, long-term antibiotic treatment; M, male; Mic, micafungin; PCR, polymerase chain reaction; Ter, terbinafine; TNR, not reported; Vz, voriconazole. View Large Table 1. Main findings in 21 patients with infection caused by Scedosporium/Lomentospora species seen at the University Hospital Virgen de las Nieves (2006–2017). Case Age (years)/ sex Localization of infection Species Risk factors and/or underlying diseases Time until diagnosis (days) Clinical manifestations Laboratory findings Radiological findings Microbiologic diagnosis Treatment Outcome 1 46/M Lung S. apiospermum Mieloma multiple CTS and IS treatment BMT Chronic GVHD 14 Fever, cough CRP 5.2 Bilateral interstitial infiltrate BAL culture AmB Cure 2 72/M Lung S. apiospermum COPD CTS treatment NR Fever, cough, dyspnea CRP 9.4 Alveolar condensation Pleural effusion BAL culture AmB Death 3 34/M Periorbital S. apiospermum Previous orbital surgery due to a severe trauma NR Periorbital abscess NR Normal Periorbital abscess culture Vz Surgery Cure 4 87/M Lung S. apiospermum CRD-Dialysis DM LTAT 9 Dyspnea, cough, chest pain CRP 10.4 Small basal condensation Sputum culture Vz Cure 5 68/M Skin S. apiospermum Liver transplantation CTS and IS treatment DM NR Cutaneous lesion, pain, asthenia, Leukopenia Neutropenia Normal Cutaneous biopsy culture Vz Death 6 63/M Lung S. apiospermum Liver transplantation CTS and IS treatment 15 Chest pain, cough CRP 1 Basal condensation Pleural effusion Sputum culture Vz Cure 7 75/M Lung S. apiospermum COPD CTS treatment DM 18 Dyspnea, cough NR Lung multiple nodules Cavitation Sputum culture Vz Cure 8 45/M Lung S. apiospermum COPD Bronchiectasias CTS treatment NR Productive cough, dyspnea NR Bronchiectasias Bullous emphysema Sputum culture Vz Chronic infection 9 16/M Lung S. apiospermum Cystic fibrosis Bronchiectasias LTAT NR Productive cough, fever CRP 11.2 Bilateral interstitial pattern Bronchiectasias Sputum culture Itr Chronic infection 10 34/F Pleural S. apiospermum Hodgkin lymphoma Chronic GVHD CTS and IS treatment 3 Dyspnea CRP 387.7 Pleural effusion Pleural fluid culture PCR Maldi-tof Vz Death 11 71/F Lung S. apiospermum Bronchiectasias Pneumonectomy due to lung polycystoses LTAT CTS treatment 19 Dyspnea, productive cough, hemoptysis CRP 1.43 Bronchiectasias Cysts Sputum culture Vz Cure 12 78/M Lung S. apiospermum Cervical metastasis from a cutaneous epidermoid cancer Radiotherapy CTS and IS treatment 8 Increase of secretions Nodular lesion in lung NR Nodule in lower left lobe Sputum culture NR NR 13 26/M Mediastinum S. apiospermum CGD CTS treatment 10 Cervical pain, mediastinal abscess CRP 44.18 Alveolar condensation Mediastinal and pulmonar abscesses Mediastinal abscess drainage PCR Vz + terb Vz + mic Cure 14 74/F Lung S. apiospermum CRD CTS treatment 7 Cough, dyspnea CRP 4.8 Alveolar condensation Sputum culture Vz Cure 15 53/M Blood L. prolificans Acute myeloid leukemia CTS and IS treatment NR Asthenia, fever abdominal pain Neutropenia Normal Blood cultures Vz + ter Death 16 64/M Lung L. prolificans Lymphoblastic B lymphoma CTS and IS treatment 18 Fever, productive cough, dyspnea NR Multiple alveolar infiltrate Nodules Sputum culture Vz Death 17 80/F Lung L. prolificans Chronic lymphatic leukemia CTS and IS treatment 24 Asthenia, fever, dyspnea NR Alveolar condensation Bronchiectasias Sputum culture Vz Death 18 38/F Pleural L. prolificans Pulmonary sarcoidosis CTS treatment NR Dyspnea, chest pain NR Pleural effusion Pleural fluid culture Vz Cure 19 65/M Lung L. prolificans Pulmonary transplantation CTS and IS treatment NR Productive cough, dyspnea CRP 0.9 Condensation lower right lobe Sputum culture Vz Moved to other hospital 20 72/M Lung L. prolificans COPD Psoriasis CTS and IS treatment 20 Productive cough, dyspnea, chest pain, chills CRP 17.56 Condensation lower right lobe Pleural effusion Bronchial aspirate culture Vz Cure 21 53/M Lung L. prolificans Aplastic anemia BMT Chronic GVHD DM CTS and IS treatment 13 Cough, dyspnea, anorexia, chest pain NR Alveolar infiltration Bronchiectasias Multiple disseminated nodules Sputum culture AmB + Vz Chronic infection Case Age (years)/ sex Localization of infection Species Risk factors and/or underlying diseases Time until diagnosis (days) Clinical manifestations Laboratory findings Radiological findings Microbiologic diagnosis Treatment Outcome 1 46/M Lung S. apiospermum Mieloma multiple CTS and IS treatment BMT Chronic GVHD 14 Fever, cough CRP 5.2 Bilateral interstitial infiltrate BAL culture AmB Cure 2 72/M Lung S. apiospermum COPD CTS treatment NR Fever, cough, dyspnea CRP 9.4 Alveolar condensation Pleural effusion BAL culture AmB Death 3 34/M Periorbital S. apiospermum Previous orbital surgery due to a severe trauma NR Periorbital abscess NR Normal Periorbital abscess culture Vz Surgery Cure 4 87/M Lung S. apiospermum CRD-Dialysis DM LTAT 9 Dyspnea, cough, chest pain CRP 10.4 Small basal condensation Sputum culture Vz Cure 5 68/M Skin S. apiospermum Liver transplantation CTS and IS treatment DM NR Cutaneous lesion, pain, asthenia, Leukopenia Neutropenia Normal Cutaneous biopsy culture Vz Death 6 63/M Lung S. apiospermum Liver transplantation CTS and IS treatment 15 Chest pain, cough CRP 1 Basal condensation Pleural effusion Sputum culture Vz Cure 7 75/M Lung S. apiospermum COPD CTS treatment DM 18 Dyspnea, cough NR Lung multiple nodules Cavitation Sputum culture Vz Cure 8 45/M Lung S. apiospermum COPD Bronchiectasias CTS treatment NR Productive cough, dyspnea NR Bronchiectasias Bullous emphysema Sputum culture Vz Chronic infection 9 16/M Lung S. apiospermum Cystic fibrosis Bronchiectasias LTAT NR Productive cough, fever CRP 11.2 Bilateral interstitial pattern Bronchiectasias Sputum culture Itr Chronic infection 10 34/F Pleural S. apiospermum Hodgkin lymphoma Chronic GVHD CTS and IS treatment 3 Dyspnea CRP 387.7 Pleural effusion Pleural fluid culture PCR Maldi-tof Vz Death 11 71/F Lung S. apiospermum Bronchiectasias Pneumonectomy due to lung polycystoses LTAT CTS treatment 19 Dyspnea, productive cough, hemoptysis CRP 1.43 Bronchiectasias Cysts Sputum culture Vz Cure 12 78/M Lung S. apiospermum Cervical metastasis from a cutaneous epidermoid cancer Radiotherapy CTS and IS treatment 8 Increase of secretions Nodular lesion in lung NR Nodule in lower left lobe Sputum culture NR NR 13 26/M Mediastinum S. apiospermum CGD CTS treatment 10 Cervical pain, mediastinal abscess CRP 44.18 Alveolar condensation Mediastinal and pulmonar abscesses Mediastinal abscess drainage PCR Vz + terb Vz + mic Cure 14 74/F Lung S. apiospermum CRD CTS treatment 7 Cough, dyspnea CRP 4.8 Alveolar condensation Sputum culture Vz Cure 15 53/M Blood L. prolificans Acute myeloid leukemia CTS and IS treatment NR Asthenia, fever abdominal pain Neutropenia Normal Blood cultures Vz + ter Death 16 64/M Lung L. prolificans Lymphoblastic B lymphoma CTS and IS treatment 18 Fever, productive cough, dyspnea NR Multiple alveolar infiltrate Nodules Sputum culture Vz Death 17 80/F Lung L. prolificans Chronic lymphatic leukemia CTS and IS treatment 24 Asthenia, fever, dyspnea NR Alveolar condensation Bronchiectasias Sputum culture Vz Death 18 38/F Pleural L. prolificans Pulmonary sarcoidosis CTS treatment NR Dyspnea, chest pain NR Pleural effusion Pleural fluid culture Vz Cure 19 65/M Lung L. prolificans Pulmonary transplantation CTS and IS treatment NR Productive cough, dyspnea CRP 0.9 Condensation lower right lobe Sputum culture Vz Moved to other hospital 20 72/M Lung L. prolificans COPD Psoriasis CTS and IS treatment 20 Productive cough, dyspnea, chest pain, chills CRP 17.56 Condensation lower right lobe Pleural effusion Bronchial aspirate culture Vz Cure 21 53/M Lung L. prolificans Aplastic anemia BMT Chronic GVHD DM CTS and IS treatment 13 Cough, dyspnea, anorexia, chest pain NR Alveolar infiltration Bronchiectasias Multiple disseminated nodules Sputum culture AmB + Vz Chronic infection AmB, amphotericin B; BAL, bronchoalveolar lavage; BMT, bone marrow transplantation; CGD, chronic granulomatous disease; COPD, chronic obstructive pulmonary disease; CRD, chronic renal disease; CRP, C-reactive protein (acceptable values 0.02–5 mg/l);; CTS, corticosteroids; DM, diabetes mellitus; F, female; GVHD, graft-versus-host-disease; IS, immunosuppressive; Itr, itraconazole; LTAT, long-term antibiotic treatment; M, male; Mic, micafungin; PCR, polymerase chain reaction; Ter, terbinafine; TNR, not reported; Vz, voriconazole. View Large Risk factors or underlying diseases for fungal infection were found in all patients (100%).0 Major risk factors for fungal infection were corticosteroids and/or immunosuppressive (IS) therapy in 18 (85.7%) cases, lung diseases in seven (33.3%) patients, hematologic malignancies in six (28.5%) patients, and transplantation and graft-versus-host disease (GVHD) in three (32.8%) patients each. Twenty (95.2%) patients had more than one risk factor for fungal infection. Clinical manifestations Clinical findings depended on location of infection. Pulmonary or pleural location was found in the majority of patients (17/80.9%), followed by periorbital, mediastinal, blood and skin location in one patient each. Nineteen (90.4%) patients had more than one sign or symptom of disease. As the main location was the lung, cough and dyspnea were reported in 12 (57.1%) patients each. The second most frequent symptom was fever in six (28.5%) patients, and chest pain was found in five (23.8%) cases. Microbiology, laboratory and radiological findings At the diagnosis of fungal infection, data on the CRP level were reported in 11 (52.3%) patients. The mean CRP level was 44.8 mg/L (range 0.9–387.7). On the other hand, neutropenia (neutrophils <1500/μl) was only found in 2 (15.3%) from 13 patients in whom laboratory data were reported. The most frequently isolated Scedosporium/Lomentospora species was S. apiospermum/S. boydii, found in 14 (66.6%) patients, and L. prolificans in 7 (33.3%). These species were diagnosed by culture of sputum in 12 (57.1%) cases, culture of pleural or bronchoalveolar lavage fluid in 2 (9.5%) cases each one, and culture of periorbital and medistinal abscess, skin biopsy and blood in 1 (4.7%) each one. Susceptibility tests for S. apiospermun/S. boydii were only performed in 2 isolates (cases 10 and 13). In the case 10, the MIC obtained were as follows (mcg/mL): amphotericin B 4, itraconazole >8, voriconazole 8, posaconazole >8, terbinafine >16, caspofungin 16, micafungin 0.25, and anidulafungin >4. On the other hand, in the case 13 the MICs were as follows (mcg/mL): amphotericin B 1, itraconazole >8, voriconazole 1, posaconazole 2, terbinafine >16, caspofugin 2, micafungin 0.25, and anidulafungin 8. Regarding radiological alterations, condensation signs were observed in eight (44.4%) patients, followed by both pleural effusion and bronchiectasias in five (27.7%) of each; nodules were seen in four (22.2%) patients. Eleven (61.1%) patients had more than one radiological finding. Antifungal treatment Twenty (95.2%) patients underwent antifungal treatment, with a single drug in 17 (80.9%) cases, with two drugs in two (10%) cases, and more than two in one case (5%). The majority of them were treated with voriconazole (17/80.9%) and three (14.2%) with amphotericin B. One patient (case 3) was treated with both voriconazole and surgery (debridement and abscess drainage). Outcome The final outcome was not obtained in two patients. A favorable outcome was recorded in nine (45%) patients after antifungal treatment and in one patient after antifungal plus surgical treatment. Six patients (30%) died, and three patients (20%) had recurrent infection attributable to the original fungal microorganism after antifungal treatment. Discussion Infections caused by Scedosporium/Lomentospora species are still a rare event, although the incidence is increasing due to the largest number of immunossupressed patients or with other underlying diseases for this infection.10 Recently, several case reports of Scedosporium/Lomentospora infection have been published in the medical literature.11–15 Endocarditis and osteomyelitis in transplanted patients have been described11,12 but also epidural abscess, disseminated infection, and tenosynovitis caused in immunocompetent patients.13–15 We were able to trace 21 cases of Scedosporium/Lomentospora infection from our institution reported in sufficient detail for comparison, showing that S. apiospermum/S. boydii is the main species responsible in our health area. Risk factors for fungal infection, including IS therapy and/or corticosteroids use, pulmonary or haematologic diseases, presence of neutropenia or GVHD play a decisive role in the development of invasive fungal infections. The majority of Scedosporium/Lomentospora infections are associated with IS and/or corticosteroids treatment (85.7%), and the presence of haematologic malignancies and pulmonary diseases, so the absence of any of these factors may make the diagnosis doubtful or unlikely. These data are similar to a previous published series of patients with Scedosporium/Lomentospora infection in whom 80% of them received corticosteroids after diagnosis.16 However, Idígoras et al.17 found only 22% of patients receiving IS and/or corticosteroids treatment. Classically, neutropenia has been considered as a risk factor for IFI. However, only two of our patients demonstrate to have a low neutrophils count. Other studies have reported neutropenia percentages ranging 44 to 52%.16,17 A possible explanation of these differences may be due to the fact that in eight of our patients there were not laboratory records for this item. According to our results, lung and/or pleura is the most frequent location in these kinds of patients, as previously has been reported17; thus, the symptomatology referred to this area such as cough, dyspnea, and chest pain is the most common, and the presence of other symptoms depend on the location of infection. Disseminated infection, however, was the most common presentation in another study.16 although 88% of patients with disseminated infection had concomitant pneumonia. The onset of symptoms is generally acute and development of the disease can be rapid. Based on data for 13 patients, the mean time between onset of symptoms and diagnosis was 13.6 days; therefore, this infection should be suspected in cases with acute symptoms. One of the main issues to elucidate is whether the presence of Scedosporium/Lomentospora species in samples can be considered as a contaminant or not, because there is still no standard diagnostic criteria for invasive fungal infections (IFI). Respiratory tract is the most frequent colonization site in these pathogens, although the colonization rate in health people is unknown.18 Moreover, Scedosporium/Lomentospora species are frequent colonizers of the respiratory tract in cystic fibrosis patients.3 In 2002, an international consensus defining opportunistic IFI in immunocompromised patients was published.4 Three levels of probability were proposed but only patients with “proven” or “probable” infection levels may be intended for use in the context of clinical and/or epidemiological research but not for clinical decision making. Moreover, the Spanish Society of Clinical Microbiology and Infectious diseases (SEIMC), established in 2010 a guideline for the diagnosis of IFI,5 in which several recommendations for the diagnosis were given. However, further studies are urgently needed in order to definitively establish criteria for opportunistic IFI. In this review, the majority of patients were diagnosed by culture of sputum specimens; however, the bronchoalveolar lavage fluid is the sample of choice for the diagnosis of the infection located at the low respiratory tract (cases 1 and 2). Sputum or tracheal aspirate samples only have a presumptive value in infections caused by opportunistic fungi, because there are not any criteria for differentiation between infection, colonization and contamination. In these cases, its value is very conditioned by the sample quality.19 When the sample is not the most appropriate for diagnosis, the inclusion in the “proven” or “probable” levels of infection should be established by the presence of additional factors such as the existence of clinical symptomatology and radiological findings consistent with infection.4 The antifungal treatment of choice for Scedosporium/Lomentospora infection has not yet been established due to its rarity, and management of these infections depends on the underlying condition of the host. The use of antifungal agents is still a challenging issue, because of the high resistance of these fungi to most antifungal and the severity of the underlying diseases in the host. S. apiospermum/S. boydii is resistant to amphotericin B and flucytosine, and demonstrated variable susceptibility to itraconazole, voriconazole, posaconazole, and micafungin.20,21L. prolificans is resistant to caspofungin, azoles, and polyenes.22 Overall, voriconazole showed the strongest in vitro activity,23 and a recent study reported synergistic activity of colistin plus voriconazole against Scedosporium/Lomentospora species.24 Voriconazole represents the first-line treatment, and recently it has been demonstrated that voriconazole MICs are predictive for the outcome of disseminated scedosporiosis.25 Regarding L. prolificans, no drug appears to be effective against this pathogen,26 whereas surgical treatment of affected tissue plus recovery of the immunocompetent status may contribute to the prognosis improvement. Due to the high rate of resistance to antifungal agents and the high degree of variability to antifungal treatments, combination of antifungal drugs is highly recommended, especially in L. prolificans. Several antifungal combinations have demonstrated efficacy in S. apiospermum/S. boydii27,28 and in L. prolificans a few reports of successful treatment with voriconazole plus terbinafine have been published,29,30 so this combination may be of choice for this infection. Lamaris et al.16 find better responses to triazoles with in vitro activity against S. apiospermum/S. boydii. However, combination therapy with amphotericin B offers no advantage.16 On the other hand, any of the treatments administered in the series from Idigoras et al. showed advantages, alone or in combination.17 In line with this latest work, any of the treatments administered to our patients showed higher survival rate. This seems clear that in localized cases in immunocompetent patients (case 3), treatment with an antifungal drug plus surgical debridement may lead to eradicate the infection. Some factors such as the immunossupression level, underlying diseases, and location of infection may be determinant for patient survival. In our patients, the mortality rate in L. prolificans infection is higher than in S. apiospermium/S. boydii (42.8 vs. 21.4%). The heterogeneity of studies and scarcity of data prevents any conclusion being drawn on antifungal treatments, and further research is required on this important issue. It appears evident that these patients should be treated with drugs selected after antifungal susceptibility tests, but the absence of standardization of the methods and that these techniques are usually performed in reference centres, make it very difficult to carry out. In conclusion, infections caused by Scedosporium/Lomentospora species are still rare and difficult to diagnose and treat. These infections should be suspected especially in patients with corticosteroids and/or IS treatment as well as in those with hematologic malignancies or pulmonary diseases. Due to the absence of diagnostic criteria clearly established for IFI and that these opportunistic pathogens are frequent colonizers, the diagnosis should be confirmed microbiologically, taking adequate samples from the affected tissue, and leaning on clinical and radiological diagnosis criteria. Despite the above mentioned difficulties, antifungal susceptibility testing of isolates is also highly recommended in order to detect the presence of resistances. The treatment is still a challenge issue, and it is not clearly defined, being the mortality rate high in this kind of infections, especially in those caused by L. prolificans. Acknowledgements We would like to acknowledge to Dr. Ana Alastruey (National Centre of Microbiology, Majadahonda, Madrid, Spain) for performing the molecular study of cases 10 and 13, and for her advice. Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and the writing of the paper. References 1. Gilgado F , Cano J , Gené J , Suton DA , Guarro J . Molecular and phenotypic data supporting distinct species statuses for Scedosporium apiospermum and Pseucoallescheria boydii and the proposed new species Scedosporium dehoogii . J Clin Microbiol . 2008 ; 46 : 766 – 771 . Google Scholar Crossref Search ADS PubMed 2. Lackner M , de Hoog GS , Yang L et al. Proposed nomenclature for Pseucoallescheria, Scedosporium and related genera . Fungal Diversity . 2014 ; 67 : 1 – 10 . Google Scholar Crossref Search ADS 3. Schwarz C , Brandt C , Antweiler E et al. Prospective multicenter German study on pulmonary colonization with Scedosporium/Lomentospora species in cystic fibrosis: epidemiology and new association factors . PLOS One . 2017 ; 12 : e0171485 . Google Scholar Crossref Search ADS PubMed 4. Ascioglu S , Rex JH , de Pauw B et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cells transplants: an international consensus . Clin Infect Dis . 2002 ; 34 : 7 – 14 . Google Scholar Crossref Search ADS PubMed 5. Ayats J , Martín-Mazuelos E , Pemán J et al. Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC) guidelines for the diagnosis of invasive fungal infections. 2010 update . Enferm Infect Microbiol Clin . 2011 ; 29 : 39.e1 – 39.e15 . [Recomendaciones sobre el diagnóstico de la enfermedad fúngica invasora de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC). Actualización 2010] . Google Scholar Crossref Search ADS 6. De Hoog GS , Guarro J , Gené J et al. Atlas of Clinical Fungi , 2nd ed . Washington, DC : American Society for Microbiology , 2001 . 7. Cruse M , Telerant R , Gallagher T , Lee T , Taylor J . Cryptic species in Stachybotrys chartarum . Mycologia . 2002 ; 94 : 814 – 822 . Google Scholar Crossref Search ADS PubMed 8. Coulibaly O , Marinach-Patrice C , Cassagne C , Piarroux R , Mazier D , Ranque S . Pseudoallescheria/Scedosporium complex species identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry . Med Mycol . 2011 ; 49 : 621 – 626 . Google Scholar PubMed 9. EUCAST technical note on the method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia-forming moulds . Clin Microbiol Infect . 2008 ; 14 : 982 – 984 . Crossref Search ADS PubMed 10. Ramana KV , Kandi S , Bharatkumar V et al. Invasive fungal infections: a comprehensive review . Am J Infect Dis Microbiol . 2013 ; 1 : 64 – 69 . 11. Clement ME , Maziarz EK , Schroder JN , Patel CB , Perfect JR . Scedosporium apiospermum infection of the “native” valve: fungal endocarditis in an orthotopic heart transplant recipient . Med Mycol Case Rep . 2015 ; 9 : 34 – 36 . Google Scholar Crossref Search ADS PubMed 12. Denton EJ , Smibert O , Gooi J et al. Invasive Scedosporium sternal osteomyelitis following lung transplant: cured . Med Mycol Case Rep . 2016 ; 12 : 14 – 16 . Google Scholar Crossref Search ADS PubMed 13. Cruysmans C , Rodríguez-Villalobos H , Fomekong E , Dumitriu D , Nassogne MC , Van der Linden D . Epidural abscess caused by Scedosporium apiospermum in an immunocompetent child . Pediatr Infect Dis J . 2015 ; 34 : 1277 – 1278 . Google Scholar Crossref Search ADS PubMed 14. Chen TC , Ho MW , Chien WC , Lin HH . Disseminated Scedosporium apiospermum infection in a near-drowning patient . J Form Med Assoc . 2016 ; 15 : 213 – 214 . Google Scholar Crossref Search ADS 15. Kim CM , Lim SC , Kim J et al. Tenosynovitis caused by Scedosporium apiospermum infection misdiagnosed as an Alternaria species: a case report . BMC Infect Dis . 2017 ; 17 : 72 . Google Scholar Crossref Search ADS PubMed 16. Lamaris GA , Chamilos G , Lewis RE , Safdar A , Raad II , Kontoyiannis DP . Scedosporium infection in a tertiary care center: a review of 25 cases from 1989 to 2006 . Clin Infect Dis . 2006 ; 43 : 1580 – 1584 . Google Scholar Crossref Search ADS PubMed 17. Idígoras P , Pérez-Trallero E , Piñeiro L et al. Disseminated infection and colonization by Scedosporium prolificans: a review of 18 cases, 1990–1999. Clin Infect Dis . 2001 ; 32 : e158 – 165 . Google Scholar Crossref Search ADS PubMed 18. Pemán J , Salavert M . Invasive fungal disease due to Scedosporium, Fusarium and mucorales . Rev Iberoam Micol . 2014 ; 31 : 242 – 248 [Enfermedad fúngica invasora por Scedosporium, Fusarium y Mucor] . Google Scholar Crossref Search ADS PubMed 19. Sánchez F. Lower respiratory tract sample processing . En : Pemán J , Martín-Mazuelos E , Rubio MC , editores. Guía práctica de identificación y diagnóstico en micrología clínica . 2ª edición . Bilbao. Rev Iberoam Micol . 2007 ; 5 : 1 – 12 [Procesamiento de las muestras del tracto respiratorio inferior] . 20. Perfect JR , Marr KA , Walsh TJ et al. Voriconazole treatment for less-common, emerging, or refractory fungal infections . Clin Infect Dis . 2003 ; 36 : 1122 – 1131 . Google Scholar Crossref Search ADS PubMed 21. Tortorano AM , Richardson M , Roilides E et al. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp., and others . Clin Microbiol Infect . 2014 ; 20 : 27 – 46 . Google Scholar Crossref Search ADS PubMed 22. Cuenca-Estrella M , Gómez-López A , Mellado E , Buitrago MJ , Monzón A , Rodríguez-Tudela JL . Head-to-head comparison of the activities of currently available antifungal agents against 3,378 Spanish clinical isolates of yeasts and filamentous fungi . Antimicrob Agents Chemother . 2006 ; 50 : 917 – 921 . Google Scholar Crossref Search ADS PubMed 23. Meletiadis J , Meis JF , Mouton JW et al. In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates . Antimicrob Agents Chemother . 2002 ; 46 : 62 – 68 . Google Scholar Crossref Search ADS PubMed 24. Schemuth H , Dittmer S , Lackner M et al. In vitro activity of colistin as single agent and in combination with antifungals against filamentous fungi occurring in patients with cystic fibrosis . Mycoses . 2013 ; 56 : 297 – 303 . Google Scholar Crossref Search ADS PubMed 25. Martin-Vicente A , Guarro J , González GM , Lass-Flörl C , Lackner M , Capilla J . Voriconazole MICs are predictive for the outcome of experimental disseminated scedosporiosis . J Antimicrob Chemother . 2017 ; 72 : 1118 – 1122 . Google Scholar PubMed 26. Husain S , Muñoz P , Forrest G et al. Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome . Clin Infect Dis . 2005 ; 40 : 89 – 99 . Google Scholar Crossref Search ADS PubMed 27. Schwartz S , Reisman A , Troke PF . The efficacy of voriconazole in the treatment of 192 fungal central nervous system infections: a retrospective analysis . Infection . 2011 ; 39 : 201 – 210 . Google Scholar Crossref Search ADS PubMed 28. Verweij PE , Cox NJ , Meis JF . Oral terbinafine for treatment of pulmonary Pseudoallescheria boydii infection refractory to itraconazole therapy . Eur J Clin Microbiol Infect Dis . 1997 ; 16 : 26 – 28 . Google Scholar Crossref Search ADS PubMed 29. Bhat SV , Paterson DL , Rinaldi MG , Veldkamp PJ . Scedosporium prolificans brain abscess in a patient with chronic granulomatous disease: successful combination therapy with voriconazole and terbinafine . Scand J Infect Dis . 2007 ; 39 : 87 – 90 . Google Scholar Crossref Search ADS PubMed 30. Li JY , Yong TY , Grove DI , Coates PT . Successful control of Scedosporium prolificans septic arthritis and probable osteomyelitis without radical surgery in a long-term renal transplant recipient . Transpl Infect Dis . 2008 ; 10 : 63 – 65 . Google Scholar Crossref Search ADS PubMed © The Author(s) 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Medical Mycology Oxford University Press

Infections caused by Scedosporium/Lomentospora species: Clinical and microbiological findings in 21 cases

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Oxford University Press
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© The Author(s) 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.
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1369-3786
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1460-2709
DOI
10.1093/mmy/myx147
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Abstract

Abstract The clinical and microbiological characteristics of infections caused by Scedosporium/ Lomentospora species in 21 patients are described. We searched retrospectively the records for Scedosporium/ Lomentospora species seen at the University Hospital Virgen de las Nieves from 2006 to 2017. Out of them, 16 were male; mean age at diagnosis was 57.8 (±SD 15) years; all patients had risk factors for fungal infection such as corticosteroids and/or immunosuppressive treatment in 18 (85.7%) patients, pulmonary diseases in seven (33.3%) cases, hematological malignancies in six (28.5%), and organ transplantation in three (14.2%) patients. Most patients had infection in the lung/pleura (17/80.9%); cough was present in 12 patients and dyspnea in another 12, and the mean interval until diagnosis was 13.6 days. The most frequent species was S. apiospermum/S. boydii in 14 patients (66.6%), followed by L. prolificans in seven. The diagnosis was obtained from sputum in 12 (57.1%) cases, followed by pleural fluid and bronchoalveolar lavage in two of each. The most frequently used antifungals were voriconazole and amphotericin B, but combination of more than one antifungal drug was only used in three patients. Ten patients were cured, and six patients died as a consequence of the infection; three patients had chronic infection. In general, infections caused by Scedosporium/Lomentospora species are rare, serious, and difficult to diagnose and treat, having a high index or mortality especially in those caused by L. prolificans. Scedosporium/Lomentospora species, infection, antifungal drugs, invasive fungal disease, colonization Introduction Scedosporium spp. are fungal opportunistic pathogens causing serious infections difficult to treat. S. prolificans and S. apiospermum are the only recognized species that recently belonged to this genus, although molecular studies have demonstrated that S. apiospermum is a complex composed by five species.1,2 Moreover, S. prolificans is genetically distinct from the other Scedosporium species, and it was reassigned to the genus Lomentospora and is now called L. prolificans.2 Both species may cause invasive fungal disease with similar pathogeny, clinical manifestations, and severity, although they may act as surface or body cavities colonizers such as in patients with cystic fibrosis.3 In the last years, the infections caused by Scedosporium/Lomentospora species have increased, especially in immunossupressed patients, and are characterized by both their virulence and resistance to the majority of antifungals. Recently, we were confronted with a fatal case of pleural infection due to S. apiospermium (case 10). Due to its rarity, we have retrospectively reviewed the records of all cases seen in our hospital in the last 11 years, and we have analysed the most important clinical and microbiologic findings. Methods We describe the clinical and microbiologic characteristics of 21 patients with Scedosporium/Lomentospora infection seen at the University Hospital Virgen de las Nieves (Granada, Spain) during the period 2006–2017. We traced 41 cases caused by Scedosporium/Lomentospora described in sufficient detail through their clinical histories. We defined Scedosporium/Lomentospora infection according previous published guidelines.4,5 Of the 41 patients with positive cultures for Scedosporium/Lomentospora, only 21 met the criteria for “proven” or “probable” infection.4 Data on age and sex, localization of infection, fungal species, risk factors and/or underlying diseases, time until diagnosis, clinical manifestations, laboratory and radiological findings, microbiologic diagnosis, treatment, and outcome were recorded. Inoculation of media was performed according the type of sample following the standardized procedures in our laboratory. Overall, the specimens were inoculated in aerobic and anaerobic blood agar (BD Columbia Agar 5% Sheepblood®, Becton Dickinson, Franklin Lakes, NJ, USA), chocolate agar (BD Choco Agar, Becton Dickinson), and thioglycolate broth (in pleural fluid, bronchoalveolar lavage fluid and abscesses) (BDTM Fluid Thioglycollate Medium, Becton Dickinson), all incubated at 37 °C. Because fungal infection was suspected, Sabouraud agar and Sabouraud agar with cycloheximide (BD SAB, Becton Dickinson) were also used and incubated at 30 °C. Definitive diagnosis was performed by specimen culture and macroscopic appearance (Fig. 1), observation of fungal elements by microscopy (Fig. 2)6 and, in some instances (cases 10 and 13), by molecular methods such as polymerase chain reaction (PCR), performing sequentiation of both the ITS and the β-tubulin with the TUB-F and TUB-R primers7 and proteomic techniques such as Maldi-tof (Bruker Biotyper, Billerica, MA, USA).8 Figure 1. View largeDownload slide Macroscopic colonies of Scedosporium apiospermium in Sabouraud agar (from case 10). It can observe the grayish white colonies aspect. This Figure is reproduced in color in the online version of Medical Mycology. Figure 1. View largeDownload slide Macroscopic colonies of Scedosporium apiospermium in Sabouraud agar (from case 10). It can observe the grayish white colonies aspect. This Figure is reproduced in color in the online version of Medical Mycology. Figure 2. View largeDownload slide Cotton blue lactophenol stain (from case 10) (×400). Long and short hyaline conidiophores as well as oval conidia may be observed. This Figure is reproduced in color in the online version of Medical Mycology. Figure 2. View largeDownload slide Cotton blue lactophenol stain (from case 10) (×400). Long and short hyaline conidiophores as well as oval conidia may be observed. This Figure is reproduced in color in the online version of Medical Mycology. In two cases (10 and 13), the strain was sent to the National Centre of Microbiology (Majadahonda, Madrid, Spain) for susceptibility study, which was performed according to the EUCAST method.9 Results General characteristics Table 1 summarizes the clinical and microbiologic findings for the 21 patients with infection due to Scedosporium/Lomentospora. There were 16 (76.1%) men and the mean age of patients was 57.8 (±SD 15) years (range, 16–87 years). The mean interval from onset of symptoms to infection diagnosis was 13.6 days (range, 3–24 days), although for eight patients this interval was not reported. Table 1. Main findings in 21 patients with infection caused by Scedosporium/Lomentospora species seen at the University Hospital Virgen de las Nieves (2006–2017). Case Age (years)/ sex Localization of infection Species Risk factors and/or underlying diseases Time until diagnosis (days) Clinical manifestations Laboratory findings Radiological findings Microbiologic diagnosis Treatment Outcome 1 46/M Lung S. apiospermum Mieloma multiple CTS and IS treatment BMT Chronic GVHD 14 Fever, cough CRP 5.2 Bilateral interstitial infiltrate BAL culture AmB Cure 2 72/M Lung S. apiospermum COPD CTS treatment NR Fever, cough, dyspnea CRP 9.4 Alveolar condensation Pleural effusion BAL culture AmB Death 3 34/M Periorbital S. apiospermum Previous orbital surgery due to a severe trauma NR Periorbital abscess NR Normal Periorbital abscess culture Vz Surgery Cure 4 87/M Lung S. apiospermum CRD-Dialysis DM LTAT 9 Dyspnea, cough, chest pain CRP 10.4 Small basal condensation Sputum culture Vz Cure 5 68/M Skin S. apiospermum Liver transplantation CTS and IS treatment DM NR Cutaneous lesion, pain, asthenia, Leukopenia Neutropenia Normal Cutaneous biopsy culture Vz Death 6 63/M Lung S. apiospermum Liver transplantation CTS and IS treatment 15 Chest pain, cough CRP 1 Basal condensation Pleural effusion Sputum culture Vz Cure 7 75/M Lung S. apiospermum COPD CTS treatment DM 18 Dyspnea, cough NR Lung multiple nodules Cavitation Sputum culture Vz Cure 8 45/M Lung S. apiospermum COPD Bronchiectasias CTS treatment NR Productive cough, dyspnea NR Bronchiectasias Bullous emphysema Sputum culture Vz Chronic infection 9 16/M Lung S. apiospermum Cystic fibrosis Bronchiectasias LTAT NR Productive cough, fever CRP 11.2 Bilateral interstitial pattern Bronchiectasias Sputum culture Itr Chronic infection 10 34/F Pleural S. apiospermum Hodgkin lymphoma Chronic GVHD CTS and IS treatment 3 Dyspnea CRP 387.7 Pleural effusion Pleural fluid culture PCR Maldi-tof Vz Death 11 71/F Lung S. apiospermum Bronchiectasias Pneumonectomy due to lung polycystoses LTAT CTS treatment 19 Dyspnea, productive cough, hemoptysis CRP 1.43 Bronchiectasias Cysts Sputum culture Vz Cure 12 78/M Lung S. apiospermum Cervical metastasis from a cutaneous epidermoid cancer Radiotherapy CTS and IS treatment 8 Increase of secretions Nodular lesion in lung NR Nodule in lower left lobe Sputum culture NR NR 13 26/M Mediastinum S. apiospermum CGD CTS treatment 10 Cervical pain, mediastinal abscess CRP 44.18 Alveolar condensation Mediastinal and pulmonar abscesses Mediastinal abscess drainage PCR Vz + terb Vz + mic Cure 14 74/F Lung S. apiospermum CRD CTS treatment 7 Cough, dyspnea CRP 4.8 Alveolar condensation Sputum culture Vz Cure 15 53/M Blood L. prolificans Acute myeloid leukemia CTS and IS treatment NR Asthenia, fever abdominal pain Neutropenia Normal Blood cultures Vz + ter Death 16 64/M Lung L. prolificans Lymphoblastic B lymphoma CTS and IS treatment 18 Fever, productive cough, dyspnea NR Multiple alveolar infiltrate Nodules Sputum culture Vz Death 17 80/F Lung L. prolificans Chronic lymphatic leukemia CTS and IS treatment 24 Asthenia, fever, dyspnea NR Alveolar condensation Bronchiectasias Sputum culture Vz Death 18 38/F Pleural L. prolificans Pulmonary sarcoidosis CTS treatment NR Dyspnea, chest pain NR Pleural effusion Pleural fluid culture Vz Cure 19 65/M Lung L. prolificans Pulmonary transplantation CTS and IS treatment NR Productive cough, dyspnea CRP 0.9 Condensation lower right lobe Sputum culture Vz Moved to other hospital 20 72/M Lung L. prolificans COPD Psoriasis CTS and IS treatment 20 Productive cough, dyspnea, chest pain, chills CRP 17.56 Condensation lower right lobe Pleural effusion Bronchial aspirate culture Vz Cure 21 53/M Lung L. prolificans Aplastic anemia BMT Chronic GVHD DM CTS and IS treatment 13 Cough, dyspnea, anorexia, chest pain NR Alveolar infiltration Bronchiectasias Multiple disseminated nodules Sputum culture AmB + Vz Chronic infection Case Age (years)/ sex Localization of infection Species Risk factors and/or underlying diseases Time until diagnosis (days) Clinical manifestations Laboratory findings Radiological findings Microbiologic diagnosis Treatment Outcome 1 46/M Lung S. apiospermum Mieloma multiple CTS and IS treatment BMT Chronic GVHD 14 Fever, cough CRP 5.2 Bilateral interstitial infiltrate BAL culture AmB Cure 2 72/M Lung S. apiospermum COPD CTS treatment NR Fever, cough, dyspnea CRP 9.4 Alveolar condensation Pleural effusion BAL culture AmB Death 3 34/M Periorbital S. apiospermum Previous orbital surgery due to a severe trauma NR Periorbital abscess NR Normal Periorbital abscess culture Vz Surgery Cure 4 87/M Lung S. apiospermum CRD-Dialysis DM LTAT 9 Dyspnea, cough, chest pain CRP 10.4 Small basal condensation Sputum culture Vz Cure 5 68/M Skin S. apiospermum Liver transplantation CTS and IS treatment DM NR Cutaneous lesion, pain, asthenia, Leukopenia Neutropenia Normal Cutaneous biopsy culture Vz Death 6 63/M Lung S. apiospermum Liver transplantation CTS and IS treatment 15 Chest pain, cough CRP 1 Basal condensation Pleural effusion Sputum culture Vz Cure 7 75/M Lung S. apiospermum COPD CTS treatment DM 18 Dyspnea, cough NR Lung multiple nodules Cavitation Sputum culture Vz Cure 8 45/M Lung S. apiospermum COPD Bronchiectasias CTS treatment NR Productive cough, dyspnea NR Bronchiectasias Bullous emphysema Sputum culture Vz Chronic infection 9 16/M Lung S. apiospermum Cystic fibrosis Bronchiectasias LTAT NR Productive cough, fever CRP 11.2 Bilateral interstitial pattern Bronchiectasias Sputum culture Itr Chronic infection 10 34/F Pleural S. apiospermum Hodgkin lymphoma Chronic GVHD CTS and IS treatment 3 Dyspnea CRP 387.7 Pleural effusion Pleural fluid culture PCR Maldi-tof Vz Death 11 71/F Lung S. apiospermum Bronchiectasias Pneumonectomy due to lung polycystoses LTAT CTS treatment 19 Dyspnea, productive cough, hemoptysis CRP 1.43 Bronchiectasias Cysts Sputum culture Vz Cure 12 78/M Lung S. apiospermum Cervical metastasis from a cutaneous epidermoid cancer Radiotherapy CTS and IS treatment 8 Increase of secretions Nodular lesion in lung NR Nodule in lower left lobe Sputum culture NR NR 13 26/M Mediastinum S. apiospermum CGD CTS treatment 10 Cervical pain, mediastinal abscess CRP 44.18 Alveolar condensation Mediastinal and pulmonar abscesses Mediastinal abscess drainage PCR Vz + terb Vz + mic Cure 14 74/F Lung S. apiospermum CRD CTS treatment 7 Cough, dyspnea CRP 4.8 Alveolar condensation Sputum culture Vz Cure 15 53/M Blood L. prolificans Acute myeloid leukemia CTS and IS treatment NR Asthenia, fever abdominal pain Neutropenia Normal Blood cultures Vz + ter Death 16 64/M Lung L. prolificans Lymphoblastic B lymphoma CTS and IS treatment 18 Fever, productive cough, dyspnea NR Multiple alveolar infiltrate Nodules Sputum culture Vz Death 17 80/F Lung L. prolificans Chronic lymphatic leukemia CTS and IS treatment 24 Asthenia, fever, dyspnea NR Alveolar condensation Bronchiectasias Sputum culture Vz Death 18 38/F Pleural L. prolificans Pulmonary sarcoidosis CTS treatment NR Dyspnea, chest pain NR Pleural effusion Pleural fluid culture Vz Cure 19 65/M Lung L. prolificans Pulmonary transplantation CTS and IS treatment NR Productive cough, dyspnea CRP 0.9 Condensation lower right lobe Sputum culture Vz Moved to other hospital 20 72/M Lung L. prolificans COPD Psoriasis CTS and IS treatment 20 Productive cough, dyspnea, chest pain, chills CRP 17.56 Condensation lower right lobe Pleural effusion Bronchial aspirate culture Vz Cure 21 53/M Lung L. prolificans Aplastic anemia BMT Chronic GVHD DM CTS and IS treatment 13 Cough, dyspnea, anorexia, chest pain NR Alveolar infiltration Bronchiectasias Multiple disseminated nodules Sputum culture AmB + Vz Chronic infection AmB, amphotericin B; BAL, bronchoalveolar lavage; BMT, bone marrow transplantation; CGD, chronic granulomatous disease; COPD, chronic obstructive pulmonary disease; CRD, chronic renal disease; CRP, C-reactive protein (acceptable values 0.02–5 mg/l);; CTS, corticosteroids; DM, diabetes mellitus; F, female; GVHD, graft-versus-host-disease; IS, immunosuppressive; Itr, itraconazole; LTAT, long-term antibiotic treatment; M, male; Mic, micafungin; PCR, polymerase chain reaction; Ter, terbinafine; TNR, not reported; Vz, voriconazole. View Large Table 1. Main findings in 21 patients with infection caused by Scedosporium/Lomentospora species seen at the University Hospital Virgen de las Nieves (2006–2017). Case Age (years)/ sex Localization of infection Species Risk factors and/or underlying diseases Time until diagnosis (days) Clinical manifestations Laboratory findings Radiological findings Microbiologic diagnosis Treatment Outcome 1 46/M Lung S. apiospermum Mieloma multiple CTS and IS treatment BMT Chronic GVHD 14 Fever, cough CRP 5.2 Bilateral interstitial infiltrate BAL culture AmB Cure 2 72/M Lung S. apiospermum COPD CTS treatment NR Fever, cough, dyspnea CRP 9.4 Alveolar condensation Pleural effusion BAL culture AmB Death 3 34/M Periorbital S. apiospermum Previous orbital surgery due to a severe trauma NR Periorbital abscess NR Normal Periorbital abscess culture Vz Surgery Cure 4 87/M Lung S. apiospermum CRD-Dialysis DM LTAT 9 Dyspnea, cough, chest pain CRP 10.4 Small basal condensation Sputum culture Vz Cure 5 68/M Skin S. apiospermum Liver transplantation CTS and IS treatment DM NR Cutaneous lesion, pain, asthenia, Leukopenia Neutropenia Normal Cutaneous biopsy culture Vz Death 6 63/M Lung S. apiospermum Liver transplantation CTS and IS treatment 15 Chest pain, cough CRP 1 Basal condensation Pleural effusion Sputum culture Vz Cure 7 75/M Lung S. apiospermum COPD CTS treatment DM 18 Dyspnea, cough NR Lung multiple nodules Cavitation Sputum culture Vz Cure 8 45/M Lung S. apiospermum COPD Bronchiectasias CTS treatment NR Productive cough, dyspnea NR Bronchiectasias Bullous emphysema Sputum culture Vz Chronic infection 9 16/M Lung S. apiospermum Cystic fibrosis Bronchiectasias LTAT NR Productive cough, fever CRP 11.2 Bilateral interstitial pattern Bronchiectasias Sputum culture Itr Chronic infection 10 34/F Pleural S. apiospermum Hodgkin lymphoma Chronic GVHD CTS and IS treatment 3 Dyspnea CRP 387.7 Pleural effusion Pleural fluid culture PCR Maldi-tof Vz Death 11 71/F Lung S. apiospermum Bronchiectasias Pneumonectomy due to lung polycystoses LTAT CTS treatment 19 Dyspnea, productive cough, hemoptysis CRP 1.43 Bronchiectasias Cysts Sputum culture Vz Cure 12 78/M Lung S. apiospermum Cervical metastasis from a cutaneous epidermoid cancer Radiotherapy CTS and IS treatment 8 Increase of secretions Nodular lesion in lung NR Nodule in lower left lobe Sputum culture NR NR 13 26/M Mediastinum S. apiospermum CGD CTS treatment 10 Cervical pain, mediastinal abscess CRP 44.18 Alveolar condensation Mediastinal and pulmonar abscesses Mediastinal abscess drainage PCR Vz + terb Vz + mic Cure 14 74/F Lung S. apiospermum CRD CTS treatment 7 Cough, dyspnea CRP 4.8 Alveolar condensation Sputum culture Vz Cure 15 53/M Blood L. prolificans Acute myeloid leukemia CTS and IS treatment NR Asthenia, fever abdominal pain Neutropenia Normal Blood cultures Vz + ter Death 16 64/M Lung L. prolificans Lymphoblastic B lymphoma CTS and IS treatment 18 Fever, productive cough, dyspnea NR Multiple alveolar infiltrate Nodules Sputum culture Vz Death 17 80/F Lung L. prolificans Chronic lymphatic leukemia CTS and IS treatment 24 Asthenia, fever, dyspnea NR Alveolar condensation Bronchiectasias Sputum culture Vz Death 18 38/F Pleural L. prolificans Pulmonary sarcoidosis CTS treatment NR Dyspnea, chest pain NR Pleural effusion Pleural fluid culture Vz Cure 19 65/M Lung L. prolificans Pulmonary transplantation CTS and IS treatment NR Productive cough, dyspnea CRP 0.9 Condensation lower right lobe Sputum culture Vz Moved to other hospital 20 72/M Lung L. prolificans COPD Psoriasis CTS and IS treatment 20 Productive cough, dyspnea, chest pain, chills CRP 17.56 Condensation lower right lobe Pleural effusion Bronchial aspirate culture Vz Cure 21 53/M Lung L. prolificans Aplastic anemia BMT Chronic GVHD DM CTS and IS treatment 13 Cough, dyspnea, anorexia, chest pain NR Alveolar infiltration Bronchiectasias Multiple disseminated nodules Sputum culture AmB + Vz Chronic infection Case Age (years)/ sex Localization of infection Species Risk factors and/or underlying diseases Time until diagnosis (days) Clinical manifestations Laboratory findings Radiological findings Microbiologic diagnosis Treatment Outcome 1 46/M Lung S. apiospermum Mieloma multiple CTS and IS treatment BMT Chronic GVHD 14 Fever, cough CRP 5.2 Bilateral interstitial infiltrate BAL culture AmB Cure 2 72/M Lung S. apiospermum COPD CTS treatment NR Fever, cough, dyspnea CRP 9.4 Alveolar condensation Pleural effusion BAL culture AmB Death 3 34/M Periorbital S. apiospermum Previous orbital surgery due to a severe trauma NR Periorbital abscess NR Normal Periorbital abscess culture Vz Surgery Cure 4 87/M Lung S. apiospermum CRD-Dialysis DM LTAT 9 Dyspnea, cough, chest pain CRP 10.4 Small basal condensation Sputum culture Vz Cure 5 68/M Skin S. apiospermum Liver transplantation CTS and IS treatment DM NR Cutaneous lesion, pain, asthenia, Leukopenia Neutropenia Normal Cutaneous biopsy culture Vz Death 6 63/M Lung S. apiospermum Liver transplantation CTS and IS treatment 15 Chest pain, cough CRP 1 Basal condensation Pleural effusion Sputum culture Vz Cure 7 75/M Lung S. apiospermum COPD CTS treatment DM 18 Dyspnea, cough NR Lung multiple nodules Cavitation Sputum culture Vz Cure 8 45/M Lung S. apiospermum COPD Bronchiectasias CTS treatment NR Productive cough, dyspnea NR Bronchiectasias Bullous emphysema Sputum culture Vz Chronic infection 9 16/M Lung S. apiospermum Cystic fibrosis Bronchiectasias LTAT NR Productive cough, fever CRP 11.2 Bilateral interstitial pattern Bronchiectasias Sputum culture Itr Chronic infection 10 34/F Pleural S. apiospermum Hodgkin lymphoma Chronic GVHD CTS and IS treatment 3 Dyspnea CRP 387.7 Pleural effusion Pleural fluid culture PCR Maldi-tof Vz Death 11 71/F Lung S. apiospermum Bronchiectasias Pneumonectomy due to lung polycystoses LTAT CTS treatment 19 Dyspnea, productive cough, hemoptysis CRP 1.43 Bronchiectasias Cysts Sputum culture Vz Cure 12 78/M Lung S. apiospermum Cervical metastasis from a cutaneous epidermoid cancer Radiotherapy CTS and IS treatment 8 Increase of secretions Nodular lesion in lung NR Nodule in lower left lobe Sputum culture NR NR 13 26/M Mediastinum S. apiospermum CGD CTS treatment 10 Cervical pain, mediastinal abscess CRP 44.18 Alveolar condensation Mediastinal and pulmonar abscesses Mediastinal abscess drainage PCR Vz + terb Vz + mic Cure 14 74/F Lung S. apiospermum CRD CTS treatment 7 Cough, dyspnea CRP 4.8 Alveolar condensation Sputum culture Vz Cure 15 53/M Blood L. prolificans Acute myeloid leukemia CTS and IS treatment NR Asthenia, fever abdominal pain Neutropenia Normal Blood cultures Vz + ter Death 16 64/M Lung L. prolificans Lymphoblastic B lymphoma CTS and IS treatment 18 Fever, productive cough, dyspnea NR Multiple alveolar infiltrate Nodules Sputum culture Vz Death 17 80/F Lung L. prolificans Chronic lymphatic leukemia CTS and IS treatment 24 Asthenia, fever, dyspnea NR Alveolar condensation Bronchiectasias Sputum culture Vz Death 18 38/F Pleural L. prolificans Pulmonary sarcoidosis CTS treatment NR Dyspnea, chest pain NR Pleural effusion Pleural fluid culture Vz Cure 19 65/M Lung L. prolificans Pulmonary transplantation CTS and IS treatment NR Productive cough, dyspnea CRP 0.9 Condensation lower right lobe Sputum culture Vz Moved to other hospital 20 72/M Lung L. prolificans COPD Psoriasis CTS and IS treatment 20 Productive cough, dyspnea, chest pain, chills CRP 17.56 Condensation lower right lobe Pleural effusion Bronchial aspirate culture Vz Cure 21 53/M Lung L. prolificans Aplastic anemia BMT Chronic GVHD DM CTS and IS treatment 13 Cough, dyspnea, anorexia, chest pain NR Alveolar infiltration Bronchiectasias Multiple disseminated nodules Sputum culture AmB + Vz Chronic infection AmB, amphotericin B; BAL, bronchoalveolar lavage; BMT, bone marrow transplantation; CGD, chronic granulomatous disease; COPD, chronic obstructive pulmonary disease; CRD, chronic renal disease; CRP, C-reactive protein (acceptable values 0.02–5 mg/l);; CTS, corticosteroids; DM, diabetes mellitus; F, female; GVHD, graft-versus-host-disease; IS, immunosuppressive; Itr, itraconazole; LTAT, long-term antibiotic treatment; M, male; Mic, micafungin; PCR, polymerase chain reaction; Ter, terbinafine; TNR, not reported; Vz, voriconazole. View Large Risk factors or underlying diseases for fungal infection were found in all patients (100%).0 Major risk factors for fungal infection were corticosteroids and/or immunosuppressive (IS) therapy in 18 (85.7%) cases, lung diseases in seven (33.3%) patients, hematologic malignancies in six (28.5%) patients, and transplantation and graft-versus-host disease (GVHD) in three (32.8%) patients each. Twenty (95.2%) patients had more than one risk factor for fungal infection. Clinical manifestations Clinical findings depended on location of infection. Pulmonary or pleural location was found in the majority of patients (17/80.9%), followed by periorbital, mediastinal, blood and skin location in one patient each. Nineteen (90.4%) patients had more than one sign or symptom of disease. As the main location was the lung, cough and dyspnea were reported in 12 (57.1%) patients each. The second most frequent symptom was fever in six (28.5%) patients, and chest pain was found in five (23.8%) cases. Microbiology, laboratory and radiological findings At the diagnosis of fungal infection, data on the CRP level were reported in 11 (52.3%) patients. The mean CRP level was 44.8 mg/L (range 0.9–387.7). On the other hand, neutropenia (neutrophils <1500/μl) was only found in 2 (15.3%) from 13 patients in whom laboratory data were reported. The most frequently isolated Scedosporium/Lomentospora species was S. apiospermum/S. boydii, found in 14 (66.6%) patients, and L. prolificans in 7 (33.3%). These species were diagnosed by culture of sputum in 12 (57.1%) cases, culture of pleural or bronchoalveolar lavage fluid in 2 (9.5%) cases each one, and culture of periorbital and medistinal abscess, skin biopsy and blood in 1 (4.7%) each one. Susceptibility tests for S. apiospermun/S. boydii were only performed in 2 isolates (cases 10 and 13). In the case 10, the MIC obtained were as follows (mcg/mL): amphotericin B 4, itraconazole >8, voriconazole 8, posaconazole >8, terbinafine >16, caspofungin 16, micafungin 0.25, and anidulafungin >4. On the other hand, in the case 13 the MICs were as follows (mcg/mL): amphotericin B 1, itraconazole >8, voriconazole 1, posaconazole 2, terbinafine >16, caspofugin 2, micafungin 0.25, and anidulafungin 8. Regarding radiological alterations, condensation signs were observed in eight (44.4%) patients, followed by both pleural effusion and bronchiectasias in five (27.7%) of each; nodules were seen in four (22.2%) patients. Eleven (61.1%) patients had more than one radiological finding. Antifungal treatment Twenty (95.2%) patients underwent antifungal treatment, with a single drug in 17 (80.9%) cases, with two drugs in two (10%) cases, and more than two in one case (5%). The majority of them were treated with voriconazole (17/80.9%) and three (14.2%) with amphotericin B. One patient (case 3) was treated with both voriconazole and surgery (debridement and abscess drainage). Outcome The final outcome was not obtained in two patients. A favorable outcome was recorded in nine (45%) patients after antifungal treatment and in one patient after antifungal plus surgical treatment. Six patients (30%) died, and three patients (20%) had recurrent infection attributable to the original fungal microorganism after antifungal treatment. Discussion Infections caused by Scedosporium/Lomentospora species are still a rare event, although the incidence is increasing due to the largest number of immunossupressed patients or with other underlying diseases for this infection.10 Recently, several case reports of Scedosporium/Lomentospora infection have been published in the medical literature.11–15 Endocarditis and osteomyelitis in transplanted patients have been described11,12 but also epidural abscess, disseminated infection, and tenosynovitis caused in immunocompetent patients.13–15 We were able to trace 21 cases of Scedosporium/Lomentospora infection from our institution reported in sufficient detail for comparison, showing that S. apiospermum/S. boydii is the main species responsible in our health area. Risk factors for fungal infection, including IS therapy and/or corticosteroids use, pulmonary or haematologic diseases, presence of neutropenia or GVHD play a decisive role in the development of invasive fungal infections. The majority of Scedosporium/Lomentospora infections are associated with IS and/or corticosteroids treatment (85.7%), and the presence of haematologic malignancies and pulmonary diseases, so the absence of any of these factors may make the diagnosis doubtful or unlikely. These data are similar to a previous published series of patients with Scedosporium/Lomentospora infection in whom 80% of them received corticosteroids after diagnosis.16 However, Idígoras et al.17 found only 22% of patients receiving IS and/or corticosteroids treatment. Classically, neutropenia has been considered as a risk factor for IFI. However, only two of our patients demonstrate to have a low neutrophils count. Other studies have reported neutropenia percentages ranging 44 to 52%.16,17 A possible explanation of these differences may be due to the fact that in eight of our patients there were not laboratory records for this item. According to our results, lung and/or pleura is the most frequent location in these kinds of patients, as previously has been reported17; thus, the symptomatology referred to this area such as cough, dyspnea, and chest pain is the most common, and the presence of other symptoms depend on the location of infection. Disseminated infection, however, was the most common presentation in another study.16 although 88% of patients with disseminated infection had concomitant pneumonia. The onset of symptoms is generally acute and development of the disease can be rapid. Based on data for 13 patients, the mean time between onset of symptoms and diagnosis was 13.6 days; therefore, this infection should be suspected in cases with acute symptoms. One of the main issues to elucidate is whether the presence of Scedosporium/Lomentospora species in samples can be considered as a contaminant or not, because there is still no standard diagnostic criteria for invasive fungal infections (IFI). Respiratory tract is the most frequent colonization site in these pathogens, although the colonization rate in health people is unknown.18 Moreover, Scedosporium/Lomentospora species are frequent colonizers of the respiratory tract in cystic fibrosis patients.3 In 2002, an international consensus defining opportunistic IFI in immunocompromised patients was published.4 Three levels of probability were proposed but only patients with “proven” or “probable” infection levels may be intended for use in the context of clinical and/or epidemiological research but not for clinical decision making. Moreover, the Spanish Society of Clinical Microbiology and Infectious diseases (SEIMC), established in 2010 a guideline for the diagnosis of IFI,5 in which several recommendations for the diagnosis were given. However, further studies are urgently needed in order to definitively establish criteria for opportunistic IFI. In this review, the majority of patients were diagnosed by culture of sputum specimens; however, the bronchoalveolar lavage fluid is the sample of choice for the diagnosis of the infection located at the low respiratory tract (cases 1 and 2). Sputum or tracheal aspirate samples only have a presumptive value in infections caused by opportunistic fungi, because there are not any criteria for differentiation between infection, colonization and contamination. In these cases, its value is very conditioned by the sample quality.19 When the sample is not the most appropriate for diagnosis, the inclusion in the “proven” or “probable” levels of infection should be established by the presence of additional factors such as the existence of clinical symptomatology and radiological findings consistent with infection.4 The antifungal treatment of choice for Scedosporium/Lomentospora infection has not yet been established due to its rarity, and management of these infections depends on the underlying condition of the host. The use of antifungal agents is still a challenging issue, because of the high resistance of these fungi to most antifungal and the severity of the underlying diseases in the host. S. apiospermum/S. boydii is resistant to amphotericin B and flucytosine, and demonstrated variable susceptibility to itraconazole, voriconazole, posaconazole, and micafungin.20,21L. prolificans is resistant to caspofungin, azoles, and polyenes.22 Overall, voriconazole showed the strongest in vitro activity,23 and a recent study reported synergistic activity of colistin plus voriconazole against Scedosporium/Lomentospora species.24 Voriconazole represents the first-line treatment, and recently it has been demonstrated that voriconazole MICs are predictive for the outcome of disseminated scedosporiosis.25 Regarding L. prolificans, no drug appears to be effective against this pathogen,26 whereas surgical treatment of affected tissue plus recovery of the immunocompetent status may contribute to the prognosis improvement. Due to the high rate of resistance to antifungal agents and the high degree of variability to antifungal treatments, combination of antifungal drugs is highly recommended, especially in L. prolificans. Several antifungal combinations have demonstrated efficacy in S. apiospermum/S. boydii27,28 and in L. prolificans a few reports of successful treatment with voriconazole plus terbinafine have been published,29,30 so this combination may be of choice for this infection. Lamaris et al.16 find better responses to triazoles with in vitro activity against S. apiospermum/S. boydii. However, combination therapy with amphotericin B offers no advantage.16 On the other hand, any of the treatments administered in the series from Idigoras et al. showed advantages, alone or in combination.17 In line with this latest work, any of the treatments administered to our patients showed higher survival rate. This seems clear that in localized cases in immunocompetent patients (case 3), treatment with an antifungal drug plus surgical debridement may lead to eradicate the infection. Some factors such as the immunossupression level, underlying diseases, and location of infection may be determinant for patient survival. In our patients, the mortality rate in L. prolificans infection is higher than in S. apiospermium/S. boydii (42.8 vs. 21.4%). The heterogeneity of studies and scarcity of data prevents any conclusion being drawn on antifungal treatments, and further research is required on this important issue. It appears evident that these patients should be treated with drugs selected after antifungal susceptibility tests, but the absence of standardization of the methods and that these techniques are usually performed in reference centres, make it very difficult to carry out. In conclusion, infections caused by Scedosporium/Lomentospora species are still rare and difficult to diagnose and treat. These infections should be suspected especially in patients with corticosteroids and/or IS treatment as well as in those with hematologic malignancies or pulmonary diseases. Due to the absence of diagnostic criteria clearly established for IFI and that these opportunistic pathogens are frequent colonizers, the diagnosis should be confirmed microbiologically, taking adequate samples from the affected tissue, and leaning on clinical and radiological diagnosis criteria. Despite the above mentioned difficulties, antifungal susceptibility testing of isolates is also highly recommended in order to detect the presence of resistances. The treatment is still a challenge issue, and it is not clearly defined, being the mortality rate high in this kind of infections, especially in those caused by L. prolificans. Acknowledgements We would like to acknowledge to Dr. Ana Alastruey (National Centre of Microbiology, Majadahonda, Madrid, Spain) for performing the molecular study of cases 10 and 13, and for her advice. Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and the writing of the paper. References 1. Gilgado F , Cano J , Gené J , Suton DA , Guarro J . Molecular and phenotypic data supporting distinct species statuses for Scedosporium apiospermum and Pseucoallescheria boydii and the proposed new species Scedosporium dehoogii . J Clin Microbiol . 2008 ; 46 : 766 – 771 . Google Scholar Crossref Search ADS PubMed 2. Lackner M , de Hoog GS , Yang L et al. Proposed nomenclature for Pseucoallescheria, Scedosporium and related genera . Fungal Diversity . 2014 ; 67 : 1 – 10 . Google Scholar Crossref Search ADS 3. Schwarz C , Brandt C , Antweiler E et al. 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Google Scholar Crossref Search ADS PubMed 30. Li JY , Yong TY , Grove DI , Coates PT . Successful control of Scedosporium prolificans septic arthritis and probable osteomyelitis without radical surgery in a long-term renal transplant recipient . Transpl Infect Dis . 2008 ; 10 : 63 – 65 . Google Scholar Crossref Search ADS PubMed © The Author(s) 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Journal

Medical Mycology – Oxford University Press

Published: Nov 1, 2018

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