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Atypical Presentation of Scedosporium Pneumonia Gabriel Johnson, DO Leslie Spikes, MD Department of Internal Medicine University of Kansas Medical Center Kansas City, KS Introduction Provide a brief overview of scedosporium epidemiology Present an unusual case of a life-threatening Scedosporium infection in a patient without typical risk factors for fungemia Identify diagnostic and therapeutic challenges Scedosporium Infections in Humans Localized infections: Bronchiectatic lungs Mycetomas Disseminated infections: Transplant wards Up to 10% of cystic fibrosis patients colonized in transplant wards Near drowning events Rarely in the immuno-competent Cortez et. Al. Infections Caused by Scedosporium spp. Clin Microbiol Rev. 2008 January; 21(1): 157–197. Complication of organ transplant Study of 80 cases of scedosporium infection in transplant patients at 5 academic institutions 23 hematopoietic stem cell transplants 57 solid organ transplants Disseminated infection 2 noncontiguous organs or + blood culture 69% of HSCT with scedosporium 53% of SOT with scedosporium Husein et. al. Infections due to Scedosporium in Transplant Recipients: Clinical Characteristics. Clinical Infectious Disease 2005 Jan 1;40 Scedosporium - overview Ubiquitous white mold Tolerates aerobic and anaerobic conditions and wide range of temperature and osmolarity Transmission Direct inoculation (mycetoma) Inhalation of airborne particles Williamson et. al. Genetic Epidemiogy of Scedosporium in Patients with Chronic Lung Disease. J Clin Microbiol. 2001 January; 39(1): 47–50. Species Scedosporium apiospermum Typically sensitive to multi-agent antifungal therapy Voriconazole associated with survival improvement over amphotericin Scedosporium prolificans Treatment generally requires immunosuppression reversal and surgical intervention. Cortez et. Al. Infections Caused by Scedosporium spp. Clin Microbiol Rev. 2008 January; 21(1): 157–197. American Society for Microbiology: Clinical Microbiology Reviews Infection sites 2000-2007 Lungs Sinuses Bone/joint Eyes Hands Feet CNS Blood Abdomen 59% 36% 8% 7% 4% 4% 3% 3% 2% Cortez et. Al. Infections Caused by Scedosporium spp. Clin Microbiol Rev. 2008 January; 21(1): 157–197. Case Report A 72 year old woman presented to ER 3 months of progressive hemoptysis Diffuse pulmonary nodules on recent imaging 5 days of fever, chills, and myalgias Past Medical History Pulmonary arterial hypertension Diagnosed 2 years prior Likely secondary to chronic pulmonary emboli On continuous infusion intravenous treprostinil On warfarin for chronic thromboemboli Breast cancer Right mastectomy and radiation 8 years prior No history of atypical or recurrent infections Recent Medical History CT guided needle biopsy of pulmonary nodule had been performed 3 weeks prior Histology: necrotic tissue, peribronchial fibrosis and chronic inflammatory changes without granulomas Gram stain/culture: no bacterial or fungal growth Cytology: no malignant cells Social History Independently performs activities of daily living 25 pack years but quit 2 years prior No occupational or environmental exposures Physical Exam T 36.7 BP 121/70 P 99 R 24 Pulse ox: 95% on room air HEENT – Unremarkable Chest – right sided indwelling Hickman catheter Heart – Unremarkable Lungs Diminished breath sounds bilaterally, no rales, rhonchi, or wheezing Abdomen: Unremarkable Extremities/Skin: Unremarkable Laboratory Data Fungitell: 257 (41 previously) [Normal < 40] Blood Culture: Scedosporium elements The following were negative Histoplasma Ab HIV screen WBC Hgb 12.9 12.3 Galactomannan Aspergillus Ab ANA CMV, EBV pcr RVP Hep A,B,C Plt Neut INR 239 80% 3.4 Scl70 Anti-dsDNA Mycoplasma Chlamydia 3 weeks prior Hospital Course Sudden hemoptysis of 600 ml frank blood Resolved with reversal of anticoagulation Bronchoscopy with lavage performed Hemorrhagic fluid with negative cultures Repeat CT guided biopsy of left lobe nodule Pathologic findings unchanged and unremarkable Hickman catheter removed No fungal or bacterial growth on tip culture Hospital Course Amphotericin and voriconazole initiated Repeat CT 2 weeks later showed progression Patient requested to discontinue all IV medications and go home with home health care Oral voriconazole and terbinafine Oral sildenafil New 2 L oxygen requirement Speciation and Sensitivity Speciation: Scedosporium Apiospermum Sensitivity testing: Amphotericin Caspofungin Micafungin Voriconazole Itraconazole Posaconazole R R S S S S Resolution Patient’s hypoxia improved and she was able to titrate off oxygen No recurrence of fever or hemoptysis She completed 6 months of antifungal therapy with voriconazole and terbinafine Radiographic regression 4 months later Case Summary Atypical presentation of a rare fungal pathogen Diagnostic difficulties Voriconazole as preferred agent Questioning her risk factors Acknowledgments Dr. Leslie Spikes Associate Professor of Internal Medicine University of Kansas Medical Center European Society for Imunodeficiencies Unusual infections or unusually severe course of infections T lymphocyte deficiency WAS STAT1 deficiency Hypermorphic mutations in IκBα X–linked lymphoproliferative syndrome DeVries et.al. Clinical & Experimental Immunology vol. 145, iss. 2. pages 204–214, August 2006