1. Fungus Danielle Hansen, DO Internal Medicine Lecture Series April 4, 2007

2. Predisposing Factors Immunosuppressed Immunosuppressed Broad-Spectrum Antibiotics Broad-Spectrum Antibiotics Central Venous Catheters Central Venous Catheters Trauma Trauma Burns Burns Total Parenteral Nutrition Total Parenteral Nutrition Hemodialysis or Peritoneal Dialysis Hemodialysis or Peritoneal Dialysis Abdominal Surgery Abdominal Surgery GI Tract Perforations and Anastomotic Leaks GI Tract Perforations and Anastomotic Leaks Gradual Onset Gradual Onset

3. Dermatophytes Ringworm Ringworm 5 Million DO Visits Annually 5 Million DO Visits Annually >$200 Million >$200 Million Types Types Epidermophyton Epidermophyton Trichophyton Trichophyton Microsporum Microsporum Diagnosis Diagnosis KOH Test KOH Test Culture Culture

4. Gray Patch Tinea Capitis Microsporum Canis Microsporum Canis Animal to Person Spread Animal to Person Spread Erythematous, Scaling, Well-Demarcated Erythematous, Scaling, Well-Demarcated Spreads Weeks – Months Spreads Weeks – Months Persists for Years Persists for Years Hair Breaks off at 1-2mm Hair Breaks off at 1-2mm Kerion Kerion Fluoresce under Woods Lamp Fluoresce under Woods Lamp

5. Black Dot Tinea Capitits African Americans African Americans Person to Person Spread Person to Person Spread Erythematous, Scaling Erythematous, Scaling Slowly Enlarges Slowly Enlarges Hair Breaks off Flush Hair Breaks off Flush Kerion Kerion Do Not Fluoresce Do Not Fluoresce

6. Tinea Capitis Treatment Griseofulvin 250mg PO BID x 6-12 weeks Griseofulvin 250mg PO BID x 6-12 weeks Terbinafine 250mg PO QD x 4 weeks Terbinafine 250mg PO QD x 4 weeks Itraconazole Itraconazole Fluconazole Fluconazole

7. Tinea Pedis ACUTECHRONIC Trichophyton Mentagrophytes Trichophyton Rubrum Vesicular Lesions Interdigital Fissures Sole, Between Toes Sole, Between Toes, Top Self-Limited Persists Indefinitely

8. Tinea Pedis Treatment Topical Antifungal x 4 weeks Topical Antifungal x 4 weeks Oral Antifungal Oral Antifungal Griseofluvin 250 – 500mg BID Griseofluvin 250 – 500mg BID Terbinafine 250mg QD Terbinafine 250mg QD Itraconazole 200mg QD Itraconazole 200mg QD Foot Powder Foot Powder Non-occlusive Footwear Non-occlusive Footwear

9. Topical Antifungals

10. Tinea Corporis Pruritic, Circular, Erythematous Scaling Lesion Pruritic, Circular, Erythematous Scaling Lesion Spreads Centifugally Spreads Centifugally Central Clearing Central Clearing Raised, Advancing Border Raised, Advancing Border

11. Tinea Corporis Treatment

12. Topical Antifungals

13. Tinea Cruris Men > Women Men > Women Obesity Obesity Foot to Groin Foot to Groin Macular, Erythematous Macular, Erythematous Speads Centrifugally Speads Centrifugally Partial Central Clearing Partial Central Clearing Raised, Sharply Demarcated Border Raised, Sharply Demarcated Border Tiny Vesicles Tiny Vesicles

14. Tinea Cruris Treatment Topical Antifungals Topical Antifungals Systemic Antifungals if Resistant to Topicals Systemic Antifungals if Resistant to Topicals Recurs if Fail to Treat Tinea Pedis Recurs if Fail to Treat Tinea Pedis Talcum or Desiccant Powder Talcum or Desiccant Powder No Hot Baths No Hot Baths Loose Fitting Clothing Loose Fitting Clothing

15. Topical Antifungals

16. Candidal Intertrigo Skin Friction Skin Friction Obesity Obesity Chafing Clothing Chafing Clothing Rubbing Activities Rubbing Activities Moisture Moisture Obesity Obesity Occlusive Clothing Occlusive Clothing Hyperhidrosis Hyperhidrosis DM DM Corticosteroids Corticosteroids ABX ABX HIV HIV Chemotherapy Chemotherapy Immunosuppresants Immunosuppresants Occupational Exposure to Sugar Occupational Exposure to Sugar

17. Candidal Intertrigo Erythematous, Macerated Plaques and Erosions Erythematous, Macerated Plaques and Erosions Peripheral Scaling Peripheral Scaling Satelite Papulopustules Satelite Papulopustules Pruritic Pruritic KOH Test KOH Test Culture Culture

18. Candidal Intertrigo Treatment Topical Antifungal Topical Antifungal Drying Agents Drying Agents Antifungal Powders Antifungal Powders Aluminum Acetate Solution Aluminum Acetate Solution Gentian Violet Gentian Violet Talcum Powder Talcum Powder Systemic Antifungals Systemic Antifungals

19. Topical Antifungals

20. Onychomycosis Distal Subungual Proximal Subungual White Superficial Yeast Great Toe HIV Fingernails, Immunodeficient White/Brown/Yellow Dull White Spots Thick, Yellow/Brown Distal to Cuticle Proximal to Distal Centrifugally

21. Onychomycosis Treatment Indications for Treatment Indications for Treatment Cellulitis in LE Cellulitis in LE Diabetics with Additional Risk Factor for Cellulitis Diabetics with Additional Risk Factor for Cellulitis Pain Pain Cosmetics Cosmetics Terbinafine 250mg/day x 6-12wks Terbinafine 250mg/day x 6-12wks Itraconazole 200mg/day x 6-12wks or 200mg/day x 7days/month x 2 mo Itraconazole 200mg/day x 6-12wks or 200mg/day x 7days/month x 2 mo Surgery Surgery

22. Otomycosis External Auditory Canal External Auditory Canal 6.5 – 12.5% of Otitis Externa 6.5 – 12.5% of Otitis Externa 61+ Species of 28 Genera 61+ Species of 28 Genera Aspergillus Niger Aspergillus Niger Candida Candida Tropical and Subtropical Regions Tropical and Subtropical Regions Swimming, Canal Cleaning Swimming, Canal Cleaning Antibiotic Ear Drops Antibiotic Ear Drops

24. Otomycosis Clinical Manifestations Itching Itching Sensation of Something in Ear Sensation of Something in Ear Discomfort Discomfort Discharge Discharge

25. Otomycosis Treatment Clean Canal Clean Canal Steroids Steroids Antiseptics Antiseptics Gentian Violet Gentian Violet Cresylate Cresylate Merthiolate Merthiolate Acidifying Solutions Acidifying Solutions VoSol VoSol Otic Domeboro Otic Domeboro Antifungals Antifungals Drying Agents Drying Agents A. Niger C. Albicans C. Parapsilosis Amphotericin B +++++ Clotrimoazole++++++ Flucytosine000 Miconazole+++++ Natamycin++++ Nystatin+++++ Tolnaftate000

26. Fungal Endophthalmitis Epidemiology Epidemiology Trauma Trauma Surgery Surgery Hematogenous Seeding of Retina and Choroid Hematogenous Seeding of Retina and Choroid Clinical Manifestations Clinical Manifestations Eye Pain Gradual Decrease in Visual Acuity Focal, Glistening, White, Infiltrative, Mound-like Lesion on Retina Vitreal Haze Fluffy, White Balls in Vitreous

27. Fungal Endophthalmitis IV Antifungal IV Antifungal Intravitreal Antifungal Intravitreal Antifungal Surgical Removal of Vitreous and Foreign Material Surgical Removal of Vitreous and Foreign Material

28. Oropharyngeal Candidiasis Epidemiology Epidemiology Elderly with Dentures Elderly with Dentures Antibiotics Antibiotics Inhaled Corticosteroids Inhaled Corticosteroids Chemotherapy Chemotherapy Radiation of Head and Neck Radiation of Head and Neck Cellular Immune Deficiency Cellular Immune Deficiency Xerostomia Xerostomia Clinical Manifestations Clinical Manifestations Cotton Mouth Cotton Mouth Loss of Taste Loss of Taste Odynophagia Odynophagia Pain with Dentures Pain with Dentures

29. Oropharyngeal Candidiasis Diagnosis Diagnosis White Plaques on Buccal Mucosa, Palate, Tongue, Oropharynx, under Dentures White Plaques on Buccal Mucosa, Palate, Tongue, Oropharynx, under Dentures Budding Yeast with or without Pseudohyphae from Scraping Budding Yeast with or without Pseudohyphae from Scraping Treatment Treatment Nystatin Swish and Swallow 5x/day Fluconazole 200mg x1, then 100mg QD Chlorhexidine Gluconate Soak for Dentures Duration of Treatment 7-14 days

30. Candida Esophagitis Epidemiology Epidemiology HIV HIV Hematologic Malignanies Hematologic Malignanies Thrush Thrush Clinical Manifestations Clinical Manifestations Odynophagia Odynophagia Diagnosis Diagnosis White Mucosal Plaque-like Lesions on EGD Biopsy Shows Yeast and Pseudohyphae Invading Mucosal Cells Culture + Candida Treatment Treatment Fluconazole 100-200mg QD x 14-21 days

31. Candida Pneumonia Epidemiology Epidemiology Infection vs Colonization vs Contamination Infection vs Colonization vs Contamination Primary Candida Pneumonia < 1% Primary Candida Pneumonia < 1% Aspiration of Oropharyngeal Contents Aspiration of Oropharyngeal Contents Clinical Manifestations Clinical Manifestations Fever Fever Tachypnea Tachypnea Nonspecific Patchy Infiltrates on CXR Nonspecific Patchy Infiltrates on CXR

32. Candida Pneumonia Diagnosis Diagnosis Sputum Culture Sputum Culture Sensitivity 85% Sensitivity 85% Specificity 60% Specificity 60% Bronchoalveolar Lavage Bronchoalveolar Lavage Sensitivity 71% Sensitivity 71% Specificity 57% Specificity 57% Treatment Treatment No Treatment Immunocompetent with + Sputum Amphotericin B 0.7-1.0 mg/kg daily Isolated Pneumonia Treatment for Disseminated Disease Secondary Pneumonia

33. Pulmonary Histoplasmosis Ohio and Mississippi River Valleys Ohio and Mississippi River Valleys Mediastinal or Hilar Mass or Lymphadenopathy on CXR Mediastinal or Hilar Mass or Lymphadenopathy on CXR Diagnosis Diagnosis Biopsy Biopsy Cultures Cultures Antigen Detection Antigen Detection Treatment Treatment Self-Limiting – No Therapy Self-Limiting – No Therapy Systemic Antifungals for Systemic Antifungals for Immunosuppressed or Severely Ill Itraconazole 200mg PO TID x 3 Days, Itraconazole 200mg PO TID x 3 Days, then 200mg QD-BID

34. Fungal Endocarditis Epidemiology Epidemiology Prosthetic Heart Valves Prosthetic Heart Valves IV Drug Users IV Drug Users Central Venous Catheters Central Venous Catheters Prolonged Fungemia Prolonged Fungemia Clinical Manifestations Clinical Manifestations Fever Murmur Signs and Symptoms of Heart Failure Peripheral Embolism 50-100% Mortality

35. Candida Endocarditis Diagnosis Diagnosis Persistent Candidemia Persistent Candidemia Vegetations on Echocardiography Vegetations on Echocardiography Treatment Treatment Amphotericin B +/- Flucytosine x 6 weeks Surgical Resection

36. Fungal Peritonitis Epidemiology Epidemiology Gut Perforation Gut Perforation Anastomotic Leaks Anastomotic Leaks Acute Necrotizing Pancreatitis Acute Necrotizing Pancreatitis Peritoneal Dialysis Peritoneal Dialysis Gangrenous Cholecystitis Gangrenous Cholecystitis C. Albicans > C. Galbrata > Others C. Albicans > C. Galbrata > Others Clinical Manifestations Clinical Manifestations Fevers/Chills Abdominal Pain Diagnosis Diagnosis Culture of Aspirate CT guided U/S Guided Culture at time of Surgery Culture from Drain Inadequate

37. Fungal Peritonitis Treatment Fluconazole 400mg daily Fluconazole 400mg daily Preferred unless C. Galbrata Preferred unless C. Galbrata Amphotericin B 0.7mg/kg daily Amphotericin B 0.7mg/kg daily C. Galbrata C. Galbrata Caspofungin Caspofungin C. Galbrata C. Galbrata Duration of Therapy at Least 2 Weeks Duration of Therapy at Least 2 Weeks Surgical Intervention Surgical Intervention

38. Fungal Infection of Bladder and Kidneys Candida Candida Aspergillus Aspergillus Trichosporon Trichosporon Zygomycetes Zygomycetes Dematiaceous Molds Dematiaceous Molds Cryptococcus Neoformans Cryptococcus Neoformans Dimorphic Fungi Dimorphic Fungi

39. Fungal UTI Risk Factors

40. Characteristics Bladder Infection Vs. Colonization Bladder Infection Vs. Colonization Acute Renal Infection Acute Renal Infection Hematogenous Seeding Hematogenous Seeding Multiple Micro-abscesses Multiple Micro-abscesses Chronic Renal Infection Chronic Renal Infection Unilateral, Ascending Seeding Unilateral, Ascending Seeding Perinephric Abscess or Bezoar Perinephric Abscess or Bezoar

41. Efficacy of Funguria Treatment No Affect on Mortality No Affect on Mortality Resolution of Funguria Resolution of Funguria No Treatment 76% No Treatment 76% Catheter Removal 35% Catheter Removal 35% Fluconazole or Amphotericin B 50% Fluconazole or Amphotericin B 50%

42. Fungal UTI Treatment Guidelines Symptomatic UTI Symptomatic UTI Fluconazole 400mg x 1, then 200mg/day x 13 Fluconazole 400mg x 1, then 200mg/day x 13 Amphotericin B 0.3-0.7 mg/kg/day IV x 1-7 Amphotericin B 0.3-0.7 mg/kg/day IV x 1-7 Flucytosine 25mg/kg/day PO x 5-7 Flucytosine 25mg/kg/day PO x 5-7 Asymptomatic UTI Asymptomatic UTI Only Treat if Neutropenic Only Treat if Neutropenic Perinephric Abscess Perinephric Abscess Surgical Drainage + Systemic Antifungal Surgical Drainage + Systemic Antifungal

43. Candida Vulvovaginitis Epidemiology Epidemiology Increased Estrogen Levels Increased Estrogen Levels Antibiotics Antibiotics Corticosteroids Corticosteroids Diabetes Mellitus Diabetes Mellitus HIV HIV IUD IUD Diaphragm Diaphragm Clinical Manifestations Clinical Manifestations Itch Discharge Dyspareunia Dysuria Vaginal Irritation

44. Candida Vulvovaginitis Diagnosis Vulvar Erythema and Swelling Vulvar Erythema and Swelling Vaginal Erythema and White, Curd-like Discharge Vaginal Erythema and White, Curd-like Discharge Budding Yeast with or without Pseudohyphae on Wet Mount or KOH Prep of Vaginal Secretions Budding Yeast with or without Pseudohyphae on Wet Mount or KOH Prep of Vaginal Secretions

45. Candida Vulvovaginitis Treatment Fluconazole 150mg x 1 Repeat q 72 hours for Complicated Cases

46. Candida Osteoarticular Infections Epidemiology Epidemiology Hematogenous Spread Hematogenous Spread Trauma Trauma Intraarticular Injection Intraarticular Injection Surgery Surgery Injection Drug Use Injection Drug Use Native > Prosthetic Joints Native > Prosthetic Joints Months-Years after Insult Months-Years after Insult Clinical Manifestations Clinical Manifestations Pain Decreased Range of Motion

47. Candida Osteoarticular Infections Diagnosis Diagnosis Candidemia in 50-60% Candidemia in 50-60% WBC WNL WBC WNL ESR ESR Erosion on Xray or MRI Erosion on Xray or MRI Culture of Infected Site Culture of Infected Site Treatment Treatment Systemic Therapy Amphotericin B 0.5- 1mg/kg/day x 2-3 weeks then Fluconazole 400mg/day x 6-12 months I & D Remove Prosthesis

48. Candida Mediastinitis Epidemiology Epidemiology Thoracic Surgery Thoracic Surgery Prior Antibiotic Therapy Prior Antibiotic Therapy Time from Insult to Infection 11 Days Time from Insult to Infection 11 Days Range 6 - 100 Range 6 - 100 Hematogenous Spread Hematogenous Spread Mortality Rate 55% Mortality Rate 55% Clinical Manifestations Clinical Manifestations Chest Wall Erythema Chest Wall Drainage Fever Sternal Instability Treatment Amphotericin B 0.7 – 1.0 mg/kg daily Fluconazole 400mg daily Surgical Drainage

49. Fungal Meningitis Ventricular Drainage Devices Ventricular Drainage Devices Ventriculoperitoneal Shunt Ventriculoperitoneal Shunt Ventriculoatrial Shunt Ventriculoatrial Shunt Craniotomy Craniotomy Hematogenous Spread Hematogenous Spread CSF CSF Low Glucose Low Glucose High Protein High Protein

50. Candidal Meningitis C. Albicans > C. Paraspilosis > C. Tropicalis C. Albicans > C. Paraspilosis > C. Tropicalis Immunosuppressed Immunosuppressed Fever, Nuchal Rigidity, Altered MS, Headache Fever, Nuchal Rigidity, Altered MS, Headache Culture CSF Culture CSF Micro-abscesses on MRI Micro-abscesses on MRI Amphotericin B + Flucytosine Amphotericin B + Flucytosine Follow up LP in 1 Week Follow up LP in 1 Week

51. Coccidiodal Meningitis C. Immitis > C. Posadasii C. Immitis > C. Posadasii Southwestern US Southwestern US Headache Headache Persistent or Progressively Worsening Persistent or Progressively Worsening Unusual Severity Unusual Severity Nausea/Vomitting Nausea/Vomitting Blurred Vision Blurred Vision Mental Status Change Mental Status Change +Culture or Anti-Coccidioidal Antibodies in CSF +Culture or Anti-Coccidioidal Antibodies in CSF Untreated 95% Mortality Untreated 95% Mortality Fluconazole 400-1000mg/day PO Indefinitely Fluconazole 400-1000mg/day PO Indefinitely Intrathecal Amphotericin B for Nonresponders Intrathecal Amphotericin B for Nonresponders

52. Cryptococcal Meningitis C. Neoformans C. Neoformans Inhalation Inhalation Immunosuppressed Immunosuppressed Headache, Fever, Lethargy, Mental Status Changes, Memory Loss Headache, Fever, Lethargy, Mental Status Changes, Memory Loss CSF Culture, India Ink, Cryptococcal Antigen Assay CSF Culture, India Ink, Cryptococcal Antigen Assay Fatal if Untreated Fatal if Untreated Amphotericin B + Flucytosine x 2 Weeks Amphotericin B + Flucytosine x 2 Weeks Followed with 3 – 6 months of Fluconazole PO Followed with 3 – 6 months of Fluconazole PO Intrathecal for Nonresponders Intrathecal for Nonresponders Follow up LP in 2 Weeks Follow up LP in 2 Weeks

53. Fungemia Immunosuppressed Immunosuppressed Hematologic Malignancies Hematologic Malignancies Transplant Recipients Transplant Recipients Chemotherapy Chemotherapy ICU ICU Trauma Trauma Burns Burns Central Lines Central Lines TPN TPN ABX ABX Hemodialysis Hemodialysis Abdominal Surgical Procedures Abdominal Surgical Procedures GI Tract Perforations and Anastomotic Leaks GI Tract Perforations and Anastomotic Leaks Hematogenous Spread Hematogenous Spread C. Albicans C. Albicans C. Galbrata C. Parapsilosis C. Tropicalis C. Krusei

54. Candidemia Clinical Manifestations Fever Fever Sepsis Sepsis Skin Lesions Skin Lesions Eye Lesions Eye Lesions Muscle Abscesses Muscle Abscesses Multiorgan System Failure Multiorgan System Failure

55. Candidemia Diagnosis and Treatment Diagnosis Diagnosis + Blood Cultures + Blood Cultures Biopsy of Involved Sites Biopsy of Involved Sites Treatment Treatment Ophthalmologic Exam Catheter Removal Systemic Antifungal Fluconazole 800mg x1, then 400mg QD x 14 Days after -BC Caspofungin for C. Krusei and C. Galbrata

57. Questions 1. The mortality rate associated with fungal endocarditis is: a) < 10% b) 20-30% c) 30-40% d) > 50%

58. Questions 2. 67y/o female admitted to the ICU with sepsis. Broad spectrum antibiotics were initiated. She continues to decline. Blood cultures finally grow Candida Albicans. After initiating the appropriate antifungal, you: a) Consult Opthalmology b) Consult GI c) Consult Orthopedics d) Consult Psychiatry

59. Questions 3. All of the following are susceptible to Fluconazole except: a) C. Albicans b) C. Krusei c) C. Parapsilosis d) C. Tropicalis