Case Studies in Fungal Infections and Antifungal Therapy Wayne L. - PowerPoint PPT Presentation

Case Studies in Fungal Infections and Antifungal Therapy Wayne L. Gold MD, FRCPC Annual Meeting of the Canadian Society of Internal Medicine November 4, 2017

Disclosures  No financial disclosures or industry relations.

Objectives 1. Review infections caused by two medically important classes of fungi that may be seen by specialists in Internal Medicine 2. Recognize risk factors for these infections 3. Understand diagnostic approaches to patients with these infections

Objectives 4. Review available antifungal therapies Classes of antifungal agents  Polyenes - Amphotericin B   Triazoles Echinocandins  Spectrums of activity  Appropriate selection by clinical syndrome 

Case 1

History 57-year-old woman  PMH  Type 2 diabetes mellitus  Dyslipidemia  Hypertension  Alcohol use disorder

History of Present Illness  Three-day history  Nausea, vomiting  Epigastric abdominal pain  Recent alcohol binge  Dx: acute pancreatitis (imaging, biochemistry)

History of Present Illness  Course complicated by ARDS and sepsis  infected pancreatic necrosis requiring percutaneous drainage  ICU admission  Intubation, ventilation  Pressor support  IV piperacillin/tazobactam  Total parenteral nutrition - central venous catheter

History of Present Illness  Defervescence followed by recurrence of fever  Cultures:  Blood  Endotracheal secretions  Drainage fluid

Blood culture …

Candida species

Candida species  Normal human commensal organisms  Skin  Gastrointestinal tract (mouth to anus)  Female genital tract  Expectorated sputum (oropharynx)  Most common species:  C. albicans, C. glabrata C. parapsilosis, C. tropicalis, C. krusei

Mucocutaneous Candidiasis  Oropharyngeal  Esophageal  AIDS  Malignancies and their treatments  Proton pump inhibitor therapy  Vaginal

Invasive Candidiasis  Normally non-pathogenic  Invasive candidiasis is the price paid for advances in modern medical therapies  Primarily a nosocomial infection or associated with ambulatory “medicalized” patients

Host Defenses Against Invasive Candidiasis  Intact skin  Intact mucous membranes  Normal sphincter function  Normal neutrophil number and function

Risk Factors for Invasive Candidiasis  Exposure to broad-spectrum antimicrobial therapy  Indwelling venous devices  Total parenteral nutrition (CVC, alimentation solution)  Gastrointestinal surgery  Neutropenia Cytotoxic chemotherapy  Intestinal mucositis  Solid organ transplantation  Intravenous drug use  Low-birth-weight . Adapted from Edwards JE Jr. Candida Species In Principles and Practice of Infectious Diseases 8 th Edition

Risk Factors for Invasive Candidiasis  Exposure to broad-spectrum antimicrobial therapy  Indwelling venous devices  Total parenteral nutrition (CVC, alimentation solution)  Gastrointestinal surgery  Neutropenia Cytotoxic chemotherapy  Intestinal mucositis  Solid organ transplantation  Intravenous drug use  Low-birth-weight . Adapted from Edwards JE Jr. Candida Species In Principles and Practice of Infectious Diseases 8 th Edition

Invasive / Disseminated Candidiasis  Bloodstream  Dissemination to:  Eyes (2-20%)  Bones/joints  Skin  Liver / spleen (immunocompromised hosts)  Heart

Invasive Candidiasis - Diagnosis  Culture-based techniques  Blood, tissue, fluids  Diagnostic imaging

What antifungal agent would you select from empiric treatment of this patient with candidemia?

How would you treat this patient? A. An echinocandin Caspofungin, micafungin, anadulafungin  B. Fluconazole C. Voriconazole D. Lipid-formulation amphotericin B

How would you treat this patient? A. An echinocandin Caspofungin, micafungin, anadulafungin  B. Fluconazole C. Voriconazole D. Lipid-formulation amphotericin B

Empiric Treatment of Candidemia – Non-Neutropenic Patients  Fluconazole 800 mg iv/po in patients who are not critically ill and without prior azole exposure  An echinocandin is recommended as empiric therapy when fluconazole is patients not meeting these criteria  Voriconazole offers little advantage over fluconazole for most Candida species (enhanced mould activity)  Amphotericin B has a greater potential for toxicity than other classes

Treatment of Candidemia – Non-Neutropenic Patients  Antifungal susceptibility testing is recommended for all bloodstream isolates  Candida glabrata is less susceptible to azole therapy  Candida krusei is intrinsically resistant to fluconazole  Candida parapsilosis is less susceptible to echinocandins  Transition from an echinocandin (if used as initial therapy) to fluconazole is recommended once patient has stabilized and if isolate is susceptible

What other processes of care are indicated for this patient?

Which of the following statements is false in patients with candidemia? A. A dilated ophthalmologic examination is indicated for all patients B. Follow-up blood cultures should be performed daily until candidemia is cleared C. An echocardiogram is indicated for all patients D. All venous catheters should be removed / changed E. Recommended duration of therapy is 2 weeks after documented clearance of candidemia in patients without metastatic complications

Which of the following statements is false? A. A dilated ophthalmologic examination is indicated for all patients B. Follow-up blood cultures should be performed daily until candidemia is cleared C. An echocardiogram is indicated for all patients D. All venous catheters should be removed E. Recommended duration of therapy is 2 weeks after documented clearance in patients without metastatic complications

Treatment of Candidemia – Neutropenic Patients  An echinocandin or lipid formulation of amphotericin B is recommended as initial therapy  During persistent neutropenia, transition to fluconazole can be done once patient has stabilized and if isolate is susceptible

Blood culture … Candida albicans

Management and Outcome  Treatment initiated with caspofungin  Hemodynamically unstable  Lines changed  Dilated ophthalmologic examination - normal  Day 2 – afebrile  Day 3 – blood culture negative

Case 2

History 65-year-old man  PMH  Colorectal cancer - 2004  Resection, adjuvant chemotherapy  Metastatic progression (lung, pelvis) - 2006  Combination chemotherapy capecitabine, irinotecan, bevacizumab   Treatment complicated by pulmonary embolism

History of Present Illness  Four weeks prior to presentation  Fever, dry cough treated with course of po antibiotics  Two-week history of purulent sputum, night sweats  Prescribed moxifloxacin

Chest Radiograph

History of Present Illness  Fever resolved  Increasing dyspnea, streaky hemoptysis, anorexia, fatigue, night sweats  No cigarette smoking, IVDU  No recent travel  No history of TB exposure

CT Thorax – Cavitary Lung Disease

How would you investigate this patient?

In consideration of a diagnosis of aspergillosis, which test is not recommended for diagnosis in this patient? A. Expectorated sputum for microbiologic and cytologic examination B. Fine needle aspiration of lesion with specimens sent for microbiologic and cytologic investigations C. Bronchoscopy with specimens sent for microbiologic and cytologic investigations D. Serum galactomannan

In consideration of a diagnosis of aspergillosis, which test is not recommended for diagnosis in this patient? A. Expectorated sputum for microbiologic and cytologic examination B. Fine needle aspiration of lesion with specimens sent for microbiologic and cytologic investigations C. Bronchoscopy with specimens sent for microbiologic and cytologic investigations D. Serum galactomannan

Invasive Aspergillosis - Diagnosis  Diagnostic imaging  Culture-based techniques  Tissue, fluids

Galactomannan in the Diagnosis of Aspergillosis  A cell wall constituent that is released extracellularly  Recommended as a test for the diagnosis of invasive aspergillosis in high-risk populations  Hematologic malignancy, HSCT  Lacks sensitivity and specificity in other populations  Can be applied to bronchoscopy specimens  May be used for screening in high-risk populations – serial measurements

Case – Sputum Examination  Sputum culture  Negative for bacteria and fungi  AFB smear –negative

Case – Fine Needle Aspiration  Microbiology  Gram-stain - negative  No fungal elements seen  No bacterial or fungal pathogens isolated

Cytology - Fine Needle Aspiration

Cytology - Fine Needle Aspiration  Fungal elements seen – septate hyphae, 45 o angles  Foreign material seen  Morphology compatible with Aspergillus species

Aspergillus species  Filamentous moulds  Environmental organisms – ubiquitous in soil, water