Clin Med - Fungal infections and mycobacterial diseases

Mycotic or fungal infections are classified as

primary or opportunistic infections.

Primary infections

those that develop in immunocompetent hosts and opportunistic infections develop in immunocompromised hosts.

Fungal infections can also be

local or systemic (aka disseminated).

Local infections

involve one part of the body including the skin, oral cavity, and vaginal and occur in immunocompetent or immunocompromised hosts.

Systemic infections are

infections that are noted in more than one area of the body and spread in the bloodstream.

Most fungi are

opportunists and are typically not pathogenic except in an immunocompromised host.

What are candidiasis, aspergillosis, and mucormycosis

opportunistic systemic fungal infections

What is a common cause of primary fungal infections

inhalation of fungal spores, causing localized pneumonia.

What has a geographic distribution

many primary fungal infections (dimorphic fungi)

Coccidioidomycosis

noted in the southwest United States, northern Mexico, and Central and South America

Histoplasmosis

noted in the Midwestern United States and areas of Central and South America, Africa, Asia, and Australia

Blastomycosis

noted in North America and Africa

Paracoccidioidomycosis

noted in South America

Cryptococcosis

fungus that can lead to chronic meningitis

Histoplasmosis

fungus that can disseminate involving the reticuloendothelial system

Blastomycosis

fungus that can lead to skin lesions or involve the central nervous system and bone

Coccidioidomycosis

fungus that can cause bone and joint infections, skin lesions, and meningitis

Systemic infections are important due to

increased number of immunocompromised patients and antibiotic overuse.

Yeast and mold differ in structural complexity and reproduction, yeast is and reproduces by __

unicellular (single-celled), budding

Yeast and mold differ in structural complexity, mold is and reproduces by _

multicellular (forms hyphae and mycelium), sexually (spores or hyphae) and asexually (fusion of hyphae)

Candida Species

Fungal infection cause by a yeast (candida albicans common)

What can occur with indwelling urinary catheter, focal renal infection, or disseminated disease

Candiduria

What is the work up for candiduria

urinalysis and urine culture treatment focused if needed

What would you prescribe for candiduria for a patient with normal renal function

oral fluconazole 200 mg QD x 7-14 days

What imaging would you order for candida albicans

endoscopy indication, esophagitis (white plaques in esophagus)

What is the 1st line of treatment for candida albicans, localized infection and immunocompetent

Nystatin

What is the 1st line of treatment for candida albicans, more severe local and systemic infections

Azoles (if fungus not resistant)

What is useful in detecting the presence of cerebral histoplasmosis prior to performing a lumbar puncture

CT scanning

What is useful if adrenal involvement is suspected

Abdominal CT scanning

What is the surgical management of histoplasmosis

Resection of pulmonary cavitary lesions when repeated relapses or progressive disease occurs despite repeated intensive medical therapy.

What is the emergency management of histoplasmosis

Perform thoracentesis or pericardiocentesis with severe pleural effusions or pericardial tamponade

What would you use to treat histoplasmosis with AIDS and HIV

lifelong itraconazole suppression 200 mg daily

What would you use to treat patient with histoplasmosis with mild pulmonary disease

observation

What causes dissemination of cryptococcosis

immunocompromised state (HIV, long term steroids, treatment of hematologic cancer (hodgkin’s), and solid organ treatment (b/c of drugs that cause immuno-suppression)

What is the surgical management of cryptococcosis

Rarely, patients develop complete obstruction of the ventricles and require a CSF shunt to relieve intracranial pressure.

What is the emergency management of cryptococcosis

not applicable

What is used as maintenance treatment of cryptococcosis

Fluconazole x 6 months (HIV or immune compromised up to 12 months)

What would you diagnose for a patient who presents with a cough with hemoptysis

Aspergillomas

Fungal infections are acquired through:

• Inhalation of spores into lungs and paranasal sinuses

• Direct contact

What is this referred to

• Candida albicans

• Candida glabrata

• Candida lusitaniae

• Candida krusei

• Candida auris

• Cryptococcus

Yeasts: eg, Candida sp. (Pathologic fungi)

What is this referred to

• Aspergillus, mucor

  • Aspergillus flavus

  • Aspergillus niger

  • Rhizopus

Molds (pathologic fungi)

What is this referred to 

• Blastomyces

• Paracoccidiodomycoses

• Coccidiodomycoses

• Histoplasma

Fungi

What has the risk factors below

• Patients with neutropenia

• Immunocompromised

• Indwelling (intravascular) catheter

• Hospital admission

• Recent use of antibiotics (abx)

• Recent use of corticosteroids

• Uncontrolled diabetes mellitus (DM)

 Risk factors 

What is the etiology below 

• Yeast with budding and pseudohyphae

• Common gut flora

• Opportunistic infection if immunocompromised

• Incubation period unknown

• Vulvovaginal candidiasis associated with pregnancy

Candida Albicans

In Candida Albicans, who does this apply to 

• Usually present with systemic disease

  • Esophagitis

  • Endocarditis

Immunocompromised

In Candida Albicans, who does this apply to 

• Usually present with skin and mucous membrane infections

  • Oral thrush

    • Inhaled corticosteroids

    • HIV patients CD4+ cell count < 500/mm3

  • Candidal intertrigo

  • Diaper rash

  • Vulvovaginitis

  • Perleche or angular cheilitis

Immunocompetent

What causes oral thrush

Candida Albicans

What is this physical exam

intertrigo from Candida Albicans

What is this physical exam

Esophageal candidiasis

What is this physical exam

Vulvovaginitis from candida albicans

What causes macronodular skin lesions associated with hematogenously disseminated Candida

Invasive Candidias

What can cause endocarditis

Candida Albicans

What is the below 

• Bacterial infection

• Other fungal pathogen

• Cutaneous

  • eczema, psoriasis, cellulitis, seborrheic dermatitis

• Esophageal

  • Cardiac origin (MI, 

  • GI origin gastroesophageal reflux (GERD)

• Vulvovaginal

  • Herpes simplex, molluscum contagiosum

• Deep invasive

  • Bacterial or viral origin

• Oral thrush

  • Strep throat, abscess

• Developing abscess

Candida Albicans 

What is the lab work up for candida albicans

• Blood/tissue culture

• KOH (wet mount)

• Biopsy

• Systemic Illness/Sepsis

  • CBC w. diff

  • CMP

  • Lactic Acid

  • Blood culture

  • UA + urine culture

  • +/- Procalcitonin

  • EKG/Cardiac biomarkers/echocardiogram

How is Candida Albicans diagnosed

• Germ tube formation at 37°C (98.6F)

  • True hyphae sprout from yeast

• Definitive diagnosis

  • Blood or other tissue culture

  • Wet mount (vaginal fluid)

    • Yeast and pseudohyphae  KOH

  • Biopsy

What is the clinical intervention of Candida Albicans

• Remove any central vascular or urinary catheters if possible

• Consult with Infectious Disease

• Limit use of systemic steroids if possible

What is the surgical management of candida albicans

• ______________

• Surgical drainage of abscess + antifungal therapy

• Prosthetic joint infection → removal of prosthesis

• Splenic abscess → splenectomy

• Endocarditis → valve replacement

What should you use to treat fungus resistant to azoles

• Echinocandins

  • Can also use with systemic infections

  • Could be considered 1st line due to increased resistance to azoles

• Amphotericin B

  • More severe systemic infections

  • Typically considered 2nd line

    • Safe for use in pregnancy

What is the prognosis of candida albicans

• complication of infection → disseminated 

• Invasive candidiasis has a high mortality 

What does this refer to 

• Histoplasma capsulatum is a dimorphic fungus  

• Grows in soil as spore-bearing mold 

• Converts to yeast phase at body temperature 

Etiology of histoplasmosis

What does this refer to 

• Worldwide 

• Endemic in eastern and central U.S.  Mostly Ohio,  Mississippi, Missouri river valleys.

  • Most common endemic mycosis in the U.S.

• Facilitated by bird, bat and chicken droppings

• Inhalation of spores causes infection

  • No person-to-person transmission

• Variable incubation period, but usually 1 to 3 weeks 

 Epidemiology of histoplasmosis 

What does this refer to 

• Think in terms of

  • Site

    • Pulmonary (MC), extrapulmonary or disseminated

• Duration

  • Acute, chronic

• Pattern

  • Primary vs. reactivation

• Often Asymptomatic 

• Symptomatic mild flu-like illness across the spectrum to an atypical pneumonia presentation 

• Post infection recognized by incidental findings on chest x-ray - calcifications

Clinical Presentation of Histoplasmosis 

What does this refer to 

• Epidemics can occur after contaminated soil disturbed

• Primary histoplasmosis

  • Often asymptomatic

  • May present with fever, chills, non-productive cough, myalgia, and chest discomfort 

• Diffuse pneumonia on chest x-ray

• Rarely fatal

Acute histoplasmosis 

What causes this 

• Most often affects the severely immunocompromised (HIV) 

• Multiorgan involvement 

• Fever

• Cough

• Dyspnea

• Weight loss

• Often fatal

Progressive Disseminated Histoplasmosis (PDH)

What does this refer to 

• Older patient

• Variety of lesions on chest x-ray

  • Cavitation nodules, etc

• History of COPD, fever, fatigue, anorexia, weight loss, productive cough, and night sweats. 

• Death from retraction and cavitation of the lungs can occur.

Chronic Progressive Pulmonary Histoplasmosis 

What does this apply to 

• Tuberculosis 

• Pneumocystosis

• Lung cancer

• Pneumonia

• Lymphoma

• Mycoplasma

• Blastomyces

• Aspergillosis

• Blastomycosis

Differential Diagnosis of Histoplasmosis 

What does this refer to

Workup for histoplasmosis

What does this refer to

Primary ______

• Hilar adenopathy

• Acute pneumonia

Chronic pulmonary

• Unilateral or bilateral upper lobe infiltrates with multiple cavities and extensive fibrosis in the lower lobes

Disseminated _________

• Diffuse pulmonary infiltrates

  

Histoplasmosis

What is the arrow pointing at

Histoplasmosis on CXR

What will show you 

• if valvular involvement is suspected; 

• endocarditis with Histoplasma species is rarely associated with positive blood cultures.

echocardiography of histoplasmosis 

What does the following refer to 

• Determine the extent of pulmonary involvement by evaluating 

  • the degree of restrictive defect

  • the presence of a small airway obstruction

  • the extent of diffusion impairment

  • the presence of hypoxemia.

Pulmonary function tests of Histoplasmosis 

What would you use to treat histoplasmosis in mild to moderate Disseminated Non-Meningeal Disease

• Itraconazole 200mg TID for 3 days then 

• qd – bid for weeks to months depending on severity 

What would you use to treat histoplasmosis for patients with the following

• Unable to take p.o. 

• Failed itraconazole  

• Meningitis 

• Severe disseminated disease in immunocompetent patients  

 Amphotericin b 

What does the following refer to 

• Educate individuals residing or traveling in endemic areas

  • Exposure risks, including both leisure and work activities

  • Advance preparation reduces exposure to contaminated soil, bat and bird dwellings, and inoculum. 

• Many exposed immunocompetent individuals from endemic areas do not develop extensive clinical manifestations

  • Reactivation can occur

Patient education/maintenance/prevention for histoplasmosis

 What does the following refer to 

• Prior infection does not prevent future reinfection

  • Take precautions when facing increased exposure risk.

• Acute pulmonary histoplasmosis is associated with a good outcome. 

• Relapse rate in chronic pulmonary histoplasmosis ~20%.

Prognosis histoplasmosis 

What is the following 

• Pulmonary or disseminated infection acquired by inhalation of soil contaminated with the encapsulated yeasts

• Encapsulated yeast

• C. Neoformans

  • Predominately seen in immunocompromised

• C. Gatti

  • Rarely seen in humans

  • When found more likely in immunocompetent

Cryptococcosis

What is this referring to 

• Seen worldwide

• Affects 5-10% of adults with HIV/AIDS

Epidemiology of cryptococcosis 

What does this refer to 

• Found in

  • Soil

  • Bird (pigeon) droppings

• Inhalation

  • No person-to-person transmission

• Incubation period unknown

Etiology

that cause immuno-suppression)

What clinical presentation is below 

• Cough 

• Chest Pain 

• Nausea

• Fever 

• Cutaneous Nodules or Ulcers

• Lytic Bone Lesions 

• Dissemination to any organ 

• CNS is the major concern

  • Meningitis 

  • Slow Onset Headache 

  • Mental status changes 

  • Behavior changes 

  • Nuchal rigidity 

Cryptococcosis

What does this refer to 

• Acanthamoeba

• Basal Cell Carcinoma

• Histoplasmosis

• Lipomas

• Molluscum Contagiosum

• Pneumocystis Carinii Pneumonia

• Syphilis

• Toxoplasmosis

• Tuberculosis

Differential diagnosis of cryptococcosis 

How is cryptococcosis diagnosed

• Culture

  • Isolate  organism from body  fluids or tissue 

• CSF stain

  • Encapsulated yeast cells

  • Cryptococcal capsular antigen in CSF plus 

• Positive culture gives a 90% diagnosis rate

• MRI is better than CT for CNS abnormalities

What do these images refer to

Cryptococcus

What is used as treatment of cryptococcosis in patient with Meningitis or other serious (usually systemic) infection

• Amphotericin B PLUS Flucytosine or Fluconazole

• Change from Amphotericin B when clinically improved and sterile CSF

What is patient education/maintenance/prevention for immunocompromised patients with cryptococcosis

Early medical treatment

• Onset of severe HA or neurologic sx

• May allow for tx of cryptococcal disease before permanent damage occurs

What does the following refer to 

• Clinical syndromes 

  • Invasive aspergillosis (lung)

  • Aspergilloma

    • Mycetoma (“fungal ball”)

    • Non-invasive

  • Allergic bronchopulmonary aspergillosis (ABPA)

    • MC in patients with cystic fibrosis

• Found in soil and decomposed material

• Transmission via spore inhalation

Aspergillus

What does this refer to 

• Risk Factors

  • Immunocompromised status

    • Neutropenia

    • Steroids or cytotoxic drugs

    • Hematologic malignancy

    • Chronic granulomatous disease

    • Asthma

• Pre-existing lung disease

Aspergillus Epidemiology 

What would you diagnosis a patient with

• Persistent fever

• Cough (hemoptysis)

• Dyspnea

• Chest pain

Invasive Aspergillosis 

What does this refer to 

• Invasive aspergillosis

  • MC immunocompromised (suppressed) patients

    • Spores germinate and produce invasive hyphal structures

• ABPA

  • Local inflammatory reaction that can result allergic response

  • Cystic Fibrosis and Asthma are significant RF

Etiology of Aspergillosis

What does this refer to 

• Atopic diseases

  • Atopic dermatitis

  • Allergic rhinitis

  • Asthma

  • Food allergies

• Hyper IgE syndrome

Associated conditions of Allergic Bronchopulmonary Aspergillosis (ABPA) 

What does this refer to

Clinical presentationAllergic Bronchopulmonary Aspergillosis (ABPA)

What labs would you order for allergic bronchopulmonary aspergillosis (ABPA)

_____ skin test

• Hypersensitivity screening

• + skin test = wheal

Eosinophilia and ↑ IgE

Aspergillus-specific antibodies

• IgG and IgE

Precipitin antibodies

What imaging would you order for allergic bronchopulmonary aspergillosis (ABPA)

CXR often initial imaging

• Transient consolidations

CT chest

• Gold standard

• Central bronchiectasis and normal peripheral bronchi

What does this refer to

Patient’s WITHOUT Cystic Fibrosis (Rosenberg-Patterson diagnostic criteria) at least 6

• Asthma

• Transient pulmonary opacities on imaging

• Positive Aspergillus skin testing

• Peripheral eosinophilia

• Positive Aspergillus-specific antibodies IgG or IgE

• Elevated peripheral IgE

• Bronchiectasis on imaging

• Positive precipitin antibodies

Patient’s WITH cystic fibrosis

• New findings on imaging that do not clear with antibiotics

How to diagnose allergic bronchopulmonary aspergillosis (ABPA)

What does this refer to

1st line management

• Systemic corticosteroids

2nd line management

• Itraconazole

  • Severe disease refractory to monotherapy with systemic steroid therapy

Other treatment

• Omalizumab (Xolair)

  • Reduce exacerbations

Clinical pharmcotherapeutics allergic bronchopulmonary aspergillosis (ABPA)

What does this refer to

• Pneumocystis pneumonia

• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Differential diagnosis for aspergillosis

What does this refer to

Labs/work up for aspergillosis

What does this refer to

Imaging/workup for aspergillosis

What does this refer to

• Invasive ______

  • Pathology + invasive hyphae in tissue OR

  • Aspergillus positive culture

• ABPA

  • Clinical findings

  • + eosinophilia OR  IgE

• _________

  • Abnormal sputum culture OR aspergillus positive culture or serology

  • Aspergilloma seen on imaging

Aspergillosis (how its diagnosed)

What does this refer to

• Infectious disease consult

• Pulmonology consult

• Surgical resection may be indicated for aspergilloma

Clinical intervention Aspergillosis

What does this refer to

• ABPA

  • Steroids 1st line

• Invasive _______

  • Voriconazole (Vfend)

  • Caspofungin (Cancidas)

  • If voriconazole CI

  • Amphotericin B may be used as adjunct with voriconazole

Clinical pharmacotherapeuticsAspergillosis