MICROBIOLOGY AND IMMUNOLOGY
Opportunistic Mycosis
Candida albicans
Classification
yeast with budding and pseudohyphae
germ tube formation at 37°C (diagnostic)
can be part of normal flora
Risk factors
immunocompromised status
hospital admission, especially in the ICU
Clinical syndrome
immunocompetent hosts present with skin and mucous membrane infections
oral thrush
white plaque on the tongue that can be scraped off
associated with use of inhaled corticosteroids
candidal intertrigo
well-demarcated, erythematous, and itchy plaques in the skin folds
vulvovaginitis
thick "cottage cheese" white discharge
itchiness
immunocompromised hosts usually present with systemic disease
local infection is due to T-cell deficiency while systemic infection is due to neutropenia
esophagitis
dysphagia and throat pain
endoscopy shows white plaques along the esophagus
endocarditis
associated with IV drug users
fevers and a new murmur
disseminated/invasive candidiasis
fever and septic shock
Studies
definitive diagnosis requires blood or other tissue culture
wet mount with potassium hydroxide prep of vaginal fluid shows yeast with pseudohyphae
germ tube formation at 37°C
Treatment
nystatin
local infections
azoles
local and systemic infections
first-line if the fungus is not resistant
echinocandins
systemic infections
first-line due to increased resistance to azoles
amphotericin B
systemic infections
second-line or for pregnant women
Cryptococcus neoformans
Classification
urease-positive monomorphic encapsulated yeast with 5-10 μm narrow budding
transmitted via inhalation and found in soil and pigeon droppings
Risk factors
immunocompromised status
HIV/AIDS patients
Clinical syndrome
cryptococcosis
cryptococcal meningitis
cryptococcal encephalitis
presents with fevers, headaches, and generalized malaise
Studies and imaging
head imaging with computed tomography (CT) or magnetic resonance imaging (MRI)
soap bubble lesions
variable enhancing lesions
hydrocephalus
detection of capsular antigen in serum or cerebrospinal fluid (CSF)
latex agglutination test
CSF studies
culture on Sabouraud agar
India ink stain shows yeast with clear halos
mucicarmine shows yeast with red inner capsules
Treatment
amphotericin B + flucytosine
for 10-14 days
fluconazole
after treatment with amphotericin B and flucytosine
maintenance and suppressive therapy
Aspergillus spp.
Classification
most commonly Aspergillus fumigatus
monomorphic fungus with septate hyphae branching at acute angles (45 degrees)
found in soil and decomposed material
transmission via inhalation of spores called conidia
Risk factors
immunocompromised status
hematologic malignancy
asthma
pre-existing lung disease
Clinical syndrome
invasive aspergillosis
invasive infection of the lung
causes persistent fever and cough with hemoptysis
aspergilloma
mycetoma ("fungal ball") in pre-existing cavity (i.e., tuberculosis)
causes cough with hemoptysis or asymptomatic
allergic bronchopulmonary aspergillosis (ABPA)
hypersensitivity reaction in patients with cystic fibrosis or asthma
causes bronchiectasis and eosinophilia
causes cough with hemoptysis, brownish black mucus plugs in expectorate, and wheezing
Studies and imaging
invasive aspergillosis
nodules with halo sign and cavitary lesions on computed tomography (CT)
pathologic examination showing invasive hyphae into tissue
positive cultures or serology
aspergilloma
mobile round or ovoid mass on chest CT
positive cultures or serology
ABPA
bronchiectasis on CT
elevated eosinophils or IgE in ABPA
Treatment
invasive aspergilloma
voriconazole + amphotericin B
first-line
caspofungin
second-line
aspergilloma
surgical resection
ABPA
steroids
first-line
Mucormycosis
Classification
Mucor and Rhizopus spp.
fungi with irregular, broad, and nonseptate hyphae branching at wide or right angles
found in soil and decomposed material
transmission via inhalation of spores or direct inoculation through trauma
Risk factors
diabetic ketoacidosis
immunocompromised status
trauma or burns
Clinical syndrome
mucormycosis (rhinocerebral infection)
headache
congestion
sinus pressure and pain
black necrotic eschar on face, particular nares or palate
Studies and imaging
computed tomography (CT) shows air-fluid levels in the sinuses and bony destruction
biopsy of affected tissue shows nonseptate hyphae with wide-angle branching
Treatment
amphotericin B
first-line
isavuconazole
second-line
surgical debridement
for patients who need it, in addition to antifungals
Pneumocystis jiroveci
Classification
a yeast-like fungus
transmission via airborne
Risk factors
immunocompromised status (e.g., hyper IgM syndrome)
HIV
smoking
Clinical syndrome
interstitial pneumonia
progressive exertional dyspnea
chest pain
nonproductive cough
fever and chills
hemoptysis is rare
Imaging
chest radiograph will show bilateral infiltrates
computed tomography will show patchy ground-glass opacities sand pneumatoceles
Studies
histology with methenamine silver, Diff-Quik, or Wright stain of lung tissue
disc-shaped yeast
Treatment
trimethoprim-sulfamethoxazole (TMP-SMX)
prophylaxis (CD4+ count < 200 cells/mm3) and first-line therapy
corticosteroids
severe cases
pentamidine, atovaquone, or dapsone
second-line therapy if resistant to TMP-SMX or allergic
Mycobacterium Tuberculosis
Introduction
Classification
acid-fast, rod-shaped, obligate aerobic, intracellular bacteria
Epidemiology
risk factors
traveling to endemic areas (e.g., Angola and the Central African Republic)
close contact (e.g., prisons, nursing homes, homeless shelters, and hospitals)
immunocompromised (e.g., HIV, immunosuppressive medications, and diabetes)
Transmission
airborne spread of droplet nuclei from patients with infectious tuberculosis (TB)
Microbiology
acid-fast on Ziehl-Neelsen staining
immune system itself causes damage
TB contains no endotoxins or exotoxins
cord factor
inhibits leukocyte migration
causes characteristic serpentine growth pattern
induces TNF-α release
tuberculin
triggers cell-mediated immunity → caseation and granulomas
triggers delayed hypersensitivity reaction
a surface protein
sulfatides
prevent phagosome-lysosome fusion
Pathogenesis
the infected person coughs up small droplets containing the bacteria that reaches the terminal alveoli of the uninfected person
alveolar macrophages are recruited, which eventually become infected, transporting the microbe to deeper tissues
more alveolar macrophages are recruited, leading to granuloma formation
granulomas are formed to "wall off" TB, where it lies dormant
secondary TB occurs when the patient's immune system is weakened (e.g., newly acquired HIV infection, being on immunosuppressant medications, malignancy, and poor nutrition)
macrophages' ability to maintain their barrier decreases, facilitating possible dissemination
TB infection typically manifests in the apical/posterior segments of the lung due to its increased oxygen tension
Presentation
TB can lead to pulmonary and extrapulmonary manifestations
lymph nodes (tuberculous lymphadenitis)
pleura
genitourinary
skeleton (can lead to Pott disease with spinal involvement)
meninges
gastrointestinal system
pericardium (tuberculous pericarditis)
Symptoms
typically asymptomatic in primary TB
cough
hemoptysis
fever
night sweats
malaise
Physical exam
weight loss
lymphadenopathy
dullness to percussion or decreased/absent breath sounds if there is a pleural effusion
back pain in spinal TB (Pott disease)
Imaging
Chest radiograph
indication
initial imaging study in the evaluation of TB
findings
middle or lower lung infiltrate (suggestive of primary infection)
upper lobe infiltrate (suggestive of latent TB reactivation)
apices have higher oxygen tension and reduced perfusion/lymph clearance compared to the base
cavitary lesions
Ghon complex (lobar or perihilar lymph node involvement)
Studies
Sputum acid-fast testing
demonstrates acid-fast bacilli
Real-time nucleic acid amplification
rapidly confirms TB and is considered the first-line diagnostic study
Tuberculin skin test (TST)
most widely used to screen for latent TB infection
a delayed-type hypersensitivity reaction against purified protein derivative (PPD) is induced
the size of the induration is assessed after 48-72 hours
note, patients who received the Bacille Calmette-Guerin (BCG) vaccination will have false positive results
a false negative result can be seen in immunocompromised patients
interpretation (positive results)
≥ 15 mm in patients with no risk factors
≥ 10 mm in patients with risk factors (e.g., healthcare worker, traveling to endemic areas, and being in prison)
≥ 5 mm in immunocompromised patients (e.g., HIV, on immunosuppressants, and organ transplant recipients)
positive tests require a chest radiograph
Interferon-γ release assay
measures interferon levels released by the patient's immune system in response to TB antigens
the results are not affected by previous BCG vaccination
Differential
Lung cancer
differentiating factor
patients will not have positive TB studies
Treatment
Medical
rifampin, isoniazid, pyrazinamide, and ethambutol therapy
indication
first-line treatment for active pulmonary TB infection for 4 months
after 4 months, treatment involves isoniazid and rifampin
comments
isoniazid can cause peripheral neuropathy as well as sideroblastic anemia due to vitamin B6 deficiency, thus warranting pyridoxine in hopes to prevent this development from occurring
can also cause hepatitis
ethambutol can cause optic neuropathy
mutations in RNA polymerase lead to rifampin resistance
isoniazid monotherapy
indication
prophylactic treatment for latent primary TB after active TB has been excluded
Complications
Pott disease
Miliary or disseminated TB
Meningitis
Pericarditis
Lymphadenitis
Adrenal insufficiency