TB - MedPath

What does this refer to

• Infection caused by Mycobacterium tuberculosis, an acid-fast bacillus

• Leading cause of death from a curable infectious disease throughout the world

Tuberculosis

What does this refer to

• Acid-fast bacillus with mycolic acid cell wall

• Slow-growing, intracellular pathogen

• Resistant to desiccation and common disinfectants

Mycobacterium tuberculosis

What does this refer to

• High prevalence in Africa, Asia

• Risk groups: immunosuppressed, homeless, healthcare workers

• Rising multi-drug resistant (MDR) and extensively drug-resistant (XDR) TB strains

Epidemiology of TB

What does this refer to

• Inhalation of droplet nuclei

• Requires prolonged close contact

• Bacilli reach alveoli and are phagocytosed

TB Transmission

What does this refer to

• Tranmitted by inhalation of respiratory droplets

• Requires prolonged close contact

• Bacilli reach alveoli and are phagocytosed

• Tubercle formation: Granulomatous lesion

  • Isolation of bacilli by enclosing them in tubercles and surrounding the tubercles with scar tissue

• Caseous necrosis: Cheeselike material

• May remain dormant for life or cause active disease

Tuberculosis Transmission and Infection

What does this refer to

• Cell-mediated immunity essential

• Activation of macrophages by IFN-gamma

• Granuloma formation contains infection

Immune Response to TB

What does this refer to

• Central necrosis surrounded by epithelioid cells, lymphocytes

• Caseating necrosis hallmark of TB

• May calcify or cavitate

Granuloma Formation

What does this refer to

• Cheese-like necrosis due to hypoxia and immune attack

• Diagnostic of TB in histology

• Associated with cavitary lesions

Caseating Necrosis

What does this refer to

• Formation of Ghon focus and Ghon complex

• Most cases resolve or become latent

• Initial immune containment by macrophages and T cells

Primary TB Infection

What does this refer to

• _______: positive test, no symptoms, non-contagious

Latent TB

What does this refer to

• ________: symptomatic, contagious, radiologic abnormalities

Active TB

What does this refer to

• Latent tuberculosis infection: Asymptomatic

• Fatigue, weight loss, lethargy, anorexia (loss of appetite), a low-grade fever that usually occurs in the afternoon, and night sweats; purulent cough

Clinical Manifestations of TB

What does this refer to

• Positive tuberculin skin test (TST) a purified protein derivative (PPD): Does not differentiate past, latent, or active disease

• Sputum culture, immunoassays, indirect drug susceptibility testing

• Chest radiographs

Diagnosis of TB

What does this refer to

• TB lymphadenitis (scrofula), CNS TB (meningitis), miliary spread

• Bone (Pott’s disease), GI, genitourinary TB

• More common in immunocompromised

Extrapulmonary TB

What does this refer to

• Occurs when immunity wanes (HIV, steroids)

• Apical lung involvement due to higher oxygen tension

• Constitutional symptoms and productive cough

Reactivation TB

What does this refer to

• Failure of immune containment

• Seen in young children and immunosuppressed

• Dissemination to hilar nodes and bloodstream

Progressive Primary TB

What does this refer to

• Hematogenous dissemination of bacilli

• Tiny nodules throughout lung fields

• High mortality if untreated

Miliary TB Pathophysiology

What does this refer to

• Often lacks typical granulomas

• More extrapulmonary involvement

• May require biopsy and PCR for diagnosis

TB in Immunocompromised

What does this refer to

• Rapid progression and atypical presentation

• Overlapping toxicity of treatments

• Higher risk of MDR-TB

TB-HIV Coinfection

What does this refer to

• CXR: upper lobe cavitation, lymphadenopathy

• Histology: granulomas with caseation

• Ziehl-Neelsen stain shows acid-fast bacilli

Radiographic and Histologic Findings

What does this refer to

• Three early morning samples recommended

• AFB smear: rapid but low sensitivity

• Culture: gold standard, takes weeks

Sputum Testing

What does this refer to

• GeneXpert MTB/RIF: rapid TB and rifampin resistance

• PCR-based assays detect DNA

• Useful in smear-negative, HIV-positive patients

NAAT and Molecular Tests

Which anti-TB drug is the following

• ________: inhibits mycolic acid synthesis

• Rifampin: inhibits RNA polymerase

• Pyrazinamide: effective in acidic pH

• Ethambutol: inhibits cell wall synthesis

Isoniazid

Which anti-TB drug is the following

• Isoniazid: inhibits mycolic acid synthesis

• ______: inhibits RNA polymerase

• Pyrazinamide: effective in acidic pH

• Ethambutol: inhibits cell wall synthesis

RIfampin

Which anti-TB drug is the following

• Isoniazid: inhibits mycolic acid synthesis

• Rifampin: inhibits RNA polymerase

• ________: effective in acidic pH

• Ethambutol: inhibits cell wall synthesis

Pyrazinamide

Which anti-TB drug is the following

• Isoniazid: inhibits mycolic acid synthesis

• Rifampin: inhibits RNA polymerase

• Pyrazinamide: effective in acidic pH

• ________: inhibits cell wall synthesis

Ethambutol

What is the TB treatment regimen for intensive phase (2 months)

RIPE

What is the TB treatment regimen for continuation phase (4-7 months)

INH + RIB

What does this refer to

• Isoniazid, rifampin, pyrazinamide, and ethambutol

• Drug-resistant bacilli: Combination of at least four drugs to which the microorganism is susceptible, administering for 18 months

  • Review drug effectiveness at 6 months.

Treatment of TB

What does this refer to

• Resistant to at least INH and RIF

• Requires second-line agents: fluoroquinolones, injectables

• Longer duration and more toxic regimen

MDR-TB

What does this refer to

• DOT: directly observed therapy

• Contact tracing and screening

• TB control programs and vaccination (BCG)

Public Health Measures

What size leads to a positive diagnosis of TB in the general population

> 15 mm

What size leads to a positive diagnosis of TB in healthcare workers

> 10 mm

What size leads to a positive diagnosis of TB in immunocompromised population

> 5 mm induration

What does this refer to

• Infection of the lower respiratory tract

• Responsible for more disease and death than any other infection

Pneumonia

What does this refer to

• Hospital-acquired

• Ventilator-associated pneumonia

Nosocomial pneumonia

What does this refer to

• Streptococcus pneumoniae

Community-acquired pneumonia

What does this refer to

• Aspiration

• Inhalation

• Endotracheal tubes and suctioning

• Bacteremia in lungs

• Respiratory defenses cannot destroy the microorganism

Routes of infection for pneumonia

What form of pneumonia is commonly seen in the form of influenza

Viral pneumonia

What does this refer to

• Inhalation of airborne droplets or spores

• Aspiration of oropharyngeal contents

• Hematogenous spread from distant sites

• Direct extension from contiguous structures

Pathogen Entry and Transmission

What does this refer to

• Recognition by pattern recognition receptors (PRRs)

• Activation of innate immunity

• Recruitment of neutrophils and macrophages

• Release of cytokines and chemokines

Immune Response to Inhaled Pathogens

What does this refer to

• Inflammatory infiltrate disrupts alveolar architecture

• Increased capillary permeability → alveolar flooding

• Surfactant inactivation and atelectasis

Inflammation and Alveolar Damage

What does this refer to

• Shunting and V/Q mismatch

• Decreased diffusion capacity due to edema

• Hypoxemia leads to increased respiratory effort

Hypoxemia and Impaired Gas Exchange

What does this refer to

• Dysregulated immune response

• High levels of IL-6, TNF-alpha, and others

• Capillary leak syndrome, hypotension, multiorgan failure

Cytokine Storm and Systemic Effects

What does this refer to

• Sudden onset, short duration, exudative phase

• CAP

Acute pulmonary infections

What does this refer to

• prolonged, granuloma formation, fibrosis

• TB or fungal infections

Chronic pulmonary infections

What does this refer to

• Preceded by an upper respiratory infection

• Cough, dyspnea, and fever

• Chills, malaise, and pleuritic chest pain

Clinical manifestations of pneumona

What does this refer to

• Prevention of aspiration

• Respiratory isolation of immunocompromised individuals

• Vaccination for appropriate populations

• Reduction of ventilator-associated pulmonary infections through a variety of oral hygiene and endotracheal tube interventions

Prevention of pneumonia

What does this refer to

• Gram stain and culture

• AFB smear and culture for TB

• PCR and multiplex panels for rapid ID

Sputum Analysis and Microbiologic Testing

What does this refer to

• Establishment of adequate ventilation and oxygenation

• May require mechanical ventilation

• Adequate hydration

• Good pulmonary hygiene (e.g., deep breathing, coughing, chest physical therapy)

• Bacterial pneumonia: Antibiotics

• Viral pneumonia: Supportive therapy alone, unless secondary bacterial infection is present

  • Severe cases: Antiviral medications and/or antifungal, multiple drugs

Treatment for pneumonia

What does this refer to

• Community-acquired vs. healthcare-associated

• Common organisms: S. pneumoniae, H. influenzae, Legionella

• Pathogenesis: alveolar invasion → exudate formation

• Clinical: fever, productive cough, pleuritic chest pain

Bacterial Pneumonia

What does this refer to

• Gram-positive diplococcus

• Virulence factors: capsule, pneumolysin

• Lobar consolidation on imaging

• Rust-colored sputum, positive urine antigen test

Streptococcus pneumoniae

What does this refer to

• __________: thick, mucoid sputum; cavitating pneumonia

Klebsiella

What does this refer to

• ________: common in CF, ventilator-associated infections

Pseudomonas

What does this refer to

• __________: common in CF, ventilated-associated infections

Pseudomonas

What does this refer to

• _____________: necrotizing pneumonia, empyema risk

MRSA

What type of atypical bacteria is the following

• __________: walking pneumonia, extrapulmonary signs

Mycoplasma pneumoniae

What type of atypical bacteria is the following

• __________: slow onset, pharyngitis

Chlamydia pneumoniae

What type of atypical bacteria is the following

• ___________: high fever, GI symptoms, hyponatremia

Legionella

What does this refer to

• Influenza, RSV, adenovirus, SARS-CoV-2

• Direct cytopathic effects and immune-mediated injury

• Diffuse alveolar damage, ground-glass opacities

Viral Pneumonia

What does this refer to

• Viral replication → epithelial cell death

• Disruption of tight junctions

• Induction of pro-inflammatory cytokines

Pathophysiology of Viral Lung Injury

What type of fungal pneumonia is the following

• ____________: inhaled spores, granulomas in immunocompetent

Histoplasmosis

What type of fungal pneumonia is the following

• _____________: desert exposure, nodular infiltrates

Coccidioidomycosis

What type of fungal pneumonia is the following

• ________: invasive disease in neutropenic patients

Aspergillus

What does this refer to

• Broad range of pathogens including PCP, CMV

• Atypical presentations and rapid progression

• Requires aggressive diagnostics and empiric therapy

Immunocompromised Host Infections

What does this refer to

• Entry of gastric/oropharyngeal contents

• Mixed flora: anaerobes, streptococci

• Seen in altered mental status, stroke, intoxication

Aspiration Pneumonia

What does this refer to

• Tissue necrosis and liquefaction

• Complication of severe bacterial infection

• Empyema: pus in pleural space, requires drainage

Necrotizing Pneumonia and Empyema

What does this refer to

• ICU and ventilator-associated pneumonia

• Biofilm formation, MDR organisms

• Prevention: hand hygiene, VAP bundles

Nosocomial Infections

What does this refer to

• Circumscribed area of suppuration and destruction of lung parenchyma

• Follows consolidation of lung tissue, in which inflammation causes alveoli to fill with fluid, pus, and microorganisms.

• Necrosis (death and decay) of consolidated tissue: abscess empties into the bronchus, leaving a cavity

• Cavitation: Process of abscess emptying and cavity formation

• Most common cause: Aspiration

Abscess formation and cavitation

What does this refer to

• Fever, cough, chills, sputum production, and pleural pain

• Bronchus involvement: Severe cough, copious amounts of often foul-smelling sputum, and occasionally hemoptysis

Clinical manifestation of abscess

What does this refer to

• Antibiotics

• Chest physical therapy, including chest percussion and postural drainage

• Bronchoscopy: To drain the abscess

Treatment for Abscess