For which of the following patients would you recommend prophylaxis against mycobacterium avium-intracellulare?

30-year old HIV positive male with CD4 count of 20 cells/microliter and a viral load of < 50 copies/mL

22-year old HIV positive female with CD4 count of 750 cells/microliter and a viral load of 500,000 copies/mL

45-year old HIV positive female with CD4 count of 250 cells/microliter and a viral load of 100,000 copies/mL

50-year old HIV positive female with CD4 count of 150 cells/microliter and a viral load of < 50 copies/mL

36-year old HIV positive male with CD4 count of 75 cells/microliter and an undetectable viral load

You are seeing a patient in clinic who recently started treatment for active tuberculosis. The patient is currently being treated with rifampin, isoniazid, pyrazinamide, and ethambutol. The patient is not used to taking medicines and is very concerned about side effects. Specifically regarding the carbohydrate polymerization inhibiting medication, which of the following is a known side effect?

Paresthesias of the hands and feet

A 28-year-old woman comes to the physician because of a two-month history of fatigue and low-grade fevers. Over the past 4 weeks, she has had increasing shortness of breath, a productive cough, and a 5.4-kg (11.9-lb) weight loss. Three months ago, the patient returned from a two-month trip to China. The patient appears thin. Her temperature is 37.9°C (100.2°F), pulse is 75/min, and blood pressure is 125/70 mm Hg. Examination shows lymphadenopathy of the anterior and posterior cervical chain. Rales are heard at the left lower lobe of the lung on auscultation. Laboratory studies show a leukocyte count of 11,300/mm3 and an erythrocyte sedimentation rate of 90 mm/h. An x-ray of the chest shows a patchy infiltrate in the left lower lobe and ipsilateral hilar enlargement. Microscopic examination of the sputum reveals acid-fast bacilli; polymerase chain reaction is positive. Sputum cultures are pending. After placing the patient in an airborne infection isolation room, which of the following is the most appropriate next step in management?

Administer isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months

Administer only isoniazid for 9 months

Await culture results before initiating treatment

Perform interferon-γ release assay

A 55-year-old woman comes to the physician because of fevers for 2 weeks. She works as a nurse and recently returned from a charity work trip to India, where she worked in a medically-underserved rural community. A tuberculin skin test 3 months ago prior to her trip showed an induration of 3 mm. Physical examination is unremarkable. An x-ray of the chest shows right-sided hilar lymphadenopathy. A sputum culture shows acid-fast bacilli. Which of the following immunologic processes most likely occurred first?

Replication of bacteria within alveolar macrophages

Production of interferon-gamma by T-helper cells

Migration of T-helper cells to the lungs

Formation of a nodular tubercle in the lung

Transportation of bacterial peptides to regional lymph nodes

A 43-year-old man with a history of chronic alcoholism presents with a chronic cough and dyspnea. He says he traveled to Asia about 4 months ago and his symptoms started shortly after he returned. His temperature is 40.2°C (104.4°F) and pulse is 92/min. Physical examination reveals poor personal hygiene and a cough productive of foul blood-streaked sputum. Auscultation reveals decreased breath sounds on the right. A chest radiograph reveals an ill-defined circular lesion in the right middle lobe. Which of the following is true regarding this patient’s most likely diagnosis?

Inoculation of a sputum sample into selective agar media needs to be incubated at 35–37°C (95.0–98.6°F) for up to 8 weeks.

A positive tuberculin test would be diagnostic of active infection.

DNA polymerase chain reaction (PCR) has poor sensitivity when applied to smear positive specimens.

Stains of gastric washing and urine have a high diagnostic yield on microscopy.

Ziehl-Neelsen staining is more sensitive than fluorescence microscopy with auramine-rhodamine stain.

M. tuberculosis and non-tuberculous mycobacteria for USMLE Step 3: High-Yield Microbiology Lessons

M. tuberculosis - The Great White Plague

Characteristics: Acid-fast bacillus (Ziehl-Neelsen stain), obligate aerobe, facultative intracellular in macrophages.
Virulence Factors: Mycolic acid (waxy lipid cell wall), Cord factor (serpentine growth, inhibits neutrophil migration).
Culture: Slow-growing on Lowenstein-Jensen (LJ) medium.

Chest X-ray: Tuberculosis with upper lobe cavitation

Pathogenesis:

Diagnosis:
- PPD/TST Induration: >5 mm (immunocompromised, close contacts), >10 mm (high-risk), >15 mm (no risk factors).
- IGRAs: QuantiFERON-TB Gold, T-SPOT.TB.
- AFB smear, culture (gold standard), NAAT.

⭐ M. tuberculosis is an obligate aerobe, explaining its predilection for the well-ventilated lung apices during reactivation.

Non-Tuberculous Mycobacteria - The Atypical Cousins

Organism	Source/Transmission	Classic Presentation	Buzzwords
M. avium complex (MAC)	Ubiquitous (water, soil)	Disseminated disease in AIDS (CD4 < 50); prophylaxis with azithromycin. Pulmonary disease in COPD.	-
M. kansasii	Tap water	TB-like pulmonary disease, often in patients with underlying lung conditions.	-
M. scrofulaceum	Environmental sources	Scrofula: painless cervical lymphadenitis, typically seen in children.	-
M. marinum	Aquariums, saltwater	Papule on hand/arm that ulcerates and spreads along lymphatics after minor trauma.	'Fish tank granuloma'
M. leprae (Hansen's Dis.)	Armadillos, resp. droplets	Spectrum: Tuberculoid (strong Th1, few lesions) to Lepromatous (weak Th2, many lesions).	'Leonine facies'

⭐ Mycobacterium avium complex (MAC) is the most common NTM causing human disease, typically presenting as a disseminated infection in severely immunocompromised patients (CD4 < 50).

Anti-Mycobacterial Drugs - RIPE for Action

Drug	Mechanism of Action	Key Adverse Effect(s)
Rifampin	Inhibits DNA-dependent RNA polymerase	Red-orange body fluids
Isoniazid (INH)	Inhibits mycolic acid synthesis	Hepatotoxicity, peripheral neuropathy
Pyrazinamide	Active in acidic pH of phagolysosomes	Hyperuricemia, gout
Ethambutol	Inhibits arabinosyltransferase (cell wall)	Optic neuropathy (red-green color blindness)

⭐ Co-administration of pyridoxine (Vitamin B6) with Isoniazid is standard practice to prevent peripheral neuropathy.

High‑Yield Points - ⚡ Biggest Takeaways

M. tuberculosis is an acid-fast bacillus requiring an aerobic environment, explaining its predilection for lung apices.

Primary infection is marked by a Ghon complex; reactivation leads to caseating granulomas with central necrosis.

Diagnosis relies on acid-fast staining, culture on Löwenstein-Jensen medium, and interferon-gamma release assays (IGRAs).

Standard treatment is multi-drug RIPE therapy (Rifampin, Isoniazid, Pyrazinamide, Ethambutol).

M. avium complex (MAC) causes disseminated disease in AIDS patients (CD4 < 50); prophylaxis with azithromycin.

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