Microbiology for USMLE Step 1

A 22-year-old college student has a 3-week history of fatigue, sore throat and fever. Examination shows posterior cervical lymphadenopathy, exudative pharyngitis and splenomegaly. He is given amoxicillin and develops a diffuse maculopapular rash. Which cell does the causative organism primarily infect?

1. B lymphocytes, via CD21 correct Correct. Epstein–Barr virus (EBV) gets into B cells through CD21 (a receptor also called complement receptor CR2). The unusual-looking lymphocytes seen on the blood smear are not infected B cells. They are reactive CYTOTOXIC T CELLS reacting to the infected B cells, a difference examiners test again and again.
2. Hepatocytes Wrong. EBV often causes mild liver inflammation, a rise in liver enzymes (transaminitis), but liver cells (hepatocytes) are not the main cell EBV infects.
3. Respiratory epithelial cells only Wrong. EBV does multiply in the lining cells of the throat (oropharyngeal epithelium), but its main target, and the reason it causes the lymph node and spleen swelling seen here, is B cell infection.
4. CD4+ T lymphocytes, via gp120 Wrong. CD4+ T cells infected through the gp120 receptor describe HIV. Acute HIV infection (acute retroviral syndrome) can look like mononucleosis, but it would not cause the amoxicillin rash described here.
5. Neutrophils Wrong. Neutrophils are not where EBV lives. The blood picture in mononucleosis shows more lymphocytes (lymphocytosis), not more neutrophils (neutrophilia).

The point: EBV infects B cells through CD21. The atypical lymphocytes seen on the smear are reactive T cells, not infected B cells. A rash after ampicillin or amoxicillin is almost a defining sign of EBV mononucleosis. Patients should avoid contact sports for at least three weeks because the spleen is at risk of rupture.

Source: USMLE Content Outline — microbiology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator

A 34-year-old woman is treated with ceftriaxone for pyelonephritis. Cultures grow a Gram-negative rod that is resistant to ceftriaxone and cefotaxime but susceptible to meropenem. The organism produces an enzyme that hydrolyzes the beta-lactam ring of extended-spectrum cephalosporins, and this enzyme is inhibited by clavulanic acid. Which resistance mechanism is described?

1. Efflux pump upregulation Wrong. Efflux pumps actively pump the drug back out of the bacteria. This is not an enzyme-based mechanism, so clavulanate does not stop it.
2. Carbapenemase production Wrong. Carbapenemase production would make the bacteria resistant to meropenem too, but the question says the bacteria is still susceptible to meropenem. Carbapenemases, such as KPC and NDM, are a step beyond ESBLs in resistance.
3. Porin channel loss reducing drug entry Wrong. Losing porin channels, the pores that let drugs into the bacteria, is a real resistance mechanism in Pseudomonas and Acinetobacter, but it blocks many different drugs at once and is not reversed by clavulanate.
4. Extended-spectrum beta-lactamase production correct Correct. Extended-spectrum beta-lactamases (ESBLs) are enzymes that break down penicillins and extended-spectrum cephalosporins. They are blocked by clavulanate, and the gene for them is usually carried on a plasmid, a small loop of DNA that can spread between bacteria, in Escherichia coli and Klebsiella. Carbapenem antibiotics still work reliably against these bacteria.
5. Alteration of penicillin-binding proteins Wrong. Changing the penicillin-binding proteins is the mechanism in MRSA (from the mecA gene making a protein called PBP2a) and in penicillin-resistant pneumococcus. This method is not blocked by clavulanate, because there is no enzyme for clavulanate to block.

The point: Resistance to beta-lactam antibiotics falls into four mechanisms: breaking the drug down with an enzyme (beta-lactamase, ESBL, carbapenemase, AmpC), changing the drug's target (PBP changes in MRSA), blocking drug entry (porin loss), and pumping the drug back out (efflux). The clavulanate clue in this question points specifically to a serine beta-lactamase enzyme.

Source: USMLE Content Outline — microbiology and antimicrobial resistance NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator

A 58-year-old smoker develops pneumonia with high fever, confusion, diarrhea and a sodium of 128 mEq/L. Sputum Gram stain shows neutrophils but no organisms. He had recently stayed in a hotel with an air-conditioning fault. Which test confirms the diagnosis fastest?

1. Silver stain of induced sputum Wrong. Silver stain of induced sputum is used for Pneumocystis jirovecii, which causes a dry cough and severe low oxygen (hypoxia) in a patient with a weakened immune system.
2. Routine blood agar culture Wrong. Legionella will not grow on routine blood agar. It needs buffered charcoal yeast extract media with cysteine and iron added.
3. Cold agglutinin titre Wrong. A cold agglutinin titer points to Mycoplasma pneumoniae, a milder 'walking pneumonia' usually seen in younger patients, without the low sodium (hyponatremia) and diarrhea seen here.
4. Urinary antigen test correct Correct. Legionella pneumophila serogroup 1 can be detected with a urinary antigen test within hours. It is hard to see on a Gram stain because it stains only faintly as a weak Gram-negative rod. Growing it in culture needs special charcoal yeast extract media with cysteine and iron added.
5. Acid-fast stain Wrong. Acid-fast stain is used for mycobacteria and Nocardia, neither of which fits a sudden illness over days with diarrhea and low sodium (hyponatremia).

The point: A triad worth remembering for Legionella: pneumonia plus diarrhea plus low sodium (hyponatremia), often with raised liver enzymes (transaminases) and a heart rate that is slower than expected for the fever (relative bradycardia). Treat with a macrolide or a respiratory fluoroquinolone. Beta-lactam antibiotics do not work, because Legionella lives inside cells.

Source: USMLE Content Outline — microbiology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator