Master Microbiology
for USMLE Step 1

Core Concepts

Microorganisms are classified into Bacteria, Viruses, Fungi, and Parasites, each with distinct structures, replication methods, and pathogenic mechanisms. Bacteria: Prokaryotic. Gram-positive (thick peptidoglycan, teichoic acids) vs. Gram-negative (thin peptidoglycan, outer membrane with LPS/endotoxin). Virulence factors include capsules (antiphagocytic), pili (adherence), flagella (motility), endospores (survival, e.g., Bacillus, Clostridium). Exotoxins (proteins, specific targets, potent) vs. Endotoxins (LPS, G- only, induces TNF-α, IL-1, fever, shock). Viruses: Obligate intracellular parasites. Classified by genome (DNA/RNA), envelope (enveloped/naked), and replication strategy. Lack cell wall/ribosomes. Fungi: Eukaryotic. Cell wall with chitin, cell membrane with ergosterol. Yeasts (unicellular, budding) vs. Molds (multicellular, hyphae). Dimorphic fungi (mold in cold, yeast in heat: Histoplasma, Blastomyces, Coccidioides, Sporothrix). Parasites: Eukaryotic. Protozoa (unicellular, e.g., Plasmodium, Giardia) vs. Helminths (multicellular worms, e.g., nematodes, cestodes, trematodes). Often complex life cycles. Antimicrobial Mechanisms: Target bacterial cell wall synthesis (Penicillins, Cephalosporins, Vancomycin), protein synthesis (Tetracyclines, Macrolides, Aminoglycosides), DNA replication (Fluoroquinolones), or folic acid synthesis (Sulfonamides, Trimethoprim). Resistance commonly due to β-lactamases, altered target sites, or efflux pumps.

Clinical Presentation

• Bacteria:
• Staphylococcus aureus: Skin/soft tissue infections (abscess, cellulitis), osteomyelitis, endocarditis, toxic shock syndrome, food poisoning.
• Streptococcus pyogenes: Pharyngitis, cellulitis, impetigo, scarlet fever, rheumatic fever, glomerulonephritis.
• Streptococcus pneumoniae: Community-acquired pneumonia, otitis media, meningitis, sinusitis.
• Escherichia coli: Urinary tract infections, sepsis, hemolytic uremic syndrome (EHEC).
• Neisseria meningitidis: Meningitis, meningococcemia (petechial rash).
• Clostridioides difficile: Pseudomembranous colitis (diarrhea post-antibiotics).
• Mycoplasma pneumoniae: Atypical pneumonia ("walking pneumonia").
• Treponema pallidum: Syphilis (chancre, rash, gummas, neurosyphilis).
• Borrelia burgdorferi: Lyme disease (erythema migrans, arthritis, heart block, facial palsy).
• Viruses:
• Herpes Simplex Virus (HSV): Oral/genital herpes (vesicular lesions), encephalitis.
• Varicella-Zoster Virus (VZV): Chickenpox, shingles (dermatomal rash).
• HIV: Immunodeficiency, opportunistic infections (e.g., PCP, candidiasis, Kaposi sarcoma).
• Influenza virus: Acute respiratory illness (fever, myalgia, cough).
• Hepatitis A/B/C: Jaundice, elevated LFTs (acute/chronic hepatitis).
• Measles (Rubeola): Prodrome, Koplik spots, maculopapular rash (descending).
• Mumps: Parotitis, orchitis, meningitis.
• Fungi:
• Candida albicans: Oral thrush, vaginitis, esophagitis (immunocompromised), candidemia.
• Aspergillus fumigatus: Allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, invasive aspergillosis (immunocompromised).
• Cryptococcus neoformans: Meningitis (immunocompromised, esp. HIV), pulmonary disease.
• Pneumocystis jirovecii: PCP pneumonia (immunocompromised, esp. HIV with low CD4).
• Endemic Mycoses (Histoplasma, Blastomyces, Coccidioides): Granulomatous lung disease, disseminated disease (geographic context).
• Parasites:
• Plasmodium spp.: Malaria (cyclic fever, hemolytic anemia).
• Giardia lamblia: Chronic diarrhea, steatorrhea, bloating.
• Toxoplasma gondii: Chorioretinitis, encephalitis (immunocompromised), congenital toxoplasmosis.

Diagnosis (Gold Standard)

Bacteria: Gram stain & Culture (blood, CSF, urine, sputum), PCR (e.g., C. difficile, Chlamydia, N. gonorrhoeae, M. tuberculosis GeneXpert), Serology (e.g., Syphilis: RPR/VDRL + FTA-ABS; Lyme: ELISA + Western Blot), Acid-fast stain for Mycobacteria. Viruses: PCR (viral load/identification: HIV, HBV, HCV, CMV, HSV), Serology (antibody detection for immunity/past infection: HAV IgM/IgG, HIV Ab/Ag combo), Tzanck smear for HSV/VZV (multinucleated giant cells). Fungi: KOH prep (skin, hair, nails), Fungal culture, Antigen detection (Cryptococcal antigen in CSF/serum, Histoplasma urinary antigen), Biopsy with special stains (GMS, PAS). Parasites: O&P (Ova and Parasites) stool exam (Giardia, Entamoeba), Blood smear (Plasmodium for malaria), Serology (Toxoplasma IgG/IgM).

Management (First Line)

Bacteria:

• MSSA: Nafcillin/Oxacillin. MRSA: Vancomycin, Linezolid.
• S. pyogenes: Penicillin.
• S. pneumoniae: Amoxicillin (mild), Ceftriaxone (severe).
• E. coli (UTI): TMP-SMX, Nitrofurantoin, Ciprofloxacin.
• N. meningitidis: Ceftriaxone.
• C. difficile: Oral Vancomycin, Fidaxomicin.
• Mycoplasma pneumoniae: Macrolides (Azithromycin) or Tetracyclines (Doxycycline).
• Treponema pallidum: Penicillin G.
• Borrelia burgdorferi: Doxycycline (early), Ceftriaxone (late/disseminated).
• M. tuberculosis: RIPE (Rifampin, Isoniazid, Pyrazinamide, Ethambutol).

• HSV/VZV: Acyclovir, Valacyclovir.
• HIV: HAART (multi-drug regimen).
• Influenza: Oseltamivir.
• Hepatitis B: Entecavir, Tenofovir.
• Hepatitis C: Direct-acting antivirals (DAAs).

• Candida: Fluconazole (oral/esophageal), Echinocandins (invasive).
• Aspergillus: Voriconazole, Amphotericin B.
• Cryptococcus: Amphotericin B + Flucytosine, then Fluconazole.
• Pneumocystis jirovecii: Trimethoprim-sulfamethoxazole (prophylaxis & treatment).
• Endemic Mycoses: Itraconazole (mild/moderate), Amphotericin B (severe).

• Plasmodium: Chloroquine (sensitive), Artemisinin-based Combination Therapy (resistant).
• Giardia: Metronidazole.
• Toxoplasma: Pyrimethamine + Sulfadiazine + Leucovorin.

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