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📚 Staphylococcus aureus — Lesson Notes

Source: Harrison's Principles of Internal Medicine, 22nd Edition (2025), Chapter 152 — Franklin D. Lowry & Anne-Catrin Uhlemann

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1. INTRODUCTION

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2. MICROBIOLOGY & TAXONOMY

📌 Note: S. pseudintermedius and S. argenteus are also coagulase-positive but are non-S. aureus staphylococci (NSaS). The older term "coagulase-negative staphylococci" is being replaced by NSaS (non-S. aureus staphylococci).

Identification Methods

• Latex kits detecting protein A + clumping factor
• MALDI-TOF mass spectrometry (increasingly used for speciation)
• Molecular typing: pulsed-field gel electrophoresis (PFGE), SpA typing
• Whole-genome sequencing = gold standard for outbreak discrimination

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3. EPIDEMIOLOGY

• Normal flora on skin, anterior nares, oropharynx, and vagina
• ~30% of individuals are colonized at any one time
• Most infections arise from the patient's own commensal flora (autoinfection)
• Transmission: mainly direct personal contact with infected site; rarely aerosols

High-Risk Groups

• Diabetes mellitus (↑ colonization + insulin injections + impaired leukocyte function)
• Neutropenia (chemotherapy)
• Chronic granulomatous disease (CGD)
• Hyper-IgE (Job syndrome), Chédiak-Higashi syndrome
• End-stage renal disease, HIV infection
• Patients with prosthetic devices, intravascular catheters, surgical wounds
• Injection drug users (IDU) — especially infective endocarditis

MRSA Epidemiology

• Hospital-acquired MRSA (HA-MRSA): Nosocomial, often multidrug resistant
• Community-acquired MRSA (CA-MRSA): Established community pathogen since 1990s
  • Most common cause of community-acquired SSTIs
  • Risk factors: poor hygiene, close contact, contaminated material, broken skin
  • Groups: children, prisoners, athletes, Native Americans, IDU
  • Dominant US clone: ST8 / USA300
  • 5–10% of CA-MRSA infections are invasive; can affect immunocompetent individuals

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4. PATHOGENESIS

General Concept

Virulence Factors

A. Structural/Surface Components

B. Secreted Toxins

C. Immune Evasion Mechanisms

• Protein A — blocks opsonization
• Catalase — neutralizes H₂O₂ from PMNs
• Coagulase / clumping factor — fibrin coat protects against phagocytosis
• Leukocidins (PVL, γ-hemolysin) — kill phagocytes
• Intracellular persistence within osteoblasts, endothelial cells

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5. CLINICAL DISEASES

A. Skin & Soft Tissue Infections (SSTIs) — Most Common

B. Bacteremia & Sepsis

• S. aureus is the #1 cause of surgical wound infections and #2 cause of primary bacteremia (after NSaS)
• Bacteremia seeds distant sites → metastatic infections (endocarditis, osteomyelitis, epidural abscess, septic arthritis)
• Mortality ~20–40%
• Always conduct echocardiogram when bacteremia identified

C. Infective Endocarditis (IE)

• Native-valve IE: especially in IDU (right-sided → tricuspid valve)
• Prosthetic-valve IE: S. aureus + NSaS are leading causes
• Can present as acute endocarditis with rapid valve destruction
• Complications: emboli, abscesses, metastatic foci

D. Pneumonia

• Hematogenous (bacteremia) or direct inhalation (post-influenza)
• Cavitating/necrotizing pneumonia especially with PVL-producing CA-MRSA
• Classic: follows influenza infection — "secondary bacterial pneumonia"

E. Osteomyelitis & Septic Arthritis

• #1 cause of both hematogenous osteomyelitis and septic arthritis
• Children: long bones (metaphysis)
• Adults: vertebral osteomyelitis (check MRI spine in prolonged bacteremia)

F. Central Nervous System Infections

• Brain abscess, meningitis (especially with shunts/catheters)
• Epidural abscess (presents with back pain + fever → emergency)

G. Toxin-Mediated Diseases

1. Food Poisoning

• Preformed, heat-stable enterotoxin — disease occurs without viable bacteria
• Onset: 1–6 hours after ingestion
• Symptoms: vomiting, diarrhea, cramping — no fever
• Self-limited (~24–48 hours)
• Sources: improperly stored/cooked food (meats, dairy, salads)

2. Toxic Shock Syndrome (TSS)

• Agent: TSST-1 (menstrual) or enterotoxins (non-menstrual)
• Mechanism: Superantigen binds MHC-II directly → massive T-cell activation → cytokine storm

Lab: Negative blood/CSF cultures for other pathogens; negative serology for RMSF, leptospirosis, measles. Blood cultures may be positive for S. aureus.

• Menstrual TSS: associated with superabsorbent tampons
• Non-menstrual: wound infections, nasal packing, post-partum
• Recurrences possible if antibody to TSST-1 fails to develop
• Illness only in persons lacking anti-TSST-1 antibody

3. Staphylococcal Scalded Skin Syndrome (SSSS)

• Caused by exfoliative toxins A & B (serine proteases cleaving desmoglein-1)
• Primarily affects newborns and children (adults rare — have neutralizing antibodies + better renal clearance)
• Spectrum: localized blisters → generalized exfoliation
• Nikolsky's sign positive: gentle lateral pressure → shear of superficial epidermis
• Mucous membranes spared (distinguishes from Stevens-Johnson syndrome)
• Thin-walled, fluid-filled bullae → denuded underlying skin

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6. DIAGNOSIS

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7. TREATMENT

Antibiotic Selection

⚠️ Empirical therapy should always cover MRSA until susceptibilities are known.

Management Principles

• Localized infections (furuncles, abscesses): Incision & drainage (I&D) is primary — antibiotics often not needed unless systemic signs
• Bacteremia: Minimum 2 weeks IV antibiotics; 4–6 weeks if complicated (endocarditis, osteomyelitis)
• Food poisoning: Supportive only (replace fluids); identify source for public health control
• TSS: Remove source of toxin; aggressive IV fluids; vancomycin ± IVIG
• SSSS: Antistaphylococcal antibiotics; wound care; fluids

Resistance Mechanism of MRSA

• mecA gene (on SCCmec element) encodes PBP2a — a modified penicillin-binding protein with low affinity for all β-lactams → resistance to all penicillins, cephalosporins, and carbapenems
• CA-MRSA (USA300) typically carries SCCmec type IV (smaller, more mobile)
• HA-MRSA typically carries SCCmec types I–III (larger; more resistance genes)

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8. PREVENTION & CONTROL

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9. QUICK-RECALL HIGH-YIELD SUMMARY

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