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Staphylococcus — Comprehensive Review

1. Taxonomy and General Characteristics

• Catalase positive (distinguishes from Streptococcus)
• Coagulase positive = S. aureus (distinguishes from all CoNS)
• Grows aerobically AND anaerobically
• Tolerates 10% NaCl and temperatures 18–40°C
• Protein A present (IgG Fc binding)

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2. Microbiology of S. aureus

Culture

• Forms large, smooth, β-hemolytic colonies on blood agar within 24 hours
• Golden-yellow pigment (carotenoid) on prolonged incubation
• Selective media: mannitol-salt agar (7.5–10% NaCl) or chromogenic agar
• MALDI-TOF mass spectrometry and coagulase testing for definitive ID
• PCR/NAAT used for MSSA/MRSA nasal screening

Cell Structure

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3. Virulence Factors

Toxins

Enzymes

Regulation of Virulence

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4. Epidemiology

• Colonization: 20–30% of healthy adults are persistent nasal carriers; ~60% are intermittent carriers. Primary niche: anterior nares, with secondary sites at oropharynx, perineum, axilla, groin.
• Higher carriage rates: atopic dermatitis, insulin-dependent diabetes, dialysis, HIV infection, injection drug use
• Transmission: predominantly direct contact (hand carriage); environmental surface contamination plays a secondary role; aerosol transmission is minimal.
• MRSA: ~50% of S. aureus infections in US healthcare settings are MRSA. Two distinct epidemiologic strains:
  • HA-MRSA (healthcare-associated): restricted to healthcare environments; resistant to multiple drug classes
  • CA-MRSA (community-associated): circulates in community AND hospitals; frequently carries PVL; causes primary skin abscesses and necrotizing pneumonia; typically susceptible to more non-beta-lactam agents
• S. aureus is responsible for millions of infections per year in the US; ~5–10% are invasive, with ¾ of those involving bacteremia.

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5. Clinical Diseases

Toxin-Mediated Diseases

• Predominantly in neonates and children (<5 years); rare in adults (renal failure, immunosuppression)
• Exfoliative toxins A/B cleave desmoglein-1 → intraepidermal split at the granular layer
• Presentation: abrupt perioral erythema → generalized tender erythroderma → bullae → large sheet-like desquamation (Nikolsky sign positive)
• No organisms in the blisters (toxin acts remotely from distant focus, e.g., nasopharynx)
• Treat with anti-staphylococcal antibiotics + supportive care

• Preformed heat-stable enterotoxin (most commonly A) in contaminated food (salted ham, cream, dairy)
• Incubation: 1–6 hours (short — toxin is preformed)
• Explosive onset: nausea, profuse vomiting, abdominal cramps ± diarrhea
• Resolves spontaneously within 24–48 hours; treatment is supportive

• Caused by TSST-1 (accounts for 75% of cases) or staphylococcal enterotoxins acting as superantigens
• Two settings: menstrual TSS (tampon use, vaginal colonization) and non-menstrual TSS (wound infections, surgery, nasal packing)
• Classic triad: fever ≥38.9°C + diffuse macular erythroderma + hypotension
• Multi-system involvement (≥3 organ systems): renal failure, hepatic dysfunction, thrombocytopenia, CNS encephalopathy, desquamation (especially palms/soles, 1–2 weeks after onset)
• Management: fluid resuscitation, anti-staphylococcal antibiotics + clindamycin (to suppress toxin synthesis), source control

Suppurative/Pyogenic Infections

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6. Coagulase-Negative Staphylococci (CoNS)

S. epidermidis

• Normal skin flora, usually non-pathogenic
• Virulence: biofilm ("slime layer") production → adherence to foreign bodies + resistance to phagocytosis and antibiotics
• Causes: subacute endocarditis (particularly prosthetic valves), infected IV catheters, CSF shunts, prosthetic joint infections, urinary catheters
• Treatment: vancomycin ± rifampin; removal of the foreign body is often required

S. saprophyticus

• Predilection for urinary tract of young sexually active women
• Causes dysuria, pyuria; rarely causes asymptomatic colonization
• Treatment: TMP-SMX or nitrofurantoin; responds rapidly; reinfection uncommon

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7. Laboratory Diagnosis

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8. Antimicrobial Resistance — MRSA

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9. Treatment

MSSA Infections

• Drug of choice: Nafcillin/oxacillin (antistaphylococcal penicillins) IV for serious infections
• Cefazolin: equivalent efficacy, less toxicity — preferred in many institutions; 2 g IV q8h for bacteremia/endocarditis
• Oral (mild-moderate SSTI): dicloxacillin, cephalexin

MRSA Infections

Recent evidence update: A 2025 systematic review and meta-analysis (PMID 40349971) found cefazolin non-inferior or superior to antistaphylococcal penicillins for MSSA bacteremia with a more favorable tolerability profile. A 2025 meta-analysis (PMID 39290168) found oral step-down therapy is reasonable for select patients with S. aureus bacteremia/endocarditis after initial IV stabilization.

Alternative/Salvage Agents

• Linezolid (600 mg IV/PO q12h) — useful for vancomycin MIC creep (MIC ≥2 µg/mL), pulmonary MRSA
• Daptomycin — avoid for pulmonary infections (inactivated by surfactant)
• Ceftaroline — 5th-generation cephalosporin active against MRSA; bactericidal
• Tedizolid, oritavancin, dalbavancin — newer agents for MRSA SSTI
• Tigecycline — broad-spectrum alternative; not for bacteremia
• Fosfomycin, fusidic acid — combination use for MRSA

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10. Prevention and Control

• Hand hygiene — single most effective intervention (healthcare workers)
• MRSA surveillance screening: nasal swabs (NAAT) for high-risk patients on admission
• Decolonization: intranasal mupirocin + chlorhexidine baths for high-risk patients (pre-operatively or prior to dialysis)
• Proper wound care, aseptic catheter insertion, and maintenance bundles
• Covering exposed skin; isolation precautions (contact precautions) for MRSA
• No licensed S. aureus vaccine as of 2026 (multiple attempts failed in phase 3 trials)

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Summary Table: S. aureus vs CoNS

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