Staphylococcal Infections¶

Chapter 152 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 152

Key Clinical Points¶

S. aureus is a pyogenic pathogen known for its capacity to induce abscess formation at both local and distant sites (i.e., metastatic infections).
Approximately 20–40% of healthy persons are colonized with S. aureus, with ~10% persistently colonized with the same strain.
CA-MRSA strains cause increasing nosocomial infections and enhanced disease in immunocompetent individuals.
MRI is the most reliable imaging modality for diagnosing osteomyelitis; findings may be normal for up to 14 days after symptom onset.
S. aureus bacteremia may be complicated by sepsis, endocarditis, vasculitis, or metastatic seeding (frequency ~31%).
TSST-1 and enterotoxins bind to MHC invariant regions, causing T-cell clone overexpansion (up to 20% of total T-cells).
S. aureus is the most common cause of surgical wound infections and second only to NSaS as a primary bacteremia cause.
Prosthetic-valve endocarditis often requires urgent valve replacement due to limited efficacy of medical therapy alone.
Uniformly positive blood cultures over time suggest endovascular infection (e.g., endocarditis), not contamination.
The agr regulatory gene is part of a quorum-sensing pathway that responds to bacterial density.

1. DEFINITION & OVERVIEW¶

Staphylococci are gram-positive cocci in the family Micrococcaceae, forming grapelike clusters on Gram's stain. S. aureus is distinguished by coagulase production and other biochemical markers (mannitol fermentation, DNAse production). Coagulase-negative staphylococci (NSaS) are less virulent but significant in prosthetic device infections. Modern identification methods include MALDI-TOF mass spectrometry and whole-genome sequencing for strain discrimination.

1.1 Microbiology and Taxonomy¶

• Characteristics: Catalase-positive, nonmotile, aerobic, and facultatively anaerobic. • Differentiation: Distinguished from NSaS by coagulase production, mannitol fermentation, and protein A positivity. • Molecular Typing: Methods such as pulsed-field gel electrophoresis and whole-genome sequencing enable outbreak tracking and strain discrimination.

2. EPIDEMIOLOGY¶

S. aureus is a commensal organism colonizing 20–40% of healthy individuals (10% persistent colonization). Risk factors include diabetes, injection drug use, and immunosuppression. CA-MRSA has emerged as a major community pathogen with outbreaks linked to poor hygiene and close contact. In the US, sequence type 8 (USA300) is the predominant clone. S. aureus causes 5–10% of invasive infections despite being primarily a skin flora organism.

2.1 Risk Factors and Colonization Sites¶

• Primary Colonization Sites: Anterior nares (70–90%), oropharynx, and damaged skin. • Risk Factors for Persistence: Diabetes, HIV, hemodialysis, and injection drug use. • CA-MRSA Reservoirs: Skin, groin, and perineum; transmission occurs via direct contact and contaminated materials.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

S. aureus virulence depends on genetic elements including SCCmec (methicillin resistance) and pathogenicity islands containing toxin genes. The agr regulatory gene controls quorum-sensing pathways that regulate virulence factor expression. Key virulence factors include: • Adhesins for tissue colonization • Enzymes (coagulase, DNAse) for tissue invasion • Toxins: α-toxin, Panton-Valentine leukocidin (PVL), exfoliative toxins • Immune evasion mechanisms: protein A (Fc receptor mimicry), capsule (abscess formation), and intracellular survival in phagocytes

3.1 Pathogenesis of Toxin-Mediated Disease¶

• Superantigens: TSST-1 and enterotoxins bind to MHC class II invariant regions → activate up to 20% of T-cell clones → trigger cytokine storm (IL-6, TNF-α) mimicking endotoxin shock. • Exfoliative Toxins: ETA and ETB cleave desmosomal cadherins, leading to staphylococcal scalded skin syndrome (SSSS). • Enterotoxins: Cause food poisoning via vagus nerve stimulation and increased intestinal peristalsis.

3.2 Host Response to S. aureus Infection¶

• Innate Immunity: PMN recruitment via formyl peptides, peptidoglycan, and cytokines (TNF-α, IL-1). • Adaptive Immunity: Antibodies to capsular polysaccharides and MSCRAMMs show protective effects in animal models. • Vaccine Development: Currently no approved vaccine; challenges include insufficient clinical efficacy despite in vitro opsonization.

4. CLINICAL FEATURES¶

Clinical manifestations vary by infection site: • Skin infections: folliculitis (superficial), furuncles (abscesses), carbuncles (coalesced abscesses) • Musculoskeletal: osteomyelitis (children: long bones; adults: vertebrae), septic arthritis (knees, hips), pyomyositis • Respiratory: neonatal pneumonia with pneumatoceles, post-influenza pneumonia • Systemic: bacteremia with 31% metastatic seeding risk; endocarditis (injection drug use, prosthetic valves)

4.1 Skin and Soft Tissue Infections¶

• Impetigo: Superficial blisters with honey-colored crusts. • Mastitis: Affects 1–3% of nursing mothers; presents as cellulitis/abscess with fever. • Recurrence: Linked to persistent colonization and quiescent bacterial reservoirs.

4.2 Musculoskeletal Infections¶

• Hematogenous Osteomyelitis: Common in children (long bones) and adults (vertebrae). • Septic Arthritis: Affects knees and shoulders; can cause rapid joint destruction if untreated. • Epidural Abscess: May lead to neurologic compromise with back pain and radicular symptoms.

4.3 Respiratory Tract Infections¶

• Neonatal Pneumonia: Characterized by respiratory failure and pneumatoceles on CXR. • Post-influenza Pneumonia: Presents with bloody sputum and midlung infiltrates. • Nosocomial Infections: Common in ICU patients, particularly those requiring intubation.

4.4 Bacteremia and Infective Endocarditis¶

• S. aureus Bacteremia: 31% risk of metastatic seeding (bones, joints, lungs). • Endocarditis Types: Right-sided (injection drug use), native valve, prosthetic valve, and nosocomial. • Prosthetic Valve Endocarditis: Often follows a fulminant course; requires urgent surgery due to limited efficacy of medical therapy alone.

5. DIFFERENTIAL DIAGNOSIS¶

Key distinguishing features: • Skin infections: differentiate from fungal infections (e.g., tinea) and viral exanthems. • Osteomyelitis: rule out tuberculosis, malignancy, and reactive arthritis. • Endocarditis: distinguish from other bacterial endocarditis (e.g., viridans streptococci). • Toxin-mediated diseases: differentiate TSS from septic shock or other superantigen syndromes.

6. INVESTIGATIONS & DIAGNOSIS¶

Diagnostic approach: • Blood cultures (gold standard for bacteremia/endocarditis) • Imaging: MRI for osteomyelitis (sensitive after 14 days), CT for abscesses, CXR for pneumonia • Molecular tests: PCR for toxin genes (TSST-1, PVL), SCCmec typing • Serology: limited utility; no widely available vaccine

6.1 Diagnostic Criteria and Algorithms¶

• Endocarditis: Duke criteria (major/minor) including positive blood cultures, echocardiographic findings, and clinical signs (Osler's nodes, Janeway lesions). • Osteomyelitis: MRI > X-ray; bone biopsy required if culture-negative. • SSTI: Clinical evaluation with Gram stain/culture confirmation.

7. MANAGEMENT & TREATMENT¶

Treatment principles: • Empiric therapy for MRSA: vancomycin, daptomycin, or linezolid • Surgical intervention: abscess drainage, debridement, and urgent valve replacement in endocarditis • Prophylaxis: decolonization (mupirocin, chlorhexidine) for recurrent infections • Special considerations: MRSA in immunocompromised hosts, pediatric patients

7.1 General Principles¶

Initial Empiric Therapy: Vancomycin or daptomycin for suspected MRSA.
Duration of Treatment: 2–6 weeks for deep infections (osteomyelitis, endocarditis).
Monitoring: Renal function with vancomycin; target trough levels >15–20 μg/mL.

7.2 Parenteral Therapy for Serious Infections¶

Sensitive to Penicillin: ◦ Drug of Choice: Penicillin G (4 mU q4h). ◦ Alternatives: Nafcillin or oxacillin (2 g q4h), cefazolin (2 g q8h), vancomycin (15–20 mg/kg q8h). ◦ Note: Lab must verify strain is not a β-lactamase producer.
Resistant to Methicillin: ◦ Primary Options: Vancomycin (15–10 mg/kg q8–12h), daptomycin (6–10 mg/kg IV q24h,d). ◦ Alternatives: Linezolid (600 mg q12h PO or IV), ceftaroline (600 mg IV q8–12h), telavancin (7.5–10 mg/kg IV q24h), TMP-SMX (5 mg [based on TMP]/kg IV q8–12h). ◦ Additional Agents: Tedizolid (200 mg once daily IV), oritavancin (1200 mg single dose), dalbavancin (1500 mg single dose), delafloxacin (300 mg q 12 h IV), omadacycline (100 mg OD).
Empirical Therapy (Unknown Sensitivity): ◦ Vancomycin (15–20 mg/kg q8–12h) or daptomycin (6–10 mg/kg q24h,d). If vancomycin MIC ≥ 1.5 μg/mL is common in the community, daptomycin may be preferred.

7.3 Oral Therapy for Skin and Soft Tissue Infections¶

Standard Options: Dicloxacillin (500 mg qid), cephalexin (500 mg qid), or cefadroxil (1 g q12h).
Alternative Options: Minocycline or doxycycline (100 mg q12h), TMP-SMX (1 or 2 DS tablets bid), clindamycin (300–450 mg tid), linezolid (600 mg bid), tedizolid (200 mg once daily).
Specific Agents for MRSA: Delafloxacin (450 mg q12 h) or omadacycline (300 mg once a day).

8. PROGNOSIS & COMPLICATIONS¶

Prognostic factors: • Mortality: ~20% in endocarditis, higher with prosthetic valves • Recurrence risk: 30–50% without decolonization • Complications: septic shock, metastatic abscesses, valvular insufficiency, chronic osteomyelitis

8.1 Mortality and Morbidity¶

• Bacteremia: 20–30% mortality without source control. • Endocarditis: ~30% with native valves; >50% with prosthetic valves.

9. SPECIAL CONSIDERATIONS¶

• Immunocompromised Hosts: Higher virulence (PVL strains), prolonged courses. • Pediatric Patients: SSSS in neonates, rapid progression of infections. • Resource-Limited Settings: Endemic CA-MRSA strains with high community transmission.

10. KEY PEARLS & CLINICAL TRAPS¶

• Clinical Trap: Never assume a positive blood culture for S. aureus is a contaminant; it is the second most common cause of primary bacteremia (after NSaS). • Diagnostic Pitfall: MRI may be normal in early osteomyelitis (up to 14 days). • Therapeutic Challenge: MRSA requires specific agents like vancomycin or daptomycin; source control is critical. • TSS Criteria (Table 2/4): ◦ Clinical Criteria: Fever ≥102.0°F (≥38.9°C); rash (diffuse macular erythroderma); desquamation (1–2 weeks post-rash); hypotension (SBP ≤90 mmHg for adults or <5th percentile for children <16 years). ◦ Multisystem Involvement: ≥3 of: Gastrointestinal (vomiting/diarrhea at onset), Muscular (severe myalgia or CK ≥2x ULN), Mucous membrane (hyperemia), Renal (BUN/Cr ≥2x ULN or pyuria ≥5 leukocytes per HPF without UTI), Hepatic (Bili/ALT ≥2x ULN), Hematologic (Platelets <10^5/muL), CNS (disorientation/altered consciousness without focal signs). • Surgical Urgency: Prosthetic-valve endocarditis is a medical emergency requiring urgent surgery.

Reference Tables¶

TABLE 152-1 Common Illnesses Caused by Staphylococcus aureus Skin and Soft Tissue Infections¶

Harrison's 22e, p.1199

Skin and Soft Tissue Infections
Folliculitis
Abscess, furuncle, carbuncle
Cellulitis
Impetigo
Mastitis
Surgical wound infections
Musculoskeletal Infections
Septic arthritis
Osteomyelitis (hematogenous or contiguous spread)
Pyomyositis
Psoas abscess
Respiratory Tract Infections
Ventilator-associated or nosocomial pneumonia
Septic pulmonary emboli
Postviral pneumonia (e.g., influenza)
Empyema
Bacteremia and Its Complications
Sepsis, septic shock
Metastatic foci of infection (kidney, joints, bone, lung)
Infective endocarditis
Infective Endocarditis
Injection drug use–associated
Native-valve
Prosthetic-valve
Nosocomial
Device-Related Infections (e.g., intravascular catheters, prosthetic
joints)
Toxin-Mediated Illnesses
Toxic shock syndrome
Food poisoning
Staphylococcal scalded-skin syndrome
Invasive Infections Associated with Community-Acquired Methicillin-
Resistant S. aureus
Necrotizing fasciitis
Waterhouse-Friderichsen syndrome
Necrotizing pneumonia
Purpura fulminans

TABLE 152-2 Case Definition of Staphylococcus aureus Toxic Shock Syndrome Clinical Criteria An illness with the…¶

Harrison's 22e, p.1201

Clinical Criteria
An illness with the following clinical manifestations:
• Fever: temperature ≥102.0°F (≥38.9°C)
• Rash: diffuse macular erythroderma
• Desquamation: 1–2 weeks after rash onset
• Hypotension: systolic blood pressure ≤90 mmHg for adults or less than the fifth
percentile, by age, for children <16 years old
• Multisystem involvement (≥3 of the following organ systems)
• Gastrointestinal: vomiting or diarrhea at illness onset
• Muscular: severe myalgia or creatine phosphokinase level at least twice
ULN
• Mucous membrane: vaginal, oropharyngeal, or conjunctival hyperemia
• Renal: blood urea nitrogen or creatinine level at least twice ULN for
laboratory or urinary sediment with pyuria (≥5 leukocytes per high-power
field) in the absence of urinary tract infection
• Hepatic: total bilirubin or aminotransferase level at least twice ULN for
laboratory
• Hematologic: platelet count <105/μL
• Central nervous system: disorientation or alterations in consciousness
without focal neurologic signs in the absence of fever and hypotension
Laboratory Criteria
Negative results in the following tests, if obtained:
• Blood or cerebrospinal fluid cultures for another pathogena
• Serologic tests for Rocky Mountain spotted fever, leptospirosis, or measles
Case Classification
Probable: a case that meets the laboratory criteria and in which four of the five
clinical criteria are fulfilled
Confirmed: a case that meets the laboratory criteria and in which all five of the
clinical criteria are fulfilled, including desquamation (unless the patient dies
before desquamation occurs)

TABLE 152-3 Antimicrobial Therapy for Staphylococcal Infections a¶

Harrison's 22e, p.1203

SENSITIVITY/ RESISTANCE OF ISOLATE	DRUG OF CHOICE	ALTERNATIVE(S)	COMMENTS
Parenteral Therapy for Serious Infections
Sensitive to penicillin	Penicillin G (4 mU q4h)	Nafcillin or oxacillin (2 g q4h), cefazolin (2 g q8h), vancomycin (15–20 mg/kg q8hb)	Fewer than 5% of isolates are sensitive to penicillin. The clinical microbiology laboratory must verify that the strain is not a β-lactamase producer.
	Nafcillin or oxacillin (2 g q4h), cefazolin (2 g q8h)	Daptomycin (6–10 mg/kg IV q24hb,d), vancomycin (15–20 mg/kg q8hb), ceftobiprole (500 mg IV q6hg)
Resistant to methicillin	Vancomycin (15–20 mg/kg q8–12hb), daptomycin (6–10 mg/kg IV q24hb,d) for bacteremia, endocarditis, osteomyelitis, and complicated skin infections	Linezolid (600 mg q12h PO or IV), ceftaroline (600 mg IV q8–12h), telavancin (7.5–10 mg/kg IV q24h)b, TMP-SMX (5 mg [based on TMP]/kg IV q8–12h)f Additional agents include tedizolid (200 mg once daily IV), oritavancin (single dose of 1200 mg), dalbavancin (single dose of 1500 mg), delafloxacin (300 mg q 12 h IV), omadacycline 100 mg OD). Ceftobiprole (500 mg IV q6hg)	Sensitivity testing is necessary before an alternative drug is selected. The efficacy of adjunctive therapy is not well established in many settings. Linezolid, ceftaroline, and telavancin have in vitro activity against most VISA and VRSA strains. See footnote for treatment of prosthetic- valve endocarditis.c
	Daptomycin (6–10 mg/kg q24hb,d) for bacteremia, endocarditis, osteomyelitis, and complicated skin infections	Same as for methicillin-resistant strains (check antibiotic susceptibilities) or
		Ceftaroline (600 mg IV q8–12h) Newer agents include tedizolid (200 mg once daily IV or PO), oritavancin (single dose of 1200 mg), and dalbavancin (single dose of 1500 mg). These drugs are approved only for the treatment of skin and soft tissue infections.
Not yet known (i.e., empirical therapy)	Vancomycin (15–20 mg/kg q8–12hb), daptomycin (6–10 mg/kg q24hb,d) for bacteremia, endocarditis, osteomyelitis, and complicated skin infections	—	Empirical therapy is given when the susceptibility of the isolate is not known. Vancomycin with or without a β-lactam is recommended for suspected community- or hospital-acquired Staphylococcus aureus infections because of the increased frequency of methicillin-resistant strains in the community. If isolates with an elevated MIC to vancomycin (≥1.5 μg/mL) are common in the community, daptomycin may be preferable.
Oral Therapy for Skin and Soft Tissue Infections
	Dicloxacillin (500 mg qid), cephalexin (500 mg qid), or cefadroxil (1 g q12h)	Minocycline or doxycycline (100 mg q12hb), TMP- SMX (1 or 2 DS tablets bid), clindamycin (300–450 mg tid), linezolid (600 mg PO q12h), tedizolid (200 mg PO q24h)
Resistant to methicillin	Clindamycin (300–450 mg tid), TMP-SMX (1 or 2 DS tablets bid), minocycline or doxycycline (100 mg q12hb), linezolid (600 mg bid), or tedizolid (200 mg once daily)	Delafloxacin 450 mg q12 h, omadacycline 300 mg once a day	It is important to know the antibiotic susceptibility of isolates in the specific geographic region. All collections should be drained, and drainage should be cultured.