Methicillin-resistant Staphylococcus aureus — predominant cause of purulent SSTI; treatment centers on incision and drainage plus MRSA-active oral or IV antibiotics.
Also known as: MRSA, methicillin-resistant Staphylococcus aureus, CA-MRSA, HA-MRSA
Overview
Skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus, which carries the mecA gene encoding altered penicillin-binding protein 2a (PBP2a) and is resistant to all beta-lactams except certain advanced cephalosporins (ceftaroline). Community-associated (CA-MRSA, often USA300 strain, PVL toxin-positive) differs epidemiologically and microbiologically from healthcare-associated MRSA (HA-MRSA).
Epidemiology
CA-MRSA emerged in the 2000s and now causes the majority of US purulent SSTI presenting to emergency departments. Increased among athletes, military personnel, prisoners, MSM, IV drug users, and households with close contact.
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Question 1Infectious DiseaseEasy
A 65-year-old man two weeks after right total knee arthroplasty presents with fever to 38.6 C, wound erythema, and purulent drainage from the surgical site. Two sets of blood cultures grow methicillin-resistant Staphylococcus aureus (MRSA). Which of the following is the most appropriate initial antimicrobial therapy?
AOral cephalexin
BIntravenous vancomycin
CTrimethoprim-sulfamethoxazole
DIntravenous oxacillin
Reveal answer & full explanation
Correct answer: B — Intravenous vancomycin
AOral cephalexin
BIntravenous vancomycin✓
CTrimethoprim-sulfamethoxazole
DIntravenous oxacillin
Why Intravenous vancomycin is correct
For MRSA bacteremia or prosthetic joint infection, IV vancomycin is first-line
Dosing is AUC/MIC-guided
Why the others are wrong
Oral cephalexin — a first-generation oral cephalosporin with no MRSA activity, inadequate for bacteremia or prosthetic joint infection
Trimethoprim-sulfamethoxazole — has MRSA activity but oral monotherapy is not first-line for MRSA bacteremia or prosthetic joint infection
Intravenous oxacillin — excellent for methicillin-susceptible S. aureus but ineffective against MRSA by definition
Additional high-yield points
Daptomycin is an alternative if vancomycin MIC is ≥1.5 mcg/mL
Treatment duration is at least 2 weeks for uncomplicated bacteremia and at least 6 weeks for prosthetic joint infection
Source control is required alongside antimicrobial therapy
Question 2Infectious DiseaseMedium
A 19-year-old college wrestler is treated for a culture-confirmed PVL-positive community-associated MRSA abscess of the forearm with incision and drainage plus oral trimethoprim-sulfamethoxazole. Two weeks later, during a campus influenza outbreak, he returns with a 2-day history of high fever, pleuritic chest pain, dyspnea, and hemoptysis. Chest radiograph shows rapidly expanding bilateral cavitary infiltrates, and he becomes hypotensive requiring ICU admission. Which of the following complications is most likely responsible for his current presentation?
AAcute respiratory distress syndrome
BHemorrhagic necrotizing pneumonia
CLoculated empyema with effusion
DSeptic pulmonary embolic disease
Reveal answer & full explanation
Correct answer: B — Hemorrhagic necrotizing pneumonia
AAcute respiratory distress syndrome
BHemorrhagic necrotizing pneumonia✓
CLoculated empyema with effusion
DSeptic pulmonary embolic disease
Why Hemorrhagic necrotizing pneumonia is correct
Panton-Valentine leukocidin (PVL)-positive CA-MRSA is the classic cause of rapidly progressive hemorrhagic necrotizing pneumonia, which characteristically follows or coincides with influenza that disrupts the respiratory epithelium.
High fever, hemoptysis, and rapidly expanding bilateral cavitary infiltrates with hemodynamic collapse in a young, previously healthy host with documented PVL-positive MRSA is the textbook presentation.
Per IDSA MRSA guidance, treat with vancomycin or linezolid; daptomycin is NOT used because it is inactivated by pulmonary surfactant, and linezolid may be favored for its toxin-suppressing effect in PVL-positive disease.
Why the others are wrong
Septic pulmonary embolic disease produces multiple peripheral nodular infiltrates, classically from right-sided endocarditis or an infected catheter/thrombus, rather than the rapidly cavitating post-influenza pattern driven by PVL.
Loculated empyema with effusion presents with a pleural fluid collection and a layering or loculated effusion, not the expanding bilateral cavitary parenchymal infiltrates and hemoptysis seen here.
Acute respiratory distress syndrome causes diffuse non-cavitary alveolar infiltrates from increased capillary permeability; it can accompany sepsis but does not by itself produce the cavitary, hemoptysis-predominant picture central to this case.
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Contact sports, gym/locker room exposure, sharing personal items
Crowded living conditions (jails, military barracks, daycare)
Recent antibiotics, healthcare exposure
Diabetes, HIV, dialysis
Nasal/skin colonization
Pathophysiology
S. aureus colonizes ~30% of healthy adults; MRSA colonization is the primary reservoir for autoinfection. Virulence factors include Panton-Valentine leukocidin (PVL, associated with severe SSTI and necrotizing pneumonia), alpha-hemolysin, staphylococcal protein A, biofilm formation. mecA-encoded PBP2a confers beta-lactam resistance.
Clinical presentation
Symptoms
Painful, erythematous, indurated skin lesion with central fluctuance or pustular drainage
Often described as 'spider bite' by patient
Furuncles (boils), carbuncles (clusters of furuncles), abscesses, complicated cellulitis
Fever, systemic symptoms in severe disease
Recurrent or family-wide outbreaks suggest colonization
Signs / physical exam
Localized warm, tender, erythematous nodule or abscess with fluctuance
Central pustule, necrotic black-eschar in PVL-producing strains
Lymphangitic streaking, regional adenopathy
Systemic signs of sepsis in severe infections
Classic findings
An athlete or close-contact-setting patient with a painful, fluctuant 'spider bite' lesion — almost always purulent SSTI, most commonly MRSA in current US epidemiology.
Differential diagnosis
MSSA SSTI — Indistinguishable clinically; identified by culture susceptibility — cefazolin/oxacillin preferred when MSSA confirmed
Group A streptococcal infection — Often non-purulent cellulitis, lymphangitis; penicillin-susceptible
Spider bite — Brown recluse may cause necrotizing wound — often misdiagnosed; many 'spider bites' are MRSA
Folliculitis — Inflammatory papules around hair follicles; can progress to furuncles
Hidradenitis suppurativa — Chronic recurrent abscesses in apocrine areas (axilla, groin, inframammary)
Pilonidal cyst/abscess — Sacrococcygeal midline cyst, hair-bearing area
Bartholin gland abscess — Labial swelling at posterior introitus; can be polymicrobial
Diagnostic workup
Diagnostic criteria
MRSA on culture from purulent SSTI material with confirmed resistance to oxacillin/methicillin or mecA gene detection.
Labs
Wound culture with susceptibility testing — incise and drain first; submit purulent material
Gram stain helpful — gram-positive cocci in clusters
Blood cultures only for severe disease, systemic toxicity, or immunocompromised
Routine CBC, BMP if hospitalized or systemic features
Consider MRSA nasal swab for decolonization decisions in recurrent disease (not for acute diagnosis)
Imaging
Bedside ultrasound distinguishes cellulitis (cobblestoning) from abscess (anechoic fluid collection)
CT/MRI if necrotizing infection or deeper involvement suspected
Diagnostic algorithm
Setting
Severity
Recommended Therapy
Outpatient — small abscess
Mild
I&D ± TMP-SMX or doxycycline x 5-7 d
Outpatient — large abscess or cellulitis
Moderate
I&D + TMP-SMX or doxycycline; add cephalexin if strep concern
Inpatient — severe SSTI/sepsis
Severe
Vancomycin IV (or linezolid, daptomycin)
MRSA bacteremia
Severe
Vancomycin or daptomycin; ID consult; source control
MRSA pneumonia (PVL-positive)
Severe
Vancomycin or linezolid; AVOID daptomycin
Recurrent SSTI
Outpatient
Decolonize: mupirocin nares BID x 5-10 d + chlorhexidine washes
MRSA-active therapy by clinical scenario (IDSA 2011/2014).
Treatment
First-line
Cornerstone: incision and drainage (I&D) for any fluctuant abscess
Outpatient MRSA-active oral antibiotics (recommended for abscesses >2 cm, surrounding cellulitis, systemic signs, immunocompromise, age extremes — per IDSA 2014):
• TMP-SMX DS 1-2 tablets PO BID — first-line; covers MRSA but not group A strep
• Doxycycline 100 mg PO BID — alternative; also covers MRSA, not group A strep
• Clindamycin 300-450 mg PO QID — covers MRSA and strep; high C. difficile risk; check D-test for inducible resistance
• Linezolid 600 mg PO BID — expensive; reserve for resistant cases; risk of serotonin syndrome and cytopenias
If group A strep coverage also needed (non-purulent component), add cephalexin or use clindamycin alone
Decolonization for recurrent disease (≥2 episodes despite I&D): intranasal mupirocin BID × 5-10 days + chlorhexidine body washes for 5 days; consider household decolonization
Complications
Recurrent SSTI (common — 30% within 6 months)
Bacteremia, sepsis, endocarditis
Necrotizing pneumonia (PVL-positive CA-MRSA — devastating, especially post-influenza)
Osteomyelitis, septic arthritis, epidural abscess
Toxic shock syndrome
Necrotizing fasciitis
PANCE pearls
'Spider bite' presentation in the US is almost never a spider — assume CA-MRSA until proven otherwise.
I&D is the most important intervention for abscess; many small uncomplicated abscesses (<2 cm) resolve with drainage alone, though IDSA endorses adjunctive antibiotics for most.
TMP-SMX and doxycycline cover MRSA but NOT group A streptococcus — combine with a beta-lactam for non-purulent cellulitis where strep is the dominant concern.
Recurrent MRSA infections in a household — decolonize the patient AND consider household-wide decolonization (mupirocin + chlorhexidine).
Severe MRSA pneumonia — do NOT use daptomycin (inactivated by surfactant); use vancomycin or linezolid (linezolid may be preferred for toxin suppression in PVL-positive disease).
References
IDSA 2014 — Stevens et al., Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections (Clin Infect Dis)
IDSA 2011 — Liu et al., Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of MRSA Infections in Adults and Children (Clin Infect Dis)
CDC — Methicillin-resistant Staphylococcus aureus (MRSA): Clinicians' Information
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