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 rifampin
CIntravenous vancomycin
DOral trimethoprim-sulfamethoxazole
EIntravenous clindamycin
Reveal answer & full explanation
Correct answer: C — Intravenous vancomycin
AOral cephalexin
BIntravenous rifampin
CIntravenous vancomycin✓
DOral trimethoprim-sulfamethoxazole
EIntravenous clindamycin
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
Oral trimethoprim-sulfamethoxazole — has MRSA activity but oral monotherapy is not first-line for MRSA bacteremia or prosthetic joint infection
Intravenous clindamycin — active against many MRSA skin and soft tissue isolates, but it is bacteriostatic, is undermined by inducible resistance, and is not a recommended agent for adult MRSA bacteremia, for which IDSA guidance uses vancomycin or daptomycin
Intravenous rifampin — the classic adjunct for staphylococcal prosthetic joint infection with retained hardware because of its biofilm activity, but S. aureus rapidly becomes resistant when rifampin is used alone, so it is only ever combined with another active agent such as vancomycin and is never initial monotherapy for MRSA bacteremia
Additional high-yield points
Daptomycin (6-10 mg/kg IV daily) is an accepted first-line alternative to vancomycin for MRSA bacteremia (IDSA 2011) and is the usual switch when the vancomycin MIC is >2 mcg/mL or the patient fails to respond to vancomycin
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 productive cough. Serial chest radiographs show rapidly progressive multilobar consolidation, and he becomes hypotensive requiring ICU admission. Which of the following complications is most likely responsible for his current presentation?
AAcute respiratory distress syndrome
BPrimary influenza viral pneumonia
CLoculated empyema with effusion
DSeptic pulmonary embolic disease
EHemorrhagic necrotizing pneumonia
Reveal answer & full explanation
Correct answer: E — Hemorrhagic necrotizing pneumonia
AAcute respiratory distress syndrome
BPrimary influenza viral pneumonia
CLoculated empyema with effusion
DSeptic pulmonary embolic disease
EHemorrhagic necrotizing pneumonia✓
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 and rapidly progressive multilobar consolidation with hemodynamic collapse in a young, previously healthy host with documented PVL-positive MRSA is the textbook presentation; hemoptysis, leukopenia, and cavitation are characteristic of this toxin-mediated necrosis.
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
Acute respiratory distress syndrome - a noncardiogenic permeability edema that produces diffuse bilateral opacities and hypoxemia; it can complicate severe pneumonia and sepsis, but it is a secondary lung injury that does not explain the fever, pleuritic chest pain, and productive cough of the primary PVL-driven infection.
Loculated empyema with effusion - presents with a pleural fluid collection and a layering or loculated effusion, not the rapidly progressive multilobar parenchymal consolidation seen here.
Septic pulmonary embolic disease - produces multiple peripheral nodular infiltrates, classically from right-sided endocarditis or an infected catheter/thrombus, rather than the rapidly progressive post-influenza consolidation driven by PVL.
Primary influenza viral pneumonia - the campus outbreak makes this tempting, and influenza is likely the trigger here, but primary viral pneumonia classically produces diffuse bilateral interstitial infiltrates with scant sputum; rapidly progressive multilobar consolidation with productive cough and shock in a host with recent PVL-positive MRSA signals bacterial necrotizing superinfection.
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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 — abscess, no SIRS
Mild
I&D ± TMP-SMX or doxycycline x 5-7 d
Outpatient — abscess with SIRS or surrounding 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 after I&D (IDSA 2014/2011; no abscess-size cutoff): SIRS or systemic signs, extensive surrounding cellulitis, multiple sites, immunocompromise, extremes of age, difficult-to-drain site (face, hand, genitalia), or failure of I&D alone:
• 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; IDSA 2014 adds MRSA-active antibiotics based on SIRS or host factors, not abscess size. Trials (Talan NEJM 2016; Daum NEJM 2017) show modestly higher cure rates with TMP-SMX after drainage, so antibiotics for an uncomplicated abscess are a shared decision.
TMP-SMX and doxycycline cover MRSA but NOT group A streptococcus — for purulent SSTI with a surrounding cellulitis component, add cephalexin or use clindamycin alone. Typical non-purulent cellulitis is treated with a beta-lactam alone; add MRSA coverage only with risk factors (penetrating trauma, injection drug use, MRSA elsewhere, SIRS).
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).
S. aureus (including MRSA) is the most common organism in surgical site infections overall; incisional SSI typically appears around POD 5-7 with erythema, warmth, and purulent drainage. Remove sutures, open and drain the wound, and culture; add antibiotics for systemic signs or erythema extending >5 cm from the wound edge (IDSA 2014).
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
Talan 2016 — Talan et al., Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess (NEJM 2016;374:823-832)
Daum 2017 — Daum et al., A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses (NEJM 2017;376:2545-2555)
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