MD Nexus

Staphylococcus Aureus

Epidemiology

Risk Factors

Immune Defect

Implantable Device

Other

Microbiology

Staphylococcus Aureus is a Member of Staphylococcus Genus (see Staphylococcus)

  • Staphylococcus Aureus is a Gram-Positive Bacterium
  • Like Other Staphylococci, Staphylococcus Aureus Appears Microscopically as Grape-Like Clusters

Methicillin-Resistant Staphylococcus Aureus (MRSA)

Definitions

  • By Definition, All MRSA Isolates Carry the mecA Gene or the mecC Gene
    • These Genes Confer Resistance to All β-Lactam Antibiotics (Including Cephalosporins and Carbapenems)

Risk Factors for Methicillin-Resistant Staphylococcus Aureus (MRSA)

  • Factors Associated with Healthcare-Associated MRSA (HA-MRSA)
    • Antibiotic Use
      • Related to Selective Pressure of the Antibiotic (Highest Risk is Associated with Cephalosporin and Fluoroquinolone Use) (Emerg Infect Dis, 2007) [MEDLINE] (J Antimicrob Chemother, 1998) [MEDLINE] (Infect Control Hosp Epidemiol, 1996) [MEDLINE]
        • In a UK Case-Control Study, the Odds Ratio of MRSA Diagnosis for Patients Who were Prescribed 1, 2-3, or ≥4 antimicrobial drugs were 1.57 (95% CI: 1.36-1.80), 2.46 (CI: 2.15-2.83), and 6.24 (95% CI: 5.43-7.17), Respectively (Emerg Infect Dis, 2007) [MEDLINE]
        • In a UK Case-Control Study, the Risk for Community-Acquired MRSA Increased with the Number of Antimicrobial Drug Prescriptions, Appeared to Vary According to Antimicrobial Drug Classes Prescribed During the Previous Year, and was Highest for Fluoroquinolone (Odds Ratio 3.37; CI: 2.80-4.09) and Macrolides (Odds Ratio 2.50; CI: 2.14-2.91)
    • Indwelling Hemodialysis Catheter/Hemodialysis (see Hemodialysis) (MMWR Morb Mortal Wkly Rep, 2007) [MEDLINE]
    • Proximity to Others with MRSA Colonization or Infection (Ann Intern Med, 1982) [MEDLINE] (Infect Dis Clin North Am, 1989) [MEDLINE] (Clin Infect Dis, 2004) [MEDLINE]
    • Recent Hospitalization (Especially Intensive Care) (Ann Intern Med, 1982) [MEDLINE] (Infect Dis Clin North Am, 1989) [MEDLINE] (Clin Infect Dis, 2004) [MEDLINE]
    • Recent Surgery
    • Residence in Long-Term Care Facility
      • Healthcare-Associated MRSA (HA-MRSA) is Prevalent in Long-Term Care Facility Residents (and They are Frequently Transferred Between Hospitals and Long-Term Care Facilities, Facilitating the Spread of MRSA) (Infect Control Hosp Epidemiol, 1995) [MEDLINE]
  • Factors Associated with Community-Associated MRSA (CA-MRSA) Outbreaks
    • Childcare Center Use
    • Close Contact with Others with MRSA Colonization or Infection
    • Incarceration
    • Men Who Have Sex with Men
    • Military Service
    • Residence in Native/Aboriginal Community
    • Sharing Needles (Injection Drug Abuse)/Razors/Tattooing/Body Shaving/Other Sharp Objects (see Injection Drug Abuse)
    • Sharing Sports Equipment
  • Other Factors
    • Human Immunodeficiency Virus (HIV) Infection (see Human Immunodeficiency Virus)
      • HIV Infection Increases the Risk of MRSA Colonization and Infection
      • Risk Factors for MRSA Infection in the Setting of HIV Infection (J Acquir Immune Defic Syndr, 2005) [MEDLINE]
        • Advanced Immunosuppression (CD4 Count <50 cells/microL)
        • High Plasma HIV RNA (>100,000 Copies/microL)
        • Lack of Antiretroviral Therapy

Healthcare-Associated Methicillin-Resistant Staphylococcus Aureus (HA-MRSA) vs Community-Associated Methicillin-Resistant Staphylococcus Aureus (CA-MRSA) Infection

  • General Comments
    • Patients Can Develop MRSA Colonization in the Hospital and Manifest Infection While in the Community
    • Alternately, Patients Can Develop MRSA Colonization in the Community and Then Manifest Infection in the Hospital
      • In a Review of 352 Patients with HA-MRSA, the Percentage of Isolates with CA-MRSA Molecular Typing Increased from 17% to 56% Between 1999-2004 (Emerg Infect Dis, 2007) [MEDLINE]
  • Healthcare-Associated Methicillin-Resistant Staphylococcus Aureus (HA-MRSA) Infection: HA-MRSA is defined as an MRSA infection which occurs >48 hrs following hospitalization (hospital-onset HA-MRSA) or an MRSA infection which occurs outside of the hospital within 12 mos of exposure to health care such as a history of surgery/hospitalization/dialysis/residence in a long-term care facility (community-onset HA-MRSA) (JAMA, 2007) [MEDLINE]
    • Epidemiology
      • MRSA is the Leading Etiology of Surgical Site Infections in Both Community and Tertiary Hospitals
      • Since the 1960’s, HA-MRSA Has Been a Problem in Hospital Settings with a Progressive Increase in the Prevalence of Antimicrobial Resistance in Hospital-Acquired Staphylococcus Aureus Infections
        • In a US Study of Over 24,000 Cases of Hospital-Acquired Staphylococcus Aureus Bloodstream Infections, MRSA Isolates Increased from 22% to 57% Between 1995 and 2001 (Clin Infect Dis, 2004) [MEDLINE]
        • In a VA Study Employing Multifaceted Infection Control Measures Between 2005-2017, There was a 43% Decline in Staphylococcus Aureus Infections (Accounted for Mostly by a 55% Decrease in MRSA Infections) (MMWR Morb Mortal Wkly Rep, 2019) [MEDLINE]
    • Risk Factors for HA-MRSA Infection (Ann Intern Med, 1982) [MEDLINE] (Infect Dis Clin North Am, 1989) [MEDLINE] (Clin Infect Dis, 2004) [MEDLINE]
      • Antibiotic Use
      • Hemodialysis
      • Intensive Care
      • MRSA Colonization
      • Prolonged Hospitalization
      • Proximity to Others with MRSA Colonization or Infection
    • Risk Factors for Post-Discharge MRSA Infection (Clin Infect Dis, 2016) [MEDLINE]
      • Discharge to Nursing Home
      • Discharge with a Central Venous Catheter/Other Invasive Device
      • MRSA Colonization
      • Presence of a Chronic Wound
    • Microbiology
      • HA-MRSA Strains Tend to Possess Multidrug Resistance and Carry Staphylococcal Cassette Chromosome (SCCmec) Type II (JAMA, 2003) [MEDLINE]
      • HA-MRSA Strains Generally Demonstrate a USA100 or USA200 Pulse-Field Electrophoresis (PFGE) Pattern
    • Clinical
      • HA-MRSA is Associated with Severe, Invasive Disease (Such as Skin/Soft Tissue Infection, Bloodstream Infection, and Pneumonia) and is Routinely Implicated in Nearly Every Type of Hospital-Acquired Infection (Ventilator-Associated Pneumonia, Skin/Soft Tissue Infection, etc)
        • Due to Propensity of MRSA to Form Biofilms on Invasive Devices (Such as Endotracheal Tubes, Urinary Catheters, and Intravascular Catheters) (Clin Infect Dis, 2007) [MEDLINE]
        • Biofilms Facilitate MRSA Survival and Multiplication on Surfaces, Prolonging the Duration of Organism Exposure to Antibiotics and Facilitating the Potential Transfer of Antibiotic Resistance Genes Between Organisms
    • Prognosis
      • Patients with MRSA Infection Have Higher Mortality, Longer Hospital Stays, and Higher Health Care Costs, as Compared to Patients with MSSA Infection (Arch Intern Med, 2002) [MEDLINE]
  • Community-Associated Methicillin-Resistant Staphylococcus Aureus (CA-MRSA) Infection: defined as an MRSA infection which occurs in the absence of healthcare exposure (JAMA, 2007) [MEDLINE]
    • Epidemiology
      • CA-MRSA was Initially Reported in Injection Drug Users in the Early 1980’s, But Has Since Become the Most Common Etiology of Skin/Soft Tissue Infections Presenting to US Emergency Departments and Ambulatory Clinics
      • USA300 Appears to Be More Transmissible Among Household Members than Other CA-MRSA Types
      • Community Outbreaks Have Been Reported in Multiple Settings (Including Native/Aboriginal Communities, Sports Teams, Childcare Centers, Military Personnel, Meen Who Have Sex with Men, and Prison Inmates and Guards) (JAMA, 2001) [MEDLINE] (NEJM, 2005;352(5):468 [MEDLINE] (Ann Intern Med, 2008) [MEDLINE] (Clin Infect Dis, 2009) [MEDLINE]
      • Animals Have Also Been Identified as a Source of CA-MRSA Transmission
      • However, Many Patients with CA-MRSA Have No Identifiable Risk Factors (Clin Infect Dis, 2007) [MEDLINE]
    • Risk Factors for CA-MRSA (with Relatively Poor Predictive Value for CA-MRSA) (J Infect Dis, 1998) [MEDLINE] (JAMA, 1998) [MEDLINE] (MMWR Morb Mortal Wkly Rep, 2001) [MEDLINE] (JAMA, 2001) [MEDLINE] (JAMA, 2003) [MEDLINE] (MMWR Morb Mortal Wkly Rep, 2003) [MEDLINE] (J Clin Microbiol, 2004) [MEDLINE] (Clin Infect Dis, 2004) [MEDLINE] (NEJM, 2005) [MEDLINE] (NEJM, 2005) [MEDLINE] (Lancet Infect Dis, 2006) [MEDLINE] (MMWR Morb Mortal Wkly Rep, 2006) [MEDLINE] (Clin Infect Dis, 2015) [MEDLINE] (MMWR Morb Mortal Wkly Rep, 2018) [MEDLINE]
      • Close Contact with Others with MRSA Colonization or Infection
      • Cosmetic Body Shaving
      • Incarceration
      • Sharing Equipment Which is Not Cleaned Between Users
      • Skin Trauma (Abrasions, Lacerations, Tattoos, Injection Drug Abuse)
    • Microbiology
      • CA-MRSA Strains Frequently Carry the SCCmec Type IV or V and Frequently Carry Genes for the Panton-Valentine Leukocidin (PVL) Cytotoxin Which Confers Enhanced Virulence (Lancet, 2006) (Antimicrob Agents Chemother, 2002) [MEDLINE] ( Lancet, 2002) [MEDLINE] [MEDLINE] (J Clin Microbiol, 2006) [MEDLINE] (J Infect Dis, 2006) [MEDLINE] (Ann Intern Med, 2006) [MEDLINE]
      • CA-MRSA Strains Generally Demonstrate a USA300 or USA400 Pulse-Field Electrophoresis (PFGE) Pattern
    • Clinical
      • CA-MRSA is Most Commonly Associated with Skin and Soft Tissue Infections in Young Healthy Patients (NEJM, 2005) [MEDLINE]
      • CA-MRSA Has Also Been Associated with Necrotizing Pneumonia, Osteomyelitis, Urinary Tract Infection, Infective Endocarditis, and Sepsis (with or without Waterhouse-Friderichsen Syndrome)
    • Treatment
      • Most CA-MRSA Strains are Sensitive to Non-β-Lactam Antibiotics
        • However, Drug-Resistant Isolates Have Been Reported in Men Who Have Sex with Men (Isolates Contain the pUSA03 Plasmid, Which Carries Resistance Genes for β-Lactams, Fluoroquinolones, Tetracycline, Macrolides, Clindamycin, and Mupirocin) (Lancet, 2006) [MEDLINE] (Ann Intern Med, 2008) [MEDLINE]

Physiology

Staphylococcus Aureus Colonization (Carriage)

Sites of Staphylococcus Aureus Colonization (Eur J Clin Microbiol Infect Dis, 2001) [MEDLINE] (J Clin Microbiol, 2006) [MEDLINE] (Diagn Microbiol Infect Dis, 2008) [MEDLINE]

  • Anterior Nares
    • Anterior Nares are the Primary Site of Colonization
    • A Majority of Individuals with Nasal Colonization are Also Colonized on Other Areas of Intact Skin (Such as the Hands, Axillae, Perineum, and in the Umbilicus in Infants)
  • Other Anatomic Sites
    • General Comments
      • These Other Non-Nasal Sites (Oropharynx, Axilla, etc) Have Lower Sensitivity for the Detection of Staphylococcus Aureus Possibly Due to Lower Staphylococcus Aureus Colonization Rates or Higher Quantities of Competing Microbiologic Flora at these Sites
    • Oropharynx
      • Some Studies Suggest that Oropharyngeal Colonization May Occur without Nasal Colonization (Thereby Being Missed on Routine Nasal Screening)
        • Swiss Study of Sites of Staphylococcus Aureus Colonization (n = 3,464) (Arch Intern Med, 2009) [MEDLINE]: 48% of Patients were Staphylococcus Aureus Nasal Carriers, While 12% of Patients were Exclusive Staphylococcus Aureus Throat Carriers
    • Axilla
    • Decubitus Ulcer (see Decubitus Ulcer)
    • Genitourinary Tract
    • Groin/Perineum
    • Intravascular Catheter (Central Venous Catheter, Arterial Line, etc)/Invasive Device
    • Sputum
    • Stool

Incidence of Nasal Methicillin-Resistant Staphylococcus Aureus (MRSA) Colonization

  • Study Using Data from the National Health and Nutrition Examination Survey (NHANES) in the Early 2000’s (J Infect Dis, 2008) [MEDLINE]
    • Prevalence of Colonization with Staphylococcus Aureus Decreased from 32.4% in 2001-2002 to 28.6% in 2003-2004 (p < 0.01)
    • Prevalence of Colonization with Methicillin-Resistant Staphylococcus Aureus (MRSA) Increased from 0.8% to 1.5% (p < 0.05)
    • Risk Factors for MRSA Colonization in Males
      • Healthcare Exposure
    • Risk Factors for MRSA Colonization in Females
      • Having Been Born in the US
      • Age ≥60 y/o
      • Diabetes Mellitus
      • Poverty
    • In 2003-2004, 19.7% (95% CI: 12.4%-28.8%) of MRSA-Colonized Persons Carried a Pulse-Field Gel Electrophoresis (PFGE) Pattern Associated with Community Transmission (i.e. CA-MRSA)
    • Data Suggest that Community-Associated (CA-MRSA) May Cause Disease in the Absence of Prior Nasal Colonization and/or that CA-MRSA Favors Other Sites of Colonization (Skin, Throat, Gastrointestinal Tract, etc)
    • Nasal MRSA Colonization is Present in Approximately 7% of Hospitalized Patients in the US (Am J Infect Control, 2012) [MEDLINE]
    • Nasal MRSA Colonization is Present in Approximately 4-15% of Healthcare Workers (Ann Emerg Med, 2008) [MEDLINE] (Ann Emerg Med, 2008) [MEDLINE]

Duration of Methicillin-Resistant Staphylococcus Aureus (MRSA) Colonization (Infect Control Hosp Epidemiol, 2006) [MEDLINE] (Arch Intern Med, 2009) [MEDLINE] (BMC Infect Dis, 2014) [MEDLINE] (Am J Infect Control, 2014) [MEDLINE] (Clin Infect Dis, 2015) [MEDLINE]

  • Previously Nasal MRSA Colonized Patients Should Be Considered to Be at Risk for Continued Nasal MRSA Carriage for at Least 4 Years (Clin Infect Dis, 2009) [MEDLINE]
    • During the First Year After the Positive Nasal MRSA Culture Result was Obtained, 48.8% of the Patients (95% CI: 45.8%-51.7%) Remained Colonized
    • At 4 Years, 21.2% of the Patients (95% CI: 13.1%-31.4%) Remained Colonized
  • In Other Studies, the Median Time to Nasal MRSA Clearance Has Been Reported to Be Around 88 wks (BMC Infect Dis, 2014) [MEDLINE]
  • Tobacco Smoke Exposure Increases the Degree of Nasal Staphylococcus Aureus Colonization
    • In Experimental Models of Nasal Inoculation, Smokers Had Higher Nasal Staphylococcus Aureus Organism Loads than Non-Smokers (Infect Immun, 2018) [MEDLINE]
      • Smoking Cessation Improved Clearance of Staphylococcus Aureus Nasal Colonization
    • Tobacco Smoke Enhanced Staphylococcus Aureus Biofilm Formation (Sci Rep, 2019) [MEDLINE]

Staphylococcus Aureus Colonization Increases the Risk of Subsequent Staphylococcus Aureus Infection

  • In a Study of Hospitalized Patients (n = 758), Nasal MRSA Colonization Present at the Time of Admission Increased the Risk for MRSA Infection within 1 Year, as Compared to No Staphylococcal Colonization (Relative Risk 9.5; 95% CI: 3.6-25) (Clin Infect Dis, 2004) [MEDLINE]
    • Acquisition of Nasal MRSA Colonization During Hosptalization Also Increased the Risk for Subsequent MRSA Infection within 1 Year, as Compared to No Acquisition (Relative Risk 12; 95% CI: 4.0-38)
  • In the National Nosocomial Infections Surveillance (NNIS) System, Baseline Nasal MRSA Colonization Increased the Risk for MRSA Infection (19%) in the Year Following Hospital Admission, as Compared to 2% in Those without Baseline Nasal MRSA Colonization (Am J Infect Control, 2004) [MEDLINE]
  • In a Large VA Study of MRSA Carriage Rates and MRSA Infection Rates in Hospitalized Patients, MRSA Colonization Significantly Increased the Risk of Subsequent MRSA Infection (Approximatly 60% of MRSA Infections Occurred After Discharge from the Hospital (Clin Infect Dis, 2019) [MEDLINE]
  • Because MRSA Colonization Increases the Risk for MRSA Infection Following Invasive Medical/Surgical Procedures, Preoperative Testing for Nasal MRSA Colonization is Common

Staphylococcus Aureus Transmission

  • Reservoirs for Staphylococcus Aureus Transmission
    • Individuals Colonized with Methicillin-Resistant Staphylococcus Aureus (MRSA)
    • Methicillin-Resistant Staphylococcus Aureus (MRSA)-Contaminated Surfaces
  • Modes of Staphylococcus Aureus Transmission and Colonization (J Clin Pathol, 1961) [MEDLINE] (Eur J Clin Microbiol Infect Dis, 1994) [MEDLINE]
    • Via the Contaminated Hands of Healthcare Workers
      • Most Common Mode of Transmission for Healthcare-Associated MRSA (HA-MRSA)
    • Via Contact with Contaminated Wounds or Dressings of Infected Patients
    • Via Contact with Another Individual’s Colonized Intact Skin
    • Via Contact with Contaminated Inanimate Objects/Fomites (Razors, Towels, Environmental Surfaces, etc)
      • Contaminated Environmental Surfaces are a Common Source for Healthcare-Associated MRSA (HA-MRSA)
      • Contaminated Inanimate Objects/Fomites are a Common Source for Community-Associated MRSA (CA-MRSA)
    • Via Inhalation of Aerosolized Droplets from Chronic Nasal Carriers
  • Transmission of Healthcare-Associated MRSA (HA-MRSA) to Household Contacts
    • Study of Transmission of Healthcare-Associated MRSA (HA-MRSA) to Household Contacts of Patients Who are Colonized on Hospital Discharge (Arch Intern Med, 2009) [MEDLINE]: n = 148 patients discharged to home healthcare
      • 75% of Colonized Patients Cleared the HA-MRSA within 1 yr (Estimated Median Time to Clearance of 282 Days) (95% CI: 233-313 days)
      • Clearance of MRSA was Associated with Self-Sufficiency in Daily Activities (Hazard Ratio 0.63; 95% CI: 0.40-1.00; P = 0.049)
      • Of the 188 included household contacts, 36 acquired MRSA (19.1%)
      • Transmission Occurred in Nearly 20% of Household Contacts
      • Factors Associated with Household MRSA Acquisition
        • Older Age (Adjusted Odds Ratio 1.71 Per Life Decade; 95% CI: 1.32-2.21; P = 0.001)
        • Participation in the Health Care of the Index Patient (Adjusted Odds Ratio 3.58; 95% CI: 1.33-9.62; P = 0.01)

Risk Factors for Nosocomial Staphylococcus Aureus Bacteremia

(mechanical ventilation, underlying malignancy, and severity of illness at the time of ICU admission (by SAPS score) are not risk factors for Staph aureus bacteremia)

Diagnosis

Nasal Methicillin-Resistant Staphylococcus Aureus (MRSA) Testing (see Nasal Methicillin-Resistant Staphylococcus Aureus Testing)

Clinical Efficacy

  • Meta-Analysis of Methicillin-Resistant Staphylococcus Aureus (MRSA) Nasal Screening to Rule Out MRSA Pneumonia (Clin Infect Dis, 2018) [MEDLINE]: n = 1,563 (22 studies)
    • For All MRSA Pneumonia Types
      • Pooled Sensitivity of MRSA Nare Testing for All MRSA Pneumonia Types: 70.9%
      • Pooled Specificity of MRSA Nare Testing for All MRSA Pneumonia Types: 90.3%
      • With a 10% Prevalence of Potential MRSA Pneumonia, the Calculated Positive Predictive Value was 44.8% and the Negative Predictive Value was 96.5%
    • For Community-Acquired Pneumonia (CAP) and Healthcare-Associated MRSA Pneumonia (HCAP)
      • Pooled Sensitivity of MRSA Nare Testing for All MRSA Pneumonia Types: 85%
      • Pooled Specificity of MRSA Nare Testing for All MRSA Pneumonia Types: 92.1%
      • With a 10% Prevalence of Potential MRSA Pneumonia, the Calculated Positive Predictive Value was 56.8% and the Negative Predictive Value was 98.1%
    • For Ventilator-Associated MRSA Pneumonia
      • Pooled Sensitivity of MRSA Nare Testing for All MRSA Pneumonia Types: 40.3%
      • Pooled Specificity of MRSA Nare Testing for All MRSA Pneumonia Types: 93.7%
      • With a 10% Prevalence of Potential MRSA Pneumonia, the Calculated Positive Predictive Value was 35.7% and the Negative Predictive Value was 94.8%
  • Data Supporting the Negative Predictive Value of Rapid Methicillin-Resistant Staphylococcus Aureus (MRSA) Testing are Robust (American Thoracic Society and Infectious Diseases Society of America 2019 Clinical Practice Guidelines for the Diagnosis and Treatment of Adults with Community-Acquired Pneumonia) (Am J Respir Crit Care Med, 2019) [MEDLINE]
    • Treatment for Methicillin-Resistant Staphylococcus Aureus (MRSA) Pneumonia Can Generally Be Withheld When the Nasal Methicillin-Resistant Staphylococcus Aureus (MRSA) Swab is Negative, Especially in Non-Severe Community-Acquired Pneumonia
    • However, the Positive Predictive Value of Methicillin-Resistant Staphylococcus Aureus (MRSA) Culture is Not as High
      • Therefore, When the Nasal Methicillin-Resistant Staphylococcus Aureus (MRSA) Swab is Positive, Coverage for Methicillin-Resistant Staphylococcus Aureus (MRSA) Pneumonia Should Generally Be Initiated (In the Specific Clinical Situations Noted Below), But Blood/Sputum Cultures Should Be Obtained and Therapy Deescalated if Cultures are Negative

Clinical Manifestations

Cardiovascular Manifestations

Automatic Implantable Cardioverter-Defibrillator (AICD) or Cardiac Pacemaker Infection (see Automatic Implantable Cardioverter-Defibrillator and Cardiac Pacemaker)

  • Epidemiology
    • In Patients with a Cardiac Device Who Have Staphylococcus Aureus Bacteremia, Rate of Device Infection Can Be as High as 45%
  • Mechanism of Infection
    • Contamination During Implantation
    • Hematogenous Seeding (via Bacteremia)

Endocarditis (see Endocarditis)

  • Epidemiology
    • Staphylococcus Aureus is the Most Common Etiology of Infective Endocarditis in Resource-Rich Settings (JAMA, 2005) [MEDLINE] (Eur J Clin Microbiol Infect Dis, 2016) [MEDLINE] (Open Forum Infect Dis, 2021) [MEDLINE]
    • Incidence of Endocarditis in the Setting of Staphylococcus Aureus Bacteremia is About 10-15% (J Am Coll Cardiol, 1997) [MEDLINE] (J Clin Oncol, 2000) [MEDLINE] (Arch Intern Med, 2003) [MEDLINE] (Medicine-Baltimore, 2003) [MEDLINE] (Am Heart J, 2004) [MEDLINE] (J Heart Valve Dis, 2005) [MEDLINE] (JAMA, 2014) [MEDLINE] (Am J Med, 2005) [MEDLINE]
    • Risk Factors for Infective Endocarditis in the Setting of Staphylococcus Aureus Bacteremia (Ann Intern Med, 1993) [MEDLINE] (J Clin Oncol, 2000) [MEDLINE] (Mayo Clin Proc, 2007) [MEDLINE] (PLoS One, 2015) [MEDLINE]
      • Bacteremia of Unclear Origin
      • Intravascular Catheter Infection
      • Intravenous Drug Abuse (IVDA)
      • Persistent Bacteremia
      • Pre-Existing Cardiac Abnormality
      • Prosthetic Heart Valve
    • Infective Endocarditis Due to Staphylococcus Aureus is More Severe Than Infective Endocarditis Due to Other Organisms (Heart, 2005) [MEDLINE]
      • Staphylococcus Aureus Infective Endocarditis Has a Higher Incidence of Sepsis
      • Staphylococcus Aureus Infective Endocarditis Has a Higher Incidence of Major Neurologic Events
      • Staphylococcus Aureus Infective Endocarditis Has a Higher Incidence of Multi-Organ Failure
      • Staphylococcus Aureus Infective Endocarditis Has a Higher Mortality Rate: 34% (vs 10% with other organisms)
  • Mechanism of Infection
    • Hematogenous Seeding (Via Bacteremia)

Dermatologic Manifestations

Cellulitis (see Cellulitis)

  • Epidemiology
    • Staphylococcus Aureus is the Most Common Organism Isolated from Purulent Cellulitis, Skin Abscess, and Surgical Site Infection (Clin Microbiol Rev, 2015) [MEDLINE] (Nat Rev Microbiol, 2019) [MEDLINE]
  • Mechanism of Infection
    • Skin Breach

Erysipelas (see Erysipelas)

  • Mechanism of Infection
    • Skin Breach

Folliculitis

  • Mechanism of Infection
    • Skin Breach

Hidradenitis Suppurativa

  • Mechanism of Infection
    • Skin Breach

Impetigo (see Impetigo)

  • Mechanism of Infection
    • Skin Breach

Mastitis (see Mastitis)

  • Mechanism of Infection

Purpura Fulminans (see Purpura Fulminans)

  • Mechanism

Scarlet Fever (see Scarlet Fever)

  • Epidemiology: less common etiology of scarlet fever than Streptococcus Pyogenes
  • Mechanism:

Skin Abscess (see Skin Abscess)

  • Epidemiology
    • Staphylococcus Aureus is the Most Common Organism Isolated from Purulent Cellulitis, Skin Abscess, and Surgical Site Infection (Clin Microbiol Rev, 2015) [MEDLINE] (Nat Rev Microbiol, 2019) [MEDLINE]
  • Mechanism of Infection
    • Skin Breach

Staphylococcal Scalded Skin Syndrome (Ritter Disease) (see Staphylococcal Scalded Skin Syndrome)

  • Mechanism of Infection
    • Skin Breach

Surgical Site Infection

  • Epidemiology
    • Staphylococcus Aureus is the Most Common Organism Isolated from Purulent Cellulitis, Skin Abscess, and Surgical Site Infection (Clin Microbiol Rev, 2015) [MEDLINE] (Nat Rev Microbiol, 2019) [MEDLINE]
  • Mechanism of Infection
    • Skin Breach
  • Clinical
    • Superficial Skin/Soft Tissue Infections Caused by Staphylococcus Aureus Usually Present with Purulence or Abscess

Gastroenterologic Manifestations

Staphylococcus Aureus Toxinosis

  • Mechanism
    • Ingestion of Food-Borne Toxin
  • Clinical
    • Diarrhea

Hematologic Manifestations

Hemolytic Anemia (see Hemolytic Anemia)

  • Physiology
    • Due to Mechanical Red Blood Cell Destruction

Splenic Abscess (see Splenic Abscess)

  • Mechanism of Infection
    • Hematogenous Seeding (Via Bacteremia)

Neurologic Manifestations

Intracranial Epidural Abscess (see Intracranial Epidural Abscess)

  • Epidemiology
    • Usually Results from Neurosurgical Intervention
  • Mechanism of Infection
    • XXXXX

Meningitis (see Meningitis)

  • Mechanisms of Infection
    • Neurosurgical Intervention: most common mechanism
    • Hematogenous Seeding (Via Bacteremia): less common mechanism

Spinal Epidural Abscess (see Spinal Epidural Abscess)

  • Mechanisms of Infection
    • Hematogenous Seeding (Via Bacteremia)
    • Direct Extension from Contiguous Source

Otolaryngologic Manifestations

Acute Hospital-Acquired Bacterial Rhinosinusitis (see Acute Rhinosinusitis)

  • Epidemiology –XXXX

Pulmonary Manifestations

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

  • Epidemiology
    • XXXX

Bronchiolitis Obliterans (see Bronchiolitis Obliterans)

  • Epidemiology
    • Cases Have Been Reported in Patients with Influenza and Staphylococcus Aureus Co-Infection (Arch Bronconeumol, 2017) [MEDLINE]

Interstitial Pneumonia (see Interstitial Lung Disease)

  • Epidemiology
    • XXXX
  • Clinical

Necrotizing Pneumonia (see Necrotizing Pneumonia and Pulmonary Gangrene)

  • Epidemiology
    • Community-Associated MRSA (CA-MRSA) Infection is Often Associated with Severe Necrotizing Pneumonia (Clin Infect Dis, 2002) [MEDLINE] (Lancet, 2002) [MEDLINE] (Clin Infect Dis, 2005) [MEDLINE] (Emerg Infect Dis, 2006) [MEDLINE] (Clin Infect Dis, 2007) [MEDLINE] (MMWR Morb Mortal Wkly Rep, 2007) [MEDLINE] (Clin Infect Dis, 2008) [MEDLINE] (Chest, 2010) [MEDLINE]
  • Physiology
    • The Tendency to Produce Necrotizing Pneumonia Has Been Suggested to Be Mediated Via by the Panton-Valentine Leukocidin (PVL) Toxin, Which is Typically Present in Community-Associated MRSA (CA-MRSA) Strains (Lancet, 2002) [MEDLINE] (Clin Infect Dis, 2005) [MEDLINE] (Emerg Infect Dis, 2006) [MEDLINE] (MMWR Morb Mortal Wkly Rep, 2007) [MEDLINE]
      • However, Later Studies Have Disproven the Role of PVL as a Virulence Factor in MRSA Pneumonia (PLoS One, 2008) [MEDLINE] (J Infect Dis, 2010) [MEDLINE] (Lancet, 2010) [MEDLINE] (Am J Pathol, 2010) [MEDLINE] (Clin Infect Dis, 2011) [MEDLINE]
  • Diagnosis

Necrotizing Tracheobronchitis (see Acute Bronchitis)

  • Epidemiology
    • Cases of Necrotizing Tracheobronchitis Have Been Reported in the Setting of Influenza and Staphylococcus Aureus Co-Infection (see Influenza Virus) (Int J Legal Med, 2005) [MEDLINE] (Tuberc Respir Dis (Seoul), 2015) [MEDLINE] (J Bronchology Interv Pulmonol, 2017) [MEDLINE] (Infection, 2018) [MEDLINE]

Pneumatocele (see Cystic-Cavitary Lung Lesions)

Community-Acquired Pneumonia (CAP) (see Community-Acquired Pneumonia)

  • Epidemiology
    • EMERGEncy ID NET Study of Staphylococcus Aureus Community-Acquired Pneumonia in the Emergency Department Setting (Clin Infect Dis, 2012) [MEDLINE]: n = 627 patients with community-acquired pneumonia from 12 university-affiliated emergency departments during the winter-spring of 2006 and 2007
      • A Pathogen was Identified in 17% of Cases
      • Staphylococcus Aureus was Isolated in 4% of All Cases
        • MSSA: 2% of All Cases
        • MRSA: 2.4% (Range: 0-5%) of All Cases
        • MRSA was Isolated in 5% of Cases Admitted to the Intensive Care Unit
      • Features Associated with MRSA Isolation
        • Patient History of MRSA
        • Nursing Home Admission in the Previous Year
        • Close Contact in the Previous Month with Someone with a Skin Infection
        • Multiple Infiltrates or Cavities on Chest Radiograph
        • Comatose State
        • Death in the Emergency Department
    • Multi-Country Global Initiative for Methicillin-Resistant Staphylococcus Aureus Pneumonia (GLIMP) Study in Community-Dwelling Adults (Requiring Hospitalization) (Lancet Infect Dis, 2016) [MEDLINE]: n = 3193 community-dwelling adult patients hospitalized for pneumonia
      • MRSA Accounted for Approximately 3% of Community-Acquired Pneumonias (Requiring Hospitalization) in Community-Dwelling Adults
        • Prevalence Varied Across Countries in the Study
      • Risk Factors Associated with MRSA Pneumonia
        • Previous MRSA Infection/Colonization (Odds Ratio 6.21; 95% CI: 3.25-11.85)
        • Recurrent Skin Infections (2.87, ; 95% CI: 1.10-7.45)
        • Severe Pneumonia (2.39, ; 95% CI: 1.55-3.68)
      • Among All Staphylococcus Aureus Isolates, 49% were MSSA and 51% were MRSA
    • Vanderbilt Study of Staphylococcus Aureus Community-Acquired Pneumonia (Requiring Hospitalization) in Adults (Clin Infect Dis, 2016) [MEDLINE]: n = 2259 hospitalized adults with community-acquired pneumonia
      • Staphylococcus Aureus Accounted for 1.6% of Community-Acquired Pneumonias (Requiring Hospitalization) in Adults
        • MSSA: 1.0%
        • MRSA: 0.7%
      • Streptococcus Pneumoniae Accounted for 5.1% of Community-Acquired Pneumonias (Requiring Hospitalization) in Adults
      • Vancomycin/Linezolid was Administered to 29.8% of Patients within the First 3 Days of Hospitalization
      • Chronic Hemodialysis Use was More Common Among Patients with MRSA (20.0%) than Pneumococcal (2.6%) and All-Cause Non-Staphylococcus Aureus (3.7%) CAP
      • Otherwise, Clinical Features at Admission were Similar (Including Concurrent Influenza Infection, Hemoptysis, Multilobar Infiltrates, and Prehospital Antibiotics)
      • Patients with MRSA CAP Had More Severe Clinical Outcomes Than Those with Pneumococcal CAP, Including Intensive Care Unit Admission (86.7% vs 34.8%) and Inpatient Mortality (13.3% vs 4.4%)
    • Community-Acquired Staphylococcus Aureus Pneumonia is Usually a Post-Influenza Pneumonia (see Influenza Virus) (Clin Infect Dis, 2005) [MEDLINE] (Emerg Infect Dis, 2006) [MEDLINE] (MMWR Morb Mortal Wkly Rep, 2007) [MEDLINE] (Ann Emerg Med, 2009) [MEDLINE] (Infect Dis Clin North Am, 2013) [MEDLINE]
  • Mechanisms of Infection
    • Seeding of Airways From Staphylococcus Aureus Colonization of Nares/Skin
      • Particularly Occurs in Hospitalized Patients Due to Intubation or Other Respiratory Tract Procedures
    • Right-Sided Endocarditis with Septic Emboli to Lungs
  • Clinical
  • Clinical Case
  • Prognosis
    • Some Studies Report that MRSA Pneumonia has a Higher Mortality Rate than MSSA Pneumonia (Eur Resp J, 2008) [MEDLINE]
      • However, the Observed Mortality Differences May Be Due to the Confounding Variable of Appropriateness of the Initial Antibiotic (Chest, 2005) [MEDLINE]

Tracheobronchitis (see Acute Bronchitis)

  • Epidemiology
    • Staphylococcus Aureus Tracheobronchitis Has Been Described in Patients with Acute COPD Exacerbation (J Antimicrob Chemother, 1995) [MEDLINE] (Curr Med Res Opin, 2007) [MEDLINE] (see Chronic Obstructive Pulmonary Disease)
    • Staphylococcus Aureus Tracheobronchitis May Occur Following Airway Instrumentation (Tracheostomy, Endotracheal Intubation) or Associated
    • MRSA Tracheobronchitis Has Been Reported in a Patient with Tracheobronchomalacia (Respiration, 2010) [MEDLINE]
    • Staphylococcus Aureus Tracheobronchitis Has Been Reported in an Immunocompromised Patient on Infliximab (Klin Padiatr, 2015) [MEDLINE]
  • Clinical
    • XXXXXXX

Renal Manifestations

Acute Interstitial Nephritis (see Acute Interstitial Nephritis)

  • Epidemiology
    • XXXX

Staphylococcus Aureus Bacteriuria (see Urinary Tract Infection)

  • Epidemiology
    • XXXX
  • Mechanisms of Infection
    • Ascending Infection Due to Foley Catheter
    • Hematogenous Seeding (via Bacteremia)
  • Clinical
    • In Presence of Foley Catheter: in absence of systemic signs of infection, work-up for bacteremia is not necessary
    • In Absence of Foley Catheter: may be indicative of bacteremia, therefore, work-up for bacteremia is required

Reproductive Manifestations

Postpartum Endometritis (see Postpartum Endometritis)

  • Epidemiology
    • XXXX
  • Clinical
    • XXXXX

Rheumatologic/Orthopedic Manifestations

Necrotizing Fasciitis (see Necrotizing Fasciitis)

  • Mechanism of Infection
    • XXXX

Osteomyelitis (see Osteomyelitis)

  • Mechanisms of Infection
    • Hematogenous Seeding (via Bacteremia): usually vertebral osteomyelitis (possibly with associated Discitis or spinal epidural abscess)
    • Direct Extension from Contiguous Source

Prosthetic Septic Arthritis (see Septic Arthritis)

  • Mechanisms of Infection
    • Early Infection (<3 mo after Surgery):
    • Delayed Infection (3-12 mo After Surgery): usually due to acquisition during implantation
    • Late Infection (>12 mo After Surgery): usually due to hematogenous seeding of joint (via bacteremia)

Pyomyositis (see Pyomyositis)

  • Mechanism of Infection
    • Hematogenous Seeding (via Bacteremia)

Septic Arthritis (see Septic Arthritis)

  • Mechanism of Infection
    • Direct Inoculation of Joint During Joint Surgery
    • Extension of Bone Infection Into Joint Space
    • Hematogenous Seeding (via Bacteremia): most common mechanism
      • Joint Space Synovium is Highly Vascular But Lacks a Basement Membrane
    • Joint Trauma

Septic Bursitis (see Septic Bursitis)

  • Epidemiology
    • XXXX
  • Clinical
    • XXXXX

Vascular Manifestations

Bacteremia (see Bacteremia)

  • Epidemiology
    • Staphylococcus Aureus Bacteremia is Defined as a Blood Culture Positive for Staphylococcus Aureus
    • Staphylococcus Aureus is a Common Etiology of Both Community-Acquired and Hospital-Acquired Bacteremia
  • Physiologic Mechanisms (NEJM, 1998) [MEDLINE] (Clin Infect Dis, 2005) [MEDLINE]
    • Primary Staphylococcus Aureus Infection (of Skin/Soft Tissue/Bone/Joint/Pneumonia/Vascular Catheter) with Subsequent Bacteremia
    • Staphylococcus Aureus Bacteremia with Seeding of a Previously Sterile Site (Heart Valve/Prosthetic Device/Spinal Epidural Space)
  • Clinical

Intravascular Catheter Infection

Thrombophlebitis (see Thrombophlebitis)

  • Clinical
    • Erythema/Pain at Site of Catheter
    • Cord

Other Manifestations

Staphylococcal Toxic Shock Syndrome (see Staphylococcal Toxic Shock Syndrome)

  • xxxxx

Waterhouse-Friderichsen Syndrome (see Waterhouse-Friderichsen Syndrome)

  • xxx

Henoch-Schonlein Purpura (HSP) (see Henoch-Schonlein Purpura)

  • Mechanism
    • May Be Due to Staphylococcus Aureus Superantigen Action on T-Cells

Prevention

Prevention of Methicillin-Resistant Staphylococcus Aureus (MRSA) Infection in the ICU

  • Agents
  • Clinical Efficacy
    • Randomized Evaluation of Decolonization versus Universal Clearance to Eliminate MRSA (REDUCE MRSA) Trial (from CDC Prevention Epicenters Program and the AHRQ DECIDE Network and Healthcare-Associated Infections Program) of Universal vs Targeted Decolonization to Prevent Infections in the ICU (NEJM, 2013) [MEDLINE]
      • Universal Decolonization (Daily Chlorhexidine Bathing + Nasal Mupirocin BID) was the Most Effective Strategy to Prevent the Rate of MRSA Isolates and Bloodstream Infection from Any Pathogen
      • Targeted Decolonization of MRSA Carriers (Daily Chlorhexidine Bathing + Nasal Mupirocin BID) was the Second Most Effective Strategy to Prevent the Rate of MRSA Isolates and Bloodstream Infection from Any Pathogen
      • MRSA Screening and Isolation of MRSA Carriers was the Least Effective Strategy to Prevent the Rate of MRSA Isolates and Bloodstream Infection from Any Pathogen: this strategy did not decrease the rate of any infections
      • Universal Decolonization Prevented 1 Bloodstream Infection Per Each 54 Patients
      • Adverse Events, Which Occurred in 7 Patients, Were Mild and Related to Chlorhexidine
    • Trial of Body Surface Decolonization on Bacteriuria and Candiduria in the ICU (Lancet Infect Dis, 2016) [MEDLINE]
      • Universal Decolonization (Chlorhexidine) and Short-Course Nasal Mupirocin Significantly Decreased Candiduria and Any Bacteriuria, But Not for Women

Treatment of Methicillin-Sensitive Staphylococcus Aureus (MSSA)

Anti-Staphylococcal (Penicillinase-Resistant) Penicillins (see Penicillins)

  • Nafcillin (see Nafcillin): one of the preferred agents for treatment of MSSA
  • Oxacillin (see Oxacillin): one of the preferred agents for treatment of MSSA

Other Penicillins (see Penicillins)

Carbapenems (see Carbapenems)

Cephalosporins (see Cephalosporins)

  • Cefazolin (Ancef) (see Cefazolin): one of the preferred agents for treatment of MSSA
  • Cefepime (Maxipime) (see Cefepime)

Fluoroquinolones (see Fluoroquinolones)

Treatment of Methicillin-Resistant Staphylococcus Aureus (MRSA)

Uncomplicated Methicillin-Resistant Staphylococcus Aureus (MRSA) Bacteremia

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Definition
    • Positive Blood Cultures for MRSA
    • Exclusion of Endocarditis
    • No Implanted Prosthetics
    • Follow-Up Negative Blood Cultures 2-4 Days After Initial Set
    • No Metastatic Foci of Infection
    • Defervescence within 72 hrs of Initiating Effective Therapy
  • Agents
    • Vancomycin IV (see Vancomycin): 2 wk course (A-II Recommendation)
    • Daptomycin (Cubicin) IV (see Daptomycin): 6 mg/kg/IV qday x 2 wk course (A-I Recommendation)

Complicated Methicillin-Resistant Staphylococcus Aureus (MRSA) Bacteremia

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis. 2011) [MEDLINE]

  • Definition
    • Patients with Positive Blood Cultures for MRSA Who Do Not Meet the Criteria for Uncomplicated Bacteremia
  • Agents
    • Vancomycin IV (see Vancomycin): 4-6 wk course
    • Daptomycin (Cubicin) IV (see Daptomycin): 6 mg/kg/IV qday x 4-6 wk course
      • Some Experts Recommend 8-10 mg/kg/IV qday x 4-6 wk course (B-III Recommendation)

Methicillin-Resistant Staphylococcus Aureus (MRSA) Native Valve Infective Endocarditis (see Endocarditis)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Agents
    • Vancomycin IV (see Vancomycin): 6 wk course (A-II Recommendation)
    • Daptomycin (Cubicin) IV (see Daptomycin): 6 mg/kg/IV qday x 6 wk course (A-I Recommendation)
      • Some Experts Recommend 8-10 mg/kg/IV qday x 6 wk course (B-III Recommendation)
  • Other Recommendations
    • Addition of Gentamicin to Vancomycin is Not Recommended for the Treatment of MRSA Bacteremia or Native Valve Endocarditis (A-II Recommendation)
    • Addition of Rifampin to Vancomycin is Not Recommended for the Treatment of MRSA Bacteremia or Native Valve Endocarditis (A-I Recommendation)
    • Additional Blood Cultures 2-4 Days After Initial Positive Set Should Be Obtained to Document Clearance of Bacteremia (A-II Recommendation)
    • Echocardiogram (Transesophageal Preferred Over Transthoracic Echocardiogram) is Recommended for All Patients with MRSA Bacteremia (A-III Recommendation)
    • Evaluation for Valve Replacement is Recommended for Large Vegetation (>10 mm Diameter), Occurrence or ≥1 Embolic Event During the First 2 Weeks of Therapy, Severe Valvular Insufficiency, or Valvular Perforation or Dehiscence Decompensated Heart Failure, Perivalvular or Myocardial Abscess, New Heart Block, or Persistent Fevers or Bacteremia (A-II Recommendation)

Methicillin-Resistant Staphylococcus Aureus (MRSA) Prosthetic Valve Infective Endocarditis (see Endocarditis)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Agents
    • Combination Vancomycin IV + Rifampin PO/IV 300 mg q8hrs x 6 wks, with Gentamicin 1 mg/kg IV q8hrs x 2 wks (B-III Recommendation) (see Vancomycin, Rifampin, and Gentamicin)
  • Other Recommendations
    • Early Evaluation for Valve Replacement Surgery is Recommended

Community-Acquired Methicillin-Resistant Staphylococcus Aureus (CA-MRSA) Skin and Soft Tissue Infections (SSTI)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

Outpatient Skin and Soft Tissue Infections (SSTI)
  • Simple Skin Abscess/Boil (see Skin Abscess): incision and drainage is the primary treatment (A-II Recommendation)
    • Antibiotic Therapy is Recommended for Skin Abscess with Any of the Following Characteristics (A-III Recommendation)
      • Abscess in an Area that is Difficult to Drain: such as face, hand, genitalia
      • Associated Comorbidities or Immunosuppression
      • Associated Septic Phlebitis
      • Extremes of Age
      • Lack of Response to Incision and Drainage
      • Rapid Progression in the Presence of Associated Cellulitis
      • Severe or Extensive Disease (Multiple Sites of Infection)
      • Symptoms/Signs of Systemic Illness
  • Outpatient Purulent Cellulitis (Cellulitis Associated with Purulent Drainage/Exudate in the Absence of a Drainable Abscess): antibiotic therapy directed against CA-MRSA is recommended -> 5-10 day course (should be individualized based on patient’s clinical response) (A-II Recommendation)
    • Empiric Therapy Against β-Hemolytic Streptococci is Likely to Be Unnecessary
    • Agents Directed Against CA-MRSA
  • Outpatient Non-Purulent Cellulitis (Cellulitis with No Purulent Drainage/Exudate in the Absence of a Drainable Abscess): antibiotic therapy directed against β-hemolytic streptococci is recommended for -> 5-10 day course (should be individualized based on patient’s clinical response) (A-II Recommendation)
    • The Role of CA-MRSA Coverage in This Setting is Unknown
    • Empiric CA-MRSA Coverage is Recommended for Patients Who Do Not Respond to β-Lactam Therapy and Those with Systemic Toxicity
    • Agents Directed Against Both CA-MRSA and β-Hemolytic Streptococci
  • Other Recommendations
    • Culture from Abscess or Other Purulent SSTI is Recommended in Patients Treated with Antibiotic Therapy, Patients with Severe Local Infection, Patients with Signs of Systemic Toxicity, Patients Who Have Not Responded Adequately to Initial Treatment, or if there is a Concern for Cluster or Outbreak (A-III Recommendation)
    • Use of Rifampin Alone or as an Adjunct for the Treatment of Skin and Soft Tissue Infection is Not Recommended (A-III Recommendation)
Inpatient Complicated Skin and Soft Tissue Infections (cSSTI)
  • Definition
    • Cellulitis
    • Deeper Soft Tissue Infection
    • Infected Ulcers/Burns
    • Major Abscess
    • Surgical/Traumatic Wound Infection
  • Agents
    • Vancomycin IV (see Vancomycin) (A-I Recommendation)
    • Dalbavancin (Dalvance) (see Dalbavancin)
    • Daptomycin (Cubicin) (see Daptomycin): 4 mg/kg/dose IV qday x 7-14 days (A-I Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid): 600 mg BID x 7-14 days (A-I Recommendation)
    • Tedizolid (Sivextro) (see Tedizolid)
    • Telavancin (Vibativ) IV (see Telavancin): 10 mg/kg/dose qday x 7-14 days (A-I Recommendation)
    • Clindamycin PO/IV (see Clindamycin): 600 mg TID x 7-14 days (A-III Recommendation)
  • Other Recommendations
    • Surgical Debridement and Broad-Spectrum Antibiotics are Recommended
    • Culture from Abscess or Other Purulent SSTI is Recommended in Patients Treated with Antibiotic Therapy, Patients with Severe Local Infection, Patients with Signs of Systemic Toxicity, Patients Who Have Not Responded Adequately to Initial Treatment, or if there is a Concern for Cluster or Outbreak (A-III Recommendation)

Methicillin-Resistant Staphylococcus Aureus (MRSA) Community-Acquired Pneumonia (CAP) (see Community-Acquired Pneumonia)

Clinical Efficacy

  • VA Retrospective Multicenter Cohort Study of the Impact of Empiric Anti-MRSA Antibiotic Therapy (within the First Day of Hospitalization) in Patients Hospitalized for Community-Acquired Pneumonia (CAP) (JAMA Intern Med, 2020) [MEDLINE]: n = 88, 605 hospitalized patients (from 2008-2013)
    • VA Study: population consisted of predominantly males (86 ,851 out of 88,605), median age 70 years (interquartile range: 62-81 y/o)
    • Subgroup Analysis was Performed in Patients with Initial Intensive Care Unit Admission, MRSA Risk Factors, Positive Results of a MRSA Surveillance Test, and/or Positive Results of an MRSA Admission Culture
    • Empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR], 1.4 [95% CI, 1.3-1.5]), kidney injury (aRR, 1.4 [95% CI, 1.3-1.5]), and secondary C difficile infections (aRR, 1.6 [95% CI, 1.3-1.9]), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 [95% CI, 1.0-2.3]), and secondary gram-negative rod infections (aRR, 1.5 [95% CI, 1.2-1.8])
    • Empirical Anti-MRSA Antibiotic Therapy was Not Associated with Decreased 30-Day Mortality for Any Group of Patients Hospitalized for Pneumonia

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Recommended Agents
    • Vancomycin IV (see Vancomycin) (A-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid): 600 mg BID (A-II Recommendation)
    • Clindamycin IV/PO (see Clindamycin): 600 mg TID (B-III Recommendation)
      • May Be Used if the Strain is Susceptible

Recommendations for Empiric Antibiotic Therapy for Community-Acquired Pneumonia (American Thoracic Society and Infectious Diseases Society of America 2019 Clinical Practice Guidelines for the Diagnosis and Treatment of Adults with Community-Acquired Pneumonia) (Am J Respir Crit Care Med, 2019) [MEDLINE]

  • Outpatient Adult with Risk Factors for Methicillin-Resistant Staphylococcus Aureus (MRSA) (Prior Respiratory Isolation of Methicillin-Resistant Staphylococcus Aureus or Recent Hospitalization with Intravenous Antibiotics in the Last 90 Days)
    • Monotherapy with Respiratory Fluoroquinolone (Strong Recommendation, Moderate Quality of Evidence)
    • Combination Therapy with β-Lactam and Macrolide (or Doxycycline) (Strong Recommendation, Moderate Quality of Evidence for Combination Therapy with Macrolides; Conditional Recommendation, Low Quality of Evidence for Combination Therapy with Doxycycline)
  • Inpatient Adult with Non-Severe Community-Acquired Pneumonia and Prior Respiratory Isolation of Methicillin-Resistant Staphylococcus Aureus (MRSA)
    • Monotherapy with Respiratory Fluoroquinolone
    • Combination Therapy with β-Lactam and Macrolide (or Doxycycline) (Strong Recommendation, High Quality of Evidence for Combination Therapy with Macrolide; Conditional Recommendation, Low Quality of Evidence for Combination Therapy with Doxycycline)
    • Add Methicillin-Resistant Staphylococcus Aureus Coverage and Obtain Cultures/Nasal PCR to Allow Deescalation or Confirm Need for Continued Methicillin-Resistant Staphylococcus Aureus (MRSA) Therapy
      • Linezolid (see Linezolid): 600 mg PO/IV q12hrs
      • Vancomycin (see Vancomycin): 15 mg/kg IV q12hrs (adjust based on levels)
  • Inpatient Adult with Non-Severe Community-Acquired Pneumonia and Recent Hospitalization with Intravenous Antibiotics and Locally Validated Risk Factors for Methicillin-Resistant Staphylococcus Aureus (i.e Whether Methicillin-Resistant Staphylococcus Aureus is Prevalent in Patients with Community-Acquired Pneumonia and What Risk Factors for Infection are at a Local Hospital/Catchment Area Level) (Strong Recommendation, Moderate Quality of Evidence)
    • Monotherapy with Respiratory Fluoroquinolone
    • Combination Therapy with β-Lactam and Macrolide (or Doxycycline)
    • Obtain Cultures, But Withhold Methicillin-Resistant Staphylococcus Aureus Coverage Unless Culture Results are Positive
      • If Methicillin-Resistant Staphylococcus Aureus Rapid Nasal PCR Testing is Negative, Withhold Additional Empiric Therapy Against Methicillin-Resistant Staphylococcus Aureus
      • If Methicillin-Resistant Staphylococcus Aureus Rapid Nasal PCR Testing is Positive, Add Methicillin-Resistant Staphylococcus Aureus Coverage and Obtain Cultures
  • Inpatient Adult with Severe Community-Acquired Pneumonia and with Prior Respiratory Isolation of Methicillin-Resistant Staphylococcus Aureus (MRSA) or Recent Hospitalization with Intravenous Antibiotics and Locally Validated Risk Factors for Methicillin-Resistant Staphylococcus Aureus (MRSA) Therapy (i.e. Whether Methicillin-Resistant Staphylococcus Aureus is Prevalent in Patients with Community-Acquired Pneumonia and What Risk Factors for Infection are Present at a Local Hospital/Catchment Area Level) (Strong Recommendation, Moderate Quality of Evidence)
    • Combination Therapy with β-Lactam and Macrolide (or Respiratory Fluoroquinolone)
    • Add Methicillin-Resistant Staphylococcus Aureus (MRSA) Coverage and Obtain Cultures/Nasal PCR to Allow Deescalation or Confirmation of Need for Continued Methicillin-Resistant Staphylococcus Aureus MRSA) Therapy
      • Linezolid (see Linezolid): 600 mg PO/IV q12hrs
      • Vancomycin (see Vancomycin): 15 mg/kg IV q12hrs (adjust based on levels)

Methicillin-Resistant Staphylococcus Aureus (MRSA) Empyema (Pleural Effusion-Parapneumonic)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis. 2011) [MEDLINE]

  • Recommended Agents: as above for MRSA pneumonia
  • Pleural Drainage (A-III Recommendation)
    • Chest Tube (see Chest Tube)
    • Surgical Pleural Drainage/Decortication

Methicillin-Resistant Staphylococcus Aureus (MRSA) Meningitis (see Meningitis)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Recommended Agents
    • Vancomycin IV (see Vancomycin): 2 wk course (B-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid): 600 mg BID (B-II Recommendation)
    • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) IV (see Sulfamethoxazole-Trimethoprim): 5 mg/kg q8-12 hrs (C-III Recommendation)
  • Other Recommendations
    • Optional Addition of Rifampin PO/IV (see Rifampin): 600 mg BID (B-III Recommendation)
      • Recommended by Some Experts
    • For Central Nervous System Shunt Infection: shunt removal is recommended and it should not be replaced until cerebrospinal fluid cultures are repeatedly negative (A-II Recommendation)

Methicillin-Resistant Staphylococcus Aureus (MRSA) Brain Abscess/Intracranial Epidural Abscess/Subdural Empyema/Spinal Epidural Abscess (see Brain Abscess, Intracranial Epidural Abscess, Subdural Empyema, and Spinal Epidural Abscess)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Recommended Agents
    • Vancomycin IV (see Vancomycin): 4-6 wk course (B-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid): 600 mg BID (B-II Recommendation)
    • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) IV (see Sulfamethoxazole-Trimethoprim): 5 mg/kg q8-12 hrs (C-III Recommendation)
  • Other Recommendations
    • Optional Addition of Rifampin PO/IV (see Rifampin): 600 mg qday or 300-450 mg BID (B-III Recommendation)
      • Recommended by Some Experts
    • Neurosurgical Evaluation for Incision and Drainage is Recommended (A-II Recommendation)

Methicillin-Resistant Staphylococcus Aureus (MRSA) Septic Thrombosis of Cavernous or Dural Venous Sinus (see xxxx)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Recommended Agents
    • Vancomycin IV (see Vancomycin): 4-6 wk course (B-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid): 600 mg BID (B-II Recommendation)
    • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) IV (see Sulfamethoxazole-Trimethoprim): 5 mg/kg q8-12 hrs (C-III Recommendation)
  • Other Recommendations
    • Optional Addition of Rifampin PO/IV (see Rifampin): 600 mg qday or 300-450 mg BID (B-III Recommendation)
      • Recommended by Some Experts
    • Neurosurgical Evaluation for Incision and Drainage of Contiguous Sites is Recommended (A-II Recommendation)
    • Role of Anticoagulation is Controversial

Methicillin-Resistant Staphylococcus Aureus (MRSA) Osteomyelitis (see Osteomyelitis)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Agents
    • Vancomycin IV (see Vancomycin) (B-II Recommendation)
    • Daptomycin (Cubicin) (see Daptomycin): 6 mg/kg/dose IV qday at least 8 wk course (B-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid): 600 mg BID (B-II Recommendation)
    • Clindamycin IV/PO (see Clindamycin): 600 mg TID (B-III Recommendation)
    • Combination Sulfamethoxazole-Trimethoprim (Bactrim, Septra) 4 mg/kg/dose PO BID + Rifampin 600 mg PO qday (see Sulfamethoxazole-Trimethoprim and Rifampin) (B-II Recommendation)
  • Other Recommendations
    • Surgical Debridement and Drainage of Associated Soft Tissue Abscesses is Recommended (A-II Recommendation)
    • Optional Addition of Rifampin PO/IV (see Rifampin): 600 mg qday or 300-450 mg BID (B-III Recommendation)
      • Recommended by Some Experts
      • For Patients with Concurrent Bacteremia, Rifampin Should Be Added After the Clearance of the Bacteremia
    • Optimal Route of Antibiotic Administration is Unknown (A-III Recommendation)
    • Optimal Duration of Antibiotic Administration is Unknown: at least 8 wk course is recommended (A-II recommendation)
      • Some Experts Recommend an Additional 1-3 mo (and Possibly Longer for Chronic Infection or if Debridement is Not Performed) of Oral Rifampin-Based Combination Therapy with Sulfamethoxazole-Trimethoprim, Doxycycline/Minocycline, Clindamycin, or Fluoroquinolone Chosen Based on Susceptibilities (C-III Recommendation)
    • Magnetic Resonance Imaging is the Imaging Procedure of Choice, Particularly for the Detection of Early Osteomyelitis and/or Associated Soft Tissue Disease (A-II Recommendation)
    • Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) May Be Helpful to Guide Response to Therapy (B-III Recommendation)

Methicillin-Resistant Staphylococcus Aureus (MRSA) Septic Arthritis (see Septic Arthritis)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Agents: same as for osteomyelitis above
  • Other Recommendations
    • Debridement and Drainage of Joint Space is Recommended in All Cases (A-II Recommendation)
    • Duration of Antibiotic Therapy: 3-4 wk course is suggested (A-III Recommendation)

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Early-Onset (<2 mo Post-Op) or Acute Hematogenous Prosthetic Joint Infections with a Stable Implant of Short Duration (≤3 wks) of Symptoms and Debridement (But Device Retention)
    • Agents: same as for osteomyelitis above with the addition of Rifampin 600 mg PO qday or 300-450 mg PO BID x 2 wks, followed by Rifampin + Fluoroquinolone/Sulfamethoxazole-Trimethoprim/Tetracycline/Clindamycin x 3 mo (for hip) or 6 mo (for knee) (A-II Recommendation)
  • Late-Onset Infection, Unstable Implant, or Long Duration of Symptoms with Hip/Knee Implant: device removal is recommended (A-II Recommendation)
  • Early-Onset (≤30 Days Post-Op) Spinal Implant Infection or Implant in Actively Infected Site: same as for osteomyelitis above with the addition of Rifampin, followed by prolonged oral therapy (B-II Recommendation)
    • Optimal Duration of Antibiotic Administration is Unknown: oral component should be continued until spine fusion has occurred (B-II Recommendation)
  • Late-Onset (>30 Days Post-Op) Spinal Implant Infection: device removal is recommended (B-II Recommendation)
  • Long-Term Oral Suppressive Therapy: Sulfamethoxazole-Trimethoprim/Tetracycline/Fluoroquinolone/Clindamycin in combination with Rifampin are recommended (particularly if device removal is not possible

Other Therapies

Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

  • Intravenous Immunoglobulin (IVIG) (see Intravenous Immunoglobulin): not routinely recommended for invasive MRSA disease (A-III Recommendation), although may be used as adjunctive therapy in selected clinical scenarios, such as necrotizing fasciitis or severe sepsis (C-III Recommendation)
  • Protein Synthesis Inhbitors: not routinely recommended for invasive MRSA disease (A-III Recommendation), although may be used as adjunctive therapy in selected clinical scenarios, such as necrotizing fasciitis or severe sepsis (C-III Recommendation)

Specific Agents with Activity Against Methicillin-Resistant Staphylococcus Aureus (MRSA)

MRSA AGENTS

Vancomycin (see Vancomycin)

  • Tissue Penetration is Highly Variable and Dependent on the Degree of Inflammation
    • Limited Penetration into Bone
    • Limited Penetration into Lung Epithelial Fluid
    • Limited Penetration into Cerebrospinal Fluid
  • Vancomycin Administration Recommendations (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]
    • Standard Vancomycin Dosing: 15-20 mg/kg/dose (Actual Body Weight) q8-12 hrs (Max: 2 g Per Dose) in Patients with Normal Renal Function (B-III Recommendation)
      • Dosing in Patients with Serious Disease (Sepsis, Meningitis, Pneumonia, Infective Endocarditis): loading dose of 25-30 mg/kg (actual body weight) may be considered
        • Due to Risk of Red Man Syndrome and Possible Anaphylaxis with Large Vancomycin Dose, Prophylactic Antihistamine Should Be Used and Vancomycin Infusion Time Should Be Prolonged to 2 hrs
    • Monitor Serum Vancomycin Trough Levels: troughs are the most accurate method to guide vancomycin dosing (B-II Recommendation)
      • Vancomycin Trough Should Be Obtained at Steady State Condition Prior to 4th-5th Dose
      • Target Vancomycin Trough Level in Serious Infections: 15-20 μg/mL (B-II Recommendation)
      • Patients with Skin and Soft Tissue Infections (SSTI) and Normal Renal Function: standard dosing of 1g q12hrs is adequate and trough level measurement is not necessary (B-II Recommendation)
      • Vancomycin Trough Measurement is Recommended in Patients with Serious Infections, Who are Morbidly Obese, Have Renal Insufficiency (Including Those on Dialysis), and Those with Fluctuating Volumes of Distribution (A-II Recommendation)
    • Measurement of Peak Serum Vancomycin Levels are Not Recommended (B-II Recommendation)
    • Continuous Vancomycin Infusion Regimens are Not Recommended (A-II Recommendation)
  • Vancomycin Susceptibility Testing (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]
    • Isolates with Vancomycin Minimum Inhibitory Concentration (MIC) ≤2 μg/mL (Susceptible): clinical response should determine the continued use of vancomycin (A-III Recommendation)
      • If Patient Does Not Have Clinical/Microbiologic Response Despite Adequate Debridement and Removal of Other Foci of Infection, an Alternative to Vancomycin is Recommended, Regardless of the MIC
    • Isolates with Vancomycin Minimum Inhibitory Concentration (MIC) >2 μg/mL (Vancomycin-Intermediate Staphylococcus Aureus, VISA, or Vancomycin-Resistant Staphylococcus Aureus, VRSA): an alternative to vancomycin should be used (A-III Recommendation)

Linezolid (see Linezolid)

  • Clinical Efficacy
    • Retrospective Analysis Comparing Linezolid with Vancomycin for MRSA Hospital-Acquired Pneumonia (Chest, 2003) [MEDLINE]
      • Initial Therapy with Linezolid was Associated with Improved Survival and Cure Rates, as Compared to Vancomycin
    • Comparison of Linezolid with Vancomycin in the Treatment of MRSA Ventilator-Associated Pneumonia (Chest, 2008) [MEDLINE]
      • No Difference in Early Microbiological Cure Rates with Linezolid, as Compared to Vancomycin
        • Trends in the Secondary Outcomes Appeared to Favor Linezolid

Tedizolid (Sivextro) (see Tedizolid)

  • XXXXXXXX

Tigecycline (see Tigecycline)

  • FDA-Approved for the Treatment of cSSTIs and Intraabdominal Infections
  • Clinical Efficacy
    • FDA Warning of Increased Mortality Rates with Tigecycline, as Compared to Other Agents (2010) [LINK]
    • Review of Tigecycline Non-Inferiority Trials (Clin Infect Dis, 2012) [MEDLINE]
      • Authors Concluded that Tigecycline is Associated with Higher Rates of Lack of Cure and Mortality than Comparators

Dalbavancin (Dalvance) (see Dalbavancin)

  • XXXXX

Daptomycin (see Daptomycin)

  • Clinical Features
    • FDA-approved to treat skin and soft tissue infections due to Gram-positive organisms
    • FDA-approved to treat endocarditis due to Staphyloccocus Aureus

Ceftaroline (Teflaro, Zinfloro) (see Ceftaroline)

  • Pharmacology
    • XXX
  • Penetration
    • XXX
  • Side Effects
    • XXX
  • Contraindications
    • XXX

Telavancin (Vibativ) (see Telavancin)

  • Pharmacology
    • XXX
  • Penetration
    • XXX
  • Clinical Features
    • XXX
  • Side Effects
    • XXX
  • Contraindications
    • XXX

Prognosis

Methicillin-Sensitive Staphylococcus Aureus Infection (MSSA) vs Methicillin-Resistant Staphylococcus Aureus (MRSA)

  • Single VA Study of the Outcomes of Staphylococcus Aureus Infection (Infect Control Hosp Epidemiol, 2007) [MEDLINE]: n = 438
    • Patients with Non-Pneumonia MRSA Infections Have a Higher Mortality Rate than Patients with Non-Pneumonia MSSA Infections, Independent of the Severity of Patient’s Underlying Illness
  • Mortality Rate MRSA with Panton-Valentine Leukocidin Toxin: 75%
  • Mortality Rate with Associated Bacteremia: 30%

References

General

Epidemiology

Physiology

Microbiology

Diagnosis

Clinical Manifestations

Cardiovascular Manifestations

Dermatologic Manifestations

Pulmonary Manifestations

Bronchitis Obliterans (see xxxx)
Pneumonia (see Community-Acquired Pneumonia)
Tracheobronchitis (see Acute Bronchitis)

Vascular Manifestations

Prevention

Treatment