Staphylococcus Aureus

Microbiology

  • Member of Staphylococcus Genus (see Staphylococcus, [[Staphylococcus]])

  • Panton-Valentine Leukocidin (PVL) toxin-producing strains are more likely to produce pleural effusion, hemoptysis, rapid onset of ARDS, and leukopenia

  • Panton-Valentine Leukocidin (PVL) Toxin: binds to G-protein coupled receptor on neutrophils, which causes neutrophil adhesion to endothelial cells
    • Highly prevalent in community-acquired strains of MRSA
    • Associated with primary skin infections

Epidemiology

Risk Factors

  • Immune Defect
  • Implantable Device
    • Artificial Joint
    • Heart Valve
    • Pacemaker/AICD
  • Other

  • MRSA cases may present with a preceding influenza-like illness

Risk Factors for Nosocomial Staph Aureus Bacteremia

  • MRSA Colonization
    • Staph aureus bacteremia occurs almost exclusively in patients with previous nasal colonization
    • Up to 25% of patients admitted to the hospital will become nasal Staph aureus carriers (often with prevalent hospital strains)
      • This rate may climb to 60% in those with ESRD, diabetes, and HIV
    • MRSA carriers have 3.9x the rate of Staph aureus bacteremia than MSSA carriers
      • Relative risk was 0.04 for patients receiving antibiotics (especially beta-lactams and glycopeptides), as compared to those not receiving antibiotics
    • MSSA nasal carriage is predominantly community-acquired and is more prevalent than MRSA nasal carriage
    • Most cases of Staph aureus bacteremia are related to line infection

(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

Sputum GS/Cult+Sens:
-MRSA: recent community-acquired MRSA strains have been found to cause human disease (Daum, 2002; Frank, 2002)
–Unlike institutional strains of MRSA, these typically are sensitive to vanco, clinda, tetracyclines, aminoglycosides, fluoroquinolones, bactrim, and erythro
-Vanco-Intermediate Sensitivity Staph aureus (VISA): present in US since 2002/refractory to vanco therapy
-Vanco-Resistant Staph aureus (VRSA): cases reported in US in 2002
-Linezolid-Resistant Staph aureus: reported in one case in 2001


Clinical Manifestations

Cardiovascular Manifestations

Automatic Implantable Cardioverter-Defibrillator (AICD) Infection (see Automatic Implantable Cardioverter-Defibrillator, [[Automatic Implantable Cardioverter-Defibrillator]])

  • 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)

Cardiac Pacemaker Infection (see Cardiac Pacemaker, [[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, [[Endocarditis]])

  • Epidemiology
    • Incidence of endocarditis in setting of Staphylococcus Aureus bacteremia is 10-15%
    • Endocarditis due to Staphylococcus Aureus is more severe than that due to other organisms
      • Higher incidence of sepsis
      • Higher incidence of major neurologic events
      • Higher incidence of multi-organ failure
      • Higher mortality rate: 34% (vs 10% with other organisms)
  • Predisposing Factors for Endocarditis in Setting of Staphylococcus Aureus Bacteremia
    • Bacteremia of Unclear Origin/Persistent Bacteremia
    • Intravascular Catheter Infection
    • Intravenous Drug Abuse (IVDA)
    • Pre-Existing Cardiac Abnormality
    • Prosthetic Heart Valve
  • Mechanism of Infection
    • Hematogenous Seeding (Via Bacteremia)

Dermatologic Manifestations

Cellulitis (see Cellulitis, [[Cellulitis]])

  • Mechanism of Infection
    • Skin Breach

Erysipelas (see Erysipelas, [[Erysipelas]])

  • Mechanism of Infection
    • Skin Breach

Folliculitis

  • Mechanism of Infection
    • Skin Breach

Hidradenitis Suppurativa

  • Mechanism of Infection

Impetigo (see Impetigo, [[Impetigo]])

  • Mechanism of Infection

Mastitis (see Mastitis, [[Mastitis]])

  • Mechanism of Infection

Purpura Fulminans (see Purpura Fulminans, [[Purpura Fulminans]])

  • Mechanism

Scarlet Fever (see Scarlet Fever, [[Scarlet Fever]])

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

Skin Abscess (see Skin Abscess, [[Skin Abscess]])

  • Mechanism of Infection
    • Skin Breach

Staphylococcal Scalded Skin Syndrome (Ritter Disease) (see Staphylococcal Scalded Skin Syndrome, [[Staphylococcal Scalded Skin Syndrome]])

  • xxx

Gastroenterologic Manifestations

Staphylococcus Aureus Toxinosis

  • Mechanism: ingestion of food-borne toxin
  • Clinical
    • Diarrhea

Hematologic Manifestations

Hemolytic Anemia (see Hemolytic Anemia, [[Hemolytic Anemia]])

  • Physiology: due to mechanical RBC destruction

Splenic Abscess (see Splenic Abscess, [[Splenic Abscess]])

  • Mechanism of Infection
    • Hematogenous Seeding (Via Bacteremia)

Neurologic Manifestations

Intracranial Epidural Abscess (see Intracranial Epidural Abscess, [[Intracranial Epidural Abscess]]): usually results from neurosurgical intervention

  • Mechanism of Infection: xxx

Meningitis (see Meningitis, [[Meningitis]])

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

Spinal Epidural Abscess (see Spinal Epidural Abscess, [[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, [[Acute Rhinosinusitis]])

  • Epidemiology

Pulmonary Manifestations

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])

  • Epidemiology

Interstitial Pneumonia (see Interstitial Lung Disease, [[Interstitial Lung Disease]])

  • Epidemiology
  • Clinical
    • Chest X-Ray (CXR) (see Chest X-Ray, [[Chest X-Ray]]): miliary pattern

Pneumonia (see Pneumonia, [[Pneumonia]])

  • Epidemiology
    • Some Studies Cite 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]
  • 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
    • Cough (see xxxx, [[xxxx]])
    • Dyspnea (see xxxx, [[xxxx]])

Pneumatocele (see Cystic-Cavitary Lung Lesions, [[Cystic-Cavitary Lung Lesions]])

  • Epidemiology: occurs mainly in childhood cases

Necrotizing Pneumonia (see Necrotizing Pneumonia and Pulmonary Gangrene, [[Necrotizing Pneumonia and Pulmonary Gangrene]])

  • Epidemiology: associated with MRSA with Panton-Valentine leukocidin toxin
  • Diagnosis
    • Leukopenia (see Leukopenia, [[Leukopenia]]): associated with rapidly progressive, severe disease

Renal Manifestations

Acute Interstitial Nephritis (see Acute Interstitial Nephritis, [[Acute Interstitial Nephritis]])

  • Epidemiology

Staphylococcus Aureus Bacteriuria (see Urinary Tract Infection, [[Urinary Tract Infection]])

  • Epidemiology
  • 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

Rheumatologic/Orthopedic Manifestations

Necrotizing Fasciitis (see Necrotizing Fasciitis, [[Necrotizing Fasciitis]])

  • Mechanism of Infection: xxx

Osteomyelitis (see Osteomyelitis, [[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, [[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, [[Pyomyositis]])

  • Mechanism of Infection
    • Hematogenous Seeding (via Bacteremia)

Septic Arthritis (see Septic Arthritis, [[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, [[Septic Bursitis]])

  • xxx

Vascular Manifestations

Central Venous Catheter (CVC) Infection (see Central Venous Catheter, [[Central Venous Catheter]])

  • xxx

Other Intravascular Catheter Infection

  • xxx

Thrombophlebitis

  • Clinical: erythema and pain occur at site of catheter insertion

Other Manifestations

Staphylococcal Toxic Shock Syndrome (see Staphylococcal Toxic Shock Syndrome, [[Staphylococcal Toxic Shock Syndrome]])

Waterhouse-Friderichsen Syndrome (see Waterhouse-Friderichsen Syndrome, [[Waterhouse-Friderichsen Syndrome]])

  • xxx

Henoch-Schonlein Purpura (HSP) (see Henoch-Schonlein Purpura, [[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
    • DECIDE Trial of Universal vs Targeted Decolonization to Prevent Infections in the ICU (NEJM, 2013) [MEDLINE]
      • Universal Decolonization (Chlorhexidine) was Superior to Targeted Decolonization of MRSA Carriers (Chrlorhexidine + Nasal Mupirocin) and MRSA Screening and Isolation Strategies in Preventing the Rate of MRSA Isolates and Bloodstream Infection from Any Pathogen: targeted decolonization was intermediate in effectiveness, while screening and isolation did not decrease the rate of any infections
      • Universal Decolonization Prevented 1 Bloodstream Infection Per Each 54 Patients
    • 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-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, [[Vancomycin]]): 2 wk course (A-II Recommendation)
    • Daptomycin (Cubicin) (see Daptomycin, [[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, [[Vancomycin]]): 4-6 wk course
    • Daptomycin (Cubicin) (see Daptomycin, [[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, [[Endocarditis]])

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

  • Agents
    • Vancomycin IV (see Vancomycin, [[Vancomycin]]): 6 wk course (A-II Recommendation)
    • Daptomycin (Cubicin) (see Daptomycin, [[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, [[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, [[Vancomycin]], Rifampin, [[Rifampin]], and Gentamicin, [[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, [[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
      • Clindamycin PO (see Clindamycin, [[Clindamycin]]) (A-II Recommendation)
      • Doxycycline/Minocycline PO (see Doxycycline, [[Doxycycline]] or Minocycline, [[Minocycline]]) (A-II Recommendation)
      • Linezolid (Zyvox) PO (see Linezolid, [[Linezolid]]) (A-II Recommendation)
      • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) PO (see Sulfamethoxazole-Trimethoprim, [[Sulfamethoxazole-Trimethoprim]]) (A-II Recommendation)
  • 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
      • Clindamycin PO (see Clindamycin, [[Clindamycin]]) (A-II Recommendation)
      • Combination Doxycycline/Minocycline PO + β-Lactam (Amoxicillin) PO (see Doxycycline, [[Doxycycline]] or Minocycline, [[Minocycline]], and Amoxicillin, [[Amoxicillin]]) (A-II Recommendation)
      • Linezolid (Zyvox) PO (see Linezolid, [[Linezolid]]) (A-II Recommendation)
      • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) PO (see Sulfamethoxazole-Trimethoprim, [[Sulfamethoxazole-Trimethoprim]]) (A-II Recommendation)
  • 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, [[Vancomycin]]) (A-I Recommendation)
    • Daptomycin (Cubicin) (see Daptomycin, [[Daptomycin]]): 4 mg/kg/dose IV qday x 7-14 days (A-I Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid, [[Linezolid]]): 600 mg BID x 7-14 days (A-I Recommendation)
    • Telavancin (Vibativ) IV (see Telavancin, [[Telavancin]]): 10 mg/kg/dose qday x 7-14 days (A-I Recommendation)
    • Clindamycin PO/IV (see Clindamycin, [[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 Pneumonia (see Pneumonia, [[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, [[Vancomycin]]) (A-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid, [[Linezolid]]): 600 mg BID (A-II Recommendation)
    • Clindamycin IV/PO (see Clindamycin, [[Clindamycin]]): 600 mg TID (B-III Recommendation)
      • May Be Used if the Strain is Susceptible

Methicillin-Resistant Staphylococcus Aureus Empyema (Pleural Effusion-Parapneumonic, [[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, [[Chest Tube]])
    • Surgical Pleural Drainage/Decortication

Methicillin-Resistant Staphylococcus Aureus Meningitis (see Meningitis, [[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, [[Vancomycin]]): 2 wk course (B-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid, [[Linezolid]]): 600 mg BID (B-II Recommendation)
    • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) IV (see Sulfamethoxazole-Trimethoprim, [[Sulfamethoxazole-Trimethoprim]]): 5 mg/kg q8-12 hrs (C-III Recommendation)
  • Other Recommendations
    • Optional Addition of Rifampin PO/IV (see Rifampin, [[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 Brain Abscess/Intracranial Epidural Abscess/Subdural Empyema/Spinal Epidural Abscess (see Brain Abscess, [[Brain Abscess]], Intracranial Epidural Abscess, [[Intracranial Epidural Abscess]], Subdural Empyema, [[Subdural Empyema]], and Spinal Epidural Abscess, [[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, [[Vancomycin]]): 4-6 wk course (B-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid, [[Linezolid]]): 600 mg BID (B-II Recommendation)
    • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) IV (see Sulfamethoxazole-Trimethoprim, [[Sulfamethoxazole-Trimethoprim]]): 5 mg/kg q8-12 hrs (C-III Recommendation)
  • Other Recommendations
    • Optional Addition of Rifampin PO/IV (see Rifampin, [[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 Septic Thrombosis of Cavernous or Dural Venous Sinus (see xxxx, [[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, [[Vancomycin]]): 4-6 wk course (B-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid, [[Linezolid]]): 600 mg BID (B-II Recommendation)
    • Sulfamethoxazole-Trimethoprim (Bactrim, Septra) IV (see Sulfamethoxazole-Trimethoprim, [[Sulfamethoxazole-Trimethoprim]]): 5 mg/kg q8-12 hrs (C-III Recommendation)
  • Other Recommendations
    • Optional Addition of Rifampin PO/IV (see Rifampin, [[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 Osteomyelitis (see Osteomyelitis, [[Osteomyelitis]])

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

  • Agents
    • Vancomycin IV (see Vancomycin, [[Vancomycin]]) (B-II Recommendation)
    • Daptomycin (Cubicin) (see Daptomycin, [[Daptomycin]]): 6 mg/kg/dose IV qday at least 8 wk course (B-II Recommendation)
    • Linezolid (Zyvox) IV/PO (see Linezolid, [[Linezolid]]): 600 mg BID (B-II Recommendation)
    • Clindamycin IV/PO (see Clindamycin, [[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, [[Sulfamethoxazole-Trimethoprim]] and Rifampin, [[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, [[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 Septic Arthritis (see Septic Arthritis, [[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)

Methicillin-Resistant Staphylococcus Aureus Device-Related Osteoarticular Infection

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, [[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, [[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, [[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

Tigecycline (see Tigecycline, [[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

Daptomycin (see Daptomycin, [[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, [[Ceftaroline]])

  • Mechanism:
  • Penetration:
  • Clinical Features:
  • Side Effects:
  • Contraindications:

Telavancin (Vibativ) (see Telavancin, [[Telavancin]])

  • Mechanism:
  • Penetration:
  • Clinical Features:
  • Side Effects:
  • Contraindications:

Prognosis

  • Mortality Rate MRSA with Panton-Valentine Leukocidin Toxin: 75%
  • Mortality Rate with Associated Bacteremia: 30%

References

  • Methicillin-resistant StaphylococcuS aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management. Am J Med 1993; 94:313-328
  • Nosocomial StaphylococcuS aureus bacteremia among nasal carriers of methicillin-resistant and methicillin-sensitive strains. Am J Med 1996; 100:509-516
  • Purpura fulminans due to Staphylococcus aureus. Clin Infect Dis. 2005 Apr 1;40(7):941-7 [MEDLINE]
  • Fifteen-year study of the changing epidemiology of methicillin-resistant Staphylococcus aureus. Am J Med 2006; 119:943

Prevention

  • Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med. 2011 Apr 14;364(15):1419-30. doi: 10.1056/NEJMoa1007474 [MEDLINE]
  • Infection prevention practices in adult intensive care units in a large community hospital system after implementing strategies to reduce healthcare-associated methicillin-resistant Staphylococcus aureus infections. Am J Infect Control 2013;41:126-130 [MEDLINE]
  • DECIDE Trial. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368:2255–2265 [MEDLINE]
  • Screening inpatients for MRSA—case closed. N Engl J Med. 2013;368:2314–2315 [MEDLINE]
  • Effect of body surface decolonisation on bacteriuria and candiduria in intensive care units: an analysis of a cluster-randomised trial. Lancet Infect Dis. 2016 Jan;16(1):70-9. doi: 10.1016/S1473-3099(15)00238-8. Epub 2015 Nov 27 [MEDLINE]

Treatment

  • Linezolid versus vancomycin: analysis of two double blind studies of patients with MRSA pneumonia. Chest 2003;124:1787 [MEDLINE]
  • Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients. Clin Ther. 2004 May;26(5):704-14 [MEDLINE]
  • Antimicrobial activity of tigecycline tested against organisms causing community-acquired respiratory tract infection and nosocomial pneumonia. Diagn Microbiol Infect Dis. 2005 Jul;52(3):187-93 [MEDLINE]
  • Epidemiology, treatment, and outcomes of nosocomial bacteremic Staphylococcus aureus pneumonia. Chest. 2005 Sep;128(3):1414-22 [MEDLINE]
  • Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother. 2005; 49:2260-2266 [MEDLINE]
  • High-dose vancomycin therapy for MRSA infections: efficacy and toxicity. Arch Intern Med 2006;123:2138-2144 [MEDLINE]
  • In vitro activities of ceftobiprole, tigecycline, daptomycin, and 19 other antimicrobials against methicillin-resistant Staphylococcus aureus strains from a national survey of Belgian hospitals. Antimicrob Agents Chemother. 2006 Aug;50(8):2680-5 [MEDLINE]
  • Early Microbiologic Response to Linezolid Versus Vancomycin in Ventilator-Associated Pneumonia (VAP) Due to Methicillin-Resistant Staphylococcus aureus (MRSA) Chest 2008 Dec;134(6):1200-7 [MEDLINE]
  • Impact of methicillin resistance on mortality in Staphylococcus aureus VAP: a systematic review. Eur Respir J. 2008 Mar;31(3):625-32 [MEDLINE]
  • Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4 [MEDLINE]
  • US Food and Drug Administration. FDA Drug Safety Communication. Increased risk of death with Tygacil (tigecycline) compared to other antibiotics used to treat similar infections. 2010. Available at: http:// www.fda.gov/Drugs/DrugSafety/ucm224370.htm

  • Systematic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infec- tious disease. Antimicrob Agents Chemother 2011; 55:1162–72

  • Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis 2011; 11:834–44
  • Efficacy and safety of tigecy- cline: a systematic review and meta-analysis. J Antimicrob Chemother 2011; 66:1963–71
  • Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis 2012; 54:1699–709 [MEDLINE]

  • Methicillin-resistant Staphylococcus aureus therapy: past, present, and future. Clin Infect Dis. 2014 Jan;58 Suppl 1:S20-7. doi: 10.1093/cid/cit614 [MEDLINE]

  • Clinical practice. Community-acquired pneumonia. N Engl J Med. 2014 Feb 6;370(6):543-51. doi: 10.1056/NEJMcp1214869 [MEDLINE]
  • Management of Skin Abscesses in the Era of Methicillin-Resistant Staphylococcus aureus. N Engl J Med 2014; 370:1039-1047March 13, 2014DOI: 10.1056/NEJMra1212788 [MEDLINE]