Staphylococcus Aureus

Reviewed and revised 3 September 2015

OVERVIEW

• aerobic gram positive cocci
• has developed beta-lactamase activity thus is not susceptible to penicillin (use flucloxacillin at doses of 2g 4-6 hrly)
• because of increasing MRSA in the community, empiric treatment should be vancomycin in many settings
• prevalence of hospital acquired MRSA varies from unit to unit
• if no obvious source consider occult sources:
  — epidural abscess
  — psoas abscess
  — endocarditis

PATHOPHYSIOLOGY

• commensal bacterium that colonizes the nares (its primary reservoir), axillae, vagina, pharynx, and/or damaged skin surfaces
• S. aureus is unique in its ability to invade and cause disease in previously normal tissue at virtually all sites

Staphylococcus aureus is intrinsically to penicillin by 3 mechanisms:

• hyperproduction of β-lactamases
• modification of the normal penicillin-binding proteins (PBPs), and
• presence of an acquired penicillin-binding protein (PBP2a)

CLINICAL MANIFESTATIONS

• local and systemic features of infection

Common sites

• skin and soft-tissue, e.g. cellulitis, pyomyositis, abscess and necrotizing fasciitis
• respiratory, e.g. necrotizing pneumonia, lung abscess and empyema
• bone and joint, e.g. osteomyelitis and septic arthritis
• endovascular infections, e.g. endocarditis, septicaemia
• infected prosthesis, e.g. joint replacements, valve replacements

Toxin mediated syndromes

• Toxic shock syndrome
• Staphylococcus scalded skin syndrome

INVESTIGATIONS AND MANAGEMENT

• all patients with staphylococcal bacteremia should have echocardiography
• consider pan-scan CT to identify occult source (e.g psoas abscess)
• consider MRI to rule out epidural abscess

ANTIBIOTIC CHOICE, DOSE AND FREQUENCY

Choice of antibiotic consideration

• ensure Staphyloccocus coverage
• actual Staph (aureus vs coag –ve)
• hospital or Community Acquired
• site of infection and ability of drug to penetrate infected area
• endemic resistance patterns (MRSA, VISA, hVISA, VRSA, VRSE)
• presence of Toxic Shock Syndrome (addition of Clindamycin for endotoxin activity)
• allergies
• previous treatment with antibiotics with treatment failure and previous sensitivity patterns

Dosing Regimen

• high dose for life threatening infections
• give IV
• loading dose
• appropriate interval dosing
• reduce if renal impairment
• reduced if develop side effects
• dose reduced if Na+ load unacceptable to patient

MSSA (METHICILLIN SENSITIVE)

Sensitive to:

• flucloxaciliin 100mg/kg/day in divided doses
• clindamycin 4mg/kg Q6hrly
• co-trimoxazole 80-100mg/kg of sulphamethoxazole
• erythromycin 20mg/kg/day in divided doses
• fusidic acid 1g Q8hrly
• gentamicin 3-5mg/kg LD -(titrate to trough)
• tetracycline 500mg Q12hrly

Also treated by:

• vancomycin 10mg/kg LD -> dose as per trough level
• linezolid 600mg Q12hrly (adult)
• meropenem 1g Q8hrly (adult)
• quinpristin-dalfopristin 7.5mg/kg Q8hrly
• rifampicin 20mg/kg /day
• teicoplanin 400mg LD, 400mg @ 12 hrs, 400mg Q24hrly
• tigecycline 100mg LD, 50mg Q12hrly

MRSA (METHICILLIN RESISTANT)

Hospital Acquired Methicillin Resistant (HA-MRSA)

• penicillin-binding protein mutation coded by the mecA gene on a transposon
• also produces to multiple other classes (tetracyclines, macrolides, sulphonamides, aminoglycosides)
• resistant to carbapenems
• treatment: vancomycin, teicoplanin, rifampicin, fusidic acid, ciprofloxacin, linezolid, tigecycline, streptogranins

Community Acquired Methicillin Resistant (CA-MRSA)

• similar mechanism to Hospital-acquired MRSA + Panton-Valentine leukocidin (PVL) gene
• often seen in Pacific Island born patient and Indigenous communities
• resistant to carbapenems
• treatment: vancomycin, teicoplanin, clindamycin, sometimes rifampicin, fusidic acid, ciprofloxacin, co-trimoxazole, erythromycin, linezolid

VISA (VANCOMYCIN INTERMEDIATE RESISTANT)

Heterogenous Vancomycin Intermediate Resistant (h-VISA)

• significance of hVISA is uncertain as the MIC is the same for MRSA but daughter strains have higher MIC
• MIC range of 1-4mcg/mL
• continued stress from vancomycin leads to VISA

Vancomycin Intermediate Resistant (VISA) or Glycopeptide Intermediate Resistant (GISA)

• genes code for factors such as additional peptidoglycan synthesis and reduced need for peptidoglycan cross-linking
• CDC definition:
  (1) MIC between 8-16mcg/mL with a broth micro-dilution test
  (2) MIC > 6mcg/mL with E-testing
  (3) growth within 24 hours on commercially prepared brain-heart infusion agar containing 6mcg/mL of vancomycin
• can’t use disc diffusion for VISA detection
• treatment: teicoplanin, linezolid, quinupristin-dalforpristin, or cotrimoxazole

VRSA (VANCOMYCIN RESISTANT)

• MIC > 32 mcg/mL
• first reported in US in 2002
• contains vanA determinant that mediates the high level of vancomycin resistance seen in VRE (MIC was > 1024 mcg/mL)
• treatment: linezolid

References and Links

Journal articles

• Boucher H, Miller LG, Razonable RR. Serious infections caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2010 Sep 15;51 Suppl 2:S183-97. [pubmed]
• Rehm SJ. Staphylococcus aureus: the new adventures of a legendary pathogen. Cleve Clin J Med. 2008 Mar;75(3):177-80, 183-6, 190-2. .[pubmed]
• Rehm SJ, Tice A. Staphylococcus aureus: methicillin-susceptible S. aureus to methicillin-resistant S. aureus and vancomycin-resistant S. aureus. Clin Infect Dis. 2010 Sep 15;51 Suppl 2:S176-82. [pubmed]
  

FOAM and web resources

• FET — What we really know about controlling MRSA – Geoff Bellingan (2011)
• FET — MRSA in the ICU – Geoff Bellingan (2010)