Empiric Antibiotics: MRSA (HINT: not just Vanc!)

Basics

  • Uncomplicated Bacteremia
    • Must meet all of following: No IE (by TEE); No prostheses; Negative f/u blood cultures at 2-4 days; Defervescence within 72 h of effective therapy; No metastatic infection
    • Vancomycin or Daptomycin for minimum 2 weeks
  • Complicated Bacteremia or Endocarditis
    • 4-6 weeks at minimum
    • No benefit to adding gentamicin or rifampin for native valve IE
  • Treatment Failure
    • Generally defined as persistent bacteremia around day 7 of therapy (median time to clearance of MRSA bacteremia is 7-9 days)
    • May also define failure as patient getting worse on current tx
    • Remember SOURCE CONTROL!!!

Antibiotic Choices

  • MRSA Abx
  • PO options acceptable for SSTI or completion of osteo Rx; IV preferred for invasive disease
  • Vancomycin is the empiric drug of choice in most serious infections (duh!)
    • Vanc MIC ≥ 2 associated with higher rates of Rx failure so consider alternative agents
  • If vancomycin intolerance or failure:
    • PNA: Linezolid, Ceftaroline
    • Bacteremia/Endocarditis: Daptomycin, Ceftaroline
    • CNS: Linezolid
    • Osteo: Dapto, Ceftaroline

Inclusion Body Myositis 101

General information

  • Most common muscle disease in patients older than 50 years. More common in white men, but can affect any group
  • Thought to be degenerative, rather than auto-immune. Associated with systemic autoimmune or connective-tissue diseases in up to 15 %

Clinical Manifestations

  • Difficulty with everyday tasks predominantly requiring the use of proximal muscles, such as getting up from a chair, climbing steps, stepping onto a curb, lifting objects, or combing their hair
  • Fine-motor movements that depend on the strength of distal muscles (especially foot extensors and finger flexors), such as buttoning a shirt, sewing, knitting, or writing, are affected fairly early in the course
  • The pharyngeal and neck-flexor muscles are often involved, causing dysphagia or fatigue and difficulty in holding up the head
  • May also progress slowly for years, and its clinical features may simulate those of limb-girdle muscular dystrophy.
  • Consider IBM in patients with polymyositis or dermatomyositis that is resistant to treatment.

Diagnostic Criteria

  • Muscle strength – myopathic muscle weakness with early involvement of the distal muscles
  • EMG – myopathic with mixed potentials
  • Muscle enzymes – normal or elevated
  • Muscle biopsy – definitive
  • Light microscopy —  endomysial inflammation, rimmed vacoules distributed around the edge, eosinophilic cytoplasmic inclusions
  • EM — granules contain membranous whorls. Filamentous inclusions in the cytoplasm or nucleus, prominent in the vicinity of the rimmed vacuoles, are pathognomonic

Treatment

  • Inclusion-body myositis is generally resistant to all therapies, and its rate of progression also appears to be unaffected by treatment.
  • Failed therapies — Steroids, MTX, Cyclophosphamide, Beta-interferon, TNF-a inhibitors, ATGAM, IVIg
  • Future possibilities
    • Alemtuzumab, a T-cell–depleting monoclonal antibody; reported slowed disease progression, improvement of strength in some patients, and reduction in endomysial inflammation
    • Follistatin, an antagonist of the myostatin pathway, has been shown to produce a dramatic increase in muscle mass in animals
    • Arimoclomol, a heat shock protein (HSP) coinducer may slow down the process of protein misfolding and aggregation

PCSK9 Inhibitors…Closer to Approval?

This week the FDA Endocrinologic and Metabolic Drugs Advisory Committee will discuss the safety and efficacy of two PCSK9 inhibitor drugs (Praluent and Repatha) and may recommend approval of these drugs to lower cholesterol. Recently published research in NEJM showed reduced cardiovascular outcomes with these inhibitors and has sparked guarded optimism from the medical community. UT Southwestern cardiologist, Dr. Amit Khera, was recently quoted in Medscape regarding these powerful cholesterol lowering medications, “If you’re a cardiologist, you must not have a pulse if you’re not excited.” Click on the link below to read more from The Washington Post!

Could these New Cholesterol Drugs Save Many Americans from Heart Attacks?

UPDATE!

The FDA panel today recommended approval of the cholesterol drug, alirocumab, in a 13-3 vote. Click on the link below to read a summary from today’s developments from The New York Times.

Federal Panel Recommends Approving New Cholesterol Drug