MRSA The Growing Dilemma

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MRSA The Growing Dilemma

• J. Sydney James DPM FACFAS
• Chief of Podiatry
• Southwest Medical Associates

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Methicillin Resistant Staph Aureus

• First Described in Europe in 1961
• Noted in the US in 1968
• Soon after the introduction of methicillin
• Originally considered nosocomial
• Originally rarely seen in the community

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Staphylococcus aureus

• 1940s penicillin sensitive
• 1st organism to develop pen resistance
• Late 1950s most staph pen resistant
• 1961 methicillin 1st semi-sythetic pen

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MRSA Spreads

• 1970-1980 MRSA becomes prevalent in Southern and
  Eastern Europe
• 1980s MRSA strain on almost every continent
• 1990s Pharmaceuticals develop drugs effective on
  Gram (-) organisms
• Today most states have a 50 or greater
  prevalence of MRSA in Staph cultures

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From where are thou MRSA?

• Mutant Coagulase negative Staph strain
• Quinolones mutate Staph aureus to MRSA eid nov
  2003
• Over use of qunolone thru the1990s
• mecA gene alters surface protein

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MRSA the evil brother of MSSA

• MRSA is more virulent
• Studies show increase
• Morbidity
• Hospital time/cost
• Disability
• Engemann 2003

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Hospital and Community Associated Strains

• CDC identifies genetic differences
• Hospital associated strain SCCmec type III gene
• Community associated strain SCCmec type IV gene
  is longer
• Both contain the mecA gene which alters the
  bacterial protein coat

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HA-MRSA Risk Factors

• Hospital stay in the last 12 months
• Long term care residence
• Indwelling catheter or medical device

• Dialysis
• Renal Failure
• Diabetes
• Contact with infected or colonized person

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CA-MRSA Risk Factors

• Athletes especially wrestling and football
• Weakened immune system
• Crowded living conditions
• Correctional facility

• Population-Pacific Islander/Alaskan
  Native/American Native
• IV drug user
• Close association with infected/colonized person

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CDC Recommendations for contact with infected
persons

• Hand washing
• Gloving
• Masking
• Appropriate instrument handling
• Appropriate laundry handling

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HA-MRSA vs CA-MRSA
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CA-MRSA the Bad Boy

• More sensitive to antibiotic therapy
• i.e. minocycline/doxycycline, trimeth/sulfa,clidam
  ycin (D test)
• BUT
• More virulent due to the production of
• Endotoxins Staph Enterotoxin, Leukocidin

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Does it matter HA vs CA?California hospital
study found 30.2-37 of hospital isolates
CA-MRSATreatment is culture and sensitivity
driven!
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MRSA Infection Categories

• Superficial colonization w/o signs
• Superficial Skin and Soft Tissue / Cellulitis
• Complex Skin Soft Tissue Infection
• Osteomyelitis
• Bacteremia/Endocarditis

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Signs of Local Infection

• Swelling / Induration
• Erythema
• Pain
• Increased Exudates

• Increased Temperature
• Foul Odor
• Progressive Wound Breakdown

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Signs of Systemic Infection

• Fever
• Chills
• Nausea

• Vomiting
• Hypotension
• Multi-Organ Failure

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Old PO Antibiotic Tx of MRSA

• 1. Fluroquinolones-Sorry
• 2. Minocycline/doxycy
• 100mg po bid no peds
• 3. Trimeth/sulfa bid
• 4. Rifampin 300mg po bid x 5 days (never
  monotherapy) drug interactions
• 5. Clindamycin 300-450mg qid
• High resistance/ D test

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New Boys on the Block

• Daptomycin
• Quinpristin-Dalfopristin
• Tigecycline
• Dalbavacin
• Oritavancin
• Zyvox

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Daptomycin

• Approved Nov 03
• Bacteriacidal
• Unique Mechanism
• No Cell Rupture or Endotoxin Release
• Very Fast Bacteriacidal Response

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Bactericidal Action of CUBICIN Against MRSA In
Vivo
50 mg/kg at 2 hours post dosing
Saline
Daptomycin
Vancomycin
Mortin LI, et al. 41st ICAAC 2001.
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Excellent Replacement For Vanco

• Vanco onset 26 hrs vs 15 mins
• No Peak/Trough Monitoring
• 4mg/kg/Q48
• Recent approval bacteremia/endocarditis
• No Osteomyelytis Approval
• Vanco 20/day vs 70-150 Wt Based

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Daptomycin use

• 4mg/kg qd
• ½ hr infusion
• Renal insufficiency
• Creatinine lt30ml/min
• Dose same q48

• No peaks/troughs
• CPK weekly to evaluate muscle breakdown
• CPKx10 baseline D/C
• rapidly reversible

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Quinpristin-Dalfopristin

• Streptogramin-gives a synergistic response
• Approved in1999
• Broad spec Gram ()
• Out of Favor because
• 1. Myalgia/arthralgia
• 2. Infusion difficult
• 3.Tissue penetration

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Drugs in the Pipe
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Vancomycin the Gold Standard

• Glycopeptide-approved in1958
• IV only
• Interferes with polypeptide cell wall development
  causing cell lysis
• Questionable tissue and bone penetration
• Ototoxicity / nephrotoxicity
• Developing resistance

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Vanco the silver bullet is getting tarnished

• Resistance to vanco (VRSA) on rise
• 1st and 2nd reported cases of VRSA in the foot in
  Michigan/Pennsylvania 2004
• 2004 cases reported of VRSA with no Hx of Vanco
  use
• Prolonged vanco use.
• Hemodialysis
• Indwelling Catheters

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Vanco Resistance

• VRSA-Vanco resistant staph aureus
• VISA-Vanco intermediate staph aureus Japan 1999
• 54 resistance to Vanco/MIC 2ug/ml
• JAMA Oct 06

• VRE-Vanco resistant Enterococcus 1989
• 10of all hospital acquired infections
• Vanhex gene accumulation cause vanco resistance

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Linezolid / Zyvox

• New class of antibiotic
• 1st new MRSA drug in 40 years
• PO equal to IV in bioavailability
• Myelosupression-Requires complete CBC after 10
  days
• Neuropathy- long use

• No resistance seen to
• VRSA
• VISA
• VRE
• MRSA
• MRSE (epidermidis)
• 28 day usage
• Cost

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Linezolid / Zyvox use

• 600 mg PO q 12 h
• 28 day PO q 12 h
• Greater than 10 day use monitor for
  myelosuppression (anemia, leukopenia,
  pancytopenia,and thrombocytopenia )

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Linezolid How Does it Work

• Within the cell linezolid prevents RNA
  replication and translation by reversible and
  non- selective inhibition of monoamine oxidase

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Mechanism of Action of Linezolid
Adapted from French G. Int J Clin Pract.
20015559-63.
Please see full prescribing information available
in this kit.
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Linezolid vs VancoAmerican Journal of Surgery
January 2005
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Protocol for Tx of MRSA

• Health of the patient
• Hospital vs outpatient
• Sensitivity/Culture
• Wound type
• Ability of patient to pay

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MRSA infections categories

• Superficial colonization without signs of
  infection (SC only)
• Superficial infection of soft tissue/cellulitis
  (SSTI)
• Complex skin and soft tissue structure infection
  (CSSTI)
• Osteomyelitis infection
• Bacteremia / Endocarditis

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Superficial colonization only

• Regular cleansing with hibiclens, betadine
• Silver dressing such as acticoat, silvasorb
• Mupuricin 2 ointment
• Close monitoring for signs of infection
• No antibiotic PO or IV

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SSTI

• Local wound clean
• Local debridement
• Silver dressing
• Antibiotics 10 days or longer as needed

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First Choice SSTI

• Bactrim- 1 PO bid
• Minocycline or Doxycycline-100mg PO bid
• Rifampin (Adult dose 300mg PO bid x 5d
  Pediatric dose 10-21mg/kg/day 2 doses
• Never use as monotherapy / resistance

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Second Choice SSTI

• Zyvox (Linezolid)- 600mg PO Q12H
• Appears to achieve bio-availability
  equal to IV
• Use empirically in Hx of previous MRSA
• 10 day course usually sufficient

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CSSTI

• Aggressively debride infected/necrotic tissue
• Ensure vascular adequacy or consult
• Proper Antibiotic
• Daily wound care/monitor

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Vanco vs Dapto vs Zyvox

• Zyvox use in lieu of
• Vanco when
• 1 Short therapylt21days
• 2. IV therapy not option
• 3. Renal Failure
• 4. Vanco Resistance

• Dapto use in lieu of
• Vanco when
• IV therapy needed
• Vanco Resistance
• Vanco P/T problems
• Renal problems

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MRSA Osteomyelitis

• Aggressive surgical bone and soft tissue
  resection.
• Establish vascular status or seek consult
• Consider Vanco if Renal status is good
• If Vanco used do renal labs closely monitor
  peaks/troughs
• Watch for VRSA
• 6 week antibiotic therapy

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MRSA Osteo continued

• Daptomycin used in cases where
• Renal problems
• Unresponsive to Vanco
• Vanco MICgt1
• Vanco P/T difficult to maintain
• 6 weeks of IV therapy needed

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Daptomycin use in osteo

• Dose increases from 4mg to 6mg/kg qd
• ½ hour infusion rate
• No peaks and troughs
• Renal insufficiency (creatinine clearance less
  than 30ml/min) Same dose convert to Q48
• CPK baseline (D/C at 10x baseline)

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MRSA is a complex and growing problem that is not
going away. Get comfortable with or work with
someone who is competent treating this growing
dilemma
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Respect MRSA like Tantor