ORSA Soft Tissue Infections

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ORSA Soft Tissue Infections

• Michelle Floris-Moore, MD, MS
• M. Andrew Greganti, MD

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Disclosure of Financial Relationships

• Please note that I have had no financial
  relationships with commercial interests related
  to this educational activity within the past 12
  months .

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Community-Acquired ORSA

• Definition
• Diagnosis of ORSA made in outpatient setting or
  culture positive within 48 hours of
  hospitalization.
• AND
• No history within past 1 year of any of the
  following
• Hospitalization or residence in long-term care
  facility
• Surgery or dialysis
• Indwelling catheter or percutaneous medical
  device.

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Comparing CA-ORSA to HA-ORSA
CA-ORSA HA-ORSA
Epidemiology Clusters and outbreaks in closed populations Healthcare-associated outbreaks
Underlying condition Often otherwise healthy Risk factors for HA infections. Usually underlying comorbidity.
Age group Younger Older
Resistance pattern Susceptible to multiple antibiotics Resistant to multiple antibiotics
Genotype SCCmec IV SCCmec I, II, or III
Virulence PVL present PVL absent
Diederen BMW, et al. JID 200652157-168
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Mechanism of Resistance

• Acquisition of genes that code for altered
  penicillin-binding proteins - PBP 2A.
• PBP2A has low affinity for ß-lactams is
  resistant to oxacillin and all other ß-lactams.
• PBP2A encoded for by mecA gene.
• mec A carried by a mobile genomic element, SCCmec.

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Mechanisms of Resistance

• CA-ORSA and HA-ORSA have different SCCmec
• SCCmec I, II, and III are found in HA-ORSA clones
• SCCmec IV found in CA-ORSA
• Does not carry multiple antibiotic resistance
  genes
• Associated with other elements including PVL and
  other exotoxin genes

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Panton-Valentine Leukocidin

• Virulence factor reported in 1932 by Panton and
  Valentine.
• Damages cell membranes, lyses WBCs.
• Encoded by a mobile genetic element .
• Highly prevalent in CA-ORSA but rarely found in
  HA-ORSA.
• Associated with
• Furunculosis
• Severe, rapidly progressing SSTIs.
• Necrotizing PNA

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Factors predisposing to S. aureus infection

• Defects in chemotaxis
• - Job syndrome Chediak-Higashi syndrome Down
  syndrome
• - Decompensated DM Rheumatoid arthritis.
• Staphylocidal defects of PMNs
• Chronic Granulomatous Disease
• AML CML Lymphoblastic leukemia.

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Risk Factors for CA-ORSA
SKIN CONTACT
Crowded facilities Shelters Prisons
Sex partners
SHARING PERSONAL ITEMS
COMPROMISED SKIN INTEGRITY
Sports teams
Atopic dermatitis Psoriasis IDU Tattoos Military
recruits
Household contacts
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Other High Risk Groups

• People with HIV infection 1,2
• Men who have sex with men 2,3
• Native Americans living in rural areas 4
• Pacific-Islanders 5

1. Crum-Cianflone N et al, AIDS Patient Care STDS
200923499-502. 2. Lee NE et al , Clin Infect
Dis 2005 401529-34. 3. Centers for Disease
Control Prevention, MMWR 2003 5288. 4.
Centers for Disease Control Prevention, MMWR
2004 53767-770.
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CA-ORSA Prevalence

• Exact prevalence of CA-ORSA in North Carolina is
  unknown Individual cases not reportable.
• Estimates suggest 60 - 80 of community acquired
  - S. aureus infections in U.S. caused by ORSA.
  1,2
• Studies in children in NC show that 75 - 85 of
  community acquired-S. aureus isolates were ORSA.
  3,4
• Lab data at UNC suggest that about 50 of ORSA
  isolates from the inpatient units are CA-ORSA.

1.Daum RS. N Engl J Med 2007357380-390. 2. King
MD et al, Ann Intern Med 2006144309-317. 3.Magil
ner D et al, NC Med J 200869351-54. 4. Shapiro
A, et al. NC Med J 200970102-7.
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Clinical Presentation of ORSA

• Skin and soft tissue infections
• Impetigo, cellulitis
• Folliculitis, furuncles, abscesses
• Invasive soft tissue infections necrotizing
  fasciitis, pyomositis
• Spider bite ? Always suspect S. aureus
• Osteomyelitis, Septic arthritis, Septic bursitis
• Necrotizing pneumonia (isolated or
  post-influenza)
• Bactermia
• Endocarditis

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Necrotizing Fasciitis

• Bullae often present, crepitus may be absent
• Pain out of proportion to exam
• May progress very rapidly, however may also have
  evolved over course of a few days
• Requires emergent surgical debridement and
  drainage
• Initial antibiotics should provide broad spectrum
  coverage
• Include optimal agents against ORSA (Vanco) and
  Strep (a PCN) as well as Gram negatives and
  anaerobes.

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Incision Drainage

• Obtain specimen for culture whenever possible.
• I D is part of primary therapy for
  furuncles/abscesses.
• If not amenable to ID can perform aspiration
• Small furuncles can apply moist heat
• Limited data 1,2 suggest that I D may be
  adequate therapy for otherwise healthy patients
  with mild, limited (lt 5cm diameter) SSTI in a
  site amenable to complete drainage if
• no evidence of rapid progression
• no signs of systemic infection
• no other co-morbidities

1. Lee MC, Pediatr Infect Dis J. 200423123-7.
2. Young DM, Arch Surg 2004139947-51.

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Outpatient vs. Inpatient Treatment

• Unstable co-morbidity (e.g. decompensated DM)
• Unstable clinical status
• Toxic-appearing
• Rapidly progressive infection
• Limb-threatening infection (e.g. necrotizing
  fasciitis)
• Sepsis syndrome

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Spectrum of ORSA Skin Soft Tissue Infections
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Options for Oral Antibiotic Therapy

• Trimethoprim-Sulfamethoxazole (TMP-SMX)
• Clindamycin
• Doxycycline ( Rifampin, if not contraindicated)
• Minocycline ( Rifampin, if not contraindicated)
• Linezolid
• should not be used routinely
• possibility of inducible resistance
• risk of bone marrow suppression
• high cost

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TMP-SMX and Rx of CA-ORSA

• No randomized trials of TMP-SMX for CA-ORSA.
• Trial of IV TMP-SMX vs. Vanco for S. aureus
  infection (ORSA and OSSA) ? Vanco superior
  overall but no treatment failures among ORSA
  infections in TMP-SMX group.1
• Most clinicians consider TMP-SMX as first-line
  oral therapy for CA-ORSA.
• Dosage (normal renal function) 2 DS tabs BID
• Use of lower dose associated with higher
  treatment failure rate.

1. Markowitz et al, Ann Intern Med
1992117390-398
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Clindamycin and Rx of CA-ORSA

• Widely used in treatment of SSTI. Can treat both
  S. aureus and Streptococci. No randomized trials
  for treatment of CA-ORSA.
• Possibility of inducible resistance to
  clindamycin if lab results show organism
  sensitive to clindamycin but resistant to
  erythromycin
• If resistance due to inducible expression of erm
  gene then single step mutation ? methylation of
  binding site for macrolides, clinda, and
  streptogramin ? resistance to all (MLSB
  resistance).
• If erythromycin resistance due to efflux pump,
  organism remains sensitive to clindamycin.
• UNC Micro lab routinely does D-test for
  clindamycin susceptibility on Staph aureus
  isolates . If using other labs need to
  specifically request.

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D-zone Test for Inducible Clindamycin Resistance
Daum et al, NEJM 2007357(40)380
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Options for IV Therapy

• Vancomycin
• Linezolid
• Daptomycin should not use to treat pneumonia.
  Inactivated by surfactant.
• Tigecycline

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Monitoring While on Therapy

• Vancomycin
• Renal function and vanco serum levels at least 1x
  per week (more frequent if unstable renal
  function)
• Aim to maintain adequate trough level (gt10mg/ml,
  may be higher for complicated infections) while
  avoiding toxicity.
• Daptomycin CPK 1x per week stop if CPK gt5x ULN
  (symptomatic) or gt10x ULN (asymptomatic).
• Linezolid CBC platelets 1x / week stop if
  platelets lt50,000/mm3 or ? in WBC or RBC.

Rybak MJ et al. Vancomycin Therapeutic
Guidelines. CID 200949325-327.
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CAUTION

• Quinolones NOT RECOMMENDED for treatment of ORSA.
• Macrolides NOT RECOMMENDED for treatment of ORSA.
• Daptomycin NOT RECOMMENDED for pneumonia
  treatment.
• Rifampin
• should NOT be used as monotherapy (resistance
  develops rapidly).
• need to evaluate carefully for drug-drug
  interactions and other contra-indications to use
  of rifampin.

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Consequences of Inadequate Treatment of Staph
Aureus Infections

• Persistent infection at initial site.
• Contiguous spread.
• Bacteremia
• Endocarditis
• Metastatic infection
• e.g. Osteomyelitis (vertebral, pubic symphisis)

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What about Strep?

• Difficult to distinguish strep from staph
  cellulitis based solely on clinical exam.
• Folliculitis most often caused by Staph. Abrupt
  onset of large abscess often seen with CA-ORSA
  (PVL).
• Regional lymphadenopathy favors Strep.
• Both may cause necrotizing fasciitis.

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What about Strep?

• TMP-SMX and Tetracyclines NOT RECOMMENDED for
  treatment of Strep.
• Clindamycin and ß-lactams offer superior coverage
  for Strep.
• May need to use combination therapy if concerned
  about possibility of both ORSA and Strep
  infection.

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Algorithm available online - http//www.unc.edu/d
epts/spice/CA-ORSA.html
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Decolonization Does it help?

• 15-35 of normal hosts carry S. aureus in the
  nares or pharynx. Nasal carriage is a risk factor
  for infection.1
• Intranasal muciporin eliminates colonization but
  recolonization occurs frequently.2
• No data to support efficacy of decolonization
  agents for patients with ORSA .
• Reasonable to try decolonization
• When individual has multiple recurrent ORSA
  infections.
• There is ongoing ORSA transmission within
  well-defined group.

1. Tacconelli E, et al. Clin Inf Dis 2003
371629-1638. 2. Huang J, et al. Pediatrics
2009123e808-814.
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Agents Used for Decolonization

• Mupirocin ointment applied intranasally BID for
  10 days.
• Mupirocin ointment under fingernails BID
• Chlorhexidine 4 solution used to wash the body
  once daily for 10 days.
• Chlorhexidine-based oral spray 3-4X day.

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THE HANDS GIVE IT AWAY
A Culture of a health care workers ungloved
hand taken after performing an abdominal exam on
a patient who had ORSA on surveillance
cultures. B Culture taken after hand cleaned
with alcohol foam.
Donskey CJ, Eckstein BS. NEJM 2009360e3
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Isolation Precautions for ORSA

• Contact isolation
• Private room
• Gown
• Gloves
• Hand hygiene before and after patient contact
• Before leaving patients room Remove gown ?
  Remove gloves ? Wash hands.
• Dedicated equipment (e.g. stethoscope)

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Reporting Requirements for CA-ORSA

• In NC required to report outbreaks but not
  individual cases.
• Outbreak Two or more cases linked in time or
  space.
• If at UNC Hospitals, report to Infection Control
• 966-1636. On-call pager 216-6652 available 24/7.
• If outside UNC, report to County Dept. of Health.

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Todays Case

• Has Diabetes Mellitus
• Close contact with recent ORSA cellulitis.
• Is a nurse with frequent patient contact
• Has h/o cervical fusion increases risk for
  complications if infection not eradicated
• Treated initially with TMP-SMX DS 1 tab PO BID
• Clinical worsening on initial therapy
• I D done at 2nd presentation. Clindamycin
  added but poorly tolerated.

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