ORSA Soft Tissue Infections – Outpatient Managment

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					ORSA Soft Tissue Infections

  Michelle Floris-Moore, MD, MS
     M. Andrew Greganti, MD
     Disclosure of Financial

Please note that I have had no financial
relationships with commercial interests
related to this educational activity within
the past 12 months .
   Community-Acquired ORSA
    Diagnosis of ORSA made in outpatient setting or
     culture positive within 48 hours of hospitalization.
    No history within past 1 year of any of the following:
      - Hospitalization or residence in long-term care
      - Surgery or dialysis;
      - Indwelling catheter or percutaneous medical
Comparing CA-ORSA to HA-ORSA
                            CA-ORSA                   HA-ORSA
Epidemiology                Clusters and outbreaks    Healthcare-
                            in closed populations     associated outbreaks

Underlying                  Often otherwise healthy Risk factors for HA
condition                                           infections. Usually
Age group                   Younger                   Older
Resistance                  Susceptible to multiple   Resistant to multiple
pattern                     antibiotics               antibiotics

Genotype                    SCCmec IV                 SCCmec I, II, or III

Virulence                   PVL present               PVL absent

Diederen BMW, et al. JID 2006;52:157-168
        Mechanism of Resistance
   Acquisition of genes that code for altered penicillin-
    binding proteins - PBP 2A.

   PBP2A has low affinity for β-lactams; is resistant to
    oxacillin and all other β-lactams.

 PBP2A encoded for by mecA gene.

 mec A carried by a mobile genomic element,
     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
      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
Factors predisposing to S. aureus infection

  Defects in chemotaxis
    - Job syndrome; Chediak-Higashi syndrome; Down
    - Decompensated DM; Rheumatoid arthritis.

  Staphylocidal defects of PMNs
    - Chronic Granulomatous Disease;
    - AML; CML; Lymphoblastic leukemia.
         Risk Factors for CA-ORSA
                         Crowded facilities:   CONTACT

COMPROMISED                                         SHARING
SKIN                                                PERSONAL
INTEGRITY                                           ITEMS
            Atopic dermatitis
               Psoriasis                Household
               IDU; Tattoos             contacts
               Military recruits
               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 2009;23:499-502.
2. Lee NE et al , Clin Infect Dis 2005; 40:1529-34.
3. Centers for Disease Control & Prevention, MMWR 2003; 52:88.
4. Centers for Disease Control & Prevention, MMWR 2004; 53:767-770.
                         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 2007;357:380-390.      2. King MD et al, Ann Intern Med 2006;144:309-317.
3.Magilner D et al, NC Med J 2008;69:351-54.   4. Shapiro A, et al. NC Med J 2009;70:102-7.
     Clinical Presentation of ORSA
 Skin and soft tissue infections
   Impetigo, cellulitis
   Folliculitis, furuncles, abscesses
   Invasive soft tissue infections – necrotizing fasciitis,
   “Spider bite” → Always suspect S. aureus

 Osteomyelitis, Septic arthritis, Septic bursitis

 Necrotizing pneumonia (isolated or post-influenza)

 Bactermia

 Endocarditis
         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.
             Incision & Drainage
 Obtain specimen for culture whenever possible.

 I & D is part of primary therapy for furuncles/abscesses.
    If not amenable to I&D 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 (< 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. 2004;23:123-7.
                                   2. Young DM, Arch Surg 2004;139:947-51.
 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
 Sepsis syndrome
     Spectrum of ORSA
Skin & Soft Tissue Infections
  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
      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

 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 1992;117:390-398
  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.
        D-zone Test for Inducible
        Clindamycin Resistance

Daum et al, NEJM 2007;357(40):380
      Options for IV Therapy

 Vancomycin
 Linezolid
 Daptomycin – should not use to treat
 pneumonia. Inactivated by surfactant.
 Tigecycline
          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 (>10mg/ml, may be higher
        for complicated infections) while avoiding toxicity. *

  Daptomycin: CPK 1x per week; stop if CPK >5x ULN (symptomatic)
   or >10x ULN (asymptomatic).

  Linezolid: CBC & platelets 1x / week; stop if platelets <50,000/mm3
   or ↓ in WBC or RBC.

* Rybak MJ et al. Vancomycin Therapeutic Guidelines. CID 2009;49:325-327.
 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.
      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)
           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.
          What about Strep?
 TMP-SMX and Tetracyclines NOT
  RECOMMENDED for treatment of Strep.
 Clindamycin and β-lactams offer superior
  coverage for Strep.
 May need to use combination therapy if
  concerned about possibility of both ORSA and
  Strep infection.
Algorithm available online - http://www.unc.edu/depts/spice/CA-ORSA.html
         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; 37:1629-1638.
2. Huang J, et al. Pediatrics 2009;123:e808-814.
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.

                  A: Culture of a health
                  care worker’s 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 2009;360:e3
   Isolation Precautions for ORSA
 Contact isolation
   Private room
   Gown
   Gloves
   Hand hygiene before and after patient contact
   Before leaving patient’s room: Remove gown
    → Remove gloves → Wash hands.
   Dedicated equipment (e.g. stethoscope)
   Reporting Requirements for
 In NC required to report outbreaks but not
  individual cases.
 Outbreak = Two or more cases linked in time or
 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.
                Today’s 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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