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ORSA Soft Tissue Infections. Michelle Floris-Moore, MD, MS M. Andrew Greganti , MD. 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. Community-Acquired ORSA.

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orsa soft tissue infections

ORSA Soft Tissue Infections

Michelle Floris-Moore, MD, MS

M. Andrew Greganti, MD

disclosure of financial relationships
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 .

community acquired orsa
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.
comparing ca orsa to ha orsa
Comparing CA-ORSA to HA-ORSA

Diederen BMW, et al. JID 2006;52:157-168

mechanism of resistance
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, SCCmec.
mechanisms of resistance
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
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
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.
risk factors for ca orsa
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

other high risk groups
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
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
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
necrotizing fasciitis
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
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
  • Lee MC, Pediatr Infect Dis J. 2004;23:123-7.
  • Young DM, Arch Surg 2004;139:947-51.
outpatient vs inpatient treatment
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
slide16

Spectrum of ORSA

Skin & Soft Tissue Infections

options for oral antibiotic therapy
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
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 1992;117:390-398

clindamycin and rx of ca orsa
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
D-zone Test for Inducible Clindamycin Resistance

Daum et al, NEJM 2007;357(40):380

options for iv therapy
Options for IV Therapy
  • Vancomycin
  • Linezolid
  • Daptomycin – should not use to treat pneumonia. Inactivated by surfactant.
  • Tigecycline
monitoring while on therapy
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.

caution
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.
consequences of inadequate treatment of staph aureus infections
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
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 strep1
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.
slide31

Algorithm available online - http://www.unc.edu/depts/spice/CA-ORSA.html

decolonization does it help
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. TacconelliE, et al. ClinInfDis 2003; 37:1629-1638.

2. Huang J, et al. Pediatrics 2009;123:e808-814.

agents used for decolonization
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.
the hands give it away
“THE HANDS GIVE IT AWAY”

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
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 ca orsa
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.
today s case
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.