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 .
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
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
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.
- 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
IDU; Tattoos contacts
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
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.
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
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)
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
Rapidly progressive infection
Limb-threatening infection (e.g. necrotizing
Spectrum of ORSA
Skin & Soft Tissue Infections
Options for Oral Antibiotic Therapy
Doxycycline (+ Rifampin, if not contraindicated)
Minocycline (+ Rifampin, if not contraindicated)
- 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
Daum et al, NEJM 2007;357(40):380
Options for IV Therapy
Daptomycin – should not use to treat
pneumonia. Inactivated by surfactant.
Monitoring While on Therapy
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.
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.
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-
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
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.
“THE HANDS GIVE IT AWAY”
A: Culture of a health
care worker’s ungloved
hand taken after
abdominal exam on a
patient who had ORSA
on surveillance cultures.
B: Culture taken after
hand cleaned with
Donskey CJ, Eckstein BS.
Isolation Precautions for ORSA
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
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.
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.