ORSA Soft Tissue Infections

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

2. 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 .

3. 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.

4. Comparing CA-ORSA to HA-ORSA Diederen BMW, et al. JID 2006;52:157-168

5. 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.

6. 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

7. 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

8. 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.

9. 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

10. 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.

11. 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.

12. 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

13. 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.

14. 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.

15. 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

16. Spectrum of ORSA Skin & Soft Tissue Infections

19. 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

20. 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

21. 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.

22. D-zone Test for Inducible Clindamycin Resistance Daum et al, NEJM 2007;357(40):380

23. Options for IV Therapy • Vancomycin • Linezolid • Daptomycin – should not use to treat pneumonia. Inactivated by surfactant. • Tigecycline

24. 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.

25. 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.

26. 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)

27. 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.

28. 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.

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

32. 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.

33. 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.

34. “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

35. 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)

36. 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.

37. 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.