Disclosures Update in Management of Skin and Soft Tissue None - PDF document

5/25/16 Disclosures Update in Management of Skin and Soft Tissue • None Infections Catherine Liu, MD Associate Professor UCSF, Division of Infectious Diseases Overview • Purulent SSTI (abscesses) • Non-purulent SSTI (cellulitis) • Recurrent SSTIs • Necrotizing SSTI • Potpourri of cases IDSA Guidelines on SSTI. 2014 1

5/25/16 IDSA Guidelines on SSTI. 2014 IDSA Guidelines on SSTI. 2014 How would you manage this Case 1 patient? 32 y/o M with 3 days of an A. Incision and drainage alone enlarging, painful lesion on his L thigh that he attributes to a “ spider B. Incision and drainage plus cephalexin bite ” C. Incision and drainage plus TMP-SMX T 36.9 BP 118/70 P 82 D. TMP-SMX alone 2

5/25/16 Abscesses: Do antibiotics provide IDSA Guideline Recommendations benefit over I&D alone? • MRSA Guidelines (2011) 100% – For a cutaneous abscess, I&D is the primary treatment. For simple abscesses or boils, I&D alone is likely to be adequate , but additional data 80% are needed to further define the role of antibiotics, if any, in this setting % patients cured (AII ) Placebo 60% – Antibiotic Rx is recommended for abscesses associated with: severe/ extensive disease, signs/ sx of systemic illness, associated comorbidities, Antibiotic immunosuppression , extremes of age, abscess in area difficult to drain, 40% associated septic phlebitis, lack of response to I&D alone (AIII) p=.25 p=.12 p=.52 20% • Skin and Soft Tissue Infection Guidelines (2014) Cephalexin TMP-SMX TMP-SMX – The decision to administer antibiotics in addition to I&D should be based 0% on presence/ absence of SIRS and pts with severely impaired host Rajendran '07 Duong '09 Schmitz '10 defenses (strong, low) – The addition of systemic antibiotics to I&D of cutaneous abscesses does 1 Rajendran AAC 2007; 2 Schmitz G Ann Emerg Med 2010; 3 Duong Ann Emerg Med 2009 not improve cure rates , even in those due to MRSA Results from NIH Trials: Secondary Outcomes: NIH trials Antibiotics + I&D vs. I&D alone • Chambers: Recurrence Rates after 1 month: – Clinda (7%) vs TMP/SMX (14%) vs placebo (12%) • Talan: Complications TMP-SMX Placebo New infected site at TOC 3.1% 10.3%* Surgical procedure at TOC 3.4% 8.6%* Infection in household member 1.7% 4.1%* Invasive infection 0.4% 0.4% GI side effects 42.7% 36.1% Rx d/c due to AE 1.9% 0.6% N=786 N=1247 *p<.05 Personal communication, Chip Chambers M.D.; Talan NEJM 2016 Personal communication, Chip Chambers, M.D.; Talan NEJM 2016 3

5/25/16 NEJM Poll Results: Should Patient be Rx with I&D alone or I&D + TMP-SMX? (N=767) • Case: 22 yo F p/w 2 cm abscess on L thigh. Afebrile, VSS, no other systemic symptoms. • Exam: 2 cm area of fluctuance with 2 cm area of surrounding erythema Wilbur NEJM 2016 Should We Change Clinical Microbiology of Purulent SSTIs Practice? • Summary: – Cure rates among pts receiving I&D alone are high – Very low risk of serious, invasive infections – Abx provide a modest benefit (~ 10%) over I&D alone • Recommendations: Shared decision-making approach with patients – Risks vs benefits Moran NEJM 2006 Talan CID 2011 4

5/25/16 Empiric PO Antibiotics for Purulent SSTIs TMP-SMX: 1 or 2 DS tabs BID? (MRSA active agents) Strep Dosing Comments 1. IDSA guidelines says 1 or 2 active 2. Prospective study compared 1 vs. 2 tab BID PO agents • No difference in cure rate: 73% vs. 75% (P=0.79) TMP-SMX +/- Q12h HyperK+ 3. Recent NIH studies Doxy/mino +/- Q12h GI; Photosensitivity • Chambers (1 DS BID) – 93% cure rate Clindamycin ++ Q8h Diarrhea, ↑ resistance • Talan (2 DS BID) – 93% cure rate 4. Risk factors for SSTI treatment failure: Linezolid ++ Q12h $$$; T ox - heme, SSRI • Retrospective study -- Weight > 100 kg Rx 1 DS BID T edizolid ++ QD $$$; better safety Summary: 1 DS BID ok, consider 2 DS BID in obese profile vs linezolid Cadena J. AAC. 2011; Halilovic J. Infect. 2012 Microbiology of SSTI: FDA Approved Agents for Treatment of Complicated SSTI Hospitalized Patients Agent Dose Duration Cost/day Vancomycin 15-20 mg/kg q8-12h 7-14 days $16 Daptomycin IV 4 mg/kg q24h, push 7-14 days $350 Linezolid PO/IV 600 mg q12h 10-14 days $280 T elavancin IV 10 mg/kg q24h 7-14 days $310 Ceftaroline IV 600 mg q12h 5-14 days $250 T edizolid PO/IV 200 mg 6 days $235 Oritavancin IV 1200 mg once over 3h 1 day $2900 Dalbavancin IV 1000 mg x1, 500 mg x1 one 8 days $3000/ wk later , over 30 min $1500 Slide courtesy of Chip Chambers, M.D. Jenkins T Clin Inf Dis 2010 5

5/25/16 Antibiotic Utilization Among Hospitalized Antibiotic Utilization Among Hospitalized Patients with SSTI: Baseline Patients with SSTI: Post-QI Intervention *Recommended empiric vanco *Discouraged gram neg/ anaerobic N=169 *Suggested Rx for 7 days p<.001 Jenkins T Arch Intern Med 2011 Jenkins T Arch Intern Med 2011 S aureus Other Outcomes (MRSA) • ¯ Median duration of Rx (13 vs. 10d, p<.001) • No differences in clinical outcomes +/- abx – Clinical failure (7.7% vs. 7.4%, p=NS) – Recurrent infection – Rehospitalization due to SSTI EMPIRIC RX – Length of hospital stay T edizolid Dalbavancin • Take home : Gram negative and anaerobic coverage Oritavancin unnecessary in most cases. – Exceptions: perirectal/ periorbital infections, critically ill pts with necrotizing SSTI, severe immunocompromise (malignancy on chemotherapy, neutropenia), animal bites, water exposure, severe diabetic foot Jenkins T Arch Intern Med 2011 IDSA Guidelines on SSTI. 2014 6

5/25/16 How would you manage this Case 2 patient? 28 y/o woman presents with erythema of her left A. Clindamycin 300 mg TID foot over past 48 hrs No purulent drainage, B. Cephalexin 500 mg QID exudate, or fluctuance. C. Cephalexin 500 mg QID + TMP/ SMX 1 DS BID T 37.0 BP 132/70 P 78 Eels SJ et al Epidemiology and Infection 2010 Nonpurulent Cellulitis: pathogen? Cephalexin vs. Cephalexin + TMP-SMX in patients with Uncomplicated Cellulitis -hemolytic strep vs. S. aureus ? b • Prospective study, hospitalized patients (N=248) N=146 Methods – Acute and convalescent titers (ASO and anti-DNaseB) – Rx with b -lactam antibiotics (cefazolin/oxacillin) Results – 73% due to b -hemolytic strep; 27% none identified – 96% response rate to b -lactam antibiotic • Prospective study, hospitalized patients (N=216) – Similar methods as above; 72% due to BHS; 13% probable BHS Siljander T . Clin Infect Dis . 2008 Jeng A. Medicine 2010. Elliott Pediatrics 2009; Bruun Pallin CID 2013;56: 1754-1762 OFID 2016 7

5/25/16 What about TMP-SMX for B-hem olytic Strep (GA S/ GB S) Uncomplicated Cellulitis? • Multicenter RCT (n=524) of adult/ peds outpts with abscess, cellulitis or both – Mean age 27, excluded significant comorbidities – Cure rates: TMP-SMX (78%) vs clindamycin (80%) • Nonpurulent cellulitis subgroup (n=280) – Cure rates: TMP-SMX (76%) vs clindamycin (81%) Summary: TMP-SMX is an option for TMP-SMX* nonpurulent, uncomplicated cellulitis for younger pts without significant comorbidities IDSA Guidelines on SSTI. 2014 Miller LG NEJM 2015 How Long to Treat? Case 3 • Patient presents with 4 th abscess in 4 months • Uncomplicated SSTI: – 5 days, extend if infection has not improved within • Prior abscesses have involved different this time period locations and have been treated with I&D and • Complicated SSTI antibiotics with resolution – 7-14 days, individualize duration based on clinical • He asks if there is anything he can do to response prevent recurrences Stevens CID 2014; Liu CID 2011 8

5/25/16 How would you manage this How to Manage Recurrent Skin and patient? Soft Tissue Infections? A. Emphasize personal hygiene measures Host B. Decolonize with mupirocin and chlorhexidine C. Decolonize with TMP-SMX and rifampin D. A and B E. A and C Environment Pathogen Combination therapy? Decolonization strategies Mupirocin vs. mupirocin + chlorhexidine vs. mupirocin + bleach bath • Intranasal mupirocin: + data in MSSA SSTI w/ + nasal Cx, 80% no benefit among MRSA colonized military personnel 70% Colon. Clear 4m Repeat SSTI 6 m p<.02 60% • Chlorhexidine washes alone: not effective % of patients 50% • Mupirocin + CHG: Household >> individual decol 40% 30% • Bleach baths: no benefit vs hygiene education 20% • Oral antibiotics: Mup + hexachlorophene + TMP-SMX or 10% doxy x 10 d ↓ recurrent MRSA SSTI (31 pts); Anecdotal 0% experience with rifampin-based therapy Control Mup Mup+Chlor Mup+Bleach (Hygiene education alone) Raz Arch Intern Med 1996; Whitman ICHE 2010; Fritz ICHE 2012; Kaplan CID 2013; Miller AAC 2012 Fritz SA. Infect Control Hosp Epi. 2011 9