Update in Management of Skin and So1 Tissue Infec7ons. Disclosures. None 4/23/15
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1 Update in Management of Skin and So1 Tissue Infec7ons Catherine Liu, MD Associate Professor UCSF, Division of Infec7ous Diseases None Disclosures 1
2 Overview Purulent SSTI (abscesses) Non- purulent SSTI (celluli;s) Recurrent SSTIs IDSA Guidelines on SSTI
3 IDSA Guidelines on SSTI IDSA Guidelines on SSTI
4 B-hemolytic Strep (GAS/GBS) S aureus (MRSA) EMPIRIC RX NEW DRUGS! IDSA Guidelines on SSTI Purulent SSTI Non- purulent SSTI Recurrent SSTIs Overview 4
5 32 y/o M with 3 days of an enlarging, painful lesion on his L thigh that he ajributes to a spider bite Case 1 T 36.9 BP 118/70 P 82 How would you manage this pa;ent? A. Incision and drainage alone B. Incision and drainage plus cephalexin C. Incision and drainage plus TMP- SMX 5
6 Abscesses: Do an;bio;cs provide benefit over I&D alone? 100% 80% % pa7ents cured 60% 40% 20% p=.25 p=.12 p=.52 Placebo An7bio7c Cephalexin TMP-SMX TMP-SMX 0% Rajendran '07 Duong '09 Schmitz '10 1 Rajendran AAC 2007; 2 Schmitz G Ann Emerg Med 2010; 3 Duong Ann Emerg Med 2009 Is treatment failure the only important endpoint? Recurrent SSTI? Duong : 10 days 9% TMP- SMX vs. 28% placebo, p =.02 Schmitz: 30 days 13% TMP- SMX vs 26% placebo, p=.04 Schmitz G Ann Emerg Med 2010; Duong Ann Emerg Med
7 Microbiology of Purulent SSTIs Moran NEJM 2006 An;bio;c therapy is recommended for abscesses associated with: Severe disease, rapidly progressive with associated celluli;s or sep;c phlebi;s Signs or symptoms of systemic illness Associated comorbidi;es, immunosuppressed Extremes of age Difficult to drain area (face, hand, genitalia) Failure of prior I&D Liu C. Clin Infect Dis
8 Empiric PO An7bio7cs for Purulent SSTIs PO agents Strep ac7ve Dosing Comments TMP- SMX +/- Q12h HyperK+ Doxy/mino +/- Q12h GI; Photosensi;vity Clindamycin ++ Q8h resistance Linezolid ++ Q12h $$$; Tox - heme, SSRI TMP- SMX: 1 or 2 DS tabs BID 1. IDSA guidelines says 1 or 2 2. Prospec;ve study compared 1 vs. 2 tab BID No difference in cure rate: 73% vs. 75% (P=0.79) 3. Risk factors for SSTI treatment failure: Weight > 100 kg, OR 5.20, p=0.01 Morbid obese DCed on low dose clinda or TMP- SMX Summary: 1 DS BID ok, consider 2 DS BID in obese Cadena J. AAC. 2011; Halilovic J. Infect
9 Risk factors for hyperkalemia with TMP- SMX High dose vs. low dose ACE- I or ARB use Age > 58 NSAID use Baseline elevated Cr Summary: Consider checking K if on ACE- I/ARB or high dose TMP- SMX and have other RFs Gentry CA. Ann Pharmacother Empiric IV An7bio7cs for Purulent SSTIs Dosing Comments Vancomycin Q12h OK for bacteremia, PNA Daptomycin Q24h OK for bacteremia, not PNA Telavancin Q24h Approved for PNA, renal tox Cemaroline Q12h Ac;ve vs. Gram - (not pseudo) Dalbavancin Q7d x 2 Oritavancin x1 VRE ac;vity *Linezolid and tedizolid come in IV formulation as well 9
10 New an;- MRSA drugs for 2014 Semisynthe;c lipoglycopep;de Dalbavancin (Dalvance) Oritavancin (Orbac;v) New Oxazalidinone Tedizolid (Sivextro) Boucher H. NEJM. 2014; Morgan GF Lancet ID 2014; Corey GR NEJM 2014 Semisynthe;c lipoglycopep;de analogues Dalbavancin: 1000 mg IV x 1, 500 mg x 1 on day 7 via IV push Study: Dalba (90.6%) vs. vanco - > linezolid (93.8%) Oritavancin: Dose 1200 mg IV x 1 (t 1/2 > 100 hrs) via 3h infusion Study: Orita (82%) vs. vanco q12 x 7-10 day (79%) Spectrum: Ac;ve vs. VRSA and VRE Boucher H. NEJM. 2014; Morgan GF Lancet ID 2014; Corey GR NEJM
11 Tedizolid: A less toxic linezolid? Study: Tedizolid (6d) vs. Linezolid (10d) Dose: 200 mg po/iv once daily X 6 days Adverse effects: Less BM suppression? Spectrum: VRE, nocardia, NTMs, TB??? Prokocimer P JAMA 2013; Moran GJ Lancet ID 2014 S aureus (MRSA) EMPIRIC RX Tedizolid Dalbavancin Oritavancin IDSA Guidelines on SSTI
12 Purulent SSTI Non- purulent SSTI Recurrent SSTIs Overview 28 y/o woman presents with erythema of her lem foot over past 48 hrs No purulent drainage, exudate, or fluctuance. Case 2 T 37.0 BP 132/70 P 78 Eels SJ et al Epidemiology and Infection
13 How would you manage this pa;ent? A. Clindamycin 300 mg TID B. Cephalexin 500 mg QID, monitor clinically with addi;on of TMP/SMX if no response C. Cephalexin 500 mg QID + TMP/ SMX 1 DS BID Nonpurulent Celluli;s: pathogen? β- hemoly;c strep vs. S. aureus? Prospec;ve study, hospitalized pa;ents (N=248) Methods Acute and convalescent ;ters (ASO and an;- DNaseB) Rx with β - lactam an;bio;cs (cefazolin/oxacillin) Results 73% due to β- hemoly;c strep; 27% none iden;fied 96% response rate to β- lactam an;bio;c Siljander T. Clin Infect Dis Jeng A. Medicine Elliott Pediatrics
14 Cephalexin vs. Cephalexin + TMP- SMX in pa;ents with Uncomplicated Celluli;s N=146 Pallin CID 2013; 56: What about TMP- SMX for Uncomplicated Celluli;s? Mul;center RCT (n=524) of adult/ peds outpts with abscess, celluli;s or both Mean age 27, excluded significant comorbidi;es Cure rates: TMP- SMX (78%) vs clindamycin (80%) Celluli;s w/o abscess subgroup (n=280) Cure rates: TMP- SMX (76%) vs clindamycin (81%) Summary: TMP- SMX may be op7on for nonpurulent, uncomplicated celluli7s for younger pts without significant comorbidi7es Miller LG NEJM
15 Empiric An7bio7cs for Non- purulent SSTIs PO IV MSSA ac7ve MRSA ac7ve Dosing Penicillin - Q6h Cephalexin + Q6h Dicloxacillin + Q6h Clindamycin ++ + Q8h Penicillin - Q6h Cefazolin + Q8h Cemriaxone + Q24h B-hemolytic Strep (GAS/GBS) IDSA Guidelines on SSTI
16 Purulent SSTI Non- purulent SSTI Recurrent SSTIs Overview Case 3 Pa;ent presents with 4 th abscess in 4 months Prior abscesses have been treated with I&D and an;bio;cs with resolu;on He asks if there is anything he can do to prevent recurrences 16
17 How would you manage this pa;ent? A. Emphasize personal hygiene measures B. Decolonize with mupirocin and chlorhexidine C. Decolonize with TMP- SMX and rifampin D. Give daily low dose clindamycin How to Manage Recurrent Skin and Som Tissue Infec;ons? Host Environment Pathogen 17
18 Decoloniza;on strategies Intranasal mupirocin: + data in MSSA SSTI w/ + nasal Cx, no benefit among MRSA colonized military personnel Chlorhexidine washes alone: not effeceve Mupirocin + CHG: Household >> individual decol Bleach baths: no benefit vs hygiene educaeon Oral an;bio;cs: Mup + hexachlorophene + TMP- SMX or doxy x 10 d recurrent MRSA SSTI (31 pts); Anecdotal experience with rifampin- based therapy Raz Arch Intern Med 1996; Whitman ICHE 2010; Fritz ICHE 2012; Kaplan CID 2013; Miller AAC 2012 % of pa;ents Combina;on therapy? Mupirocin vs. mupirocin + chlorhexidine vs. 80% 70% 60% 50% 40% 30% 20% 10% 0% mupirocin + bleach bath Colon. Clear 4m Repeat SSTI 6 m p<.02 Control Mup Mup+Chlor Mup+Bleach Fritz SA. Infect Control Hosp Epi
19 Recurrent SSTI among Cases and Household Contacts (Mupirocin plus chlorhexidine) 100%# 80%# Individual$ Household$ p=.008 p=.02 60%# p=.02 40%# p=.12 20%# 0%# SSTI$$1$mo$ SSTI$$3$mo$ SSTI$$6$mo$ SSTI$$12$mo$ Fritz CID 2012; 54: PCN for Preven;on of Recurrent Celluli;s Blinded, RCT 274 pts with recurrent celluli;s Penicillin 250 mg BID vs. placebo x 12 months Pa;ent characteris;cs: Edema (66%), venous stasis (25%), ;nea pedis (36%) Outcomes: Recurrence: 22% (PCN) vs. 37% (placebo), p=.01 Amer treatment stopped, no difference Thomas NEJM 2013; 368:
20 IDSA Guideline Summary Recommenda;ons: Recurrent SSTI Recurrent Abscesses: Mupirocin + daily CHG baths, and daily decontamina;on of personal items (towels, sheets, clothes) x 5 days Recurrent Celluli;s: Treat predisposing/ underlying condi;ons Prophylac;c PO penicillin 250 BID or IM benzathine PCN Q 2-4wks Stevens CID 2014 Thank you! 20
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