Overview Skin and So) Tissue Infec1ons: MRSA and Beyond Catherine Liu, M.D. Assistant Clinical Professor Division of Infec1ous Diseases University of California, San Francisco 2011 IDSA MRSA Treatment Guidelines Management of skin and so) 1ssue infec1ons (SSTI) Abscesses Celluli1s (purulent vs. non- purulent) Recurrent SSTI Complicated SSTI Necro1zing fascii1s Other SSTI 32 y/o M with 3 days of an enlarging, painful lesion on his L thigh that he avributes to a spider bite. T 36.9 BP 118/70 P 82 Case 1 What is the appropriate management of this pa1ent? A. Incision and drainage alone B. Incision and drainage plus oral an1- MRSA an1microbial agent C. Oral an1- MRSA an1microbial agent 1
Abscesses Incision and drainage is the primary treatment (AII). For simple abscesses or boils, I&D alone likely adequate Do an1bio1cs provide addi1onal benefit? Mul1ple, observa1onal studies: high cure rates with or without abx 3 RCTs of uncomplicated skin abscesses; 2 large NIH trials pending Is clinical cure the only important endpoint? Development of recurrent lesions Clinical cure p=.25 p=.12 p=.52 cephalexin TMP-SMX TMP-SMX p=.04 p=.58 p=.02 1 Rajendran AAC 2007; 2 Duong Ann Emerg Med 2009; 3 Schmitz G Ann Emerg Med 2010 Duong Ann Emerg Med 2009 ;Schmitz G Ann Emerg Med 2010; Talan Ann Em Med 2010; Spellburg Ann Em Med 2011 An1bio1c therapy is recommended for abscesses associated with: Severe, extensive disease, rapidly progressive with associated celluli1s or sep1c phlebi1s Signs & sx of systemic illness Associated comorbidi1es, immunosuppressed Extremes of age Difficult to drain area (e.g. face, hand, genitalia) Failure of prior I&D (AIII) Liu CID 2011; 52: 285-322 Microbiology of Purulent SSTIs: ER Pa1ents viridans strep; 2% coag neg staph; 6% B- hemoly3c strep; 2% MSSA 16% other/ unknown, 15% 2004 2008 MRSA 59% Moran NEJM 2006; Talan CID 2011 2
Purulent Celluli1s Celluli1s associated with purulent drainage or exudate without a drainable abscess Empiric Rx for CA- MRSA is recommended (AII). Empiric Rx for β- hemoly1c strep unlikely needed (AII). Dura1on of therapy: 5-10 days, individualize based on clinical response Outpa1ent purulent celluli1s: Empiric Rx for CA- MRSA Drug Adult Dose Comments TMP/SMX 1-2 DS BID - Very low rates of resistance - MRSA & MSSA - Unreliable for group A strep Doxycycline, Minocycline Clindamycin 100 BID - Low resistance - MRSA & MSSA - - Unreliable for group A strep 300-450 TID - MRSA, MSSA, & group A strep - Excellent 1ssue & abscess penetra1on - C. difficile risk Linezolid 600 BID - MRSA, MSSA, & group A strep - Most expensive op1on Liu CID 2011; 52: 285-322 28 year old woman with erythema of her le) foot x 48 hours. No purulent drainage, exudate or abscess. Case 2 T 37.0 BP 132/70 P 78 Eells SJ et al Epidemiology and Infec1on 2010 What is the appropriate management of this pa1ent? A. Clindamycin 300 mg PO 1d B. Cephalexin 500 mg QID, monitor clinically with addi1on of TMP/SMX if no response C. Cephalexin 500 mg QID and TMP/ SMX 2 DS tab PO bid 3
Nonpurulent Celluli1s: β- hemoly1c strep vs. staph? Empiric Rx for β- hemoly1c strep recommended (AII) Prospec1ve study 1, 248 hospitalized pts 73% due to β- hemoly1c strep (diagnosis by serologies for ASO and an1- DNAse- B, blood cultures); 27% with no iden1fied cause. Overall 96% response rate to β- lactam an1bio1c (cefazolin, oxacillin, cephalexin, dicloxacillin). Retrospec1ve study 2 treatment failures with TMP- SMX vs. β- lactam or clindamycin The role of CA- MRSA is unknown. Empiric Rx for MRSA if fails to respond to β- lactam Outpa1ent nonpurulent celluli1s: Empiric Rx for β- hemoly1c streptococci, +/- MRSA Drug Cephalexin Dicloxacillin Clindamycin* Linezolid* *Also have ac1vity against MSSA and MRSA Adult Dose 500 QID 500 QID 300-450 TID 600 BID 1 Jeng et al Medicine 2010; 2 EllioV et al Pediatrics 2009; Liu CID 2011; 52: 285-322 Microbiology of SSTI: Hospitalized Pa1ents An1microbial Usage 322 hospitalized pa1ents with celluli1s, abscess, complicated SSTI 97% of cases had S. aureus or Streptococcus spp. 74% S. aureus or Streptococcus ONLY Enterococci 3% Jenkins CID 2010; 51: 895-903 Jenkins CID 2010; 51: 895-903 4
Implementa1on of a clinical prac1ce guideline for inpa1ent celluli1s and abscess An1bio1c U1liza1on Post- Interven1on July 2009-2010: Empiric Rx: IV vancomycin, then tailor to culture, step- down to PO therapy for 5-7 days Specifically discouraged: Gram nega1ve and an1- anaerobic agents ESR CRP Plain films, CT, MRI Developed electronic admission order set Educa1onal campaign for faculty and housestaff peer champions from 5 departments (ER, adult urgent care, internal medicine, general surgery, orthopedic surgery) * * * * *p<.05 Audit/ feedback Jenkins Arch Intern Med 2011; 171: 1072-9 Jenkins Arch Intern Med 2011; 171: 1072-9 Other Outcomes Median dura1on of Rx (13 vs. 10d, p<.001) pa1ents treated for < 10d (14% vs. 38%, p <.001) pa1ents treated for > 14d (33% vs. 12%, p <.001) No differences in clinical outcomes: Clinical failure (7.7% vs. 7.4%, p=ns) Recurrent infec1on Rehospitaliza1on due to SSTI Length of hospital stay Considera1ons for Clinical Prac1ce S. aureus (esp. MRSA) and streptococci are the dominant pathogens in hospitalized pts with SSTI Broad- spectrum gram nega1ve and anaerobic agent use very common but unnecessary in most cases Shorter dura1ons of therapy (7 days) likely adequate Jenkins Arch Intern Med 2011; 171: 1072-9 Jenkins CID 2010; 51: 895-903 5
Complicated SSTI Surgical debridement & empiric Rx for MRSA pending cx An1bio1c Adult Evidence Grade Vancomycin 15-20 mg/kg IV Q8-12 AI Linezolid 600 mg PO/ IV BID AI Daptomycin 4 mg/kg IV QD AI Telavancin 10 mg/kg IV QD AI Clindamycin 600 mg PO/IV Q8 AIII Ce)aroline 600 mg IV Q12 FDA approved a)er guidelines Tigecycline 100 mg IV x 1, then 50 IV Q12 Consider alternate agent as associated with mortality Summary: empiric management of SSTIs Uncomplicated Complicated I&D Purulent (MRSA) Consider addi1on of an1- MRSA an1bio1c in select situa1ons 1 I&D plus vancomycin (or alterna1ve) 2,no gram neg in most cases 3 Non- purulent (β- hemoly1c strep) Cephalexin 500 QID Dicloxacillin 500 QID Consider addi1on of MRSA ac1ve agent if no response 1 Vancomycin (or alterna1ve) 2, no gram neg in most cases 3 1. Systemic illness, purulent celluli1s/wound infec1on, comorbidi1es, extremes of age, abscess difficult to drain or face/hand, sep1c phlebi1s, lack of response of to I&D alone. PO an1bio1c : TMP- SMX 1 DS BID, Clindamycin 300 mg TID, Doxycycline 100 PO BID 2. Daptomycin, linezolid, telavancin, ce)aroline 3. Except: cri1cally ill pts with serious SSTI (nec fasc), perirectal/ periorbital infec1ons, decubitus ulcer infec1ons, severe diabe1c foot infec1ons, animal bites, water- exposure Liu CID 2011; 52: 285-322 Host Personal Hygiene/ Wound Care (AIII) - Cover draining wounds - Hand hygiene Host - Avoid sharing personal items if ac1ve infec1on Environment Pathogen Environment Pathogen Environmental Hygiene (CIII) - Clean high- touch surfaces Decoloniza3on (CIII) - If above measures fail - If ongoing household transmission 6
Does Decoloniza1on Prevent Recurrent SSTI? Open- label, RCT: 300 subjects with community- onset SSTI and S. aureus coloniza1on in nares, axilla, or inguinal folds * *p.05 Household vs. Individual Decoloniza1on? Open- label RCT children with community- onset SSTI and S. aureus coloniza1on (nares, axilla, inguinal) 2 Index case vs. household decoloniza1on (mupirocin + CHG baths x 5d) All received hygiene educa1on: Avoid sharing personal hygiene items Use liquid pump or pour soaps and lo1ons (vs. bar soaps and lo1on jars) Launder towels and washcloths a)er each use Launder bed linens once weekly No difference in rate of eradica1on of S. aureus carriage. @ 1 month: 50% vs. 51% (p = 1.0) @ 12 months: 54% vs. 66% (p=.28) Fritz ICHE 2011; 32:872-80 Fritz CID 2012; 54:743-51 SSTI among Cases and Household Contacts p=.02 p=.008 p=.02 p=.04 p=.10 p=.12 p=.005 p=.01 Fritz CID 2012; 54: 743-51 Liu CID 2011; 52: 285-322 7
Summary: Decoloniza1on for Preven1on of SSTI Case 3 Mupirocin containing regimens reduce S. aureus coloniza1on S1ll no clear data that shows decoloniza1on prevents recurrent SSTI In one study of children, decoloniza1on of en1re household reduced subsequent SSTI in cases and their contacts compared with individual decoloniza1on. 54 yo F with DM, pimple in R groin 5 days ago, erythema, worsening pain, swelling, and blistering x 24 hours T 38.8 P110 BP124/50 R18 98%RA Dufel S, Martino M. J Fam Pract. 2006;55(5):396. What would your empiric therapy be in this case? A. Admit, IV penicillin and clindamycin B. Admit, IV vancomycin and piperacillin- tazobactam C. Call surgery, IV vancomycin and clindamycin D. Call surgery, IV vancomycin, piperacillin- tazobactam, clindamycin Necro1zing skin and so) infec1ons Monomicrobial (Group A strep > S. aureus, Clostridia, gram neg rare) Polymicrobial (gram +, gram -, anaerobes) associated w/ abdominal surgery, decub ulcers, IVDU, spread from GU tract 8
Risk Factors for Necro3zing SSTI Clinical Presenta1on IVDU Diabetes Obesity Chronic immunosuppression O)en no precipita1ng factor Anaya DA. Clin Infect Dis. 2007 Nonspecific complaints: pain, GI (N/V/D), influenza- like symptoms Physical exam difficult to dis1nguish from celluli1s, some1mes only mild local erythema pain out of propor3on Missed Dx of Necro1zing Fascii1s Ini3al Diagnoses by PCP/ ER No. Musculoskeletal Pain 6 (40%) Influenza 3 (20%) Gastroenteri1s 2 (13%) Hemorrhoids 1 (6%) Gout 1 (6%) 1 burn 1 (6%) Varicella 1 (6%) Bisno CID 2000 Wong CH Crit Care Med 2004 % of pa3ents 100 90 80 70 60 50 40 30 20 10 0 Necro1zing so) 1ssue infec1ons: physical findings on admission Tenderness Erythema Warmth Bullae Indura1on Fluctuance n=89; 14% dx with nec fasc on admit Late findings Crepitus Necrosis Sensory/ motor deficits Hypotension Fever Tachycardia Wong CH. Jour of Bone and Joint Surg. 2003 Necro1zing so) 1ssue infec1ons: radiographic techniques Plain films Low sensi1vity Helpful if gas present CT and ultrasound May iden1fy other Dx (abscess) MRI Enhanced sensi1vity, low specificity Dufel S, Martino M. J Fam Pract. 2006;55(5):396. 9
Why is Early Diagnosis So Important? Summary: Management of necro1zing skin and so) 1ssue infec1ons Early surgical consult/ interven3on Empiric an1microbial therapy Piperacillin/tazobactam or carbapenem (group A strep, other gram pos, gram negs and anaerobes) plus Clindamycin (group A strep toxin inhibiaon) plus Vancomycin (MRSA) Wong CH. J of Bone and Joint Surg. 2003 53 yo M ER physician presents with 9 day history of progressive celluli1s of L forearm. Ini1ally noted a pustule self I&D, started keflex + clindamycin x 4 days. Progressive erythema and drainage. Started IV vanco + ce)riaxone with no improvement a)er 3 days. Case 4 Further history History of chronic benign neutropenia 3 weeks ago, trip to Arizona where cleared brush in order to replace a water drip line and scraped his arm 2 weeks ago, worked in home (Merced) vegetable garden clearing eggplant and pepper brushes 7 days ago, cleaned his fish tank No animal or 1ck bites Only recent travel to Arizona 10
All of the following are possible causes of his infec1on EXCEPT: Gram stain from wound culture A. Mycobacterium marinum B. Coccidioides immias C. Nocardia brasiliensis D. Brucella melitensis E. Sporothrix schenkii Nocardia brasiliensis Nocardia Soil inhabitant Worldwide distribu1on Incuba1on period: <1-6 weeks O)en with mild systemic symptoms Nocardia brasiliensis > asteroides for cutaneous disease Diagnosis: biopsy and culture Par1ally acid- fast, gram variable branching rods. Treatment: TMP- SMX x 4-6 months 26 yo M with 6 week history of R hand papule ulcer Mul1ple visits to ED and urgent care, Receives several courses of abx, no improvement 11
Leishmania panamensis Approach to Nodular lymphangi1s Take a good history Obtain biopsy Pathology: stain for fungi and mycobacteria Cultures: bacterial, fungal, and mycobacterial Consider empiric therapy based on severity of disease and history prior to biopsy results Common causes: Sporothrix schenckii, Nocardia, Mycobacterium marinum, Francisella tularensis, Leishmania spp. Which of the following reflect true infec1ous celluli1s? 12
Which of the following reflect true infec1ous celluli1s? True celluli1s Acute on chronic stasis derma11s Acute stasis derma11s Contact derma11s David Derm Online J 2011 Masqueraders of Infec1ous Celluli1s Stasis derma11s Superficial thrombophlebi1s and deep venous thrombosis Contact derma11s Insect s1ngs/1ck bites Drug reac1ons Gouty arthri1s Foreign body reac1on (e.g. surgical mesh, orthopedic implants) Lymphedema Malignancy (e.g. T- cell lymphoma) Falagas ME Ann Intern Med 2005 Summary Thank you! catherine.liu@ucsf.edu 13