Overview Management of Skin and Soft Tissue Infections in the MRSA Era April 2011 2011 IDSA MRSA Treatment Guidelines Skin and soft tissue infections (SSTIs) Management of Recurrent SSTIs Necrotizing soft tissue infection Management of Animal Bites Brian S. Schwartz, MD Assistant Clinical Professor UCSF, Division of Infectious Diseases 32 y/o M with 3 days of an enlarging, painful lesion on his L thigh that he attributes to a spider bite T 36.9 BP 118/70 P 82 Case 1 How would you manage this patient? A. Incision and drainage alone B. Incision and drainage plus oral anti-mrsa antimicrobial agent C. Oral anti-mrsa antimicrobial agent 40% 51% 10% A. B. C. 1
Microbiology of Purulent SSTIs Abscesses: Do antibiotics provide benefit over I&D alone? 100% 80% % patients cured 60% 40% 20% p=.25 p=.12 p=.52 Placebo Antibiotic 0% Cephalexin TMP-SMX TMP-SMX Rajendran '07 Duong '09 Schmitz '10 Moran NEJM 2006 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 Antibiotic therapy is recommended for abscesses associated with: Severe disease, rapidly progressive with associated cellulitis or septic phlebitis Signs or symptoms of systemic illness Associated comorbidities, immunosuppressed Extremes of age Difficult to drain area (face, hand, genitalia) Schmitz G Ann Emerg Med 2010; Duong Ann Emerg Med 2009 Failure of prior I&D Liu C. Clin Infect Dis. 2011 2
When to culture a purulent SSTI? Empiric oral antibiotic Rx for uncomplicated purulent SSTI Patients Rx with antibiotics Patients with severe local infections Patients with signs of systemic illness Patient has not responded to initial Rx Concern for outbreak or cluster Drug TMP/SMX DS Doxycycline, Minocycline Clindamycin Linezolid Adult Dose 1-2 BID 100 BID 300-450 TID 600 BID *Rifampin is NOT recommended for routine treatment of SSTIs Liu C. Clin Infect Dis. 2011 28 y/o woman presents with erythema of her left foot over past 48 hrs No purulent drainage, exudate, or fluctuance. T 37.0 BP 132/70 P 78 Case 2 How would you manage this patient? A. Clindamycin 300 mg TID B. Cephalexin 500 mg QID, monitor clinically with addition of TMP/SMX if no response C. Cephalexin 500 mg QID + TMP/ SMX 2 DS BID 21% 54% 25% A. B. C. Eels SJ et al Epidemiology and Infection 2010 3
Nonpurulent Cellulitis: pathogen? β-hemolytic strep vs. S. aureus? Prospective study, hospitalized patients (N=248) Methods Acute and convalescent titers (ASO and anti-dnaseb) Rx with β-lactam antibiotics (cefazolin/oxacillin) Results 73% due to β-hemolytic strep; 27% none identified 96% response rate to β-lactam antibiotic Empiric treatment of uncomplicated nonpurulent cellulitis? Anti-β-hemolytic strep antibiotic (+/- anti-mssa) Drug Cephalexin Dicloxacillin Clindamycin* Linezolid* *Have activity against MRSA Adult Dose 500 QID 500 QID 300-450 TID 600 BID If poor response, add anti-mrsa antibiotic Siljander T. Clin Infect Dis. 2008 Jeng A. Medicine 2010. Elliott Pediatrics 2009 Summary: empiric management of SSTIs Empiric antibiotics for complicated SSTI Uncomplicated I&D Purulent (MRSA) Consider addition of anti-mrsa antibiotic in select situations 1 Non-purulent (β-hemolytic strep) Cephalexin 500 QID Dicloxacillin 500 QID Consider addition of MRSAactive agent if no response 1 Antibiotic Adult Pediatric Vancomycin 15-20 mg/kg IV Q8-12 15 mg/kg IV Q6 Linezolid 600 mg PO/ IV BID 10 mg/kg PO/IV Q8 Daptomycin 4 mg/kg IV QD Ongoing study Complicated I&Dplus vancomycin (or alternative) 2 Vancomycin (or alternative) 2 Telavancin 10 mg/kg IV QD *No data 1. Systemic illness, purulent cellulitis/wound infection, comorbidities, extremes of age, abscess difficult to drain or face/hand, septic phlebitis, lack of response of to I&Dalone. PO antibiotic : TMP-SMX 1 DS BID, Clindamycin 300 mg TID, Doxycycline 100 PO BID 2. Daptomycin, linezolid, telavancin, ceftaroline Ceftaroline 600 mg IV Q12 *No data 4
Impetigo Impetigo Classic impetigo Ecythema Bullous impetigo Definition: superficial, intra-epidermal infection Epi: Common in children, highly communicable Pathogens: S. aureus, Group A strep Treatment: Few lesions (topical = systemic) Mupirocin or Retapamulin ointment Multiple lesions (systemic >> topical) Pick agent(s) active against CA-MRSA and Group A strep Case 3 Patient presents with 4 th abscess in 4 months Prior abscesses have been treated with I&D and antibiotics with resolution He asks if there is anything he can do to prevent recurrences How would you manage this patient? A. Emphasize personal hygiene measures B. Decolonize with mupirocin and chlorhexidine C. Decolonize with TMP-SMX and rifampin D. All the above 9% 65% 11% 15% A. B. C. D. 5
How to Manage Recurrent Skin and Soft Tissue Infections? Host What is the Management of Recurrent Skin and Soft Tissue Infections? Personal Hygiene/ Wound Care (AIII) Host -Cover draining wounds -Hand hygiene -Avoid sharing if active infection Environment Pathogen Environment Pathogen Environmental Hygiene (CIII) -Clean high-touch surfaces Decolonization* (CIII) Liu C. Clin Infect Dis. 2011 Decolonization strategies Intranasal mupirocin Chlorhexidine washes Suppressive oral antibiotics Oral therapy with rifamycins Intra-nasal mupirocin to prevent recurrent MSSA SSTI? Methods: 3 SSTIs in 2 years pluss. aureus nasal carriage Randomized study Intervention: Nasal mupirocin BID 1 wk/mo x 1 yr Results: (N=40) Primary endpoint: recurrent SSTI 6% (mupirocin) vs. 47% (placebo); p < 0.02 RazR. Arch IntMed. 1996 6
Intra-nasal mupirocin to prevent CA-MRSA SSTI? 1 prophylaxis (prospective RCT) 134 soldiers with CA-MRSA nasal colonization Mupirocin (5d) vs. placebo SSTI: 10.6% mupirocin vs. 7.7% placebo 2 prophylaxis (retrospective) 38 HIV+ with CA-MRSA SSSI and nasal colonization Mupirocin vs. no treatment Recurrent SSTI: 32%mupirocin vs. 52%no treatment Ellis et al, AAC 07. Rahimain et al, ICHE 07 Chlorhexidine to prevent SA SSTI RCT of military recruits to prevent SSTI Chlorhexidine wipes vs. placebo 3 x/week Results: SSTI rate at 6 weeks 9.4% (chlorhexidine) vs. 7.1% (placebo); p=0.13 Results: S. aureus colonization (45% baseline) 52.6% (chlorhexidine) vs. 67% (placebo) Whitman TJ. Infect Control Hosp Epidemiol. 2010 Daily clindamycin to prevent recurrent SSTI? Subjects: 3 abscesses in prior 6 months Rx: clindamycin 150 mg QD vs. placebo Results: Abscess during Rx period 33% (clinda) vs. 81% (placebo); p=0.04 High recurrence rate after stopping clindamycin Klempner MS. JAMA 1988. % S. aureus carriage 100 90 80 70 60 50 40 30 20 10 0 Rifampin for eradication of S. aureus colonization? Rx period Control Rifampin Cloxacillin Rifampin and Cloxacillin 0 0.5 1 2 3 4 5 6 7 8 9 10 11 12 Weeks Wheat J. JID. 1981. 7
Case 4 34 y/o M comes in with arm pain, fever Temp 38.9, HR 105, SBP 100, RR 20 Appears ill and in more pain than what you would expect for cellulitis What would your empiric therapy be in this case? A. Cephalexin plus TMP-SMX, send home B. Clindamycin, piperacillintazobactam, and vancomycin C. Call surgery, vancomycin and ceftriaxone D. Call surgery, clindamycin, piperacillin-tazobactam, and vancomycin 0% 13% 40% 47% A. B. C. D. Necrotizing skin and skin structure infections Definition: infections of any layer within the soft tissue compartment that are associated with necrotizing changes Monomicrobial associated w/ minor injuries Polymicrobial associated w/ abdominal surgery, decub ulcers, IVDU, spread from GI tract Necrotizing soft tissue infections: risk factors IVDU Diabetes Obesity Chronic immune suppression Anaya DA. Clin Infect Dis. 2007 8
Why is early diagnosis so important? Mortality rate: > 30% % of patients 100 90 80 70 60 50 40 30 20 10 0 Necrotizing soft tissue infections: clinical clues Late findings Wong CH. Jour of Bone and Joint Surg. 2003 Wong CH. Jour of Bone and Joint Surg. 2003 Necrotizing soft tissue infections: radiographic techniques Necrotizing Skin and Soft Tissue Infection: Pathogens Plain films Low sensitivity Helpful if gas present CT and ultrasound May identify other Dx (abscess) MRI Enhanced sensitivity, low specificity Monomicrobial Group A strep Staphylococcus aureus Clostridia sp Gram negatives Vibrio vulnificus Polymicrobial Aerobic gram +/gram - PLUS. Anaerobes Wong CH. J Bone and Joint Surg. 2003 9
Empiric treatment of necrotizing soft tissue infections Early surgical intervention Antimicrobial therapy Piperacillin/tazobactam or carbapenem (anaerobes, GNR, streptococci) plus Vancomycin (MRSA) plus Clindamycin (GAS) *Consider IVIG in severe cases of streptococcal toxic shock syndrome 37 y/o male presents to clinic 4 days after receiving a dog bite to his forearm. He complains of pain, some purulent drainage. Case 5 Which antibiotic regimen would be most appropriate for this patient? Animal Bites A. Amoxicillin/clavulanic acid B. Cephalexin C. Clindamycin 73% 50% of Americans are bit by animals 20% require medical attention D. Metronidazole E. No antibiotics needed 7% 16% 2% 2% Animal bites account for 1% of ER visits Bites result in 10,000 inpt admits/year A. B. C. D. E. 10
Animal bites: bacteriology What s in their mouth and on your skin Average 5 organisms (range 0-16) per wound Dogs Cats Pasturella sp 50% 75% Streptococcus sp. 46% 46% Staphylococcus aureus 20% 4% Anaerobes mixed w/ aerobes 48% 63% Anaerobes alone 1% 0% Talan DA. NEJM. 1999 Antibiotic coverage for Pasturella What you want to use but won t work 1 st generation cephalosporin anti-staphylococcal penicillins clindamycin What works amoxicillin doxycycline fluoroquinolone Animal bites Empiric treatment regimens Amoxicillin/clavulanic acid +/- MRSA agent Pen allergy: cipro + clindamycin or moxifloxacin Prophylaxis? Moderate-severe bites or on face/hands Immunocompromised (splenectomized) Cat bites Bacteriology Human bites Mixed infection with streptococci, anaerobes and gram negatives (Haemophilus sp., Eikinella sp.) High rates of infection Treatment Same as animal bites Prophylaxis everyone, same as animal bites 11
Rabies what type of bites are high risk? Rabies - Post-exposure prophylaxis Animal Type Evaluation and disposure of animal Post-exposure prophylaxis Wound cleansing: virucidal agent (iodine) Dog, cats, ferrets Skunk, raccoons, foxes, bats Livestock, small rodents, rabbits, large rodents Suspected/confirmed rabid Healthy Animal lost Regarded as rabid unless proven negative by lab test Consider individually Prophylaxis 10 days observation/test Contact DPH Immediate prophylaxis Almost never require prophylaxis Rabies Immune Globulin 20 IU/kg body weight Infiltrated full dose around the wound(s) and remaining volume IM at site distant from vaccine Vaccinate: Days 0,3,7, and 14 http://www.cdc.gov/rabies/resources/contacts.html http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e507a1.htm, http://www.cdc.gov/mmwr/pdf/rr/rr5902.pdf 45 y/o man presents with several weeks of progressive painful bumps spreading up his left forearm. Case 6 Which of these questions should you ask? A. Do you have a fish tank? B. Have you been around a sick rabbit? C. Do you garden? D. Have you been traveling in S. America? E. All of the above 25% 21% 48% 5% 1% A. B. C. D. E. 12
Nodular lymphangitis: management? 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 Nodular Lymphangitis: DDx Short incubation (days) Francisella tularensis (rabbits, ticks) Medium incubation (2-4 weeks) Nocardia (brasiliensis >> asteroides) (soil) Long incubation (weeks-months) Mycobacterium marinum (fish tanks) Sporothrix schenkii (vegetation) Leishmania sps (sandfly) 13