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UPDATE SKIN AND SOFT TISSUE(SST) INFECTIONS: Features of Management

UPDATE SKIN AND SOFT TISSUE(SST) INFECTIONS: Features of Management. Thomas M File, Jr MD MSc MACP, FIDSA, FCCP Professor of Internal Medicine Northeast Ohio Medical University; Chair, Infectious Disease Division Summa Health System Akron, Ohio, USA.

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UPDATE SKIN AND SOFT TISSUE(SST) INFECTIONS: Features of Management

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  1. UPDATE SKIN AND SOFT TISSUE(SST) INFECTIONS: Features of Management Thomas M File, Jr MD MSc MACP, FIDSA, FCCP Professor of Internal Medicine Northeast Ohio Medical University; Chair, Infectious Disease Division Summa Health System Akron, Ohio, USA • IDSA Guidelines. Stevens D. et al. www.idsociety.org; • MRSA Guideline. Liu et al. www.idsociety.org; • File TM Jr. and Stevens DL. Skin and Soft-tissue Infections. 3rd Ed. Published by Handbooks in Health Care Co. Newton, PA, 2011

  2. BACTERIAL SKIN AND SOFT TISSUE INFECTIONS • Primary Pyoderma • Impetigo, erysipelas, folliculitis, carbuncles • Infections secondary to pre-existing conditions • Surgical wounds, trauma, bites, decubitus infections, diabetic foot infections • Necrotizing infections • Polymicrobial • Monomicrobial (Grp A Strep; Clostridium) Photos courtesy T File MD

  3. BACTERIAL SST INFECTIONSGeneral approach to therapy • Antimicrobial therapy • Directed against likely pathogens • Common organisms • Specific pathogens based on epidemiology • Emerging antimicrobial resistance • Community-onset MRSA; macrolide-Resist S. pyogenes • Healthcare-associated pathogens • Surgical I& D, Debridement, Excision

  4. Acute allergic reaction Contact dermatitis Stasis dermatitis Toxin (eg chemical) Trauma Thermal reaction Acute gout Polychondritis Mimics of Skin and Soft Tissue Infections Acute gout (www.definegout.com Stasis dermatitis (dermnet.com) Recurrent polychondritis; courtesy of N Scalera MD

  5. Common Skin Infections (Primary Pyoderma)

  6. Pyoderma-Antimicrobial therapy • S. pyogenes • Beta-lactams: penicillins, cephalosporins, carbapenems • Others: macrolides (some resistance), clindamycin, tetracycline ?? • S. aureus • MSSA: antistaphylococcal penicillins (i.e., dicloxacillin, nafcillin, oxacillin); cephalosporins; clindamycin; macrolides • MRSA • Hosp-acquired: Vancomycin, linezolid, daptomycin, televancin, ceftaroline, tigecycline • Comm-assoc: above plus Trimethoprim/sulfamethoxazole; doxcycline; clindamycin

  7. CASE: A 45 y/o healthy male presents to the ED with one day of fever and painful red leg. Temp 100.4F; BP 130/80; P 84; Leg area shownAccording to the 2014 IDSA Skin infection Guideline, what is most appropriate therapy? • Cefepime • Penicillin G • Vancomycin • Vancomycin + piperacillin/tazobactam • Linezolid Photo courtesy T File MD

  8. IDSA Guidleine 2014

  9. Nonpurulent Cellulitis: -hemolytic strep vs. S. aureus? • Empiric Rx for -hemolytic strep recommended • Prospective study1, 248 hospitalized pts • 73% due to -hemolytic strep ; 27% with no identified cause. • Overall 96% response rate to -lactam antibiotic.MRSAis unknown. • Empiric Rx for MRSA if fails to respond to -lactam • Consider in patients with systemic toxicity IDSA MRSA guideline www.idsociety.org; 1Jeng et al Medicine 2010; 89:217-26 2Elliott et al Pediatrics 2009; 123:e959-66

  10. Cellulitis: Duration of Antimicrobial Therapy • In cases of uncomplicated 4 cellulitis, a 5-day course of antimicrobial therapy is as effective as 10-days, if clinical 5 improvement has occurred by 5 days* • In some patients, cutaneous inflammation and systemic features worsen after initiating therapy, probably because sudden destruction of the pathogens releases potent enzymes that increase local inflammation. • New FDA criteria: No extension of erythema at 72 hrs. (FDA Guidance Aug 2010 www.fda.gov/Drugs/Guidances) *Hepburn MJ, et al. Arch Intern Med 29 2004; 164:1669-74

  11. Prospective study 216 patients cellulitis • Cultures: blood, tissue, swabs; paired serology-ASO • Finding: Data on 203 • 173/203 (85%)—Beta-Strep • 24 had S aureus; 18 also Beta Strep (13 treated with PCN did well) Open Forum Infect Dis. Nov 2015; DOI: 10.1093/ofid/ofv181

  12. Pasquale TR et al. Am J Health Syst Pharm. 2014 Jul 1;71(13):1136-9.

  13. CASE: A 60 y/o healthy female presents to you with a ‘boil’. She is afebrile and has a 3 cm carbuncle on her neck. There is no significant surrounding erythemaWhat is most appropriate therapy? • Incision and drainage • Antimicrobial therapy—amoxicillin/clavulanate • Antimcrobial therapy—trimethoprim/sulfamethoxazole • Antimicrobial therapy—amoxicillin + trimethoprim/sulfamethoxazole • Incision and drainage + ciprofloxacin

  14. Community-associated (CA)MRSA • Increasing cause of Community skin infections • Genotypically and phenotypically unique from nosocomical MRSA Less resistant to non-beta-lactam agents Often susceptible to trim/sulfa, clindamycin, tetracyclines Panton-Valentine leukocidin-- virulence factor • Risk factors athletes, inmates, military recruits, men who have sex with men, injection drug user, prior antibiotic use • Increases need to culture

  15. And erythromycin File T. Cleve Clinic Med J. 2007

  16. Treatment of focal, pustular skin infections (furuncles, carbuncles) • For simple abscesses or boils, incision and drainage alone is likely to be adequate • Antibiotic therapy is recommended for abscesses associated with the following conditions: • severe or extensive disease • presence of associated cellulitis, • signs and symptoms of systemic illness, • associated comorbidities or immunosuppression, • extremes of age • abscess in an area difficult to drain (eg, face, hand, and genitalia), lack of response to incision and drainage alone From InfDis Soc Am Guidelines 2011. www.idsociety .org

  17. NIH study • >1000 patients, 2009-2013 • I&D + Trim/Sulf 2 DS BD vs I&D + placebo • Results: • Better test of cure with T/S • Other findings: • Decrease new lesions within 3 weeks • Decrease household infections • Trend for fewer hospitalizations. • Slightly more GI Adverse effects (42 vs 36%) Talan era l. NEJM 2016; 374: 823-

  18. Another NIH study:Prelim report • 786 patients: Single Abscess < 5 cm; CURE (ITT/Eval) Chambers H. Am Society Micro meeting June 17, 2016

  19. Serious Skin Infection • 36 y/o female noted onset tender nodule of leg 4 days earlier; increasing pain, fever, surrounding erythema • T-102.50 F; BP 100/60; P 110; 10 X 7 cm erythema with central pustule • WBC 18,000; creat 1.6 Photo courtesy of T. File MD

  20. MRSA SSTI: 2014 Guidance From IDSA1 *Guidelines published before FDA approval of tedizolid, dalbavancin and oritavancin

  21. New Therapeutic Options for Skin/Soft Tissue Infections (focus on MRSA )

  22. Treating Skin Infections: a New Paradigm • Dalbavancin and Oritavancin make in possible to treat complicated skin structure infections on outpatient basis without compromising efficacy and without need for indwelling IV • “..could profoundly affect how these infections are managed, by reducing or in some cases eliminating costs and risks of hospitalization.” Chambers HF NEJM 2014; 270: 2238-9

  23. 3/21/05 3/22/05 18 y/o male treated with amox/clav for ‘spider’ bite at local urgent care center. Photos courtesy of T. File MD

  24. 20 y/o female with recurrent sores; on amox/clav for 4 days without improvement Photo courtesy of T. File MD

  25. Patient with recurrent Furunculosis • Usually in immunocompetent patients • R/O diabetes, other condition • Often colonized with S. aureus • Nasal, perineum • Therapy • Antibacterial soap ( chlorhexidine) • Nasal Bactroban • Systemic antimicrobials-? benefit • Antistaph agent + rifampin (10 days) • Clindamycin (best nasal secretion levels), 150 mg/d for up to 3 months • Klempner MS, Styrt B. Prevention of recurrent staphylococcal skin infections with low-dose oral clindamycin therapy. JAMA 1988 11;260:2682-5.

  26. INFECTIONS ASSOCIATED WITH UNDERLYING CONDTIONS • Infections • Post Op wound infections • Lower extremity cellulitis • Diabetic foot ulcers • Decubitus ulcers • Bite wound infections • Post Trauma infections • Perforated bowel Photo courtesy of T. File MD

  27. BACTERIOLOGY: SST Infections associated with underlying conditions • Gram positive Cocci • S aureus • MSSA • MRSA (Hospital-acquired; Community-acquired) • VIRSA, VRSA • Streptococcal spp (including Grp B and other spp) • Enterococci (VRE) • Gram negative Bacilli • Enterobacteriaciae • Pseudomonas sp • Anaerobes

  28. ANTIMICROBIAL ACTIVITY Agents Staph**/Strep GNB Anaerobes Nafcillin/Cefazolin + 0 0 Cefoxitin/ + +/-* + Cefotetan Ceftaroline + +* Amp/sulb (amox/clav) + +/-* + Pip/tazo; Ticar/C + + + Ertapenem + +* + Imipenem/Mero + + + FQ + Clinda (metronid) + + + * not for Pseudomonas ** If MRSA: Vancomycin (>99%), Linezolid (>99%), Daptomycin (>99%), Ceftaroline [Others: Trim/sulf (60-80%), Minocin (90%),

  29. DIABETIC FOOT INFECTIONS 62 y/o postman with fever and draining foot ulcer Photo courtesy of T. File MD

  30. DIABETIC FOOT INFECTIONS • Predisposing factors • Peripheral neuropathy • Maldistribution of weight (trohic ulsers) • Failure to sense problems (corns, calluses) • Vascular insufficiency • Bacterial etiology • Early,superficial--Staph, Strep • Late, deep--Mixed • Therapy-Surgery and antimicrobial agents; Multi-disciplinary approach

  31. Post-Op 6 Weeks later Photos courtesy of T. File MD

  32. Effect of Early Surgery on SubsequentAbove Ankle Amputation(Tan JS et al. Clin Infect Dis1996;23:286-291)

  33. Other Specific Skin Infections IDSA Guidelines. Stevens D. et al. Clin Infect Dis 2005;42:1379-406

  34. NECROTIZING SKIN INFECTIONSCharacteristics • Often perineal or lower extremity(esp for mixed infections) • Abnormal inflammatory response(less “purulent”) • Often rapidly spreading • Putrid discharge(what organisms?)/crepitance often present • Often associated with: Diabetes Vascular disease Trauma(including bites) Surgery

  35. NECROTIZING SKIN INFECTIONSPathophysiology • Mixed aerobic/anaerobic infection • Synergistic infection • Presence of faculatative organisms creates better anaerobic environment for anaerobes • virulence factors of one organism assists another organsm(anti-phagocytic effect of B. fragilis capsule • Growth factors • Monomicrobial (e.g.,Strep; Staph; Clostridia) • toxins • enzymes

  36. S. Aureus Polymicrobial

  37. NECROTIZING SKIN INFECTIONS • Manifestations • Tissue necrosis, spreading, bullae, severe pain • Often severe intensity of illness • REQUIRES EXPEDITIOUS SURGERY • Several anatomical syndromes • E.g., Necrotizing fasciitis; Gas Gangrene; others • Cannot easily differentiate syndromes on basis of initial clinical presentation • Initial approach is similar: Early surgery and antibiotics • Microbiology • Mixed anaerobes/aerobes • Monomicrobial • Streptococcus pyogenes/Staphylococcus aureus (CA-MRSA) • Clostridia sp (perfringens most common)

  38. Diabetic woman with rapidly spreading gangrenous infection Photo courtesy of T. File MD

  39. Photo courtesy of T. File MD

  40. Infection 8 hours after amputation Photo courtesy of T. File MD

  41. Gas Gangrene due to C. perfringens Photos courtesy of T. File MD

  42. S. PYOGENES NECROTIZING FASCIITIS • Increasing frequency over past decade • Result of specific toxins-Streptococcal pyrogenic exotoxins(SPE). These cause release of cytokines(e.g.., TNF) which can mediate fever, shock, and tissue injury • Most cases sporadic(occasional 2nd spread); often in normal host • Bacteremia in approx 50% • Mortality-20-40% • Therapy-Rapid surgery, antibiotics

  43. Photo courtesy of T. File MD

  44. CLUES SUGGESTING NECROTIZING FASCIITIS RATHER THAN CELLULITIS • Pain more severe than expected(followed by anesthesia) • Rapidly spreading swelling and inflammation • Bullae(but can be seen with cellulitis as well) • Necrosis • Toxic shock syndrome • Elevated creatine kinase level(why?) • Risks: Varicella, NSAID

  45. NECROTIZING FASCIITIS Diagnosis • CT or MRI • Edema alone fascia • Direct Inspection (surgical) • Swollen, dull gray, string • Thin exudate (not ‘pus’) • Tissue easily dissected • Biopsy IDSA Guidelines. Stevens D. et al. Clin Infect Dis 2005;42:1379-406

  46. NECROTIZING INFECTIONS;THERAPEUTIC APPROACH • Surgical debridement/excision • Antimicrobial therapy • Directed initially against mixed aerobic/anaerobic flora • Ampicillin/sulbactam or Piperacillin/tazobactam PLUS Clindamycin (theoretically to inhibit protein synthesis and suppress bacterial toxin) PLUS Ciprofoxacin; Other Regimens: Imipenem, meropenem, ertapenem, Clindamycin PLUS Aminoglycoside or Fluoroquinolone • Recommendation to use intravenous immunoglobulin cannot be made with certainty • (Kaul et al. Clin Inf Dis, 1999; Norrby-Teglund et al. Curr Rep Inf Dis, 2001; Low et al. ICAAC 2003) IDSA Guidelines. Stevens D. et al. Clin Infect Dis 2005;42:1379-406

  47. BACTERIAL SST INFECTIONSGeneral approach to therapy • Surgical I& D, Debridement, Excision • Antimicrobial therapy • Directed against likely pathogens • Common organisms • Specific pathogens based on epidemiology • Emerging antimicrobial resistance • Community-onset MRSA; macrolide-R S. pyogenes • Healthcare-associated pathogens

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