5/26/10. Abscess, cellulitis Recurrent skin and soft tissue infections Necrotizing fasciitis Animal bites Unusual skin and soft tissue infections

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1 Catherine Liu, M.D. Assistant Clinical Professor Division of Infectious Diseases University of California, San Francisco Abscess, cellulitis Recurrent skin and soft tissue infections Necrotizing fasciitis Animal bites Unusual skin and soft tissue infections 32 y/o F with 3 days of an enlarging, painful lesion just below her L shoulder which she attributes to a spider bite. T 37.3 BP 118/70 P 82 1

2 A. Incision and drainage alone B. Incision and drainage plus oral anti-mrsa antimicrobial agent C. Oral anti-mrsa antimicrobial agent The primary treatment is incision and drainage (AII) Benefit of additional abx unclear High cure rates (~85-90%) whether active antibiotic used Indications for antibiotic therapy (AIII): Severe, extensive disease, rapidly progressive with associated cellulitis or septic phlebitis Signs & sx of systemic illness Associated comorbidities, immunosuppressed Extremes of age Difficult to drain area (e.g. face, hand, genitalia) Failure of prior I&D 1 Lee MC PIDJ 04; Young DM Arch Surg 04; Fridkin SK NEJM 05; Moran G NEJM 06 2 Rajendran PM AAC 07 MSSA MRSA Moran NEJM

3 For patients with purulent cellulitis (and no associated abscess), treat empirically for CA- MRSA pending culture data (A-II). Empiric therapy for β-hemolytic streptococci is not typically needed. Duration of therapy: 5-7 days, individualize based on clinical response Drug Adult Dose Advantages Disadvantages TMP/SMX 1-2 DS BID - Extremely low rate of resistance - MRSA & MSSA Doxycycline, Minocycline Clindamycin TID 100 BID - Low resistance - MRSA, MSSA - MRSA, MSSA, group A strep Linezolid 600 BID - MRSA, MSSA, group A strep - Complicated SSTI - Unreliable for group A strep - Unreliable for group A strep - Potential for inducible resistance - C. difficile risk - Adverse events with longterm use - Expensive Rifampin 600 QD - Do not recommend for use as a single agent or as adjunctive therapy with another active agent Introduction of methicillin 1 st MRSA isolate identified Report of MMWR MRSA infxn in report of 4 children w/o deaths due classic risk to MRSA in factors previously healthy children Outbreaks of CA- MRSA reported in multiple diverse populations CA-MRSA predominant cause of SSTI 3

4 Annual U.S. ED Visits for Skin and Soft Tissue Infections, Pallin D et al, Ann of Emerg Med, 2007 USA300 Miller and Diep Clinical Infectious Diseases

5 A. CA-MRSA likely originated from the spread of hospital strains into the community B. Skin and soft tissue infections are the most common clinical presentation of CA-MRSA C. CA-MRSA lacks multiple antibiotic resistance genes compared to HA-MRSA D. CA-MRSA is more common than HA-MRSA in some geographic regions 2 hypotheses: 1) Hospital strains were carried out into the community 2) De novo acquisition of resistance by a methicillin-susceptible strain Horizontal transfer of meca gene into a community strain Novel SCC mec element (type IV) ccr meca CA-MRSA Antibiotic resistance genes ccr meca HA-MRSA Type IV Type I-III Lack of multiple antibiotic resistance genes Presence of additional genetic elements, potential virulence factors (Panton-Valentine leukocidin, ACME, phenol-soluble modulins etc.) 5

6 32 year old M presents w/ erythema of his L inner thigh x 24 hours. T 37.0 BP 132/70 P 78 A. Clindamycin 300 mg PO tid B. Amoxicillin 875 mg PO bid, monitor clinically with addition of TMP/SMX if no response C. Amoxicillin 875 mg PO bid and TMP/ SMX 2 DS tab PO bid Relative contribution of CA-MRSA vs. β-hemolytic strep unknown Clindamycin = β-lactams > TMP-SMX in children with non-purulent cellulitis 1 Cover for β-hemolytic strep; consider empiric Rx for CA-MRSA (CIII). CA-MRSA only TMP-SMX Doxycycline Minocycline β-hemolytic streptococci and CA-MRSA Clindamycin Linezolid β-lactam (e.g. amoxicillin) + TMP-SMX 1 Elliot Pediatrics

7 Empiric therapy for MRSA in complicated SSTI Vancomycin, linezolid 1,daptomycin 2, tigecycline 3, telavancin 4 (AI) Clinical success rates vs. p-value (95% CI) comparator Daptomycin 71.5% vs. 71.1% ( ) Linezolid 92.2% vs. 88.5%.057 ( ) Tigecycline* 84.3% vs. 86.9%.47 ( ) Telavancin 82% vs. 85%.37 ( ) *modified ITT analysis 1 Kollef MH CID 2008; Miller LG NEJM 2005; Young LM Surgical Infections Arbeit RD et al CID 2004; 3 Weigelt J et al AAC 2005; 4 Breedt J AAC 2005 The patient in case 1 returns 8 weeks later with another abscess on her R thigh. She undergoes incision and drainage and receives a 7 day course of TMP-SMX. A. Emphasize personal hygiene measures B. Decolonize using nasal mupirocin and topical chlorhexidine baths C. Decolonize using TMP-SMX and rifampin D. A, B E. A, B, C 7

8 Host Environment Pathogen Personal Hygiene - Cover draining wounds - Hand hygiene after touching infected skin Host - Avoid reusing/ sharing personal items Environment Pathogen Environmental Hygiene Decolonization* - Clean high-touch surfaces -If above measures fail -If ongoing household transmission 1 Raz Arch Intern Med Ellis MW AAC 2007; 3 Whitman L-774 ICAAC-IDSA 2008; 4 Bode NEJM

9 Oral antimicrobials not routinely recommended (AIII). Consider oral agent in combination with rifampin only if other measures fail (CIII): Cochrane Review 1 : No benefit in HA-MRSA eradication or reduction in infection rates Systematic review 2 : Rifampin-based combination regimen vs. monotherapy with other antibiotic S. aureus colonization; no studies evaluated impact on infection rates Watch out for rifampin resistance, side effects 1 Cochrane Review 2003; 2 Falagas ME AJIC 2007; 35: TMP-SMX DS BID + Rifampin 300mg BID X 5 days: repeat every 6 weeks for 8 courses Chlorhexidine (hibiclens) 2 X per week Personal Hygiene Change clothes daily Wash towels Q 3 days Wash sheets Q week Vitamin C (1 gram/day) Courtesy of Richard Jacobs, M.D. Ph.D. 39 yo M with 1 day history of L leg pain and erythema, worsening pain and swelling x 24 hours T 39.2 P120 BP96/60 R22 98%RA 18>40<425, left shift 9

10 A. IV penicillin and clindamycin B. IV vancomycin and clindamycin C. IV vancomycin and piperacillin-tazobactam D. IV vancomycin and piperacillin-tazobactam and clindamycin Monomicrobial Group A > other β-hemolytic streptococcus Staphylococcus aureus (including CA-MRSA) Clostridia spp Gram negatives (rare) Polymicrobial Aerobic gram + Streptococcus spp., Staphylococcus aureus, Enterococci, Bacillus spp Aerobic gram E. coli, Acinetobacter baumannii, Enterobacter spp., Pseudomonas aeruginosa, Klebsiella spp, Proteus spp. Anaerobes Bacteroides spp., Clostridium spp., Peptostreptococcus spp Wong CH. J Bone and Joint Surg Risk Factors for Necrotizing SSTI IVDU Diabetes Obesity Chronic immunosuppression Often no precipitating factor Anaya DA. Clin Infect Dis

11 Stage 1 (Early) Tenderness to palpation (beyond apparent area of skin involvement) Erythema Swelling Warmth Stage 2 (Intermediate) Blister or bullae formation Skin fluctuance Skin induration Stage 3 (Late) Hemorrhagic bullae Skin anesthesia Crepitus Skin necrosis with dusky discoloration progressing to frank gangrene Wong CH Curr Opin ID 2005 Clinical findings may not be diagnostic Laboratory Risk Indicator For Necrotizing Fasciitis (LRINEC) C-Reactive protein, WBC, hemoglobin, sodium, creatinine, glucose Score 6 PPV 92%, NPV 96% Imaging studies Plain X-ray: subcutaneous gas (specific, not sensitive) CT/ MRI: Improved sensitivity for inflammatory changes (fascial edema and thickening), but less specific Operative exploration = gold standard Wong CH Crit Care Med 2004 Wong CH. J of Bone and Joint Surg

12 What is the role of clindamycin? Consider use for invasive group A strep infections Clindamycin is able to Decrease toxin synthesis Act on organisms in stationary phase of growth (when concentrations of PBPs) Clinical data: retrospective, unblinded study: Use of protein synthesis inhibitor as part of their regimen had a significantly better outcome for deep soft tissue infections Zimberlam J. Pediatric Infectious Disease Journal, 1999; 18(2): IVIG May bind toxin Limited clinical data in streptococcal TSS One retrospective study: maybe some benefit? Small RCT organ failure scores at 2, 3 days, no mortality benefit at 28 days How to extrapolate to necrotizing fasciitis? Hyperbaric O 2 Inhibit infection (esp anaerobic, e.g. clostridia), augment leukocyte killing Conflicting data, no clear morbidity or mortality benefit Most benefit likely in clostridial infection Kaul R. Clin Infect Dis. 1999; Darenberg J. Clin Infect Dis. 2003; Sarani B J Am Coll Surg 2009 Early surgical consult/ intervention Empiric antimicrobial therapy Piperacillin/tazobactam or carbapenem (group A strep, other gram pos, gram negs and anaerobes) plus Clindamycin (group A strep toxin inhibition) plus Vancomycin (MRSA) 12

13 21 yo M is tossing a ball in Golden Gate Park with a friend. As he goes after the ball, he passes close to a dog that was resting in the shade with his owner. The dog jumps up and bites him on the leg inflicting several deep puncture wounds on the calf. A. Antibiotic prophylaxis with clindamycin B. Antibiotic prophylaxis with amoxicillin/ clavulanate C. Administer rabies immunoglobulin and rabies vaccine for post-exposure prophylaxis D. A and C E. B and C Infection Risk Biting species Cat (30-50%) > human (15-30%) > dog (2-4%) Wound Location Hand Over a joint Foot Scalp or face (esp infant) Wound Type Interval to medical care Host factors Puncture wounds, crush injuries Treatment delay > 12 hours Elderly, diabetes mellitus, vascular disease, alcoholism, immunosuppression (asplenism, e.g. Capnocytophaga canimorsus), steroids) Griego J Am Acad Derm

14 Microbiology of Animal Bites 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 NEJM 1999 Antibiotic Coverage for Pasteurella What you want to use but won t work cephalexin dicloxacillin clindamycin What works penicillin/amoxicillin doxycycline fluoroquinolones Indications for Antibiotic Prophylaxis High risk animal: most cat bites High risk wound: moderate-severe puncture or crush injury, bone/ joint involvement High risk location: hands, face High risk individual: diabetes, immunocompromised, splenectomy 14

15 Amoxicillin/ clavulanate 875 mg BID or IV β-lactam/ β- lactamase inhibitor combinations, ertapenem for more serious infections If penicillin allergy: Moxifloxacin 400 mg QD Ciprofloxacin 500 BID + clindamycin 300 mg TID Azithromycin mg QD (PCN-allergic pregnant woman) Treatment duration: For prophylaxis: 3-5 days Cellulitis: 5-10 days Complicated infections: septic arthritis (3-4 weeks); osteomyelitis (4-6 weeks) When to Consider Rabies Prophylaxis? Animal Dog, cats, ferrets Evaluation and disposure of animal If healthy retain for 10 days of observation Rabid or suspected rabid Unknown (e.g. escaped) Post-exposure prophylaxis Do not begin prophylaxis unless animal rabid or suspected rabid Immediately vaccinate Consult with public health Skunk, raccoons, foxes, bats Livestock, small rodents rabbits and hares, large rodents (woodchucks, beavers) Regarded as rabid unless proven negative by lab test Consider individually Consider immediate vaccination Consult public health. Bites from guinea pigs, gerbils, chipmunks, rats, mice, rabbits almost never require prophylaxis Clean Wound Clean thoroughly with soap & water, irrigate with povidone-iodine Rabies Immune Globulin Administer 20 IU/kg body weight If anatomically feasible, the full dose should be infiltrated into and around the wound(s) and any remaining volume should be administered IM at an anatomical site distant from vaccine administration. Vaccinate (*March 2010 guidelines) Days 0 &,3,7, and

16 Human Bites Bacteriology: Oral flora Polymicrobial: streptococci (e.g. viridans group), gram negatives (Haemophilus sp., Eikenella sp.), anaerobes (Fusobacterium, prevotella, peptostreptococcus) High rates of infection (esp. clenched fist injuries) Treatment Irrigate, topical wound cleansing Clenched-fist injuries: evaluate for joint or bone penetration Prophylaxis everyone - amoxicillin/clavulanic acid Treatment - amoxicillin/ clavulanate or IV β-lactam/ β-lactamase inhibitor combinations, ertapenem for more serious infections Talan CID yo M ER physician presents with 9 day history of progressive cellulitis of L forearm. Initially noted a pustule self I&D. Despite keflex + clindamycin x 4 days, progressive erythema and drainage. Started IV vanco + ceftriaxone with no improvement after 3 days. 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 tick bites Only recent travel to Arizona 16

17 A. Mycobacterium marinum B. Coccidioides immitis C. Nocardia brasiliensis D. Brucella melitensis E. Sporothrix schenkii Nocardia brasiliensis Soil inhabitant Worldwide distribution Incubation period: <1-6 weeks Often with mild systemic symptoms Nocardia brasiliensis > asteroides for cutaneous dz Diagnosis: biopsy Partially acid-fast, gram variable branching rods. Culture: may grow in a few days, but typically require 2 to 3 weeks of incubation. 17

18 26 yo M with 6 week history of R hand papule ulcer Multiple visits to ED and urgent care, Receives several courses of abx, no improvement Leishmania panamensis 18

19 Coccidioides immitis Superficial thrombophlebitis and deep venous thrombosis Contact dermatitis Insect stings/tick bites Drug reactions Gouty arthritis Sweet syndrome Foreign body reaction (e.g. surgical mesh, orthopedic implants) Lymphedema Malignancy (e.g. T-cell lymphoma) Falagas ME Ann Intern Med

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