Abscess, cellulitis Recurrent skin and soft tissue infections Necrotizing fasciitis Animal bites Unusual skin and soft tissue infections Catherine Liu, M.D. Assistant Clinical Professor Division of Infectious Diseases University of California, San Francisco Annual U.S. ED Visits for Skin and Soft Tissue Infections, 1993-2005 USA300 Pallin D et al, Ann of Emerg Med, 2007 Miller and Diep Clinical Infectious Diseases 2008 1
HA-MRSA CA-MRSA Demographics Older age (60-70) White Younger age (20-40) Nonwhite Genotype USA100, USA200 USA300, USA400 SCC mec type I, II, III IV Potential virulence factors PVL, ACME, phenolsoluble modulins 32 y/o F with 3 days of an enlarging, painful lesion just below her L shoulder which she attributes to a spider bite. Clinical manifestations Nosocomial infections (CRBSI, HCAP, SSI) SSTI, bacteremia, CAP, osteomyelitis T 37.3 BP 118/70 P 82 Antimicrobial resistance Multiple agents Few agents A. Incision and drainage alone B. Incision and drainage plus oral anti-mrsa antimicrobial agent C. Oral anti-mrsa antimicrobial agent Incision and d... 32% Incision and d... 68% 0% Oral anti-mrsa... The primary treatment is incision and drainage (AII) Do antibiotics provide additional benefit? YES Observational studies Szumowski JD AAC 2007 Ruhe JJ CID 2007 NO Observational studies Lee MC PIDJ 2004 Young DM Arch Surgery 2004 Fridkin SK NEJM 2005 Moran G NEJM 2006 Randomized clinical trials Rajendran PM AAC 2007 (keflex vs. placebo) Duong M Ann Emerg Med 2010 (TMP-SMX vs. placebo)* Schmitz G Ann Emerg Med 2010 (TMP-SMX vs. placebo)* *Abx may prevent development of recurrent lesions in the short-term 2
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 β-hemolytic strep 4.5% 2.6% 8.1% 17.0% MSSA 9.0% MRSA 59.0% MRSA B-hemolytic strep other MSSA non-b hemolytic strep unknown Moran NEJM 2006 For patients with purulent cellulitis,treat empirically for CA-MRSA pending culture data (A-II). Empiric therapy for β-hemolytic streptococci is not typically needed. Duration of therapy: 5-10 days, individualize based on clinical response Drug Adult Dose Advantages Disadvantages TMP/SMX 1-2 DS BID Doxycycline, Minocycline Clindamycin 300-450 TID - Extremely low rate of resistance - MRSA & MSSA 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 3
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 31% 43% 26% Clindamycin 30... Amoxicillin 87... Amoxicillin 87... 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 in selected cases (CIII). CA-MRSA only TMP-SMX Doxycycline Minocycline β-hemolytic streptococci and CA-MRSA Clindamycin Linezolid β-lactam (e.g. amoxicillin) + TMP-SMX Purulent cellulitis: Cover for MRSA; β-hemolytic strep therapy likely unnecessary in most cases. Non-purulent cellulitis: Cover for β-hemolytic strep ± CA-MRSA. 1 Elliot Pediatrics 2009 4
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% (-5.8 5.0) Linezolid 92.2% vs. 88.5%.057 (-0.11-7.47) Tigecycline* 84.3% vs. 86.9%.47 (-9.0-3.8) Telavancin 82% vs. 85%.37 (-.04-0.11) *modified ITT analysis 1 Kollef MH CID 2008; Miller LG NEJM 2005; Young LM Surgical Infections 2008. 2 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 Emphasize pers... 19% Decolonize usi... 6% Decolonize usi... 2% 63% 10% A, B A, B, C Survey of 483 ID physicians (EIN network) on management of recurrent SSTI 85 % prescribed decolonization regimens 56% decolonized other family members Majority prescribed antiseptic body washes (chlorhexidine, hexachlorophene) and/or nasal therapy (mupirocin, bacitracin) Significant variability in frequency of application and duration of use 55% used oral antimicrobials Significant variability in agents and duration of use West SK ICHE 2007; 28:1111-1113 5
Environment Environmental Hygiene -Clean high-touch surfaces Personal Hygiene -Cover draining wounds -Hand hygiene after touching infected skin Host -Avoid reusing/ sharing personal items Pathogen Decolonization* -If above measures fail -If ongoing household transmission Mupirocin twice daily x 5-10 days (CIII) Potentially effective in recurrent MSSA SSTI 1 in nasal colonization but no 1 st time SSTI 2 Mupirocin twice daily x 5-10 days AND topical skin antiseptic (e.g. chlorhexidine or dilute bleach baths) x 5-14 days (CIII) CHG wipes alone not SSTI rates 3, transient effect on colonization Combination surgical site infection rates 4 Bleach baths: ¼ cup per ¼ tub of water for 15 min, 2x/week for 3 mths 1 Raz Arch Intern Med 1996 2 Ellis MW AAC 2007; 3 Whitman L-774 ICAAC-IDSA 2008; 4 Bode NEJM 2010 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 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 1 Cochrane Review 2003; 2 Falagas ME AJIC 2007; 35: 106-14 6
A. IV penicillin and clindamycin B. IV vancomycin and clindamycin C. IV vancomycin and piperacillintazobactam D. IV vancomycin and piperacillintazobactam and clindamycin IV penicillin... 5% IV vancomycin... 26% 26% IV vancomycin... 42% IV vancomycin... 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. 2003 Risk Factors for Necrotizing SSTI Often no precipitating factor IVDU Diabetes Obesity Chronic immunosuppression 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 Anaya DA. Clin Infect Dis. 2007 Wong CH Crit Care Med 2004 7
What is the role of clindamycin? Consider for invasive group A strep infections Clindamycin: Decreases toxin synthesis Acts 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 Wong CH. J of Bone and Joint Surg. 2003 Zimberlam J. Pediatric Infectious Disease Journal, 1999; 18(2): 1096-1100. 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 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) Kaul R. Clin Infect Dis. 1999; Darenberg J. Clin Infect Dis. 2003; Sarani B J Am Coll Surg 2009 8
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 Antibiotic pro... 7% Antibiotic pro... 55% Administer rab... 5% A and C 9% 25% B and C Microbiology of Animal Bites Infection Risk Biting species Cat (30-50%) > human (15-30%) > dog (2-4%) Wound Location Wound Type Interval to medical care Host factors Hand Over a joint Foot Scalp or face (esp infant) 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 1995 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 9
Antibiotic Coverage for Pasteurella What you want to use but won t work cephalexin dicloxacillin clindamycin What works penicillin/amoxicillin doxycycline fluoroquinolones 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 250-500 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 Evaluation and disposure of animal Post-exposure prophylaxis Clean Wound Dog, cats, ferrets If healthy retain for 10 days of observation Do not begin prophylaxis unless animal rabid or suspected rabid Clean thoroughly with soap & water, irrigate with povidone-iodine Rabies Immune Globulin Rabid or suspected rabid Immediately vaccinate Administer 20 IU/kg body weight Skunk, raccoons, foxes, bats Livestock, small rodents rabbits and hares, large rodents (woodchucks, beavers) Unknown (e.g. escaped) Regarded as rabid unless proven negative by lab test Consider individually Consult with public health Consider immediate vaccination Consult public health. Bites from guinea pigs, gerbils, chipmunks, rats, mice, rabbits almost never require prophylaxis 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. Rabies Vaccine (*new 2010 guidelines) Days 0 &,3,7, and 14 http://www.cdc.gov/mmwr/pdf/rr/rr57e507.pdf http://www.cdc.gov/mmwr/pdf/rr/rr5902.pdf 10
53 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 A. Mycobacterium marinum B. Coccidioides immitis 48% C. Nocardia brasiliensis D. Brucella melitensis E. Sporothrix schenkii 5% 13% 10% 25% Mycobacterium... Coccidioides i... Nocardia brasi... Brucella melit... Sporothrix sch... Nocardia brasiliensis 11
Soil inhabitant Worldwide distribution Incubation period: <1-6 weeks Often with mild systemic symptoms Nocardia brasiliensis > asteroides for cutaneous dz Diagnosis: biopsy and culture Partially 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 Multiple visits to ED and urgent care, Receives several courses of abx, no improvement Leishmania panamensis 12
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) Drainage/ debridement is the mainstay of therapy of all purulent skin and soft tissue infections. For purulent SSTI requiring antibiotic therapy, cover for CA-MRSA. For non-purulent cellulitis, cover for β-hemolytic strep ± CA-MRSA. Amoxicillin/ clavulanate is drug of choice for prophylaxis following dog, cat, and human bites. For patients not responding to standard antibiotic therapy for SSTI, consider alternative diagnoses (e.g. unusual infections, noninfectious etiologies), BIOPSY for culture and pathology. Falagas ME Ann Intern Med 2005 13