SSTIs Sarah Doernberg, MD, MAS Assistant Professor 2.20.2018 - - PDF document

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SSTIs

Sarah Doernberg, MD, MAS Assistant Professor

2.20.2018

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730933/
• https://www.journalofhospitalmedicine.com/jhospmed/article/12829

6/evidence-based-care-cellulitis

• J Hosp Med. 2016 Aug;11(8):587-90. doi: 10.1002/jhm.2593.
• Overtreatment of nonpurulent cellulitis.
• https://acphospitalist.org/archives/2017/02/rethinking-cellulitis.htm
• https://academic.oup.com/cid/article/51/8/895/331695

2/7/2018

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Disclosures

• Grant/funding from: Antibacterial Research Leadership Group

(NIH), Infectious Diseases Society of America

• Consultant: Actelion, Genentech

Outline

• Cellulitis
• Necrotizing infections
• Special populations and exposures
• Abscess

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Skin anatomy

• Impetigo: Superficial infection of the skin

with pustules/vesicles that crust or form bullae

• Cellulitis: Deep dermis + fat
• Erysipelas: Superficial infection

involving lymphatics; tender, erythematous, well-demarcated plaque

• Folliculitis: Superficial infection of hair

follicle with purulence in epidermis

• Furuncle: Infection of hair follicle with

subcutaneous abscess

• Carbuncle: Cluster of furuncles
• Abscess: Pus within dermis and deeper

skin

• Pyomyositis: Purulent ifxn of muscle
• Necrotizing fasciitis: Infection of

subcutaneous tissue spreading along fascial planes

• Gas gangrene: Necrotizing ifxn of

muscle

By Don Bliss (artist) [Public domain], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/5/5d/Anatomy_The_Skin_-_NCI_Visuals_Online.jpg

Case #1: 63 y/o M with DMII, chronic venous stasis, and CHF presents to your clinic with 1 day of LLE erythema and warmth. He lives at home, has no recent hospitalizations, and denies prior history of skin

• infections. NKDA. Exam: Afebrile, well-appearing,

cellulitis of LLE to knee without purulence. What antibiotic would you like to prescribe?

• A. Cephalexin + tmp/smx PO
• B. Clindamycin PO
• C. Linezolid PO
• D. Cephalexin PO
• E. Vancomycin IV

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Cephalexin +/- TMP/SMX for cellulitis #1

• Multicenter double-blind, placebo-controlled RCT in 3 EDs of

patients > 12 y/o with cellulitis not being admitted

• Failure = subsequent hospitalization for the same infection, change

in antibiotics, drainage of an abscess, or recurrence w/i 30 days

• Allowed < 24 hours IV cefazolin or nafcillin (~25%)

Pallin DJ et al. Clin Infect Dis. 2013 Jun;56(12):1754-62. doi: 10.1093/cid/cit122. Epub 2013 Mar 1.

Population Cephalexin Ceph + TMP/SMX 95% CI 30-day cure 82% 85% 2.7% (−9.3 to 15) abscess 6.8% 6.8% 0% (−8.2 to 8.2) AE 53% 49% −4.1 (−20% to 12%)

Cephalexin +/- TMP/SMX for cellulitis #2

• Multicenter, double-blind, placebo-controlled superiority RCT at 5

US EDs

• Outpatients > 12 yrs with cellulitis treated for 7 days
• No wound, abscess, or purulence
• 1○ endpoint: clinical cure
• significant difference: >10%
• Populations well-matched on DM, fever, hx MRSA, site of ifxn
• Median length of lesion: 13 cm (IQR 8-21)
• Median width of lesion: 10 cm (IQR: 6-15)
• 257 (51.8%) were 100% adherent;122 (24.6%) took 76% to 99% of

doses

Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653.

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Results

Population Cephalexin Ceph + TMP/SMX 95% CI Per protocol 85.5% 83.5%

• 2.0% (-9.7 to 5.7)

mITT1 69.0% 76.2% 7.3% (-1.0 to 15.5) mITT2 82.8% 83.8% 1.0% (-6.1 to 8.1) Hospitalization 5.2% 7.8% 2.6% (-2.6 to 7.8) AE 73.4% 75.0%

Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653.

mITT1 = took at least 1 dose and had f/u @ TOC mITT2 = took at least 1 dose and had f/u at some point

• Failures were mostly abscess or purulent drainage
• 68% MRSA (if cultures done), no difference by rx

group

• No invasive infection developed

Who was left out

• DM
• Peripheral vascular disease
• Renal insufficiency
• Requires admission
• Purulent discharge
• Cellulitis associated with

hardware or device

• Immunocompromised
• Face, perianal, periungual
• Bite
• Immersion
• IVDU
• Multifocal infection
• Underlying skin disease
• Pregnant/lactating

Pallin DJ et al. Clin Infect Dis. 2013 Jun;56(12):1754-62. doi: 10.1093/cid/cit122. Epub 2013 Mar 1. Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653.

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How long to treat?

• Randomized, double-blind RCT of 5 versus 10 days of

levofloxacin for 77 patients with cellulitis

• Could get up to 24 hours of another abx
• Inpatient or outpatient, sickest excluded
• Endpoint: Resolution @ 14 days without relapse @ 28

days

• Result: 43/44 (98%) in the 5 day group versus 42/43 (98%)

in the 10 day group met endpoint

• Most subjects still had mild residual signs of cellulitis at

day 5 that resolved without further antibiotics

Hepburn MJ et al. Arch Intern Med. 2004 Aug 9-23;164(15):1669-74.

Bottom line

• Cephalexin is first-line for uncomplicated outpatient

cellulitis

• 5 days unless slow resolution or complicated course
• In those patients, even if failure, invasive infection rare
• Often failure due to unrecognized abscess
• May need to consider MRSA or other coverage if:
• Immunocompromised
• IVDU
• Associated with ulceration or hardware
• Animal exposure
• Immersion

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Brief antibiotic review

GAS MSSA MRSA Enterobacteriaceae Pseudomonas Penicillin +++

• Amoxicillin

+++

• +/-
• Cephalexin/

cefazolin +++ +++

• +
• Clindamycin +++

++ ++

• Doxycycline ++

+++ ++

• TMP/SMX

+ +++ +++ ++

• Linezolid

+++ +++ +++

• Ceftriaxone

+++ +

• +++
• Piperacillin/

tazobactam +++ +++

• +++

+++

Case, con’t: Your patient returns to clinic two days later for a scheduled wound check. He reports excellent adherence with the antibiotics, but states that his leg is not improved. On exam, temp is 38, other vitals stable; well-appearing, erythema now extends 2 inches above the

• knee. No purulence noted. What is your next step?
• A. Switch to linezolid and schedule a follow-up in 2 days
• B. Switch to linezolid, obtain an ultrasound, and schedule a follow-

up in 2 days

• C. Admit, obtain an ultrasound, switch to vancomycin
• D. Admit, obtain an ultrasound, switch to vancomycin and

piperacillin/tazobactam

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IDSA recommendations

Patients who have failed oral antibiotic treatment = severe infection Treat as a severe infection (i.e. vancomycin + piptazo)

• Is this really needed?

Stevens DL et al. CID 2014; 59(2), e10–e52

Reasons for failing outpatient therapy

• Medication nonadherence or malabsorption
• Wrong diagnosis
• Resistant bacteria
• Nonbacterial infection
• Abscess/deep infection
• Anatomic issues (e.g. lymphedema, venous stasis) slowing

response

• Organism is eradicated but inflammation persists

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DDx to revisit in a stable patient

• Drug reaction
• Contact dermatitis
• Venous stasis dermatitis
• DVT
• Superficial thrombophlebitis
• Hematoma
• Gout
• Vasculitis
• Erythema nodosum
• Sarcoidosis
• Eosinophilic cellulitis
• Panniculitis
• Neoplasia (Paget’s dz of the

breast, CTCL)

• Insect bite reaction
• Injection site reaction
• IV line infiltration
• Erythema migrans
• HSV, VZV
• Fungal infection
• Abscess, septic

arthritis/bursitis, osteomyelitis, mycotic aneurysm

Raff AB and Korshinsky D. JAMA. 2016;316(3):325-337. doi:10.1001/jama.2016.8825

Cellulitis can be challenging to diagnose

• Retrospective study of 74 Derm consults for cellulitis at 4 academic

medical centers

• 55 (74%) diagnosed with pseudocellulitis
• Common final diagnoses: stasis dermatitis (31%), contact

dermatitis (15%), inflammatory tinea (9%)

• Non-blinded RCT of Dermatology consults for patients dx’d with

cellulitis by PCP

• All got Derm consults with Dx disclosed to those randomized to

consult arm and not to the “placebo” arm

• Only 3/29 (10%) diagnosed by PCP with cellulitis were confirmed

by Dermatologist

• 100% of patients in control arm versus 10% of those in consult

arm given abx

Strazzula L et al. J Am Acad Derm 2015; 73(1): 70-75 Arakaki RY et al. JAMA Dermatol. 2014;150(10):1056-1061. doi:10.1001/jamadermatol.2014.1085

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ID consults can help, too

• London, Ontario3 EDs referred outpatients with cellulitis

needing IV antibiotics to an ED-staffed clinic, then staffing changed to be an ID-run clinic

• Pre versus post analysis

Jain SR et al. Diag Micro and ID 2017; 87(4): 371-375

ED (149) ID (136) P value Cellulitis confirmed 133 (89%) 82 (60%) < 0.0001 Antibiotics stopped 16 (11%) <0.0001 Admission 11 (7%) 2 (1.5%) 0.01

Oral antibiotic failure risk factors

• Prospective cohort study of 497 pts presenting to Canadian ED

with cellulitis

• Could be on PO or home/ED IV antibiotics
• Failure = hospitalization or change of antibiotics for worsening ifxn
• 102 (21%) failed rx; 78% for ∆ abx and 22% for hospitalization
• Risk factors for failure (OR, 95% CI):
• Fever at triage: 4.3 (1.6-11.7)
• Leg ulcers: 2.5 (1.1-5.2)
• Lymphedema: 2.5 (1.5-4.2)
• Prior cellulitis: 2.1 (1.3-3.5)

Quirke M et al. BMJ Open. 2015 Jun 25;5(6):e008150. doi: 10.1136/bmjopen-2015-008150.

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Microbiology of oral antibiotic failure

• Multicenter retrospective cohort study of inpatients with

SSTIs

• N = 533; 179 (34%) got prior abx
• Those failing outpatient abx had fewer comorbidities, less

fever, and lower WBCs and CRP

• 100% of those failing outpatient PO rx survived to

discharge

Jenkins TC et al. Am J Emerg Med. 2016 Jun;34(6):957-62. doi: 10.1016/j.ajem.2016.02.013. Epub 2016 Feb 12.

Organism No PO abx PO abx P value Any 139 (39) 63 (35) 0.4 MRSA 38 (27) 26 (41) 0.05 GNR 18 (13) 2 (3) 0.03

Key interventions if outpatient rx fails

• Revisit the diagnosis
• Ensure adequate drainage
• Address underlying anatomical issues
• Edema, tinea
• Coverage of MRSA
• GNR coverage probably not needed unless

unstable

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When is MRSA coverage indicated?

• Hemodynamic instability
• Overlying/associated with an indwelling medical device
• Known MRSA colonization
• Recent prior MRSA infection
• Heavy hospital exposure (including dialysis, longterm care)
• Injection drug use
• Lack of response to a regimen not covering MRSA

Case, con’t: You switch your patient to IV vancomycin, and he responds well to therapy with regression of the erythema and resolution of the fever. On day #3, he is ready to go home. What oral antibiotic will you give him and for what duration?

• A. Cephalexin; 5 days from admission
• B. Cephalexin; 10 days from admission
• C. TMP/SMX plus amoxicillin; 5 days from admission
• D. TMP/SMX plus amoxicillin; 10 days from admission
• E. Oritavancin x 1 dose
• F. Place a PICC and administer vancomycin x 10 days

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What about these new long-acting abx?

• Dalbavancin and oritavancin = long-acting lipoglycopeptides
• Potential to decrease or eliminate admissions
• Bottom line: Thusfar, difficult to operationalize and implement,

unclear if cost effective

Boucher HW et al. N Engl J Med. 2014 Jun 5;370(23):2169-79. doi: 10.1056/NEJMoa1310480. Corey GR et al. N Engl J Med. 2014 Jun 5;370(23):2180-90. doi: 10.1056/NEJMoa1310422. Corey GR et al. Clin Infect Dis. 2015 Jan 15;60(2):254-62. doi: 10.1093/cid/ciu778.

Study Drug Comparator Outcome DISCOVER I and II Dalbavancin day 1 and 8 Vancolinezolid x 10-14 days Noninferior response @ 48-72 hrs and EOT ↓AEs SOLO I and II Oritavancin x 1 Vanco x 7-10 days Noninferior response @ 48-72 hrs and EOT Similar AEs Dalba dosing trial Dalbavancin 1500 mg x 1 Dalbavancin 1000 mg day 1 and 500 mg day 8 Noninferior response @ 48-72 hrs and EOT Similar AEs

Case, con’t: Your patient recovers from his infection and does well. He is diligent about wearing compression stockings and has treated his tinea pedis. However, over the next several months, he presents with another episode of cellulitis of the same leg on 3 different

• ccasions. He has complete resolution of symptoms

between episodes. He wants to know if there’s anything he can do to prevent this in the future. What do you recommend?

• A. Swab nares for MRSA and treat with chlorhexidine if positive
• B. Obtain an MRI to look for bone infection
• C. Obtain a skin biopsy
• D. Start penicillin VK 250 mg po twice daily
• E. Start erythromycin 250 mg po twice daily

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Pathophysiology of recurrent cellulitis

Risk factors:

• Tinea
• Lymphedema
• Venous stasis
• Obesity

Cellulitis Impaired drainage, worsening anatomic issues

Prophylaxis for recurrent cellulitis

Dalal A et al. Cochrane Database Syst Rev. 2017 Jun 20;6:CD009758. doi: 10.1002/14651858.CD009758.pub2.

• ↑adverse events with erythromycin
• No difference in hospitalizations
• Effect disappeared after prophylaxis stopped

Erythromycin Penicillin

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Options for prophylaxis

• Penicillin V 250 mg po twice daily (preferred)
• Benzathine PCN G 1.2 million units q2-4 weeks (600,000

units if < 27 kg)

• PCN allergy: erythromycin 250 mg po twice daily
• Increased risk of Aes
• Alternative: Early patient-initiated therapy, not well studied
• Do not forget non-antibiotic interventions
• Treat tinea
• Address edema
• Weight loss

Thomas KS et al. N Engl J Med. 2013 May 2;368(18):1695-703. doi: 10.1056/NEJMoa1206300; Kremer M, et al. J

• Infect. 1991 Jan;22(1):37-40; Dalal A et al. Cochrane Database Syst Rev. 2017 Jun 20;6:CD009758. doi:

10.1002/14651858.CD009758.pub2.

Case, con’t. You start your patient on penicillin VK, and he does well. The next time you see him, though, is in the ICU where he is visiting his wife. She has presented to the hospital with erythema of her elbow after falling while playing tennis, resulting in an abrasion. On PE: T39C, HR 120s, BP 100/50. She appears uncomfortable and is disoriented. Her elbow is erythematous, swollen, and exquisitely tender to palpation. What is the most important next step?

• A. Start vancomycin, piperacillin/tazobactam, and clindamycin
• B. Start vancomycin and meropenem
• C. Obtain a stat CT scan
• D. Obtain a surgical consultation

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Necrotizing soft tissue infection features

Stage I

Tenderness Erythema Warmth Swelling

Stage II

Serous blister/bullae Fluctuance Woody induration Antibiotic failure

Stage III

Hemorrhagic bullae Skin anesthesia Crepitus Skin necrosis, dusky discoloration (ecchymosis), gangrene

Wong CH and Wang YS. Curr Opin Infect Dis. 2005 Apr;18(2):101-6.

Increasing systemic toxicity

LRINEC score

• Single-center development cohort: 89 patients with

necrotizing fasciitis and 225 control cases with non- necrotizing SSTIs

• Second center validation
• Score incorporates CRP, WBC, Hb, Cr, Na, glucose
• Risk groups: Low ≤ 5, moderate 6–7, or high ≥ 8
• Score ≥ 6: PPV 92.0% (95% CI, 84.3–96.0), NPV 96.0%

(95% CI, 92.6–97.9).

• Can help in cases where clinical suspicion is equivocal;

should NOT replace clinical judgement

Wong CH et al. Crit Care Med. 2004 Jul;32(7):1535-41.

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Other diagnostic modalities

• Radiographic imaging
• Xray: Gas specific but not sensitive
• CT: Can evaluate for abscess
• MRI: Can be helpful but slow
• Bottom line: If high suspicion, do not delay surgery
• Interventional tools:
• Frozen section biopsy at the bedside: Uncontrolled studies

suggest ↓ mortality but requires pathology presence

• Surgery: Macroscopic exam in the ORgray necrotic tissue,

lack of bleeding, thrombosis, “dishwater,” positive “finger test”once confirmed, can easily proceed with debridement

Anaya DA and Dellinger EP. Clin Infect Dis. 2007 Mar 1;44(5):705-10.

Necrotizing infection microbiology

• Monomicrobial (type II)
• S. pyogenes
• S. aureus
• V. vulnificus
• A. hydrophila
• Clostridium spp
• Anaerobic streptococci

(Peptostreptococcus)

• Polymicrobial (type I)
• Perianal abscesses,

abdominal trauma, or bowel surgery

• Decubitus ulcers
• IDU injection sites
• Spread from a genital site

such as Bartholin abscess, episiotomy wound, or a minor vulvovaginal infection ‒ Incl Fournier’s gangrene

Stevens DL et al. CID 2014; 59(2), e10–e52

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Management

• Source control: Surgical debridement with repeat take-backs daily
• W/o surgery, mortality approaches 100% even with abx on board
• More aggressive debridement tied to better outcomes
• Antibiotics until at least 48-72 hours after clinical improvement and

defervescence

• Empirical: Cover MRSA, GNRs, and anaerobes
• Vancomycin + piperacillin/tazobactam is a good option
• Clindamycin if GAS or clostridium
• Definitive therapy: Narrow as appropriate
• Supportive care
• Data lacking for hyperbaric oxygen, IVIG

Stevens DL et al. CID 2014; 59(2), e10–e52 Anaya DA and Dellinger EP. Clin Infect Dis. 2007 Mar 1;44(5):705-10. Kadri SS et al. Clin Infect Dis. 2017 Apr 1;64(7):877-885. doi: 10.1093/cid/ciw871. Darenberg J et al. Clin Infect Dis 2003 37 333 40

GAS/toxic shock

• Most often occurs with invasive GAS infection, including nec fasc
• Same principles of source control and supportive care
• Definitive therapy: Penicillin PLUS clindamycin
• At high inocula, beta-lactams may be less effective
• CLI is a protein-synthesis inhibitor, may ↓virulence factors
• Retrospective peds study: 83% vs. 14% “favorable” outcome with

CLI + beta-lactam vs. beta-lactam alone (p < 0.01)

• Prospective surveillance for iGAS in large population in Australia:

CLI pts had more severe dz but ↓ mortality (OR 0.28, 0.01-0.8)

• Swedish prospective surveillance, lack of CLI = OR for death 8.6

(p = 0.007)

• Some support for IVIG but mixed results and not convincing

Zimbelman J et al. Pediatr Infect Dis J. 1999 Dec;18(12):1096-100. Carpetis JR et al. Clin Infect Dis. 2014 Aug 1;59(3):358-65. doi: 10.1093/cid/ciu304 Andrenoi F et al. J Infect Dis. 2017 Jan 15;215(2):269-277. doi: 10.1093/infdis/jiw229. Linner A et al. Clin Infect Dis. 2014 Sep 15;59(6):851-7. doi: 10.1093/cid/ciu449. Epub 2014 Jun 13.

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DDx for SSTI in immunocompromised hosts

• Infection
• Bacterial (usual gm+,

GNRs—ecthyma gangrenosum, Nocardia)

• Fungal (molds, candida,

histo, crypto)

• NTM, TB
• Viral (VZV, HSV)
• Crusted scabies
• Noninfectious
• Sweets
• Leukemia cutis
• GVHD
• Erythema nodosum
• Pyoderma gangrenosum
• Drug reaction

Lopez FA, Sanders CV. Infect Dis Clin North Am. 2001 Jun;15(2):671-702, xi.

SSTI management in immunocompromise

• Dx:
• Low threshold for Dermatology consultation with biopsy
• Fungal markers
• Rx:
• Start empirical therapy promptly; anti-MRSA and broad-

spectrum GNR coverage is appropriate

• Consider anti-fungal coverage based on host and

morphology

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SSTI association with exposures

Exposure/population Organism Cat bite Pasteurella multocida Human bite Eikenella corrodens, viridans group Strep Dog bite Capnocytophaga, Pasteurella Rat bite Streptobacillus moniliformis Hot tubs Nontuberculous mycobacteria, Pseudomonas Brackish water, cirrhosis Vibrio vulnificus and other species Fresh water Aeromonas Fish/fish tanks Mycobacterium marinum, Erysipelothrix rhusiopathiae

Bites

• Follow routine wound care, including irrigation
• Decision to prophylax with antibiotics based on:
• Host factors: Immunocompromised/asplenic/cirrhotic/DM
• Injury mechanism: Severe/deep injury, location (hand, face,

joint), cat>dog (sharp teeth)

• Drug of choice: amoxicillin/clavulanic acid x 3 days
• Severe β-lactam allergy: TMP/SMX or FQ + clinda (human and

dog) or doxycycline + clinda (cat)

• Severe infection: Consult with ID, many IV options are active
• Discuss rabies vaccine with local health department
• Tetanus vaccine if prior vaccination > 10 years ago (clean wounds)
• r > 5 years ago (dirty wounds)

Stevens DL et al. CID 2014; 59(2), e10–e52

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Some other cellulitis points

• Blood cultures usually unnecessary
• At one center, only 11/710 (2%) of Bcx sent for cellulitis

yielded an organism (73% strep) with contaminants in 20/710 (4%)

• Exceptions: Immunocompromised, bites, immersion,

surgical debridement needed

• Elevate the affected area aggressively
• Search for onychomycosis and treat
• Treat anatomic factors like edema, eczema

Stevens DL et al. CID 2014; 59(2), e10–e52 Perl B et al. CID 1999; 29(6): 1483-1488

Nonpurulent cellulitis summary

Stevens DL et al. CID 2014; 59(2), e10–e52

MRSA risk factors:

• Unstable
• Device-assoc
• MRSA colonization
• Recent MRSA ifxn
• Hospital exposure

(dialysis, LTCF)

• Injection drug use
• Lack of response to

a regimen not covering MRSA

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Case #2. 32 y/o F presents with a “spider bite” on her L thigh. You examine her and note a 3 cm abscess with minimal surrounding erythema so perform an I+D in your office and send the material for culture. She is otherwise healthy, has no allergies, and is hemodynamically stable. What would you like to do next?

• A. Observation only with clinical follow-up in 7 days
• B. TMP/SMX 1 DS tab po twice daily x 5 days
• C. TMP/SMX 1 DS tab po twice daily x 10 days
• D. Clindamycin 300 mg po three times daily x 5 days
• E. Clindamycin 300 mg po three times daily x 10 days

Antibiotics for abscess? Con

• Retrospective single-center review of 376 patients with 450

infections undergoing drainage at a soft tissue infection clinic at a large urban county hospital, 2000-2001

• ~60% associated with IV drug use
• Categorized into appropriate versus inappropriate abx based on

final culture data

• Failure = persistence of infection requiring further treatment
• 259/284 (91.2%) of MRSA cultures and 4/157 (2.5%) MSSA

cultures got inappropriate antibiotics

• Loss to f/u: 33/441 (7.5%)
• Failure in those with f/u: 2/166 (1.2%) appropriate versus 1/242

(0.4%) inappropriate rx

Paydar KZ et al. Arch Surg. 2006;141(9):850-856. doi:10.1001/archsurg.141.9.850

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Antibiotics for abscess? Pro #1

• Multicenter, double-blind, placebo-controlled superiority RCT of

1247 ED patients with abscess requiring drainage

• TMP/SMX (2 DS tabs bid) versus placebo x 7 days
• 45% MRSA, 16% MSSA

Talan DA et al. N Engl J Med 2016; 374:823-832

Population TMP/SMX Placebo Diff (95% CI) mITT 80.5% 73.6% 6.9% (2.1 to 11.7) Per protocol 92.9% 85.7% 7.2% (3.2 to 11.2) Rx-related adverse event 34.3% 31.0% Additional surgical drainage 8.0% 13.0%

• 4.9% (-8.8 to -1.1)

Hospitalization 3.6% 6.4%

• 2.8% (-5.6 to 0.1)

New ifxn @ diff site 10.9% 19.1%

• 8.3% (-12.7 to -3.8)

Antibiotics for abscess? Pro #2

• Multicenter, prospective, double-blinded, placebo-controlled superiority

RCT of 786 outpatients with skin abscess ≤ 5 cm

• 3 arms: tmp/smx (1 DS tab) vs clinda vs placebo, all x 10 days
• Staph aureus present in 67% (74% of those MRSA)
• Failure mainly d/t new lesion @ different site or rescue med, rarely

worsening at the same site

• 54% response for clinda-R SA versus 85% clinda-S (p = 0.01)

Daum RS et al. N Engl J Med. 2017 Jun 29;376(26):2545-2555. doi: 10.1056/NEJMoa1607033.

Population Clinda (266) TMP/SMX (263) Placebo (257) ITT 83.1% (78.3-87.9) 81.7% (76.8-86.7) 68.9% (62.0-74.9) SA isolated 83.5% (77.9-89.1) 83.2% (77.5-89.0) 63.8% (56.0-71.5) No SA isolated 83.8% (74.3-93.3) 81.9% (72.4-91.5) 83.1% (74.5-91.8) Adverse event 21.9% 11.1% 12.5%

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Antibiotics for abscess? Pro #3

• Multicenter, prospective, double-blinded superiority RCT or

524 patients with cellulitis, abscess > 5 cm, or both

• TMP/SMX (1 DS) versus clindamycin x 10 days
• Abscess: 30.5%, cellulitis: 53.4%, both:15.6%
• Drainage done in 44.5%
• 296 (56.5%) had cxs: 73% SA of which 77% MRSA

‒ Only 15% of cellulitis only had SA vs. 69% in abscess and 80% in mixed ifxn ‒ 12.4% of SA were clinda-R, only 0.5% tmp/smx-R

Miller LG et al. N Engl J Med 2015; 372:1093-1103

Pro #3 results

Population Clinda (264) TMP/SMX (260) Diff ITT 80.3% 77.7%

• 2.6% (-10.2 to 4.9)

Evaluable 89.5% 88.2%

• .12% (-7.6 to 5.1)

Cellulitis alone ITT 80.9% 76.4%

• 4.5% (-15.1 to 6.1)

Abscess alone ITT 78.8% 80.0% 1.3% (-12.9 to 15.4) Mixed ifxn ITT 83.0% 80.0%

• 3.0% (-23.0 to 17.0)

Clinda-R MRSA 73.3% 91.7% p = 0.06

Miller LG et al. N Engl J Med 2015; 372:1093-1103

“Although it is not appropriate to claim that there are no differences on the basis of the negative result of the superiority test, important differences can reasonably be ruled out”

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Summary of antibiotics for abscess

• Most people (>70%) will get better without

antibiotics

• Antibiotics add a quantifiable benefit
• TMP/SMX and clinda both reasonable options
• More clinda resistance
• More GI intolerability with clinda
• Patient-centered decision-making about antibiotics

appropriate Case, con’t. You drain your patient’s abscess and provide tmp/smx x 10 days. She does well. At her follow-up visit 6 months later, she mentions she has been to the ED three more times to have small abscesses drained. She has grown MRSA when cultured. Besides careful attention to cleaning personal hygiene items and surfaces around the house, she wants to know if there’s anything she can do to prevent further infections?

• A. Doxycycline and rifampin x 10 days
• B. Mupirocin ointment to nares and chlorhexidine baths for 10 days
• C. TMP/SMX x 5 days monthly x 3-6 months
• D. Dilute bleach baths x 3 months
• E. Mupirocin ointment to nares and chlorhexidine baths x 10 days

for her and all family members

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Recurrent MRSA SSTI workup

• Same anatomic siteconsider local defect (e.g. pilonidal

cleft cyst, hidradenitis suppurativa)

• Screening for HIV, DM, injection drug use
• Recurrent infections at a young age or recurrent

severe/deep infectionsimmunological w/u

• Granulocyte disorders: CBC/diff, neutrophil function

testing (CGD)

• Quantitative immunoglobulins (hyper IgE syndrome)
• Lymphocyte subsets

Stevens DL et al. CID 2014; 59(2), e10–e52 Liu C et al. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4.

Recurrent MRSA SSTI management

• Clean surfaces that contact affected skin
• More info: https://www.cdc.gov/mrsa/community/environment/index.html
• Cover infected skin/draining wounds
• Do not share personal items (razors, towels, bottles of lotion, etc.)
• Launder linens at least weekly, towels more frequently
• Decolonization options (data limited):
• Mupirocin 2% nasal BID x 5-10 days
• Mupirocin 2% x 5-10 days + chlorhexidine 4% baths x 5-10 days
• Dilute bleach baths (1/4 cup per 1/4 tub) twice weekly x 3 mths
• Retapamulin 1% nasal BID x 5 days
• PO TMP/SMX or doxycycline PLUS rifampin x 5-10 days

Liu C et al. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4. Creech B, Al-Zubeidi DN, and Fritz S. Infect Dis Clin North Am. 2015 Sep; 29(3): 429–464.

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Household eradication

• Open-label RCT of 183 children with MRSA or MSSA SSTIs

(healed) and ongoing colonization

• All got mupirocin and chlorhexidine x 5 days
• Families randomized to also get treated or not
• Primary outcome = eradication @ 1 mth
• Secondary outcomes = SSTIs, persistent eradication
• Results:
• No significant differences in eradication at any time point
• Household group had fewer recurrent SSTIs @ 3 months (28%

vs 47%; P = .02), 6 months (38% vs 61%; P = .008), and 12 months (52% vs 72%; P = .02)

• Household contacts also had fewer SSTIs

Fritz FA et al. Clin Infect Dis. 2012 Mar;54(6):743-51. doi: 10.1093/cid/cir919.

Bleach is an inexpensive alternative

• Open-label RCT comparing 4 regimens to eradicate SA from 300

pts with CA-SSTI and SA colonization (~45% had recurrent SSTI) 1. Hygiene education only 2. Education + mupirocin x 5 days 3. Education + mupirocin + CHG washes x 5 days 4. Education + mupirocin + bleach washes (1/4 cup/bath) x 5 dd

• Results (1 vs. 2, 3, and 4):
• 1 mth eradication: 38% vs. 56% (0.03) vs. 55% (0.05) vs. 63%

(0.006)

• 4 mth eradication: 48% vs. 56% (0.4) vs. 54% (0.51) vs. 71% (0.02)
• Recurrent SSTI in 20% @ 1 mth, 36% @ 4 mths, 49% @ 6 mths, no

difference by arm

Fritz SA et al. Infect Control Hosp Epidemiol. 2011 Sep;32(9):872-80. doi: 10.1086/661285.

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Topical antibiotic resistance

• Mupirocin resistance: 2.5%-15% of CA-MRSA
• Chlorhexidine resistance: 1-17% or CA-MRSA
• Resistance to retapamulin also reported
• Genes for resistance carried on plasmids, which can

confer resistance to systemic antibiotics

• Stewardship of topical antibiotics should not be overlooked

Creech B, Al-Zubeidi DN, and Fritz S. Infect Dis Clin North Am. 2015 Sep; 29(3): 429–464.

Approach to recurrent Staph infections

Creech B, Al-Zubeidi DN, and Fritz S. Infect Dis Clin North Am. 2015 Sep; 29(3): 429–464.

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Purulent cellulitis summary

Stevens DL et al. CID 2014; 59(2), e10–e52

Thank you! Questions?

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