13 SSTIs Doernberg - UCSF CME · 2018-02-13 · [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS] 3 2/7/2018 Skin anatomy Impetigo: Superficial infection

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2/7/20181

SSTIsSarah Doernberg, MD, MASAssistant Professor2.20.2018

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730933/

https://www.journalofhospitalmedicine.com/jhospmed/article/128296/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


2/7/20182

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


2/7/20183

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 Commonshttps://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


2/7/20184

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.


2/7/20185

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 @ TOCmITT2 = 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.


2/7/20186

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


2/7/20187

Brief antibiotic reviewGAS 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


2/7/20188

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


2/7/20189

DDx to revisit in a stable patientDrug 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): 70-75Arakaki RY et al. JAMA Dermatol. 2014;150(10):1056-1061. doi:10.1001/jamadermatol.2014.1085


2/7/201810

ID consults can help, too

London, Ontario3 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 0 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.


2/7/201811

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


2/7/201812

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


2/7/201813

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

Dalbavancinday 1 and 8

Vancolinezolid 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 EOTSimilar AEs

Dalbadosing trial

Dalbavancin1500 mg x 1

Dalbavancin 1000 mg day 1 and 500 mg day 8

Noninferior response @ 48-72 hrs and EOTSimilar 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 occasions. 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


2/7/201814

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


2/7/201815

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 lossThomas 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


2/7/201816

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.


2/7/201817

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 ORgray 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



2/7/201818

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, IVIGStevens DL et al. CID 2014; 59(2), e10–e52Anaya 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 convincingZimbelman 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/ciu304Andrenoi 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.


2/7/201819

DDx for SSTI in immunocompromised hosts

Infection

• Bacterial (usual gm+, GNRs—ecthymagangrenosum, 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


2/7/201820

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, Erysipelothrixrhusiopathiae

BitesFollow 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) or > 5 years ago (dirty wounds)



2/7/201821

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–e52Perl B et al. CID 1999; 29(6): 1483-1488

Nonpurulent cellulitis summary


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


2/7/201822

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


2/7/201823

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)


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%


2/7/201824


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”


2/7/201825

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 siteconsider 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 infectionsimmunological 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–e52Liu 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 alternativeOpen-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


Thank you!Questions?


2/7/201830

13 SSTIs Doernberg - UCSF CME · 2018-02-13 · [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS] 3 2/7/2018 Skin anatomy Impetigo: Superficial infection

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