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[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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.
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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.
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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.
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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.
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
Stevens DL et al. CID 2014; 59(2), e10–e52
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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.
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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)
Stevens DL et al. CID 2014; 59(2), e10–e52
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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
[ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]
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)
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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2/7/201824
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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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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2/7/201826
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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2/7/201827
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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2/7/201829
Purulent cellulitis summary
Stevens DL et al. CID 2014; 59(2), e10–e52
Thank you!Questions?
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