A Whirlwind Tour of Skin/Soft Tissue Infections

Steven P. LaRosa, M.D.Division of Infectious Disease

Beverly Hospitalslarosamd@gmail.com

Disclosure InformationSteven P. LaRosa, M.D.

• I have received fees as a member of the Scientific Advisory Board for the following companies:– Leading Biosciences– SciClone, Inc.– Atox Bio– ExThera Medical

• Consultant:– Cubist→Merck – Daptomycin, Tedizolid

THE USUAL

Patients Prone to Group A Strep Cellulitis

• Prior LN resection or irradiation (Breast CA, Vulvar CA)

• H/O SVG harvesting for CABG• H/O Lymphedema

Non-culturable cellulitis(no purulent material or wound present)Suspected organisms: β-hemolytic strep, S. aureus

Cefazolin 1 g IV q8h (<80kg), 2 g IV q8h (>80kg)

Oxacillin 2 g IV q4h Unasyn 3gms IV q 6h Penicillin allergy: clindamycin 600 mg

IV q8h (ID approval required), vancomycin 15 mg/kg IV q12h

If culture documented streptococcal infection: Aqueous PCN G 2 MU IV q4h

DO YOU NEED TO HAVE MRSA COVERAGE FOR UNCOMPLICATED CELLULITIS?

Uncomplicated Cellulitis

• Randomized, Multi-center, double blind, placebo-controlled study

• Evidence of cellulitis• Exclusions:

– DM– PVD– Hospital admission required– > 1 cc purulence– Immunocompromised or pregnant

III. Antibiotic dosing

Weight Cephalexin

Trimethoprim-sulfamethoxazole (mg trimethoprim)

Children <30 kg: 15–19 kg: 300 mg 4 times daily 40/200 mg qid 20–24 kg: 400 mg 4 times daily 60/300 mg qid 25–29 kg: 500 mg 4 times daily 72/360 mg qidAdults and children ≥30 kg: <60 kg: 500 mg 4 times daily 80/400 mg qid 60–80 kg: 1000 mg 3 times daily 160/800 mg tid >80 kg: 1000 mg 4 times daily 160/800 mg qid

153 Patients randomized to Cephalexin + TMP/SMX or placebo

Total Participants: 146Trimethoprim-Sulfamethoxazole n (% of total = 73)

Placebo n (% of total = 73)

Risk Difference % (95%CI) PValue

Cure (no failure by final follow-up at 30 d) (%) 62 (85) 60 (82) 2.7 (−9.3% to 15%) .66

Progression to abscess (%) 5 (6.8) 5 (6.8) 0 (−8.2% to 8.2%) 1.0

Any adverse event (%) 36 (49) 39 (53) −4.1 (−20% to 12%) .62

Diarrhea (%) 21 (29) 25 (34) −5.5 (−21% to 10%) .48

Nausea (%) 15 (21) 13 (18) 2.7 (−10% to 16%) .67

Vomiting (%) 5 (6.9) 8 (11) −4.1 (−13% to 5.1%) .38

Rash (%) 4 (5.5) 3 (4.1) 1.4 (−5.6% to 8.3%) .70

Pruritus (%) 5 (6.9) 3 (4.1) 2.7 (−4.6% to 10%) .47

Candidiasis (%) 1 (1.4) 3 (4.1) −2.7 (−8.0% to 2.5%) .31

Clostridium difficilecolitis (%) 0 (0) 1 (1.4) −1.4 (−4.0% to 1.3%) .32

Othera(%) 3 (4.1) 3 (4.1) 0 (−6.4% to 6.4%) 1.0

Non-culturable cellulitis(no purulent material or wound present)Suspected organisms: β-hemolytic strep, S. aureus

Cephalexin 500 mg PO q6h (<60kg), 1000 mg PO q8h (60-80kg), 1000 mg PO q6h (>80kg)

Dicloxacillin 500 mg PO q6h Penicillin allergy: clindamycin 300 mg PO q8h

Purulent cellulitis or cutaneous abscess (pus) OR h/o penetrating trauma, IVDU, MRSA infection elsewhereSuspected organisms: S. aureus (MRSA concern), β-hemolytic strep

Cephalexin 500 mg PO q6h (<60kg), 1000 mg PO q8h (60-80kg), 1000 mg PO q6h (>80kg) PLUS o TMP/SMX 1 single strength tab PO q6h

(<60kg), 1 double strength tab PO q8h (60-80kg), 1 double strength tab PO q6h (>80kg) OR

o Doxycycline 100 mg PO q12h Penicillin allergy: clindamycin 300 mg PO q8h

Recurrent Group A Strep cellulitis• Randomized, placebo-controlled of patients with at least 2

episode of leg cellulitis in previous 3 years, last recurrence in previous 24 weeks

• Randomized to;– PCN 250mg po BID or placebo X 12 months

• Primary outcome= Recurrence of cellulitis

Thomas KS ,et al. N Engl Jnl Med 2013;368:1695-1703

PCN prophylaxis for recurrent cellulitisPCN Placebo difference p

Median time to recurrence

626 days 532 days

Recurrence in first 12 months: prophylaxis phase

30/136 (22%) 51/138 (37%) -15% 0.01

Recurrence in years 2 and 3

26/97 (27%) 22/81 (27%) 0 0.78

NNT=5

Purulent cellulitis or cutaneous abscess (pus) OR h/o penetrating trauma, IVDU, MRSA infection elsewhereSuspected organisms: S. aureus (MRSA concern), β-hemolytic strep

Vancomycin 15 mg/kg IV q12h Vancomycin allergy:

o Ceftaroline 600 mg IV q12h (ID approval required)

o Daptomycin 500 mg IV q24h (not critically ill), 750 mg IV q24h (critically ill) (ID approval required) (STOP STATINS)

o Linezolid 600 mg IV or PO q12h (ID approval required) (NOT WITH SSRIs)

Detecting MRSA Colonization

• Study of 162 adults seeking care in ED for cutaneous abscesses

• 160 bilateral nares specimens , 142 inguinal specimens

• 19% of nares samples were positive• 26% of inguinal samples were positive• Combining culture sites detected 31% with

MRSA colonization

May L, et al. Diagn Mibrobiol Infect Dis 2014;80-79-82

DO PATIENTS WITH UNCOMPLICATED ABSCESSES NEED ANTIBIOTICS?

TMP/SMX vs placebo in patients following I&D of abscess

• Double-Blind RCT• >12 years of age• Lesion < 1 week• Lesion > or = 2cm in

diameter• Outpatient care

• Excluded:– Perineal lesion/bite– Foreign body– Chronic skin condition– Immunocompromised– Drug intolerance– Pregnancy

Talan DA, Moran GJ. ID WEEK 2014

TMP/SMX vs placebo in patients following I&D of abscess

• 1265 Patients randomized 1:1 to TMP/SMX 2 DS tabs po BID vs placebo x 7 days

• Primary Outcome: Test of cure visit Day 14-21• Secondary Outcomes:

– New skin infections– Fewer infections in household– Missed days of nl activity

TMP/SMX vs placebo in patients following I&D of abscess

Outcome TMP/SMX Placebo difference

Lesion cure rate 92.9% 85.7% -7.2% (95%CI 3.2-11.2)

New Skin infection -7.3%

Infections in household members

-2.4%

Missed days of nl activity

-0.4%

NNT to prevent 1 failure= 14

Recurrent MRSA Infections• Decolonization Regimen:

– Chlorhexidine washes daily x 7 days– Mupirocin 2% ointment to bilat ant nares TIDx 7 days– Rifampin 300mg po BID x 7 days– Doxycycline 100mg po BID x 7 days– Significantly lower MRSA colonization rate at 3 and 8 months

compared with placeboSimor AE et al. Clin Infect Dis 2007;44:178-185

Adjunctive Measures:1) FeSO4 supplementation if Iron deficiency anemia2) Vitamin C 1gm po daily- improved neutrophil function

Diabetic Foot Ulcers with Infection• Assess for arterial insufficiency and serious soft tissue

infections• Debride ulcers and get deep cultures (no superficial swabs)• Before any thought of MRI:

• If no findings of Osteo- treat for 2 weeks as SSTI• If Osteo treat for 6 weeks

Probe to Bone test

Chronic wounds, diabetic ulcerSuspected organisms: Strep, S.aureus, if chronic and previously treated Enteric GNR and Pseudomonas 

Oral Therapy Choices: Cephalexin, Clinda, Levofloxacin, Augmentin

Parenteral Therapy: Ampicillin/sulbactam 3 g IV q6h Ertapenem 1 g IV q24h (ID approval required) If Pseudomonas concern:

o Piperacillin/tazobactam 3.375 g IV q8h infused over 4 hours

o If MRSA concern: consider vancomycin 15 mg/kg IV q12h

Penicillin allergy: vancomycin + levofloxacin 750 mg IV daily

Newly FDA-approved agents for Cellulitis

Dalbavancin (Dalvance) Oritavancin (Orbactiv) Tedezolid (Sivextro)

1000mg IV Day 1, 500mg on Day 8

1200mg IV X 1 200mg IV or po x 6 days

$ 4470 $2900 $235

Non-inferior to Vanco/Linezolid

Non inferior to 7-10 days of Vanco

Non inferior to linezolid

Efficacy good in Streptococcal Infections

Response rates in Strep infections don’t look as good

No SSRI interaction, less myelosuppressive

Clearance of bacteremia in patients with positive blood cxs

Increased LFT abnormalities

GI side effects, can see “red man” syndrome

Can falsely elevate PTT and PT, can increase risk of bleeding with warfarin

THE BAD

Predictors of bacteremia or poor outcome warranting admission

• Predictors of bacteremia or poor outcome warranting admission– Predictors of bacteremia:

• Absolute neutrophil count (ANC): Absolute lymphocyte count (ALC) > 10• ALC < 1000 cells/mm3

– Altered Mental status– Hypotension – Acute kidney injury (increase in creatinine 0.3 mg/dl from baseline) or a

new elevation in BUN >19mg/dl– Lactate > 2.5mmol/L– CRP > 13mg/L– CPK > 300 U/L (2X ULN)– Immunocompromised host– Non-compliant patient

Signs/Symptoms of complicated Skin/Soft Tissue Infections

-Unstable vital signs-Pain out of proportion to physical exam findings-Rapidly progressing cellulitis-Violaceous/ hemorrhagic bullae-Skin anesthesia-Skin sloughing-Gas in tissue-Cutaneous hemorrhage

Necrotizing Fasciitis TypesNF Type Incidence Etiology Organisms Clinical Progress

I 70-80% ImmunocompromisedAbdominal surgeryPeri-anal process

Polymicrobial-mixed aerobes, anaerobes, Pseudomonas, Bacteroides

More indolentBetter prognosis

II 20-30% Skin or throat derivedFollowing trauma or direct inoculationpharyngitis./ vaginitis/proctitis

Monomicrobial- Group A Strep, S. aureus

Easily missed, rapid progression, STSS

III rare Marine related organisms, seafood ingestion contaminated wounds

Vibrio vulnificusAeromonas

High mortality

IV rare Trauma, burns, immunocompromised

Candida, Zygomycetes

>47% mortality in immunocompromised

Machado NO. North American Journal of Medical Sciences 2011;3:107-118

Six different variables included in the laboratory risk indicator for necrotizing fasciitis (LRINEC) score to help discriminate between necrotizing and nonnecrotizing soft-tissue

infections.

Goldstein E J C et al. Clin Infect Dis. 2007;44:705-710

© 2007 by the Infectious Diseases Society of America

Score >6 has a PPV of 92% and a NPV of 96%

Diagnosis

• The diagnosis of necrotizing fasciitis is surgical– Finger test:

• 2cm incision down to deep fascia under local anesthesia

• Index finger probing– Lack of bleeding– Dishwater pus– Lack of tissue resistance

– Radiologic tests are adjunct measures and one should not lose time waiting for a CT scan or MRI

Diagnosis –Rapid Ultrasound “STAFF exam”

• ST= subcutaneous thickening• A= air• FF= fascial fluid

– 88% sensitive and 93% specific for NF.

Castleberg E, et al. West J Emerg Med 2014;15:111-113

The Importance of Timely DebridementTime from DX to surgery

Adjusted OR 95%CI p value

< or = 14 hours 1 -

>14 hours 34.5 2.05-572 0.007

33 patients with NSTI and septic shock

Boyer A et al. Intensive Care Med 2009;35:847-853

Necrotizing fasciitis 

ID consultation Piperacillin/tazobactam 3.375 g IV q8h infused

over 4 hours PLUS clindamycin 900 mg IV q8h (ID approval required)

Meropenem 500 mg IV q6h PLUS clindamycin 900 mg IV q8h (ID approval required)

Penicillin allergy: consider levofloxacin + clindamycin or aztreonam + clindamycin (ID approval required)

If MRSA concern: consider vancomycin 15 mg/kg IV q12h

Proven Group A Strep infection: Aqueous PCN G 2-4 MU IV q4h PLUS clindamycin 900 mg IV q8h (ID approval required)

Clindamycin & IVIG: Role in Group A Strep Necrotizing Fasciitis

• 84 cases of invasive Group A Strep infection of which 29 were necrotizing fasciitis

• 30 day mortality:– Clindamycin + IVIG= 7%– Clindamycin= 15%– No Clinda= 39%

Carapetis JR, et al Clin Infect Dis 2014:59:358-365

Bites

Cat Bite

- Deep penetrating injury

- Multiple Organisms including Pasteurella and anaerobes

- Often need surgery

Human BitesSuspected organisms: S. viridans S. aureus, Haemophilus spp., Eikenella corrodens, Peptostreptococcus, Fusobacterium, Porphyromonas, Prevotella

Ampicillin/sulbactam 3 g IV q6h Cefoxitin 2 g IV q8h Clindamycin 900 mg IV q8h (ID approval

required) PLUS o Levofloxacin 750 mg PO q24h OR o TMP/SMX DS 1 tab PO q12h

Animal BitesDog/cat bite suspected organisms: Pasteurella multocida, streptococci, staphylococci, Fusobacterium, Bacteroides, Porphyromonas, Prevotella Consider Capnocytophaga canimorsus in splenectomized dog bite patients.

Ampicillin/sulbactam 3 g IV q6h Ceftriaxone 1 g (2 g if >80kg) IV q24h +

metronidazole 500 mg IV q8h Levofloxacin 750 mg IV q24h + metronidazole

500 mg IV q8h

ODD DUCKS

ERYSPELIOID

-Eryspelothrix rhusopathiae- Gram positive rods-Animal Exposure- including pigs and fish-Disease of butchers and fisherman and fishmongers-Usually confined to a finger-PCN is drug of choice

Sporotrichosis

-Sporothrix schenkii- dimorphic fungus-”Rose Growers” disease-rose thorns, sphagnum moss, soil, timber-subcutaneous nodules along lymphatics-Treatment is Itraconazole

Ecthyma gangrenosum

- Occurs in immunocompromised host

- Usually chemo with prolonged neutropenia

- Pseudomonas aeruginosa to blood vessel and surrounding dermis

- Erythematous macule to hemorrhagic bullae then ulcerates with erythematous halo

- Treatment is anti-pseudomonal antibiotics

- Surgical debridement if doesn’t respond

Mimickers of Cellulitis

Pyoderma gangrenosum

Erythema migrans