MANAGEMENT OF SKIN AND SOFT TISSUE INFECTIONS

MANAGEMENT OF SKIN AND SOFT TISSUE INFECTIONS

Jose A. Vazquez, M.D.Senior Staff

Division of Infectious DiseaseHenry Ford Hospital

Professor of MedicineWayne State University

Skin and Soft Tissue InfectionsGeneral ConsiderationsSkin and Soft Tissue InfectionsGeneral Considerations Primary vs. Secondary infectionsPrimary vs. Secondary infections Portal of entryPortal of entry Status of host defensesStatus of host defenses Associated manifestationsAssociated manifestations

Toxicity, severity of illnessToxicity, severity of illness Localization and morphology of lesionsLocalization and morphology of lesions Environmental exposureEnvironmental exposure

PRIMARY PYODERMASPRIMARY PYODERMAS

Impetigo Bullous impetigo Staphylococcal Scalded Skin Syndrome Folliculitis Furuncles and Carbuncles Erysipelas Cellulitis

PRIMARY PYODERMASImpetigo

PRIMARY PYODERMASImpetigo

>90% due to group A Streptococcus Most occur in children <10% mixture of Staph with Strep Manifestations

- small vesicles with erythematous halo- pustulates - ruptures

- characteristic golden-yellow thick stuck-on crusts

- painless

- minimal constitutional symptoms

PRIMARY PYODERMASImpetigo Therapy

PRIMARY PYODERMASImpetigo Therapy

Penicillin still drug of choice Alternatives:

- 1st generation cephalosporin

(Duricef, Keflex)

- If Pen allergic:

Erythromycin or Azithromycin Local wound care wet-to-dry dressings Topical antimicrobials far inferior

PRIMARY PYODERMASBullous Impetigo

PRIMARY PYODERMASBullous Impetigo

Primarily in kids Due to Staphylococcus group II (Type 71) Manifestations:

- Begin as vesicles that turn into bullae

- Bullae rupture and leave moist red surface

- No Nikolsky sign

- Finally form a thin “varnish”-like” light brown crust Therapy

- Dicloxacillin

- 1st generation ceph

- Erythromycin or Azithromycin

PRIMARY PYODERMASErysipelas

PRIMARY PYODERMASErysipelas

A superficial cellulitis of the skin with prominent lymphatic involvement

Generally due to group A Strep (rarely group C or G) Most common in:

- infants

- young kids

- older adults

- immunocompromised

(diabetics, alcoholic, nephrotic syndrome,

venous statsis, paraparesis) Portal of entry - skin ulcers, local trauma, abrasions, primary

dermatologic conditions, Tineas

PRIMARY PYODERMASErysipelas - ManifestationsPRIMARY PYODERMAS

Erysipelas - Manifestations

70-80% of lesions are on the lower extremity

5-20% are on the fact A painful lesion with a bright red edematous indurated

appearance and an advancing raised border-sharply demarcated

Fever Bacteremia ~ 5% Occasional spread to deeper structures Leukocytosis very common

PRIMARY PYODERMASErysipelas - ManifestationsPRIMARY PYODERMAS

Erysipelas - Manifestations

Penicillin oral vs parenteral

Alternatives

- 1st generation ceph.

- Erythromycin or Azithromycin

PRIMARY PYODERMASCellulitis

PRIMARY PYODERMASCellulitis

Acute spreading infection of the skin extending into the subcutaneous tissue

Etiology:

- Staph and Strep most common

- Erysipeloid- E. rhusiopathiae - salt water fish, poultry

- Anthrax - Bacillus - raw wool

- Pseudomonas - spas, heel tennis shoe puncture wounds

- Aeromonas - lesions in water

- Sporotrichosis

- Blastomycosis

PRIMARY PYODERMASCellulitis

PRIMARY PYODERMASCellulitis

Generally due to:

- Previous trauma

- Underlying skin condition Skin lesion: borders are not sharply demarcated

with erythema, tenderness, warmth, edema Fever - malaise - chills Regional adenopathy Bacteremia ~ 20%

PRIMARY PYODERMASCellulitis

PRIMARY PYODERMASCellulitis

If strong suspicion of etiologic agent treat with specific antimicrobial.

If etiologic agent unknown:

- No underlying risk factors

1st generation ceph (cover Staph and Strep)

Alternative: if Pen allergic

- Erythromycin or Azithromycin (Zithromax)

Staphylococcus aureusStaphylococcus aureus Frequent cause of cellulitis, especially in diabetic Frequent cause of cellulitis, especially in diabetic

patientspatients 22ndnd – 3 – 3rdrd most common cause of BSIs in hospitalized most common cause of BSIs in hospitalized

patients.patients. Etiology: > 80 % line infections:Etiology: > 80 % line infections: Susceptibility has evolved dramatically over the past Susceptibility has evolved dramatically over the past

few yearfew year

What about resistant S. aureus ??

What about resistant S. aureus ??

Resistance in S. aureusResistance in S. aureus HA-MRSAHA-MRSA CA-MRSACA-MRSA VISA or GISAVISA or GISA

MIC 8-16 to vancomycinMIC 8-16 to vancomycin

VRSAVRSA MIC > 32 to vancomycinMIC > 32 to vancomycin

HR-SAHR-SA MIC < 4 (susceptible) to vancomycinMIC < 4 (susceptible) to vancomycin subpopulations that are VISAsubpopulations that are VISA

Cosgrove SE. et al CID;39:539-45.

Community-Associated MRSACommunity-Associated MRSA

Prevalence ~ 36 % Prevalence ~ 36 % Risk Factors:Risk Factors:

Recent hospitalizationRecent hospitalization Recent antimicrobialsRecent antimicrobials SurgerySurgery Exposure to MRSA colonized personExposure to MRSA colonized person Athletes (wrestlers, football players)Athletes (wrestlers, football players) Chronic illnessChronic illness Nursing home, jails, IVDUNursing home, jails, IVDU

Eguia JM, Chambers HF. Hosp Epidemiol 5:2003

Community-Associated MRSACommunity-Associated MRSA Most common infections are SSTI and Resp. tractMost common infections are SSTI and Resp. tract Many remain susceptible to: clindamycin (89 v 21%); genta (94 Many remain susceptible to: clindamycin (89 v 21%); genta (94

v 80%);rifampin (96 v94%); TCN (92%); Bactrim (95v90%)v 80%);rifampin (96 v94%); TCN (92%); Bactrim (95v90%) ~ 60 % probably originate from hospitals or long-term care ~ 60 % probably originate from hospitals or long-term care

facilities facilities Risk Factors:Risk Factors:

Recent hospitalization`Recent hospitalization` OR OR

• 0-6 months 0-6 months 3.53.5

• 6-12 months6-12 months 2.22.2 Nursing homeNursing home 2.12.1

Charlebois ED. Et al. CID 2004;39:47-54: Naimi TS. Et al. JAMA;290:2976-84.

Community-Associated MRSAManagement

Community-Associated MRSAManagement

OutpatientOutpatient Mild InfectionMild Infection

• Clindamycin 450mg q8 hrs Clindamycin 450mg q8 hrs • Doxycycline 100mg BIDDoxycycline 100mg BID• Bactrim DS 2 tabs po BIDBactrim DS 2 tabs po BID

Moderate to severeModerate to severe• Zyvox 600mg BIDZyvox 600mg BID

InpatientInpatient Vancomycin 15mg/kg q12 hrsVancomycin 15mg/kg q12 hrs Zyvox (linezolid) 600mg IV/PO BIDZyvox (linezolid) 600mg IV/PO BID Daptomycin (Cubicin) 4mg/kg Daptomycin (Cubicin) 4mg/kg

Charlebois ED. Et al. CID 2004;39:47-54

Management of Gram PositivesManagement of Gram Positives

MSSAMSSA Nafcillin 2 gm q4 hNafcillin 2 gm q4 h Cefazolin (ancef) 2gm q 8 h IVCefazolin (ancef) 2gm q 8 h IV PCN allergy (vanco or linezolid) IVPCN allergy (vanco or linezolid) IV Linezolid oralLinezolid oral

MRSAMRSA VancomycinVancomycin LinezolidLinezolid DaptomycinDaptomycin

VRSA – Its All About SexVRSA – Its All About Sex Michigan Case 1Michigan Case 1 Gangrenous foot – VRE, MRSA, Gangrenous foot – VRE, MRSA,

multiple courses of vancomultiple courses of vanco VRE + MRSA = VRSA ( van A )VRE + MRSA = VRSA ( van A )

PA Case 2PA Case 2 Foot ulcer, VRE in the past. Foot ulcer, VRE in the past.

Allergic to VancoAllergic to Vanco MRSA 1:132 ( van A)MRSA 1:132 ( van A)

Vancomycin-Resistant Staphylococcus aureus Vancomycin-Resistant Staphylococcus aureus

The isolate was resistant to: The isolate was resistant to: – Oxacillin (MIC>16 Oxacillin (MIC>16 μμg/mL) g/mL) – Vancomycin (MIC>128 Vancomycin (MIC>128 μμg/mL)g/mL)

The isolate contained:The isolate contained:– The oxacillin resistance gene The oxacillin resistance gene mecAmecA– The The vanA vanA vancomycin resistance gene from enterococcivancomycin resistance gene from enterococci

MIC = minimal inhibitory concentration.

CDC. MMWR. 2002;51:565-567.

June 2002: First case of vancomycin-resistant S aureus (VRSA) isolated from a swab obtained from a catheter exit site.

SECONDARY PYODERMASSECONDARY PYODERMAS

Bite wounds

Infections of burns, wounds, or underlying dematitis

Diabetic wound infections

Decubitus ulcers

Surgical wound infections

BITE WOUNDS AND INFECTIONS ANIMAL

- Dog

- Cat

- Snake ~ 8,000/year

- few get infected

- venom is sterile

- Exotic animals

- monkey tend to be the most serious

- organisms will reflect habitat of animals HUMAN

- Occlusional bites

- Clenched-fist injuries

CAT BITESEpidemiology

~ 400,000/year

Primarily in women

Infection rates > 50%/bite

- Teeth slender, sharp, closer together

- High colony counts

- Teeth penetrate into bones, capsules, and bones easier

CAT BITESMICROBIOLOGY

Pasturella multocida isolated > 50% of bites Otherwise same isolates as dog Rochalimea spp.

- R. hensenulae

May cause Cat Scratch Disease

May produce disseminated disease in immunocompromised host

Tx. Erythromycin

BITE WOUNDS AND INFECTIONSDog Bites

~ 80% of all animal bites ~ 15-20% become infected Generally a polymicrobial infection Role of prophylactic antimicrobial therapy ???

- No good prospective studies Probably prudent to provide antimicrobial coverage

for at least 3-5 days after the bite

DOG BITESMicrobiology

Gram positive cocci

- alpha hemolytic streptococci ~ 30%

- S. aureus ~ 15%

- S. intermedium ~ 27%

- generally in dogs < 40 lbs.

- Beta-hemolytic streptococci

- Enterococci

- Micrococcus

DOG BITESMicrobiology

Gram negative rods

- Haemophilus

- Proteus

- E. coli

- Enterobacter cloacae

DOG BITESMicrobiology

Pasturella multocida

~ 10-15%

Eikinella corrodens

Capnocytophagia carimorsus

Actinomyces

Bacteroides spp. non Fragilis

Fusobacterium

Peptostreptococci

Peptococci

Veillonella

Eubacterium Rods

Anaerobes

HUMAN BITES/CLENCHED FIST INJURIESEpidemiology

Like monkey bites, generally more serious and more prone to develop infection and complications than are animal bites

Most tend to occur during fights

~ 20% of injuries are “love nips” and are related to sexual activity

HUMAN BITES/CLENCHED-FIST INJURIES

Unfortunately most patients tend to wait until the infection has set in before seeking medical attention

Generally results in cellulitis Frequently however, it produces:

- deep-space infection

- septic arthritis

- osteomyelitis ~ 20% of injuries require amputation if no antibiotic

is provided

HUMAN BITESMicrobiology

~ 55% are mixed polymicrobial infections with anaerobes

E. corrodens ~ 25% S. aureus Streptococci Hemophilus influenzae

BITE WOUND AND INFECTIONMANAGEMENT

Tetanus immunization Rabies vaccintion/Rabies immune globulin

- if indicated Incision/Drainage/Debridement

- if indicated Gram stain and culture of all material Elevation of injured area

- frequent cause of failure Follow-up

- preferably within 24-48 hours

BITE WOUNDS AND INFECTIONSAntimicrobial Therapy - Outpatient

Amoxicillin-clavulanate (Augmentin)

250-500 mg TID oral

Doxycycline 100 mg BID oral

Tetracycline 500 mg QID oral

BITE WOUNDS AND INFECTIONSAntimicrobial Therapy - Inpatient

Ampicillin-sulbactam (Unasyn)

3.0 gm IVPB Q 6 hrs. Cefoxitin or cefotetan 2 gm Q 8-12 hrs. IVPB

(No enterococcal coverage) Imipenem/cilastin (Primaxin)

500-1000 mg IVPB QID Piperacillin/tazobactam (Zosyn)

3.75 gm Q 8 hrs.

Building a better mouse trap ?

Zyvox (Linezolid)Zyvox (Linezolid)

11stst oxazolidinone – inhibits protein synthesis oxazolidinone – inhibits protein synthesisat the initiation of 50S ribosomeat the initiation of 50S ribosome Spectrum: gram positive pathogens:Spectrum: gram positive pathogens:

Staph aureusStaph aureus (MSSA or MRSA) (MSSA or MRSA) EnterococcusEnterococcus

E. fecalisE. fecalis or or E. faeciumE. faecium and VRE and VRE StreptococcusStreptococcus Group A Group A S. pneumoniaS. pneumonia including (PCN-Resistant SP) including (PCN-Resistant SP) NocardiaNocardia spp. spp.

Zyvox (Linezolid)Zyvox (Linezolid)

Dose : 600mg BIDDose : 600mg BID Oral and IVOral and IV Bioavailability ~ 100%Bioavailability ~ 100% Metabolism:Metabolism:

~ 65 % non-renal~ 65 % non-renal AE: diarrhea ~ 8-10 %AE: diarrhea ~ 8-10 %

thrombocytopenia ~ 2.5%thrombocytopenia ~ 2.5%

CUBICIN™ (daptomycin) OverviewCUBICIN™ (daptomycin) Overview Lipopeptide natural product Lipopeptide natural product Activity in Gram-positive organisms onlyActivity in Gram-positive organisms only Bactericidal in vitro and in vivoBactericidal in vitro and in vivo Safety profile similar to vancomycin Safety profile similar to vancomycin Long T1/2 (once-daily IV dosing) Long T1/2 (once-daily IV dosing) No oral formulationNo oral formulation FDA approved for SSTI only.FDA approved for SSTI only.

Future Antimicrobial Agents For Gram Positives OrganismsFuture Antimicrobial Agents For Gram Positives Organisms

GlycopeptidesGlycopeptides TelavancinTelavancin OritavancinOritavancin DalbavancinDalbavancin

TetracyclinesTetracyclines Tigecycline (broad spectrum activity)Tigecycline (broad spectrum activity)

CephalosporinsCephalosporins Ceftibiprole (5Ceftibiprole (5thth generation) generation)

Excellent gram positive activity (MRSA & Excellent gram positive activity (MRSA & EnterococcusEnterococcus))

ConclusionsConclusions Recent data has shown us:Recent data has shown us:

Emerging resistanceEmerging resistance CA-MRSA greatest concen ??CA-MRSA greatest concen ?? MRSA, GISA, VRSAMRSA, GISA, VRSA

Better understanding of mechanisms of antimicrobial Better understanding of mechanisms of antimicrobial resistanceresistance- e.g., selective pressure - e.g., selective pressure

Better understanding of risk factors predisposing to CA-Better understanding of risk factors predisposing to CA-MRSA infectionMRSA infection

FutureFuture Molecular testing for resistance organismsMolecular testing for resistance organisms Newer antimicrobialsNewer antimicrobials