Skin and Soft Tissue Infections

Question 1

Primary Pyoderma- Impetigo

Answer 1

Vesicular, later crusted, superficial infection of skin
Non-bullous impetigo
-Streptococcus pyogenes (20-30%)
-Staphylococcus aureus – now most common
-Mixed infection
Clinical findings
-Begin as erythematous papules that evolve into vesicles and pustules that rupture
-Dries to form honey-colored crusts on erythematous base
-Typically heals without scarring

Question 2

Bullous Impetigo

Answer 2

Strain of S. aureus producing exfoliating toxin

Toxin cleaves dermal-epidermal junction

Question 3

Ecthyma

Answer 3

Ulcerative pyoderma of skin – deeper form of impetigo
Follows insect bites or minor trauma
Etiology – S. aureus and/or S. pyogenes
Heals with scarring

Question 4

Primary Pyoderma- Purulent

Answer 4

Cutaneous abscess
Collections of pus within dermis and deeper tissue
Etiology – typically S. aureus; can be polymicrobial

Folliculitis, carbuncles and furuncles
Folliculitis - pyoderma located within hair follicle
Furuncle (boil) – inflammatory nodule extending into subcutaneous tissue; follows folliculitis
Carbuncle – coalescent process involving multiple follicles
Etiology – S. aureus

Question 5

Chancriform Lesions- Ulcerative lesions

Answer 5

Cutaneous anthrax
Direct inoculation with Bacillus anthracis
Begins as painless pruritic papule; enlarges, vesiculates (malignant pustule), becomes necrotic and covered by eschar
Local edema due to edema factor
Venereal infections - Treponema pallidum and Haemophilus ducreyi
Other infections – Francisella tularensis, Mycobacterium ulcerans, Mycobacterium marinum

Question 6

Cellulitis

Answer 6

Infection involving upper dermis and subcutaneous fat
Follows previous trauma, often minor, or underlying skin lesion, e.g., furuncle or ecthyma
Pain, erythema, involved area very red, hot and swollen
Etiology: Streptococci – Group A and others; less often S. aureus
Rarely, other bacteria – clues include trauma, water contact or animal, insect or human bites

Question 7

Erysipelas and Cellulitis

Answer 7

Diffuse, superficial, spreading skin infections
Not associated with collections of pus – clinically important
Purulent lesions (discharging pus) require drainage, e.g., abscess, furuncle or carbuncle
Cellulitis requires antimicrobial therapy

Question 8

Erysipelas

Answer 8

Superficial cellulitis with prominent lymphatic involvement
Painful; sharp demarcation from adjacent normal skin
Etiology – almost entirely S. pyogenes

Question 9

Necrotizing Fasciitis

Answer 9

Aggressive subcutaneous infection that tracks along the superficial fascia – all tissue between skin and underlying muscle
Most often an extension from a skin lesion
Systemic toxicity
Etiology – S. pyogenes, S. aureus, Vibrio vulnificus, Aeromonas hydrophila; often polymicrobic

Question 10

Systemic bacterial infections producing rash or lesions

Answer 10

Bacteremia – S. aureus, group A Streptococcus, N. meningitidis
Leptospirosis (Weil’s disease) – Leptospira interrogans
Rat-bite fever – Streptobacillus moniliformis
Annular erythema – Lyme disease – Borrelia burgdorferi
Rocky mountain spotted fever – Rickettsia rickettsii

Question 11

Toxin Induced Reactions

Answer 11

Scarlet fever
Scalded skin syndrome
Toxic shock syndrome

Question 12

Scarlet Fever

Answer 12

Follows pharyngitis by group A streptococcus

Streptococcal pyogenic exotoxin A (SpeA)

Question 13

Scaled Skin Syndrome

Answer 13

Follows local infection by Staphylococcus aureus

Staphylococcal exfoliating toxin

Question 14

Toxic Shock Syndrome

Answer 14

Follows infection by Staphylococcus aureus

Staphylococcal TSST-1 - superantigen

Question 15

Pyomyositis

Answer 15

Presence of pus within individual muscle groups
Usually S. aureus (90%)
Most cases in tropics

Question 16

Myonecrosis/ Gas gangrene

Answer 16

Necrotic damage to muscle tissue
Occurs after muscle injury and contamination with soil or other material containing spores
Extreme pain, crepitus due to gas formation, yellowish/bronze discoloration
Etiology: Clostridium perfringens (most common) and other clostridial species

Question 17

General features of streptococci

Answer 17

Gram-positive cocci in pairs or chains
Most are facultative anaerobes
Typically require complex media – blood or serum
Catalase-negative
CLASSIFICATION
Hemolytic patterns on blood agar
Antigenic – Lancefield grouping
Biochemical (physiological) properties
Complex classification – two general groups
β-hemolytic streptococci classified by Lancefield grouping
α- and γ-hemolytic streptococci classified by biochemical testing

Question 18

Alpha hemolytic streptococci

Answer 18

Partial hemolysis - greening of agar
Numerous species: S. salivaris, S. mitis
Normal flora of mucous membranes

Question 19

Beta Hemolytic streptococci

Answer 19

Complete hemolysis - clear zone

Streptolysins O and S

Question 20

Gamma hemolytic or non hemolytic streptococci

Answer 20

No hemolysis

Misc. normal flora, opportunists and anaerobes

Question 21

Streptococci Groups

Answer 21

Carbohydrate antigen in cell wall (C-carbohydrate); primarily beta hemolytic streptococci. method to differentiate beta hemolytic streptococci

Group A - S. pyogenes; most human pathogens
Groups B, C, F, G, H, K, L - normal flora of mucous membranes, occasional pathogens
Groups E, M, N - lower animals
Group D – enterococcus; now Enterococcus faecalis

Question 22

Lancefield Carbohydrate (C carbohydrate)

Answer 22

Group specific - all S. pyogenes are group A
Polymer of rhamnose and N-acetyl-glucosamine
Located in matrix of cell wall

Question 23

M protein

Answer 23

Type specific
Subdivides group A into >100 types
Induces type-specific protective immunity

Question 24

Streptococci extracellular enzymes

Answer 24

streptolysin O, DNAse, hyaluronidase

Question 25

Group A strep skin and wound infections

Answer 25

Impetigo – colonization of healthy skin; infection via minor trauma Erysipelas - dermal infection with spreading erythema and edema Cellulitis – subcutaneous tissues Myositis and necrotizing fasciitis – deep subcutaneous tissues; destruction of muscle and fat

Question 26

Group A strep Toxemia

Answer 26

Scarlet fever | Toxic shock-like syndrome (TSLS)

Question 27

Virulence Factors for streptococci- Adherence

Answer 27

Lipoteichoic acid – adhesion to epithelial cells F protein (SfbI – streptococcal fibronectin binding protein I) -Binds fibronectin -Adhesion to nasopharyngeal epithelial cells M protein – binding to epithelial cells Hyaluronic acid capsule -Facilitates adhesion to nasal mucosa -Essential for early colonization

Question 28

Virulence Factors for streptococci- avoiding phagocytosis

Answer 28

``` Hyaluronic acid capsule M protein -Antiphagocytic -Essential for virulence -Induces solid type-specific immunity; > 100 types -Candidate for vaccine development ```

Question 29

Virulence Factors for streptococci- toxins

Answer 29

Streptococcal pyrogenic exotoxins (Spe) -Synonyms: Erythrogenic toxin, scarlet fever -toxin -Rash of scarlet fever -Role in toxic shock-like syndrome (TSLS) -Superantigens - Stimulate release of IL-1, IL-2, -IL-6, TNF-a and IFN-g -Coded by lysogenic bacteriophage Lipoteichoic acid -Activates steps in inflammation and septic shock, e.g., complement cascade, cytokine secretion, coagulation cascade

Question 30

Virulence Factors for streptococci- tissue damage and spreading

Answer 30

Hemolysins, enzymes, etc. Streptolysin O - porin; oxygen labile; antigenic - anti-streptolysin O (ASO) Streptolysin S - oxygen stable; non-antigenic Streptokinase - converts plasminogen to plasmin; lyses blood clots Streptodornase – DNase; reduces viscosity of abscess material Hyaluronidase

Question 31

Serological tests for streptococci

Answer 31

Anti-streptolysin O: Typically negative in patients with skin infection Useful for diagnosis of rheumatic fever Not helpful with glomerulonephritis Anti-DNase: Antibodies produced after skin infection Particularly useful if glomerulonephritis is suspected

Question 32

Treatment of streptococcal infections

Answer 32

Penicillin – unless there are other issues All strains sensitive Prompt use reduces antibody response – essential that infection be treated quickly and completely

Question 33

Other issues with treating streptococcal infections

Answer 33

Possible mixed infection, e.g., S. aureus – oxacillin or vancomycin Necrotizing fasciitis: High dose penicillin + clindamycin Need for drainage and surgical debridement Allergy – clindamycin or a narrow spectrum cephalosporin; perhaps a macrolide – check current AHA recommendations Antibiotic prophylaxis for patients at risk for rheumatic fever

Question 34

General feature of staph

Answer 34

Gram positive cocci in grape-like clusters; aerobic Catalase positive May have golden pigment Beta- or non-hemolytic; depends on hemolysins Relatively resistant to physical and chemical agents Carry multiple plasmids and bacteriophage Penicillinase (beta lactamase) Toxin production, e.g., enterotoxin, toxic shock, etc.

Question 35

80% of the S. aureus genome is a core genome conserved among all Staphylococcus species and strains Remainder of genome is mobile DNA (mobile genome). what is the composition, function and regulation of the mobile DNA

Answer 35

Composition - Bacteriophage - Plasmids - Transposons - -Staphylococcal chromosomal cassette – much like a transposon Function - Virulence factors - Antibiotic resistance - Regulation Operon-like Example - accessory gene regulator (agr) – quorum sensing

Question 36

Staph aureus infections of skin and subcutaneous tissue

Answer 36

Impetigo – bullous and pustular; S. aureus accounts for ~80%; S. pyogenes alone or in combination with S. aureus is the remainder Abscesses, folliculitis, furuncles and carbuncles

Question 37

S. aureus deep infections

Answer 37

Bacteremia Osteomyelitis and septic arthritis Pneumonia Staphylococcal enterocolitis - follows upset of normal flora by broad spectrum antibiotics

Question 38

Diseases caused by staph toxins

Answer 38

Food poisoning Scalded skin syndrome and bullous impetigo Toxic shock syndrome

Question 39

Virulence factors of S. aureus- structural components

Answer 39

Capsule – antiphagocytic; 75% of clinical isolates are type 5 or 8 Peptidoglycan and lipoteichoic acids – contributes to inflammation Protein A – high affinity for IgG Fc fragment

Question 40

Virulence factors of S. aureus- enzymes

Answer 40

Coagulase -Converts fibrinogen to fibrin; helps localize lesions -Marker for species Catalase – facilitates intracellular survival Penicillinase

Question 41

Staph Cytotoxins

Answer 41

Alpha, beta, delta and gamma toxins; P-V leukocidin | Toxic via various mechanisms for erythrocytes, leukocytes and platelets

Question 42

Exfoliating toxin (ETA and ETB)

Answer 42

scalded skin syndrome

Question 43

Pyrogenic exotoxins of staph

Answer 43

Encoded by plasmids (enterotoxins) or bacteriophage (TSST) Superantigens - Induce release of IL-1, TNF-a, and other toxins - Related to Streptococcal pyrogenic exotoxins - Have specific toxic activities distinct from superantigen effects Staphylococcal enterotoxin (SEA, SEB, SEC, SED, SEE) Toxic shock syndrome toxin (TSST-1)

Question 44

Staph food poisoning

Answer 44

Ingestion of preformed staphylococcal enterotoxin Resistant to heat (boiling for 30 min) and gastric enzymes 1-6 hr. incubation Targets sensory nerve endings in smooth muscle of intestine Nausea, cramps, vomiting, diarrhea Recovery in 24 hr.

Question 45

Staphylococcal Scaled Skin Syndrome

Answer 45

Syn., exfoliative skin disease Toxemia - infection at distant site; release of exfoliating toxin Bullous impetigo is local form Toxin is a serine protease Cleaves dermal-epidermal junction to form fragile, thin-roofed vesicopustules Usually in children

Question 46

Staphylococcal Toxic Shock Syndrome

Answer 46

Toxemia producing fever, vomiting, diarrhea, rash, shock Possible mechanisms -Induction of cytokine release, e.g., IL-1 and TNFa -Increased susceptibility to endogenous endotoxin -Direct effects on vascular endothelial cells TSST-1 production stimulated by poor growth conditions Blood cultures usually negative

Question 47

Staph lab differential characteristics

Answer 47

Gram-positive coccus Catalase positive - distinguishes Staphylococci from Streptococci Coagulase positive - distinguishes S. aureus from other Staphylococci Ferments mannitol

Question 48

Lab recognition of MRSA

Answer 48

Chromogenic media with disks of oxacillin or cefoxitin | PCR for mecA

Question 49

Staph treatment

Answer 49

Drain lesion; remove foreign body if present Control underlying disease Antibiotics – in the era of MRSA, this is a complete lecture in itself Weapons in the arsenal – in no particular order -Penicillinase-resistant penicillins, e.g., oxacillin -Clindamycin -TMP-SMX -Doxycycline -Linezolid -Vancomycin -Daptomycin Recommendations vary with clinical disease*

Question 50

Staph antibiotic resistance

Answer 50

Penicillinase producing S. aureus - very common Resistance to intermediate levels of vancomycin (VISA) Thicker, more disorganized cell wall with free ala-ala groups Acts as a decoy for vancomycin Vancomycin resistant S. aureus (VRSA) Due to vanA gene operon – encodes ala-lactate production Requires rigorous susceptibility testing Still relatively rare

Question 51

Antibiotic resistance- MRSA

Answer 51

Lies on a mobile genetic element – staphylococcal chromosome cassette – SCCmec SCCmec Includes regulator genes – negative repressor operon mecA – encodes PBP 2a with low affinity for beta lactam antibiotics

Question 52

Health care-associated MRSA (HCA-MRSA)

Answer 52

Associated with risk factors, e.g., surgery, indwelling catheter, etc. Multi-resistant

Question 53

Community-associated MRSA (CA-MRSA)

Answer 53

No/limited risk factors Most common cause of skin and soft tissue infections in community Usually carries the PV leukocidin Pauci-resistant

Question 54

MRSA control

Answer 54

Control - decolonization of colonized patients or carriers – 1 week of body washing with chlorhexidine + nasal mupirocin