CN1: Integumentary System (Bacterial infections) Flashcards
Honey-colored, thin, friable crust spreading peripherally with central clearing
Staphylococcus aureus infxn
Predisposition to infection:
- Chronic S. aureus carrier state (nares, axilla, perineum, vagina)
- Warm weather/climate, high humidity
- Skin disease, especially atopic dermatitis, familial pemphigus
- Social situation: poor hygiene, crowded living conditions, neglected minor trauma
- Chronic disease: obesity, diabetes mellitus, HIV/AIDS
- Immune deficiency: cancer, chemotherapy
- Pre existing tissue injury or inflammation (surgical wound, burn, trauma, retained foreign body)
What is a nonmotile coccus, 0.8 to 1.0 um in diameter, that divides into three planes?
Staphylococcus aureus
- irregular clusters or in short chains
What are found characteristically in smears from cultures grown on solid media, whereas in broth cultures short chains and diplococcal forms are common?
Staphylococcus aureus
In a few strains of S. aureus, what enhances the virulence of the organisms?
capsule or slime layer
The cell wall of S. aureus consists of three major components:
- peptidoglycan
- teichoic acids
- protein A
What is a facultative anaerobic but growth is more abundant under aerobic conditions?
S. aureus
Growth occurs over a wide temperature range from 6.5C to 46C, with an optimum for S. aureus of _______.
30C to 37C
optimum temperature
What is the pH optimum of S. aureus with growth occurring over a range of pH 4.2 to 9.3?
7.0 to 7.5
optimum pH
Staphylococci grow well on most routine laboratory media such as
nutrient agar or trypticase soy agar
For primary isolation from clinical materials, what is recommended?
Sheep blood agar
On agar plates colonies, Staphylococcus aureus are:
smooth, opaque, round, low-convex, 1 to 4mm in diameter
on primary isolation: golden yellow colonies
The color can be attributed to _________________
Carotenoid pigments
extremely variable ranging from deep orange to pale yellow
What is the most convenient and reliable property for diagnostic purposes?
Coagulase - test tube method
an enzyme that cause the coagulation of plasma
What is useful for screening purposes and usually, correlating well with test tube results, detects a clumping factor in the surface of an organism that is distinct from the free coagulase?
Slide test
What is less reliable than the test tube method?
Slide test
What is a crucial factor in determining the initiation and the outcome of
staphylococcal infections?
Phagocytic response
Major determinants
In this process of host recognition and immunity, the cellular antigens of the staphylococcal cells, especially the surface ones
Antigenic structures and virulence factors of S. aureus:
- Teichoic Acid
- Protein A
- Peptidoglycan
- Clumping Factor
- Capsular Polysaccharide
- Polysaccharides
- Hyaluronidase
- Staphylokinase (Fibrinolysin)
- Nuclease
- Cytolytic Toxins
- Protein Receptors
- Enterotoxins
A major antigenic determinant of all strains of S. aureus is the group-specific ____ of the cell wall
Ribitol Teichoic Acid
What is the serologic determinant of this polysaccharide (teichoic acid)?
N-acetylglucosamine
What is not found in S. epidermis, which contains instead glycerol teichoic acid?
Ribitol teichoic acid
In the CW, TA is associated with peptidoglycan in an insoluble state, and requires ________ for its release.
Lytic enzymes
Most adults have a this type of reaction to teichoic acid, and low levels of precipitating antibodies are found in their sera.
cutaneous hypersensitivity reaction of the immediate type
Elevated levels of teichoic acid antibodies can result from:
staphylococcal disease, such as endocarditis or bacteremia
with metastatic foci of abscesses in which **drainage or antibiotic ther
What are infrequent in transient staphylococcal bacteremia?
Increases in teichoic acid antibodies
What is responsible for the rapid consumption of early-reacting complement components up to and including C5 in human serum?
Extracellular teichoic acid
What occurs as a consequence of immune complex formation between the antigen and specific human IgG antibodies?
Complement activation
What is found in the cell wall covalently linked to the peptidoglycan?
Protein A
is a group-specific antigen unique to S. aureus strains.
By induction of abortive, complement-consuming reactions, what protects staphylococci from complement-dependent opsonization?
Teichoic acid
Virtually all healthy donors have antibodies to the \_\_\_\_\_\_\_\_\_\_ in their serum. They are primarily of the IgG class and can cross the placenta.
peptidoglycan
What elicits both humoral and cellular immune responses?
Staphylococcal peptidoglycan
Peptidoglycan are primarily of what immunoglobulin class?
IgG
What can cross the placenta?
IgG
What increases the antipeptidoglycan IgG level especially when accompanied by a bacteremic phase?
S. aureus infections
What are potentially beneficial because of their opsonizing capacity, increased levels may predispose some patients to immune complex disorders?
Ab
The component on the cell wall of S. aureus that results in the clumping of whole staphylococci in the presence of plasma is referred to as the
Clumping factor
S. aureus expresses surface receptors for fibrinogen
Clumping factor binds ____ and differs from free coagulase in both its mechanism of action and its antigenic properties.
human fibrinogen
What is found almost exclusively in strains that produce the extracellular coagulase?
Cellular fibrinogen – binding component
What can give a negative clumping reaction, presumably because the clumping factor is covered by extracellular polysaccharides?
Encapsulated strains
When tested with ____, most strains isolated from clinical material are found to carry immunologically significant polysaccharide surface antigens.
monospecific antisera
What is a characteristic of a capsular polysaccharide?
Antiphagocytic
They interfere with the interaction between the underlying teichoic acid – peptidoglycan complex and complement, which is activated primarily through the alternative pathway.
Capsular Polysaccharide
these antigens are antiphagocytic
What encodes proteins involved in antibiotic resistance and other virulent factors?
Plasmids
S. aureus expresses surface receptors and uses these molecules as a bridge to bind to host endothelial cells:
- Fibrinogen (called
clumping factor) - Fibronectin
- Vitronectin
What has a polysaccharide capsule that allows them to attach to the artificial materials and to resist host cell phagocytosis?
Staphylococci infecting prosthetic valves
and catheters
What degrades lipids on the skin surface, and its expression is correlated with the ability of the bacteria to produce skin abscesses?
Lipase of S. aureus
Staphylococci also have protein A on their surface which binds in what portion of the Ig?
Fc
What is the pore-forming protein that intercalates into the plasma membrane or host cells and depolarizes them?
a-toxin
- a damaging hemolytic toxin
What is a sphingomyelinase?
B-toxin
What is a detergent-like peptide?
delta-toxin
Toxin on: Erythrocytes
Staphylococcal gamma-toxin
Toxin on: Phagocytic cells
Leukocidin
What is produced by S. aureus are serine proteases that split the skin by cleaving the protein desmoglein 1 which is part of the desmosomes that hold epidermal cells tightly together?
Exfoliative toxins
What can cause the superficial epidermis to split away from the deeper skin, making the patient vulnerable to secondary infections?
Exfoliative toxins
Exfoliation can occur at the site of what?
Staphylococcal skin infection (bullous impetigo)
What can be widespread when secreted toxin from a localized infection causes disseminated loss of the superficial epidermis?
Staphylococcal scalded-skin syndrome
What are the enzymes facilitating establishment of the organism on the skin and mucous membranes of the host?
Proteases
Lipases
Esterases
Lyases
By protecting the organisms from the complement-mediated attack of polymorphonuclear leukocytes, encapsulated staphylococci are able to what?
Spread rapidly through tissues
For colonization to occur, however, and the infectious process to be sustained, what is the essential initiating event?
Adhesion of the organisms to a biosurface
What enzyme hydrolyzes the hyaluronic acid present in the intracellular ground substance of connective tissue, thereby facilitating the spread of the infection?
Hyaluronidase
90% in S. aureus
The determinant for staphylokinase/fibrinolysin production is dependent on what?
A phage genome
and is expressed during lysogeny
In the dissolution of clots by the staphylococcal enzyme, what proenzyme is converted to the fibrinolytic enzyme plasmin?
Plasminogen
The enzyme, which is present in, at, or near the cell surface, is a compact globular protein
consisting of a single polypeptide chain.
Nuclease
What is among the best defined of the cytolytic toxins, a group of toxins that also includes streptolysin O and S and various toxins of Clostridium?
Hemolysins and leukocidin
What are produced by S. aureus, although strains may vary in the levels that they express?
Four distinct hemolytic toxins (a-, B-, d-, y-hemolysins)
These receptors provide the organism with an adhesion mechanism by which infective foci become established.
Protein Receptors
What are the plasma proteins that bind specifically to S. aureus?
fibronectin, fibrinogen, IgG, and C1q
Staphylococci also bind to components of what matrix?
Extracellular matrix (e.g., laminin, collagen, and fibronectin)
What exotoxins are members of a large group of pyrogenic protein toxins that mediate a spectrum of diseases with similar clinical manifestations and organ involvements?
Enterotoxins
1/3 S. aureus isolates produce exotoxins
What are the causes and manifestations of Staph infection?
- Respiratory infection
- Wound infxn
- Impetigo
- Focal skin infxns (abscess, furuncle, carbuncle)
- Endocarditis
- Food poisoning
- Toxic shock syndrome
Presumptive test/evidence of staphylococci:
typical irregular clusters of G (+) cocci on direct exam of purulent material
Staph infection: Definitive identification requires laboratory isolation of what?
pus, purulent fluids should be streaked directly on a blood agar plate and inoculated into a tube of thioglycollate broth
What are small to medium; translucent, gray-white colonies, most colonies nonhemolytic?
on 5% sheep blood agar
Staphylococcus epidermidis
What have slime-producing strains are extremely sticky and adhere to agar surface?
Staphylococcus epidermidis
What enhances organism adhesion and provides mechanical barrier to antibiotics and host defense mechanism?
Production of exopolysaccharide “slime” or biofilm
What are normal flora of human skin and mucous membranes; distributed widely, often in large numbers over body surface?
Staphylococcus epidermidis
What are the key determinants of S. aureus when you distinguish them from S. epidermidis based on biochemical properties?
S. aureus in Coagulase, Anaerobic growth and fermentation of glucose, Mannitol – acid anaerobically, a-toxin, Heat resistant endonucleases, Ribitol, and Protein A are ALL POSITIVE.
S. au is NEGATIVE in Biotin required for growth and Glycerol
What are the differences key determinants of S. epidermidis when you distinguish them from S. aureus based on biochemical properties?
S. epidermidis in Anaerobic growth and fermentation, Biotin required for growth, and Glycerol are ALL POSITIVE.
S. epi is NEGATIVE in Coagulase, Mannitol – acid anaerobically, a-toxin, Heat resistant endonucleases, Ribitol, and Protein A.
The only same biochemical properties that both S. aureus & S. epidermidis are positive:
Anaerobic growth and fermentation of glucose
What are less virulent than S. aureus and are opportunistic?
Staphylococcus epidermidis
What is S. epidermidis in coagulase test?
Negative
What include nosocomial bacteremia associated with indwelling vascular catheter: endocarditis involving prosthetic cardiac valves?
Staphylococcus epidermidis
Tend to be non – hemolytic; and cause disease in immunosuppressed persons
Staphylococcus epidermidis
The sequence of spread of S. aureus is from
nose to normal skin (about 11 days later) and skin lesions (after another 11 days)
What are spherical to ovoid organisms, 0.5 to 1.0 um in diameter?
S. pyogenes (group A B-Hemolytic Strep.)
G (+) cocci, pairs or chains
What is the preferred culture media for primary isolation of Group A streptococci?
Sheep blood agar (or with blood products)
Why is it recommended that agar be slashed by the loop at the primary site of inoculation?
To ensure subsurface growth
since hemolysis is enhanced under anaerobic conditions
S. pyogenes catalase test
Negative
What is the optimal pH or growth for Group A streptococci?
7.4 to 7.6 at 37C
What are gram positive and catalase negative?
Streptococci
This is specific to the species, and is composed of a branched polymer of L-rhamnose and
N-acetyl-Dglucosamine in 2:1 ratio, the latter being the antigenic determinant:
C-polysaccharide
What is linked by the phosphate-containing bridges to the peptidoglycan, which consists of N-acetlyl-D glucosamine, N-acetyl-D-muramic acid, D-glutamin acid, L-lysine, and D- and L-alanine?
C-polysaccharide
What does Group A streptococci produce which are two major classes of protein antigens that are responsible for type specificity in the group?
M and T antigens
both are suff stable and immunologically distinct to provide Sero typing
What is resistant to heat and acid but is destroyed by trypsin?
M antigen
What is heat and acid stable but are resistant to trypsin?
T antigens
What is performed by capillary tube precipitin tests using a hydrochloric acid extract to harvested cells as an antigen against absorbed rabbit type-specific hyperimmune sera?
Routine M typing
For its expression, organisms should be grown on media containing peptides
M protein
To avoid destruction of the M protein by proteinase activity, the pH should not be allowed to fall below what?
Below 6.5
What is an antiphagocytic fibrillar molecule located on the surface of group A organisms?
Streptococcal M protein
What is a surface protein that prevents bacteria from being phagocytosed?
M protein
expressed by S. pyogenes
What degrades this chemotactic peptide?
C5a peptidase
What is probably an autoimmune disease caused by antistreptococcal M protein antibodies that cross-react with cardiac myosin?
Poststreptococcal acute rheumatic fever
What has been referred to as flesh-eating bacteria because they cause a rapidly progressive
necrotizing fasciitis?
Virulent S. pyogenes
What is a cytosolic bacterial protein released on disruption of S. pneumoniae?
Pneumolysin
What inserts into target cell membranes and lyses them, greatly increasing tissue damage?
Pneumolysin
activates the classical comp pathway, reducing the comp available for opso
What can secrete a phage-encoded pyrogenic exotoxin that causes fever
and rash in scarlet fever?
Streptococci
What produces caries by metabolizing sucrose to lactic acid (which causes demineralization of tooth enamel) and by secreting high-molecular-weight glucans that promote aggregation of bacteria and plaque formation?
S. mutans
It has been shown that adherence to buccal epithelial cells is mediated by
Lipoteichoic Acid
What is an is amphipathic, highly cytotoxic, and amphoteric molecule? Also forms a complex network with M protein and binds via its lipid moiety to fibronectin on epithelial cells
Lipoteichoic Acid
Able to resist phagocytosis by killing leukocytes proliferate and begin to invade local tissues:
Organisms rich in M protein
The CW of group A streptococci have been shown to react with ________ in a nonimmune manner similar to that of staphylococcal protein A.
IgG
What has been attributed to the inhibition of complement, mediated by the binding of factor H, the serum control protein of the alternative complement pathway?
The antiphagocytic activity of streptococcal M protein
What is located on the cell surface, destroys chemotactic signals by removing a six-amino-acid peptide from the carboxyterminus of the complement component C5a?
C5a peptidase
What is the major virulence factor of group A streptococci and renders the
organisms resistant to phagocytosis?
M protein
What happens when there is the absence of type-specific Ab?
Streptococci producing M protein persists in infected tissues until Ab appear.
The antiphagocytic activity of M protein is attributed to an interference with the deposition of what?
Complement component C3b onto the streptococcal cell surface
What does many group A streptococci produce which mimics the ground substance of animal tissue?
Diffuse hyaluronic acid capsule
What is responsible for the clear zones of Beta-hemolysis around the colonies in BA media?
Hemolysins
What is an immunogenic single-chain protein (ca 60 kDa) released into the culture medium during growth?
STREPTOLYSIN O
It is the prototype of a group of oxygen-labile or thiol-activated bacterial cytolytic protein toxins produced by diverse species of Streptococcus, Bacillus, Clostridium, and Listeria.
STREPTOLYSIN O
Their toxins are inactivated irreversibly by cholesterol and structurally related sterols.
STREPTOLYSIN O
G (+) and are immunologically cross-reactive
- their biologic and lethal effects are rapidly lost by oxidation
- but are completely restored by thiols or other reducing agents
The toxins SLO are inactivated irreversibly by:
Cholesterol also structurally related sterols
The toxins (SLO) bind to the membrane and oligomerize in the membrane to form:
Large arc- and ring- shape structures composed of 25-100 toxin monomers
What is an oxygen-stable, nonantigenic toxin that is extractable from streptococcal cells only when a carrier or inducer is added to the culture or to resting cell suspension?
STREPTOLYSIN S
SLS is ____ for RBC and WBC and also for wall-less forms (protoplasts and L-forms) from various species.
lytic
lytic effects are inhibited by phospholipids, has cytolytic involvement
What is responsible for the surface hemolysis seen on blood agar plates?
STREPTOLYSIN S.
occasional strains that lack SLS may appear nonhemolytic on surface growth
There are at least three different serotypes (A, B, and C), which have molecular weights of:
A: 8 kDa
B: 17.5 kDa
C: 13.2 kDa
What are heat labile but are stable to acid, alkali, and pepsin?
Pyrogenic Exotoxins (Erythrogenic Toxins)
90% of all grp A streptococci produce this
The structural gene for pyrogenic exotoxins in the case w diphtheria toxin, is carried by a:
Temperate bacteriophage
What causes increased permeability of the blood-brain barrier to endotoxin and bacteria and exerts its pyretic effect by direct action on the hypothalamus?
Type C toxin
What VF in S. pyo assist in the liquefaction of pus and preseumably help to generate substrates for growth?
Nucleases
has 4 (A, B, C, D)
- all strains of S. pyo produce at least 1 nuclease,
Nucleases A and C have only what activity?
DNase activity
B and D also possess what?
RNase activity
After 18 to 24 hours of growth on agar, their colonies are 0.5mm in diameter, doomed, grayish to opalescent, and surrounded by a zone of B hemolysis several times greater than the diameter of the colony.
S. pyogenes
What is distinguished from B-hemolytic streptococci by a variety of
techniques such as Lancefield extraction and precipitation, fluorescent antibody or coagglutination?
Group A streptococci
MoT: direct contact
Pathophysiology of the Infectious Process (Transient Stage)
- S. aureus (most common) & group A beta-hemolytic strep.
- Immunocompromised, Traumatized, Poor hygiene, Malnourished
- Transient stage
- Disruption of the integrity of epidermis (skin barrier) e.g. Alcohol spraying, insect bites, abrasion, maceration, shaving, chronic wounds
- Pathogens invades skin
- Produce infxn w vesicopustule formation just beneath the stratum corneum
The development and evaluation of bacterial infection involve three major factors:
- The portal of entry
- The host defenses and inflammatory response to microbial invasion – natural resistance of the skin
- The pathogenic properties of the organism
What colonizes the skin shortly after birth?
Coagulase negative staphylococci
What is always caused by coagulase-positive S. aureus, group A Beta hemolytic streptococcus (GABHS) are implicated in the development of some lesion?
Bullous impetigo
Staphylococci generally spread from nose to normal skin then infect the skin.
In contrast, the skin becomes colonized with *GABHS an average of 10 days before development of *impetigo, GABHS then colonize the nasopharynx and average of ________ wks after the appearance of lesions of impetigo.
2-3 weeks
skin - serves as a sources of acquisition of GABHS in the respi tract
also the probable primary source of spread of impetigo
Flat (Non palpable)
MACULE
PATCH
various sized, flat, even with the surface level of the skin, circumscribed, is a change in the skin color without elevation or depression.
MACULE
> 1cm, like a macule, flat area on skin or mucous membrane with a different color from surrounding areas.
-PATCH
Raised (Palpable)
PAPULE
PLAQUE
NODULE
Circumscribed, solid elevations w no visible fluid varying in size from pinhead to 1 cm
PAPULE
Broad papule (or confluence of papules) 1cm or > in diameter, generally flat but maybe centrally depressed
PLAQUE
Is a palpable lesion greater than 1 cm with domed, spherical or ovoid shape. May be solid or cystic.
Have 5 main types:
- Epidermal
- Epidermal-dermal
- Dermal
- Dermal-sub-dermal
- Subcutaneous
-NODULE
Fluid filled
VESICLES (Blisters)
BULLAE
PUSTULES
1-10mm well circumscribed fluid filled lesions, epidermal elevations. May have pale or yellow (from serous exudates) or red (serum + blood)
The wall is thin and translucent enough to visualize the contents, which may be clear, serous or hemorrhagic.
VESICLES (Blisters)
> 1cm Rounded or irregular shaped blisters containing serous or seropurulent fluid and larger than vesicles.
BULLAE
Well circumscribed, raised pus filled lesion arising from the epidermis or infundibulum. The purulent exudate may be white or yellow, composed of leukocytes with or without cellular debris, may contain organisms or may be sterile.
1-10mm
PUSTULES
SECONDARY CHANGES (Epidermal or surface change)
SCALES
CRUST (Scabs)
LICHENIFICATION
FISSURE
Macroscopic finding indicating a change in the epidermis. Dry or greasy laminated
masses of keratin, with varying sizes, may be thick, fine, brawny, delicate, greasy, micaceous.
SCALES
Dried fluid on the skins surface due to serum, blood, pus or a
combination.
CRUST (Scabs)
Is a thickening and accentuation of the skin lines that results from
repeated rubbing or scratching of the skin
-LICHENIFICATION
Is a linear loss of continuity of the skins surface or mucosa that results
from excessive tension
-FISSURE
= History of recent exposure to offending allergic agent
= Affected area involved exposed to offending agent
Allergic contact dermatitis
= History of drug intake or recent herpes simplex infection prior to the appearance of lesions
= “Target lesions” – edematous looking, pale, erythematous macules
with a vesicle or erosion in the center surrounded by concentric rings
Erythema Multiforme
= History of recent burns
Thermal burns
= Involves primarily the feet
= (+) fungal spores/hyphae on KOH
Bullous tinea pedis
= involves the head, beard, face and hands
= (+) fungal spores/hyphae on KOH
Fungal – Tinea corporis – for non-bullous impetigo
S. aureus isolates from impetigo, ecthyma and folliculitis are more frequently caused by
methicillin-sensitive S. aureus
Systemic - Penicillinase resistant penicillin is the drug of choice because they are effective against penicillinase – producing Staphylococcus aureus.
Dicloxacillin, Cloxacillin, Oxacillin, Methicillin and Nafcillin
Topical: Mupirocin ointment/cream
(adults: 300 to 450 mg 3 to 4 times a day;
children: 20 to 40 mg/kg/day in 3-4 divided doses
Clindamycin
If CA-MRSA is suspected as the causative organism,
______ (Adults: 100 mg twice daily; Children: not
recommended for children younger than age 8 years),
______ (adults: 500 mg orally 4 times a day;
children 50 to 100 mg/kg/day divided 3 to 4 times
per day) is recommended.
Doxycycline
Cephalexin
For patients allergic to penicillin or B-lactams, _________ could serve as a substitute (adults: 250 to 500 mg orally 4 times
a day; children: 40 mg/kg/day divided 3 to
4 times per day).
Erythromycin
Topical
- Mupirocin 2% topical ointment
- Retapamulin 1% ointment BID for 5-7 days or
- Fusidic acid cream BID 5-7 days
Bactericidal drug.
It acts to inhibit cell wall synthesis and growth.
Dicloxacillin is the most active and most strains of S. aureus are inhibited by concentration of 0.05 to 0.8 ug / ml.
Pharmacodynamics
Rapidly but incompletely (30% to 40%) is absorbed from the gastrointestinal tract.
Absorption is more efficient when taken in an empty stomach and preferably when administered one hour or two hours after meals or ensure better absorption.
Oral dose of Dicloxacillin yields peak plasma concentration of 15 ug/mL by one hour.
It is rapidly excreted by the kidneys.
The drug is excreted in the urine in the first 6 hours after a conventional oral dose.
Pharmacokinetics
Untoward effects
- Hypersensitivity reactions are the most common adverse effects noted
with penicillins. The most serious hypersensitivity reactions produced by
penicillins are angioedema and anaphylaxis.
Others include serum sickness, vasculitis of the skin, fever maybe the only
evidence of a hypersensitivity reaction to penicillins, eosinophilia is an
occasional accompaniment of other allergic reactions to penicillin. - Gastrointestinal disturbances such as nausea and diarrhea may occur
with oral penicllin.
Other effective alternative therapies (Systemic – 2nd line).
Erythromycin in the penicillin allergic patient
Amoxicillin plus clavulanic acid – for impetigo caused by erythromycin resistant
S. aureus
Cephalexin
Ceproxil
Clindamycin
Azithromycin
infection deeply penetrating the epidermis producing a shallow crusted ulcer
Ecthyma
Acute spreading inflammation involving deeper subcutaneous tissue
Cellulitis
Inflammatory condition involving subcutaneous lymphatic channels
Lymphangitis
Major serious sequelae 1
Acute poststreptococcal glomerulonephritis
Secondary BI: ECLA, Bacteremia, Septicemia, Osteomyelitis, Pnemonitis
