B4M1C3: Cardiovascular System

Question 1

MORPHOLOGY OF STREPTOCOCCUS PYOGENES (GROUP A Β-HEMOLYTIC STREP)

Answer 1

• spherical to ovoid organisms
• 0.5 to 1.0 μm in diameter
• gram-positive cocci that grows in pairs or chains

Question 2

What are the cultural characteristics of S. pyogenes (GABHS)?

Answer 2

Preferred culture media for primary isolation of Group A streptococci contains blood or blood products.

○ Sheep blood agar is preferred.
○ The optimal pH for growth is 7.4 to 7.6 at 37 C.

● Most group A streptococci are β-hemolytic on sheep blood agar.
○ Hemolysis is enhanced under anaerobic conditions, so it is recommended that the agar be slashed by the loop at the primary site of inoculation to ensure subsurface growth.

● Streptococci are gram positive and catalase negative.

Question 3

After 18 to 24 hours of growth on agar, S. pyogenes colonies are:

Answer 3

0.5mm in diameter
doomed, grayish to opalescent, and surrounded by a zone of β-hemolysis several times greater than the diameter of the colony

Question 4

Group A streptococci is distinguished from β-hemolytic streptococci by a variety of techniques such as

Answer 4

Lancefield extraction and precipitation, fluorescent antibody or coagglutination

Question 5

ANTIGENIC STRUCTURES AND VIRULENCE FACTORS:

Answer 5

○ C-polysaccharide
○ Proteins
○ M protein

Question 6

What is specific to the species, and is composed of a branched polymer of L-rhamnose and N-acetyl-D-glucosamine in 2:1 ratio?

Answer 6

C-polysaccharide

Question 7

What is the antigenic determinant of C-polysaccharide?

Answer 7

N-acetyl-D-glucosamine

Question 8

The polysaccharide is linked by the phosphate-containing bridges to the peptidoglycan, which consists of:

Answer 8

● N-acetyl-D-glucosamine
● N-acetyl-D-muramic acid
● D-glutamic acid
● L-lysine
● D- and L-alanine.

Question 9

Group A streptococci produce two major classes of protein antigens, the _________, that are responsible for type specificity in the group.

Answer 9

M and T antigens

○ Both antigens are sufficiently stable and immunologically distinct to provide useful serologic methods of typing. More than 90% of all group A strains may be typed by use of these antigens.

Question 10

What are resistant to heat and acid but are destroyed by trypsin?

Answer 10

M antigens

Question 11

What are heat and acid stable but are resistant to trypsin?

Answer 11

T antigens

Question 12

What is performed by capillary tube precipitin tests using hydrochloric acid extract to harvested cells as antigens against absorbed rabbit-type specific hyperimmune sera?

Answer 12

Routine M typing

Question 13

For expression of the M protein, organisms should be grown on media containing what?

Answer 13

Peptides

Question 14

To avoid destruction of the M protein by proteinase activity, the pH should not be allowed to fall below

Answer 14

6.5

Question 15

What is an antiphagocytic fibrillar molecule located on the surface of group A organisms?

Answer 15

Streptococcal M protein

Question 16

PATHOGENESIS

Answer 16

● The different species of streptococci produce many virulence factors and toxins.

● Many streptococci, including S. pyogenes also express M protein, that resist phagocytosis. S. pyogenes also expresses M protein, a surface protein that prevents bacteria from being phagocytosed, and a complement C5a peptidase, which degrades this chemotactic peptide.

● Poststreptococcal acute rheumatic fever is probably an autoimmune disease caused by antistreptococcal M protein antibodies that cross-react with cardiac myosin.

● Virulent S. pyogenes have been referred to as flesh-eating bacteria because they cause rapidly progressive necrotizing fasciitis.

● Pneumolysin is a cytosolic bacterial protein released on disruption of S. pneumoniae.
○ Pneumolysin inserts into target cell membranes and lyses them, greatly increasing tissue damage.
○ This toxin also activates the classical pathway of complement, reducing the complement available for opsonization of bacteria.

● Streptococci secrete a phage-encoded pyrogenic exotoxin that causes fever and rash in scarlet fever.

● S. mutans 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.

Question 17

What can resist phagocytosis?

Answer 17

M protein

Question 18

What is a surface protein that prevents bacteria from being phagocytosed that also can be expressed by S. pyogenes?

Answer 18

M protein

Question 19

degrades this chemotactic peptide

Answer 19

complement C5a peptidase

Question 20

What is probably an autoimmune disease caused by antistreptococcal M protein antibodies that cross-react with cardiac myosin?

Answer 20

Poststreptococcal acute rheumatic fever

Question 21

Virulent S. pyogenes have been referred to as flesh-eating bacteria because they cause

Answer 21

rapidly progressive necrotizing fasciitis

Question 22

What is a cytosolic bacterial protein released on disruption of S. pneumoniae?

Answer 22

Pneumolysin

Question 23

This inserts into target cell membranes and lyses them, greatly increasing tissue damage.

○ This toxin also activates the classical pathway of complement, reducing the complement available for opsonization of bacteria.

Answer 23

Pneumolysin

Question 24

What does streptococci secrete that causes fever and rash in scarlet fever?

Answer 24

phage-encoded pyrogenic exotoxin

Question 25

This 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.

Answer 25

S. mutans

Question 26

Determinants of Pathogenicity

Answer 26

● The pathogenicity of S. pyogenes is multifactorial. A number of virulence factors are produced, which are of survival value and permit the organism to interact with tissue receptors, resist host defenses, and multiply within the host.

● Some of these have recently been shown to belong to a common operon that is globally controlled in response to environmental changes and the general physiologic state of the cell.

Question 27

Cellular Components:

Answer 27

1. Lipoteichoic acid (LTA)
2. M protein
3. Capsular polysaccharide

Question 28

● For an organism to infect its intended host, it must be able to gain a foothold on the surface of cells at the portal of entry. It has been shown that adherence to buccal epithelial cells is mediated by the __________ that is present in the cell wall of group A streptococci.

Answer 28

lipoteichoic acid

Question 29

What is an amphipathic and amphoteric molecule? It is highly cytotoxic for a variety of host cells and is capable of a wide array of biologic activities.

Answer 29

LTA

Question 30

LTA has been identified as the _____________ that forms a complex network with M protein and binds via its lipid moiety to fibronectin on epithelial cells.

Answer 30

streptococcal colonization ligand

Question 31

● Once adherence has taken place, those strains that are able to resist phagocytosis and killing leukocytes (i.e., those organisms rich in M protein) proliferate and begin to invade local tissues. Local pharyngeal or cutaneous infection may ensue, or the organism may invade contiguous tissues or distant tissues via the bloodstream.

● Once an antibody response is induced, organisms may be rapidly engulfed and killed by phagocytes.

Answer 31

M protein

Question 32

M protein

Answer 32

○ The cell walls of group A streptococci have been shown to react with immunoglobulin (IgG) in an nonimmune manner similar to that of staphylococcal protein A.

○ The cell walls are also potent activators of the alternative complement pathway.

○ The presence of M protein on the surface of the cell wall prevents these reactions from occurring and hence may explain the rapid recognition and phagocytosis of M-negative strains.

○ The antiphagocytic activity of streptococcal M protein has been attributed to the inhibition of complement, mediated by the binding of factor H, the serum control protein of the alternative complement pathway.

Question 33

In addition to M protein, which has long been thought to be the key determinant of virulence for S. pyogenes, the organism possesses additional virulence factors, at least some of which appear to be under the control of a virulence region.

○ One of these, a ___________, which is located on the cell surface, destroys chemotactic signals by removing a six-amino acid peptide from the carboxy terminus of the complement component C5a.

Answer 33

C5a peptidase

Question 34

What is the major virulence factor of group A streptococci and renders the organisms resistant to phagocytosis?

Answer 34

M protein

○ In the absence of type-specific antibodies, streptococci producing M protein persists in infected tissues until antibodies appear.

○ The antiphagocytic activity of the M protein is attributed to an interference with the deposition of the complement component C3b onto the streptococcal cell surface.

○ Activation of the alternate complement pathway and opsonization of the streptococcus is thus inhibited.

○ With the appearance of type-specific antibodies, M protein activity is nullified. The immunity that develops is type-specific and long-lasting.

Question 35

● Many group A streptococci produce a diffuse hyaluronic acid capsule, which mimics the ground substance of animal tissue.

● Although less important as a virulence factor than M protein, it assists the organism in avoiding the phagocytic defenses of the host.

Answer 35

Capsular Polysaccharide

Question 36

Extracellular Products:

Answer 36

1. Hemolysins
   - Streptolysin O
   - Streptolysin S
2. Pyrogenic exotins (erythrogenic toxins)
3. Nucleases

Question 37

What are produced by most stains of group A streptococci and many strains of group C and G? They are responsible for the clear zones of beta-hemolysis around the colonies in blood agar media.

Answer 37

Two hemolytic and cytolytic toxins – streptolysin O (SLO) and streptolysin S (SLS)

Question 38

What is an immunogenic single-chain protein (ca 60kDa) released into the culture medium during growth?

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.

Answer 38

SLO

Question 39

SLO:

Answer 39

○ The toxins produced by these gram-positive organisms are immunologically cross-reactive and share a number of common biochemical and physical properties.

○ Their biological and lethal effects are rapidly lost by oxidation but are completely restored by thiols or other reducing agents.

The toxins are inactivated irreversibly by cholesterol and structurally related sterols.

○ Their cytolytic activity, which is attributed to their damage to cholesterol-containing membranes, extends to a wide range of eukaryotic cells, including red blood cells, polymorphonuclear leukocytes, and platelets.

○ The toxins bind to the membrane and oligomerize in the membrane to form large arc- and ring-shape structures composed of 25 to 100 toxin monomers.

The role of toxin oligomers has not been clearly established, but they appear to span the membrane, and concomitant with their formation, high-molecular weight cytoplasmic components leak from the cell, resulting in cell death.

Question 40

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 suspensions?

Answer 40

SLS

Question 41

SLS:

Answer 41

○ It is lytic for red and white blood cells and also for wall-less forms (protoplasts and L forms) from various species.

○ The lytic effects are inhibited by phospholipids, which suggest their involvement in the cytolytic activity of the toxin.

○ Most strains of group A streptococci produce SLS, which is responsible for the surface hemolysis seen on blood agar plates.

○ Those occasional strains that lack SLS may appear nonhemolytic on surface growth.

Question 42

Pyrogenic Exotoxins (Erythrogenic Toxins)

Answer 42

More than 90% of all group A streptococci isolates produce pyrogenic exotoxins.

There are at least three different serotypes (A, B, and C), which have molecular weights of 8, 17.5 and 13.2 kDa, respectively.

They are heat labile but are stable to acid, alkali, and pepsin. The structural gene for these toxins, as in the case with diphtheria toxin, is carried by a temperate bacteriophage.

The type C toxin causes increased permeability of the blood-brain barrier to endotoxin and bacteria and exerts its pyretic effect by direct action on the hypothalamus.

Question 43

There are four antigenically distinct nucleases (A, B, C, and D) in S. pyogenes that assist in the:

Answer 43

liquefaction of pus and presumably help to generate substrates for growth

Question 44

All strains of S. pyogenes produce at least one nuclease, usually the

Answer 44

B enzyme

Question 45

Nuclease A and C have only ____ activity, whereas B and D also possess ____ activity.

Answer 45

Nuclease A and C have only DNase activity, whereas B and D also possess RNase activity.

Question 46

What is an acute, immunologically mediated multisystem inflammatory disease that occurs a few weeks after an episode of a group A (β-hemolytic) streptococcal pharyngitis and often involves the heart?

Answer 46

RF

Question 47

What is probably an autoimmune disease caused by anti streptococcal M protein antibodies that cross-react with cardiac myosin?

Answer 47

Post streptococcal acute rheumatic fever

Question 48

INCIDENCE OF RF

Answer 48

● Mainly a disease of children aged 5-14 years.
● Initial episodes are rare in persons aged >30 years.
● Recurrent episodes remain relatively common in adolescents and young adults.
● There is no clear gender association

Question 49

PATHOGENESIS

Answer 49

● When a susceptible host encounters a group A streptococcus, an autoimmune reaction results, which lead to damage to human tissues as a result of cross-reactivity between epitopes on the organism and the host.

● Only a minority of infected patients develop rheumatic fever, it is suspected that genetic susceptibility regulates the hypersensitivity reaction.

● It is currently thought that the initial damage is due to cross-reactive antibodies attaching at the cardiac valve epithelium, allowing the entry of primed CD4+ T cells, leading to subsequent T cell mediated inflammation.

● The most important consequence is chronic rheumatic heart disease, characterized principally by deforming fibrotic valvular disease (particularly mitral stenosis), which can produce permanent dysfunction and severe, sometimes fatal, cardiac dysfunction.

● The chronic sequelae result from progressive fibrosis because of both healing of the acute inflammatory lesions and the turbulence induced by ongoing valvular deformities.

Question 50

Some factors associated with the development of the disease (Epidemiologic Risk Factors)

Answer 50

1. Lower standards of living, especially crowding.
2. The organism itself – “rheumatogenecity” of specific strains (e.g. serotypes 1, 3, 5, 6, 18, 19, 24, 27, and 29)
3. The degree of host or herd immunity to the prevalent serotypes in an affected community.

Question 51

Natural History of Untreated Rheumatic Fever

Answer 51

● Approximately 3% of individuals with untreated group A streptococcal pharyngitis will develop rheumatic fever.

● The most important consequence of rheumatic fever is chronic rheumatic heart disease, characterized principally by deforming fibrotic valvular disease (particularly mitral stenosis), which can produce permanent dysfunction and severe, sometimes fatal, cardiac dysfunction decades later.

Page 3 diagram

Question 52

PATHOLOGIC FEATURES OF RHEUMATIC FEVER

Answer 52

1. Aschoff bodies which constitute foci of fibrinoid degeneration surrounded by lymphocytes primarily T cells, occasional plasma cells and anitschkow cells
2. Anitschkow cells are plump macrophages with abundant amphophilic cytoplasm and central round-to-ovoid nuclei in which the chromatin is disposed in a central, splender, wavy ribbon. These cells are pathognomonic for rheumatic fever.
3. Small vegetations (verrucae) along the line of closure of the mitral valve leaflets.
4. Myocardial interstitium has a circumscribed collection of mononuclear inflammatory cells, including some large histiocytes with prominent nucleoli, a prominent binuclear histiocyte, and central necrosis.
5. Subendocardial lesions may induce irregular thickenings called MacCallum plaques, usually located in the left atrium.

Page 3 pictures

Question 53

Jones Criteria

Answer 53

● There is a latent period of ~3 weeks (1-5 weeks) between the precipitating group A streptococcal infection and the appearance of the clinical features.

● The exceptions are chorea and indolent carditis, which may follow prolonged latent periods lasting up to 6 months.

● The most common clinical presentation is polyarthritis and fever.

Question 54

5 Major Criteria (Jones)

Answer 54

1. Carditis
   ● Present in 50-60% of cases and progress to RHD
   ● The endocardium, pericardium, or myocardium may be affected.
   ● Valvular damage is the hallmark of rheumatic carditis.
   ● The mitral valve is almost always affected, sometimes together with the aortic valve; isolated aortic valve involvement is rare.
   ● Early valvular damage leads to regurgitation.
   ● Leaflet thickening, scarring, calcification and valvular stenosis may develop as a result of recurrent episodes.
   ● The characteristic manifestation of carditis in previously unaffected individuals is mitral regurgitation, sometimes accompanied by aortic regurgitation.
   ● There is softening of the first heart sound and prolongation of PR interval on ECG.
2. Polyarthritis
   ● Present in 60-75% of cases
   ● Hot, swollen, red and/or tender joints and involvement of more than one joint.
   ● Migratory, moving from one joint to another over a period of hours.
   ● Almost always affects large joints – most commonly the knees, ankles, hips and elbows and is asymmetrical
   ● Pain is severe and usually disabling.
   ● Highly responsive to salicylates and other NSAIDs.
   ● Joint involvement that persist more than 1 to 2 days after starting salicylates is unlikely to be due to ARF.
3. Syndenham’s Chorea
   ● Occurs in <2% - 30%
   ● A neurologic disorder with involuntary purposeless, rapid movements that affects particularly the head (causing characteristics darting movements of the tongue) and the upper limbs.
   ● Commonly occurs in the absence of other manifestations, following a prolonged latent period after group A streptococcal infection.
   ● Found mainly in females
   ● Eventually resolves completely, usually within 6 weeks.
4. Subcutaneous Nodules
   ● Found in less than 5% of cases
   ● Painless, small (0.5-2 cm), mobile lumps beneath the skin overlying bony prominences, particularly of the hands, feet, elbows, occiput and occasionally the vertebrae.
   ● A delayed manifestations, appearing 2-3 weeks after the onset of disease, lasts for a few days up to 3 weeks
   ● Commonly associated with carditis
5. Erythema marginatum
   ● Found in less than 5% of cases
   ● This is the classic rash of ARF which begins as pink macules that clear centrally, leaving a serpiginous, spreading edge.
   ● The rash is evanescent, appearing and disappearing before the examiner’s eyes.
   ● Occurs usually on the trunk, sometimes on the limbs, but almost never on the face.

Question 55

Other Features of ARF

Answer 55

● Fever
○ Occurs in most cases
○ As a rule, fever is high-grade (≥39C)

● Elevated C-reactive protein (CRP)

● Elevated Erythrocyte sedimentation rate (ESR)

● Mildly elevated peripheral leukocyte count

Question 56

Minor Criteria

Answer 56

Clinical - fever and arthralgia
Laboratory - elevated acute phase reactants
Prolonged PR interval

Plus (for major and minor):
- supporting evidence of a recent group A streptococcal infection (e.g., positive throat culture or rapid antigen detection test; and/or elevated or increasing streptococcal antibody test)

Question 57

Diagnostic Categories and their Criteria

Answer 57

Primary episode of rheumatic fever
- two major or one major and two minor manifestations plus evidence of preceding group A streptococcal infxn

Recurrent attack of rheumatic fever in a patient WITHOUT established rheumatic heart dse
- two major or one major and two minor manifestations plus evidence of preceding group A streptococcal infxn

Recurrent attack of rheumatic fever in a patient WITH established rheumatic heart dse
- two minor manifestations plus evidence of preceding group A streptococcal infxn

Rheumatic chorea Insidious onset rheumatic carditis
- other major manifestations or evidence of group A streptococcal infxn not required

Chronic valve lesions of rheumatic heart dse (patients presenting for the first time with pure mitral stenosis or mixed mitral valve dse and/or aortic valve dse)
- do not require any other criteria to be diagnosed as having rheumatic heart dse

Major manifestations
- carditis
- polyarthritis
- chorea
- erythema marginatum
- subcutaneous nodules

Minor manifestations
- clinical: fever, polyarthralgia
- laboratory: elevated erythrocyte sedimentation rate or leukocyte count
- ECG: prolonged PR interval

Supporting evidence of a preceding streptococcal infxn within the last 45 days
- elevated or rising anti-streptolysin O or other streptococcal antibody, or A positive throat culture, or Rapid antigen test for group A streptococcus, or Recent scarlet fever

Question 58

Minimum Criteria

Answer 58

● Either two major criteria, or one major criterion and two minor criteria, plus evidence of an antecedent streptococcal infection.

● Note: in Asian countries, the major manifestations of Jones criteria don’t occur as frequently as compared to Western countries.

Question 59

LABORATORY TEST FOR THE CONFIRMATION OF DIAGNOSIS OF RHEUMATIC FEVER

Answer 59

There is no specific laboratory test that can establish a diagnosis of rheumatic fever. The diagnosis, therefore, is a clinical one but requires supporting evidence from the clinical microbiology and immunology laboratories.

Question 60

What are the recommended tests in cases of possible acute rheumatic fever?

Answer 60

Recommended for All Cases
- WBC ct
- ESR
- CRP
- Blood cultures if febrile
- ECG (if prolonged PR interval or other rhythm abnormality, repeat in 2 wksand again at 2 months if still abnormal)
- Chest x-ray if clinical or echocardiographic evidence of carditis
- ECG (consider repeating after 1 month if negative)
- Throat swab (preferably before giving antibiotics) — culture for group A streptococcus
- Antistreptococcal serology: both anti-streptolysin O and anti-DNAse B titers, if available (repeat 10-14 days later if first test not confirmatory)

Tests for Alternative Diagnoses, Depending on Clinical Features
- repeated blood cultures if possible endocarditis
- joint aspirate (microscopy and culture) for possible septic arthritis
- copper, ceruloplasmin, antinuclear antibody, drug screen for choreiform movements
- serology and autoimmune markers for arboviral, autoimmune, or reactive arthritis

Question 61

MANAGEMENT OF RHEUMATIC FEVER
● There are 2 necessary therapeutic approaches to patient with acute rheumatic fever:

Answer 61

Anti-Streptococcal Antibiotic Therapy and Therapy for the Clinical Manifestations of the Disease

Question 62

Anti-Streptococcal Antibiotic Therapy

Answer 62

● A complete 10-day course of either:

○ Phenoxymethyl Penicillin
■ Children ≤27kg – 250 mg BID PO
■ Adults - 500 mg BID PO

○ Amoxicillin 50 mg/kg (max 1g) daily PO
■ For those with Penicillin allergy use:
● Erythromycin
○ Adults – 250mg QID PO
○ Children – 40mg/kg/24 hours PO

○ or Benzathine Penicillin G
■ Adults – 1.2 million units IM single dose
■ Children – ≤27kg – 600,000 million units IM
single dose

Question 63

Therapy for the Clinical Manifestations of the Disease

Answer 63

● For Arthritis only:
○ Aspirin – drug of choice
○ Initial dose:
■ Adults – 4-8g/day in 4-5 doses up to 2 weeks
■ Children – 100mg/kg/day 3-5 days in 4 divided doses
○ Reduce to
■ Adults – 60-70 mg/kg/day for a further 2-4 weeks
■ Children – 75mg/kg/day for 4 weeks

● For Mild Carditis:
○ Aspirin alone
■ 75 mg/kg/day x 6-8 weeks then taper gradually in adults and children

● For Moderate and Severe Carditis:
○ Prednisone
■ Adults – 1-2 mg/kg/day(maximum, 80mg) for 2-3 weeks, then taper
■ Children – 2 mg/kg/day in 4 doses for 2-3 weeks
○ Aspirin
■ Adults and Children – 75mg/kg/day 6-8 weeks
○ Salicylates should be given during the tapering of the steroid dose.

■ In children it should be given at the beginning of the tapering of steroid therapy and continued for approximately 3-4 weeks after the steroids have been discontinued.

Question 64

PENICILLINS
Chemistry

Answer 64

● The structure of penicillin consists of a thiazolidine ring (A) connected to a beta-lactam ring (B), to which is attached a side chain (R).
○ The beta-lactam ring is essential for antibacterial activity.

● All penicillins are derived from 6-aminopenicillanic acid.

● The various penicillins differ in their side chain structure.

Question 65

What is the mechanism of action of penicillin?

Answer 65

● Beta-lactam antibiotics are bactericidal drugs. They act to inhibit cell wall synthesis by the following steps:

1. Binding of the drug to specific receptors (penicillin-binding proteins (OBPs)) located in the bacterial cytoplasmic membrane.
2. Inhibition of transpeptidase enzymes that act to cross-link linear peptidoglycan chains that form part of the cell wall
3. Activation of autolytic enzymes that cause lesions in the bacterial cell wall

Question 66

Penicillin: Mechanisms of Bacterial Resistance

Answer 66

● Enzymatic hydrolysis of the beta-lactam ring results in loss of antibacterial activity.

● Formation of beta-lactamases (penicillinases)by microorganisms is a major mechanism of bacterial resistance.

● Structural change in target penicillin-binding proteins is another mechanism of resistance and is responsible for methicillin resistance in staphylococci and for resistance to Penicillin G in pneumococci.

● Changes in the porin structure in the outer membrane of gram-negative rods may contribute to the resistance by impeding access of penicillins to penicillin-binding proteins (PBPs).

Question 67

Classification and Summary of their Pharmacological Properties

Answer 67

1. Penicillin G and its close congener Penicillin V
   ● Highly active against strains of gram positive cocci, but are readily hydrolyzed by penicillinase.
   ● Ineffective against most strains of S. aureus.
2. The penicillinase-resistant penicillins (Methicillin, Nafcillin, Oxacillin, and Dicloxacillin)
   ● Have less potent antimicrobial activity against microorganisms that are sensitive to Penicillin G.
   ● Effective against penicillinase-producing S. aureus and S. epidermidis that are not methicillin-resistant.
3. Ampicillin, Amoxicillin, Bacampicillin, and others make up a group of penicillins whose antimicrobial activity is extended to include such gram-negative microorganisms as H. influenzae, E.coli, and P. mirabilis.
   ● These drugs are the others listed below are
   hydrolyzed readily by broad-spectrum β-lactamases that are found with increasing frequency in clinical isolates of these gram-negative bacteria.
4. The antimicrobial activity of Carbenicillin, its indanyl ester (carbenicillin indanyl), and Ticarcillin is extended to include Pseudomonas, Enterobacter, and Proteus spp.
   ● These agents are inferior to Ampicillin against gram-positive cocci and Listeria monocytogenes.
5. Mezlocillin, Azlocillin, and Piperacillin have excellent antimicrobial activity against many isolates of Pseudomonas, Klebsiella, and certain other gram-negative microorganisms.
   ● Piperacillin retains the excellent activity of Ampicillin against gram-positive cocci and L. monocytogenes.

Question 68

Penicillin: General Pharmacokinetic Properties

Answer 68

● Following absorption of orally administered penicillins, these agents are widely distributed throughout the body

● Therapeutic concentrations are achieved readily in tissues and in secretions such as joint fluid, pleural fluid, and bile.

● Low concentrations are found in prostatic secretions, brain tissue, and intraocular fluids.

● Do not penetrate living phagocytic cells to a significant extent.

● Most penicillins cross the blood-brain barrier only when the meninges are inflamed.

● Concentrations in CSF are less than 1% of those in plasma when the meninges are normal but may increase to as much as 5% of the plasma value when there is inflammation.

● Eliminated rapidly, particularly by glomerular filtration and renal tubular secretion, such that their half-lives in the body are short; values of 30-90 minutes are typical.

● Concentrations in urine are high.

Question 69

Penicillin Untoward Responses

Answer 69

1. Hypersensitivity Reactions – most common adverse effects
   ● These agents probably are the most common cause of drug allergy.
   ● In order of decreasing frequency, manifestations of allergy include maculopapular rash, urticarial rash, Fever, bronchospasm, vasculitis, serum sickness, exfoliative dermatitis, Stevens-Johnson syndrome, and anaphylaxis
   ● Allergy to one penicillin exposes the patient to a greater risk of reaction if another is given.
   ● The most serious hypersensitivity reactions are angioedema and anaphylaxis.
2. Toxic Effects – bone marrow depression, granulocytopenia, hepatitis
3. Irritative Responses:
   ● Pain and sterile inflammatory reactions at the sites of IM injection.
   ● Phlebitis or thrombophlebitis when injected intravenously

Question 70

Penicillin G and Penicillin V: Antimicrobial Activity

Answer 70

● Antimicrobial spectra of Penicillin G (benzyl-penicillin) and Penicillin V (the phenoxymethyl derivative) are very similar for aerobic gram-positive microorganisms.

● Penicillin G is 5-10 times more active against Neisseria spp. sensitive to penicillins and against certain anaerobes.

● Most streptococci are very susceptible to Penicillin G; concentrations of less than 0.01μg/ml usually are effective.

● Most anaerobic microorganisms are highly sensitive, Bacteroides fragilis is an exception.

● Most Leptospira spp. are moderately susceptible.

● One of the most exquisitely sensitive microorganisms is Treponema pallidum.

Question 71

Penicillin G and Penicillin V: Pharmacokinetics

1. Absorption
2. Distribution
3. Excretion

Answer 71

1. Absorption
   ● About 1/3 of an orally administered dose of Penicillin G is absorbed from the intestinal tract.
   ○ Gastric juice at pH 2 rapidly destroys the drug.
   ● Absorption is rapid, and maximal concentrations in blood are attained in 30-60 minutes.
   ● Ingestion of food may interfere with enteric absorption of all penicillins, perhaps by adsorption of the antibiotic into food particles.
   ● Oral Penicillin G should be administered at least 30 minutes before a meal or 2 hours after.
   ● Penicillin V is more stable in an acidic medium and is better absorbed from the GIT.
   ○ Yields plasma concentrations 2-5 times greater than those provided by Penicillin G.
   ● Peak plasma concentrations are reached 15-30 minutes after 1M injection of Penicillin G.
   ○ Half-life is 30 minutes.
   ● Probenecid blocks renal tubular secretion of
   penicillin but it is rarely used for this purpose.
   ○ More commonly, repository preparations
   of Penicillin G are employed: Pencillin G procaine and Penicillin benzathine - these agents release Penicillin G slowly from the site of injection and produce relatively low but persistent concentrations of antibiotic in the blood.
   ● Penicillin G procaine suspension is an aqueous preparation of the crystalline salt that is only 0.4% soluble in water.
   ○ The anesthetic effect of the procaine accounts in part for the fact that injections are virtually painless
   ○ Injection of 300,000 U produces a peak concentration in plasma of about 0.9 ug / ml within 1-3 hours.
   ● Penicillin G benzathine suspension is the aqueous suspension of the salt obtained by the combination of 1 mol of an ammonium base and 2 mol of Penicillin G to yield N, N1-dibenzylethylenediamine dipenicillin G.
   ● Absorbed very slowly from intramuscular depot and produces the longest duration of detectable
   antibiotic of all the available repository penicillins.
   ● The average duration of demonstrable antimicrobial activity in the plasma is about 26 days.
2. Distribution
   ● Penicillin G is widely distributed throughout the body.
   ● Approximately 60% of penicillin G in plasma is reversibly bound to albumin.
   ● Significant amounts appear in liver, bile, kidney, semen, joint fluid, lymph, and intestine.
3. Excretion
   ● Penicillin G is rapidly eliminated from the body, mainly by the kidney but in small part in the bile
   and other routes.
   ● Clearance values are considerably lower in neonates and infants because of incomplete development of renal function.
   ○ In babies less than 1 week old, half-life is 3 hours; by 14 days of age it is 1.4 hour.
   ● Anuria increased the half-life of penicillin G from a normal value of 0.5 hours to about 10 hours.
   ● The half-life will be prolonged even further in hepatic insufficiency.

Question 72

Penicillin G and Penicillin V Therapeutic Uses

Answer 72

1. Agent of choice for the management of infections caused by sensitive strains of S. pneumoniae.
2. Streptococcal pharyngitis caused by S. pyogenes
   ● Penicillin V 500mg every 6 hours for 10 days
   ● Penicillin G procaine 600,000 U IM OD for 10 days
   ● Penicillin G benzathine 1.2M units IM single
   dose
3. Drug of choice for meningococcal disease caused by N. meningitides
   ● Penicillin G 20-24M units by constant IV infusion or divided into boluses every 2-3 hours for 14 days
4. Infectious endocarditis caused by penicillin-sensitive S. viridians
   ● Penicillin G procaine 1.2M units QID for 2 weeks or Penicillin G 12-20M units IV daily for 2 weeks, both regimens in combination with Streptomycin 500 mg IM every 12 hours or Gentamicin 1 mg/kg every 8 hours
5. Syphilis
   ● Primary, secondary, and latent syphilis of less than 1 year’s duration – Penicillin G procaine 2.4M units IM per day + Probenecid 1.0g oral daily for 10 days or Penicillin G benzathine 2.4M units 1 to 3 weekly IM doses.
6. Agent of choice for the treatment of all forms of actinomycosis
   ● Penicillin 12-20M units IV per day for 6 weeks
7. Agent of choice in the treatment of all clinical forms of anthrax
   ● Penicillin G 12-20M units per day
8. Agent of choice for gas gangrene
   ● Penicillin G 12-20M units per day
9. Gingivostomatitis caused Leptotrichia buccalis and spirochetes
   ● Penicillin V oral every 6 hours
10. Therapeutic agent of choice for rat-bite fever.
    ● Penicillin G 12-15M units parenteral daily for 3-4 weeks
11. One of the drugs of choice in the management of infections due to Listeria monocytogenes
    ● Penicillin G 15-20M units parenterally per day for at least 2 weeks
12. Erysipeloid caused by Erysipelothrix rhusiopathiae
    ● For uncomplicated infection – Penicillin G benzathine 1.2M units single injection
    ● Presence of endocarditis – Penicillin G 12-20M units per day for 4-6 weeks.

Question 73

What is the prototype for the drug group salicylates?

Answer 73

Aspirin

Question 74

What is the enzyme responsible for the biosynthesis of the prostaglandins?

Answer 74

Inhibition of cyclooxygenase (COX)

Question 75

What is found in most normal cells and tissues? Expressed in the
stomach.

Answer 75

Cyclooxygenase-1 (COX-1)

Question 76

What is induced in settings of inflammation by cytokines and inflammatory mediators? Also expressed in certain areas of the kidney and brain.

Answer 76

Cyclooxygenase-2 (COX-2)

Question 77

What are Nonselective COX Inhibitors?

Answer 77

Salicylic acid derivatives:
Aspirin
Sodium salicylate
Cholinemagnesium trisalicylate
Salsalte
Diflunisal
Sulfasalazine
Olsalazaine

Para-aminophenol derivatives:
Acetaminophen

Indole and indene acetic acids
Indomethacin
Sulindac

Heteroaryl acetic acids
Tolmetin
Diclofenac
Ketorolac

Arylpropionic acids
Ibuprofen
Naproxen
Flubiprofen
Ketoprofen
Fenoprofen
Oxaprozin

Anthranilic acids
Mefenamic acid
Meclefenamic acid

Enolic acids
Oxicams (Piroxicam, Meloxicam)

Alkanones
Nabumetone

Question 78

What are Selective COX-2 Inhibitors?

Answer 78

Diaryl-substituted furanones
Rofecoxib

Diaryl-substituted pyrazoles
Celecoxib

Indole acetic acids
Etodolac

Sulfonanilides
Nimesulide

Question 79

Shared Therapeutic Activities and Side E ects of Nonsteroidal Inflammatory Drugs (NSAIDs)

Answer 79

● All NSAIDs, including selective COX-2 inhibitors are antipyretic, analgesic, and anti-inflammatory.
○ Exception is Acetaminophen which is largely devoid of anti-inflammatory activity. This drug effectively inhibits cyclooxygenase in the brain but not at the sites of inflammation in peripheral tissues.

● As analgesic, have the following characteristics
○ Effective only against pain of low-to-moderate intensity, such as dental pain.
○ Lack the unwanted effects of the opioids on the CNS, including respiratory depression and the development of physical dependence.
○ Don’t change the perception of sensory modalities other than pain.
○ Pain arising from the hollow viscera usually is not relieved.

● As antipyretics, these agents reduce the body temperature in febrile states.

● As anti-inflammatory, these agents provide only symptomatic relief from the pain and inflammation associated with the disease and do not arrest the progression of pathological injury to tissue

Question 80

Side effects of Salicylates:

Answer 80

a. Induce gastric or intestinal ulceration that sometimes can be accompanied by anemia from the resultant blood loss – most common
● Exception is the highly selective COX-2 inhibitors which lack the propensity to gastric ulceration.
● Gastric damage can be brought about by two distinct mechanisms:
1. Local irritation – caused by back diffusion of acid into the gastric mucosa → tissue damage – oral administration
2. Inhibition of the biosynthesis of gastric
prostaglandins, especially PGI2 and PGE2 that serves as cytoprotective agents in the gastric mucosa.
● PGI2 and PGE2 inhibit acid secretion by the stomach, enhance mucosal blood flow, and promote the secretion of cytoprotective mucus in the intestine.

b. Impairment of platelet function – increase bleeding time
● NSAIDs prevent the formation by the platelet of thromboxane A2 (TXA2), a potent aggregating agent.
● A single dose of Aspirin will inhibit the platelet cyclooxygenase for the life of the platelet (8-11 days). In humans, a daily dose as small as 40 mg is sufficient to produce this effect.

c. Prolongation of gestation or spontaneous labor.
● Prostaglandins of the E and F series are potent uterotrophic agents and their biosynthesis by the uterus increases dramatically in the hours before parturition.

d. Premature closure of the patent ductus arteriosus
● Prostaglandins have been implicated in the maintenance of the patency of the ductus.

e. Change in renal functions
● NSAIDs promote the retention of salt and water by reducing the prostaglandin-induced inhibition of both the reabsorption of chloride and the action of antidiuretic hormones.

f. Hypersensitivity reaction – vasomotor rhinitis with profuse watery secretions, angioneurotic edema, generalized urticaria, and bronchial asthma to laryngeal edema and bronchoconstriction, flushing, hypotension, and shock
● Hypersensitivity to Aspirin is a contraindication to therapy with any of the NSAIDs; administration of any one of these could provoke a life-threatening reaction reminiscent of anaphylactic shock

Question 81

What are the side effects shared by Nonselective COX Inhibitors and Selective COX-2 Inhibitors?

Answer 81

Only shared by Nonselective COX Inhibitors
Gastric ulceration and intolerance
Inhibition of platelets function

Shared by Nonselective COX Inhibitors & Selective COX-2 Inhibitors
Inhibition of induction of labor
Alterations in renal function

Shared by Nonselective COX Inhibitors
Hypersensitivity reactions

Question 82

SALICYLATES Chemistry

Answer 82

● Two large classes of salicylic acid synthesized for systemic use:

1. Esters of salicylic acid obtained by the substitution in the carboxyl group.
2. Salicylate esters of organic acids, in which the carboxyl group of salicylic acid is retained and substitution is made in the hydroxyl group.
   ● Aspirin is an ester of acetic acid

Question 83

Salicylates Structure

Answer 83

● Aspirin has the capacity to acetylate proteins.

● In the structure of COX-1, aspirin acetylates serine 350, preventing the binding of arachidonic acid to the active site of the enzyme and thus the ability of the enzyme to make prostaglandins.

● In COX-2, Aspirin acetylates a homologous serine at position 516.

● The duration of action of aspirin is determined by the rate of synthesis of new cyclooxygenase enzymes.

Question 84

Pharmacological Properties
SALICYLATES

Answer 84

1. Analgesia
   ● PGI2 and PGE2 α cause intense pain.
   ● Types of pain relieved by salicylates are those of low intensity that arise from integumental structures rather than from viscera, especially headache, myalgia, and arthralgia.
   ● Alleviate pain by virtue of a peripheral action.
2. Antipyresis
   ● PGE2 via increases in cAMP, triggers the hypothalamus to elevate body temperature by promoting increases in heat generation and decrease in heat loss. The hypothalamus regulates the set point at which body temperature is maintained. In fever, the set point is elevated.
   ● Lower elevated body temperature rapidly and effectively.
   ● Promote the return of the set point to normal.
3. Respiration
   ● Stimulates respiration directly and indirectly.
   ● Full therapeutic doses increase oxygen
   consumption and CO2 production. Increased production of CO2 stimulates respiration.
   ● Directly stimulates the respiratory center in the medulla. This results in marked hyperventilation, characterized by an increase in depth and a pronounced increase in rate → respiratory alkalosis.
4. Acid-Base Balance and Electrolyte Pattern
   ● Therapeutic doses produce definite changes in the acid-base balance and electrolyte pattern. The initial event is respiratory alkalosis. Compensation for the respiratory alkalosis is achieved by increased renal excretion of bicarbonates, which is accompanied by increased Na+ and K+ excretion; plasma bicarbonate is lowered, and blood pH returns toward normal.
   ○ This is the stage of compensated respiratory alkalosis. This stage is most often seen in adults given intensive salicylate therapy and seldom proceeds further.
   ● In toxic doses, the acid-base state at this stage is essentially an uncompensated respiratory acidosis since the concentration of bicarbonate in plasma already is low. Superimposed is a true metabolic acidosis caused by accumulation of acids.
5. Cardiovascular Effects
   ● Large doses of Aspirin such as the doses in acute rheumatic fever produce increase in circulating plasma volume, decrease hematocrit, and increase cardiac output.
6. Gastrointestinal Effects
   ● Epigastric distress, nausea, and vomiting occur primarily with acetylated salicylate (aspirin)
   ● Aspirin-induced gastric bleeding sometimes is painless and if unrecognized, may lead to an iron-deficiency anemia.
   ● The incidence of bleeding is highest with salicylates that dissolve slowly and deposit as particles in the gastric mucosal folds.
7. Hepatic and Renal Effects
   ● High dose can cause hepatic injury which is reversible upon discontinuation of the drug.
   ● The use of salicylates had been implicated as an important factor in the severe hepatic injury and encephalopathy observed in Reye’s syndrome.
   ● Can cause retention of salt and water by reducing the prostaglandin-induced inhibition of both the reabsorption of chloride and the action of antidiuretic hormone.
   ● Prolonged and excessive ingestion of analgesic mixtures containing salicylates in combination with other compounds can produce papillary necrosis and interstitial nephritis.
8. Uricosuric Effects
   ● The effect on uric acid excretion is markedly dependent on dose.
   ● Low doses (1-2g/day) decrease urate excretion and elevate plasma urate concentration
   ● Intermediate doses (2-3g/day) usually do not alter urate excretion
   ● Large doses (over 5g/day) induce uricosuria and lower plasma urate levels.
9. Effects on the Blood
   ● Cause prolongation of the bleeding time due to irreversible acetylation of platelet cyclooxygenase and the consequent reduced formation of thromboxane A2 (TXA2)
   ● Aspirin therapy should be stopped at least one week prior to surgery.
10. Effects on Rheumatic, Inflammatory, and Immunological Process, and on Connective Tissue Metabolism
    ● Have the capacity to suppress a variety of antigen-antibody reactions:
    ○ Inhibition of antibody production, of antigen-antibody aggregation, and of antigen-induced release of histamine.
    Induce a nonspecific stabilization of capillary permeability during immunological insults. Suppress the clinical signs and even improve the histological picture in acute rheumatic fever.
    ○ Can affect the composition, biosynthesis, or metabolism of connective tissue mucopolysaccharides in the ground substance that provides barriers to spread of infection and inflammation
11. Metabolic Effects
    ● Inhibition of a number of ATP-dependent reactions
    ● Hyperglycemia, glycosuria, depletion of liver and muscle glycogen – large doses
    ● Negative nitrogen balance characterized by an amino-aciduria – toxic doses
    ● Reduce lipogenesis by partially blocking incorporation of acetate into fatty acids
    ● Inhibit epinephrine - stimulated lipolysis in fat cells and displace long-chain fatty acids from binding sites on human plasma proteins
    ● Stimulate steroid by the adrenal cortex – very large doses
    ● Decrease thyroidal uptake and clearance of iodine – long term administration
12. Salicylates and Pregnancy
    ● No evidence that moderate therapeutic doses are teratogenic in human beings
    ● Babies born to women who ingest salicylates for long periods may have significantly reduced weights at birth.
    ● Increase in perinatal mortality, anemia, antepartum and postpartum hemorrhage, prolonged gestation and complicated deliveries.
    ● Can cause premature closure of the ductus arteriosus.
13. Local Irritant Effects
    ● Salicylic acid is irritating to skin and mucosa and destroys epithelial cells.
    ○ Has keratolytic action and is employed for the local treatment of warts, corns, fungal infection and certain types of eczematous dermatitis.
    ● Methyl salicylate (oil of wintergreen) is irritating to both skin and gastric mucosa and is used only externally.

Question 85

Pharmacokinetics: Salicylates

Answer 85

● Absorbed rapidly after oral administration, partly from the stomach but mostly from the upper small intestine.

● After a single dose, a peak value is reached in about 1 hour and then gradually declines.

● Rate of absorption is determined by many factors:
○ Disintegration and dissolution rates if tablets are given
○ The pH at the mucosal surfaces ○ Gastric emptying time

● Absorption occurs by passive diffusion primarily of non dissociated salicylic acid or acetylsalicylic acid across G1 membrane and hence is influenced by gastric pH.
○ A rise in pH increases the solubility of salicylates and dissolution of tablets —> enhance absorption.

● Rectal absorption is slower than oral absorption and is incomplete and unreliable.
○ Not advisable when high plasma concentrations of the drug is required.

● Distributed throughout most body tissues and most transcellular fluids, primarily by pH-dependent passive processes.

● Readily crosses the placental barrier.

● 80-90% of salicylate is bound to plasma proteins especially albumin
○ Hypoalbuminemia is associated with a proportionately higher level of free
salicylate in the plasma

● Competes with a variety of compounds for plasma protein binding sites – thyroxine, triiodothyronine, penicillin, phenytoin, sulfinpyrazone, bilirubin, uric acid.

● Biotransformation takes place in many tissues, but particularly in the hepatic endoplasmic reticulum and mitochondria.

● Excreted in the urine as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl glucuronides (5%), and gentisic acid (<1%)

● Changes in urinary pH have significant effects on salicylate excretion.

● Plasma half-life for Aspirin is approximately 15 minutes; that for salicylate is 2-3 hours in low doses, and about 12 hours at usual anti-inflammatory doses.

Question 86

Therapeutic Eff ects of Salicylates

Answer 86

1. Antipyresis
   ● Antipyretic therapy is reserved for patients in whom fever in itself may be deleterious and for those who experience considerable relief when a fever is lowered
   ● Dosage:
   ○ Adults – 325-650 mg every 4 hours, oral
   ○ Children – 50-75mg/kg/day in 4-6 divided in doses, not to exceed a total daily dose of 3.6g
   ● Parenteral administration is rarely necessary
2. Analgesia
   ● For the nonspecific relief of certain types of pain, for example, headache, arthritis, dysmenorrhea, neuralgia, and myalgia
   ● Prescribed in the same doses and manner as for antipyresis.
3. Rheumatoid Arthritis
   ● Dosage: 4-6g daily (dose used for rheumatic fever)
4. Other Uses
   ● Treatment or prophylaxis of disease associated with platelet hyperaggregability, such as coronary artery disease and postoperative deep vein thrombosis.
   ○ Dosage of aspirin is 40-80 mg/day.

Question 87

Toxic Effects of Salicylates:

Answer 87

Salicylate Intoxication
● Fatal Dose
○ Adults – 10-30g of sodium salicylate or aspirin
○ Children – 4ml (4.7g) of methyl salicylate

● Signs and Symptoms
○ Mild chronic salicylate intoxication is termed salicylism when fully developed, characterized by headache, dizziness, tinnitus, hearing loss, dimness of vision, drowsiness, sweating, nausea and vomiting.
■ Fever is usually prominent especially in children.
○ Prominent features are the distribution in acid-base balance and electrolyte composition of the plasma.
○ Another prominent feature is severe toxic encephalopathy which may be difficult to differentiate from rheumatic encephalopathy.
○ Toxicity in adults may not be diagnosed readily because such patients usually become intoxicated from their therapeutic regimen; there is no history of acute overdosage.

● Treatment
○ Directed at CV and respiratory support and correction of acid-base abnormalities, plus use of measures to accelerate excretion of salicylate.
○ Use of *activated charcoal is the currently preferred method to reduce GI absorption of this drug.
○ Adequate amounts of IV fluids must be given promptly.
○ Bicarbonate solution should be infused intravenously in sufficient quantity to maintain alkaline dieresis.
○ Measures to rid the body of salicylate rapidly should be undertaken immediately
■ Forced diuresis with alkalizing solution appears not to be better than alkali alone.
■ Hemodialysis is the most effective measure available and considered in patients with salicylate concentrations above 1000ug/mL

Question 88

Aspirin Hypersensitivity

Answer 88

● The nonacetylated salicylates appear to be considerably less apt to produce hypersensitivity reactions than are Aspirin and other NSAIDs

● For acute anaphylactic reactions, Epinephrine is the drug of choice.

Question 89

NONPHARMACOLOGICAL APPROACHES

Answer 89

● In the past, patients with ARF were kept at complete bed rest for months. This is inappropriate unless there is a specific reason such as persistent active carditis or severe heart failure.

● Patients with arthritis who feel better after administration of salicylates had started, may be released from bed rest but should not resume full activity until signs of inflammatory process have abated and the acute-phase reactants have returned to normal.

Question 90

PROPHYLAXIS AGAINST RHEUMATIC F

Answer 90

1. Primary Prophylaxis
2. Secondary Prophylaxis

Question 91

What refers to antibiotic treatment of the streptococcal upper respiratory tract infection to prevent an initial attack of rheumatic fever?

Answer 91

Primary prophylaxis

Question 92

Primary Prophylaxis

Answer 92

● Benzathine Penicillin G
○ Adults and children >60lb – 1.2M units IM single dose
○ Children <60lb – 600,000 units

● Penicillin V
○ Adults – 500mg BID for 10 days
○ Children – 250-500 mg BID-TID for 10 days

● Erythromycin
○ Adults – 250 mg QID for 10 days
○ Children – 40mg/kg/24 hours for 10 days

Question 93

What refers to the prevention of colonization or infection of the upper respiratory tract with group A β-hemolytic streptococci in individuals who have already had a precious attack of acute rheumatic fever?

Answer 93

Secondary prophylaxis

Question 94

Secondary prophylaxis

Answer 94

● Benzathine Penicillin G
○ Adults and Children – 1.2M units IM single dose every 3-4 weeks

● Penicillin V
○ Adults and Children – 250 mg oral BID

● Sulfadiazine or Sulfisoxazole
○ Patients ≤ 27kg (≤ 60lbs) – 0.5gm OD
○ Patients > 27kg (> 60lbs) – 1.0gm OD

Question 95

American Heart Association Recommendations for Duration of Secondary Prophylaxis:

Category of Patient & Duration of Prophylaxis

Answer 95

Rheumatic fever without carditis: for 5 years after the last attack or 21 years of age (whichever is longer)

Rheumatic fever with carditis but no residual valvular dse: for 10 years after the last attack or 21 years of age (whichever is longer)

Rheumatic fever with persistent valvular dse, evident clinically or on echocardiography: for 10 years after the last attack, or 40 years of age (whichever is longer); sometimes lifelong prophylaxis