Lecture 5: Waves of Resistance - Streptococcus pneumoniae Flashcards

(29 cards)

1
Q

What are 3 key facts about Streptococcus pneumoniae?

A

Diplococci

Gram positive

Most prevalent cause of respiratory infection

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2
Q

What are some of the risk factors for morbidity and mortality from pneumonia in children in developing countires?

A

Low birth weight
Absence of breast feeding
Missing EPI vaccinations
Malnutrition
Vitamin A deficiency
Indoor air pollution
Low socioeconomic status
Poor hygiene

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3
Q

What is the empirical therapy to streptococcus pneumoniae?

A

Initiation of treatment prior to determination of a firm diagnosis in the upper respiratory tract infection

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4
Q

What percentage of broad spectrum antibiotics are used as empirical first-line therapy?

A

78% of cases

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5
Q

What is the sensitivity and specificity associated with a plate sample for diagnosing S. Pneumoniae?

A

Sensitivity: 60%

Specificity: 85%

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6
Q

What is the sensitivity and specificity associated with a sputum sample for diagnosing S. Pneumoniae?

A

Sensitivity: 57%

Specificity: 98%

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7
Q

What is the sensitivity and specificity associated with a urine sample for diagnosing S. Pneumoniae?

A

Sensitivity: 86%

Specificity: 94%

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8
Q

What is the sensitivity and specificity associated with a cerebral spinal fluid sample for diagnosing S. Pneumoniae?

A

Sensitivity: 88%

Specificity: 99%

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9
Q

When was the early identification of penicillin resistance in Papa New Guinea?

A

1967

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10
Q

When was the early identification of multiple resistance of penicillin in South Africa?

A

1971

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11
Q

When was the very high prevalence of penicillin resistance identified?

A

1990s

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12
Q

What is responsible for the global clonal spread of penicillin resistant pneumococci?

A

Global traffic and air travel

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13
Q

What are the main way resistance to Beta-lactam antibiotics has arisen?

A

Production of Beta-lactamases

Reduced outer membrane permeability

Altered antibiotic targets

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14
Q

What are the key targets of beta-lactam antibiotics in the pneumococcus?

A

Essential transpeptidase enzymes involved in the final stages of peptidoglycan synthesis

(Penicillin binding proteins)

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15
Q

What are penicillin binding proteins responsible for?

A

Cross linking adjacent stem peptides on opposite strands of the peptidoglycan carbohydrate backbone

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16
Q

What happens when penicillin binds to the transpeptidase domain of the penicillin binding protein?

A

Active site serine is acylated

Results in the irreversible inactivation of the penicillin binding protein

17
Q

What happens when the cross-linking of the adjacent stem peptides is prevented?

A

Production of a weakened peptidoglycan

Triggers a cascade of events that leads to cell lysis

18
Q

What occurs by altering the active site of low affinity penicillin binding proteins in penicillin resistant pneumococci?

A

Penicillin can no longer bind and acylate the active site serine

19
Q

What are the penicillin binding protein involved in beta-lactam resistance?

A

PBP1A

PBP2X

PBP2B

20
Q

What penicillin binding protein has the highest affinity? (altered first)

21
Q

What is the serotype present in all penicillin resistant strains?

A

Thr(S)/Ala(r)

22
Q

How does penicillin resistance evolve?

A

Selective pressure pulls out advantageous changes

Recombination events causing integration

23
Q

Why is S. mitis a biological donor for many resistant genes?

A

Easily transforms to pneumococcus

24
Q

How many different pneumococci serotypes are there and how are they identified?

A

91 serotypes

Defined by differences in immunochemistry of their polysaccharide capsule

25
How many pneumococcal serotypes cause the great majority of invasive disease?
15 serotypes
26
What does invasive pneumococcal disease include?
Septicaemia Pneumonia Meningitis
27
Why is a capsular serotype more important than genotype in the ability of pneumococci to cause invasive disease?
Different clones of the same serotype have the same invasive potential Isolates of the same genotype, but different serotype have different invasive potentials
28
What serotypes are significantly more common in children?
14, 6B, 19F, 18C Children <4 months - 7F Children >4 months - 19F
29
What serotypes are more prevalent among adults?
Serotypes 3 an 4