Lecture 5: Waves of Resistance - Streptococcus pneumoniae

Question 1

What are 3 key facts about Streptococcus pneumoniae?

Answer 1

Diplococci

Gram positive

Most prevalent cause of respiratory infection

Question 2

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

Answer 2

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

Question 3

What is the empirical therapy to streptococcus pneumoniae?

Answer 3

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

Question 4

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

Answer 4

78% of cases

Question 5

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

Answer 5

Sensitivity: 60%

Specificity: 85%

Question 6

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

Answer 6

Sensitivity: 57%

Specificity: 98%

Question 7

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

Answer 7

Sensitivity: 86%

Specificity: 94%

Question 8

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

Answer 8

Sensitivity: 88%

Specificity: 99%

Question 9

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

Answer 9

1967

Question 10

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

Answer 10

1971

Question 11

When was the very high prevalence of penicillin resistance identified?

Answer 11

1990s

Question 12

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

Answer 12

Global traffic and air travel

Question 13

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

Answer 13

Production of Beta-lactamases

Reduced outer membrane permeability

Altered antibiotic targets

Question 14

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

Answer 14

Essential transpeptidase enzymes involved in the final stages of peptidoglycan synthesis

(Penicillin binding proteins)

Question 15

What are penicillin binding proteins responsible for?

Answer 15

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

Question 16

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

Answer 16

Active site serine is acylated

Results in the irreversible inactivation of the penicillin binding protein

Question 17

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

Answer 17

Production of a weakened peptidoglycan

Triggers a cascade of events that leads to cell lysis

Question 18

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

Answer 18

Penicillin can no longer bind and acylate the active site serine

Question 19

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

Answer 19

PBP1A

PBP2X

PBP2B

Question 20

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

Answer 20

PBP2X

Question 21

What is the serotype present in all penicillin resistant strains?

Answer 21

Thr(S)/Ala(r)

Question 22

How does penicillin resistance evolve?

Answer 22

Selective pressure pulls out advantageous changes

Recombination events causing integration

Question 23

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

Answer 23

Easily transforms to pneumococcus

Question 24

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

Answer 24

91 serotypes

Defined by differences in immunochemistry of their polysaccharide capsule

Question 25

How many pneumococcal serotypes cause the great majority of invasive disease?

Answer 25

15 serotypes

Question 26

What does invasive pneumococcal disease include?

Answer 26

Septicaemia
Pneumonia
Meningitis

Question 27

Why is a capsular serotype more important than genotype in the ability of pneumococci to cause invasive disease?

Answer 27

Different clones of the same serotype have the same invasive potential

Isolates of the same genotype, but different serotype have different invasive potentials

Question 28

What serotypes are significantly more common in children?

Answer 28

14, 6B, 19F, 18C

Children <4 months - 7F

Children >4 months - 19F

Question 29

What serotypes are more prevalent among adults?

Answer 29

Serotypes 3 an 4