Lecture 5: Waves of Resistance - Streptococcus pneumoniae Flashcards
What are 3 key facts about Streptococcus pneumoniae?
Diplococci
Gram positive
Most prevalent cause of respiratory infection
What are some of the risk factors for morbidity and mortality from pneumonia in children in developing countires?
Low birth weight
Absence of breast feeding
Missing EPI vaccinations
Malnutrition
Vitamin A deficiency
Indoor air pollution
Low socioeconomic status
Poor hygiene
What is the empirical therapy to streptococcus pneumoniae?
Initiation of treatment prior to determination of a firm diagnosis in the upper respiratory tract infection
What percentage of broad spectrum antibiotics are used as empirical first-line therapy?
78% of cases
What is the sensitivity and specificity associated with a plate sample for diagnosing S. Pneumoniae?
Sensitivity: 60%
Specificity: 85%
What is the sensitivity and specificity associated with a sputum sample for diagnosing S. Pneumoniae?
Sensitivity: 57%
Specificity: 98%
What is the sensitivity and specificity associated with a urine sample for diagnosing S. Pneumoniae?
Sensitivity: 86%
Specificity: 94%
What is the sensitivity and specificity associated with a cerebral spinal fluid sample for diagnosing S. Pneumoniae?
Sensitivity: 88%
Specificity: 99%
When was the early identification of penicillin resistance in Papa New Guinea?
1967
When was the early identification of multiple resistance of penicillin in South Africa?
1971
When was the very high prevalence of penicillin resistance identified?
1990s
What is responsible for the global clonal spread of penicillin resistant pneumococci?
Global traffic and air travel
What are the main way resistance to Beta-lactam antibiotics has arisen?
Production of Beta-lactamases
Reduced outer membrane permeability
Altered antibiotic targets
What are the key targets of beta-lactam antibiotics in the pneumococcus?
Essential transpeptidase enzymes involved in the final stages of peptidoglycan synthesis
(Penicillin binding proteins)
What are penicillin binding proteins responsible for?
Cross linking adjacent stem peptides on opposite strands of the peptidoglycan carbohydrate backbone
What happens when penicillin binds to the transpeptidase domain of the penicillin binding protein?
Active site serine is acylated
Results in the irreversible inactivation of the penicillin binding protein
What happens when the cross-linking of the adjacent stem peptides is prevented?
Production of a weakened peptidoglycan
Triggers a cascade of events that leads to cell lysis
What occurs by altering the active site of low affinity penicillin binding proteins in penicillin resistant pneumococci?
Penicillin can no longer bind and acylate the active site serine
What are the penicillin binding protein involved in beta-lactam resistance?
PBP1A
PBP2X
PBP2B
What penicillin binding protein has the highest affinity? (altered first)
PBP2X
What is the serotype present in all penicillin resistant strains?
Thr(S)/Ala(r)
How does penicillin resistance evolve?
Selective pressure pulls out advantageous changes
Recombination events causing integration
Why is S. mitis a biological donor for many resistant genes?
Easily transforms to pneumococcus
How many different pneumococci serotypes are there and how are they identified?
91 serotypes
Defined by differences in immunochemistry of their polysaccharide capsule
How many pneumococcal serotypes cause the great majority of invasive disease?
15 serotypes
What does invasive pneumococcal disease include?
Septicaemia
Pneumonia
Meningitis
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
What serotypes are significantly more common in children?
14, 6B, 19F, 18C
Children <4 months - 7F
Children >4 months - 19F
What serotypes are more prevalent among adults?
Serotypes 3 an 4
