Epidemiology of Streptococcus pneumoniae

bacteria

Since the last update on pneumococcal vaccination in 1991 , a number of developments have taken place which may potentially impact on decisions regarding vaccine.

The first is the appearance of resistance amongst Streptococcuspneumoniae (pneumococci) to penicillin. The other is the publication of a meta-analysis of all randomized controlled trials of pneumococcal vaccination.

Pneumoniae is the commonest single cause of community acquired infections including bacterial pneumonia, bacteremia, and otitis media . The organism has remained exquisitely susceptible to penicillin until the 1990’s despite the first report of clinical resistance in 1967 in Papua, New Guinea.

High rates (44% to 70%) of resistance have been reported from Spain , South Africa , Hungary, and Korea and moderately high rates (24 to 29%) in Hong Kong , Japan , the United States , and Bulgaria . In the United States, reports in the latter part of the 1980’s suggested resistance rates of pneumococci to penicillin of the order of 30%.

Until recently, rates of resistance in Canada were consistently under 3% . However, surveys conducted in the 1990’s have observed rates of 7% and 12% with higher rates in the more recent studies.

Unlike the resistance seen with Haemophilus influenzae and Moraxella catarrhalis, which is due to elaboration of beta lactamase, an enzyme which breaks down beta lactam antibiotics such as penicillins and cephalosporins, resistance among S. pneumoniae develops through alterations in penicillin binding proteins.

Because there are 6 different penicillin binding proteins, increasing resistance occurs as chromosomal changes alter the structures of each of these proteins . Pneumococci may be divided into susceptible strains, with a minimal inhibitory concentration (MIC) 0.1 m g/ml and non-susceptible strains with MIC ^(3) 0.1 m g/ml.

The subgroup among the non-susceptible strains with MIC ^(3) 2 m g/ml are considered resistant . Furthermore, because cephalosporins also bind to penicillin binding proteins, alterations in specific proteins also confer cephalosporin resistance. Equally concerning, however, is the much higher predilection for penicillin non susceptible pneumococci vs. penicillin susceptible pneumococci to also exhibit resistance to other classes of antibiotics.

This resistance is not dependent on penicillin binding proteins and has been described with quinolones, macrolides, tetracyclines, chloramphenicol, and trimethoprim-sulfa . Thus, pneumococci that are penicillin non-susceptible also show less susceptibility to most antibiotic alternatives as well.

Risk factors for infection

The relevance of reduced pneumococcal susceptibility depends on the site of infection. Because of the high achievable levels of penicillins in blood and lung fluid, outcome in patients with bacteremia and pneumonia due to penicillin non-susceptible organisms does not appear to be worsened.

Similarly, because of the benign outcome of acute otitis media, amoxicillin remains the first line antibiotic for this indication . On the other hand, because of the much lower achievable drug levels in the cerebrospinal fluid relative to the MIC of the pneumococcus and because of reports of failures with empiric therapy with third generation cephalosporins, vancomycin is added to the regimen for treatment of possible pneumococcal meningitis.

Risk factors for infection with resistant organisms include recent hospitalization, recent receipt of antibiotics, and day care attendance . Recent receipt of antibiotics increases nasopharyngeal colonization from 9 to 21% to 39 to 67% and invasive disease from 4 to 39% to 30 to 77% . The confluence of these three factors in young children may explain the high frequency of infection in children in particular.

In summary, the increase in antibiotic resistance rates amongst pneumococci appears to be increasing in Canada. This has led to changes in empiric therapy of meningitis in children. Because serotypes in the vaccine include resistant strains, use of vaccine is an attractive option to reduce the morbidity due to infection by these strains.

However, currently available vaccine is not conjugated and does not stimulate an adequate response in children under two years of age, who are at greatest risk of pneumococcal meningitis. Hopes for conjugate pneumococcal vaccine to mimic the success of conjugate Haemophilus influenzae type b vaccine has spurred clinical trials of such a vaccine in children.

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