Executive Summary
Acute respiratory infections (ARI) are a leading cause of childhood mortality, causing 25–33% of all deaths in children in developing countries. Bacterial ARI are associated with higher case-fatality
ratios than infections caused by viruses. Streptococcus pneumoniae is the most common cause of bacterial
ARI, and pneumococcal resistance is the principal cause for concern regarding treatment failures for ARI and meningitis. Therefore, this review focuses on pneumococcal resistance.
ARI are often treated empirically with antibiotics. Drug-resistance trends are not well documented in most developing countries due to limited laboratory capacity. It is clear, however, that the prevalence of strains resistant to penicillin-related compounds and to co-trimoxazole is increasing. The clinical impact of pneumococcal resistance varies with the site of infection and is better documented for meningitis and otitis media than for pneumonia.
The ecological niche of S. pneumoniae is the human nasopharynx, where it can be carried asymptomatically and transmitted from person to person. Children carry S. pneumoniae more commonly than adults. In contrast to a majority of other pathogens where drug resistance is a problem, the evolution of drug resistance within a patient during the course of antibiotic therapy is not common in S. pneumoniae. This is because resistance conferred by single-point mutations alone is rare in pneumococcal clinical isolates. Transformation (the uptake of free DNA from the environment) and conjugative transposons (the transfer of segments of genomic DNA during bacterial fusion) are the two primary genetic mechanisms conferring pneumococcal resistance.
Epidemiological studies have demonstrated that recent antibiotic use is strongly associated with carriage of resistant pneumococci both at the community and individual levels. Among individuals who develop invasive pneumococcal disease, recent antibiotic use is also associated with an increased risk of infection with a resistant strain. The biological mechanisms behind the association between recent antibiotic use and carriage of resistant strains are not completely understood and require further research.
A key factor influencing the emergence and spread of resistant pneumococci is unnecessary antibiotic use for viral respiratory illnesses in humans. This is due to misdiagnosis of conditions because both viral and bacterial agents can cause symptoms of ARI, as well as physician and patient pressures to prescribe antibiotics. However, while antibiotic overuse is a problem in some developing settings, in others, poor access to adequate health care is still a primary problem and children requiring antibiotic therapy do not receive it.
Pneumococcal resistance can also be inadvertently driven by the use of drugs for unrelated conditions.
This may pose a particularly serious problem as mass antibiotic prophylaxis campaigns to eliminate trachoma are introduced in a number of African countries. To date, the pneumococcal polysaccharide vaccine is the principal established intervention to protect against pneumococcal disease. Because this
vaccine only protects against bacteraemic pneumococcal pneumonia, is not indicated for children under 2 years of age, and has no impact on pneumococcal carriage, it is not an effective intervention against ARI or the spread of drug resistance in most developing countries.
A pneumococcal conjugate vaccine has now been approved for routine infant use in the United States.
This vaccine has been shown to be highly effective at preventing pneumococcal pneumonia and meningitis in young children and infants. Moreover, the vaccine has some efficacy at protecting against
otitis media, and also protects against carriage of vaccine-included pneumococcal serotypes. Because
of its unique features, this vaccine holds great potential as an “anti-resistance vaccine” which
simultaneously reduces the burden of invasive disease and the prevalence of resistant strains. Prophylactic use of xylitol, a sugar which inhibits pneumococcal growth, may also represent a feasible
intervention against non-invasive disease and resistance in developing countries.
Xylitol sugar
Xylitol is a sugar that has been used as a sweetening substitute for sucrose because it has a preventive effect against dental caries. Recent evidence suggests that in addition to inhibiting growth of Streptococcus mutans, the primary cause of dental caries, this sugar can inhibit the growth of S.pneumoniae, and possibly also of other bacterial colonizers of the nasopharynx such as H. influenza (99, 100).
A controlled trial of healthy children attending day-care centres in Finland randomized children to control groups which received syrup, chewing gum and lozenges sweetened with sucrose and a low concentration of xylitol, or treatment groups which received a high daily dose of xylitol in the form of syrup, chewing gum or lozenges (99). The children were then followed for a 3-month period and information on respiratory infections, acute otitis media, and antibiotic therapy was collected. While the xylitol exposure did not reduce the mean number of respiratory infections in treatment groups relative to their respective control groups, children who regularly received xylitol in the form of syrup or chewing gum had a significant 30–40% reduction in the occurrence of acute otitis media, and all treatment groups received fewer antibiotic prescriptions than controls (99).
Prophylactic use of xylitol may thus protect against acute otitis media, particularly for children with high exposure to S. pneumoniae, such as those attending day-care centres. In this study, xylitol in all groups was administered 5 times per day; such frequent dosing may be difficult to achieve and studies of the minimum dosing required to get a significant protective effect would be useful. Xylitol syrup or chewing gum may be a feasible prophylactic measure in some developing settings, with the potential of reducing antibiotic use. Top of Page.
