Microbiological effects and clinical use of xylitol in preventing acute otitis media

Tapiainen, Terhi (2002-08-23)
 
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Tapiainen, Terhi
University of Oulu
23.08.2002
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Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium of the Department of Paediatrics, on August 23rd, 2002, at 12 noon.
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Abstract

The purpose was to evaluate the microbiological mechanism of action of xylitol and to assess its use in clinical practice for preventing acute otitis media (AOM).

To test whether the effect of xylitol on S. pneumoniae is inhibited by fructose, a total of 20 strains of S. pneumoniae were exposed to xylitol in the presence of fructose and other carbon sources. Addition of 5% xylitol to the media resulted in marked growth inhibition, an effect which was totally eliminated in the presence of 1%, 2.5% or 5% fructose but not in the presence of 1% or 5% glucose, 1% galactose or 1% sucrose. The inhibition of pneumococcal growth is probably mediated via a fructose phosphotransferase system in a similar manner to that seen in mutans streptococci. Sorbitol alone did not affect the growth of pneumococci, and thus sorbitol is unlikely to provide any clinical benefit in the prevention of AOM.

To evaluate the effect of xylitol on the ultrastructure of S. pneumoniae and Haemophilus influenzae (H. influenzae) and on the pneumococcal phenotype, five strains of S. pneumoniae and one strain of H. influenzae were examined by electron microscopy after xylitol exposure. Xylitol damaged the ultrastructure of the pneumococci. Some of the bacteria were lysed and the cell wall of the remaining ones became more diffuse and the polysaccharide capsule was ragged. The resulting morphology was identical to that of the transparent pneumococcal phenotypic variant. The properties of the transparent variants of pneumococci could explain the clinical efficacy of xylitol in preventing AOM despite the lack of effect on the nasopharyngeal carriage of pneumococci. The cell wall of H. influenzae became slightly thicker, but the morphology remained otherwise unchanged.

To evaluate the pharmacokinetics of xylitol locally in the nasopharynx, xylitol concentrations were measured in the saliva of 65 children by enzymatic assay after giving them xylitol chewing gum or syrup at doses equal to those used in clinical trials. Concentrations high enough to have an antimicrobial effect were attained, but the xylitol disappeared from the saliva within 15 minutes, which indicates that high peak concentrations may be more important for efficacy than the time for which the concentration exceeds the level needed for an antimicrobial effect.

To find a more convenient dosing regime for xylitol prophylaxis, xylitol was administered to 1277 children only during an acute respiratory infection (ARI) in a randomised placebo-controlled trial. The occurrence of AOM during ARI was 34/166 (20.5%) in the xylitol mixture group as compared with 32/157 (20.4%) among the children receiving the control mixture. Among older children receiving control chewing gum, xylitol chewing gum or xylitol lozenges, AOM was experienced by 24/218 (11.0%), 31/220 (14.1%) and 34/219 (15.5%) respectively. None of the differences between the groups was statistically significant. Xylitol should be used continuously in AOM prophylaxis, as it proved ineffective when used only during URI.

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