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research-article2014
AOPXXX10.1177/1060028014542150Annals of PharmacotherapyWargo and Campbell
Letter to the Editor
Is Xylitol Effective in the Prevention of
Acute Otitis Media?
Acute otitis media (AOM) is a highly prevalent illness in
childhood and remains the most common condition for
which antibacterial agents are prescribed for children in the
United States.1 Avoidance of unnecessary treatment is espe-
cially important with increased concern for antimicrobial
resistance.1,2 Strategies for the prevention of AOM include
the following: administration of pneumococcal conjugate
vaccine and influenza vaccine, breastfeeding for at least 6
months, and lifestyle changes such as avoidance of tobacco
smoke exposure.1 The use of xylitol for the treatment and
prevention of AOM has also been discussed. Xylitol is a
5-carbon polyol that has been used widely as a sweetening
substitute for sucrose because of its potential preventive
effect on dental caries through its inhibition of the growth
and metabolism of cariogenic bacteria.3,4 Additionally, xyli-
tol has been shown to inhibit the growth of Streptococcus
pneumoniae, and its use in the prevention of AOM was first
described in 1996.5
Several randomized controlled clinical trials have ana-
lyzed various dosage forms of xylitol, including gum, loz-
enge, and syrup, for the prevention and treatment of AOM
(Table 1). Two early studies evaluating the use of xylitol
demonstrated moderate efficacy of some xylitol formula-
tions in reducing occurrence of AOM in children when
administered 5 times daily over 3-month periods.5,6 The
impracticality of high-frequency, long-term administration
of xylitol as a prophylactic measure for AOM prompted
researchers to examine limiting the use of xylitol for AOM
prophylaxis to periods of acute upper-respiratory tract
infection, but no efficacy was established when xylitol was
administered during upper-respiratory tract infection.7 Two
additional trials, including a recent 2014 publication that
evaluated less-frequent, 3 times daily administration of
xylitol formulations, were unable to show efficacy for the
prevention of AOM.8,9
In 2011, a Cochrane Review assessed the efficacy and
safety of xylitol in preventing AOM in children up to 12
years of age.10 Reviewers evaluated 4 of the 5 trials sum-
marized above—all but the most recent—and came to the
conclusion that there is fair evidence that prophylactic
administration of xylitol in any form reduces the
occurrence of AOM by 25% compared with controls (rela-
tive risk [RR] = 0.75; CI = 0.65 to 0.88). The differences in
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Annals of Pharmacotherapy
2014, Vol. 48(10) 1389­–1391
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DOI: 10.1177/1060028014542150
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AOM occurrence as a function of xylitol dosage forms were
examined as part of the Cochrane assessment. Of the dos-
age forms analyzed, xylitol chewing gum was found to be
superior to xylitol syrup for prevention among healthy chil-
dren (RR = 0.59; CI = 0.39 to 0.89), and there was no differ-
ence between xylitol lozenges and syrups in preventing
AOM among healthy children (RR = 0.73; CI = 0.47 to
1.13). The number of patients included in the meta-analysis
who received lozenges compared with the other dosage
forms is a limitation of the direct comparison, but the non-
difference perhaps denotes that the dosage form has little
influence on overall prophylactic benefits of xylitol for
AOM.
The use of xylitol for the prevention of AOM is limited
for several reasons. Perhaps most notable is the required
frequency of dosing regardless of formulation. Even 3 times
daily dosing would be unpractical for most children, and
conclusive efficacy at a frequency less than 5 times daily
has not been established. In published trials, xylitol content
per dosage unit (0.7 to 1.6 g) was similar to that in commer-
cially available products, and to achieve total daily doses, it
required 6 to 15 pieces of gum or lozenge. With 4 of the 5
trials published by the same research group in Finland, one
may question potential bias and the lack of generalizability
of the results. However, the reported data were not homoge-
neous, and there is no indication of conflict of interest.
Xylitol use as a possible adjunct to AOM prevention is dis-
cussed in the most recent AOM guidelines, and there is a
suggestion that perhaps chewing gum and lozenges appear
to be more effective than syrup; however, no recommenda-
tions for use are made.1 Although the meta-analysis of the
Cochrane Review demonstrated that xylitol can reduce
AOM occurrence when compared with controls, it does not
warrant routine use. This is based on practical purposes
regarding dosing frequency and compliance required for
clinical effectiveness.
Brief Explanation of Topic Significance
Acute otitis media (AOM) is one of the most common rea-
sons for pediatric physician visits and accounts for a large
portion of antibiotic prescribing. Current guidelines provide
recommendations to reduce the overall incidence of AOM,
1390 Annals of Pharmacotherapy 48(10)

Table 1.  Review of Xylitol Trials.

Formulation(s),
Daily Dose of Administration Duration of
n Age (months) Xylitol (g) Frequency Therapy Clinical Outcomes
Uhari et al (1996)5 336 12-60 Gum, 8.4 5 Times/d 2 Months AOM occurrence decreased
significantly for xylitol users
compared with sucrose:
  •• Difference = 8.7%; (CI = 0.4%-
17%; P = 0.04)
Uhari et al (1998)6 857 12-60 Gum, 8.4; 5 Times/d 3 Months AOM occurrence decreased for each
syrup, 10; group compared with the controls
lozenge, 10 but was only statistically significant
for the gum and syrup formulations:
  •• Gum difference = 40% (CI =
10.0%-71.1%; P = 0.025)
  •• Syrup difference = 30% (CI =
4.6%-55.4%; P = 0.028)
  •• Lozenge difference = 20% (CI =
−12.9% to 51.4%; P = 0.30)
Tapianinen et al 1277 10-84 Gum, 8.4; 5 Times/d 1-3 Weeks, AOM occurrence was not
(2002)7 syrup, 10; during significantly different between xylitol
lozenge, 10 acute URTI users of any formulation compared
with controls:
  •• Gum difference = −3.1% (CI=
−7.6% to 2.5%; P = 0.32)
  •• Syrup difference = −0.1% (CI =
−8.9% to 8.8%; P = 0.98)
  •• Lozenge difference = −4.5% (CI =
−11% to 1.8%; P = 0.16)
Hautalahti et al 663 7-84 Gum, 9.6; 3 Times/d 3 Months AOM occurrence was not
(2007)8 syrup, 9.6 significantly different between
xylitol and controls:
  •• Difference = 0.26% (CI = −0.71 to
0.19; P = 0.25)
Vernacchio et al 326 6-71 Syrup, 15 3 Times/d 6 Months AOM occurrence was not
(2014)9 significantly different between
xylitol and controls:
  •• HR = 0.88 (CI = 0.61-1.3; P = 0.5)

Abbreviations: AOM, acute otitis media; URTI, upper respiratory tract infection.

but its impact on the health care system remains burden- Osteopathic Medicine Center for Drug Information and Research.
some. Xylitol has been considered an alternative preventive These responses are not published.
strategy to AOM for a little over a decade, despite limited Ryan Wargo, PharmD,
evidence. A recent Cochrane Review claimed fair evidence LECOM–Bradenton, Florida, USA
that the prophylactic administration of xylitol among
healthy children attending day care centers reduces the Marcus Campbell, PharmD,
LECOM–Bradenton, Florida, USA
occurrence of AOM. However, this review was based on
limited data. Since this review, new evidence has been
released regarding the effect of xylitol in the prevention of Declaration of Conflicting Interests
AOM. The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Explanation of Any Similar Works by the
Author(s) Funding
Authors routinely provide responses to drug information inquiries The author(s) received no financial support for the research,
as part of the services provided by the Lake Erie College of authorship, and/or publication of this article.

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Wargo and Campbell 1391
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