An update on vulvovaginal candidiasis (thrush) SUMMARY V 14

Transcription

An update on vulvovaginal candidiasis (thrush) SUMMARY V 14
e e
VOLUME 14
NUMBER 4
An update on vulvovaginal candidiasis (thrush)
SUMMARY
This Bulletin outlines the correct diagnosis and treatment of vulvovaginal candidiasis
(thrush) by patients and by health care professionals. It also discusses some of the
commonly held but often incorrect beliefs about the infection.
• Thrush is the second most common vaginal infection after bacterial vaginosis and up to
75% of women suffer an episode at some point in their life.
• Some women suffer from recurrent episodes of thrush and can suffer psychosexual
problems and depression as a consequence.
• It would seem wise to prescribe the most cost-effective product that is acceptable to the
individual.
• Women sometimes restrict their lives unnecessarily by following preventive measures that
have little evidence to support them or because they feel embarrassed that they have thrush.
It is important to provide them with informed reassurance.
Although it is sometimes dismissed as a minor
infection, thrush is the second most common
vaginal infection after bacterial vaginosis.1 Up
to 75% of women suffer an episode of thrush at
some point in their life and about half of these
have more than one episode.2
Candida albicans is the usual cause of thrush
and is isolated in 80 to 95% of swabs taken
from women with the infection.2 However, many
women with no symptoms or clinical signs of
thrush are colonised with candida and it could
be part of the normal vaginal flora.2 It is likely,
therefore, that changes to the vaginal
environment are required for symptoms to
develop but it is not known what these are.2 The
second most common species to cause thrush
is C. glabrata, which occurs in about 5% of
infections. C. glabrata tends to be more resistant
to antifungal treatment than C. albicans and is
harder to treat.2
Women of childbearing age are most likely to
develop thrush, because oestrogens enhance
the proliferation, germination and adherence
of C. albicans to the vaginal epithelium.3 Thrush
is more common in women with diabetes
mellitus, and in women who have recently
taken broad-spectrum antibiotics.2 This could
be because high glucose levels may increase
adhesion of C. albicans to the vaginal
epithelium, and broad spectrum antibiotics
eliminate the normal protective bacterial flora.1,4
Pregnant women are particularly susceptible
to candida infection, because increased levels
of reproductive hormones favour the growth of
yeasts.1 However, there is no evidence that
thrush harms the fetus.5 Thrush is thought to be
less common in postmenopausal women but
a diagnosis of candidiasis in such women
should not be discounted. Symptomatic
infection in postmenopausal women is usually
associated with uncontrolled diabetes mellitus,
hormone replacement therapy, antibiotic use,
severe underlying disease, immunosuppressive agents or tamoxifen.3
Diagnosis of thrush
Patients and GPs often attribute symptoms
such as pruritus and vaginal discharge to thrush
and a diagnosis is made without physical
examination.2 However, bacterial vaginosis is
a more common infection, can have similar
symptoms and can occur at the same time as
thrush in up to 10% of cases.2,6 Guidelines from
a working group of the British Society for Medical
Mycology state that swabs for fungal culture
need not be taken on a first visit if typical signs
and symptoms of thrush are present, unless
the patient could have a sexually transmitted
disease. 2 However, if symptoms persist
despite empirical antifungal treatment, the
patient should be examined and mycological
and microbiological investigations made
(e.g. vaginal specimen culture and/or vaginal
pH test).2,6
Bacterial vaginosis
is more common
than thrush and
can have similar
symptoms
Classification of thrush
Thrush is classified in a number of ways in
clinical trials, which can be confusing,
Date of preparation:
January 2004
This MeReC Publication is produced by the NHS for the NHS
MeReC Bulletin Volume 14, Number 4
13
An update on vulvovaginal candidiasis (thrush)
especially as the US and UK use different
definitions. Various categories of thrush are
explained below.
Single-dose oral
antifungal
treatment is as
effective as
multiple-dose
topical treatments
of varying length
In the UK, thrush is considered as being either
acute or recurrent (i.e. four or more episodes of
symptomatic thrush each year), in accordance
with a 1999 guideline on thrush management
put together by the Association of Genitourinary
Medicine and the Medical Society for the Study
of Venereal Diseases.7 However, some studies
also refer to chronic thrush (meaning continuous
or recurrent infection).
A more recent US guideline classifies thrush
into uncomplicated or complicated infection. It
defines uncomplicated thrush as being infection
that is mild-to-moderate, infrequent and likely
to be caused by C. albicans, and that responds
well to topical or oral antifungal treatment.8 It
subdivides complicated thrush into recurrent
infection (defined as above), severe infection,
non-albicans infection, infection in immunocompromised women (e.g. those with HIV or
women who are taking corticosteroids) and
infection during pregnancy.8 Severe infection
gives rise to fissures and extensive erythema
and oedema of the vulva. It does not respond
well to short courses of treatment.8
Which treatment?
There is conflicting
evidence about
the efficacy of
lactobacillus
preparations and
live yoghurt
Uncomplicated infection
Five imidazole derivatives are available for
treatment of thrush in a number of topical
formulations (i.e. pessaries and intravaginal
creams) — clotrimazole, econazole, fenticonazole, ketoconazole and miconazole. Topical
nystatin can also be used but has a 14-day
course of treatment and can stain clothes
yellow, which may reduce acceptability. 2,9
However, it can be useful in women whose
thrush has not responded to imidazoles.2 In
addition, some preparations of clotrimazole,
miconazole and povidone-iodine are licensed
for treatment of mixed (i.e. bacterial and fungal)
infections.
Patients should apply a topical cream to the
vulva as well as inserting intravaginal cream or
pessaries into the vagina, because this is
another area that becomes colonised by
candida.10 Itraconazole and fluconazole are
licensed for oral treatment of candidiasis, and
oral ketoconazole can be given but has been
associated rarely with fulminant hepatitis.
Therefore, it is only used in patients with thrush
that has not responded to other treatments.6,11
A Cochrane review of 17 randomised controlled
trials (RCTs) reporting 19 comparisons of oral
versus intravaginal antifungals, states that
topical imidazoles and oral antifungals are
equally effective at both long- and short-term
follow-up. 12 It adds that single-dose oral
antifungal treatment is as effective as multipledose topical treatments of varying length, except
in pregnant women, who require multiple doses
14
of topical treatment. At short-term follow-up,
80% of women were cured clinically by either
oral or intravaginal treatment. At long-term
follow-up, 83% of women were cured clinically
by oral treatment and 82% by intravaginal
antifungals. Short term follow-up was defined
as five to 15 days after a course of treatment and
long term as two to 12 weeks after a course of
treatment.
The review also concludes that there is no
statistically significant difference between
mycological cures achieved with oral and
intravaginal treatment at short- or long-term
follow-up. At short-term follow-up, over 80% of
women achieved mycological cure with either
route of administration but, long term, the figures
decreased to 72% for oral treatment and 66%
for intravaginal treatment. The review
comments that the 20% of women who were
not cured may not have had candida infection or
may have been infected with a non-albicans
strain. It adds that the decrease in mycological
cure long term might be a result of regrowth of
candida as part of the vaginal flora.
The decision to prescribe or recommend for
purchase an antifungal treatment should be
based on efficacy, safety, cost and patient
preference. Oral treatment is more expensive
than topical treatment and may cause more
serious systemic adverse effects.12 Nevertheless, the Cochrane review recommends it
as the treatment of choice in non-pregnant
women, although it adds that prescribers and
patients who treat themselves should consider
whether the higher cost of oral treatment is
worth the gain in convenience and patient
preference, as both are equally effective.
Patients have different reasons for preferring a
certain route of treatment. Some women prefer
to take a capsule rather than using pessaries
and creams, because insertion can be painful
if the vulva is very inflamed.2 However, others
might find a cream soothing.10 Therefore, it
would seem wise to prescribe the most
inexpensive product that is acceptable to the
patient.
It is important to remember that if a patient is
prescribed topical or oral treatment and also
cream to apply externally, they may have to pay
two prescription charges.
Symptoms should begin to resolve once
treatment begins but some women find that
vulval itching and burning disappear more quickly
if an antifungal cream is applied to the vulva in
addition to oral or intravaginal treatment.9 If
symptoms do not respond within seven to 14
days, the patient should return to her GP.13–15
Some women use tampons impregnated with
tea tree oil to treat thrush but this can cause
severe allergic reactions.16 Other measures
include inserting lactobacillus-containing
preparations into the vagina, and eating live
yoghurt.16 Lactobacillus preparations sold for
MeReC Bulletin Volume 14, Number 4
An update on vulvovaginal candidiasis (thrush)
correcting the vaginal flora may not always
contain the species most commonly found in a
healthy vagina and their usefulness is
questionable. Similarly, there is conflicting
evidence about the usefulness of yoghurt at
preventing infection.16 However, anecdotally,
some women say they derive benefit from both
types of preparation.2,16
Complicated infection
Women with chronic or recurrent thrush seldom
have recognisable precipitating factors and the
condition can lead to psychosexual problems
(e.g. feeling unclean or not wanting to have sex)
and depression, which should be taken into
account as part of diagnosis and treatment.2,6
Physical examination, investigation for underlying disease and mycological investigation
are recommended.2
Recurrent and severe infection Recurrent and
severe infection are treated in a similar way.8
PRODIGY recommends an initial one- to twoweek course of topical clotrimazole, or oral
itraconazole or fluconazole, followed by oncea-week (twice a week for itraconazole)
maintenance treatment for six months.6 This is
an unlicensed use of these drugs in the UK.
After symptoms have been suppressed for
three to six months, prophylaxis can be
discontinued and the woman reassessed.2
However, at least half of women suffer a
recurrence once the drugs are stopped and
some women may need maintenance treatment
for years.6 The US guideline recommends using
a seven- to 14-day course of topical treatment
or a 150mg oral fluconazole dose with a second
one given three days later (this is an unlicensed
use in the UK).8 Anecdotal reports suggest that
some women with recurrent thrush develop
symptoms around the time of their period.
Therefore, using treatment just before, during
or immediately after menstruation may improve
the outcome in recurrent thrush.6
Non-albicans infection Women with nonalbicans infections are often referred to a
specialist2 and drug regimens used include
topical nystatin or a seven- to 14-day course of
a topical imidazole.6,8 If the infection is recurrent,
boric acid in a gelatine capsule can be inserted
vaginally, although case reports have
associated this treatment with systemic boron
toxicity.8,11 Flucytosine has been used but the
long-term safety of this drug is not known.8 A
maintenance regimen of nystatin pessaries
(100,000 units daily) can also be used. 8
However, none of these treatment regimens
are licensed in the UK.
Immunocompromised patients Women who
are immunocompromised may need seven- to
14-day courses of topical treatment.8
Pregnancy All topical antifungal products can
be used during pregnancy but oral treatment
should not be given to either pregnant women
or to nursing mothers.13–15 A recent Cochrane
MeReC Bulletin Volume 14, Number 4
review of 10 RCTs in pregnant women with
thrush concluded that topical imidazoles were
more effective than topical nystatin for treating
symptoms but added that a seven-day course
might be necessary in pregnant women.5
PRODIGY recommends topical clotrimazole as
the drug of choice, because it is supported by
the most data in pregnant women, followed by
topical miconazole and econazole.6 Applicators
can be used to insert topical preparations into
the vagina during pregnancy but expectant
mothers may prefer to insert pessaries using
a finger.6
What about over-the-counter products?
Many treatments for thrush can be bought over
the counter (OTC). When OTC antifungals were
first made available, two concerns were
expressed — that women might misdiagnose
their symptoms and that there would be an
increase in drug resistance in candida species.
Have these concerns been realised?
Misdiagnosis
There is some evidence that women do
misdiagnose thrush. The results of a US study
of 95 women who purchased OTC antifungal
products for presumed thrush showed that
only one-third had the infection.17 Of the rest,
19% had bacterial vaginosis, 21% had mixed
vaginosis, 14% had no infection, 11% had
other diagnoses and 2% had trichomoniasis.
Women with a previous physician-confirmed
diagnosis of thrush and women who read the
label on the product packaging were no more
accurate than other women at self-diagnosis.
Oral treatment
should not be
given to pregnant
women or nursing
mothers
A Finnish study showed that out of 299 women
who purchased intravaginal antifungal drugs,
44% were using drug treatment against
recommendations.18 Of these, 14% had never
had their thrush diagnosed by a physician, 30%
had already used two or more treatments over
the past year without visiting a physician, 3%
were pregnant and had not been recommended
the treatment by a health care professional and
two users were under 16 years of age.
Panel 1: When to refer a woman to her GP13,19
A patient should see her GP if she:
• Is a first-time sufferer whose thrush has not previously been diagnosed
by a physician
• Is younger than 16 or older than 60 years of age
• Has had at least two episodes of thrush in the past six months but has
not consulted her GP about the condition for more than a year
• Has a previous history of sexually transmitted disease or has been
exposed to a partner with one
• Is or might be pregnant
• Has foul-smelling vaginal discharge
• Has abnormal or irregular vaginal bleeding or blood-stained discharge
• Has pain in the lower abdomen
• Has experienced an adverse reaction to antifungal products
• Has dysuria — pain on urination is rare with thrush, although external
dysuria can occur
• Has vulval or vaginal sores, ulcers or blisters. These are more commonly
associated with herpes infections
• Experiences no improvement after seven days’ empirical treatment.
15
An update on vulvovaginal candidiasis (thrush)
Women need information about all vaginal
infections and their symptoms, to help them
judge whether or not they have thrush. Health
care professionals should help prevent incorrect
self-diagnosis or continual use of OTC
medications by providing this information. The
situations in which a woman should see their
GP are listed in Panel 1.
Resistance
There is no surveillance network for monitoring
resistance to antifungals in the UK.20 Fears that
making imidazole treatments available OTC
would result in an increase in resistant strains
of C. albicans do not seem to have been
realised.20 However, strains that are inherently
less sensitive to the drugs (e.g. C. glabrata)
might be on the increase.20 The reason why
some women infected with highly susceptible
strains of C. albicans occasionally do not
respond clinically, and why many more improve
clinically but remain colonised with C. albicans,
is not known. However, it might be because
imidazoles are fungistatic rather than fungicidal.21
Conclusion
The trigger for most cases of thrush is not known.
This can be frustrating both for women and for
health care professionals. Women with thrush
often treat themselves, either with OTC products
or with alternative therapies but may not make a
correct diagnosis. It is therefore important that
health care professionals help women to obtain
appropriate treatment by providing them with
information and advice about all vaginal infections and the various formulations available for
treatment of thrush. In addition, health care
professionals should know when to refer patients
for further investigation.
The evidence for some commonly-held beliefs about thrush
Resources
Although our understanding of thrush has improved, there are still myths that
some women and health care professionals believe about the disease. It is
important to discuss with women the evidence (or lack of it) for these, to prevent
them from feeling embarrassed about the condition or from unnecessarily
restricting their lives.
PRODIGY has produced a patient information
leaflet about thrush, which can be downloaded
from its website: http://www.prodigy.nhs.uk.
Tight-fitting clothing can precipitate an attack
The evidence that clothing can trigger an attack of thrush is controversial, as
study results have been conflicting. However, women who are frequently
affected by thrush may prefer to wear loose cotton underwear.2,16
Sanitary towels are more likely to bring on an attack than tampons
Study results have been inconclusive about whether women who use
sanitary towels are more likely to have episodes of thrush than those who
use tampons.6,16
Reducing sugar intake prevents thrush
Some women with recurrent thrush decrease their intake of sugary foods in
an attempt to reduce the number of episodes of the condition. However, there
is currently not enough evidence to support this practice.16
Infection is spread from the rectum
Thrush is no longer thought to be spread from the rectum.1 Several studies have
shown that candidiasis is not always found in the rectum of thrush sufferers,
even when vaginal infection is present. Also, reducing intestinal colonisation
with C. albicans does not prevent vaginal recurrence.2 Relapse may occur
because of incomplete eradication of organisms after treatment. As a general
health precaution, it seems wise to advise women to wipe from front to back
after defaecation and to avoid vaginal intercourse after anal penetration.5,16
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Thrush can be caught from sexual partners
Treating the genitals of asymptomatic male partners of women with thrush is
not usually necessary, because it appears to have no effect on the rate of
recurrence of infection.2,7 If a male partner develops symptoms of penile thrush,
he can be treated with a topical antifungal. Any activity that causes minor
abrasions to the vaginal mucosa can lead to an episode and the mouth might
be a source of reinfection. Two studies have indicated that oral sex is
associated with recurrence of symptoms.16
13.
Oral contraceptives can cause thrush
The evidence that oral contraceptives can increase the risk of developing thrush
is contradictory.11
18.
Thrush always produces discharge
Thrush does not always produce vaginal discharge. Any discharge present
can vary in consistency from a thin, watery fluid to cottage cheese-like white
curds.2 Discharge produced by thrush does not smell offensive — if an
offensive discharge is present, bacterial vaginosis should be suspected.2
20.
14.
15.
16.
17.
19.
21.
Sobel JD. Genital candidosis. Medicine 2001;29:67–71.
DenningDW.Fortnightlyreview:managementofgenitalcandidiasis(working
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Nwokolo NC, Boag FC. Chronic vaginal candidiasis: management in
the postmenopausal patient. Drugs Aging 2000;16:335–9.
Donders GGG, Prenen H, Verbeke G, et al. Impaired tolerance for glucose
in women with recurrent vaginal candidiasis. Gynecol 2002;187:989–93.
Young GL, Jewell D. Topical treatment for vaginal candidiasis (thrush)
in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 1,
2004. Chichester, UK: John Wiley & Sons, Ltd.
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Informatics at Newcastle. Available from: URL: http://www.prodigy.nhs.uk
Clinical Effectiveness Group (Association of Genitourinary Medicine
and the Medical Society for the Study of Venereal Diseases). National
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Inf 1999;75:S19–S20.
Scharbo-DeHaan M, Anderson DG. The CDC 2002 guidelines for the
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Royal Pharmaceutical Society of Great Britain; 2003.
Bingham JS. What to do with the patient with recurrent vulvovaginal
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evidence. 9th ed. London: BMJ Publishing Group; 2003. p. 1980–94.
Watson MC, Grimshaw JM, Bond CM, Mollison J, Ludbrook A. Oral
versus intra-vaginal imidazole and triazole anti-fungal treatment of
uncomplicated vulvovaginal candidiasis (thrush). (Cochrane Review).
In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley &
Sons, Ltd.
Diflucan One. Summary of product characteristics. Available from:
URL: http://www.medicines.org.uk/.
Sporanox. Summary of product characteristics. Available from: URL:
http://www.medicines.org.uk/.
Nizoral. Summary of product characteristics. Available from: URL:
http://www.medicines.org.uk/.
Mårdh PA, Rodrigues AG, Mehmet G, et al. Facts and myths on recurrent
vulvovaginal candidosis — a review of epidemiology, clinical manifestations,
diagnosis, pathogenesis and therapy. Int J STDs AIDS 2002;13:522–39.
Ferris DG, Nyirjesy P, Sobel J, et al. Over-the-counter antifungal drug
misuse associated with patient-diagnosed vulvovaginal candidiasis.
Obstet Gynecol 2002;99:419–25.
Sihvo S, Ahonen R, Mikander H, et al. Self-medication with vaginal
antifungal drugs: physicians’ experiences and women’s utilization
patterns. Fam Pract 2000;17:145–9.
Canestan Once. Summary of product characteristics. Available from:
URL: http://www.medicines.org.uk/.
Communicable disease surveillance centre: England and Wales.
Antimicrobial resistance in 2000. London: Public Health Laboratory
Service. Available from: URL: http://www.hpa.org.uk. Accessed 23/1/04.
Sobel JD, Zervos M, Reed BD, et al. Fluconazole susceptibility of vaginal
isolates obtained from women with complicated Candida vaginitis: clinical
implications. Antimicrob Agents Chemother 2003;47:34–8.
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provides NICE with the ability to secure value for money in the use of NHS funds invested in its work and enables it to influence topic selection, methodology
and dissemination practice. NICE considers the work of this organisation to be of value to the NHS in England and Wales and recommends that it be used
to inform decisions on service organisation and delivery. This publication represents the views of the authors and not necessarily those of the Institute.
© The National Prescribing Centre, The Infirmary, 70 Pembroke Place, Liverpool, L69 3GF.
Telephone: 0151 794 8146
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Fax: 0151 794 8139
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MeReC Bulletin Volume 14, Number 4

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