Aust N Z J Obstet Gynaecol 2017; 1–7

DOI: 10.1111/ajo.12592

REVIEW ARTICLE

Recurrent vulvovaginal candidiasis: A review of

guideline recommendations

Alexia Matheson1 and Danielle Mazza2

1
Department of General Practice,
School of Primary Healthcare, Monash
University, Notting Hil, Victoria,
Australia
2
Department of General Practice,
School of Primary Health Care, Monash
University, Notting Hill, Victoria,
Australia
Correspondence: Danielle Mazza,
Department of General Practice,
School of Primary Health Care, Monash
University, Building 1, 270 Ferntree
Gully Rd, Notting Hill, Vic. 3168,
Australia.
Email: Danielle.mazza@monash.edu
Received: 17 April 2016;
Accepted: 9 December 2016
Background: Recurrent vulvovaginal candidiasis (VVC) is a difficult-­to-­manage con-
dition that affects 5–8% of women of reproductive age. Current treatment regimes
have high relapse rates, resulting in poor quality of life for the women affected.
Aim: To compare the quality and content of current guidelines concerned with
recurrent VVC and to develop a summary of recommendations to assist in the
management of women with this condition.
Methods: Relevant clinical guidelines were identified through a search of several da-
tabases (MEDLINE, SCOPUS and The Cochrane Library) and relevant websites. Five
guidelines were identified. Each guideline was assessed for quality using the AGREE II
instrument. Guideline recommendations were extracted, compared and contrasted.
Results: The identified guidelines were of mixed quality. This is not related to the
level of evidence supporting them but is because of poor stakeholder involvement,
applicability and lack of clarity concerning editorial independence. Current interna-
tional guidelines for recurrent VVC are consistent in terms of their definition of the
condition, diagnostic techniques and utilising induction and maintenance therapy as
the treatment of choice. However, the regimen suggested by most guidelines (flu-
conazole weekly for six months) is not particularly effective; only 42.9% of patients
are disease free after 12 months. An alternative regimen put forward by one of the
guidelines cites a 77% cure rate after 12 months. Most guidelines lacked specific rec-
ommendations for the induction part of induction and maintenance treatment.
Conclusion: The current most recommended treatment of recurrent VVC is sub-­
optimal. Studies performed on a larger scale are required to identify more
­effective treatments.

KEYWORDS
candidiasis, practice guidelines as topic, recurrence, vaginitis, vulvovaginal

BACKGROUND lifetime.2–4 It is more likely to occur in an oestrogenised environ-

Recurrent vulvovaginal candidiasis (VVC) is a challenging gynae-
cological infection that many women and doctors struggle with.
Both difficult to live with and difficult to treat, the condition is
under-­researched and therefore treatment is often inconsistent
1
with what evidence exists.
Vulvovaginal candidiasis, typically known as thrush, is a com-
mon fungal infection experienced by up to 75% of women in their
ment and therefore often affects pregnant women.2 Recurrent
thrush is rarer, affecting between 5–8% of women of reproduc-
tive age3,4 but can greatly affect the quality of life of women,
causing symptoms such as itching and soreness of the vulva, dys-
pareunia, dysuria and the classic ‘cottage cheese-­like’ discharge.
It is most commonly caused by Candida albicans, but other spe-
cies such as C. glabrata, C. krusei, C. tropicals and C. parapsilosis al-
though rarer, are more commonly associated with recurrence.5,6

wileyonlinelibrary.com/journal/anzjog © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 1
2 Recurrent VVC: a guideline review

Indeed, Candida is a commensal organism found in 10–20% of
7
women.
Recurrent VVC may be caused by treatment-­resistant Candida,
species other than C. albicans, and has been associated with frequent
antibiotic therapy, use of the oral contraceptive pill, immunocom-
promised states such as human immunodeficiency virus (HIV) and
8,9
hyperglycaemia. However, overall the cause for VVC recurrence re-
mains largely controversial. Sexual transmission, use of panty liners
and tampons, douching, diet and atopy all have potential links to re-
4,10,11
current VVC, but evidence is limited and at times contradictory.
The most widely used form of treatment involves an intense
induction therapy with antifungals, followed by an extended pe-
riod of maintenance therapy. Despite this being the standard
treatment, many variations exist. Many different therapeutic
agents and durations are available;12,13 however, none are par-
ticularly efficacious. Current evidence suggests that in the case of
fluconazole induction and maintenance therapy, up to 57.1% of
14
patients experience relapse after six months.
In addition to risk factors and treatment specificities, other
controversies of recurrent VVC include the management of non-­
albicans related infections15 and asymptomatic colonisation.
The intricacies and failures of the management of the condition
all contribute to the challenge practitioners face when treating
women with recurrent VVC, and demonstrate the need for a con-
cise review of recommended strategies for how to deal with this
difficult clinical practice problem.
to ascertain eligibility for this review. The six guidelines that were
read that did not meet the criteria were excluded for the following
reasons: three of the articles were not guidelines,16–18 two did not
pertain to VVS but other forms of the fungal infection19,20 and one
only concerned screening and not treatment.21 Five guidelines
met the inclusion criteria 22–26 (Figure 127). It should be noted that
while these five guidelines did meet the inclusion criteria, none
were concerned with recurrent VVC alone. They all encompassed
either vaginitis or vaginal discharge in a broader sense (Table 1).
These guidelines were then appraised for their quality by two
assessors using the AGREE II instrument.28 Guideline authors were
contacted via email for clarification about level of stakeholder
involvement and editorial independence. The authors of the
International Union against Sexually Transmitted Infections and
the World Health Organisation (IUSTI/WHO) and Mycoses replied,
while the remaining authors did not. Recommendations in each
guideline were compared according to the following content areas:
definition of recurrent thrush, diagnostic techniques, indications
for therapy, approaches to management, treatments in pregnancy,
risk factor reduction and recommendations for partner treatment
(Table 2). Using these topics, a summary of ­recommendations for
recurrent thrush was made for use by physicians.

AIM

To compare the quality and content of current guidelines c­ oncerned

with recurrent VVC and to develop a summary of recommenda-
tions to assist in the management of women with this condition.

MA TERIALS AND METHODS

A search was conducted of Ovid Medline, the Cochrane Library

and SCOPUS as well as the national guideline websites of
Australia (National Health and Medical Research Council),
England and Wales (National Institute for Health and Care
Excellence), Scotland (Scottish Intercollegiate Guideline Network),
the United States (National Guideline Clearinghouse), and the
Guidelines International Network. ‘Vulvovaginal candidiasis’ and
‘Practice Guidelines as Topic’ were searched as subject headings,
and thrush, vaginitis, vulvovaginal candidiasis, recur, recurrent,
recurring, guideline and guidelines were searched as keywords.
Inclusion criteria were English language guidelines, published be-
tween the years 2005 and 2015. Excluded were results that per-
tained to a paediatric population or HIV-­infected persons. Most
articles returned by the search could be excluded using screening
tools provided by the search engines. Eleven results, including the F I G U R E   1   PRISMA (preferred reporting items for systematic
five that met the criteria, required a more thorough assessment reviews and meta-­analyses) flow chart.
A. Matheson and D. Mazza3

T A B L E   1   Summary of organising body, purpose, scope and year published in each guideline

Year
Title Organising body Purpose and scope published

European (IUSTI/WHO) guideline of the International Journal of
management of vaginal discharge Sexually Transmitted
Diseases and AIDS
Guideline: Vulvovaginal Candidosis Mycoses
(AWMF 015/072), S2k (excluding chronic
mucocutaenous candidosis)
Vulvovaginitis: Screening for and Society of Obstetrics
Management of Trichomoniasis, and Gynaecology
vulvovaginal Candidiasis and Bacterial Canada
Vaginosis
Vaginitis American College of
Obstetrics and
Gynecology
Management of vaginal discharge in Faculty of Sexual and
non-­genitourinary medicine settings Reproductive
Healthcare
Management of vaginal discharge, specifically 2011
bacterial vaginosis, trichomoniasis and
candidiasis.
Diagnosis and treatment of vulvovaginal 2015
candidiasis, including acute, non-­C. albicans and
chronically recurring forms.
To review the evidence and provide recommen- 2015
dations on screening for and management of
trichomoniasis, vulvovaginal candidasis and
bacterial vaginosis.
Diagnosis and treatment of vaginitis, specifically 2006
bacterial vaginosis, vulvovaginal candidiasis,
trichomoniasis, atrophic vaginitis, vulvar
dermatological conditions and vulvodynia.
Management of vaginal discharge, specifically 2012
bacterial vaginosis, vulvovaginal candidiasis and
trichomoniasis

AWMF, Association fo the Scientific Medical Societies in Germany; IUSTI/WHO, International Union against Sexually Transmitted Infections and the
World Health Organization

T A B L E   2   Comparison of guideline quality using the AGREE II tool

IUSTI/WHO (%) Mycoses (%) JOGC (%) ACOG (%) FSRH (%)

Scope and purpose 81 36 78 89 97

Stakeholder involvement 33 33 33 39 75
Rigour of development 60 73 57 65 68
Clarity and presentation 92 92 97 89 100
Applicability 12.5 13 8 27 35
Editorial independence 29 67 38 25 79

ACOG, American College of Obstetrics and Gynecology; FSRH, Faculty of Sexual and Reproductive Healthcare; IUSTI/WHO, International Union
against Sexually Transmitted Infections and the World Health Organization; JOGC, Journal of Obstetrics and Gynaecology Canada

RESULTS
The guidelines included in this review were from IUSTI/WHO,22
Mycoses,23 the Journal of Obstetrics and Gynaecology Canada (JOGC),24
the American College of Obstetricians and Gynecologists (ACOG),25
26
and the Faculty of Sexual and Reproductive Healthcare (FSRH).
no competing interests, FSRH was the only guideline that did not
neglect to overtly mention the funding body of the guideline. IUSTI/
WHO and Mycoses declared that there was no funding body over
email. Overall, the FSRH guideline was of highest quality according
to AGREE II guidelines and IUSTI/WHO the lowest; however, IUSTI/
WHO, Mycoses, JOGC and ACOG all scored quite similarly.

Comparison of guideline quality Comparison of guideline recommendations

Analysis of each guideline using the AGREE II instrument showed
that there were marked differences in overall scores between the
guidelines (Table 2). While each guideline was viewed as high qual-
ity in terms of scope and purpose and clarity of presentation, they
all scored quite low in applicability. The failure to consider any re-
source implications of applying the guidelines and lack of any men-
tion of facilitators and barriers to each guideline application led
to these low scores. Editorial independence also scored poorly in
each guideline, excluding Mycoses and FSRH. Despite all guidelines
excepting IUSTI/WHO and ACOG declaring that their members had
Each guideline covered common areas such as the definition, di-
agnostic techniques, indications for therapy, approaches to man-
agement, treatments in pregnancy, risk factor management and
partner treatment of recurrent thrush. Similarities and ­differences
are outlined in detail below and are summarised in Table 3.
Definition
Each guideline classified recurrent thrush as being four episodes or
more per year. However, FSRH had a caveat to this diagnosis, stating
 4

T A B L E   3   A comparison of guidelines for recurrent thrush

IUSTI/WHO Mycoses JOGC ACOG FSRH

Definition Four or more sympto- Four or more sympto- Four or more symptomatic Four or more symptomatic Four or more symptomatic, mycologically
matic episodes per year matic episodes per year episodes per year episodes per year proven episodes per year
Diagnostic techniques
History ✓ ✓ ✓ ✓
Examination ✓ ✓ Erythema and oedema of ✓ ✓
vulvar and vaginal tissues in
conjunction with thick, white
clumped vaginal discharge
Culture ✓ ✓ ✓ ✓ ✓
Wet mount microscopy ✓ ✓ ✓ ✓ ✓
KOH microscopy ✓ ✓
Gram stain ✓ ✓ ✓
Whiff test ✓ ✓ ✓
pH measurement ✓ ✓ ✓ ✓
Nucleic acid amplification If at risk of STI
test
Indications for therapy Symptomatic and Candida Symptoms OR asympto- Only in conjunction with Only with symptoms
found on microscopy or matic colonisation symptoms.
culture
Approaches to management
Induction and mainte- ✓ ✓ ✓ ✓ ✓
nance therapy
Vulval moisturiser ✓
Ovulation suppressing ✓
progesterone
contraception
Treatments in pregnancy
Topical therapies ✓ ✓ ✓ ✓ ✓
Risk factor management
Exclusion of diabetes ✓ ✓
Exclusion of HIV/ ✓ ✓
immunodeficiency
Removal of IUDs ✓
Partner treatment Not recommended Not if asymptomatic. Not recommended

ACOG, American College of Obstetrics and Gynecology; FSRH, Faculty of Sexual and Reproductive Healthcare; HIV, human immunodeficiency virus; IUDs, intrauterine devices; IUSTI/WHO, International
Union against Sexually Transmitted Infections and the World Health Organization; JOGC, Journal of Obstetrics and Gynaecology Canada; KOH, potassium hydroxide; STI, sexually transmitted infection
Recurrent VVC: a guideline review
A. Matheson and D. Mazza5
that each episode of thrush can only be defined as such once it is my-
cologically proven. The reason for this was not explicitly mentioned.
Diagnostic techniques
All guidelines, excepting JOGC that only mentioned examination,
agree that a thorough history and physical examination is neces-
sary, but not sufficient to diagnose VVC. It is agreed by all that a
culture and wet mount microscopy is paramount to the correct di-
agnosis of recurrent VVC, although the recommendations for other
tests are not unanimous. For example, a potassium hydroxide
microscopy was suggested as an alternative to a wet preparation
only in Mycoses and ACOG. The other three guidelines made no
such proposal, but they did all encourage the use of Gram staining.
ACOG’s mention of Gram staining was only in reference to its help-
fulness in diagnosing bacterial vaginosis. Furthermore, the use of
the ‘whiff test’ as a means to rule out other potential diagnoses was
recommended in JOGC and ACOG alone. There is also quite a broad
range of suggestions when it comes to assessing the pH in patients;
Mycoses states it can be done ‘if necessary’ (although neglects to
mention what features might make a case necessary), JOGC and
FSRH state a reading of less than 4.5 supports the diagnosis of VVC,
IUSTI/WHO says all pH ranges can be found in women with VVC
and therefore it is not diagnostic, and ACOG simply states that it
should be performed. The final investigation mentioned is nucleic
acid amplification tests (NAAT). This is only recommended in the
FSRH guideline which states endocervical NAATs must be carried
out in the setting of recurrent infection to exlcude chlamydia and
gonorrhoea. Evidence levels were only provided for these recom-
mendations in IUSTI/WHO (level III, grade B), ACOG (microscopy as
first line -­ grade B) and FSRH (history is essential, recurrent infec-
tion necessitates high vaginal swab -­Good Practice Points).
Indications for therapy
Each guideline differs slightly on their recommendations for indica-
tions for therapy. Symptoms alone were reason enough to treat a
patient with VVC according to JOGC and ACOG, whereas IUSTI/WHO
specified that symptoms in conjunction with findings on ­microscopy
or culture should be treated. All agreed on not ­treating asympto-
matic individuals that have cultured Candida e
­ xcepting Mycoses.
T A B L E   4   Regimen comparison
Sobel14
Regimen 150 mg fluconazole weekly for six
months
Percentage illness free after 42.9%
12 months
Recommended by IUSTI/WHO, Mycoses, JOGC, ACOG, FSRH
ACOG, American College of Obstetrics and Gynecology; FSRH, Faculty of Sexual and Reproductive Healthcare; IUSTI/WHO, International Union
against Sexually Transmitted Infections and the World Health Organization; JOGC, Journal of Obstetrics and Gynaecology Canada
Approaches to management
Induction and maintenance therapy were recommended by every
guideline, with evidence stemming from a broad, but usually
common pool of references (IUSTI/WHO,12,14,29–31 Mycoses,14,32–34
JOGC,13,14,35,36 ACOG,12,37,38 FSRH14,39). These studies have all been
undertaken prior to the year 2008, are a mixture of randomised
controlled trials, prospective studies, other guidelines and one
meta-­analysis. The sample size of each study is typically small,
generally under 100 participants, although the largest study
does involve 556.37
Each guideline stated that an initial intensive therapy regi-
men should be followed by an oral antifungal weekly for six
months. Fluconazole was the most commonly recommended,
featuring in the Mycoses, JOGC, ACOG and FSRH guidelines.
IUSTI/WHO did not recommend any specific therapy; however,
they did reference several studies that use fluconazole, keto-
conazole or fluconazole and cetirizine in combination. All of
these studies report that 42.9% of women will be disease-­free
in 12 months,12,14,30 excepting the cetirizine/fluconazole com-
bination.31 This appears more effective but is only applicable
to women who have a history of allergies. Mycoses and JOGC
also stated that results were comparable between fluconazole,
clotrimazole and ketoconazole. JOGC offered boric acid inserts
as an appropriate maintenance alternative, with similar rates
of relapse (54.5% after six months).36 Mycoses provided an al-
ternative regimen using the Donders et al.32 treatment sched-
ule. This quotes greater success (77% with no recurrence after
12 months) and involves a year-­long process of gradually wean-
ing down oral fluconazole to provide remission (Table 4). ACOG
suggests 500 mg of topical clotrimazole weekly may be used but
only if the patients are ‘unable or unwilling’ to take oral fluco-
nazole. Specific induction therapies are only mentioned in JOGC,
which suggests either fluconazole, imidazole cream or a boric
acid insert.
The only advice outside of induction and maintenance therapy
comes from IUSTI/WHO, which suggest ‘giving permission’ to use
a vulval moisturiser due to dermatitis either being concomitant or
a possible differential diagnosis. Furthermore, they also suggest
an ovulation-­suppressing progesterone contraception may have
‘some benefit’.
Donders32
3 × 200 mg fluconazole in week one
If symptom free, fluconazole once a week from weeks 2–8
200 mg fluconazole every two weeks from months 3–6
200 mg fluconazole every four weeks from months 7–12
77%
Mycoses
6
T A B L E   5   A summary of recommendations
Summary of recommendations
• A woman has recurrent thrush when she has four or more
episodes in a 12 month period.
• Culture and wet microscopy is essential for diagnosis of
recurrent thrush
• Unless other diagnoses (STIs, BV) are suspected, other tests are
not required
• Asymptomatic colonisation does not require therapy
• Induction and maintenance therapy is the preferred treatment.
• Six months of weekly fluconazole is the most commonly
recommended. The suspected efficacy should be 42.9% after
12 months.
• An alternative is a year-long regimen where fluconazole is
gradually weaned from 200 mg three times a week during
week one, once a week from week two to eight, once a
fortnight from month three to six and once a month from
month seven to twelve. The suspected efficacy should be
77%.
• Topical therapy is recommended in the treatment of patients
who are pregnant.
• Diabetes and human immunodeficiency virus should be
excluded
• Partner treatment is not required
Treatments in pregnancy
Each guideline suggested that topical, rather than oral medica-
tions should be used in pregnancy. IUSTI/WHO suggested nys-
tatin pessaries, JOGC, ACOG and FSRH recommended external
imidazole creams, and all dissuaded the use of oral fluconazole in
particular due to its association with the congenital malformation
tetralogy of Fallot.
Risk factor management
Despite pregnancy, recent use of antibiotics, diabetes and HIV
being listed in all guidelines in varying combinations as predispos-
ing factors for developing VVC, only IUSTI/WHO and JOGC men-
tioned that tests should be performed excluding them. Mycoses
also mentions that intrauterine devices (IUD) should be removed as
Candida may attach to the IUDs containing levonorgestrel. There is
a study cited supporting this statement, but it is in German.
Partner treatment
Partner treatment is not recommended by the IUSTI/WHO,
Mycoses or FSRH. It is not mentioned by JOGC or ACOG.
DISCUSSION
Current guidelines on recurrent VVC are of mixed quality. This
is not related necessarily to the level of evidence supporting
them but concerns issues such as poor stakeholder involvement,
­applicability and editorial independence.
Recurrent VVC: a guideline review
There was commonality in the following areas: the defini-
tion of recurrent thrush, the use of cultures and wet mount mi-
croscopy for diagnosis and utilising induction and maintenance
therapy as the treatment of choice. Small differences do exist in
these overall similar recommendations; for example FSRH men-
tions recurrent thrush being defined as four or more episodes
per year, but unlike the other guidelines, it also specifies that
each episode must be mycologically proven. They do not offer a
level of evidence for this recommendation but perhaps it is the
lone guideline in making this recommendation because it may
increase costs and delay onset of treatment. Furthermore, the
guidelines that did not suggest ordering investigations to rule out
differential diagnoses and risk factors for developing recurrent
thrush may be failing to view the patient holistically. In guide-
lines that discuss other forms of vaginitis besides Candida22,24–26
investigations are segmented according to the condition.
However, in clinical practice the diagnosis may not be clear. This
makes it hard to apply recommendations for investigations as
they focus only on diagnosing VVC rather than ruling out other
causes of vaginitis.
Moreover, specific clinical practice recommendations were
rarely made for the induction part of treatment, which may
lead to inconsistencies between treating physicians. Research
has shown poor adherence by Australian clinicians to recurrent
VVC guidelines, choosing instead to tailor treatment to their
­patients due to lack of good evidence of effective treatments
to guide them.1
A significant difference in the guidelines was in their manage-
ment of risk factors. Only two guidelines22,24 supported exclud-
ing diabetes and HIV which is concerning considering the poor
success rate of treatment. Given this poor success rate in the
treatment of recurrent thrush, it is interesting to consider that
only one guideline (Mycoses23) suggested a regimen that had
greater success than the standard six months of anti-­fungals.
It cited the Donders et al.32 treatment schedule, which involves
a longer period of medications but apparently a much greater
remission rate; 77% compared to 42.9% after 12 months.14 It is
unclear why the other guidelines failed to refer to this strategy
but it may be the trial it comes from is quite small scale, that is
only 136 patients compared to 387 women in the fluconazole
trial.14
More extensive trials with a greater number of participants
may be required before international guidelines accept and inte-
grate findings into clinical practice. Indeed, Sobel’s approach of
using fluconazole for six months14 does not come from a large
study either. It may be more widely accepted by international
guidelines as it was published earlier and therefore may be more
trusted by clinicians despite its poorer clinical outcome.
The strength of this review is that the quality of the guide-
lines have been assessed. The limitation of this review is
the omission of non-­English language guidelines and also the
chance that ­
guidelines may not have been found with the
­selected search strategy.
A. Matheson and D. Mazza7
CONCLUSION
International guidelines for the treatment of recurrent thrush
are consistent. However, the suggested treatments are not par-
ticularly effective and a majority of women relapse following
the prescribed therapy. They do provide practitioners with clear
guidelines for diagnosis, but the question of duration of therapy
remains. Despite most guidelines agreeing on six months of oral
anti-­fungals as the appropriate treatment, the results from this
regimen are disappointing. A longer course may be appropri-
ate, but this is not yet supported by large-­scale studies. Further
­research is needed to address this issue.
AC K NO WL EDGEM E N TS
We would like to thank Rosie Latimer for assisting with the
­appraisal of each guideline.
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