1

BASHH Guideline on the Management of Vulvovaginal 1

Candidiasis (2018) 2

3

Clinical Effectiveness Group (CEG) 4

British Association for Sexual Health and HIV (BASHH) 5

6

Guideline Development Group 7

Cara Saxon (Lead Author), Anne Edwards, Riina Rautemaa-Richardson, Caroline Owen, Bavithra 8

Nathan, Bret Palmer, Clare Wood, Humera Ahmed, Sameena Ahmad, Patient Representatives (2), 9

Mark FitzGerald (CEG Editor) 10

11

New in the 2018 guidelines: 12

Terminology: 13

the new guidelines refer to ‘acute’, ‘recurrent’ and ‘chronic’ vulvovaginal candidiasis (VVC) and 14

no longer use the terms ‘uncomplicated’ and ‘complicated’ VVC; the new definitions are felt to 15

be more reflective of how women with VVC typically present to clinical services and are 16

subsequently managed 17

the elements of complicated VVC are still covered within the guideline 18

Diagnosis: 19

culture is no longer required in the setting of acute VVC 20

culture is still recommended for recurrent or chronic VVC with appropriate speciation and 21

sensitivity testing depending on clinical indication 22

greater emphasis has been placed on ensuring that other vulval pathologies are not missed in 23

the setting of possible recurrent or chronic VVC 24

interpretation of antifungal susceptibility testing is dependent on the pH at which the test is 25

performed 26

27

2

Treatment: 1

Oral azoles – continue to avoid in pregnancy, risk of pregnancy and breast feeding 2

Ketaconazole is no longer recommended for the treatment of VVC 3

Non-azole therapies to be reserved for azole resistance and certain non-albicans Candida species 4

Licensed nystatin pessaries are no longer available; various unlicensed brands of nystatin 5

pessaries are available but some are imported so the patient information leaflet may not be in 6

English and there have been intermittent supply issues 7

8

9

INTRODUCTION AND METHODOLOGY 10

Objectives 11

This guideline offers recommendations on the diagnostic tests, treatment regimens and health 12

promotion principles for the effective management of vulvovaginal candidiasis (VVC). It covers the 13

management of acute, recurrent and chronic VVC. 14

It is aimed at individuals aged 16 years and older (see specific guideline for under 16 year olds) 15

presenting to healthcare professionals working in departments offering level 3 care in sexually 16

transmitted infections (STIs) management within the UK. 17

However, the principles of the recommendations can be applied in other settings using local care 18

pathways where appropriate. Guidelines for the management of vaginal discharge in non-19

genitourinary medicine settings can be found at www.fsrh.org/guidelines. 20

21

Search strategy 22

This document was produced in accordance with the guidance set out in the CEG’s document 23

‘Framework for guideline development and assessment’ at http://www.bashh.org/guidelines. The 24

GRADE system was used to assess the evidence and make recommendations as detailed in the 25

guidance. 26

The following reference sources were used to provide a comprehensive basis for the guideline: 27

1. Medline, Embase, Cochrane and CINAHL Search 28

a. January 2007-August 2016+ 29

3

b. The search strategy comprised the following terms in the title or abstract: [Vagina* 1

OR vulva* OR vulvovaginal OR vulvo-vaginal OR vaginosis OR vaginitis OR vulvitis OR 2

thrush (NOT oral)] AND [Candida OR candidiasis OR candidosis OR yeast]. The search 3

was limited to English language and human subjects. 1412 citations were identified. 4

2. 2007 UK National Guidelines on the Management of Vulvovaginal Candidiasis. 5

+ The search period was extended to March 2018 during the peer review of first draft of the 6

guideline to identify any new relevant evidence. 7

8

Methods 9

The broad search terms used above were necessary given the various international terminology 10

used for VVC but resulted in a large number of citations (1412). 11

The article titles and abstracts of all 1412 citations were reviewed for relevance. Citations clearly 12

from animal studies, non-patient based studies, single case reports, studies in children, and 13

those on subjects not relevant to the diagnosis or management of VVC were excluded on first 14

review. 15

The titles and abstracts of the remaining citations (800) were reviewed by at least two members 16

of the writing group. Priority was given to randomised controlled trials, systematic review 17

evidence, and studies related to pertinent clinical questions to be addressed by the guideline. 18

The full texts of approximately 210 citations were obtained and reviewed using the GRADE 19

system by at least two members of the writing group. Recommendations were made and graded 20

on the basis of best available evidence. 21

22

Equality impact assessment 23

To be included in final publication 24

25

Piloting & feedback 26

The first draft was produced by the writing group and then circulated to BASHH CEG for using the 27

AGREE appraisal tool. The second draft of the guideline is posted on BASHH website for wider 28

consultation and simultaneously reviewed by the BASHH Public Panel. The final draft will be 29

presented to the CEG for review and piloting in their clinics. 30

4

Once the guideline is published to the BASHH website the CEG will keep it under review should 1

critical new evidence become available that affects the current recommendations. The guideline will 2

be formally reviewed and updated every 5 years. 3

4

5

DEFINITIONS 6

Acute VVC 7

first or single isolated presentation of vulvovaginal candidiasis (VVC) 8

patients typically present with signs and symptoms of acute vulvovaginitis and are usually 9

microscopy and culture positive for a Candida sp. 10

11

Recurrent VVC 12

at least 4 episodes per 12 months with 2 episodes confirmed on microscopy or culture when 13

symptomatic (at least one must be culture) 14

patients typically report good or complete responses to therapy and are asymptomatic between 15

episodes. 16

17

Chronic VVC 18

Patients present with chronic, continuous symptoms, which may improve during menses and 19

typically remit with antifungal therapy, often recurring when this is ceased, particularly after 20

short course therapy (usually but not always confirmed on microscopy or culture at 21

presentation), OR 22

recurrent episodes or chronic symptoms suggestive of VVC confirmed on microscopy or culture 23

whilst patients are symptomatic and reporting poor or partial response to therapy. 24

25

26

27

5

AETIOLOGY 1

Candidiasis is a fungal infection caused by yeasts that belong to the genus Candida. Yeasts are 2

eukaryotic, unicellular microorganisms which have the ability to develop multicellular characteristics 3

by forming pseudohyphae and biofilms. Candida yeasts are present in low numbers on healthy skin 4

in moist areas and are part of the normal flora of the mucous membranes of the respiratory, 5

gastrointestinal and female genital tracts; overgrowth of these organisms can cause infection to 6

develop. There are over 20 species that can cause infections in humans, of which Candida albicans is 7

the most common. Candida can also cause serious systemic infections, but these do not originate 8

from the genital tract infections. 9

Vulvovaginal candidiasis (VVC) is caused by: 10

Candida albicans in 80-89% 1, 2, 3 11

other Candida species or yeasts such as C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, 12

and Saccharomyces cerevisiae in the remainder 13

Despite the widespread availability of antifungal agents in the UK and other countries there has not 14

been a significant increase in azole resistance in C. albicans species or increased prevalence of non-15

albicans Candida species. 3-5 There remains conflicting evidence on the virulence of non-albicans 16

Candida species compared with C. albicans. 6, 7 17

An estimated 75% of women will have at least one lifetime episode of VVC, and 40%–45% will have 18

two or more episodes. 8 Previous studies have reported that approximately 5% of women of 19

reproductive age with a primary episode of VVC will develop recurrent disease. 9, 10 A large internet-20

based survey across five European countries (including the UK) and the US found that over 20% of 21

women reporting at least one episode of vaginal yeast infection also reported a 12-month period 22

with four or more infections. The probability of developing recurrent VVC after an initial infection 23

was 10% by the age of 25 years and 25% by the age of 50 years. 11 24

25

Risk factors and pathogenesis 26

Recurrent and chronic VVC are thought to be related to host factors rather than a more virulent 27

strain or the reintroduction of the organism to the genital tract. The majority are usually due to C. 28

albicans. 12 For many women an identifiable host factor is not found but can include: 29

persistence of Candida sp (as detected by PCR although culture-negative between attacks) 13 30

poorly controlled diabetes mellitus 31

6

immunosuppression 1

hyperoestrogenaemia (including HRT and the combined oral contraceptive pill) 14-18 2

recent (up to three months before the episodes) antibiotic use causing a disturbance in the 3

vaginal flora 14, 19, 20 4

Studies have also identified a link to allergy (allergic rhinitis, asthma and hay fever)17, 21 and pro-5

inflammatory genetic markers. However women suffering from allergic diseases are more likely to 6

have used corticosteroids, so it is unclear as to whether the steroid use, or concomitant atopic 7

disease makes them more susceptible. 17 Perceived increased stress and a lower mean cortisol 8

(which may correspond to chronic stress) have been weakly associated with recurrent VVC however 9

the evidence is limited and further research is required. 22 10

It is unclear if iron deficiency anaemia is associated with recurrent VVC. A previous study found no 11

evidence of low iron levels in women with VVC23 however a more recent study suggests a possible 12

link between iron deficiency anaemia and recurrent VVC. 24 The earlier study reported statistically 13

significant lower serum level of zinc, magnesium and calcium in patients with recurrent VVC, 14

although all levels were still within the normal range; other studies have not supported the link with 15

serum zinc levels. 23, 25 16

Mannose binding lectin (MBL) deficiency is genetic condition that affects the immune system. 17

Several studies have shown that MBL codon 54 gene polymorphism is associated with recurrent and 18

acute VVC. In particular, possessing the MBL variant allele B heterozygous genotype increases the 19

susceptibility of women to recurrent or acute VVC compared to healthy controls, while the risk of 20

recurrent VVC is also increased for women carrying the allele B homozygote genotype. 26-28 21

22

23

CLINICAL FEATURES 24

Vulvovaginal candidiasis (VVC) typically presents with: 29-33 25

vulval itch and 26

a non-offensive vaginal discharge 27

28

Other symptoms can include: 29, 32-34 29

soreness or burning 30

7

superficial dyspareunia 1

cyclical symptoms 2

3

Clinical signs may include: 29-34 4

erythema 5

fissuring 6

swelling/oedema 7

vaginal discharge typically non-offensive and curdy but may be thin or absent 8

there may also satellite lesions and excoriation marks 9

10

None of these features are pathognomonic for VVC and there can be a significant discrepancy 11

between symptoms and signs particularly in chronic disease. 34, 35 Although Candida albicans is the 12

most pathogenic of the Candida species clinical symptoms or signs cannot be used to guide which 13

Candida sp is the cause for the infection. 35, 36 Health-related quality of life both physical and 14

psychological is significantly affected in recurrent VVC. 32 15

16

Differential diagnoses and colonisation 17

Many women (more than half of self-diagnosed women in one study 37) presenting with these 18

symptoms may have other conditions such as: 19

o dermatitis/eczema 20

o lichen sclerosus 21

o other infections 22

o vulvodynia 23

the preponderance of certain symptoms and signs, whilst not pathognomonic can be more 24

suggestive of other conditions (table 1 and 2) 25

it should also be noted that some women may have dual pathology with VVC and one of these 26

other conditions 27

up to 20% of women during reproductive years may be colonized with Candida spp. but have no 28

clinical signs or symptoms; 38,39 these women do not require treatment 29

8

it is also possible that women with vulval symptoms due to other conditions (such as eczema, 1

lichen sclerosus) may have colonization with Candida which is not necessarily contributing to the 2

symptoms. 3

4

DIAGNOSIS 5

Vulvovaginal candidiasis (VVC) is a clinical diagnosis based on typical features supported by 6

laboratory confirmation of Candida sp. from a vaginal sample 7

In women presenting with clinical features of acute VVC to a service providing level 3 STI care 8

supporting the diagnosis with routine microscopy is good clinical practice 35, 40-45 (Grade 1B) 9

(figure 1) 10

Recurrent or chronic VVC is defined as four or more symptomatic episodes over a 12-month 11

period; at least two of these episodes should be confirmed by microscopy or culture, one of 12

these should be a positive culture with moderate or heavy growth of Candida sp. 46-49 (Grade 1C) 13

14

Clinical examination and syndromic management 15

Clinical examination of the external genitalia is recommended in women presenting with 16

symptoms suggestive of acute VVC in order to exclude alternative or co-existing vulvovaginal 17

pathologies 18

Women presenting with features suggesting recurrent or chronic VVC should always have a 19

clinical examination 50 (Grade 1C) 20

Empirical treatment for acute VVC based on the reported symptoms may be given in non-21

specialist settings 51; if the symptoms do not resolve, or if they recur, examination and 22

microbiological testing (as below) should be performed 50 23

24

Microscopy 25

A vaginal swab taken from the anterior fornix 52 (Grade 1C) for Gram stain and/or dark field wet 26

film microscopy 27

Presence of spores, pseudohyphae and neutrophils is indicative of infection caused by Candida 28

species 29

Presence of spores only and neutrophils may reflect infection caused by C. glabrata 30

9

Neutrophils in vaginal secretions suggest an inflammatory response and therefore presence of 1

infection which may or may not be due to Candida seen on microscopy. Absence of neutrophils 2

in the presence of Candida is likely to represent colonisation. 3

4

Culture 5

Acute VVC: 6

fungal culture is no longer considered a cost-effective addition to microscopy nor a reliable test 7

on its own for the diagnosis of VVC due to its inability to differentiate colonisation from infection 8

9

Recurrent or chronic VVC: 10

a vaginal swab should be taken from the anterior fornix 52 (Grade 1C) for direct plating onto solid 11

fungal growth medium (Sabouraud plate) 12

any fungal growth should ideally be identified to species level, or at least as C. albicans/non-13

albicans Candida 46-49 (Grade 1B) and sensitivity to fluconazole tested 14

mixed infection with C. albicans and a non-albicans Candida species are not rare and should be 15

sought for in the laboratory 16

in cases of recurrent or chronic VVC with poor or partial response to therapy, full speciation and 17

sensitivity testing to fluconazole, clotrimazole, flucytosine, amphotericin B and nystatin is 18

preferred 19

of note clotrimazole is broader spectrum and used at higher concentrations than fluconazole so 20

fluconazole susceptibility cannot be used as a marker for clotrimazole resistance 21

where clinical examination is not possible or required self-collected vaginal swab for microscopy 22

and or culture is a reasonable alternative to clinician taken samples 53 (Grade 1C) 23

self-collected swabs done at home can be considered in recurrent or chronic VVC where initial 24

samples collected in clinic have come back negative 54, 55 (Grade 2C) 25

for patients reporting poor or partial response to sensitivity guided antifungal therapy a negative 26

post-treatment fungal culture (implying mycological cure) indicates the need to consider 27

alternative or additional diagnoses with similar clinical features. 28

29

10

Interpretation of anti-fungal sensitivity testing 1

It is useful to know that standard in vitro susceptibility testing for Candida spp. is performed at 2

pH 7.0 because the activity of most azole antifungals is significantly decreased in acidic 3

environment 4

in cases of VVC, the vaginal pH is usually in the range of 4 to 4.5, therefore, isolates with 5

elevated MICs are unlikely to respond to standard doses of azole treatment despite still 6

designated as susceptible: 7

o e.g. C. glabrata has variable intrinsic resistance to azole antifungals and their marginal 8

efficacy is lost at pH 4.5 9

if standard neutral pH is used for susceptibility testing caution is needed when interpreting the 10

results as standard breakpoints may not apply. 56 (Grade 1B) 11

12

Molecular and point of care testing for VVC 13

A number of studies have looked at molecular and rapid antigen detection point of care tests for 14

Candida. 57-59 There are significant differences between the tests and their sensitivity and specificity 15

when compared with the agreed standard of care (microscopy and culture). Some tests are highly 16

sensitive and unable to differentiate between colonization and infection. Further research and 17

evaluation of cost-effectiveness is required before any recommendations can be made regarding 18

their use in level 3 STI services. 19

20

STI screening 21

VVC is not a sexually transmitted infection (STI) or a marker for STIs. The offer of STI screening 22

should be based on a risk assessment and consideration that some of the clinical features of VVC are 23

similar to those of STIs. For comprehensive guidance on screening for STIs please refer to the 2015 24

BASHH CEG group guidance on tests for STIs [https://www.bashhguidelines.org/media/1084/sti-25

testing-tables-2015-dec-update-4.pdf]. 26

27

28

29

30

11

MANAGEMENT 1

General advice for all women with VVC symptoms 2

Patients should also be provided with information about the importance of good skin care: 3

avoiding the use of local irritants such as perfumed soaps or wipes 4

the use an emollient cream for personal hygiene as a soap substitute, as a moisturiser and a 5

barrier cream (patient needs to be informed that this does not constitute “internal use”). 6

7

General advice for recurrent and chronic VVC 8

In patients with recurrent or chronic VVC careful review of their daily hygiene routine may identify 9

potential local irritants not perceived as such by the patient for example washing hair in bath water 10

or excessive cleaning. (grade 2D) No genital hygiene practices have been definitively linked with 11

recurrent or chronic VVC however a number have shown weak associations which may be worth 12

considering in certain patients: 13

wearing of tight fitting synthetic clothing 14, 60, 61 (grade 2C) 14

using intermenstrual or daily panty liners 61-64 (grade 2C) 15

vaginal douching 20, 61, 65, 66 (grade 2C) 16

Vulval emollients may give symptomatic relief as vulval dermatitis (eczema) both primary and 17

secondary is commonly present. 18

An association between sexual intercourse and Candida colonisation levels or vaginal symptoms has 19

not been identified although there is a paucity of research in this area. 67 Patients reporting a link 20

between symptoms and sexual activity may wish to consider the use of a gentle water-based 21

lubricant. (grade 2D) 22

23

Further Investigation 24

No additional investigations are routinely recommended in patients presenting with acute VVC 25

unless clinically indicated. 26

In recurrent or chronic VVC screening for the following conditions may be considered particularly if 27

there are additional indicators: 28

diabetes with urinalysis or random blood glucose (grade 2C) 29

12

iron-deficiency anaemia with a full blood count or serum ferritin (grade 2C) 1

mannose binding lectin deficiency* (grade 2B) 2

3

*Some women with recurrent VVC can spend considerable time searching for answers as to why 4

they are affected by the condition often trialing extreme lifestyle measures to reduce symptoms. 5

Identifying MBL deficiency or the MBL 54 gene polymorphism may help a patient better understand 6

their condition, offer additional reassurance and reduce the need for significant lifestyle changes 7

that can impact on quality of life and are unlikely to improve symptoms. Additionally, patients with 8

the B allele polymorphism have been found to have an improved response to a reducing 9

maintenance regimen with fluconazole therapy. 27 (grade 2C) 10

11

12

TREATMENTS 13

Acute VVC 14

Treatment choice: 15

Studies and data published over the past 10 years on the treatment of acute vulvovaginal candidiasis 16

(VVC) support the treatment regimen recommended in the 2007 guidelines: 17

all intravaginal imidazoles and oral azoles give a clinical and mycological cure rate of over 80% in 18

acute VVC 68, 69 (Grade 1B) 19

intravaginal imidazoles and oral azoles are equally effective and tolerable in the management of 20

acute VVC with no difference in treatment outcomes 69-72 (Grade 1B) 21

recommended and alternative regimens have been made for this guideline update based on 22

differences in cost and convenience of dosing: 23

o Fluconazole 150mg stat PO is the recommended treatment for acute VVC due to 24

comparative cost and convenience of the stat dose (7-30 times cheaper than all other 25

listed regimens; current UK prices June 2018) 26

o Clotrimazole 500mg pessary PV stat is the recommended topical treatment when an oral 27

imidazole is contraindicated, due to comparative cost (with other topical agents) and 28

convenience of the stat dose (current UK list prices June 2018) 29

13

one RCT suggested that a single dose of oral fluconazole may be more effective than prolonged 1

intravaginal clotrimazole 200mg (for 6 days) at clinical cure at 7 days. 70 (Grade 1C) 2

3

Treatment considerations: 4

oral therapies must be avoided in pregnancy, risk of pregnancy and breast feeding 39, 60, 69 (Grade 5

1B) 6

oral azoles also prolong the QT time and caution should be taken if prescribed in combination 7

with other drugs with a similar effect 8

as there is minimal absorption of topically applied imidazoles from the vulvo-vaginal mucosae 9

there is limited risk of systemic side effects 10

topical therapies can cause vulvovaginal irritation and this should be considered if symptoms 11

worsen or persist 12

intravaginal and topical treatments can also damage latex condoms and diaphragms with case 13

reports of unplanned pregnancies 70; women must be appropriately counselled about this risk 14

a medication history should be taken to advise women that oral fluconazole and other azoles as 15

can interact with medications; fluconazole is a potent inhibitor of cytochrome P450 (CYP) 16

isoenzyme 2C9 and a moderate inhibitor of CYP3A4O 17

18

Nystatin preparations give a 70-90% cure rate in the setting of acute VVC. 39 There is insufficient 19

evidence to show a significant difference between intravaginal imidazoles and nystatin pessaries in 20

the treatment outcomes. There is data showing that intravaginal nystatin is well tolerated with cure 21

rates comparable to fluconazole. 73 One study showed that boric acid was cheap and tolerable to use 22

in the treatment of acute VVC. 74 However: 23

both nystatin and boric acid are unlicensed drugs and should be reserved for the management 24

of infections caused by azole resistant Candida strains. 25

26

Recommended regimen: 27

Fluconazole* capsule 150mg stat PO (1B) 28

29

14

Recommended topical regimen (if oral therapy contraindicated): 1

Clotrimazole pessary 500mg stat PV** (1B) 2

3

Alternative regimens: 4

Clotrimazole vaginal cream (10%) 5g stat** (1B) 5

Clotrimazole pessary 200mg nocte for 3 days or 100mg nocte for 6 days** (1C) 6

Econazole pessary 150mg stat or 150mg nocte for 3 days** (1B) 7

Fenticonazole pessary 600mg stat or 200mg nocte for 3 nights** (1B) 8

Itraconazole 200mg bd for 1 day PO* (1B) 9

Miconazole pessary 100mg nocte for 14 nights** (1B) 10

11

* Oral therapies must be avoided in pregnancy, risk of pregnancy and breast feeding 39, 60, 69 (Grade 12

1B) 13

**Creams and pessaries may damage diaphragms and latex condoms. 14

15

Recurrent VVC 16

The principle of therapy involves an induction regimen to ensure clinical remission, followed 17

immediately by a maintenance regimen: 18

Fluconazole 150mg every 72 hours for 3 doses followed by 150mg weekly for a six-month period 19

has been shown to have good efficacy and tolerability in two randomized control trials achieving 20

clinical remission in 82-90% 75 (Grade 1A) 21

Fluconazole reduced the frequency of recurrent VVC in 88% immediately after the cessation of 22

therapy, 64% at 3 months after and 61% at 6 months after the end of treatment 75 23

when oral therapy needs to be avoided 500 mg of intravaginal clotrimazole administered weekly 24

may used as an alternative (Grade 1B) 25

there is no evidence for the superiority of itraconazole over fluconazole and microbiological 26

cross-resistance is common whereby it is not likely to be helpful in clinically fluconazole-resistant 27

cases 28

15

if a patient relapses between doses consider twice-weekly 150mg fluconazole or 50mg 1

fluconazole daily; (Grade 2C)alternatively consider the addition of cetirizine 10mg od 76 2

there is a low risk of idiosyncratic drug-induced hepatitis with oral azoles, although fluconazole is 3

less frequently associated with hepatotoxicity than itraconazole (see later ‘Reactions to 4

treatment’); the production of Ketaconazole has stopped globally due to toxicity. 5

6

There are no trials addressing the optimal duration of suppressive therapy with the majority of trials 7

using 6 months maintenance as standard: 8

if recurrences after maintenance regimen are infrequent, each episode should be treated 9

independently 10

if recurrent disease is re-established the induction and maintenance regimens should be 11

repeated (Grade 2C) 12

13

One study achieved clinical remission in 90% of women at 6 months and 77% of women at 12 14

months using an individualized reducing regimen of fluconazole. 77 However it is not clear how this 15

strategy compares to the standard 6 month regimens. A study comparing these strategies is 16

required before recommendations on reducing regimens can be made. 17

18

Recommended Regimen: 19

Induction: fluconazole 150mg every 72 hours x 3 doses* (1A) 20

Maintenance: fluconazole 150mg once a week for 6 months* (1A) 21

22

Alternative Regimens: 23

Induction: topical imidazole therapy can be increased to 10-14 days according to 24

symptomatic response(Grade 2C) 25

Maintenance for 6 months: 26

o Clotrimazole pessary 500mg once a week (1B) 27

o Itraconazole 50-100mg daily*(2C) 28

29

16

* Oral therapies must be avoided in pregnancy, risk of pregnancy and breast feeding 39, 60, 69 (Grade 1

1B) 2

3

Chronic VVC 4

Patients reporting chronic, continuous symptoms, which may improve during menses and remit with 5

antifungal therapy have only recently been recognized as having a distinct condition to recurrent 6

VVC 33: 7

symptoms often recur when therapy is stopped, particularly after short course therapy 8

management is often challenging and further research into appropriate treatment strategies and 9

duration is needed 10

general advice should be given as above 11

suppressive treatment regimens such as those recommended for recurrent VVC should be 12

trialed 13

rescue doses of antifungal therapy during antibiotic courses may be considered, especially if this 14

was a known previous precipitant of flares 33 (Grade 2C) 15

refer patients in this category to specialized vulval services. 16

17

One retrospective study of 208 patients found long-term maintenance regimens of fluconazole or 18

itraconazole were well tolerated in women with chronic VVC (mean duration of follow up 26.2 19

months; range 5 months to 8.5 years). 78 A study comparing maintenance regimens and durations is 20

required before specific recommendations can be made. 21

It’s important to note that patients reporting recurrent episodes or chronic symptoms of VVC with 22

poor or partial response to therapy may have a non-albicans Candida species and/or azole 23

resistance. A sustained resolution of symptoms may be achievable for these patients with the 24

correct treatment following species identification with antifungal sensitivity testing. 25

26

27

28

29

17

Non-albicans Candida species and azole resistance 1

Candida albicans is normally susceptible to all yeast-active antifungals although resistance may 2

rarely develop on prolonged or repeated azole treatment courses; resistance to other yeast-3

active antifungals is very rare 4

the most common non-albicans Candida species causing vulvovaginitis are Candida glabrata and 5

Candida krusei: 6

o these can be the sole cause of infection or in combination with C. albicans 7

o most vaginal C. glabrata strains are reported as susceptible to azoles 79 but with 8

elevated MICs and often with poor clinical response to standard dose treatment 9

o Candida krusei is intrinsically resistant to fluconazole 80 10

some non-albicans Candida species such as C. guilliermondii and C. parapsilosis are normally 11

susceptible to azoles and patients clinically respond to treatment with these 12

for an infection caused by an azole resistant Candida species longer courses are advised 13

although there is no data on optimum duration; two weeks is suggested 14

for isolates with an elevated MIC but still designated susceptible, higher and more frequent 15

dosing of fluconazole may be effective (200-300 mg od over 48 hrs for 1 week) 16

17

Treatment options and availability: 18

Nystatin pessaries are the only licensed alternative to azole therapy and are therefore the usual first 19

line treatment for non-albicans Candida infection. (Grade 1B) Unfortunately the licensed nystatin 20

product is no longer available (March 2018). Various unlicensed brands of Nystatin pessaries are 21

available but some are imported so the patient information leaflet may not be in English and there 22

have been intermittent supply issues. An alternative would be local pharmacy production of 23

Amphotericin B vaginal suppositories 50mg once a day for 14 days which is has a 70% success rate 24

but there can also be sourcing difficulties. 80(Grade 2C) 25

Boric acid vaginal suppositories 600mg daily for 14 days are a safe and effective alternative. 79, 82 26

(Grade 1B) If mucosal irritation occurs the dose can be reduced to 300mg daily (additional cost likely 27

as it needs to be compounded specially). 83 There may be a teratogenic risk so boric acid should be 28

avoided in pregnancy or risk of pregnancy. 84 29

Intravaginal flucytosine (5g cream or 1g pessary) either alone 79, 85 or with amphotericin 5, 85 to reduce 30

the chances of resistance (for which there is a low genetic barrier) can also be used for two weeks. 31

(Grade 2C) 32

18

In patients with recurrent or chronic VVC due to fluconazole resistant Candida species, 14 days of 1

nystatin pessaries a month for 6 months has been shown to be effective and is more likely to 2

achieve mycological cure than fluconazole regimens. 86 (Grade 2C) There is no evidence for the 3

treatment protocols for the alternative treatment options but it would seem reasonable to consider 4

extrapolating this suggested regimen of 14 days a month for 6 months to the alternative options. 5

(Grade 2D) 6

There are no studies where the efficacy and tolerability of these drugs has been compared. Where 7

there is reduced sensitivity increasing the dose or combining topical and oral agents may be 8

beneficial. 9

10

Recommended Regimen: 11

Nystatin pessaries 100,000units nocte for 14 days (1B) 12

13

Alternative Regimens: 14

Boric acid suppositories 600mg daily for 14 days* (1B) 15

Amphotericin B vaginal suppositories 50mg once a day for 14 days (2C) 16

Flucytosine 5g cream or 1g pessary +/- amphotericin daily for 14 days (2C) 17

18

Recurrent or chronic VVC due to azole resistant Candida: 19

Nystatin pessaries 100,000units nocte for 14 days/month for 6 months (2C) 20

Consider 14 days per month for 6 month of the alternative regimens (2D) 21

22

*Avoid in pregnancy or risk of pregnancy 23

24

Severe Vulvovaginal Candidiasis 25

In patients with severe VVC (i.e., extensive vulvar erythema, oedema, excoriation, and fissure 26

formation) 87 regardless of a history of recurrence, fluconazole 150mg should be repeated after 27

three days as this improves symptomatic response but does not influence the risk or rate of 28

recurrence. 88 (Grade 1B) There is no benefit of a seven day topical treatment course over a single 29

19

oral dose of fluconazole. 89 If oral treatment is contra-indicated it is more logical to repeat a single 1

dose pessary after three days. Two doses of clotrimazole 500mg vaginal tablet or miconazole nitrate 2

vaginal suppository 1,200 mg were as effective as two doses of an oral fluconazole 150 mg regimen 3

in the treatment of patients with severe VVC. 90, 91 (Grade 1B). Due to significant differences in cost 4

fluconazole is the recommended regimen. 5

6

Recommended regimen: 7

Fluconazole 150mg on day 1 and 4 (1B) 8

9

Alternative regimens: 10

Clotrimazole 500mg tablet or pessary on day 1 and 4 (1B) 11

Miconazole nitrate vaginal suppository 1200mg on day 1 and 4 (1B) 12

13

Low-potency corticosteroids are also thought by some experts to improve symptomatic relief in 14

conjunction with adequate antifungal therapy. 92 (Grade 2D) 15

16

Pregnancy & Breastfeeding 17

Asymptomatic colonization with Candida species is more common (30-40%) 15 and symptomatic 18

candidiasis is more prevalent throughout pregnancy 19

oral therapies must be avoided in pregnancy, risk of pregnancy and breast feeding 39, 60, 69 (Grade 20

1B) 21

topical imidazoles should be used for symptomatic VVC in pregnancy and breast feeding (Grade 22

1B) 23

there is no evidence that any one topical imidazole is more effective than another 24

longer courses are recommended in pregnancy; a four day course will cure just over 50% 25

whereas a seven day course cures over 90%. 93 (Grade 1B) 26

27

28

20

Fluconazole in pregnancy 1

Given the conflicting evidence we continue to advise against the use of fluconazole and other oral 2

azoles in pregnancy (Grade 1B): 3

there is accumulating evidence that that treatment with fluconazole in the first trimester does 4

not appear to increase the overall risk of congenital malformations although one study reported 5

a possible link with tetralogy of Fallot 94 6

the United States National Birth Defects Prevention Study (NBDPS) found associations between 7

fluconazole use in the first trimester of pregnancy with cleft lip with cleft palate and d-8

transposition of the great arteries although overall fluconazole use in the NBDPS was low 95 9

a nationwide register-based cohort study in Denmark (1997-2013) with a cohort of 1405500 10

pregnancies found a statistically significant increased risk of spontaneous abortion in women 11

exposed to fluconazole between 7-22 weeks gestation compared with risk among unexposed 12

women and women with topical imidazole exposure in pregnancy. 96 13

14

VVC and pregnancy outcome 15

Previous studies did not find evidence of an association between Candida colonization and 16

premature delivery or low birth weight (BASHH 2007 26, 27) 17

Currently there is very limited evidence around the significance of detecting asymptomatic VVC 18

in pregnancy and the theoretical risk of pre-term birth or low birth weight; in the absence of well 19

designed studies we are not in a position to make specific recommendations. 97-99 20

21

Recommended regimens (Acute VVC): 22

Clotrimazole pessary 500mg PV nocte for 7 days (1B) 23

24

Alternative regimens (Acute VVC): 25

Clotrimazole vaginal cream (10%) 5g nocte for 7 days** (1C) 26

Clotrimazole pessary 200mg or 100mg nocte for 7 days** (1C) 27

Econazole pessary 150mg nocte for 7 days** (1C) 28

Fenticonazole pessary 600mg stat or 200mg nocte for 7 days** (1C) 29

21

Miconazole pessary 100mg nocte for 14 nights** (1C) 1

2

Recommended regimen (Recurrent/Chronic VVC): 3

Induction: topical imidazole therapy can be increased to 10-14 days according to symptomatic 4

response(Grade 2C) 5

Maintenance: Clotrimazole pessary 500mg weekly (1C) 6

7

Breastfeeding: 8

Treatment regimens using topical imidazoles only should be as per the recommendations listed 9

above for non-pregnant women with acute, recurrent and chronic VVC. 10

11

Alternative or Supplementary Treatments 12

Proven benefit: 13

Antihistamines: 14

o Zafirlukast 20mg bd for 6 months may induce remission. 100 15

o Zafirlukast may be considered as maintenance prophylaxis for recurrent VVC, 16

particularly in women with a history of atopy76 17

o Cetirizine 10mg daily for 6 months may cause remission in women who fail to get 18

complete resolution of symptoms with suppressive fluconazole. 76(Grade 1C) 19

20

Insufficient or no evidence of benefit: 21

Probiotics: there continues to be insufficient evidence to support the use of oral or vaginal 22

probiotics (mainly Lactobacilli) for the treatment or prevention of VVC: 23

o An increasing number of studies suggest that their adjunctive use may improve clinical 24

outcomes or reduced the likelihood of recurrence 70, 101, 102 25

o However, the quality of evidence is variable and inconsistent in terms of the probiotic or 26

regimen used 103, 104 27

22

o the mode of action might be via modulation of inflammatory processes rather than 1

competition with Candida. 105 2

Tea tree and other essential oils: are antifungal in vitro but they may cause hypersensitivity 3

reactions. 70, 106 There is insufficient evidence to recommend use in recurrent VVC. 70 4

Dermasilk® briefs: are made of a pure fibroin fabric impregnated with a permanent 5

antimicrobial protection. Small studies have shown a reduction in itching, burning, erythema and 6

recurrences than cotton briefs in women with recurrent VVC on a standard fluconazole 7

suppressive regimen. 107 8

Yoghurt and honey mixes: there is insufficient evidence to support the use of vaginal 9

applications of yoghurt and honey mixes although there have been some reports of benefit with 10

symptom improvement. 109, 110 11

Diet:there is no evidence to support any dietary modifications, including reducing carbohydrate 12

or yeast intake. 92, 108 13

Oral garlic: there is no evidence of benefit from oral garlic on Candida colonization. 111 14

Observational studies have shown that garlic taken orally may cause heartburn, nausea, 15

diarrhoea, flatulence, bloating, and an offensive body odour. 70 16

17

Diabetes Mellitus 18

Symptomatic VVC is more prevalent in diabetic women and most problematic in those with poor 19

glycaemic control. Non-albicans Candida species are more prevalent than in non-diabetic women, in 20

particular C. glabrata. 112-114 21

In diabetic women with symptomatic VVC where C. albicans is isolated single-dose fluconazole 22

(150mg) gives a similar response to non-diabetics. 113(Grade 1C) In diabetic women with 23

symptomatic VVC due to C. glabrata treatment with boric acid 600mg intravaginal suppository once 24

a day for 14 days achieved a higher mycological cure rate at 15 days compared to fluconazole 25

150mgs stat. 115 (Grade 1B) 26

27

Recommendations: 28

Known diabetic women with poor glycaemic control should be encouraged to improve this 29

23

Fluconazole 150mg stat dose for confirmed C. albicans in diabetic women with acute VVC 1

(1C) 2

Boric acid 600mg intravaginal suppository once a day 14 for confirmed C. glabrata in 3

diabetic women with acute VVC (1B) 4

5

HIV Infection 6

VVC occurs more frequently and with greater persistence in HIV-infected women. 116, 117 Increased 7

HIV shedding in the vagina, plasma HIV load above 1000 copies/mL, CD4 lymphocyte count below 8

200 cells/mm3 and the absence of antiretroviral therapy (ART) have been associated with an 9

increased risk of symptomatic VVC. 29, 117 There is no evidence to suggest that HIV-infected women 10

respond less well to conventional methods than HIV-negative women. Treatment for HIV-infected 11

women should be as for HIV-negative women following the recommendations above including the 12

use of suppression therapy as necessary. 118 (Grade 1C) 13

It is important to state that VVC is not a risk factor in the acquisition of HIV. 119 14

15

Recommendation: 16

Treatment regimens for HIV-positive women should be the same as for HIV-negative women 17

(1C) 18

Please refer to www.hiv-druginteractions.org.uk to check for drug interaction between 19

antifungals and antiretrovirals. 20

21

Hormones and Contraception 22

In immunocompetent women there is a strong link between Candida and hormonal status. This is 23

evidenced by Candida species only being found in pubertal/post pubertal and not pre-pubertal 24

females. 120 Also postmenopausal women taking HRT are significantly more prone to develop VVC 25

than women who are not and those with VVC are likely to have been susceptible to it before 26

menopause. 18 27

There is some evidence that combined oral contraceptive (COC) users may have an increased risk of 28

VVC however there are inconsistencies with some studies not finding an association and the quality 29

of the evidence is mixed.119, 121 Women with recurrent or chronic VVC using the COC may wish to 30

24

trial alternative contraception but should be cautioned that the evidence supporting the association 1

between the COC and VVC is weak. (Grade 2C) 2

There is limited evidence for the progestogen-only injection with one systematic review identifying 3

four studies with conflicting results (two found no difference in VVC compared with controls, one 4

found a significant decreased risk and one found a significant increased risk of VVC). 119 There is no 5

available evidence regarding the progestogen-only pill or implant or vaginal rings in relation to VVC. 6

While there is some evidence of higher rates of Candida infection in copper intrauterine device (Cu-7

IUD) and levonorgestrel intrauterine system (LNG-IUS) users, other studies show an increase in 8

Candida present but no difference in symptomatic cases. 122-125 9

10

Recommendations: 11

HRT is associated with an increased risk of VVC 12

Women with recurrent or chronic VVC using the COC may wish to trial alternative 13

contraception but should be cautioned that the evidence supporting the association 14

between the COC and VVC is weak (2C) 15

Cu-IUD/LNG-IUS users with recurrent or chronic VVC may wish to consider an alternative 16

method of contraception* (2C) 17

18

*The Cu-IUD and LNG-IUS are highly effective methods of contraception particularly the Cu-IUD in 19

patients unable to tolerate hormonal methods. Removal of either device should only be considered 20

if a suitably effective alternative can be used. A careful risk-benefit assessment should be made 21

taking into consideration that keeping the Cu-IUD or LNG-IUS and controlling the recurrent VVC 22

symptoms may be a more appropriate option for some patients. 23

24

Reactions to Treatment 25

The most common treatment-related adverse events reported in the patients who received 150 26

mg single dose fluconazole for VVC were headache, nausea, and abdominal pain. 27

anaphylaxis has been reported rarely with fluconazole and itraconazole 28

there is a low risk of idiosyncratic drug-induced hepatitis with oral azoles; fluconazole is less 29

frequently associated with hepatotoxicity than itraconazole 30

25

oral azoles also prolong the QT time and caution should be taken if prescribed in combination 1

with other similar drugs 2

topical azole therapies and other topical agents can cause vulvovaginal irritation and this should 3

be considered if symptoms worsen or persist. 4

5

6

FOLLOW-UP 7

Follow-up and test of cure for patients with acute VVC is unnecessary if symptoms resolve. 8

Patients with recurrent or chronic VVC should be advised to return if they experience poor or 9

partial response to therapy; repeat microscopy and culture is indicated to assess for 10

microbiological cure or new resistance 11

Patients that demonstrate microbiological response but not clinical response to therapy should 12

be reassessed for alternative causes of their symptoms 13

On completion of suppressive therapy patients should be advised about the management of 14

future acute episodes (as per acute VVC) and when to return for review (e.g. if frequency of 15

recurrence >4 episodes per year or acute symptoms don’t settle with treatment). 16

17

18

CONTACT TRACING & TREATMENT 19

There is no evidence to support the treatment of asymptomatic male sexual partners in any of 20

acute, recurrent or chronic VVC. 126-129 (Grade 1A) 21

22

23

CONSIDERATION OF RESOURCE IMPLICATIONS 24

It is acknowledged that some tests, e.g. for the precise speciation of Candida, may not be able in 25

all settings 26

Some treatment preparations, e.g. flucytosine cream, may not be available on local formularies. 27

It is advised that such preparations are discussed with the unit pharmacist prior to prescribing. 28

26

QUALIFYING STATEMENT 1

The recommendations in this guideline may not be appropriate for use in all clinical situations. 2

Decisions to follow these recommendations must be based on the professional judgement of the 3

clinician and consideration of individual patient circumstances and available resources. 4

All possible care has been taken to ensure the publication of the correct dosage of medication and 5

route of administration. However, it remains the responsibility of the prescribing physician to ensure 6

the accuracy and appropriateness of the medication they prescribe. 7

8

9

AUDITABLE OUTCOMES 10

Fluconazole used first line for acute VVC in non-pregnant women and women with no evidence 11

of pregnancy risk. Target 97%. 12

All women with recurrent or chronic VVC to be offered a genital examination performed by an 13

appropriately trained clinician. Target 97% 14

All women with suspected recurrent or chronic VVC should have microscopy and/or culture with 15

full speciation and sensitivity testing for at least 2 (of the ≥4 per year) episodes (including at 16

least one culture). Target 97%. 17

Documentation of a discussion around the offer of suppressive or alternative long term therapy 18

for all women with proven recurrent and chronic VVC. Target 97% 19

Documentation of a discussion about what constitutes good vulval skin care for all women with 20

recurrent or chronic VVC. Target 97% 21

22

23

RECOMMENDATIONS FOR FUTURE RESEARCH 24

Further assessment of sensitivity and specificity of molecular and rapid antigen detection point 25

of care diagnostic tests and the value of their use in a service providing level 3 STI care 26

Appropriate regimen and duration of therapy for women that have a recurrence of symptoms 27

after completing 6 months of treatment for recurrent or chronic VVC 28

27

Further assessment of the benefit of treating asymptomatic colonization with Candida in 1

pregnancy on pregnancy outcome 2

3

4

ACKNOWLEDGEMENTS 5

Stephen Woods (Deputy Library Manager, Academy Library, Wythenshawe Hospital, Manchester 6

University Hospitals NHS Foundation Trust, Manchester, UK) for performing the literature searches 7

and obtaining full text articles for review. 8

Two patient representatives from clinics of the writing group reviewed the first draft of the 9

guideline. They provided feedback from their perspective as a patient, in particular looking at: 10

treatment preferences 11

ensuring the guideline covers all issues important to patients 12

the language of the guideline is appropriately respectful to patients (acknowledging the 13

intended audience is healthcare professionals). 14

15

16

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17

18

EDITORIAL INDEPENDENCE 19

This guideline was commissioned, edited and endorsed by the BASHH CEG. 20

21

22

CONFLICTS OF INTEREST 23

All members of the guideline writing committee completed the BASHH conflict of interest 24

declaration at the time the guideline’s final draft was submitted to the CEG. 25

26

27

WRITING GROUP AFFILIATIONS 28

Cara Saxon (Lead Author): Consultant Physician in Genitourinary Medicine, Withington Clinic, 29

Manchester University Hospitals NHS Foundation Trust, Manchester, UK 30

37

Anne Edwards: Consultant Physician in Genitourinary Medicine, Oxford University Hospitals NHS 1

Foundation Trust, Oxford, UK 2

Riina Rautemaa-Richardson: Consultant in Medical Mycology, Wythenshawe Hospital, Manchester 3

University Hospitals NHS Foundation Trust, Manchester, UK 4

Caroline Owen: Consultant Physician in Dermatology, East Lancashire Hospitals NHS Trust, 5

Blackburn, UK 6

Bavithra Nathan: Consultant Physician in Genitourinary Medicine, Kingston Hospital NHS Foundation 7

Trust, Kingston-upon-Thames, UK 8

Bret Palmer: Specialty Trainee in Genitourinary Medicine, Oxford Deanery, UK 9

Clare Wood: Specialty Trainee in Genitourinary Medicine, North Western Deanery, UK 10

Humera Ahmed: Pharmacist, Manchester, UK 11

Sameena Ahmad: Consultant Physician in Genitourinary Medicine, Withington Clinic, Manchester 12

University Hospitals NHS Foundation Trust, Manchester, UK 13

Patient Representatives (see acknowledgments) 14

Mark FitzGerald: Clinical Effectiveness Group Editor 15

16

17

MEMBERSHIP OF THE CLINICAL EFFECTIVENESS GROUP 18

Dr Keith Radcliffe (Chair) 19

Dr Mark FitzGerald 20

Dr Deepa Grover 21

Dr Steve Higgins 22

Dr Margaret Kingston 23

Dr Michael Rayment 24

Dr Darren Cousins 25

Dr Ann Sullivan 26

Dr Helen Fifer 27

Dr Craig Tipple 28

38

Dr Sarah Flew 1

Dr Cara Saxon 2

39

Table 1. Clinical Features of Vulvovaginal Candidiasis and Common Differential Diagnoses – Symptoms* 1

Vulvovaginal Candidiasis Lichen Sclerosus Vulvo- / vestibulodynia

Contact Dermatitis/Eczema

Chronic Lichen Simplex/Chronic Eczema

Vulval Itch Yes Yes, severe No Yes Yes

Vulval soreness Yes – but not always; ‘prickling’

Yes, severe Burning is predominant symptom

Yes Possible

Discharge Yes - odourless, typically ‘curdy’ but may be thin or absent (absence doesn’t exclude diagnosis)

No+ No+ Possible, but this is exudate from inflamed skin, not a true discharge

No+

Superficial Dyspareunia

Possible Yes (especially if loss of vulval architecture)

Yes – point penetration pain

Possible Possible

Superficial dysuria

Possible Possible Not usually Possible Not usually

Swelling Possible No No Possible Possible (secondary to lichenification – thickening of skin from chronic scratching)

Response to topical steroid

Improvement/no change/worse

Improvement but requires high potency

No Improvement Improvement

* the symptoms and signs listed in this table are not pathognomic of the conditions but an indication of a ‘typical clinical presentation’ and to highlight the potential 2 differences and similarities between each of these conditions, further information about the alternative conditions listed can be found at www.bad.org.uk “ 3 + unless dual pathology 4

5

40

Table 2. Clinical Features of Vulvovaginal Candidiasis and Common Differential Diagnoses – Signs* 1 2

VV Candidiasis Lichen Sclerosus Vulvodynia Contact Dermatitis Chronic Lichen Simplex

Erythema Yes Yes but usually in conjunction with other features

Possible Yes Possible

Fissuring Possible Possible No Possible Possible

Discharge Yes - odourless, typically ‘curdy’ but may be thin or absent (absence doesn’t exclude diagnosis)

No+ No+ Possible, but this is exudate from inflamed skin, not a true discharge

No+

Oedema Possible No No Possible Possible

Other features Satellite lesions Pallor, atrophy, loss of vulval architecture, areas of haemorrhage, introital narrowing

Cotton tip provoked tenderness

Erythema, exudate Lichenification, (thickening of affected skin caused by long term scratching)

Excoriations (scratch marks)

Possible Possible No Often Often

* the symptoms and signs listed in this table are not pathognomic of the conditions but an indication of a ‘typical clinical presentation’ and to highlight the potential 3 differences and similarities between each of these conditions, further information about the alternative conditions listed can be found at www.bad.org.uk “ 4 + unless dual pathology 5

6

41

Table 3. Vulvovaginal candidiasis treatment options 1

Preferred Alternative

Acute VVC

Non-pregnant women

Fluconazole 150mg PO stat (1B) If oral therapy is contraindicated: Clotrimazole 500mg PV stat (1B)

Clotrimazole vaginal cream (10%) 5g stat** (1B)

Clotrimazole pessary 200mg nocte for 3 days or 100mg nocte for 6 days**

(1C)

Econazole pessary 150mg stat or 150mg nocte for 3 days** (1B)

Fenticonazole pessary 600mg stat or 200mg nocte for 3 nights** (1B)

Itraconazole 200mg bd for 1 day PO* (1B)

Miconazole pessary 100mg nocte for 14 nights** (1B)

Pregnancy Clotrimazole pessary 500mg PV nocte for 7

days (1B)

Clotrimazole vaginal cream (10%) 5g nocte for 7 days** (1C)

Clotrimazole pessary 200mg or 100mg nocte for 7 days** (1C)

Econazole pessary 150mg nocte for 7 days** (1C)

Fenticonazole pessary 600mg stat or 200mg nocte for 7 days** (1C)

Miconazole pessary 100mg nocte for 14 nights** (1C)

NAC sp & azole

resistance

Nystatin pessaries 100,000units nocte for

14 days (1B)

Boric acid suppositories 600mg daily for 14 days* (1B)

Amphotericin B vaginal suppositories 50mg once a day for 14 days (2C)

Flucytosine 5g cream or 1g pessary +/- amphotericin daily for 14 days (2C)

Recurrent or Chronic VVC

Non-pregnant women

Induction: fluconazole 150mg every 72 hours x 3 doses* (1A) Maintenance: fluconazole 150mg once a week for 6 months* (1A)

Induction: topical imidazole therapy can be increased to 10-14 days according

to symptomatic response(Grade 2C) Maintenance for 6 months: Clotrimazole pessary 500mg once a week (1B) or Itraconazole 50-100mg daily*(2C)

Pregnancy Induction: topical imidazole therapy can be increased to 10-14 days according to symptomatic response(Grade 2C) Maintenance: Clotrimazole pessary 500mg weekly (1C)

NAC sp & azole

resistance

Nystatin pessaries 100,000units nocte for

14 days/month for 6 months (2C)

Consider 14 days per month for 6 month of the alternative regimens (2D)

Severe VVC

Fluconazole 150mg on day 1 and 4 (1B)

Clotrimazole 500mg tablet or pessary on day 1 and 4 (1B)

Miconazole nitrate vaginal suppository 1200mg on day 1 and 4 (1B)

Breast feeding

Treatment regimens using topical imidazoles only should be as per the recommendations listed above for non-pregnant women with acute,

recurrent and chronic VVC.

NAC – Non-albicans Candida; * Oral therapies must be avoided in pregnancy, risk of pregnancy and breast feeding (1B); **Creams and pessaries may damage diaphragms and latex condoms. 2

42

Figure 1. Summary of the Vulvovaginal Candidiasis diagnostic and management pathway 1

2

Acute VVC

Chronic VVC

1st line: Fluconazole 150mg PO stat; 2nd line: Clotrimazole 500mg PV*

Microscopy & HVS for fungal culture, identification and sensitivity testing for fluconazole

Presentation Diagnostics Therapy

Recurrent VVC

Microscopy & HVS for fungal culture, identification and sensitivity testing for fluconazole, clotrimazole, flucytosine, amphotericin B and nystatin

100,000 IU nystatin pessaries for 14 nights*

Fluconazole resistant Candida

Fluconazole susceptible Candida

Consider alternative or additional diagnoses (lichen sclerosus, vulval pain syndromes, etc)

Suppressive therapy with induction (150mg 3x/week) then weekly 150mg fluconazole for 6 months*

Azole resistant Candida

Nystatin resistant Candida

600mg boric acid pessaries for 14 nights*

Microscopy for spores/hyphae (in level 3 GUM setting)

*See relevant section for more detail and other treatment options