Guideline vulvovaginal candidosis (2010) of the german society for gynecology and obstetrics, the working group for infections and infectimmunology in gynecology and obstetrics, the german society of dermatology, the board of german dermatologists and the german speaking mycological society
Diagnosis,Therapy and Prophylaxis of Fungal Diseases
Guideline vulvovaginal candidosis (2010) of the german society forgynecology and obstetrics, the working group for infections andinfectimmunology in gynecology and obstetrics, the german societyof dermatology, the board of german dermatologists and the germanspeaking mycological society
Prof. Dr. med. Werner Mendling, Vivantes – Klinikum im Friedrichshain and Am Urban, Clinics for Obstetrics and Gynecology (2011 retired), 10249 Berlin,Landsberger Allee 49Prof. Dr. med. Jochen Brasch, University Hospitals of Schleswig – Holstein, Campus Kiel, Department of Dermatology, Venerology and Allergology,Schittenhelmstrasse 7, 24105 Kiel, Germany
Candida (C.) species colonize the estrogenized vagina in at least 20% of all women. Thisstatistic rises to 30% in late pregnancy and in immunosuppressed patients. The mostoften occurring species is Candida albicans. Host factors, especially local defense deficiencies, gene polymorphisms, allergic factors,serum glucose levels, antibiotics, psychosocial stress and estrogens influence the riskfor a Candida vulvovaginitis. In less than 10% of all cases, non-albicans species,especially C. glabrata, but in rare cases also Saccharomyces cerevisiae, cause avulvovaginitis, often with fewer clinical signs and symptoms. Typical symptoms include premenstrual itching, burning, redness and non-odorousdischarge. Although pruritus and inflammation of the vaginal introitus are typicalsymptoms, only less than 50% of women with genital pruritus suffer from a Candidavulvovaginitis. Diagnostic tools are anamnesis, evaluation of clinical signs, the microscopicinvestigation of the vaginal fluid by phase contrast (400 x), vaginal pH-value and,in clinically and microscopically uncertain or in recurrent cases, yeast culture withspecies determination. The success rate for treatment of acute vaginal candidosis is approximately 80%. Vaginal preparations containing polyenes, imidazoles and ciclopiroxolamine or oraltriazoles, which are not allowed during pregnancy, are all equally effective. C. glabratais resistant to the usual dosages of all local antimycotics. Therefore, vaginal boric acidsuppositories or vaginal flucytosine are recommended, but not allowed or available inall countries. Therefore, high doses of 800 mg fluconazole ⁄ day for 2–3 weeks arerecommended in Germany. Due to increasing resistence, oral posaconazole2 · 400 mg ⁄ day plus local ciclopiroxolamine or nystatin for 15 days was discussed. C. krusei is resistant to triazoles. Side effects, toxicity, embryotoxicity and allergy are notclinically important. A vaginal clotrimazole treatment in the first trimester ofpregnancy has shown to reduce the rate of preterm births in two studies. Resistance of C. albicans does not play a clinically important role in vulvovaginalcandidosis. Although it is not necessary to treat vaginal candida colonization in healthy women, itis recommended in the third trimester of pregnancy in Germany, because the rate oforal thrush and diaper dermatitis in mature healthy newborns, induced by thecolonization during vaginal delivery, is significantly reduced through prophylaxis. Chronic recurrent vulvovaginal candidosis requires a ‘‘chronic recurrent’’ suppressiontherapy, until immunological treatment becomes available. Weekly to monthly oral
Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13
fluconazole regimes suppress relapses well, but cessation of therapy after 6 or12 months leads to relapses in 50% of cases. Decreasing-dose maintenance regime of200 mg fluconazole from an initial 3 times a week to once monthly (Donders 2008)leads
immunological trials. Probiotics should also be considered in further studies. Over the counter (OTC) treatment must be reduced.
microscopic investigation (400fold phase contrast) ofthe vaginal fluid. In doubtful, in recurrent or in
A MedLine ⁄ PubMed research with the term ‘‘vulvova-
complicated cases a yeast culture with species determi-
ginal candidosis’’ resulted in 2886 titles and limited to
nation is necessary. Serological blood tests are not
‘‘vulvovaginal candidosis therapy studies’’ resulted in
recommended (Level of evidence (LoE) 1b, Grade of
237 reviews (2 ⁄ 2010). All were screened for title and
abstract, but very few of the recent studies were
3.2 Treatment of an acute vulvovaginal candidosis is
randomized and ⁄ or conducted as prospective controlled
possible with polyenes, imidazoles or ciclopiroxolamine
trials (Fong 1992, Quereux et al. 2000, Upmalis et al.
in the form of vaginal tablets, suppositories or creams
2000, Lowe, Neal and Ryan-Wenger 2004, Sobel et al.
and with skin cream for the vulva, or with oral triazoles
2004, Meyer, Go¨ttlicher and Mendling 2006, Donders
with a treatment duration of 1–6 days. All clinical and
et al. 2008). There were 3 meta-analyses or Cochrane
mycological treatment results are similar.
analyses (Pitsouni, Iavazzo and Falagas 2008, Watson
An asymptomatic colonization needs not to be
et al. 2002, Young and Jewell 2001) and two guidelines
treated, if there is no immunosuppression or chronic
(Mendling and Seebacher 2008, Bond et al. 2003). The
recurrent vulvovaginal candidosis. (LoE 1a, GoR A).
rating in level of evidence and strength of recommen-
For treatment of vaginal colonization during preg-
dation was performed according to Abrams, Khoury and
3.3 Treatment of chronic recurrent Candida albicans
vulvovaginitis involves – due to a lack of a causal
immunological treatment – suppressive intermittentantimycotic treatment over a period of months with
Vulvovaginal candidosis is an infection of the estroge-
an oral triazole. The best results are obtained with the
nized vagina and the vestibulum, which can extend to
fluconazole regime described by Donders et al. (table 4)
the outside of the labia minora, the labia majora and the
intercrural region. A candidosis of the cervix or the
3.4 Common vaginal or oral treatments fail in C.
endometrium is not known. Connatal fetal candidosis
glabrata vaginitis. Therefore, vaginal boric acid 600 mg
and a candida amnionitis are rare events.
capsules for 14 days, amphotericin B suppositories, vag-
The terminus ‘‘vulvovaginal candidosis’’ or ‘‘Candida
inal 17% flucytosine or oral 800 mg fluconazole ⁄ day for
albicans vulvovaginitis’’ are recommended (Odds et al.
2–3 weeks are recommended (LoE 2a, GoR B). Posaco-
1992), The ending ‘‘- iasis’’ should be used for parasitic
nazole 2 · 400 mg ⁄ day in combination with local
infections (e. g. trichomoniasis). (Loeffler 1983), but is
ciclopiroxolamine and ⁄ or nystatin for 15 days have been
also frequently used and accepted in the English
successfully used in Germany recently. C. krusei vaginitis
is resistant to oral triazoles and should therefore be treatedwith local clotrimazole ⁄ imidazoles (or boric acid, which isnot allowed in Germany) (LoE 2b, GoR B).
3.5 There is a German recommendation for local
3.1 The diagnosis of vulvovaginal candidosis is always a
antimycotic treatment of vaginal Candida colonization
combination of clinical signs and symptoms and the
during the last 6 weeks of pregnancy to inhibit vertical
presence of yeasts, which is usually performed by
transmission to healthy, mature babies during vaginal
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German guideline vulvovaginal candidosis 2010
delivery. Neonatal Candida infection rates of more than
hematooncology and is thus often mentioned also in
10% in the 2nd to the 4th weeks are shown to be
gynecology (Walker et al. 2000, Sobel et al. 2004,
significantly reduced (LoE 2a, GoR B).
There is evidence for different genotypes of C. albicans
strains in asymptomatic women and in those with acute
Candida albicans is able to form blastospores, pseud-omycelia, true mycelia and chlamydospores. Candia
Blastospores use usually formed in colonized women
Due to estrogenization of the vagina (Dennerstein and
and together with (pseudo–) mycelia in vaginitis
Ellis 2007) and estrogen receptors of C. albicans (Powell
patients (Mendling 2006, Sobel 2007).
1984, Tarry et al. 2005) premenarchal girls and
85–95% of the colonizing vaginal Candida species in
postmenopausal women are less frequently vaginally
colonized and therefore do not usually suffer from
healthy women and in women with acute Candida
Candida vaginitis. Approximately 20–30% of healthy,
vaginitis are Candida albicans, whereas non-albicans
non pregnant and premenopausal women are vaginally
species, especially C. glabrata, are more frequent in
colonized (by culture methods), while at least 30% of
postmenopausal, in diabetic and in immunosuppressed
pregnant women in the third trimenon and immuno-
women (Odds 1988, Goswami et al. 2000, de Leon et al.
deficient women are colonized (Odds 1988, Mendling,
2002, Corsello et al. 2003, Paulitsch et al. 2006,
Niemann and Tintelnot 2007) (Tables 1-2). Vaginal
Goswami et al. 2006, Mendling, Niemann, and Tintel-
colonization can change individually over time, how-
not 2007) (Tables 1 and 2). There are regional differ-
ever: in a one year longitudinal cohort study with 1248
ences in the distribution of Candida species.
asymptomatic healthy young women, 70% had once
C. krusei, C. guilliermondii, C. tropicalis, C. parapsilosis
been colonized, but only 4% of them were colonized at
and others can cause a vulvovaginitis with typical
all visits, which took place every 3 months. Risk factors
symptones (Spinillo et al. 1995, Singh et al. 2002,
included recent sexual intercourse, injection of medr-
Nyirjesy et al. 2005, Mendling et al. 2007, Sobel 2007).
oxyprogesteronacetate and concurrent colonization
Saccharomyces cerevisiae is rarely able to cause vaginal
with lactobacilli and B-streptococci (Beigi et al. 2004).
symptoms (Sobel 1993, Mendling 2006), but is identi-
The partnerÕs sperm can also be colonized by the
fied in about 1–2% of cultures (Mendling et al. 2007,
identical Candida strain found in the vagina (Mendling et
al. 1998), although the partner is free of symptoms.
Ranging between 80–95%, Candida albicans is also the
Candida prostatits is a very rare event seen only in
most frequent yeast in chronically recurrent vulvova-
immunosuppressed men (Golz and Mendling 1991,
ginal candidosis, with small regional differences (Sobel
Sobel, Fischer and Kauffman 2010). Nonetheless, the
role of the partnerÕs genital colonization or the orointes-
There is no evidence of an increase of non – albicans
tinal colonization of both partners as source of recurrence
species in either acute or in recurrent vaginal candido-
of recurrent Candida vaginitis is not clear (Sobel 2007).
sis, although this has been proven in intensive care and
The step from colonization to vaginitis is not well
understood and appears to involve underlying host
Table 1 Candida colonization of the vagina in healthy women
factors (Fidel 2005). As infection is colonization plus
disposition, (‘‘Candidosis is an illness of the ill’’),especially immunosuppressed people develop candidos-
es. Nonetheless 75% of obviously healthy women
develop a vaginal candidosis once in their lifetime, and
probably up to 10% of them experience more than four
episodes per year (chronic recurrent vulvovaginal
candidosis ⁄ CRVVC) (Corsello et al. 2003, Sobel 2007).
The first step from colonization to infection is the
attachment of the Candida cell to the vaginal wall
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Table 2 Distribution of vaginal Candida species in HIV-negative colonized women (Mendling et al. 2007).
Table 3 Distribution of Candida species in 472 cases of acute
‘‘virulent’’, more women with type 2 diabetes are
vaginal candidosis in Poland and Germany (Mendling et al. 2004).
colonized than healthy women (de Leon et al. 2002,Ray et al. 2007), which underlines the importance of
Diabetic patients suffer more frequently from vaginal
candidoses, and treatment fails, if the serum glucose
levels are not normalized (Bohanna 1998).
Modern oral contraceptives with low estrogen levels,
which do not significantly influence the carbohydrate
metabolism (Gaspard et al. 2003), do not increasevaginal Candida colonization, (Davidson and Oates
through mannoproteins (Sobel et al. 1981, Farrell,
1985) or the frequency of infection rates (Foxmann
Hawkins and Ryder 1983, Thrumbore and Sobel 1986).
1990). Some results do contradict this finding, however
The most important virulence factors are probably
the secreted aspartate proteinases (SAP 1–10) and
Vaginal colonization rates are higher in women with
proteases which are secreted especially from the top of
a well estrogenized vagina, especially during pregnancy.
germinating pseudomycelia (Ru¨chel, Fegeler and Trost
Women, who are already vaginally colonized by
1982, de Bernardis et al. 1990, Naglik et al. 2004) and
Candida, have up to a 33% risk of developing Candida
correlate with pathogenicity (Cassone et al. 1987,
vaginitis after antibiotic treatment (Eckert et al. 1998,
Pirotta et al. 2003, Pirotta and Garland 2006, Xu et al.
Iron binding by host cells through siderophores
(Ismail and Lupan 1986, Ghannoum and Abu-El Teen
Candida albicans can also form an adherent biofilm at
1990), a strong pH-tolerance from 2 to 11 (Meinhof
the surface of intrauterine devices (Auler et al. 2010,
1974) and enzymes, which enable C. albicans to survive
in macrophages, are also important virulence factors
Although vaginal candidosis often occurs in women
with normal lactobacillus flora, lactobacilli have beenfound in lower numbers, when women have vaginalcandidosis (Auger and Joly 1980). The potential
protective role of lactobacilli or their special strains
As Candida strains and species differ in pathogenicity,
against yeast infections is not yet understood. Coexis-
candidosis develops due to the Candida strain and to
tence of bacterial vaginosis and vaginal candidosis is
weakened local defense mechanisms (de Bernardis et al.
rare and occurs in about 5% of cases.
Sobel underlines the probably underestimated role of
An impaired tolerance for glucose was found in about
sexual behaviour for the recurrence of vaginal candidosis
25% more women with CRVVC than in controls
(Sobel 2007), suggested by repeated infections following
(Donders et al. 2002). Although C. glabrata is less
sexual intercouse (Eckert et al. 1998, Reed et al. 2003).
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German guideline vulvovaginal candidosis 2010
Table 4 Individualized decreasing – dose maintencance fluconaz-
development of the clinical symptoms, especially redness
ole regime for recurrent Candida albicans vulvovaginitis (Donders et
and itching (Witkin et al. 2000, Sobel 2007).
Women with a history of recurrent Candida vaginitis
express immunologically important vaginal heat shockproteins in the symptom-free interval (Geraldo et al.
Psychosocial stress is also an important risk factor for
Candida vulvovaginitis (Meyer et al. 2006, Ehrstro¨met al. 2007), probably by causing immunosuppression. But vice versa recurrent vaginal candidoses have a
significant negative impact on work and social life
(Birkner et al. 2005, Nyijesy et al. 2006).
Due to the estrogen-induced conditions, premenopausalwomen suffer primarily from vaginal candidosis which
can extend to the vulva, while postmenopausal womenonly suffer from a vulva and ⁄ or intercrural candidosis.
The clinical symptoms typically occur premenstrually
due to higher sugar levels in the vagina after the
In approximately 90%, pruritus is the most typical,
but not reliable symptom, because only 35–40% ofwomen with itching have a Candida vaginitis (Anderson,
Klink and Cohrsson 2004, Mendling, Niemann, and
Discharge can vary from a thin fluid often at the
beginning of an acute vaginal candidosis to cottage-
cheese-like or no discharge at all (Spacek et al. 2005).
From clinical and treatment aspects, the classification of
although (pseudo-)hyphae, which are mentioned as adistinguishing factor, are not found in all cases ofuncomplicated candidosis.
There is vaginal redness, soreness, burning, dyspa-
reunia and dysuria. Symptoms alone do not allowpatients or clinicians to confidently distinguish betweencauses of a vaginitis, but a lack of itching and
inflammation makes vaginal candidosis less likely
(Anderson, Klink and Cohrssen 2004). In contrast to
bacterial vaginosis there is no unusual odour. The labiaminora can be swollen, and burning fissures can occurespecially in recurrent cases.
Last but not least, genetic factors are responsible for
Dermatologists differentiate vesiculopustulous, ecze-
recurrences since mannose-binding lectin gene poly-
matoid and follicular forms of vulvar candidosis (Mendling
morphisms (Babula et al. 2005, Donders, et al. 2008)
and the blood group ABO-Lewis non-secretor phenotype
An adherent white layer of discharge can be seen on
(Chaim et al. 1997) have been identified as risk factors.
the vaginal wall in serious cases, which can cause
Women with atopic dermatitis more frequently
develop vaginal candidosis (Neves et al. 2005) and
The rare Candida glabrata vaginitis, which usually
allergic phenomena are found to be important for the
occurs in the late pre- and the perimenopausal decades
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(Mendling 1984, Sobel 1998, Spinillo et al. 1995, Fidel
this superficial vaginal disease does not cause significant
et al. 1999), Candida krusei vaginitis (Singh et a. 2002),
Candida parapsilosis vaginitis (Nyirjesy et al. 2005), and,as a rare event, Saccharomyces cerevisiae vaginitis (Sobel
1993, Mendling 2006, Savini et al. 2008) are associ-ated with mild clinical symptoms.
There are many conventional and alternative therapies
Polyenes form complexes with ergosterole of the yeast
cell wall and thus change its permeability (Scheklakow
The diagnosis of a vaginal candidosis always involves a
Azoles inhibit the transformation of lanosterole to
combination of anamnesis, clinical signs and symptoms
ergosterole in the yeast cell wall (Plempel 1980).
Ciclopiroxolamine inhibits probably important iron-
dependent enzymes through chelate formation (Nie-werth et al. 2003).
Patients often prefer oral treatment, if they are given
Clinical anamnesis, gynaecological examination, pH
measurement and microscopic investigation of thevaginal fluid with 10% potassium hydroxide or saline
solution of the vaginal fluid (400fold phase contrast) arediagnostically essential. Budding cells or (pseudo-)
Asymptomatic, vaginally colonized women do not
hyphae can be detected in only 50–80% of patients
require treatment, if they are immunocompetent and
with vaginal candidosis (Mu¨ller et al. 1981, Sobel
the candidosis is not chronically recurrent.
2007). The vaginal white blood cell count may be, butneeds not be elevated. Unfortunately there is a lack of
experience and teaching in many hospitals and privatepractices around the world (Donders 2001, Ledger et al.
Nearly all healthy, mature neonates, who were colo-
nized by their mothers Candida during vaginal delivery,
If no blastospores or (pseudo-)hyphae are seen
develop oral thrush and diaper dermatitis during their
microscopically and in chronic recurrent or complicated
first year with a peak of 10–13% in the 2nd to 4th weeks
cases, a species identification by culture is necessary
of life (Blaschke – Hellmessen 1968, 1998).
(Nyirjesy et al. 1995, Eckert et al. 1998, Mendling
In Germany prophylactic treatment of asymptomatic
vaginal Candida colonization is recommended in the last
Routine cultures are not necessary, if yeasts are found
weeks of pregnancy to protect the baby during vaginal
delivery. This significantly reduces the risk of neonatal
The typical culture medium is Sabouraud agar, but
candidosis from more than 10% to only about 2% in the
there are other suitable media commercially available,
4th week of life (Schnell 1982, Blaschke-Hellmessen
for example Chrom Agar, Microstix – Candida and
A retrospective randomized (Czeizel and Rocke-
It is possible, that two different Candida species will be
nbauer 1999, Czeizel, Fladung and Varga 2004, Hay
cultured in one candida vaginitis, for example C. albicans
and Czeizel 2007, Czeizel, Puko and Kazy 2007) and a
and C. glabrata. The patient suffers in such a case from a
prospective randomized (Kiss, Petricevic and Husslein
C. albicans vaginitis. After treatment, C. glabrata (resis-
2004) study surprisingly showed a decrease in preterm
tant!) remains in situ, only colonizing the vagina, and
deliveries after a vaginal treatment with clotrimazole
in the first trimester, which requires further investiga-tion.
Serological tests are not useful for the diagnosis ofvulvovaginal candidosis because low antibody levels
Acute vulvovaginal candidosis can be treated topically
can be found in most women with or without vaginal
with polyenes (Nystatin, Amphotericin B or Pimaricin)
candidosis due to intestinal colonization and because
or imidazoles (clotrimazole, miconazole nitrate, econaz-
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German guideline vulvovaginal candidosis 2010
ole nitrate, fenticonazole nitrate, sertaconazole nitrate,
Clinical resistance does not correlate to laboratory
tioconazole nitrate, terconazole nitrate and others)
MIC tests and vice versa, a well known problem in
(Mendling 1988, Sobel 2007), or with ciclopiroxol-
Therefore, MIC – tests are usually not recommended
Oral treatment with the imidazole ketoconazole (no
longer typically used in Germany) or with the triazolesfluconazole or itraconazole or others is also possible.
There are vaginal suppositories or vaginal creams
with dosages and formulations for treatment durations
Common vaginal and oral treatments usually fail in
varying from one to three to six or seven days without
Candida glabrata vaginitis. Sobel et al. (2003) therefore
recommend vaginal boric acid 600 mg capsules for
All mycological and clinical success rates are equal
14 days, while Philips (2005) recommends amphoter-
and range between approximately 85% after 1 to
icin B suppositories. In particularly persistent cases a
2 weeks and 75% after 4 to 6 weeks after the end of
two week course of topical treatment with 17% flucy-
treatment (Cohen 1985, Mendling, Krauss and Fladung
tosine has been shown to be successful in 90% of cases
2004, Sobel 2005, Nurbhai et al. 2007, Pitsouni et al.
Boric acid is not allowed in Germany and other
Cure rates during pregnancy are significantly better
countries and vaginal flucytosine is not available there.
with imidazoles than with polyenes (Young and Jewell
High daily doses of 800 mg fluconazole for 2–3 weeks
are therefore recommended in Germany according to
If the candidosis involves an area of the vulva outside
resistance tests (Kunzelmann et al. 1996, Mendling and
the introitus or the inguinal region, the application of
Seebacher 2008). There is an increasing failure rate
an antimycotic skin cream twice daily treatment for up
associated with this treatment. Tietz (2009) therefore
A ‘‘blind’’ treatment of the asymptomatic sexual
within 30 minutes of a high fat meal in combination
partner is of no benefit for the patient (Buch and Skytte-
with local ciclopiroxolamine and ⁄ or nystatin for
Christensen 1982, Bisshop et al. 1986, Sobel 2007).
15 days, which had been proven effective. Because thistreatment regime is very expensive and is normallyreserved for life - threatening mycoses, it is not accepted
All topically applied antimycotics are well tolerated, but
C. krusei vaginitis is resistant to fluconazole and
topical azoles and ciclopiroxolamine can cause local
flucytosine, but topical clotrimazole or other imidazoles
burning in 1–10% of cases (Mendling 1988, Mendling,
or boric acid are mostly successful (Singh et al. 2002).
Krauss, and Fladung, 2004). Allergic reactions are
Due to the rareness of cases, systematic studies are
The oral imidazole ketoconazole can cause side effects
in about 5% of cases, for example headaches and non-
10.7. Chronically recurrent C. albicans vulvovaginitis
viral hepatitis in 1 of 500000 to 1000000 gynecolog-ical patients (Cauwenberg 1984).
Since infection is colonization + disposition and no
The hydrophilic fluconazole and the lipophilic itrac-
therapy against disposition (immunological local in-
onazole cause fewer side effects due to the inhibition of a
compentence) exists, local or oral maintenance thera-
yeast-selective cytochrome P450 – dependend enzyme,
pies to prevent relapses are recommended (Davidson
but like ketoconazole, however, they are not recom-
and Mould 1978, Sobel 1985, Roth et al. 1990, Sobel
Whether topical clotrimazole 500 mg, oral ketozo-
nazole 100 mg or fluconazole 150 mg were given, the
results were comparably effective, but recurrence occurs
Although vaginal Candida albicans strains with higher
in half of the patients shorty after cessation of the
minimum inhibitory concentrations (MIC) to fluconaz-
therapy (Sobel 1985, Sobel et al. 2004). In a placebo -
ole can be found (Richter et al. 2005), cases of
controlled trial involving 387 women randomly
azoleresistance are rare in gynecology (Mathema et al.
assigned to treatment groups receiving 150 mg fluco-
nazole weekly for 6 months, the percentages of disease
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free women after 12 months were 42.9% in the
Pirotta et al. 2004, Falagas, Betsi and Athanasiou
fluconazole group and 21.9% in the placebo group
2005) have shown encouraging, but controversial
results and require further investigation.
Donders, Bellen et al. (2008) showed that an initial
Watson and Calabretto (2007) complain the lack of
dose of 3 · 200 mg fluconazole in the first week
randomized controlled trials for both conventional and
followed by a decreasing dose maintenance regime
non conventional management of recurrent vulvova-
(Table 4) in 117 women (without a placebo control
group) achieved 90% disease free patiens after 6 months
Meanwhile Lactobacilli strains have been identified,
and 77% disease free patients after one year.
which have in vitro candidacidal and immunestimulat-ing effects (Maila¨nder – Sanchez, Wagener and Schaller2009, Martinez et al. 2009).
Many open questions nonetheless remain in regard to
the treatment of Candida vaginitis. Why and how doimmunological defense mechanisms allow acute and
OTC-therapy for vulvovaginal candidosis with clotrim-
chronically recurrent candidosis or inflammation?
azole or in some countries also with fluconazole
represents meanwhile more than 80% of all treatment,although reports in the early 1990s optimisticallysuggested that patients might be able to successfully
self-diagnose their Candida vaginitis have not proven
Until now no proven immunotherapy for (chronically
correct (Walker et al. 2000, Beigi et al. 2004, Hoffstetter
recurrent) vaginal candidoses has been shown to exist,
et al. 2004). Only 33% of a study group of 95 women,
although Rosedale and Brown (1978) reported encour-
who purchased OTC vaginal antimycotics, were indeed
aging initial results from hypersensitization over thirty
found to have a Candida vaginitis (Ferris et al. 2002).
years ago. The authorÕs own in vitro studies with an
Treatment with vaginal antimycotics should only be
autologous membrane bound Candida albicans antigen in
initiated after Candida vaginitis has been correctly
a patient with chronically recurrent Candida albicans
vaginitis showed improved immunological reactions inthe patientÕs T lymphocytes as compared to results with
commercially available Candida antigens (Koldovsky,Kariger and Mendling 1999). Meanwhile, Rigg, Miller
There are numerous gaps in our knowledge of Candida
and Metzger (1990) reported Candida allergen therapy
host reactions which require further research.
and Moraes et al. (2000) and Rusch and Schwiertz
How can we, for example, act against Candida albicans
(2006) reported first clinical results with Candida
virulence factors and how can we inhibit the adhesion
autovaccination. Antibodies against aspartyl-proteases,
of Candida cells to the vaginal epithelium? How can we
adhesins and allergens could potentially play a role in
improve the vaginaÕs resistence to infections (T-lym-
the future (Cassone, de Bernardis and Torososantucci
phocyte stimulation, humoral factors, allergy)? Is a
2005, Cassone 2009). Despite significant efforts to
vaccination against Candida possible and successful?
understand the immunopathogenesis of Candida vagini-
Which new antimicotics are able to satisfactory treat
tis, a breakthrough still has not yet been made (de
vaginal C. glabrata or C. krusei infections?
Bernardis et al. 1990, Mendling and Koldovsky 1996,
This guideline was consented in 2010 by the German
Witkin, Geraldo and Linhares 2000, Fidel et al. 2004, Ip
Society of Gynecology and Obstetrics (DGGG), the
and Lan 2004, Babula et al. 2005, Birkner et al. 2005,
Working Group for Infections and Infectimmunology
Cassone, de Bernardis and Torososantuccii 2005, Fidel
in Gynecology and Obstetrics (AGII), the German
2005, Neves et al. 2005, Raska et al. 2008, Wozniak
Society of Dermatology (DDG), the Board of German
et al. 2005, Weissenbacher et al. 2009).
Dermatologists (BDD) and the German-Speaking Myco-logical Society (DMykG), represented by an expert teamof the following persons:
Prof. Werner Mendling, Berlin (DGGG, AGII,
Intramuscular injection of not H2O2 – producing
lactobacilli to induce antibodies (Birkner et al. 2005)
and probiotics (Hilton et al. 1992, Jeavons 2003,
Priv.-Doz. Ioannis Mylonas, Munich (DGGG, AGII)
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German guideline vulvovaginal candidosis 2010
Prof. Heinz Spitzbart (deceised), Erfurt (DGGG, AGII,
recurrent vulvovaginal candidiasis. Clin Infect Dis 2005;
Prof. Ernst – Rainer Weissenbacher, Munich (DGGG,
6 Beigi RH, Meyn LA, Moore DM, Krohn MA, Hillier SL.
Vaginal yeast colonization in nonpregnant women: A
longitudinal study. Obstet Gynecol 2004; 104: 926–30.
7 de Bernardis F, Agatensi L, Ross IK, et al. Evidence for a
role for secretory asparatate proteinase of Candida albicans
in vulvovaginal candidosis. J Infect Dis 1990; 161:
Prof. Isaak Effendy, Giessen (DDG, DMykG)
8 de Bernardis F, Boccanera M, Cassone A. The role of
Prof. Gabriele Ginter – Hanselmayer, Graz ⁄ Austria
immunity against vaginal Candida infection. In: Fidel PL,
Huffnagle GB (eds.) Fungal immunity: From an Organ
perspective. Springer, Heidelberg New York 2005,
Priv.-Doz. Christina Hipler, Jena (DMykG, DDG)
9 Birkner V Essers M, Bu¨hring M, Koldovsky U, Mendling
W. Randomisierte 3-armige, offene, kontrollierte, klini-
Prof. Hans – Christian Korting (deceised), Munich
sche Therapiestudie zur Behandlung der chronisch-rezi-divierenden vaginalen Kandidose mit einer
systematischen apparativen Heliotherapie im Vergleich
zu einer antimykotischen Standardtherapie und einer
Vakzinationsbehandlung mit Gynatren. Mycoses 2005;
Prof. Martin Schaller, Tu¨bingen (DDG, DMykG)
Prof. Claus Seebacher, Dresden (DDG, DMykG)
10 Bisshop MPJM, Merkus JMWM, Schleygrond H, van
Cutsem J. Co-treatment of the male partner in vaginal
Dr. Martin Schlaeger, Oldenburg (DDG, BDD)
candidosis: a double-blind randomised controlled-study. Br J Obstet Gynecol 1986; 93: 79–81.
11 Blaschke- Hellmessen R. Subpartale U¨bertragung von
Candida und ihre Konsequenzen. Mycoses 1998;
The responsible author (WM) received royalties by Dr.
12 Blaschke- Hellmessen R. Epidemiologische Untersuch-
August Wolff GmbH, Bielefeld, Strathmann GmbH and
ungen zum Vorkommen von Hefepilzen bei Kindern und
Co. KG, Hamburg (both Germany), Pevion Biotech
deren Mu¨ttern. Mykosen 1968; 611–6.
Ittigen and Polichem S.A., Lugano (both Switzerland).
13 Bohanna NJ. Treatment of vulvovaginal candidiasis in
The responsible author (JB) received no royalties
patients with diabetes. Diabetes care 1998; 21: 451–6.
14 Bond CM, Watson MC, Grampian Evidence Based Com-
munity Pharmacy Guidelines Group. The development ofevidence-based guidelines for the over-the-counter
treatment of vulvovaginal candidiasis. Pharm World Sci2003; 25: 177–81.
1 Abrams P, Khoury S, Grant A. Evidence – based medicine
15 Buch A, Skytte-Christensen E. Treatment of vaginal
overview over the main steps for developing and grading
candidosis with natamycin and effect of treating the
guideline recommendations. Prog Urol 2007; 17:
partner at the same time. Acta Obstet Gynecol Scand 1982;
2 Anderson MR, Klink K, Cohrsson A. Evaluation of vagi-
16 Cassone A. Immunization against Candida albicans vagi-
nal complaints. JAMA 2004; 291: 1368–79.
3 Auger P, Joly J. Microbial flora associated with Candida
17 Cassone A, de Bernardis F, Mondell F, Ceddia T, Agatensil .
albicans vulvovaginitis. Am J Obstet Gynecol 1980; 55:
Evidence for a correlation between proteinase secretion and
vulvovaginal candidosis. J Inf Dis 1987; 156: 777–82.
4 Auler ME, Morreiva D, Rodriguez FF, Abr Ao MS, Mar-
18 Cassone A, de Bernardis F, Torososantucci A. An outline
gavido PF, Matsumoto FE, Silva BC, Schneider RP, Paula
of the role of anti-candida antibodies within the context
CR. Biofilm formation on intrauterine devices in patients
of passive immunization and protection from candidiasis.
with recurrent vulvovaginal candidiasis. Med Mycol
19 Cauwenberg G. International experience with Ketoco-
5 Babula O, Lazdane G, Kroica J, Linhares JM, Ledger WJ,
nazole in vaginal candidosis. In: Eliot BW (ed) Oral
Witkin SS. Frequency of interleukin – 4 (IL – 4) – 589
therapy in vaginal candidosis. Medicine Publishing Foun-
gene polymorphism and vaginal concentrations of IL – 4,
nitric oxide, and mannosebinding lectin in women with
Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13
20 Cetin M, Ocak S, Gungoren A, Hakverdi AU. Distribution
37 Falagas ME, Betsi GI, Athanasiou S. Probiotics for
of Candida species in women with vulvovaginal symptoms
prevention of recurrent vulvovaginal candidiasis : a
and their association with different ages and contracep-
review. A Antimicrob Chemother. 2006; 58(2): 266–72.
tive methods. Scand J Infect Dis. 2007; 7: 584–8.
38 Farrell SM, Hawkins DF, Ryder TT. Scanning electron
21 Chassot F, Negri MF, Swidsinski AF, Donati L, Peralta
microscope study of Candida albicans, invasion of cultural
RM, Swidsinski S, Consolavo ME. Can intrauterine con-
human cervical epithelial cells. Sabouraudia 1983; 25:
traceptive devices be a Candida albicans reservoir? Con-
39 Ferris GD, Nyirjesy P, Sobel JD, Soper D, Pavlitic A, Li-
22 Chaim W, Foxman B, Sobel JD. Association of recurrent
taker MS. Over-the-counter antifungal drug misuse
vaginal Candidiasis and secretory ABO and Lewis phe-
associated with patient diagnosed vulvovaginal candi-
notype. J Inf Dis 1997; 176: 828–30.
dosis. Obstet Gynecol 2002; 99: 419–25.
23 Cohen L. Is more than one application of an antifungal
40 Fidel PL Jr. Immunity in vaginal candidiasis. Curr Opin
necessary in the treatment of an acute vaginal candido-
sis? Am J Obstet Gynecol 1985; 152: 961–4.
41 Fidel PL Jr. Vazquez JA, Sobel JD. Candida glabrata: review
24 Corsello S, Spinillo A, Osnengo G, et al. An epidemio-
of epidemiology, pathogenesis, and clinical disease with
logical survey of vulvovaginal candidiasis in Italy. Eur J
comparison to C. albicans. Clin Microbiol Rev 1999; 12:
Obstet Gynecol Reprod Biol 2003; 110: 66–72.
25 Czeizel M, T. , M Rockenbauer. No Teratogenic Effect after
42 Fong JW. The value of chronic suppressive therapy with
Clotrimazole Therapy during Pregnancy. Epidemiology
itraconazole versus clotrimazole in women with chronic
recurrent vaginal candidiasis. Genitourin Med 1992; 68:
26 Czeizel AE, Fladung B, Varga P. Preterm birth reduction
after clotrimazole treatment during pregnancy. Eur J
43 Foxman B. The epidemiology of vulvovaginal candidiasis:
Obstet Gynecol Reprod Biol 2004; 116: 157–63.
risk factors. Am J Public Health 1990; 80: 329–331.
27 Czeizel AE, Puho EH, Kazu Z. The use of data set of the
44 Gaspard U, Scheen A, et al. Randomized study over 13
Hungarian case – control surveillance of congenital
cycles to assess the influence of oral contraceptives con-
abnormalities for evaluation of birth outcomes beyond
taining ethinylestradiol combined with drospirenone or
birth defects. Centr Eur J Public Health 2007; 15: 147–
desogestrel on carbohydrate metabolism. Contraception
28 Davidson F, Mould RF. Recurrent vaginal candidosis in
45 Geraldo P, Neuer A, Korneeva IL, Ribeiro-Filho A, Simoes
women and the effect of intermittent prophylactic treat-
JA, Witkin SS. Vaginal heat shock protein expression in
ment. BJ Vener Dis 1978; 54: 176–83.
symptom-free women with history of recurrent
29 Davidson F, Oates JK. The pill does not cause thrush. Brit
vulvovaginitis. Am J Obstet Gynecol 1999; 180:
30 Dennerstein GJ, Ellis DH. Oestrogen, glycogen and vagi-
46 Ghannoum MA, Abu-El Teen. Pathogenecity determi-
nal candidiasis. Austr. NZ J Obstet Gynecol 2001; 41:
nants of Candida. Mycoses 1990; 33: 265–82.
47 Ghannoum MA. Potential role of phospholipases in vir-
31 Donders G. We, specialists in vulvovaginitis. Am J Obstet
ulence and fungal pathogenesis. Clin Microbiol Rev 2000;
32 Donders G, Babula O, Bellen G, Linhares IM, Witkin SS.
48 Golz R, Mendling W. Candidosis of the prostate. Rare
Mannose-bindling lectin gene polymorphism and resis-
form of endomycosis. Mycoses 1991; 34: 381–4.
tance to therapy in women with recurrent vulvovaginal
49 Goswami R, Dadhwal V, Tejaswi S, et al. Species-specific
candidiasis. BJOG. 2008; 115(10): 1223–31.
prevalence of vaginal candidiasis amoung patients with
33 Donders G, Bellen G, Byttebier G, et al. Individualized
diabetes mellitus and its relation to their glycaemic sta-
decreasing dose maintenance fluconazole regimen for
tus. J Infect Dis 2000; 41: 162–6.
recurrent vulvovaginal candidiasis (ReCiDiF trial). Am J
50 Goswami D, Goswami R, Banerjee U, et al. Pattern of
Candida species isolated from patients with diabetes
34 Donders G, Prenen H, Verbeke G, Reybrouck R. Impaired
mellitus and vulvovaginal candidiasis and their response
tolerance for glucose in women with recurrent vaginal
to single dose oral fluconazole therapy. J Infect 2006; 52:
candidiasis. Am J Obstet Gynecol 2002; 187: 989–93.
35 Eckert Hawes SE, et al. Vulvovaginal Candidiasis: Clinical
51 Hay PH, Czeizel AE. Asymptomatic trichomonas and
Manifestations, Risk Factors, Management Algorithm.
candida colonization and pregnancy outcome. Best Pract
Res Clin Obstet Gynecol 2007; 21(3): 403–9.
36 Ehrstro¨m SM, Kornfeld D, Thuresson J, Rylander E. Signs
52 Hilton E, Isenberg HD, Alperstein P, et al. Ingestion of
of chronic stress in women with recurrent candida
yoghourt containing Lactobacillus acidophilus as prophy-
vulvovaginitis. Am J Obstet Gynecol 2005; 193: 1376–
laxis for candidal vaginitis. Ann Intern Med 1992; 116:
Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13
German guideline vulvovaginal candidosis 2010
53 Hoffstetter SE, Barr S, LeFevre C, Leong FC, Leet T. Self-
Candida albicans to infect cells and induce inflammation.
reported yeast symptoms compared with clinical wet
Microbiol Immunol 2009; 53: 487–95.
mount analysis and vaginal yeast culture in a specialty
68 Mathema B, Cross E, Dun E, et al. Prevalence of vaginal
clinic setting. J Reprod Med. 2008; 53(6): 402–6.
colonization by drug-resistent Candida species in college-
54 Ip WK, Lan YL. Role of mannose-binding lectin in the
age women with previous exposure to over-the-counter
innate defense against Candida albicans: enhancement of
azole antifungals. Clin Inf Dis 2001; 33: E–23.
complement activation, but lack of opsonic function, in
69 Meinhof W. Die Salzsa¨ure-Toleranz von Candida albicans.
Phagocytosis by human dendritic cells. J Inf Dis 2004;
70 Mendling W. Die Torulopsidose in der Frauenheilkunde,
55 Ismail A, Lupan DM. Utilisation of siderophores by Can-
Geburtsh ⁄ Frauenheilk 1984; 44: 583–6.
dida albicans. Mycopath 1986; 96: 109–13.
71 Mendling W. Azoles in the therapy of vaginal candidosis.
56 Jeavons HS. Prevention and treatment of vulvovaginal
In: Berg D, Plempel M (eds) Sterol biosynthesis inhibitors.
candidosis using exogenous lactobacilli. J Obstet Gynecol
Ellis Horwood, Chichester 1988, pp 480–506.
72 Mendling W, Koldovsky U. Investigations by cell-medi-
57 Kiss H, Petricevicz L, Husslein P. Prospective randomised
ated immunologic tests of therapeutic trials with thym-
controlled trial of an infection screening program to
opentin in vaginal mycoses. Inf Dis Obstet Gynecol 1996;
reduce the rate of preterm delivery. BMJ 2004; 329:
73 Mendling W, Gutschmidt J, Gantenberg R, Andrade P,
58 Koldowsky H, Kariger U, Mendling W. Herstellung eines
Scho¨nian G. Vergleich der Stammspezifita¨t von
autologen membrangebundenen Candida-Antigens und
Hefepilzen verschiedener Lokalisationen bei Frauen
in-vitro-Untersuchungen zu seinen immunologischen
mit Vaginalcandidosen. Mycoses 1998; 41(Suppl. 2):
Reaktionen. In Metzner G, Weissenbacher ER (Hrsg.)
Candida-Infektionen des weiblichen Genitaltraktes. Medifact
74 Mendling W, Krauss C, Fladung B. A clinical multi-cen-
ter-study comparing afficacy and tolerability of topical
59 Kunzelmann V, Tietz HJ, Roßner D, Czaika V, Hopp M,
combination therapy with Clotrimazole (Canesten, two
Schmalreck A, Sterry W. Voraussetzungen fu¨r eine ef-
formats) with oral single dose fluconazole (Diflucan) in
fektive Therapie chronisch rezidivierender Vaginalkan-
vulvovaginal mycoses. mycoses 2004; 47: 136–42.
didosen. Mycoses 1996; 39(Suppl. 1): 65–72.
75 Mendling W, Niemann D, Tintelnot K. Vaginal Coloni-
60 Lattif AA, Prasard R, et al. The glyzolate cycle enzyme
sation with Candida Species with Special Focus on Candida
activities in the pathogenitic isolates of Candida albicans
dubliniensis A. Prospective Study. Geburtsh Frauenheilk
obtained from HIV ⁄ AIDS, diabetic and burn patients.
76 Mendling W, Seebacher C. Vulvovaginalkandidose.
61 Ledger WJ, Polaseczky MM, Yih MC, Jeremias J, Tolbert
V, Witkin SS. Difficulties in the diagnosis of Candida
77 Mendling W, Spitzbart H. Antimykotische Therapie der
vaginitis. Inf Dis Clin Bact 2000; 9: 66–9.
vaginalen Hefepilz-Kolonisation von Schwangeren zur
62 Leon de E, Jacober SJ, Sobel JD, Foxman B. Prevalence
Verhu¨tung von Kandidamykosen beim Neugeborenen.
and risk factors for vaginal Candida colonization in wo-
AMWF, Guideline 015 ⁄ 042 (S1) 2008.
men with type I and type 2 diabetes. BMC Infect Dis
78 Mendling W. Vaginose, Vaginitis, Zervizitis und Salpingitis.
2. Auflage, Springer Verlag Heidelberg 2006.
63 Li J, Fan SR, Liu XP, et al. Biased genotype distributions of
79 Meyer H, Go¨ttlicher S, Mendling W. Stress as a cause of
Candida albicans strains associated with vulvovaginal
chronic recurrent vulvovaginal candidosis and the
candidosis and candidal balanoposthitis in China. Clin
effectiveness of the conventional antimycotic therapy.
64 Loeffler W. Terminologie der Humanmykosen. Mykosen
80 Mendling W, Koldovsky U. Investigations by cell – med-
iated immunological tests of therapeutic trials with
65 Lowe NK, Neal JL, Ryan-Wenger NA. Accuracy of the
thymopentin in vaginal mycoses. Inf Dis Obstet Gynecol
clinical diagnosis of vaginitis compared with a DNA
probe laboratory standard. Obstet Gynecol 2009; 113:
81 Moraes PSA, de Lima Goiaba S, Taketoni EA. Candida albi-
cans allergen immunotherapy in recurrent vaginal candi-
66 Maila¨nder-Sanchez D, Wagener I, Schaller M.
diasis. Invest Allergol Clin Immunol 2000; 10: 305–9.
Characterization of the protective immunmodulation of
82 Mu¨ller J, Nold B, Kubitza D, Baumert J. Quantitative
probiotic bacteria in localized candidiasis. Mycoses 2009;
Untersuchungen u¨ber die Do¨derlein – Flora gesunder
sowie mykosekranker Probandinnen unter lokaler
67 Martinez RC, Seney SL, Summers KL, Nomitzo A, de
Isoconazo-Nitrat – Therapie. In: Seeliger HPR (ed)
Martinis FC, Reid G. Effect of Lactobacillus rhamnosus GR –
Gyno-Travogen-Monographie, Excerta Medica, Amsterdam
1 and Lactobacillus reuteri RC – 14 on the ability of
Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13
83 Naglik J, Albrecht A, Bader O, Huber B. Candida albicans
99 Quereux C, Gelas B, Chevallier T, Petit F, Micheletti MC.
proteinases and host ⁄ pathogen interactions. Cellular
Evaluation of the efficacy and speed of action of ser-
toconazole nitrate suppository and cream combined
84 Neves NA, Carvallho LP, de Oliveira MA, et al. Associa-
treatment for vulvovaginal candidiasis. Gynecol Obstet
tion between atopy and recurrent vaginal candidosis.
Clin Exp Immunol 2005; 142: 167–71.
100 Raska M, Belakova J, Horynova M, Krupka M, Novotny J,
85 Niewerth M, Kunze D, Seibold M, Schaller M, Korting HC,
Sebestova M, Weigl E. Systemic and mucosal immuni-
Hube B. Ciclopirox Olamine Treatment Affects the
zation with Candida albicans hsp 90 elicits hsp 90 specific
Expression Pattern of Metabolism Proteins, and Drug
humoral response in vaginal mucosa which is further
Resistance Factors. Antimicrob Agents Chemother 2003;
enhanced during experimental vaginal candidiasis. Med
86 Nurbhai M, Grimshaw J, Watson M, Bond C, Mollison J,
101 Ray D, Goswami R, Bomerjee U, et al. Prevalence of
Ludbrook A. Oral versus intra-vaginal imidazole and
Candida glabrata and its response to boric acid vaginal
triazole anti-fungal treatment of uncomplicated vulv-
suppositories in comparison with oral fluconazole in
ovaginal candidiasis (thrush). Cochrane Database Syst Rev.
patients with diabetes and vulvovaginal candidiasis.
87 Nyirjesy P, Seeney SM, Grody MHT, Jordan CA, Buckeley
102 Reed BD, Zazone P, Pierson LL, Gorenflo DW, Horreocks
HR. Chronic fungal vaginitis: The value of cultures. Am J
J. Candida transmission and sexual behaviour as risk for a
repeated episode of Candida vulvovaginitis. J Womens
88 Nyirjesy P, Alexander AB, Weitz MV. Vaginal candida
parapsilosis: pathogen or bystander? Infect Dis Obstet
103 Richter SS, Galask RP, Messer SA, Hollis RJ, Diekema DJ,
Pfaller MA. Antifungal susceptibilities of Candida species
89 Odds Fc. Candida and Candidosis, 2nd edn. England: Bail-
causing vulvovaginitis and epidemiology of recurrent
cases. J Clin Microbiol 2005; 42: 2155–62.
90 Odds FC, Arai T, Disalvo AF, et al. Nomenclature of fungal
104 Rigg D, Miller MM, Metzger WJ. Recurrent allergic
diseases : a report and recommendations from a sub-Com-
vulvo-vaginitis treatment with Candida albicans allergen
mittee of the International Society for Human and Animal
immunotherapy. Am J Obstet Gynecol 1990; 162:
Mycology (ISHAM). J Med Vet Mycol 1992; 30: 1–10.
91 Paulitsch A, Weger W, Ginter-Hanselmayer G, Marth E,
105 Ritter W. Pharmacokinetics of azole compounds. In: Berg
Buzina W. A 5-Year (2000 – 2004) epidemiological
D, Plempel M (eds), Sterol biosynthesis inhibitors. Ellis
survey of Candida and non-Candida yeasts species causing
Horwood, Chichester 1988, pp 397–429.
vulvovaginal candidiasis in Graz, Austria. Mycoses 2006;
106 Rosedale N, Browne K. Hyposensitation in the manage-
ment of recurring vaginal candidiasis. Ann Allergy 1979;
92 Phillips AJ. Treatment of non-albicans Candida vaginitis
with amphotericin B vaginal suppositories. Am J Obstet
107 Roth AC, Milsom I, Forssman L, Wa´hle´n P.
Intermittend prophylactic treatment of recurrent vaginal
93 Pirotta MV, Gunn JM, Chondros P. ‘‘Not thrush again’’
candidiasis by postmenstrual application of a 500 mg
WomenÕs experience of post-antibiotic vulvovaginitis.
clotrimazole vaginal tablet. Genitourin Med 1990; 66:
94 Pirotta M, et al. Effect of lactobacillus in preventing post-
108 Ru¨chel R, Fegeler R, Trost M. Comparison of secretory
antibiotic vulvovaginal candidiasis: a randomized con-
proteinases from different strains of Candida albicans.
trolled trial. BMJ 2004; 329: 548–51.
95 Pirotta MV, Garland SM. Genital Candida species detected
109 Rusch K, Schwiertz A. Candida autovaccination in the
in samples from women in Melbourne, Australia, before
treatment of vulvovaginal Candida infections. Int J Gyne-
and after treatment with antibiotics. J Clin Mecrobiol
110 Savini V, Catavitello C, Manua A, Talia M, febbo F, Balbinot
96 Pitsoni E, Lavazzo C, Falagas ME. Itraconazole vs fluco-
A, dÕAntonio D. Two cases of vaginitis caused by Itraco-
nazole for the treatment of uncomplicated acute vaginal
nazole – resistant Saccharomyces cerevisiae and review of
and vulvovaginal candidiasis in nonpregnant women: a
recently published studies. Mycopathologia 2008; 166:
metaanalysis of randomised controlled trials. Am J Obstet
111 Scheklakow ND, Deletorski WW, Goldoa OA.
97 Plempel M. Pharmakokinetik der Imidazol-Antimykotika.
Vera¨nderungen der Ultrastruktur von Candida albicans
unter Einwirkung von Polyen-Antibiotika. Mykosen
98 Powell BL. Identification of a 17 b-estradiol-binding
protein in Candida albicans and Candida (Torulopsis) glab-
112 Schnell JD. Epidemiology and prevention of peripartal
mycoses. Chemother 1982; 28(Suppl. I): 66–72.
Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13
German guideline vulvovaginal candidosis 2010
113 Schnell JD, Voigt WH. Das Verhalten von Sprosspilzen
129 Upmalis DH, Cone FL, Lamia CA, Reisman H, Rodriguez–
am nicht verhornenden Plattenepithel. Arch Gynaekol
Gomez G, Gilderman G, Bradley L. Single – dose mico-
nazole nitrate vaginal ovule in the treatment of vulv-
114 Singh S, Sobel JD, Bhargava P, Boikov D, Vasquez JA.
ovaginal candidiasis.: two single – blind, controlled
Vaginitis due to Candida krusei: epidemiology, clinical
studies versus miconazole nitrate 100 mg cream for
aspects, and therapy. Clin Inf Dis 2002; 35: 1066–70.
7 days. J Womens Health Gend Based Med 2000; 9:
115 Sobel JD. Management of recurrent vulvovaginal candi-
diasis with intermittent ketoconazole prophylaxis. Obstet
130 Wajnberg M, Wajnberg A. Doppelblind-Vergleichsstudie
mit Ciclopyroxolamin- und Miconazol-Vaginalcreme
116 Sobel JD. Vaginitis due to Saccharomyces cereviseae: Epi-
bei vulvovaginaler Kandidose. Mykosen 1981; 24: 721–
demiology, clinical aspects, and therapy. Clin Inf Dis
131 Walker PP, Reynolds MT, Ashbee HR, Bown C, Evans FG.
117 Sobel JD. Vulvovaginitis due to Candida glabrata. An
Vaginal Yeasts in the era of ‘‘over the counter’’ anti-
emerging problem. Mycoses 1998; 41(Suppl. 2): 18–21.
fungals. Sex Transm Infect 2000; 76: 437–8.
118 Sobel JD. Vulvovaginal candidosis. Lancet. 2007; 369:
132 Watson C, Grimshaw JM, Bond CM, Mollison J, Ludbrook
A. Oral versus intra-vaginal imidazole and triazole anti-
119 Sobel JD, Harold C, Wiesenfeld MD, et al. Maintenance
fungal treatment of uncomplicated candidiasis (thrush):
Fluconazole Therapy for Recurrent Vulvovaginal Candi-
A systemic review. BJOG 2002; 109: 85–9.
diasis. N Engl J Med 2004; 351: 876–83.
133 Watson C, Calabretto H. Comprehensive review of con-
120 Sobel JD, Myers PG, Kaye D, Leviston ME. Adherence of
ventional and non-conventional methods of managment
Candida albicans to human vaginal and buccal epithelial
of recurrent vulvovaginal candidiasis. Aust N Z J Obstet
cells. J Infect Dis 1981; 143: 76–82.
121 Sobel JD, Zervos M, Reed BD, et al. Fluconazole suscep-
134 Weissenbacher TM, Witkin SS, Gingelmaier A, Scholz C,
tibility of vaginal isolates obtained from women with
Friese K, Mylonas I. Relationship between recurrent
complicated Candida vaginitis: Clinical implications. An-
vulvovaginal candidosis and immune mediators in vagi-
timicrob Agents Chemother 2003; 47: 34–8.
nal fluid. Eur J Obstet Gynecol Reprod Biol 2009; 144: 59–
122 Sobel JD, Fisher J, Kauffman CA. Guidelines for the treat-
ment of fungal urinary tract infections. In: Naber KG et al.
135 Wilson C. Recurrent vulvovaginal candidiasis; an over-
(eds), Urogenital Infections. Europ Assoc Urol ⁄ Intern Con-
view of traditional and alternative therapies. Adv Nurse
sult Urol Dis 2010; Arnhem ⁄ Netherlands, pp 903–11.
123 Spacek J, Jilek P, Buchtav , Fo¨rstl M, Hronek M, Ho-
136 Witkin SS, Jeremias J, Ledger WJ. A localized vaginal
leckova M. The serum levels of calcium, magnesium, iron
allergic response in women with recurrent vaginitis. J
and zinc in patients with recurrent vulvovaginal candi-
Allergy Clin Immunol 1988; 81: 412–6.
dosis during attack, remission and in healthy controls.
137 Witkin SS, Giraldo P, Linhares D. New insights into the
immune pathogenesis of recurrent vulvovaginal candi-
124 Spinillo A, Capuzzo E, Egbe TO, Baltaro P, Nicola S, Piazzi
diasis. Int J Gynecol Obestet 2000; 3: 114–8.
G. Torulopsis glabrata vaginitis. Obstet Gynecol 1995; 85:
138 Wozniak KL, Palmer G, Kutner R, Fidel PL Jr. Immuno-
therapeutic approaches to enhance protective immunity
125 Tarry W, Fisher M, Shen S, Mawhinney M. Candida
against Candida vaginitis. Med Mycol. 2005; 43: 589–
albicans: The estrogen target for vaginal colonization.
139 Xu J, Schwartz K, Bartoces M, Monsur J, Severson RK,
126 Thrumbore DJ, Sobel JD. Recurrent vulvovaginal candi-
Sobel JD. Effect of antibiotics on vulvovaginal candidiasis:
diasis: vaginal epithelial cells susceptibility to Candida
a MetroNet study. J Am Board Fam Med 2008; 21:
albicans adherence. Obstet Gynecol 1986; 67: 810–2.
127 Tietz HJ. Gezieltes Vorgehen gegen Problemkeime. Gyn
140 Young GL, Jewell D. Topical treatment for vaginal can-
didiasis (thrush in pregnancy) (review). The Cochrane
128 Tooley PJ. Patient and doctor preferences in the treat-
Database of systematic Reviews 2001, Issue 4 Art No CD
ment of vaginal candidosis. Practitioner 1985; 229:
000225. The Cochrane Collaboration. John Wiley &
Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13
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