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 Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 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 Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 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).
Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 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 Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 (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- Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 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 Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 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) Ó 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 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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