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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 W. Mendling and J. Brasch 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 ! 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 W. Mendling and J. Brasch 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 Recommendation (GoR) B).
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 nancy see 3.5.
Grant (2007).
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 (LoE 2a, GoR B).
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 language literature .
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. Summary of recommendations 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 ! 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).
Donders et al. 2008).
There is evidence for different genotypes of C. albicans strains in asymptomatic women and in those with acute Candida vaginitis (Li et al. 2008).
Candida albicans is able to form blastospores, pseud-omycelia, true mycelia and chlamydospores. Candia 5. Genital colonization glabrata forms only blastospores.
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 partner!s 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 Paulitsch et al. 2006) (Table 3).
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 partner!s 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 (Mendling et al. 2007).
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).
6. Candida virulence factors The first step from colonization to infection is the attachment of the Candida cell to the vaginal wall ! 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 W. Mendling and J. Brasch Table 2 Distribution of vaginal Candida species in HIV-negative colonized women (Mendling et al. 2007).
all patients with positive cultures 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 host factors.
Acute Candida vulvovaginitis 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, Other (C. tropicalis, C. kefyr, which do not significantly influence the carbohydrate C. africana, S. cereviciae) 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 (Cetin et al. 2007).
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, Ghannoum 2000).
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 Chassot et al. 2008).
in macrophages, are also important virulence factors Although vaginal candidosis often occurs in women (Lattif et al. 2006).
with normal lactobacillus flora, lactobacilli have beenfound in lower numbers, when women have vaginalcandidosis (Auger and Joly 1980). The potential 7. Predisposing host factors 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).
! 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.
1999, Raska et al. 2008).
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).
8. Clinical symptoms 200 mg once/week 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 ovulation (Eckert et al. 1998).
In approximately 90%, pruritus is the most typical, but not reliable symptom, because only 35–40% ofwomen with itching have a Candida vaginitis (Anderson, 200 mg once/2 weeks Klink and Cohrsson 2004, Mendling, Niemann, and Tintelnot 2007).
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.
200 mg once/month 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 Seebacher 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 bleeding, if it is removed.
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 ! 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 W. Mendling and J. Brasch (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), antibody levels.
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 The cervix is not infected.
Polyenes form complexes with ergosterole of the yeast cell wall and thus change its permeability (Scheklakow et al. 1980).
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).
and the presence of yeasts.
Ciclopiroxolamine inhibits probably important iron- dependent enzymes through chelate formation (Nie-werth et al. 2003).
9.1. Necessary ⁄ Obligate Patients often prefer oral treatment, if they are given Clinical anamnesis, gynaecological examination, pH a choice (Tooley 1985).
measurement and microscopic investigation of thevaginal fluid with 10% potassium hydroxide or saline 10.1. Colonization 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 10.2 Colonization during pregnancy experience and teaching in many hospitals and privatepractices around the world (Donders 2001, Ledger et al.
Nearly all healthy, mature neonates, who were colo- 2000, Mendling 2006).
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 2006, Hoffstetter et al. 2008).
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 1998, Mendling and Spitzbart 2008).
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 needs not be treated.
in the first trimester, which requires further investiga-tion.
10.3. Acute Candida vulvovaginitis 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- ! 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- medical mycology.
amine (Wajnberg and Wajnberg 1981).
Therefore, MIC – tests are usually not recommended Oral treatment with the imidazole ketoconazole (no (Sobel et al. 2003).
longer typically used in Germany) or with the triazolesfluconazole or itraconazole or others is also possible.
10.6. Non-albicans Vaginitis 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 toxicity (Ritter 1988).
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.
(Sobel et al. 2003).
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 to 6 days is recommended.
2 · 400 mg ⁄ day 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 10.4. Side effects for other indications.
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 possible, but rare.
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 mended during pregnancy.
et al. 2004).
Whether topical clotrimazole 500 mg, oral ketozo- nazole 100 mg or fluconazole 150 mg were given, the 10.5. Resistance of Candida albicans? 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- 2001, Richter et al. 2005).
nazole weekly for 6 months, the percentages of disease ! 2012 Blackwell Verlag GmbH • Mycoses 55 (Suppl. 3), 1–13 W. Mendling and J. Brasch 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 (Sobel et al. 2004).
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 ginal candidoses.
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).
11. Open questions.
Many open questions nonetheless remain in regard to 11.3 Over-the-counter (OTC-) therapy 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 Antimycotics are not the solution! represents meanwhile more than 80% of all treatment,although reports in the early 1990s optimisticallysuggested that patients might be able to successfully 11.1. Immunological therapies? 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 author!s 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 patient!s T lymphocytes as compared to results with 12. Future research 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 vagina!s 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: 11.2 Lactobacilli? Alternatives? Prof. Werner Mendling, Berlin (DGGG, AGII, Intramuscular injection of not H2O2 – producing DMykG) (responsible) lactobacilli to induce antibodies (Birkner et al. 2005) Prof. Klaus Friese, Munich (DGGG, AGII) and probiotics (Hilton et al. 1992, Jeavons 2003, Priv.-Doz. Ioannis Mylonas, Munich (DGGG, AGII) ! 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; 40: 1258–62.
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.
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