Bacterial Vaginosis: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/028, June 2023)

Abstract

Aim This official guideline was coordinated and published by the DGGG, OEGGG and SGGG with the involvement of additional professional societies. The aim of the guideline is to evaluate the relevant literature and use it to provide a consensus-based overview of the diagnosis and management of bacterial vaginosis.

Methods This S2k-guideline was developed by representative members from different medical professional societies on behalf of the guidelines commission of the above-listed societies using a structured consensus process.

Recommendations This guideline provides recommendations on the diagnosis, management, counselling, prophylaxis, and other aspects related to bacterial vaginosis.

Key words

bacterial vaginosis - infection - guideline

I  Guideline Information

Guidelines program of the DGGG, OEGGG and SGGG

For information on the guidelines program, please refer to the end of the guideline.

Citation format

Bacterial Vaginosis: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/028, June 2023). Geburtsh Frauenheilk 2023; 83: 1331–1349

Guideline documents

The complete German-language long version and a slide version of these guidelines as well as a list of the conflicts of interest of all the authors are available on the homepage of the AWMF: http://www.awmf.org/leitlinien/detail/ll/015-028.html

Guideline authors

See [Tables 1] and [2].

Table 1 Lead and/or coordinating guideline author.

Author	AWMF professional society
Ap.Prof. Priv.-Doz. Dr. Dr. Alex Farr, MPH	Austrian Society for Gynecology and Obstetrics (Österreichische Gesellschaft für Gynäkologie und Geburtshilfe, OEGGG) European Society for Infectious Diseases in Obstetrics and Gynecology (ESIDOG) Austrian Society for Pre- and Perinatal Medicine (Österreichische Gesellschaft für Prä- und Perinatale Medizin, ÖGfPPM)

Table 2 Contributing guideline authors.

Author Mandate holder	DGGG working group (AG)/ AWMF/non-AWMF professional society/ organization/association
* This person attended as an expert (not eligible to vote in the consensus process).
Alex Farr	OEGGG, ÖGfPPM, ESIDOG
Brigitte Frey Tirri	SGGG
Udo Hoyme*	AGII
Werner Mendling	DGGG, AGII
Inge Reckel-Botzem	BVF
Daniel Surbek	SGGG
Sonja Swidsinski	DGHM
Gisela Walter	DSTIG, AEGGF
Birgit Willinger	OEGHMP

The following professional societies/working groups/organizations/associations stated that they wished to contribute to the guideline text and participate in the consensus conference and nominated representatives to attend the conference ([Table 2]).

Abbreviations

BV: bacterial vaginosis

BVAB: BV-associated bacteria

CDC: Center for Disease Control and Prevention

CFU: colony-forming units

CST: community state types

FISH: fluorescence in situ hybridization

HIV: human immunodeficiency virus

HPV: human papillomaviruses

HSV: herpes simplex virus

IVF: in vitro fertilization

KOH: potassium hydroxide

NAAT: nucleic acid amplification test

NGS: next generation sequencing

PID: pelvic inflammatory disease

spp.: abbreviation of species (plural)

STI: sexually transmitted infection

VVC: vulvovaginal candidiasis

WSW: women having sex with women

II  Guideline Application

Purpose and objectives

The aim of this guideline is to provide optimal care to patients with bacterial vaginosis, whether they are outpatients, day patients or inpatients. The intention must be to provide targeted therapy depending on the symptoms. The aim is also to prevent unnecessary or inadequate therapies. The prevention and early detection of bacterial vaginosis is also one of the aims of this guideline.

Targeted areas of care

Outpatient care, day-patient care, inpatient care and specialized cared.

Target user groups/target audience

This guideline is addressed to the following groups of people: hospital-based gynecologists and gynecologists in private practice, hospital-based microbiologists, and microbiologists in private practice. Other target groups (providing them with information) include: general practitioners, hospital-based midwives and midwives in private practice, nursing staff, biomedical analysts, professional medical societies and associations, public health institutions und decision-makers at national and federal state levels, and funding agencies.

Adoption and period of validity

The validity of this guideline was confirmed by the executive boards/representatives of the participating medical professional societies, working groups, organizations, and associations and the boards of the DGGG, SGGG, and OEGGG and the DGGG/OEGGG/SGGG Guidelines Commission in June 2023 and was thereby approved in its entirety. This guideline is valid from 1 June 2023 through to 30 May 2027. The guideline can be updated earlier if urgently necessary. Similarly, the guidelineʼs period of validity can be extended if the guideline still reflects the current state of knowledge.

III  Methodology

Basic principles

The method used to prepare this guideline was determined by the class to which this guideline was assigned. The AWMF Guidance Manual (version 1.0) has set out the respective rules and requirements for different classes of guidelines. Guidelines are differentiated into lowest (S1), intermediate (S2), and highest (S3) class. The lowest class is defined as consisting of a set of recommendations for action compiled by a non-representative group of experts. In 2004, the S2 class was divided into two subclasses: a systematic evidence-based subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class combines both approaches.

This guideline was classified as: S2k.

Grading of recommendations

The grading of evidence based on the systematic search, selection, evaluation, and synthesis of an evidence base which is then used to grade the recommendations is not envisaged for S2k guidelines. The individual statements and recommendations are only differentiated by syntax, not by symbols ([Table 3]).

Table 3 Grading of recommendations (based on Lomotan et al., Qual Saf Health Care 2010).

Description of binding character	Expression
Strong recommendation with highly binding character	must/must not
Regular recommendation with moderately binding character	should/should not
Open recommendation with limited binding character	may/may not

Statements

Expositions or explanations of specific facts, circumstances, or problems without any direct recommendations for action included in this guideline are referred to as “statements.” It is not possible to provide any information about the level of evidence for these statements.

Achieving consensus and level of consensus

At structured NIH-type consensus-based conferences (S2k/S3 level), authorized participants attending the session vote on draft statements and recommendations. The process is basically as follows. A recommendation is presented, its contents are discussed, proposed changes are put forward, and all proposed changes are voted on. If a consensus (> 75% of votes) is not achieved, there is another round of discussions, followed by a repeat vote. Finally, the extent of consensus is determined, based on the number of participants ([Table 4]).

Table 4 Level of consensus based on extent of agreement.

Symbol	Level of consensus	Extent of agreement in percent
+++	Strong consensus	> 95% of participants agree
++	Consensus	> 75 – 95% of participants agree
+	Majority agreement	> 50 – 75% of participants agree
–	No consensus	< 51% of participants agree

Expert consensus

As the term indicates, this refers to consensus decisions taken relating specifically to recommendations/statements issued without a prior systematic search of the literature (S2k) or where evidence is lacking (S2e/S3). The term “expert consensus” (EC) used here is synonymous with terms used in other guidelines such as “good clinical practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation is graded as previously described in the chapter Grading of recommendations but without the use of symbols; it is only expressed semantically (“must”/“must not” or “should”/“should not” or “may”/“may not”).

IV  Guideline

1  Summary of recommendations

Bacterial vaginosis (BV) is characterized by a strong increase in the number of bacteria (bacterial overgrowth), especially of Gardnerella (G.) species (spp.), a high microbial diversity as well as the displacement of potentially protective lactobacilli in the vaginal fluid.

Gardnerella spp. is the predominant bacterial species in BV and is also the species with the highest virulence potential. They are integrated in a biofilm matrix with other BV-associated types of bacteria (BVAB), and this is what appears to be responsible for treatment failures and chronic recurrences. Chronically recurrent BV is when the patient has at least 3 episodes per year; this may be an indication that the pathogenesis of BV could be biofilm-related. BV is associated with specific risk factors, and particular attention should be paid to them when making the diagnosis. The aim should be to eliminate predisposing host factors where possible.

In clinical practice, women with vulvovaginal symptoms must be investigated for BV, particularly if they present with a thin homogeneously gray discharge (with or without a fishy odor) and an alkaline vaginal pH. Diagnostic investigations must be guided by the patientʼs prior medical history, clinical findings, and the microscopic evidence of clue cells in the unfixed vaginal smear as well as an evaluation based on the Amsel criteria if necessary. Lab diagnostics should include Gram staining with quantitative comparison of different morphotypes using the Nugent scoring system. Lab diagnostics based on molecular genetic procedures only play a minor role and should currently only be used in special cases.

Treatment for BV must only be initiated after a proper diagnostic investigation has been carried out and medically confirmed. Women with vulvovaginal symptoms and confirmed BV must be treated in accordance with medical guidelines, and therapy must consist of oral or topical clindamycin or metronidazole. Alternatively, local antiseptics may be used. The treatment of bacterial vaginosis in pregnancy must consist primarily of vaginal clindamycin or antiseptics. In cases with chronically recurrent BV, treatment should consist of local antiseptics or suppressive maintenance therapy with topical metronidazole followed by vaginal probiotics to reduce the probability of recurrence.

Lactic acid and probiotics appear to have a positive impact in therapy and as recurrence prophylaxis and may be used as a complementary approach after the completion of therapy to regenerate the lactobacilli flora. Treating the patientʼs partner may be considered in cases with chronic recurrence, although the evidence for this is limited. Women with BV must always be informed about which measures could prevent the recurrence of bacterial vaginosis in their case. Women with BV who wish to become pregnant very soon should be treated even if they are asymptomatic. The same applies to women with aerobic or desquamative inflammatory vaginitis.

Future research into BV should focus on reducing the high rate of recurrence and chronic recurrence of disease.

2  Definition

Consensus-based statement 2.S1
Expert consensus	Level of consensus +++
Bacterial vaginosis is characterized by excessive numbers of bacteria, especially Gardnerella species, a high microbial diversity of anaerobic and facultatively anaerobic bacterial species, as well as the displacement of potentially protective lactobacilli in vaginal fluid.

Consensus-based recommendation 2.E1
Expert consensus	Level of consensus +++
Chronic recurrent bacterial vaginosis is defined as the occurrence of at least 3 episodes per year and may indicate that the pathogenesis is biofilm-related.

BV is the most common vaginal disease worldwide with a prevalence of between 23% and 29% in sexually active women [1]. It is considered a form of vaginal dysbiosis where the vaginal microbiota is significantly different to that of healthy women without BV. The difference includes a strong increase in the numbers of bacteria, especially of Gardnerella spp., a high microbial diversity of facultatively and strictly anaerobic bacteria, and the displacement of protective lactobacilli. There are some indications for the presence of a biofilm on vaginal epithelium consisting predominantly of Gardnerella spp. but also including numerous other BVAB. The existence of such a biofilm would explain some of the changes to the vaginal microbiota and could be considered a pathogenetic factor [2].

3  Microbiology

Consensus-based statement 3.S2
Expert consensus	Level of consensus +++
Gardnerella species is the predominant bacterial species found in bacterial vaginosis and the species with the highest virulence potential. It forms part of a biofilm matrix which includes other BV-associated bacterial species and appears to be responsible for the ultimate failure of therapy and for chronically recurrent disease.

Gardnerella spp. is the predominant bacterial species in 95 – 100% of women with BV [3], and includes four different named species (G. vaginalis, G. piotii, G. leopoldii, and G. Swidsinskii) and a further 9 as yet unnamed species [4]. Gardnerella spp. are gram-positive bacteria and is part of the Bifidobacteriaceae family [5]. Because of their unusually thin cell walls, in gram-stained specimens they appear as gram-negative or gram-variable coccobacilli [6]. The specific virulence properties of Gardnerella spp. include its pronounced ability to adhere to vaginal epithelial cells and its biofilm-producing capacity [7]. The BV biofilm consists mainly of tightly packed adjacent Gardnerella spp. Many other different BVAB are integrated in its matrix. Their concentrations are significantly higher than in normal vaginal microbiota but still lower than the concentrations of Gardnerella spp. With the exception of Fannyhessia vaginae (previously Atopobium vaginae), none of the non-Gardnerella species are present in > 60% of BV biofilms. The range of different BVAB is enormous; in addition to the most common species Fannyhessia vaginae, Fusobacterium nucleatum, Mobiluncus mulieris, Mycoplasma hominis, Prevotella bivia, and Ureaplasma urealyticum, it also includes lactobacilli such as L. iners [8], [9]. The Gardnerella spp. dominate the polymicrobial biofilm; they are responsible for the increased resistance to hydrogen peroxide, lactic acid, bactericides, and host immune defense [10] and are the main cause of the high failure rate of standard antibiotic therapy and for BV recurrence [11]. STI pathogens also benefit from ecological interactions with the BV biofilm. The risk of contracting sexually transmissible infections is significantly higher for women with BV compared to women with a normal vaginal microbiota [12], [13]. Women with BV are also more susceptible to other genital infections [14].

4  Host, virulence and risk factors

Consensus-based recommendation 4.E2
Expert consensus	Level of consensus +++
BV is associated with certain risk factors, and particular attention should be paid to them when making the diagnosis. The aim should be to eliminate predisposing host factors where possible.

No definite gene locus which could be partly responsible for developing BV has been identified yet [15]. However, an association with womenʼs ethnic affiliations has been reported [16], [17]. The incidence of BV is higher in women from South and East Africa than in women from West Africa, Europe, Australia, or New Zealand. In the USA, the reported prevalence of BV was 51% in Afro-American women, 32% in Hispanic women, 23% in white American women and 33% in native American women [11], [18], [19]. Exogenous host factors for BV include smoking, excessive vaginal hygiene, chronic stress, frequent changes of sexual partner, and imminent menstruation [18], [20], [21], [22]. Brookheart et al. [23] reported that BV occurred more often in women with a high body weight or body mass index. There are some indications that BV biofilms may be sexually transmitted. Women who have been previously treated for BV have a higher risk of recurrence if they have sexual intercourse with the same partner again without using a condom [24], [25], [26]. Women with same-sex partners (WSW, women having sex with women) have a higher risk per se of BV [27]. Taking combined oral contraceptives is associated with a lower prevalence of BV [28] – [30], although this appears to be associated with the estradiol in the contraceptive [31]. The use of copper intrauterine devices appears to be associated with an increased risk of BV [32].

5  Symptoms

Consensus-based recommendation 5.E3
Expert consensus	Level of consensus +++
Women with vulvovaginal symptoms, especially with a thin homogeneous grayish discharge (with or without a fishy odor) and an alkaline vaginal pH, must be investigated for bacterial vaginosis.

The characteristic symptom of BV is increased homogeneous vaginal discharge [33], [34]. The discharge is thin with a grayish, slightly milky color [35], [36], [37], and is accompanied by a fishy smell and a vaginal pH of > 4.5 [34]. Additional irritations in the genital area include burning sensation, redness, itching, dyspareunia, or dysuria. Many women present to their GP because of menstrual disorders or bladder infection symptoms [33], [38]. In pregnancy, BV may present with symptoms such as preterm labor, cervical shortening, or premature rupture of membranes [39], [40]. In women with sexually transmissible infections including HIV, the other infections may mask the symptoms of BV making it more difficult to arrive at the correct diagnosis [41], [42], [43]. Vulvovaginal candidiasis (VVC) is the most important differential diagnosis, although the main symptom of VVC is vestibular itching [44], [45]. The majority of women (85%) with trichomoniasis are asymptomatic [46], [47], although one third of these women go on to develop symptoms within 6 months [48]. Classic symptoms also include vaginal discharge, which is often foul-smelling and has a yellow-green color, accompanied by dysuria, itchiness, and abdominal pain. In contrast to BV, infection with Chlamydia trachomatis is usually characterized by a limited cervical discharge, cervical contact bleeding, urethritis, menstrual disorders, and in some cases endometritis, salpingitis and lower abdominal pain [44].

6  Diagnosis

Consensus-based recommendation 6.E4
Expert consensus	Level of consensus +++
Diagnostic investigations for bacterial vaginosis must be guided by the patientʼs prior medical history, clinical findings, and the microscopic evidence of clue cells in the unfixed vaginal smear, as well as an evaluation based on the Amsel criteria if necessary.

Consensus-based recommendation 6.E5
Expert consensus	Level of consensus +++
After the initial diagnostic workup, lab diagnostics for bacterial vaginosis should include Gram staining with quantitative comparison of different morphotypes using the Nugent scoring system.

Consensus-based recommendation 6.E6
Expert consensus	Level of consensus +++
Lab diagnostics for bacterial vaginosis based on molecular genetic procedures only play a minor role in clinical practice and should currently only be used in special cases.

The correct diagnosis of BV is of special clinical importance for women with recurrent disease and women with failure of first-line therapy [49] as well as for women wanting to have children or women being investigated for a history of preterm birth [50], [51]. Classic microscopic examinations such as unfixed vaginal smear and gram-staining of specimens are still recommended as the reference methods [49], [50]. But these methods can only identify the morphotypes and therefore only permit general statements to be made about the existing changes to the vaginal microbiota. In recent years, molecular genetic methods (FISH, NAAT/PCR, NGS) have been developed to diagnose BV, which provide much more detailed information about changes to the vaginal microbiota, permitting a more precise diagnosis and therefore a more targeted therapy [52].

In patients with the typical symptoms of BV, the diagnosis can be made based on the patientʼs medical history, local findings, examination of an unfixed vaginal smear, and determination of the vaginal pH [44]. With BV, an unfixed smear obtained from the vaginal discharge (phase-contrast microscopy × 400) will show numerous short coccobacilli on the epithelial cells of the vagina, which Gardner has called clue cells [53]. Lactobacilli and other morphotypes or leukocytes cannot be detected or are almost undetectable [44]. The Amsel criteria are met if 3 of the 4 following characteristics are present: homogeneous grayish-white vaginal discharge; vaginal pH > 4.5; vaginal discharge has a fishy smell, especially after the addition of a drop of 10% potassium hydroxide (KOH); and/or confirmation of at least 20% clue cells in relation to the total number of epithelial cells in the unfixed vaginal smear visible in the field of vision [54].

The Nugent scoring system is a standardized assessment method for Gram-stained vaginal smears where points (0 to 10) are used for a semiquantitative assessment; large gram-positive bacilli are scored as 0 to 4, small gram-variable and gram-negative bacilli as 0 to 4, and curved Mobiluncus-like bacilli as 0 to 2 [55]. With this scoring system, women with clinical symptoms of BV usually have scores between 7 and 10, whereas healthy women have scores between 0 and 3. Scores from 4 to 6 are considered “intermediate” and do not permit clinically relevant statements to be made [56]. The Hay-Ison score may be used as an alternative scoring system. It differentiates between 5 categories (grades 0 to 4), whereby grade 0 indicates that only epithelial cells without lactobacilli or indications of BV are present. Grade 1 constitutes a normal state with a predominance of vaginal lactobacilli, grade 2 represents intermediate mixed vaginal flora with some Gardnerella and Mobiluncus morphotypes, grade 3 stands for typical BV with clue cells dominated by anaerobes (without lactobacilli or with only a few lactobacilli). Grade 4 indicates gram-positive cocci, with indications of BV or lactobacilli morphotypes [57].

Fluorescence in situ hybridization (FISH) is used to obtain a clear taxonomic identification of the microorganisms and to assess the spatial organization and morphological features of the investigated specimen [58]. Next generation sequencing (NGS) is used to identify the genotype of microorganisms in microbial communities even if only small amounts are present in the clinical sample [59]. Quantitative multiplex polymerase chain reaction (qPCR) has a sensitivity of 80% and a specificity of up to 92% [60]. But this method should be reserved for women who wish to become pregnant, women who are already pregnant, and women undergoing IVF, or to screen patients with an increased risk of STI. Additional laboratory tests include the BD Affirm VPIII assay, a synthetic oligonucleotide probe test [61], [62], [63], [64], and diverse point-of-care tests such as the OSOM BVBLUE test which is based on the detection of sialidase activity [65], [66], and the FemExam test which detects the metabolite trimethylamine and proline aminopeptidase activity [64], [67].

7  Therapy

Consensus-based recommendation 7.E7
Expert consensus	Level of consensus +++
Women with vulvovaginal symptoms and confirmed bacterial vaginosis must be treated in accordance with medical guidelines.

Consensus-based recommendation 7.E8
Expert consensus	Level of consensus +++
The treatment of bacterial vaginosis must consist of oral or topical clindamycin or metronidazole. Alternatively, local antiseptics may be used.

Consensus-based recommendation 7.E9
Expert consensus	Level of consensus +++
The treatment of chronically recurrent bacterial vaginosis should consist of local antiseptics or suppressive maintenance therapy using topical metronidazole, followed by vaginal probiotics to reduce the probability of recurrence after completing therapy.

Consensus-based recommendation 7.E10
Expert consensus	Level of consensus +++
Pregnant women with symptomatic bacterial vaginosis must be treated to reduce symptoms and reduce complications in pregnancy and puerperium.

Consensus-based recommendation 7.E11
Expert consensus	Level of consensus +++
Therapy for symptomatic bacterial vaginosis in pregnancy must consist primarily of treatment with clindamycin. Alternatively vaginal antiseptics may be used.

Consensus-based recommendation 7.E12
Expert consensus	Level of consensus +++
Treatment for bacterial vaginosis must only be initiated after a proper diagnostic workup and a medically confirmed diagnosis.

Consensus-based recommendation 7.E13
Expert consensus	Level of consensus +++
Lactic acid and probiotics appear to have a positive impact during therapy and as recurrence prophylaxis and may be used as a complementary approach.

Consensus-based statement 7.E14
Expert consensus	Level of consensus +++
If a woman suffers from chronic recurrent BV, treating her partner may be considered although the evidence for this is limited.

Consensus-based recommendation 7.E15
Expert consensus	Level of consensus +++
Women with bacterial vaginosis must be informed about measures which can prevent the recurrence of bacterial vaginosis in their case.

Consensus-based recommendation 7.E16
Expert consensus	Level of consensus +++
Women with bacterial vaginosis who wish to become pregnant soon should be treated even if they are asymptomatic. The same applies to women with aerobic or desquamative inflammatory vaginitis.

Treatment of BV is indicated for all patients with vulvovaginal symptoms [49]. But asymptomatic women with BV also benefit indirectly from therapy as treatment reduces the risk of endometritis, PID and STIs, which are associated with possible subsequent infertility [68]. BV can have a significant negative impact on the quality of life of women with recurrent disease or failure of first-line therapy, and treatment is often difficult and protracted.

If metronidazole is used as first-line therapy for BV, the resistance mechanisms of Gardnerella spp. often lead to treatment failure [69]. If oral therapy consists of 500 mg metronidazole, the recommended treatment is to take it twice a day for 7 days or once or twice within 48 hours for 2 g metronidazole. Therapy with 300 mg clindamycin taken two to three times a day for 7 days is less often limited by treatment resistance. Recommended alternative topical therapies include vaginal metronidazole or 2% clindamycin cream once a day for 7 days, as well as vaginal clindamycin ovules for 3 days. In some randomized controlled studies, antiseptics such as 10 mg dequalinium chloride administered once a day for 6 days, octenidine vaginal spray or iodine-containing preparations were found to have good results when treating BV [70] – [74]. Using antiseptics as a treatment alternative appears to be useful, especially given the fact that metronidazole is often ineffective against the BV biofilm and the increasing resistance to antibiotics, even though antiseptics reduce the already low percentage of lactobacilli in women with BV even further [75], [76], [77]. More rarely used treatment alternatives include 2 g secnidazole taken orally as a one-off therapy or 2 g oral tinidazole for 2 days or 1 g tinidazole taken orally for 5 days. The administration of probiotics after completing antibiotic or antiseptic therapy aims to restore vaginal microbiota [78]. The risk of repeatedly suffering the same symptoms after completing first-line BV therapy is high. Review articles report a recurrence rate of 80% within 3 – 12 months after completion of therapy [34], [79]. The biofilms which are usually responsible for recurrence cannot be removed with standard first-line antibiotics [80], [81], although a disruptive effect has been reported in vitro for dequalinium chloride [82]. Local antiseptics could therefore represent a useful alternative to treat recurrent disease [72]. There have been attempts to use some regimens to suppress recurrence but none of them have been consistently effective, meaning that suppressive maintenance therapy may be proposed, as is used to treat chronically recurrent VVC. Topical metronidazole administered twice a week for a total of 16 weeks may be an appropriate therapeutic approach [83].

Antibiotic treatment of BV is effective in pregnancy, although it does not significantly reduce the overall risk of preterm birth [84]. But treatment is recommended for all symptomatic pregnant women to reduce their symptoms and because symptomatic BV during pregnancy has been found to be associated with premature rupture of membranes, preterm birth, amniotic infection syndrome and postpartum endometritis [85], [86], [87]. In addition to symptomatic women, there are indications that the diagnosis and therapy of asymptomatic BV before the 23rd week of gestation can reduce the rate of preterm births [88]. Because of its anti-inflammatory and cytokine-inhibiting effect as well as its broad antibiotic spectrum, clindamycin appears to be more suitable for use during pregnancy than metronidazole [49]. The administration of tinidazole should be avoided during pregnancy. Because of their clinically comparable efficacy, other antiseptics such as dequalinium chloride or octenidine may be considered suitable alternatives [71], [73]. Povidone-iodine should not be administered during pregnancy.

According to the research to date, full-blown BV and chronically recurrent BV cannot be cured with lactic acid or lactobacilli preparations alone [89]. In their systematic review, Plummer et al. [90] reported that because of the divergent methods and results it is not possible to make a clear recommendation for or against the use of lactic acid as prophylaxis or treatment against BV. Similarly, the administration of vaginal or oral lactobacilli and probiotics as prophylaxis or therapy to treat BV is still controversial [91], [92], [93], even though individual studies have shown significant benefits associated with the use of probiotics during or after BV [78]. Oral probiotics are only detectable about 1 – 2 weeks later in the vagina and remain there as long as they continue to be taken orally [94], [95]. Other alternative and complementary therapeutics include a vaginal preparation with ascorbic acid [96] and a polymer made of a combination of Aloe barbadensis and lactic acid [97].

The rate of BV recurrence depends on a number of factors; re-infection with BVAB and re-infection through endogenous sources but also re-infection via the patientʼs sexual partner all play a role [31], [98]. However, the Center for Disease Control and Prevention (CDC) does not recommend routine co-treatment of the partner in cases with recurrent BV. The rate of recurrence may be reduced by avoiding other predisposing host or risk factors, for example avoiding stress, having a healthy life style and a normal body weight [99]. There is an association between BV and infertility although the precise pathomechanism of this is not clear. On the one hand, women with BV have a higher risk of developing ascending infections such as cervicitis, endometritis and pelvic inflammatory disease (PID) [68]. Chronic endometritis may often be clinically inapparent for years, leading to inflammatory processes which can interfere with implantation of the fertilized oocyte and may lead to tubal sterility [100] – [104]. On the other hand, BV biofilms also appear to play a role in fertility [58]. Overall, poor IVF outcomes have been reported for women with low microbial diversity and women with a higher percentage of abnormal vaginal microbiota [105]. Antibiotic therapy with doxycycline after hysteroscopy and endometrial scratching improves the pregnancy rate [106].

8  Outlook

Consensus-based recommendation 8.E17
Expert consensus	Level of consensus +++
Future research into bacterial vaginosis should focus on preventing the high rates of recurrence and chronic recurrence of disease.

Avoiding resistance and chronic recurrence as well as the prevention of BV are therefore at the top of the agenda for future research. The efficacy of alternative therapies and the current treatment plan should be expanded and amended based on the results of new clinical studies into modern approaches and precision medicine [28], [31], [107], [108]. Treatment with Lactobacillus crispatus CTV-05 (LACTIN-V) could also be an interesting approach as it has been shown that the application of LACTIN-V after initial treatment with vaginal metronidazole resulted in a significantly lower rate of BV recurrence after 12 weeks [109]. The current evidence on the efficacy of astodrimer is relatively limited [110], [111] as is the evidence for a vaginal polycarbophil cream consisting of 0.04% lauryl glucoside and glycerides, although the data obtained for polycarbophil regarding a reduction in the rate of BV recurrence has been promising [112], [113]. The data from clinical studies into TOL-463, an antiseptic based on boric acid which is especially effective against vaginal biofilms of bacteria and fungi, are still not in [114], [115]. Finally, research is also increasingly focusing on co-treatment of the patientʼs partner [116].

Acknowledgements

The authors would like to thank Alexander Swidsinski and Paul Gaß for their enduring support.

• Literatur

• 1 Peebles K, Velloza J, Balkus JE. et al. High Global Burden and Costs of Bacterial Vaginosis: A Systematic Review and Meta-Analysis. Sex Transm Dis 2019; 46: 304-311
• 2 Swidsinski A, Mendling W, Loening-Baucke V. et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol 2005; 106: 1013-1023
• 3 Hill GB. The microbiology of bacterial vaginosis. Am J Obstet Gynecol 1993; 169: 450-454
• 4 Vaneechoutte M, Guschin A, Van Simaey L. et al. Emended description of Gardnerella vaginalis and description of Gardnerella leopoldii sp. nov., Gardnerella piotii sp. nov. and Gardnerella swidsinskii sp. nov., with delineation of 13 genomic species within the genus Gardnerella. Int J Syst Evol Microbiol 2019; 69: 679-687
• 5 van Esbroeck M, Vandamme P, Falsen E. et al. Polyphasic approach to the classification and identification of Gardnerella vaginalis and unidentified Gardnerella vaginalis-like coryneforms present in bacterial vaginosis. Int J Syst Bacteriol 1996; 46: 675-682
• 6 Sadhu K, Domingue PA, Chow AW. et al. Gardnerella vaginalis has a gram-positive cell-wall ultrastructure and lacks classical cell-wall lipopolysaccharide. J Med Microbiol 1989; 29: 229-235
• 7 Patterson JL, Stull-Lane A, Girerd PH. et al. Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes. Microbiology (Reading) 2010; 156: 392-399
• 8 Wertz J, Isaacs-Cosgrove N, Holzman C. et al. Temporal Shifts in Microbial Communities in Nonpregnant African-American Women with and without Bacterial Vaginosis. Interdiscip Perspect Infect Dis 2008; 2008: 181253
• 9 Shipitsyna E, Roos A, Datcu R. et al. Composition of the vaginal microbiota in women of reproductive age–sensitive and specific molecular diagnosis of bacterial vaginosis is possible?. PLoS One 2013; 8: e60670
• 10 Rosca AS, Castro J, Sousa LGV. et al. Gardnerella and vaginal health: the truth is out there. FEMS Microbiol Rev 2020; 44: 73-105
• 11 Bradshaw CS, Sobel JD. Current Treatment of Bacterial Vaginosis-Limitations and Need for Innovation. J Infect Dis 2016; 214 (Suppl. 01) S14-S20
• 12 Swidsinski A, Verstraelen H, Loening-Baucke V. et al. Presence of a polymicrobial endometrial biofilm in patients with bacterial vaginosis. PLoS One 2013; 8: e53997
• 13 Sewankambo N, Gray RH, Wawer MJ. et al. HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis. Lancet 1997; 350: 546-550
• 14 Cauci S, Monte R, Driussi S. et al. Impairment of the mucosal immune system: IgA and IgM cleavage detected in vaginal washings of a subgroup of patients with bacterial vaginosis. J Infect Dis 1998; 178: 1698-1706
• 15 Verstraelen H, Verhelst R, Nuytinck L. et al. Gene polymorphisms of Toll-like and related recognition receptors in relation to the vaginal carriage of Gardnerella vaginalis and Atopobium vaginae. J Reprod Immunol 2009; 79: 163-173
• 16 Ravel J, Gajer P, Abdo Z. et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 2011; 108 (Suppl. 01) 4680-4687
• 17 Borgdorff H, van der Veer C, van Houdt R. et al. The association between ethnicity and vaginal microbiota composition in Amsterdam, the Netherlands. PLoS One 2017; 12: e0181135
• 18 Bautista CT, Wurapa E, Sateren WB. et al. Bacterial vaginosis: a synthesis of the literature on etiology, prevalence, risk factors, and relationship with chlamydia and gonorrhea infections. Mil Med Res 2016; 3: 4
• 19 Kenyon C, Colebunders R, Crucitti T. The global epidemiology of bacterial vaginosis: a systematic review. Am J Obstet Gynecol 2013; 209: 505-523
• 20 Martin DH. The microbiota of the vagina and its influence on womenʼs health and disease. Am J Med Sci 2012; 343: 2-9
• 21 Marrazzo JM, Fiedler TL, Srinivasan S. et al. Extravaginal reservoirs of vaginal bacteria as risk factors for incident bacterial vaginosis. J Infect Dis 2012; 205: 1580-1588
• 22 Bradshaw CS, Walker SM, Vodstrcil LA. et al. The influence of behaviors and relationships on the vaginal microbiota of women and their female partners: the WOW Health Study. J Infect Dis 2014; 209: 1562-1572
• 23 Brookheart RT, Lewis WG, Peipert JF. et al. Association between obesity and bacterial vaginosis as assessed by Nugent score. Am J Obstet Gynecol 2019; 220: 476.e1-476.e11
• 24 Swidsinski A, Doerffel Y, Loening-Baucke V. et al. Gardnerella biofilm involves females and males and is transmitted sexually. Gynecol Obstet Invest 2010; 70: 256-263
• 25 Swidsinski A, Dorffel Y, Loening-Baucke V. et al. Desquamated epithelial cells covered with a polymicrobial biofilm typical for bacterial vaginosis are present in randomly selected cryopreserved donor semen. FEMS Immunol Med Microbiol 2010; 59: 399-404
• 26 Zozaya M, Ferris MJ, Siren JD. et al. Bacterial communities in penile skin, male urethra, and vaginas of heterosexual couples with and without bacterial vaginosis. Microbiome 2016; 4: 16
• 27 Vodstrcil LA, Walker SM, Hocking JS. et al. Incident bacterial vaginosis (BV) in women who have sex with women is associated with behaviors that suggest sexual transmission of BV. Clin Infect Dis 2015; 60: 1042-1053
• 28 Bradshaw CS, Morton AN, Hocking J. et al. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis 2006; 193: 1478-1486
• 29 Francis SC, Looker C, Vandepitte J. et al. Bacterial vaginosis among women at high risk for HIV in Uganda: high rate of recurrent diagnosis despite treatment. Sex Transm Infect 2016; 92: 142-148
• 30 Vodstrcil LA, Hocking JS, Law M. et al. Hormonal contraception is associated with a reduced risk of bacterial vaginosis: a systematic review and meta-analysis. PLoS One 2013; 8: e73055
• 31 Bradshaw CS, Sobel JD. Current Treatment of Bacterial Vaginosis-Limitations and Need for Innovation. J Infect Dis 2016; 214 (Suppl. 01) S14-S20
• 32 Li XD, Wang CC, Zhang XJ. et al. Risk factors for bacterial vaginosis: results from a cross-sectional study having a sample of 53,652 women. Eur J Clin Microbiol Infect Dis 2014; 33: 1525-1532
• 33 Klebanoff MA, Schwebke JR, Zhang J. et al. Vulvovaginal symptoms in women with bacterial vaginosis. Obstet Gynecol 2004; 104: 267-272
• 34 Bagnall P, Rizzolo D. Bacterial vaginosis: A practical review. JAAPA 2017; 30: 15-21
• 35 Onderdonk AB, Delaney ML, Fichorova RN. The Human Microbiome during Bacterial Vaginosis. Clin Microbiol Rev 2016; 29: 223-238
• 36 Pepin J, Deslandes S, Giroux G. et al. The complex vaginal flora of West African women with bacterial vaginosis. PLoS One 2011; 6: e25082
• 37 Mendling W. Vaginal Microbiota. Adv Exp Med Biol 2016; 902: 83-93
• 38 Hoyme UB, Eschenbach DA. [Bacterial vaginitis. Microbiology, diagnosis, therapy and complications]. Dtsch Med Wochenschr 1985; 110: 349-353
• 39 Lamont RF, Duncan SL, Mandal D. et al. Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora. Obstet Gynecol 2003; 101: 516-522
• 40 Joergensen JS, Kjaer Weile LK, Lamont RF. The early use of appropriate prophylactic antibiotics in susceptible women for the prevention of preterm birth of infectious etiology. Expert Opin Pharmacother 2014; 15: 2173-2191
• 41 Mirmonsef P, Krass L, Landay A. et al. The role of bacterial vaginosis and trichomonas in HIV transmission across the female genital tract. Curr HIV Res 2012; 10: 202-210
• 42 Atashili J, Poole C, Ndumbe PM. et al. Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. AIDS (London, England) 2008; 22: 1493-1501
• 43 Wanga V, Mackelprang RD, Thomas KK. et al. Brief Report: Bacterial Vaginosis and Risk of HIV Infection in the Context of CD101 Gene Variation. J Acquir Immune Defic Syndr 2020; 85: 584-587
• 44 Mendling W. Gynäkologische Infektiologie – Diagnostik und Therapie beim Symptom Fluor. Frauenarzt 2018; 59: 65
• 45 Sustr V, Foessleitner P, Kiss H. et al. Vulvovaginal Candidosis: Current Concepts, Challenges and Perspectives. J Fungi (Basel) 2020; 6: 267
• 46 Sutton M, Sternberg M, Koumans EH. et al. The prevalence of Trichomonas vaginalis infection among reproductive-age women in the United States, 2001–2004. Clin Infect Dis 2007; 45: 1319-1326
• 47 Sena AC, Miller WC, Hobbs MM. et al. Trichomonas vaginalis infection in male sexual partners: implications for diagnosis, treatment, and prevention. Clin Infect Dis 2007; 44: 13-22
• 48 Petrin D, Delgaty K, Bhatt R. et al. Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev 1998; 11: 300-317
• 49 Workowski KA, Bachmann LH, Chan PA. et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021; 70: 1-187
• 50 Sherrard J, Wilson J, Donders G. et al. 2018 European (IUSTI/WHO) International Union against sexually transmitted infections (IUSTI) World Health Organisation (WHO) guideline on the management of vaginal discharge. Int J STD AIDS 2018; 29: 1258-1272
• 51 Fischer T, Mortl M, Reif P. et al. Statement by the OEGGG with Review of the Literature on the Mode of Delivery of Premature Infants at the Limit of Viability. Geburtshilfe Frauenheilkd 2018; 78: 1212-1216
• 52 Sobel JD, Kaur N, Woznicki NA. et al. Prognostic Indicators of Recurrence of Bacterial Vaginosis. J Clin Microbiol 2019; 57: e00227-19
• 53 Gardner HL, Dukes CD. Haemophilus vaginalis vaginitis: a newly defined specific infection previously classified non-specific vaginitis. Am J Obstet Gynecol 1955; 69: 962-976
• 54 Amsel R, Totten PA, Spiegel CA. et al. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983; 74: 14-22
• 55 Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 1991; 29: 297-301
• 56 Abele-Horn M, Blenk H, Clad A. Genitalinfektionen Teil I in mikrobiologisch-infektiologische Qualitätsstandards (MIQ), MIQ 10. Elsevier Verlag, Urban & Fischer; 2011
• 57 Ison CA, Hay PE. Validation of a simplified grading of Gram stained vaginal smears for use in genitourinary medicine clinics. Sex Transm Infect 2002; 78: 413-415
• 58 Swidsinski A, Loening-Baucke V, Mendling W. et al. Infection through structured polymicrobial Gardnerella biofilms (StPM-GB). Histol Histopathol 2014; 29: 567-587
• 59 Hong KH, Hong SK, Cho SI. et al. Analysis of the Vaginal Microbiome by Next-Generation Sequencing and Evaluation of its Performance as a Clinical Diagnostic Tool in Vaginitis. Ann Lab Med 2016; 36: 441-449
• 60 van den Munckhof EHA, van Sitter RL, Boers KE. et al. Comparison of Amsel criteria, Nugent score, culture and two CE-IVD marked quantitative real-time PCRs with microbiota analysis for the diagnosis of bacterial vaginosis. Eur J Clin Microbiol Infect Dis 2019; 38: 959-966
• 61 Eschenbach DA, Hillier S, Critchlow C. et al. Diagnosis and clinical manifestations of bacterial vaginosis. Am J Obstet Gynecol 1988; 158: 819-828
• 62 Krohn MA, Hillier SL, Eschenbach DA. Comparison of methods for diagnosing bacterial vaginosis among pregnant women. J Clin Microbiol 1989; 27: 1266-1271
• 63 Spiegel CA, Amsel R, Holmes KK. Diagnosis of bacterial vaginosis by direct gram stain of vaginal fluid. J Clin Microbiol 1983; 18: 170-177
• 64 Coleman JS, Gaydos CA. Molecular Diagnosis of Bacterial Vaginosis: an Update. J Clin Microbiol 2018; 56: e00342-18
• 65 Myziuk L, Romanowski B, Johnson SC. BVBlue test for diagnosis of bacterial vaginosis. J Clin Microbiol 2003; 41: 1925-1928
• 66 Bradshaw CS, Morton AN, Garland SM. et al. Evaluation of a point-of-care test, BVBlue, and clinical and laboratory criteria for diagnosis of bacterial vaginosis. J Clin Microbiol 2005; 43: 1304-1308
• 67 West B, Morison L, Schim van der Loeff M. et al. Evaluation of a new rapid diagnostic kit (FemExam) for bacterial vaginosis in patients with vaginal discharge syndrome in The Gambia. Sex Transm Dis 2003; 30: 483-489
• 68 Ravel J, Moreno I, Simon C. Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease. Am J Obstet Gynecol 2021; 224: 251-257
• 69 Landlinger C, Oberbauer V, Podpera Tisakova L. et al. Preclinical Data on the Gardnerella-Specific Endolysin PM-477 Indicate Its Potential to Improve the Treatment of Bacterial Vaginosis through Enhanced Biofilm Removal and Avoidance of Resistance. Antimicrob Agents Chemother 2022; 66: e0231921
• 70 Weissenbacher ER, Donders G, Unzeitig V. et al. A comparison of dequalinium chloride vaginal tablets (Fluomizin(R)) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-blind, randomized clinical trial of efficacy and safety. Gynecol Obstet Invest 2012; 73: 8-15
• 71 Mendling W, Palmeira-de-Oliveira A, Biber S. et al. An update on the role of Atopobium vaginae in bacterial vaginosis: what to consider when choosing a treatment? A mini review. Arch Gynecol Obstet 2019; 300: 1-6
• 72 Novakov Mikic A, Budakov D. Comparison of local metronidazole and a local antiseptic in the treatment of bacterial vaginosis. Arch Gynecol Obstet 2010; 282: 43-47
• 73 Briese V, Neumann G, Waldschlager J. et al. Efficacy and tolerability of a local acting antiseptic agent in the treatment of vaginal dysbiosis during pregnancy. Arch Gynecol Obstet 2011; 283: 585-590
• 74 Novakov Mikic A, Stojic S. Study results on the use of different therapies for the treatment of vaginitis in hospitalised pregnant women. Arch Gynecol Obstet 2015; 292: 371-376
• 75 Swidsinski A, Dorffel Y, Loening-Baucke V. et al. Response of Gardnerella vaginalis biofilm to 5 days of moxifloxacin treatment. FEMS Immunol Med Microbiol 2011; 61: 41-46
• 76 Swidsinski A, Loening-Baucke V, Swidsinski S. et al. Clue Cells and Pseudo Clue Cells in Different Morphotypes of Bacterial Vaginosis. Front Cell Infect Microbiol 2022; 12: 905739
• 77 McGough SF, MacFadden DR, Hattab MW. et al. Rates of increase of antibiotic resistance and ambient temperature in Europe: a cross-national analysis of 28 countries between 2000 and 2016. Euro Surveill 2020; 25: 1900414
• 78 Petricevic L, Witt A. The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal flora after antibiotic treatment of bacterial vaginosis. BJOG 2008; 115: 1369-1374
• 79 Coudray MS, Madhivanan P. Bacterial vaginosis-A brief synopsis of the literature. Eur J Obstet Gynecol Reprod Biol 2020; 245: 143-148
• 80 Gottschick C, Deng ZL, Vital M. et al. Treatment of biofilms in bacterial vaginosis by an amphoteric tenside pessary-clinical study and microbiota analysis. Microbiome 2017; 5: 119
• 81 Swidsinski A, Mendling W, Loening-Baucke V. et al. An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am J Obstet Gynecol 2008; 198: 97.e1-97.e6
• 82 Gaspar C, Rolo J, Cerca N. et al. Dequalinium Chloride Effectively Disrupts Bacterial Vaginosis (BV) Gardnerella spp. Biofilms. Pathogens 2021; 10: 261
• 83 Sobel JD, Ferris D, Schwebke J. et al. Suppressive antibacterial therapy with 0.75 % metronidazole vaginal gel to prevent recurrent bacterial vaginosis. Am J Obstet Gynecol 2006; 194: 1283-1289
• 84 Brocklehurst PGA, Heatley E, Milan SJ. Antibiotics for treating bacterial vaginosis in pregnancy (Review). John Wiley & Sons; 2013
• 85 Laxmi U, Agrawal S, Raghunandan C. et al. Association of bacterial vaginosis with adverse fetomaternal outcome in women with spontaneous preterm labor: a prospective cohort study. J Matern Fetal Neonatal Med 2012; 25: 64-67
• 86 Nelson DB, Hanlon A, Hassan S. et al. Preterm labor and bacterial vaginosis-associated bacteria among urban women. J Perinat Med 2009; 37: 130-134
• 87 Koumans EH, Kendrick JS. CDC Bacterial Vaginosis Working Group. Preventing adverse sequelae of bacterial vaginosis: a public health program and research agenda. Sex Transm Dis 2001; 28: 292-297
• 88 Berger R, Abele H, Bahlmann F. et al. Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, February 2019) – Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and the Management of Preterm Premature Rupture of Membranes. Geburtshilfe Frauenheilkd 2019; 79: 813-833
• 89 Boeke AJ, Dekker JH, van Eijk JT. et al. Effect of lactic acid suppositories compared with oral metronidazole and placebo in bacterial vaginosis: a randomised clinical trial. Genitourin Med 1993; 69: 388-392
• 90 Plummer EL, Bradshaw CS, Doyle M. et al. Lactic acid-containing products for bacterial vaginosis and their impact on the vaginal microbiota: A systematic review. PLoS One 2021; 16: e0246953
• 91 Wang ZB, Xin SS, Ding LN. et al. The Potential Role of Probiotics in Controlling Overweight/Obesity and Associated Metabolic Parameters in Adults: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med 2019; 2019: 3862971
• 92 Li C, Wang T, Li Y. et al. Probiotics for the treatment of women with bacterial vaginosis: A systematic review and meta-analysis of randomized clinical trials. Eur J Pharmacol 2019; 864: 172660
• 93 Mastromarino P, Vitali B, Mosca L. Bacterial vaginosis: a review on clinical trials with probiotics. New Microbiol 2013; 36: 229-238
• 94 Strus M, Chmielarczyk A, Kochan P. et al. Studies on the effects of probiotic Lactobacillus mixture given orally on vaginal and rectal colonization and on parameters of vaginal health in women with intermediate vaginal flora. Eur J Obstet Gynecol Reprod Biol 2012; 163: 210-215
• 95 De Alberti D, Russo R, Terruzzi F. et al. Lactobacilli vaginal colonisation after oral consumption of Respecta((R)) complex: a randomised controlled pilot study. Arch Gynecol Obstet 2015; 292: 861-867
• 96 Petersen EE, Genet M, Caserini M. et al. Efficacy of vitamin C vaginal tablets in the treatment of bacterial vaginosis: a randomised, double blind, placebo controlled clinical trial. Arzneimittel-Forschung 2011; 61: 260-265
• 97 Bojovic T, Bojovic D, Boyer de la Tour FX. et al. First Line Treatment and Relief of Bacterial Vaginosis-related Vaginal Complaints with Metronidazole and Multi-Gyn(R) ActiGel. Eur Obstet Gynecol 2012; 7: 103-106
• 98 Bradshaw CS, Brotman RM. Making inroads into improving treatment of bacterial vaginosis – striving for long-term cure. BMC Infect Dis 2015; 15: 292
• 99 Nansel TR, Riggs MA, Yu KF. et al. The association of psychosocial stress and bacterial vaginosis in a longitudinal cohort. Am J Obstet Gynecol 2006; 194: 381-386
• 100 Gaudoin M, Rekha P, Morris A. et al. Bacterial vaginosis and past chlamydial infection are strongly and independently associated with tubal infertility but do not affect in vitro fertilization success rates. Fertil Steril 1999; 72: 730-732
• 101 Liversedge NH, Turner A, Horner PJ. et al. The influence of bacterial vaginosis on in-vitro fertilization and embryo implantation during assisted reproduction treatment. Hum Reprod 1999; 14: 2411-2415
• 102 Wilson JD, Ralph SG, Rutherford AJ. Rates of bacterial vaginosis in women undergoing in vitro fertilisation for different types of infertility. BJOG 2002; 109: 714-717
• 103 Campisciano G, Florian F, DʼEustacchio A. et al. Subclinical alteration of the cervical-vaginal microbiome in women with idiopathic infertility. J Cell Physiol 2017; 232: 1681-1688
• 104 Wee BA, Thomas M, Sweeney EL. et al. A retrospective pilot study to determine whether the reproductive tract microbiota differs between women with a history of infertility and fertile women. Aust N Z J Obstet Gynaecol 2018; 58: 341-348
• 105 Haahr T, Humaidan P, Elbaek HO. et al. Vaginal Microbiota and In Vitro Fertilization Outcomes: Development of a Simple Diagnostic Tool to Predict Patients at Risk of a Poor Reproductive Outcome. J Infect Dis 2019; 219: 1809-1817
• 106 Park HJ, Kim YS, Yoon TK. et al. Chronic endometritis and infertility. Clin Exp Reprod Med 2016; 43: 185-192
• 107 Schwebke JR, Desmond RA. A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis. Clin Infect Dis 2007; 44: 213-219
• 108 Donders GG, Zodzika J, Rezeberga D. Treatment of bacterial vaginosis: what we have and what we miss. Expert Opin Pharmacother 2014; 15: 645-657
• 109 Cohen CR, Wierzbicki MR, French AL. et al. Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis. N Engl J Med 2020; 382: 1906-1915
• 110 OʼLoughlin J, Millwood IY, McDonald HM. et al. Safety, tolerability, and pharmacokinetics of SPL7013 gel (VivaGel): a dose ranging, phase I study. Sex Transm Dis 2010; 37: 100-104
• 111 McGowan I, Gomez K, Bruder K. et al. Phase 1 randomized trial of the vaginal safety and acceptability of SPL7013 gel (VivaGel) in sexually active young women (MTN-004). AIDS (London, England) 2011; 25: 1057-1064
• 112 Ardolino LI, Meloni M, Brugali G. et al. Preclinical Evaluation of Tolerability of a Selective, Bacteriostatic, Locally Active Vaginal Formulation. Curr Ther Res Clin Exp 2016; 83: 13-21
• 113 Murina F, Crisan C, Biris M. et al. Efficacy and safety of a novel vaginal medical device in recurrent bacterial vaginosis: a multicenter clinical trial. Minerva Ginecol 2020; 72: 292-298
• 114 Reichman O, Akins R, Sobel JD. Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis. Sex Transm Dis 2009; 36: 732-734
• 115 Marrazzo JM, Dombrowski JC, Wierzbicki MR. et al. Safety and Efficacy of a Novel Vaginal Anti-infective, TOL-463, in the Treatment of Bacterial Vaginosis and Vulvovaginal Candidiasis: A Randomized, Single-blind, Phase 2, Controlled Trial. Clin Infect Dis 2019; 68: 803-809
• 116 Plummer EL, Vodstrcil LA, Danielewski JA. et al. Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: Acceptability, tolerability and impact on the genital microbiota of couples – A pilot study. PLoS One 2018; 13: e0190199

Publication History

Received: 28 August 2023

Accepted: 29 August 2023

Article published online:
03 November 2023