A4_201

First Line Treatment and Relief of Bacterial Vaginosis-related Vaginal
Complaints with Metronidazole and Multi-Gyn® ActiGel
T a t j a n a B o j o v i c , 1 D j o r d j e B o j o v i c , 1 F r a n ç o i s - X a v i e r B o y e r d e L a T o u r 2 a n d B a b e t t e L a m e r s 3 1. Gynaecologist, Gao Bojovic, Belgrade, Serbia; 2. Gynaecologist and Obstetrician, Policlinique Saint Claude, Saint Quentin, France; 3. Resident, Department of Gynaecology and Obstetrics, Reinier de Graaf Gasthuis, Delft, The Netherlands Abstract
Metronidazole has been the treatment of choice prescribed for bacterial vaginosis (BV). Interfering with the bacterial adhesion
mechanism may offer an alternative. Multi-Gyn® ActiGel is a vaginal gel based on a high molecular polysaccharide complex that intervenes in microbial adhesion. During this open label study, 47 age-matched women with BV and related complaints received as first line treatment either a course of prescribed oral metronidazole or ActiGel intra-vaginally. Results: Oral metronidazole was slightly more effective at one week post treatment; ActiGel was equally as effective as metronidazole at three months post treatment. Conclusion: Physicians may encourage the use of this vaginal gel for self-care in order to treat and relieve BV related symptoms and thus reduce the prescription of antibiotics and the emergence of resistance.
Keywords
Bacterial vaginosis (BV), vaginal complaints, anti-adhesion, metronidazole, vaginal gel, Multi-Gyn® ActiGel, polysaccharides
Disclosure: The authors have no conflicts of interest to declare.
Acknowledgements: The authors acknowledge the data processing by L Matthijs Boon, statistician of Leiden Cytological and Pathological Laboratory, Leiden, The Netherlands.
Received: 30 July 2012 Accepted: 14 August 2012 Citation: European Obstetrics & Gynaecology, 2012;7(2):103–6
Correspondence: Tatjana Bojovic, Gao Bojovic, Bulevar Zorana Djindica 62/1, 11000 Novi Beograd, Serbia. E: [email protected]
Support: The publication of this article was funded by BioClin BV.
A healthy vagina is generally dominated by hydrogen-peroxide-producing The less-than-optimal cure rates, coupled with the high recurrence rates lactobacilli which inhibit the growth of microorganisms such as and the potential for adverse effects for oral metronidazole has prompted Gardnerella vaginalis (G. vaginalis).1 A depletion of lactobacilli a search for an alternative therapy for the treatment of BV. The low and an over-colonisation of anaerobic bacteria such as G. vaginalis, pH of a normal microflora significantly increases the binding capacity Bacteroides, beta-Streptococci, Mobiluncus/Falcivibrio, Prevotella bivia, of lactobacilli to vaginal epithelial cells. The adhesion of G. vaginalis Lachnospiraceae and Mycoplasma hominis leads to a dysbacteriosis to vaginal epithelial cells is also pH dependent and binds maximally at a called bacterial vaginosis (BV).2–5 This is a prevalent vaginal disorder pH between 5–6.17 Due to these properties, vaginal acidification has which affects many women of a reproductive age with an infection rate been examined as a means of treating BV, but has been shown to be of 15–50 %. The condition is associated with complaints such as ineffective in discouraging the growth of BV-associated micro-organisms, malodour of the discharge, excessive discharge, burning and itching. BV and in promoting vaginal re-colonisation with lactobacilli.18 is associated with serious complications such as pelvic inflammatory disease, cervicitis, pre-term labour and an increased risk for acquiring In order to avoid clearance via urine flow and vaginal secretion, a pathogen must first adhere to host cells, thus adherence of anaerobic bacteria is a critical step for pathogenesis. A treatment aimed at Oral metronidazole is most frequently prescribed for the treatment of preventing adherence of G. vaginalis, together with vaginal acidification, BV and is the treatment of choice recommended by the Centers for could increase clinical cure rate and decrease recurrence of BV. Disease Control and Prevention. Metronidazole results in a cure rate Multi-Gyn® ActiGel (ActiGel) is an acidic gel based on 2QR-complex. of 70–80 % at four weeks follow up. However, up to 40 % of the 2QR-complex is a negatively charged, high molecular, multi-branched women treated with metronidazole for BV have a recurrent infection polysaccharide complex that interferes with the adhesive mechanism one to three months following treatment.11–13 One of the concerns, of bacteria.19 This suggests the potential of ActiGel in BV and its following the use of systemic metronidazole, are the potential adverse related vaginal complaints. As an acid gel, ActiGel also maintains an effects. These include: nausea, vomiting, anorexia, heartburn, optimal vaginal pH of 4.1. ActiGel is not an antiseptic or an antibiotic headache, a metallic taste in the mouth and decrease of libido.14 such as metronidazole and has no adverse effects.
Of concern is also the interaction with medication such as lithium and coumarines as well as the frequent occurrence of candida after The aim of this study was to compare the short and long term efficacy of metronidazole versus the over the counter (OTC) topical ActiGel in an open label, randomised study for the treatment and relief of BV score 0). After one week treatment these percentages increased to 91 % (metronidazole) and 87 % (ActiGel group). In week 12 this was 78 % for the metronidazole patients and 79 % for the ActiGel Materials and Methods
patients. A reduction was also found for the pain symptom score in Fourty-seven consenting age-matched women entered this open-label which at start 30 % of the women in the metronidazole group and 52 % study, which was performed at a gynaecological practice Belgrade, in the ActiGel group did not experience pain (symptom score 0). Serbia. All of the women had experienced vaginal complaints during After one week treatment these percentages increased to 96 % the previous year. Exclusion criteria for the study were pregnancy, (metronidazole) and 78 % (ActiGel group). In week 12 this was 87 % for hypersensitivity for metronidazole and vaginal bleeding of unknown the metronidazole patients and 88 % for the ActiGel patients. In regard origin. Diagnosis of BV was established based on the personal history to malodour, at start 9 % of the women in the metronidazole group and included the presence of at least three out of four Amsel criteria: and 0 % in the ActiGel group did not experience malodour (symptom increased vaginal discharge, elevated vaginal pH > 4.5, the presence of score 0). After one week treatment these percentages increased to clue cells on microscopic examination and an amino odour after the 87 % (metronidazole) and 52 % (ActiGel group). This was 83 % for the addition of potassium hydroxide to the specimen.3 Although Nugent's metronidazole patients versus 70 % for the ActiGel patients, in week score is a laboratory method with higher reproducibility, in daily clinical 12. Finally, upon examining the excessive discharge symptom score, at practice the Amsel criteria method is a convenient and inexpensive start 13 % of the women in the metronidazole group and 4 % in the means of diagnosing and first line treatment of BV.20,21 ActiGel group did not experience excessive discharge (symptom score 0). After one week treatment these percentages increased to 87 % Patients were evaluated at presentation (week 0) and during two (metronidazole) and 48 % (ActiGel group). This was 83 % for the follow-up visits: one week (week 1) and 12 weeks post treatment (week metronidazole patients versus 70 % for the ActiGel patients in week 12.
12). During each visit vaginal pH was measured using an indicator strip (Duotest, Macherey-Nagel, pH 3.5–6.8), Amsel criteria and vaginal Discussion
complaints were noted by the clinician, and cell samples were To date, oral metronidazole has been the treatment of choice collected following a pelvic examination. Vaginal complaints included: prescribed for BV. Alternative therapies have been examined due to the itch, pain, malodour and vaginal discharge and were assessed during less-than-optimal cure rates, high recurrence rates and the potential each visit. Symptoms were categorised into a symptom score in adverse effects of oral metronidazole and particularly the frequent which no symptoms = 0, mild symptoms = 1, moderate symptoms = 2 post-treatment occurrence of candida. Vaginal acidification has been examined as a means of treating BV, but the use of acidic vaginal gels has been shown to be controversial in discouraging the growth of When entering the clinic, patients were alternately placed in the BV-associated micro-organisms and in promoting vaginal re-colonisation metronidazole group or the ActiGel group by the investigator. The even numbered patients (n=23) received 400 mg oral metronidazole every eight hours, three times a day for a period of seven days. The In order to examine the combination of vaginal acidification and odd-numbered patients (n=24) received over the counter ActiGel prevention of adherence of G. vaginalis for the clinical cure a intravaginally in the mornings and in the evenings for a period of five decrease in the recurrence of BV and its related complaints, we days. Patients in ActiGel group were given the option of terminating compared the efficacy of short- and long-term effects of the acidic the use of ActiGel and receiving metronidazole instead. None of the vaginal gel ActiGel with 2QR-complex and its property to prevent adherence of G. vaginalis versus oral metronidazole in a randomised, Results
In this study 23 consenting women with an average age of 34 years
Vaginal pH was high for both groups at presentation and reduced in both received oral metronidazole treatment and 24 consenting women groups one week and three months post treatment showing that vaginal with an average age of 33 years received ActiGel vaginal gel for pH restores in both groups. As in most first line consultancy practices, the treatment of BV. Statistical evaluation doesn’t apply for the diagnosis of BV was based on the patient’s complaints, personal history parameters of this number of patients and results were evaluated by and the presence of at least three out of four Amsel criteria. When the statistician with the use of percentages. examining Amsel criteria and the symptom scores: pain, malodour and excessive discharge, all results improved more in the metronidazole Average vaginal pH of 5.9 was reduced in both groups in week 1 to 4.5 group one week post treatment compared to the ActiGel group.
and remained reduced to 4.5 in both groups in week 12. One week However, three months post treatment an equal reduction in Amsel post-treatment all the women in the metronidazole group and 84 % criteria, pain-, malodour- and excessive discharge- symptom scores of the women in the ActiGel group presented with less than three of was obtained for both the metronidazole and the ActiGel group. The the Amsel criteria. After 12 weeks, 83 % in the metronidazole group symptom score for itch was reduced equally in the ActiGel group when and 87 % of the women in the ActiGel group had less than three of the compared to metronidazole for both follow-up visits. Taken together these results imply that though oral metronidazole is Figure 1 presents the number of patients diagnosed with BV in the somewhat more effective one week post treatment, these results cytology, with itch (A), pain (B), malodour (C) and excessive discharge show that equal results are obtained three months post treatment.
(D) complaints as established by the clinician. In regard to the itch The Amsel criteria nor the symptom scores reached a 100 % cure symptom scores, at start 26 % of the women in the metronidazole rate for the metronidazole or the ActiGel group one week and three group and 30 % in the ActiGel group did not experience itch (symptom month post treatment implying that these patients were not yet E U R O P E A N O B S T E T R I C S & G Y N A E C O L O G Y First Line Treatment and Relief of Bacterial Vaginosis Figure 1: Number of Patients Diagnosed with Bacterial Vaginosis in the Cytology with Itch (A), Pain (B),
Malodour (C) and Excessive Discharge (D)
Complaints as established by the clinician. Left in week 0, middle in week 1 and right in week 12. completely cured and should be treated further.The effectiveness of These results are confirmed by this study in which long term analysis the ActiGel can be attributed to its main component: 2QR-complex, shows that ActiGel is as effective as metronidazole. Moreover, patients which consists of a negatively charged, high molecular, multi-branched were equally satisfied with both treatments for the relief and treatment polysaccharide complex derived from Aloe vera. A previous study has shown that these polysaccharides have a potent anti-adhesive effect against Helicobacter pylori by physically inhibiting their Conclusions
adherence to gastric cells in vitro.23 Preventing adherence of The promising results of this study suggests that ActiGel with G. vaginalis could prevent infection and the formation of a biofilm.
anti-adhesive polysaccharides that neutralise pathogens by interfering Microscopic analysis of vaginal biopsies of women with BV has with adhesion mechanism offers an alternative pathway to antibiotic revealed the presence of a bacterial biofilm on the vaginal epithelial intervention as a first line treatment for BV and related symptoms.
cells.24 Biofilm formation is an important virulence factor as the Further studies with larger patient groups are warranted. However, presence of a biofilm is correlated to increased antibiotic tolerance physicians may already start to encourage the use of this non-toxic and resistance to host immune defences.25 As adherence is the first OTC gel for self-care in order to treat as well as prevent recurrence of step in the formation of a biofilm, a treatment aimed at adherence BV and thus reduce the prescription of antibiotics and emergence inhibition could increase clinical cure rate and recurrence of BV.
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placebo for the treatment of symptomatic bacterial E U R O P E A N O B S T E T R I C S & G Y N A E C O L O G Y

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