Prevotella bivia (P. bivia) is an anaerobic, non-pigmented, gramnegative bacillus which is naturally present in the human female vaginal tract, and it is also occasionally seen in the oral cavity. It has a high proliferative potential in the presence of estrogen. Therefore, its involvement in, vaginal tract infections such as endometritis and pelvic inflammatory disease, has been well described in the literature. If left untreated, it may cause more serious conditions, such as cuff abscess, abdominal wall empyema, or septic arthritis.
The DNA of P. bivia has been detected from human vaginal epithelia in 40% of healthy women. The prevalence is relatively higher in women with bacterial vaginosis (BV). Its detection from the glans penis indicates that it is a causative factor of BV in female sex partners. It is also probable, however, that traumatic events such as human bite might cause P. bivia infections leading to suppurative inguinal adenitis during orogenital sex. It is also a normal oral and vaginal flora as well as a predominant type of bacillus isolated from the respiratory tract infections and their complications, including aspiration pneumonia, lung abscess, chronic otitis media, chronic sinusitis, abscesses in the oral cavity, human bites, brain abscesses, and osteomyelitis. Moreover, P. bivia is the important pathogen in obstetric and gynecologic infections.
There is a report suggesting that the concentrations of P. bivia and lipopolysaccharide in the vaginal fluid may contribute to the severity of BV and to the development of adverse pregnancy outcomes, such as preterm labor, premature rupture of membranes, postpartum endometritis, and postoperative pelvic infection.
References:
1. Riesbeck K. Paronychia due to Prevotella bivia that resulted in amputation: fast and correct bacteriological diagnosis is crucial. J Clin Microbiol 2003;41: 4901-3. [L]
2. Hsu GJ, Chen CR, Lai MC, Luh SP. Chest wall abscess due to Prevotella bivia. J Zhejiang Univ Sci B 2009;10: 233-6. [L]
3. Laiho K, Kotilainen P. Septic arthritis due to Prevotella bivia after intra-articular hip joint injection. Joint Bone Spine 2001;68: 443-4. [L]
4. Purushothaman B, Lakshmanan P, Gatehouse S, Fender D. Spondylodiscitis due to Prevotella associated with ovarian mass: a rare case report and review of literature. World Neurosurg 2010;73: 119-22. [L]
5. Salman SA, Baharoon SA. Septic arthritis of the knee joint secondary to Prevotella bivia. Saudi Med J 2009;30: 426-8.
6. Mirza A, Bove JJ, Litwa J, Appelbe G. Mixed Infections of the Paronychium with Prevotella bivia. J Hand Microsurg 2012;4: 77-80.
7. Srinivasan S, Fredricks DN. The human vaginal bacterial biota and bacterial vaginosis. Interdiscip Perspect Infect Dis 2008;2008: 750479. [L]
8. Price LB, Liu CM, Johnson KE, Aziz M, Lau MK, Bowers J, et al. The effects of circumcision on the penis microbiome. PLoS One 2010;5: e8422. [L]
9. Aroutcheva A, Ling Z, Faro S. Prevotella bivia as a source of lipopolysaccharide in the vagina. Anaerobe 2008;14: 256-60. [L]
10. Smayevsky J, Canigia LF, Lanza A, Bianchini H. Vaginal microflora associated with bacterial vaginosis in nonpregnant women: reliability of sialidase detection. Infect Dis Obstet Gynecol 2001;9: 17-22. [L]
11. Managing recurrent bacterial vaginosis, J Wilson [L]
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Prescribable antibiotics are included as prescribing options due to lack of detected antibiotic resistance genes. Physicians should use this as a guide and prescribe antibiotics based upon patient symptoms and medical history, including such factors as allergies, other medications, and pregnancy status: Metronidazole, Secnidazole, Tinidazole
What therapeutic options do we have to manage or try to prevent further recurrences of BV?
Bacteriotherapy
Bacteriotherapy, using harmless bacteria to displace pathogenic organisms is considered ‘‘natural’’ and without any side effects, but there is lack of efficacy data with few randomised controlled trials (RCT). The lactobacilli (LB) used need to be able to adhere to vaginal epithelial cells, and to produce hydrogen peroxide. If given orally the LB need to pass through the intestinal tract and ascend from the perianal area into the vagina. There have been several publications of attempts to restore vaginal flora by recolonising with LB using both intravaginal and oral administration. However, the LB used have not been vaginal strains. LB strains from yoghurt adhere less well to vaginal cells than clinical isolates. In a double blind RCT looking at LB as a treatment for BV, vaginal pessaries containing L acidophilus were used for 6 days. With active therapy 57% of women cleared their infection compared with 0% of those given placebo, but only three remained BV free after menstruation.
It was thought there was a problem with LB adherence. One group of researchers has published case reports and small case series of vaginal and oral LB replacement. They report successful vaginal colonisation following administration by both routes. This group have recently published a RCT of oral capsules of L rhamnosus GR-1 and L fermentum RC-14 for 60 days. Microscopy showed restoration to normal flora from asymptomatic BV in 37% women receiving LB treatment compared with 13% receiving placebo. This significant improvement in vaginal flora was also accompanied by a significant increase in LB at day 60.
These results are encouraging but we do not know if the nonvaginal LB will remain in the vagina to protect against further episodes of BV. A RCT of oral Lactobacillus GG drink for the prevention of recurrent urinary tract infection (UTI) showed no reduction in UTIs over 12 months. The principles of UTI prevention by this method are similar to that of BV prevention—that is, LB replacement to protect against bacterial overgrowth, so it is unlikely that oral Lactobacillus GG would be beneficial for BV prevention. In a study looking at mechanisms of LB blockage of uropathogen adherence to vaginal epithelial cells, L crispatus showed greater capacity to block uropathogen adherence than other LB. A study looking at sustained vaginal colonisation of LB showed 40% of women remained colonised with L crispatus and L jensenii for over 8 months compared with 5% of women colonised with other LB spp indicating better ability to adhere to vaginal cells.
There is currently a RCT using vaginal pessaries containing L crispatis to attempt to recolonise the vagina with LB (S Hillier, personal communication). This is the first study of replacement with one of the main vaginal hydrogen peroxide producing LB.
Maintaining vaginal pH at 4.5
The main goal of therapy here is to keep the vaginal pH at 4.5 or less, in order to prevent overgrowth of pathogens until the normal LB are re-established and able to maintain the pH themselves. In a RCT of 42 women with recurrent BV using intravaginal lactate gel to try to prevent BV recurrences, 17 women used lactate gel for 3 days immediately after menstruation for 6 months, the remainder used placebo. The 6 months on-treatment analysis showed that 88% were clear of BV with active treatment compared with only 10% with placebo. Intent to treat analysis at 6 months showed 71% were clear with treatment and 4.8% were clear with placebo. The treatment was well tolerated but there was a large dropout rate, particularly in the placebo arm because of malodour. The authors suggested more intensive treatment might have improved this.
Preventing overgrowth of BV associated organisms
Although intermittent therapy, on an episodic or prophylactic basis, is frequently used for recurrent BV, there are very few publications on this. Hay et al advised women with recurrent BV to collected daily vaginal specimens for between 1– 12 months, to try to identify the times of recurrence. BV recurrences most often arose within the first 7 days of the menstrual cycle, and frequently followed candida infection.2 Consequently they advised oral or intravaginal metronidazole for 3 days at the onset of menstruation for 3– 6 months, and add antifungal treatment if there is a history of candidiasis.
Better treatments and/or combined treatments
Using oral or vaginal preparations of metronidazole and clindamycin, 80–90% of women will have an initial response to treatment but 15–30% will get a recurrence within 3 months.
In women with recurrent BV the initial response rate appears to be lower. The heterogeneity of microorganisms involved in BV may contribute to treatment failure and high recurrence rates. Clindamycin has better activity against M hominis, Mobiluncus spp, and G vaginalis than metronidazole, but metronidazole has the advantage of not affecting LB. In trials comparing treatments, cure rates for metronidazole 400 mg or 500 mg twice daily for 7 days have been equivalent to clindamycin vaginal cream daily for 3–7 days, and to metronidazole vaginal gel once or twice per day for 5 days. In the absence of better treatments would women with recurrent BV benefit from longer courses of current treatment? This question remains unanswered. In view of the association between lactobacilli, hydrogen peroxide production, vaginal pH, and overgrowth of BV associated bacteria, just trying to adjust one of these may help some women with recurrent BV, but it may not be enough to resolve all cases. Would a combined approach work better? There are very few publications on this, but they do suggest that the answer might be yes. A small study using single dose oral metronidazole followed by vaginal lactate tablets compared to no vaginal maintenance treatment reported an improved rate of normal vaginal flora of 94% compared to 71%.
Another small study compared tinidazole 2 g single oral dose followed by acidic vaginal gel for 3 weeks with 2% clindamycin vaginal cream 5 g per night for 7 nights. At 4 weeks the clinical cure rate was 94% versus 77%. The vaginal pH was ,4.5 in 78% and 38% respectively.
Conclusions
There is an important inter-relation between lactobacilli, hydrogen peroxide production, vaginal pH, and overgrowth of BV associated bacteria, but the initiating factor for BV remains a mystery. From current evidence it appears that a rise in vaginal pH allowing the overgrowth of bacteria may be more important than reduction of LB+. However long term colonisation with LB+ is necessary to help maintain an acidic pH and support the LB+/myeloperoxidase/chloride system. Therapies aimed at one aspect of this inter-relation may help some women with recurrent BV, but a combined approach might work better. Probably the ideal way of managing recurrent BV would be to tackle all aspects of the interrelation by replacing the lactobacilli, at the same time maintaining the vaginal pH at 4.5, and if necessary also adding in prophylactic treatment to control overgrowth of bacteria. If the current RCT of vaginal LB+ replacement proves successful this approach may soon be possible.
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