Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis

Abstract

The human vagina harbor a rich microbiota. The optimal state is dominated by lactobacilli that help to maintain health and prevent various diseases. However, the microbiota may rapidly change to a polymicrobial state that has been linked to a number of diseases. In the present study, the temporal changes of the vaginal microbiota in patients treated for sexually transmitted diseases or bacterial vaginosis (BV) and in untreated controls were studied for 26 days. The patients included 52 women treated with azithromycin, tetracyclines or moxifloxacin for present or suspected infection with Chlamydia trachomatis or Mycoplasma genitalium. Women with concurrent BV were also treated with metronidazole. The controls were 10 healthy women of matching age. The microbiota was analyzed by 16S rRNA gene deep sequencing, specific qPCRs and microscopy. There was generally good correlation between Nugent score and community state type (CST) and qPCR confirmed the sequencing results. By sequencing, more than 600 different taxa were found, but only 33 constituted more than 1 ‰ of the sequences. In both patients and controls the microbiota could be divided into three different community state types, CST-I, CST-III and CST-IV. Without metronidazole, the microbiota remained relatively stable regarding CST although changes were seen during menstrual periods. Administration of metronidazole changed the microbiota from CST-IV to CST-III in approximately 50% of the treated patients. In contrast, the CST was generally unaffected by azithromycin or tetracyclines. In 30% of the BV patients, Gardnerella vaginalis was not eradicated by metronidazole. The majority of women colonized with Ureaplasma parvum remained positive after azithromycin while U. urealyticum was eradicated.

Temporal Changes in Vaginal Microbiota and Genital Tract Cytokines Among South African Women Treated for Bacterial Vaginosis

“…Although limited by sample size, our findings are in agreement with other studies that showed a shift towards increased relative abundance of lactobacilli (mainly L. iners ) following 1g of oral azithromycin treatment. It has been shown that women with high relative abundance of L. iners were associated with increased susceptibility to C. trachomatis infection, suggesting that azithromycin treatment increase probabilities of transitioning to diverse disease-associated states or reinfection ( 40 , 41 ). Considering that both metronidazole and azithromycin favor increased relative abundance of unstable L. iners communities, there is a need to use Gardnerella specific-biofilm dissolving treatment, boosted with Lactobacilli-based live biotherapeutic products to restore an optimal vaginal microbiota after antibiotic treatment.…”

The Female Vaginal Microbiome in Health and Bacterial Vaginosis

“…Although these antibiotics are effective against BV-associated bacteria and somewhat relieve symptoms, the remission is usually temporary, and many patients relapse after treatment (Bradshaw et al, 2006;Hay, 2009;Mayer et al, 2015). The high recurrence rate (50%-67%) may be the result of the inability of antibiotics to eliminate the biofilm-associated bacteria of BV in vagina (Figure 2) (Swidsinski et al, 2008;Swidsinski et al, 2011;Javed et al, 2019;Ahrens et al, 2020;Verwijs et al, 2020). For example, Ahrens et al reported that G. vaginalis and other BVassociated bacteria are eradicated or are largely decreased in 58% of the patients treated with metronidazole.…”

“…Meanwhile, none of these bacteria are eliminated in the remaining half of the patients. This phenomenon is attributed to the sheltering of G. vaginalis and other bacteria by biofilms (Ahrens et al, 2020). In addition, Swidsinski et al observed the persistence of G. vaginalis biofilms after oral metronidazole therapy (Swidsinski et al, 2008).…”

Proteome-wide prediction of bacterial carbohydrate-binding proteins as a tool for understanding commensal and pathogen colonisation of the vaginal microbiome

“…The specific changes within the vaginal mucosal micro-environment that supports their expansion and colonisation remains poorly defined. We propose that the strategy for binding glycans has evolved more in vaginal confirmed and potential pathogens than in commensals, with the former producing a much larger variety of lectins and CBMs that enhances their capacity to adhere and bind to targets following disruption of the vaginal microbiome caused by menses 63 , contraceptives 64 , sexual activity 65 or antibiotic use 66 . Our findings are consistent with previous reports on the occurrence of a large number of lectin domains in different species of streptococci; these participate in the architecture of toxins, adhesins and pilins 67 .…”