Nonoxynol-9 (N-9) is virucidal in vitro, and is therefore a candidate microbicide for preventing sexual transmission of HIV. However, the activity of N-9 is nonspecific, suggesting that virucidal levels may produce adverse effects including epithelial disruption, inflammation of the genital mucosa, or both. A randomized placebo controlled trial of daily use of 100 mg of N-9 took place for 1 week in 40 female volunteers. Outcome measures included symptoms, colposcopic and histologic changes in the genital tract, and impact on vaginal flora. Genital irritation was reported by 10 of the N-9 and 5 of the placebo group. Colposcopy showed erythema in 9 of the N-9 group and 2 of the placebo group. Histologic inflammation was found in 7 of the N-9 group and 2 of the placebo group. Inflammatory changes were characterized by patchy infiltration of the lamina propria predominantly with CD8+ lymphocytes and macrophages, in the absence of epithelial disruption. A transient reduction in numbers of lactobacilli was observed in 9 of the 15 women using N-9, and 6 of 18 women using placebo. N-9 used for 7 days in a standard spermicidal dose was associated with increased irritation, colposcopic and histologic evidence of inflammation and was more frequently associated with reduction in numbers of lactobacilli during gel use. The clinical significance of the recruitment of cells susceptible to HIV infection to the genital mucosa is unknown but raises concerns about the suitability of N-9 as a microbicide when given in this dose.

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Vaginal swabs for microbiological culture were taken from 174 pregnant women whose vaginal flora had been evaluated by Gram's stain; 50 had grade I11 flora (bacterial vaginosis, BV), 50 grade I1 (intermediate), 41 had vaginal flora graded as abnormal which then reverted to grade I (revertants) and 33 had normal flora (controls). The aim was to determine whether bacterial species isolated from women with grade I1 flora differed from those with grade 111 flora. Isolation of Lactobacillus spp. decreased from grade I to grade I11 and that of other aerobic and anaerobic bacterial species increased. There was little difference in the species isolated from women with grade I1 and grade 111 flora, but there was a distinct order in which organisms in different species increased in numbers. The vaginal flora of revertants was intermediate between that of healthy controls and those with grade I1 flora. Coagulase-negative Staphylococcus spp. were isolated from a greater number of revertants than grade I controls but the incidence did not increase in grade I1 or grade 111. Bifidobacterium spp. were isolated from a greater number of revertants than grade I controls and increased further in grade I1 and grade 111. However, Gardnerella vaginalis and Mycoplasma hominis were isolated from a much larger number of women with grade 111 flora than the other groups. The conclusion is that grade I1 is a transitional phase between grade I and grade I11 and that some organisms such as G. vaginalis and M. hominis only reach large numbers in the late stage. The sequence of appearance of the various bacterial species may be a result of the pathophysiological alteration of the vaginal ecosystem associated with BV.

The effect on normal vaginal flora of three intravaginal microbicides potentially active against human immunodeficiency virus type 1 was examined. Volunteers received dextrin sulfate (D 2 S), nonoxynol-9 (N-9), or docusate sodium in separate placebo-controlled studies. High vaginal swabs were obtained for bacterial culture before and after microbicide application. D 2 S did not affect the vaginal flora. However, lactobacilli decreased by §10 2 cfu/mL in 9 (56%) of 16 women given N-9 and in 5 (63%) of 8 women given docusate sodium. Women using N-9 were also significantly more likely to become colonized abnormally (usually with aerobic gram-negative rods) than were those using placebo, as were women using docusate sodium. Women with reduced lactobacilli were less likely to regain normal flora than were those whose lactobacilli were unaffected. However, coliform colonization occurred whether lactobacilli produced H 2 O 2 or not. Continuous use of N-9 could induce susceptibility to urinary and gynecological infection. It is essential that potential microbicides are examined for activity against normal vaginal flora.

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