Effect Of Metronidazole On The Growth Of Vaginal Lactobacilli In Vitro

Objective: To determine whether metronidazole has an adverse effect on the growth of Lactobacillus. Methods: Hydrogen peroxide- and bacteriocin-producing strains of Lactobacillus were used as test strains. Concentrations of metronidazole used ranged from 128 to 7000 μg/ml. Susceptibility to metronidazole was conducted by the broth microdilution method recommended by the National Committee for Clinical Laboratory Standards. Results: Growth of Lactobacillus was partially inhibited at concentrations between 1000 and 4000 μg/ml (p = 0.014). Concentrations ≥ 5000 μg/ml completely inhibited growth of Lactobacillus. Concentrations between 128 and 256 μg/ml stimulated growth of Lactobacillus (p = 0.025 and 0.005, respectively). Concentrations of metronidazole between 64 and 128 μg/ml or ≥ 512 μg/ml did not have an inhibitory or a stimulatory effect on the growth of Lactobacillus compared to the control. Conclusions: High concentration of metronidazole, i.e. between 1000 and 4000 μg/ml, partially inhibited the growth of Lactobacillus. Concentrations ≤ 5000 μg/ml completely suppressed the growth of Lactobacillus. Concentrations between ≥ 128 and ≤ 256 μg/ml stimulated the growth of Lactobacillus. Further investigation to determine the ideal concentration of metronidazole is needed in order to use the antimicrobial agent effectively in the treatment of bacterial vaginosis.914145Ugwumadu, A.H.N., Hay, P., Bacterial vaginosis: Sequelae and management (1999) Curr Opin Infect Dis, 12, pp. 53-591998 Guidelines for treatment of sexually transmitted diseases (1998) Morb Mortal Wkly Rep, 47, pp. 70-79McGregor, J.A., Larsson, P.G., King Holmes, bacterial vaginosis and women and babies (1999) Int J Gynecol Obstet, 67 (SUPPL. 1), pp. S9-S11Paavonen, J., Mangioni, C., Martin, M.A., Wajszczuk, C.P., Vaginal clindamycin and oral metronidazole for bacterial vaginosis (2000) Obstet Gynecol, 96, pp. 256-260Hillier, S.L., Holmes, K.K., Bacterial vaginosis (1999) Sexually Transmitted Diseases, 3rd edn., pp. 563-586. , Holmes KK, Sparling PF, Mardh P-A, et al, eds. New York: McGraw HillAgnew, K.J., Hillier, S.L., The effect of treatment regimens vaginitis and cervicitis on vaginal colonization by lactobacilli (1995) Sex Transm Dis, 22, pp. 269-273Hillier, S.L., Lipinski, C., Briselden, A.M., Eschenbach, D.A., Efficacy of intravaginal 0.75% metronidazole gel for the treatment of bacterial vaginosis (1993) Obstet Gynecol, 81, pp. 963-967(1999) Performance Standards for Antimicrobial Susceptibility TestingNinth Informational Supplement, 19. , NCCLS document M100-S9, vol 19 no 1. Wayne, PA: National Committee for Clinical Laboratory StandardsSobel, J.D., Schmitt, C., Meriwether, C., Long-term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin (1993) J Infect Dis, 167, pp. 783-784Boris, J., Pahlson, C., Larsson, P.G., Six years observation after successful treatment of bacterial vaginosis (1997) Infect Dis Obstet Gynecol, 5, pp. 297-302Ralph, E.D., Clarke, D.A., Inactivation of metronidazole by anaerobic and aerobic bacteria (1978) Antimicrob Agents Chemother, 14, pp. 377-383Bayer, A.S., Chow, A.W., Conception, N., Guze, L.B., Susceptibility of 40 lactobacilli to six antimicrobial agents with broad gram-positive anaerobic spectra (1978) Antimicrob Agents Chemother, 14, pp. 720-722Cunningham, F.E., Kraus, D.M., Brubaker, L., Fischer, J., Pharmacokinetics of intravaginal metronidazole gel (1994) J Clin Pharmacol, 34, pp. 1060-1065Davis, B., Glover, D.D., Larsen, B., Analysis of metronidazole penetration into vaginal fluid by reversed-phase high-performance liquid chromatography (1984) Am J Obstet Gynecol, 149, pp. 802-803Livengood, C.H., McGregor, J.A., Soper, D.E., Bacterial vaginosis: Efficacy and safety of intravaginal metronidazole treatment (1994) Am J Obstet Gynecol, 170, pp. 759-764Livengood, C.H., Soper, D.E., Sheehan, K.L., Comparison of once-daily and twice-daily dosing of 0.75% metronidazole gel in the treatment of bacterial vaginosis (1999) Sex Transm Dis, 26, pp. 137-14