Objective: Efficacy study of suppressive vaginal metronidazolein reducing recurrent symptomatic episodes of bacterial vaginosis.Study design: Multicenter prospective study with initial 10- day open-label metronidazole...Objective: Efficacy study of suppressive vaginal metronidazolein reducing recurrent symptomatic episodes of bacterial vaginosis.Study design: Multicenter prospective study with initial 10- day open-label metronidazole gel in which asymptomatic responders randomly assigned to receive twice weekly metronidazole vaginal gel or placebo for 16 weeks and off therapy for 12 weeks. Results: Of 157 eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable women (88.2% ) responded clinically and were randomly assigned.During suppressive therapy, recurrent bacterial vaginosis occurred in 13 women (25.5% ) receiving metronidazole and 26 (59.1% ) receiving placebo (MITT analysis, relative risk [RR]- 0.43, 95% CI = 0.25- 0.73, P = .001). During the entire 28- week follow- up, recurrence occurred in 26 (51.0% ) on treatment compared with 33 (75% ) on placebo (RR 0.68, 95% CI = 0.49- 0.93, P = .02). Probability for remaining cured was 70% for metronidazole compared with 39% on placebo, which declined to 34% and 18% , respectively, by 28 weeks follow-up. Adverse effects were uncommon; however, secondary vaginal candidiasis occurred significantly more often in metronidazole-treated women (P = .02). Conclusion: Suppressive therapy with twice-weekly metronidazole gel achieves a significant reduction in the recurrence rate of bacterial vaginosis; however, secondary vaginal candidiasis is common.展开更多
Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections ...Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections has led to the evolution and spread of drug resistance.As a universal antimicrobial technique unapt to induce drug resistance,photothermal therapy(PTT)is attracting extensive attention in recent years.However,its unspecific killing capability and side effects towards adjacent mammalian cells severely impede the practical applications.Herein,we proposed a metabolic engineering strategy to selectively inactivate Gram-positive bacteria by PTT.A bioorthogonal photothermal agent was prepared by the conjugation of IR-780 iodide and dibenzocyclooctyne(IR780-DBCO).Upon pre-metabolizing with 3-azido-D-alanine,Gram-positive bacteria rather than Gramnegative ones,such as Staphylococcus aureus and vancomycinresistant Enterococcus faecalis(VRE),could be specifically tied up by the explosive IR780-DBCO via copper-free click chemistry.Thereafter,they spontaneously detonated under 15 min near-infrared light irradiation and inactivated nearly 100% Gram-positive bacteria in vitro.Moreover,superbug VRE-induced infection was significantly inhibited by this approach in a mouse skin wound model.This metabolic labelling-based photothermal ablation strategy specific to Gram-positive microbes would stimulate the development of precise antibacterial candidates for preclinical applications.展开更多
文摘Objective: Efficacy study of suppressive vaginal metronidazolein reducing recurrent symptomatic episodes of bacterial vaginosis.Study design: Multicenter prospective study with initial 10- day open-label metronidazole gel in which asymptomatic responders randomly assigned to receive twice weekly metronidazole vaginal gel or placebo for 16 weeks and off therapy for 12 weeks. Results: Of 157 eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable women (88.2% ) responded clinically and were randomly assigned.During suppressive therapy, recurrent bacterial vaginosis occurred in 13 women (25.5% ) receiving metronidazole and 26 (59.1% ) receiving placebo (MITT analysis, relative risk [RR]- 0.43, 95% CI = 0.25- 0.73, P = .001). During the entire 28- week follow- up, recurrence occurred in 26 (51.0% ) on treatment compared with 33 (75% ) on placebo (RR 0.68, 95% CI = 0.49- 0.93, P = .02). Probability for remaining cured was 70% for metronidazole compared with 39% on placebo, which declined to 34% and 18% , respectively, by 28 weeks follow-up. Adverse effects were uncommon; however, secondary vaginal candidiasis occurred significantly more often in metronidazole-treated women (P = .02). Conclusion: Suppressive therapy with twice-weekly metronidazole gel achieves a significant reduction in the recurrence rate of bacterial vaginosis; however, secondary vaginal candidiasis is common.
基金supported by the National Natural Science Foundation of China(52003222 and 21875189)Ningbo Natural Science Foundation(202003N4064)+2 种基金the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0752)the Joint Research Funds of Department of Science&Technology of Shaanxi Province and Northwestern Polytechnical University(2020GXLH-Z-013)the Fundamental Research Funds for the Central Universities.
文摘Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections has led to the evolution and spread of drug resistance.As a universal antimicrobial technique unapt to induce drug resistance,photothermal therapy(PTT)is attracting extensive attention in recent years.However,its unspecific killing capability and side effects towards adjacent mammalian cells severely impede the practical applications.Herein,we proposed a metabolic engineering strategy to selectively inactivate Gram-positive bacteria by PTT.A bioorthogonal photothermal agent was prepared by the conjugation of IR-780 iodide and dibenzocyclooctyne(IR780-DBCO).Upon pre-metabolizing with 3-azido-D-alanine,Gram-positive bacteria rather than Gramnegative ones,such as Staphylococcus aureus and vancomycinresistant Enterococcus faecalis(VRE),could be specifically tied up by the explosive IR780-DBCO via copper-free click chemistry.Thereafter,they spontaneously detonated under 15 min near-infrared light irradiation and inactivated nearly 100% Gram-positive bacteria in vitro.Moreover,superbug VRE-induced infection was significantly inhibited by this approach in a mouse skin wound model.This metabolic labelling-based photothermal ablation strategy specific to Gram-positive microbes would stimulate the development of precise antibacterial candidates for preclinical applications.
