Gepotidacin for the Treatment of Uncomplicated Urogenital Gonorrhea: A Phase 2, Randomized, Dose-Ranging, Single-Oral Dose Evaluation

Background: In this phase 2 study, we evaluated the efficacy and safety of oral gepotidacin, a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor, for the treatment of uncomplicated urogenital gonorrhea. Methods: Adult participants with suspected urogenital gonorrhea were enrolled and completed baseline (day 1) and test-of-cure (days 4-8) visits. Pretreatment and posttreatment urogenital swabs were collected for Neisseria gonorrhoeae (NG) culture and susceptibility testing. Pharyngeal and rectal swab specimens were collected if there were known exposures. Participants were stratified by gender and randomized 1:1 to receive a 1500-mg or 3000-mg single oral dose of gepotidacin. Results: The microbiologically evaluable population consisted of 69 participants, with NG isolated from 69 (100%) urogenital, 2 (3%) pharyngeal, and 3 (4%) rectal specimens. Microbiological eradication of NG was achieved by 97%, 95%, and 96% of participants (lower 1-sided exact 95% confidence interval bound, 85.1%, 84.7%, and 89.1%, respectively) for the 1500-mg, 3000-mg, and combined dose groups, respectively. Microbiological cure was achieved in 66/69 (96%) urogenital infections. All 3 failures were NG isolates that demonstrated the highest observed gepotidacin minimum inhibitory concentration of 1 µg/mL and a common gene mutation. At the pharyngeal and rectal sites, 1/2 and 3/3 NG isolates, respectively, demonstrated microbiological cure. There were no treatment-limiting adverse events for either dose. Conclusions: This study demonstrated that single, oral doses of gepotidacin were ≥95% effective for bacterial eradication of NG in adult participants with uncomplicated urogenital gonorrhea

A Review of Evidence-Based Care of Symptomatic Trichomoniasis and Asymptomatic Trichomonas vaginalis Infections

Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of this infection, which affects 11% of women aged ≥40 years and a disproportionately high percentage of black women. Particularly high prevalences have been identified among sexually transmitted disease (STD) clinic patients and incarcerated individuals. This article reviews and updates scientific evidence in key topic areas used for the development of the 2015 STD Treatment Guidelines published by the Centers for Disease Control and Prevention. Current evidence is presented regarding conditions associated with Trichomonas vaginalis infection, including human immunodeficiency virus (HIV) and pregnancy complications such as preterm birth. Nucleic acid amplification tests and point-of-care tests are newly available diagnostic methods that can be conducted on a variety of specimens, potentially allowing highly sensitive testing and screening of both women and men at risk for infection. Usually, trichomoniasis can be cured with single-dose therapy of an appropriate nitroimidazole antibiotic, but women who are also infected with HIV should receive therapy for 7 days. Antimicrobial resistance is an emerging concern

Trichomonas vaginalis Genital Infections: Progress and Challenges

Trichomonas vaginalis (TV) infection is the most prevalent curable sexually transmitted infection in the United States and worldwide. Most TV infections are asymptomatic, and the accurate diagnosis of this infection has been limited by lack of sufficiently sensitive and specific diagnostic tests, particularly for men. To provide updates for the 2010 Centers for Disease Control and Prevention’s Sexually Transmitted Diseases Treatment Guidelines, a PubMed search was conducted of all TV literature published from 9 January 2004 through 24 September 2008. Approximately 175 pertinent abstracts and articles were reviewed and discussed with national experts. This article describes advances in TV diagnostics which have led to an improved understanding of the epidemiology of this pathogen, as well as potential biologic and epidemiological interactions between TV and human immunodeficiency virus (HIV). New data on treatment outcomes, metronidazole-resistant TV, management of nitroimidazole-allergic patients, frequency of recurrent TV infection following treatment, and screening considerations for TV in certain populations are also presented

Рекомендації щодо лікування захворювань, які передаються статевим шляхом (2015)

These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 30–May 2, 2013. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2010.These updated guidelines discuss 1) alternative treatment regimens for Neisseria gonorrhoeae; 2) the use of nucleic acid amplification tests for the diagnosis of trichomoniasis; 3) alternative treatment options for genital warts; 4) the role of Mycoplasma genitalium in urethritis/cervicitis and treatment-related implications; 5) updated HPV vaccine recommendations and counseling messages; 6) the management of persons who are transgender; 7) annual testing for hepatitis C in persons with HIV infection; 8) updated recommendations for diagnostic evaluation of urethritis; and 9) retesting to detect repeat infection. Physicians and other health-care providers can use these guidelines to assist in the prevention and treatment of STDs.Данные рекомендации по лечению лиц, которые имеют или подвергаются риску заболеваний, передающихся половым путем (ЗППП), были обновлены Центрами по контролю и профилактике заболеваний США после консультации с группой специалистов в области ЗППП, которые встретились в Атланте весной 2013 г. Это обновленная версия Руководства по лечению ЗППП от 2010 г.В обновленной версии руководства обсуждаются: 1) альтернативные схемы лечения Neisseria gonorrhoeae; 2) применение методов амплификации нуклеиновых кислот для диагностики трихомониаза; 3) альтернативные способы лечения остроконечных кондилом; 4) роль Mycoplasma genitalium в развитии уретритов/цервицитов и последствия, связанные с лечением; 5) обновленные рекомендации по консультированию и вакцинации против вируса папилломы человека; 6) менеджмент пациентов-транссексуалов; 7) ежегодное тестирование на гепатит С лиц с ВИЧ-инфекцией; 8) обновленные рекомендации по диагностической оценке уретрита; 9) повторное тестирование с целью выявления нового инфицирования. Данное руководство могут использовать врачи и другие медицинские работники для оказания помощи в профилактике и лечении ЗППП.Дані рекомендації щодо лікування осіб, які мають або піддаються ризику захворювань, що передаються статевим шляхом (ЗПСШ), були оновлені Центрами з контролю і профілактики захворювань США після консультації з групою фахівців у сфері ЗПСШ, які зустрілися в Атланті навесні 2013 р. Це оновлена версія Керівництва з лікування ЗПСШ від 2010 р.В оновленій версії керівництва обговорюються: 1) альтернативні схеми лікування Neisseria gonorrhoeae; 2) застосування методів ампліфікації нуклеїнових кислот для діагностики трихомоніазу; 3) альтернативні способи лікування гострих кондилом; 4) роль Mycoplasma genitalium у розвитку уретритів/цервіцитів і наслідки, пов’язані з лікуванням; 5) оновлені рекомендації з консультування та вакцинації проти вірусу папіломи людини; 6) менеджмент пацієнтів-транссексуалів; 7) щорічне тестування на гепатит С осіб із ВІЛ-інфекцією; 8) оновлені рекомендації з діагностичної оцінки уретриту; 9) повторне тестування з метою виявлення нового інфікування. Дане керівництво можуть використовувати лікарі та інші медичні працівники для надання допомоги з профілактики та лікування ЗПСШ

Decreases in markers of monocyte/macrophage activation after hepatitis C eradication in HIV/HCV co-infected women

OBJECTIVE: Eradication of hepatitis C virus (HCV) in HIV disease decreases liver and non-liver-related morbidity and mortality. Elevated markers of monocyte/macrophage activation (soluble CD163 and sCD14) are associated with excess non-AIDS morbidity and mortality in HIV. We examined the effect of HCV eradication on these markers in relation to change in hepatic fibrosis. DESIGN: Nested substudy within a longitudinal observational cohort METHODS: We studied 126 HIV/HCV coinfected women successfully treated for HCV, with undetectable HCV RNA at least 12 weeks after therapy completion. sCD163 and sCD14 were measured in serum collected before and after HCV eradication. Results were correlated with changes in markers of hepatic fibrosis. RESULTS: Mean age of participants was 56.3 years, mean CD4 was 615, 72% had suppressed HIV RNA. After treatment, sCD163 and sCD14 levels significantly decreased from pre-treatment levels in unadjusted analyses. After adjusting for age, race, hepatic fibrosis status, baseline HCV RNA, CD4 count and HIV RNA status, cigarette smoking, and alcohol use, the decreases in sCD163 and sCD14 remained significant. Decrease in pre-treatment to post-treatment sCD163 were significantly positively correlated with changes in FIB-4 (r=.250, p=.005) and APRI (r=.262, p=.003); similarly decrease in sCD14 was significantly positively correlated with changes in FIB-4 (r=.333, p=.0001) and APRI (r=.457, p<.0001). CONCLUSIONS: HCV eradication is associated with significant reductions in monocyte/macrophage activation markers that correlate with reductions in markers of hepatic fibrosis. These findings support broad access to and early initiation of HCV treatment in order to decrease immune activation and improve health in HIV-infected persons

Impaired Hepatitis C Virus (HCV)-Specific Effector CD8+ T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection▿

A majority of patients infected with hepatitis C virus (HCV) do not sustain an effective T-cell response, and viremia persists. The mechanism leading to failure of the HCV-specific CD8+ T-cell response in patients developing chronic infection is unclear. We investigated apoptosis susceptibility of HCV-specific CD8+ T cells during the acute and chronic stages of infection. Although HCV-specific CD8+ T cells in the blood during the acute phase of infection and in the liver during the chronic phase were highly activated and expressed an effector phenotype, the majority was undergoing apoptosis. In contrast, peripheral blood HCV-specific CD8+ T cells during the chronic phase expressed a resting memory phenotype. Apoptosis susceptibility of HCV-specific CD8+ T cells was associated with very high levels of programmed death-1 (PD-1) and low CD127 expression and with significant functional T-cell deficits. Further evaluation of the “death phase” of HCV-specific CD8+ T cells during acute HCV infection showed that the majority of cells were dying by a process of cytokine withdrawal, mediated by activated caspase 9. Contraction during the acute phase occurred rapidly via this process despite the persistence of the virus. Remarkably, in the chronic phase of HCV infection, at the site of infection in the liver, a substantial frequency of caspase 9-mediated T-cell death was also present. This study highlights the importance of cytokine deprivation-mediated apoptosis with consequent down-modulation of the immune response to HCV during acute and chronic infections