Oral fosfomycin for treatment of acute bacterial prostatitis caused by multidrug-resistant Enterobacterales

Acute prostatitis; Fosfomycin-tromethamine; Multidrug resistanceProstatitis aguda; Fosfomicina-trometamina; Resistència a múltiples medicamentsProstatitis aguda; Fosfomicina-trometamina; Resistencia a múltiples medicamentosTo assess the feasibility of oral fosfomycin-tromethamine (FT) for the management of acute bacterial prostatitis (ABP) caused by multidrug-resistant (MDR) Enterobacterales. An observational study of adult patients diagnosed with ABP from Vall d’Hebron University Hospital (Barcelona, Spain), treated with oral FT. The primary outcome was clinical cure defined as symptom relief at the control visit, 2–4 weeks post-end of treatment. Secondary outcomes included microbiological cure, relapse, and adverse events related to the treatment. Eighteen patients with ABP caused by Enterobacterales (15 Escherichia coli and three Klebsiella pneumoniae) were included. Microorganisms were MDR bacteria [14 extended-spectrum beta-lactamase (ESBL) producers and two carbapenemase producing K. pneumoniae]. Patients received treatment with FT 3 g/48 hours during a median of 14 days (Q25–Q75, 12–17.75). Fifteen patients received a lead-in phase of intravenous suitable antimicrobial during a median of 7 days (Q25–Q75, 3.75–8). No patient had to stop treatment due to adverse events, and the only side effect reported in two patients was diarrhea. Clinical cure was achieved in all (18/18) patients and microbiological cure in 11/12 patients. After a median of follow-up of 5 months (Q25–Q75, 2–11), 2/18 patients relapsed with an orchitis and a new episode of ABP. FT is an attractive step-down therapy for ABP in patients with resistance or side effects to first-line drugs. The availability of oral treatment could reduce the use of the carbapenems, with a benefit in the quality of life of the patient, health costs, and an ecological impact

Early syphilis: risk factors and clinical manifestations focusing on HIV-positive patients

Condomless anal sex; HIV; SyphilisSexo anal sin condón; VIH; SífilisSexe anal sense preservatiu; VIH; SífilisBACKGROUND: Since 2000, substantial increases in syphilis in men who have sex with men (MSM) have been reported in many cities. Condomless anal sex (CAS) is one of the factors, along with drugs for sex and sex in group. This study identified factors and clinical manifestations as well as Treponema pallidum (T.pallidum) strains that could be related to early syphilis in Barcelona. METHODS: This prospective study was conducted in a sexually transmitted infections unit in 2015. Epidemiological, behavioral, clinical and microbiological variables were collected in a structured form. Univariate and multivariate statistical analyses were performed focusing on HIV-positive patients. RESULTS: Overall, 274 cases were classified as having early syphilis (27.5% primary, 51.3% secondary, and 21.2% early latent syphilis). In all, 94% of participants were MSM and 36.3% were HIV-positive. The median number of sexual contacts in the last 12 months was 10; 72.5% practiced CAS, 50.6% had sex in group, and 54.7% consumed drugs. HIV-positive cases had more anonymous sex contacts (p = 0.041), CAS (p = 0.002), sex in group (p < 0.001) and drugs for sex (p < 0.001). In the multivariate analysis, previous syphilis (adjusted odds ratio [aOR] 4.81 [2.88-8.15]), previous Neisseria gonorrhoeae infection (aOR 3.8 [2.28-6.43]), and serosorting (aOR 20.4 [7.99-60.96]) were associated with having syphilis. Clinically, multiple chancres were present in 31% of cases with no differences on serostatus, but anal chancre was most common in HIV-positive patients (p = 0.049). Molecular typing did not conclusively explain clinical presentation in relation to specific T.pallidum strains. CONCLUSION: Control of syphilis remains a challenge. Similar to prior studies, HIV-positive patients were found to engage more often in sexual behaviors associated with syphilis than HIV-negative patients. Clinical manifestations were rather similar in both groups, although anal chancre was most common in HIV-positive patients. Various strain types of syphilis were found, but no clinical associations were identified

Impact of very early antiretroviral therapy during acute HIV infection on long-term immunovirological outcomes

Acute HIV infection; Antiretroviral treatment; Immune recoveryInfección aguda por VIH; Tratamiento antirretroviral; Recuperación inmunitariaInfecció aguda per VIH; Tractament antiretroviral; Recuperació immunitàriaObjectives We aimed to determine if starting antiretroviral therapy (ART) in the first 30 days after acquiring HIV infection has an impact on immunovirological response. Methods Observational, ambispective study including 147 patients with confirmed acute HIV infection (January/1995-August/2022). ART was defined as very early (≤30 days after the estimated date of infection), early (31-180 days), and late (>180 days). We compared time to viral suppression (viral load [VL] <50 copies/ml) and immune recovery (IR) (CD4+/CD8+ ratio ≥1) according to the timing and type of ART using survival analysis. Results ART was started in 140 (95.2%) patients. ART was very early in 24 (17.1%), early in 77 (55.0%), and late in 39 (27.9%) cases. Integrase strand transfer inhibitor (INSTI)-based regimens were the most used in both the overall population (65%) and the very early ART group (23/24, 95.8%). Median HIV VL and CD4+/CD8+ ratio pre-ART were higher in the very early ART group (P <0.05). Patients in the very early and early ART groups and treated with INSTI-based regimens achieved IR earlier (P <0.05). Factors associated with faster IR were the CD4+/CD8+ ratio pre-ART (hazard ratio: 9.3, 95% CI: 3.1-27.8, P <0.001) and INSTI-based regimens (hazard ratio: 2.4, 95% CI: 1.3-4.2, P = 0.003). Conclusions The strongest predictors of IR in patients who start ART during AHI are the CD4+/CD8+ ratio pre-ART and INSTI-based ART regimens.This work was founded by Instituto de Salud Carlos III (Acción Estratégica en Salud) and Fondo Europeo de Desarrollo Regional (FEDER) through grant PI20/00823. The study was also supported by the Spanish Network for AIDS Research (RIS) through the Instituto de Salud Carlos III – Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R+D+I and by ISCIII Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER). For this project, PS has received a grant from the Catalan Society of Infectious Diseases and Clinical Microbiology (SCMIMC) funded by ViiV Healthcare. MJB is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CPII22/00005). The funders had no role in the study design, data collection, and interpretation, or the decision to submit the work for publication

Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis.

Funder: Queensland GovernmentSyphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p. pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides

La reemergencia de la sífilis en Barcelona 2003-2015

En muchas ciudades europeas y norteamericanas se ha visto un incremento importante de los casos de sífilis, en relación a las conductas de riesgo. Esta tesis analiza la situación en Barcelona a partir de 2 estudios, uno retrospectivo y otro prospectivo realizados en la unidad de ITS de Vall d’Hebron-Drassanes. En el estudio retrospectivo se ha observado un incremento del 300% de los casos de sífilis precoz durante el periodo 2003-2013, afectando, sobre todo, a HSH, de los cuales el 30% presentaban una coinfección con el VIH. Dicho aumento se ha correlacionado con el número de contactos sexuales y el sexo anal desprotegido, conductas observadas más frecuentemente en pacientes VIH positivos. Desde el punto de vista clínico, el estadio más frecuente ha sido el secundarismo sifilítico, seguido de sífilis primaria y sífilis latente precoz. Durante el periodo del estudio, al aumentar la frecuencia de cribado, aumentaron también los casos de sífilis latente precoz, sobre todo en VIH negativos. Los pacientes que tenían antecedente de sífilis presentaron menos frecuentemente una sífilis primaria, probablemente relacionado con la inmunidad. Tanto los pacientes VIH positivos como los que tenían antecedente de sífilis presentaron títulos del RPR superiores, sin que influyese ninguno de los dos en la evolución de la misma. En el estudio prospectivo, desde el punto de vista epidemiológico se observó que más de dos tercios de los participantes había tenido ocasionalmente relaciones sexuales desprotegidas (con una mediana de 10 contactos en los 12 meses previos), más de la mitad había practicado sexo en grupo y había consumido drogas con la intención de mantener relaciones sexuales. Enfocando el análisis en pacientes VIH positivos se observó que estos tenían con mayor frecuencia sexo anal desprotegido con un mayor número de contactos. Además, practicaban más frecuentemente sexo en grupo, serosorting y chemsex. Tanto a nivel global como en los pacientes VIH positivos el secundarismo sifilítico fue el estadio que más frecuentemente se observó. Clínicamente, la única diferencia observada entre ambos grupos fue que los pacientes VIH positivos presentaron más frecuentemente chancro anal en la sífilis primaria. Se realizó la tipificación del T. pallidum para determinar si un tipo concreto podría explicar algunas manifestaciones clínicas, sin obtener un resultado conclusivo debido a la alta variedad de tipos y el número pequeño de la muestra. Los títulos del RPR fueron superiores en pacientes VIH positivos, incluso tras estratificar por el estadio y antecedente de sífilis, sin que hubiese diferencias en la tasa de curación tras recibir el mismo tratamiento. Un tercio de los pacientes presentó reacción de Jarisch-Herxheimer, observándose de forma más prevalente en sífilis primaria y secundaria que, en sífilis latente precoz, siendo la fiebre la presentación más común. Al analizar los factores de riesgo, la reacción no se relacionó con el VIH, antecedente de sífilis o títulos del RPR, observándose que se daba con menos probabilidad en pacientes tratados con doxiciclina. Al analizar mediante la tipificación del T. pallidum no se pudo determinar una relación entre la reacción de J-H y alguno de ellos. Para determinar qué factores estaban más estrechamente relacionados con la adquisición de la sífilis, se realizó un subestadio en pacientes que habían acudido por estudio de contactos, describiéndose como factor determinante el mantener relaciones anales desprotegidas, demostrando a su vez la importancia del tratamiento epidemiológico precoz en dichos pacientes. Tras este amplio estudio, concluiría que para el control de la sífilis es necesario mantener básicamente el enfoque tradicional con la correspondiente actualización: cribados generalizados, tratamiento precoz, estudio de contactos, implicación de las autoridades de salud pública, educación a la población diana, formación de los profesionales sanitarios, e investigación continua.Since 2000, substantially higher syphilis rates have been reported in association with high-risk factors in metropolitan areas of Western countries. This thesis analyzes the situation in Barcelona based on two studies: a retrospective study and a prospective study, both undertaken at the Vall d’Hebron-Drassanes STI Unit in Barcelona and described herein. In the retrospective study, the same upward trend was also observed from 2003 to 2013. In fact, a 300% increase in cases of early syphilis was found especially among men who have sex with men, 30% of whom were HIV-positive. This surge was related to high numbers of contacts and condomless anal sex, which were more common risk factors in HIV-positive patients. Clinically, secondary syphilis was seen most often, followed by primary syphilis and early latent syphilis. During the study period, a rise was observed in the number of syphilis cases diagnosed during routine screening and, consequently, also in the number of latent syphilis cases, especially in HIV-negative patients. Patients with a history of syphilis presented less often with primary syphilis, probably in relation to immunological factors. HIV-positive patients and/or patients with previous syphilis had higher RPR titers than patients who were HIV-negative and/or had no history of syphilis, with similar clinical progress seen in both groups. A detailed analysis of the epidemiological, clinical, and microbiological findings was undertaken in patients with early syphilis diagnosed in 2015. In terms of epidemiology, two-thirds of participants had engaged in occasional condomless anal sex with a median of 10 contacts in the previous 12 months, and over half had participated in group sex and/or used drugs for sex. In the comparative study, HIV-positive patients were more likely to have had condomless anal sex with a higher number of contacts, to have participated in group sex, to have practiced serosorting, and to have chemsex. Clinically, secondary syphilis was the most common stage in both the overall study population and in HIV-positive patients, with primary syphilis seen less often in the latter group. In primary syphilis, anal chancre was more common in HIV positive patients. T. pallidum typification was performed to determine if a specific type might explain some clinical manifestations, but the results were not conclusive due to the wide variety of types observed and the small sample size. RPR titers were higher in HIV-positive patients, a finding also true after stratifying by stage and previous syphilis, with no difference in cure rates between HIV-positive and HIV-negative patients. One-third of patients experienced a Jarisch-Herxheimer reaction, a response seen more often in patients with primary and secondary syphilis and less often in early latent syphilis. The most common sign was fever. An analysis of the risk factors associated with J-H reaction suggested no relationship with HIV serostatus, history of syphilis, or RPR titers, with patients treated with doxycycline found to be less likely to experience this reaction. When analyzing whether the reaction might be related to a particular serovar, no specific trends were observed, as T. pallidum type varied considerably. In the study of patients who consulted in the context of contact tracing, condomless anal sex was the only variable still significant when comparing risk factors between patients with versus without post-contact syphilis, demonstrating the importance of early epidemiological treatment in these patients. In view of this large study, we concluded that the approaches used to control syphilis should be similar as those proposed almost one hundred years ago: widespread screening, timely treatment, contact tracing, patient education, professional training and participation, public health measures and ongoing research

La reemergencia de la sífilis en Barcelona 2003-2015 /

Departament responsable de la tesi: Departament de Medicina.En muchas ciudades europeas y norteamericanas se ha visto un incremento importante de los casos de sífilis, en relación a las conductas de riesgo. Esta tesis analiza la situación en Barcelona a partir de 2 estudios, uno retrospectivo y otro prospectivo realizados en la unidad de ITS de Vall d'Hebron-Drassanes.En el estudio retrospectivo se ha observado un incremento del 300% de los casos de sífilis precoz durante el periodo 2003-2013, afectando, sobre todo, a HSH, de los cuales el 30% presentaban una coinfección con el VIH. Dicho aumento se ha correlacionado con el número de contactos sexuales y el sexo anal desprotegido, conductas observadas más frecuentemente en pacientes VIH positivos. Desde el punto de vista clínico, el estadio más frecuente ha sido el secundarismo sifilítico, seguido de sífilis primaria y sífilis latente precoz. Durante el periodo del estudio, al aumentar la frecuencia de cribado, aumentaron también los casos de sífilis latente precoz, sobre todo en VIH negativos. Los pacientes que tenían antecedente de sífilis presentaron menos frecuentemente una sífilis primaria, probablemente relacionado con la inmunidad. Tanto los pacientes VIH positivos como los que tenían antecedente de sífilis presentaron títulos del RPR superiores, sin que influyese ninguno de los dos en la evolución de la misma.En el estudio prospectivo, desde el punto de vista epidemiológico se observó que más de dos tercios de los participantes había tenido ocasionalmente relaciones sexuales desprotegidas (con una mediana de 10 contactos en los 12 meses previos), más de la mitad había practicado sexo en grupo y había consumido drogas con la intención de mantener relaciones sexuales. Enfocando el análisis en pacientes VIH positivos se observó que estos tenían con mayor frecuencia sexo anal desprotegido con un mayor número de contactos. Además, practicaban más frecuentemente sexo en grupo, serosorting y chemsex. Tanto a nivel global como en los pacientes VIH positivos el secundarismo sifilítico fue el estadio que más frecuentemente se observó. Clínicamente, la única diferencia observada entre ambos grupos fue que los pacientes VIH positivos presentaron más frecuentemente chancro anal en la sífilis primaria. Se realizó la tipificación del T. pallidum para determinar si un tipo concreto podría explicar algunas manifestaciones clínicas, sin obtener un resultado conclusivo debido a la alta variedad de tipos y el número pequeño de la muestra. Los títulos del RPR fueron superiores en pacientes VIH positivos, incluso tras estratificar por el estadio y antecedente de sífilis, sin que hubiese diferencias en la tasa de curación tras recibir el mismo tratamiento. Un tercio de los pacientes presentó reacción de Jarisch-Herxheimer, observándose de forma más prevalente en sífilis primaria y secundaria que, en sífilis latente precoz, siendo la fiebre la presentación más común. Al analizar los factores de riesgo, la reacción no se relacionó con el VIH, antecedente de sífilis o títulos del RPR, observándose que se daba con menos probabilidad en pacientes tratados con doxiciclina. Al analizar mediante la tipificación del T. pallidum no se pudo determinar una relación entre la reacción de J-H y alguno de ellos.Para determinar qué factores estaban más estrechamente relacionados con la adquisición de la sífilis, se realizó un subestadio en pacientes que habían acudido por estudio de contactos, describiéndose como factor determinante el mantener relaciones anales desprotegidas, demostrando a su vez la importancia del tratamiento epidemiológico precoz en dichos pacientes.Tras este amplio estudio, concluiría que para el control de la sífilis es necesario mantener básicamente el enfoque tradicional con la correspondiente actualización: cribados generalizados, tratamiento precoz, estudio de contactos, implicación de las autoridades de salud pública, educación a la población diana, formación de los profesionales sanitarios, e investigación continua.Since 2000, substantially higher syphilis rates have been reported in association with high-risk factors in metropolitan areas of Western countries. This thesis analyzes the situation in Barcelona based on two studies: a retrospective study and a prospective study, both undertaken at the Vall d'Hebron-Drassanes STI Unit in Barcelona and described herein. In the retrospective study, the same upward trend was also observed from 2003 to 2013. In fact, a 300% increase in cases of early syphilis was found especially among men who have sex with men, 30% of whom were HIV-positive. This surge was related to high numbers of contacts and condomless anal sex, which were more common risk factors in HIV-positive patients. Clinically, secondary syphilis was seen most often, followed by primary syphilis and early latent syphilis. During the study period, a rise was observed in the number of syphilis cases diagnosed during routine screening and, consequently, also in the number of latent syphilis cases, especially in HIV-negative patients. Patients with a history of syphilis presented less often with primary syphilis, probably in relation to immunological factors. HIV-positive patients and/or patients with previous syphilis had higher RPR titers than patients who were HIV-negative and/or had no history of syphilis, with similar clinical progress seen in both groups. A detailed analysis of the epidemiological, clinical, and microbiological findings was undertaken in patients with early syphilis diagnosed in 2015. In terms of epidemiology, two-thirds of participants had engaged in occasional condomless anal sex with a median of 10 contacts in the previous 12 months, and over half had participated in group sex and/or used drugs for sex. In the comparative study, HIV-positive patients were more likely to have had condomless anal sex with a higher number of contacts, to have participated in group sex, to have practiced serosorting, and to have chemsex. Clinically, secondary syphilis was the most common stage in both the overall study population and in HIV-positive patients, with primary syphilis seen less often in the latter group. In primary syphilis, anal chancre was more common in HIV positive patients. T. pallidum typification was performed to determine if a specific type might explain some clinical manifestations, but the results were not conclusive due to the wide variety of types observed and the small sample size. RPR titers were higher in HIV-positive patients, a finding also true after stratifying by stage and previous syphilis, with no difference in cure rates between HIV-positive and HIV-negative patients. One-third of patients experienced a Jarisch-Herxheimer reaction, a response seen more often in patients with primary and secondary syphilis and less often in early latent syphilis. The most common sign was fever. An analysis of the risk factors associated with J-H reaction suggested no relationship with HIV serostatus, history of syphilis, or RPR titers, with patients treated with doxycycline found to be less likely to experience this reaction. When analyzing whether the reaction might be related to a particular serovar, no specific trends were observed, as T. pallidum type varied considerably. In the study of patients who consulted in the context of contact tracing, condomless anal sex was the only variable still significant when comparing risk factors between patients with versus without post-contact syphilis, demonstrating the importance of early epidemiological treatment in these patients. In view of this large study, we concluded that the approaches used to control syphilis should be similar as those proposed almost one hundred years ago: widespread screening, timely treatment, contact tracing, patient education, professional training and participation, public health measures and ongoing research

Early syphilis : Risk factors and clinical manifestations focusing on HIV-positive patients

Background: Since 2000, substantial increases in syphilis in men who have sex with men (MSM) have been reported in many cities. Condomless anal sex (CAS) is one of the factors, along with drugs for sex and sex in group. This study identified factors and clinical manifestations as well as Treponema pallidum (T.pallidum) strains that could be related to early syphilis in Barcelona. Methods: This prospective study was conducted in a sexually transmitted infections unit in 2015. Epidemiological, behavioral, clinical and microbiological variables were collected in a structured form. Univariate and multivariate statistical analyses were performed focusing on HIV-positive patients. Results: Overall, 274 cases were classified as having early syphilis (27.5% primary, 51.3% secondary, and 21.2% early latent syphilis). In all, 94% of participants were MSM and 36.3% were HIV-positive. The median number of sexual contacts in the last 12 months was 10; 72.5% practiced CAS, 50.6% had sex in group, and 54.7% consumed drugs. HIV-positive cases had more anonymous sex contacts (p = 0.041), CAS (p = 0.002), sex in group (p < 0.001) and drugs for sex (p < 0.001). In the multivariate analysis, previous syphilis (adjusted odds ratio [aOR] 4.81 [2.88-8.15]), previous Neisseria gonorrhoeae infection (aOR 3.8 [2.28-6.43]), and serosorting (aOR 20.4 [7.99-60.96]) were associated with having syphilis. Clinically, multiple chancres were present in 31% of cases with no differences on serostatus, but anal chancre was most common in HIV-positive patients (p = 0.049). Molecular typing did not conclusively explain clinical presentation in relation to specific T.pallidum strains. Conclusion: Control of syphilis remains a challenge. Similar to prior studies, HIV-positive patients were found to engage more often in sexual behaviors associated with syphilis than HIV-negative patients. Clinical manifestations were rather similar in both groups, although anal chancre was most common in HIV-positive patients. Various strain types of syphilis were found, but no clinical associations were identified