Gut resistome linked to sexual preference and HIV infection.

BACKGROUND: People living with HIV (PLWH) are at increased risk of acquisition of multidrug resistant organisms due to higher rates of predisposing factors. The gut microbiome is the main reservoir of the collection of antimicrobial resistance determinants known as the gut resistome. In PLWH, changes in gut microbiome have been linked to immune activation and HIV-1 associated complications. Specifically, gut dysbiosis defined by low microbial gene richness has been linked to low Nadir CD4 + T-cell counts. Additionally, sexual preference has been shown to strongly influence gut microbiome composition in PLWH resulting in different Prevotella or Bacteroides enriched enterotypes, in MSM (men-who-have-sex-with-men) or no-MSM, respectively. To date, little is known about gut resistome composition in PLWH due to the scarcity of studies using shotgun metagenomics. The present study aimed to detect associations between different microbiome features linked to HIV-1 infection and gut resistome composition. RESULTS: Using shotgun metagenomics we characterized the gut resistome composition of 129 HIV-1 infected subjects showing different HIV clinical profiles and 27 HIV-1 negative controls from a cross-sectional observational study conducted in Barcelona, Spain. Most no-MSM showed a Bacteroides-enriched enterotype and low microbial gene richness microbiomes. We did not identify differences in resistome diversity and composition according to HIV-1 infection or immune status. However, gut resistome was more diverse in MSM group, Prevotella-enriched enterotype and gut micorbiomes with high microbial gene richness compared to no-MSM group, Bacteroides-enriched enterotype and gut microbiomes with low microbial gene richness. Additionally, gut resistome beta-diversity was different according to the defined groups and we identified a set of differentially abundant antimicrobial resistance determinants based on the established categories. CONCLUSIONS: Our findings reveal a significant correlation between gut resistome composition and various host variables commonly associated with gut microbiome, including microbiome enterotype, microbial gene richness, and sexual preference. These host variables have been previously linked to immune activation and lower Nadir CD4 + T-Cell counts, which are prognostic factors of HIV-related comorbidities. This study provides new insights into the relationship between antibiotic resistance and clinical characteristics of PLWH.

In vitro antibacterial activity of antiretroviral drugs on key commensal bacteria from the human microbiota.

Introduction: Antiretroviral therapy has improved life expectancy in HIV-infected patients. However, people living with HIV under antiretroviral therapy are at higher risks of developing chronic complications and acquiring multidrug resistant bacteria than healthy population. These factors have been associated with shifts in gut microbiome composition and immune activation. It is unclear how antiretroviral drugs affect gut microbiota composition, but it has been observed that antiretroviral treatment is not able to fully restore gut health after HIV infection. Additionally, some antiretroviral drugs have shown antibacterial activity suggesting that these drugs could have a direct impact on the human microbiome composition. Methods: We determined the in vitro antibacterial activity of 16 antiretroviral drugs against a set of key clinically relevant and human commensal bacterial strains. Results: Our results demonstrate that 5 antiretroviral drugs have in vitro antibacterial activity against gut and vaginal human commensal bacteria. Zidovudine has antibacterial activity against Escherichia coli, Klebsiella pneumoniae and Prevotella bivia, abacavir against Gardnerella vaginalis, efavirenz against G. vaginalis and P. bivia and bictegravir against Enterococcus spp. and G. vaginalis. Moreover, we describe for the first time that elvitegravir has antibacterial activity against G. vaginalis and P. bivia and, most importantly, against vancomycin-resistant Enterococcus spp. and methicillin-resistant Staphylococcus aureus strains with MIC values of 4-16 and 4 µg/mL, respectively showing high level of effectiveness against the tested multidrug-resistant bacteria. Discussion: Our results underscore that some antiretroviral drugs may influence the human microbiota composition. In addition, we report the potential use of elvitegravir to treat multidrug-resistant Gram-positive bacteria warranting the need of clinical studies to repurpose this antiretroviral drug.

Aspergillosis by cryptic Aspergillus species: A case series and review of the literature.

BACKGROUND: The cryptic Aspegillus species are rare, these microorganisms are usually more resistant to common antifungal therapies. Therefore, a correct identification is important when evaluating the impact of such species in aspergillosis. AIMS: We aimed to describe the frequency, clinical and microbiological characteristics, and the outcomes of those cases of aspergillosis caused by cryptic species in a tertiary hospital. METHODS: We retrospectively identified all microbiologically documented cases of aspergillosis between January 2013 and December 2018. Definitive species identification of clinically significant isolates was achieved via sequencing methods. The polymerase chain reaction (PCR) products were sequenced, and the results obtained were compared to sequences deposited in GenBank. Antifungal susceptibility testing was performed using the Sensititre® YeastOne® panel. RESULTS: A total of 679 Aspergillus isolates were recovered from 489 patients, of which 109 were clinically relevant. Ten (9.2%) isolates were identified as cryptic species: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) and Aspergillus montevidensis (1). Most patients already suffered some type of immunosuppression. Half of these patients had required intensive care before the infection showed up, and most of them had a pulmonary infection. Mortality at the 100-day follow-up was 40%. Antifungal susceptibility testing was performed on three of the isolates (A. arcoverdensis, A. tubingensis and A. nomius), which showed high minimum inhibitory concentrations (MIC) for azoles and amphotericin B. CONCLUSIONS: The frequency of cryptic species in our centre was 9.2%. Most patients had some degree of immunosuppression, and the mortality rate was 40%.

Aspergillosis by cryptic Aspergillus species: A case series and review of the literature

Background:The cryptic Aspegillus species are rare, these microorganisms are usually more resistant to common antifungal therapies. Therefore, a correct identification is important when evaluating the impact of such species in aspergillosis.Aims:We aimed to describe the frequency, clinical and microbiological characteristics, and the outcomes of those cases of aspergillosis caused by cryptic species in a tertiary hospital.Methods:We retrospectively identified all microbiologically documented cases of aspergillosis between January 2013 and December 2018. Definitive species identification of clinically significant isolates was achieved via sequencing methods. The polymerase chain reaction (PCR) products were sequenced, and the results obtained were compared to sequences deposited in GenBank. Antifungal susceptibility testing was performed using the Sensititre® YeastOne® panel.Results:A total of 679 Aspergillus isolates were recovered from 489 patients, of which 109 were clinically relevant. Ten (9.2%) isolates were identified as cryptic species: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) and Aspergillus montevidensis (1). Most patients already suffered some type of immunosuppression. Half of these patients had required intensive care before the infection showed up, and most of them had a pulmonary infection. Mortality at the 100-day follow-up was 40%. Antifungal susceptibility testing was performed on three of the isolates (A. arcoverdensis, A. tubingensis and A. nomius), which showed high minimum inhibitory concentrations (MIC) for azoles and amphotericin B.Conclusions:The frequency of cryptic species in our centre was 9.2%. Most patients had some degree of immunosuppression, and the mortality rate was 40%. (AU)

Antecedentes:Las especies crípticas dentro del género Aspergillus son poco habituales, pero suelen mostrar una mayor resistencia al tratamiento antifúngico convencional. Por tanto, una correcta identificación de la especie es necesaria para evaluar el impacto de estas especies crípticas en el desarrollo de la aspergilosis.Objetivos:El objetivo de este estudio fue describir las características clínicas, epidemiológicas y microbiológicas, así como la evolución clínica, de los casos de aspergilosis por especies crípticas en un hospital de tercer nivel.Métodos:Se analizaron de forma retrospectiva todos los casos documentados de aspergilosis con identificación microbiológica entre enero de 2013 y diciembre de 2018. La identificación definitiva de los aislamientos clínicos se realizó mediante métodos de secuenciación. Los productos de amplificación obtenidos por la reacción en cadena de la polimerasa (PCR) fueron secuenciados, y los resultados se analizaron utilizando la base de datos del GenBank. Para el análisis de susceptibilidad a los antifúngicos de los aislamientos identificados se utilizó el panel Sensititre® YeastOne®.Resultados:Se identificaron un total de 679 aislamientos de Aspergillus de 489 pacientes, de los cuales un total de 109 eran clínicamente relevantes. Diez (9,2%) de los aislamientos correspondían a especies crípticas: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) y Aspergillus montevidensis (1). La mayoría de los pacientes tenían algún tipo de inmunosupresión previa. La mitad de estos pacientes habían requerido de cuidados intensivos antes de la infección, y la mayoría sufría una infección pulmonar. La mortalidad a los 100 días de seguimiento fue del 40%. (AU)

[Molecular diagnostic methods of respiratory infections. Has the scheme diagnosis changed?]. / Métodos moleculares de diagnóstico de infecciones respiratorias. ¿Ha cambiado el esquema diagnóstico?

Lower respiratory tract infections remain one of the most common causes of mortality worldwide, which is why early diagnosis is crucial. Traditionally the microbiological diagnosis of these infections has been based on conventional methods including culture on artificial media for isolation of bacteria and fungi and cell cultures for virus and antibody or antigen detection using antigen-antibody reactions. The main drawback of the above mentioned methods is the time needed for an etiological diagnosis of the infection. The techniques based on molecular biology have drawn much attention in recent decades as tools for rapid diagnosis of infections. Some techniques are very expensive, especially those that can detect various microorganisms in the same reaction, therefore the question that arises is whether the cost of such testing is justified by the information obtained and by the clinical impact that its implementation will determine. In this article we make a review of the various techniques of molecular biology applied to the diagnosis of pneumonia and focus primarily on analysing the impact they may have on the management of patients with acute respiratory tract infections.

Métodos moleculares de diagnóstico de infecciones respiratorias. ¿Ha cambiado el esquema diagnóstico? / Molecular diagnostic methods of respiratory infections. Has the scheme diagnosis changed?

Las infecciones respiratorias bajas siguen siendo una de las causas más frecuentes de mortalidad en todo el mundo, de ahí que el diagnóstico precoz sea fundamental. Tradicionalmente, el diagnóstico microbiológico de este tipo de infecciones se ha basado en métodos convencionales que incluyen cultivos en medios artificiales para aislamiento de bacterias y hongos y cultivos celulares para virus, así como en la detección antigénica o de anticuerpos mediante reacciones antígeno-anticuerpo. El principal inconveniente de las metodologías anteriormente citadas es el tiempo necesario para obtener un diagnóstico etiológico de la infección. Las técnicas basadas en la biología molecular han irrumpido con fuerza en las últimas décadas como herramientas de diagnóstico rápido de las infecciones. Algunas de estas técnicas -sobre todo aquellas que pueden detectar diversos microorganismos en la misma reacción- acostumbran a ser caras, por lo que la cuestión que se plantea es si el gasto de tales ensayos se ve justificado por la información obtenida y por el impacto clínico que su implementación determina. En este artículo se pretende hacer una revisión de las diversas técnicas de biología molecular aplicadas al diagnóstico de las infecciones respiratorias, centrándose fundamentalmente en la neumonía, y analizar el impacto que pueden tener en el manejo del paciente con infección respiratoria aguda

Lower respiratory tract infections remain one of the most common causes of mortality worldwide, which is why early diagnosis is crucial. Traditionally the microbiological diagnosis of these infections has been based on conventional methods including culture on artificial media for isolation of bacteria and fungi and cell cultures for virus and antibody or antigen detection using antigen-antibody reactions. The main drawback of the above mentioned methods is the time needed for an etiological diagnosis of the infection. The techniques based on molecular biology have drawn much attention in recent decades as tools for rapid diagnosis of infections. Some techniques are very expensive, especially those that can detect various microorganisms in the same reaction, therefore the question that arises is whether the cost of such testing is justified by the information obtained and by the clinical impact that its implementation will determine. In this article we make a review of the various techniques of molecular biology applied to the diagnosis of pneumonia and focus primarily on analysing the impact they may have on the management of patients with acute respiratory tract infections