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Argentine hemorrhagic fever (AHF) is a severe hemorrhagic fever caused by a New World arenavirus, Junin virus (JUNV), which was discovered in 1958 (1). The virus reservoir consists of rodents [...]

Objective To review the effectiveness of antibiotic stewardship interventions in hospitals in low- and middle-income countries. Methods We searched MEDLINE[R], Embase[R], Cochrane Central Register of Controlled-Trials and regional indexes for studies of interventions to improve appropriate prescribing and use of antibiotics for hospitalized patients in low- and middle-income countries. We included controlled trials, controlled before-and-after studies and interrupted time-series studies published up to December 2017. We report prescribing, clinical and microbiological outcomes using a narrative approach. Findings We screened 7342 original titles and abstracts, assessed 241 full-text articles and included 27 studies from 2 low-income and 11 middle-income countries. We found a medium (11 studies) or high risk (13 studies) of bias. Generally, all types of interventions (structural, persuasive and enabling) and intervention bundles were reported to improve prescribing and clinical outcomes. However, the studied interventions and reported outcomes varied widely. The most frequent intervention was procalcitonin-guided antibiotic treatment (8 of 27 studies, all randomized controlled trials). The intervention was associated with a relative risk for patients receiving antibiotics ranging between 0.40 and 0.87. Conclusion The majority of studies reported a positive effect of hospital antibiotic stewardship interventions. However, we cannot draw general conclusions about the effectiveness of such interventions in low- and middle-income countries because of low study quality, heterogeneity of interventions and outcomes, and under-representation of certain settings. To strengthen the evidence base, action needs to be taken to address these shortcomings. Objectif Etudier l'efficacite des interventions visant un usage plus rationnel des antibiotiques dans les hopitaux de pays a revenu faible et intermediaire. Methodes Nous avons consulte MEDLINE[R], Embase[R], le registre central Cochrane des essais controles ainsi que des index regionaux afin de rechercher des etudes portant sur des interventions menees pour ameliorer la prescription et l'usage des antibiotiques pour les patients hospitalises, dans des pays a revenu faible et intermediaire. Nous avons inclus des essais controles, des etudes controlees avant/ apres et des etudes en series temporelles interrompues, publies jusqu'a decembre 2017. Nous evoquons ici, en adoptant uneapproche narrative, les resultats obtenus en termes de prescription et aux niveaux clinique et microbiologique. Resultats Nous avons selectionne 7342 resumes et titres originaux, evalue 241 articles dans leur version integrale et inclus 27 etudes, pour 2 pays a faible revenu et 11 pays a revenu intermediaire. Nous avons identifie un risque de biais moyen (11 etudes) ou eleve (13 etudes). En regle generale, ces publications indiquent que tous les types utilisation rationnelle des antibiotiques en milieu hospitalier, d'interventions (structurelles, persuasives et capacitantes) ainsi que toutes les interventions combinees ont permis d'ameliorer les resultats en termes de prescription et au niveau clinique. Cependant, les interventions etudiees et les resultats publies sont extremement varies. L'intervention la plus frequente a consiste a guider les antibiotherapies en utilisant la procalcitonine (8 etudes sur 27; toutes correspondent a des essais controles randomises). Pour les patients, cette intervention a ete associee a un risque relatif de prescription d'antibiotiques compris entre 0,40 et 0,87. Conclusion La majorite des etudes font etat d'un effet positif des interventions visant a promouvoir l'usage rationnel des antibiotiques en milieu hospitalier. Neanmoins, nous ne pouvons pas tirer de conclusions generales sur l'efficacite de ces interventions dans les pays a revenu faible ou intermediaire, compte tenu de la mauvaise qualite des etudes, de l'heterogeneite des interventions et des resultats ainsi que de la sous-representation de certains contextes. Pour consolider les donnees disponibles, des actions doivent etre entreprises afin de combler ces lacunes. Objetivo Revisar la eficacia de las Intervenciones de administracion de antibioticos en hospitales de paises con ingresos medios y bajos. Metodos Se realizaron busquedas en MEDLINE [R], Embase [R], en el Registro Central de Ensayos Controlados Cochrane y en indices regionales en relacion a estudios de intervenciones para mejorar la prescripcion y el uso adecuado de antibioticos para pacientes hospitalizados en paises con ingresos medios y bajos. Incluimos ensayos controlados, estudios controlados de tipo antes y despues y estudios de series de tiempo interrumpido publicados hasta diciembre de 2017. Informamos acerca de los resultados de prescripcion, clinicos y microbiologicos usando un enfoque narrativo. Resultados Revisamos 7342 titulos orlginalesy resumenes,evaluamos 241 articulos de texto completos, incluidos 27 estudios de 2 paises con ingresos bajos y 11 con ingresos medios. Encontramos riesgo medio de sesgo (11 estudios) o riesgo alto (13 estudios). Por lo general, se informo de que todos los tipos de intervenciones (estructurales, persuasivas y permisivas) y conjuntos de intervenciones mejoran los resultados de prescripcion y los resultados clinicos. Sin embargo, las Intervenciones estudiadas y los resultados sobre los que se informo varian considerablemente. La Intervencion mas frecuente fue el tratamiento antibiotico guiado de procalcltonlna (8 de 27 estudios, todos ellos ensayos controlados aleatorlzados). La intervencion se asocio aun riesgo relativo para pacientes que recibian antibioticos que oscilan entre 0,40 y 0,87. Conclusion La mayoria de los estudios informaron sobre un efecto positivo de las intervenciones hospitalarias con administracion de antibioticos. Sin embargo, no podemos extraer conclusiones generales acerca de la efectividad de tales Intervenciones en paises con ingresos medios y bajos debido a la baja calidad del estudio, a la heterogeneidad de las intervenciones y los resultados y a la baja representacion de ciertas regiones. Para fortalecer la base de las evidencias, es necesario tomar medidas para abordar estas deficiencias., Introduction Antibiotic resistance is a problem of global importance. (1) Representative data on the extent of the problem in low-and middle-income countries are relatively scarce, but high levels of resistance [...]

Objective To assess the antibiotic prescribing practices of doctors working in the Lao People's Democratic Republic and their knowledge of local antibiotic resistance patterns. Methods Doctors attending morning meetings in 25 public hospitals in four provinces were asked to complete a knowledge, attitude and practice survey. The questionnaire contained 43 multiple choice questions that the doctor answered at the time of the meeting. Findings The response rate was 83.4% (386/463).Two hundred and seventy doctors (59.8%) declared that they had insufficient information about antibiotics. Only 14.0% (54/386) recognized the possibility of cephalosporin cross-resistance in methicillin-resistant Staphylococcus aureus. Most participants had no information about local antibiotic resistance for Salmonella Typhi (211/385, 54.8%) and hospital-acquired pneumonia (253/384, 65.9%). Unnecessary antibiotic prescriptions were considered as harmless by 115 participants and 148 considered locally-available generic antibiotics to be of poor quality. Nearly three- quarters (280/386) of participants agreed that it was difficult to select the correct antibiotics. Most participants (373/386) welcomed educational programmes on antibiotic prescribing and 65.0% (249/383) preferred local over international antibiotic guidelines. Conclusion Doctors in the Lao People's Democratic Republic seem to favour antibiotic prescribing interventions. Health authorities should consider a capacity building programme that incorporates antibiotic prescribing and hospital infection control. Objectif Evaluer les pratiques de prescription d'antibiotiques des medecins travaillant en Republique democratique populaire lao et leur connaissance des profils locaux de resistance aux antibiotiques. Methodes Les medecins participant aux reunions matinales dans 25 hopitaux publiques dans 4 provinces ont ete invites a repondre a une enquete sur leurs connaissances, leur attitude et leur pratique. Le questionnaire contenait 43 questions a choix multiples auxquelles les medecins repondaient au moment de la reunion. Resultats Le taux de reponse etait de 83,4% (386/463). Deux cent soixante-dix medecins (59,8%) ont declare ne pas avoir suffisamment d'informations sur les antibiotiques. Seuls 14,0% des medecins (54/386) ont admis la possibilite d'une resistance croisee pour la cephalosporine chez la bacterie Staphylococcus aureus resistante a la methicilline. La plupart des participants n'avaient aucune information sur la resistance locale aux antibiotiques pour la bacterie Salmonella Typhi (211/385, 54,8%) et la pneumonie nocosomiale (253/384,65,9%). Les prescriptions inutiles d'antibiotiques etaient considerees comme inoffensives par 115 participants et 148 participants consideraient que les antibiotiques generiques disponibles localement etaient de mauvaise qualite. Pres de trois-tiers des participants (280/386) convenaient qu'il etait difficile de selectionner les antibiotiques appropries. La plupart des participants (373/386) ont bien accueilli les programmes de formation relatifs a la prescription des antibiotiques et 65,0% (249/383) preferaient recevoir des recommandations locales pour les antibiotiques plutot que des recommandations internationales. Conclusion Les medecins en Republique democratique populaire lao semblaient soutenir les interventions en matiere de prescription d'antibiotiques. Les autorites de sante devraient envisager l'etablissement d'un programme de renforcement des capacites qui integre la prescription des antibiotiques et le controle des infections a l'hopital. Objetivo Evaluar las practicas de prescripcion de antibioticos de los medicos que prestan servicio en la Republica Democratica Popular Lao y sus conocimientos de los patrones de resistencia a antibioticos locales. Metodos Se solicito a los medicos que asistian a reuniones por la manana en 25 hospitales publicos de cuatro provincias que completaran una encuesta sobre conocimientos, actitudes y practicas. El cuestionario contenia 43 preguntas de opcion multiple que los medicos contestaron en la reunion. Resultados La tasa de respuesta fue del 83,4 % (386/463). 270 medicos (59,8 %) declararon que no disponian de informacion suficiente acerca de los antibioticos. Solo el 14,0 % (54/386) reconocio la posibilidad de resistencia cruzada con cefalosporlna del Staphylococcus aureus resistente a la meticilina. La mayoria de los participantes no tenia informacion sobre la resistencia antlbiotlca local para la Salmonela typhi (211/385, 54,8 %) y la neumonia adquirida en el hospital (253/384, 65,9 %). 115 participantes consideraron Inofensivas las prescripciones innecesarias de antibioticos y 148 consideraron que los antibioticos genericos disponibles localmente eran de mala calidad. Casi tres cuartas partes (280/386) de los participantes convinieron en que era dificil elegir los antibioticos correctos. La mayoria de los participantes (373/386) acogieron bien los programas educativos sobre la prescripcion de antibioticos y el 65,0 % (249/383) prefirio pautas locales para el uso de antibioticos frente a las internacionales. Conclusion Los medicos en la Republica Democratica Popular Lao parecen favorecer las intervenciones de prescripcion de antibioticos. Las autoridades sanitarias deberian considerar un programa de capacitacion que incorpore la prescripcion de antibioticos y el control de las Infecciones hospitalarias., Introduction Antimicrobial resistance is caused by pathogens changing in ways that render medicines ineffective against the infections they were previously used to treat, and is considered a global public health [...]

Melioidosis, an infectious disease caused by Burkholderia pseudomallei, is endemic to Southeast Asia and tropical Australia (1,2). B. pseudomallei is a gram-negative bacterium that causes lung or soft tissue infections [...]

The authors describe 2 patients with life-threatening multidrug-resistant HIV-1 infection who responded very well to a treatment regimen containing darunavir and enfuvirtide. They discuss the availability of several new treatment [...]

Abstract Background Colistin is used as last treatment option for pneumonia associated with multidrug-resistant (MDR) Pseudomonas spp.. Literature about the best administration mode (inhalation versus parenteral treatment) is lacking. Methods A retrospective study of 20 intensive care patients with a pneumonia associated with MDR P. aeruginosa receiving colistin sulphomethate sodium (Colistineb®) between 2007 and 2009 was performed. A strain was considered multidrug-resistant if it was resistant to at least 6 of the following antibiotics: piperacillin-tazobactam, ceftazidime, cefepime, meropenem, aztreonam, ciprofloxacin, and amikacin. The administration mode, predicted mortality based on the SAPS3 score, SOFA score at onset of the colistin treatment, clinical and microbiological response, and mortality during the episode of the infection were analysed. The non parametric Kruskal-Wallis and Fisher's Exact test were used for statistical analysis of respectively the predicted mortality/SOFA score and mortality rate. Results Six patients received colistin by inhalation only, 5 were treated only parenterally, and 9 by a combination of both administration modes. All patients received concomitant beta-lactam therapy. The mean predicted mortalities were respectively 72%, 68%, and 69% (p = 0.91). SOFA scores at the onset of the treatment were also comparable (p = 0.87). Clinical response was favorable in all patients receiving colistin by inhalation (6/6) and in 40% (2/5) of the patients receiving colistin parenterally (p = 0.06). In the patients with colistin administered both via inhalation and parenterally, clinical response was favorable in 78% of the patients (7/9) (p = 0.27 as compared to the treatment group receiving colistin only parenterally). When all patients with inhalation therapy were compared to the group without inhalation therapy, a favorable clinical response was present in respectively 87% and 40% (p = 0.06). In none of the patients, the Pseudomonas spp. was eradicated from the follow-up cultures. All patients in the parenterally treated group died. None of the patients receiving colistin by inhalation, and 3 of 9 patients of the combination group eventually died (p = 0.002 and p = 0.03 respectively as compared to the group receiving colistin only parenterally). Conclusions Aerosolized colistin could be beneficial as adjunctive treatment for the management of pneumonia due to MDR P. aeruginosa.

Abstract Background During HIV infection and/or antiretroviral therapy (ART), monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions. Results Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19) for the development of the abacavir hypersensitivity reaction were suggested. Conclusions Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV. Background Both macrophages and T lymphocyte subsets express the CD4 receptor and either the CXCR4 and/or the CCR5 coreceptor which confer susceptibility to infection with the Human Immunodeficiency Virus (HIV). Upon infection, CD4+ T lymphocytes typically succumb to the cytopathic effect of the virus 1, and the gradual depletion of the CD4+ T lymphocyte pool has been considered a hallmark of HIV infection and the development of the Acquired Immune Deficiency Syndrome (AIDS) since the early days of the HIV pandemic. Macrophages, on the other hand, do not tend to suffer from the cytopathic effects mediated by the virus 23, but instead develop a wide array of dysfunctions which contribute significantly to the pathogenesis of HIV infection. Despite the recognition of macrophage contribution to HIV pathogenesis early on in HIV research 45, most studies have focused and continue to focus on T lymphocyte depletion and/or dysfunction, and many of the molecular mechanisms underlying the macrophage dysfunction during HIV infection remain poorly characterised. Nevertheless, as pointed out by other authors 6, in the combination Antiretroviral Therapy (ART) era where viral suppression in T lymphocytes is increasingly more efficient, the understanding of the viral mechanisms in other reservoir cells such as macrophages becomes ever more crucial. Aberrant HIV-induced macrophage behaviour can be classified as relatively straightforward loss of function, such as reduced phagocytosis 78 and antigen presentation 9, or as more complex dysfunction. Such dysfunctions include a direct contribution to the establishment, spread and persistence of the infection: as long-living primary target cells of HIV with a wide-spread dissemination and a persistent failure to enter apoptosis upon infection 1011, they represent an important cellular reservoir for the virus 12. Additionally, macrophages exacerbate disease progression by contributing to T lymphocyte depletion: HIV infected macrophages have been documented to participate in the killing of uninfected CD4+ and CD8+ T lymphocytes, while at the same time protecting infected CD4+ T lymphocytes from apoptosis 13. Furthermore, infected and uninfected macrophages can contribute to sustained chronic immune activation during HIV infection, e.g. through the perturbation of cytokine and chemokine networks 141516. With the acknowledged notion of chronic immune activation as a paradoxical driving force of immune suppression 17, this pro-inflammatory macrophage phenotype during HIV infection may be a crucial parameter in disease progression. Yet other macrophage dysfunctions are associated with more peripheral HIV- or ART-associated disorders such as atherosclerosis 18, lipodystrophy 19, and metabolic syndrome during HIV infection and/or combination ART 2021. Monocytes, for their part, are much less permissive to infection with HIV, both in vitro 22 and in vivo, where estimates of infected circulating monocytes are consistently low 2324. Circulating monocytes represent the most accessible primary model for macrophage dysfunction during HIV infection, however, and are furthermore of sufficient importance to study in their own right. Infectious virus can be recovered from circulating monocytes, both in untreated patients 24 and in patients undergoing long-term successful combination ART 25. Additionally, the circulating monocyte pool as a whole does seem to be affected during HIV infection, despite the low frequency of actually infected monocytes. Transcriptome studies, in particular, show a form of hybrid phenotype exhibiting both increased and decreased pro-inflammatory features 2627. This modulation of the non-infected monocyte population could be due to the virus itself through mechanisms which do not require direct infection 28, or to other factors contributing to (aberrant) immune activation occurring during HIV infection, such as perturbed cytokine networks 29 or other inflammatory stimulants 30. Several key factors in the described dysregulated processes have been identified 1831, but many molecular components remain elusive. Furthermore, other aspects of HIV and combination ART pathogenesis in which monocyte/macrophage dysfunction is involved may only now be emerging or remain yet to be discovered, in particular in view of the limited number of studies focussing on the monocyte response to ART 32. In order to generate novel hypotheses rather than test pre-existing ones in the context of monocyte-HIV interactions, we performed a transcriptome analysis on monocyte samples from patients in different stages of HIV infection and/or combination ART treatment, using a parallel approach of genome-wide microarray analysis and focused gene expression profiling to identify broad areas of monocyte dysfunction and to pinpoint genes which are potentially involved in one or several of these dysfunctions. In particular the factors which are exploited by the monocyte/macrophage to communicate with and/or modulate other immune cells were of interest, as they represent a particularly relevant population 3334 which is a primary target for intervention.