Geographical variation in therapy for bloodstream infections due to multidrug-resistant enterobacteriaceae: a post hoc analysis of the INCREMENT study

We aimed to describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). 1,482 patients in 12 countries were included from an observational study of BSI caused by ESBL-E or CPE. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ?-lactam/?-lactamase inhibitors (BLBLI) or carbapenems, targeted use of BLBLI for ESBL-E and use of targeted combination therapy for CPE. The use of BLBLI for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.2) and Turkey (aOR 2.09, 95% CI 1.14-3.81), compared to Spain as a reference. Empirical carbapenems were more likely to be used in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89; 95% CI 1.05-3.39), and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLI for ESBL-E was more likely in sites from Italy. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. A better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.PH is supported by an Australian Postgraduate Award from the University of Queensland. The study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund "A way to achieve Europe" ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). BGG, JRB, APH and YC also received funds from the COMBACTE-CARE project (grant agreement 115620), Innovative Medicines Initiative (IMI), the European Union's Seventh Framework Programme (FP7/2007-2013) and in-kind contributions from EFPIA companies

Relevancia de los factores de virulencia de escherichia coli en el desarrollo de síndrome de respuesta inflamatoria sistémica y mortalidad en pacientes con bacteriemia por e. coli

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 28 de Junio de 201

Evidence for Previously Unidentified Sexual Transmission of Protozoan Parasites

Knowing the mode of transmission of a disease can affect its control and prevention. Here, we identify 5 protozoan parasites with demonstrated presence in seminal fluid, only 1 of which has been identified as a sexually transmitted disease among humans

Broad neutralizing activity against ebolaviruses lacking the mucin-like domain in convalescent plasma specimens from patients with Ebola virus disease

[Background] In Ebola virus (EBOV) infection, the specific neutralizing activity of convalescent plasma against other members of the Ebolavirus genus has not been extensively analyzed. [Methods] We measured the neutralizing activity in plasma from 3 survivors of the recent outbreak due to the Makona variant of EBOV and tested its neutralizing potency against other variants of EBOV (ie, Mayinga and Kikwit) and against Sudan virus (SUDV), Bundibugyo virus (BDBV), and Reston virus (RESTV), using a glycoprotein (GP)–pseudotyped lentiviral system both with fulllength GP and in vitro–cleaved GP (GPCL). [Results] Convalescent plasma specimens from survivors of EBOV infection showed low neutralizing activity against full-length GPs of SUDV, BDBV, RESTV, and EBOV variants Mayinga and Kikwit. However, broad and potent neutralizing activity was observed against the GPCL forms of SUDV, BDBV, and RESTV. [Discussion] Removal of the mucin-like domain and glycan cap from the GP of members of the Ebolavirus genus presumably exposes conserved epitopes in or in the vicinity of the receptor binding site and internal fusion loop that are readily amenable to neutralization. These types of broad neutralizing antibodies could be induced by using immunogens mimicking GPCL.This work was supported by Instituto de Investigación Carlos III (grants FIS PI 1400708 and DTS 1500171) and by the European Union Commission VIRUSCAN Future and Emerging Technologies Proactive 2016, under the 731868-Horizon 2020 Framework Programme by the European Union Commission Horizon 2020 Framework Programme: Project VIRUSCAN FETPROACT-2016: 731868.Peer reviewe

Response to Combined Antiretroviral Therapy According to Gender and Origin in a Cohort of Naive HIV-Infected Patients: GESIDA-5808 Study

We analyzed differences in response to combined antiretroviral therapy (cART) according to sex and geographic origin in a retrospective comparative study of Spanish-born and immigrant patients initiating cART. The primary endpoint was time to treatment failure (TTF), defined as virological failure, death, opportunistic infection, interruption of cART, or loss to follow-up. Late diagnosis was defined as a CD4+ cell count ≤ 200 cells/mm3 and/or AIDS at initiation of cART. Survival was analyzed using Kaplan-Meier analysis and Cox regression. We followed 1,090 patients, of whom 318 were women (45.6% immigrant women [IW]). At initiation of treatment, women had a higher CD4+ count than men (217 vs 190 cells/mm3), a lower viral load (4.7 vs 5 log), and fewer were late starters (49% vs 59%). The adjusted risk of TTF between women and men was not significantly different (hazard ratio [HR], 1.10; 95% CI, 0.79-1.53). TTF was shorter among IW than Spanish-born women (124 weeks [95% CI, 64-183] vs 151 [95% CI, 127-174]) and loss to follow-up was double that of Spanish-born women (25.5% vs 11.6%). Although response to cART was similar for both sexes, men started treatment later. IW were more frequently lost to follow-up and switched treatment. Measures to improve medical follow-up after initiation of cART should be promoted among this minority group. Response to Combined Antiretroviral Therapy According to Gender and Origin in a Cohort of Naïve HIV-Infected Patients: GESIDA-5808 Study. Available from: https://www.researchgate.net/publication/224971412_Response_to_Combined_Antiretroviral_Therapy_According_to_Gender_and_Origin_in_a_Cohort_of_Naive_HIV-Infected_Patients_GESIDA-5808_Study.2.304 JCR (2012) Q2, 122/261 Pharmacology & pharmacy; Q3, 42/70 Infectious disease

Do HIV-Infected Immigrants Initiating HAART have Poorer Treatment-Related Outcomes than Autochthonous Patients in Spain? Results of the GESIDA 5808 Study

Objective: Currently, 12% of the Spanish population is foreign-born, and a third of newly diagnosed HIV-infected patients are immigrants. We determined whether being an immigrant was associated with a poorer response to antiretroviral treatment. Methods: Historical multicenter cohort study of naive patients starting HAART. The primary endpoint was time to treatment failure (TTF) defined as virological failure (VF), death, opportunistic disease, treatment discontinuation (D/C), or missing patient. Secondary endpoints were TTF expressed as observed data (TFO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/C not due to VF). A multivariate analysis was performed to control for confounders. Results: A total of 1090 treatment-naive HIV-infected patients (387 immigrants and 703 autochthonous) from 33 hospitals were included. Most immigrants were from Sub-Saharan Africa (28.3%) or South-Central America/Caribbean (31%). Immigrants were significantly younger (34 y vs 39 y), more frequently female (37.5% vs 24.6%), with less HCV coinfection than autochthonous patients (7% vs 31.3%). There were no differences in baseline viral load (4.95 Log(10) vs 4.98 Log(10)), CD4 lymphocyte count (193.5/mu L vs 201.5/mu L), late initiation of HAART (56.4% vs 56.0%), or antiretrovirals used. Cox-regression analysis (HR; 95%CI) did not show differences in TTF (0.89; 0.66-1.20), TFO (0.95; 0.66-1.36), or TVF (1.00; 0.57-1.78) between immigrants and autochthonous patients. Losses to follow-up were more frequent among immigrants (17.8% vs 12.1; p=0.009). Sub-Saharan African patients and immigrant females had a significantly shorter TTF. Conclusions: The response to HAART among immigrant patients was similar to that of autochthonous patients, although they had a higher rate of losses to follow-up. Sub-Saharan Africans and immigrant females may need particular measures to avoid barriers hindering antiviral efficacy.1.923 JCR (2010) Q3, 23/33 Virology; Q4, 103/134 Immunology, 44/58 Infectious Disease