Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

First report of a carbapenemase OXA-48-producing Hafnia alvei clinical isolate.

Introduction: Carbapenems are usually used in the treatment of infections caused by cephalosporin-resistant Enterobacterales ; however, the increase in carbapenem-resistant Enterobacterales (CRE) has become one of the most important problems in public health. Hafnia alvei is associated with intestinal and extraintestinal infections, especially in patients with any chronic disease or some type of immunosupression. H. alvei is resistant to first-generation aminopenicillins and cephalosporins owing to the ß-lactamase (Amp C) in their chromosome; the only carbapenem-resistant Hafnia strain described until now was due to a lack of the OmpK36 protein that plays an important role in permeability to carbapenems. Case presentation: We present the case of a 65-year-old male diagnosed with acute lithiasic cholecystitis. Culture of the biliary prosthesis yielded a OXA-48-producing H. alvei that was identified by MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) MS. Carbapenemase production was detected by immunochromatography and confirmed by sequencing. Conclusion: To our knowledge, this is the first report of OXA-48-producing H. alvei probably obtained by horizontal transfer from Enterobacter cloacae OXA-48 isolated in previous samples.

First confirmation of importation and transmission in Spain of the newly identified SARS-CoV-2 B.1.1.7 variant.

INTRODUCTION: A newly identified SARS-CoV-2 variant, VOC202012/01 originating lineage B.1.1.7, recently emerged in the United Kingdom. The rapid spread in the UK of this new variant has caused other countries to be vigilant. MATERIAL AND METHODS: We based our initial screening of B.1.1.7 on the dropout of the S gene signal in the TaqPath assay, caused by the 69/70 deletion. Subsequently, we confirmed the B.1.1.7 candidates by whole genome sequencing. RESULTS: We describe the first three imported cases of this variant from London to Madrid, subsequent post-arrival household transmission to three relatives, and the two first cases without epidemiological links to UK. One case required hospitalization. In all cases, drop-out of gene S was correctly associated to the B.1.1.7 variant, as all the corresponding sequences carried the 17 lineage-marker mutations. CONCLUSION: The first identifications of the SARS-CoV-2 B.1.1.7 variant in Spain indicate the role of independent introductions from the UK coexisting with post-arrival transmission in the community, since the early steps of this new variant in our country.

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort.

Background: Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort. Methods: Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata. Results: A total of 57 patients were recruited, with median age of 63 years (IQR [53-81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age. Conclusion: In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

Subcutaneous IL-6 Inhibitor Sarilumab vs. Standard Care in Hospitalized Patients With Moderate-To-Severe COVID-19: An Open Label Randomized Clinical Trial.

Background: The use of IL-6 blockers in COVID-19 hospitalized patients has been associated with a reduction in mortality compared to standard care. However, many uncertainties remain pertaining to optimal intervention time, administration schedule, and predictors of response. To date, data on the use of subcutaneous sarilumab is limited and no randomized trial results are available. Methods: Open label randomized controlled trial at a single center in Spain. We included adult patients admitted with microbiology documented COVID-19 infection, imaging confirmed pneumonia, fever and/or laboratory evidence of inflammatory phenotype, and no need for invasive ventilation. Participants were randomly assigned to receive sarilumab, a single 400 mg dose in two 200 mg subcutaneous injections, added to standard care or standard care, in a 2:1 proportion. Primary endpoints included 30-day mortality, mean change in clinical status at day 7 scored in a 7-category ordinal scale ranging from death (category 1) to discharge (category 7), and duration of hospitalization. The primary efficacy analysis was conducted on the intention-to-treat population. Results: A total of 30 patients underwent randomization: 20 to sarilumab and 10 to standard care. Most patients were male (20/30, 67%) with a median (interquartile range) age of 61.5 years (56-72). At day 30, 2/20 (10%) patients died in the sarilumab arm vs. none (0/10) in standard care (Log HR 15.11, SE 22.64; p = 0.54). At day 7, no significant differences were observed in the median change in clinical status (2 [0-3]) vs. 3 [0-3], p = 0.32). Median time to discharge (days) was similar (7 [6-11] vs. 6 [4-12]; HR 0.65, SE 0.26; p = 0.27). No significant differences were detected in the rate of progression to invasive and noninvasive mechanical ventilation. Conclusions and Relevance: Our pragmatic pilot study has failed to demonstrate the benefit of adding subcutaneous sarilumab to standard care for mortality by 30 days, functional status at day 7, or hospital stay. Findings herein do not exclude a potential effect of sarilumab in severe COVID-19 but adequately powered blinded randomized phase III trials are warranted to assess the impact of the subcutaneous route and a more selected target population. Trial Registration: www.ClinicalTrials.gov, Identifier: NCT04357808.

In vitro activity of cefiderocol and comparators against isolates of Gram-negative bacterial pathogens from a range of infection sources: SIDERO­WT­2014-2018 studies in Spain.

OBJECTIVES: The incidence of antimicrobial resistance in Europe is rising. Cefiderocol is approved in Europe for treatment of aerobic Gram-negative bacterial (GNB) infections in adults with limited treatment options. We report the in vitro activity of cefiderocol versus comparators against GNB clinical isolates from Spain. METHODS: MICs were determined by broth microdilution according to International Organization for Standardization guidelines. Cefiderocol was tested using iron-depleted cation-adjusted Mueller-Hinton broth. Susceptibility rates were based on EUCAST breakpoints; if a species-specific breakpoint was unavailable, pharmacokinetic/pharmacodynamic breakpoints were used. RESULTS: Of 2303 isolates [1502 (65.2%) Enterobacterales and 801 (34.8%) non-fermenters], 2260 (98.1%) were susceptible to cefiderocol compared with 80.8-86.9% for comparators. By infection source, susceptibility to cefiderocol ranged from 97.3% (721/741) in isolates from patients with nosocomial pneumonia to 98.9% (349/353) in bloodstream infection isolates and was greater than susceptibility to comparators (70.7-93.6% across infection sources). Overall, 368/2303 isolates (16.0%) were meropenem-resistant. A high proportion of meropenem-resistant Acinetobacter baumannii [169/175 (96.6%)] and Pseudomonas aeruginosa [48/50 (96.0%)] were cefiderocol-susceptible, similar to colistin [169/175 (96.6%) and 47/50 (94.0%), respectively] but higher than ceftazidime/avibactam [26/175 (14.9%) and 20/50 (40.0%), respectively] and ceftolozane/tazobactam [17/175 (9.7%) and 25/50 (50.0%), respectively]. All meropenem-resistant Stenotrophomonas maltophilia isolates [120/120 (100%)] were cefiderocol-susceptible, including one trimethoprim/sulfamethoxazole-resistant isolate, with fewer susceptible to colistin [86/120 (71.7%)], ceftazidime/avibactam [42/120 (35.0%)] and ceftolozane/tazobactam [35/120 (29.2%)]. CONCLUSION: A high proportion of clinical isolates from Spain, representing a wide range of pathogens across multiple infection sources, were susceptible to cefiderocol. Cefiderocol retained activity against meropenem-resistant isolates.

Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients.

COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48-72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50-60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8-22.6] for Roche, OR 10.3 [3.6-29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13-23.57] for TFS viremia and HR = 7.09 [3.3-14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.

First confirmation of importation and transmission in Spain of the newly identified SARS-CoV-2 B.1.1.7 variant.

INTRODUCTION: A newly identified SARS-CoV-2 variant, VOC202012/01 originating lineage B.1.1.7, recently emerged in the United Kingdom. The rapid spread in the UK of this new variant has caused other countries to be vigilant. MATERIAL AND METHODS: We based our initial screening of B.1.1.7 on the dropout of the S gene signal in the TaqPath assay, caused by the 69/70 deletion. Subsequently, we confirmed the B.1.1.7 candidates by whole genome sequencing. RESULTS: We describe the first three imported cases of this variant from London to Madrid, subsequent post-arrival household transmission to three relatives, and the two first cases without epidemiological links to UK. One case required hospitalization. In all cases, drop-out of gene S was correctly associated to the B.1.1.7 variant, as all the corresponding sequences carried the 17 lineage-marker mutations. CONCLUSION: The first identifications of the SARS-CoV-2 B.1.1.7 variant in Spain indicate the role of independent introductions from the UK coexisting with post-arrival transmission in the community, since the early steps of this new variant in our country.

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study.

BACKGROUND: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. OBJECTIVE: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. METHODS: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. RESULTS: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. CONCLUSIONS: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.

Can COVID-19 cause severe neutropenia?

This is the first case of acquired severe neutropenia in the context of COVID-19 reported to date. This could illustrate another less frequent hematological disorder related to this novel viral infection.

COVID-19 in 7 multiple sclerosis patients in treatment with ANTI-CD20 therapies.

BACKGROUND AND AIM: In December 2019, the first cases of SARS-CoV-2 infection were detected in Wuhan. Within two months, it had begun to spread around the world in what became an unprecedented pandemic. Patients with Multiple Sclerosis (MS) in a state of immunosuppression may be considered at risk for complications in the COVID-19 pandemic, although there is increasing evidence postulating a possible protective role of selective immunosuppression. One group of such immunosuppressants used in MS comprises the anti-CD20 monoclonal antibodies (mAbs) ocrelizumab and rituximab. Anti-CD20 mAbs bind to the surface of B cells, causing their depletion. We describe our experience in seven cases of patients with multiple sclerosis who have been affected by SARS-COV-2 (with a clinical/serological diagnosis or PCR diagnosis) and who were being treated with anti-CD20+ monoclonal antibodies. MATERIAL AND METHODS: We review the development of patients during infection as well as the resolution of their clinical picture. We also analyze the serology status against SARS-CoV-2 after resolution of the infection. RESULTS: Although the severity of the clinical pictures was variable, patients' development was good. Not all patients, however, developed antibodies against SARS-CoV-2. CONCLUSIONS: Patients treated with anti-CD20+ have adequate resolution of COVID-19 despite the fact that the presence of antibodies against SARS-CoV-2 was not detected in all cases. It is possible that the presence of humoral immunity is not always necessary fora good clinical course of SARS-CoV-2 infection.

Estudio de resistencias de citomegalovirus en pacientes receptores de trasplante alogénico de progenitores hematopoyéticos / Study of cytomegalovirus resistance in allogeneic hematopoietic cell transplant recipients

INTRODUCCIÓN: El citomegalovirus (CMV) es el patógeno oportunista más importante asociado al trasplante. El objetivo de este trabajo fue la caracterización de mutaciones de resistencia de CMV en pacientes receptores de trasplante alogénico de progenitores hematopoyéticos (alo-TPH) y el estudio de factores asociados. MÉTODOS: Se llevó a cabo un estudio retrospectivo de una cohorte de pacientes receptores de alo-TPH con reactivaciones postrasplante de CMV con cargas virales (CV) estables o en aumento, a pesar de un adecuado tratamiento antiviral al menos durante 2semanas. Se realizó el estudio de mutaciones de resistencia de los genes UL97 y UL54 mediante secuenciación Sanger. RESULTADOS: La infección refractaria de CMV de nuestro grupo de pacientes alo-TPH se correspondió con una tasa de infección por virus resistente del 21,43% (3 de 14 pacientes). Todos los pacientes con mutaciones de resistencia presentaron múltiples episodios de reactivación (p-valor 0,01). Las mutaciones encontradas fueron A594V y H520Q en el gen UL97 que confieren resistencia de alto grado a ganciclovir (GCV). Uno de los 3 casos con resistencia antiviral, se documentó con una CV baja (< 1.000 copias/ml) y tras corto tratamiento acumulado de GCV (41 días). CONCLUSIÓN: La mayor parte de los fracasos en el tratamiento del CMV se debió posiblemente a resistencia clínica; la falta de respuesta satisfactoria al tratamiento antiviral no siempre se acompaña de resistencia virológica. No obstante, la aparición de resistencias puede ocurrir de forma temprana tras el inicio del tratamiento anticipado y con CV por debajo de 1.000 copias/ml. El número de episodios de reactivación fue mayor entre los pacientes que se demostró resistencia virológica frente a los que no

INTRODUCTION: Cytomegalovirus (CMV) is the most important opportunistic pathogen associated with transplant. The objective of this study was the characterization of CMV resistance mutations in allogeneic haematopoietic cell transplant recipients (allo-TPH) and the study of associated factors. METHODS: A retrospective study of a cohort of allo-TPH recipients with post-transplant CMV reactivations with stable or increasing viral loads (CV), despite adequate antiviral treatment for at least 2weeks. The study of resistance mutations of the UL97 and UL54 genes was carried out by Sanger sequencing. RESULTS: Refractory CMV infection in our group of allo-TPH patients corresponded with a 21.43% rate of resistant virus infection (3 of 14 patients). All patients with resistance mutations had multiple reactivation episodes (P-value .01). The mutations found were A594V and H520Q in the UL97 gene that confers high-grade resistance to ganciclovir (GCV). One of the 3 cases with antiviral resistance was documented with a low VL (< 1000 copies/ml) and short accumulated GCV treatment (41 days). CONCLUSION: Most of the failures in the treatment of CMV were possibly due to clinical resistance; the lack of satisfactory response to antiviral treatment is not always accompanied by virological resistance. However, the appearance of resistances can occur early after the start of the treatment and with VL below 1000 copies / ml. The number of episodes of reactivation was higher among patients with virological resistance than those who did not

Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease.

Graft versus host disease (GvHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). Here we report studies of a patient with chronic GvHD (cGvHD) carrying persistent CD4+ T cell clonal expansion harboring somatic mTOR, NFKB2, and TLR2 mutations. In the screening cohort (n = 134), we detect the mTOR P2229R kinase domain mutation in two additional cGvHD patients, but not in healthy or HSCT patients without cGvHD. Functional analyses of the mTOR mutation indicate a gain-of-function alteration and activation of both mTORC1 and mTORC2 signaling pathways, leading to increased cell proliferation and decreased apoptosis. Single-cell RNA sequencing and real-time impedance measurements support increased cytotoxicity of mutated CD4+ T cells. High throughput drug-sensitivity testing suggests that mutations induce resistance to mTOR inhibitors, but increase sensitivity for HSP90 inhibitors. Our findings imply that somatic mutations may contribute to aberrant T cell proliferations and persistent immune activation in cGvHD, thereby paving the way for targeted therapies.

Evaluation of therapeutic targeting of CCR7 in acute graft-versus-host disease.

Graft-versus-host disease (GVHD) is the main complication after allogeneic hematopoietic stem cell transplantation. We previously unveiled a correlation between proportions of C-C motif chemokine receptor 7 (CCR7)+ T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in vivo whether apheresis with low proportion of CCR7+ cells or treatment with an anti-human CCR7 monoclonal antibody (mAb) were suitable strategies to prevent or treat acute GVHD in preclinical xenogeneic models. Therapeutic anti-CCR7 mAb was the most effective strategy in both prophylactic and therapeutic settings where antibody drastically reduced in vivo lymphoid organ infiltration of donor CCR7+ T cells, extended lifespan and solved clinical signs. The antibody neutralized in vitro migration of naïve and central memory T cells toward CCR7 ligands and depleted target CCR7+ subsets through complement activation. Both mechanisms of action spared CCR7- subsets, including effector memory and effector memory CD45RA+ T cells which may mediate graft versus leukemia effect and immunity against infections. Accordingly, the numbers of donor CCR7+ T cells in the apheresis were not associated to cytomegalovirus reactivation or the recurrence of the underlying disease. These findings provide a promising new strategy to prevent and treat acute GVHD, a condition where new specific, safety and effective treatment is needed.

Study of cytomegalovirus resistance in allogeneic hematopoietic cell transplant recipients. / Estudio de resistencias de citomegalovirus en pacientes receptores de trasplante alogénico de progenitores hematopoyéticos.

INTRODUCTION: Cytomegalovirus (CMV) is the most important opportunistic pathogen associated with transplant. The objective of this study was the characterization of CMV resistance mutations in allogeneic haematopoietic cell transplant recipients (allo-TPH) and the study of associated factors. METHODS: A retrospective study of a cohort of allo-TPH recipients with post-transplant CMV reactivations with stable or increasing viral loads (CV), despite adequate antiviral treatment for at least 2weeks. The study of resistance mutations of the UL97 and UL54 genes was carried out by Sanger sequencing. RESULTS: Refractory CMV infection in our group of allo-TPH patients corresponded with a 21.43% rate of resistant virus infection (3 of 14 patients). All patients with resistance mutations had multiple reactivation episodes (P-value .01). The mutations found were A594V and H520Q in the UL97 gene that confers high-grade resistance to ganciclovir (GCV). One of the 3 cases with antiviral resistance was documented with a low VL (< 1000 copies/ml) and short accumulated GCV treatment (41 days). CONCLUSION: Most of the failures in the treatment of CMV were possibly due to clinical resistance; the lack of satisfactory response to antiviral treatment is not always accompanied by virological resistance. However, the appearance of resistances can occur early after the start of the treatment and with VL below 1000 copies / ml. The number of episodes of reactivation was higher among patients with virological resistance than those who did not.

Infection with multiple hepatitis C virus genotypes detected using commercial tests should be confirmed using next generation sequencing.

Current HCV genotyping methods may have some limitations in detecting mixed infections. We aimed to determine the accuracy of genotyping and the detection of mixed-genotype infections using the Abbott-RealTime HCV Genotype II assay (Abbott-RT-PCR) in comparison with a Roche-Next Generation Sequencing assay (Roche-NGS). Plasma samples collected from 139 HCV-infected patients tested with Abbott-RT-PCR, 114 with single genotype (GT) and 25 with mixed GTs were genotyped using Roche-NGS. Roche-NGS confirmed all single GTs obtained with Abbott-RT-PCR. One case of Abbott GT 4 was found as GT 1a using Roche-NGS. Genotype 5 was confirmed using Roche-NGS in 75% cases (3 out of 4 cases). Twenty-five patients were identified as having mixed HCVinfections using Abbott-RT-PCR. The concordance between Abbott-RT-PCR and Roche-NGS was 76% (19 out of 25 cases). Three mixed-GT infections identified with the Abbott assay (two (1b + 4); one (1a + 3)) were reported as pure 1b using Roche-NGS. Very divergent results were found for the other three samples. When compared to Roche-NGS, Abbott-RT-PCR has performed excellently for the determination of patients infected with single GTs. For patients that are categorized as having a mixed infection using Abbott-RT-PCR, we recommend an NGS assay as a confirmation test.

Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital / Resultados clínicos iniciales y variables pronósticas en la implementación de un Código Sepsis en un Hospital Universitario de alta complejidad

OBJECTIVES: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient's epidemiological and clinical characteristics and prognostic factors. MATERIALS AND METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p < 0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p < 0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs

OBJETIVO: Evaluar el impacto de un programa educativo y organizativo llamado Código Sepsis, en los primeros siete meses de su aplicación en un hospital de alta complejidad. MATERIAL Y MÉTODOS: Se realizó un estudio observacional durante un período consecutivo de siete meses (Febrero 2015-Septiembre 2015). Se analizó la relación con la mortalidad de los factores de riesgo y los valores analíticos usando análisis uni y multivariante. RESULTADOS: Se incluyeron un total de 237 pacientes. La mortalidad intrahospitalaria a los 30 días fue del 24 % y del 27% a los 60 días. La mortalidad de los pacientes ingresados en Unidades de Cuidados Críticos fue del 30%. Se encontraron diferencias significativas entre los pacientes que murieron y los que sobrevivieron en sus valores medios de creatinina (2,30 vs 1,46 mg/dL, p <0,05), ácido láctico (6,10 vs 2,62 mmol/L, p <0,05) y procalcitonina (23,27 vs 12,73 mg/dL, p <0,05). Se encontró una tendencia lineal estadísticamente significativa entre los valores de la escala SOFA y la mortalidad (p <0,05). En el análisis multivariante se identificaron otros factores de riesgo independientes asociados con la muerte: edad > 65 años (OR 5,33, p <0,05), ácido láctico > 3 mmol/L (OR 5,85, p <0,05), creatinina > 1,2 mgr/dL (OR 4,54, p <0,05) y el shock (OR 6,57, P <0,05). CONCLUSIONES: La mortalidad en este estudio se encuentra dentro de los límites de los ensayos clínicos más recientes de sepsis. El estudio ha identificado varios marcadores que podrían ser útiles a nivel local para estimar el riesgo en pacientes sépticos. Estudios como éste son necesarios para hacer mejoras en los programas de Código Sepsis

Peritonitis caused by Blastomonas natatoria in a patient submitted to peritoneal dyalisis / Blastomonas natatoria en un paciente sometido a diálisis peritoneal

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