Search

The present outbreak of Human Monkeypox (HMPX) that has begun in May 2022 and has spread across all continents in less than two months has qualitative and quantitative characteristics that make it different from the pattern of human disease previously caused by this virus. It has spread with enormous ease, affects almost exclusively adults, behaves as a sexually transmitted disease and focuses on very specific groups and transmission conditions. The high incidence in the city of Madrid in males that have sex with males (MSM) has allowed us to observe and report the experience with the first 30 cases diagnosed in our institution. Patients presented with febrile symptoms, genital and paragenital skin lesions reminiscent of smallpox, but less extensive and severe. The disease may also cause proctitis, pharyngitis and perioral lesions. The PCR test for diagnostic confirmation has been shown to be very sensitive and effective, not only in skin lesions but also in blood and other fluids such as pharyngeal, rectal exudates and blood. A very high proportion of patients with HMPX also have other sexually transmitted diseases that must be actively detected in this context. The spontaneous evolution of our patients has been good and hospitalization has been practically unnecessary. Transmission to non-sexual cohabitants and health personnel has been nonexistent and the lesions have disappeared in less than 30 days without leaving sequelae and no need for specific antiviral treatment.

Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19., This study has been funded by Pharmamar, S.A. (Madrid, Spain). This work was supported by grants from the Government of Spain (PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E043). The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. We also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N.I.U. has non-restrictive funding from PharmaMar to study the antiviral effect of Plitidepsin. N.J.K. was funded by grants from the National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302); by the Excellence in Research Award (ERA) from the Laboratory for Genomics Research (LGR), a collaboration between UCSF, UCB, and GSK (#133122P); by the Roddenberry Foundation, and gifts from QCRG philanthropic donors. This work was supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement #HR0011-19-2-0020. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. This research was partly funded by CRIP (Center for Research for Influenza Pathogenesis), a NIAID supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), by DARPA grant HR0011-19-2-0020, by supplements to NIAID grants U19AI142733, U19AI135972 and DoD grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to AG-S. S.Y. received funding from a Swiss National Foundation (SNF) Early Postdoc Mobility fellowship (P2GEP3_184202).

BackgroundWe aimed to determine the impact of tocilizumab use in severe COVID-19 pneumonia mortality.MethodsWe performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain, from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by Inverse Probability of the Treatment Weights (IPTW). Tocilizumab effect in patients receiving steroids during the 48h following inclusion was analyzed.ResultsDuring the study period, 506 patients with severe COVID-19 fulfilled inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days (IQR 8-14). Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls (16.8% versus 31.5%, HR 0.514 [95CI 0.355-0.744], p< 0.001; weighted HR 0.741 [95CI 0.619-0.887], p = 0.001). Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment (RRR 46.7%). We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in patients treated with tocilizumab than in those treated with steroids alone (10.9% versus 40.2%, HR 0.511 [95CI 0.352-0.741], p = 0.036; weighted HR 0.6 [95CI 0.449-0.804], p< 0.001) (Interaction p = 0.094).ConclusionsThese results show that survival of patients with severe COVID-19 is higher in patients treated with tocilizumab than in those not treated, and that tocilizumab effect adds to that of steroids administered to non-intubated cases with COVID-19 during the first 48 hours of presenting with respiratory failure despite of oxygen therapy. Randomised controlled studies are needed to confirm these results.SummaryWe investigated in-hospital mortality of patients with severe SARS-CoV-2 pneumonia in a multicenter series of patients treated with tocilizumab compared to controls, and adjusted using IPTW. Our results show a beneficial impact of tocilizumab treatment in SARS-CoV-2 pneumonia, that adds to that of steroids.

8 páginas, 4 figuras, 1 tabla. Información suplementaria accesible en: https://doi.org/10.1038/s41598-020-59373-w, It is relevant to evaluate MDR-tuberculosis in prisons and its impact on the global epidemiology of this disease. However, systematic molecular epidemiology programs in prisons are lacking. A health-screening program performed on arrival for inmates transferred from Peruvian prisons to Spain led to the diagnosis of five MDR-TB cases from one of the biggest prisons in Latin America. They grouped into two MIRU-VNTR-clusters (Callao-1 and Callao-2), suggesting a reservoir of two prevalent MDR strains. A high-rate of overexposure was deduced because one of the five cases was coinfected by a pansusceptible strain. Callao-1 strain was also identified in 2018 in a community case in Spain who had been in the same Peruvian prison in 2002-5. A strain-specific-PCR tailored from WGS data was implemented in Peru, allowing the confirmation that these strains were currently responsible for the majority of the MDR cases in that prison, including a new mixed infection., This work was supported by ERANet-LAC [ELAC2015/T08–0664, E035-ERANet-LAC/J110-2016/FONDECYT, PER-2012-ELAC2015/T08-0664] and Instituto de Salud Carlos III [AC16/00057, FIS15/01554, FIS13/01207] and cofunded by European Regional Development Funds from the European Commission: “A way of making Europe”. FA holds a grant from IFARHUSENACYT [270-2016-293].

BACKGROUND: Screening strategies based on interferon-? release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. METHODS: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. RESULTS: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). CONCLUSIONS: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. CLINICAL TRIALS REGISTRATION: NCT01223534.

The Architect HIV Ag/Ab Combo Assay, a fourth-generation ELISA, has proven to be highly reliable for the diagnosis of HIV infection. However, its high sensitivity may lead to false-positive results.To evaluate the diagnostic performance of Architect in a low-prevalence population and to assess the role of the sample-to-cutoff ratio (S/CO) in reducing the frequency of false-positive results.We conducted a retrospective study of samples analyzed by Architect between January 2015 and June 2017. Positive samples were confirmed by immunoblot (RIBA) or nucleic acid amplification tests (NAATs). Different S/CO thresholds (1, 2.5, 10, 25, and 100) were analyzed to determine sensitivity, specificity, and negative and positive predictive values (NPV, PPV). ROC analysis was used to determine the optimal S/CO.A total of 69,471 samples were analyzed. 709 (1.02%) were positive by Architect. Of these, 63 (8.89%) were false-positive results. Most of them (93.65%) were in samples with S/CO 100. However, most confirmations by NAATs (12 out of 19 cases) were also recorded for these samples. The optimal S/CO was 2.5, which provided the highest area under the ROC curve (0.9998) and no false-negative results. With this S/CO, sensitivity and specificity were 100.0%, and PPV and NPV were 95.8% and 100.0%, respectively. In addition, the frequency of false-positive results decreased significantly to 4.15%.Although Architect generates a relatively high number of false-positive results, raising the S/CO limit too much to increase specificity can lead to false-negative results, especially in newly infected individuals.

SummaryObjectives This study evaluates the effectiveness, safety and costs of switching to a rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) regimen in treatment-experienced HIV-1-infected patients with sustained virological suppression. Methods Observational, prospective study. Study population included all treatment-experienced patients with sustained virological suppression who switched to RPV/FTC/TDF during 2013 in a tertiary hospital. Patients were followed until they completed 96 weeks of treatment. The effectiveness end-point was defined as the proportion of patients who maintained virological suppression at week 96 by intention-to-treat analysis (discontinuation=failure). The safety of RPV/FTC/TDF (incidence of adverse events leading to discontinuation and laboratory abnormalities) and adherence to this regimen were evaluated, and the cost of switching was analysed. Results One-hundred forty-six patients were included. At week 96, 71.9% of patients remained virologically suppressed; 6.8% experienced virological failure. During follow-up, 25.3% of patients discontinued RPV/FTC/TDF (14.4% because of adverse events, mainly renal impairment). Throughout the 96 weeks, there were significant decreases in total cholesterol (TC) (14.0 mg/dL, P

A voriconazole-resistant isolate of Aspergillus fumigatus was recovered from an immunocompetent patient receiving long-term antifungal therapy for cerebral aspergillosis. A G448S amino acid substitution in the azole target (Cyp51A) was identified as the cause of the resistance phenotype. This article describes the first isolation of a voriconazole-resistant A. fumigatus isolate from an immunocompetent patient in Spain.

Background There is little clinical information about community-onset bloodstream infections (COBSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC). We investigated the prevalence and risk factors for COBSI due to ESBLEC, and described their clinical features and the impact of COBSI caused by ESBLEC on 14-day mortality. Methods Risk factors were assessed using a multicenter case-control-control study. Influence of ESBL production on mortality was studied in all patients with COBSI due to E. coli. Isolates and ESBLs were microbiologically characterized. Statistical analysis was performed using multivariate logistic regression. Thirteen tertiary care Spanish hospitals participated in the study. Results We included 95 case patients with COBSI due to ESBLEC, which accounted for 7.3% of all COBSI due to E. coli. The ESBL in 83 of these (87%) belonged to the CTX-M family of ESBL, and most were clonally unrelated. Comparison with both control groups disclosed association with health care (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.8), urinary catheter use (OR, 3.1; 95% CI, 1.5-6.5), and previous antimicrobial use (OR, 2.7; 95% CI, 1.5-4.9) as independent risk factors for COBSI due to ESBLEC. Mortality among patients with COBSI due to ESBLEC was lower among patients who received empirical therapy with beta-lactam/beta-lactam inhibitor combinations or carbapenems (8%-12%) than among those receiving cephalosporins or fluoroquinolones (24% and 29%, respectively). Mortality among patients with COBSI due to E. coli was associated with inappropriate empirical therapy irrespective of ESBL production. Conclusions ESBLEC is an important cause of COBSI due to E. coli. Clinicians should consider adequate empirical therapy with coverage of these pathogens for patients with risk factors.

Our aim was to explore the association among ACSM4 and PECI polymorphisms and AIDS progression in 454 HIV- infected patients never treated with antiretroviral drugs (146 long- term nonprogressors, 228 moderate progressors, and 80 rapid progressors). For ACSM4 polymorphisms, rs7137120 AA/AG and rs7961991 CC/CT genotypes had higher odds of having a rapid AIDS progression (odds ratio (OR) = 3.21; 95% of confidence inter- val (95% CI) = 1.26 to 8.16; P = 0.014 and OR = 3.60; 95% CI = 1.38 to 9.36; P = 0.009, respectively). Additionally, the ACSM4 haplotype integrated for both rs7961991 A and rs7137120 C alleles had higher odds of having a rapid AIDS progression (OR = 2.85; 95% CI = 1.28 to 6.25; P = 0.010). For PECI polymorphisms, no significant associations were found. In conclusion, ACSM4 polymor- phisms might play a significant role in AIDS progression.

Methods based on real-time polymerase chain reaction (PCR) can speed up the diagnosis of invasive aspergillosis but are limited by a lack of standardization. We evaluated the commercially available MycAssay™ Aspergillus test for the diagnosis of invasive aspergillosis in patients without hematological cancer. We prospectively collected 322 lower respiratory tract samples (November 2009-January 2011) from 175 patients with lower respiratory tract infection and the following predisposing conditions: solid cancer (16.8%), cirrhosis (16.8%), corticosteroid therapy (71.7%), HIV infection (15.6%), chronic obstructive pulmonary disease (COPD, 52.6%), solid organ transplantation (kidney [1.2%], heart [3%], liver [4.6%]), or none (3.5%). Specimens were obtained when clinically indicated and analyzed in the microbiology laboratory. Aspergillus DNA was extracted and amplified by means of MycXtra® and MycAssay™ Aspergillus. Aspergillus spp. was isolated from 65 samples (31 patients). According to the European Organization for Research and Treatment of Cancer and Bulpa's criteria (for patients with COPD), 15 had probable invasive aspergillosis. MycAssay™ Aspergillus results were negative (n = 254), positive (n = 54), or indeterminate (n = 14). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio of the MycAssay™ (first sample/any sample) were 86.7/93, 87.6/82.4, 34.1/34.1, 92.2/100, and 48/68.75. The differences between the proportion of samples with positive PCR determinations (63%) and the proportion of samples with Aspergillus spp. isolation (75%) did not reach statistical significance (P = 0.112). The median time from sample culture to visualization of fungal growth was 3 days, compared with ∼4 hours for MycAssay™ Aspergillus PCR. MycAssay™ Aspergillus showed high sensitivity for the diagnosis of invasive aspergillosis in patients without hematological cancer. Sensitivity increased when multiple samples were used. Compared with fungal culture, PCR significantly reduced the time to diagnosis.

The presence of Aspergillus antigens in blood transfusion components from different manufacturers was analyzed. Galacomannans were found in transfused patients, pooled platelet concentrates, fresh frozen plasma, and packed red cells collected using Fresenius Kabi bags. Galacomannans were also found in blood collection anticoagulant and platelet additive solution from this manufacturer.

Extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli (ESBLEC) is an increasing cause of community and nosocomial infections worldwide. However, there is scarce clinical information about nosocomial bloodstream infections (BSIs) caused by these pathogens. We performed a study to investigate the risk factors for and prognosis of nosocomial BSIs due to ESBLEC in 13 Spanish hospitals. Risk factors were assessed by using a case-control-control study; 96 cases (2 to 16% of all nosocomial BSIs due to E. coli in the participating centers) were included; the most frequent ESBL was CTX-M-14 (48% of the isolates). We found CTX-M-15 in 10% of the isolates, which means that this enzyme is emerging as a cause of invasive infections in Spain. By repetitive extragenic palindromic sequence-PCR, most isolates were found to be clonally unrelated. By multivariate analysis, the risk factors for nosocomial BSIs due to ESBLEC were found to be organ transplant (odds ratio [OR] = 4.8; 95% confidence interval [CI] = 1.4 to 15.7), the previous use of oxyimino-β-lactams (OR = 6.0; 95% CI = 3.0 to 11.8), and unknown BSI source (protective; OR = 0.4; 95% CI = 0.2 to 0.9), and duration of hospital stay (OR = 1.02; 95% CI = 1.00 to 1.03). The variables independently associated with mortality were a Pitt score of >1 (OR = 3.9; 95% CI = 1.2 to 12.9), a high-risk source (OR = 5.5; 95% CI = 1.4 to 21.9), and resistance to more than three antibiotics, apart from penicillins and cephalosporins (OR = 6.5; 95% CI = 1.4 to 30.0). Inappropriate empirical therapy was not associated with mortality. We conclude that ESBLEC is an important cause of nosocomial BSIs. The previous use of oxyimino-β-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.

We studied 75 patients with non-hematological conditions from whom Aspergillus spp. were recovered from clinical specimens during the period March 2003 to August 2006. The patients were classified according to EORTC criteria and the presence of galactomannan (Platelia Aspergillus) in their sera was evaluated. Ten of these patients (13.3%) had proven or probable invasive aspergillosis, i.e., chronic obstructive pulmonary disease in five (50%), HIV infection in one (10%), lymphoma in one (10%), liver transplant in one (10%), solid malignancies in one (10%), and corticosteroid treatment in one (10%). The sensitivity, specificity, and positive and negative predictive values for the detection of galactomannan, using cut-offs of > or =0.5 ng/ml and > or =1 ng/ml were 60%/50%, 89.23%/100%, 46.15%/100%, and 93.55%/92.86% (p=0.001 and p

Propionibacterium spp. are common flora of human skin. Nevertheless, currently recommended culture procedures do not include anaerobic processing with the result that this organism may go undetected on a colonized catheter. To determine the rate of catheter colonization by Propionibacterium spp., a sample of 1000 vascular catheters was processed by the roll-plate technique and, after conventional aerobic processing, all primary culture plates were reincubated in an anaerobic atmosphere. Propionibacterium acnes was detected in significant counts in the vascular catheters of 39 patients. This represents 14.7% (95% CI, 12.5-16.9) of all positive catheters. Propionibacterium is the second most frequent genus-colonizing catheter tips after Staphylococcus spp. Methodological shortcomings impair the detection and proper adscription of P. acnes as a potential cause of catheter-related infections.