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.
Novel mechanisms of COVID-19 vaccines raised concern about their potential immunogenicity in patients with rheumatoid arthritis (RA) undergoing immunomodulatory treatments. We designed a ...retrospective single-center study to investigate their effectiveness and safety in this population, analyzing data from the first vaccination program (December 2020–October 2021). Inclusion criteria were availability of post-vaccination serology and a minimum subsequent follow-up of 6 months. Binding antibody units (BAU/mL) ≥ 7.1 defined an adequate serological response. Post-vaccine COVID-19 incidence and its timing since vaccination, adverse events (AEs), and RA flares were recorded. Adjusted logistic and linear multivariate regression analyses were carried out to identify factors associated with vaccine response. We included 118 patients (87.2% women, age 65.4 ± 11.6 years, evolution 12.0 ± 9.6 years), of whom 95.8% had a complete vaccination schedule. Adequate humoral immunogenicity was achieved in 88.1% of patients and was associated with previous COVID-19 and mRNA vaccines, whereas smoking, aCCP, age, and DMARDs exerted a negative impact. Post-vaccine COVID-19 occurred in 18.6% of patients, a median of 6.5 months after vaccination. Vaccine AE (19.5%) and RA flares (1.7%) were mostly mild and inversely associated with age. Our results suggest that COVID-19 vaccines induce adequate humoral immunogenicity, with an acceptable safety profile in RA patients.
Sepsis is the main cause of death in hospitals and the implementation of diagnosis and treatment bundles has shown to improve its evolution. However, there is a lack of evidence about patients ...attended in conventional units.
A 3-year retrospective cohort study was conducted. Patients hospitalized in Internal Medicine units with sepsis were included and assigned to two cohorts according to Sepsis Code (SC) activation (group A) or not (B). Baseline and evolution variables were collected.
A total of 653 patients were included. In 296 cases SC was activated. Mean age was 81.43 years, median Charlson comorbidity index (CCI) was 2 and 63.25% showed some functional disability. More bundles were completed in group A: blood cultures 95.2% vs 72.5% (p <0.001), extended spectrum antibiotics 59.1% vs 41.4% (p < 0.001), fluid resuscitation 96.62% vs 80.95% (p < 0.001). Infection control at 72 hours was quite higher in group A (81.42% vs 55.18%, odds ratio 3.55 2.48-5.09). Antibiotic was optimized more frequently in group A (60.77% vs 47.03%, p 0.008). Mean in-hospital stay was 10.63 days (11.44 vs 8.53 days, p < 0.001). Complications during hospitalization appeared in 51.76% of patients, especially in group B (45.95% vs 56.58%, odds ratio 1.53 1.12-2.09). Hospital readmissions were higher in group A (40% vs 24.76%, p < 0.001). 28-day mortality was significantly lower in group A (20.95% vs 42.86%, odds ratio 0.33 0.23-0.47).
Implementation of SC seems to be effective in improving short-term outcomes in IM patients, although therapy should be tailored in an individual basis.
Abstract 2225
Poster Board II-202
In spite of significant advances in the diagnosis and treatment of CMV infection post-allogeneic SCT it continues to be associated with significant morbidity and ...mortality. The human herpesvirus 6 (HHV-6) reactivation has been associated with different complications, including delayed neutrophil and platelet engraftment, interstitial pneumonia, skin rash, severe graft versus host disease (GvHD), and central nervous system disorders. HHV-6 is considered an immunomodulatory and immunosuppressive agent, and thereby, it may the increase the risk of active CMV infection and disease in the transplantation setting
To determine if the HHV-6 facilitates the CMV reactivation or influences the kinetic of CMV replication and its specific immune replication during the first 100 days after allogeneic hematopoietic SCT.
Between Nov-05 and Feb-08, sixty-eight patients were monitored for plasma HHV-6 and CMV DNAemia by PCR once/week until day +100 after Allo-SCT. Characteristics of patients: median age: 45 yo (18-70); sex (M/F): 37/31. Diagnosis: AML/MDS(n=27), ALL(n=10), lymphoproliferative syndrome(n=17), MM (n=4), CML (n=3), Others(n=7). CMV seropositive (R/D)(%): 88/60. Cell source: PBSC: 53(78%);CB:13(19%);BM:2(3%). Conditioning treatment: RIC: 40 pts, myeloablative: 28 pts. pp65 antigenemia in PMN leucocytes (Light Diagnostics, Chemicon Intern). Positive if ≥1cel+/200.000. Plasma DNA-CMV: PCR-RT Abbott or Amplicor CMV Monitor Roche. Plasma DNA-HHV6: Q-PCR Alert Amplimix, Nanogen Adv. Diag., detection limit: 10 copies/mL plasma. Enumeration of pp65 and IE-1 IFNγ CD4+ and CD8+ T cells was performed by intracellular cytokine staining. (BD Fastimmune, BD-Beckton Dickinson). Pre-emptive antiviral treatment was initiated if pp65 Ag +.
HHV-6 DNAemia occurred in 27 out of 68 pts (40%), after a median time of 20 days post-SCT with a peak value of 345 copies (26-13,661) reached on the fourth week in the 52% of patients, with a median duration of 10 days (3-35). Twenty-three out of the 27 patients were HHV-6 seropositive before transplantation. Clearance of most episodes (21 out of 27) occurred in the absence of (val)ganciclovir treatment, which was initiated in the course of the remaining 6 episodes because of the development of antigenemia-positive active CMV infection. HHV-6 DNAemia was significantly associated with subsequent CMV DNAemia in univariate (P=.01), but not in multivariate analysis (P=.056) that included transplant from URD, HLA non identical donor, myeloablative conditioning, CBT, use of prednisone as GVHD prophylaxis and plasma HHV-6 DNA detection. HHV-6 DNAemia was not predictive of development of CMV DNAemia. Timing and kinetics of active CMV infection were comparable in patients either with or without a preceding episode of HHV-6 DNAemia. Occurrence of HHV-6 DNAemia had no impact on the level of CMV-specific T-cell immunity reconstitution early after transplant. The receipt of a graft from an unrelated donor was the principal variable associated with HHV-6 and CMV coactivation.
The results of this study suggest that a basal immunosuppressive state, specially the receipt of a graft from an unrelated donor, leads to HHV-6 and CMV coactivation, and argue against an effect of active HHV-6 infection on CMV replication either by a direct interaction or indirectly by suppressing CMV-specific T-cell responses.
No relevant conflicts of interest to declare.
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.
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.
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).
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.
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.
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.
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;
= 0.54). At day 7, no significant differences were observed in the median change in clinical status (2 0-3) vs. 3 0-3,
= 0.32). Median time to discharge (days) was similar (7 6-11 vs. 6 4-12; HR 0.65, SE 0.26;
= 0.27). No significant differences were detected in the rate of progression to invasive and noninvasive mechanical ventilation.
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.
www.ClinicalTrials.gov, Identifier: NCT04357808.
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.
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.
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.
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.
Recientemente, ha surgido en Reino Unido una nueva variante de SARS-CoV-2, VOC202012/01, que origina el linaje B.1.1.7. Su rápida distribución en Reino Unido ha alertado a otros países a vigilar su presencia.
El rastreo inicial de la variante B.1.1.7 se basó en la ausencia de amplificación del gen S en el ensayo TaqPath, causado por la deleción 69/70. Todos los casos candidatos de corresponder a la variante B.1.1.7 con este criterio fueron posteriormente confirmados por secuenciación de genoma completo.
Describimos los primeros 3 casos importados de esta variante, desde Londres hasta Madrid, con la posterior transmisión domiciliaria de uno de estos casos a 3 familiares y, adicionalmente, los 2 primeros casos con la variante sin vínculo epidemiológico con Reino Unido. Uno de los casos requirió hospitalización. En todos los casos el criterio de no amplificación del gen S identificó con precisión la variante B.1.1.7, como demostró posteriormente la presencia de las 17 mutaciones marcadoras de este linaje.
Las primeras identificaciones de la variante B.1.1.7 de SARS-CoV-2 indican un papel solapante de las introducciones independientes desde Reino Unido, con eventos de transmisión comunitaria, incluso desde los primeros momentos de la presencia de esta variante en nuestro país.
INTRODUCTIONCervical lymphadenitis is the most common nontuberculous mycobacteria (NTM) infection in immunocompetent children, mainly in those under 5years. For many years Mycobacterium lentiflavum ...(M. lentiflavum) has been considered a rare NTM causing lymphadenitis. METHODSA restrospective study was performed in pediatric patients with microbiologically confirmed NTM cervical lympahdenitis at the Niño Jesús Hospital in Madrid during 2009-2016. RESULTSDuring the period studied, 28 cases of cervical lymphadenitis were recorded. In 23 (82.14%) and in 5 (17,85%) cases, M. lentiflavum and Mycobacterium avium were isolated, respectively. In those patients infected with M. lentiflavum, the most frequent location was sub-maxilar (43.47%); 15 (65.21%) were boys, global median age was 30,8 months and all cases showed a satisfactory evolution. CONCLUSIONWe propose that M. lentiflavum should be considered an important emergent pathogen cause of cervical lymphadenitis in the pediatric population.
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.
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.
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%).
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.
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