Background. Influenza vaccine effectiveness is not optimal in solid organ transplant recipients (SOTR). We hypothesized that a booster dose might increase it. Methods. TRANSGRIPE 1–2 is a phase 3, ...randomized, controlled, multicenter, open-label clinical trial. Patients were randomly assigned (1:1 stratified by study site, type of organ, and time since transplantation) to receive 1 dose (control group) or 2 doses (booster group) of the influenza vaccine 5 weeks apart. Results. A total of 499 SOTR were enrolled. Although seroconversion at 10 weeks did not meet significance in the modified intention-to-treat population, seroconversion rates were significantly higher in the booster arm for the per-protocol population (53.8% vs 37.6% for influenza A(H1N1)pdm; 48.1% vs 32.3% for influenza A(H3N2); and 90.7% vs 75% for influenza B; P < .05). Furthermore, seroprotection at 10 weeks was higher in the booster group: 54% vs 43.2% for A(H1N1)pdm; 56.9% vs 45.5% for A(H3N2); and 83.4% vs 71.8% for influenza B (P < .05). The number needed to treat to seroprotect 1 patient was <10. The clinical efficacy (99.2% vs 98.8%) and serious adverse events (6.4% vs 7.5%) were similar for both groups. Conclusions. In SOTR, a booster strategy 5 weeks after standard influenza vaccination is safe and effective and induces an increased antibody response compared with standard influenza vaccination consisting of a single dose. Clinical Trials Registration. EudraCT (2011-003243-21).
•Non-HACEK endocarditis affects elderly patients with high comorbidity.•There are difference between Enterobacterales and NF-GNB cases.•Advanced age and prosthetic valve confer a worse ...prognosis.•Surgery may not be indicated in all cases.
Infective endocarditis (IE) due to non-HACEK bacilli (Haemophilus species, Actinobacillus, Cardiobacterium, Eikenella, or Kingella) is uncommon and poorly described. The objectives of this study were to describe non-HACEK Gram-Negative Bacilli (GNB) IE cases and compare characteristic of IE produced by Enterobacterales and non-fermenting (NF) GNB.
From January 2008 to December 2018, 3910 consecutive patients with definitive IE diagnosis, defined with Modified Duke criteria, either clinical or pathological criteria (e.g. demonstration of non-HACEK GNB in valve culture)were prospectively included.
A total of 104 IE cases were caused by non-HACEK GNB (2.6%). Compared to IE due to other microorganisms (excluding HACEK GNB), patients with non-HACEK GNB IE presented with higher age (71 years IQR 62–78 vs 68 years IQR: 57–77; p = 0.026), higher proportion of women (52% vs 31.5%, p < 0.001), higher Charlson Index (5 IQR: 4–8 vs 4 IQR 3–7, p = 0.003) and higher in-hospital mortality (36.5% vs 27.1%, p = 0.034). Enterobacterales cases were more frequently associated with genitourinary focus (32.8% vs 5.0%, p = 0.001). NFGNB endocarditis more frequently affected right valves (20.0% vs. 6.3%, p = 0.033), had more common healthcare-related acquisition (67.5% vs. 43.7%, p = 0.030) and venous catheter as focus (40.0% vs. 17.2%, p = 0.019). In the multivariant model, factors related with hospital mortality were: age (OR 1.05, 95%CI 1.00–1.09, p = 0.042), prosthetic valve (OR 2.31, 95%CI 0.90–5.88, p = 0.080), and not performing surgery when indicated (OR 3.60, 95%CI 1.17–11.05, p = 0.025).Patients treated with quinolone combination had lower mortality (OR 0.29; 95%CI 0.09–0.96; p = 0.043).
Non-HACEK GNB IE is a rare infection characterized by affecting elderly patients with high comorbidity, nosocomial acquisition and unfavorable outcome. Age, prosthetic valve and not performing surgery when indicated are associated with mortality.
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•Raman Spectroscopy combined with 1-D CNN as a tool for classifying K. pneumoniae isolates.•Accuracies of 96 % for capsular serotypes and 94 % for hypermucoviscous vs. non-mucoid ...isolates.•Less than 30 spectral features are needed for high-accuracy classification.•Advanced AI techniques enhance interpretability via feature reduction and saliency maps.
Antimicrobial resistance poses a significant challenge in modern medicine, affecting public health. Klebsiella pneumoniae infections compound this issue due to their broad range of infections and the emergence of multiple antibiotic resistance mechanisms. Efficient detection of its capsular serotypes is crucial for immediate patient treatment, epidemiological tracking and outbreak containment. Current methods have limitations that can delay interventions and increase the risk of morbidity and mortality. Raman spectroscopy is a promising alternative to identify capsular serotypes in hypermucoviscous K. pneumoniae isolates. It provides rapid and in situ measurements with minimal sample preparation. Moreover, its combination with machine learning tools demonstrates high accuracy and reproducibility. This study analyzed the viability of combining Raman spectroscopy with one-dimensional convolutional neural networks (1-D CNN) to classify four capsular serotypes of hypermucoviscous K. pneumoniae: K1, K2, K54 and K57. Our approach involved identifying the most relevant Raman features for classification to prevent overfitting in the training models. Simplifying the dataset to essential information maintains accuracy and reduces computational costs and training time. Capsular serotypes were classified with 96 % accuracy using less than 30 Raman features out of 2400 contained in each spectrum. To validate our methodology, we expanded the dataset to include both hypermucoviscous and non-mucoid isolates and distinguished between them. This resulted in an accuracy rate of 94 %. The results obtained have significant potential for practical healthcare applications, especially for enabling the prompt prescription of the appropriate antibiotic treatment against infections.
The aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger ...sequencing and assessing risk factors and the clinical impact of resistance.
Using Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016.
Among 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in <20% of the sequenced population, being located in the UL97 gene and conferring high-level resistance to ganciclovir. The presence of DRM by NGS was associated with lung transplantation (p = 0.050), the administration of prophylaxis (p = 0.039), a higher mean time between transplantation and suspicion of resistance (p = 0.038) and longer antiviral treatment duration before suspicion (p = 0.024). However, the latter was the only factor independently associated with the presence of DRM by NGS in the multivariate analysis (OR 2.24, 95% CI 1.03 to 4.87).
NGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.
Clinical experience of cefiderocol Fariñas, M C
Revista española de quimioterapia,
09/2022, Letnik:
35 Suppl 2, Številka:
Suppl2
Journal Article
Odprti dostop
Infections by antibiotic-resistant microorganisms could be considered a "stealth pandemic" that we fight daily in most hospitals. Some estimates suggest that today 700,000 deaths per year can be ...attributed to antimicrobial resistance. By the year 2050, it is estimated that this will increase to ten million deaths per year as a result of infections by multidrug-resistant microorganisms. In this context, the availability of antimicrobial therapy that is effective against these pathogens is essential to be able to "save the lives" of our patients. Cefiderocol, a new cephalosporin with a different mechanism of action, will be an essential treatment in many infections caused by resistant aerobic gram-negative bacteria. Cefiderocol has been used to treat patients with complicated urinary tract infections (cUTI); hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), healthcare-associated pneumonia (HAP); in patients with sepsis and bacteremia, some without an identified primary focus of infection.
To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients.
Multicentre, open-label, ...parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed.
MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24–2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea.
DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.
Background. Infective endocarditis (IE) in older patients is associated with a high morbidity, mortality, and functional impairment. The purpose of this study was to describe the current profile of ...IE in octogenarians and to analyze the prognostic impact of baseline comorbidities in this population. Methods. Patients ≥ 80 years and definite IE from the Spanish IE Prospective Database were included. The effect of Charlson Comorbidity Index (CCI) on in-hospital and 12-month mortality was analyzed. Results. From 726 patients, 357 (49%) had CCI ≥ 3 and 369 (51%) CCI < 3. A total of 265 patients (36.6%) died during hospital admission and 338 (45.5%) during 1-year follow-up. CCI ≥ 3 was an independent predictor of in-hospital and 1-year mortality (odds ratio 1.46, 95% confidence interval 1.07−1.99, p = 0.017; hazard ratio 1.34, 95% confidence interval 1.08−1.66, p = 0.007, respectively). Surgical management was less common in patients with high comorbidity (CCI ≥ 3 68 19.0% vs. CCI < 3 112 ((30.4%) patients, p < 0.01). From 443 patients with surgical indication, surgery was only performed in 176 (39.7%). Patients with surgical indication treated conservatively had higher mortality than those treated with surgery (in-hospital mortality: 147 (55.1%) vs. 55 (31.3%), p < 0.001), (1-year mortality: 172 (64.4%) vs. 68 38.6%, p < 0.001). Conclusion. About half of octogenarians with IE had high comorbidity with CCI ≥ 3. CCI ≥ 3 was a strong independent predictor of in-hospital and 1-year mortality. Our data suggest that the underperformance of cardiac surgery in this group of patients might have a role in their poor prognosis.
Abstract Background Infective endocarditis (IE) is a severe complication associated with high mortality. Objectives To examine the clinical characteristics of IE in hemodialysis (HD) patients and to ...determine prognostic factors related to HD. Methods From January 2008 to April 2015, 2488 consecutive patients with definite IE were included. Clinical characteristics of IE patients on HD were compared with those of IE patients who were not on HD. Results A total of 126 patients (63% male, median age: 66 years; IQR: 54–74 years) with IE (5.1%) were on HD. Fifty-two patients died during hospitalization (41%) and 17 additional patients (14%) died during the first year. The rate of patients who underwent surgery during hospitalization was lower in HD patients (38 patients, 30%) than in non-HD patients (1177 patients, 50%; p < 0.001). Age > 70 years (OR: 4.1, 95% CI: 1.7–10), heart failure (OR: 3.3, 95% CI: 1.4–7-6), central nervous system (CNS) vascular events (OR: 6.7, 95% CI: 2.1–22) and septic shock (OR: 4.1, 95% CI: 1.4–12.1) were independently associated with fatal outcome in HD patients. Of the 38 patients who underwent surgery, 15 (39.5%) died during hospitalization. Conclusions HD patients with IE present a high mortality. Advanced age and complications, such as heart failure, CNS stroke or septic shock, are associated with mortality.
The objective of this study is to analyze the factors that are associated with the adequacy of empirical antibiotic therapy and its impact in mortality in a large cohort of patients with ...extended-spectrum β-lactamase (ESBL)--producing Escherichia coli and Klebsiella spp. bacteremia.
Cases of ESBL producing Enterobacteriaceae (ESBL-E) bacteremia collected from 2003 through 2008 in 19 hospitals in Spain. Statistical analysis was performed using multivariate logistic regression.
We analyzed 387 cases ESBL-E bloodstream infections. The main sources of bacteremia were urinary tract (55.3%), biliary tract (12.7%), intra-abdominal (8.8%) and unknown origin (9.6%). Among all the 387 episodes, E. coli was isolated from blood cultures in 343 and in 45.71% the ESBL-E was multidrug resistant. Empirical antibiotic treatment was adequate in 48.8% of the cases and the in hospital mortality was 20.9%. In a multivariate analysis adequacy was a risk factor for death adjusted OR (95% CI): 0.39 (0.31-0.97); P = 0.04, but not in patients without severe sepsis or shock. The class of antibiotic used empirically was not associated with prognosis in adequately treated patients.
ESBL-E bacteremia has a relatively high mortality that is partly related with a low adequacy of empirical antibiotic treatment. In selected subgroups the relevance of the adequacy of empirical therapy is limited.
To evaluate molecular tools to detect low-level parasitemia and the five species of
that infect humans for use in control and elimination programs, and in reference laboratories.
We evaluated 145 ...blood samples from patients who tested positive by nested polymerase chain reaction (nPCR), from asymptomatic individuals and from the WHO Global Malaria Programme/United Kingdom National External Quality Assessment Service. Samples were assayed using the genus-specific RealStar
Malaria PCR Kit 1.0 (alt-Gen; altona Diagnostics) and the RealStar
Malaria Screen & Type PCR Kit (alt-S altona Diagnostics). The results from the molecular tests were compared with those from quantitative PCR (qPCR), nPCR and thick blood smear.
The levels of parasitemia ranged from 1 to 518 000 parasites/µL, depending on the species. Compared with nPCR, alt-S&T had a sensitivity of 100%, except for identifying
, for which the sensitivity was 93.94%. All samples positive by alt-Gen were also positive by nPCR. When comparing alt-Gen to qPCR, the sensitivity was 100% for
and
. For all
species, the correlation between cycle threshold values of alt-S&T and alt-Gen compared with qPCR was significant (
< 0.0001, Spearman's test), with
= 0.8621 for alt-S&T and
= 0.9371 for alt-Gen. When all
species were considered, there was a negative correlation between the level of parasitemia and real-time PCR cycle threshold values (
< 0.0001). In this study, only 2 of 28 samples from asymptomatic individuals were positive by thick blood smear; however, all 28 of these samples were positive by alt-S&T.
The alt-Gen and alt-S&T assays are suitable for detecting submicroscopic infections for distinct epidemiological purposes, such as for use in surveys and reference laboratories, and screening in blood banks, which will contribute to global efforts to eliminate malaria.
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