Addressing catheter lock therapy: Does heparin reduce the bioactivity of dalbavancin when together in solution during freezing?

INTRODUCTION: The possible use of dalbavancin as a catheter lock solution was previously demonstrated by our study group. However, it was needed to assess whether heparin could affect dalbavancin bioactivity during freezing storage. METHODS: We tested the bioactivity of a dalbavancin+heparin (DH) vs. dalbavancin (D) against Staphylococcal biofilms comparing DH median value of cfu counts and metabolic activity with that obtained for D before and during storage under freezing up to 6 months. RESULTS: Despite there was a slight decrease in the median percentage reduction of metabolic activity at month 3 in Staphylococcus epidermidis between DH and D (97.6 vs. 100, p=0.037), considering the clinical criteria, no significant reduction in any of the variables tested was observed at the end of the experiment between D and DH solutions. CONCLUSION: The addition of heparin to a dalbavancin lock solution did not affect its bioactivity against staphylococcal biofilms irrespective of its preservation time under freezing.

Isavuconazole Versus Voriconazole as the First-line Therapy for Solid Organ Transplant Recipients With Invasive Aspergillosis: Comparative Analysis of 2 Multicenter Cohort Studies.

BACKGROUND: Isavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients. METHODS: We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (n = 57) or VORI (n = 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation. RESULTS: Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027). CONCLUSIONS: Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion.

Prevalence and prognostic impact of stroke in a national cohort of infective endocarditis.

BACKGROUND: Stroke is a common complication of infective endocarditis (IE). Our aim was to describe the prevalence and prognostic impact of stroke in a national cohort of IE. METHODS: Consecutive inclusion at 46 Spanish hospitals between 2008 and 2021. RESULTS: Out of 5667 IE cases, 1125 had acute stroke (19.8%): 818 ischemic strokes (811 cardioembolic strokes (193 with hemorrhagic transformation), 4 transient ischemic attacks, 3 lacunar infarctions), 127 intracranial hemorrhages, and 27 other neurological complications (cerebral abscesses, encephalitis, and meningitis). Compared to patients without stroke, those with stroke had a similar mean age (69 years) but were more frequently female (68.2% vs 63.7%, p = 0.04) and had a higher incidence of intracardiac complications (35% vs 30%, p = 0.01), surgical indication (69.9% vs 65.9%, p = 0.001), in-hospital mortality (40.9% vs 22.0%, p < 0.001), and 1-year mortality (46.2% vs 27.9%, p < 0.001). The following variables were independently associated with stroke: mitral location (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.34-1.8, p < 0.001), vascular phenomenon (OR = 2.9, 95% CI = 2.4-3.6, p = 0.0001), acute renal failure (OR = 1.2, 95% CI = 1.0-1.4, p = 0.021), septic shock (OR = 1.3, 95% CI = 1.1-1.6, p = 0.007), sepsis (OR = 1.3, 95% CI = 1.1-1.6, p = 0.005), surgery indicated but not performed (OR = 1.4, 95% CI = 1.2-1.7, p < 0.001), community-acquired IE (OR = 1.2, 95% CI = 1-1.4, p = 0.017), and peripheral embolization (OR = 1.6, 95% CI = 1.4-1.9, p < 0.001). Stroke was an independent predictor of in-hospital (OR = 2.1, 95% CI = 1.78-2.51, p < 0.001) and 1-year mortality (hazard ratio = 1.9, 95% CI = 1.6-2.5). CONCLUSION: One-fifth of patients with IE have concomitant stroke. Stroke is associated with mortality.

Validation of the antibacterial effect of topically applied tranexamic acid using in vitro and in vivo models.

Background: Several studies have shown that tranexamic acid (TXA), an antifibrinolytic, reduces postoperative infection rates. Recent in vitro research showed that TXA alone and in combination with vancomycin and gentamicin had a synergistic effect against some staphylococcal strains. In the present study, this synergistic effect was validated in samples from patients with staphylococcal periprosthetic infection (PPI) and in an in vivo model. Methods: We tested 19 clinical strains (5 Staphylococcus aureus and 14 coagulase-negative staphylococci [CoNS]) against 10 mg/ml TXA alone and in combination with serial dilutions of vancomycin and gentamicin. The standardized microtiter plate method was used. The minimal inhibitory concentration (MIC) were calculated using standard visualization of well turbidity. We also used an S. aureus (ATCC29213) murine subcranial PPI model to compare the synergistic effect of TXA and gentamicin with that of TXA or gentamicin alone after 4 days of monitoring. The mice were euthanized, and disks were removed for analysis of cfu/ml counts and cell viability rate. Biofilm structure of both in vitro and in vivo samples was also analyzed using scanning electron microscopy (SEM). Results: When TXA was combined with vancomycin or gentamicin, the MIC decreased in 30% of the strains studied. According to species, the MIC50 for vancomycin and gentamicin alone and in combination with TXA against S. aureus strains was the same. This was also the case for CoNS with vancomycin and its corresponding combination, whereas with gentamicin and TXA, a reduction in MIC50 was observed (2 dilutions). In addition, in the in vivo model, the mean (SD) log cfu/ml and cell viability rate obtained from the implant was lower in the group of mice treated with TXA and gentamicin than in those treated only with TXA or gentamicin. SEM images also corroborated our findings in strains in which the MIC was reduced, as well as the in the mice implants, with the area occupied by biofilm being greater in samples treated only with gentamicin or TXA than in those treated with TXA+gentamicin. Conclusion: We confirm that combining TXA with vancomycin or gentamicin exerts a synergistic effect. However, this only occurs in selected strains.

Azole resistance screening in Aspergillus fumigatus sensu stricto using the azole-containing agar method (EUCAST E.Def 10.2): conidial suspension filtration and inoculum adjustment before inoculum preparation may not be needed.

Azole resistance screening in Aspergillus fumigatus sensu stricto can be routinely carried out by using azole-containing agar plates (E.Def 10.2 procedure); however, conidial suspension filtering and inoculum adjustment before inoculum preparation are time-consuming. We evaluated whether skipping the filtration and inoculum adjustment steps negatively influenced the performance of the E.Def 10.2 procedure. A. fumigatus sensu stricto isolates (n = 98), previously classified as azole susceptible or azole resistant (E.Def 9.4 method), were studied. Azole-resistant isolates had either the wild-type cyp51A gene sequence (n = 1) or the following cyp51A gene substitutions: TR34-L98H (n = 41), G54R (n = 5), TR46-Y121F-T289A (n = 1), or G448S (n = 1). In-house azole-containing agar plates were prepared according to the EUCAST E.Def 10.2 procedure. Conidial suspensions obtained by adding distilled water (Tween 20 0.1%) were either filtered and the inocula adjusted to 0.5 McFarland or left unfiltered and unadjusted. Agreements between the agar screening methods using inocula prepared by each procedure were high for itraconazole (99%), voriconazole (100%), and posaconazole (94.9%). Sensitivity and specificity (considering the susceptibility category as per the microdilution E.Def 9.4 method as the gold standard) of E.Def 10.2 were 100% to rule in or rule out resistance when unfiltered and unadjusted suspensions were used; the resistance phenotype of isolates harboring the TR34-L98H, G54R, or TR46-Y121F-T289A substitutions was correctly detected. Unfiltered and unadjusted conidial suspensions do not negatively influence the performance of the E.Def 10.2 method when screening for azole resistance in A. fumigatus sensu stricto. IMPORTANCE: Azole resistance screening in Aspergillus fumigatus sensu stricto can be routinely carried out by using azole-containing plates (E.Def 10.2 procedure); however, conidial suspension filtering and inoculum adjustment before inoculation of plates are time-consuming. We, here, showed that unfiltered and unadjusted conidial suspensions do not negatively influence the performance of the E.Def 10.2 method when screening for azole resistance in A. fumigatus sensu stricto.

Invasive aspergillosis: A comprehensive review.

Invasive aspergillosis (IA) is a severe fungal infection caused by Aspergillus species, particularly Aspergillus fumigatus, although new species, sometimes resistant to antifungals are becoming more common. IA predominantly affects immunocompromised patients, such as those with haematological malignancies, solid organ transplant recipients, and critically ill patients. However, new at-risk populations have emerged in recent years, such as IA associated with severe viral infections. Advanced diagnostic methods are crucial, especially considering the rising concern of antifungal resistance. Early detection is critical for successful treatment, typically involving antifungal medications like voriconazole or amphotericin B, but new antifungals are arriving to complete the therapeutic strategies. Despite advancements, mortality rates remain high, underscoring the importance of timely interventions and ongoing research. Healthcare providers should maintain a high index of suspicion, especially in immunocompromised patients and other new risk factors that are arising, to promptly diagnose and manage invasive aspergillosis.

A solution to achieve sequencing from SARS-CoV-2 specimens with low viral loads: concatenation of reads from independent reactions.

BACKGROUND: During the pandemic, whole genome sequencing was critical to characterize SARS-CoV-2 for surveillance, clinical and therapeutical purposes. However, low viral loads in specimens often led to suboptimal sequencing, making lineage assignment and phylogenetic analysis difficult. We propose an alternative approach to sequencing these specimens that involves sequencing in triplicate and concatenation of the reads obtained using bioinformatics. This proposal is based on the hypothesis that the uncovered regions in each replicate differ and that concatenation would compensate for these gaps and recover a larger percentage of the sequenced genome. RESULTS: Whole genome sequencing was performed in triplicate on 30 samples with Ct > 32 and the benefit of replicate read concatenation was assessed. After concatenation: i) 28% of samples reached the standard quality coverage threshold (> 90% genome covered > 30x); ii) 39% of samples did not reach the coverage quality thresholds but coverage improved by more than 40%; and iii) SARS-CoV-2 lineage assignment was possible in 68.7% of samples where it had been impaired. CONCLUSIONS: Concatenation of reads from replicate sequencing reactions provides a simple way to access hidden information in the large proportion of SARS-CoV-2-positive specimens eliminated from analysis in standard sequencing schemes. This approach will enhance our potential to rule out involvement in outbreaks, to characterize reinfections and to identify lineages of concern for surveillance or therapeutical purposes.

Surface Engineering of Escherichia coli to Display Its Phytase (AppA) and Functional Analysis of Enzyme Activities.

Escherichia coli phytase (AppA) is widely used as an exogenous enzyme in monogastric animal feed mainly because of its ability to degrade phytic acid or its salt (phytate), a natural source of phosphorus. Currently, successful recombinant production of soluble AppA has been achieved by gene overexpression using both bacterial and yeast systems. However, some methods for the biomembrane immobilization of phytases (including AppA), such as surface display on yeast cells and bacterial spores, have been investigated to avoid expensive enzyme purification processes. This study explored a homologous protein production approach for displaying AppA on the cell surface of E. coli by engineering its outer membrane (OM) for extracellular expression. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of total bacterial lysates and immunofluorescence microscopy of non-permeabilized cells revealed protein expression, whereas activity assays using whole cells or OM fractions indicated functional enzyme display, as evidenced by consistent hydrolytic rates on typical substrates (i.e., p-nitrophenyl phosphate and phytic acid). Furthermore, the in vitro results obtained using a simple method to simulate the gastrointestinal tract of poultry suggest that the whole-cell biocatalyst has potential as a feed additive. Overall, our findings support the notion that biomembrane-immobilized enzymes are reliable for the hydrolysis of poorly digestible substrates relevant to animal nutrition.

In Vivo Detection of Staphylococcus aureus Infections Using Radiolabeled Antibodies Specific for Bacterial Toxins.

Purpose: The Gram-positive Staphylococcus aureus bacterium is one of the leading causes of infection in humans. The lack of specific noninvasive techniques for diagnosis of staphylococcal infection together with the severity of its associated complications support the need for new specific and selective diagnostic tools. This work presents the successful synthesis of an immunotracer that targets the α-toxin released by S. aureus. Methods: [89Zr]Zr-DFO-ToxAb was synthesized based on radiolabeling an anti-α-toxin antibody with zirconium-89. The physicochemical characterization of the immunotracer was performed by high-performance liquid chromatography (HPLC), radio-thin layer chromatography (radio-TLC), and electrophoretic analysis. Its diagnostic ability was evaluated in vivo by positron emission tomography/computed tomography (PET/CT) imaging in an animal model of local infection-inflammation (active S. aureus vs. heat-killed S. aureus) and infective osteoarthritis. Results: Chemical characterization of the tracer established the high radiochemical yield and purity of the tracer while maintaining antibody integrity. In vivo PET/CT image confirmed the ability of the tracer to detect active foci of S. aureus. Those results were supported by ex vivo biodistribution studies, autoradiography, and histology, which confirmed the ability of [89Zr]Zr-DFO-ToxAb to detect staphylococcal infectious foci, avoiding false-positives derived from inflammatory processes. Conclusions: We have developed an immuno-PET tracer capable of detecting S. aureus infections based on a radiolabeled antibody specific for the staphylococcal alpha toxins. The in vivo assessment of [89Zr]Zr-DFO-ToxAb confirmed its ability to selectively detect staphylococcal infectious foci, allowing us to discern between infectious and inflammatory processes.

Impact of the Mediterranean Diet on the Gut Microbiome of a Well-Defined Cohort of Healthy Individuals.

A comprehensive understanding of gut microbiota in a clearly defined group of healthy individuals is essential when making meaningful comparisons with various diseases. The Mediterranean diet (MD), renowned for its potential health benefits, and the influence of adherence thereto on gut microbiota have become a focus of research. Our aim was to elucidate the impact of adherence to the MD on gut microbiota composition in a well-defined cohort. In this prospective study, healthy volunteers completed a questionnaire to provide demographic data, medical history, and dietary intake. Adherence was evaluated using the Med-DQI. The V4 region of the 16S rRNA gene was sequenced. Analysis of sequencing data and statistical analysis were performed using MOTHUR software and R. The study included 60 patients (51.7% females). Adherence correlated with alpha diversity, and higher values were recorded in good adherers. Good adherers had a higher abundance of Paraprevotella and Bacteroides (p < 0.001). Alpha diversity correlated inversely with fat intake and positively with non-starch polysaccharides (NSPs). Evenness correlated inversely with red meat intake and positively with NSPs. Predicted functional analysis highlighted metabolic pathway differences based on adherence to the MD. In conclusion, our study adds useful information on the relationship between the MD and the gut microbiome.

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

Microevolution, reinfection and highly complex genomic diversity in patients with sequential isolates of Mycobacterium abscessus.

Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections. Fifty-three sequential isolates from 14 patients were sequenced to determine SNV-based distances, assign resistance mutations and characterize plasmids. Genomic analysis revealed 12 persistent cases (0-13 differential SNVs), one reinfection (15,956 SNVs) and one very complex case (23 sequential isolates over 192 months), in which a first period of persistence (58 months) involving the same genotype 1 was followed by identification of a genotype 2 (76 SNVs) in 6 additional alternating isolates; additionally, ten transient genotypes (88-243 SNVs) were found. A macrolide resistance mutation was identified from the second isolate. Despite high diversity, the genotypes shared a common phylogenetic ancestor and some coexisted in the same specimens. Genomic analysis is required to access the true intra-patient complexity behind persistent infections involving M. abscessus.

Epidemiology and Risk Factors of Mycotic Aneurysm in Patients With Infective Endocarditis and the Impact of its Rupture in Outcomes. Analysis of a National Prospective Cohort.

Background: Several aspects of the occurrence and management of mycotic aneurysm (MA) in patients with infective endocarditis (IE) have not been studied. Objectives: To determine the incidence and factors associated with MA presence and rupture and to assess the evolution of those initially unruptured MA. Methods: Prospective multicenter cohort including all patients with definite IE between January 2008 and December 2020. Results: Of 4548 IE cases, 85 (1.9%) developed MA. Forty-six (54.1%) had intracranial MA and 39 (45.9%) extracranial MA. Rupture of MA occurred in 39 patients (45.9%). Patients with ruptured MA had higher 1-year mortality (hazard ratio, 2.33; 95% confidence interval, 1.49-3.67). Of the 55 patients with initially unruptured MA, 9 (16.4%) presented rupture after a median of 3 days (interquartile range, 1-7) after diagnosis, being more frequent in intracranial MA (32% vs 3.3%, P = .004). Of patients with initially unruptured MA, there was a trend toward better outcomes among those who received early specific intervention, including lower follow-up rupture (7.1% vs 25.0%, P = .170), higher rate of aneurysm resolution in control imaging (66.7% vs 31.3%, P = .087), lower MA-related mortality (7.1% vs 16.7%, P = .232), and lower MA-related sequalae (0% vs 27.8%, P = .045). Conclusions: MA occurred in 2% of the patients with IE. Half of the Mas occurred in an intracranial location. Their rupture is frequent and associated with poor prognosis. A significant proportion of initially unruptured aneurysms result from rupture during the first several days, being more common in intracranial aneurysms. Early specific treatment could potentially lead to better outcomes.

Fluconazole-resistant Candida parapsilosis genotypes from hospitals located in five Spanish cities and one in Italy: Description of azole-resistance profiles associated with the Y132F ERG11p substitution.

BACKGROUND: Fluconazole-resistant Candida parapsilosis is a matter of concern. OBJECTIVES: To describe fluconazole-resistant C. parapsilosis genotypes circulating across hospitals in Spain and Rome and to study their azole-resistance profile associated with ERG11p substitutions. PATIENTS/METHODS: We selected fluconazole-resistant C. parapsilosis isolates (n = 528 from 2019 to 2023; MIC ≥8 mg/L according to EUCAST) from patients admitted to 13 hospitals located in five Spanish cities and Rome. Additionally, we tested voriconazole, posaconazole, isavuconazole, amphotericin B, micafungin, anidulafungin and ibrexafungerp susceptibility. RESULTS: Of the 53 genotypes found, 49 harboured the Y132F substitution, five of which were dominating city-specific genotypes involving almost half the isolates. Another genotype involved isolates harbouring the G458S substitution. Finally, we found two genotypes with the wild-type ERG11 gene sequence and one with the R398I substitution. All isolates were fully susceptible/wild-type to amphotericin B, anidulafungin, micafungin and ibrexafungerp. The azole-resistance patterns found were: voriconazole-resistant (74.1%) or voriconazole-intermediate (25.2%), posaconazole-resistant (10%) and isavuconazole non-wild-type (47.5%). Fluconazole-resistant and voriconazole non-wild-type isolates were likely to harbour substitution Y132F if posaconazole was wild type; however, if posaconazole was non-wild type, substitution G458S was indicated if isavuconazole MIC was >0.125 mg/L or substitution Y132F if isavuconazole MIC was ≤0.125 mg/L. CONCLUSIONS: We detected a recent clonal spread of fluconazole-resistant C. parapsilosis across some cities in Spain, mostly driven by dominating city-specific genotypes, which involved a large number of isolates harbouring the Y132F ERG11p substitution. Isolates harbouring substitution Y132F can be suspected because they are non-susceptible to voriconazole and rarely posaconazole-resistant.

Bloodstream infections: trends and evolution of incidence and etiology in a 12-year period (2010-2021).

INTRODUCTION: The epidemiological evolution of bloodstream infections (BSIs) in the last decade is not clearly defined. Our aim was to analyze the changes in the workload in our institution and to describe the evolution of the incidence and etiology of BSIs in a 12-year period, including the COVID-19 pandemic. METHODS: All blood cultures received in the laboratory of a tertiary general hospital between 2010 and 2021 were analyzed. Bloodstream infection episodes refer to each episode of bacteremia or fungemia in each patient. Incidence rates per 1000 admissions and per 100,000 population were calculated. RESULTS: No significant changes in the incidence of BSI episodes/1000 admissions were observed (mean, 31.1), while estimated population-based incidences showed declining trends (mean, 182.8/100,000 inhabitants). There was a slight increase in BSI episodes per 1000 admissions caused by Gram-negatives (mean, 16.6/1000 admissions) and E. coli was the most frequent pathogen (mean, 8.5/1000 admissions). There was no significant rise in episodes caused by ESBL- and carbapenemase-producing E. coli or K. pneumoniae, with a decline in those caused by methicillin-resistant S. aureus. A spike in BSI episodes, fungal BSIs and catheter-related infections was detected in 2020, during the COVID-19 outbreak. CONCLUSIONS: No clear increase in the incidence of BSI episodes was detected in our center over this period. Gram-negatives are the most frequent etiology, with no clear rise in antimicrobial resistance phenotypes. The COVID-19 pandemic accounted for a small increase in BSI episodes in 2020, probably related to the increase of catheter-related infections.

Aspergillus granulosus femoral osteomyelitis in a cardiac transplant patient: first reported case and literature review.

Aspergillus osteomyelitis is a rare complication of extrapulmonary invasive aspergillosis, which usually presents as spondylodiscitis. The clinical picture is usually paucisymptomatic and of long evolution, which leads to diagnostic difficulties, especially in immunosuppressed patients presenting a delayed systemic host response. We report a case of femoral osteomyelitis caused by Aspergillus granulosus in a heart transplant recipient successfully treated with a combined surgical and antifungal approach. A 65-year-old heart transplant male presented with left knee pain lasting 3 months. X-ray and magnetic resonance imaging identified a lesion with aggressive characteristics at the distal third of the left femur, due to which the patient underwent excisional surgery. Aspergillus granulosus was cultured from the removed material and antifungal treatment with oral isavuconazole was started. Chest imaging excluded pulmonary aspergillosis, while the positron emission tomography/computed tomography (PET/CT) identified a remnant of a prosthetic vascular graft sewn to the proximal third of the right axillary artery, through which a catheter-based micro-axial left ventricular assist device was implanted previously as bridge to transplant therapy. The patient presented a rapid clinical improvement with complete functional recovery following the surgical treatment and the antifungal therapy and finally underwent surgical removal of the residual vascular graft. This is the first reported episode of long bone osteomyelitis due to A. granulosus that occurred in a heart transplant recipient without pulmonary infection and was successfully treated with isavuconazole. The PET/CT was useful in supporting the diagnostic process and follow-up. Cryptic fungal species can cause invasive infections, particularly in immunocompromised patients. Molecular methods are crucial in fungal identification.

Corrigendum: Tranexamic acid in combination with vancomycin or gentamicin has a synergistic effect against staphylococci.

[This corrects the article DOI: 10.3389/fmicb.2022.935646.].

Impact of an interventional bundle on complications associated with peripheral venous catheters in elderly patients.

PURPOSE: Elderly patients admitted to geriatrics departments often require peripheral venous catheters (PVC), which should be inserted and maintained following a series of preventive recommendations. Our objective was to evaluate the impact of a training bundle comprising measures aimed at reducing complications associated with the use of PVC in elderly patients admitted to a tertiary teaching hospital. METHODS: We performed a prospective study of patients who received a PVC within 24 h of admission to a geriatrics department. After a 10-month pre-interventional period, we implemented an educational and interventional bundle over a 9-month period. Follow-up was until catheter withdrawal. We analyzed and compared clinical and microbiological data between both study periods. RESULTS: A total of 344 patients (475 PVC) were included (pre-intervention period, 204 patients (285 PVC); post-intervention period, 140 patients (190 PVC)). No statistically significant differences in demographic characteristics were observed between the study periods. The colonization and phlebitis rates per 1000 admissions in both periods were, respectively, 36.7 vs. 24.3 (p = 0.198) and 81.5 vs. 65.1 (p = 0.457). The main reason for catheter withdrawal was obstruction/malfunctioning (33.3%). Obstruction rate was higher for those inserted in the hand than for those inserted at other sites (55.7% vs. 44.3%, p = 0.045). CONCLUSIONS: We found no statistically significant differences regarding phlebitis and catheter tip colonization rates. It is necessary to carry out randomized studies assessing the most cost-effective measure to reduce complications associated with PVC.

Neutralizing antibody levels detected early after mRNA-based vaccination do not predict by themselves subsequent breakthrough infections of SARS-CoV-2.

The development of mRNA vaccines represented a significant achievement in response to the global health crisis during the SARS-CoV-2 pandemic. Evaluating vaccine efficacy entails identifying different anti-SARS-CoV-2 antibodies, such as total antibodies against the Receptor Binding Domain (RBD) of the S-protein, or neutralizing antibodies (NAbs). This study utilized an innovative PETIA-based kit to measure NAb, and the investigation aimed to assess whether levels of anti-RBD IgG and NAb uniformly measured 30 days after vaccination could predict individuals at a higher risk of subsequent infection in the months following vaccination. Among a cohort of healthy vaccinated healthcare workers larger than 6,000, 12 mRNA-1273- and 115 BNT162b2-vaccinated individuals contracted infections after the first two doses. The main finding is that neither anti-RBD IgG nor NAb levels measured at day 30 post-vaccination can be used as predictors of breakthrough infections (BI). Therefore, the levels of anti-SARS-CoV-2 antibodies detected shortly after vaccination are not the pivotal factors involved in antiviral protection, and other characteristics must be considered in understanding protection against infection. Furthermore, the levels of anti-RBD and NAbs followed a very similar pattern, with a correlation coefficient of r = 0.96. This robust correlation would justify ceasing the quantification of NAbs, as the information provided by both determinations is highly similar. This optimization would help allocate resources more efficiently and speed up the determination of individuals' humoral immunity status.