Efficacy and safety of a preventive strategy against tuberculosis in liver transplantation recipients including the treatment of latent infection with moxifloxacin.

BACKGROUND: Preventive management of tuberculosis in liver transplantation (LT) is challenging due to difficulties in detecting and treating latent tuberculosis infection (LTBI). The aim of this study was to analyze the safety and efficacy of a screening strategy for LTBI with the inclusion of moxifloxacin as treatment. METHODS: We performed a retrospective single-center study of all LTs performed between 2016 and 2019 with a minimum 4-year follow-up and a standardized protocol for the evaluation of LTBI. RESULTS: Pretransplant LTBI screening was performed in 191/218 (87.6%) patients, and LTBI was diagnosed in 27.2% of them. Treatment for LTBI was administered to 71.2% of the patients and included moxifloxacin in 75.6% of the cases. After a median follow-up of 1628 days, no cases of active tuberculosis occurred among moxifloxacin-treated patients. The incidence of Clostridioides difficile (0.46 vs. 0.38 episodes/1000 transplant-days; p =  .8) and multidrug-resistant gram-negative bacilli infection (0 vs. 0.7 episodes per 1000 transplant-days; p =  .08) were not significantly higher in comparison to patients who did not receive moxifloxacin. CONCLUSION: A preventive strategy based on systematic LTBI screening and moxifloxacin treatment before LT in positive cases appears safe and effective in preventing the development of tuberculosis in LT recipients. However, our findings are limited by a small sample size; thus, larger studies are required to validate our observations.

Management of cytomegalovirus in adult solid organ transplant patients: GESITRA-IC-SEIMC, CIBERINFEC, and SET recommendations update.

Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel.

Initial empirical antibiotic therapy in kidney transplant recipients with pyelonephritis: A global survey of current practice and opinions across 19 countries on six continents.

BACKGROUND: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management. METHODS: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate. RESULTS: A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd-generation cephalosporin (37%) or piperacillin-tazobactam (21%) monotherapy. Several patient-level factors dictated the selection of broader-spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended-spectrum ß-lactamase-producing organisms, 90% for carbapenemase-producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries. CONCLUSION: High-quality studies are needed to guide the empirical management of post-transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post-transplant pyelonephritis.

Spatial Relationship between a Regional Outbreak and a Higher-than-Expected Incidence of Leishmaniasis in Urban Southern Madrid, Spain.

The largest outbreak of human leishmaniasis in Europe took place in Fuenlabrada, Spain, between 2009 and 2017. The University Hospital "12 de Octubre" in Madrid serves the population residing in three districts of Madrid located just north of the outbreak area (Villaverde, Usera, and Carabanchel). Villaverde and Usera are connected by rail to the outbreak area, unlike Carabanchel. We performed a retrospective study including all cases of leishmaniasis diagnosed between 2011 and 2020. Fifty-one cases were documented. In the districts connected by rail to the outbreak area, a higher-than-expected incidence was observed (13.45-15.55 versus 5.2 per 100,000 inhabitants). Apart from the linear distance from the place of residence to the railway tracks, no differences in terms of demographics or risk factors were detected between the populations of the districts. We hypothesize that the direct connection with the outbreak area by rail could explain the higher incidence observed in Villaverde and Usera.

Novel intervention based on an individualized bundle of care to decrease infection in kidney transplant recipients.

BACKGROUND: Infection remains a relevant complication after kidney transplantation (KT). A well-established strategy in modern medicine is the application of bundles of evidence-based practice in clinical settings. The objective of this study is to explore the application of a personalized bundle of measures aimed to reduce the incidence of infection in the first 12 months after KT. METHODS: A single-center prospective cohort of 148 patients undergoing KT between February 2018 and September 2019 that received an individualized infection prevention strategy was compared to a preintervention cohort (n = 159). The bundle comprised a review of the patient's immunization history, infection risk by country of origin, screening for latent tuberculosis infection (LTBI), antimicrobial prophylaxis, and immunological assessment. Individualized recommendations were accordingly provided at a scheduled visit at day +30 after transplantation. RESULTS: The intervention cohort showed a higher compliance rate with the recommended vaccine schedule, screening for geographically restricted infections and LTBI, and intravenous immunoglobulin and vitamin D supplementation (p values <.001). The 1-year incidence rate of infection was lower in the intervention cohort (42.6% vs. 57.9%; p value = .037), as was the rate of infection-related hospitalization (17.6% vs. 32.1%; p value = .003) and the incidence of severe bacterial infection. There were no differences in graft rejection or mortality rates between groups. CONCLUSIONS: A multifaceted intervention, including a bundle of evidence-based practices, enhanced compliance with recommended preventive measures and was correlated with a reduction in the 12-month incidence of infection after KT.

A new type of Class C ß-lactamases defined by PIB-1. A metal-dependent carbapenem-hydrolyzing ß-lactamase, from Pseudomonas aeruginosa: Structural and functional analysis.

Antibiotic resistance is one of most important health concerns nowadays, and ß-lactamases are the most important resistance determinants. These enzymes, based on their structural and functional characteristics, are grouped in four categories (A, B, C and D). We have solved the structure of PIB-1, a Pseudomonas aeruginosa chromosomally-encoded ß-lactamase, in its apo form and in complex with meropenem and zinc. These crystal structures show that it belongs to the Class C ß-lactamase group, although it shows notable differences, especially in the Ω- and P2-loops, which are important for the enzymatic activity. Functional analysis showed that PIB-1 is able to degrade carbapenems but not cephalosporins, the typical substrate of Class C ß-lactamases, and that its catalytic activity increases in the presence of metal ions, especially zinc. They do not bind to the active-site but they induce the formation of trimers that show an increased capacity for the degradation of the antibiotics, suggesting that this oligomer is more active than the other oligomeric species. While PIB-1 is structurally a Class C ß-lactamase, the low sequence conservation, substrate profile and its metal-dependence, prompts us to position this enzyme as the founder of a new group inside the Class C ß-lactamases. Consequently, its diversity might be wider than expected.

Clinical Management and Outcomes of Nontuberculous Mycobacterial Infections in Solid Organ Transplant Recipients: A Multinational Case-control Study.

BACKGROUND: The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients. METHODS: Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases. RESULTS: In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40-62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4-42] versus 11 [3-21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died. CONCLUSIONS: NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.

Infective endocarditis in pediatric patients: a decade of insights from a leading Spanish heart surgery reference center.

Infective endocarditis (IE) is a rare disease in children and is associated with significant morbidity and mortality. In recent years, significant changes have occurred in pediatric care that could have influenced the microbiology and presentation of IE. The aim of this work was to study epidemiological, microbiological, and clinical features of IE treated at a Pediatric Cardiac Surgery Reference Center located in Madrid (Spain) in a 10-years' period. A descriptive observational retrospective study was performed, including pediatric patients < 16 years old with definite or possible IE admitted to a reference center between January 2012 and December 2021. Thirty-two IE episodes were identified. Twenty-eight (87.5%) had congenital heart disease (CHD), 8 (25.0%) were preterm infants, 1 (3.1%) was immunocompromised and 6 (18.8%) had other chronic conditions; in 11 (34.4%) episodes more than one underlying condition was associated. In 20 (62.5%) episodes there was an indwelling central venous catheter (CVC); children with other comorbidities (preterm, immunocompromised, other chronic conditions) were more likely to have a CVC at diagnosis compared with patients with isolated CHD (p < 0.001). Thirty-six microbiological isolates were obtained in the 32 episodes; 4 (12.5%) episodes had 2 isolated microorganisms. Microbiological isolates were 20 (55.6%) Gram-positive bacteria (GPB), 10 (27.8%) non-HACEK Gram-negative bacteria (GNB), 1 (2.8%) HACEK-group bacterium, 4 (11.1%) fungi and 1 (2.8%) Coxiella burnetii. In 10 (31.3%) episodes, patients were colonized by multidrug-resistant bacteria (MDRB) and the etiology of IE in 3 (30.0%) of those episodes was the colonizing MDRB. MDRB colonization was associated with MDRB IE (p = 0.007). The most common complication was septic embolism: 11 (34.4%) episodes (9 pulmonary and 2 cerebral). In-hospital mortality was 6.3% (n = 2), all of them due to underlying conditions and not to IE or its complications. Clinical features and complications of IE episodes caused by non-HACEK GNB and those caused by GPB were compared, finding no statistically significant differences.    Conclusion: Risk factors for developing IE, the proportion of embolic complications, and mortality rate were consistent with previously published findings. Proportion of IE cases attributed to non-HACEK GNB was higher than previously reported, suggesting an evolving epidemiology of IE. One-third of children colonized with MDRB subsequently developed IE caused by the same MDRB strains, so empirical coverage of MDRB organisms must be considered when IE is suspected in MDRB colonized patients. No significant differences in clinical features and complications were observed when comparing IE episodes caused by non-HACEK GNB and those caused by GPB, however larger cohort studies are needed. What is Known: • Infective endocarditis (IE) is a rare disease in children, associated with significant morbidity and mortality. • The main risk factor for developing IE in children is an underlying congenital heart disease. What is New: • With current changing epidemiology in pediatric IE, a higher proportion of IE caused by non-HACEK Gram-negative bacteria should be expected. • A significant percentage of children colonized by multidrug-resistant bacteria can develop an IE due to those bacteria.

Design of Wearable Textile Electrodes for the Monitorization of Patients with Heart Failure.

Heart failure is a severe medical condition with an important worldwide incidence that occurs when the heart is unable to efficiently pump the patient's blood throughout the body. The monitoring of edema in the lower limbs is one of the most efficient ways to control the evolution of the condition. Impedance spectroscopy has been proposed as an efficient technique to monitor body volume in patients with heart failure. It is necessary to research new wearable devices for remote patient monitoring, which can be easily worn by patients in a continuous way. In this work, we design and implement new wearable textile electrodes for the monitoring of edema evolution in patients with heart failure. Impedance spectroscopy measurements were carried out in 5 healthy controls and 2 patients with heart failure using our wearable electrodes for 3 days. The results show the appropriateness of impedance spectroscopy and our wearable electrodes to monitor body volume evolution. Impedance spectroscopy is shown to be an efficient marker of the presence of edema in heart failure patients. Initial patient positive feedback was obtained for the use of the wearable device.

Dalbavancin as sequential therapy in infective endocarditis: Real-life experience in elder and comorbid patients.

OBJECTIVES: This study aimed to evaluate the effectiveness of dalbavancin as sequential therapy in patients with infective endocarditis (IE) due to gram positive bacteria (GPB) in a real-life heterogenous cohort with comorbid patients. METHODS: A single center retrospective cohort study including all patients with definite IE treated with dalbavancin between January 2017 and February 2022 was developed. A 6-month follow-up was performed. The main outcomes were clinical cure rate, clinical and microbiological relapse, 6-month mortality, and adverse effects (AEs) rate. RESULTS: The study included 61 IE episodes. The median age was 78.5 years (interquartile range [IQR] 63.2-85.2), 78.7% were male, with a median Charlson comorbidity index of 7 (IQR 4-9) points. Overall, 49.2% suffered native valve IE. The most common microorganism was Staphylococcus aureus (26.3%) followed by Enterococcus faecalis (21.3%). The median duration of initial antimicrobial therapy and dalbavancin therapy were 27 (IQR 20-34) and 14 days (IQR 14-28) respectively. The total reduction of hospitalization was 1090 days. The most frequent dosage was 1500mg of dalbavancin every 14 days (96.7%). An AE was detected in 8.2% of patients, only one (1.6%) was attributed to dalbavancin (infusion reaction). Clinical cure was achieved in 86.9% of patients. One patient (1.6%) with Enterococcus faecalis IE suffered relapse. The 6-month mortality was 11.5%, with only one IE-related death (1.6%). CONCLUSION: This study shows a high efficacy of dalbavancin in a heterogeneous real-world cohort of IE patients, with an excellent safety profile. Dalbavancin allowed a substantial reduction of in-hospital length of stay.

Severe Presentation of Mpox With Skin, Lung and Pleural Involvement in a Non-HIV-Infected Kidney Transplant Recipient.

Monkeypox (mpox) is an orthopoxviral zoonotic disease with a similar but less severe clinical presentation as smallpox. However, immunocompromised patients such as solid organ transplant recipients are at higher risk of developing severe forms of the disease. Herein, we describe the case of a 43-year-old female kidney transplant recipient that manifested severe skin ulcers alongside nodular lung opacities and pleural effusion attributed directly to the monkeypox virus. Notwithstanding the initiation of early treatment with tecovirimat, a satisfactory response was not achieved until a reduction in immunosuppression to everolimus monotherapy, coupled with the transition to cidofovir for antiviral treatment. In conclusion, mpox has the potential to produce a severe form of systemic infection in individuals who have undergone solid organ transplantation, demanding a meticulous approach involving sequential antiviral treatment and modifications to immunosuppressive regimens in order to achieve complete healing.

[Prognostic value of electrical bioimpedance measured with a portable and wireless device in acute heart failure]. / Valor pronóstico de la bioimpedancia eléctrica medida con el dispositivo IVOL en la insuficiencia cardiaca aguda.

INTRODUCTION AND OBJECTIVES: The current evaluation of acute heart failure (HF) does not allow an adequate prediction of its evolution. The electrical bioimpedance (BI) allows knowing the state of blood volume, until now only with fixed equipment. We have developed and validated a portable and wireless device to measure BI at the ankle (IVOL). The objective of the study is to know the long-term prognostic value of the point measurement of BI with IVOL in patients with acute HF. METHODS: A prospective cohort study of unselected patients admitted for acute HF in a tertiary hospital. The association between BI and different clinical, analytical and echocardiographic variables on admission and clinical evolution were analyzed. RESULTS: 76 patients were included (mean age 66.1 years, 71.1% men, 68.4% hypertensive, 34.2% diabetic, mean NT-ProBNP: 7,103 pg / ml). Of these, 52.6% with non-preserved left ventricular ejection fraction (LVEF) (<50%) and 56.6% with right ventricular (RV) dysfunction. 26.3% died during a mean follow-up of 35.8 months. Survival in patients with BI≤21,8Ω was lower, globally and in the subgroups of patients without preserved LVEF and with RV dysfunction, P<.008). In the multivariate analysis, a BI≥21.8Ω was an independent survival factor (HR: 0.242; 95% CI: 0.86-0.681; P=.007). CONCLUSIONS: BI values measured with IVOL may be an independent predictor of long-term mortality in patients hospitalized for acute HF. This prognostic value is maintained in patients without preserved LVEF function and with RV dysfunction.

Fungal microbiota in newborn infants with and without respiratory distress syndrome.

BACKGROUND: Pneumocytis jirovecii infection in preterm newborns has recently been associated with neonatal respiratory distress syndrome and bronchopulmonary dysplasia. Changes in the bacterial microbiota of the airways have also been described in infants with bronchopulmonary dysplasia. However, until now there has been no information on the airway mycobiota in newborns. The purpose of this study was to describe the airway mycobiota in term and preterm newborns and its possible association with respiratory distress syndrome. METHODS: Twenty-six matched preterm newborns with and without respiratory distress syndrome were studied, as well as 13 term babies. The identification of the fungal microbiota was carried out using molecular procedures in aspirated nasal samples at birth. RESULTS: The ascomycota phylum was identified in 89.7% of newborns, while the basidiomycota phylum was found in 33.3%. Cladosporium was the predominant genus in both term and preterm infants 38.4% vs. 73% without statistical differences. Candida sake and Pneumocystis jirovecii were only found in preterm infants, suggesting a potential relationship with the risk of prematurity. CONCLUSIONS: This is the first report to describe the fungal microbiota of the airways in term and preterm infants with and without respiratory distress syndrome. Although no differences have been observed, the number of cases analyzed could be small to obtain conclusive results, and more studies are needed to understand the role of the fungal microbiota of the airways in neonatal respiratory pathology.

Acute heart failure - an EFIM guideline critical appraisal and adaptation for internists.

BACKGROUND: Over the past two decades, several studies have been conducted that have tried to answer questions on management of patients with acute heart failure (AHF) in terms of diagnosis and treatment. Updated international clinical practice guidelines (CPGs) have endorsed the findings of these studies. The aim of this document was to adapt recommendations of existing guidelines to help internists make decisions about specific and complex scenarios related to AHF. METHODS: The adaptation procedure was to identify firstly unresolved clinical problems in patients with AHF in accordance with the PICO (Population, Intervention, Comparison and Outcomes) process, then conduct a critical assessment of existing CPGs and choose recommendations that are most applicable to these specific scenarios. RESULTS: Seven PICOs were identified and CPGs were assessed. There is no single test that can help clinicians in discriminating patients with acute dyspnoea, congestion or hypoxaemia. Performing of echocardiography and natriuretic peptide evaluation is recommended, and chest X-ray and lung ultrasound may be considered. Treatment strategies to manage arterial hypotension and low cardiac output include short-term continuous intravenous inotropic support, vasopressors, renal replacement therapy, and temporary mechanical circulatory support. The most updated recommendations on how to treat specific patients with AHF and certain comorbidities and for reducing post-discharge rehospitalization and mortality are provided. Overall, 51 recommendations were endorsed and the rationale for the selection is provided in the main text. CONCLUSION: Through the use of appropriate tailoring process methodology, this document provides a simple and updated guide for internists dealing with AHF patients.

Evolution of the impact of the COVID-19 pandemic on heart transplant recipients: Decreasing risk, improving perspective.

BACKGROUND AND METHODS: Heart transplant recipients (HTr) have a higher probability of suffer from severe coronavirus disease-2019 (COVID-19) in comparison to general population, but their risk has changed over the course of the pandemic in relation to various factors. We conducted a prospective study including all HTr at risk of COVID-19 in a tertiary center between February 2020 and October 2022. The aim was to analyze how the prognosis (incidence of pneumonia and mortality) of COVID-19 in HTr has evolved over time, contextualizing variants, vaccination, and other treatments. RESULTS: Of 308 HTr included, 124 got the infection (39.2%). COVID and non-COVID HTr had similar baseline characteristics. COVID-19 patients with pneumonia had a poorer prognosis than those with less severe presentations, with a higher rate of hospitalization (93.3 vs. 14.1%, p < .001) and death (41.0 vs. 1.2%, p < .001). Multivariate analysis identified age ≥60 years (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.16-11.49, p = .027), and chronic kidney disease ≥3a (OR 4.95, 95% CI 1.39-17.54, p = .014) as predictors of pneumonia. Two-dose vaccination (OR 0.20, CI 95% 0.05-0.72, p = .02) and early remdesivir administration (OR 0.17, CI 0.03-0.90, p = .037) were protective factors. Over the course of the pandemic considering three periods in the follow-up (prevaccination February-December 2020, postvaccination January-December 2021, and post early remdesivir indication January-October 2022), we observed a reduction in pneumonia incidence from 62% to 19% (p < .001); and mortality (from 23% to 4%, p < .001). CONCLUSIONS: The prognosis of COVID-19 in HTr has improved over time, likely due to vaccination and early administration of remdesivir.

Human microRNA sequencing and cytomegalovirus infection risk after kidney transplantation.

Cytomegalovirus (CMV)-seropositive kidney transplant recipients (KTRs) with detectable CMV-specific cell-mediated immunity according to the QuantiFERON-CMV assay (QTF-CMV) are expected to have adequate immune protection. Nevertheless, a proportion of patients still develop CMV infection. Human microRNAs (hsa-miRNAs) are promising biomarkers owing to their high stability and easy detection. We performed whole blood miRNA sequencing in samples coincident with the first reactive QTF-CMV after transplantation or cessation of antiviral prophylaxis to investigate hsa-miRNAs differentially expressed according to the occurrence of CMV infection. One-year incidence of CMV viremia was 55.0% (median interval from miRNA sequencing sampling of 29 days). After qPCR validation, we found that hsa-miR-125a-5p was downregulated in KTRs developing CMV viremia within the next 90 days (ΔCt: 7.9 ± 0.9 versus 7.3 ± 1.0; P = .011). This difference was more evident among KTRs preemptively managed (8.2 ± 0.9 versus 6.9 ± 0.8; P < .001), with an area under the receiver operating characteristic curve of 0.865. Functional enrichment analysis identified hsa-miR-125a-5p targets involved in cell cycle regulation and apoptosis, including the BAK1 gene, which was significantly downregulated in KTRs developing CMV viremia. In conclusion, hsa-miR-125a-5p may serve as biomarker to identify CMV-seropositive KTRs at risk of CMV reactivation despite detectable CMV-CMI.

Peptidyl nitroalkene inhibitors of main protease rationalized by computational and crystallographic investigations as antivirals against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic continues to represent a global public health issue. The viral main protease (Mpro) represents one of the most attractive targets for the development of antiviral drugs. Herein we report peptidyl nitroalkenes exhibiting enzyme inhibitory activity against Mpro (Ki: 1-10 µM) good anti-SARS-CoV-2 infection activity in the low micromolar range (EC50: 1-12 µM) without significant toxicity. Additional kinetic studies of compounds FGA145, FGA146 and FGA147 show that all three compounds inhibit cathepsin L, denoting a possible multitarget effect of these compounds in the antiviral activity. Structural analysis shows the binding mode of FGA146 and FGA147 to the active site of the protein. Furthermore, our results illustrate that peptidyl nitroalkenes are effective covalent reversible inhibitors of the Mpro and cathepsin L, and that inhibitors FGA145, FGA146 and FGA147 prevent infection against SARS-CoV-2.

Predictive value of fecal calprotectin and lactoferrin levels for negative outcomes in Clostridioides difficile infection.

PURPOSE: We investigated the role of fecal calprotectin (FC) and lactoferrin (FL) as predictive biomarkers in Clostridioides difficile infection (CDI). METHODS: We assembled a prospective cohort including all patients with a laboratory-confirmed CDI diagnosis between January and December 2017. FL and FC levels were measured at diagnosis by commercial ELISA and EIA kits. We investigated the diagnostic accuracy of FC and FL to predict CDI recurrence and severity (study outcomes) and explored optimal cut-off values in addition to those proposed by the manufacturers (200 µg/g and 7.2 µg/mL, respectively). RESULTS: We included 170 CDI cases (152 first episodes and 18 recurrences). The rates of recurrence (first episodes only) and severity (entire cohort) were 9.2% (14/152) and 46.5% (79/170). Both FL and FC levels were significantly higher in patients who developed study outcomes. Optimal cut-off values for FC and FL to predict CDI recurrence were 1052 µg/g and 6.0 µg/mL. The optimal cut-off value for FC yielded higher specificity (60.9%) and positive predictive value (PPV) (16.9%) than that proposed by the manufacturer. Regarding CDI severity, the optimal cut-off value for FC (439 µg/g) also provided higher specificity (43.9%) and PPV (54.1%) than that of the manufacturer, whereas the optimal cut-off value for FL (4.6 µg/mL) resulted in an improvement of PPV (57.5%). CONCLUSION: By modifying the thresholds for assay positivity, the measurement of FC and FL at diagnosis is useful to predict recurrence and severity in CDI. Adding these biomarkers to current clinical scores may help to individualize CDI management.

Production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in Klebsiella pneumoniae infection.

PURPOSE: To know whether the production of OXA-48 carbapenemase exerts an independent impact on the outcome of Klebsiella pneumoniae infection, once adjusted by clinical syndrome and baseline risk factors. METHODS: We performed a case-cohort study including 117 infectious episodes due to OXA-48-producing K. pneumoniae (OXA-48-Kp) and 117 episodes due to non-OXA-48-producing strains (non-OXA-48-Kp). Both groups were matched (1:1 ratio) by clinical syndrome (source of infection, preceding invasive procedures and indwelling devices, and associated bacteremia) and hospitalization ward at infection onset. Multivariate Cox regression was used to investigate the association between OXA-48-Kp infection and clinical cure by day 14 (primary outcome) and 30-day all-cause mortality (secondary outcome). RESULTS: Both study groups were well balanced regarding underlying conditions and comorbidity burden. Sepsis or septic shock were more frequent in OXA-48-Kp cases than non-OXA-48-Kp controls (41 [35.0%] vs. 17 [14.5%]; P-value < 0.0001). Clinical cure by day 14 was less commonly achieved in OXA-48-Kp cases (49 [41.9%] vs. 95 [81.2%]; P-value < 0.001), whereas 30-day all-cause mortality was higher (33 [28.2%] vs. 18 [15.4%]; P-value = 0.018). Multivariate analysis confirmed that OXA-48-Kp infection was independently associated with the lack of 14-day clinical cure (adjusted hazard ratio [aHR]: 0.45; 95% confidential interval [95%CI]: 0.29-0.70; P-value < 0.0001). A non-significant association was observed for 30-day all-cause mortality (aHR: 1.65; 95%CI: 0.92-2.94; P-value = 0.093). CONCLUSION: Our matched analysis suggests that the production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in K. pneumoniae infection as compared to episodes due to non-carbapenemase-producing strains.

The Impact of the Second Wave of the COVID-19 Pandemic on Non-COVID Hospital Care in a Tertiary Hospital in Spain.

In 2020, Spain ranked fourth among European countries with the highest excess mortality due to COVID-19 disease. This study evaluates the impact of the COVID-19 pandemic on non-COVID patients in a tertiary hospital during the second pandemic wave in Spain (22 June 2020-6 December 2020). Data from Virgen del Rocío University Hospital in Seville during that timeframe were compared with the data from the same period in the preceding two years (2018-2019). Between-group comparisons were performed using the Chi-squared test, Student's t-test, or Mann-Whitney U tests, as appropriate. A total of 63,137 non-COVID patients were included in this study. During the second pandemic wave, a 19% decrease was observed in the annual number of non-COVID admissions overall (18,260 vs. 22,439, p < 0.001), but a 10% increase in the proportion of emergency admissions (60.6% vs. 54.93%, p < 0.001), a higher severity level of patients (1.79 vs. 1.72, p < 0.001), a longer in-hospital stay (7.02 vs. 6.74 days, p < 0.001), a 26% increase in non-COVID mortality (4.9% vs. 3.9%, p < 0.001), and a 50% increase in global mortality (5.9 vs. 3.9, p < 0.001) were also observed. In terms of both medical and surgical diagnoses, a significant reduction in the number of admissions and an increase in in-hospital mortality were observed. These results demonstrate the significant impact of the pandemic on hospital care, similar to what was previously observed during the initial wave in the same hospital. Our findings emphasize the need to include non-COVID patients when assessing the broad impact of the pandemic on healthcare, beyond its direct effects on COVID-19 patients.