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OBJECTIVES: Patients with haematologic malignancies (HM) COVID-19 have more severe disease, with increased risk of mortality. Therefore, this study aimed to evaluate the effect of SARS-CoV-2 RNAemia and the specific humoral immune responses on the clinical outcomes of patients with HM and COVID-19. METHODS: Interferon-α/γ (IFN-α/IFN-γ) serum levels, neutralizing antibodies and RNAemia at COVID-19 diagnosis, and persistent RNAemia during the follow-up were evaluated. RESULTS: Overall, 63 (58.9%) out of 107 patients had RNAemia, which was persistent in 26 (41.3%) patients. RNAemia at diagnosis and persistent RNAemia were associated with the need for high-flow nasal oxygen therapy during admission. Persistent RNAemia, age >70 years, and CURB-65 score ≥2 in patients with pneumonia were associated with increased 90-day mortality (P = 0.009, P = 0.030 and P = 0.001, respectively). The 90-day overall survival was lower (P = 0.006) in patients with persistent RNAemia. In addition, dexamethasone administration was associated with a COVID-19 episode with persistent RNAemia. CONCLUSION: Our results suggest that in patients with HM, RNAemia at the time of COVID-19 diagnosis and during the follow-up can be used to stratify patients with HM according to their clinical evolution and to guide clinical decisions tailored to the specific needs of each patient.
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Vacinas contra COVID-19 , COVID-19 , Neoplasias Hematológicas , RNA Viral , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/imunologia , Masculino , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/imunologia , Idoso , Pessoa de Meia-Idade , RNA Viral/sangue , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Interferon gama/sangue , Interferon-alfa/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Dexametasona/uso terapêutico , Dexametasona/administração & dosagemRESUMO
BACKGROUND: Community-acquired (CA) and healthcare-associated (HCA) infections caused by carbapenemase-producing Enterobacterales (CPE) are not well characterized. The objective was to provide detailed information about the clinical and molecular epidemiological features of nosocomial, HCA and CA infections caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp) and Escherichia coli (CP-Ec). METHODS: A prospective cohort study was performed in 59 Spanish hospitals from February to March 2019, including the first 10 consecutive patients from whom CP-Kp or CP-Ec were isolated. Patients were stratified according to acquisition type. A multivariate analysis was performed to identify the impact of acquisition type in 30-day mortality. RESULTS: Overall, 386 patients were included (363 [94%] with CP-Kp and 23 [6%] CP-Ec); in 296 patients (76.3%), the CPE was causing an infection. Acquisition was CA in 31 (8.0%) patients, HCA in 183 (47.4%) and nosocomial in 172 (48.3%). Among patients with a HCA acquisition, 100 (54.6%) had been previously admitted to hospital and 71 (38.8%) were nursing home residents. Urinary tract infections accounted for 19/23 (82.6%), 89/130 (68.5%) and 42/143 (29.4%) of CA, HCA and nosocomial infections, respectively. Overall, 68 infections (23%) were bacteremia (8.7%, 17.7% and 30.1% of CA, HCA and nosocomial, respectively). Mortality in infections was 28% (13%, 14.6% and 42.7% of CA, HCA and nosocomial, respectively). Nosocomial bloodstream infections were associated with increased odds for mortality (adjusted OR, 4.00; 95%CI 1.21-13.19). CONCLUSIONS: HCA and CA infections caused by CPE are frequent and clinically significant. This information may be useful for a better understanding of the epidemiology of CPE.
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OBJECTIVES: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSION: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.
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Antifúngicos , Infecções Fúngicas Invasivas , Nitrilas , Piridinas , Triazóis , Humanos , Nitrilas/uso terapêutico , Nitrilas/efeitos adversos , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Estudos Retrospectivos , Antifúngicos/uso terapêutico , Antifúngicos/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Triazóis/uso terapêutico , Triazóis/efeitos adversos , Idoso , Infecções Fúngicas Invasivas/tratamento farmacológico , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais , Aspergilose/tratamento farmacológico , Adulto JovemRESUMO
This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.
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BACKGROUND: Significant variations in the variables collected in clinical studies focusing on bacteraemia lead to inconsistency in the evaluation of risk factors for mortality. OBJECTIVE: We aimed to define a minimum set of risk factors that should be assessed and reported in all studies assessing survival in bacteraemia. STUDY ELIGIBILITY: We conducted a systematic review including observational prospective and retrospective cohort studies that assessed all-cause mortality among patients with bacteraemia. We included only studies computing an adjusted analysis for mortality, with >500 participants. EXPOSURES: Independently significant risk factors for all-cause, preferably 30-day, mortality. DATA SOURCES: PubMed was used to identify eligible studies published between 2000 and 2020. A Delphi survey among experts was used to evaluate and prioritize the factors identified by the systematic review. RISK OF BIAS: SIGN checklist complemented by risk of bias assessment of the adjusted analysis. DATA SYNTHESIS: Definite universal risk factors were defined as those assessed in >50% of all included studies and significant in >50% of those. Potential universal risk factors were defined as those significant in >50% of studies evaluating the factor and a subgroup analysis was performed for studies of Staphylococcus aureus bacteraemia. RESULTS: We included in the systematic review 62 studies, comprising more than 300,000 patients, from which a list of 17 risk factors was derived, whose association with all-cause mortality was statistically significant in most studies. The factors address baseline patient variables, the setting of infection acquisition, factors associated with the specific infection, the inflammatory response at onset of sepsis and management parameters where relevant. There were 14 risk factors for S. aureus bacteraemia. CONCLUSION: We identified a minimum set of universal factors to be collected, reported, and assessed, in all future studies evaluating factors associated with mortality in bacteraemia to improve study quality and harmonization.
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Bacteriemia , Técnica Delphi , Humanos , Bacteriemia/mortalidade , Fatores de Risco , Infecções Estafilocócicas/mortalidade , Estudos ProspectivosRESUMO
OBJECTIVES: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. METHODS: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. RESULTS: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24). DISCUSSION: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.
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Assistência ao Convalescente , Gammaproteobacteria , Humanos , Estudos de Coortes , Alta do Paciente , Estudos Prospectivos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Estudos de Casos e ControlesRESUMO
OBJECTIVES: To evaluate the appropriateness of antimicrobial treatment and the risk factors for mortality in patients with negative blood cultures (BC), in order to evaluate whether this population would be a suitable target for antimicrobial stewardship (AMS) interventions. METHODS: A multicentre prospective cohort study of patients with negative BC in three Spanish hospitals between October 2018 and July 2019 was performed. The main endpoints were the appropriateness of antimicrobial treatment (evaluated by two investigators according to local guidelines) and 30-day mortality. Cox-regression was performed to estimate the association between variables and 30-day mortality. RESULTS: Of 1011 patients in whom BC was obtained, these were negative in 803 (79%) and were included; 30-day mortality was 9% (70 patients); antibiotic treatment was considered inappropriate in 299 (40%) of 747 patients evaluated at day 2, and in 266 (46%) of 573 at day 5-7. The variables independently associated with increased risk of 30-day mortality were higher age (HR 1.05; 95% CI 1.03-1.07), neoplasia (HR 2.73; 95% CI 1.64-4.56), antibiotic treatment in the 48 h prior to BC extraction (HR 2.06; 95% CI 1.23-3.43) and insufficient antibiotic coverage at day 2 after BC obtainment (HR 2.35; 95% CI 1.39-4.00). Urinary, catheter and biliary sources of infection were associated with lower risk (HR 0.40; 95% CI 0.20-0.81). CONCLUSIONS: Antimicrobial treatment is frequently inappropriate among patients with negative BC; insufficient antibiotic coverage at day 2 was associated with mortality. These results suggest that patients with negative BC are a suitable population for AS interventions. SUMMARY: Antimicrobial treatment in patients with negative blood culture was frequently inappropriate, and inappropriate coverage at day 2 was associated with increased risk of death. These data support the consideration of this population as a potential target for antimicrobial stewardship interventions.
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Antibacterianos , Gestão de Antimicrobianos , Humanos , Antibacterianos/uso terapêutico , Estudos Prospectivos , Hemocultura , AntibioticoprofilaxiaRESUMO
[This corrects the article DOI: 10.3389/fmicb.2022.918362.].
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INTRODUCTION: Enterococcus spp is responsible for 8%-15% of total bacteraemias with an associated global mortality around 23%-30%. Regarding the clinical management of enterococcal bacteraemia, the evidence on the duration of antibiotic treatment is scarce and the studies do not discriminate between complicated and uncomplicated bacteraemia. METHODS: The INTENSE study is a multicentre, open-label, randomised, pragmatic, phase-IV clinical trial to demonstrate the non-inferiority of a 7-day vs 14-day course for the treatment of uncomplicated enterococcal bacteraemia and incorporating the early switching to oral antibiotics when feasible. The primary efficacy endpoint is the clinical cure at day 30±2 after the end of the treatment. Secondary endpoints will include the rate of relapse or infective endocarditis, length of stay, duration of intravenous therapy, Clostridioides difficile infection and the evaluation of the safety of both treatment arms through the recording and analysis of adverse events. For a 6% non-inferiority margin and considering a 5% withdrawal rate, 284 patients will be included. ANALYSIS: The difference in proportions with one-sided 95% CIs will be calculated for the clinical cure rate using the control group as reference. For secondary categorical endpoints, a similar analysis will be performed and Mann-Whitney U-test will be used to compare median values of quantitative variables. A superiority analysis applying the response adjusted for days of antibiotic risk will be performed if there were incidents in recruitment; will allow obtaining results with 194 patients recruited. ETHICS AND DISSEMINATION: The study has obtained the authorisation from the Spanish Regulatory Authority, the approval of the ethics committee and the agreement of the directors of each centre. Data will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05394298.
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Bacteriemia , Infecções Bacterianas , Endocardite , Humanos , Bacteriemia/tratamento farmacológico , Antibacterianos/efeitos adversos , Grupos Controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase IV como AssuntoRESUMO
Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs. Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677. Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively). Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials. Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424.
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The 2020-21 West Nile Virus (WNV) outbreak in Andalusia, Spain, was the largest reported in the country, with eight cases of West Nile Neuroinvasive Disease (WNND) diagnosed in a tertiary hospital. Diagnosis of WNND is based on detecting WNV RNA, viral isolation, or demonstrating a specific immune response against the virus, with additional tests used to support the diagnosis. Treatment remains supportive, with variable outcomes. The potential efficacy of plasma exchange (PLEX) in select cases raises the possibility of an autoimmune component secondary to infectious pathology of the central nervous system. The influence of climate change on the expansion of WNV into new regions is a significant concern. It is crucial for physicians practicing in high-risk areas to be knowledgeable about the disease for early prevention and effective control measures.
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Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Humanos , Vírus do Nilo Ocidental/genética , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/diagnóstico , Espanha/epidemiologia , Sistema Nervoso Central/patologia , Surtos de DoençasRESUMO
OBJECTIVES: The study aim was to assess predictors of negative antibody response (AbR) in solid organ transplant (SOT) recipients after the first booster of SARS-CoV-2 vaccination. METHODS: Solid organ transplant recipients receiving SARS-CoV-2 vaccination were prospectively enrolled (March 2021-January 2022) at six hospitals in Italy and Spain. AbR was assessed at first dose (t0), second dose (t1), 3 ± 1 month (t2), and 1 month after third dose (t3). Negative AbR at t3 was defined as an anti-receptor binding domain titre <45 BAU/mL. Machine learning models were developed to predict the individual risk of negative (vs. positive) AbR using age, type of transplant, time between transplant and vaccination, immunosuppressive drugs, type of vaccine, and graft function as covariates, subsequently assessed using a validation cohort. RESULTS: Overall, 1615 SOT recipients (1072 [66.3%] males; mean age±standard deviation [SD], 57.85 ± 13.77) were enrolled, and 1211 received three vaccination doses. Negative AbR rate decreased from 93.66% (886/946) to 21.90% (202/923) from t0 to t3. Univariate analysis showed that older patients (mean age, 60.21 ± 11.51 vs. 58.11 ± 13.08), anti-metabolites (57.9% vs. 35.1%), steroids (52.9% vs. 38.5%), recent transplantation (<3 years) (17.8% vs. 2.3%), and kidney, heart, or lung compared with liver transplantation (25%, 31.8%, 30.4% vs. 5.5%) had a higher likelihood of negative AbR. Machine learning (ML) algorithms showing best prediction performance were logistic regression (precision-recall curve-PRAUC mean 0.37 [95%CI 0.36-0.39]) and k-Nearest Neighbours (PRAUC 0.36 [0.35-0.37]). DISCUSSION: Almost a quarter of SOT recipients showed negative AbR after first booster dosage. Unfortunately, clinical information cannot efficiently predict negative AbR even with ML algorithms.
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COVID-19 , Transplante de Fígado , Transplante de Órgãos , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Vacinas contra COVID-19 , SARS-CoV-2 , Formação de Anticorpos , COVID-19/diagnóstico , COVID-19/prevenção & controle , Transplantados , Vacinação , Aprendizado de Máquina , Anticorpos AntiviraisAssuntos
COVID-19 , SARS-CoV-2 , Humanos , Síndrome de COVID-19 Pós-Aguda , Fatores de Risco , Estudos de Coortes , RNA Viral/genéticaRESUMO
Main aim of this systematic review is to quantify the risk and identify predictors of clinical evolution of SARS-CoV-2 in hematological patients compared to different control populations. Two independent reviewers screened the literature assessing clinical outcomes of SARS-CoV-2 infection in adult patients with active hematological malignancies published up to June 2021. Primary outcome was COVID-19 related mortality, secondary outcomes were hospital and intensive-care admission, mechanical ventilation (MV), and thromboembolic events. Variables related to study setting, baseline patients' demographic, comorbidities, underlying hematological disease, ongoing chemotherapy, COVID-19 presentation, and treatments were extracted. A total of 67 studies including 10,061 hematological patients and 111,143 controls were included. Most of the studies were retrospective cohorts (51 studies, 76%) and only 19 (13%) provided data for a control group. A significant increased risk of clinical progression in the hematological population compared to the controls was found in terms of COVID-19 related mortality (OR, 2.12; 95% CI, 1.77-2.54), hospitalization (OR, 1.98; 95% CI, 1.15-3.43), intensive-care admission (OR, 1.77; 95% CI, 1.38-2.26), and MV (OR, 2.17; 95% CI, 1.71-2.75). The risk remained significantly higher in the subgroup analysis comparing hematological patients versus solid cancer. Meta-regression analysis of uncontrolled studies showed that older age, male sex, and hypertension were significantly related to worse clinical outcomes of COVID-19 in hematological population. Older age and hypertension were found to be associated also to thromboembolic events. In conclusion, hematological patients have a higher risk of COVID-19 clinical progression compared to both the general population and to patients with solid cancer.
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COVID-19 , Hipertensão , Neoplasias , Adulto , Humanos , Masculino , SARS-CoV-2 , Estudos Retrospectivos , Progressão da DoençaRESUMO
The objective of this study was to assess the association between patients' epidemiological characteristics and comorbidities with SARS-CoV-2 infection severity and related mortality risk. An umbrella systematic review, including a meta-analysis examining the association between patients' underlying conditions and severity (defined as need for hospitalization) and mortality of COVID-19, was performed. Studies were included if they reported pooled risk estimates of at least three underlying determinants for hospitalization, critical disease (ICU admission, mechanical ventilation), and hospital mortality in patients diagnosed with SARS-CoV-2 infection. Evidence was summarized as pooled odds ratios (pOR) for disease outcomes with 95% confidence intervals (95% CI). Sixteen systematic reviews investigating the possible associations of comorbidities with severity or death from COVID-19 disease were included. Hospitalization was associated with age > 60 years (pOR 3.50; 95% CI 2.97−4.36), smoking habit (pOR 3.50; 95% CI 2.97−4.36), and chronic pulmonary disease (pOR 2.94; 95% CI 2.14−4.04). Chronic pulmonary disease (pOR 2.82; 95% CI 1.92−4.14), cerebrovascular disease (pOR 2.74; 95% CI 1.59−4.74), and cardiovascular disease (pOR 2.44; 95% CI 1.97−3.01) were likely to be associated with increased risk of critical COVID-19. The highest risk of mortality was associated with cardiovascular disease (pOR 3.59; 95% CI 2.83−4.56), cerebrovascular disease (pOR 3.11; 95% CI 2.35−4.11), and chronic renal disease (pOR 3.02; 95% CI 2.61−3.49). In conclusion, this umbrella systematic review provides a comprehensive summary of meta-analyses examining the impact of patients' characteristics on COVID-19 outcomes. Elderly patients and those cardiovascular, cerebrovascular, and chronic renal disease should be prioritized for pre-exposure and post-exposure prophylaxis and early treatment.
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Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.
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Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. We aimed to describe the Point Prevalence Surveys (PPS) methodology implemented in our hospital as an efficient tool to guide ASP strategies. Annually repeated PPS were conducted from 2012 to 2019 at a 750-bed university hospital in South Spain. Key quality indicators and inappropriateness of antimicrobial treatment, defined strictly according to local guidelines, were described. Variables associated with inappropriate treatment were identified by bi/multivariable analysis. A total of 1,600 patients were included. We found that 49% of the prescriptions were inappropriate due to unnecessary treatment (14%), not first line drug recommended (14%), inadequate drug according to microbiological results (9%), unsuitable doses (8%), route (3%) or duration (7%). Samples collection presented a significant protective effect together with sepsis presentation at onset and intensive care unit admission. However, age, receiving an empirical treatment and an unknown or urinary source of the infections treated were independent risk factors for inappropriateness. Site and severity of infection were documented in medical charts by prescribers (75 and 61% respectively). PPS may allow identifying the main risk factors for inappropriateness. This simple methodology may be useful for ASP to select modifiable factors to be prioritized for targeted interventions.
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Objectives: CARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain. Methods: In total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis. Results: In total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were bla OXA-48 (263/377), bla KPC-3 (62/377), bla VIM-1 (28/377), and bla NDM-1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5). Conclusion: This study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3.