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BACKGROUND: There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. METHODS: We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. RESULTS: A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission. CONCLUSIONS: Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.
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COVID-19 , Humanos , RNA Subgenômico , SARS-CoV-2 , Tempo de Internação , Tratamento Farmacológico da COVID-19 , Antivirais/uso terapêuticoRESUMO
Hospitalized patients with coronavirus disease 2019 (COVID-19) experiencing respiratory symptoms have different complications (inflammatory, co-infection, and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (odds ratio [OR] .144; 95% confidence interval [CI] .03-.686; Pâ =â .015). Increasing age (OR 1.06; Pâ =â .038) and therapeutic effort limitation (OR 9.684; Pâ <â .001) were associated with higher mortality.
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COVID-19 , Hospitalização , Humanos , Razão de Chances , SARS-CoV-2RESUMO
We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. A multicenter retrospective study (2010 to 2019) of two prospective cohorts compared BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Of 1,563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% versus 15%, P < 0.001). Gram-negative bacilli caused 81% of episodes with septic shock, Gram-positive cocci caused 22%, and Candida species caused 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical ß-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific Gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% versus 51%, P = 0.002). Age of >70 years (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2 to 4.7), IEAT for Candida spp. or Gram-negative bacilli (OR, 3.8; 95% CI, 1.3 to 11.1), acute kidney injury (OR, 2.6; 95% CI, 1.4 to 4.9), and amikacin as the only active antibiotic (OR, 15.2; 95% CI, 1.7 to 134.5) were independent risk factors for mortality, while the combination of ß-lactam and amikacin was protective (OR, 0.32; 95% CI, 0.18 to 0.57). Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active ß-lactam and amikacin results in the best outcomes.
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Bacteriemia , Sepse , Choque Séptico , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológicoRESUMO
PURPOSE: Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19. METHODS: Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days. RESULTS: Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%). CONCLUSIONS: The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals.
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COVID-19 , SARS-CoV-2 , Antivirais , Hospitais , Humanos , Carga ViralRESUMO
BACKGROUND: The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. METHODS: Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. RESULTS: In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54-77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4-6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218-0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days). CONCLUSIONS: Patients with ≤3 days and 4-6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.
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Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Idoso , Alanina/análogos & derivados , Antivirais/uso terapêutico , Humanos , Masculino , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2RESUMO
Background: This study aimed to describe documented infections associated with postinfusion fever after CAR T-cell therapy and to evaluate daily changes in vital signs, laboratory results, and the National Early Warning Score (NEWS) in patients with and without confirmed bacterial infections following fever onset, with the objective of assisting in antibiotic stewardship. Methods: This was a retrospective, observational study including all consecutive adult patients who received CAR T-cell therapy. Documented infection in the first fever episode after infusion, and clinical and analytic trend comparison of patients with bacterial documented infections and those without documented infections, are described. Results: Among 152 patients treated with CAR T-cell therapy, 87 (57.2%) had fever within 30 days of infusion, with a median time from infusion to fever of 3 (interquartile range, 2-5) days. Of these 87 patients, 82 (94.3%) received broad-spectrum antibiotics. Infection was documented in 9 (10.3%) patients and only 4 (4.6%) had bacterial infections. Clinical signs and biomarkers were similar in patients with bacterial documented infection and in those without documented infection at fever onset. Fever, tachycardia, and high C-reactive protein levels remained high during the first 3 days after CAR T-cell infusion, even when no infection was documented. Conclusions: Fever is a common symptom following CAR T-cell infusion and is largely treated with broad-spectrum antibiotics. However, confirmed bacterial documented infections after the first fever post-CAR T-cell infusion are very unusual. Because clinical parameters and biomarkers are not useful for identifying infectious fever, other methods should be assessed to ensure the proper use of antibiotics.
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OBJECTIVES: Access and appropriateness of therapeutics for COVID-19 vary because of access or regulatory barriers, the severity of the disease, and for some therapies, the stage of the pandemic and circulating variants. Remdesivir has shown benefits in clinical recovery and is the treatment of choice for selected patients, both hospitalized and nonhospitalized, in main international guidelines. The use of remdesivir in alternatives to conventional hospitalization such as hospital at home (HaH) units remains incompletely explored. In this study, we aim to describe the real-life experience of outpatient remdesivir infusion for COVID-19 in a HaH unit. METHODS: We selected all the consecutive patients receiving remdesivir from a prospective cohort of 507 COVID-19 patients admitted at a HaH unit. Admission criteria included COVID-19 with a fraction of inspired oxygen requirement under 0.35 and respiratory rate under 22 rpm. Patients were daily assessed in person by a nurse and a physician. RESULTS: A total of 236 patients admitted at the HaH unit received remdesivir, 172 of whom were treated at home. Only 2% presented any adverse event related to the infusion, all of them mild. HaH saved 1416 day-beds, with only 5% of the patients requiring transfer back to the hospital. CONCLUSION: Remdesivir infusion in HaH units seems to be a safe and efficient alternative to conventional hospitalization for treating patients with nonsevere COVID-19.
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COVID-19 , Humanos , Estudos Prospectivos , Tratamento Farmacológico da COVID-19 , Alanina/uso terapêutico , HospitaisRESUMO
We aimed to describe the characteristics and outcomes of biliary source bloodstream infections (BSIs) in oncological patients. Secondarily, we analyzed risk factors for recurrent BSI episodes. All episodes of biliary source BSIs in oncological patients were prospectively collected (2008-2019) and retrospectively analyzed. Logistic regression analyses were performed. A rule to stratify patients into risk groups for recurrent biliary source BSI was conducted. Four hundred biliary source BSIs were documented in 291 oncological patients. The most frequent causative agents were Escherichia coli (42%) and Klebsiella spp. (27%), and 86 (21.5%) episodes were caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The rates of MDR-GNB increased over time. Overall, 73 patients developed 118 recurrent BSI episodes. Independent risk factors for recurrent BSI episodes were prior antibiotic therapy (OR 3.781, 95% CI 1.906-7.503), biliary prosthesis (OR 2.232, 95% CI 1.157-4.305), prior admission due to suspected biliary source infection (OR 4.409, 95% CI 2.338-8.311), and BSI episode caused by an MDR-GNB (OR 2.857, 95% CI 1.389-5.874). With these variables, a score was generated that predicted recurrent biliary source BSI with an area under the receiver operating characteristic (ROC) curve of 0.819. Inappropriate empirical antibiotic treatment (IEAT) was administered in 23.8% of patients, and 30-d mortality was 19.5%. As a conclusion, biliary source BSI in oncological patients is mainly caused by GNB, with high and increasing MDR rates, frequent IEAT, and high mortality. Recurrent BSI episodes are frequent. A simple score to identify recurrent episodes was developed to potentially establish prophylactic strategies. IMPORTANCE This study shows that biliary source bloodstream infections (BSIs) in oncological patients are mainly caused by Gram-negative bacilli (GNB), with high and increasing rates of multidrug resistance. Importantly, recurrent biliary source BSI episodes were very frequent and associated with delays in chemotherapy, high rates of inappropriate empirical antibiotic therapy, and high 30-d mortality (19.5%). Using the variable independently associated with recurrent BSI episodes, a score was generated that predicted recurrent biliary source BSI with high accuracy. This score could be used to establish prophylactic strategies and lower the risk of relapsing episodes and the associated morbidity and mortality.
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We documented a hematologic patient with prolonged SARS-CoV-2 viral replication in whom emergence of viral mutations was documented after the consecutive use of antivirals and convalescent plasma. The virus detected in the last of 12 clinical samples (day 237) had accumulated 22 changes in amino acids and 29 in nucleotides. Some of these changes, such as the E484Q, were mutations of concern as defined by WHO. This finding represents an enormous epidemiological threat and poses a major clinical challenge. Combined antiviral strategies, as well as specific strategies related to the diagnostic approach of prolonged infections for this specific population, may be needed.
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BACKGROUND: The cryptic Aspegillus species are rare, these microorganisms are usually more resistant to common antifungal therapies. Therefore, a correct identification is important when evaluating the impact of such species in aspergillosis. AIMS: We aimed to describe the frequency, clinical and microbiological characteristics, and the outcomes of those cases of aspergillosis caused by cryptic species in a tertiary hospital. METHODS: We retrospectively identified all microbiologically documented cases of aspergillosis between January 2013 and December 2018. Definitive species identification of clinically significant isolates was achieved via sequencing methods. The polymerase chain reaction (PCR) products were sequenced, and the results obtained were compared to sequences deposited in GenBank. Antifungal susceptibility testing was performed using the Sensititre® YeastOne® panel. RESULTS: A total of 679 Aspergillus isolates were recovered from 489 patients, of which 109 were clinically relevant. Ten (9.2%) isolates were identified as cryptic species: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) and Aspergillus montevidensis (1). Most patients already suffered some type of immunosuppression. Half of these patients had required intensive care before the infection showed up, and most of them had a pulmonary infection. Mortality at the 100-day follow-up was 40%. Antifungal susceptibility testing was performed on three of the isolates (A. arcoverdensis, A. tubingensis and A. nomius), which showed high minimum inhibitory concentrations (MIC) for azoles and amphotericin B. CONCLUSIONS: The frequency of cryptic species in our centre was 9.2%. Most patients had some degree of immunosuppression, and the mortality rate was 40%.
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Antifúngicos , Aspergilose , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus , Humanos , Testes de Sensibilidade Microbiana , Estudos RetrospectivosRESUMO
OBJECTIVES: We described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19. METHODS: Observational cohort study was performed at the Hospital Clinic of Barcelona (February 2020-February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included. RESULTS: A total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p<0.001, and p<0.001, respectively). In multivariate analysis, oxygen saturation ≤94% (OR 2.47, CI 1.57-3.86), ferritin levels <338 ng/mL (OR 2.63, CI 1.69-4.07), and PCT higher than 0.2 ng/mL (OR 1.74, CI 1.11-2.72) were independent risk factors for co-infection at hospital admission owing to COVID-19. CONCLUSIONS: Bacterial co-infection in patients hospitalized for COVID-19 is relatively common. However, clinicians could spare antibiotics in patients with PCT values <0.2, especially with high ferritin values and oxygen saturation >94%.
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Infecções Bacterianas , COVID-19 , Coinfecção , Adulto , Infecções Bacterianas/microbiologia , COVID-19/epidemiologia , Coinfecção/epidemiologia , Ferritinas , Hospitais , Humanos , Pró-Calcitonina , Estudos Retrospectivos , SARS-CoV-2RESUMO
Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein.
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Anticorpos Monoclonais Humanizados , Proteína C-Reativa , Tratamento Farmacológico da COVID-19 , Dexametasona , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Proteína C-Reativa/metabolismo , Dexametasona/uso terapêutico , Feminino , Humanos , Masculino , Estudos Retrospectivos , SARS-CoV-2RESUMO
INTRODUCTION: Increased mortality has been reported in the Latin American population. The objective is to compare the clinical characteristics and outcome of Latin American and Spanish populations in a cohort of patients hospitalized with COVID-19 during the first year of the pandemic. METHODS: We retrospectively analysed all the Latin American patients (born in South or Central America) hospitalized in our centre from February 2020 to February 2021 and compared them with an age- and gender-matched group of Spanish subjects. Variables included were demographics, co-morbidities, clinical and analytical parameters at admission and treatment received. The primary outcomes were ICU admission and mortality at 60 days. A conditional regression analysis was performed to evaluate the independent baseline predictors of both outcomes. RESULTS: From the 3216 patients in the whole cohort, 216 pairs of case-controls (Latin American and Spanish patients, respectively) with same age and gender were analysed. COPD was more frequent in the Spanish group, while HIV was more prevalent in the Latin American group. Other co-morbidities showed no significant difference. Both groups presented with similar numbers of days from symptom onset, but the Latin American population had a higher respiratory rate (21 vs. 20 bpm, P = 0.041), CRP (9.13 vs. 6.22 mg/dl, P = 0.001), ferritin (571 vs. 383 ng/ml, P = 0.012) and procalcitonin (0.10 vs. 0.07 ng/ml, P = 0.020) at admission and lower cycle threshold of PCR (27 vs. 28.8, P = 0.045). While ICU admission and IVM were higher in the Latin American group (17.1% vs. 13% and 9.7% vs. 5.1%, respectively), this was not statistically significant. Latin American patients received remdesivir and anti-inflammatory therapies more often, and no difference in the 60-day mortality rate was found (3.2% for both groups). CONCLUSION: Latin American patients with COVID-19 have more severe disease than Spanish patients, requiring ICU admission, antiviral and anti-inflammatory therapies more frequently. However, the mortality rate was similar in both groups.
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BACKGROUND: We aimed to describe the epidemiology of catheter-related bloodstream infections (CRBSIs) in onco-hematological neutropenic patients during a 25-year study period, to evaluate the risk factors for Gram-negative bacilli (GNB) CRBSI, as well as rates of inappropriate empirical antibiotic treatments (IEAT) and mortality. MATERIALS/METHODS: All consecutive episodes of CRBSIs were prospectively collected (1994-2018). Changing epidemiology was evaluated comparing five-year time spans. A multivariate regression model was built to evaluate risk factors for GNB CRBSIs. RESULTS: 482 monomicrobial CRBSIs were documented. The proportion of CRBSIs among all BSIs decreased over time from 41.2% to 15.8% (p<0.001). CRBSIs epidemiology has been changing: the rate of GNB increased over time (from 11.9% to 29.4%; p<0.001), as well as the absolute number and rate of multidrug-resistant (MDR) GNB (from 9.5% to 40.0%; p = 0.039). P. aeruginosa increased and comprised up to 40% of all GNB. Independent factors related with GNB-CRBSIs were: longer duration of in-situ catheter (OR 1.007; 95%CI 1.004-1.011), older age (OR 1.016; 95%CI 1.001-1.033), prior antibiotic treatment with penicillins (OR 2.716; 95%CI 1.306-5.403), and current antibiotic treatment with glycopeptides (OR 1.931; 95%CI 1.001-3.306). IEATs were administered to 30.7% of patients, with the highest percentage among MDR P. aeruginosa (76.9%) and S. maltophillia (92.9%). Mortality rate was greater among GNB than GPC-CRBSI (14.4% vs 5.4%; p = 0.002), with mortality increasing over time (from 4.5% to 11.2%; p = 0.003). CONCLUSION: A significant shift towards GNB-CRBSIs was observed. Secondarily, and coinciding with an increasing number of GNB-MDR infections, mortality increased over time.
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Infecções Relacionadas a Cateter/epidemiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Neoplasias Hematológicas/patologia , Neutropenia/patologia , Adulto , Idoso , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/sangue , Neutropenia/tratamento farmacológico , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologiaRESUMO
INTRODUCTION: We aimed to compare the clinical characteristics and outcomes of bloodstream infections (BSI) in cancer patients presenting febrile neutropenia with and without HIV infection, and analyze the prognostic factors for mortality. METHODS: BSI episodes in febrile neutropenic patients following chemotherapy were prospectively collected (1997-2018). A case (HIV-infected)-control (non-HIV-infected) sub-analysis was performed (1:2 ratio), matching patients by age, gender, baseline disease, and etiological microorganism. RESULTS: From 1755 BSI episodes in neutropenic cancer patients, 60 (3.4%) occurred in those with HIV. HIV characteristics: 51.7% were men who have sex with men; 58.3% had < 200 CD4; 51.7% had a detectable HIV-1 RNA viral load before the BSI episode; 70.0% met AIDS-defining criteria; and 93.3% were on antiretroviral therapy, with a protease inhibitor-based regimen being the most common (53.0%). HIV-infected patients were younger, more frequently male and more commonly presenting chronic liver disease (p < 0.001 for all). BSI due to Enterococcus spp. was significantly more frequent among patients with HIV (p = 0.017) with no differences in other pathogens. HIV-infected patients with cancer presented with shock more frequently (p = 0.014) and had higher mortality (31.7% vs. 18.1%, p = 0.008). In the case-control analysis, cases (HIV-infected) had chronic liver disease (p = 0.003) more frequently, whereas acute leukemia (p = 0.013) and hematopoietic stem-cell transplant (p = 0.023) were more common among controls. There was a non-significant trend for cases to have higher mortality (p = 0.084). However, in multivariate analysis, HIV infection was not associated with mortality (p = 0.196). CONCLUSION: HIV-infected patients with cancer developing febrile neutropenia and BSI have different epidemiological and clinical profiles, and experience higher mortality. However, HIV infection by itself was not associated with mortality.
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INTRODUCTION: We aimed to assess risk factors for multidrug-resistant Gram-negative bacilli (MDR-GNB) from a large amount of data retrieved from electronic health records (EHRs) and determine whether machine learning (ML) may be useful in assessing the risk of MDR-GNB infection at febrile neutropenia (FN) onset. METHODS: Retrospective study of almost 7 million pieces of structured data from all consecutive episodes of FN in hematological patients in a tertiary hospital in Barcelona (January 2008-December 2017). Conventional multivariate analysis and ML algorithms (random forest, gradient boosting machine, XGBoost, and GLM) were done. RESULTS: A total of 3235 episodes of FN in 349 patients were documented; MDR-GNB caused 180 (5.6%) infections in 132 patients. The most frequent MDR-GNBs were MDR-Pseudomonas aeruginosa (53%) and extended-spectrum beta-lactamase-producing Enterobacterales (46%). According to conventional logistic regression analysis, independent factors associated with MDR-GNB infection were age older than 45 years (OR 2.07; 95% CI 1.31-3.24), prior antibiotics (2.62; 1.39-4.92), first-ever FN in this hospitalization (2.94; 1.33-6.52), prior hospitalizations for FN (1.72; 1.02-2.89); at least 15 prior hospital visits (2.65; 1.31-5.33), high-risk hematological diseases (3.62; 1.12-11.67), and hospitalization in a room formerly occupied by patients with MDR-GNB isolation (1.69; 1.20-2.38). ML algorithms achieved the following AUC and F1 score for MDR-GNB prediction: random forest, 0.79-0.9711; GMB, 0.79-0.9705; XGBoost, 0.79-0.9670; and GLM, 0.78-0.9716. CONCLUSION: Data generated in EHRs proved useful in assessing risk factors for MDR-GNB infections in patients with FN. The great number of analyzed variables allowed us to identify new factors related to MDR infection, as well as to train ML algorithms for infection predictions. This information may be used by clinicians to make better clinical decisions.
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BACKGROUND: We aimed to describe changes in characteristics and treatment strategies of hospitalised patients with COVID-19 and detail the mortality trend over time. METHODS: Observational cohort study of all consecutive patients admitted ≥ 48 h to Hospital Clinic of Barcelona for COVID-19 (1 March-30 September 2020). FINDINGS: A total of 1645 consecutive patients with COVID-19 were assessed over a 7-month period. Overall mortality (≤30 days) was 9.7% (159 patients), 7.7% in patients hospitalised in regular wards and 16.7 % in patients requiring ICU admission. Overall mortality decreased from 11.6% in the first month to 1.4% in the last month, reflecting a progressive, significant downward trend (p for trend <0.001). Patients' age changed over time, peaking in June. Most changes in the use of antivirals and anti-inflammatory treatments were documented. Age (OR 1.1, CI 1.1-1.12), chronic heart disease, (OR 1.7, CI 1.1-2.9), D-dimer>700 ng/mL (OR 2.3, CI 1.3-4.1), ferritin>489 ng/mL (OR 1.9; CI 1.5-3.2), C-RP>7 mg/dL (OR 2.6; CI 1.5-4.6), and shorter duration from symptom onset to hospital admission (OR 1.11; CI 1.04-1.17) were factors associated with 30-day mortality at hospital admission. Conversely, hospital admission in the last months (OR 0.80; CI 0.65-0.98) was significantly associated with lower mortality. INTERPRETATION: In-hospital mortality has decreased in patients with COVID-19 over the last, few months, even though main patient characteristics remain similar. Several changes made when managing patients may explain this decreasing trend. Our study provides current data on mortality of patients hospitalised with COVID-19 that might be useful in establishing quality of standard of care. FUNDING: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme), EDRD. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061], have received grants from Ministerio de Sanidad y Consumo, ISCIII.
CONTEXTO: Nuestro objetivo es describir los cambios en las características y las estrategias de tratamiento de los pacientes hospitalizados por COVID-19, y detallar la tendencia de la mortalidad en el tiempo. MÉTODOS: Estudio observacional de cohortes de todos los pacientes consecutivos, ingresados por COVID-19 durante más de 48 horas, en el Hospital Clínic de Barcelona (del 1 de marzo al 30 de septiembre de 2020). RESULTADOS: Un total de 1645 pacientes consecutivos fueron evaluados durante un período de 7 meses. La mortalidad global (≤30 días) fue del 9.7% (159 pacientes): 7.7% en pacientes hospitalizados en salas convencionales, y 16.7% en pacientes que requirieron ingreso en UCI. La mortalidad global disminuyó del 11.6% en el primer mes al 1.4% en el último mes evaluado, reflejando una progresiva y significativa tendencia a la baja (p para la tendencia <0.001). La edad de los pacientes ha cambiado con el tiempo, habiendo alcanzado su pico en junio. La mayoría de cambios en el uso de antivirales y antiinflamatorios se han documentado. La edad (OR 1.1; CI 1.11.12), cardiopatía crónica (OR 1.7; CI 1.12.9), dímero-D>700 ng/mL (OR 2.3; CI 1.34.1), ferritina>489 ng/mL (OR 1.9; CI 1.53.2), PCR>7 mg/dL (OR 2.6; CI 1.54.6), y una menor duración desde el inicio de síntomas a la hospitalización (OR 1.11; CI 1.041.17) fueron factores asociados a la mortalidad intrahospitalaria a 30 días. Por el contrario, el ingreso hospitalario previo en los últimos meses (OR 0.80; CI 0.650.98) se asoció significativamente a una menor mortalidad. DISCUSIÓN: La mortalidad intrahospitalaria ha disminuido en los pacientes con COVID-19 durante los últimos meses, incluso siendo similares las características de los pacientes. Algunos cambios realizados en el manejo de estos pacientes podrían explicar esta tendencia decreciente. Nuestro estudio aporta datos actualizados en la mortalidad de los pacientes hospitalizados con COVID-19, que podrían ser útiles de cara a establecer unos cuidados estándar de calidad. FINANCIACIÓN: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme, EDRD. PPA [CM18/00132], NGP [FI19/00133] y CGV [FIS PI18/01061], han recibido becas del Ministerio de Sanidad y Consumo, ISCIII.
RESUMO
In recent years, important epidemiologic changes have been described in hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infection (BSI), with increases in gram-negative bacilli and multidrug resistant (MDR) gram-negative bacilli. These changes have been linked to a worrisome increase in mortality. We aimed to define the risk factors for mortality of HSCT patients experiencing BSI. All episodes of BSI in patients with HSCT between 2008 and 2017 were prospectively collected. Multivariate analyses were performed. A total of 402 BSI episodes were documented in 293 patients who had undergone HSCT (75.4% allogenic, 32.3% autologous, 19.3% second HSCT). The median time from HSCT to BSI was 62 days (interquartile range, 9 to 182 days). Gram-positive cocci accounted for 56.7% of the episodes; gram-negative bacilli, for 42%. The most common microorganisms were coagulase-negative staphylococci (30.6%) and Pseudomonas aeruginosa (15.9%). MDR gram-negative bacilli caused 11.9% of all episodes. Clinical characteristics, source of BSI, etiology, and outcomes changed depending on time since HSCT. Globally, 26.6% of episodes were treated with inappropriate empiric antibiotic therapy, more frequently in BSI episodes caused by P. aeruginosa, MDR P. aeruginosa, and MDR gram-negative bacilli. The 30-day mortality was 19.2%. Independent risk factors for mortality were BSI occurring ≥30 days after HSCT (odds ratio [OR], 11.21; 95% confidence interval [CI], 4.63 to 27.19), shock (OR, 7.10; 95% CI, 2.98 to 16.94), BSI caused by MDR P. aeruginosa (OR, 4.45; 95% CI, 1.12 to 17.72), and inappropriate empiric antibiotic therapy for gram-negative bacilli or Candida spp. (OR, 3.73; 95% CI, 1.27 to 10.89). HSCT recipients experiencing BSI have high mortality related to host and procedure factors, causative microorganism, and empiric antibiotic therapy. Strategies to identify HSCT recipients at risk of MDR P. aeruginosa and reducing inappropriate empiric antibiotic therapy are paramount to reduce mortality.