Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors.

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.

Dynamics of the Immune Response in Hospitalized SARS-CoV-2-infected Cancer Patients.

Seroconversion rates were compared between oncological and nononcological patients infected with SARS-CoV-2 during a 14-day hospitalization time. All COVID-19 non-oncological and solid malignancies patients reached 100% seroconversion at day 14, while less than half of the hematological patients were seroconverted at the same time point. Despite the limited number and variability of the patient's cohort, we conclude that there is a delayed seroconversion in the hematological malignancies group, which may be linked to changes in the hematological parameters, immune suppression and/or oncological treatments that are typically associated with these patients.

Effect of Combination Antibiotic Empirical Therapy on Mortality in Neutropenic Cancer Patients with Pseudomonas aeruginosa Pneumonia.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006−2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01−2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27−0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76−2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.

COVID-19 in HSCT recipients: a collaborative study of the Brazilian Society of Marrow Transplantation (SBTMO).

In the COVID-19 scenario, patients undergoing hematopoietic stem cell transplantation (HSCT) infected with SARS-CoV-2 may have an increased risk of death. Through a national multicenter study, we aimed to describe the impact of COVID-19 on the survival of HSCT recipients in Brazil. Eighty-six patients with a confirmed diagnosis of SARS-CoV-2 (92% by RT-PCR) were included. There were 24 children and 62 adults receiving an autologous (n = 25) and allogeneic (n = 61) HSCT for malignant (n = 72) and non-malignant (n = 14) disorders. Twenty-six patients died, (10 on autologous (38%) and 16 patients (62%) on allogeneic group). The estimated overall survival (OS) at day 40 was 69%. Adults had decreased OS compared to children (66% vs 79%, p = 0.03). The severity of symptoms at the time of diagnosis, ECOG score, laboratory tests (C-reactive protein, urea values) were higher in patients who died (p < 0.05). In conclusion, HSCT recipients infected with SARS-CoV-2 have a high mortality rate mainly in adults and patients with critical initial COVID-19 presentation. These findings show the fragility of HSCT recipients with SARS-CoV-2 infection. Therefore, the importance of adherence to preventive measures is evident, in addition to prioritizing the vaccination of family members and the HSCT team.

Essential properties and pitfalls of colorimetric Reverse Transcription Loop-mediated Isothermal Amplification as a point-of-care test for SARS-CoV-2 diagnosis.

BACKGROUND: SARS-CoV-2 Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) colorimetric detection is a sensitive and specific point-of-care molecular biology technique used to detect the virus in only 30 min. In this manuscript we have described a few nuances of the technique still not properly described in the literature: the presence of three colors clusters; the correlation of the viral load with the color change; and the importance of using an internal control to avoid false-negative results. METHODS: To achieve these findings, we performed colorimetric RT-LAMP assays of 466 SARS-CoV-2 RT-qPCR validated clinical samples, with color quantification measured at 434 nm and 560 nm. RESULTS: First we determinate a sensitivity of 93.8% and specificity of 90.4%. In addition to the pink (negative) and yellow (positive) produced colors, we report for the first time the presence of an orange color cluster that may lead to wrong diagnosis. We also demonstrated using RT-qPCR and RT-LAMP that low viral loads are related to Ct values > 30, resulting in orange colors. We also demonstrated that the diagnosis of COVID-19 by colorimetric RT-LAMP is efficient until the fifth symptoms day when the viral load is still relatively high. CONCLUSION: This study reports properties and indications for colorimetric RT-LAMP as point-of-care for SARS-CoV-2 diagnostic, reducing false results, interpretations and optimizing molecular diagnostics tests application.

Predictive factors, outcomes, and molecular epidemiology of Clostridioides difficile diarrhea in Brazilian hospitals.

Little is known about the role of lineage of strains of Clostridioides difficile (CD) on the clinical presentation of CD infection (CDI) in Latin America, especially regarding the treatment response. We conducted a multicenter, prospective study to investigate the predictive factors and treatment outcomes of CDI in hospitalized patients and to performed phenotypical and molecular characterization of CD strains. A total of 361 diarrheic patients at 5 hospitals from different regions of the country were enrolled. All stool samples were tested for glutamate dehydrogenase (GDH), toxins A and B, and toxin genes using a nucleic acid amplification test (NAAT). Specimens were cultured and susceptibility profile and whole-genome sequencing (WGS) were performed. CDI positivity was 15% (56/377). Predictive factors for CDI were prior use of meropenem (OR 4.09, 95% CI 2.097-7.095; p<0.001), mucus in stools (OR 3.29; 95% CI 1.406-7.722; p=0.006) and neutrophil left-shift with >20% of bands (OR 3.77; 95% IC 1.280-11.120; p=0.016). Overall mortality was 19%, with no deaths attributed to CDI. Oral metronidazole was used in 74% of cases, with 85% of cure and 14% of recurrence. A total of 35 CD isolates were recovered, all of them susceptible to metronidazole and vancomycin. The WGS revealed 17 different STs, six of which were novel. ST42 was the most common ST and hypervirulent strains were not found. Severe CDI were caused by ST42, ST5, ST8, ST48, ST33 and a novel ST667. The ermB gene was more frequently found in isolates of ST42 (p=0.004).

Multicenter study of the epidemiology of Clostridioides difficile infection and recurrence in southern Brazil.

Clostridioides (Clostridium) difficile is the main etiology underlying antibiotic-associated diarrhea (AAD). Still, few Brazilian data are available on this infection. The aims of this multicenter study were to identify the prevalence, clinical characteristics, and outcomes of C. difficile infection (CDI) in patients with antibiotic associated diarrhea at eight hospitals in Curitiba, southern Brazil, during the years 2017-2019. Stool samples were tested using enzyme immunoassay for glutamate dehydrogenase antigen (GDH) and A/B toxins. Positive GDH samples were further evaluated by real-time polymerase chain reaction (PCR) for the presence of genes encoding toxin B (tcdB), binary toxin (cdt), and marker of hypervirulent C. difficile strain (tcdC deletion). The prevalence of CDI in 351 patients with AAD included in the study was 17.7% (n = 62). Among the CDI cases, tcdB was positive in all 62 stool samples, while cdt was positive in 10 samples, and tcdC deletion was positive in only two. Carriage of carbapenem-resistant Gram-negative bacilli, previous hospitalization, and use of broad-spectrum cephalosporin and carbapenem were associated with CDI. Among patients with CDI, 64.5% presented with severe diarrhea, and 8% (5/62) progressed with colitis and required intensive care. The 30-day mortality was 24% (15/62), and the CDI-associated mortality was 4.8% (3/62). Overall, 83.8% (52/62) of the patients achieved primary cure, and 20.8% of the evaluated patients (10/48) presented CDI recurrence. The treatment administered was not significantly associated with the 60-day recurrence or mortality. In conclusion, we reported in this study data of prevalence and recurrence rates of CDI in patients with AAD and evaluated the number of severe cases and infection-related mortality, which were up to now unknown in Southern Brazilian hospitals.

Infectious complications in pediatric allogeneic hematopoietic stem cell transplantation recipients-A retrospective clinical and epidemiological cohort study.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an important therapeutic strategy for several hematologic diseases. In the absence of a matched related donor, allogeneic HSCT has been associated with increased risk of infectious complications. Here, we present the clinical and epidemiological characteristics of early infectious complications in children undergoing HSCT from Southern Brazil. METHODS: This is a retrospective unicentric cohort study of infections in all children receiving their first HSCT during the period between 2010 and 2017. RESULTS: Data from 292 patients were analyzed; bone marrow failures (52.7%) comprised most of the baseline diagnosis. Bone marrow (BM) was the stem cell source in 254 (87%), followed by cord blood (CB) in 34 (11.6%) children. The use of alternative donors (77.8%) and presence of acute graft-vs-host disease (GVHD) (23.6%) were associated with an increased risk of viral and fungal infection. Bacterial infection was observed in 79 patients (27%); 220 patients (75.3%) were diagnosed with viral infection, and 35 patients (12%) developed fungal infection. The presence of fungal disease together with the presence of multiple infections during follow-up was associated with an increased risk of death (P < .001). CONCLUSIONS: The clinical profile of HSCT-related infections in this cohort suggests that prognosis in allogeneic HSCT is influenced by the source of stem cells (CB having worse prognosis), presence of acute GVHD and complications arising from fungal infections. The appropriate management of these factors has the potential to improve the overall prognosis rates in pediatric allogeneic HSCT recipients.

Impact of antibiotic resistance on outcomes of neutropenic cancer patients with Pseudomonas aeruginosa bacteraemia (IRONIC study): study protocol of a retrospective multicentre international study.

INTRODUCTION: Pseudomonas aeruginosa (PA) has historically been one of the major causes of severe sepsis and death among neutropenic cancer patients. There has been a recent increase of multidrug-resistant PA (MDRPA) isolates that may determine a worse prognosis, particularly in immunosuppressed patients. The aim of this study is to establish the impact of antibiotic resistance on the outcome of neutropenic onco-haematological patients with PA bacteraemia, and to identify the risk factors for MDRPA bacteraemia and mortality. METHODS AND ANALYSIS: This is a retrospective, observational, multicentre, international study. All episodes of PA bacteraemia occurring in neutropenic onco-haematological patients followed up at the participating centres from 1 January 2006 to 31 May 2018 will be retrospectively reviewed. The primary end point will be overall case-fatality rate within 30 days of onset of PA bacteraemia. The secondary end points will be to describe the following: the incidence and risk factors for multidrug-resistant and extremely drug-resistant PA bacteraemia (by comparing the episodes due to susceptible PA with those produced by MDRPA), the efficacy of ceftolozane/tazobactam, the rates of persistent bacteraemia and bacteraemia relapse and the risk factors for very early (48 hours), early (7 days) and overall (30 days) case-fatality rates. ETHICS AND DISSEMINATION: The Clinical Research Ethics Committee of Bellvitge University Hospital approved the protocol of the study at the primary site. To protect personal privacy, identifying information of each patient in the electronic database will be encrypted. The processing of the patients' personal data collected in the study will comply with the Spanish Data Protection Act of 1998 and with the European Directive on the privacy of data. All data collected, stored and processed will be anonymised. Results will be reported at conferences and in peer-reviewed publications.

Sepsis risk assessment: a retrospective analysis after a cognitive risk management robot (Robot Laura®) implementation in a clinical-surgical unit

Abstract Introduction This study aimed at evaluating the impact of the implementation of a cognitive robot (Robot Laura™) on processes related to the identification and care of patients with risk of sepsis in a clinical-surgical unit of a private hospital in Curitiba-PR. Methods The study data were obtained from the retrospective review of medical records of patients identified with infection and/or sepsis, in the period of six months before and after the implementation of such technology in the hospital. In addition, the Average Attendance Time (AAT) was obtained from the autonomous reading of the robot. Results The average time/median until antibiotic prescription from the first identified sign of infection, with or without sepsis, was 390/77 and 109/58 minutes, respectively, in the six months before and after implementation of the technology. However, this difference was not statistically significant (p = 0.85). Regarding AAT, it was possible to observe a reduction from 305 to 280 minutes when comparing the periods of six months before and after the implementation of the technology (p = 0.02). Conclusion Technologies such as this may be promising in helping healthcare professionals to identify risky situations for patients, as well as in assisting them to optimize the care required. However, further studies, with a greater number of subjects and with different scenarios, are necessary to consistently validate the results found.

Prevalência de prolapso de valva mitral e doença tireoidiana em pacientes com artrite reumatóide de um hospital universitário / Mitral valve prolapse and thyroid diseases in patients with rheuma-toid arthritis in a university hospital

A correlação entre doença auto-imune tireoidiana e artrite reumatóide tem sido demonstrada de longa data. A incidência de prolapso de valva mitral é maior em populações com doença tireoidiana. Acredita-se haver algum componente auto-imune relacionado ao prolapso de valva mitral. Nesse estudo foram avaliados 203 prontuários de pacientes com Artrite reumatóide com ecocardiograma com o objetivo de estabelecer a prevalência de prolapso de valva mitral e doença tireoidiana nessa população. Desses 19 (9,3%) eram homens e 184 (90,6%) eram mulheres. A idade média foi de 53,50±13.67 anos) e o tempo médio de doença de 102±105.8 meses. O prolapso de valva mitral foi visto em 18 (8,86%) pacientes. A avaliação da função tireoidiana foi realizada em 186 indivíduos e desses 3 (1,6%) tinham hipertireoidismo, 28 (15,05%) hipotireoidismo e 155 (83,33%) eram eutireoideos. Pacientes com prolapso de válvula mitral não diferenciaram dos sem prolapso quanto à presença do látex (p=0,5), titulo do látex (p=0,51), presença de FAN (p=0,76), presença de hipotireoidismo (p=0,47), sexo (p=1,0) e idade de aparecimento da doença (p=0,1). Pacientes com prolapso de válvula mitral tinham artrite reumatóide de maior duração (p=0,0021). Conclusão: Os pacientes de artrite reumatóide com prolapso de valva mitral não se diferenciam da população sem prolapso quanto a sexo, idade de início da artrite reumatóide, presença e titulo do fator reumatóide, presença de FAN e de hipotireoidismo.

There is a well established correlation between auto-immune thyroid diseases and rheuma-toid arthritis. The mitral valve prolapse incidence is higher among the patients with thyroid diseases and it´s believed that there is an auto-immune component in its origins. The objective of this study was to explore the prevalence of mitral valve prolapse and thyroid disease in 203 patients with rheumatoid arthritis. The results showed that 19 (9, 3%) were men and 184 (90,6%) were women. The average age was 53, 50±13.67 years and the average time of disease was 102±105.8 months. The mitral valve prolapse prevalence was 8, 86% (18 pa-tients). The thyroid function was studied in 186 patients. Among these, 3 (1, 6%) had hyperthyroidism, 28 (15, 05%) hypothyroidism and in 155 (83, 33%) the thyroid function were normal. There was no difference between individuals with mitral valve prolapse and without on rheumatoid factor presence (p=0,5), latex title (p=0,51), antinuclear antibody presence (p=0,76), hipothyroidism (p=0,47), gender (p=1,0) and age of rheumatoid arthritis onset (p=0,1). Patients with mitral valve prolapse had longer disease duration (p=0,0021). Conclusion: The rheumatoid arthritis patients with mitral valve prolapse from this study have no significant differences from the population without mitral valve prolapse in gender, age of disease onset, presence and levels of rheumatoid factor, presence of antinuclear anti-bodies and hypothyroidism.