Comparing the Real-World Use of Isavuconazole to Other Anti-Fungal Therapy for Invasive Fungal Infections in Patients with and without Underlying Disparities: A Multi-Center Retrospective Study.

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with underlying malignancies and prior transplants. FDA approved Isavuconazole as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. This study aims to compare the real-world clinical outcomes and safety of isavuconazole to voriconazole and an amphotericin B-based regimen in patients with underlying malignancies and a transplant. In addition, the response to anti-fungal therapy and the outcome were compared among patients with a disparity (elderly, obese patients, patients with renal insufficiency and diabetes mellitus) versus those with no disparity. We performed a multicenter retrospective study, including patients with cancer diagnosed with an invasive fungal infection, and treated primarily with isavuconazole, voriconazole or amphotericin B. Clinical, radiologic findings, response to therapy and therapy related adverse events were evaluated during 12 weeks of follow-up. We included 112 patients aged 14 to 77 years, and most of the IFIs were classified into definite (29) or probable (51). Most cases were invasive aspergillosis (79%), followed by fusariosis (8%). Amphotericin B were used more frequently as primary therapy (38%) than isavuconazole (30%) or voriconazole (31%). Twenty one percent of the patients presented adverse events related to primary therapy, with patients receiving isavuconazole presenting less adverse events when compared to voriconazole and amphotericin (p < 0.001; p = 0.019). Favorable response to primary therapy during 12 weeks of follow-up were similar when comparing amphotericin B, isavuconazole or voriconazole use. By univariate analysis, the overall cause of mortality at 12 weeks was higher in patients receiving amphotericin B as primary therapy. However, by multivariate analysis, Fusarium infection, invasive pulmonary infection or sinus infection were the only independent risk factors associated with mortality. In the treatment of IFI for patients with underlying malignancy or a transplant, Isavuconazole was associated with the best safety profile compared to voriconazole or amphotericin B-based regimen. Regardless of the type of anti-fungal therapy used, invasive Fusarium infections and invasive pulmonary or sinus infections were the only risk factors associated with poor outcomes. Disparity criteria did not affect the response to anti-fungal therapy and overall outcome, including mortality.

Abscesso cerebral em escolar com cardiopatia congênita cianogênica complexa: quando pensar em neurotuberculose? / Brain abscess in a schoolchild with complex cyanotic congenital heart disease: when to think about neurotuberculosis?

INTRODUÇÃO E/OU FUNDAMENTOS: Crianças portadoras de cardiopatias congênitas cianogênicas podem evoluir com diversas complicações secundárias à hipoxemia crônica. A policetemia e hiperviscosidade sanguínea podem levar à formação de trombos e microtrombos na microcirculação de vários órgãos e sistemas, incluindo o sistema nervoso central, sendo um fator de risco para a formação e desenvolvimento de abcessos cerebrais. RELATO DO CASO: Menino, 8 anos, 16.4 kg, com diagnóstico cardiológico de inversão ventricular, atresia pulmonar, CIV ampla não relacionada e PCA. Aos 4 meses, submetido à ligadura e secção do canal arterial e interposição de tubo VD-TP (PTFE 8 mm) com bandagem. Aos 3 anos, realizada angioplastia do tubo e, aos 5, oclusão de colaterais sistêmico-pulmonares, ambas por via percutânea. Durante toda a evolução, manteve SO2 basal de 75-80%. Aos 7 anos, admitido via pronto-socorro por febre hár 14 dias, cefaleia, confusão mental e hipoxemia grave (SO2 50%). Realizada extensa investigação infecciosa. Ecocardiograma: ausência de vegetações. TC crânio: lesão hipodensa encapsulada em região occipital. Hemograma: policitemia. Hemocultura: Stenotrophomonas maltophilia multissensível. Líquor cefalorraquidiano: celularidade aumentada (polimorfonucleares), proteinorraquia aumentada, glicorraquia e ADA normais e culturas negativas. Iniciada terapia antibiótica e antifúngica de amplo espectro, sem regressão da febre após 1 mês. Revisão detalhada do caso constatou história materna de tratamento incompleto para tuberculose pulmonar, sem profilaxia familiar. Na ocasião, com 1 ano de idade, paciente apresentara febre e tosse por 2 meses, sem investigação adequada. Aos 3 anos, apresentou PPD fortemente reagente. Por questões sociais, houve má adesão ao serviço ao longo de todo seguimento. Diante da falha terapêutica inicial, da somatória de fatores de riscos (cianose e desnutrição crônicas, epidemiologia positiva e risco social) e da imagem tomográfica sugestiva, foi instituído tratamento empírico para neurotuberculose (rifampicina, isoniazida e pirazinamida), obtendo-se resposta clínica inicial satisfatória e regressão do abscesso cerebral, permitindo alta hospitalar. CONCLUSÕES: A neurotuberculose é um importante diagnóstico diferencial na investigação de abscessos cerebrais em pacientes cianóticos crônicos. Apesar dos agentes mais comuns nesse contexto serem espécies de estafilococos e estreptococos, a alta incidência da Mycobacterium tuberculosis a alta incidência da Mycobacterium tuberculosis, sobretuda na falha terapêutica.

Distinct systemic immune networks define severe vs. mild COVID-19 in hematologic and solid cancer patients.

Introduction: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has impacted health across all sectors of society. A cytokine-release syndrome, combined with an inefficient response of innate immune cells to directly combat the virus, characterizes the severe form of COVID-19. While immune factors involved in the development of severe COVID-19 in the general population are becoming clearer, identification of the immune mechanisms behind severe disease in oncologic patients remains uncertain. Methods: Here we evaluated the systemic immune response through the analysis of soluble blood immune factors and anti-SARS-CoV-2 antibodies within the early days of a positive SARS-CoV-2 diagnostic in oncologic patients. Results: Individuals with hematologic malignancies that went on to die from COVID-19 displayed at diagnosis severe leukopenia, low antibody production against SARS-CoV-2 proteins, and elevated production of innate immune cell recruitment and activation factors. These patients also displayed correlation networks in which IL-2, IL-13, TNF-alpha, IFN-gamma, and FGF2 were the focal points. Hematologic cancer patients that showed highly networked and coordinated anti-SARS-CoV-2 antibody production, with central importance of IL-4, IL-5, IL-12A, IL-15, and IL-17A, presented only mild COVID-19. Conversely, solid tumor patients that had elevated levels of inflammatory cytokines IL-6, CXCL8, and lost the coordinate production of anti-virus antibodies developed severe COVID-19 and died. Patients that displayed positive correlation networks between anti-virus antibodies, and a regulatory axis involving IL-10 and inflammatory cytokines recovered from the disease. We also provided evidence that CXCL8 is a strong predictor of death for oncologic patients and could be an indicator of poor prognosis within days of the positive diagnostic of SARS-CoV-2 infection. Conclusion: Our findings defined distinct systemic immune profiles associated with COVID-19 clinical outcome of patients with cancer and COVID-19. These systemic immune networks shed light on potential immune mechanisms involved in disease outcome, as well as identify potential clinically useful biomarkers.

Excess mortality by specific causes of deaths in the city of São Paulo, Brazil, during the COVID-19 pandemic.

BACKGROUND: To investigate the excess of deaths by specific causes, in the first half of 2020 in the city of São Paulo-Brazil, during the COVID-19 pandemic. METHODS: Ecological study conducted from 01/01 to 06/30 of 2019 and 2020. Population and mortality data were obtained from DATASUS. The standardized mortality ratio (SMR) by age was calculated by comparing the standardized mortality rate in 2020 to that of 2019, for overall and specific mortality. The ratio between the standardized mortality rate due to COVID-19 in men as compared to women was calculated for 2020. Crude mortality rates were standardized using the direct method. RESULTS: COVID-19 was responsible for 94.4% of the excess deaths in São Paulo. In 2020 there was an increase in overall mortality observed among both men (SMR 1.3, 95% CI 1.17-1.42) and women (SMR 1.2, 95% CI 1.06-1.36) as well as a towards reduced mortality for all cancers. Mortality due to COVID-19 was twice as high for men as for women (SMR 2.1, 95% CI 1.67-2.59). There was an excess of deaths observed in men above 45 years of age, and in women from the age group of 60 to 79 years. CONCLUSION: There was an increase in overall mortality during the first six months of 2020 in São Paulo, which seems to be related to the COVID-19 pandemic. Chronic health conditions, such as cancer and other non-communicable diseases, should not be disregarded.

Differences in mortality of cancer patients with COVID-19 in a Brazilian cancer center.

INTRODUCTION: To analyze COVID-19 mortality in cancer patients and associated factors such as age, sex, type of insurance, situation at COVID-19 diagnosis, and cancer histology during the pandemic at a cancer center in Brazil. METHODS: Cross-sectional study carried out from April 02, 2020 to August 31, 2020 at A.C. Camargo Cancer Center (ACCCC), in São Paulo, Brazil. Cases were extracted from the Hospital Cancer Registry. COVID-19 lethality rates by histology were calculated; multiple logistic regression was used to identify factors associated with COVID-19 mortality. The log-rank test was applied to compare the survival curves for each variable. RESULTS: Of the 411 patients analyzed, 51 (12.4%) died due to COVID-19. Death occurred at an average age of 63 years. The fatality rate was higher for lung (0.333) and hematological (0.213) cancers and was associated with age over 60 years. The greatest chances of death from COVID-19 were in cases of lung (odds ratio, OR, 4.05, 95% confidence interval, CI 1.33-12.34) and hematological (OR 2.17, 95% CI 0.96-4.90) cancers, and in patients currently undergoing cancer treatment (OR 2.77, 95% CI 1.25-6.13). There were no statistical differences in survival by sex, age group, type of insurance, situation at the diagnosis of COVID-19, and histology of cancer for COVID-19. CONCLUSIONS: Mortality due to COVID-19 in cancer patients is heterogeneous. These findings reinforce the need for individualized strategies for the management of different types of cancer that reduce the risk of death from COVID-19.

Is it cost effective to use a 2% chlorhexidine wipes bath to reduce central-line associated blood stream infection? A quasi-experimental study.

BACKGROUND: Bathing with 2% chlorhexidine (CHG) wipes is an important measure regarding infection prevention in critically ill patients. The aim of this study was to evaluate the impact of CHG wipes bath to prevent central-line associated bloodstream infection (CLABSI) in critically ill patients and determine if such measure is cost-saving. METHODS: a quasi-experimental study, conducted from July 2017 to April 2019. Daily bath with 2% CHG was used in all patients at the unit in the intervention period. The following were evaluated: CLABSI incidence density in both periods, 30- day mortality, guided antimicrobials used to treat CLABSI and 2% CHG costs. RESULTS: CLABSI incidence density dropped from 8.69 to 1.83 per 1.000 central line-days (p = 0.001), mainly by Klebsiella pneumoniae Carbapenen Resistant (Kp-KPC) (p = 0.05). Costs with guided antimicrobials for the treatment in pre-intervention were US$ 46,114.36, and in the intervention period, US$ 4,177.50. The 2% CHG monthly cost was US$ 2,698.00, achieving 30% savings when comparing both periods. DISCUSSION: An expressive reduction of 79% in CLABSI incidence density was observed, mainly due to Kp-KPC infection and also a reduction in guided antimicrobial costs. CONCLUSIONS: Bathing with 2% CHG led to evident CLABSI reduction.

Is it cost effective to use a 2% chlorhexidine wipes bath to reduce central-line associated blood stream infection? A quasi-experimental study

BACKGROUND: Bathing with 2% chlorhexidine (CHG) wipes is an important measure regarding infection prevention in critically ill patients. The aim of this study was to evaluate the impact of CHG wipes bath to prevent central-line associated bloodstream infection (CLABSI) in critically ill patients and determine if such measure is cost-saving. METHODS: a quasi-experimental study, conducted from July 2017 to April 2019. Daily bath with 2% CHG was used in all patients at the unit in the intervention period. The following were evaluated: CLABSI incidence density in both periods, 30- day mortality, guided antimicrobials used to treat CLABSI and 2% CHG costs. RESULTS: CLABSI incidence density dropped from 8.69 to 1.83 per 1.000 central line-days (p = 0.001), mainly by Klebsiella pneumoniae Carbapenen Resistant (Kp-KPC) (p = 0.05). Costs with guided antimicrobials for the treatment in pre-intervention were US$ 46,114.36, and in the intervention period, US$ 4,177.50. The 2% CHG monthly cost was US$ 2,698.00, achieving 30% savings when comparing both periods. DISCUSSION: An expressive reduction of 79% in CLABSI incidence density was observed, mainly due to Kp-KPC infection and also a reduction in guided antimicrobial costs. CONCLUSIONS: Bathing with 2% CHG led to evident CLABSI reduction.

Coronary artery bypass surgery in patients with COVID-19: What have we learned ?

COVID-19 caused by the novel coronavirus SARS-CoV-2 led to the pandemic, causing unprecedented health and social crisis worldwide. Acute coronary syndromes patients, especially when coronary artery bypass graft (CABG) surgery is needed, may present with higher severity risk if affected by COVID-19. Extracorporeal circulation leads to activation of endothelium and microcirculatory network, which activates the coagulation, platelet aggregation and inflammation 1. COVID-19 may also course with severe inflammation, massive secretion of inflammatory cytokines, plaque rupture and a procoagulant state 2. Therefore, it is advisable to postpone surgeries interventions when possible. However, our institution is a public tertiary referral hospital for high-risk cardiovascular patients even in SARS-CoV-2 pandemic. We describe a series of thirteen high risk coronary artery disease patients submitted to CABG and who had COVID-19 infection during the same hospitalization, six patients had COVID-19 before surgery, three patients were operated with active infection and four patients were infected after surgery…

Sacroileíte como primeira manifestação clínica de endocardite infecciosa - relato de caso / Sacroiliitis as the first clinical manifestation of infective endocarditis - case report

A endocardite infecciosa (EI) permanece sendo uma doença altamente prevalente. Muitas vezes, há dificuldade em seu diagnóstico, devido às várias manifestações sistêmicas sugestivas de outras patologias. As culturas podem encontrar-se negativas em 10-15% dos casos. Paciente masculino, 60 anos, branco, HAS, com diagnóstico prévio de prolapso de valva mitral, sem outras comorbidades. Refere ter iniciado quadro de febre aferida e, após cinco dias, dor no quadril à esquerda com piora à deambulação. Procurou pronto socorro (PS) geral, onde realizou constatou-se alteração laboratorial sugestiva de infecção. Procedeu-se a internação hospitalar, com realização de ressonância magnética (RM), recebendo diagnóstico de sacroileíte. Foi tratado com Ceftriaxona durante 7 dias, com melhora do da febre. Recebeu alta e após, iniciou seguimento ambulatorial com reumatologista, sendo descartada etiologia reumática. Foi realizado ecocardiograma transesofágico (ECOTE), devido a ausculta de sopro sistólico em foco mitral e quadro febril recente, o qual demonstrava insuficiências mitral e aórtica importantes e presença de vegetação em valva mitral. Referia procedimento odontológico cinco dias antes do início da febre. Foi encaminhado ao PS do nosso serviço, onde foi internado e repetido ECOTE, no qual não foi visualizada vegetação, mas sim ruptura de cordoalha tendínea. Iniciada antibioticoterapia empírica com Ceftriaxona, Oxacilina e Gentamicina, tendo cursado com cinco pares de hemoculturas negativas. Solicitada fundoscopia, com presença de Manchas de Roth. Paciente encaminhado a cirurgia para dupla troca valvar, com material enviado a anatomo-patológico, com diagnóstico de EI. Percebe-se, então, o caso de um paciente previamente hígido, apresentando quadro febril, sopro à ausculta cardíaca e artrite séptica. Não houve a confirmação de EI pelos Critérios de Duke. Todavia, analisando-se os critérios de Duke Modificados, o paciente enquadra-se em endocardite provável, devido à presença de três critérios menores (febre, fator predisponente e fenômenos imunológicos). Na vigência da suspeita clínica, o diagnóstico do paciente só foi possível devido à insistência em buscar critérios menores que corroborassem com a hipótese, mostrando assim a importância de valorizar os mesmos para evitar casos não diagnosticados.