RESUMO
PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.
Assuntos
Antibacterianos , Bacteriemia , Infecções por Enterobacteriaceae , Neutropenia , Humanos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Neutropenia/complicações , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/mortalidade , Infecções por Enterobacteriaceae/microbiologia , Adulto , Idoso , Enterobacteriaceae/efeitos dos fármacos , Resultado do Tratamento , Tempo de Internação , Neoplasias Hematológicas/complicações , Adulto JovemRESUMO
BACKGROUND: Invasive Aspergillosis (IA) is a disease of significant clinical relevance, especially among immunosuppressed patients, and is associated with high mortality rates. In this study, we evaluated the epidemiological features and clinical outcomes in children and adults with IA. METHODS: This was an observational, multicentre, prospective surveillance study of inpatients with IA at two different hospitals in Campinas, Brazil, between 2018 and 2021. RESULTS: A total of 44 patients were identified (54.5% males), with a median age of 42 years (interquartile range (IQR):19.25-59 years, varying between 1 and 89 years). The following baseline conditions were identified: 61.4% were oncohaematological patients and 20.5% were solid organ transplant recipients. Among oncohaematological patients, 77.8% exhibited severe or persistent neutropenia. The median time between the onset of neutropenia and the diagnosis of fungal infection was 20 days (IQR: 10.5-26 days; range, 0-68 days). The interval between neutropenia onset and fungal infection was longer in paediatric than in general hospital (average, 29 vs. 13.4 days; median 26 vs 11 days; p=0.010). After the diagnosis of IA, the survival rates were 44.2% and 30.0% at 180 and 360 days, respectively. Survival was greater in patients aged ≤ 21 years (p = 0.040; log-rank test). They observed no difference in IA mortality related to COVID-19 pandemic. CONCLUSION: High mortality associated with IA was observed in both hospitals. Individuals over the age of 21 have a lower survival rate than younger patients.
Assuntos
Aspergilose , Infecções Fúngicas Invasivas , Micoses , Neutropenia , Masculino , Humanos , Criança , Adulto , Feminino , Brasil/epidemiologia , Estudos Prospectivos , Pacientes Internados , Pandemias , Fatores de Risco , Aspergilose/microbiologia , Micoses/epidemiologia , Neutropenia/complicações , Neutropenia/epidemiologia , Infecções Fúngicas Invasivas/epidemiologiaRESUMO
BACKGROUND: WHIM syndrome corresponds to an inborn error of innate and intrinsic immunity, characterized by: warts (Warts), Hypogammaglobulinemia, Infections and Myelocathexis, for its acronym in English. CASE REPORT: 4-year-old male, with severe neutropenia and B-cell lymphopenia from birth, without severe infections or warts; the panel genetic sequencing study of primary immunodeficiencies with the CXCR4 c.1000C>T (p.Arg334*) variant, which is associated with WHIM syndrome. CONCLUSIONS: The diagnosis of severe neutropenia from birth should include the search for inborn errors of immunity, through genetic sequencing studies, especially in asymptomatic or oligosymptomatic patients.
ANTECEDENTES: El síndrome WHIM corresponde a un error innato de la inmunidad innata e intrínseca, caracterizada por verrugas (Warts), hipogammaglobulinemia, infecciones y mielocatexis, por sus siglas en inglés. REPORTE DE CASO: Paciente masculino de 4 años, con neutropenia severa y linfopenia de células B desde el nacimiento, sin infecciones severas ni verrugas. El estudio de secuenciación genética informó la variante CXCR4 c.1000C>T (p.Arg334*), relacionada con el síndrome de WHIM. CONCLUSIÓN: El diagnóstico de neutropenia severa desde el nacimiento debe incluir la búsqueda de errores innatos de la inmunidad, mediante estudios de secuenciación genética, especialmente en pacientes asintomáticos u oligosintomáticos.
Assuntos
Agamaglobulinemia , Síndromes de Imunodeficiência , Neutropenia , Doenças da Imunodeficiência Primária , Verrugas , Masculino , Humanos , Pré-Escolar , Doenças da Imunodeficiência Primária/diagnóstico , Verrugas/diagnóstico , Verrugas/etiologia , Agamaglobulinemia/diagnóstico , Neutropenia/complicações , Neutropenia/diagnóstico , Neutropenia/genética , Síndromes de Imunodeficiência/diagnósticoRESUMO
BACKGROUND: Bloodstream infections are a leading cause of death in patients who undergo hematopoietic stem cell transplantation (HSCT) and are more severe when caused by multidrug-resistant (MDR) bacteria. This study proposed to investigate if colonization by MDR bacteria negatively affects the clinical outcomes in hematological patients after HSCT, as well as to evaluate possible risk factors for death due to bacteremia by the same colonizing agent. METHODS: A single-center retrospective cohort study was conducted with 405 hematological patients submitted to a single HSCT procedure between 2015 and 2021. Patients were classified as colonized (n = 132) or noncolonized (n = 273) based on the surveillance cultures from D-30 to D+30 of transplantation, and their relevant clinical and laboratory data were collected until D+100. RESULTS: Colonization by MDR bacteria increased blood culture positivity by all micro-organisms and also specifically by MDR bacteria, with a more pronounced effect when caused by carbapenemase-producing Klebsiella pneumoniae. Patients colonized with carbapenem-resistant K. pneumoniae had increased overall mortality (HR = 4.07, 95% CI 1.85-8.91, P = .0005) and had prolonged hospital length of stay in the context of autologous transplantation. Risk factors for death due to bacteremia by the same colonizing agent were neutropenia, colonization by carbapenem-resistant K. pneumoniae and use of high-dose total body irradiation in conditioning. CONCLUSION: Hematological patients colonized by MDR bacteria presented a higher incidence of bloodstream infections, and colonization by carbapenemase-producing K. pneumoniae was associated with reduced overall survival.
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Bacteriemia , Transplante de Células-Tronco Hematopoéticas , Neutropenia , Sepse , Humanos , Estudos Retrospectivos , Farmacorresistência Bacteriana Múltipla , Bacteriemia/microbiologia , Sepse/tratamento farmacológico , Neutropenia/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Klebsiella pneumoniae , Carbapenêmicos , Antibacterianos/uso terapêuticoRESUMO
INTRODUCTION: Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico. METHODS: A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval. RESULTS: 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352). CONCLUSIONS: The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.
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Infecções por HIV , Neutropenia , Pneumonia por Pneumocystis , Humanos , Adulto , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Estudos de Coortes , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/epidemiologia , Pneumonia por Pneumocystis/complicações , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , México/epidemiologia , Estudos Retrospectivos , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Neutropenia/complicaçõesRESUMO
BACKGROUND: Candida bloodstream infection (CBSI) is a growing problem among patients with cancer. AIM: To describe the main clinical and microbiological characteristics in patients with cancer who suffer CBSI. METHODS: We reviewed the clinical and microbiological characteristics of all patients with CBSI diagnosed between January 2010 and December 2020, at a tertiary-care oncological hospital. Analysis was done according to the Candida species found. Multivariate logistic regression analysis was used to determine the risk factors associated with 30-day mortality. RESULTS: There were 147 CBSIs diagnosed, 78 (53%) in patients with hematologic malignancies. The main Candida species identified were Candida albicans (n=54), Candida glabrata (n=40) and Candida tropicalis (n=29). C. tropicalis had been mainly isolated from patients with hematologic malignancies (79.3%) who had received chemotherapy recently (82.8%), and in patients with severe neutropenia (79.3%). Seventy-five (51%) patients died within the first 30 days, and the multivariate analysis showed the following risk factors: severe neutropenia, a Karnofsky Performance Scale score under 70, septic shock, and not receiving appropriate antifungal treatment. CONCLUSIONS: Patients with cancer who develop CBSI had a high mortality related with factors associated with their malignancy. Starting an empirical antifungal therapy the soonest is essential to increase the survival in these patients.
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Candidemia , Candidíase , Neoplasias Hematológicas , Neoplasias , Neutropenia , Humanos , Candida , Antifúngicos/uso terapêutico , Estudos Retrospectivos , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candida tropicalis , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/complicações , Neutropenia/tratamento farmacológico , Neoplasias Hematológicas/complicações , Fatores de RiscoRESUMO
Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.
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Antineoplásicos , Enterocolite Neutropênica , Enterocolite , Neoplasias , Neutropenia , Antineoplásicos/uso terapêutico , Criança , Enterocolite/complicações , Enterocolite/diagnóstico , Enterocolite/tratamento farmacológico , Enterocolite Neutropênica/diagnóstico , Enterocolite Neutropênica/tratamento farmacológico , Enterocolite Neutropênica/etiologia , Humanos , Hospedeiro Imunocomprometido , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/complicaçõesRESUMO
Resumen La enterocolitis neutropénica (ECN) es una enfermedad heterogénea de foco digestivo, pero afectación sistémica, que corresponde a una condición clínica grave que amenaza la vida de pacientes inmunocomprometidos, particularmente oncológicos pediátricos. De patogenia aún poco definida y aunque de causa multifactorial, la ECN se asocia a los efectos citotóxicos de la quimioterapia empleada y se caracteriza por la triada clásica que incluye fiebre, neutropenia y dolor abdominal, donde la principal injuria se localiza en la mucosa intestinal, provocando su alteración como barrera y facilitando la invasión bacteriana intramural. La ECN constituye un reto diagnóstico para el equipo tratante, que requiere ser oportuno y contar con apoyo de un óptimo laboratorio general e imagenológico, para iniciar un completo manejo multidisciplinario en unidades y centros de alta complejidad. Se presenta una revisión actualizada del tema incorporando aspectos epidemiológicos, factores de riesgo, elementos de apoyo diagnóstico, consideraciones terapéuticas y medidas de prevención a fin de aportar en el conocimiento de esta patología, y reducir morbimortalidad en estos pacientes.
Abstract Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.
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Humanos , Criança , Enterocolite Neutropênica/diagnóstico , Enterocolite Neutropênica/etiologia , Enterocolite Neutropênica/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/complicações , Antineoplásicos/uso terapêutico , Hospedeiro Imunocomprometido , Enterocolite/complicações , Enterocolite/diagnóstico , Enterocolite/tratamento farmacológicoRESUMO
Typhlitis, is also known as neutropenic enterocolitis, affects the cecum and distal ileum. It was frequently encountered in pediatric patients who were undergoing treatment for leukemia. Nonetheless, it can affect adult patients, regardless of the cause of the immunosuppression. We report the case of a 20-year-old patient who was receiving chemotherapy for Osteosarcoma, who had a 6-day history of nausea and vomiting, fever sensation, diarrhea, and diffuse abdominal pain. Physical examination was relevant for hemodynamic instability, a distended and tender abdomen predominantly in the right iliac fossa. The laboratory workup showed severe neutropenia, thrombocytopenia, and electrolyte disturbances. The image studies evidenced edema of the ascending colon and cecum. Treatment was started with vasopressor support, correction of electrolyte alterations, blood cell and platelet transfusion, G-CSF, hydration, broad spectrum antibiotic therapy, initially with adequate clinical and laboratory response. After a few days, he presented lower gastrointestinal bleeding which was treated by conservative management. In conclusion, typhlitis must be suspected in every patient developing neutropenia as a reaction to chemotherapy and who also presents gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and intense abdominal pain.