RESUMO
Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN). OBJECTIVE: To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group. METHOD: Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021. RESULTS: 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04). CONCLUSION: VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.
Assuntos
Antibacterianos , Bacteriemia , Hemocultura , Neutropenia Febril , Neoplasias , Humanos , Criança , Neoplasias/microbiologia , Estudos Prospectivos , Pré-Escolar , Neutropenia Febril/microbiologia , Neutropenia Febril/tratamento farmacológico , Chile/epidemiologia , Bacteriemia/microbiologia , Bacteriemia/epidemiologia , Bacteriemia/diagnóstico , Feminino , Masculino , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Adolescente , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/efeitos dos fármacosRESUMO
During last few decades, role of microbiota and its importance in several diseases has been a hot topic for research. The microbiota is considered as an accessory organ for maintaining normal physiology of an individual. These microbiota organisms which normally colonize several epithelial surfaces are known to secrete several small molecules leading to local and systemic effects on normal biological processes. The role of microbiota is also established in carcinogenesis as per several recent findings. The effects of microbiota on cancer is not only limited to their contribution in oncogenesis, but the overall susceptibility for oncogenesis and its subsequent progression, development of coinfections, and response to anticancer therapy is also found to be affected by microbiota. The information about microbiota and subsequent contributions of microbes in anticancer response motivated researchers in development of microbes-based anticancer therapeutics. We provided current status of microbiota contribution in oncogenesis with special reference to their mechanistic implications in different aspects of oncogenesis. In addition, the mechanistic implications of bacteria in anticancer therapy are also discussed. We conclude that several mechanisms of microbiota-mediated regulation of oncogenesis is known, but approaches must be focused on understanding contribution of microbiota as a community rather than single organisms-mediated effects.
Assuntos
Microbiota , Neoplasias/etiologia , Humanos , Neoplasias/microbiologiaRESUMO
El cáncer constituye la segunda de causa de muerte a nivel mundial y se estima será la primera, superando a las cardiovasculares. El estudio de sus bases moleculares ha permitido el desarrollo de la quimioterapia clásica, como de nuevas terapias biológicas. Si bien estos avances han redundado en un aumento en la sobrevida, no ha impactado en una menor incidencia de los casos. Esto último se debe, en parte, al desconocimiento de los múltiples factores carcinogénicos existentes y los efectos de sus interacciones para cada uno de los tumores. En este sentido, es interesante notar que, en los currículos de las escuelas de salud de las universidades chilenas, el cáncer u oncología como tal, no constituye una cátedra en sí misma, siendo sus contenidos tangencialmente abordados en distintos momentos de la formación; en biología celular, medicina interna y cirugía, entre otros. Con estos antecedentes, el propósito de este trabajo es ofrecer un propuesta sencilla y accesible para los estudiantes, respecto de los contenidos que, a nuestro juicio, son esenciales para comprender las bases biológicas de esta enfermedad y enfrentar con mejores conocimientos el ciclo clínico posterior. A continuación, el lector se encontrará con principios fundamentales de la biología humana normal (como el ciclo celular y el dogma central de la biología molecular), que permiten obtener una visión global de los mecanismos fisiológicos cuya desregulación conlleva a una neoplasia maligna. Luego se entregarán algunas definiciones amplias en relación con los conceptos de neoplasia, tumor benigno y maligno. Para, finalmente, abordar las principales etapas que permiten el desarrollo del cáncer; (i) iniciación, (ii) promoción y (iii) progresión. En esta última, se profundizará por separado, en angiogénesis, degradación de la matriz extracelular, migración y evasión de la respuesta inmune. Este trabajo no aborda materias relacionadas con la hipótesis metabólica del cáncer.
Cancer constitutes the second most common cause of death worldwide and is expected to become the leading one, even above cardiovascular diseases. The understanding of the cellular and molecular basis of cancer has led not only to the proper development of chemotherapy but also of target therapies. Although these advances are related with improved survival rates among cancer patients, it has poorly impacted its incidences. In this regard, the lack of knowledge regarding the impact that the several carcinogenic factors and their interactions have on different types of cancers may explain at least in part the difficulties to reduce incidence rates. However, is worth noticing that in several health schools of chilean universities, cancer does not constitute a formal course, being only partially approached during other courses, such as cell biology, internal medicine, and surgery. Thus, the aim of our work is to provide students a simple and resumed manuscript about essential topics necessary to understand the biological basis of cancer. First, the reader will find some fundamentals about human biology including the cell cycle and the central dogma of molecular biology, which offers an overview of the physiological mechanisms leading to malignant neoplasia. Then, we will provide current definitions of neoplasia, benign and malignant tumors are provided. Finally, the different stages of tumor progression will be approached to allow the understanding of cancer development. These stages include (i) initiation, (ii) promotion, and (iii) progression. For the last one, metastasis, angiogenesis, extracellular matrix degradation, migration, and immune evasion will also be addressed. This work will not consider the metabolic hypothesis of cancer.
Assuntos
Educação de Graduação em Medicina , Neoplasias/microbiologia , CurrículoRESUMO
Cancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Epidemiological studies have further demonstrated the efficacy of antibiotic therapy on the probability of patients' response to ICIs and predictability of the short-term survival of cancer patients. Disturbance to the intestinal microbiota significantly affects ICIs-mediated immune reconstitution and is considered a possible mechanism underlying the development of adverse effects during antibiotic-based ICIs treatment. Intestinal microbiota, antibiotics, and ICIs have gradually become important considerations for the titer of immunotherapy. In the case of immunotherapy, the rational use of antibiotics and intestinal microbiota is expected to yield a better prognosis for patients with malignant tumors.
Assuntos
Antibacterianos/administração & dosagem , Bactérias/imunologia , Microbioma Gastrointestinal , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Microambiente Tumoral , Humanos , Neoplasias/imunologia , Neoplasias/microbiologia , PrognósticoRESUMO
Streptococcus agalactiae is a recognized pathogen associated with infections in neonates, elderly, and immunocompromised adults, particularly those with cancer. In the present investigation, clinical-epidemiological features, multidrug resistance profiles, and virulence genes of S. agalactiae strains isolated from cancer patients were investigated. S. agalactiae capsular distribution assays demonstrated that Ia (43.6%) and V (23.6%) types were predominantly detected among 55 clinical isolates tested; only one strain (GBS1428) was capsular type III/ST-17. The fbsB and hylB genes were detected in all isolates, while the iag, lmb, and fbsA genes were detected in 94.5%, 91%, and 91% of oncological isolates, respectively. The combination of PI-1 and PI-2a was the most common (60%) among S. agalactiae strains isolated from oncologic patients. S. agalactiae strains were resistant to tetracycline (85.5%), erythromycin (9%), and clindamycin (5.5%). Norfloxacin non-susceptible was detected in 7.3% of S. agalactiae strains. Our findings reinforce the need for S. agalactiae control measures in Brazil, including cancer patients.
Assuntos
Neoplasias/complicações , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/genética , Streptococcus agalactiae/isolamento & purificação , Adolescente , Adulto , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Brasil/epidemiologia , Farmacorresistência Bacteriana Múltipla , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neoplasias/microbiologia , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/patogenicidade , Fatores de Virulência/genética , Adulto JovemRESUMO
Given the increasing evidence that the oral microbiome is involved in obesity, diabetes, and cancer risk, we investigated baseline oral microbiota profiles in relation to all-cancer incidence among nonsmoking women enrolled in a Texas cohort of first- and second-generation immigrants of Mexican origin. We characterized the 16Sv4 rDNA microbiome in oral mouthwash samples collected at baseline from a representative subset of 305 nonsmoking women, ages 20-75 years. We evaluated within- (alpha) and between-sample (beta) diversity by incident cancer status and applied linear discriminant analysis (LDA) effect size analysis to assess differentially abundant taxa. Diversity and candidate taxa in relation to all-cancer incidence were evaluated in multivariable-adjusted Cox regression models. Over 8.8 median years of follow-up, 31 incident cancer cases were identified and verified. Advanced age, greater acculturation, and cardiometabolic risk factors were associated with all-cancer incidence. Higher alpha diversity (age-adjusted P difference < 0.01) and distinct biological communities (P difference = 0.002) were observed by incident cancer status. Each unit increase in the Shannon diversity index yielded >8-fold increase in all-cancer and obesity-related cancer risk [multivariable-adjusted HR (95% confidence interval), 8.11 (3.14-20.94) and 10.72 (3.30-34.84), respectively] with similar findings for the inverse Simpson index. Streptococcus was enriched among women who did not develop cancer, while Fusobacterium, Prevotella, Mogibacterium, Campylobacter, Lachnoanaerobaculum, Dialister, and Atopobium were higher among women who developed cancer (LDA score ≥ 3; q-value < 0.01). This initial study of oral microbiota and overall cancer risk in nonsmoking Mexican American women suggests the readily accessible oral microbiota as a promising biomarker. PREVENTION RELEVANCE: Mexican American women suffer a disproportionate burden of chronic health conditions that increase cancer risk. Few investigations of the microbiome, a key determinant of host health, have been conducted among this group. Oral microbiota profiles may provide early and accessible cancer biomarker data on invasive bacteria or community disruptions.
Assuntos
Bactérias/patogenicidade , Disbiose/complicações , Americanos Mexicanos/estatística & dados numéricos , Microbiota , Boca/microbiologia , Neoplasias/epidemiologia , Adulto , Idoso , Disbiose/microbiologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias/microbiologia , Neoplasias/patologia , Prognóstico , Estudos Prospectivos , Texas/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: This study determined the prevalence of Candida spp. in the saliva of cancer patients. Furthermore, we assessed the antimicrobial activity of mouthwashes against the isolated strains and its susceptibility to amphotericin B and fluconazole. METHODS: Thirty-four cancer patients undergoing radiotherapy, chemotherapy alone or combined treatment were investigated for oral Candida spp. colonization and compared in regard to mucositis presence. The maximum inhibitory dilution was used to assess the antimicrobial activity of Periogard®, Cepacol® Cool Ice and 0.12 % Chlorhexidine Digluconate mouthwashes against the isolates. In parallel, susceptibility to amphotericin B and fluconazole was determined by agar-based E-test. Data did not adhere to normal distribution as inferred by the Shapiro-Wilk test and statistical analysis was conducted by non-parametric McNemar test (α0.05). RESULTS: Twenty-seven participants (79.4 %) were male, 19 (55.9 %) had mucositis and 9 (26.5 %) were colonized by Candida spp. 12 different strains of Candida spp. were isolated, being Candida albicans the most prevalent strain. Risk of Candida spp. colonization was increased by almost twofold among the participants with mucositis (odds ratio: 1.84; 95 % confidence interval: 0.37-9.07). Mouthwash Cepacol® Cool Ice presented better antimicrobial activity against Candida spp. while 0.12 % Chlorhexidine exhibited the worst activity. All strains were sensitive to amphotericin B, and 2 non-albicans strains were dose-dependent sensitive to fluconazole. CONCLUSION: Considering the increased risk of colonization byCandida spp. in patients with mucositis, and the emergence of antifungal drug resistance, the antiseptics use could benefit the maintenance of cancer patient's oral health.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Antissépticos Bucais/farmacologia , Neoplasias/microbiologia , Anfotericina B/farmacologia , Farmacorresistência Fúngica , Feminino , Fluconazol/farmacologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Prevalência , Saliva/microbiologiaRESUMO
BACKGROUND: Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE) infections are frequent and highly impact cancer patients. We developed and validated a scoring system to identify cancer patients harboring ESBL-PE at the National Institute of Cancer of Colombia. METHODS: We retrospectively analyzed medical records of 1695 cancer patients. Derivation phase included 710 patients admitted between 2013 to 2015, ESBL-PE positive culture (n = 265) paired by month and hospitalization ward with Non-ESBL-PE (n = 445). A crude and weighted score was developed by conditional logistic regression. The model was evaluated in a Validation cohort (n = 985) with the same eligibility criteria between 2016 to 2017. RESULTS: The score was based on eight variables (reported with Odds Ratio and 95% confidence interval): Hospitalization ≥7 days (5.39 [2.46-11.80]), Hospitalization during the previous year (4, 87 [2.99-7.93]), immunosuppressive therapy during the previous 3 months (2.97 [1.44-6.08]), Neutropenia (1.90 [1.12-3.24]), Exposure to Betalactams during previous month (1.61 [1.06-2.42]), Invasive devices (1.51 [1.012-2.25]), Neoplasia in remission (2.78 [1.25-1.17]), No chemotherapy during the previous 3 months (1.90 [1.22-2.97]). The model demonstrated an acceptable discriminatory capacity in the Derivation phase, but poor in the Validation phase (Recipient Operating Characteristic Curve: 0.68 and 0.55 respectively). CONCLUSIONS: Cancer patients have a high prevalence of risk factors for ESBL-PE infection. The scoring system did not adequately discriminate patients with ESBL-PE. In a high-risk population, other strategies should be sought to identify patients at risk of resistant ESBL-PE infection.
Assuntos
Infecções por Enterobacteriaceae/etiologia , Enterobacteriaceae/metabolismo , Neoplasias/complicações , beta-Lactamases/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Colômbia/epidemiologia , Enterobacteriaceae/patogenicidade , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/microbiologia , Razão de Chances , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
ABSTRACT Introduction: Multidrug-resistant gram-negative rods (MDR GNR) represent a growing threat for patients with cancer. Our objective was to determine the characteristics of and risk factors for MDR GNR bacteremia in patients with cancer and to develop a clinical score to predict MDR GNR bacteremia. Material and Methods: Multicenter prospective study analyzing initial episodes of MDR GNR bacteremia. Risk factors were evaluated using a multiple logistic regression (forward-stepwise selection) analysis including variables with a p < 0.10 in univariate analysis. Results: 394 episodes of GNR bacteremia were included, with 168 (42.6 %) being MDR GNR. Five variables were identified as independent risk factors: recent antibiotic use (OR = 2.8, 95 % CI 1.7-4.6, p = 0.001), recent intensive care unit admission (OR = 2.9, 95 % CI 1.1-7.8, p = 0.027), hospitalization ≥ 7 days prior to the episode of bacteremia (OR = 3.5, 95 % CI 2-6.2, p = 0.005), severe mucositis (OR = 5.3, 95 % CI 1.8-15.6, p = 0.002), and recent or previous colonization/infection with MDR GNR (OR = 2.3, 95 % CI 1.2-4.3, p = 0.028). Using a cut-off value of two points, the score had a sensitivity of 66.07 % (95 % CI 58.4-73.2 %), a specificity of 77.8 % (95 % CI 71.4-82.7 %), a positive predictive value of 68 % (95 % CI 61.9-73.4 %), and a negative predictive value of 75.9 % (95 % CI 71.6-79.7 %). The overall performance of the score was satisfactory (AUROC 0.78; 95 % CI 0.73-0.82). In the cases with one or none of the risk factors identified, the negative likelihood ratio was 0.18 and the post-test probability of having MDR GNR was 11.68 %. Conclusions: With the growing incidence of MDR GNR as etiologic agents of bacteremia in cancer patients, the development of this score could be a potential tool for clinicians.