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This study examines the biological effects of palbociclib and ribociclib in hormone receptor-positive breast cancer, pivotal to the HARMONIA prospective phase III clinical trial. We explore the downstream impacts of these CDK4/6 inhibitors, focusing on cell lines and patient-derived tumor samples. We treated HR+ breast cancer cell lines (T47D, MCF7, and BT474) with palbociclib or ribociclib (100 nM or 500 nM), alone or combined with fulvestrant (1 nM), over periods of 24, 72, or 144 h. Our assessments included PAM50 gene expression, RB1 phosphorylation, Lamin-B1 protein levels, and senescence-associated ß-galactosidase activity. We further analyzed PAM50 gene signatures from the CORALLEEN and NeoPalAna phase II trials. Both CDK4/6 inhibitors similarly inhibited proliferation across the cell lines. At 100 nM, both drugs partially reduced p-RB1, with further decreases at 500 nM over 144 h. Treatment led to reduced Lamin-B1 expression and increased senescence-associated ß-galactosidase activity. Both drugs enhanced Luminal A and reduced Luminal B and proliferation signatures at both doses. However, the HER2-enriched signature significantly diminished only at the higher dose of 500 nM. Corresponding changes were observed in tumor samples from the CORALLEEN and NeoPalAna studies. At 2 weeks of treatment, both drugs significantly reduced the HER2-enriched signature, but at surgery, this reduction was consistent only with ribociclib. Our findings suggest that while both CDK4/6 inhibitors effectively modulate key biological pathways in HR+/HER2- breast cancer, nuances in their impact, particularly on the HER2-enriched signature, are dose-dependent, influenced by the addition of fulvestrant and warrant further investigation.
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Aminopiridinas , Neoplasias da Mama , Proliferação de Células , Piperazinas , Purinas , Piridinas , Humanos , Aminopiridinas/farmacologia , Piperazinas/farmacologia , Purinas/farmacologia , Piridinas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Receptores de Estrogênio/metabolismo , Fulvestranto/farmacologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Quinase 4 Dependente de Ciclina/metabolismo , Receptores de Progesterona/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Quinase 6 Dependente de Ciclina/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Background: Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks. Methods: Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients F12 gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured. Results: Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for D-dimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 vs. baseline) and D-dimer in 71% (p=0.001 vs. baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema. Conclusion: The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE.
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Angioedemas Hereditários , Biomarcadores , Inflamação , Humanos , Feminino , Masculino , Adulto , Angioedemas Hereditários/sangue , Angioedemas Hereditários/diagnóstico , Pessoa de Meia-Idade , Biomarcadores/sangue , Idoso , Inflamação/sangue , Adolescente , Criança , Adulto Jovem , Idoso de 80 Anos ou mais , Proteína Inibidora do Complemento C1/genética , Proteína Inibidora do Complemento C1/metabolismo , Proteína Amiloide A Sérica/metabolismo , Fator XII/genética , Fator XII/metabolismo , Sedimentação Sanguínea , Mediadores da Inflamação/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/análiseRESUMO
Background: Drug provocation tests (DPT) are considered the gold standard procedure to ascertain the diagnosis of beta-lactam (BL) allergy. Regarding route of administration, current recommendations prioritize oral challenges, considering them safer, and reserving the intravenous route for drugs for which this is the only formulation. Objective: To compare in terms of tolerance and safety two protocols of BL DPT, using an oral protocol (OR-DPT) and an intravenous protocol (IV-DPT). Methods: A descriptive, retrospective study was performed, including adult patients who underwent IV-DPT or OR-DPT for suspected immediate or delayed hypersensitivity to BL antibiotics, over a period of 4 years (between January 2018 and December 2021). Demographical data, index hypersensivity reactions' characteristics and tolerance to DPT were reviewed. Results: A total of 1036 patients underwent DPT, mean age of 56.8 (standard deviation, SD, 17.8) years, 655 were women (63.2%). Immediate drug hypersensitivity reactions (DHR) had occurred in 564 of patients (54.4%). OR-DPT were performed in 439 (42.4%) and IV-DPT in 597 (57.6%). The frequency of reactions during DPT, regardless of the route used, was low (3.6%): only 16 (3.6%) in OR-DPT and 21 (3.5%) in IV-DPT. From IV-DPT, 16 out 21 DHR during DPT were immediate compared with 4 out of 16 in OR-DPT. Adjusted relative risk of developing a hypersensitivity reaction during IV-DPT versus OR-DPT was 1.13 (95% confidence interval (CI)0.57-2.22). Conclusion: The results suggest that OR-DPT and IV-DPT are both safe procedures when adequately performed. However, IV-DPT protocols showed a higher rate of immediate DHR during DPT probably due to the selection of basal high-risk patients to undergo IV-DPT. In conclusion, IV-DPT may be considered as an option for challenges in drug-allergy studies, entailing a precise administration.
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Immune-checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of cancer. However, optimal patient selection is still an unmet need. One-hundred-forty-six patients with metastatic cancer candidates to ICI at the Hospital Clinic of Barcelona Clinical Trials Unit were prospectively recruited in this observational study. Blood samples were collected at different timepoints, baseline LIPI score calculated and pre-ICI archived tissues retrieved to evaluate PD-L1, tumor-infiltrating lymphocytes (TILs) and PD1 mRNA levels. Tumor assessments were centrally reviewed by RECIST 1.1 criteria. Associations with overall response rates (ORR), durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) were performed with univariable/multivariable logistic and Cox regressions, where appropriate. At a median follow-up of 26.9 months, median PFS and OS were 2.7 and 12.9 months. Response rates were 17.8% with duration of response (DOR) of 4.4 months. LIPI score was independently associated with PFS (p = 0.025) and OS (p < 0.001). Immunotherapy-naïve status was independently associated with better PFS (p = 0.005). Time-to-best response (TTBR) and ORR (p < 0.001 both) were associated with better OS at univariate analysis. PFS and DOR were moderately correlated with OS (p < 0.001 both). A PD-L1 10% cut-off detected worse/best responders in terms of ORR (univariate p = 0.011, multivariate p = 0.028) and DCB (univariate p = 0.043). PD1 mRNA levels were strikingly associated to complete responses (p = 0.021). To resume, in our prospective observational pan-cancer study, baseline LIPI score, immunotherapy-naïve status, cancer type and RT before starting ICI were the most relevant clinical factors independently correlated with immunotherapy outcomes. Longer TTBR seemed to associate with better survival, while PD1 mRNA and PD-L1 protein levels might be tumor-agnostic predictive factors of response to ICI and should be furtherly explored.
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Antineoplásicos Imunológicos , Neoplasias Pulmonares , Neoplasias , Humanos , Antígeno B7-H1 , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Neoplasias/tratamento farmacológico , RNA Mensageiro/genética , RNA Mensageiro/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
BACKGROUND: HER2DX is a prognostic and predictive assay in early-stage HER2-positive breast cancer based on clinical features and the expression of 4 gene signatures (immune, proliferation, luminal differentiation and HER2 amplicon), including ERBB2 mRNA levels. Here, we evaluated the ability of HER2DX to predict efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HER2-positive/hormone receptor-positive breast cancer. METHODS: HER2DX was evaluated on pre-treatment tumour samples from the PerELISA phase II study focused on postmenopausal patients with operable HER2-positive/hormone receptor-positive breast cancer. Patients received 2-weeks of letrozole, and then underwent a re-biopsy for Ki67 evaluation. Patients with endocrine therapy sensitive disease (ESD) (i.e., >20.0% Ki67 relative reduction at week 2) continued letrozole and 5 cycles of trastuzumab and pertuzumab. Primary aim was to test the ability of HER2DX risk-score, HER2DX pCR score and HER2DX ERBB2 mRNA score (as continuous variables and group categories) to predict pathological complete response (pCR) in patients with ESD. Logistic regression and receiver...operator curve (ROC) analysis assessed associations of HER2DX scores with pCR and ESD. FINDINGS: HER2DX was evaluated in 55 patients (86.0%) enrolled in PerELISA and 40 patients (73.0%) had ESD. The pCR rate in patients with ESD was 22.5% (9/40). In this group, HER2DX pCR score and HER2DX ERBB2 mRNA score were significantly associated with pCR (p.ß=.ß0.008 and p.ß=.ß0.003, univariate logistic regression model; area under ROC [AUC].ß=.ß0.803 and 0.896). The pCR rate in low, medium, and high HER2DX pCR score groups was 7.7% (2/26), 46.2% (6/13) and 100.0% (1/1), respectively. The pCR rate in low, medium, and high HER2DX ERBB2 score groups was 0.0% (0/12), 7.7% (1/13) and 53.3% (8/15), respectively. HER2DX pCR score was also significantly associated with Ki-67 response following 2-weeks of letrozole (p.ß=.ß0.002, univariate logistic regression model; AUC.ß=.ß0.775). The rate of ESD in low, medium, and high HER2DX pCR score groups was 89.7% (26/29), 65.0% (13/20) and 16.7% (1/6), respectively. INTERPRETATION: HER2DX predicts response following neoadjuvant letrozole in combination with dual HER2 blockade with trastuzumab and pertuzumab in early-stage HER2-positive/hormone receptor-positive breast cancer. FUNDING: This study received funding from Reveal Genomics.
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Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Trastuzumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Antígeno Ki-67/genética , Letrozol/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , RNA Mensageiro/uso terapêutico , Genômica , Resultado do TratamentoRESUMO
Two subsets of eosinophils have been described: resident eosinophils with homeostatic functions (rEOS) in healthy subjects and in patients with nonallergic eosinophilic asthma, and inflammatory eosinophils (iEOS) in blood and lung samples from patients with allergic asthma. We explored if it would be possible to identify different subsets of eosinophils using flow cytometry and the gating strategy applied to induced sputum. We conducted an observational cross-sectional single-center study of 62 patients with persistent allergic asthma. Inflammatory cells from induced sputum samples were counted by light microscopy and flow cytometry, and cytokine levels in the supernatant were determined. Two subsets of eosinophils were defined that we call E1 (CD66b-high and CD15-high) and E2 (CD66b-low and CD15-low). Of the 62 patients, 24 were eosinophilic, 18 mixed, 10 paucigranulocytic, and 10 neutrophilic. E1 predominated over E2 in the eosinophilic and mixed patients (20.86% vs. 6.27% and 14.42% vs. 4.31%, respectively), while E1 and E2 were similar for neutrophilic and paucigranulocytic patients. E1 correlated with IL-5, fractional exhaled nitric oxide, and blood eosinophils. While eosinophil subsets have been identified for asthma in blood, we have shown that they can also be identified in induced sputum.
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Asma , Eosinófilos , Humanos , Escarro/metabolismo , Interleucina-5 , Estudos Transversais , Contagem de Leucócitos , Asma/metabolismo , Pulmão/metabolismoAssuntos
Síndrome de Li-Fraumeni , Neoplasias da Próstata , Masculino , Humanos , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/terapia , Aconselhamento Genético , Mutação em Linhagem Germinativa , Proteína Supressora de Tumor p53/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Predisposição Genética para DoençaRESUMO
PURPOSE OF REVIEW: The purpose of the current review is to highlight the most recent findings in molecular allergy and its applicability in precision medicine for allergic patients. RECENT FINDINGS: Molecular allergy provides useful information in areas of respiratory allergy (house dust mites, pet dander and pollen allergy), food allergy (tree nuts, peanuts, fruits and vegetables), hymenoptera venom allergy and others, in order to improve management of patients. Regional differences in sensitization profiles, assay characteristics and interpretation of molecular sensitization in relation to whole extracts and total immunoglobulin E need to be taken into account. Studies of the impact of such strategies are needed. SUMMARY: Molecular allergy diagnosis represents a major contribution for personalized medicine. It aids in the assesment of risk prediction, disease severity, genuine/cross-reactive sensitization, and finally to apply precise management strategies.
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Venenos de Artrópodes , Hipersensibilidade Alimentar , Alérgenos , Animais , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/terapia , Humanos , Imunoglobulina E , Medicina de PrecisãoRESUMO
BACKGROUND: Rapid drug desensitization (RDD) becomes a crucial procedure to allow treatment continuation in patients who suffer drug hypersensitivity reactions (DHRs) to chemotherapeutic (CMT) and biological agents (BA). OBJECTIVE: The aim of the study was to compare the efficacy and safety of a one-bag dilution protocol (1DP) with a conventional three-bag dilution protocol (3DP) for desensitization of patients with CMT or BA hypersensitivity. METHODS: Retrospective analysis of patients with immediate DHRs to CMT or BA who underwent at least 1 RDD procedure in our department between 2014 and 2019 was performed. Demographical data, clinical history, skin tests, tryptase levels, and risk assessment were registered. The safety, tolerability, occurrence, and severity of breakthrough reactions (BTR) with 3DP and 1DP were compared. RESULTS: After the allergy workup, 157 patients fulfilled criteria to undergo RDD (137 females, mean age: 60.44 ± 12.6 years). A total of 639 RDDs (543 CMT and 96 BA) were performed using 3DP in 205 (48 patients) and 1DP in 434 (109 patients). Almost all procedures (636) were completed successfully. No BTR occurred in the first RDD in 52% and 51% of the 3DP and 1DP, respectively. Most BTR were mild. Moderate-severe BTR occurred in 17% with 3DP and 9% with 1DP. There were no statistical differences between protocols regarding the rate and severity of BTR. CONCLUSIONS: RDD with 1DP to CMT and BA has equivalent outcomes to a 3DP desensitization in a selected population of patients in terms of efficacy, tolerability, and safety. Moreover, 1DP reduces the time required for RDD and simplifies the logistics.
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Antineoplásicos , Hipersensibilidade a Drogas , Idoso , Antineoplásicos/uso terapêutico , Fatores Biológicos/uso terapêutico , Dessensibilização Imunológica , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the efficacy of hyperbaric oxygen therapy (HBOT) in the treatment of hemorrhagic radiation cystitis (HRC). MATERIAL AND METHOD: Retrospective study of patients diagnosed with hematuria secondary to HRC after pelvic radiation from January 2005 to January 2017 who were treated with HBOT. Demographic and clinical variables were collected. A descriptive univariate and multivariate statistical analysis using Cox regression was carried out. The treatment was considered effective when there was a total or partial remission of the hematuria based on the Radiation Therapy Oncology Group (RTOG) scoring schema. Partial remission was defined as the presence of hematuria grade 2 or less. RESULTS: A total of 67 patients with a mean age of 68,6 years (39-87) were included. 65,7% men and 34,3% women. The RT was administered in 64,2% of the cases by urological cause, prostate cancer. The av-erage dose of RT was 75,24 Gy (45-180). The mean from the RT to the HBOT treatment was 55,97 months (4-300) and from the beginning of the hematuria until the treatment was 11,3 months (1-48). Response was observed in 51 (76,1%) patients, total in 50,7% and partial in 25,4% of cases. Patients with a degree of hematuria less than 3, those who were administered more than 30 sessions and those who did not require transfusion or hospital admission, responded significantly bet-ter to treatment with HBOT (p<0.05) according to the univariate and multivariate analysis. No adverse effects related to treatment were reported, only one patient was excluded due to claustrophobia. CONCLUSIONS: Hyperbaric oxygen therapy is an effective and safe treatment for the management of hematuria due to radiological cystitis secondary to radiotherapy. A better response was observed in patients with a lower degree of hematuria and those who could be administered a greater number of sessions.
OBJETIVO: Evaluación la eficacia de la oxigenoterapia hiperbárica (OHB) en el tratamiento de la cistitis rádica hemorrágica (CRH) postradioterapia.MATERIAL Y MÉTODO: Estudio retrospectivo que incluyó a los pacientes diagnosticados de hematuria secundaria a CRH postradioterapia pélvica desde enero de 2005 hasta enero del 2017 tratados con OHB. Se recogieron variables demográficas y clínicas. Se efec-tuó un análisis estadístico descriptivo, univariante y multivariante mediante regresión de Cox. El tratamiento se consideró eficaz cuando se produjo una remisión total o parcial de la hematuria en base a la escala del Grupo Oncológico de Radioterapia (RTOG). La respuesta parcial se definió como la presencia de hematuria grado 2 o menor tras el tratamiento. RESULTADOS: Se recogieron un total de 67 pacientes con una edad media de 68,6 años (39-87). Un 65,7% hombres y 34,3% mujeres. La RT fue administrada en el 64,2% de los casos por causa urológica, la más frecuente fue el cáncer de próstata. La dosis media de RT fue 75,24 Gy (45- 180). La media desde la RT hasta el tratamiento con OHB fue de 55,97 meses (4-300) y desde el inicio de la hematuria hasta el tratamiento de 11,3 meses (1-48). Se observó algún tipo de respuesta en 51 (76,1%) pacientes, siendo una respuesta total en el 50,7% y parcial en el 25,4% de los casos. Los pacientes con un grado de hematuria menor a 3, aquellos que recibieron más de 30 sesiones, y aquellos que no precisaron transfusión ni ingreso hospitalario, respondieron significativamente mejor al tratamiento (p<0,05), según el análisis univariante y multivariante. No fueron reportados efectos adversos relacionados con el tratamiento, solo un paciente fue excluido por claustrofobia. CONCLUSIONES: La terapia con OHB es una tratamiento efectivo y seguro para el manejo de la hematuria por CRH secundaria a radioterapia. Se observó una mejor respuesta en los pacientes con un menor grado de hematuria, en aquellos que recibieron mayor número de sesiones y que no precisaron transfusión ni ingreso hospitalario.
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Cistite , Oxigenoterapia Hiperbárica , Lesões por Radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistite/etiologia , Cistite/terapia , Feminino , Hematúria/etiologia , Hematúria/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/complicações , Lesões por Radiação/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: Epinephrine is the first-line treatment for anaphylaxis. Patients at risk should always carry an epinephrine autoinjector (EAI). Several EAI gaps have been identified. We sought to evaluate satisfaction using a medical device (digital technology comprising an EAI smart case connected to a mobile APP) with functions that overcome most of the EAI limitations and to determine whether patient behaviour and anaphylaxis management improve with its use. METHODS: This was a randomized, open-label, crossover clinical trial in a tertiary hospital involving patients with history of anaphylaxis carrying an EAI. The study was conducted in two three-month periods, one with and one without the medical device. The primary endpoint was satisfaction with the medical device. Usability, adherence, anxiety and anaphylaxis episodes were evaluated as secondary endpoints. RESULTS: A total of 100 patients were included (mean age 38.1 years, 74% female), and 95 completed the trial. The satisfaction visual analogue scale (VAS) after using the medical device was higher than before its use (89.1 [95% CI, 60.2-99.1] vs 56.3 [95% CI, 48.1-81.4]; P < .0001). The adherence VAS improved from 59.7 (95% CI, 54.0-65.3) to 88.6 (95% CI, 84.2-92.9) (P < .0001). Overall, 90% patients found the medical device easy to use. Patients' anxiety decreased from 52.2% to 29.3% (P < .001). Seven episodes of anaphylaxis occurred during the study, all in patients without the medical device (P = .025). Eighty-eight per cent of patients felt more involved in the management of anaphylaxis when using the medical device. CONCLUSION: This is the first clinical trial evaluating digital technology for EAIs, showing a change of behaviour in patients at risk of anaphylaxis, increasing satisfaction, improving adherence, and reducing anxiety, with good usability.
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Anafilaxia , Adulto , Anafilaxia/tratamento farmacológico , Estudos Cross-Over , Tecnologia Digital , Epinefrina/uso terapêutico , Feminino , Humanos , Injeções , MasculinoRESUMO
OBJECTIVE: The increase of isolation of beta-lactamase resistant Escherichia coli (BREC) strains makes treatment difficult. The objective of this study is to evaluate the situation in our environment. METHODS: Retrospective study including patients who presented positive urine cultures for E. coli in the Department of Health of Castellon between January 2012 and December 2015. We analyzed variables such as age, gender, patient`s origin (outpatient or hospital) and other risk factors. We performed a descriptive analysis to study the prevalence of BREC. RESULTS: 9113 cultures were positive for E Coli, 273(2.9%) of them were BREC. The annual percentage of BREC ranged from 1.7% to 3,4% with no increase over the last years. Mean age was 70 years, without gender differences. 247 cultures came from outpatient patients (90%), being 96% of them women. The factors most frequently associated with BREC were to present UTI over the last year and have received antibiotic treatment the previous 3 months; 50% of these received a beta lactam. CONCLUSIONS: In our environment, the isolation of BREC is similar to other series. Most patients come from the outpatient environment, were previously treated with antibiotics and had recurrent UTIs.
OBJETIVO: El aumento de aislamiento de cepas Escherichia coli resistentes a las betalactamasas (ECRB) dificulta su tratamiento. El objetivo de este estudio es evaluar la situación en nuestro entorno. MATERIAL Y MÉTODO: Estudio retrospectivo entre enero 2012 y diciembre de 2015, incluyendo pacientes que presentaban cultivos de orina positivos para E. coli en el Departamento de Salud de Castellón. Analizamos variables como: edad, sexo, procedencia del paciente (medio ambulatorio u hospitalario) y otros factores de riesgo. Se ha realizado un análisis descriptivo para estudiar la prevalencia de ECRB. RESULTADOS: Se obtuvieron 9113 cultivos positivos para E. coli, de estos 273 (2,9%) fueron ECRB. El porcentaje por año de ECRB fue entre un 1,7% y un 3,4% sin observarse incremento en los últimos años. La edad media fue 70 años, sin diferencias entre sexos. 247 cultivos procedían de pacientes ambulatorios (90%), correspondiendo el 96% de estos a mujeres. Los factores de riesgo más asociados a ECBR fueron presentar ITU el último año y haber recibido tratamiento antibiótico en los 3 meses previos, de estos un 50% recibió un betalactámico. CONCLUSIONES: En nuestro medio el aislamiento de ECRB es similar a otras series. La mayoría de pacientes fueron procedentes de medio ambulatorio, tratados previamente con antibióticos y con episodios de ITU recurrentes.