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1.
J Hosp Infect ; 147: 123-132, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38467251

RESUMO

BACKGROUND: Surgical site infections (SSIs), mainly caused by Staphylococcus aureus, pose a significant economic burden in Europe, leading to increased hospitalization duration, mortality, and treatment costs, particularly with drug-resistant strains such as meticillin-resistant S. aureus. AIM: To conduct a case-control study on the economic impact of S. aureus SSI in adult surgical patients across high-volume centres in France, Germany, Spain, and the UK, aiming to assess the overall and procedure-specific burden across Europe. METHODS: The SALT study is a multinational, retrospective cohort study with a nested case-control analysis focused on S. aureus SSI in Europe. The study included participants from France, Germany, Italy, Spain, and the UK who underwent invasive surgery in 2016 and employed a micro-costing approach to evaluate health economic factors, matching S. aureus SSI cases with controls. FINDINGS: In 2016, among 178,904 surgical patients in five European countries, 764 developed S. aureus SSI. Matching 744 cases to controls, the study revealed that S. aureus SSI cases incurred higher immediate hospitalization costs (€8,810), compared to controls (€6,032). Additionally, S. aureus SSI cases exhibited increased costs for readmissions within the first year post surgery (€7,961.6 versus €5,298.6), with significant differences observed. Factors associated with increased surgery-related costs included the cost of hospitalization immediately after surgery, first intensive care unit (ICU) admission within 12 months, and hospital readmission within 12 months, as identified through multivariable analysis. CONCLUSION: The higher rates of hospitalization, ICU admissions, and readmissions among S. aureus SSI cases highlight the severity of these infections and their impact on healthcare costs, emphasizing the potential benefits of evidence-based infection control measures and improved patient care to mitigate the economic burden.


Assuntos
Infecções Estafilocócicas , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/economia , Infecção da Ferida Cirúrgica/epidemiologia , Estudos Retrospectivos , Masculino , Estudos de Casos e Controles , Feminino , Pessoa de Meia-Idade , Infecções Estafilocócicas/economia , Infecções Estafilocócicas/epidemiologia , Idoso , França/epidemiologia , Europa (Continente) , Espanha/epidemiologia , Reino Unido/epidemiologia , COVID-19/economia , COVID-19/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Adulto , Alemanha/epidemiologia , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Staphylococcus aureus
2.
Rev Esp Quimioter ; 36(3): 236-258, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37017117

RESUMO

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.


Assuntos
Antineoplásicos , Neoplasias Hematológicas , Humanos , Antifúngicos/efeitos adversos , Voriconazol , Azóis/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico
3.
Rev Esp Quimioter ; 35 Suppl 3: 94-96, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36285867

RESUMO

Tuberculosis continues to be a major public health problem. A priority objective is the implementation of early diagnosis, contact investigation and latent tuberculosis infection (LTBI) testing. World Health Organization (WHO) concludes that there is no gold standard for the diagnosis of LTBI; both the tuberculin test and IGRA (interferon gamma release assays) indirectly identify tuberculosis infection; both tests are considered acceptable but imperfect. WHO recommends that regimens that include rifamycins are equally effective but less toxic and more adherent than long regimens with isoniazid.


Assuntos
Tuberculose Latente , Rifamicinas , Tuberculose , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Isoniazida/uso terapêutico , Testes de Liberação de Interferon-gama , Tuberculose/diagnóstico , Rifamicinas/uso terapêutico
5.
Rev Esp Quimioter ; 35 Suppl 1: 97-103, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35488836

RESUMO

Aspergillus spp. is the fungus most frequently producing ventilator-associated pneumonia (VAP), constituting 8% of them. This risk is significantly increased in onco-hematological patients: solid organ transplant recipients, chronic obstructive pulmonary disease (COPD), corticotherapy, cirrhosis, solid cancer, or viral pneumonias. The European Organization for Research and Treatment of Cancer Mycoses (EORT/MSG criteria) developed for onco-hematological patients with angioinvasive forms of aspergillosis have important limitations for broncho-pulmonary forms, such as aspergillosis cases in the ICU. In recent years, new diagnostic criteria were developed to have a greater role in broncho-alveolar lavage, especially GM and lateral flow assay (LFA). Voriconazole and isavuconazole are the first treatment option. However, drug-drug interaction, level requirements, toxicity, and QT-interval modification are limitations that may favor isavuconazole or liposomal amphotercin B in the ICU.


Assuntos
Aspergilose , Influenza Humana , Micoses , Pneumonia , Aspergilose/diagnóstico , Aspergillus , Estado Terminal , Humanos
6.
Open Forum Infect Dis ; 8(6): ofab250, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34104670

RESUMO

BACKGROUND: There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. METHODS: This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007-2016). The impact of ED and factors associated with mortality were assessed. RESULTS: Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48-10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94-9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14-5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48-10.61), and prior surgery (OR, 0.29; 95% CI, 0.08-0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16-1.53). CONCLUSIONS: Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.

7.
Antimicrob Agents Chemother ; 65(8): e0004521, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-33972253

RESUMO

To test the hypothesis that the addition of an aminoglycoside to a ß-lactam antibiotic could provide better outcomes than ß-lactam monotherapy for the initial empirical treatment of hematological neutropenic patients with subsequently documented Gram-negative bacillus (GNB) bloodstream infection (BSI), a multinational, retrospective, cohort study of GNB BSI episodes in hematological neutropenic patients in six centers (2010 to 2017) was conducted. Combination therapy (ß-lactam plus aminoglycoside) was compared to ß-lactam monotherapy. The primary endpoint was the case fatality rate, assessed at 7 and 30 days from BSI onset. Secondary endpoints were nephrotoxicity and persistent BSI. Propensity score (PS) matching was performed. Among 542 GNB BSI episodes, 304 (56%) were initially treated with combination therapy, with cefepime plus amikacin being most common (158/304 [52%]). Overall, Escherichia coli (273/304 [50.4%]) was the main etiological agent, followed by Pseudomonas aeruginosa, which predominated in the combination group (76/304 [25%] versus 28/238 [11.8%]; P < 0.001). Multidrug resistance rates were similar between groups (83/294 [28.2%] versus 63/233 [27%]; P = 0.95). In the multivariate analysis, combination therapy was associated with a lower 7-day case fatality rate (odds ratio [OR], 0.37; 95% CI, 0.14 to 0.91; P = 0.035) with a tendency toward lower mortality at 30 days (OR, 0.56; 95% CI, 0.29 to 1.08; P = 0.084). After PS matching, these differences remained for the 7-day case fatality rate (OR, 0.33; 95% CI, 0.13 to 0.82; P = 0.017). In addition, aminoglycoside use was not significantly associated with renal function impairment (OR, 1.12; 95% CI, 0.26 to 4.87; P = 0.9). The addition of an aminoglycoside to the initial empirical therapy regimen for febrile neutropenic hematological patients should be considered.


Assuntos
Bacteriemia , Infecções por Bactérias Gram-Negativas , Sepse , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Estudos de Coortes , Quimioterapia Combinada , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Estudos Retrospectivos , Sepse/tratamento farmacológico
8.
Rev. neurol. (Ed. impr.) ; 72(7): 250-260, Abr 1, 2021.
Artigo em Espanhol | IBECS | ID: ibc-227865

RESUMO

Introducción: La reciente disponibilidad de vacunas contra el SARS-CoV-2 ha suscitado dudas en determinados colectivos de pacientes, como los que padecen esclerosis múltiple. Sin embargo, en la actualidad hay pocas publicaciones que ofrezcan información en este sentido. Se recopila la información disponible sobre la seguridad y la eficacia de la vacunación contra el SARS-CoV-2 en pacientes con esclerosis mú ltiple, con y sin tratamiento modificador de la enfermedad.Desarrollo: Búsqueda bibliográfica enfocada en los tipos de vacunas contra el SARS-CoV-2, la situación actual de su aprobación, y los datos disponibles sobre la eficacia y la seguridad de las vacunas en pacientes con esclerosis múltiple, incluidas las nuevas vacunas frente a la COVID-19. A partir de esta búsqueda, se ha diseñado el documento recogiendo la evidencia actual y las recomendaciones de expertos. No existen datos sobre la seguridad y la eficacia de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple. Sin embargo, los datos disponibles permiten prever que las vacunas de tipo ARN mensajero (ARNm) frente al SARS-CoV-2 son tan seguras en ellos como en el resto de los individuos. Algunos de los tratamientos inmunosupresores podrían reducir la efectividad de las vacunas y requerir la planificación del momento de su administración, preferentemente antes del inicio del tratamiento en caso de ser posible.Conclusión: Los datos disponibles permiten recomendar las vacunas de tipo ARNm frente al SARS-CoV-2 en los pacientes con esclerosis múltiple. En los pacientes con fingolimod, cladribina, alemtuzumab, ocrelizumab y rituximab, sería recomendable la vacunación previa al inicio de la medicación cuando sea posible.(AU)


Introduction: The recent availability of SARS-CoV-2 vaccines has raised concerns in certain patient groups, such as those with multiple sclerosis. However, there are currently few publications that provide information on this issue. We pooled the information available on the safety and efficacy of vaccination against SARS-CoV-2 in patients with multiple sclerosis, with and without disease-modifying therapy. Development: The study consisted in a literature search focused on the types of SARS-CoV-2 vaccines, the current status of their approval, and the data available on the safety and efficacy of vaccines in patients with multiple sclerosis, including the new COVID-19 vaccines. Based on this search, the document has been designed taking into account current evidence and expert recommendations. There are no data on the safety and efficacy of SARS-CoV-2 vaccines in patients with multiple sclerosis. However, evidence does exist to suggest that messenger RNA (mRNA) vaccines against SARS-CoV-2 are as safe in these patients as in other individuals. Some therapies with immunosuppressants might reduce the effectiveness of these vaccines and require the scheduling of their administration, preferably before the start of treatment if possible. Conclusion: The data available make it possible to recommend mRNA vaccines against SARS-CoV-2 in patients with multiple sclerosis. In patients on fingolimod, cladribine, alemtuzumab, ocrelizumab and rituximab, vaccination prior to the initiation of medication administration would be recommendable whenever possible.(AU)


Assuntos
Humanos , Masculino , Feminino , Anticorpos Antivirais/biossíntese , Esclerose Múltipla/imunologia , Formação de Anticorpos/efeitos dos fármacos , /imunologia , /administração & dosagem , /imunologia , Imunossupressores/farmacologia , Esclerose Múltipla/tratamento farmacológico , /prevenção & controle , /efeitos adversos , /imunologia , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Controle de Doenças Transmissíveis , Neurologia
9.
Rev Neurol ; 72(7): 250-260, 2021 04 01.
Artigo em Espanhol | MEDLINE | ID: mdl-33764494

RESUMO

INTRODUCTION: The recent availability of SARS-CoV-2 vaccines has raised concerns in certain patient groups, such as those with multiple sclerosis. However, there are currently few publications that provide information on this issue. We pooled the information available on the safety and efficacy of vaccination against SARS-CoV-2 in patients with multiple sclerosis, with and without disease-modifying therapy. DEVELOPMENT: The study consisted in a literature search focused on the types of SARS-CoV-2 vaccines, the current status of their approval, and the data available on the safety and efficacy of vaccines in patients with multiple sclerosis, including the new COVID-19 vaccines. Based on this search, the document has been designed taking into account current evidence and expert recommendations. There are no data on the safety and efficacy of SARS-CoV-2 vaccines in patients with multiple sclerosis. However, evidence does exist to suggest that messenger RNA (mRNA) vaccines against SARS-CoV-2 are as safe in these patients as in other individuals. Some therapies with immunosuppressants might reduce the effectiveness of these vaccines and require the scheduling of their administration, preferably before the start of treatment if possible. CONCLUSION: The data available make it possible to recommend mRNA vaccines against SARS-CoV-2 in patients with multiple sclerosis. In patients on fingolimod, cladribine, alemtuzumab, ocrelizumab and rituximab, vaccination prior to the initiation of medication administration would be recommendable whenever possible.


TITLE: Vacunación frente al SARS-CoV-2 en pacientes con esclerosis múltiple.Introducción. La reciente disponibilidad de vacunas contra el SARS-CoV-2 ha suscitado dudas en determinados colectivos de pacientes, como los que padecen esclerosis múltiple. Sin embargo, en la actualidad hay pocas publicaciones que ofrezcan información en este sentido. Se recopila la información disponible sobre la seguridad y la eficacia de la vacunación contra el SARS-CoV-2 en pacientes con esclerosis múltiple, con y sin tratamiento modificador de la enfermedad. Desarrollo. Búsqueda bibliográfica enfocada en los tipos de vacunas contra el SARS-CoV-2, la situación actual de su aprobación, y los datos disponibles sobre la eficacia y la seguridad de las vacunas en pacientes con esclerosis múltiple, incluidas las nuevas vacunas frente a la COVID-19. A partir de esta búsqueda, se ha diseñado el documento recogiendo la evidencia actual y las recomendaciones de expertos. No existen datos sobre la seguridad y la eficacia de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple. Sin embargo, los datos disponibles permiten prever que las vacunas de tipo ARN mensajero (ARNm) frente al SARS-CoV-2 son tan seguras en ellos como en el resto de los individuos. Algunos de los tratamientos inmunosupresores podrían reducir la efectividad de las vacunas y requerir la planificación del momento de su administración, preferentemente antes del inicio del tratamiento en caso de ser posible. Conclusión. Los datos disponibles permiten recomendar las vacunas de tipo ARNm frente al SARS-CoV-2 en los pacientes con esclerosis múltiple. En los pacientes con fingolimod, cladribina, alemtuzumab, ocrelizumab y rituximab, sería recomendable la vacunación previa al inicio de la medicación cuando sea posible.


Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , Imunossupressores/efeitos adversos , Esclerose Múltipla/imunologia , SARS-CoV-2/imunologia , Vacinação , Anticorpos Antivirais/biossíntese , Formação de Anticorpos/efeitos dos fármacos , COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Controle de Doenças Transmissíveis/métodos , Humanos , Esquemas de Imunização , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Vacinas contra Influenza/administração & dosagem , Máscaras , Esclerose Múltipla/tratamento farmacológico , Vacinação/efeitos adversos
10.
Med Mycol ; 58(6): 789-796, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31811285

RESUMO

Multiplex quantitative real-time PCR (MRT-PCR) using blood can improve the diagnosis of intra-abdominal candidiasis (IAC). We prospectively studied 39 patients with suspected IAC in the absence of previous antifungal therapy. Blood cultures, MRT-PCR, and ß-D-glucan (BDG) in serum were performed in all patients. IAC was defined according to the 2013 European Consensus criteria. For MRT-PCR, the probes targeted the ITS1 or ITS2 regions of ribosomal DNA. Candidaemia was confirmed only in four patients (10%), and IAC criteria were present in 17 patients (43.6%). The sensitivity of MRT-PCR was 25% but increased to 63.6% (P = .06) in plasma obtained prior to volume overload and transfusion; specificity was above 85% in all cases. BDG performance was improved using a cutoff > 260 pg/ml, and improvement was not observed in samples obtained before transfusion. In this cohort of high risk of IAC and low rate of bloodstream infection, the performance of non-culture-based methods (MRT-PCR or BDG) was moderate but may be a complementary tool given the limitations of diagnostic methods available in clinical practice. Volume overload requirements, in combination with other factors, decrease the accuracy of MRT-PCR in patients with IAC.


Assuntos
Candidíase Invasiva/sangue , Candidíase Invasiva/diagnóstico , Infecções Intra-Abdominais/microbiologia , Reação em Cadeia da Polimerase Multiplex , beta-Glucanas/sangue , Antifúngicos/farmacologia , Sondas de DNA , Feminino , Humanos , Infecções Intra-Abdominais/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Open Forum Infect Dis ; 6(6): ofz180, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31198815

RESUMO

BACKGROUND: We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. METHODS: From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. RESULTS: The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered "high risk" for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid-related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. CONCLUSIONS: The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid-related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

13.
Mycopathologia ; 184(2): 239-250, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30903580

RESUMO

BACKGROUND: Experience with aerosolized lipid amphotericin B (aeLAB) as therapy or secondary prophylaxis in patients with invasive pulmonary aspergillosis (IPA) is anecdotal. METHODS: We performed a single-center retrospective cohort study to evaluate the efficacy of systemic antifungal therapy with and without aeLAB in patients with proven or probable IPA. Complete or partial response at 3 months was the primary end-point. Clinical response and mortality at 12 months, occurrence of adverse drug reactions and respiratory fungal colonization were secondary end-point. RESULTS: Eleven patients (39%) received aeLAB in addition to systemic antifungal therapy (group A), and 22 (61%) received systemic antifungal therapy only (group B). The use of aeLAB was not standardized. Amphotericin B lipid complex was used in all patients but one, who received liposomal amphotericin B. Five patients received aeLAB as antifungal complementary therapy and 6 received it as secondary prophylaxis. Except for the requirement of inhaled corticosteroids and home oxygen therapy, more frequent in group A, both groups were similar in baseline conditions. A better (nonsignificant) clinical outcome was observed at 3 months in patients receiving aeLAB. Only uncontrolled baseline condition was associated with one-year mortality in univariate analysis (p = 0.002). A multivariate Cox regression analysis suggests that aeLAB, corrected for uncontrolled underlying disease, reduces mortality at 12 months (HR 0.258; 95% CI 0.072-0.922; p = 0.037). CONCLUSION: Although no significant difference was observed in the main variable (3-month clinical response) and in spite of methodological limitations of the study, the possible survival benefit of aeLAB, adjusted for the control of the underlying disease, could justify the performance of well-controlled studies with a greater number of patients.


Assuntos
Aerossóis , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Quimioprevenção/métodos , Terapias Complementares/métodos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Prevenção Secundária/métodos , Adulto , Idoso , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Aspergilose Pulmonar Invasiva/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Clin Microbiol Infect ; 25(3): 381.e1-381.e10, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29803844

RESUMO

OBJECTIVE: Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-centre designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicentre cohort of intermediate-risk kidney transplant (KT) recipients. METHODS: We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction pre-emptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T cells were counted through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and immediate early-1 peptides (mean of six measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T cells were calculated at baseline and day 15. RESULTS: Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8+ T-cell count <1.0 cells/µL had greater risk of CMV events (adjusted hazard ratio (aHR) 2.84; p 0.054). When the CMI assessment was performed in the immediate post-transplant period (day 15), the presence of <2.0 CD8+ T cells/µL (aHR 2.18; p 0.034) or <1.0 CD4+ T cells/µL (aHR 2.43; p 0.016) also predicted the subsequent development of a CMV event. In addition, lower counts of CMV-specific CD4+ (but not CD8+) T cells at days 60 and 180 were associated with a higher incidence of late-onset events. CONCLUSIONS: Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.


Assuntos
Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Transplante de Rim , Monitorização Imunológica/métodos , Linfócitos T/imunologia , Idoso , Feminino , Humanos , Imunidade Celular , Interferon gama/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Linfócitos T/citologia , Linfócitos T/metabolismo , Transplantados
15.
Reproduction ; 157(1): R15-R31, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30390610

RESUMO

Infertility is relatively common affecting approximately 1-in-6 couples. Although the genetic basis of infertility is increasingly being uncovered, the contribution of male infertility often remains unexplained. The leading cause of pregnancy loss and cognitive impairment in humans is chromosome aneuploidy. Sperm aneuploidy is routinely evaluated by fluorescence in situ hybridization. The majority of studies have reported similar findings, namely: (1) all men produce aneuploid sperm; (2) certain chromosomes are more prone to undergo chromosome nondisjunction; (3) infertile men typically have significantly higher levels of sperm aneuploidy compared to controls and (4) the level of aneuploidy is often correlated with the severity of the infertility. Despite this, sperm aneuploidy screening is rarely evaluated in the infertility clinic. Within recent years, there appears to be renewed interest in the clinical relevance of sperm aneuploidy. We shall examine the gender differences in meiosis between the sexes and explore why less emphasis is placed on the paternal contribution to aneuploidy. Increased sperm aneuploidy is often perceived to be modest and not clinically relevant, compared to the female contribution. However, even small increases in sperm aneuploidy may impact fertility and IVF cycle outcomes. Evidence demonstrating the clinical relevance of sperm aneuploidy will be discussed, as well as some of the challenges precluding widespread clinical implementation. Technological developments that may lead to widespread clinical implementation will be discussed. Recommendations will be suggested for specific patient groups that may benefit from sperm aneuploidy screening and whether preimplantation genetic testing for aneuploidy should be discussed with these patients.


Assuntos
Aneuploidia , Infertilidade Masculina/genética , Meiose/genética , Não Disjunção Genética/fisiologia , Espermatozoides/metabolismo , Aberrações Cromossômicas , Humanos , Infertilidade Masculina/patologia , Masculino , Espermatozoides/patologia
16.
Rev Esp Quimioter ; 32(1): 31-39, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30547501

RESUMO

OBJECTIVE: In recent years, the introduction of new antifungals for the prevention of invasive fungal infections (IFIs) in hemato- oncological patients, particularly extended-spectrum azoles, has led to a change in the diagnostic and therapeutic strategies for established or suspected breakthrough IFI. The aim of the study was to identify the diagnostic and therapeutic strategies used in the management of IFIs in hemato-oncological patients in Spain, and to assess compliance with the recommendations of the consensus documents and clinical practice guidelines. METHODS: An online, anonymous, cross-sectional survey was conducted between January and September 2016 involving 137 specialists from third-level hospitals in Spain with Departments of Hematology that regularly deal with IFIs. RESULTS: Galactomannan test was available to 95.6% of specialists, and was used in 61.7% of the cases for diagnostic confirmation and early treatment. The (1 → 3) ß-D-glucan test was only available to 10.2%. A total of 75.3% of the participants estimated the incidence of breakthrough IFI due to filamentous fungus as being 1-10%. In turn, 83.3% of the participants decided a change in antifungal class after failure of prophylaxis, in concordance with the recommendations of the national and international consensus documents. CONCLUSIONS: The present study, the first of its kind conducted in Spain, shows that a high percentage of the medical professionals implicated in the management of hemato-oncological patients at high risk of suffering IFIs follow the recommendations of the national and international consensus documents and guidelines.


Assuntos
Antifúngicos/uso terapêutico , Fungos , Neoplasias Hematológicas/complicações , Infecções Fúngicas Invasivas/complicações , Infecções Fúngicas Invasivas/tratamento farmacológico , Azóis/uso terapêutico , Consenso , Estudos Transversais , Galactose/análogos & derivados , Guias como Assunto , Pesquisas sobre Atenção à Saúde , Humanos , Incidência , Infecções Fúngicas Invasivas/epidemiologia , Mananas/análise , Fatores de Risco , Espanha/epidemiologia
17.
Rev Esp Quimioter ; 31(4): 329-335, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29963817

RESUMO

OBJECTIVE: Although the incidence of human immunodeficiency virus (HIV)-associated tuberculosis (TB) has decreased, changes in other characteristics of the disease are largely unknown. To describe the trends in TB in patients infected with HIV from 1995 to 2013. METHODS: We review all cases of TB in a tertiary hospital in Madrid, Spain. RESULTS: Among 1,284 patients diagnosed of TB, 298 (23%) were coinfected with HIV. The prevalence of HIV infection during the period of study has decreased from 40% to 14% (p for the trend < 0.001). Clinical presentation has also changed. Although pulmonary and extrapulmonary TB has remained unchanged, miliary presentation has significantly decreased (from 36% to 22%, p = 0.005). The 4-drug regimen was the preferable scheme, with higher implementation at the end of the study period (82% from 1995-1999 to 95% in 2010-2013, p = 0.43). Factors such as treatment failure (OR: 11.7; CI 95%: 3.12-44.1) and miliary form (OR: 2.8; CI 95%; 1.09-7.3) were independently associated with TB related mortality, while the longer duration of treatment was as a protective factor (OR 0.7; CI 95%: 0.6-0.8). CONCLUSIONS: HIV has decreased very significantly as a risk factor for the development of TB. Despite improvement in the treatment of both TB and HIV, and in overall mortality, deaths attributable to the disease in this population remain high mostly in miliary and relapsing forms.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Tuberculose/complicações , Tuberculose/epidemiologia , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Prevalência , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Centros de Atenção Terciária , Resultado do Tratamento , Tuberculose/mortalidade , Tuberculose Miliar/epidemiologia , Tuberculose Miliar/mortalidade
18.
Clin Microbiol Infect ; 24 Suppl 1: e1-e38, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29544767

RESUMO

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus/isolamento & purificação , Gerenciamento Clínico , Anticorpos Antifúngicos/sangue , Antifúngicos/farmacologia , Aspergilose/complicações , Aspergilose/imunologia , Aspergillus/efeitos dos fármacos , Aspergillus/imunologia , Biópsia/métodos , Lavagem Broncoalveolar , Diagnóstico Precoce , Flucitosina/farmacologia , Flucitosina/uso terapêutico , Galactose/análogos & derivados , Humanos , Hospedeiro Imunocomprometido , Testes Imunológicos , Aspergilose Pulmonar Invasiva/diagnóstico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Imageamento por Ressonância Magnética , Mananas/análise , Testes de Sensibilidade Microbiana , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Tomografia Computadorizada por Raios X , Triazóis/farmacologia , Triazóis/uso terapêutico , Voriconazol/farmacologia , Voriconazol/uso terapêutico
19.
Clin Microbiol Infect ; 24 Suppl 2: S53-S70, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29454849

RESUMO

BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biologic therapies. AIMS: To review, from an infectious diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. SOURCES: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: Although BCR-ABL tyrosine kinase inhibitors modestly increase the overall risk of infection, dasatinib has been associated with cytomegalovirus and hepatitis B virus reactivation. BRAF/MEK kinase inhibitors do not significantly affect infection susceptibility. The effect of Bruton tyrosine kinase inhibitors (ibrutinib) among patients with B-cell malignancies is difficult to distinguish from that of previous immunosuppression. However, cases of Pneumocystis jirovecii pneumonia (PCP), invasive fungal infection and progressive multifocal leukoencephalopathy have been occasionally reported. Because phosphatidylinositol-3-kinase inhibitors (idelalisib) may predispose to opportunistic infections, anti-Pneumocystis prophylaxis and prevention strategies for cytomegalovirus are recommended. No increased rates of infection have been observed with venetoclax (antiapoptotic protein Bcl-2 inhibitor). Therapy with Janus kinase inhibitors markedly increases the incidence of infection. Pretreatment screening for chronic hepatitis B virus and latent tuberculosis infection must be performed, and anti-Pneumocystis prophylaxis should be considered for patients with additional risk factors. Cancer patients receiving mTOR inhibitors face an increased incidence of overall infection, especially those with additional risk factors (prior therapies or delayed wound healing). IMPLICATIONS: Specific preventive approaches are warranted in view of the increased risk of infection associated with some of the reviewed agents.


Assuntos
Terapia Biológica/efeitos adversos , Doenças Transmissíveis/terapia , Proteínas Tirosina Quinases/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Terapia Biológica/métodos , Ensaios Clínicos como Assunto , Humanos , Hospedeiro Imunocomprometido , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico
20.
Med Intensiva (Engl Ed) ; 42(1): 5-36, 2018.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29406956

RESUMO

Catheter-related bloodstream infections (CRBSI) constitute an important cause of hospital-acquired infection associated with morbidity, mortality, and cost. The aim of these guidelines is to provide updated recommendations for the diagnosis and management of CRBSI in adults. Prevention of CRBSI is excluded. Experts in the field were designated by the two participating Societies (the Spanish Society of Infectious Diseases and Clinical Microbiology and [SEIMC] and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units [SEMICYUC]). Short-term peripheral venous catheters, non-tunneled and long-term central venous catheters, tunneled catheters and hemodialysis catheters are covered by these guidelines. The panel identified 39 key topics that were formulated in accordance with the PICO format. The strength of the recommendations and quality of the evidence were graded in accordance with ESCMID guidelines. Recommendations are made for the diagnosis of CRBSI with and without catheter removal and of tunnel infection. The document establishes the clinical situations in which a conservative diagnosis of CRBSI (diagnosis without catheter removal) is feasible. Recommendations are also made regarding empirical therapy, pathogen-specific treatment (coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus spp., Gram-negative bacilli, and Candida spp.), antibiotic lock therapy, diagnosis and management of suppurative thrombophlebitis and local complications.


Assuntos
Bacteriemia/etiologia , Técnicas Bacteriológicas/normas , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecção Hospitalar/etiologia , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Técnicas de Tipagem Bacteriana/métodos , Técnicas de Tipagem Bacteriana/normas , Biofilmes/efeitos dos fármacos , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Candidemia/tratamento farmacológico , Candidemia/etiologia , Catéteres/efeitos adversos , Catéteres/microbiologia , Tratamento Conservador , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Remoção de Dispositivo , Gerenciamento Clínico , Farmacorresistência Bacteriana Múltipla , Endocardite Bacteriana/etiologia , Contaminação de Equipamentos , Humanos , Micologia/métodos , Tromboflebite/etiologia
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