Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Crit Care ; 23(1): 383, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779711

RESUMO

BACKGROUND: Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined. METHODS: A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7-14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved. RESULTS: A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of - 2.16 (- 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015). CONCLUSIONS: This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.

2.
Artigo em Inglês | MEDLINE | ID: mdl-30617096

RESUMO

Colistin resistance in Acinetobacter baumannii is of great concern and is a threat to human health. In this study, we investigate the mechanisms of colistin resistance in four isogenic pairs of A. baumannii isolates displaying an increase in colistin MICs. A mutation in pmrB was detected in each colistin-resistant isolate, three of which were novel (A28V, I232T, and ΔL9-G12). Increased expression of pmrC was shown by semi-quantitative reverse transcription-PCR (qRT-PCR) for three colistin-resistant isolates, and the addition of phosphoethanolamine (PEtN) to lipid A by PmrC was revealed by mass spectrometry. Interestingly, PEtN addition was also observed in some colistin-susceptible isolates, indicating that this resistance mechanism might be strain specific and that other factors could contribute to colistin resistance. Furthermore, the introduction of pmrAB carrying the short amino acid deletion ΔL9-G12 into a pmrAB knockout strain resulted in increased pmrC expression and lipid A modification, but colistin MICs remained unchanged, further supporting the strain specificity of this colistin resistance mechanism. Of note, a mutation in the pmrC homologue eptA and a point mutation in ISAba1 upstream of eptA were associated with colistin resistance and increased eptA expression, which is a hitherto undescribed resistance mechanism. Moreover, no cost of fitness was observed for colistin-resistant isolates, while the virulence of these isolates was increased in a Galleria mellonella infection model. Although the mutations in pmrB were associated with colistin resistance, PEtN addition appears not to be the sole factor leading to colistin resistance, indicating that the mechanism of colistin resistance is far more complex than previously suspected and is potentially strain specific.

3.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30268590

RESUMO

INTRODUCTION: Antimicrobial defined daily dose (DDD), has limitations for antimicrobial consumption measurement in paediatrics. An alternative DDD design applicable for children is proposed. METHODS: Children (<16 years-old) from 10 Spanish hospitals during a 12-months period were included. Weight for age (50th percentile) was calculated for the median age of the cohort using standardized World Health Organization tables. DDD (g) for each antimicrobial was calculated by multiplying the obtained weight times the recommended dose (mg/kg) of the antimicrobial for the most common infectious indication. RESULTS: A total of 40,575 children were included. Median age was 4.17 (IQR: 1.36-8.98) and 4.81 (IQR: 1.42-9.60) years for boys and girls, respectively. Mean weight for this age was 17.08kg. Standardized DDD for representative antimicrobials were calculated. CONCLUSIONS: A useful method for antimicrobial DDD measurement in paediatrics has been proposed and should be validated in future studies for its use in paediatric antimicrobial stewardship programmes.

6.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 35(10): 638-644, dic. 2017. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-169563

RESUMO

Objective: The time to positivity (TTP) of blood cultures in patients with bloodstream infections (BSIs) has been considered to be a possible prognostic tool for some bacterial species. However, notable differences have been found between sampling designs and statistical methods in published studies to date, which makes it difficult to compare results or to derive reliable conclusions. Our objective was to evaluate the clinical and microbiological implications of TTP among patients with BSI caused by the most common pathogens. Methods: A total of 361 episodes of BSI were reported for 332 patients. The survival of the entire cohort was measured from the time of blood culture sampling. In order to compare our results with those of previous studies, TTP was divided in three different groups based on log rank (short TTP <12h; medium TTP ≥12h to ≤27h, and long TTP >27h). Cox proportional hazard models were used to calculate crude and adjusted hazard ratios (HR). Results: The Cox proportional hazard model revealed that TTP is an independent predictor of mortality (HR=1.00, p=0.031) in patients with BSIs. A higher mortality was found in the group of patients with the shortest TTP (<12h) (HR=2.100, p=0.047), as well as those with longest TTP (>27h) (HR=3.277, p=0.031). Conclusions: It seems that TTP may provide a useful prognostic tool associated with a higher risk of mortality, not only in patients with shorter TTP, but also in those with longer TTP (AU)


Objetivo: El tiempo de positividad (TP) de los hemocultivos en pacientes con bacteriemia ha sido considerado como una posible herramienta pronóstica. Sin embargo, en los estudios publicados hasta la fecha, hemos observado importantes diferencias tanto en el diseño experimental como en la metodología utilizada. Esto dificulta el poder comparar los resultados obtenidos u obtener conclusiones consistentes. El objetivo de este estudio ha sido evaluar las implicaciones clínicas y microbiológicas del TP en pacientes con bacteriemia causada por los microorganismos más frecuentes, revisando la metodología utilizada en estudios anteriores. Métodos: Se estudiaron un total de 361 episodios de bacteriemia de 332 pacientes. La supervivencia de nuestra cohorte se midió desde que se tomó la muestra de hemocultivo. El TP fue dividido en tres grupos en base al log rank (TP cortos <12h; TP medios ≥12h y ≤27h; TP largos >27h), con el objetivo de comparar nuestros resultados con los obtenidos en estudios previos. Se utilizó el modelo de riesgos proporcionales (Cox) para calcular los hazard ratios (HR) tanto crudos como ajustados. Resultados: El modelo Cox mostró que el TP es un factor independiente relacionado con la mortalidad en pacientes con bacteriemia (HR = 1,00, p = 0,031). Concretamente, encontramos una mayor mortalidad en aquellos pacientes con TP cortos (<12 horas) (HR=2.100, p=0,047), así como en pacientes con TP largos (>27h) (HR=3.277, p=0,031). Conclusiones: En el presente estudio demostramos que el TP puede ser utilizado como una herramienta pronóstica útil de mortalidad no solo en pacientes con TP cortos, sino también en aquellos con TP largos (AU)


Assuntos
Humanos , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Hemocultura/métodos , Prognóstico , Sensibilidade e Especificidade , Técnicas Microbiológicas/métodos , Estudos Prospectivos , Análise Estatística , Estimativa de Kaplan-Meier , Análise Multivariada , Bibliometria
7.
Clin Infect Dis ; 65(12): 1992-1999, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29020166

RESUMO

Background: The global crisis of bacterial resistance urges the scientific community to implement intervention programs in healthcare facilities to promote an appropriate use of antibiotics. However, the clinical benefits or the impact on resistance of these interventions has not been definitively proved. Methods: We designed a quasi-experimental intervention study with an interrupted time-series analysis. A multidisciplinary team conducted a multifaceted educational intervention in our tertiary-care hospital over a 5-year period. The main activity of the program consisted of peer-to-peer educational interviews between counselors and prescribers from all departments to reinforce the principles of the proper use of antibiotics. We assessed antibiotic consumption, incidence density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). Results: A quick and intense reduction in antibiotic consumption occurred 6 months after the implementation of the intervention (change in level, -216.8 defined daily doses per 1000 OBDs; 95% confidence interval, -347.5 to -86.1), and was sustained during subsequent years (average reduction, -19,9%). In addition, the increasing trend observed in the preintervention period for the incidence density of candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence interval, -.003 to .039) reverted toward a decreasing trend of -0.130 per quarter (change in slope, -0.029; -.051 to -.008), and so did the mortality rate (change in slope, -0.015; -.021 to -.008). Conclusions: This education-based antimicrobial stewardship program was effective in decreasing the incidence and mortality rate of hospital-acquired candidemia and MDR BSI through sustained reduction in antibiotic use.


Assuntos
Gestão de Antimicrobianos/métodos , Candidemia/sangue , Candidemia/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Candidemia/microbiologia , Candidemia/mortalidade , Infecção Hospitalar/microbiologia , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/tendências , Humanos , Análise de Séries Temporais Interrompida , Mortalidade/tendências , Papel do Médico , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , Centros de Atenção Terciária
8.
Enferm Infecc Microbiol Clin ; 35(10): 638-644, 2017 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27916290

RESUMO

OBJECTIVE: The time to positivity (TTP) of blood cultures in patients with bloodstream infections (BSIs) has been considered to be a possible prognostic tool for some bacterial species. However, notable differences have been found between sampling designs and statistical methods in published studies to date, which makes it difficult to compare results or to derive reliable conclusions. Our objective was to evaluate the clinical and microbiological implications of TTP among patients with BSI caused by the most common pathogens. METHODS: A total of 361 episodes of BSI were reported for 332 patients. The survival of the entire cohort was measured from the time of blood culture sampling. In order to compare our results with those of previous studies, TTP was divided in three different groups based on log rank (short TTP <12h; medium TTP ≥12h to ≤27h, and long TTP >27h). Cox proportional hazard models were used to calculate crude and adjusted hazard ratios (HR). RESULTS: The Cox proportional hazard model revealed that TTP is an independent predictor of mortality (HR=1.00, p=0.031) in patients with BSIs. A higher mortality was found in the group of patients with the shortest TTP (<12h) (HR=2.100, p=0.047), as well as those with longest TTP (>27h) (HR=3.277, p=0.031). CONCLUSIONS: It seems that TTP may provide a useful prognostic tool associated with a higher risk of mortality, not only in patients with shorter TTP, but also in those with longer TTP.

9.
Antimicrob Agents Chemother ; 60(5): 2601-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26856841

RESUMO

The increasing number of infections produced by beta-lactam-resistant Gram-positive bacteria and the morbidity secondary to these infections make it necessary to optimize the use of vancomycin. In 2009, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Disease Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of ≥400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of ≥400 for a MIC of ≤1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated.


Assuntos
Vancomicina/sangue , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Esquema de Medicação , Humanos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Vancomicina/administração & dosagem , Vancomicina/farmacocinética , Vancomicina/uso terapêutico
11.
Transpl Int ; 27(12): 1253-62, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25070273

RESUMO

The aim of this study was to characterize timing, kinetic, and magnitude of CMV-specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV-specific T-cell response was measured in blood, while CMV viral load and chimerism were determined by real-time PCR. Patients that reconstituted CMV-specific T-cell response within 6 weeks after Allo-SCT showed a more robust immune response (CD8(+) : 0.7 cells/µl vs. 0.3/µl; P-value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P-value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P-value = 0.04), and better overall survival (72%; CI: 0.53-0.96 vs. 42% CI: 0.24-0.71; P-value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant-related mortality than nonviremic patients after 1 year (33% CI: 0.15-0.52 vs. 0% CI: 0.05-0.34; P-value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV-positive serostatus (P-value = 0.02) and acquiring CMV-specific T-cell response after 6 weeks post-transplantation (P-value = 0.009). In conclusion, timing of acquiring a positive CMV-specific T-cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.


Assuntos
Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas , Memória Imunológica , Complicações Pós-Operatórias/imunologia , Subpopulações de Linfócitos T/imunologia , Viremia/imunologia , Adolescente , Adulto , Aloenxertos , Antivirais/uso terapêutico , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Feminino , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Especificidade do Receptor de Antígeno de Linfócitos T , Fatores de Tempo , Carga Viral , Viremia/etiologia , Ativação Viral , Replicação Viral , Adulto Jovem
12.
J Infect ; 69(5): 500-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25037022

RESUMO

OBJECTIVES: The most frequent adverse events associated with valganciclovir treatment are hematological disturbances such as neutropenia. However, the consequences of neutropenia are unknown. We investigated the clinical impact of neutropenia during CMV preemptive therapy and its relationship with the length of antiviral therapy. METHODS: An observational, prospective cohort of 67 solid organ transplant recipients receiving CMV preemptive therapy was studied. RESULTS: Severe neutropenia occurred in 21.8% of the patients at a median of three weeks after initiating antiviral therapy. No association was observed between neutropenia and infection risk in these patients. Liver transplant recipients had 6.7 fold increased risk of neutropenia during CMV therapy compared to kidney transplant recipients (p = 0.012). Patients who developed severe neutropenia received antiviral therapy a median of six days longer than patient who did not (p = 0.457). CONCLUSIONS: Despite the frequency of neutropenia during CMV preemptive therapy, the incidence of infections is not increased. Adjusting the length of preemptive therapy during the episodes of viremia may be recommended, especially in patients with concurrent risk factors for neutropenia such as liver recipients. Further trials are warranted to confirm the safety of this approach.


Assuntos
Antivirais/efeitos adversos , Antivirais/uso terapêutico , Infecções Bacterianas/epidemiologia , Infecções por Citomegalovirus/tratamento farmacológico , Neutropenia/induzido quimicamente , Transplantados , Feminino , Ganciclovir/efeitos adversos , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Humanos , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Fatores de Risco , Valganciclovir
13.
Antimicrob Agents Chemother ; 57(10): 4664-72, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23856767

RESUMO

New approaches of empirical antifungal therapy (EAT) in selected hematological patients with persistent febrile neutropenia (PFN) have been proposed in recent years, but their cost-effectiveness has not been studied. The aim of this study was to compare the cost-effectiveness of two different approaches of EAT in hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT) approach versus the standard approach of EAT. A decision tree to assess the cost-effectiveness of both approaches was developed. Outcome probabilities and treatment pathways were extrapolated from two studies: a prospective cohort study following the DDAT approach and a randomized clinical trial following the standard approach. Uncertainty was undertaken through sensitivity analyses and Monte Carlo simulation. The average effectiveness and economic advantages in the DDAT approach compared to the standard approach were 2.6% and €5,879 (33%) per PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the simulations performed with average cost-effectiveness per PFN episode of €32,671 versus €52,479 in the EAT approach. The results were robust over a wide range of variables. The DDAT approach is more cost-effective than the EAT approach in the management of PFN in hematological patients.


Assuntos
Antifúngicos/uso terapêutico , Neutropenia Febril/tratamento farmacológico , Adolescente , Adulto , Idoso , Algoritmos , Antifúngicos/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
14.
Haematologica ; 97(3): 464-71, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22058202

RESUMO

BACKGROUND: Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients' risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. DESIGN AND METHODS: This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. RESULTS: Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. CONCLUSIONS: Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell transplant, the approach is useful for identifying patients who are not likely to develop invasive fungal infection and do not, therefore, require antifungal therapy. The effectiveness of the strategy is similar to that of universal empirical antifungal therapy reported in controlled trials.


Assuntos
Antifúngicos/uso terapêutico , Micoses/diagnóstico , Micoses/tratamento farmacológico , Neutropenia/diagnóstico , Neutropenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Febre/diagnóstico , Febre/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/mortalidade , Neutropenia/etiologia , Neutropenia/mortalidade , Estudos Prospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
15.
Transplantation ; 91(8): 927-33, 2011 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-21358366

RESUMO

BACKGROUND: It has been suggested that preemptive therapy against cytomegalovirus (CMV) infection after transplantation promotes a CMV-specific immune response. Our objective was to determine whether solid-organ transplant patients at high risk for CMV infection treated preemptively acquire a CMV-specific immune response and whether the acquired immune response confers immunity by controlling subsequent CMV replication episodes and by protecting from late-onset CMV disease. METHODS: Patients were followed up for 18 months after transplantation. CMV viral load was determined using real-time polymerase chain reaction assays, and the T-cell immune response was characterized by intracellular cytokine staining. RESULTS: The 21 patients studied developed CMV replication episodes at a median of 4 weeks (range 2-8 weeks) after transplantation and a CMV-specific T-cell response within a median of 12 weeks (range 10-20 weeks). The decline in the incidence of CMV replication episodes is inversely correlated with the acquisition of the CMV-specific T-cell response (linear regression r=0.781, Pearson correlation=-0.883; P=0.001). There were no CMV replication episodes after week 47 of transplantation. In addition, after acquisition of the immune response, 42 replication episodes were cleared without treatment. The time taken for immune clearance of replication correlated with the peak viral load (P=0.01). No incidence of CMV early or late-onset disease was detected. CONCLUSIONS: Our results demonstrate that preemptive therapy is a safe and an effective strategy for the control of CMV infection in solid-organ transplant recipients at high risk for CMV infection. This is the first study that reports a therapeutic effect of the acquisition of CMV-specific immune response during preemptive treatment.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/efeitos dos fármacos , Transplante de Órgãos/efeitos adversos , Adulto , Idoso , Citocinas/metabolismo , Citomegalovirus/genética , Citomegalovirus/crescimento & desenvolvimento , Citomegalovirus/imunologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Linfócitos T/imunologia , Linfócitos T/virologia , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Replicação Viral
16.
Antimicrob Agents Chemother ; 54(8): 3149-54, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20498325

RESUMO

Previous studies have sought to determine the risk factors associated with candidemia caused by non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei). Non-albicans Candida strains are a heterogeneous group that includes species with different levels of virulence, and only a limited number of C. glabrata isolates are resistant to fluconazole. We set out to identify the risk factors associated with microbiologically proven fluconazole-resistant candidemia. A prospective study including adult patients with candidemia was performed. Data were collected on patient demographics; underlying diseases; exposure to corticosteroids, antibiotics, or fluconazole; and invasive procedures. Risk factors associated either with non-albicans Candida spp. or potentially fluconazole-resistant Candida spp. (C. glabrata or C. krusei) or with Candida spp. with microbiologically confirmed fluconazole resistance were assessed using logistic regressions. We included 226 candidemia episodes. Non-albicans Candida isolates accounted for 53.1% of the fungal isolates, but only 18.2% of the cases were caused by potentially fluconazole-resistant organisms. Thirty isolates exhibited microbiologically confirmed fluconazole resistance. The multivariate analysis revealed that independent predictors associated with fluconazole-resistant Candida spp. were neutropenia (odds ratio [OR]=4.94; 95% confidence interval [CI]=1.50 to 16.20; P=0.008), chronic renal disease (OR=4.82; 95% CI=1.47 to 15.88; P=0.01), and previous fluconazole exposure (OR=5.09; 95% CI=1.66 to 15.6; P=0.004). Independently significant variables associated with non-albicans Candida bloodstream infection or with potentially fluconazole-resistant Candida spp. did not include previous fluconazole exposure. We concluded that prior fluconazole treatment is an independent risk factor only for candidemia caused by microbiologically confirmed fluconazole resistant species. Our findings may be of value for selecting empirical antifungal therapy.


Assuntos
Antifúngicos/farmacologia , Candida/isolamento & purificação , Farmacorresistência Fúngica , Fluconazol/farmacologia , Fungemia/epidemiologia , Fungemia/microbiologia , Antifúngicos/administração & dosagem , Candida/classificação , Candida/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candidíase/diagnóstico , Candidíase/microbiologia , Fluconazol/administração & dosagem , Fungemia/diagnóstico , Hospitais Urbanos , Humanos , Modelos Logísticos , Testes de Sensibilidade Microbiana , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia
17.
J Clin Microbiol ; 48(5): 1726-31, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20181897

RESUMO

Extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC) is an increasing cause of community and nosocomial infections worldwide. However, there is scarce clinical information about nosocomial bloodstream infections (BSIs) caused by these pathogens. We performed a study to investigate the risk factors for and prognosis of nosocomial BSIs due to ESBLEC in 13 Spanish hospitals. Risk factors were assessed by using a case-control-control study; 96 cases (2 to 16% of all nosocomial BSIs due to E. coli in the participating centers) were included; the most frequent ESBL was CTX-M-14 (48% of the isolates). We found CTX-M-15 in 10% of the isolates, which means that this enzyme is emerging as a cause of invasive infections in Spain. By repetitive extragenic palindromic sequence-PCR, most isolates were found to be clonally unrelated. By multivariate analysis, the risk factors for nosocomial BSIs due to ESBLEC were found to be organ transplant (odds ratio [OR]=4.8; 95% confidence interval [CI]=1.4 to 15.7), the previous use of oxyimino-beta-lactams (OR=6.0; 95% CI=3.0 to 11.8), and unknown BSI source (protective; OR=0.4; 95% CI=0.2 to 0.9), and duration of hospital stay (OR=1.02; 95% CI=1.00 to 1.03). The variables independently associated with mortality were a Pitt score of >1 (OR=3.9; 95% CI=1.2 to 12.9), a high-risk source (OR=5.5; 95% CI=1.4 to 21.9), and resistance to more than three antibiotics, apart from penicillins and cephalosporins (OR=6.5; 95% CI=1.4 to 30.0). Inappropriate empirical therapy was not associated with mortality. We conclude that ESBLEC is an important cause of nosocomial BSIs. The previous use of oxyimino-beta-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.


Assuntos
Bacteriemia/epidemiologia , Infecção Hospitalar/epidemiologia , Infecções por Escherichia coli/epidemiologia , Escherichia coli/enzimologia , beta-Lactamases/biossíntese , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Estudos de Casos e Controles , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Uso de Medicamentos , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/mortalidade , Feminino , Hospitais , Humanos , Masculino , Prognóstico , Fatores de Risco , Espanha/epidemiologia
18.
Infect Control Hosp Epidemiol ; 30(3): 257-63, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19199531

RESUMO

OBJECTIVE: To describe what is, to our knowledge, the first nosocomial outbreak of infection with pan-drug-resistant (including colistin-resistant) Acinetobacter baumannii, to determine the risk factors associated with these types of infections, and to determine their clinical impact. DESIGN: Nested case-control cohort study and a clinical-microbiological study. SETTING: A 1,521-bed tertiary care university hospital in Seville, Spain. PATIENTS: Case patients were inpatients who had a pan-drug-resistant A. baumannii isolate recovered from a clinical or surveillance sample obtained at least 48 hours after admission to an intensive care unit (ICU) during the time of the epidemic outbreak. Control patients were patients who were admitted to any of the "boxes" (ie, rooms that partition off a distinct area for a patient's bed and the equipment needed to care for the patient) of an ICU for at least 48 hours during the time of the epidemic outbreak. RESULTS: All the clinical isolates had similar antibiotic susceptibility patterns (ie, they were resistant to all the antibiotics tested, including colistin), and, on the basis of repetitive extragenic palindromic-polymerase chain reaction, it was determined that all of them were of the same clone. The previous use of quinolones and glycopeptides and an ICU stay were associated with the acquisition of infection or colonization with pan-drug-resistant A. baumannii. To control this outbreak, we implemented the following multicomponent intervention program: the performance of environmental decontamination of the ICUs involved, an environmental survey, a revision of cleaning protocols, active surveillance for colonization with pan-drug-resistant A. baumannii, educational programs for the staff, and the display of posters that illustrate contact isolation measures and antimicrobial use recommendations. CONCLUSIONS: We were not able to identify the common source for these cases of infection, but the adopted measures have proven to be effective at controlling the outbreak.


Assuntos
Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/isolamento & purificação , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla , Hospitais Universitários/estatística & dados numéricos , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Institutos de Câncer , Estudos de Casos e Controles , Estudos de Coortes , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Controle de Infecções/métodos , Controle de Infecções/normas , Fatores de Risco , Espanha/epidemiologia
19.
Transplantation ; 87(3): 424-35, 2009 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19202450

RESUMO

OBJECTIVE: The aim of this prospective, multicenter, noncomparative, open-label trial was to evaluate the prophylactic use of caspofungin in adult liver transplant recipients at high risk of developing invasive fungal infections (IFI). METHODS: Patients received caspofungin for at least 21 days. A successful treatment outcome was defined as the absence of breakthrough IFI during the first 100 days after the onset of caspofungin. RESULTS: According to study design, 71 patients were included. In the modified intention-to-treat analysis, successful treatment outcome was obtained in 88.7%. Two patients developed IFI: a Mucor and a Candida albicans surgical wound infections, respectively. Six more patients discontinued caspofungin because of drug-related altered liver function. No clinical side effects were related to caspofungin. Altered analytical data compatible with grade IV toxicity, irrespective of caspofungin attribution, were observed in 27.7% of patients at the end of caspofungin prophylaxis and in 15.4% of patients in safety visit (14 days after ending caspofungin administration) (P=0.13). Eight patients died, six during caspofungin administration and two during follow-up period, but none were attributed to IFI or caspofungin toxicity. CONCLUSION: These results show that caspofungin could be considered an efficacious and well-tolerated drug as antifungal prophylaxis in high-risk liver transplant recipients.


Assuntos
Antifúngicos/uso terapêutico , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/uso terapêutico , Micoses/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Adulto , Antifúngicos/efeitos adversos , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/efeitos adversos , Esquema de Medicação , Humanos , Transplante de Fígado/efeitos adversos , Micoses/prevenção & controle , Complicações Pós-Operatórias/tratamento farmacológico , Projetos de Pesquisa
20.
Arch Intern Med ; 168(17): 1897-902, 2008 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-18809817

RESUMO

BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an increasingly important group of community pathogens worldwide. These organisms are frequently resistant to many of the antimicrobial agents usually recommended for the treatment of infections caused by E coli, such as penicillins, cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole. Data concerning risk factors, clinical features, and therapeutic options for such infections are scarce. METHODS: A case-control study was performed to investigate the risk factors for all types of community-acquired infections caused by ESBL-producing E coli in 11 Spanish hospitals from February 2002 to May 2003. Controls were randomly chosen from among outpatients with a clinical sample not yielding ESBL-producing E coli. The clinical features of these infections were investigated in the case patients. The efficacy of fosfomycin tromethamine and amoxicillin-clavulanate potassium was observationally studied in patients with cystitis. RESULTS: A total of 122 cases were included. Risk factors selected by multivariate analysis included the following: age older than 60 years; female sex; diabetes mellitus; recurrent urinary tract infections (UTIs); previous invasive procedures of the urinary tract; follow-up in outpatient clinic; and previous receipt of aminopenicillins, cephalosporins, and fluoroquinolones. Urinary tract infections accounted for 93% of the cases; 6% of the patients were bacteremic and 10% needed hospitalization. The cure rate of patients with cystitis was 93% with fosfomycin therapy (all isolates were susceptible); among patients treated with amoxicillin-clavulanate, cure rates were 93% for those with susceptible isolates (minimum inhibitory concentration < or =8 microg/mL) and 56% for those with intermediate or resistant isolates (minimum inhibitory concentration > or =16 microg/mL) (P = .02). CONCLUSIONS: In predisposed patients, ESBL-producing E coli is a notable cause of community-acquired infection, and particularly UTI. Fosfomycin and amoxicillin-clavulanate appear to be effective for cystitis caused by susceptible isolates.


Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Escherichia coli/enzimologia , Escherichia coli/isolamento & purificação , Infecções Urinárias/microbiologia , beta-Lactamases/biossíntese , Fatores Etários , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas/tratamento farmacológico , Cistite/microbiologia , Complicações do Diabetes , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Feminino , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espanha , Infecções Urinárias/complicações , Infecções Urinárias/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA