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2.
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
3.
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
4.
J Med Microbiol ; 66(6): 713-720, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28598305

RESUMO

PURPOSE: The aim of this study was to compare the in vitro activity of ampicillin and moxifloxacin against six isolates selected from 154 invasive clinical isolates of Listeria monocytogenes and evaluate their intra- and extracellular activities with achievable central nervous system concentrations obtained using Monte Carlo simulations with conventional and unconventional dosages. METHODOLOGY: The MICs and minimal bactericidal concentrations (MBCs) of ampicillin and moxifloxacin were determined by using the broth microdilution method. The intra- and extracellular activities were compared using time-kill curves and inhibition of intracellular growth assays. RESULTS: The MICs50/90 of ampicillin were 0.125/0.5 mg l-1 and the MBC50/90 was ≥16 mg l-1, while the moxifloxacin MICs50/90 were 0.25/0.5 mg l-1 and the MBC50/90 was 0.5 mg l-1. Ampicillin did not show any extracellular bactericidal activity at 24 h, although bactericidal activity was detected at 48 h. For moxifloxacin, the bactericidal effect was evident after 6 h of incubation. Both antibiotics achieved significant reductions in intracellular inoculum after 1-24 h of incubation; however, moxifloxacin becomes bactericidal more rapidly, producing a much greater reduction in the inoculum in the first hour than ampicillin. There were no differences among the MIC and MBC values of moxifloxacin and ampicillin among the strains belonging to different serotypes and/or epidemic clones. This fact was also found in the intra- and extracellular studies. CONCLUSION: The results of this study demonstrated the faster bactericidal activity of moxifloxacin at achievable central nervous system concentrations against intra- and extracellular forms of L. monocytogenes in comparison with ampicillin.


Assuntos
Ampicilina/farmacologia , Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Células A549 , Ampicilina/líquido cefalorraquidiano , Antibacterianos/líquido cefalorraquidiano , Sistema Nervoso Central , Simulação por Computador , Humanos , Listeria monocytogenes/crescimento & desenvolvimento , Listeriose/microbiologia , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Moxifloxacina
5.
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.

6.
J Infect ; 72(3): 309-16, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26723914

RESUMO

OBJECTIVES: To compare clinical and microbiological characteristics, treatment and outcomes of MRSA bacteraemia among elderly and younger patients. MATERIAL AND METHODS: Prospective study conducted at 21 Spanish hospitals including patients with MRSA bacteraemia diagnosed between June/2008 and December/2009. Episodes diagnosed in patients aged 75 or more years old (≥75) were compared with the rest of them (<75). RESULTS: Out of 579 episodes of MRSA bacteraemia, 231 (39.9%) occurred in patients ≥75. Comorbidity was significantly higher in older patients (Charlson score ≥4: 52.8 vs. 44%; p = .037) as was the severity of the underlying disease (McCabe ≥1: 61.9 vs. 43.4%; p < .001). In this group the acquisition was more frequently health-care related (43.3 vs. 33.9%, p = .023), mostly from long-term care centers (12.1 vs. 3.7%, p < .001). An unknown focus was more frequent among ≥75 (19.9 vs. 13.8%; p = .050) while severity at presentation was similar between groups (Pitt score ≥3: 31.2 vs. 27.6%; p = .352). The prevalence of vancomycin resistant isolates was similar between groups, as was the appropriateness of empirical antibiotic therapy. Early (EM) and overall mortality (OM) were significantly more frequent in the ≥75 group (EM: 12.1 vs. 6%; p = .010 OM: 42.9 vs. 23%; p < .001). In multivariate analysis age ≥75 was an independent risk factor for overall mortality (aOR: 2.47, CI: 1.63-3.74; p < .001). CONCLUSION: MRSA bacteraemia was frequent in patients aged ≥75 of our cohort. This group had higher comorbidity rates and the source of infection was more likely to be unknown. Although no differences were seen in severity or adequacy of empiric therapy, elderly patients showed a higher overall mortality.


Assuntos
Bacteriemia/epidemiologia , Bacteriemia/patologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Feminino , Hospitais , Humanos , Masculino , Estudos Prospectivos , Espanha/epidemiologia , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento
7.
Food Chem ; 171: 212-23, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25308662

RESUMO

This study develops a new method to produce more complex wines by means of an indirect diffusion of wood aromas from yeast cell-walls. An exogenous lyophilized biomass was macerated with an ethanol wood extract solution and subsequently dried. Different times were used for the adsorption of polyphenols and volatile compounds to the yeast cell-walls. The analysis of polyphenols and volatile compounds (by HPLC/DAD and GC-MS, respectively) demonstrate that the adsorption/diffusion of these compounds from the wood to the yeast takes place. Red wines were also aged with Saccharomyces cerevisiae lees that had been impregnated with wood aromas and subsequently dried. Four different types of wood were used: chestnut, cherry, acacia and oak. Large differences were observed between the woods studied with regards to their volatile and polyphenolic profiles. Sensory evaluations confirmed large differences even with short-term contact between the wines and the lees, showing that the method could be of interest for red wine making. In addition, the results demonstrate the potential of using woods other than oak in cooperage.


Assuntos
Tecnologia de Alimentos/métodos , Vinho/análise , Madeira/química , Acacia , Biomassa , Carboidratos/química , Parede Celular/metabolismo , Cromatografia Líquida de Alta Pressão , Difusão , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Lactonas/química , Lignina/química , Polifenóis/análise , Prunus , Saccharomyces cerevisiae , Esteróis/química
8.
Int J Antimicrob Agents ; 43(2): 135-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24315790

RESUMO

This study was designed to evaluate the potential role of fosfomycin as a therapeutic agent in human listeriosis. The in vitro activity of fosfomycin against 154 Listeria monocytogenes clinical isolates under conditions that mimic the induction of prfA expression was determined and was correlated with fosfomycin intracellular antimicrobial activity. In vitro, partial induction of prfA expression is achieved through bacterial growth in brain-heart infusion agar supplemented with activated charcoal (BHIC). A fosfomycin pharmacokinetic/pharmacodynamic breakpoint of ≤64 mg/L was estimated using a Monte Carlo simulation to assess the success of an intravenous fosfomycin dose of 300 mg/kg/day over 5000 individuals. Eighty strains (51.9%) were susceptible to fosfomycin in BHIC, with minimum inhibitory concentrations (MICs) of ≤64 mg/L; 13 strains (8.4%) had the epidemic clone (EC) marker. In addition, 27 strains (17.5%) had a three doubling dilutions reduction in the MIC from ≥1024 mg/L to 128 mg/L (96-128 mg/L by Etest). The fosfomycin modal MIC is lower under prfA expression. However, this effect is smaller in terms of clinical categorisation of isolates and can be influenced by the serotype and clonal type. In A549 cells, the reductions in bacterial inocula of the two susceptible isolates studied after 1h and 24h of incubation with fosfomycin at 0.5× the human maximum serum concentration (Cmax) were 45.8% and 46.6%, and 93.8% and 99.1%, respectively. Slightly higher reductions were found with fosfomycin at 1× Cmax. The resistant strain tested showed significantly lower reductions in all assays.


Assuntos
Antibacterianos/farmacologia , Fosfomicina/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Proteínas de Bactérias/biossíntese , Linhagem Celular , Meios de Cultura/química , Células Epiteliais/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Fatores de Terminação de Peptídeos/biossíntese , Ativação Transcricional
9.
J Antimicrob Chemother ; 69(1): 136-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23920427

RESUMO

OBJECTIVES: To model the standard broth microdilution method, based on a modified Gompertz function, to obtain accurate vancomycin MIC values for methicillin-resistant Staphylococcus aureus (MRSA). The effect of these MIC values on the vancomycin therapeutic target of AUC(0-24)/MIC ≥ 400 was evaluated. METHODS: Three clinical isolates of MRSA with different vancomycin MIC values were used in this model. The optical densities (OD) of each MIC determination were modelled by a non-linear regression method using an F-test. The OD data were adjusted to the Gompertz equation to obtain the MIC values. The mean vancomycin AUC(0-24) obtained with a 30 mg/kg/day dosing schedule was calculated using a Monte Carlo simulation over 5000 subjects, using the pharmacokinetic data obtained in vancomycin-treated patients in our hospital. RESULTS: Although the MIC values obtained with this model were lower than those of the diffusion method (Etest) in all three cases, this did not affect the AUC(0-24)/MIC ratio for the strains with MICs of 1 mg/L by Etest. However, in those strains with MIC values >1 mg/L, the confidence intervals obtained for this ratio included values <400. CONCLUSIONS: The inherent variability of the broth microdilution method could explain the differences in the clinical outcome in MRSA-infected patients treated with vancomycin, mainly in those due to strains with MIC values of 1.5-2 mg/L by Etest, because the corresponding MIC values would range from 0.84 to 1.52 mg/L by the microdilution method, which could affect the therapeutic target.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Vancomicina/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana/métodos , Infecções Estafilocócicas/microbiologia
10.
J Chemother ; 24(2): 74-80, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22546761

RESUMO

We report on antimicrobial activity against E. faecalis and E. faecium collected in France, Germany, Italy, Spain, and the UK between 2004 and 2009 as part of the Tigecycline Evaluation and Surveillance Trial (UK in vitro data not included due to low isolate numbers). Overall, 1.1% (n=23/2068) of E. faecalis and 11.5% (n=103/893) of E. faecium were vancomycin-resistant. High levels of minocycline-resistant E. faecalis were reported in Germany, Spain, France, and Italy (40.2-44.2%); levofloxacin resistance was high in Germany, Italy, and Spain (31.1-41.6%). Minocycline non-susceptibility increased significantly among E. faecalis in Spain and Italy (P<0.001). No tigecycline-resistant E. faecalis were reported. Among E. faecium, resistance ranged from 72.9% (France) to 93.3% (Germany) for ampicillin, from 56.1% (France) to 90.2% (Germany) for levofloxacin, and from 75.3% (Italy) to 94.7% (Germany) for penicillin. Levofloxacin non-susceptibility increased significantly among E. faecium in France and Spain (P<0.001). The lowest rates of antimicrobial resistance among E. faecium were reported for tigecycline (2/893; 0.2%) and linezolid (3/893; 0.3%).


Assuntos
Anti-Infecciosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Acetamidas/uso terapêutico , Enterococcus faecalis/crescimento & desenvolvimento , Enterococcus faecium/crescimento & desenvolvimento , França , Alemanha , Humanos , Itália , Linezolida , Testes de Sensibilidade Microbiana , Minociclina/análogos & derivados , Minociclina/uso terapêutico , Oxazolidinonas/uso terapêutico , Espanha , Tigeciclina
11.
Enferm Infecc Microbiol Clin ; 30(10): 602-7, 2012 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-22513092

RESUMO

OBJECTIVE: The aim of this study was to perform a retrospective study by genotyping 154 isolates from human listeriosis cases occurred in the region of Andalusia (southern Spain) in the period 2005-2009. MATERIAL AND METHODS: Serotyping was performed for 1 and 4 somatic antigens using commercial Listeria antisera, and by multiplex-PCR serogrouping according to the method described by Doumith et al. (2004). The antimicrobial susceptibility was performed by Epsilon test and interpreted by CLSI criteria. PFGE was performed according to the PulseNet protocol with the ApaI enzyme. The similarity of PFGE profiles was evaluated using the Bionumerics software. The multiplex PCR protocol described by Chen and Knabel (2007) was used for the identification of isolates belonging to L. monocytogenes ECI, ECII, and ECIII epidemic clones. RESULTS: The 154 isolates were grouped into four serotypes: 4b [94 (61%)] strains, 1/2b [30 (19%)] strains, 1/2a [27 (18%)] strains, and 1/2c [3 (2%)] strains, with 100% of susceptibility to ampicillin and cotrimoxazole. A further sixty-two ApaI distinct pulsotypes were recognized. Thirty-seven isolates (24%) showed unique ApaI pulsotypes, and the remaining 117 strains (76%) were assigned to 25 ApaI clusters (60% in clusters of more than two isolates). The EC markers were found in 62 (40.3%) of the L. monocytogenes isolates tested. The ECI marker was present in 43 (46.2%) 4b serotype isolates, ECII in 10 (10.7%) 4b serotype isolates, and ECIII in 9 (33,3%) 1/2a serotype isolates. DISCUSSION: A large proportion of the human listeriosis cases under investigation could be grouped into molecular subtype clusters, and our cases could be related to international food-borne outbreaks.


Assuntos
Listeria monocytogenes/isolamento & purificação , Listeriose/microbiologia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/análise , DNA Bacteriano/genética , Resistência Microbiana a Medicamentos , Eletroforese em Gel de Campo Pulsado , Humanos , Listeria monocytogenes/classificação , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/genética , Listeriose/epidemiologia , Filogenia , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Espanha/epidemiologia
14.
Rev Esp Quimioter ; 23(1): 43-7, 2010 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-20232023

RESUMO

OBJECTIVE: The objective of the study is to evaluate the ability of standard vancomycin dosing strategies actually recommended to attain the pharmacodynamic target of an area under the curve of vancomycin serum concentration versus time from 0 to 24 hours (AUC(24h)) to minimum inhibitory concentration (MIC) ratio greater than 400:1 for patients with a suspected or documented methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia by individual analysis and Monte Carlo simulation. MATERIAL AND METHODS: The study included all patients admitted with suspected or proven MRSA infection during the years 2007-2008, and who were initially treated with vancomycin at a dose of 30 mg/kg/ day, and underwent pharmacokinetic monitoring. The area under the curve of vancomycin serum concentration versus time from 0 to 24 hours (AUC(24h)) was calculated as daily dose/ clearance total (D(24h)/CL). Additionally, we studied 45 isolates of MRSA obtained from blood cultures in the period 2007-2008. The MIC to vancomycin was determined using Epsilon-test®. The PK-PD parameter calculated was AUC(24h)/MIC. Microsoft Excel was used to perform a 10.000 subject Monte Carlo simulation. An AUC(24h)/MIC > or =400 was assumed as the target attainment. RESULTS: In the individual study, the percentage of patients with AUC(24h)/ MIC(50/90) > or = 400 was 50%. The probability (%) of attaining AUC(24h)/MIC ratio values > or = 400 by Monte Carlo simulation was of 66%. The vancomycin MIC value from which the scenario would have to wait a suboptimal treatment (target < 90%) was >1 mg/ L. DISCUSSION: This study shows that in the population studied to achieve a vancomycin AUC(24h)/MIC > or =400 is not always attained with the standard dose. Therefore, one would expect a high probability of suboptimal vancomycin AUC(24h)/MIC ratios for patients infected with organisms with vancomycin MICs of >1 mg/ L treated with doses of 30 mg/ kg/ day.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Bacteriemia/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Espanha , Infecções Estafilocócicas/microbiologia , Vancomicina/administração & dosagem , Adulto Jovem
15.
Rev. esp. quimioter ; 23(1): 43-47, mar. 2010. ilus
Artigo em Espanhol | IBECS | ID: ibc-78852

RESUMO

Objetivo: Evaluar la capacidad de la actual estrategia dedosificación de vancomicina de obtener un objetivo farmacocinético/farmacodinámico (FC/FD) de área bajo la curva CMImayor de 400 en pacientes con sospecha o bacteriemia documentadapor Staphylococcus aureus resistente a meticilina(SARM) mediante análisis individual de los pacientes y simulaciónde Monte Carlo.Material y métodos: El estudio incluyó a todos los pacientesingresados con sospecha o bacteriemia documentada porSARM durante los años 2007-2008 y que inicialmente fuerontratados con una dosis de vancomicina de 30 mg/kg/día y quefueron sometidos a seguimiento farmacocinético.El área bajo la curva de la concentración sérica de vancomicinafrente al tiempo de 0 a 24 horas (ABC24h) se calculó comola dosis diaria / aclaramiento total (D24h/CL). Además, se estudiaron45 cepas de SARM obtenidas de hemocultivospertenecientes a pacientes individuales. El CMI a vancomicinafue determinada por Epsilon-test®. Además se realizó una simulaciónde Monte Carlo sobre 10.000 individuos, un ABC24h/CMI >=400 se asumió como objetivo.Resultados: en el estudio individual, el porcentaje de pacientescon ABC24h/CMI50/90 >=400 fue del 50%. La probabilidad(%) de alcanzar ABC24h/CMI >= 400 por simulación Monte Carloen la población estudiada fue de 66%. El valor de CMI a vancomicinaa partir del cual se podría inferir un escenario subóptimode tratamiento (objetivo <90%) fue de > 1 mg/L.Discusión: Este estudio muestra que en la población estudiadaconseguir un cociente ABC24h/CMI >= 400 para vancomicinano es siempre posible con la dosis estándar especialmenteen pacientes infectados con microorganismos con CMI a vancomicina> 1 mg/L y que son tratados con dosis de vancomicinade 30 mg/kg/día(AU)


Objective: The objective of the study is to evaluatethe ability of standard vancomycin dosing strategiesactually recommended to attain the pharmacodynamictarget of an area under the curve of vancomycin serumconcentration versus time from 0 to 24 hours (AUC24h)to minimum inhibitory concentration (MIC) ratio greaterthan 400:1 for patients with a suspected or documentedmethicillin-resistant Staphylococcus aureus(MRSA) bacteraemia by individual analysis and MonteCarlo simulation.Material and methods: The study included all patientsadmitted with suspected or proven MRSA infectionduring the years 2007-2008, and who were initiallytreated with vancomycin at a dose of 30mg/kg/day, and underwent pharmacokinetic monitoring.The area under the curve of vancomycin serumconcentration versus time from 0 to 24 hours (AUC24h)was calculated as daily dose/clearance total (D24h/CL).Additionally, we studied 45 isolates of MRSA obtainedfrom blood cultures in the period 2007-2008. The MICto vancomycin was determined using Epsilon-test®.The PK-PD parameter calculated was AUC24h/MIC. MicrosoftExcel was used to perform a 10.000 subjectMonte Carlo simulation. An AUC24h/MIC ≥ 400 was assumedas the target attainment. Results: In the individual study, the percentage of patientswith AUC24h/MIC50/90 >= 400 was 50%. The probability(%) of attaining AUC24h/MIC ratio values >= 400 by MonteCarlo simulation was of 66%. The vancomycin MIC valuefrom which the scenario would have to wait a suboptimaltreatment (target <90%) was >1 mg/L.Discussion: This study shows that in the populationstudied to achieve a vancomycin AUC24h/MIC >= 400 isnot always attained with the standard dose. Therefore,one would expect a high probability of suboptimal vancomycinAUC24h/MIC ratios for patients infected with organismswith vancomycin MICs of >1 mg/L treated withdoses of 30 mg/kg/day(AU)


Assuntos
Humanos , Masculino , Feminino , Vancomicina/farmacologia , Vancomicina/farmacocinética , Bacteriemia/complicações , Bacteriemia/diagnóstico , Resistência a Meticilina , Resistência a Meticilina/fisiologia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade
16.
Enferm Infecc Microbiol Clin ; 24(10): 608-12, 2006 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-17194385

RESUMO

INTRODUCTION: The aim of this study was to assess the evolution of the population MICs for various antimicrobial drugs against Neisseria meningitidis isolates obtained from asymptomatic carriers during a chemoprophylaxis campaign carried out for an epidemic outbreak of meningococcal disease in Nerva, a small town in Huelva province (Spain). MATERIAL AND METHODS: A nasopharyngeal carrier study including 427 people was carried out to determine the incidence rate of the epidemic strain among the general population. On the basis of the results, chemoprophylaxis with rifampicin was administered to the population aged 15 to 29 years (age group showing the highest incidence of the epidemic strain among carriers) living in Nerva. Three months later a new carrier study was performed (507 people) to evaluate the effects of chemoprophylaxis. Given the evolution of the outbreak, seven months later a new intervention was required with ciprofloxacin chemoprophylaxis; a second carrier study (399 people) was performed two months later to evaluate its effect. RESULTS: The number of strains isolated during the three carrier studies was 59 (13.8%), 33 (6.5%), and 22 (5.5%), respectively. Analysis of the changes in the MIC50 and MIC90 for the various antibiotics from the first to the second carrier study (rifampicin chemoprophylaxis) showed statistical differences only in the distribution of rifampicin MICs. Similarly, when changes from the second to the third study were analyzed (ciprofloxacin chemoprophylaxis), significant variations were detected for the cefotaxime MICs. Nevertheless, although there were changes in the MICs, the percentages of susceptibility from the beginning to the end of the study did not vary. CONCLUSIONS: Massive chemoprophylaxis in the age group with the highest incidence of the epidemic strain among carriers did not clearly modify the antibiotic susceptibility of the isolates. However, a slight increase in the MIC50 and MIC90 was observed for rifampicin after the first chemoprophylactic intervention and for cefotaxime at the end of the study. Consecutive chemoprophylactic interventions with rifampicin and ciprofloxacin had an impact on the percentage of meningococcal carriers in the overall population, with a clearly decreasing trend.


Assuntos
Antibacterianos/farmacologia , Surtos de Doenças , Neisseria meningitidis/efeitos dos fármacos , Antibacterianos/uso terapêutico , Portador Sadio/microbiologia , Resistência a Medicamentos , Humanos , Nasofaringe/microbiologia , Neisseria meningitidis/isolamento & purificação , Espanha , Fatores de Tempo
17.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 24(10): 608-612, dic. 2006. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-050946

RESUMO

Introducción. El objetivo del estudio fue evaluar la evolución de las concentraciones inhibitorias mínimas (CIM) poblacionales frente a diversos antimicrobianos en aislamientos de Neisseria meningitidis obtenidos de portadores asintomáticos en el contexto de un brote epidémico de enfermedad meningocócica localizado en la provincia de Huelva en el que se realizó una intervención de quimioprofilaxis en población general. Material y métodos. El primer estudio de portadores se realizó en 427 individuos con objeto de conocer la presencia de la cepa causante del brote en población general. Como resultado se procedió a utilizar quimioproflaxis con rifampicina en la población entre 15 y 29 años (grupo etario con mayor presencia de la cepa epidémica), residentes en la población de Nerva. A los 3 meses se realizó un nuevo estudio de portadores (507 personas) para evaluar el efecto de dicha quimioprofilaxis. Dada la evolución del brote epidémico fue necesario realizar a los 7 meses una nueva intervención con ciprofloxacino y transcurridos 2 meses un nuevo estudio de portadores (399 personas) para evaluar su efecto. Resultados. El número de cepas aisladas en los 3 estudios de portadores realizados fue de 59 (13,8%), 33 (6,5%) y 22 (5,5%), respectivamente. El análisis de la evolución de la CIM50 y CIM90 de los distintos antibióticos del primer al segundo estudio de portadores (quimioprofilaxis con rifampicina) únicamente detectó cambios con significación estadística en las CIM de rifampicina. Así mismo, cuando se analizó la variación en la distribución de las CIM del segundo al tercer estudio (quimioprofilaxis con ciprofloxacino) fueron detectados cambios significativos particularmente en las CIM de cefotaxima. Aunque existieron variaciones de CIM, los porcentajes de sensibilidad al principio y final del estudio no variaron. Conclusiones. El empleo de quimioprofilaxis masiva en el grupo de edad con mayor porcentaje de portadores de la cepa de N. meningitidis responsable del brote no modificó sensiblemente la sensibilidad antibiótica de los aislados, si bien puede observarse un aumento de los valores de la CIM50 y CIM90 en el caso de la rifampicina tras la intervención con este antimicrobiano, y en el caso de la cefotaxima tras las 2 intervenciones realizadas. Las sucesivas intervenciones de quimioprofilaxis con rifampicina y posteriormente con ciprofloxacino tuvieron un claro reflejo en el porcentaje portadores en la población general, con una tendencia claramente decreciente (AU)


Introduction. The aim of this study was to assess the evolution of the population MICs for various antimicrobial drugs against Neisseria meningitidis isolates obtained from asymptomatic carriers during a chemoprophylaxis campaign carried out for an epidemic outbreak of meningococcal disease in Nerva, a small town in Huelva province (Spain). Material and methods. A nasopharyngeal carrier study including 427 people was carried out to determine the incidence rate of the epidemic strain among the general population. On the basis of the results, chemoprophylaxis with rifampicin was administered to the population aged 15 to 29 years (age group showing the highest incidence of the epidemic strain among carriers) living in Nerva. Three months later a new carrier study was performed (507 people) to evaluate the effects of chemoprophylaxis. Given the evolution of the outbreak, seven months later a new intervention was required with ciprofloxacin chemoprophylaxis; a second carrier study (399 people) was performed two months later to evaluate its effect. Results. The number of strains isolated during the three carrier studies was 59 (13.8%), 33 (6.5%), and 22 (5.5%), respectively. Analysis of the changes in the MIC50 and MIC90 for the various antibiotics from the first to the second carrier study (rifampicin chemoprophylaxis) showed statistical differences only in the distribution of rifampicin MICs. Similarly, when changes from the second to the third study were analyzed (ciprofloxacin chemoprophylaxis), significant variations were detected for the cefotaxime MICs. Nevertheless, although there were changes in the MICs, the percentages of susceptibility from the beginning to the end of the study did not vary. Conclusions. Massive chemoprophylaxis in the age group with the highest incidence of the epidemic strain among carriers did not clearly modify the antibiotic susceptibility of the isolates. However, a slight increase in the MIC50 and MIC90 was observed for rifampicin after the first chemoprophylactic intervention and for cefotaxime at the end of the study. Consecutive chemoprophylactic interventions with rifampicin and ciprofloxacin had an impact on the percentage of meningococcal carriers in the overall population, with a clearly decreasing trend (AU)


Assuntos
Humanos , Neisseria meningitidis , Testes de Sensibilidade Microbiana/métodos , Neisseria meningitidis/patogenicidade , Resistência Microbiana a Medicamentos , Surtos de Doenças , Rifampina/farmacocinética , Antibioticoprofilaxia , Ciprofloxacino/farmacocinética , Avaliação de Resultado de Intervenções Terapêuticas , Cefotaxima/farmacocinética , Portador Sadio/epidemiologia
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