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1.
Int J Antimicrob Agents ; 54(4): 442-448, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377343

RESUMO

External validation of the INCREMENT-CPE risk score (ICS) for 30-day all-cause mortality is needed. There is also scarce information about whether colistin resistance influences the prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKp) bacteraemia. In this study, the ability of ICS to predict all-cause mortality in the KAPECOR cohort was calculated using the area under the receiver operating characteristic (AUROC) curve. The association of colistin resistance with mortality was studied. The ICS showed an AUROC curve of 0.77 (95% CI 0.68-0.86). A cut-off of 8 points showed 96.8% sensitivity and 50.7% specificity. Mortality of low-risk patients was not different in those treated with monotherapy versus combination therapy. However, mortality of high-risk patients treated with combination therapy (37.8%) was significantly lower than in those treated with monotherapy (68.4%) (P = 0.008). To study the prognostic significance of colistin resistance, 83 selected cases of bacteraemia due to colistin-susceptible CRKp were obtained from the INCREMENT cohort for comparison. Colistin resistance could not be shown to be associated with higher mortality in either the high-risk ICS group [adjusted odds ratio (aOR) = 1.56, 95% CI 0.69-3.33; P = 0.29] or in 37 ICS-matched pairs (aOR = 1.38, 95% CI 0.55-3.42; P = 0.49), or in a sensitivity analysis including only KPC isolates (aOR = 1.81, 95% CI 0.73-4.57; P = 0.20), but the precision of estimates was low. These results validate ICS for all-cause mortality and to optimise targeted therapy for CRKp bacteraemia. Colistin resistance was not clearly associated with increased mortality.


Assuntos
Bacteriemia/mortalidade , Bacteriemia/patologia , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/isolamento & purificação , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Colistina/farmacologia , Farmacorresistência Bacteriana , Feminino , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Análise de Sobrevida
2.
Open Forum Infect Dis ; 6(7): ofz251, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31334296

RESUMO

Background: Echinocandins are recommended as firstline therapy in patients with candidemia. However, there is debate on their efficacy in survival outcomes. The aim of this study is to evaluate whether the choice of initial antifungal therapy improves mortality in patients with candidemia in relation to the presence of septic shock. Methods: Patients with candidemia hospitalized in internal medicine wards of 5 tertiary care centers were included in the study (December 2012-December 2014). Patient characteristics, therapeutic interventions, and outcome were reviewed. Propensity score (PS) was used as a covariate of the multivariate analysis to perform a stratified analysis according to PS quartiles and to match patients receiving "echinocandins" or "azoles." Results: Overall, 439 patients with candidemia were included in the study. A total of 172 (39.2%) patients had septic shock. Thirty-day mortality was significantly higher in patients with septic shock (45.3%) compared with those without septic shock (31.5%; P = .003). Among patients with septic shock, the use of echinocandins in the first 48 hours, compared with azoles, did not affect 30-day mortality in the PS-adjusted Cox regression analysis (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.37-1.59; P = .48), the PS-stratified analysis, or the logistic regression model in matched cohorts (adjusted HR, 0.92; 95% CI, 0.51-1.63; P = .77). Conclusions: Echinocandin therapy seems not to improve the outcome of non-intensive care unit patients with septic shock due to candidemia. These findings support the urgent need of further studies in this patient population.

3.
J Infect ; 79(3): 245-252, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31276705

RESUMO

INTRODUCTION: There is scarce information on the prognosis of urinary tract infections (UTI) caused by KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). OBJETIVE: To investigate the association between KPC-Kp aetiology and clinical failure and all cause mortality and to explore the impact of inappropriate empirical treatment. MATERIAL AND METHODS: This is a retrospective observational study of hospitalized patients with UTI due to K. pneumoniae. We explored clinical failure at day 21 and 30-day all-cause mortality using different models of adjusted analysis. RESULTS: We analyzed 142 episodes of UTI; 46 episodes (32.4%) were due to KPC-Kp and 96 episodes (67.6%) were due to non-KPC-Kp strains (62 wild type and 34 EBSL producer). Clinical failure was more frequent in the KPC-Kp group (41.3% vs. 15.6%, p = 0.001). KPC-Kp aetiology and inappropriate empirical therapy were associated in the non-adjusted analysis with clinical failure. When analysed in separate adjusted models, both were found to be associated; inappropriate empirical treatment (OR 2.51; 95% CI, 1.03-6.12; p = 0.04) and KPC-Kp (OR 2.73; 95% CI, 1.03-7.22; p = 0.04) were associated with increased risk of failure. All-cause 30-day mortality was higher in patients with KPC-Kp UTI (39.1% vs. 15.6%, p = 0.002). Bacteraemia was more frequent in patients with KPC-Kp etiology (23.9% vs. 10.4%; p = 0.034). In both cases, the association was not confirmed in the adjusted analysis. CONCLUSION: KPC-Kp UTI is associated with higher clinical failure and may be due to an increase in inappropriate empirical treatment.

4.
Expert Rev Anti Infect Ther ; 17(4): 265-273, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30876375

RESUMO

INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections are associated with high morbidity and mortality rates. A therapeutic approach based on the patient risk stratification could improve outcome and avoid antibiotic misuse. Areas covered: English literature search, from 2008 to 2018, was done using PubMed database. Risk factors for developing CR-KP infection in several settings were reviewed. Since, rectal carriage was a main risk factor for developing infection, we revised in deep clinical score to predict infection among colonized patients. Furthermore, we investigated overall and treatment-related risk factors for poor outcome in patients with CR-KP infection, in particular the carbapenem producing Enterobacteriacieae (CPE)-INCREMENT score. Finally, an algorithm, based on such scores, for the therapeutic management of patients with CR-KP colonization was commented. Expert opinion: The therapeutic approach analyzed in this review could help physicians to avoid antibiotic overuse as well as to start promptly with the most appropriate antibiotic regimen. However, it has to be validated in further studies, mainly among special population such as immunocompromised patients. The availability of new drugs, fast microbiology, and analysis of gut microbiome could significantly improve the management of CR-KP colonized and/or infected patients.

6.
Diagn Microbiol Infect Dis ; 93(1): 63-68, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30131239

RESUMO

OBJECTIVE: To investigate whether the magnitude of the change in procalcitonin (PCT) and C-reactive protein (CRP) levels between day 1 and day 2 after the blood culture date is associated with early clinical stability (ECS) on day 3 in patients with bacteremia due to Gram-negative bacteria (GNB). MATERIALS/METHODS: A prospective cohort study carried out in a 950-bed tertiary hospital in Spain between March 2013 and May 2014. Patients with GNB bacteremia were included. Changes in PCT and CRP kinetics from day 1 to day 2 (∆%PCT, ∆%CRP) were expressed as percentage of decline in blood levels. Logistic regression was used to identify predictors of ECS. Classification and regression tree analysis was performed to identify breakpoints. The discriminatory power of ∆%CRP and ∆%PCT as predictors of ECS was assessed by the area under the ROC (AUROC). RESULTS: 71 patients were included, and 53 (74.56%) reached ECS. Multivariate analyses showed that SOFA score on day 1, ∆%PCT, and ∆%CRP were associated with ECS after controlling for confounders. ∆%PCT ≥ 30% (decline) and ∆%CRP ≥ 10% (decline) predicted ECS only among patients with SOFA≤3 on day 1 (n = 54; 43 reached ECS). In these patients, the AUROCs for the prediction of ECS were 0.96 (95% CI: 0.90-1) for ∆%CRP and 0.96 (95% CI: 0.90-1) for ∆%PCT, respectively. CONCLUSIONS: In the subgroup of patients with a SOFA score on day 1 ≤3, a ≥30% decline in PCT or a ≥10% decline in CRP between day 1 and day 2 was a very good predictor of ECS (which in turn was associated with a lower 30-day mortality and a greater clinical cure on day 14). Patients who do not achieve this decrease may need more intensive workup. In this subgroup (with a SOFA on day 1 ≤3), CRP may be preferred due to its lower cost.


Assuntos
Bacteriemia/diagnóstico , Proteína C-Reativa/análise , Bactérias Gram-Negativas/isolamento & purificação , Pró-Calcitonina/análise , Sepse/diagnóstico , Idoso , Bacteriemia/sangue , Bacteriemia/fisiopatologia , Biomarcadores/sangue , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Estudos Prospectivos , Curva ROC , Sepse/sangue , Sepse/fisiopatologia
7.
Am J Transplant ; 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31891235

RESUMO

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

8.
Artigo em Inglês | MEDLINE | ID: mdl-30473785

RESUMO

Background: Escherichia coli sequence type 131 (ST131) is a successful clonal group that has dramatically spread during the last decades and is considered an important driver for the rapid increase of quinolone resistance in E. coli. Methods: Risk factors for rectal colonization by ST131 Escherichia coli (irrespective of ESBL production) were investigated in 64 household members (18 were colonized) and 54 hospital contacts (HC; 10 colonized) of 34 and 30 index patients with community and nosocomial infection due to these organisms, respectively, using multilevel analysis with a p limit of < 0.1. Result: Colonization among household members was associated with the use of proton-pump inhibitors (PPI) by the household member (OR = 3.08; 95% CI: 0.88-10.8) and higher age of index patients (OR = 1.05; 95% CI; 1.01-1.10), and among HC, with being bed-ridden (OR = 21.1; 95% CI: 3.61-160.0) and having a urinary catheter (OR = 8.4; 95% CI: 0.87-76.9). Conclusion: Use of PPI and variables associated with higher need of person-to-person contact are associated with increased risk of rectal colonization by ST131. These results should be considered for infection control purposes.


Assuntos
Infecção Hospitalar/epidemiologia , Infecções por Escherichia coli/epidemiologia , Escherichia coli/isolamento & purificação , Reto/microbiologia , Adulto , Idoso , Anti-Infecciosos/farmacologia , Estudos de Casos e Controles , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Escherichia coli/crescimento & desenvolvimento , Infecções por Escherichia coli/tratamento farmacológico , Características da Família , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Quinolonas/farmacologia , Fatores de Risco
9.
Infect Control Hosp Epidemiol ; 39(6): 660-667, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29618394

RESUMO

OBJECTIVETo compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypesMETHODSAs part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.RESULTSThe study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non-CTX-M ESBLs were detected.CONCLUSIONSClinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.CLINICAL TRIALS IDENTIFIERClinicalTrials.gov. Identifier: NCT01764490.Infect Control Hosp Epidemiol 2018;39:660-667.


Assuntos
Bacteriemia/microbiologia , Bacteriemia/mortalidade , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Infecções por Escherichia coli/mortalidade , Infecções por Klebsiella/mortalidade , Adulto , Idoso , Escherichia coli/enzimologia , Escherichia coli/genética , Feminino , Genótipo , Registros Hospitalares , Humanos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , beta-Lactamases/metabolismo
10.
Clin Microbiol Rev ; 31(2)2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29444952

RESUMO

Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum ß-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer ß-lactam-ß-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producing Enterobacteriaceae (CPE), only some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Humanos , beta-Lactamases/metabolismo
11.
Enferm Infecc Microbiol Clin ; 36(8): 484-492, 2018 10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29110928

RESUMO

INTRODUCTION: The rapid identification of bacteraemia-causing pathogens could assist clinicians in the timely prescription of targeted therapy, thereby reducing the morbidity and mortality of this infection. In recent years, numerous techniques that rapidly and directly identify positive blood cultures have been marketed, with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) being one of the most commonly used. METHODS: The aim of this systematic review and meta-analysis was to evaluate the accuracy of MALDI-TOF (Bruker®) for the direct identification of positive blood culture bottles. RESULTS: A meta-analysis was performed to summarize the results of the 32 studies evaluated. The overall quality of the studies was moderate. For Gram-positive bacteria, overall rates of correct identification of the species ranged from 0.17 to 0.98, with a cumulative rate (random-effects model) of 0.72 (95% CI: 0.64-0.80). For Gram-negative bacteria, correct identification rates ranged from 0.66 to 1.00, with a cumulative effect of 0.92 (95% CI: 0.88-0.95). For Enterobacteriaceae, the rate was 0.96 (95% CI: 0.94-0.97). CONCLUSION: MALDI-TOF mass spectrometry shows high accuracy for the correct identification of Gram-negative bacteria, particularly Enterobacteriaceae, directly from positive blood culture bottles, and moderate accuracy for the identification of Gram-positive bacteria (low for some species).


Assuntos
Bacteriemia/sangue , Bacteriemia/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Hemocultura , Humanos , Reprodutibilidade dos Testes
12.
Clin Infect Dis ; 66(8): 1204-1210, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29126110

RESUMO

Background: The management and indication of empiric treatment in Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp)-colonized patients should be improved. Methods: A prospective cohort of 94 patients colonized by KPC-Kp was followed for 90 days to validate (i) the Giannella risk score (GRS) to predict the development of any type of KPC-Kp infection and (ii) the INCREMENT-CPE score (ICS) to predict 30-day mortality in patients with infection. Both scores were combined to recommend appropriate empiric treatment. The predictive ability of the scores was measured by calculating the area under the receiver operating characteristic (AUROC) curve. Results: The GRS showed an AUROC curve for infection due to KPC-Kp of 0.92 (95% confidence interval [CI], .87-.98). The optimal cutoff point was fixed at <7 and ≥7 (92.9% sensitivity, 84.8% specificity); infection developed in 6.3% patients in the 0-6 GRS group and in 84.8% patient in the ≥7 GRS group. According to the ICS, the severity of the infection was also significantly higher in the ≥7 GRS group. The ICS showed an AUROC of 0.78 (95% CI, .65-.91) for 30-day all-cause mortality among patients with infection. A classification and regression tree analysis confirmed the GRS cutoff point at 7, and selected ≥12 points to predict a KPC-Kp infection with a high ICS. Conclusions: Our results validate the GRS and ICS for indicating empiric therapy in KPC-Kp-colonized patients.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/enzimologia , beta-Lactamases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Portador Sadio , Estudos de Coortes , Feminino , Hospitais , Humanos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reto/microbiologia , Risco , Espanha/epidemiologia , Análise de Sobrevida
13.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 35(10): 617-623, dic. 2017. tab
Artigo em Espanhol | IBECS | ID: ibc-169560

RESUMO

Algunas enfermedades infecciosas han adquirido más relevancia por el aumento de los movimientos poblacionales. La eosinofilia es un hallazgo frecuente en inmigrantes y en viajeros. Una de las causas más frecuentes de eosinofilia es la infección por helmintos y algunos protozoos intestinales. El objetivo de este trabajo es describir las características epidemiológicas de los casos con eosinofilia y su asociación con la presencia de parásitos en la red de datos REDIVI. Se trata de un estudio observacional multicéntrico prospectivo, donde se incluyen los casos diagnosticados de eosinofilia registrados en la Red cooperativa para el estudio de las infecciones importadas por viajeros e inmigrantes (+REDIVI) desde enero de 2009 hasta diciembre de 2012. Se registraron en la red un total de 5.255 episodios durante el periodo de estudio, y la eosinofilia fue un hallazgo en el 8,1 al 31,3% de los casos (dependiendo del tipo migratorio). Fueron hombres el 60,2%, con una mediana de 31,0años, inmigrantes el 72,4% y asintomáticos el 81,2%. Los parásitos más frecuentemente identificados fueron S.stercoralis(34,4%), Schistosoma sp. (11,0%) y uncinarias (8,6%). Existía asociación entre eosinofilia y presencia de parásitos para todos los helmintos (excepto para larva migrans cutánea). La sintomatología y la duración del viaje no determinaron significativamente la presencia de eosinofilia. Ante una eosinofilia en una persona que ha vivido en zonas endémicas de helmintiasis es aconsejable realizar estudios dirigidos para su diagnóstico, independientemente del tipo migratorio, la duración de la estancia o la presencia de sintomatología (AU)


The population movements during the last decades have resulted in a progressively increasing interest in certain infectious diseases. Eosinophilia is a common finding in immigrants and travelers. One of the most common causes of eosinophilia is helminth infection, and some intestinal protozoa. The aim of this paper is to describe the epidemiological characteristics of cases with eosinophilia and its association with the presence of parasites in the REDIVI data network. This is a multicenter prospective observational study that includes patients diagnosed with eosinophilia registered in the cooperative network for the study of infectious diseases in travelers and immigrants (+REDIVI) from January 2009 to December 2012. A total of 5,255 episodes were recorded in the network during the study period, and eosinophilia was observed in 8.1-31.3% of cases (depending on the immigration group). There were 60.2% men, with a median age of 31years. There were 72.4% immigrants, and 81.2% were asymptomatic. The most commonly identified parasites were S.stercoralis (34.4%), Schistosoma sp. (11.0%), and hookworm (8.6%). The relationship between eosinophilia and parasite infection was significant for all helminths (except for cutaneous larva migrans). The symptoms and duration of the journey did not significantly determine the presence of eosinophilia. In the case of eosinophilia in a person who has lived in helminth endemic areas, it is advisable to carry out targeted studies to diagnose the infection, regardless of immigration type, length of stay, or the presence of symptoms (AU)


Assuntos
Humanos , Eosinofilia/epidemiologia , Eosinofilia/prevenção & controle , Saúde do Viajante , Fatores de Risco , Emigrantes e Imigrantes , Protocolos Clínicos , Doenças Transmissíveis/epidemiologia , Estudos Prospectivos , Eosinofilia/microbiologia , Medicina de Viagem/normas , Eosinofilia/parasitologia
14.
Clin Infect Dis ; 65(10): 1615-1623, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29020250

RESUMO

Background: There is little information about the efficacy of active alternative drugs to carbapenems except ß-lactam/ß-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems. Methods: A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with OADs or carbapenems was performed. Cox regression including a propensity score for receiving OADs was performed to analyze 30-day all-cause mortality as main outcome. Clinical failure and length of stay were also analyzed. Results: Overall, 335 patients were included; 249 received empiric carbapenems and 86 OADs. The most frequent OADs were aminoglycosides (43 patients) and fluoroquinolones (20 patients). Empiric therapy with OADs was not associated with mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI], .38-1.48) in the Cox regression analysis. Propensity score-matched pairs, subgroups, and sensitivity analyses did not show different trends; specifically, the adjusted HR for aminoglycosides was 1.05 (95% CI, .51-2.16). OADs were neither associated with 14-day clinical failure (adjusted odds ratio, 0.62; 95% CI, .29-1.36) nor length of hospital stay. Conclusions: We were unable to show that empiric treatment with OAD was associated with a worse outcome compared with carbapenems. This information allows more options to be considered for empiric therapy, at least for some patients, depending on local susceptibility patterns of ESBL-E.


Assuntos
Antibacterianos , Bacteriemia , Infecções por Enterobacteriaceae , Enterobacteriaceae , Resistência beta-Lactâmica , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Carbapenêmicos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , beta-Lactamases
16.
Int J Antimicrob Agents ; 50(5): 664-672, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28782704

RESUMO

We describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Patients (n = 1482) in 12 countries from an observational study of BSI caused by ESBL-E or CPE were included. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ß-lactam/ß-lactamase inhibitors (BLBLIs) or carbapenems, targeted use of BLBLIs for ESBL-E and use of targeted combination therapy for CPE. Compared with Spain, BLBLI use for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.25) and Turkey (aOR 2.09, 95% CI 1.14-3.81). Empirical carbapenem use was more likely in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89, 95% CI 1.05-3.39) and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLIs for ESBL-E was more likely in Italian sites. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. Better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.


Assuntos
Farmacorresistência Bacteriana Múltipla , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Sepse/tratamento farmacológico , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Feminino , Saúde Global , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/microbiologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-28559247

RESUMO

Combination therapy including colistin and a carbapenem has been found to be associated with lower mortality in the treatment of bloodstream infections (BSI) due to KPC-producing Klebsiella pneumoniae when the isolates show a meropenem or imipenem MIC of <16 mg/liter. However, the optimal treatment of BSI caused by colistin- and high-level carbapenem-resistant KPC-producing K. pneumoniae is unknown. A prospective cohort study including episodes of bacteremia caused by colistin-resistant and high-level meropenem-resistant (MIC ≥ 64 mg/liter) KPC-producing K. pneumoniae diagnosed from July 2012 to February 2016 was performed. The impact of combination therapy on crude 30-day mortality was analyzed by Cox regression using a propensity score as a covariate to control for indication bias and in an inverse probability of treatment weighting (IPTW) cohort. The study sample comprised 104 patients, of which 32 (30.8%) received targeted monotherapy and 72 (69.2%) received targeted combination therapy; none of them received either colistin or a carbapenem. The 30-day crude mortality rate was 30.8% (43.8% in patients treated with monotherapy and 25% in patients receiving combination therapy). In the Cox regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (hazard ratio [HR], 6.03; 95% confidence interval [CI], 1.65 to 21.9; P = 0.006) and admission to the critical care unit (HR, 2.87; 95% CI, 0.99 to 8.27; P = 0.05). Targeted combination therapy was associated with lower mortality only in patients with septic shock (HR, 0.14; 95% CI, 0.03 to 0.67; P = 0.01). These results were confirmed in the Cox regression analysis of the IPTW cohort. Combination therapy is associated with reduced mortality in patients with bacteremia due to colistin-resistant KPC-producing K. pneumoniae with high-level carbapenem resistance in patients with septic shock.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Colistina/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Choque Séptico/tratamento farmacológico , Tienamicinas/uso terapêutico , Idoso , Bacteriemia/microbiologia , Combinação de Medicamentos , Feminino , Fosfomicina/uso terapêutico , Gentamicinas/uso terapêutico , Humanos , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/genética , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Minociclina/análogos & derivados , Minociclina/uso terapêutico , Estudos Prospectivos , Tigeciclina
18.
Lancet Infect Dis ; 17(7): 726-734, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28442293

RESUMO

BACKGROUND: The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. METHODS: In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0-7 [low mortality score] vs 8-15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. FINDINGS: Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0-33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33-0·62]; p<0·0001). Among those receiving appropriate therapy, 135 (39%) received combination therapy and 208 (61%) received monotherapy. Overall mortality was not different between those receiving combination therapy or monotherapy (47 [35%] of 135 vs 85 [41%] of 208; adjusted HR 1·63 [95% CI 0·67-3·91]; p=0·28). However, combination therapy was associated with lower mortality than was monotherapy in the high-mortality-score stratum (30 [48%] of 63 vs 64 [62%] of 103; adjusted HR 0·56 [0·34-0·91]; p=0·02), but not in the low-mortality-score stratum (17 [24%] of 72 vs 21 [20%] of 105; adjusted odds ratio 1·21 [0·56-2·56]; p=0·62). INTERPRETATION: Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to CPE. Combination therapy was associated with improved survival only in patients with a high mortality score. Patients with BSIs due to CPE should receive active therapy as soon as they are diagnosed, and monotherapy should be considered for those in the low-mortality-score stratum. FUNDING: Spanish Network for Research in Infectious Diseases, European Development Regional Fund, Instituto de Salud Carlos III, and Innovative Medicines Initiative.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/mortalidade , Idoso , Bacteriemia/tratamento farmacológico , Proteínas de Bactérias , Quimioterapia Combinada/métodos , Feminino , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , beta-Lactamases
19.
BMJ Open ; 7(4): e015365, 2017 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-28373258

RESUMO

INTRODUCTION: The rapid worldwide spread of carbapenem-resistant Enterobacteriaceae (CRE) constitutes a major challenge. The aim of the EUropean prospective cohort study on Enterobacteriaceae showing REsistance to CArbapenems (EURECA), which is part of the Innovative Medicines Initiative Joint Undertaking (IMI JU) funded COMBACTE-CARE project, is to investigate risk factors for and outcome determinants of CRE infections to inform randomised clinical trial designs and to provide a historical cohort that could eventually be used for future comparisons with new drugs targeting CRE. METHODS: A multicentre (50 sites), multinational (11 European countries), analytical observational project was designed, comprising 3 studies. The aims of study 1 (a prospective cohort study) include characterising the features, clinical management and outcomes of hospitalised patients with intra-abdominal infection, pneumonia, complicated urinary tract infections and bloodstream infections caused by CRE (202 patients in each group). The main outcomes will be 30-day all-cause mortality and clinical response. Study 2 (a nested case-control study) will identify the risk factors for target infections caused by CRE; 248 selected patients from study 1 will be matched with patients with carbapenem-susceptible Enterobacteriaceae (1:1) and with hospitalised patients (1:3) and will provide a historical cohort of patients with CRE infections. Study 3 (a matched cohort study) will follow patients in study 2 in order to assess mortality, length of stay and hospital costs associated with CRE. All patients will be followed for 30 days. Different, up-to-date statistical methods will be applied to come to unbiased estimates for all 3 studies. ETHICS AND DISSEMINATION: Before-study sites will be initiated, approval will be sought from appropriate regulatory agencies and local Ethics Committees of Research or Institutional Review Boards (IRBs) to conduct the study in accordance with regulatory requirements. This is an observational study and therefore no intervention in the diagnosis, management or treatment of the patients will be required on behalf of the investigation. Any formal presentation or publication of data collected from this study will be considered as a joint publication by the participating physician(s) and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE) for authorship. TRIAL REGISTRATION NUMBER: NCT02709408.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Carbapenêmicos , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções Intra-Abdominais/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Bacteriemia/microbiologia , Estudos de Casos e Controles , Causas de Morte , Estudos de Coortes , Enterobacteriaceae , Infecções por Enterobacteriaceae/microbiologia , Europa (Continente) , Hospitalização , Humanos , Infecções Intra-Abdominais/microbiologia , Testes de Sensibilidade Microbiana , Mortalidade , Pneumonia Bacteriana/microbiologia , Estudos Prospectivos , Resultado do Tratamento , Infecções Urinárias/microbiologia
20.
J Antimicrob Chemother ; 72(3): 906-913, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28062685

RESUMO

Background: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. Methods: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC. Results: The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC. Conclusions: We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality.


Assuntos
Bacteriemia/mortalidade , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Enterobacteriaceae/enzimologia , beta-Lactamases/biossíntese , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Humanos , Klebsiella/enzimologia , Klebsiella/isolamento & purificação , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Sepse/tratamento farmacológico
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