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1.
Med Intensiva (Engl Ed) ; 46(8): 426-435, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35868719

RESUMO

OBJECTIVE: To determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24h of admission. DESIGN: Secondary analysis of an observational and prospective cohort study. SETTING: ICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019. PATIENTS: Consecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Incidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. RESULTS: 3702 patients were analyzed in this study. AI incidence was 1.13% (n=42). Hematological malignancies (OR 4.39, 95% CI 1.92-10.04); HIV (OR 3.83, 95% CI 1.08-13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99-11.87) were factors independently associated with the presence of Aspergillus spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95-3.51), immunosuppression (OR 2.05 95% CI 1.46-2.88) and AI (OR 3.24, 95% CI 1.60-6.53) were variables independently associated with ICU mortality. CONCLUSIONS: Empirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for Aspergillus spp. should be implemented.


Assuntos
Influenza Humana , Orthomyxoviridae , Pneumonia , Aspergillus , Estado Terminal , Humanos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Estudos Prospectivos
3.
Cell Tissue Bank ; 22(4): 539-549, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34549351

RESUMO

The transmission of microbial infection through tissue allografts is one of the main risks that must be controlled in tissue banks. Therefore, microbiological monitoring controls and validated protocols for the decontamination of tissues during processing have been implemented. This study is based on the evaluation of data from microbiological cultures of arteries (mainly long peripheral arteries) processed in the tissue bank of Valencia (Spain). Donors' profile, pre- and post-disinfection tissue samples were assessed. The presence of residual antibiotics in disinfected tissues was determined and the antimicrobial potential of these tissues was tested. Our overall contamination rate was 23.69%, with a disinfection rate (after antibiotic incubation) of 87.5%. Most (76.09%) of the microbial contaminants were identified as Gram positive. Arterial allografts collected from body sites affected by prior organ removal showed higher risk of contamination. Only vancomycin was detected as tissue release. The antimicrobial effect on Candida albicans was lower than that for bacterial species. Risk assessment for microbial contamination suggested the donor's skin and the environment during tissue collection as the main sources for allograft contamination. Antibiotic-disinfected arterial allografts showed antimicrobial potential.


Assuntos
Bancos de Tecidos , Vancomicina , Aloenxertos , Artérias , Doadores de Tecidos , Transplante Homólogo
4.
Open Forum Infect Dis ; 8(6): ofab250, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34104670

RESUMO

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

5.
J Hosp Infect ; 112: 49-53, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33711353

RESUMO

BACKGROUND: Microbiological contamination is one of the main risks that must be controlled in tissue banking practices. For this reason, strict donor selection criteria are applied, disinfection protocols are used, and microbiological monitoring is performed at various stages. AIM: To detect Candida auris in arterial allografts and assess its origin. METHODS: Data on two multi-tissue donations with positive microbiological cultures for C. auris were analysed. Risk factors for microbiological contamination were assessed at procurement, processing and post storage. FINDINGS: C. auris was only isolated in cultures from arteries, and was not detected in cultures from cornea, musculoskeletal tissue or skin (even in the axillary-rectal sample taken from one donor). CONCLUSION: The donor's own skin was identified as the most likely source to explain the contamination of arteries by C. auris. Due to the pathogenicity of this fungus and difficulties associated with its correct identification, the implementation of measures for its detection in tissue donations is recommended.


Assuntos
Candida , Doadores de Tecidos , Aloenxertos , Artérias , Humanos , Medição de Risco
6.
Clin Microbiol Infect ; 26(11): 1507-1513, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32061792

RESUMO

OBJECTIVES: Candida auris is an emerging multidrug-resistant fungus that has been associated with nosocomial outbreaks with high rates of mortality and transmission. The aim of this study was to perform a retrospective cohort analysis of risk factors and to build a scoring method for estimating the risk of candidaemia in colonized critically ill patients. METHODS: We performed a retrospective observational cohort study of patients aged ≥15 years colonized by C. auris in the 3-year period between March 2016 and March 2019. Epidemiological, clinical, laboratory and microbiological data were collected. We developed a predictive model for candidaemia using elastic net multivariable logistic regression techniques, assessed its discriminative capacity, and internally validated it using bootstrap resampling. RESULTS: Two-hundred and six patients were enrolled in the cohort for derivation and internal validation. Thirty-seven out of 206 patients developed candidaemia. Total parenteral nutrition was the foremost risk factor (adjusted OR 3.73); previous surgery (adjusted OR 1.03), sepsis (adjusted OR 1.75), previous exposure to antifungal agents (adjusted OR 1.17), arterial catheters (adjusted OR 1.46), central venous catheters (adjusted OR 1.21), presence of advanced chronic kidney disease (adjusted OR 1.35) and multifocal colonization (adjusted OR of unifocal colonization 0.46) were proven to be independent predictors of candidaemia in our cohort. The corresponding area under the curve (AUC) of the elastic net regularized predictive model was 0.89 (95%CI 0.826; 0.951). After performing the internal validation by generating 500 bootstrap replications, the model still showed great accuracy, with a resulting AUC of 0.84. CONCLUSION: Our study provides evidence on the independent predisposing factors for candidaemia. It may help predict its estimated risk and may identify a high-risk population that could benefit from early or prophylactic antifungal treatment after external validation in other cohorts.


Assuntos
Candida/patogenicidade , Candidemia/epidemiologia , Adulto , Idoso , Área Sob a Curva , Comorbidade , Estado Terminal , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco
7.
Artigo em Inglês | MEDLINE | ID: mdl-30323038

RESUMO

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans, 215 C. dubliniensis, 4,418 C. glabrata species complex, 157 C.guilliermondii (Meyerozyma guilliermondii), 676 C. krusei (Pichia kudriavzevii), 298 C.lusitaniae (Clavispora lusitaniae), 911 C.parapsilosissensu stricto, 3,691 C.parapsilosis species complex, 36 C.metapsilosis, 110 C.orthopsilosis, 1,854 C.tropicalis, 244 Saccharomyces cerevisiae, 1,409 Aspergillus fumigatus, 389 A.flavus, 130 A.nidulans, 233 A.niger, and 302 A.terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 (C. albicans), ERG11 and MRR1 (C. parapsilosis), cyp51A (A. fumigatus), and CDR2 and CDR1 overexpression (C. albicans and C. glabrata, respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants.


Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Triazóis/farmacologia , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus/classificação , Aspergillus/isolamento & purificação , Candida/classificação , Candida/isolamento & purificação , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candidíase/microbiologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Fúngica , Fluconazol/farmacologia , Humanos , Hospedeiro Imunocomprometido , Itraconazol/farmacologia , Voriconazol/farmacologia
8.
J Antimicrob Chemother ; 71(12): 3449-3452, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27543657

RESUMO

OBJECTIVES: To evaluate the in vitro activity of anidulafungin combined with amphotericin B or voriconazole against Candida spp. biofilms. METHODS: Four Candida albicans, four Candida tropicalis, four Candida glabrata, two Candida parapsilosis and two Candida orthopsilosis blood isolates were tested by the microdilution chequerboard method combined with the XTT metabolic assay. Biofilm MIC was defined as the lowest concentration producing 50% metabolic inhibition with respect to control (BMIC50). Concentrations in the combinations ranged from 1/8 × BMIC50 to 4 × BMIC50 found for each antifungal tested alone. RESULTS: Anidulafungin plus amphotericin B acted synergistically against C. albicans and C. glabrata biofilms [fractional inhibitory concentration index (FICI): 0.082-0.387], but showed no interaction against C. tropicalis, C. parapsilosis and C. orthopsilosis (FICI: 0.516-2.099). The combination of these antifungals failed to completely remove biofilms of C. albicans and C. glabrata, decreasing the metabolic activity of the biofilms up to 80% and 95%, respectively, which did not occur when each antifungal was used alone. Anidulafungin plus voriconazole showed no interaction against all isolates. Using a less stringent criterion previously proposed to define synergism (FICI < 1) and antagonism (FICI > 1.25), antagonistic interactions were found against some isolates. CONCLUSIONS: Anidulafungin with amphotericin B results in a synergistic effect against C. albicans and C. glabrata biofilms at serum concentrations of the drugs, but showed no interaction against C. tropicalis and C. parapsilosis complex. Anidulafungin plus voriconazole showed no interaction against the five Candida species assayed. Biofilms of C. tropicalis were found to be the most resistant towards the combinations assayed. The results presented may be of potential interest in the clinical setting.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Equinocandinas/farmacologia , Voriconazol/farmacologia , Anidulafungina , Candida/isolamento & purificação , Candida/fisiologia , Candidemia/microbiologia , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana
9.
Eur J Clin Microbiol Infect Dis ; 35(6): 885-92, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26946511

RESUMO

This study aimed to elucidate the genetic relatedness and epidemiology of 127 clinical and environmental Candida glabrata isolates from Europe and Africa using multilocus microsatellite analysis. Each isolate was first identified using phenotypic and molecular methods and subsequently, six unlinked microsatellite loci were analyzed using automated fluorescent genotyping. Genetic relationships were estimated using the minimum-spanning tree (MStree) method. Microsatellite analyses revealed the existence of 47 different genotypes. The fungal population showed an irregular distribution owing to the over-representation of genetically different infectious haplotypes. The most common genotype was MG-9, which was frequently found in both European and African isolates. In conclusion, the data reported here emphasize the role of specific C. glabrata genotypes in human infections for at least some decades and highlight the widespread distribution of some isolates, which seem to be more able to cause disease than others.


Assuntos
Candida glabrata/classificação , Candida glabrata/genética , DNA Fúngico , Repetições de Microssatélites , Tipagem de Sequências Multilocus , África , Alelos , Candida glabrata/isolamento & purificação , Candidíase/microbiologia , Microbiologia Ambiental , Europa (Continente) , Loci Gênicos , Variação Genética , Genótipo , Haplótipos , Humanos
10.
Clin Microbiol Infect ; 22(2): 181-188, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26460064

RESUMO

We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidaemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a multicentre study of hospitalized adults with candidaemia at six hospitals in three countries. BrC episodes were compared with the remaining episodes (non-BrC). Of 409 episodes of candidaemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% versus 46%, p 0.010) whereas Candida krusei was more frequent (16% versus 2.4%, p < 0.001). BrC was associated with infections caused by fluconazole non-susceptible isolates (50% versus 18%, p < 0.001). Candida albicans BrC was associated with previous fluconazole treatment whereas Candida parapsilosis candidaemia was mostly catheter-related and/or associated with previous echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% versus 74%, p 0.055). No significant differences were found in outcomes (early and overall mortality: 11% versus 13% p 0.802 and 40% versus 40% p 0.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (adjusted OR 5.57; 95% CI 1.45-21.37). In conclusion, BrC accounted for 9% of the episodes in our multicentre cohort. The Candida spp. isolated were different depending on the previous antifungal therapy: previous azole treatment was associated with fluconazole non-susceptible strains and previous echinocandin treatment was associated with BrC caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.


Assuntos
Antifúngicos/administração & dosagem , Candida/classificação , Candidemia/epidemiologia , Candidíase/prevenção & controle , Adulto , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candidemia/tratamento farmacológico , Candidemia/microbiologia , Candidíase/microbiologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Técnicas de Tipagem Micológica , Resultado do Tratamento
11.
Antimicrob Agents Chemother ; 59(11): 6725-32, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26282428

RESUMO

Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 µg/ml for C. albicans, 0.12, 0.25, and 0.03 µg/ml for C. glabrata complex, 4, 2, and 4 µg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 µg/ml for C. tropicalis, 0.25, 1, and 0.25 µg/ml for C. krusei, 0.25, 1, and 0.12 µg/ml for C. lusitaniae, 4, 2, and 2 µg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 µg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Equinocandinas/farmacologia , Lipopeptídeos/farmacologia , Anidulafungina , Candida/genética , Caspofungina , Micafungina , Testes de Sensibilidade Microbiana , Mutação/genética
12.
Bone Marrow Transplant ; 50(11): 1465-72, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26281032

RESUMO

Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment.


Assuntos
Antifúngicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Micoses/epidemiologia , Pré-Medicação , Triazóis/uso terapêutico , Administração Oral , Adulto , Idoso , Aloenxertos , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/etiologia , Caspofungina , Causas de Morte , Quimioterapia Combinada , Equinocandinas/uso terapêutico , Feminino , Fungemia/tratamento farmacológico , Fungemia/epidemiologia , Fungemia/etiologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Hematológicas/terapia , Humanos , Hospedeiro Imunocomprometido , Incidência , Lipopeptídeos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/etiologia , Micoses/prevenção & controle , Neutropenia/prevenção & controle , Cooperação do Paciente , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Falha de Tratamento , Triazóis/administração & dosagem , Adulto Jovem
13.
Clin Microbiol Infect ; 21(7): 684.e1-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25765773

RESUMO

We aimed to develop a simple prediction score to identify fluconazole non-susceptible (Flu-NS) candidaemia using simple clinical criteria. A derivation cohort was extracted from the CANDIPOP study, a prospective, multicentre, population-based surveillance programme on candidaemia conducted in 29 hospitals in Spain from April 2010 to May 2011. The score was validated with an external, multicentre cohort of adults with candidaemia in six tertiary hospitals in three countries. The prediction score was based on three variables selected by a logistic regression model together with the severity of disease. In total, 617 and 297 cases of candidaemia were included in the derivation and validation cohorts, respectively; of these, 134 (21.7%) and 57 (19.2%) were caused by Flu-NS strains. Factors independently associated with Flu-NS were transplant recipient status (adjusted odds ratio (AOR) 2.13; 95% CI 1.01-4.55; p 0.047), hospitalization in a unit with a high prevalence (≥ 15%) of Flu-NS strains (7.53; 4.68-12.10; p < 0.001), and previous azole therapy for at least 3 days (2.04; 1.16-3.62; p 0.014). The area under the receiver operating characteristics curve (AUC) was 0.76 (0.72-0.81), and using 2 points as the Flu-NS prediction score cut-off gave a sensitivity of 82.1%, a specificity of 65.6%, and a negative predictive value of 93%. The AUC in the validation cohort was 0.72 (95% CI 0.65-0.79). Hence, the Flu-NS prediction score helped to exclude Flu-NS Candida strains. This could improve the selection of empirical treatments for candidaemia in the future.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidemia/epidemiologia , Técnicas de Apoio para a Decisão , Fluconazol/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Candidemia/microbiologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Medição de Risco , Espanha/epidemiologia , Adulto Jovem
14.
Clin Microbiol Infect ; 21(1): 87.e1-87.e10, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25636940

RESUMO

A prospective, observational, multicentre study of invasive candidosis (IC) in surgical patients in intensive care units (ICUs) was conducted from 2006 to 2008 in 72 ICUs in 14 European countries. A total of 779 patients (62.5% males, median age 63 years) with IC were included. The median rate of candidaemia was 9 per 1000 admissions. In 10.8% the infection was already present at the time of admission to ICU. Candida albicans accounted for 54% of the isolates, followed by Candida parapsilosis 18.5%, Candida glabrata 13.8%, Candida tropicalis 6%, Candida krusei 2.5%, and other species 5.3%. Infections due to C. krusei (57.9%) and C. glabrata (43.6%) had the highest crude mortality rate. The most common preceding surgery was abdominal (51.5%), followed by thoracic (20%) and neurosurgery (8.2%). Candida glabrata was more often isolated after abdominal surgery in patients ≥60 years, and C. parapsilosis was more often isolated in neurosurgery and multiple trauma patients as well as children ≤1 year of age. The most common first-line treatment was fluconazole (60%), followed by caspofungin (18.7%), liposomal amphotericin B (13%), voriconazole (4.8%) and other drugs (3.5%). Mortality in surgical patients with IC in ICU was 38.8%. Multivariate analysis showed that factors independently associated with mortality were: patient age ≥60 years (hazard ratio (HR) 1.9, p 0.001), central venous catheter (HR 1.8, p 0.05), corticosteroids (HR 1.5, p 0.03), not receiving systemic antifungal treatment for IC (HR 2.8, p <0.0001), and not removing intravascular lines (HR 1.6, p 0.02).


Assuntos
Candida , Candidíase Invasiva/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia , Antifúngicos/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/prevenção & controle , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
15.
Diagn Microbiol Infect Dis ; 80(2): 111-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25063549

RESUMO

Invasive aspergillosis is an opportunistic infection caused primarily by Aspergillus fumigatus. However, other common fungal pathogens belonging to section Fumigati are often misidentified as A. fumigatus. Thus, we have developed a multiplex real-time PCR (qPCR) assay with primers and specific TaqMan probes based on internal transcribed spacer regions or benA gene to discriminate, in less than 3 h, species of section Fumigati and, specifically, A. fumigatus. The multiplex qPCR showed a limit of detection of 20 and 50 fg of DNA for section Fumigati and A. fumigatus, respectively. Moreover, it enabled detection of a single germinated conidia. The inclusion of some PCR facilitators together with the dilution of samples makes it possible to completely avoid PCR inhibitions in all bronchoalveolar lavage (BAL) samples assayed. This technique may be a useful complementary tool in the diagnosis of invasive pulmonary aspergillosis caused by A. fumigatus using BAL fluid.


Assuntos
Aspergillus fumigatus/isolamento & purificação , Aspergilose Pulmonar Invasiva/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Primers do DNA/genética , DNA Fúngico/química , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Proteínas Fúngicas/genética , Humanos , Aspergilose Pulmonar Invasiva/microbiologia , Sondas de Oligonucleotídeos/genética , Sensibilidade e Especificidade , Fatores de Tempo
16.
J Antimicrob Chemother ; 69(11): 3134-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24970743

RESUMO

BACKGROUND: New techniques, such as those based on multiplex quantitative real-time PCR (MRT-PCR), can improve the detection of invasive candidiasis (IC). METHODS: We prospectively studied 63 intensive care unit patients with suspected IC and 40 healthy controls. Blood cultures and MRT-PCR were performed at day 0 and +2, +7, +14 and +21 days in all patients. In addition, ß-d-glucan (BDG) and Candida albicans germ tube antibody (CAGTA) were quantified. RESULTS: IC was confirmed in 27 patients. Colonization was significantly higher in patients with IC (96% versus 64%, P = 0.002). The sensitivity, specificity, positive predictive value and negative predictive value of MRT-PCR for the diagnosis of IC were 96.3%, 97.3%, 92.8% and 98.7%, respectively. The positive predictive value and specificity were significantly higher for MRT-PCR than for BDG and CATGA. MRT-PCR performed very well, especially in deep-seated IC (sensitivity 90.9% versus 45.4% for blood culture; P = 0.06). As regards the most appropriate clinical sample for DNA amplification, in this study whole blood and serum presented similar results. CONCLUSIONS: MRT-PCR appears to be a useful test for confirming a diagnosis of IC in critically ill patients, especially in those with deep-seated disease. Its high sensitivity and positive predictive value make it a much more efficient tool for the management of IC than other diagnostic procedures and clinical scores.


Assuntos
Candidíase Invasiva/sangue , Candidíase Invasiva/diagnóstico , Unidades de Terapia Intensiva/normas , Reação em Cadeia da Polimerase em Tempo Real/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Antimicrob Agents Chemother ; 57(7): 3380-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23669377

RESUMO

A population-based survey was conducted to investigate the epidemiology of and antifungal resistance in Spanish clinical strains of filamentous fungi isolated from deep tissue samples, blood cultures, and respiratory samples. The study was conducted in two different periods (October 2010 and May 2011) to analyze seasonal variations. A total of 325 strains were isolated in 29 different hospitals. The average prevalence was 0.016/1,000 inhabitants [corrected]. Strains were identified by sequencing of DNA targets and susceptibility testing by the European Committee for Antimicrobial Susceptibility Testing reference procedure. The most frequently isolated genus was Aspergillus, accounting for 86.3% of the isolates, followed by Scedosporium at 4.7%; the order Mucorales at 2.5%; Penicillium at 2.2%, and Fusarium at 1.2%. The most frequent species was Aspergillus fumigatus (48.5%), followed by A. flavus (8.4%), A. terreus (8.1%), A. tubingensis (6.8%), and A. niger (6.5%). Cryptic/sibling Aspergillus species accounted for 12% of the cases. Resistance to amphotericin B was found in 10.8% of the isolates tested, while extended-spectrum triazole resistance ranged from 10 to 12.7%, depending on the azole tested. Antifungal resistance was more common among emerging species such as those of Scedosporium and Mucorales and also among cryptic species of Aspergillus, with 40% of these isolates showing resistance to all of the antifungal compounds tested. Cryptic Aspergillus species seem to be underestimated, and their correct classification could be clinically relevant. The performance of antifungal susceptibility testing of the strains implicated in deep infections and multicentric studies is recommended to evaluate the incidence of these cryptic species in other geographic areas.


Assuntos
Antifúngicos/farmacologia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/epidemiologia , Farmacorresistência Fúngica , Fungos/efeitos dos fármacos , Anfotericina B/farmacologia , Aspergillus/efeitos dos fármacos , Aspergillus/isolamento & purificação , Sequência de Bases , Dermatomicoses/microbiologia , Fungos/classificação , Fungos/isolamento & purificação , Fusarium/efeitos dos fármacos , Fusarium/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Penicillium/efeitos dos fármacos , Penicillium/isolamento & purificação , Scedosporium/efeitos dos fármacos , Scedosporium/isolamento & purificação , Análise de Sequência de DNA , Espanha , Triazóis/farmacologia
19.
J Antimicrob Chemother ; 67(10): 2418-23, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22733651

RESUMO

OBJECTIVES: To determine the ability of voriconazole to inhibit the formation of biofilms. METHODS: A total of 38 blood isolates of Candida spp. (8 Candida albicans, 10 Candida tropicalis, 10 Candida glabrata, 7 Candida parapsilosis sensu stricto and 3 Candida orthopsilosis) and C. albicans ATCC 90028 and ATCC 64548 were assessed. Biofilm formation was quantified using XTT reduction assays. The inhibition of biofilm formation was determined (i) in the presence of 0.06 and 0.25 mg/L voriconazole, and (ii) on surfaces previously coated with 0.06, 0.25, 1, 4 and 16 mg/L voriconazole. RESULTS: Voriconazole reduced biofilm formation under both conditions, the extent depending on the species, isolate and drug concentration. In the presence of 0.25 mg/L, the highest reduction was found for C. parapsilosis (79% ±â€Š8.6%), followed by C. albicans (64.5% ±â€Š6.3%), C. tropicalis (53.3% ±â€Š13.1%) and C. glabrata (23.8% ±â€Š11.2%). This reduction was significant (P < 0.05) for all isolates tested. After coating the wells with voriconazole, biofilm formation was reduced in all Candida spp. examined, C. albicans being the species with the highest reduction (68.8% with 16 mg/L) and C. parapsilosis complex and C. glabrata the lowest. CONCLUSIONS: As voriconazole reduces biofilm formation it may be a good candidate for the prevention of Candida biofilm-related infections although further studies using voriconazole-impregnated catheter tubing or prostheses are required to confirm these results.


Assuntos
Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida/fisiologia , Pirimidinas/farmacologia , Triazóis/farmacologia , Biofilmes/efeitos dos fármacos , Candida/classificação , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase/microbiologia , Humanos , Coloração e Rotulagem/métodos , Sais de Tetrazólio/metabolismo , Voriconazol
20.
J Clin Microbiol ; 50(6): 2040-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22461672

RESUMO

Clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) have been established for several Candida spp. and the newer triazoles and echinocandins but are not yet available for older antifungal agents, such as amphotericin B, flucytosine, or itraconazole. We determined species-specific ECVs for amphotericin B (AMB), flucytosine (FC) and itraconazole (ITR) for eight Candida spp. (30,221 strains) using isolates from 16 different laboratories in Brazil, Canada, Europe, and the United States, all tested by the CLSI reference microdilution method. The calculated 24- and 48-h ECVs expressed in µg/ml (and the percentages of isolates that had MICs less than or equal to the ECV) for AMB, FC, and ITR, respectively, were 2 (99.8)/2 (99.2), 0.5 (94.2)/1 (91.4), and 0.12 (95.0)/0.12 (92.9) for C. albicans; 2 (99.6)/2 (98.7), 0.5 (98.0)/0.5 (97.5), and 2 (95.2)/4 (93.5) for C. glabrata; 2 (99.7)/2 (97.3), 0.5 (98.7)/0.5 (97.8), and 05. (99.7)/0.5 (98.5) for C. parapsilosis; 2 (99.8)/2 (99.2), 0.5 (93.0)/1 (90.5), and 0.5 (97.8)/0.5 (93.9) for C. tropicalis; 2 (99.3)/4 (100.0), 32 (99.4)/32 (99.3), and 1 (99.0)/2 (100.0) for C. krusei; 2 (100.0)/4 (100.0), 0.5 (95.3)/1 (92.9), and 0.5 (95.8)/0.5 (98.1) for C. lusitaniae; -/2 (100.0), 0.5 (98.8)/0.5 (97.7), and 0.25 (97.6)/0.25 (96.9) for C. dubliniensis; and 2 (100.0)/2 (100.0), 1 (92.7)/-, and 1 (100.0)/2 (100.0) for C. guilliermondii. In the absence of species-specific CBP values, these wild-type (WT) MIC distributions and ECVs will be useful for monitoring the emergence of reduced susceptibility to these well-established antifungal agents.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase/microbiologia , Flucitosina/farmacologia , Itraconazol/farmacologia , Brasil , Canadá , Candida/isolamento & purificação , Europa (Continente) , Humanos , Testes de Sensibilidade Microbiana/normas , Estados Unidos
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