f Candida parapsilosis is the main non-albicans Candida species isolated from patients in Latin America. Mutations in the ERG11 gene and overexpression of membrane transporter proteins have been linked to fluconazole resistance. The aim of this study was to evaluate the molecular mechanisms in fluconazole-resistant strains of C. parapsilosis isolated from critically ill patients. The identities of the nine collected C. parapsilosis isolates at the species level were confirmed through molecular identification with a TaqMan qPCR assay. The clonal origin of the strains was checked by microsatellite typing. The Galleria mellonella infection model was used to confirm in vitro resistance. We assessed the presence of ERG11 mutations, as well as the expression of ERG11 and two additional genes that contribute to antifungal resistance (CDR1 and MDR1), by using real-time quantitative PCR. All of the C. parapsilosis (sensu stricto) isolates tested exhibited fluconazole MICs between 8 and 16 g/ml. The in vitro data were confirmed by the failure of fluconazole in the treatment of G. mellonella infected with fluconazole-resistant strains of C. parapsilosis. Sequencing of the ERG11 gene revealed a common mutation leading to a Y132F amino acid substitution in all of the isolates, a finding consistent with their clonal origin. After fluconazole exposure, overexpression was noted for ERG11, CDR1, and MDR1 in 9/9, 9/9, and 2/9 strains, respectively. We demonstrated that a combination of molecular mechanisms, including the presence of point mutations in the ERG11 gene, overexpression of ERG11, and genes encoding efflux pumps, are involved in fluconazole resistance in C. parapsilosis.
BackgroundCandidemia is an increasing problem in tertiary care hospitals worldwide. Here, we report the first outbreak of candidemia caused by fluconazole-resistant C. parapsilosis (FRCP) strains in Brazil.MethodsThis was a cross-sectional study of clinical and microbiological data of all candidemic episodes diagnosed from July 2011 to February 2012 in a 200-bed tertiary care hospital. Initial yeast identification and susceptibility testing were performed using the VITEK 2 - System. Isolates of Candida spp. resistant to fluconazole were sent to a reference laboratory (LEMI-UNIFESP) for further molecular identification and confirmation of resistance by CLSI microdilution test. A multivariate analysis was conducted to identify factors associated with FRCP infection.ResultsWe identified a total of 40 critically ill patients with candidemia (15 women) with a median age of 70 years. The incidence of candidemia was 6 cases/1,000 patients admissions, including 28 cases (70 %) of infection with C. parapsilosis, 21 of which (75 %) were resistant to fluconazole. In only 19 % of FRCP candidemia cases had fluconazole been used previously. The results of our study indicated that diabetes is a risk factor for FRCP candidemia (p = 0.002). Overall, mortality from candidemia was 45 %, and mortality from episodes of FRCP infections was 42.9 %.ConclusionsThe clustering of incident cases in the ICU and molecular typing of strains suggest horizontal transmission of FRCP. Accurate vigilant monitoring for new nosocomial strains of FRCP is required.
Disseminated strongyloidiasis is a disease with high mortality rate, especially in immunocompromised individuals. Paralytic ileus and intestinal malabsorption are frequent symptoms caused by this severe disease. As there are no licensed parenteral anthelmintic drugs for human use, off-label formulations are often used in the treatment of this disease. In this case report, the use of subcutaneous ivermectin is described as a successful therapy for this life-threatening infection.
There are various strategies to improve the effectiveness of antibiotics in hospitals. In general, the implementation of guidelines for appropriate antibiotic therapy and the participation of infectious disease (ID) physicians deserve considerable attention. This study was a prospective ecological time-series study that evaluates the effectiveness of the ID physician's opinion to rationalize and control the use of antibiotics in medical-surgical intensive care units (
Introduction: Hematogenous candidiasis is an increasing problem in tertiary hospitals around the world, where there are large variations in incidence rates, mortality and agents involved. C. parapsilosis is the main species of non-albicans candida in many hospitals in Latin America, with a low resistance to various antifungal agents and lower mortality rates than C albicans. This is a report of the first outbreak of candidemia by fluconazole resistant C parapsilosis whose patients had mortality beyond the expected. Material and Methods:It is cross-sectional, observational study. We collect clinical and microbiological data of all candidemia episodes diagnosed from July/2011 to february/2012 in a tertiary hospital of 200 beds in Brasília. Initial identification and susceptibility testing were performed by the VITEK 2 -Bio-Mérieux system. Isolates of Candida parapsilosis Fluco-R were sent to reference laboratory (LEMI-UNIFESP) for confirmation of the identification by molecular typing and to antifungal resistance profile by CLSI microdilution test. Univariate (Chi Square and Fisher) and Multivariate analysis was performed to identify associated factors related to C parapsilosis fluconazole resistant (CPFR) infection. Results:We identified a total of 42 episodes of candidemia in the period, 15 in women. The median age was 72 years. The incidence of candidemia in the period was 4.05 per 1000 admissions, 30 cases (71.4%) by Candida parapsilosis, 23 of which (54.8%) were resistant to fluconazole (MIC50% = 16mcg/ml). 95.2% of patients were in the ICU at the time of diagnosis of CPRF. Previous use of fluconazole occurred in only 21.7% of cases of candidemia CPFR . The only risk factor for infection founded for CPRF was diabetes. Overall mortality of candidemia was 45.2% and 43.5% for CPFR infection . INTRODUÇÃO ______________________________________________________ 14 (2) A mutação do gene ERG11, que codifica a enzima alvo 14α-esteroldimetilase, reduzindo a afinidade pelos azois. Esse mecanismo está associado à resistência intrínseca da C. krusei ao fluconazol.(3) A hiperexpressão da enzima alvo 14α-esterol-dimetilase alterada.(4) A mutação do gene ERG3, o qual gera um substituto ao ergosterol.Há um efeito aditivo das mutações descrita, ou seja, as CIM para fluconazol são maiores na medida em que se acrescentam mutações da bomba de efluxo e da afinidade à enzima alvo (46). parapsilosis, e nenhuma em 118 amostras de C. tropicalis (52). A CANDIDA PARAPSILOSISA partir do final dos anos 90 a incidência de isolados de Candida parapsilosis, tem dramaticamente aumentado. Esta já vem frequentemente sendo identificada como a segunda mais comum espécie de cândida de isolada na hemocultura na Overall mortality from candidemia was 45.2%, and mortality from episodes of FRCP infections was 43.5%. Conclusions:The clustering of incident cases in the ICU and the limited prior exposure of infected patients to fluconazole suggest horizontal transmission of FRCP. Accurate vigilant monitoring for new nosocomial strains of FRCP is ...
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