Treatment of critically ill patients with candidemia
Early initiation of effective antimicrobial therapy is crucial for the prognosis of any infection, especially in the critically ill patient. This is particularly true in the case of candidemia. However, the earlier an empirical antimicrobial regimen is started, the greater the probability of diagnostic error and the possibility of side-effects. Recent experience of the clinical efficacy and good tolerance of echinocandins in the treatment of candidemia obliges us to review the indications for empirical antifungal treatment and the choice of antifungal agent in the critically ill patient.
Available from: sciencedirect.com
- "Candida species bloodstream infection (BSI) remains a significant cause of morbidity and mortality  . In the USA, Candida species are ranked as the fourth most common organisms responsible for all BSIs, and the third most common within the intensive-care unit , a clinical environment that is highly dependent on intravascular lines. "
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ABSTRACT: Bloodstream infections caused by Candida species remain a significant cause of morbidity and mortality in hospitalised patients. Biofilm formation by Candida species is an important virulence factor for disease pathogenesis. A prospective analysis of patients with Candida bloodstream infection (n=217) in Scotland (2012/13) was performed to assess the risk factors associated with patient mortality; in particular the impact of biofilm formation. Candida bloodstream isolates (n=280) and clinical records for 157 patients were collected through 11 different health boards across Scotland. Biofilm formation by clinical isolates was assessed in vitro by standard biomass assays. The role of biofilm phenotype on treatment efficacy was also evaluated in vitro by treating preformed biofilms by fixed concentrations of different classes of antifungals. Out of 134 available patient mortality data, the 30-day candidaemia case mortality was 41%, with predisposing factors including patient age and catheter removal. Multivariate Cox’s regression survival analysis with 42 patients showed significantly higher mortality with C. albicans infection compared to C. glabrata. Biofilm-forming ability was significantly associated with C. albicans mortality (n=34 patients). Finally, in-vitro antifungal sensitivity testing showed that LBF and HBF were differentially affected by azoles and echinocandins, but not polyenes. This study provides further evidence of the biofilm phenotype represents a significant clinical entity, and that isolates with this phenotype differentially respond to antifungal therapy based on in vitro evidence. Collectively, these findings highlight that a greater clinical understanding is required with respect to Candida biofilm infections, and the implications of isolate heterogeneity.
Clinical Microbiology and Infection 09/2015; DOI:10.1016/j.cmi.2015.09.018 · 5.77 Impact Factor
Available from: Elisa Borghi
- "Bloodstream infections (BSI) caused by Candida species remain a frequent cause of morbidity and mortality, particularly within the immunocompromised population [1,2]. Overall, Candida species have been identified as the most common fungal pathogen found in bloodstream infections in the United States, and are the fourth most common organism responsible for all BSI, and are the third most common within the intensive care unit (ICU) . "
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Candida albicans infections have become increasingly recognised as being biofilm related. Recent studies have shown that there is a relationship between biofilm formation and poor clinical outcomes in patients infected with biofilm proficient strains. Here we have investigated a panel of clinical isolates in an attempt to evaluate their phenotypic and transcriptional properties in an attempt to differentiate and define levels of biofilm formation.
Biofilm formation was shown to be heterogeneous; with isolates being defined as either high or low biofilm formers (LBF and HBF) based on different biomass quantification. These categories could also be differentiated using a cell surface hydrophobicity assay with 24 h biofilms. HBF isolates were more resistance to amphotericin B (AMB) treatment than LBF, but not voriconazole (VRZ). In a Galleria mellonella model of infection HBF mortality was significantly increased in comparison to LBF. Histological analysis of the HBF showed hyphal elements intertwined indicative of the biofilm phenotype. Transcriptional analysis of 23 genes implicated in biofilm formation showed no significant differential expression profiles between LBF and HBF, except for Cdr1 at 4 and 24 h. Cluster analysis showed similar patterns of expression for different functional classes of genes, though correlation analysis of the 4 h biofilms with overall biomass at 24 h showed that 7 genes were correlated with high levels of biofilm, including Als3, Eap1, Cph1, Sap5, Plb1, Cdr1 and Zap1.
Our findings show that biofilm formation is variable amongst C. albicans isolates, and categorising isolates depending on this can be used to predict how pathogenic the isolate will behave clinically. We have shown that looking at individual genes in less informative than looking at multiple genes when trying to categorise isolates at LBF or HBF. These findings are important when developing biofilm-specific diagnostics as these could be used to predict how best to treat patients infected with C. albicans. Further studies are required to evaluate this clinically.
BMC Microbiology 07/2014; 14(1):182. DOI:10.1186/1471-2180-14-182 · 2.73 Impact Factor
Available from: Joaquin Mould
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ABSTRACT: Objetivo: Determinar cuál de los antimicóticos disponibles en el cuadro básico del Instituto Mexicano del Seguro Social (anfotericina B, fluconazol, voriconazol, caspofungina) y de otros que no se encuentran actualmente en el mismo, como anidulafungina y anfotericina B liposomal, sería la terapia más coste-efectiva para el tratamiento de la candidiasis invasiva en pacientes adultos (>18 años) no neutropénicos en estado crítico, atendidos en Unidad de Cuidados Intensivos (UCI), desde la perspectiva del proveedor de servicios públicos de salud (IMSS).
Métodos: Evaluación económica de coste-efectividad. Se elaboró un modelo de árbol de decisiones con un horizonte temporal de 12 semanas. Las medidas de efectividad fueron el éxito clínico sin eventos adversos, la supervivencia y los días de estancia en la UCI. Se realizó un análisis de sensibilidad probabilístico con una simulación de Monte Carlo de primer orden.
Resultados: Anidulafungina tuvo los costes más bajos (26.516,76$ USD) en tanto que anfotericina B fue el que tuvo los costes más altos (34.507,62$ USD). La opción con mayor éxito clínico sin efectos colaterales fue la de anidulafungina (58,8%). La supervivencia más alta se observó con anidulafungina (88,8%) y anfotericina B liposomal (86,1%). Por lo anterior, anidulafungina podría ahorrar, en promedio, cerca de tres días de estancia en la UCI y resultó ser la opción más coste-efectiva.
Conclusiones: En el IMSS sería una buena elección seleccionar la anidulafungina como un tratamiento inicial para el manejo de los pacientes con candidiasis invasiva, lo cual aportaría importantes ahorros al sistema de atención médica.
Pharmacoeconomics - Spanish Research Articles 02/2013; 8(1). DOI:10.1007/BF03320885
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