Invasive fungal infections in patients with cancer in the Intensive Care Unit
Invasive fungal infections (IFIs) have emerged as a major cause of morbidity and mortality amongst critically ill patients. Cancer patients admitted to the Intensive Care Unit (ICU) have multiple risk factors for IFIs. The vast majority of IFIs in the ICU are due to Candida spp. The incidence of invasive candidiasis (IC) has increased over recent decades, especially in the ICU. A shift in the distribution of Candida spp. from Candida albicans to non-albicans Candida spp. has been observed both in ICUs and oncology units in the last two decades. Timely diagnosis of IC remains a challenge despite the introduction of new microbiology techniques. Delayed initiation of antifungal therapy is associated with increased mortality. Therefore, prediction rules have been developed and validated prospectively in order to identify those ICU patients at high risk for IC and likely to benefit from early treatment. These rules, however, have not been validated in cancer patients. Similarly, major clinical studies on the efficacy of newer antifungals typically do not include cancer patients. Despite the introduction of more potent and less toxic antifungals, mortality from IFIs amongst cancer patients remains high. In recent years, aspergillosis and mucormycosis have also emerged as significant causes of morbidity and mortality amongst ICU patients with haematological cancer.
[Show abstract] [Hide abstract] ABSTRACT: Invasive aspergillosis is a life-threatening lung or systemic infection caused by the opportunistic mold Aspergillus fumigatus. The disease affects mainly immunocompromised hosts, and patients with hematological malignances or who have been submitted to stem cell transplantation are at high risk. Despite the current use of Platelia™ Aspergillus as a diagnostic test, the early diagnosis of invasive aspergillosis remains a major challenge in improving the prognosis of the disease. In this study, we used an immunoproteomic approach to identify proteins that could be putative candidates for the early diagnosis of invasive aspergillosis. Antigenic proteins expressed in the first steps of A. fumigatus germination occurring in a human host were revealed using 2-D Western immunoblots with the serum of patients who had previously been classified as probable and proven for invasive aspergillosis. Forty antigenic proteins were identified using mass spectrometry (MS/MS). A BLAST analysis revealed that two of these proteins showed low homology with proteins of either the human host or etiological agents of other invasive fungal infections. To our knowledge, this is the first report describing specific antigenic proteins of A. fumigatus germlings that are recognized by sera of patients with confirmed invasive aspergillosis who were from two separate hospital units.0Comments 1Citation
- "Although candidiasis remains the most frequent IFI in critically ill patients, aspergillosis and mucormycosis have also emerged as significant causes of morbidity and mortality. HSCT recipients and patients with prolonged neutropenia represent the main risk group for invasive aspergillosis . In these patients, A. fumigatus is by far the most important etiological agent of invasive aspergillosis, especially in HSCT patients with acute leukemia (5% to 25%) and in some solid organ transplantation patients [3,7,26]. "
[Show abstract] [Hide abstract] ABSTRACT: Invasive candidiasis is an important nosocomial infection associated with high mortality among immunosuppressive or critically ill patients. We described the incidence of invasive candidiasis in our hospital over 6 years and showed the antifungal susceptibility and genotypes of the isolated yeast. The yeast species were isolated on CHROMagar Candida medium and identified using an yeast identification card, followed by analysis of the D1/D2 domain of 26S rDNA. The susceptibilities of the isolates to flucytosine, amphotericin B, fluconazole, itraconazole, and voriconazole were tested using the ATB FUNGUS 3 system, and that to caspofungin was tested using E-test strips. C. albicans was genotyped using single-strand conformation polymorphism of CAI (Candida albicans I) microsatellite DNA combined with GeneScan data. From January 2006 to December 2011, a total of 259 isolates of invasive Candida spp. were obtained from 253 patients, among them 6 patients had multiple positive samples. Ninety-one stains were from blood and 168 from sterile fluids, accounting for 6.07% of all pathogens isolated in our hospital. Most of these strains were C. albicans (41.29% in blood/59.06% in sterile body fluids), followed by C. tropicalis (18.06%/25.72%), C. parapsilosis (17.42%/5.43%), C. glabrata (11.61%/3.99%) and other Candida spp. (11.61%/5.80%). Most Candida spp. were isolated from the ICU. The new species-specific CLSI candida MIC breakpoints were applied to these date. Resistance to fluconazole occurred in 6.6% of C. albicans isolates, 10.6% of C. tropicalis isolates and 15.0% of C.glabrata isolates. For the 136 C. albicans isolates, 54 CAI patterns were recognized. The C. albicans strains from blood or sterile body fluids showed no predominant CAI genotypes. C. albicans isolates from different samples from the same patient had the same genotype. Invasive candidiasis has been commonly encountered in our hospital in the past 6 years, with increasing frequency of non-C. albicans. Resistance to fluconazole was highly predictive of resistance to voriconazole. CAI SSCP genotyping showed that all C. albicans strains were polymorphic. Invasive candidiasis were commonly endogenous infection.0Comments 8Citations
- "albicans spp. have been detected more commonly in candidemia [7,8]. Both C. albicans and non-C. "
[Show abstract] [Hide abstract] ABSTRACT: Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27 864 patients with haematological malignancies vs. 967 of 1 158 018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p <0.001). Candidaemia was caused predominantly (35/40, 87.5%) by non-Candida albicans species, particularly Candida parapsilosis (20/40, 50%). In vitro resistance to at least one antifungal agent was observed in 27% of Candida isolates. Twenty-one patients (53%) developed breakthrough candidaemia while receiving antifungal agents. Central venous catheters, hypogammaglobulinaemia and a high APACHE II score were independent risk factors for the development of candidaemia. Crude mortality at day 28 was greater in those with candidaemia than in control cases (18/40 (45%) vs. 9/80 (11%); p <0.0001). In conclusion, despite antifungal prophylaxis, candidaemia is a relatively frequent infection associated with high mortality caused by non-C. albicans spp., especially C. parapsilosis. Central venous catheters and hypogammaglobulinaemia are independent risk factors for candidaemia that provide potential targets for improving the outcome.0Comments 12Citations
- "APACHE II score has not been validated outside the ICU; however, it has been used extensively in published candidaemia studies . Previous studies have shown that increased APACHE II score at the onset of candidaemia is a clinical predictor for progression to septic shock  and is independently associated with higher hospital mortality [18,20]. This finding carries several important implications for patients with haematological malignancies. "