Invasive Candida Research Articles

Bochdaleksh hernia with volvulus and invasive candida complication

Bochdaleksh hernia with volvulus and invasive candida complication

Akut lenfoblastik lösemili üç yaşında bir çocukta invaziv mantar enfeksiyonunun posakonazolle başarılı tedavisi

Invasive fungal infections, especially non-Candida albicans, are increasing because of the increasing number of immunocompromised patients and resistance to fungal infectons. New drugs for the treatment of antifungal infections have been developed in the last decade. We report a 3-year-old girl with acute lymphoblastic leukemia who developed invasive Candida infection caused by Candida albicans. Despite single and combined therapy with liposomal amphotericin B, caspofungin and voriconazole, patient’s fever and clinical condition were improved only after addition of posaconazole to the treatment. During maintenance therapy (BFM-95 ALL treatment for standard risk group) for ALL, fungal infection remained under control and did not recur under posaconazole prophylaxis. 

Renal Impairment Related to Different Antifungal Medications in Cases of Invasive Candida Infections in Tawam Hospital Pediatric Population between 2008-2015

Background: As a tertiary hospital, Tawam Hospital has been dealing with more and more complex pediatric cases. Such cases are often at higher risk of developing Invasive Candida Infections (ICI). Amphotericin B preparations continued to provide the widest coverage for all Candida strains and have been the drug of choice for definitive and empirical therapy in our institute. However, renal complications have always been a concern with this group of antifungals. Numerous studies have reported contradicting results in terms of which Amphotericin B preparation has less renal side effects. Therefore, we are here to report our own experience.Methods:We performed a retrospective cohort study of all children (15 years and younger) with ICI who were treated at Tawam Hospital from 2008 to 2015. Results:Out of the 40 patients included in this study, 7 patients were treated with Amphotericin B Liposomal (ABL). Two of them had elevated Urea/Creatinine after initiating the therapy. 11 patients were treated with Amphotericin B Lipid Complex (ABLC). Two of them had elevated Urea/Creatinine after initiating the therapy. Fluconazole was used in 14 patients. 2 of them had high Urea/Creatinine before therapy which did not show any further deterioration while on therapy. Two patients were treated with a combination of Fluconazoleand LAB. They both had high Urea/Creatinine before and after therapy. However, one of them was known to have renal failure. While 4 cases were treated with the combination of Fluconazole and ABLCamong whom one patient had high Urea/Creatinine before therapy that went down while on therapy. Conclusions:Although Amphotericin B is known to be associated with renal side effects, the newer preparations seem to offer a much safer alternative. Among the two available preparations, ABLCseemed to be safer in our experience. Fluconazole continued to have minimal renal side effects. However, just like most of the published studies on this topic, our study was limited by the small number of patients included and the retrospective nature of the study.Keywords: Invasive candida infections, Renal impairment, Amphotericin B Lipid Complex, Amphotericin B Liposomal Fluconazole.Abbreviations:ICI: Invasive Candida Infections, Amphotericin B Lipid Complex (ABLC), Amphotericin B Liposomal (ABL), CSF: cerebrospinal fluid, CLEAR: Collaborative Exchange of Antifungal Research,

Effects of Echinocandins in Combination with Nikkomycin Z against Invasive Candida albicans Bloodstream Isolates and the fks Mutants.

ABSTRACTWe evaluated the in vitro and in vivo effects of nikkomycin Z combined with an echinocandin (anidulafungin or micafungin) against two Candida albicans isolates and their lab-derived echinocandin-resistant fks mutants with FKS1 S645Y and FKS1 S645P. Synergistic effects were observed in all tested strains (fractional inhibitory concentration index, <0.5). Enhanced survival was observed in an immunocompromised murine model (log-rank test, P < 0.02). Our study demonstrated the therapeutic potential of nikkomycin Z-echinocandin combinations in managing echinocandin resistance.

Pharmacodynamic Optimization for the Treatment of Invasive Candida auris Infection

Background Candida auris is an emerging, nosocomial multidrug-resistant threat with high treatment failure rate and mortality. The optimal antifungal agent to use and susceptibility breakpoints are based on limited clinical data.Methods Nine clinical C. auris strains were used. MICs were determined by CLSI standards. Drug treatment studies consisted of: fluconazole (FLC) dose range 0.78–200 mg/kg/12 h, micafungin (MFG) dose range 0.3125–80 mg/kg/24 h, or amphotericin B deoxycholate (AMB) dose range 0.0.78–20 mg/kg/24 hours. Plasma PK was previously determined in the murine model for all three drugs. A 96 h neutropenic murine model of invasive candidiasis (IC) was used for all studies. The Emax Hill equation was used to model the dose–response data to PK/PD index AUC/MIC (FLC and MFG) and Cmax/MIC (AMB). The static and 1 log kill doses (when achieved) and the associated PK/PD targets (AUC/MIC or Cmax/MIC) were determined and compared with previous murine IC studies with C. albicans, C. glabrata, and C. parapsilosis.ResultsMIC range: FLC 2–256 mg/l, MFG 0.125–4 mg/l, and AMB 0.38–6 mg/l. Dose-dependent activity was observed with all three drugs. Net stasis was achieved against seven strains for FLC, eight strains for MFG, and eight strains for AMB. However, MFG performed significantly better than comparators for cidal endpoints. A 1 log kill endpoint was achieved in eight strains for MFG, whereas this endpoint was only achieved in one strain for FLC and three strains for AMB. PK/PD analyses demonstrated a strong relationship between AUC/MIC and treatment outcome for FLC (R2 0.61) and MFG (R2 0.77); and Cmax/MIC and treatment outcome for AMB (R2 0.64). The median static dose and 1 log kill dose (MFG only) and associated AUC/MIC or Cmax/MIC values are shown (Table).Stasis1 log killDrugDose (mg/kg/24 hours)AUC/MIC or [Cmax/MIC]Dose (mg/kg/24 hours)AUC/MICFLC10726.3MFG1.2553.73.36130AMB3.86[0.87]ConclusionMFG was the most potent drug over the dose range achieving up to 2 log kill against eight of nine strains. PK/PD targets for C. auris against FLC and AMB were similar to other Candida species; however, MFG targets were ≥20-fold lower than C. albicans, C. glabrata, and C. parapsilosis. Using the median stasis targets and human PK for each drug, resistance thresholds could be 16 mg/l for FLC, 2–4 mg/l for MFG, and 1–2 mg/l for AMB.Disclosures All authors: No reported disclosures.

Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial.

The aim of this study was to determine the impact of a biomarker-based strategy on early discontinuation of empirical antifungal treatment. Prospective randomized controlled single-center unblinded study, performed in a mixed ICU. A total of 110 patients were randomly assigned to a strategy in which empirical antifungal treatment duration was determined by (1,3)-β-D-glucan, mannan, and anti-mannan serum assays, performed on day 0 and day 4; or to a routine care strategy, based on international guidelines, which recommend 14days of treatment. In the biomarker group, early stop recommendation was determined using an algorithm based on the results of biomarkers. The primary outcome was the percentage of survivors discontinuing empirical antifungal treatment early, defined as a discontinuation strictly before day 7. A total of 109 patients were analyzed (one patient withdraw consent). Empirical antifungal treatment was discontinued early in 29 out of 54 patients in the biomarker strategy group, compared with one patient out of 55 in the routine strategy group [54% vs 2%, p<0.001, OR (95% CI) 62.6 (8.1-486)]. Total duration of antifungal treatment was significantly shorter in the biomarker strategy compared with routine strategy [median (IQR) 6 (4-13) vs 13 (12-14)days, p<0.0001). No significant difference was found in the percentage of patients with subsequent proven invasive Candida infection, mechanical ventilation-free days, length of ICU stay, cost, and ICU mortality between the two study groups. The use of a biomarker-based strategy increased the percentage of early discontinuation of empirical antifungal treatment among critically ill patients with suspected invasive Candida infection. These results confirm previous findings suggesting that early discontinuation of empirical antifungal treatment had no negative impact on outcome. However, further studies are needed to confirm the safety of this strategy. This trial was registered at ClinicalTrials.gov, NCT02154178.

Invasive Candida Infections (ICI) in Pediatric Population of a Tertiary Care Hospital in United Arab Emirates (UAE): Management and Time to Negative Culture

Background: Invasive candida infection is a growing problem in critically ill patients. Candida species are the most common agent responsible for invasive fungal infections in children. Timely diagnosis and proper selection of antifungal therapy are of paramount importance for a favorable outcome. The increasing rate of non-albiacans candida is becoming a real challenge when choosing an empirical antifungal therapy since a large percentage of them are resistant to azoles. This study aims at identifying the most commonly used antifungal agents in our institute and their success measured by the time needed to reach a negative culture (TNC) in cases of candidemia and candiduriaMethods:We performed a retrospective cohort study of all children (15 years and younger) with invasive candida infection, admitted to Tawam Hospital from 2008 to 2015.Results: Fluconazole seems to be the most common choice of our pediatricians in treating urine ICI (65%)while Amphotericin B Lipid complex is the most common choice in treating blood ICI(56%). Amphoteric B Lipid Complex was associated with the shortest TNC both in treating urine ICI (3 days) and blood ICI (4.4 days0Conclusions: Unfortunately, there aren’t many prospective studies in the literature comparing the efficacy of the major antifungal agents in treating pediatrics ICI. Therefore, we hope that this study, despite being retrospective, will shed some light on the utilization of Amphotericin B Lipid Complex in treating pediatrics ICI.

Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment.

Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistance can be either intrinsic or acquired. Resistance mechanisms are not exchanged between Candida; thus, acquired resistance either emerges in response to an antifungal selection pressure in the individual patient or, more rarely, occur due to horizontal transmission of resistant strains between patients. Although multidrug resistance is uncommon, increasing reports of multidrug resistance to the azoles, echinocandins, and polyenes have occurred in several Candida species, most notably Candida glabrata and more recently Candida auris. Drivers are overall antifungal use, subtherapeutic drug levels at sites of infection/colonization, drug sequestration in the biofilm matrix, and, in the setting of outbreaks, suboptimal infection control. Moreover, recent research suggests that DNA mismatch repair gene mutations may facilitate acquisition of resistance mutations in C. glabrata specifically. Diagnosis of antifungal-resistant Candida infections is critical to the successful management of patients with these infections. Reduction of unnecessary use of antifungals via antifungal stewardship is critical to limit multidrug resistance emergence.

Viral, Fungal, and Atypical Infections

Viral, fungal, and “atypical” bacterial pathogens are important causes of infections in critically ill patients. Many of these pathogens predominantly cause disease in immunosuppressed patients, but immunocompetent patients can also face serious illness or death. Understanding the risk factors and clinical syndromes caused by these pathogens is necessary to quickly identify patients who may need specialized diagnostics and treatment and is an essential component of training for any provider who practices in the intensive care unit. In this review, we discuss the most relevant aspects of clinical presentation, epidemiology, diagnosis, and management of these infectious agents, with a particular focus on respiratory tract infections. New advances in the diagnosis and treatment of influenza, invasive Candida infections, aspergillosis, and Legionella are highlighted. This review contains 3 figures, 5 tables, and 94 references. Key words: Candida, influenza, invasive pulmonary aspergillosis, Legionella pneumophilia, viral pneumonia

The 1,3-β-d-glucan in critical adult patients as diagnostic tool for invasive Candida spp. infection, performance evaluation

Invasive fungal infections are important causes of morbimortality in critical patients. Most of these infections are caused by Candida spp. which diagnosis has important limitations. Initial evaluation of the utility of 1,3-β-D-glucan (BDG) as a diagnostic tool for invasive candida infections in critical patients. Adult patients over 18 years old, hospitalized in intensive care units for more than five days, with fever > 38 °C of unclear origin and two or more risk factors for invasive Candida spp. infection were included. Samples for BDG were obtained on two consecutive days. The results were compared with definitive diagnosis of candidemia/invasive candidiasis (C/IC) confirmed by cultures. Median value of BDG in patients with C/IC was 224.3 ± 213.7 pg/ml and in patients without C/IC was 63.8 ± 76.7 pg/ml (p: 0.02). Sensitivity and specificity for the diagnosis of C/IC were 60 and 92%, respectively. Positive predictive value was 60% and negative predictive value was 92%. BDG could be considered as a complementary diagnostic tool for the diagnosis of C/IC in critical patients with risk factors.

Changes in the distribution of colonising and infecting Candida spp. isolates, antifungal drug consumption and susceptibility in a French intensive care unit: A 10-year study.

Monitoring fungal ecology and resistance to antifungal agents within intensive care units (ICU) is essential for the management of invasive fungal infections. Therefore, a retrospective descriptive study was carried in the ICU of Nimes University Hospital, France, from 2007 to 2016. As the majority of invasive fungal infections in ICU are caused by Candida species, the study objectives were to describe Candida species distribution, to assess candidaemia incidence and to monitor the antifungal drug susceptibility of Candida isolates and the consumption of antifungal agents. Among the recorded invasive Candida infections (n=244), 43% were intra-abdominal and 22% bloodstream infections. Candida albicans was the most frequent species (55.8%), followed by Candida glabrata (14.1%), Candida tropicalis (10%), Candida parapsilosis (8%) and Candida krusei (5.3%). Candidaemia incidence was 4.49 per 1000 admissions. The mean consumption of antifungal agents was of 170.5 defined daily doses (DDD) for 1000 hospital days (HD) per year. Changes in antifungal drug consumption were observed, with an increased use of echinocandins (from 17.96 DDD/1000 HD in 2007 to 48.76 DDD/1000 HD in 2016), and the total treatment cost tripled during the study period. No significant change in fungal ecology or in the emergence of resistant species was observed; indeed, only 1.1% of isolates presented an unusual resistance to antifungal agents.

Pharmacodynamic Optimization for Treatment of Invasive Candida auris Infection.

Candida auris is an emerging multidrug-resistant threat. The pharmacodynamics of three antifungal classes against nine C. auris strains was explored using a murine invasive candidiasis model. The total drug median pharmacodynamic (PD) target associated with net stasis was a fluconazole AUC/MIC (the area under the concentration-time curve over 24 h in the steady state divided by the MIC) of 26, an amphotericin B Cmax/MIC (maximum concentration of drug in serum divided by the MIC) of 0.9, and a micafungin AUC/MIC of 54. The micafungin PD targets for C. auris were ≥20-fold lower than those of other Candida species in this animal model. Clinically relevant micafungin exposures produced the most killing among the three classes.

English

Invasive Candida infections have emerged as an important pathogen in the last decade, especially in immunocompromized patients. The aim of the present study was to evaluate the detection of Candida species in blood samples from pediatric patients with sepsis by blood culture method versus antigen detection method by enzyme linked immunosorbent assay (ELISA) and molecular method by polymerase chain reaction (PCR). This cross-sectional study was carried out on children at Mansoura University Children Hospital (MUCH) with the presence of clinical signs suggesting sepsis with absence of prior antifungal therapy. Laboratory diagnosis included blood culture, mannan antigen detection of Candida species by ELISA and semi-nested PCR. Candida species were detected by blood culture in 15.6% of the children and was detected by PCR and antigen detection in 20% for each. Candidemia was more frequently detected among patients with central venous lines (38.5%), children with Diabetes Mellitus (DM) (23.1%) and children with frequent blood transfusions (15.4%). However, these risk factors were not statistically significant. Mortality rate among children with candidemia was 42.9%. The sensitivity, specificity, and accuracy of antigen detection method by ELISA compared to culture, were 71.4, 89.5 and 86.7%, respectively. The sensitivity, specificity and accuracy of semi-nested PCR compared to culture were 85.7, 92.1 and 91.1% respectively. It can be concluded from this study that Candida species is a frequent pathogen associated with pediatric sepsis. Blood culture though is a reliable laboratory method for its diagnosis may lack sensitivity and requires prolonged time. Semi-nested PCR for detection of candidemia is sensitive, specific and accurate method. Mannan antigen detection by ELISA is rapid and easy; however, it may lacks specificity; it can be used as a preliminary method for screening. Further studies are recommended to detect the appropriate laboratory algorithm for early diagnosis of candidemia to start antifungal therapy appropriately. Key words: Candida, Mannan antigen, polymerase chain reaction (PCR), blood culture.

Restraining Pathogenicity in Candida albicans by Taxifolin as an Inhibitor of Ras1-pka Pathway.

Candida albicans is one of the most virulent and opportunistic fungal strains. In the present scenario, majority metabolic imbalances and unsuccessful treatments of some severe diseases including cancer, diabetes, HIV, psoriasis are because of invasive Candida emergence. Being a beneficial integral part of human biome, its elimination is not possible. The major pathogenicity characteristics in Candida involve hyphal growth, biofilm formation, HSP90 down regulation and genetic modifications. Ras1-pka pathway initiated by HSP90 down regulation is important for hyphal growth and has been focused in the present study. The principle transcriptional factors that induce hyphal growth causing invasiveness and virulence through this pathway have been identified as Tec1 and Rfg1. In the present study, taxifolin, a naturally occurring polyphenol, has been identified as inhibitor for both the transcriptional factors in parallel.

Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency.

Bacterial infections are the leading causes of morbidity and mortality in haematologic patients with chemotherapy-induced neutropenia. The only strategy shown to be effective in reducing febrile neutropenia incidence is fluoroquinolone prophylaxis, but the safety of this class of drugs in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme defect, is still controversial because of the claimed association with acute haemolytic anaemia. We retrospectively analysed 242 patients treated with 628 intensive chemotherapy courses. Of these, 59 patients were with G6PD-. All patients underwent fluoroquinolone prophylaxis and were transfused according to our single-unit transfusion policy. The principal endpoint was the incidence of acute haemolytic anaemia. Secondary endpoints included the incidence of febrile neutropenia, microbiologically and clinically documented infection (MDI and CDI) and the incidence of Gram-positive or Gram-negative infections. No episode of acute haemolytic anaemia was observed in the entire cohort. The incidence of MDI and CDI was similar, but the incidence of invasive fungal disease (IFD; P<.0001, HR 11.4, 95%CI 3.5-37.05) and Candida sepsis (P=.008, HR 37, 95%CI 2.01-680.9) was higher in patients with G6PD-. Interestingly, we observed a reduced incidence of febrile neutropenia in patients with G6PD- (P=.01, HR 0.46, 95%CI 0.25-0.8). Our data suggest that fluoroquinolone prophylaxis in patients with G6PD-, treated with intensive chemotherapy, is feasible and safe. Our findings on the incidence of IFD and febrile neutropenia suggest that G6PD may be important in susceptibility to opportunistic pathogens and host response in neutropenic patients.

Invasive Candida Infections in Liver Transplant Recipients: Clinical Features and Risk Factors for Mortality.

Invasive fungal infections remain a leading cause of morbidity and mortality among liver transplant recipients (LTRs). In this patient population, invasive Candida infections (ICIs) account for the large majority of cases. To date, only small studies and case-series analysing clinical presentation and risk factors for mortality in LTRs with ICIs are available. We performed a retrospective multicenter multinational study in 10 centers in Europe and Brazil. All consecutive LTRs developing ICIs during the period January 2011 to December 2013 were included in the study. A total of 42 LTRs were included. Median age was 52.5 years, and 78.6% of patients were men. Viral hepatitis was the most common cause for liver transplantation (42.9%). Candidemia represented the majority of cases (24, 57.1%), followed by intra-abdominal candidiasis (18, 42.9%). Overall 30-day mortality was 23.8%, with higher mortality in patients with candidemia compared with intra-abdominal candidiasis (37.5% vs 5.6%, P = 0.02). Multivariate analysis showed candidemia to be a risk factor associated with mortality among LTRs presenting ICIs (odds ratio, 11.86; 95% confidence interval, 1.5-280; P = 0.01). Candida albicans represented the most common isolate (59.5%). High rates of antifungal resistances were found, with 16.7% and 4.8% of isolates displaying resistance to azoles and caspofungin, respectively. Our study confirms the occurrence of high mortality rates in LTRs developing ICIs. Mortality rates varied according to the type of infection, with candidemia representing a risk factor for mortality. The high rates of antifungal resistance should be considered in the choice of the empiric antifungal regimen.

The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp.

We studied the antifungal activity of SCY-078 (an orally bioavailable 1,3-β -d- glucan synthesis inhibitor), micafungin and fluconazole against the planktonic and sessile forms of 178 Candida and non- Candida isolates causing fungaemia in patients recently admitted to a large European hospital. The in vitro activity of SCY-078, micafungin and fluconazole against the planktonic form of the isolates was assessed using EUCAST EDef 7.3 and CLSI M27-A3. Antibiofilm activity was assessed using the XTT reduction assay. SCY-078 and micafungin showed potent in vitro activity against Candida and non- Candida isolates. The in vitro activity of both drugs was similar, but SYC-078 displayed significantly lower MIC values than micafungin against Candida parapsilosis and non- Candida isolates, whereas micafungin displayed significantly lower MIC values for the remaining species ( P <0.001). In contrast, SCY-078 and micafungin showed essentially the same activity against the biofilms with the exception of Candida glabrata , in which the micafungin sessile MIC values were significantly lower ( P <0.001). These observations were confirmed by assessing biofilm structure by scanning electron microscopy after antifungal treatment. Our study showed that the high in vitro activity of SCY-078 against invasive Candida isolates in both sessile and planktonic forms is comparable to that of micafungin.

Human immunodeficiency virus and fungal infections.

The discovery of HIV was largely due to the presence of Pneumocystis pneumonia (PCP) in young patients that did not have the usual known causes of immune deficiencies in the early 1980s. Currently, treatment with highly active anti-retroviral therapy (HAART) and the use of prophylaxis for PCP have lowered the frequency of fungal infections; however, these infections continue to cause morbidity and mortality in those patients that fall out or are not in care. The frequency of specific fungal diseases in HIV patients will depend on the prevalence of fungi in the particular geographic location. Nowadays, superficial and invasive Candida infections, PCP, and cryptococci are the most frequent fungal infections seen in HIV positive patients worldwide. The role of pathology in diagnosing fungal infections is crucial because a lesion may be biopsied without obtaining mycology cultures, certain organisms may take several weeks to grow, or the sample sent to the mycology laboratory may not have the organism. Following we will describe fungal infections that are particularly frequent in HIV infected patients and their key pathological features.

Fluconazole Doses Used for Prophylaxis of Invasive Fungal Infection in Neonatal Intensive Care Units: A Network Meta-Analysis

To evaluate the safety and efficacy of different doses of fluconazole used for invasive prophylaxis of fungal infection in neonates. A systematic search was conducted with PubMed, Scopus, and Web of Science. A manual search was performed as well. Only randomized controlled trials of neonates in a neonatal intensive care unit (NICU) who received fluconazole prophylaxis for invasive fungal infection, regardless of the dose or therapeutic regimen, were included in this review. Data on baseline characteristics, outcomes incidence of proven invasive Candida infection, overall mortality, and invasive Candida infection-related mortality were extracted. Eleven studies were included in the review, with fluconazole doses of 3, 4, or 6?mg/kg. When the incidence of invasive Candida and invasive Candida-related mortality were considered as outcomes, the 3 and 6?mg/kg fluconazole doses were found to be statistically superior to placebo (OR, 5.48 [95% credible interval, 1.81-18.94] and 2.63 [1.18-7.02], respectively, and 15.32 [1.54-54.31] and 9.14 [1.26-142.7], respectively), but data for the 3 doses were not statistically significantly different. Use of the lowest fluconazole dose (3?mg/kg) should be recommended for Candida prophylaxis in neonates, given that increasing the fluconazole dose is not associated with higher efficacy and has greater potential for toxicity and increased cost.

Clinical and epidemiological changes of candidemia among adult patients from 2000 to 2013

Invasive Candida spp. infections have been described more frequently. To characterize the epidemiological data of candidemia in recent years. A retrospective study of adult patients in a University Hospital in Santiago, Chile, with 1 or more documented episodes of candidemia, from January 2000 to December 2013. One hundred and twenty episodes of candidemia were identified in 120 patients, annual incidence of 0.4 cases per 1000 discharges, 53.3% were male patients, 58.3% > 60 years, 77,5% had at least one co-morbidity. Candida albicans was the species most frequently identified 55%, followed by C. glabrata 18.3%, C. tropicalis 11.7% and C. parapsilosis 9.2%. Comparing 2000-2006 vs 2007-2013, increased the frequency of C. parapsilosis among non-albicans and echinocandins prescription. Patients with C. albicans showed higher APACHE-II, more requirement for invasive mechanical ventilation, greater association with CVC, and shorter incubation time compared with non-albicans species. The 30-day mortality was 31.7%. During this 14-years period we observed that C. albicans was the predominant specie and more recently a change among C. non-albicans increasing C. parapsilosis and decreasing C. glabrata 30-days and attributable mortality decreased together with more echinocandins prescription.