Epidemiology Of Invasive Candidiasis Research Articles

Genotypic Diversity of Candida parapsilosis Complex in Invasive Candidiasis at a Pediatric Tertiary Hospital: A 5-Year Retrospective Study.

Invasive candidiasis (IC) contributes to the morbidity and mortality of hospitalized patients and represents a significant burden to the healthcare system. Previous Brazilian studies have reported the presence of endemic Candida parapsilosis sensu stricto genotypes causing candidemia and clonal transmission involving fluconazole-resistant isolates. We performed a 5-year retrospective analysis of IC cases in a Brazilian tertiary pediatric hospital and conducted a molecular investigation of C. parapsilosis sensu stricto. Non-duplicate C. parapsilosis sensu stricto genotyping was performed by microsatellite analysis. Antifungal susceptibility and biofilm formation were also evaluated. A total of 123 IC episodes were identified, with an IC incidence of 1.24 cases per 1000 hospital admissions and an overall mortality of 34%. The main species were the C. parapsilosis complex (35.8%), Candida albicans (29.2%), and Candida tropicalis (21.9%). All C. parapsilosis sensu stricto were recovered from blood cultures, and 97.5% were biofilm producers. Microsatellite typing identified high genotypic diversity among the isolates. We observed that all isolates were sensitive to amphotericin B, and although one isolate was non-sensitive to fluconazole, only a silent mutation on ERG11 gene was identified. No clear evidence of clonal outbreak or emergence of fluconazole-resistant isolates was found, suggesting that multiple sources may be involved in the epidemiology of IC in children.

Deciphering the epidemiology of invasive candidiasis in the intensive care unit: is it possible?

Invasive candidiasis (IC) has emerged in the last decades as an important cause of morbidity, mortality, and economic load in the intensive care unit (ICU). The epidemiology of IC is still a difficult and unsolved enigma for the literature. Accurate estimation of the true burden of IC is difficult due to variation in definitions and limitations inherent to available case-finding methodologies. Candidemia and intra-abdominal candidiasis (IAC) are the two predominant types of IC in ICU. During the last two decades, an increase in the incidence of candidemia has been constantly reported particularly in the expanding populations of elderly or immunosuppressed patents, with a parallel change in Candida species (spp.) distribution worldwide. Epidemiological shift in non-albicans spp. has reached worrisome trends. Recently, a novel, multidrug-resistant Candida spp., Candida auris, has globally emerged as a nosocomial pathogen causing a broad range of healthcare-associated invasive infections. Epidemiological profile of IAC remains imprecise. Though antifungal drugs are available for Candida infections, mortality rates continue to be high, estimated to be up to 50%. Increased use of fluconazole and echinocandins has been associated with the emergence of resistance to these drugs, which affects particularly C. albicans and C. glabrata. Crucial priorities for clinicians are to recognize the epidemiological trends of IC as well as the emergence of resistance to antifungal agents to improve diagnostic techniques and strategies, develop international surveillance networks and antifungal stewardship programmes for a better epidemiological control of IC.

Epidemiology, antifungal susceptibility, risk factors and mortality of invasive candidiasis in neonates and children in a tertiary teaching hospital in Southwest China.

Invasive candidiasis (IC) is a major cause of morbidity and mortality in neonates and children; however, little information on the epidemiology of IC in paediatric patients in China is available. A 7-year retrospective study was conducted to analyse the prevalence, species distributions, antifungal susceptibility, risk factors and mortality among paediatric inpatients with IC in a regional tertiary teaching hospital in Southwest China. A total of 86 paediatric inpatients with IC during the seven-year study period were identified, with a mean annual incidence of 1.04 cases per 1000 admissions and a neonatal incidence of 2.72 cases per 1000 admissions. The species distributions of Candida albicans and non-albicans Candida were 48.8% and 51.2%, respectively. The total resistance rates to fluconazole (FCA), itraconazole (ITR) and voriconazole (VRC) were 8.1%, 26.7% and 14.0%, respectively. Age, length of hospital stay, respiratory dysfunction, hospitalisation duration>30days and IC due to Calbicans and Candida glabrata were associated with neonatal mortality (P<0.05) according to univariate analyses. Respiratory dysfunction [odds ratio (OR), 50.03; 95% confidence interval (CI), 3.47-721.44; P=0.004] was the only independent predictor of neonatal mortality. The overall mortality rate was 8.1%, and only neonatal IC patients died, with a neonatal mortality rate of 13.0%. This report shows that the incidence and mortality of IC among neonatal patients warrants increased attention in Southwest China. Clinical interventions should be actively applied to reduce the incidence and mortality of neonatal infection. Fluconazole was a reasonable choice for the treatment of IC prior to species identification.

Invasive candidiasis in children after hematopoietic stem cell transplantation

Invasive fungal disease due to Candida spp. – Invasive candidiasis/candidaemia, is a life-threatening complication in immunosuppressed patients. The publications on epidemiology of invasive candidiasis (IC) in children after hematopoietic stem cell transplantation (HSCT) is limited. The purpose of the study was to study the epidemiology of IC in children after HSCT for the 7 years in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation. In 2009–2016 yy have been performed 754 HSCT in children: 494 allogeneic and 260 autologous. The study was approved by the Independent Ethics Committee of the Raisa Gorbacheva Memorial Research Institute of Children's Oncology, Hematology and Transplantation. A retrospective study included 22 cases of invasive candidiasis in after HSCT. EORTC/MSG 2008 criteria were used for the diagnosis of proven invasive candidiasis as well as to evaluate response to therapy. Incidence of IC was 2.9%: allo-HSCT – 3% (n = 15), auto-HSCT – 2,7% (n = 7). The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The etiology: Candida parapsilosis – 50%, Candida albicans – 27%, Candida krusei – 14%, Candida tropicalis – 5%, Candida dubliniensis – 4%. The most frequent underlying diseases was acute leukemia – 45% (n = 10). The median age was 8 y.o. (3 month–18 years). The median day of onset of IC after allo-HSCT was 63 days (4–243), auto-HSCT – 12 days (3–20). Febrile fever was the main clinical symptom; septic syndrome develops in 32% cases. Antifungal therapy was with echinocandins – 23%, lipid ampho B – 27%, triazole (fluconazole, voriconazole) – 32%, without therapy (due to early mortality) – 18%. Overall survival (OS) at 30 days from diagnosis invasive candidiasis was 50%. The central venous catheter (CVC) removal was the only factor significantly improved OS (70% vs 33%, p = 0,035). Incidence of Invasive candidiasis in children after hematopoietic stem cell transplantation was 2.9%. The main etiology agent was Candida parapsilosis. Invasive candidiasis infections most often affect leukemia patients, after allo-HSCT developed later than auto-HSCT. Overall survival at 30 days from the diagnosis was 50%. Removing of CVC improved overall survival in children with invasive candida infections after HSCT

Five-Year National Surveillance of Invasive Candidiasis: Species Distribution and Azole Susceptibility from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study.

Data on the epidemiology of invasive candidiasis (IC) and the antifungal susceptibility of Candida isolates in China are still limited. Here we report on surveillance for IC from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study. Sixty-five tertiary hospitals collected 8,829 Candida isolates from 1 August 2009 to 31 July 2014. Matrix-assisted laser desorption ionization-time of flight mass spectrometry supplemented by ribosomal DNA sequencing was used to define the species, and the fluconazole and voriconazole susceptibilities were determined by the Clinical and Laboratory Standards Institute disk diffusion method. A total of 32 Candida species were identified. Candida albicans was the most common species (44.9%), followed by the C. parapsilosis complex (20.0%), C. tropicalis (17.2%), and the C. glabrata complex (10.8%), with other species comprising <3% of isolates. However, in candidemia, the proportion of cases caused by C. albicans was only 32.3%. C. albicans and C. parapsilosis complex isolates were susceptible to fluconazole and voriconazole (<6% resistance), while fluconazole and azole cross-resistance rates were high in C. tropicalis (13.3% and 12.9%, respectively), C. glabrata complex (18.7% and 14%, respectively), and uncommon Candida species (44.1% and 10.3%, respectively) isolates. Moreover, from years 1 to 5 of the study, there was a significant increase in the rates of resistance to fluconazole among C. glabrata complex isolates (12.2% to 24.0%) and to both fluconazole (5.7% to 21.0%) and voriconazole (5.7% to 21.4%) among C. tropicalis isolates (P < 0.01 for all comparisons). Geographic variations in the causative species and susceptibilities were noted. Our findings indicate that antifungal resistance has become noteworthy in China, and enhanced surveillance is warranted.

Changes in the epidemiological landscape of invasive candidiasis.

The epidemiology of invasive candidiasis has evolved in recent years, warranting a review of the changes and the implications for current and future diagnosis and treatment. The overall burden of invasive candidiasis remains high, particularly in the expanding populations of patients at risk of opportunistic infection, such as the elderly or immunosuppressed. Progressive shifts from Candida albicans to non-albicans Candida spp. have been observed globally. The recent emergence of novel, multiresistant species, such as Candida auris, amplifies the call for vigilance in detection and advances in treatment. Among the current treatment options, fluconazole is still widely used throughout the world. Increased resistance to fluconazole, both acquired and naturally emerging, has been observed. Resistance to echinocandins is presently low but this may change with increased use. Improvement of diagnostic techniques and strategies, development of international surveillance networks and implementation of antifungal stewardship programmes represent major challenges for a better epidemiological control of invasive candidiasis.

Epidemiology of Invasive Candidiasis in the United States, 2002–2012

Epidemiology of Invasive Candidiasis in the United States, 2002–2012

Epidemiology of invasive candidiasis in a surgical intensive care unit: an observational study.

BackgroundInvasive candidiasis (IC) is a frequent and life-threatening infection in critically ill patients. The aim of this study was to evaluate the epidemiology of IC and the antifungal susceptibility of etiological agents in patients admitted to our surgical intensive care unit (SICU) in Spain.MethodsWe designed a prospective, observational, single center, population-based study in a SICU. We included all consecutive adult patients (≥18 years old) who had documented IC, either on admission or during their stay, between January 2012 and December 2013.ResultsThere were a total of 22 episodes of IC in the 1149 patients admitted during the 24-month study. The overall IC incidence was 19.1 cases per 1000 admissions. Thirteen cases of IC (59.1 %) were intra-abdominal candidiasis (IAC) and 9 (40.9 %) were candidemias. All cases of IAC were patients with secondary peritonitis and severe sepsis or septic shock. The overall crude mortality rate was 13.6 %; while, it was 33 % in patients with candidemia. All patients with IAC survived, including one patient with concomitant candidemia. The most common species causing IC was Candida albicans (13; 59.1 %) followed by Candida parapsilosis (5; 22.7 %), and Candida glabrata (2; 9.1 %). There was also one case each (4.5 %) of Candida krusei and Candida tropicalis. Thus, the ratio of non-C. albicans (9) to C. albicans (13) was 1:1.4. There was resistance to fluconazole and itraconazole in 13.6 % of cases. Resistance to other antifungals was uncommon.ConclusionsCandida parapsilosis was the second most common species after C. albicans, indicating the high prevalence of non-C. albicans species in the SICU. Resistance to azoles, particularly fluconazole, should be considered when starting an empirical treatment. Although IAC is a very frequent form of IC in critically ill surgical patients, prompt antifungal therapy and adequate source control appears to lead to a good outcome. However, our results are closely related to our ICU and any generalization must be taken with caution. Therefore, further investigations are needed.

Prediction of the Clinical Outcome in Invasive Candidiasis Patients Based on Molecular Fingerprints of Five Anti-Candida Antibodies in Serum

Better prognostic predictors for invasive candidiasis (IC) are needed to tailor and individualize therapeutic decision-making and minimize its high morbidity and mortality. We investigated whether molecular profiling of IgG-antibody response to the whole soluble Candida proteome could reveal a prognostic signature that may serve to devise a clinical-outcome prediction model for IC and contribute to known IC prognostic factors. By serological proteome analysis and data-mining procedures, serum 31-IgG antibody-reactivity patterns were examined in 45 IC patients randomly split into training and test sets. Within the training cohort, unsupervised two-way hierarchical clustering and principal-component analyses segregated IC patients into two antibody-reactivity subgroups with distinct prognoses that were unbiased by traditional IC prognostic factors and other patients-related variables. Supervised discriminant analysis with leave-one-out cross-validation identified a five-IgG antibody-reactivity signature as the most simplified and accurate IC clinical-outcome predictor, from which an IC prognosis score (ICPS) was derived. Its robustness was confirmed in the test set. Multivariate logistic-regression and receiver-operating-characteristic curve analyses demonstrated that the ICPS was able to accurately discriminate IC patients at high risk for death from those at low risk and outperformed conventional IC prognostic factors. Further validation of the five-IgG antibody-reactivity signature on a multiplexed immunoassay supported the serological proteome analysis results. The five IgG antibodies incorporated in the ICPS made biologic sense and were associated either with good-prognosis and protective patterns (those to Met6p, Hsp90p, and Pgk1p, putative Candida virulence factors and antiapoptotic mediators) or with poor-prognosis and risk patterns (those to Ssb1p and Gap1p/Tdh3p, potential Candida proapoptotic mediators). We conclude that the ICPS, with additional refinement in future larger prospective cohorts, could be applicable to reliably predict patient clinical-outcome for individualized therapy of IC. Our data further provide insights into molecular mechanisms that may influence clinical outcome in IC and uncover potential targets for vaccine design and immunotherapy against IC.

Invasive fungal infections: treatment and novel therapies

Early antifungal therapy for systemic fungal infections is critical for optimal outcomes. Selection of antifungal agents varies with pathogen and can be assisted by <i>in vitro</i> susceptibility results. Given the shift in epidemiology of invasive candidiasis towards species with reduced susceptibility to fluconazole, the choice for an initial drug usually lies between fluconazole and an echinocandin. Appropriate dosing and consideration of pharmacokinetic parameters (including therapeutic drug monitoring) are important for azoles. Rapidly fungicidal induction therapy regimens using amphotericin B (AMB) combined with flucytosine is required to optimise outcomes in HIV/AIDS, organ transplantation and also other patient groups with cryptococcal meningitis. Fluconazole remains the cornerstone of eradication therapy. Voriconazole is preferred for treatment of all forms of invasive aspergillosis. Where voriconazole cannot be used or has failed, lipid AMB, caspofungin or posaconazole may be used. Lipid AMB is preferred for treating zygomycosis with few data to support the use of posaconazole as primary therapy; addition of deferasirox iron chelator has shown promising preclinical/clinical data. Voriconazole +/– terbinafine is recommended for invasive scedosporiosis whilst high dose lipid AMB (or voriconazole) is preferred for fusariosis. New agents are urgently needed to counter the increasing spectrum of fungal pathogens; these include isavuconazole and the iron chelators.

Management of Invasive Candidiasis in the Intensive Care Unit

Invasive candidiasis (IC) is an important infection in the intensive care unit (ICU) setting given its association with poor clinical outcomes. The epidemiology of IC is complex and, although incompletely elucidated, is characterized by considerable regional and temporal variability. Overall, there appears to be an increase in the incidence of IC and a change in distribution of the causative Candida spp. Of particular concern is an increase in the proportion of episodes caused by Candida glabrata, which is associated with reduced susceptibility to azole antifungal agents. The management of IC has been aided by the availability of several new antifungal agents. In particular, given their broad spectrum of activity and low toxicity, the use of echinocandins as first-line therapy is increasing, especially in settings where fluconazole-resistant Candida spp. are prevalent. Fluconazole remains a reliable agent where an azole-susceptible pathogen is confirmed or in settings where resistance is uncommon. Lipid formulations of amphotericin B are now generally reserved as second-line or salvage therapy. Voriconazole and posaconazole currently enjoy limited use for IC in the ICU setting. Although the poor outcomes associated with IC are, in part, related to the severity of underlying host factors, it is clear that optimization of treatment-related factors is also important. In particular, the speed of initiation of antifungal therapy and the achievement of pharmacodynamic parameters both influence outcomes. The most difficult challenge is early initiation of an effective antifungal drug, given the slow turnaround time and lack of sensitivity of conventional culture-based diagnostic techniques. New approaches, such as non-culture-based assays and/or clinical risk-predictive models are required to better target prophylactic, pre-emptive and empirical antifungal strategies.

Catheter-related fungemia caused by Candida intermedia

Candida intermedia is rarely reported as a human pathogen. We report two cases of catheter-related fungemia caused by C. intermedia which were treated successfully with intravenous fluconazole and catheter removal. The isolates were identified by commercial biochemical methods, oligonucleotide array, and partial sequencing analysis of rRNA genes.

Changing epidemiology of invasive candidiasis in intensive care units—Much ado about nothing?(*

Changing epidemiology of invasive candidiasis in intensive care units—Much ado about nothing?(*

Could Risk Assessment for Non-albicans Candida Improve Empiric Treatment for Invasive Candidiasis?

The changing epidemiology of invasive candidiasis, along with concerns for the emergence of drug resistance, necessitates the identification of patients at increased risk of non-albicans Candida (NAC) to optimize selection of antifungal therapy. The major findings of a study regarding the demographic characteristics, costs, and outcomes of nonneutropenic patients with candidemia due to NAC are discussed. Given available treatment options, such risk assessment is most relevant to initial empiric therapy in stable patients without neutropenia who might be candidates for initial therapy with an azole (eg, fluconazole). The study's investigators reinforce the need for timely antifungal therapy for patients with candidemia.

Évolution de 1'épidérmiologie des candidoses et aspergilloses invasives

According to recent international studies, the epidemiology of invasive Candidiasis has changed worldwide over these recent years, contrarily to that of invasive aspergillosis. An increase in the incidence of invasive candidiasis has been observed, as well as changes in Candida spp repartition and in the profile of patient populations with candidemia. Therefore, a re-evaluation of treatment strategies is needed on the basis of local epidemiological characteristic knowledge. Thus, current treatment strategies are more often based on patient risk factors than on results of susceptibility tests, though they are recommended by European guidelines in haematological patients.