Candidemia in Adult Patients in the ICU: A Reappraisal of Susceptibility Testing and Antifungal Therapy.

OBJECTIVE: To provide updates on the epidemiology and recommendations for management of candidemia in patients with critical illness. DATA SOURCES: A literature search using the PubMed database (inception to March 2023) was conducted using the search terms "invasive candidiasis," "candidemia," "critically ill," "azoles," "echinocandin," "antifungal agents," "rapid diagnostics," "antifungal susceptibility testing," "therapeutic drug monitoring," "antifungal dosing," "persistent candidemia," and "Candida biofilm." STUDY SELECTION/DATA EXTRACTION: Clinical data were limited to those published in the English language. Ongoing trials were identified through ClinicalTrials.gov. DATA SYNTHESIS: A total of 109 articles were reviewed including 25 pharmacokinetic/pharmacodynamic studies and 30 studies including patient data, 13 of which were randomized controlled clinical trials. The remaining 54 articles included fungal surveillance data, in vitro studies, review articles, and survey data. The current 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Management of Candidiasis provides recommendations for selecting empiric and definitive antifungal therapies for candidemia, but data are limited regarding optimized dosing strategies in critically ill patients with dynamic pharmacokinetic changes or persistent candidemia complicated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Outcomes due to candidemia remain poor despite improved diagnostic platforms, antifungal susceptibility testing, and antifungal therapy selection for candidemia in critically ill patients. Earlier detection and identification of the species causing candidemia combined with recognition of patient-specific factors leading to dosing discrepancies are crucial to improving outcomes in critically ill patients with candidemia. CONCLUSIONS: Treatment of candidemia in critically ill patients must account for the incidence of non-albicans Candida species and trends in antifungal resistance as well as overcome the complex pathophysiologic changes to avoid suboptimal antifungal exposure.

Invasive Candida infection: epidemiology, clinical and therapeutic aspects of an evolving disease and the role of rezafungin.

INTRODUCTION: Invasive Candida Infections (ICIs) have undergone a series of significant epidemiological, pathophysiological, and clinical changes during the last decades, with a shift toward non-albicans species, an increase in the rate of exogenous infections and clinical manifestations ranging from candidemia to an array of highly invasive and life-threatening clinical syndromes. The long-acting echinocandin rezafungin exhibits potent in-vitro activity against most wild-type and azole-resistant Candida spp. including C.auris. AREAS COVERED: The following topics regarding candidemia only and ICIs were reviewed and addressed: i) pathogenesis; ii) epidemiology and temporal evolution of Candida species; iii) clinical approach; iv) potential role of the novel long-acting rezafungin in the treatment of ICIs. EXPERT OPINION: Authors' expert opinion focused on considering the potential role of rezafungin in the evolving context of ICIs. Rezafungin, which combines a potent in-vitro activity against Candida species, including azole-resistant strains and C.auris, with a low likelihood of drug-drug interactions and a good safety profile, may revolutionize the treatment of candidemia/ICI. Indeed, it may shorten the length of hospital stays when clinical conditions allow and extend outpatient access to treatment of invasive candidiasis, especially when prolonged treatment duration is expected.

Prevalence, risk factors, treatment and outcome of multidrug resistance Candida auris infections in Coronavirus disease (COVID-19) patients: A systematic review.

BACKGROUND: Candida auris is an emerging multidrug-resistant pathogen in intensive care settings (ICU). During the coronavirus disease 19 (COVID-19) pandemic, ICU admissions were overwhelmed, possibly contributing to the C. auris outbreak in COVID-19 patients. OBJECTIVES: The present systematic review addresses the prevalence, underlying diseases, iatrogenic risk factors, treatment and outcome of C. auris infections in COVID-19 patients. METHODS: MEDLINE, Scopus, Embase, Web of Science and LitCovid databases were systematically searched with appropriate keywords from 1 January 2020 to 31 December 2021. RESULTS: A total of 97 cases of C. auris were identified in COVID-19 patients. The pooled prevalence of C. auris infections (encompassing candidemia and non-candidemia cases) in COVID-19 patients was 14%. The major underlying diseases were diabetes mellitus (42.7%), hypertension (32.9%) and obesity (14.6%), followed by the iatrogenic risk factors such as a central venous catheter (76.8%%), intensive care unit (ICU) stay (75.6%) and broad-spectrum antibiotic usage (74.3%). There were no significant differences in underlying disease and iatrogenic risk factors among C. auris non-candidemia/colonisation and C. auris candidemia cases. The mortality rate of the total cohort is 44.4%, whereas, in C. auris candidemia patients, the mortality was 64.7%. CONCLUSION: This study shows that the prevalence of C. auris infections remains unchanged in the COVID-19 pandemic. Hospital-acquired risk factors may contribute to the clinical illness. Proper infection control practices and hospital surveillance may stop future hospital outbreaks during the pandemic.

Treatment Practices for Adults With Candidemia at 9 Active Surveillance Sites-United States, 2017-2018.

BACKGROUND: Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non-albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines. METHODS: During 2017-2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures. RESULTS: Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29-3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate. CONCLUSIONS: A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species. Reasons for nonadherence to IDSA guidelines should be evaluated, and clinician education is needed.

Spectrum and Antifungal Resistance of Candidemia in Neonates With Early- and Late-Onset Sepsis in Pakistan.

BACKGROUND: Neonatal candidemia leads to high morbidity and mortality in developing countries. We studied the trends, spectrum and antifungal resistance in neonatal candidemia isolates from the year 2014 to 2019. METHODS: This was a cross-sectional study conducted at the Aga Khan University, Pakistan. Neonates with positive blood cultures with Candida species were retrospectively identified from the laboratory database (2014-2018) and prospectively in 2019 where clinical information was also collected as part of routine laboratory reporting. RESULTS: We identified 669 neonates with Candida species in blood cultures. Three hundred forty-six neonates had early-onset disease (EOD age ≤7 days) and 323 had late-onset disease (LOD age >7 days). Non-albicans Candida species (86.7%) were predominant versus C. albicans (13.3%; P-value 0.024) with Candida tropicalis being most common in both EOD and LOD. Candida pelliculosa and Candida guilliermondii were associated with EOD and C. albicans with LOD. Isolation of fluconazole nonsusceptible non-albicans Candida species was significantly higher in early-onset (5.9%) versus late-onset (2%) neonatal candidemia (P-value 0.005; crude odds ratio [COR] 2.73, 95% CI: 1.34-5.53). LOD in neonates was more likely associated with the use of vancomycin (COR 3.89, 95% CI: 1.39-10.89). EOD was more likely seen in patients with vaginal delivery (COR 4.16, 95% CI: 1.42-12.23) and in neonates with respiratory distress leading to intensive care unit admission (COR 3.31, 95% CI: 1.05-10.42). CONCLUSIONS: Non-albicans Candida species were increasingly isolated from neonates with candidemia during recent years from Pakistan. Amphotericin remains first-line option for neonatal candidemia in our setting as fluconazole nonsusceptible Candida species are commonly isolated.

Epidemiology, risk factors, treatment and outcome of Candida bloodstream infections because of Candida albicans and Candida non-albicans in two district general hospitals in the United Kingdom.

INTRODUCTION: Bloodstream infections caused by Candida species, known as candidemia are on the rise because of increasing complexity of surgical procedures, patient's underlying co-morbidities and shift in patient's demographics. This study was conducted to evaluate the epidemiology, risk factors, co-morbidities, antifungal treatment and outcomes of candidemia in Candida albicans (C. albicans) and Candida non-albicans (C. non-albicans) in East Sussex Healthcare Trust (ESHT), England. MATERIAL AND METHODS: This retrospective and prospective study was performed during January 2006 to June 2017. RESULT: A total of 102 episodes of candidemia on 100 patients (55 males) were identified. C. non-albicans were predominant (55%). All isolates were sensitive to amphotericin B, caspofungin and voriconazole while one C. albicans and five C. non-albicans isolates were resistant to fluconazole. The risk factors in C. albicans and C. non-albicans groups were comparable which included intensive care unit (ICU) stay (15% vs 10%), the presence of intravascular line (35% vs 42%), previous antibiotic exposure (39% vs 49%), surgical intervention (19% vs 19%), mechanical ventilation (5% vs 8%), total parenteral nutrition (30% vs 27%) and urinary catheters (33 vs 38). The comorbidities in both groups (C. albicans and C. non-albicans) were solid organ cancer (15&14), haematology malignancy (1&3), steroid use (14&13), diabetes (9&7) and chemotherapy (2&4). Main sources of candidemia in C. albicans were line (12), respiratory (10) and urinary tracts (6) while line (26) and urinary tract (9) were predominant in C. non-albicans group. Only a small number of patients underwent echocardiography (30%) and ophthalmology reviews (20%). A total of 45 fatal cases were recorded (C. albicans 23). The highest mortality was seen in patients with C. albicans and among them the risk factors were elderly age group > 65 years (17/23), surgical intervention (9/23) and the history of ICU stay (7/23). CONCLUSION: C. albicans candidemia, >65 years of age and surgical procedure is associated with significant mortality, however, the use of fluconazole has shown the increased survival rate. This study suggests the surveillance of candidemia, and antifungal susceptibility pattern in current practice and the treatment.

Candidaemia in haematological malignancy patients from a SEIFEM study: Epidemiological patterns according to antifungal prophylaxis.

BACKGROUND: Candidaemia is an important infectious complication for haematological malignancy patients. Antifungal prophylaxis reduces the incidence of candidaemia but may be associated with breakthrough candidaemia. OBJECTIVE: To analyse the Candida species' distribution and relative antifungal susceptibility profiles of candidaemia episodes in relation to the use of antifungal prophylaxis among Italian SEIFEM haematology centres. METHODOLOGY: This multicentre retrospective observational SEIFEM study included 133 single-species candidaemia episodes of haematological malignancy patients for whom antifungal susceptibility testing results of blood Candida isolates were available between 2011 and 2015. Each participating centre provided both clinical and microbiological data. RESULTS: Non-Candida albicans Candida (NCAC) species were the mostly isolated species (89, 66.9%), which accounted for C parapsilosis (35, 26.3%), C glabrata (16, 12.0%), C krusei (14, 10.5%), C tropicalis (13, 9.8%) and uncommon species (11, 8.3%). C albicans caused the remaining 44 (33.1%) episodes. Excluding 2 C albicans isolates, 23 of 25 fluconazole-resistant isolates were NCAC species (14 C krusei, 6 C glabrata, 2 C parapsilosis and 1 C tropicalis). Fifty-six (42.1%) of 133 patients developed breakthrough candidaemia. Systemic antifungal prophylaxis consisted of azoles, especially fluconazole and posaconazole, in 50 (89.3%) of 56 patients in whom a breakthrough candidaemia occurred. Interestingly, all these patients tended to develop a C krusei infection (10/56, P = .02) or a fluconazole-resistant isolate's infection (14/50, P = .04) compared to patients (4/77 and 10/77, respectively) who did not have a breakthrough candidaemia. CONCLUSIONS: Optimisation of prophylactic strategies is necessary to limit the occurrence of breakthrough candidaemia and, importantly, the emergence of fluconazole-resistant NCAC isolates' infections in haematological malignancy patients.

Impact on Antifungal Susceptibility Patterns of Previous vs. Revised Clinical and Laboratory Standards Institute Breakpoints for Candida Species Isolated from Candidemia: Experience of Two Tertiary Care Institutions in Japan.

BACKGROUND: Candidemia has a high mortality rate. Identifying prognostic factors of candidemia, based on each regional data, is essential for better management. The Clinical and Laboratory Standards Institute (CLSI) recently revised Candida species-specific breakpoints (R-BP) for antifungal agents. Few studies have investigated the detection performance of resistance in Candida species by comparing the R-BP and previous species non-specific CLSI breakpoint (P-BP) among patients with candidemia. The primary objective was to investigate the impact of the R-BP on the antifungal susceptibility patterns of Candida species, while the secondary objective was to identify the prognostic factors of candidemia. METHODS: A total of 193 Candida species isolated from 187 patients with candidemia between January 2007 and December 2016 were examined. Susceptibility based on CLSI M27-A3 was defined as the P-BP and based on species-specific CLSI M59 or M60 breakpoint was defined as the R-BP. Multivariate Cox's hazard analysis was performed to identify prognostic factors within 30 days of the diagnosis of candidemia. RESULTS: A significant difference was observed in the susceptibility rate to fluconazole (FLCZ) (P-BP; 93.0% vs. R-BP; 79.4%) and to voriconazole (VRCZ) (P-BP; 97.2% vs. R-BP; 91.0%). The susceptibilities of C. parapsilosis, C. glabrata, and C. tropicalis to azole antifungal agents were markedly lower with the R-BP. Based on the R-BP, anti-fungal therapy was regarded as inappropriate for approximately 10% of the patients. The 30-day mortality rate was 29.4%. In a multivariate Cox's hazard analysis, age, lung disease, C. albicans, and the absence of antifungal therapy were associated with a high mortality rate, whereas serum albumin, C. parapsilosis, surgical wards, the removal of central venous catheter (CVC), and follow-up blood culture tests to confirm the clearance of Candida species were associated with a lower mortality rate. CONCLUSIONS: Early initiation of antifungal therapy, removal of CVC, and follow-up blood culture tests are essential for improving the outcome. The R-BP efficiently detected non-susceptible strains to FLCZ and VRCZ, particularly in non-albicans Candida species. The present results support the importance of antifungal susceptibility tests and interpretations based on the R-BP among patients with candidemia.

The epidemiology and management of candidemia in Northern Ireland during 2002-2011, including a 12-month enhanced case review.

In Northern Ireland there are concerns about candidaemia, with rates higher than those reported in England and Wales. Our aim was to explore the epidemiology of candidaemia during a 10 year period and the clinical management upon suspicion of cases during a one year enhanced investigation in Northern Ireland.Candidaemia reports to the Public Health Agency were validated during 2002-2011 and used to examine incidence and antifungal sensitivity trends (during 2007-2011). A clinical proforma was used to collate information for all patients with candidaemia in 2011.The majority (96%) of isolates were captured through voluntary laboratory reporting. There was a year-on-year increase in candidaemia from 2002-2011, from 80 to 131 episodes (incidence rate ratio 1.09 95% CI 1.05-1.13). Rates were highest in males under 1 year and over 75 years. 83/98 (85%) of case notes were available from candidaemia patients during 2011. The most prevalent risk factors were patients on total parenteral nutrition (26 people, 31.3%), surgery in the two months prior to the candidaemia (25 people, 30.1%), significant steroid use in the previous 3 months (24 people, 28.9%) and active neoplastic disease (23 people, 27.7%),This study confirmed an increase in candidaemia rates over time, with the observed incidence in 2011 higher than England and Wales. We identified areas for improvement around the clinical management of candidaemia. We recommend raising the awareness of guidelines for fundoscopy, echocardiography and central venous catheter removal.

Candidemia due to uncommon Candida species in children: new threat and impacts on outcomes.

Many uncommon Candida spp. (species other than C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. krusei) have been shown to emerge in tertiary care facilities. We aimed to investigate these uncommon candidemia in children. Forty-six cases of candidemia caused by uncommon Candida spp. were identified during 2003-2015 from a medical center in Taiwan. The most common specie was C. guilliermondii (31.2%), followed by C. lusitaniae (18.8%) and C. metapsilosis (18.8%). These cases were analyzed and compared with 148 episodes of C. albicans candidemia. The incidence density of uncommon Candida spp. candidemia and the proportion to all candidemia episodes increased substantively during the study period. Prior exposure to azoles was uncommon in the 30 days prior to infection, but fluconazole resistant strains were significantly more common (n = 19, 41.3%). The increased incidence density of uncommon Candida spp. candidemia was associated with increasing use of antifungal agents. No differences in demographics, underlying comorbidities, risk factors, clinical features, dissemination, and 30-day mortality were found between uncommon Candida spp. and C. albicans candidemia. Patients with uncommon Candida spp. candidemia were more likely to require modifications in antifungal treatment and receive echinocandin drugs (43.5% vs 21.6%, p = 0.007). Candidemia caused by uncommon Candida spp. had poorer response to antifungal treatment, led to longer duration of candidemia (median 4.0 versus 2.5 days, p = 0.008), and had a higher treatment failure rate (56.5% vs 38.5%, p = 0.040).

Breakthrough Candidemia In Children On Micafungin.

We identified 8 pediatric patients on micafungin (MCFG; ≥3 doses) at our institution who had breakthrough candidemia (BC). The causative strains of the BC were Candida parapsilosis in 7 patients. The minimum inhibitory concentration of MCFG was ≤1 µg/mL (susceptible) in all 8 isolates. Immunocompromised patients may develop BC caused by MCFG-susceptible strains.

Breakthrough candidemia after the introduction of broad spectrum antifungal agents: A 5-year retrospective study.

Candidemia is the main invasive fungal disease among hospitalized patients. Several breakthrough candidemia (BrC) cases have been reported, but few studies evaluate the epidemiology, risk factors, molecular characterization, antifungal susceptibility profile and outcome of those patients, especially in developing countries and including patients using broad spectrum antifungals. We conducted a retrospective study from 2011 to 2016, including patients aged 12 years or older with candidemia. Epidemiological characteristics and risk factors for candidemia were evaluated and compared with patients with BrC using univariate and multivariate analysis. Sequential Candida isolates from BrC were identified by internal transcribed spacer sequencing, genotyped with amplified fragment length polymorphism fingerprinting (AFLP), and tested for antifungal susceptibility. From 148 candidemia episodes, 27 breakthrough episodes (18%) were identified, with neutropenia and mucositis being independent risk factors for BrC. Candida non-albicans was more frequent in the BrC group (P < .001). AFLP showed high correlation with conventional methods of identification among breakthrough isolates and a high genetic similarity among isolates from the same patient was observed. C. albicans was the most susceptible species with low MIC values for all antifungal agents tested. In contrast, we found isolates of C. glabrata, C. parapsilosis and C. tropicalis resistant to triazoles and echinocandins. In conclusion, BrC occurred mainly in severely immunosuppressed patients, with neutropenia and mucositis. Mortality did not differ between the groups. Candida non-albicans species were more recovered from BrC, with C. albicans being the most susceptible to antifungals.

Microbial epidemiology of candidaemia in neonatal and paediatric intensive care units at the Children's Medical Center, Tehran.

Invasive candidiasis is a major cause of morbidity and mortality in children. However, limited data are available on the epidemiology of this infection in paediatric settings in Iran. The aim of this study was to determine the prevalence, microbial epidemiology, risk factors and clinical outcomes associated with candidaemia in intensive care units at the Children's Medical Center, Tehran, Iran. All blood and other normally sterile specimen cultures positive for Candida species were included. Isolates were identified by morphological and molecular methods. Unidentified/doubtful yeast isolates were subjected to ITS sequencing. A total of 156 episodes of invasive candidiasis, with an overall incidence of 15.2 per 1000 ICU admissions, was recorded. Risk factors included presence of central venous lines (89.1%), mechanical ventilation (55.8%) and parenteral nutrition (51.3%). Candida albicans (57.1%) and Candida parapsilosis (24.4%) were the most commonly isolated species. Candida orthopsilosis, Candida glabrata, Candida dubliniensis, Candida lusitaniae, Candida kefyr and Candida intermedia accounted for about 11% of the cases. The overall mortality rate was 42.5%. Non-albicans Candida species accounted for nearly half of the cases of paediatric candidaemia. This is the first prospective study of candidaemia in paediatric settings in Iran and serves to inform necessary interventions for the prevention of candidaemia.

Clinical features, antifungal susceptibility, and outcome of Candida guilliermondii fungemia: An experience in a tertiary hospital in mid-Taiwan.

BACKGROUNDS: Candida guilliermondii is rarely isolated from clinical specimen. C. guilliermondii fungemia is seldom reported in the literature. The aims of this study were to report the clinical features, antifungal susceptibility, and outcomes of patients with C. guilliermondii fungemia. METHODS: From 2003 to 2015, we retrospectively analyzed the clinical and laboratory data of patients with C. guilliermondii fungemia in a tertiary hospital in mid-Taiwan. We performed a multivariable logistic regression analysis to identify the risk factors of mortality. The Sensititre YeastOne microtiter panel assessed the susceptibility of antifungal agents. RESULTS: In this study, we identified 36 patients with C. guilliermondii fungemia. The median age of patients was 50.5 years (range, 17 days to 96 year) and 20 cases (56%) were male. The incidence of C. guilliermondii fungemia was 0.05 per 1000 admissions. Malignancy was the most common co-morbidity, and 25 (69%) patients had central venous catheter in place. Thirty-day overall mortality was 16.7%. In multivariate logistical regression analysis, catheter retention was an independent risk factor of mortality. According to epidemiological cutoff values, most clinical isolates (21/22, 95.5%) belonged to the wild-type MIC distributions for amphotericin B and flucytosine; however, the isolates were less susceptible to fluconazole (68%) and echinocandins (77-91%). CONCLUSION: Despite the lower mortality rate associated with C. guilliermondii fungemia, the removal of a central venous catheter remained an independent factor influencing the outcome of patients. The clinical significance of less susceptibility of C. guilliermondii to triazoles and echinocandins remains to be elucidated.

Epidemiología, especies, resistencia antifúngica y evolución de las candidemias en un hospital universitario de Buenos Aires, Argentina, durante 16 años / Epidemiology, species, antifungal resistance and outcome of candidemia in a university hospital in Buenos Aires, Argentina for 16 years

Resumen Introducción: La epidemiologia de las candidemias varía en cada región. Objetivos: Conocer la epidemiología de las candidemias en un hospital durante 16 años. Material y Métodos: Se revisaron los episodios de candidemia ocurridos en el Hospital de Clínicas de Buenos Aires desde 01/01/98 al 31/12/13. Resultados: Se identificaron 374 episodios de candidemia. La incidencia fue de 2,21/1.000 egresos y aumentó de 1,96 (1998-2005) a 2,25 (2006-2013) (p = 0,023). Se diagnosticaron: 5,4% en neonatos, 1,7% en lactantes, 6,5% en niños mayores, 31,8% en adultos y 52,7% en adultos mayores de 64 años. Los episodios fueron causados por C. albicans (40,9%), C. parapsilosis (21,7%), C. tropicalis (15,5%), C. glabrata (13,9%), otras especies de Candida (5,1%) y candidemias multiespecies (2,9%). El 5,3% de los aislados fue resistente a fluconazol. Setenta y cuatro por ciento de los pacientes recibió tratamiento; 70,3% lo inició con fluconazol, 25% con anfotericina B desoxicolato y 4,7% con equinocandinas o anfotericinas lipídicas. Se retiró 81% de los catéteres venosos centrales. La mortalidad fue de 47,9%, pero fue de 60,8% para los adultos mayores. Conclusión: La incidencia de candidemias se incrementó a través de los años, fue mayor en los adultos mayores y esta población tuvo peor evolución.

Background: The epidemiology of candidemia vary by region. Aim: To determine the epidemiology of candidemia in a hospital for 16 years. Material and Methods: Episodes of candidemia occurred in the Hospital de Clinicas of Buenos Aires were reviewed, from 01/01/98 to 31/12/13. Results: 374 episodes of candidemia were identified. The incidence was 2.21/1,000 discharges and increased from 1.96 (1998-2005) to 2.25 (2006-2013) (p = 0.023). Candidemia was diagnosed: 5.4% in neonates, 1.7% in infants, 6.5% in children, 31.8% in adults and 52.7% in elderly adults over 64 years old. The episodes were caused by C. albicans (40.9%), C. parapsilosis (21.7%), C. tropicalis (15.5%), C. glabrata (13.9%), other species of Candida (5.1%) and more than one species of Candida (2.9%). The 5.3% of the isolates were resistant to fluconazole. 74% of patients were treated. Initial treatments were with fluconazole (70.3%), amphotericin B deoxycholate (25%), echinocandins or lipidic amphotericin (4,7%). The 81% of central venous catheters were taken off. Mortality rate was of 47.9%, but in the elderly adults was of 60.8%. Conclusion: The incidence of candidemia showed an increase over the years. It was higher in the elderly adults, being the group with worse outcomes.

Epidemiología y susceptibilidad antifúngica de especies causantes de candidemia en la ciudad de Valdivia, Chile / Epidemiology and antifungal susceptibility of species producing candidemia in Valdivia, Chile

Resumen Introducción: La epidemiología de la candidemia en Chile es poco conocida, a pesar de ser una enfermedad frecuente y grave. Objetivos: Analizar la incidencia y perfil de susceptibilidad in vitro de especies del género Candida causantes de candidemia en el Hospital Base Valdivia. Material y Métodos: Se identificó todos los casos de candidemia ocurridos en la institución entre marzo de 2009 y agosto de 2011. Se estudió la distribución de especies y susceptibilidad in vitro por el método de disco difusión. Resultados: Se estudiaron 27 episodios de candidemia. La incidencia varió de 0,3 a 0,7 por 1.000 egresos (según servicio clínico). Fueron factores de riesgo: la hospitalización, uso previo de antimicrobianos, edad avanzada y enfermedad de base (insuficiencia renal, enfermedad cardiaca y pulmonar). La especie más frecuente fue C. albicans seguida de C. tropicalis, C. glabrata y C. krusei. Voriconazol fue el antifúngico con mejor actividad in vitro y hubo resultados variables para anfotericina B, fluconazol e itraconazol. Discusión: La incidencia encontrada fue superior a la de países desarrollados. Candida albicans, constituye la especie más frecuente, con alta sensibilidad in vitro a fluconazol, debiendo ser vigiladas las especies de Candida no albicans. Es fundamental desarrollar nuevas investigaciones para detectar potenciales variaciones epidemiológicas.

Background: Candidemia disease in Chile is not very known, despite being a very common and serious disease. Aim: To analyze incidence and susceptibility profile of species from the genus Candida in Hospital Base Valdivia. Material and Methods: All candidemia cases presented between March 2009 and August 2011 in our institution were identified. Species distribution and susceptibility were studied through the disk diffusion method. Results: Twenty-seven candidemia episodes were studied. Incidence varied from 0.3 to 0.7 by a thousand discharges (according to clinical service). Risk factors were hospitalization, preliminary use of antibiotics, aged people and underlying disease (renal failure, heart and lung disease). The most frequent species was C. albicans, followed by C. tropicalis, C. glabrata and C. krusei. Voriconazole was the antifungal showing the best in vitro performance. Amphotericin B, fluconazole and itraconazole presented variable results. Discussion: Incidence found was superior to that described in developed countries. Candida albicans constitute the most frequent species, with high sensitivity levels to fluconazole; Candida no albicans species must be monitored. Developing new research on the topic appears as fundamental to detect potential epidemiological variations.

Candidaemia due to Candida parapsilosis species complex at a hospital in Brazil: Clinical characteristics and antifungal susceptibility profile / Candidemia por especies del complejo Candida parapsilosis en un hospital de Brasil: características clínicas y perfil de sensibilidad a los antifúngicos

Background. Recent decades have seen a global emergence of candidaemia caused by non-Candida albicans Candida species, particularly the Candida parapsilosis complex. Aims. To evaluate the clinical features and antifungal susceptibility profiles of isolates belonging to the C. parapsilosis species complex in patients with candidaemia in a midwestern Brazilian tertiary-care teaching hospital. Methods. Yeast identification was performed using an automated Vitek 2 Compact system. PCR-RFLP was employed for species differentiation. Results. Five cases of infection by C. parapsilosis sensu stricto and two by Candida orthopsilosis were found. Of the seven cases, five were adult patients undergoing haemodialysis. The only isolate of C. parapsilosis sensu stricto resistant to fluconazole (MIC=8μg/ml) was obtained from a patient on a long-term regimen with this drug. This was the only patient who evolved to death. Conclusions. Resistance to antifungal agents poses a therapeutic challenge, especially for non-C. albicans Candida species, and requires continuous monitoring using susceptibility tests because resistance in vitro can be predictive of treatment failure. In the present study, in vitro antifungal susceptibility proved consistent with clinical outcome (AU)

Antecedentes. En las últimas décadas se ha visto un surgimiento mundial de la candidemia causada por especies de Candida no-C. albicans, en particular del complejo Candida parapsilosis. Objetivos. Evaluar las características clínicas y los perfiles de sensibilidad antifúngica en aquellos aislamientos del complejo de especies C. parapsilosis responsables de candidemia en un hospital universitario de tercer nivel en la región centro-oeste de Brasil. Métodos. La identificación se realizó en un sistema automatizado Vitek 2 compact. Se utilizó PCR-RFLP para la diferenciación de las especies. Resultados. Se encontraron cinco casos de candidemia por C. parapsilosis sensu stricto y dos por Candida orthopsilosis. Cinco eran pacientes adultos sometidos a hemodiálisis. El único aislamiento de Candida parapsilosis sensu stricto resistente a fluconazol (CIM, 8μg/ml) se obtuvo de un paciente en régimen largo de tratamiento con este antifúngico. Este fue el único paciente que murió. Conclusiones. La resistencia a los antifúngicos constituye un desafío terapéutico, en especial contra las especies de Candida no-C. albicans, que requieren la monitorización continua por medio de pruebas de sensibilidad en vista de que la resistencia in vitro puede ser predictiva de fracaso del tratamiento. En el presente estudio la sensibilidad antifúngica in vitro resultó consistente con el curso clínico (AU)

[Epidemiology and antifungal susceptibility of species producing candidemia in Valdivia, Chile]. / Epidemiología y susceptibilidad antifúngica de especies causantes de candidemia en la ciudad de Valdivia, Chile.

BACKGROUND: Candidemia disease in Chile is not very known, despite being a very common and serious disease. AIM: To analyze incidence and susceptibility profile of species from the genus Candida in Hospital Base Valdivia. MATERIAL AND METHODS: All candidemia cases presented between March 2009 and August 2011 in our institution were identified. Species distribution and susceptibility were studied through the disk diffusion method. RESULTS: Twenty-seven candidemia episodes were studied. Incidence varied from 0.3 to 0.7 by a thousand discharges (according to clinical service). Risk factors were hospitalization, preliminary use of antibiotics, aged people and underlying disease (renal failure, heart and lung disease). The most frequent species was C. albicans, followed by C. tropicalis, C. glabrata and C. krusei. Voriconazole was the antifungal showing the best in vitro performance. Amphotericin B, fluconazole and itraconazole presented variable results. DISCUSSION: Incidence found was superior to that described in developed countries. Candida albicans constitute the most frequent species, with high sensitivity levels to fluconazole; Candida no albicans species must be monitored. Developing new research on the topic appears as fundamental to detect potential epidemiological variations.

[Epidemiology, species, antifungal resistance and outcome of candidemia in a university hospital in Buenos Aires, Argentina for 16 years]. / Epidemiología, especies, resistencia antifúngica y evolución de las candidemias en un hospital universitario de Buenos Aires, Argentina, durante 16 años.

BACKGROUND: The epidemiology of candidemia vary by region. AIM: To determine the epidemiology of candidemia in a hospital for 16 years. MATERIAL AND METHODS: Episodes of candidemia occurred in the Hospital de Clinicas of Buenos Aires were reviewed, from 01/01/98 to 31/12/13. RESULTS: 374 episodes of candidemia were identified. The incidence was 2.21/1,000 discharges and increased from 1.96 (1998-2005) to 2.25 (2006-2013) (p = 0.023). Candidemia was diagnosed: 5.4% in neonates, 1.7% in infants, 6.5% in children, 31.8% in adults and 52.7% in elderly adults over 64 years old. The episodes were caused by C. albicans (40.9%), C. parapsilosis (21.7%), C. tropicalis (15.5%), C. glabrata (13.9%), other species of Candida (5.1%) and more than one species of Candida (2.9%). The 5.3% of the isolates were resistant to fluconazole. 74% of patients were treated. Initial treatments were with fluconazole (70.3%), amphotericin B deoxycholate (25%), echinocandins or lipidic amphotericin (4,7%). The 81% of central venous catheters were taken off. Mortality rate was of 47.9%, but in the elderly adults was of 60.8%. CONCLUSION: The incidence of candidemia showed an increase over the years. It was higher in the elderly adults, being the group with worse outcomes.

Epidemiology of candidemia and antifungal susceptibility in invasive Candida species in the Asia-Pacific region.

In the Asia-Pacific region, Candida albicans is the predominant Candida species causing invasive candidiasis/candidemia in Australia, Japan, Korea, Hong Kong, Malaysia, Singapore and Thailand whereas C. tropicalis is the most frequently encountered Candida species in Pakistan and India. Invasive isolates of C. albicans, C. parapsilosis complex and C. tropicalis remain highly susceptible to fluconazole (>90% susceptible). Fluconazole resistance (6.8-15%), isolates with the non-wild-type phenotype for itraconazole susceptibility (3.9-10%) and voriconazole (5-17.8%), and echinocandin resistance (2.1-2.2% in anidulafungin and 2.2% in micafungin) among invasive C. glabrata complex isolates are increasing in prevalence. Moreover, not all isolates of C. tropicalis have been shown to be susceptible to fluconazole (nonsusceptible rate, 5.7-11.6% in China) or voriconazole (nonsusceptible rate, 5.7-9.6% in China).