Biofilm formation and increased mortality among cancer patients with candidemia in a Peruvian reference center.

BACKGROUND: Candidemia is an invasive mycosis with an increasing global incidence and high mortality rates in cancer patients. The production of biofilms by some strains of Candida constitutes a mechanism that limits the action of antifungal agents; however, there is limited and conflicting evidence about its role in the risk of death. This study aimed to determine whether biofilm formation is associated with mortality in cancer patients with candidemia. METHODS: This retrospective cohort study included patients treated at Peru's oncologic reference center between June 2015 and October 2017. Data were collected by monitoring patients for 30 days from the diagnosis of candidemia until the date of death or hospital discharge. Statistical analyses evaluated the association between biofilm production determined by XTT reduction and mortality, adjusting for demographic, clinical, and microbiological factors assessed by the hospital routinary activities. Survival analysis and bivariate and multivariate Cox regression were used, estimating the hazard ratio (HR) as a measure of association with a significance level of p < 0.05. RESULTS: A total of 140 patients with candidemia were included in the study. The high mortality observed on the first day of post-diagnosis follow-up (81.0%) among 21 patients who were not treated with either antifungal or antimicrobial drugs led to stratification of the analyses according to whether they received treatment. In untreated patients, there was a mortality gradient in patients infected with non-biofilm-forming strains vs. low/medium and high-level biofilm-forming strains (25.0%, 66.7% and 82.3%, respectively, p = 0.049). In treated patients, a high level of biofilm formation was associated with increased mortality (HR, 3.92; 95% p = 0.022), and this association persisted after adjusting for age, comorbidities, and hospital emergency admission (HR, 6.59; CI: 1.87-23.24, p = 0.003). CONCLUSIONS: The association between candidemia with in vitro biofilm formation and an increased risk of death consistently observed both in patients with and without treatment, provides another level of evidence for a possible causal association. The presence of comorbidities and the origin of the hospital emergency, which reflect the fragile clinical condition of the patients, and increasing age above 15 years were associated with a higher risk of death.

Clinical characteristics and outcomes of patients with candidemia during the COVID-19 pandemic: Insights from experience in the Omicron era.

BACKGROUND: In Taiwan, COVID-19 outbreaks caused by the Omicron variant occurred in 2022. We investigated the incidence of candidemia during COVID-19 pandemic and the mortality of candidemia patients with COVID-19 in Taiwan. METHODS: The incidence of candidemia and fluconazole susceptibility of Candida species before (2015-2019) and during COVID-19 pandemic (2020-2023) at Kaohsiung Chang Gung Memorial Hospital were investigated. The associated factors with mortality in candidemia patients during COVID-19 pandemic were analyzed. Candidemia patients who had COVID-19 within the prior 90 days (case group, n = 34) were propensity-score matched for age, ICU admission, and abdominal surgery in a 1:4 ratio with candidemia patients without COVID-19 (control group, n = 136). RESULTS: Age (adjusted odds ratio [AOR] = 1.02, 95% CI: 1.01-1.03), ICU stay (AOR = 1.84, 95% CI: 1.29-2.62), higher Charlson comorbidity index (AOR = 1.08, 95% CI: 1.03-1.13), corticosteroid use (AOR = 1.50, 95% CI: 1.04-2.17) were associated with increased risk of mortality; abdominal surgery (AOR = 0.47, 95% CI: 0.29-0.74) and infected by Candida parapsilosis (AOR = 0.61, 95% CI: 0.38-0.98) were associated with decreased risk of mortality. After matching, there was no significant difference in mortality rates between the case and control groups. The incidence of candidemia increased from 196 to 278 patients/100,000 admissions during COVID-19 pandemic, while the causative species of candidemia and fluconazole susceptibility rates were similar. CONCLUSION: While the incidence of candidemia increased during COVID-19 pandemic, there was no significant difference in mortality between candidemia patients with and without COVID-19 in the Omicron era.

Attributable mortality of candidemia - Results from the ECMM Candida III multinational European Observational Cohort Study.

INTRODUCTION: Despite antifungal advancements, candidaemia still has a high mortality rate of up to 40%. The ECMM Candida III study in Europe investigated the changing epidemiology and outcomes of candidaemia for better understanding and management of these infections. METHODS: In this observational cohort study, participating hospitals enrolled the first ten consecutive adults with blood culture-proven candidemia. Collected data included patient demographics, risk factors, hospital stay duration (follow-up of 90 days), diagnostic procedures, causative Candida spp., management details, and outcome. Controls were included in a 1:1 fashion from the same hospitals. The matching process ensured similarity in age (10-year range), primary underlying disease, hospitalization in intensive care versus non-ICU ward, and major surgery within 2 weeks before candidemia between cases and controls. Overall and attributable mortality were described, and a survival probability for cases and controls was performed. RESULTS: One hundred seventy-one pairs consisting of patients with candidemia and matched controls from 28 institutions were included. In those with candidemia, overall mortality was 40.4%. Attributable mortality was 18.1% overall but differed between causative Candida species (7.7% for Candida albicans, 23.7% for Candida glabrata/Nakaseomyces glabratus, 7.7% for Candida parapsilosis and 63.6% for Candida tropicalis). Regarding risk factors, the presence of a central venous catheter, total parenteral nutrition and acute or chronic renal disease were significantly more common in cases versus controls. Duration of hospitalization, and especially that of ICU stay, was significantly longer in candidemia cases (20 (IQR 10-33) vs 15 days (IQR 7-28); p = 0.004). CONCLUSIONS: Although overall and attributable mortality in this subgroup analysis of matched case/control pairs remains high, the attributable mortality appears to have decreased in comparison to historical cohorts. This decrease may be driven by improved prognosis of Candida albicans and Candida parapsilosis candidemia; whereas candidemia due to other Candida spp. exhibits a much higher attributable mortality.

Epidemiology of candidemia during COVID-19 pandemic era in a teaching hospital: A non-concurrent cohort study.

During the COVID-19 pandemic, an increase in the incidence of bloodstream infections caused by fungi of the Candida genus, also known as candidemia, was observed in patients with SARS-CoV-2 infection. This study aimed to assess the incidence of candidemia, the factors related to COVID-19-associated candidemia (CAC), and prognostic factors. A non-concurrent cohort of 87 cases of patients aged over 18 years with candidemia between March 2020 and February 2022 was evaluated. Incidence density (ID) was calculated by the number of patient-days during the period. All causes of mortality within 30 days of observation were considered. Logistic regression and Cox proportional hazards regression were used, respectively, to determine factors associated with CAC and prognostic factors. Values <0.05 were considered significant. The ID of CAC was eight times higher than candidemia in patients without COVID-19 [2.40 per 1000 person-days vs. 0.27 per 1000 person-days; P < .01]. The corticosteroid therapy was as an independent factor associated with CAC [OR = 15.98 (3.64-70.03), P < .01], while abdominal surgery was associated with candidemia in patients without COVID-19 [OR = 0.09 (0.01-0.88), P = .04]. Both patients with and without COVID-19 had a high 30 days-mortality rate (80.8% vs. 73.8%, respectively; P = .59). Liver disease [HR = 3.36 (1.22-9.27); P = .02] and the Charlson score [HR = 1.17 (1.01-1.34); P = .03] were independent factors of death, while the use of antifungals [HR = 0.15 (0.07-0.33); P < .01] and removal of the central venous catheter [HR = 0.26 (0.12-0.56); P < .01] independently reduced the risk of death. These findings highlight the high incidence of candidemia in COVID-19 patients and its elevated mortality.

This study found that bloodstream infections by Candida spp. were significantly more common in patients with than without COVID-19, and Candida glabrata played a significant role in these infections. Liver disease and a higher number of comorbidities were associated with an increased risk of death.

Candida parapsilosis candidemia in children admitted to a tertiary hospital in Turkey: clinical features and antifungal susceptibility.

In recent years, the incidence and drug resistance of Candida parapsilosis have increased. Our study aimed to determine the antifungal sensitivity of C. parapsilosis and the clinical and demographic characteristics of children with candidemia. Two hundred pediatric patients with C. parapsilosis candidemia were included in the study between 1 January 2010 and 1 August 2023. Clinical samples were evaluated on a BACTEC-FX-40 automatic blood culture device (Becton Dickinson, USA). Yeast isolates were identified to the species level via identification cards (YST) using the VITEK 2 Compact (bioMeriéux, France) system. Antifungal susceptibility was performed using antifungal cell cards (AST-YST01). Approval for the study was received from the "University Faculty of Medicine" Hospital Clinical Research Ethics Committee. Non-catheter candidemia was detected in 127 (63.5%) patients, and catheter-related candidemia was detected in 73 (36.5%) patients. It was observed that the patients' history of malignancy, mechanical ventilation, urinary catheter, nasogastric tube, and intensive care unit stay was associated with C. parapsilosis mortality. The mortality rate from candidemia was 9.5%. The most frequently preferred antifungal agents were amphotericin B and fluconazole. The fluconazole drug resistance rate was found to be 6%, and the amphotericin B drug resistance rate was 4%. Because C. parapsilosis candidemia mortality rates can be high depending on risk factors and clinical characteristics, it is important to initiate appropriate and timely antifungal therapy. We think that our study can provide important information about the clinical profiles, distributions, susceptibility profiles, and control of antifungal resistance of C. parapsilosis isolates. IMPORTANCE: It has been observed that the frequency and antifungal resistance of Candida parapsilosis have increased recently. In our study, we aimed to determine the antifungal sensitivity of C. parapsilosis and the clinical and demographic characteristics of children with candidemia. It was observed that the patients' history of malignancy, mechanical ventilation, urinary catheter, nasogastric tube, and intensive care stay was associated with C. parapsilosis mortality. The mortality rate from candidemia was 9.5%. The most frequently preferred antifungal agents were amphotericin B and fluconazole. The fluconazole drug resistance rate was found to be 6%, and the amphotericin B drug resistance rate was 4%. Because C. parapsilosis candidemia mortality rates can be high depending on risk factors and clinical characteristics, it is important to initiate appropriate and timely antifungal therapy.

Efficacy of short- versus prolonged-courses of antimicrobial therapy for carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A propensity score-matched cohort study.

BACKGROUND: As limited antibiotic options are available for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs), the optimal treatment duration for CRKP BSIs is unclear. Our objective was to investigate whether short courses (6-10 days) are as effective as prolonged courses (≥11 days) of active antibiotic therapy for CRKP BSIs. METHODS: A retrospective cohort study comprising adults with monomicrobial CRKP BSI receiving a short or prolonged course of in vitro active therapy at a medical center was conducted between 2010 and 2021. Comparisons of two therapeutic strategies were assessed by the logistic regression model and propensity score analysis. The primary endpoint was 30-day crude mortality. Secondary outcomes included recurrent BSIs, the emergence of multidrug-resistant organisms and candidemia during hospitalization after completing antibiotic therapy for CRKP BSIs. RESULTS: Of 263 eligible adults, 160 (60.8%) were male, and the median (interquartile range) age was 69.0 (53.0-76.0) years. Common comorbidities included diabetes (143 patients, 54.4%), malignancy (75, 28.5%), cerebrovascular accident (58, 22.1%), and hemodialysis (49, 18.6%). The 30-day mortality rate was 8.4% (22 patients). Of 84 propensity score well-balanced matched pairs, the 30-day mortality was similar in the short-course and prolonged-course group (6.0% and 7.1%, respectively; P = 1.00). However, there were less episodes candidemia in the short-course group (1.2% versus 13.1%; odds ratio, 0.08; 95% confidence interval, 0.01-0.63; P = 0.005). CONCLUSION: Short courses of active therapy for CRKP BSIs demonstrate comparable clinical outcomes to prolonged courses and are associated with a lower risk of subsequent candidemia.

Riesgo de mortalidad en candidemia en niños oncohematológicos: revisión sistemática / Mortality risk in candidemia in children with cancer and blood disorders: a systematic review

Introducción: La tasa de mortalidad de la candidemia es variable, pero puede estar influenciada por la patología de base, en especial aquella que condiciona la presencia de neutropenia. En niños con patología oncohematológica, son pocos los trabajos que han abordado la mortalidad relacionada a candidemias y sus factores asociados. Las preguntas que promueven esta revisión sistemática, son: ¿Cuáles son las características epidemiológicas, clínicas y de evolución de los pacientes pediátricos oncohematológicos con candidemia? ¿Cuál es la mortalidad relacionada con esta entidad? Materiales y métodos: Revisión sistemática de la literatura. Se utilizaron los siguientes términos de búsqueda: candidemia por Candida spp. y los siguientes filtros humanos, niños y adolescentes y patología oncohematológica. Se revisaron los artículos publicados en inglés, español o francés hasta el 21 de septiembre de 2023. Las referencias bibliográficas de los artículos incluidos se revisaron manualmente para identificar estudios relevantes adicionales. Resultados: Se encontraron 66 artículos. Del análisis cualitativo realizado en sus textos completos, quedaron finalmente 4 estudios que se consideró que cumplían con los criterios de inclusión. Todos los artículos seleccionados sumaron 191 pacientes con diversas patologías oncohematológicas. La presencia de accesos vasculares fue frecuente en esta serie y la no extracción del catéter venoso central fue el factor más prevalente entre los que fallecieron. El agente infectante predominante fue Candida no albicans y la mortalidad osciló entre el 11,3 y el 31% con una mediana de 25%. No fue posible establecer si la especie de Candida influía en la letalidad

Introduction: The mortality rate of candidemia is variable, but may be influenced by underlying diseases, especially those causing neutropenia. In children with cancer and blood disorders, few studies have addressed mortality related to candidemia and its associated factors. The questions that motivated this systematic review were: What are the epidemiological, clinical and outcome characteristics of pediatric cancer patients with candidemia? What is the mortality related to this condition? Materials and methods: Systematic review of the literature. The following search terms were used: Candida spp., candidemia, with the following filters: human, children and adolescents, and cancer and blood disorders. Articles published in English, Spanish, or French up to September 21, 2023 were reviewed. References of included articles were manually reviewed to identify additional relevant studies. Results: 66 articles were identified. From the qualitative analysis carried out on their full texts, 4 studies that were considered to meet the inclusion criteria were finally selected. The selected articles included a total of 191 patients with various types of cancer and blood disorders. The presence of vascular access was common in this series and failure to remove the central venous catheter was the most prevalent factor among those who died. The predominant infectious agent was non-albicans Candida and mortality ranged from 11.3% to 31% with a median of 25%. It was not possible to establish whether Candida species influenced mortality.

Increasing morbidity and mortality of candidemia over one decade in a Swiss university hospital.

BACKGROUND: The epidemiology of candidemia is evolving with raising concern about the emergence of intrinsically resistant non-albicans Candida species and acquisition of antifungal resistance. In addition to microbiological surveys, epidemiological studies including clinical data are needed to assess the impact of candidemia on morbidity and mortality. OBJECTIVES: To assess the clinical and microbiological trends of candidemia in a Swiss university hospital. PATIENTS/METHODS: This single-centre retrospective study compared the incidence of candidemia, Candida species distribution, antifungal resistance profiles, clinical characteristics and outcomes between two periods separated by one decade. RESULTS: A total of 170 candidemic episodes were included (68 from period 1, 2004-2006, and 102 from period 2, 2014-2017). Incidence of candidemia (0.85 to 0.97 episode/10,000 patient-days), species distribution (55%-57% C albicans) and antifungal susceptibilities remained unchanged. During period 2, candidemia was more frequently observed in intensive care units (ICU, 38% vs 19% in period 1, P = .01) and amongst older patients (median age 68 vs 59 years old, P < .01) with more immunosuppressive conditions (24% vs 9%, P = .01). Candidemia in period 2 was more frequently followed by septic shock (23% vs 7% in period 1, P = .01) and ICU admission (42% vs 12%, P < .01) and was associated with higher mortality (34% vs 18%, P = .03). Overall, factors associated with mortality in multivariate analyses included cirrhosis, solid malignancies and ICU stay at the time of candidemia. CONCLUSIONS: Despite stable incidence, species distribution and antifungal resistance of candidemia, an epidemiological shift of the disease towards older and more critically ill patients was observed, with higher mortality rates.

Candidemia in Children: A 16-year Longitudinal Epidemiologic Study.

BACKGROUND: Candida species are the most common cause of systemic fungal infections in children. Risk factors for candidemia vary in different patient populations, posing challenges for clinical prediction of infection. We describe the epidemiology and clinical disease of candidemia in children admitted to a tertiary pediatric hospital. METHODS: Retrospective audit of children ≤18 years of age with candidemia at a tertiary pediatric hospital over a 16-year period. RESULTS: There were 139 episodes of candidemia in 124 children. A central venous catheter was present in 94% of episodes, prior antibiotic exposure in 86% and parenteral nutrition in 43%. During the study period, the proportion of candidemia due to non-albicans Candida spp. increased primarily due to a rise in C. krusei. Colonization with Candida spp. in the 30 days before developing candidemia was identified in 40% of episodes and the species was concordant in 60%. Infection at other sites was rare, including pulmonary dissemination (9/38, 24%), renal fungal disease (9/114, 8%), fungal endophthalmitis (8/102, 8%) and hepatosplenic nodules (5/92, 5%). Overall, 8/127 (6%) isolates were fluconazole-resistant (7 C. krusei and 1 C. glabrata) and 7/127 (6%) had intermediate susceptibility to fluconazole. The overall 30-day mortality was 12% and significant risk factors for mortality on multivariate analysis were male sex, liver disease and mucositis. CONCLUSIONS: Our study outlines low rates of disseminated candidiasis and low mortality associated with candidemia at our institution. Additionally, it suggests that prior colonization may be an important risk factor, however, this should be validated in large prospective controlled studies.

Impact of biofilm production by Candida species and antifungal therapy on mortality of patients with candidemia.

BACKGROUND AND OBJECTIVES: Few studies have investigated the clinical outcomes of patients with candidemia caused by Candida species with different levels of biofilm formation. We aimed to investigate the impact of antifungal therapy on the outcome of candidemia caused by Candida species that were categorised as low biofilm formers (LBFs), moderate biofilm formers (MBFs), and high biofilm formers (HBFs). METHODS: Adults with candidemia caused by LBF and HBF/MBF Candida species that were susceptible to fluconazole and caspofungin were included to investigate the impact of treatment with fluconazole vs an echinocandin on 30-day crude mortality. RESULTS: In total, 215 patients with candidemia received fluconazole and 116 patients received an echinocandin. In multivariate analysis, Pittsburgh bacteremia score ≥ 4 (adjusted odds ratio [AOR] =2.42; 95% confidence interval [CI], 1.32-4.41), malignancy (AOR = 3.45; 95% CI, 1.83-6.51), not removing the central venous catheter within 48 hours of a positive blood culture (AOR = 4.69; 95% CI, 2.61-8.45), and treatment with fluconazole for candidemia due to HBF/MBF Candida spp. (AOR = 2.23; 95% CI, 1.22-4.06) were independent factors associated with 30-day mortality. Of the 165 patients infected by HBF/MBF Candida isolates, those who received azole therapy had a significantly higher sepsis-related mortality rate than those who received echinocandin therapy (44.9% [49/109] vs 26.8% [15/56], P = .03). CONCLUSIONS: There was a trend of an independent association between fluconazole treatment and poor outcomes in the patients infected by HBF/MBF Candida strains.

Epidemiology, species distribution, and predictive factors for mortality of candidemia in adult surgical patients.

BACKGROUND: We evaluated the epidemiology, clinical characteristics, microbiology, outcomes, and risk factors for mortality of candidemia in adult surgical patients in Shenyang from 2012 to 2018. METHODS: We designed a retrospective observational study of adult patients with candidemia in a teaching hospital including three hospital campuses. Data regarding clinical and demographic characteristics were collected from the patient's medical records. RESULTS: Of the 236 cases of candidemia, 172 (72.9%) were identified in surgical patients, including 146 (84.9%) general surgeries, 11 (6.4%) urologic surgeries, 6 (3.5%) thoracic surgeries, and others. Higher proportions of solid tumors, total parenteral nutrition, the presence of a urinary catheter, and the presence of a gastric tube were observed in surgical patients with candidemia versus non-surgical ones, whereas the percentages of hematological malignancy, diabetes mellitus, and renal replacement therapy were relatively lower in surgical patients. Renal failure, leukopenia, and thrombocytopenia were less common laboratory findings in surgical patients with candidemia than compared to non-surgical ones. Among surgical patients with candidemia, Candida parapsilosis was the predominant species (43%), followed by C. albicans (33.7%), C. glabrata (11%), C. tropicalis (8.1%), and others (4.1%). Overall susceptibility, susceptible dose dependent or intermediate susceptibility, and resistance to fluconazole were detected in 73.3, 19.8, and 3.5% Candida isolates from surgical patients, respectively, but no resistance to amphotericin B was observed. Overall, the 30-day mortality in surgical patients was 19.2%. At multivariable analysis, independent risk factors for death in surgical patients with candidemia were ICU stay, thrombocytopenia, and C. albicans infection. CONCLUSIONS: Surgical patients account for the majority of candidemia cases. Among patients with recent surgery, risk factors for species distribution, antifungal sensitivity patterns of Candida isolates causing candidemia, and independent risk factors for mortality should be evaluated and considered for a better outcome in the antifungal treatment.

Persistent vs non-persistent candidaemia in adult patients in 2007-2016: A retrospective cohort study.

OBJECTIVES: Persistent candidaemia (PC) is a recognised complication of candidaemia. Our objective was to evaluate risk factors and clinical significance of PC in adult patients. METHODS: This is a retrospective, cohort study. We compared PC with non-PC. All patients with blood cultures positive for Candida species were identified from a microbiological database in the hospital district of Helsinki and Uusimaa from 2007 to 2016. PC was defined as an isolation of the same Candida species from positive blood culture for ≥5 days. RESULTS: PC criteria were fulfilled by 75/350 patients (21.4%). No significant difference emerged between persistent and non-persistent cases caused by non-albicans Candida species (37.3% vs 35.1%, P = .742). The length of hospital stay before onset of candidaemia was longer before PC (hospital stay > 7 days; 73.3% vs 59.6%, P = .043). No significant impact on 30-day mortality was observed (20.0% vs 15.5%, P = .422). Using multivariable regression analysis, we found the presence of central venous catheter (CVC) (OR = 2.71, 95% CI 1.31-5.59), metastatic infection foci (OR 3.60, 95% CI 1.66-7.79) and ineffective empirical treatment (OR = 3.31, 95% CI 1.43-7.65) to be independent risk factors for PC. In subgroup analysis, early source control was identified as a protective factor against PC (30.5% vs 57.7%, P = .002). CONCLUSION: The presence of CVC, metastatic infection foci and ineffective empirical treatment were independently associated with PC in adult patients. Active search for and treatment of metastatic infection foci and removal of CVC are key elements for preventing PC.

Risk factors for candidemia: a prospective matched case-control study.

BACKGROUND: Candidemia is an opportunistic infection associated with high morbidity and mortality in patients hospitalized both inside and outside intensive care units (ICUs). Identification of patients at risk is crucial to ensure prompt antifungal therapy. We sought to assess risk factors for candidemia and death, both outside and inside ICUs. METHODS: This prospective multicenter matched case-control study involved six teaching hospitals in Switzerland and France. Cases were defined by positive blood cultures for Candida sp. Controls were matched to cases using the following criteria: age, hospitalization ward, hospitalization duration, and, when applicable, type of surgery. One to three controls were enrolled by case. Risk factors were analyzed by univariate and multivariate conditional regression models, as a basis for a new scoring system to predict candidemia. RESULTS: One hundred ninety-two candidemic patients and 411 matched controls were included. Forty-four percent of included patients were hospitalized in ICUs, and 56% were hospitalized outside ICUs. Independent risk factors for candidemia in the ICU population included total parenteral nutrition, acute kidney injury, heart disease, prior septic shock, and exposure to aminoglycoside antibiotics. Independent risk factors for candidemia in the non-ICU population included central venous catheter, total parenteral nutrition, and exposure to glycopeptides and nitroimidazoles. The accuracy of the scores based on these risk factors is better in the ICU than in the non-ICU population. Independent risk factors for death in candidemic patients included septic shock, acute kidney injury, and the number of antibiotics to which patients were exposed before candidemia. DISCUSSION: While this study shows a role for known and novel risk factors for candidemia, it specifically highlights important differences in their distribution according to the hospital setting (ICU versus non-ICU). CONCLUSION: This study provides novel risk scores for candidemia accounting for the hospital setting and recent progress in patients' management strategies and fungal epidemiology.

Comparison of risk factors and outcomes of Candida auris candidemia with non-Candida auris candidemia: A retrospective study from Pakistan.

Candida auris has emerged as a nosocomial multi-drug resistant pathogen. This study aimed to compare the risk factors and outcomes of C. auris candidemia patients with non-C. auris candidemia, at a single center in Pakistan. A retrospective study compared 38 C. auris with 101 non-C. auris (36 C. albicans, 38 C. tropicalis, and 27 C. parapsilosis) candidemia patients between September 2014 and March 2017 at the Aga Khan University Hospital, Pakistan. Demographics, clinical history, management and outcomes were studied. Prior history of surgery (adjusted odds ratio [aOR] 4.9, 95% confidence interval [CI]: 1.4-17.5), antifungals exposure (aOR 38.3, 95% CI: 4.1-356) and prior MDR bacteria isolation (aOR 5.09, 95% CI: 1.6-15.9) were associated with C. auris candidemia. On survival analysis both groups of patients had similar outcome in terms of mortality (62.6% vs. 52.54%, hazard ratio [HR] 1.45, 95% CI: 0.84-2.4, P-value = .17) and microbiological failure rates (42.3% vs. 32.2%, HR 0.65, 95% CI: 0.35-1.2, P-value = .17) however, C. auris patients had a higher mean hospital stay (36.32 days vs. 14.8 days, P-value = <.001) and higher >15-day in-hospital stay from positive culture (HR 2.68, 95% CI: 1.1-6.3, P-value = .025). Antifungal susceptibility was different, with C. auris more often resistant to voriconazole (29.6% vs. 0%) and amphotericin (3.7 vs. 0%); though no echinocandin resistance was detected in either group. As opposed to other Candida species, C. auris candidemia occurred after nosocomial exposure, and its source was most commonly an indwelling line. Although these patients had a higher in-hospital stay, but there was no excess mortality when compared to other Candida species.

Risk factors associated with mortality among patients who had candidemia in a university hospital

Abstract INTRODUCTION: Bloodstream infection due to Candida spp. is a primary cause of morbidity and mortality in tertiary hospitals. METHODS: In this retrospective study, we included patients with a positive blood culture for Candida spp. after 48 h of hospitalization. RESULTS A total of 335 patients who had candidemia were included in this study. Risk factors associated with mortality were hospitalization in internal medicine units and surgical clinics, age >60 years, mechanical ventilation, orotracheal intubation, hemodialysis, corticosteroids use, and C. parapsilosis infection. CONCLUSIONS: This study highlights the importance of health care related to invasive procedures and actions to improve patient immunity.

Characterisation of candidemia in patients with recent surgery: A 7-year experience.

Candidemia can complicate major surgical procedures. However, literature data are scanty on this topic. In this study, we evaluated the epidemiology, clinical and microbiologic characteristics and outcome of candidemia in adult patients with recent surgery hospitalised in a single University Hospital in Central Italy from 2010 to 2016. Of the 304 episodes of candidemia, 160 (53%) occurred in surgical patients (SPs) while the remaining 144 (47%) in patients without history of recent surgery (non-SPs). Although either underlying chronic comorbidities (ie haematological malignancies, neurological and gastrointestinal diseases) or acute complications (ie pneumonia and septic shock) were less likely to occur in SPs than in non-SPs, 30-day mortality did not differ between groups being 38% and 42%, respectively. The specific risk factors significantly more common in SPs who died within 30 days were as follows: male gender, older age, being hospitalised in ICU rather than in other wards, having a higher Charlson's score, undergoing previous invasive procedures, haemodialysis, the presence of pneumonia, septic shock, acute kidney failure and the type of surgery. In particular, either gastrointestinal or cardiovascular surgeries were characterised by the highest mortality rates. Multivariate analysis showed that the occurrence of septic shock (HR 10.3131 [CI95% 1.176-90.466; P = .035] and ICU stay (HR 2.016 [CI95% 1.178-3.448; P = .011] was independently associated with higher mortality in SPs. Overall, these data show that candidemia in SPs is characterised by significant mortality and distinctive features.

Candidaemia and a risk predictive model for overall mortality: a prospective multicentre study.

BACKGROUND: Candidaemia is associated with high mortality. Variables associated with mortality have been published previously, but not developed into a risk predictive model for mortality. We sought to describe the current epidemiology of candidaemia in Australia, analyse predictors of 30-day all-cause mortality, and develop and validate a mortality risk predictive model. METHODS: Adults with candidaemia were studied prospectively over 12 months at eight institutions. Clinical and laboratory variables at time of blood culture-positivity were subject to multivariate analysis for association with 30-day all-cause mortality. A predictive score for mortality was examined by area under receiver operator characteristic curves and a historical data set was used for validation. RESULTS: The median age of 133 patients with candidaemia was 62 years; 76 (57%) were male and 57 (43%) were female. Co-morbidities included underlying haematologic malignancy (n = 20; 15%), and solid organ malignancy in (n = 25; 19%); 55 (41%) were in an intensive care unit (ICU). Non-albicans Candida spp. accounted for 61% of cases (81/133). All-cause 30-day mortality was 31%. A gastrointestinal or unknown source was associated with higher overall mortality than an intravascular or urologic source (p < 0.01). A risk predictive score based on age > 65 years, ICU admission, chronic organ dysfunction, preceding surgery within 30 days, haematological malignancy, source of candidaemia and antibiotic therapy for ≥10 days stratified patients into < 20% or ≥ 20% predicted mortality. The model retained accuracy when validated against a historical dataset (n = 741). CONCLUSIONS: Mortality in patients with candidaemia remains high. A simple mortality risk predictive score stratifying patients with candidaemia into < 20% and ≥ 20% 30-day mortality is presented. This model uses information available at time of candidaemia diagnosis is easy to incorporate into decision support systems. Further validation of this model is warranted.

Central venous catheter unrelated candidemia influences the outcome of infection in patients with solid tumors.

Systemic infections due to Candida spp. is common among immunocompromised patients, including those with solid tumors (ST). Clinical characteristics of candidemia in 114 patients with ST were compared with those of 249 candidemic patients without ST (non-ST). Patients with ST were more likely to be hospitalized in medical departments, to have a significantly higher Charlson's score and to undergo a significantly later central venous catheter (CVC) removal (P < 0.001). Similarly, the use of total parenteral nutrition was more common in ST patients (P = 0.026). Although there was a trend toward a more appropriate use of antifungal therapy in ST (60%) than in non-ST patients (49%), the difference was not statistically significant (P = 0.059). Thirty-day mortality was significantly higher in ST (49%) than in non-ST patients (36%, P = 0.016). Multivariate analysis showed that either higher age or septic shock was an independent risk factor for mortality in both groups of patients. Conversely, a CVC-unrelated candidemia represented an independent risk factor for mortality in ST patients (HR 3.581 [CI 95% 1.412-9.087, P = 0.007]). Overall, these data show that candidemia in ST patients is characterized by an extremely high mortality rate.

[Risk factors and lethality associated with neonatal candidemia in a neonatal unit]. / Factores de riesgo y letalidad asociados a candidemia neonatal en una unidad de neonatología.

OBJECTIVE: To identify the main risk factors associated with neonatal candidemia. PATIENTS AND METHOD: A retrospective paired case-control study was conducted from January 2014 to December 2016. The cases were patients with isolation in blood culture and/or cerebrospinal fluid of Candi da spp. after their first 48 hours in the hospital and the controls cases were neonates chosen from the statistical census of neonatology paired according to their admission date (30-day range), birth weight, gestational age, and discharge condition (alive or deceased). For each case, we select two controls. The risk factors evaluated were intrahospital stay over seven days, use of broad-spectrum antibiotics, mechanical ventilation, parenteral nutrition longer than five days, invasive procedures such as central venous access and abdominal and thoracic surgeries, necrotizing enterocolitis and growth of bacterial microorganisms in blood culture before candidemia. RESULTS: During the study period, 141 patients developed candidemia. 49% of the cases corresponded to Candida parapsilosis with the highest associated lethality rate. The multivariate analysis identified as risk factors hospital stay longer than seven days (OR = 17.0, 95% CI = 2.36-122.4), use of umbilical lines (OR = 9.04, 95% CI = 1.55-52.5), abdominal and/or thoracic surgery (OR = 12.4, 95% CI = 1.76-87.3), and treatment with Meropenem (OR = 4.62, 95% CI = 1.34-15.9). CONCLUSION: Prolonged intrahospital stay longer than seven days and thoracic and/or abdominal surgery were the most significant risk factors in this study for the development of neonatal candidemia.

Clinical spectrum and factors impacting outcome of Candida auris: a single center study from Pakistan.

BACKGROUND: An outbreak of Candida auris began globally in 2014 including Pakistan and since then it has emerged as a nosocomial multi-drug resistant pathogen. The aim of this study was to assess the clinical spectrum and outcome of patients, from a single center in Pakistan, in whom C. auris was isolated. METHODS: A retrospective study was conducted on 92 patients; ≥16 years with at least one culture positive for C. auris, at the Aga Khan University Hospital Karachi, Pakistan from Sept 2014-Mar 2017.Demographics, clinical history, management and outcome were studied. A logistic regression model was used to identify the risk factors for mortality. RESULTS: We identified 92 patients with C. auris (193 isolates), of whom 52.2% were males. Mean age was 54.14 ± 20.4 years. Positive cultures were obtained after a median hospital stay of 14 days. Most patients had a history of surgery (57.6%), antibiotic use (95.6%), ICU stay (44.6%), indwelling lines (88.04%) and isolation of another multi-resistant organism (52.2%).Most patients were symptomatic (70.7%). Amongst these, 38 had candidemia while 27 had non-candidemia infections. Sites of infection included central lines (35), urinary tract (19), peritonitis (4), nosocomial ventriculitis (1), empyema (1), fungal keratitis (1) otitis externa (1) and surgical site (1). Fluconazole resistance was 100% while 28.5 and 7.9% were Voriconazole and Amphotericin resistant respectively. Overall crude mortality was 42.4% while 14-day mortality was 31.5%. Both infected and colonized cases shared similar mortality (46.2% vs 33.3%; p-value = 0.25). Among infected cases mortality was high in candidemia compared to non-candidemia (60.5% vs 25.9%) in which deaths related to C. auris were 34.2% vs 22.2% respectively. On multivariate analysis candidemia (AOR 4.2, 95% CI: 1.09-16.49; p-value = 0.037) was associated with greater mortality with source control being the only protective factor for mortality (AOR 0.22, 95% CI: 0.05-0.92; p-value0.038] while ICU stay, rapidity of blood culture clearance, DM, malignancy and MDR co-infection had no impact. CONCLUSION: Patients with C.auris from a single center in Pakistan have a wide clinical spectrum with line associated infection being the predominant site of infection. Candidemia leads to high mortality while source control improves outcome.