Unresolved issues in the diagnosis of catheter related candidemia: A position paper / Cuestiones no resueltas en el diagnóstico de la candidemia relacionada con el catéter: un documento de opinión

The incidence and recent trends of candidemia and the contribution of the COVID-19 pandemic to its evolution are not well documented. The catheter is a major focus of Candida spp. infections, but the methods used to confirm the origin of candidemia are still based on the data generated for bacterial infection. The presence of Candida spp. on the tip of a removed catheter is the gold standard for confirmation but it is not always possible to remove it. Conservative methods, without catheter removal, have not been specifically studied for microorganisms whose times of growth are different from those of bacteria and therefore these results are not applicable to candidemia. The different Candida species do not have a particular tropism for catheter colonization and fungal biomarkers have not yet been able to contribute to the determination of the origin of candidemia. Techniques such Candida T2 Magnetic Resonance (T2MR) has not yet been applied for this purpose. Finally, there is not yet a consensus of how to proceed when Candida spp. is isolated from an extracted catheter and blood cultures obtained from simultaneous peripheral veins are negative. In this lack of firm data, a group of experts has formulated a series of questions trying to answer them based on the literature, indicating the current deficiencies and offering their own opinion. All authors agree with the conclusions of the manuscript and offer it as a position and discussion paper. (AU)

La incidencia y las tendencias recientes de la candidemia y la contribución de la pandemia de COVID-19 a su evolución no están bien documentadas. El catéter es uno de los principales focos de infecciones por Candida spp., pero los métodos empleados para confirmar el origen de la candidemia siguen basándose en los datos generados para la infección bacteriana. La presencia de Candida spp. en la punta de un catéter retirado es el método de referencia para la confirmación, pero no siempre es posible proceder a dicha retirada. Los métodos conservadores, sin retirada del catéter, no han sido estudiados específicamente para microorganismos cuyos tiempos de crecimiento son diferentes a los de las bacterias y, por tanto, estos resultados no son aplicables a la candidemia. Las diferentes especies de Candida spp. no tienen un tropismo particular para la colonización del catéter y los biomarcadores fúngicos, aún no han podido contribuir a la determinación del origen de la candidemia. Técnicas como la resonancia magnética T2MR todavía no se ha empleado para este fin. Por último, todavía no existe un consenso sobre cómo proceder cuando se aísla Candida spp. en un catéter extraído y los hemocultivos obtenidos por venas periféricas simultáneas son negativos. Ante esta falta de datos firmes, un grupo de expertos ha formulado una serie de preguntas y ha tratado de responderlas en base a la literatura, indicando las carencias presentes y ofreciendo su propia opinión. Todos los autores están de acuerdo con las conclusiones del manuscrito y lo ofrecen como documento de posición y discusión. (AU)

Heterogeneidad del tratamiento para cándida parapsilosis en endocarditis micótica de válvula nativa / Types of treatments for native-valve endocarditis due to candida parapsilosis

Introducción: las infecciones por cándida en el ámbito intrahospitalario han ido en ascenso en las últimas décadas en especial en las unidades de cuidado intensivo (UCI), dado el uso cada vez más frecuente de antibióticos de amplio espectro y de procedimientos invasivos tanto diagnósticos como terapéuticos. Hoy se consideran las especies de cándida como la cuarta causa de infección del torrente sanguíneo en los Estados Unidos de Norteamérica, con alto riesgo de complicaciones que incluyen endocarditis, trombosis y embolismo séptico al sistema nervioso central (SNC) entre otros. En relación con la endocarditis por especies de cándida, se ha considerado de mal pronóstico por el alto riesgo de afectación al SNC, por lo que se ha recomendado el manejo quirúrgico como piedra angular de su tratamiento. Presentación del caso: se describe el caso clínico de un paciente con endocarditis y con candidemia por Candida parapsilosis a quien se le realizó manejo médico.

Nosocomial Candida infections have increased in the last decades particularly in the intensive care units (ICU) due to the rise in broad-spectrum antibiotics usage and invasive diagnostic and therapeutic procedures usage. Today, Candida species are recognized as the fourth causative organisms of endovascular infection in the United States of America posing a high risk of endocarditis, thrombosis and septic embolization to the central nervous system (CNS). Endocarditis due to Candida species is associated with a poor prognosis because of the increased risk of CNS involvement for which surgical approach has been recommended as the cornerstone of therapy. We hereby report a patient with endocarditis and candidemia due to Candida parapsilosis, who received medical management.

Epidemiology and Prognosis of Intensive Care Unit-Acquired Bloodstream Infection.

Intensive care unit-acquired bloodstream infections (ICU-BSI) are frequent and are associated with high morbidity and mortality rates. We conducted this study to describe the epidemiology and the prognosis of ICU-BSI in our ICU and to search for factors associated with mortality at 28 days. For this, we retrospectively studied ICU-BSI in the ICU of the Cayenne General Hospital, from January 2013 to June 2019. Intensive care unit-acquired bloodstream infections were diagnosed in 9.5% of admissions (10.3 ICU-BSI/1,000 days). The median delay to the first ICU-BSI was 9 days. The ICU-BSI was primitive in 44% of cases and secondary to ventilator-acquired pneumonia in 25% of cases. The main isolated microorganisms were Enterobacteriaceae in 67.7% of patients. They were extended-spectrum beta-lactamase (ESBL) producers in 27.6% of cases. Initial antibiotic therapy was appropriate in 65.1% of cases. Factors independently associated with ESBL-producing Enterobacteriaceae (ESBL-PE) as the causative microorganism of ICU-BSI were ESBL-PE carriage before ICU-BSI (odds ratio [OR]: 7.273; 95% CI: 2.876-18.392; P < 0.000) and prior exposure to fluoroquinolones (OR: 4.327; 95% CI: 1.120-16.728; P = 0.034). The sensitivity of ESBL-PE carriage to predict ESBL-PE as the causative microorganism of ICU-BSI was 64.9% and specificity was 81.2%. Mortality at 28 days was 20.6% in the general population. Factors independently associated with mortality at day 28 from the occurrence of ICU-BSI were traumatic category of admission (OR: 0.346; 95% CI: 0.134-0.894; P = 0.028) and septic shock on the day of ICU-BSI (OR: 3.317; 95% CI: 1.561-7.050; P = 0.002). Mortality rate was independent of the causative organism.

The Economic Burden of Candidemia and Invasive Candidiasis: A Systematic Review.

BACKGROUND: Candidemia or invasive candidiasis (IC) is an increasingly common fungal infection and has been associated with high mortality, particularly among the immunocompromised and critically ill. Although several studies have been conducted to estimate the cost of managing candidemia and IC, quality assessment on the methodological aspects of these cost studies was not performed. To date, no systematic review focusing on the economic burden of candidemia and IC has ever been conducted. OBJECTIVES: The aim of this study was to systematically review the available evidence on the economic burden of candidemia and IC worldwide. METHODS: Databases (ie, PubMed, Scopus, EconLit, HEORO, and Ovid/Embase) were searched through June 2018. Two researchers independently assessed the quality of the eligible studies. Costs reported in the included studies were converted to 2016 USD using Campbell and Cochrane Economics Methods Group-the Evidence for Policy and Practice Information (CCEMG-EPPI)-Centre Cost Converter software. RESULTS: Eight articles were included in this systematic review. The mean total cost per patient with candidemia and IC ranged from $48 487 to $157 574, whereas the mean cost per hospitalization associated with candidemia and IC was from $10 216 to $37 715. All studies were from developed Western countries and reported only direct costs of candidemia and IC. Hospitalization was the main cost driver, contributing to more than half of the total costs. CONCLUSION: Quality cost studies on candidemia and IC based on standardized methods to provide informed decision making among healthcare authorities in implementing appropriate strategies is anticipated, in particular in developing countries.

A novel approach to candidemia? The potential role of checkpoint inhibition.

Infections with Candida spp. cause significant morbidity and mortality despite intensive treatment with antifungal agents. Novel treatment options are urgently needed. Predominately immunocompromised patients are affected. This warrants the conclusion that strengthening host immunity may have the potential to improve outcome. Recent studies imply a potential benefit of checkpoint inhibition reversing hyporesponsiveness of innate and adaptive immunity during invasive fungal infections and invasive candidiasis in particular. We here give a brief overview of first preclinical data in vitro and in vivo and clinical evidence in selected cases.

[Clinical analysis of candidemia in immunocompetent patients].

OBJECTIVE: To investigate the etiological and clinical characteristics of immunocompetent patients with candidemia. METHODS: The clinical and microbiological data of patients diagnosed as candidemia admitted in Peking University Third Hospital from January 2010 to June 2016 were retrospectively analyzed. Underlying diseases, Candida spp. colonization, clinical manifestations, microbiological data, treatment and the outcome were compared between the HIV-negative immunocompromised (IC) and nonimmunocompromised (NIC) patients. RESULTS: A total of 62 cases diagnosed as candidemia were analyzed including 36 men and 26 women, with 16 to 100 years of age [(66.02±17.65) years]. There were 30 NIC and 32 HIV-negative IC patients respectively. In the NIC patients, there were 19 cases (19/30, 63.33%) with admission in intensive care unit (ICU), 21 (21/30, 70.00%) associated diabetes mellitus or uncontrolled hyperglycemia and 22 (22/30,73.33%) receiving invasive mechanical ventilation, while in the HIV-negative IC patients, there were 8 (8/32, 25.00%), 13 (13/32, 40.63%) and 7 (7/32, 21.88%) respectively (P<0.05). The NIC patients had higher acute physiology and chronic health evaluation (APACHE II) scores and sequential organ failure assessment (SOFA) scores both at admission (19.98±5.81, 6.04±6.14) and candidemia onset (25.61±6.52, 12.75±8.42) than the HIV-negative IC patients (APACHEII 15.09±5.82, 22.15±5.98) and SOFA 2.87±2.73, 7.66±5.64 respectively (P<0.05). In the NIC patients, twenty-one cases (21/30, 70.00%) died in hospital, while 14 cases (14/32, 43.75%) in HIV-negative IC. The crude mortality was significantly different between the two groups (P<0.05). By blood culture, Canidia albicans remained the the most prevalent isolates in all the patients. Clinical manifestation, Candida spp. colonization, etiology and drug susceptibility were also similar between NIC and HIV-negative IC patients (P>0.05). CONCLUSION: Candidemia in NIC patients tends to occur in those who are much more critically ill, more often admitted in ICU, and more frequently have diabetes mellitus or uncontrolled hyperglycemia and receive invasive mechanical ventilation than HIV-negative IC patients. NIC patients also have poorer prognosis than HIV-negative IC patients. Clinical manifestations, and microbiological characteristics are similar between HIV-negative IC and NIC patients.

Clinical analysis of candidemia in immunocompetent patients / 北京大学学报(医学版)

OBJECTIVE@#To investigate the etiological and clinical characteristics of immunocompetent patients with candidemia.@*METHODS@#The clinical and microbiological data of patients diagnosed as candidemia admitted in Peking University Third Hospital from January 2010 to June 2016 were retrospectively analyzed. Underlying diseases, Candida spp. colonization, clinical manifestations, microbiological data, treatment and the outcome were compared between the HIV-negative immunocompromised (IC) and nonimmunocompromised (NIC) patients.@*RESULTS@#A total of 62 cases diagnosed as candidemia were analyzed including 36 men and 26 women, with 16 to 100 years of age [(66.02±17.65) years]. There were 30 NIC and 32 HIV-negative IC patients respectively. In the NIC patients, there were 19 cases (19/30, 63.33%) with admission in intensive care unit (ICU), 21 (21/30, 70.00%) associated diabetes mellitus or uncontrolled hyperglycemia and 22 (22/30,73.33%) receiving invasive mechanical ventilation, while in the HIV-negative IC patients, there were 8 (8/32, 25.00%), 13 (13/32, 40.63%) and 7 (7/32, 21.88%) respectively (P<0.05). The NIC patients had higher acute physiology and chronic health evaluation (APACHE II) scores and sequential organ failure assessment (SOFA) scores both at admission (19.98±5.81, 6.04±6.14) and candidemia onset (25.61±6.52, 12.75±8.42) than the HIV-negative IC patients (APACHEII 15.09±5.82, 22.15±5.98) and SOFA 2.87±2.73, 7.66±5.64 respectively (P<0.05). In the NIC patients, twenty-one cases (21/30, 70.00%) died in hospital, while 14 cases (14/32, 43.75%) in HIV-negative IC. The crude mortality was significantly different between the two groups (P<0.05). By blood culture, Canidia albicans remained the the most prevalent isolates in all the patients. Clinical manifestation, Candida spp. colonization, etiology and drug susceptibility were also similar between NIC and HIV-negative IC patients (P>0.05).@*CONCLUSION@#Candidemia in NIC patients tends to occur in those who are much more critically ill, more often admitted in ICU, and more frequently have diabetes mellitus or uncontrolled hyperglycemia and receive invasive mechanical ventilation than HIV-negative IC patients. NIC patients also have poorer prognosis than HIV-negative IC patients. Clinical manifestations, and microbiological characteristics are similar between HIV-negative IC and NIC patients.

Prospects for adoptive T-cell therapy for invasive fungal disease.

PURPOSE OF REVIEW: Invasive fungal disease (IFD) is a cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. As more potent broad-spectrum antifungal agents are used in prophylaxis, drug resistance and less common fungal species have increased in frequency. Here we review current treatments available for IFD and examine the potential for adoptive T-cell treatment to enhance current therapeutic choices in IFD. RECENT FINDINGS: There is growing evidence supporting the role of T cells as well as phagocytes in antifungal immunity. T cells recognizing specific antigens expressed on fungal morphotypes have been identified and the role of T-cell transfer has been explored in animal models. The clinical efficacy of adoptive transfer of antigen-specific T cells for prophylaxis and treatment of viral infections post-HSCT has raised interest in developing good manufacturing practice (GMP)-compliant methods for manufacturing and testing fungus-specific T cells after HSCT. SUMMARY: As the outcomes of IFD post-HSCT are poor, reconstitution of antifungal immunity offers a way to correct the underlying deficiency that has caused the infection rather than simply pharmacologically suppress fungal growth. The clinical development of fungus specific T cells is in its early stages and clinical trials are needed in order to evaluate safety and efficacy.

Prognostic factors for candidaemia in intensive care unit patients: a retrospective analysis.

INTRODUCTION: Candidaemia, recognised as a fairly common disease among intensive care unit (ICU) patients, carries a poor prognosis. However, as studies on the prognostic factors associated with candidaemia in ICU patients are limited, this study aimed to establish the best prognostic factor for ICU patients with candidaemia in a tertiary care hospital in Japan. METHODS: We conducted a retrospective cohort study of patients with candidaemia in the emergency ICU at Fukuoka University Hospital, Fukuoka, Japan, from April 2010 to March 2015. Demographic and clinical data was collected from the patients' medical records and laboratory databases. RESULTS: A total of 25 patients were included in the study. However, 18 patients died during hospitalisation, resulting in an in-hospital mortality rate of 72.0%. The variables of Sequential Organ Failure Assessment (SOFA) score and cumulative number of risk factors for invasive candidiasis showed significant differences between patients in the survivor and non-survivor groups (p < 0.05). The areas under the receiver operating characteristic curves for the SOFA score and cumulative number of risk factors for invasive candidiasis were 0.873 (95% confidence interval [CI] 0.72-1.00) and 0.937 (95% CI 0.84-1.00), respectively. CONCLUSION: Our results suggest that the cumulative number of risk factors for invasive candidiasis was the most useful prognostic indicator for candidaemia in ICU patients.

Risk Factors and Scoring Systems for Patients with Candidemia at a Tertiary Hospital in Jakarta, Indonesia.

AIM: to identify the risk factors of candidemia and to develop a scoring system that could be implemented in Cipto Mangunkusumo Hospital (RSCM), Jakarta, Indonesia. METHODS: this study was a retrospective study with case control design using the medical records of patients since 2011 to 2014. All sepsis patients hospitalized in the RSCM with a positive blood culture for Candida were included in this study as a case group. The control group was all of the sepsis patients without candidemia. The ratio for case and control groups was equal (1:1). RESULTS: from 234 patients who were analyzed, the risk factors that influenced the study were length of stay of 8-14 days (OR 3.464; 95% CI 1.458-7.800), length of stay of more than 14 days (OR 6.844; 95% CI 3.0-15.330), severe sepsis (OR 16.407; 95% CI 1.458-7.800), and surgery (OR 3.03; 95% CI 1.492-6.152). The predictors for candidemia in RSCM were length of stay in hospital for 8-14 days (score 1), a length of stay ≥14 days (score 2), severe sepsis (score 3), and surgery (score 1), with a cut off score of 3.5. CONCLUSION: the results of this study have indicated that a scoring system in order to guide an empirical treatment for candidemia can be developed by using the risk factors for candidemia from patients who have been identified as patients with risk at Cipto Mangunkusumo Hospital.

Cost-Effectiveness Analysis of Multiplex PCR with Magnetic Resonance Detection versus Empiric or Blood Culture-Directed Therapy for Management of Suspected Candidemia.

Candida bloodstream infections (BSI) are associated with significant morbidity, mortality, and increased health care costs. Early treatment is essential, because delayed therapy detrimentally impacts clinical outcomes. The FDA recently approved the first culture-independent direct molecular detection method for Candida BSIs (T2Candida). The speed and sensitivity of this assay give it the potential to improve patient care, but the reagents and instrumentation are expensive. We used an analytic decision tree model to compare the cost-effectiveness of T2Candida-directed antifungal therapy (T2DT) to that of either empirical therapy (ET) or blood culture-directed therapy (BCDT). The costs included those of T2Candida testing, antifungal treatment, and hospital length of stay. The effectiveness measure was survival status at hospital discharge. T2DT was less costly and more effective than BCDT but was less costly and less effective than ET with an echinocandin (incremental cost-effectiveness ratio, $111,084 per additional survivor). One-way sensitivity analyses demonstrated that the cost-effectiveness of T2DT was highly dependent on Candida BSI prevalence and the cost of antifungal therapy and T2Candida test reagents. The use of T2DT reduced the number of unnecessarily treated patients by 98% relative to that with ET. Reduced drug exposure might lessen the possibility of drug-related adverse events and may also prevent the development of antifungal resistance or emergence of drug-resistant Candida species. The greatest benefit of T2Candida appears to be the ability to confidently withhold or stop empirical antifungal therapy in low-to-moderate-risk patients who are unlikely to benefit from treatment.

Manejo de la candidiasis invasiva en el paciente no neutropénico / Management of invasive candidiasis in non-neutropenic patient

Entre los agentes etiológicos que con mayor frecuencia producen infección nosocomial se incluye Candida spp. La candidemia cursa con tasas de mortalidad superiores al 30%. La instauración temprana de tratamiento antifúngico es esencial para mejorar el pronóstico. A falta de pruebas microbiológicas que permitan establecer un diagnóstico precoz, el tratamiento debe establecerse necesariamente de forma empírica (AU)

Among the most frequents etiological agents that causing nosocomial infections, there is included Candida spp. Candida’s bloodstream infection mortality rates are over 30%. Antifungal early treatment is essential to improve the prognosis of this type of infection. Because of the lack of fast enough microbiological tests for early diagnosis, treatment must necessarily be initiated empirically (AU)

Therapeutic approach to Candida bezoar in children.

INTRODUCTION: Candida bezoar (CB) is a rare finding in neonates and infants with candiduria, presenting as necrotic debris with proliferating mycelia in the collecting system of the kidney. If initial antifungal medical treatment does not result in clearance of candiduria and disappearance of CB on ultrasound in dilated kidneys, invasive interventions like insertion of nephrostomy tubes (NT) or surgical interventions to drain the kidney are sometimes advocated(.). However, NT placement can be a technical challenge, especially in pre- and dysmature neonates, and NT displacement or obstruction by the CB can lead to suboptimal treatment. Identification of those children who will benefit from invasive renal drainage is important. OBJECTIVE: This study evaluates the management of patients with CB in three tertiary referral hospitals to determine criteria for intervention. MATERIALS AND METHODS: A retrospective multicenter chart analysis was conducted of children with candiduria and ultrasonographic demonstration of CB (diagnosed between March 1995 and August 2012). The indication for invasive renal drainage (if performed) and subsequent clinical outcome, serum creatinine levels and ultrasound findings were assessed. RESULTS: A total of 12 children were included, two of which were premature neonates. Eight children had congenital urogenital anomalies. One older child with acute myeloid leukemia had CB during chemotherapy and one ex-premature developed CB following cerebral candidiasis. All children received systemic antifungal medication; in seven children invasive treatment was added. Indications for invasive treatment were clinical deterioration, progressive renal dilation, pyonephrosis, rising creatinine levels and persistence of CB. Two underwent a Y-cutaneous ureterostomy and nephrostomy tubes were inserted in five children. Percutaneous renal drainage by nephrostomy led to complications in 3 of 6 procedures. In all patients, irrespective of therapeutic modality, follow-up ultrasound demonstrated no de novo changes. No additional parenchymal defects or deterioration of split renal function were seen on DMSA or MAG-3 scan. DISCUSSION: In the literature renal drainage is suggested in case of complete obstruction. However dilatation is a frequent finding in children as part of the congenital renal anomaly and does not necessarily mean that there is obstruction of the urinary tract. Even in children without candida infections the diagnosis of obstruction is not straightforward, while the results of a MAG 3 scan can be obscured by compromised kidney function, parenchymal bacterial infiltration and neonatal immaturity of the kidney. If candiduria and CB persist despite intensive medical treatment, intensive consultation is required before renal drainage, because NT insertion might be a surgical challenge. Complications such as displacement of the NT, urinoma development, or NT obstruction can occur and was seen in three of six procedures. Premature neonates seem to be more prone to complications due to their small anatomical proportions, requiring medical equipment with small diameters prone to displacement and obstruction. Some studies describe successful pharmaceutical management in the majority of patients with CB. Other studies describe unilateral surgical intervention in children with bilateral CB where unilateral drainage did not influence overall renal outcome. This is in line with our results. A limitation of the present study is its retrospective design. In this population, the motivation for invasive renal drainage or conservative management was not well documented in all cases, and was mainly based on clinical and diagnostic parameters like creatinine levels and radiographic findings. CONCLUSION: Renal drainage should be considered in selected cases after failure of systemic antifungal treatment. Inserting and maintaining a nephrostomy tube in young children is associated with a high rate of complications; conservative treatment is likely to be sufficient in the majority of patients with candiduria and CB.

Antibiotic overuse as a risk factor for candidemia in an Indian pediatric ICU.

OBJECTIVE: To identify risk factors and mycological characteristics of candidemia in Pediatric ICU of a tertiary-care hospital. METHODS: Patients were screened for candidemia by blood culture. Recovered isolates were speciated and subjected to antifungal susceptibility testing. For every candidemic patient, three controls were matched for age, underlying diagnosis and period of hospitalization. Premature neonates were also matched for birth-weight. Proportion of cases and controls on specific antibiotics or indwelling devices was compared using Chi-square test, while unpaired t-test was used for comparing the number of antibiotics used and the number of days of antibiotic administration. Concordance between susceptibility testing methods was evaluated using Chi-square test. RESULTS: Significantly wider spectrum of antibiotic coverage was observed among the 28 candidemic patients. While every patient received antibiotic against enteric gram-negative bacilli, antibiotic usage for additional groups of microorganisms was significantly higher among cases. Association of candidemia with increasing use of indwelling devices was also observed. Endogenous colonization was higher in candidemic infants. Candida albicans was the commonest species (n = 18), followed by C. tropicalis (n = 7). Fluconazole and ketoconazole resistance was observed in 10.7 % cases. CONCLUSIONS: This information on pediatric candidemia could be used to devise locally-tailored strategies for identifying at-risk patients, underline the importance of routine antifungal susceptibility testing and formulate appropriate guidelines for management.

Management of infections related to totally implantable venous-access ports: challenges and perspectives.

Use of totally implantable venous-access ports (TIVAPs) is standard practice for patients with diseases such as solid-tumour cancers, haematological malignancies, and chronic digestive diseases. Use of TIVAPs allows long-term administration of venotoxic compounds, improves patients' quality of life, and reduces the risk of infection. Microbial contamination, formation of pathogenic biofilms, and infection, however, are associated with morbidity, mortality, and increased health-care costs. Local and systemic complications or infections related to specific pathogens might lead to device removal. Alternatively, conservative treatment with combined systemic antibiotics and antibiotic lock therapy might be useful. We discuss in-vitro and in-vivo basic and clinical research findings on the epidemiology, diagnosis, and prevention of TIVAP-related infections, the current challenges to management, promising strategies, and some treatments in development that are likely to improve outcomes of TIVAP-related infections, with a particular focus on antibiotic lock therapy.

Why Candida sepsis should matter to ICU physicians.

The incidence of candidemia and invasive Candida infections has increased substantially over the last 2 decades. These infections are associated with risk factors that characterize intensive care unit patients. Candidemia and invasive Candida are highly morbid and associated with significantly increased mortality. Outcomes in the intensive care setting depend on physician awareness and rapid intervention. The epidemiology of the disease, its diagnostic challenges, and management strategies, including prophylactic, preemptive, and definitive therapeutic approaches, are presented herein.

Recomendaciones para el manejo de la candidemia en neonatos en América Latina / Recommendations for the management of candidemia in neonates in Latin America

La candidemia es una de las micosis oportunistas más frecuentes en todo el mundo. El escaso número de estudios epidemiológicos llevados a cabo en América Latina indica que las tasas de incidencia en esta región son mayores que las descritas en el hemisferio norte. A menudo el diagnóstico de la infección se establece tardíamente, lo que afecta el inicio del tratamiento antimicótico. Por esta razón, para el diagnóstico y el manejo de la candidemia está justificada una estrategia más científica, basada en parámetros específicos. Recomendaciones para el diagnóstico y manejo de la candidemia constituye una serie de artículos preparados por miembros del grupo Latin America Invasive Mycosis Network. Su objetivo es proporcionar las mejores evidencias disponibles para el diagnóstico y el manejo de la candidemia. El presente artículo, Recomendaciones para el manejo de la candidemia en neonatos en América Latina, ha sido redactado con el objetivo de orientar a los profesionales de la salud en el manejo de los neonatos que padecen, o pueden padecer, candidemia. Mediante la base de datos PubMed se emprendió una búsqueda informatizada de los estudios publicados. Los miembros del grupo revisaron y analizaron exhaustivamente los datos. El grupo también se reunió en dos ocasiones para proponer preguntas, abordar los puntos de vista conflictivos y deliberar sobre las recomendaciones terapéuticas. Recomendaciones para el manejo de la candidemia en neonatos en América Latina incluye aspectos sobre profilaxis, terapia empírica, tratamiento de la candidemia demostrada, evaluación y seguimiento del paciente después del diagnóstico de candidemia, manejo de los recién nacidos con infección por Candida del catéter venoso central y manejo de otras complicaciones. Este manuscrito es el cuarto de los artículos de esta serie dedicada al diagnóstico y tratamiento de las candidiasis invasoras. Otras publicaciones de esta serie son Recomendaciones para el diagnóstico de la candidemia en América Latina, Recomendaciones para el manejo de la candidemia en adultos en América Latina, y Recomendaciones para el manejo de la candidemia en niños en América Latina (AU)

Candidemia is one of the most frequent opportunistic mycoses worldwide. Limited epidemiological studies in Latin America indicate that incidence rates are higher in this region than in the Northern Hemisphere. Diagnosis is often made late in the infection, affecting the initiation of antifungal therapy. A more scientific approach, based on specific parameters, for diagnosis and management of candidemia in Latin America is warranted. ‘Recommendations for the diagnosis and management of candidemia’ are a series of manuscripts that have been developed by members of the Latin America Invasive Mycosis Network. They aim to provide a set of best-evidence recommendations for the diagnosis and management of candidemia. This publication, ‘Recommendations for the management of candidemia in neonates in Latin America’, was written to provide guidance to healthcare professionals on the management of neonates who have, or who are at risk of, candidemia. Computerized searches of existing literature were performed by PubMed. The data were extensively reviewed and analyzed by members of the group. The group also met on two occasions to pose questions, discuss conflicting views, and deliberate on a series of management recommendations. ‘Recommendations for the management of candidemia in neonates in Latin America’ includes prophylaxis, empirical therapy, therapy for proven candidemia, patient work-up following diagnosis of candidemia, central venous catheter management, and management of complications. This manuscript is the fourth of this series that deals with diagnosis and treatment of invasive candidiasis. Other publications in this series include: ‘Recommendations for the diagnosis of candidemia in Latin America’, ‘Recommendations for the management of candidemia in adults in Latin America’, and ‘Recommendations for the management of candidemia in children in Latin America’ (AU)

Neonatal endogenous endophthalmitis: a report of six cases.

Endogenous endophthalmitis is a rare but potentially blinding complication of neonatal sepsis. Early diagnosis and aggressive treatment are essential to avoid vision loss. Therapeutic options include systemic and intravitreal antibiotics, as well as vitrectomy in selected cases. We report a series of 6 premature very low birth weight neonates who developed endogenous endophthalmitis in our NICU over the past 3 years. Endophthalmitis was part of early-onset sepsis in 2 newborns, both of whom died, and late-onset sepsis in 4 newborns, of which 1 infant died. None of the neonates had any history of previous trauma or intervention to the eye. Maternal screening for congenital infections, including HIV, was negative in all. Causative organisms included Klebsiella pneumoniae (2 cases), Pseudomonas aeruginosa (2 cases), Methicillin-resistant Staphylococcus aureus (1 case), and Candida albicans (1 case). All bacterial isolates showed resistance to first-line antibiotics. Of the 3 survivors, 2 infants had normal vision in the affected eye, and 1 developed phthisis bulbi after corneal perforation and required enucleation. This report draws attention to the emergence of endophthalmitis as a complication of neonatal sepsis in places where, although survival of very low birth weight newborns has increased significantly due to improved care, the burden of infection continues to be high. We emphasize the importance of daily examination of eyes as a part of routine clinical care in septic newborns for early diagnosis of endophthalmitis and prompt intervention in consultation with an ophthalmologist to optimize the outcome.

Impact of an antimicrobial stewardship program comprehensive care bundle on management of candidemia.

STUDY OBJECTIVE: To analyze the impact of a comprehensive care bundle directed by an antimicrobial stewardship team (AST) on the management of candidemia. DESIGN: Single-center, quasi-experimental study. SETTING: A 930-bed academic hospital. PATIENTS: Seventy-eight patients with candidemia were evaluated; 41 patients received the candidemia care bundle (AST group), and 37 did not (historical control group). MEASUREMENTS AND MAIN RESULTS: A candidemia care bundle was developed by an interdisciplinary AST, incorporating key elements from the Infectious Diseases Society of America's Clinical Practice Guidelines for the Management of Candidemia. The AST made prospective recommendations in accordance with the care bundle. Bundle elements were utilization of appropriate antifungal agents with appropriate duration of use, removal of intravenous catheters, repeat blood cultures, monitoring of time until clearance of candidemia, and performance of ophthalmologic examinations. Compliance with all candidemia care bundle elements was significantly higher in the AST group versus the control group (78.0% vs 40.5%, p=0.0016). Implementation of the care bundle significantly improved rates of ophthalmologic examination (97.6% vs 75.7%, p=0.0108), selection of appropriate antifungal therapy (100% vs 86.5%, p=0.0488), and compliance with an appropriate duration of therapy (97.6% vs 67.7%, p=0.0012). In addition, the AST group had fewer excess total days of therapy beyond the recommended duration than the control group (5 vs 83 total antifungal days). Length of hospitalization (20 vs 21 days, p=0.9184), time until clearance of candidemia (3 vs 3 days p=0.610), rate of persistent candidemia (22% vs 40.5%, p=0.126), and rate of recurrent candidemia (4.9% vs 5.4%, p=0.916) were similar in the AST group versus the control group. CONCLUSION: A comprehensive candidemia care bundle directed by our institution's AST improved the management of patients with candidemia. We encourage further exploration into the use of care bundles by ASTs as part of their multifaceted approach to promoting appropriate antimicrobial utilization and optimizing the management of patients with infectious diseases.