Epidemiology of Candidemia in Latin America: A Laboratory-Based Survey

Background

The epidemiology of candidemia varies depending on the geographic region. Little is known about the epidemiology of candidemia in Latin America.

Methods

We conducted a 24-month laboratory-based survey of candidemia in 20 centers of seven Latin American countries. Incidence rates were calculated and the epidemiology of candidemia was characterized.

Results

Among 672 episodes of candidemia, 297 (44.2%) occurred in children (23.7% younger than 1 year), 36.2% in adults between 19 and 60 years old and 19.6% in elderly patients. The overall incidence was 1.18 cases per 1,000 admissions, and varied across countries, with the highest incidence in Colombia and the lowest in Chile. Candida albicans (37.6%), C. parapsilosis (26.5%) and C. tropicalis (17.6%) were the leading agents, with great variability in species distribution in the different countries. Most isolates were highly susceptible to fluconazole, voriconazole, amphotericin B and anidulafungin. Fluconazole was the most frequent agent used as primary treatment (65.8%), and the overall 30-day survival was 59.3%.

Conclusions

This first large epidemiologic study of candidemia in Latin America showed a high incidence of candidemia, high percentage of children, typical species distribution, with C. albicans, C. parapsilosis and C. tropicalis accounting for the majority of episodes, and low resistance rates.     

High rate of Candida deep-seated infection in patients under chronic hemodialysis with extended central venous catheter use

BackgroundHemodialysis has been described as an important risk factor for the development of candidemia in patients suffering from chronic renal failure.AimsThe aim of this study was to evaluate the epidemiology of candidemia in outpatients with renal replacement therapy (RRT) by hemodialysis where the fungemia clearly represents a healthcare-associated infection.MethodsWe retrospectively collected clinical and laboratory data from patients undergoing at least 3 months of RRT by hemodialysis who developed candidemia within 48 h of hospital admission.ResultsWe identified 14 patients with candidemia with central venous catheters (CVC) in place for 11–277 days before developing fungemia. Deep-seated infection was documented in 6 out of 14 candidiasis cases (43%), including 5 cases of endocarditis (36%).ConclusionsCVC in patients under RRT should be promptly replaced by fistulas and grafts to avoid bloodstream infections. Facing a case of candidemia, adequate source control and prompt initiation of antifungal therapy are mandatory to avoid morbidity and mortality.     

Isolation of Candida auris in large hospitals in the Autonomous Community of Valencia; population-based study (2013–2017)

BackgroundCandida auris is an emerging multidrug-resistant and highly virulent yeast that spreads easily among patients.AimsTo describe the characteristics of candidemia caused by C. auris in the southeast of Spain (Autonomous Community of Valencia – ACV) through a 5-year population-based study.MethodsAn analysis of all the episodes of candidemia diagnosed in the ACV, with approximately 4,500,000 inhabitants, during 2013–2017, was done. Data were obtained from the Epidemiological Surveillance Valencian Network, a network that collects all the microbiological data from the hospitals in the study region.ResultsBased on the records, 1.9% of the isolates recovered from the positive blood cultures (corresponding to 1789 patients) were yeasts. This implies an annual rate of 7.09 cases/100,000 inhabitants. Of the 23 yeast species isolated, Candida albicans was the most frequent (37.3%), showing a higher frequency than Candida parapsilosis (28.4%) and Candida glabrata (15.6%) (p < 0.0001). It is remarkable the emergence of C. auris during 2016 and 2017, as this species became the fourth more prevalent in 2016 (9.2%), and the third in 2017 (15.7%). Fungemia was more common in hospitals with >500 beds (63.3% versus 36.7% in small hospitals) (p < 0.0001), and C. auris was mostly isolated in large hospitals (8.5% versus 0.3%); its incidence was higher in autumn and among the age group of 65–84 years.ConclusionsThe information about the local epidemiology of candidemia is essential in order to decide the best empirical treatment approach. This study reports the novel presence of C. auris in large hospitals. This pathogen has usually resistance to several antifungals and causes severe fungemia, so the results of this work reveal the need to monitor the presence of this species systematically.     

Relationship Between Susceptibility of <Emphasis Type="Italic">Candida</Emphasis> spp. Isolates to Amphotericin B and Death or Survival of Patients with Candidemia Episodes

In this study, the susceptibility to amphotericin B of Candida spp. isolates obtained from patients with candidemia was related to their respective clinical outcomes. The susceptibility tests were carried out in three culture media: RPMI 1640, Antibiotic medium 3 and Yeast Nitrogen Base dextrose. We have found that minimal inhibitory concentrations and minimal fungicidal concentrations obtained using AM3 and YNBd media were significantly higher for Candida spp. from patients who died than for those from patients who survived the candidemia (P < 0.05). The assays with RPMI 1640 medium did not show these differences.     

Aplicación de las técnicas de tipificación molecular al estudio de brotes hospitalarios de candidemia

Candidemia is an infectious complication mainly affecting hospitalized patients, particularly those admitted to intensive care units. Patient mortality can reach up to 40%. Candidemia is typically nosocomially-acquired, and horizontal transmission of Candida spp. can lead to the presence of outbreaks of candidemia. Genotyping of isolates of Candida causing candidemia can help us to understand the source of the infection, detect the hospital wards with active Candida spp. transmission and, consequently, improve the prevention of the infection. Several genotyping tools have been used for the molecular characterization of Candida isolates involved in outbreaks of candidemia. Genotyping procedures based on microsatellites are reproducible and show a high discriminatory power. Microsatellites are recommended for the study of outbreaks of candidemia. In most hospital outbreaks of candidemia, patients admitted to intensive care units are involved, mostly neonatal patients. The role of genotyping Candida isolates causing candidemia for the study of nosocomial outbreaks of candidemia is reviewed, as well as the patients more commonly affected by epidemic strains.     

Geographic Trends in Invasive Candidiasis

Candida species are one of the most important causes of bloodstream infection (BSI) in tertiary-care hospitals worldwide. The incidence of candidemia and the Candida species causing these infections may vary geographically. Although C. albicans remains the species most commonly isolated, there is clear evidence showing increasing rates of BSI caused by Candida non-albicans species around the world. C. glabrata is the second most common cause of candidemia in North America, but it is less frequently isolated in Latin America. On the other hand, C. parapsilosis complex represents the second or the third most common species found in Latin American and Iberian countries, while C. tropicalis has emerged as a frequent agent of BSI in Latin America and Asia-Pacific regions. In this context, a complex set of clinical aspects and biologic factors may contribute to the geographic trends in the epidemiology of candidemia.     

Recent changes in candidemia trends in a tertiary hospital (2011–2018)

BackgroundThe epidemiology of candidemia has changed over the last decades and varies widely among geographic areas.AimsWe examined in children (aged 0–14) with candidemia the trends in the incidence rate of this infection, as well as the clinical characteristics of the patients, in order to optimize the prognosis and the control measures of this serious disease.MethodsA retrospective cohort study of candidemia in the period 2011–2018 in the neonatal intensive care unit (NICU), pediatric ICU (PICU) and pediatric wards of a tertiary hospital, was conducted. The clinical course, Candida species isolated, antifungal susceptibility, outcome and incidence rates were analyzed and compared.ResultsWe diagnosed 68 episodes of candidemia in 62 children, 48% occurred in the NICU, 31% in the PICU and 21% in pediatric wards. Candida albicans was the most frequent species isolated in NICU infants (53%), and Candida parapsilosis predominated among PICU patients (59%) and pediatric wards (50%). One third of NICU infants had invasive candidiasis (IC), most of them having extremely low birth weight (ELBW) (35%). All isolates were susceptible to the antifungal administered. Over time, the incidence of candidemia decreased in the PICU (from 2.2 to 0.3 episodes/1000 patient-days, OR = 0.6; 95%CI 0.5–0.8), whereas in the NICU and in the wards remained stable. Mortality occurred mostly in NICU patients (26%), predominated in ELBW infants and did not change over time.ConclusionsThe higher incidence and mortality of candidemia and IC observed in preterm infants requires a continuous evaluation of practices and diagnostic methods which will allow improving the prognosis of this most vulnerable population.     

Species distribution and antifungal susceptibility profile of Candida spp. bloodstream isolates from Latin American hospitals

From March 1999 to March 2000, we conducted a prospective multicenter study of candidemia involving five tertiary care hospitals from four countries in Latin America. Yeast isolates were identified by classical methods and the antifungal susceptibility profile was determined according to the National Committee for Clinical Laboratory Standards microbroth assay method. During a 12 month-period we were able to collect a total of 103 bloodstream isolates of Candida spp. C. albicans was the most frequently isolated species accounting for 42% of all isolates. Non-albicans Candida species strains accounted for 58% of all episodes of candidemia and were mostly represented by C. tropicalis (24.2%) and C. parapsilosis (21.3%). It is noteworthy that we were able to identify two cases of C. lusitaniae from different institutions. In our casuistic, non-albicans Candida species isolates related to candidemic episodes were susceptible to fluconazole. Continuously surveillance programs are needed in order to identify possible changes in the species distribution and antifungal susceptibility patterns of yeasts that may occurs after increasing the use of azoles in Latin American hospitals.     

Candidemia in a public hospital in Northeastern Brazil: Epidemiological features and risk factors in critically ill patients

BackgroundCandidemia is a life-threatening fungal infection characterized by the presence of Candida in the blood.AimsTo describe the clinical–epidemiological features and main risk factors among patients with candidemia admitted to Intensive Care Unit.MethodsA cross-sectional, retrospective and observational study was performed between January 2015 and July 2016. Laboratory reports and medical records from ICU patients admitted to a public hospital in northeastern Brazil were analyzed.ResultsThere were 1573 admissions and 67 of them were positive for candidemia. The majority of patients were male (53.3%) and remained at the hospital for more than seven days (86.6%). Non-C. albicans Candida infections (60%) were predominant. Broad-spectrum antibiotic therapy was prescribed in 98.4% of the cases. The most frequent underlying diseases were sepsis (73.3%), presence of solid tumors (15%), respiratory condition (60%), urinary tract disease (56.6%) and gastrointestinal tract diseases (23.3%). Surgeries were carried out on 43% of the patients, consisting of 23.3% abdominal surgeries, with a mortality rate of 92.8%. Risk factors were venous central access (93.3%), mechanical ventilation (81.6%), nasoenteral tube (83.3%), nasogastric tube (25%), indwelling bladder catheter (88.3%), diabetes mellitus (55%) and tracheostomy (36.6%). Statistical analysis correlated the use of indwelling bladder catheter with a higher mortality rate (r = 0.07412, p = 0.0353).ConclusionsThe current study reveals the high case fatality rates among critically ill patients suffering from candidemia admitted to ICU. Herein, we highlight the importance of identifying non-C. albicans Candida species and reinforce the idea of carrying out epidemiological surveillances and antifungal susceptibility tests.     

The challenge of Chagas’ disease: Has the human pathogen,Trypanosoma cruzi,learned how to modulate signaling events to subvert host cells?

Chagas’ disease, caused by Trypanosoma cruzi, is an urgent and highly prevalent danger that is endemic to Latin America, and which the research community continues to ignore. Each year, Chagas’ disease kills more people in Latin America compared to any other parasite-borne disease, including malaria. In addition, between 15 and 18 million people worldwide are afflicted with this potentially lethal disease. Despite these devastating numbers, less than 0.5% of worldwide research and development for neglected diseases was aimed at Chagas’ disease. The aim of this review is to draw the attention of biotechnologists to the intriguing parasite that causes Chagas’ disease, which is T. cruzi. Additionally, we would also like to convince the community that basic science research can have a profound impact on the diagnosis and treatment of Chagas’ disease. In this review, we introduce distinct features of T. cruzi such as its complex life cycle (e.g. the potentially infective extracellular amastigote form), its genome and genomics, as well as proteomic analysis of this parasite. Notably, the PIK pathway has been widely acknowledged as an excellent target for drug discovery to combat this pathogen. Furthermore we also describe how the identification and characterization of PIK genes can aid in neutralizing Trypanosoma infections.     

Isolation of Candida in the blood cultures of patients admitted to the Emergency Room in a tertiary care hospital

BackgroundIn Spain, data of candidemia are limited to surveys conducted in specific areas or tertiary care centers. Also, in recent years, attention has shifted toward episodes of candidemia in non-ICU wards.AimsWe reviewed the cases of Candida isolates recovered from the blood of patients admitted to the Emergency Room (ER) in our tertiary care hospital.MethodsThe patients selected for this study had an isolation of Candida in the blood culture. All data were collected retrospectively from the clinical records of a 11-year period.ResultsCandida albicans and other species of the genus were present in 10 and 18 patients, respectively. The patients did not present different clinical features in comparison with other reports of hospitalized patients. All patients had several risk factors for candidemia. Only two patients had received previous antifungal therapy before admission. All the isolates of C. albicans, Candida glabrata and the only isolate of Candida tropicalis were susceptible to all the antifungal agents tested. Only one isolate of Candida parapsilosis was susceptible dose-dependent to fluconazole, and the only isolate of Candida metapsilosis was resistant to fluconazole.ConclusionsIt is essential to evaluate the risk factors, underlying conditions and clinical features in non-hospitalized patients in order to determine whether an empirical treatment for candidemia is appropriate.     

Cultivation of red seaweeds: a Latin American perspective

The Latin American seaweed industry plays an important role at a global scale as 17 % of all seaweeds and 37 % of red seaweeds for the phycocolloid industry comes from this region. Increased market demand for algal raw materials has stimulated research and development into new cultivation technologies, particularly in those countries with economically important seaweed industries such as Argentina, Brazil, Chile, México, and Peru. The marine area of Latin America includes almost 59,591 km² of coastline ranging in latitude from 30ºN to 55ºS and encompasses four different oceanic domains: Temperate Northern Pacific, Tropical Eastern Pacific, Temperate South America, and Tropical Atlantic. Commercial cultivation of red seaweed in Latin America has been basically centered in the production of Gracilaria chilensis in Chile. Attempts have been made to establish seaweed commercial cultivation in other countries, going from experimental research-oriented studies to pilot community/enterprise based cultivation trials. Some genera such as Kappaphycus and Eucheuma have been studied in Brazil and Mexico, Gracilaria species in Argentina and Brazil, Gracilariopsis in Peru and Venezuela, and Chondracanthus chamissoi in Peru and Chile. In this short review, we address the Latin America perspective on the status and future progress for the cultivation of red seaweeds and their sustainable commercial development, and discuss on the main common problems. Particular emphasis is given to the needs for comprehensive knowledge necessary for the management and cultivation of some of the most valuable red seaweed resources in Latin America.     

Free amino acids in the seeds of Acacia species

Free amino acids in the seeds of 80 species of Acacia have been determined. In addition to confirming the known difference in seed amino acid ‘patterns’ shown by species of the series Gummiferae on the one hand and species of the series Phyllodineae and Botryocephalae on the other, we have found that species of the series Vulgares Benth. show two additional ‘patterns’. One of these is common to some of the Afro-Asian species of the series which have been analysed and the other is common to species from America and Africa. One of the ‘marker’ amino acids of the Afro-Asian group is the neurotoxic lathyrogen α-amino-β-oxalylaminopropionic acid. The possible taxonomic and phylogenetic significance of these results is discussed, with special reference to five species A. albida, A. confusa, A. heterophylla, A. coulteri and A. kauaiensis.     

Visceral Leishmaniasis and HIV Coinfection in Latin America

Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for coinfections of Leishmania and HIV to improve the consistency of research on the current situation of VL-HIV coinfections. Such a network would improve the collection of vital data and samples for better understanding of the clinical manifestations and immunopathogenic aspects of VL in immunosuppressed patients. Ultimately, a concerted effort would improve trials for new diagnostic methodologies and therapeutics, which could accelerate the implementation of more specific and effective diagnosis as well as public policies for treatments to reduce the impact of VL-HIV coinfections on the Latin American population.     

Congenital cutaneous candidiasis associated with maternal peripartum candidemia

BackgroundCutaneous congenital candidiasis (CCC) is a rare condition consisting of invasive fungal infection of the epidermis and dermis that mostly affects preterm infants. Maternal vaginal candidiasis is present in half of the cases, although the occurrence of invasive candidiasis during pregnancy or peripartum period is exceptional.Case reportWe present the case of a full-term infant that was born by vacuum-assisted vaginal delivery to an apparently healthy 33 year-old woman with no history of intravenous drug use or vaginal candidiasis during pregnancy. The newborn showed a diffuse maculopapular rash with respiratory distress and bilateral interstitial lung infiltrates, requiring nasal continuous positive airway pressure support. Blood cultures obtained from the mother due to intrapartum fever yielded Candida albicans. Cultures of vaginal discharge and neonate skin also yielded C. albicans with the same in vitro susceptibly pattern. No alternative source for candidemia was identified. The clinical course after starting a systemic antifungal therapy was favorable in both the mother and the neonate, with clearance of candidemia and resolution of the skin lesions.ConclusionsCCC must be considered in full-term newborns with maculopapular rash at birth or during the first days of life. The absence of alternative sources for bloodstream infection in the present case suggests a potential etiopathogenic relationship between CCC and maternal candidemia. It is reasonable to rule out postpartum candidemia when CCC is suspected.     

Guía clínica de diagnóstico y tratamiento del prolactinoma y la hiperprolactinemia

ObjectiveTo provide practical and up to date recommendations for evaluation, differential diagnosis, and treatment of prolactinoma and hyperprolactinemia in various clinical settings.ParticipantsMembers of the Neuroendocrinology Working Group of the Spanish Society of Endocrinology.MethodsRecommendations were formulated according to the Grading of Recommendations, Assessment, Development, and Evaluation system (GRADE) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in Medline (Pubmed) for each subject, and authors’ considerations were added in areas where the literature provided scarce evidence. Finally, recommendations were jointly discussed by the Working Group.ConclusionsThe document provides evidence-based practical and updated recommendations for diagnosis and management of hyperprolactinemia and prolactinoma, including drug-induced hyperprolactinemia, treatment options for prolactinoma (drugs, surgery, and radiotherapy), prolactinoma in pregnancy, adverse effects of dopaminergic agents, and drug-resistant and malignant prolactinomas.