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On-line version ISSN 1678-9946
Rev. Inst. Med. trop. S. Paulo vol.50 no.5 São Paulo Sept./Oct. 2008
Infecção na corrente sangüínea por Candida spp. dados de um hospital universitário em Mato Grosso do Sul, Brasil
Marilene Rodrigues ChangI; Flávia Patussi CorreiaI; Leonora Correa CostaI; Paula Cristhina Niz XavierII; Durval Batista PalharesIII; Deborah Ledesma TairaI; Anamaria Mello Miranda PaniagoIV; Elenir Rose Jardim Cury PontesV; Vanessa Escobar MachadoVI
IDepartment of Pharmacy-Biochemistry, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS, Brazil
IIFaculdade Estácio de Sá, Campo Grande, MS, Brazil
IIIDepartment of Pediatrics, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil
IVDepartment of Clinical Medicine, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil
VDepartment of Public Health, Universidade Federal de Mato Grosso do Sul, MS, Brazil
VIGraduate student, Graduate Program in Clinical Analyses, Conselho Regional de Farmácia de Mato Grosso do Sul, Campo Grande, MS, Brazil
The incidence of Candida bloodstream infection has increased over the past years. In the Center-West region of Brazil, data on candidemia are scarce. This paper reports a retrospective analysis of 96 cases of Candida bloodstream infection at a Brazilian tertiary-care teaching hospital in the state of Mato Grosso do Sul, from January 1998 to December 2006. Demographic, clinical and laboratory data were collected from medical records and from the hospital's laboratory database. Patients' ages ranged from three days to 92 years, with 53 (55.2%) adults and 43 (44.8%) children. Of the latter, 25 (58.1%) were newborns. The risk conditions most often found were: long period of hospitalization, utilization of venous central catheter, and previous use of antibiotics. Fifty-eight (60.4%) patients died during the hospitalization period and eight (13.7%) of them died 30 days after the diagnosis of candidemia. Candida albicans (45.8%) was the most prevalent species, followed by C. parapsilosis (34.4%), C. tropicalis (14.6%) and C. glabrata (5.2%). This is the first report of Candida bloodstream infection in the state of Mato Grosso do Sul and it highlights the importance of considering the possibility of invasive Candida infection in patients exposed to risk factors, particularly among neonates and the elderly.
Keywords: Candidemia; Risk factors; Bloodstream infection; Candida spp.
A incidência de infecções na corrente sangüínea causada por Candida spp. tem aumentado nos últimos anos. Na região Centro-Oeste do Brasil, os dados sobre candidemia são escassos. Realizamos uma análise retrospectiva de casos de infecção na corrente sangüínea por Candida em um hospital terciário de ensino de Mato Grosso do Sul. Noventa e seis episódios diagnosticados de janeiro de 1998 a dezembro de 2006 foram incluídos no estudo. Os dados demográficos e clínicos foram obtidos de prontuários; os dados laboratoriais provieram de registros do laboratório hospitalar. Dos pacientes, 43 (44,8%) eram crianças e 53 (55,2%) adultos, com idades variando de três dias a 92 anos. Das crianças, 25 (58,1%) eram recém-nascidas. As condições de risco mais encontradas foram: prolongado tempo de internação, uso de cateter venoso central e uso prévio de antibióticos. Cinqüenta e oito (60,4%) pacientes foram a óbito durante a hospitalização e oito (13,7%) deles foram a óbito 30 dias após o diagnóstico de candidemia. Candida albicans (45,8%) foi a espécie mais prevalente seguida por C. parapsilosis (34,4%), C. tropicalis (14,6%) e C. glabrata (5,2%). Esta é a primeira descrição de infecção na corrente sangüínea por espécies de Candida em Mato Grosso do Sul, confirmando a importância da suspeita clínica de infecções invasivas por tais microrganismos na evolução de pacientes expostos a fatores de risco, principalmente no caso de idosos e neonatos.
Systemic fungal infections are pathologies that particularly affect immunocompromised and severely ill patients1. Epidemiological studies have shown an increasing incidence of bloodstream infection by yeasts of the genus Candida, given their colonization ability and opportunism and the therapeutic challenges arising from the development of resistance to some antifungal agents2,6.
Candida infections are mostly endogenous and may result from proliferation or changes of the normal human microbiota, determined by risk factors such as long-term administration of broader-spectrum antibiotics, surgery, organ transplant, prematurity, use of invasive procedures (e.g. those involving catheters for nasogastric, urinary, parenteral nutrition, hemodialysis, or mechanic ventilation purposes), and other treatment actions3,7,11.
The pathogenic potential of the genus varies considerably, and C. albicans is the species most frequently found in clinical samples1,4. C. parapsilosis and C. tropicalis, however, are also regarded as important candidemia agents10,12.
An additional aggravating factor is the high morbidity and mortality rate associated with systemic candidemia, ranging from 40% to 60%, according to different studies1,2,9,11.
Given the relevance of the issue and considering that the epidemiology of systemic Candida infections varies across regions and even across hospitals within a single region3,5,11, the present study is focused on a series of candidemia cases that occurred at a teaching hospital located in the Center-West region of Brazil.
MATERIAL AND METHODS
A retrospective study was conducted to describe the prevalence of Candida species in blood cultures and the risk factors associated with candidemia at the tertiary-care teaching hospital of Universidade Federal de Mato Grosso do Sul (UFMS), in Campo Grande, Brazil.
The patients had been admitted to various hospital divisions - namely, adult intensive care center, medical clinic, surgical clinic, hematology sector, oncology division, parasitic infectious diseases, renal unit, neonatal intensive care unit, pediatric intensive care center, pediatric clinic, and nursery.
In order to be included in the study, a patient should have tested positive to Candida spp. in at least one culture of blood drawn from a peripheral vein, in addition to exhibiting clinical evidence of sepsis.
The yeasts isolated from blood cultures were detected using a Bactec 9120 system (Becton Dickinson, INC, Sparks, MD). Positive samples were Gram-stained, grown on Sabouraud agar and brain-heart infusion agar, and incubated at 37 ºC at room temperature until growth was observed. After screening with the germ tube test, the isolates were identified according to microscopic morphology on cornmeal - Tween 80 agar, auxanogram test, growth at 42 ºC, and confirmation by means of an automated Vitek system (BioMérieux, St. Louis, MO, USA)8.
Medical records were reviewed and clinical data were analyzed in conjunction with the respective laboratory data using the software Epi Info 22.214.171.124 (Centers for Disease Control and Prevention, Atlanta, GA, USA). The study was approved by the Ethics Committee for Clinical Research of UFMS.
The cases of Candida bloodstream infection included in the study occurred in the period from January 1998 to December 2006, comprising 96 patients, 53 (55.2%) of them adults and 43 (44.8%) children. Of the pediatric patients, 20 were newborns (46.5%), 24 (55.8%) were premature, and 19 (44.2%) had very low birth weight. Fifty patients (52.1%) were male and 46 (48.2%) female. Ages ranged from three days to 92 years, with a mean of 30 years. Candidemia episodes were more frequent among newborns (20.8%) and elderly patients (21.9%).
Hospital stays lasted from four to 124 days, with a mean duration of 34 days. Most patients (63.5%) were admitted to the intensive care unit. Clinical and demographic data are reported in Table 1.
The most frequent comorbidities were pneumonia (43.8%) and gastrointestinal tract disease (33.4%). The underlying conditions more often observed were: hematological disease (leukemia, lymphoma), in 12 cases (12.5%); diabetes mellitus, in 10 (10.4%); and solid tumors, in nine (9.4%). The overall mortality rate was 56.3%, reaching as much as 80.9% (17/21) among adults older than 60 years and 70.0% (14/20) among newborns.
Table 2 shows the main conditions posing a risk of candidemia. For all age groups, invasive procedures and hospitalization for 15 days or longer were the occurrences most often associated with candidemia. Additional risk factors among pediatric patients included: hospital stay longer than 15 days (76.7%), prematurity (55.8%), and very low birth weight (44.2%). Overall, previous use of antibiotics occurred in 93 patients (97%), with 73% using four or more antibiotics. Most surgical (71.4%) and assisted-ventilation procedures (61.9%) were performed on patients older than 60 years.
C. albicans (44 cases; 45.8%) was the species most often isolated from blood cultures, followed by C. parapsilosis (33 cases; 34.4%), C. tropicalis (14; 14.6%), and C. glabrata (five; 5.2%). Table 3 shows the distribution of Candida species by three-year periods.
Mortality rates varied according to Candida species, being higher for C. tropicalis (12/14; 85.7%) and C. glabrata (4/5; 80.0%).
Fifty-nine patients (61.4%) received antifungal treatment. Fluconazole was administered to 34 patients and amphotericin B to six. Nineteen patients were treated with both antifungal drugs.
This is the first description of Candida bloodstream infection at a Brazilian tertiary-care teaching hospital in the Brazilian State of Mato Grosso do Sul. It provides information on species distribution and on the clinical features and outcomes among patients with candidemia.
The literature reports a progressive increase in candidemia frequency in hospitalized patients1,5. These infections are generally difficult to diagnose, are refractory to treatment, and have an attributable mortality rate of 40-60%1,2,5,6.
In agreement with other studies6,9,10,11, most episodes of candidemia seen in this series of cases occurred in adults and children in intensive care units - the very wards were critical patients remain bedridden and are subject to alterations in defense mechanisms or to compromised anatomical barrier, secondary to invasive medical procedures.
Patients in extreme age ranges were the most susceptible, with fatal outcomes in all those older than 80 years. Overall, the underlying conditions and comorbidities identified in this study were similar to those reported in other investigations2,4.
The present results add evidence to the already recognized risk of invasive candidemia, especially in neonatal and elderly inpatients. Use of central venous catheter and previous administration of antibiotics were the principal conditions posing a risk of candidemia, irrespective of age. Prolonged hospital stays may also have collaborated with the occurrence of bloodstream infection. These conditions are already recognized as important factors of risk for opportunistic infections, among them those caused by Candida spp.2,3,4,11.
The capacity of yeasts to attach to a wide range of inanimate surfaces (such as those of intravascular devices) and to form biofilms in glucosilated solutions seems to protect them from immune responses and antimicrobial agents7. This may explain why Candida species were associated with the use of central venous catheters and parenteral nutrition in the present study10. Gastrointestinal disorders were observed in 30-40% of the patients, an occurrence that may have favored yeast invasion into the bloodstream5.
In the present investigation, C. albicans was the species most often isolated from both adult and pediatric patients, although its yearly frequency did not significantly differ from those of other Candida species (p = 0.303).
In the past three years, however, cases of C. parapsilosis outnumbered those from previous years, while cases of C. tropicalis decreased in number (Table 3). That increase may be associated with interventional therapy, including the growing use of central venous catheters, parenteral nutrition, and large-spectrum antibiotics for long periods10. Although the literature reports C. parapsilosis as being more frequent in pediatric patients1,6,10,11,12, the present study did not reveal any significant difference between adults (34.0%) and children (34.9%).
C. tropicalis was more often isolated from adult patients, a finding consistent with other studies4,12 reporting that this species is not common in pediatric patients, and even less so among neonates. C. glabrata was more frequent in adults (4/5).
Mortality rates for each Candida species were similar to those revealed by studies carried out in southern Brazil, where C. glabrata and C. tropicalis were associated with the highest death rates2.
The high mortality rate (56.3%) in the present series, similar to that found in other studies1,2,4,5,10, is a strong reason for health teams to be aware of risk factors potentially leading to Candida spp. infection - a reminder that prevention and control methods should be pre-emptively implemented.
In the present case series, only 59 patients (61.4%) received antifungal treatment. The absence of treatment may be attributed to a lack of clinical recognition that candidemia can occur in severely ill patients or to delays in obtaining blood culture results.
These are relevant issues in the management of patients, as pre-emptive therapy should be instituted earlier whenever infections of fungal etiology are suspected.
Cases of candidemia are possibly underestimated in the hospital investigated, since this retrospective study only included documented infections, and blood cultures may often lack adequate sensitivity1. Candidemia is thus of greater prevalence than the available data may suggest, since blood culture, albeit a gold standard test, can possibly identify only a small fraction of the total number of cases. PCR-based assays are expected to provide further assistance in the future, increasing the sensitivity of screening methods12.
The present findings corroborate the relevance of epidemiological studies in monitoring bloodstream infections.
This study was supported by Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT), Brazil, grant 41/100.115/2004. Thanks are given to Floriano Campoçano and Maína O. Nunes for providing technical support.
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Prof.ª Dr.ª Marilene Rodrigues Chang
R. Uricuri 582, 79060-040 Campo Grande, MS, Brasil
Received: 22 January 2008
Accepted: 6 August 2008