Infection DOI 10.1007/s15010-014-0640-2
CLINICAL AND EPIDEMIOLOGICAL STUDY
Infective endocarditis in Rio de Janeiro, Brazil: a 5-year experience at two teaching hospitals P. V. Damasco • J. N. Ramos • J. C. D. Correal • M. V. Potsch • V. V. Vieira • T. C. F. Camello • M. P. Pereira • V. D. Marques • K. R. N. Santos • E. A. Marques M. B. Castier • R. Hirata Jr. • A. L. Mattos-Guaraldi • C. Q. Fortes
•
Received: 5 March 2014 / Accepted: 19 May 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Introduction Despite the recent advances in diagnosis and treatment, mortality rates due to infective endocarditis (IE) remain high if not aggressively treated with antibiotics, whether or not associated with surgery. Data on the prevalence, epidemiology and etiology of IE from developing countries remain scarce. The aim of this observational, prospective cohort study was to report a 5-year experience of IE at two teaching hospitals in Rio de Janeiro, Brazil. Material and methods Demographical, anamnestic and microbiological characteristics of 71 IE patients were evaluated during the period of January 2009 to March 2013. Results The mean age of the IE patients was 49.8 ± 2.4 years, of which 41 (57.7 %) were males. The median time
between the onset of symptoms and diagnosis of IE was 35.8 ± 4.8 days. A total of 31 (43.6 %) cases of community-acquired infective endocarditis (CAIE) and 40 (56.3 %) cases of healthcare-acquired infective endocarditis (HAIE) were observed. Staphylococcus aureus (30 %) was the predominant cause of IE. Streptococcus spp. (45.1 %) was the predominant cause of the CAIE while S. aureus (32.5 %) and Enterococcus spp. (27.2 %) were the main etiological agents of HAIE. For 64 (90.1 %) patients with native valve endocarditis, the mitral valve was the most commonly affected (48.3 %). The main source of IE in this cohort was intravascular catheter. The tricuspid valve and renal chronic insufficiency were more frequent in patients with HAIE than CAIE (p = 0.001). The risk factors associated with in-hospital mortality rate (46.4 %) in IE patients were: age over 45 (OR 3.4; 95 % CI 1.03–11.24;
P. V. Damasco and J. N. Ramos contributed equally for the first authorship in this manuscript. P. V. Damasco J. N. Ramos T. C. F. Camello V. D. Marques E. A. Marques R. Hirata Jr. A. L. Mattos-Guaraldi Faculdade de Cieˆncias Me´dicas, Universidade do Estado do Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil P. V. Damasco J. C. D. Correal T. C. F. Camello V. D. Marques E. A. Marques M. B. Castier Hospital Universita´rio Pedro Ernesto-HUPE, Universidade do Estado do Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil P. V. Damasco M. V. Potsch M. P. Pereira Escola de Medicina e Cirurgia, Universidade Federal do Estado do Rio de Janeiro, UNIRIO, Rio de Janeiro, RJ, Brazil J. N. Ramos V. V. Vieira Instituto Nacional de Controle de Qualidade em Sau´de, INCQS, Instituto Oswaldo Cruz, IOC, Fundac¸a˜o Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil
J. N. Ramos (&) Laborato´rio de Gene´tica Molecular de Microrganismos, Instituto Oswaldo Cruz, Fundac¸a˜o Oswaldo Cruz, Av. Brasil, 4.365, Pavilha˜o Leoˆnidas Deanne, 6 andar, sala 607, Manguinhos, Rio de Janeiro, RJ CEP: 21040-360, Brazil e-mail: [email protected] K. R. N. Santos Instituto de Microbiologia Paulo de Go´es, Laborato´rio de Infecc¸a˜o Hospitalar, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil C. Q. Fortes Departamento de Medicina Preventiva, Faculdade de Medicina, Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil
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p = 0.04) and chronic renal insufficiency (OR 38.3; 95 % CI 3.2–449.4; p = 0.004). Conclusions At two main teaching hospitals in Brazil, Streptococcus spp. was the principal pathogen of CAIE while S. aureus and Enterococcus spp. were the most frequent causes of HAIE. IE remains a serious disease associated with high in-hospital mortality rate (46.6 %); especially, in individuals over 45 years of age and with renal failure. Data suggest that early surgery may improve the outcome of IE patients. Keywords Infective endocarditis Healthcare-associated infection Community-associated infection Developing countries
Introduction Infective endocarditis (IE) is a systemic infection and a lifethreatening disease associated with high mortality rates ranging from 19 to 38 %; especially, in developing countries [1–4]. Many factors affect the outcome of this serious disease, including the virulence of the causative microorganism, the characteristics of the patients, the presence of an underlying disease, surgical indications, the timing of surgery and any delays in the diagnosis and treatment [1, 5–7]. In developing countries, the lack of resources and infrastructure, poverty, overcrowding and malnutrition, combined with social-economic instability also contribute to the persistence of a high incidence of IE [8]. A better understanding of the local epidemiology and associated risk factors is required to develop an efficient IE therapy [9, 10]. However, echocardiography and a multidisciplinary team for the diagnosis and treatment of endocarditis remain scarce in many countries, including in Brazil, which leads to the lack of knowledge of the epidemiology of IE [11, 12]. The aim of this observational, prospective cohort study was to report on the demographical, anamnestic and microbiological characteristics of 71 patients diagnosed at two University Hospitals located in Rio de Janeiro, Brazil, during the period going from January 2009 to March 2013.
Methods Study design Over a 50-month period (Jan 2009–Mar 2013), 71 consecutive patients who were diagnosed with IE—56 (78.8 %) definitively and 15 (21.2 %) possible—were analyzed by infectious diseases, cardiovascular and neurosurgery specialists at two Brazilian tertiary referral centers: Hospital Universita´rio Clementino Fraga Filho
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(HUCFF/UFRJ) and Hospital Universita´rio Pedro Ernesto (HUPE/UERJ). Community-associated infective endocarditis (CAIE) and healthcare-associated infective endocarditis (HAIE) were diagnosed according to the modified Duke criteria. Two or one major and three minor clinical criteria were used. Major clinical criteria included positive blood culture and evidence of endocardial involvement. Minor clinical criteria used were: fever [38.0 °C, predisposing heart conditions, vascular and immunologic phenomena. Written informed consent was obtained from all patients, as required by the institutional committee. HAIE subjects were considered as either IE-manifesting [48 h after admission to the hospital or IE-acquired in association with a significant invasive procedure performed in the 6 months preceding diagnosis in the following situations: (a) during a stay and/or during treatment in a hospital setting (nosocomial healthcare-associated IE); or (b) patients with extensive outpatient contact with healthcare interventions [13]. Anamnestic data A search in the clinical records and institutional databases was conducted to determine demographical and clinical characteristics of the patients with IE. The following variables were analyzed: age, sex, time between the onset of symptoms and diagnosis of IE, length of in-hospital stay, IE origin (community or healthcare-associated). Other comorbidities of the patients were recorded as well as echocardiographs, microbiological findings and final outcomes (Tables 1, 2). Microbiological data Clinical samples were processed in the Microbiology Laboratories of HUPE/UERJ and HUCFF/UFRJ university hospitals. Blood cultures were processed with the BACTEC 9240 (BacT/ALERTÒ 3D, BioMe´rieux, Durham, NC, USA)—with at least two aerobic bottles incubated for 5 days (14 days in exceptional cases). VITEKÒ 2 system (BioMe´rieux) identification cards (ID) and antibiotic susceptibility testing (AST) cards were used. The data was analyzed using the VITEKÒ 2 Advanced Expert SystemTM (AES), which permits categorization of the results into four groups: correct identification (i.e., unambiguous identification [given as excellent, very good, good, or acceptable]) to the species level or to the genus level [14, 15]. Diagnosis of microorganisms of fastidious growth were performed in a different laboratory [29]. In addition to the antimicrobial susceptibility profiles performed by the disk diffusion method vancomycin MIC measurements using the E-test were performed for vancomycin-resistant strains of
Infective endocarditis in Rio de Janeiro, Brazil Table 1 Epidemiologic and clinic aspects of infective endocarditis (IE) in two teaching hospitals in Rio de Janeiro, Brazil
Total number of IE patients
N = 71 (100 %)
Age (years, mean ± SD)
49.8 ± 2.4
Male gender
N = 41 (57.7 %)
Time between the onset of symptoms and diagnosis of IE (days, mean ± SD) Length of in-hospital stay (days. mean ± SD)
35.8 ± 4.8 49.1 ± 5.9
Origin of IE episode Healthcare-associated
N = 40 (56.3 %)
Community-associated
N = 31 (43.6 %)
Clinical findings Fever [38.0 °C
N = 63 (88.7 %)
Predisposing heart condition
N = 34 (47.8 %)
New heart murmur
N = 18 (25.3 %)
Vascular phenomena
N = 21 (29.5 %)
Immunologic phenomena
N = 4 (5.6 %)
Source of infection Intravascular catheter
N = 39 (54.9 %)
Gastrointestinal tract
N = 4 (5.6 %)
Oral cavity
N = 4 (5.6 %)
Prosthetic Valve Intracardiac devices
N = 2 (2.8 %) N = 2 (2.8 %)
Genitourinary tract
N = 1 (1.4 %)
Skin
N = 1 (1.4 %)
Unknown
N = 18 (25.3 %)
Echocardiographic findings
N = 60 (84.5 %)
Vegetation size (cm, mean ± SD)
1.4 ± 0.2
Heart valve compromised Mitral
N = 29 (48.3 %)
Aortic
N = 13 (21.6 %)
Tricuspid
N = 11 (18.3 %)
Multiple valve
N = 6 (10 %)
Native valve Definitive diagnose of IE
N = 64 (90.1 %) N = 56 (78.8 %)
Comorbidities Chronic renal insufficiency
N = 24 (33.8 %)
Diabetes mellitus Neoplasia
N = 11 (15.5 %) N = 7 (9.8 %)
HIV?
N = 3 (4.2 %)
Solid organ transplanted
N = 3 (4.2)
Autoimmune disease Structural heart disease
N = 3 (4.2 %) N = 37 (52.1 %)
Complications Heart failure
N = 20 (28.1 %)
Sepsis
N = 14 (19.7 %)
Metastatic infections
N = 11 (15.5 %)
Stroke
N = 8 (11.2 %)
Abscess
N = 7 (9.8 %)
Septic embolism
N = 7 (9.8 %)
Valve replacement
N = 12 (16.9 %)
In-hospital mortality
N = 33 (46.4 %)
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P. V. Damasco et al. Table 2 Bivariate analysis grouped by origin of infective endocarditis (IE) episodes: community (CAIE) vs. healthcare-associated (HAIE) cases Characteristics
CAIE N = 31 (43.6 %)
HAIE N = 40 (56.4 %)
Age (years, mean ± SD)
52.4 ± 3.6
47.6 ± 3.2
p value 0.9
Male gender
N = 20 (64.5 %)
N = 21 (52.5 %)
Time between the onset of symptoms and diagnosis of IE (days, mean ± SD)
48 ± 7.9
22.3 ± 3.7
\0.001
0.3
Length of in-hospital stay (days, mean ± SD)
36.6 ± 3.8
58.8 ± 9.9
0.06
Unknown etiology
N = 5 (16.1 %)
N = 6 (15 %)
0.8
Streptococcus sp. Enterococcus sp.
N = 14 (45.1 %) N = 5 (16.1 %)
N = 1 (2.5 %) N = 11 (27.5 %)
Microorganisms \0.001 0.2
Staphylococcus aureus
N = 5 (16.1 %)
N = 13 (32.5 %)
0.1
Coagulase-negative Staphylococcus spp.
N = 1 (3.2 %)
N = 4 (10 %)
0.2
Others
N = 1 (3.2 %)
N = 5 (12.5 %)
0.1 0.6
Echocardiographic findings
N = 27 (87 %)
N = 32 (82 %)
Vegetation size (cm, mean ± SD)
1.52 ± 0.1
1.4 ± 0.2
0.7
Blood cultures findings
N = 26 (83.8 %)
N = 34 (85 %)
0.9
Biopsy findings
N = 4 (12.9 %)
N = 3 (7.5 %)
0.4
N = 15 (53.5 %)
N = 14 (41.1 %)
0.3 \0.001
Heart valve compromised Mitral Tricuspid
N = 1 (3.5 %)
N = 10 (29.4 %)
Aortic
N = 9 (32.1 %)
N = 4 (11.7 %)
0.04
Multiple valve
N = 2 (7.1 %)
N = 2 (6.2 %)
0.6
Native valve Definitive IE diagnosis Comorbiditiesa
N = 30 (96.7 %)
N = 34 (85 %)
0.1
N = 26 (83.8 %)
N = 30 (75 %)
0.6 \0.001
Renal chronic insufficiency
N = 2 (6.4 %)
N = 22 (55 %)
Diabetes mellitus
N = 2 (6.4 %)
N = 9 (22.5 %)
0.06
Neoplasia
N = 3 (9.6 %)
N = 4 (10 %)
0.9
HIV?
N = 1 (3.2 %)
N = 2 (5 %)
0.7
Solid organ transplanted
N = 2 (6.4 %)
N = 1 (2.5 %)
0.4
Autoimmune diseases
N = 2 (6.4 %)
N = 1 (2.5 %)
0.4
Structural heart disease
N = 21 (67.7 %)
N = 16 (40 %)
0.02
In-hospital mortality
N = 11 (35.3 %)
N = 22 (55 %)
0.1
Enterococcus, and E-test and broth microdilution assays for MRSA strains [16]. Echocardiographic data Transthoracic and/or transesophageal echocardiography were performed to determine the size and location of vegetation, type of valve infected, and cardiac complications.
categorical variables, and the v2 test was also used (the Fisher’s exact test was used if an expected value was \5). Logistic regression was used to examine potential associations between variables, and a multivariate analysis was performed to identify risk factors independently associated with mortality. Variables with a p [ 0.05 were excluded from the final model. A p B 0.05 was considered statistically significant. This study was reviewed and approved by the institutional board of the HUPE.
Statistical analysis Results Data were input to Excel 2007 and analyzed using the STATATM statistical package version 9.1. A descriptive analysis of the variables was performed. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated for
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Epidemiological and clinical aspects from the 71 IE cases diagnosed at the two Brazilian University Hospitals are shown in Table 1. The mean age of the population was
Infective endocarditis in Rio de Janeiro, Brazil Table 3 Infective Endocarditis (IE) cases (N = 71) etiology and antibiotic treatment Positive blood cultures
N = 60 (84.5 %)
Staphylococcus aureus
N = 18 (30.0 %)
Enterococcus sp.
N = 16 (26.7 %)
Enterococcus faeacalis Enterococcus faecium Streptococcus sp.
N = 12 (75 %) N = 4 (25 %) N = 15 (25.0 %)
Streptococcus viridans
N = 5 (8.3 %)
Streptococcus bovis
N = 3 (5.0 %)
Streptococcus mitis
N = 2 (3.3 %)
Streptococcus gallolyticus
N = 2 (3.3 %)
Streptococcus mutans Streptococcus infantarius
N = 1 (1.6 %) N = 1 (1.6 %)
Streptococcus agalactiae
N = 1 (1.6 %)
Coagulase-negative staphylococci
N = 5 (8.3 %)
Staphylococcus epidermidis
N = 4 (6.6 %)
Staphylococcus hominis
N = 1 (1.6 %)
Othersa
N = 6 (8.4 %)
Abiotrophia defectiva
N = 1 (1.6 %)
Candida parapsilosis
N = 2 (3.3 %)
Candida spp.
N = 1 (1.6 %)
Serratia marcescens Antibiotic regimens
N = 1 (1.6 %) N = 71 (100 %)
Aminoglycoside
N = 44 (61.97 %)
Aminopenicillins
N = 33 (46.5 %)
Vancomycin
N = 19 (26.7 %)
Oxacillin
N = 15 (21.1 %)
Anfotericin B Ceftriaxone
N = 8 (11.2 %) N = 6 (8.4 %)
Daptomycin
N = 4 (5.6 %)
Linezolid
N = 2 (2.8 %)
Carbapenems
N = 2 (2.8 %)
Cefepime
N = 2 (2.8 %)
Piperacillin-tazobactam
N = 2 (2.8 %)
Trimethoprim-sulfamethoxazole
N = 2 (2.8 %)
Rifampin
N = 2 (2.8 %)
a
From 6 valve leaflet cultures, one gave positive result for Rhodotorula mucilaginosa
49.7 ± 2.4 years; 41 patients were males. The median time between the onset of symptoms and diagnosis of IE was 35.8 ± 4.8 days. The most relevant clinical aspect was fever (88.7 %). New vascular regurgitation murmur was physically observed only in 18 (25.3 %) patients. Endocardial involvement was evidenced in 60 (84.5 %) patients, vascular phenomena in 21 (29.5 %) patients and immunologic phenomena in four (5.6 %) patients. Moreover, there were four (5.6 %) cases of arterial embolism, two (2.8 %) mycotic aneurysms and one (1.4 %) of Janeway lesions.
Two-dimensional transthoracic (TTE) or transesophageal echocardiography TEE) of the 71 patients revealed a mean vegetation size of 1.4 ± 0.2 cm. The valve most frequently compromised was the mitral valve (48.3 %). Most IE episodes occurred in the native valve (90.1 %). Various types of comorbidities were identified (Table 2): 24 (33.8 %) patients with kidney failure, 20 (83.3 %) of which were undergoing hemodialysis, Diabetes mellitus (N = 11; 15.5 %), neoplasia (N = 7; 9.8 %), HIV (N = 3; 4.2 %), solid organs transplants (N = 3; 4.2 %) and autoimmune diseases (N = 2; 2.8 %). Structural heart disease was observed in 37 (52.1 %) patients. The main complications of IE were 28.1 % congestive heart failure, 19.7 % sepsis, 15.5 % metastatic infections, 11.2 % stroke, 9.8 % abscess and 9.8 % septic embolization. In this IE cohort, the in-hospital mortality rate was 46.4 % and valve replacement was done only 16.9 % of patients (Table 1). The main source of IE was intravascular catheter (54.9 %). A pathogenic microorganism was isolated from blood cultures in 60 patients (84.5 %) with IE. Staphylococcus aureus was the most frequent etiological agent (30 %), followed by Enterococcus spp. (26.7 %), Streptococcus spp. (25.0 %) and coagulase-negative Staphylococci (8.3 %). The main antibiotics prescribed were: aminoglycoside (61.9 %), aminopenicillins (46.5 %), vancomycin (26.7 %), oxacillin (21.1 %) (Table 3). Streptococcus spp. (45.1 %) was the predominant cause of CAIE and S. aureus (32.5 %) and Enterococcus spp. (27.5 %) were the most frequent causes of HAIE. A total of 31 (43.6 %) community-acquired infective endocarditis (CAIE) cases and 40 (56.4 %) healthcare-associated infective endocarditis (HAIE) cases were observed (Table 2). The prevalence of methicillin-resistant S. aureus (MRSA) was 5.5 %. The sole case of infection due to MRSA USA 400 was associated with hemodialysis catheters and, therefore, classified as HAIE. This CA-MRSA strain presented SCCmec type IV, negative to PVL genes, vancomycin MIC = 4 lg/ml by E-test, and 2 lg/ml by broth microdilution [10]. Furthermore, there were two HAIE cases due to vancomycin-resistant Enterococcus (VRE) strains (with vancomycin MIC [32 and MIC C64, respectively) in patients that suffered from kidney failure. Tricuspid valve involvement and chronic renal insufficiency were more frequent among HAIE patients than CAIE patients (p \ 0.001) (Table 2). In our analysis, the risk factors related to in-hospital mortality in IE patients were age being over 45 years old (OR: 3.4; 95 % CI: 1.03–11.24; p = 0.04) and chronic renal insufficiency (OR: 38.3; 95 % CI: 3.2–449.3; p = 0.004) (Table 4). The inhospital mortality rate associated with specific etiology of IE was: Streptococcus spp. (N = 3; 3 %), negative
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P. V. Damasco et al. Table 4 Multivariate analysis of infective endocarditis (IE) in-hospital mortality Characteristic
OR (95 % CI)
p value
Age [45 years
3.4 (1.03–11.24)
0.04
Chronic renal insufficiency
38.3 (3.2–449.3)
0.004
OD odds ratio; 95 % CI confidence interval
Staphylococci (N = 4; 12.1 %), S. aureus (N = 7; 21.2 %), Enterococcus spp. (N = 8; 24.2 %). The lower mortality rate was associated with Streptococcus spp. IE (p = 0.02). During this study (N = 71), ten (14.1 %) patients showed culture-negative endocarditis; five (50.0 %) CAIE and five (50.0 %) HAIE. Only two (20 %) patients had no fever. The median time between the onset of symptoms and diagnosis of culture-negative endocarditis was 29.2 (4–61) days and median age was 54.5 years. The in-hospital mortality in this IE category was 9.8 % (OR; 3.5; IC 95 %; 0.8–15.2; p = 0.08).
Discussion The etiology of IE varies according to region, but the International Collaboration on Endocarditis-Prospective Cohort Study [20] has found the most frequent microorganism to be S. aureus in industrialized countries. In developing countries the most frequently found microorganisms were: S. aureus (18–48 %), Streptococcus viridans (20–24 %) and Enterococcus spp. (1–15 %) [2, 3, 21]. This cohort study revealed a prevalence of 56.4 % of HAIE and 43.6 % of CAIE in two main University Hospitals in Rio de Janeiro, Brazil. S. aureus (30 %) was the predominant cause of the IE, 32.5 % of the HAIE and 16.1 % CAIE. Streptococcus spp. were most commonly associated with CAIE (p \ 0.001) and structural heart disease was most present in this group of patients (p = 0.02). Moreover, Enterococcus spp was isolated in 26.7 % blood cultures, making it the second most frequent agent in our study. Similar to other developing countries [11], the higher incidence of S. aureus and Enterococcus spp. was probably due to the fact that this study was conducted in tertiary care centers. Similar to the results reported from other developing countries [18, 19]; in the present study, most (57.7 %) of the patients were males, and the mean age of the population was 49.7 years. In a previous study developed in Minas Gerais, Brazil [3], a total of 62 cases of IE was observed. Most (63 %) of the patients were also males and the mean age of the population was 45 years. Pathogenic microorganisms were currently isolated from blood cultures in
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higher number (N = 60) of cases when compared with the data (N = 40) observed in Minas Gerais survey. In that opportunity, S. aureus (48 %) and Streptococcus viridans (20 %) were found the most common causative agent of IE. Regarding MDR isolates, the authors also reported 32 % cases of IE due to MRSA. Conversely, the prevalence of MRSA in our study was very low (5.5 %). In the present cohort of 71 patients, there were only three cases of HAIE due to MDR pathogens: one case due to CA-MRSA and two cases due to VRE that occurred in patients with renal insufficiency. The main source of IE in this cohort was intravascular catheter. Invasive medical technology has led to an increase in the incidence of HAIE, and careful management of vascular devices is essential to minimize the risk of bacteremia leading to HAIE [13, 17]. Tricuspid valve and renal chronic insufficiency were most frequently observed in HAIE patients than in CAIE patients. The scenario of IE studies in developing countries is the relatively young patient that presents rheumatic heart disease, fact which remains the predominant predisposing condition for IE in developing countries [22]. This is in contrast to industrialized countries where the majority of patients present beyond the fourth decade, which reflects increased healthcare-associated infections [23]. In the contemporary population-based studies of IE in industrialized countries, in-hospital mortality ranges from 15 to 22 % increased healthcare-associated infections and less rheumatic heart disease as risk factors [24, 25]. The present day morbidity and mortality of patients with IE in developing countries are the same of the early twentieth century in North America and Europe [1–4, 23]. Our observations are a consequence of medical progress in Brazil [20, 22, 26], but Streptococcus spp. is still the pathogen most associated with CAIE and structural heart diseases were more present in this patient group. The analysis of risk factors revealed that in-hospital mortality in IE episodes was related to the age over 45 years old (OR 3.4; 95 % CI 1.03–11.24; p = 0.04) and renal insufficiency (OR 38.3; 95 % CI 3.2–449.4; p = 0.004). Some microorganisms of fastidious growth found in the human microbiota as part of genitourinary, oral and intestinal tract may act as opportunistic pathogens and some are often associated with negative blood cultures [22, 23, 27, 28]. We had 10 (14.1 %) patients with culturenegative endocarditis in our series of 71 patients; 5 (50.0 %) CAIE and 5 (50.0 %) HAIE. Even though we observed a high mortality rate in this group, we did not observe statistical significance (p = 0.2). Although true culture-negative endocarditis is rare in industrialized countries, studies on IE in developing countries show a high prevalence (10–55 %) of culture-negative endocarditis. There have been various reasons proposed for this
Infective endocarditis in Rio de Janeiro, Brazil
theme. The most widely accepted being administration of antibiotics prior to the diagnosis of IE [22]. Cryptic endocarditis was caused by indolent, slow-growing microorganisms of the HACEK group and Bartonella spp., Legionella spp., Coxiella burnetti, Chlamydophila psittaci, has been reported [23]. Moreover, an observational cohort study at two university centers in Germany, during an 8-year period (2000–2007) showed Tropheryma whipplei as the most common pathogen associated with culturenegative endocarditis [27]. Molecular amplification methods may be needed for detection of these organisms as well as other less common etiologic agents. At this moment we have not screened for such species. Earlier studies also indicated the destructive feature of CAIE attributable to Corynebacterium diphtheriae in Rio de Janeiro [5]. Similar to data of IE studies in Hong Kong [28], a prevalence of 14.1 % culture-negative endocarditis cases were observed in our series. In this opportunity, only one case of culturenegative endocarditis due to Abiotrophia defectiva was diagnosed by molecular methods [29].
Conclusion In Rio de Janeiro University Hospitals, S. aureus (30 %) was the predominant cause of IE, 32.5 % was from HAIE and 16.1 % from CAIE. Streptococcus spp. (45.1 %) was the main etiology of CAIE (p = 0.001). There were 3.2 % with CAIE due to coagulase-negative Staphylococci. S. aureus (38.2 %) and Enterococcus spp. (27.5 %) were the most frequent cause of HAIE; the prevalence of methicillin-resistant S. aureus in this cohort was 5.5 %. In our analysis of risk factors related to in-hospital mortality in IE patients were: their age being over 45-years-old and chronic renal insufficiency. Further studies remain necessary to determine the etiology of culture-negative endocarditis in Rio de Janeiro; especially, in tertiary care centers. Acknowledgments This work was supported by CAPES, FAPERJ, CNPq and SR-2/UERJ. Conflict of interest The authors have no disclosures or conflicts of interest to report.
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CLINICAL AND EPIDEMIOLOGICAL STUDY
Infective endocarditis in Rio de Janeiro, Brazil: a 5-year experience at two teaching hospitals P. V. Damasco • J. N. Ramos • J. C. D. Correal • M. V. Potsch • V. V. Vieira • T. C. F. Camello • M. P. Pereira • V. D. Marques • K. R. N. Santos • E. A. Marques M. B. Castier • R. Hirata Jr. • A. L. Mattos-Guaraldi • C. Q. Fortes
•
Received: 5 March 2014 / Accepted: 19 May 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Introduction Despite the recent advances in diagnosis and treatment, mortality rates due to infective endocarditis (IE) remain high if not aggressively treated with antibiotics, whether or not associated with surgery. Data on the prevalence, epidemiology and etiology of IE from developing countries remain scarce. The aim of this observational, prospective cohort study was to report a 5-year experience of IE at two teaching hospitals in Rio de Janeiro, Brazil. Material and methods Demographical, anamnestic and microbiological characteristics of 71 IE patients were evaluated during the period of January 2009 to March 2013. Results The mean age of the IE patients was 49.8 ± 2.4 years, of which 41 (57.7 %) were males. The median time
between the onset of symptoms and diagnosis of IE was 35.8 ± 4.8 days. A total of 31 (43.6 %) cases of community-acquired infective endocarditis (CAIE) and 40 (56.3 %) cases of healthcare-acquired infective endocarditis (HAIE) were observed. Staphylococcus aureus (30 %) was the predominant cause of IE. Streptococcus spp. (45.1 %) was the predominant cause of the CAIE while S. aureus (32.5 %) and Enterococcus spp. (27.2 %) were the main etiological agents of HAIE. For 64 (90.1 %) patients with native valve endocarditis, the mitral valve was the most commonly affected (48.3 %). The main source of IE in this cohort was intravascular catheter. The tricuspid valve and renal chronic insufficiency were more frequent in patients with HAIE than CAIE (p = 0.001). The risk factors associated with in-hospital mortality rate (46.4 %) in IE patients were: age over 45 (OR 3.4; 95 % CI 1.03–11.24;
P. V. Damasco and J. N. Ramos contributed equally for the first authorship in this manuscript. P. V. Damasco J. N. Ramos T. C. F. Camello V. D. Marques E. A. Marques R. Hirata Jr. A. L. Mattos-Guaraldi Faculdade de Cieˆncias Me´dicas, Universidade do Estado do Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil P. V. Damasco J. C. D. Correal T. C. F. Camello V. D. Marques E. A. Marques M. B. Castier Hospital Universita´rio Pedro Ernesto-HUPE, Universidade do Estado do Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil P. V. Damasco M. V. Potsch M. P. Pereira Escola de Medicina e Cirurgia, Universidade Federal do Estado do Rio de Janeiro, UNIRIO, Rio de Janeiro, RJ, Brazil J. N. Ramos V. V. Vieira Instituto Nacional de Controle de Qualidade em Sau´de, INCQS, Instituto Oswaldo Cruz, IOC, Fundac¸a˜o Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil
J. N. Ramos (&) Laborato´rio de Gene´tica Molecular de Microrganismos, Instituto Oswaldo Cruz, Fundac¸a˜o Oswaldo Cruz, Av. Brasil, 4.365, Pavilha˜o Leoˆnidas Deanne, 6 andar, sala 607, Manguinhos, Rio de Janeiro, RJ CEP: 21040-360, Brazil e-mail: [email protected] K. R. N. Santos Instituto de Microbiologia Paulo de Go´es, Laborato´rio de Infecc¸a˜o Hospitalar, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil C. Q. Fortes Departamento de Medicina Preventiva, Faculdade de Medicina, Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil
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p = 0.04) and chronic renal insufficiency (OR 38.3; 95 % CI 3.2–449.4; p = 0.004). Conclusions At two main teaching hospitals in Brazil, Streptococcus spp. was the principal pathogen of CAIE while S. aureus and Enterococcus spp. were the most frequent causes of HAIE. IE remains a serious disease associated with high in-hospital mortality rate (46.6 %); especially, in individuals over 45 years of age and with renal failure. Data suggest that early surgery may improve the outcome of IE patients. Keywords Infective endocarditis Healthcare-associated infection Community-associated infection Developing countries
Introduction Infective endocarditis (IE) is a systemic infection and a lifethreatening disease associated with high mortality rates ranging from 19 to 38 %; especially, in developing countries [1–4]. Many factors affect the outcome of this serious disease, including the virulence of the causative microorganism, the characteristics of the patients, the presence of an underlying disease, surgical indications, the timing of surgery and any delays in the diagnosis and treatment [1, 5–7]. In developing countries, the lack of resources and infrastructure, poverty, overcrowding and malnutrition, combined with social-economic instability also contribute to the persistence of a high incidence of IE [8]. A better understanding of the local epidemiology and associated risk factors is required to develop an efficient IE therapy [9, 10]. However, echocardiography and a multidisciplinary team for the diagnosis and treatment of endocarditis remain scarce in many countries, including in Brazil, which leads to the lack of knowledge of the epidemiology of IE [11, 12]. The aim of this observational, prospective cohort study was to report on the demographical, anamnestic and microbiological characteristics of 71 patients diagnosed at two University Hospitals located in Rio de Janeiro, Brazil, during the period going from January 2009 to March 2013.
Methods Study design Over a 50-month period (Jan 2009–Mar 2013), 71 consecutive patients who were diagnosed with IE—56 (78.8 %) definitively and 15 (21.2 %) possible—were analyzed by infectious diseases, cardiovascular and neurosurgery specialists at two Brazilian tertiary referral centers: Hospital Universita´rio Clementino Fraga Filho
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(HUCFF/UFRJ) and Hospital Universita´rio Pedro Ernesto (HUPE/UERJ). Community-associated infective endocarditis (CAIE) and healthcare-associated infective endocarditis (HAIE) were diagnosed according to the modified Duke criteria. Two or one major and three minor clinical criteria were used. Major clinical criteria included positive blood culture and evidence of endocardial involvement. Minor clinical criteria used were: fever [38.0 °C, predisposing heart conditions, vascular and immunologic phenomena. Written informed consent was obtained from all patients, as required by the institutional committee. HAIE subjects were considered as either IE-manifesting [48 h after admission to the hospital or IE-acquired in association with a significant invasive procedure performed in the 6 months preceding diagnosis in the following situations: (a) during a stay and/or during treatment in a hospital setting (nosocomial healthcare-associated IE); or (b) patients with extensive outpatient contact with healthcare interventions [13]. Anamnestic data A search in the clinical records and institutional databases was conducted to determine demographical and clinical characteristics of the patients with IE. The following variables were analyzed: age, sex, time between the onset of symptoms and diagnosis of IE, length of in-hospital stay, IE origin (community or healthcare-associated). Other comorbidities of the patients were recorded as well as echocardiographs, microbiological findings and final outcomes (Tables 1, 2). Microbiological data Clinical samples were processed in the Microbiology Laboratories of HUPE/UERJ and HUCFF/UFRJ university hospitals. Blood cultures were processed with the BACTEC 9240 (BacT/ALERTÒ 3D, BioMe´rieux, Durham, NC, USA)—with at least two aerobic bottles incubated for 5 days (14 days in exceptional cases). VITEKÒ 2 system (BioMe´rieux) identification cards (ID) and antibiotic susceptibility testing (AST) cards were used. The data was analyzed using the VITEKÒ 2 Advanced Expert SystemTM (AES), which permits categorization of the results into four groups: correct identification (i.e., unambiguous identification [given as excellent, very good, good, or acceptable]) to the species level or to the genus level [14, 15]. Diagnosis of microorganisms of fastidious growth were performed in a different laboratory [29]. In addition to the antimicrobial susceptibility profiles performed by the disk diffusion method vancomycin MIC measurements using the E-test were performed for vancomycin-resistant strains of
Infective endocarditis in Rio de Janeiro, Brazil Table 1 Epidemiologic and clinic aspects of infective endocarditis (IE) in two teaching hospitals in Rio de Janeiro, Brazil
Total number of IE patients
N = 71 (100 %)
Age (years, mean ± SD)
49.8 ± 2.4
Male gender
N = 41 (57.7 %)
Time between the onset of symptoms and diagnosis of IE (days, mean ± SD) Length of in-hospital stay (days. mean ± SD)
35.8 ± 4.8 49.1 ± 5.9
Origin of IE episode Healthcare-associated
N = 40 (56.3 %)
Community-associated
N = 31 (43.6 %)
Clinical findings Fever [38.0 °C
N = 63 (88.7 %)
Predisposing heart condition
N = 34 (47.8 %)
New heart murmur
N = 18 (25.3 %)
Vascular phenomena
N = 21 (29.5 %)
Immunologic phenomena
N = 4 (5.6 %)
Source of infection Intravascular catheter
N = 39 (54.9 %)
Gastrointestinal tract
N = 4 (5.6 %)
Oral cavity
N = 4 (5.6 %)
Prosthetic Valve Intracardiac devices
N = 2 (2.8 %) N = 2 (2.8 %)
Genitourinary tract
N = 1 (1.4 %)
Skin
N = 1 (1.4 %)
Unknown
N = 18 (25.3 %)
Echocardiographic findings
N = 60 (84.5 %)
Vegetation size (cm, mean ± SD)
1.4 ± 0.2
Heart valve compromised Mitral
N = 29 (48.3 %)
Aortic
N = 13 (21.6 %)
Tricuspid
N = 11 (18.3 %)
Multiple valve
N = 6 (10 %)
Native valve Definitive diagnose of IE
N = 64 (90.1 %) N = 56 (78.8 %)
Comorbidities Chronic renal insufficiency
N = 24 (33.8 %)
Diabetes mellitus Neoplasia
N = 11 (15.5 %) N = 7 (9.8 %)
HIV?
N = 3 (4.2 %)
Solid organ transplanted
N = 3 (4.2)
Autoimmune disease Structural heart disease
N = 3 (4.2 %) N = 37 (52.1 %)
Complications Heart failure
N = 20 (28.1 %)
Sepsis
N = 14 (19.7 %)
Metastatic infections
N = 11 (15.5 %)
Stroke
N = 8 (11.2 %)
Abscess
N = 7 (9.8 %)
Septic embolism
N = 7 (9.8 %)
Valve replacement
N = 12 (16.9 %)
In-hospital mortality
N = 33 (46.4 %)
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P. V. Damasco et al. Table 2 Bivariate analysis grouped by origin of infective endocarditis (IE) episodes: community (CAIE) vs. healthcare-associated (HAIE) cases Characteristics
CAIE N = 31 (43.6 %)
HAIE N = 40 (56.4 %)
Age (years, mean ± SD)
52.4 ± 3.6
47.6 ± 3.2
p value 0.9
Male gender
N = 20 (64.5 %)
N = 21 (52.5 %)
Time between the onset of symptoms and diagnosis of IE (days, mean ± SD)
48 ± 7.9
22.3 ± 3.7
\0.001
0.3
Length of in-hospital stay (days, mean ± SD)
36.6 ± 3.8
58.8 ± 9.9
0.06
Unknown etiology
N = 5 (16.1 %)
N = 6 (15 %)
0.8
Streptococcus sp. Enterococcus sp.
N = 14 (45.1 %) N = 5 (16.1 %)
N = 1 (2.5 %) N = 11 (27.5 %)
Microorganisms \0.001 0.2
Staphylococcus aureus
N = 5 (16.1 %)
N = 13 (32.5 %)
0.1
Coagulase-negative Staphylococcus spp.
N = 1 (3.2 %)
N = 4 (10 %)
0.2
Others
N = 1 (3.2 %)
N = 5 (12.5 %)
0.1 0.6
Echocardiographic findings
N = 27 (87 %)
N = 32 (82 %)
Vegetation size (cm, mean ± SD)
1.52 ± 0.1
1.4 ± 0.2
0.7
Blood cultures findings
N = 26 (83.8 %)
N = 34 (85 %)
0.9
Biopsy findings
N = 4 (12.9 %)
N = 3 (7.5 %)
0.4
N = 15 (53.5 %)
N = 14 (41.1 %)
0.3 \0.001
Heart valve compromised Mitral Tricuspid
N = 1 (3.5 %)
N = 10 (29.4 %)
Aortic
N = 9 (32.1 %)
N = 4 (11.7 %)
0.04
Multiple valve
N = 2 (7.1 %)
N = 2 (6.2 %)
0.6
Native valve Definitive IE diagnosis Comorbiditiesa
N = 30 (96.7 %)
N = 34 (85 %)
0.1
N = 26 (83.8 %)
N = 30 (75 %)
0.6 \0.001
Renal chronic insufficiency
N = 2 (6.4 %)
N = 22 (55 %)
Diabetes mellitus
N = 2 (6.4 %)
N = 9 (22.5 %)
0.06
Neoplasia
N = 3 (9.6 %)
N = 4 (10 %)
0.9
HIV?
N = 1 (3.2 %)
N = 2 (5 %)
0.7
Solid organ transplanted
N = 2 (6.4 %)
N = 1 (2.5 %)
0.4
Autoimmune diseases
N = 2 (6.4 %)
N = 1 (2.5 %)
0.4
Structural heart disease
N = 21 (67.7 %)
N = 16 (40 %)
0.02
In-hospital mortality
N = 11 (35.3 %)
N = 22 (55 %)
0.1
Enterococcus, and E-test and broth microdilution assays for MRSA strains [16]. Echocardiographic data Transthoracic and/or transesophageal echocardiography were performed to determine the size and location of vegetation, type of valve infected, and cardiac complications.
categorical variables, and the v2 test was also used (the Fisher’s exact test was used if an expected value was \5). Logistic regression was used to examine potential associations between variables, and a multivariate analysis was performed to identify risk factors independently associated with mortality. Variables with a p [ 0.05 were excluded from the final model. A p B 0.05 was considered statistically significant. This study was reviewed and approved by the institutional board of the HUPE.
Statistical analysis Results Data were input to Excel 2007 and analyzed using the STATATM statistical package version 9.1. A descriptive analysis of the variables was performed. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated for
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Epidemiological and clinical aspects from the 71 IE cases diagnosed at the two Brazilian University Hospitals are shown in Table 1. The mean age of the population was
Infective endocarditis in Rio de Janeiro, Brazil Table 3 Infective Endocarditis (IE) cases (N = 71) etiology and antibiotic treatment Positive blood cultures
N = 60 (84.5 %)
Staphylococcus aureus
N = 18 (30.0 %)
Enterococcus sp.
N = 16 (26.7 %)
Enterococcus faeacalis Enterococcus faecium Streptococcus sp.
N = 12 (75 %) N = 4 (25 %) N = 15 (25.0 %)
Streptococcus viridans
N = 5 (8.3 %)
Streptococcus bovis
N = 3 (5.0 %)
Streptococcus mitis
N = 2 (3.3 %)
Streptococcus gallolyticus
N = 2 (3.3 %)
Streptococcus mutans Streptococcus infantarius
N = 1 (1.6 %) N = 1 (1.6 %)
Streptococcus agalactiae
N = 1 (1.6 %)
Coagulase-negative staphylococci
N = 5 (8.3 %)
Staphylococcus epidermidis
N = 4 (6.6 %)
Staphylococcus hominis
N = 1 (1.6 %)
Othersa
N = 6 (8.4 %)
Abiotrophia defectiva
N = 1 (1.6 %)
Candida parapsilosis
N = 2 (3.3 %)
Candida spp.
N = 1 (1.6 %)
Serratia marcescens Antibiotic regimens
N = 1 (1.6 %) N = 71 (100 %)
Aminoglycoside
N = 44 (61.97 %)
Aminopenicillins
N = 33 (46.5 %)
Vancomycin
N = 19 (26.7 %)
Oxacillin
N = 15 (21.1 %)
Anfotericin B Ceftriaxone
N = 8 (11.2 %) N = 6 (8.4 %)
Daptomycin
N = 4 (5.6 %)
Linezolid
N = 2 (2.8 %)
Carbapenems
N = 2 (2.8 %)
Cefepime
N = 2 (2.8 %)
Piperacillin-tazobactam
N = 2 (2.8 %)
Trimethoprim-sulfamethoxazole
N = 2 (2.8 %)
Rifampin
N = 2 (2.8 %)
a
From 6 valve leaflet cultures, one gave positive result for Rhodotorula mucilaginosa
49.7 ± 2.4 years; 41 patients were males. The median time between the onset of symptoms and diagnosis of IE was 35.8 ± 4.8 days. The most relevant clinical aspect was fever (88.7 %). New vascular regurgitation murmur was physically observed only in 18 (25.3 %) patients. Endocardial involvement was evidenced in 60 (84.5 %) patients, vascular phenomena in 21 (29.5 %) patients and immunologic phenomena in four (5.6 %) patients. Moreover, there were four (5.6 %) cases of arterial embolism, two (2.8 %) mycotic aneurysms and one (1.4 %) of Janeway lesions.
Two-dimensional transthoracic (TTE) or transesophageal echocardiography TEE) of the 71 patients revealed a mean vegetation size of 1.4 ± 0.2 cm. The valve most frequently compromised was the mitral valve (48.3 %). Most IE episodes occurred in the native valve (90.1 %). Various types of comorbidities were identified (Table 2): 24 (33.8 %) patients with kidney failure, 20 (83.3 %) of which were undergoing hemodialysis, Diabetes mellitus (N = 11; 15.5 %), neoplasia (N = 7; 9.8 %), HIV (N = 3; 4.2 %), solid organs transplants (N = 3; 4.2 %) and autoimmune diseases (N = 2; 2.8 %). Structural heart disease was observed in 37 (52.1 %) patients. The main complications of IE were 28.1 % congestive heart failure, 19.7 % sepsis, 15.5 % metastatic infections, 11.2 % stroke, 9.8 % abscess and 9.8 % septic embolization. In this IE cohort, the in-hospital mortality rate was 46.4 % and valve replacement was done only 16.9 % of patients (Table 1). The main source of IE was intravascular catheter (54.9 %). A pathogenic microorganism was isolated from blood cultures in 60 patients (84.5 %) with IE. Staphylococcus aureus was the most frequent etiological agent (30 %), followed by Enterococcus spp. (26.7 %), Streptococcus spp. (25.0 %) and coagulase-negative Staphylococci (8.3 %). The main antibiotics prescribed were: aminoglycoside (61.9 %), aminopenicillins (46.5 %), vancomycin (26.7 %), oxacillin (21.1 %) (Table 3). Streptococcus spp. (45.1 %) was the predominant cause of CAIE and S. aureus (32.5 %) and Enterococcus spp. (27.5 %) were the most frequent causes of HAIE. A total of 31 (43.6 %) community-acquired infective endocarditis (CAIE) cases and 40 (56.4 %) healthcare-associated infective endocarditis (HAIE) cases were observed (Table 2). The prevalence of methicillin-resistant S. aureus (MRSA) was 5.5 %. The sole case of infection due to MRSA USA 400 was associated with hemodialysis catheters and, therefore, classified as HAIE. This CA-MRSA strain presented SCCmec type IV, negative to PVL genes, vancomycin MIC = 4 lg/ml by E-test, and 2 lg/ml by broth microdilution [10]. Furthermore, there were two HAIE cases due to vancomycin-resistant Enterococcus (VRE) strains (with vancomycin MIC [32 and MIC C64, respectively) in patients that suffered from kidney failure. Tricuspid valve involvement and chronic renal insufficiency were more frequent among HAIE patients than CAIE patients (p \ 0.001) (Table 2). In our analysis, the risk factors related to in-hospital mortality in IE patients were age being over 45 years old (OR: 3.4; 95 % CI: 1.03–11.24; p = 0.04) and chronic renal insufficiency (OR: 38.3; 95 % CI: 3.2–449.3; p = 0.004) (Table 4). The inhospital mortality rate associated with specific etiology of IE was: Streptococcus spp. (N = 3; 3 %), negative
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P. V. Damasco et al. Table 4 Multivariate analysis of infective endocarditis (IE) in-hospital mortality Characteristic
OR (95 % CI)
p value
Age [45 years
3.4 (1.03–11.24)
0.04
Chronic renal insufficiency
38.3 (3.2–449.3)
0.004
OD odds ratio; 95 % CI confidence interval
Staphylococci (N = 4; 12.1 %), S. aureus (N = 7; 21.2 %), Enterococcus spp. (N = 8; 24.2 %). The lower mortality rate was associated with Streptococcus spp. IE (p = 0.02). During this study (N = 71), ten (14.1 %) patients showed culture-negative endocarditis; five (50.0 %) CAIE and five (50.0 %) HAIE. Only two (20 %) patients had no fever. The median time between the onset of symptoms and diagnosis of culture-negative endocarditis was 29.2 (4–61) days and median age was 54.5 years. The in-hospital mortality in this IE category was 9.8 % (OR; 3.5; IC 95 %; 0.8–15.2; p = 0.08).
Discussion The etiology of IE varies according to region, but the International Collaboration on Endocarditis-Prospective Cohort Study [20] has found the most frequent microorganism to be S. aureus in industrialized countries. In developing countries the most frequently found microorganisms were: S. aureus (18–48 %), Streptococcus viridans (20–24 %) and Enterococcus spp. (1–15 %) [2, 3, 21]. This cohort study revealed a prevalence of 56.4 % of HAIE and 43.6 % of CAIE in two main University Hospitals in Rio de Janeiro, Brazil. S. aureus (30 %) was the predominant cause of the IE, 32.5 % of the HAIE and 16.1 % CAIE. Streptococcus spp. were most commonly associated with CAIE (p \ 0.001) and structural heart disease was most present in this group of patients (p = 0.02). Moreover, Enterococcus spp was isolated in 26.7 % blood cultures, making it the second most frequent agent in our study. Similar to other developing countries [11], the higher incidence of S. aureus and Enterococcus spp. was probably due to the fact that this study was conducted in tertiary care centers. Similar to the results reported from other developing countries [18, 19]; in the present study, most (57.7 %) of the patients were males, and the mean age of the population was 49.7 years. In a previous study developed in Minas Gerais, Brazil [3], a total of 62 cases of IE was observed. Most (63 %) of the patients were also males and the mean age of the population was 45 years. Pathogenic microorganisms were currently isolated from blood cultures in
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higher number (N = 60) of cases when compared with the data (N = 40) observed in Minas Gerais survey. In that opportunity, S. aureus (48 %) and Streptococcus viridans (20 %) were found the most common causative agent of IE. Regarding MDR isolates, the authors also reported 32 % cases of IE due to MRSA. Conversely, the prevalence of MRSA in our study was very low (5.5 %). In the present cohort of 71 patients, there were only three cases of HAIE due to MDR pathogens: one case due to CA-MRSA and two cases due to VRE that occurred in patients with renal insufficiency. The main source of IE in this cohort was intravascular catheter. Invasive medical technology has led to an increase in the incidence of HAIE, and careful management of vascular devices is essential to minimize the risk of bacteremia leading to HAIE [13, 17]. Tricuspid valve and renal chronic insufficiency were most frequently observed in HAIE patients than in CAIE patients. The scenario of IE studies in developing countries is the relatively young patient that presents rheumatic heart disease, fact which remains the predominant predisposing condition for IE in developing countries [22]. This is in contrast to industrialized countries where the majority of patients present beyond the fourth decade, which reflects increased healthcare-associated infections [23]. In the contemporary population-based studies of IE in industrialized countries, in-hospital mortality ranges from 15 to 22 % increased healthcare-associated infections and less rheumatic heart disease as risk factors [24, 25]. The present day morbidity and mortality of patients with IE in developing countries are the same of the early twentieth century in North America and Europe [1–4, 23]. Our observations are a consequence of medical progress in Brazil [20, 22, 26], but Streptococcus spp. is still the pathogen most associated with CAIE and structural heart diseases were more present in this patient group. The analysis of risk factors revealed that in-hospital mortality in IE episodes was related to the age over 45 years old (OR 3.4; 95 % CI 1.03–11.24; p = 0.04) and renal insufficiency (OR 38.3; 95 % CI 3.2–449.4; p = 0.004). Some microorganisms of fastidious growth found in the human microbiota as part of genitourinary, oral and intestinal tract may act as opportunistic pathogens and some are often associated with negative blood cultures [22, 23, 27, 28]. We had 10 (14.1 %) patients with culturenegative endocarditis in our series of 71 patients; 5 (50.0 %) CAIE and 5 (50.0 %) HAIE. Even though we observed a high mortality rate in this group, we did not observe statistical significance (p = 0.2). Although true culture-negative endocarditis is rare in industrialized countries, studies on IE in developing countries show a high prevalence (10–55 %) of culture-negative endocarditis. There have been various reasons proposed for this
Infective endocarditis in Rio de Janeiro, Brazil
theme. The most widely accepted being administration of antibiotics prior to the diagnosis of IE [22]. Cryptic endocarditis was caused by indolent, slow-growing microorganisms of the HACEK group and Bartonella spp., Legionella spp., Coxiella burnetti, Chlamydophila psittaci, has been reported [23]. Moreover, an observational cohort study at two university centers in Germany, during an 8-year period (2000–2007) showed Tropheryma whipplei as the most common pathogen associated with culturenegative endocarditis [27]. Molecular amplification methods may be needed for detection of these organisms as well as other less common etiologic agents. At this moment we have not screened for such species. Earlier studies also indicated the destructive feature of CAIE attributable to Corynebacterium diphtheriae in Rio de Janeiro [5]. Similar to data of IE studies in Hong Kong [28], a prevalence of 14.1 % culture-negative endocarditis cases were observed in our series. In this opportunity, only one case of culturenegative endocarditis due to Abiotrophia defectiva was diagnosed by molecular methods [29].
Conclusion In Rio de Janeiro University Hospitals, S. aureus (30 %) was the predominant cause of IE, 32.5 % was from HAIE and 16.1 % from CAIE. Streptococcus spp. (45.1 %) was the main etiology of CAIE (p = 0.001). There were 3.2 % with CAIE due to coagulase-negative Staphylococci. S. aureus (38.2 %) and Enterococcus spp. (27.5 %) were the most frequent cause of HAIE; the prevalence of methicillin-resistant S. aureus in this cohort was 5.5 %. In our analysis of risk factors related to in-hospital mortality in IE patients were: their age being over 45-years-old and chronic renal insufficiency. Further studies remain necessary to determine the etiology of culture-negative endocarditis in Rio de Janeiro; especially, in tertiary care centers. Acknowledgments This work was supported by CAPES, FAPERJ, CNPq and SR-2/UERJ. Conflict of interest The authors have no disclosures or conflicts of interest to report.
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