Clinical and laboratory findings in a series of cases of infective endocarditis

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1 /03/79-05/423 Jornal de Pediatria Copyright 2003 by Sociedade Brasileira de Pediatria Jornal de Pediatria - Vol. 79, Nº5, ORIGINAL ARTICLE Clinical and laboratory findings in a series of cases of infective endocarditis Carla A.Z. Pereira, 1 Scheila C.G.P. Rocio, 1 Maria-Fátima R. Ceolin, 2 Ana-Paula N.B. Lima, 2 Felippe Borlot, 3 Roberto S.T. Pereira, 4 Sandra F. Moreira-Silva 5 Abstract Objective: To describe clinical and laboratory data of infective endocarditis (IE) in 28 children from Vitória, state of Espírito Santo, Brazil. Methods: We reviewed the medical records of 28 children aged 18 years and under admitted to the Infectious Diseases Unit of Nossa Senhora da Glória Children s Hospital with a diagnosis of IE from January 1993 to December The diagnosis of IE was based on the criteria established by the Duke Endocarditis Service (Duke University, Durham, North Carolina, USA): positive blood cultures and echocardiogram (primary criteria); and fever, history of heart disease, recent heart murmur, and vascular and immunological phenomena (secondary criteria). A specific protocol was filled out by interns and medical students and revised by physicians from the hospital medical team to obtain the following data: age, sex, clinical and laboratory findings, and results of transthoracic echocardiography. In all cases, three blood samples were collected under aseptic conditions and inoculated in aerobic and anaerobic environments. The samples were then incubated at 37º C and tested with the Vitec System automatized system (Biolab). Results: Among 28 patients, 16 were boys. Age was between 3 and 180 months (mean 70.6±59.2 months). Most children (68%) came from the metropolitan area of Vitória, and half presented a history of cardiopathy. The most frequent clinical findings which led to suspicion of IE were: prolonged fever in all cases, new or changing regurgitant murmur (67.9%), dyspnea (57.1%), hepatomegaly (57.1%), vascular phenomena (32.2%), splenomegaly (28.6%), and Osler s nodes (7.1%). Blood cultures were positive in 16 patients (57.1%), and community-acquired S. aureus was the most frequently isolated pathogen (56.6%). Despite the treatment, fever persisted for 2.5 to 30 days (median = 18.0 days). Mean leukocyte count at admission was 11,657±7,085mm 3. Transthoracic echocardiography showed endocardial lesion in all patients, evidencing vegetations in the tricuspid valve (25%), mitral valve (25%), and intraventricular communication border (28%). Thirteen (46.4%) children presented concomitant sepsis and three (10.7%) developed hospital-acquired infection. There was one death (3.6%). Conclusions: IE in our country is frequent among children younger than 2 years with congenital cardiopathy. Community-acquired S. aureus was the most frequently isolated microorganism in children with no previous cardiac lesion. J Pediatr (Rio J) 2003;79(5):423-8: Overweight, obesity, prevalence. 1. Resident physician, Hospital Infantil Nossa Senhora da Glória, Vitória, ES. 2. MD, Infectious Diseases Service, Hospital Infantil Nossa Senhora da Glória, Vitória, ES. 3. Medical student, Escola Superior de Ciências da Santa Casa de Misericórdia, Vitória, ES. 4. MD, Chief, Pediatric Heart Disease Service, Hospital Infantil Nossa Senhora da Glória, Vitória, ES. 5. Master s Degree. Coordinator, Medical Residence Program in Pediatric Infectious Diseases, Hospital Infantil Nossa Senhora da Glória, Vitória, ES. Manuscript received Oct , accepted for publication Jul

2 424 Jornal de Pediatria - Vol. 79, Nº5, 2003 Infective endocarditis in children Pereira CAZ et alii Introduction Infective endocarditis is defined as an inflammatory process of the endocardium of a valve or chamber, on a septal defect, or the chordae tendineae, as a result of an infection by bacteria, virus, fungus or mycobacteria and rickettsias, which in the majority of cases occurs in people with pre-existing abnormalities of the cardiovascular system. 1,2 It is responsible for around 0.2 to 0.5% of all pediatric hospital admissions and is a significant cause of mortality (20-64%) among children and adolescents despite advances in treatment and prophylaxis with antimicrobial agents. A number of different factors affect prognosis, clinical parameters, the type of microorganism involved and the presence of a prosthetic heart valve. 2-4 In the absence of a previous cardiac lesion the disease is considered rare in children. 5,6 In adults it is common among intravenous drug users and people more than fifty years old. 4 In children a growing increase in the number of cases have been reported, principally in newborns and young infants, with a concomitant change in the bacterial profile. The prevalence of Staphylococcus aureus and other bacteria which were previously less often identified with Infective endocarditis. 4,6 In these patients, endocarditis is acute and generally associated with congenital cardiac defects. Cases of classic subacute endocarditis, caused by Streptococcus viridans have reduced due to the reduction in the prevalence of rheumatic fever and its cardiac sequelae. In addition to the reduction in the number of rheumatic fever cases, improvements to the care of high risk newborns, an increase in invasive procedures and early surgical interventions in congenital cardiopathies have contributed to an increase in the number of patients in this age group exposed to the risk of Infective endocarditis. 2,4 Although the disease is uncommon, it is serious and is considered a significant cause of morbidity and mortality in children and therapeutic success depends upon early and precise diagnosis. Despite authors having described a number of different diagnosis criteria based on clinical and pathological parameters, the criteria currently most accepted are the Duke criteria which include echocardiographic examination parameters 7,8 (Table 1). The value of this examination has been questioned, but its validity has been confirmed if a bidimensional color Doppler echocardiogram is used and the cardiologist has experience in interpreting the results. With the publication of new Infective endocarditis diagnosis criteria by the Endocarditis Service at Duke University, it is now considered that the two main criteria for certain diagnosis of Infective endocarditis are multiple positive blood cultures for typical germs and echocardiogram evidence of myocardial lesions and/or vegetation growth on heart valves, intramyocardial abscesses, or recent partial decomposition of a prosthetic valve. 7,8 Table 1 - Duke criteria for the diagnosis of infective endocarditis 4,7 Major criteria Positive blood culture for IE Typical microorganism for IE from two isolated blood cultures: Streptococcus viridans, Streptococcus bovis, HACEK group or Staphylococcus aureus and Enterococcus sp acquired in the community without primary focus Persistent positive blood cultures Evidence of endocardiac lesion, positive echocardiogram for IE New regurgitant murmur Minor criteria Predisposition: previous heart lesion Fever higher than 38 ºC Vascular phenomena (eg.: Janeway s lesions) Immunologic phenomena (eg.: Osler s nodes) Suggestive microbiologic findings: positive blood culture, without major criteria Echocardiogram: consistent with IE, without major criteria HACEKgroup = Haemophilus sp; Actinobacillus actinomycetem comitans; Cardiobacterium hominis; Eikenella corrodens; Kingella kingae. The use of echocardiography in adults has confirmed its utility, especially the transesophageal echocardiogram, since this offers greatly amplified image observation fields. In children, the transesophageal echocardiography examination has limited uses for which reason the transthoracic echocardiogram examination is routinely used. 2,9,10 As Infective endocarditis in children is a heterogeneous entity, its management also requires careful criteria based on laboratory and clinical evidence in addition to the echocardiographic criteria. 11,12 As studies of transthoracic echocardiogram in Infective endocarditis of children have reported variable results in terms of diagnostic sensitivity, we propose to describe a series of 28 cases of Infective endocarditis treated at the Nossa Senhora da Glória Children s Hospital, in Vitória-ES, with emphasis on clinical and laboratory findings and transthoracic echocardiogram examinations, in order to verify the characteristics of the disease in our locale. Patients and Methods All children, under eighteen, diagnosed with Infective endocarditis, and interned at the Infectious Diseases Service at the Nossa Senhora da Glória Children s Hospital, Vitória - Espírito Santo, during the period between January 1993

3 Infective endocarditis in children Pereira CAZ et alii and December 2001 were included. The criteria for a diagnosis of Infective endocarditis were those published by the Duke Endocarditis Service (Duke University, Durham, North Carolina - USA), 7 in which one of the main diagnosis parameters is the demonstration of echocardiographic evidence of a myocardial lesion and/or vegetation on heart valves, intramyocardial abscesses or recent partial decomposition of a prosthetic valve. The Nossa Senhora da Glória Children s Hospital is a public hospital, part of the Espirito Santo state network where its Pediatric Infectious Diseases and Cardiology Services are centers of excellence, also caring for patients from the south of the state of Bahia and the east of the state of Minas Gerais. Using a specialized pro forma, filled out by the resident doctors and academics at the Infectious Diseases Service, and revised by the team doctors, sex, clinical and laboratory findings and the results from transthoracic echocardiography were recorded for each of the 28 children who fulfilled the clinical and laboratory criteria for a diagnosis of Infective endocarditis. All of the laboratory examinations were performed at the routine hospital laboratory. In all cases blood cultures were carried by collecting blood (three samples) under aseptic conditions and were inoculated in aerobic and anaerobic media, incubated at a temperature of 37 ºC and tested with an automated system - Vitec System (Biolab). The study was submitted to and approved by the Committee for Ethics and research at the Nossa Senhora da Glória Children s Hospital. Jornal de Pediatria - Vol. 79, Nº5, (28.6%) and small, painful intradermal nodes on the pads of the fingers (Osler nodes, 7.1%). Blood cultures were positive in 16 (57.1%) of the 28 cases. Community acquired Staphylococcus aureus was the most frequently isolated germ (9/ %). There was a statistically significant difference in the frequency of the different types of germ isolated from children older or younger than 24 months: Staphylococcus aureus was found in the eight cases which involved children older than 24 months, without previous cardiac lesions, and in only one of the cases involving children younger than 24 months. The other seven children with positive blood culture results were all younger than 24 months old and the microorganisms isolated from them were: Streptococcus viridans in two cases (12.5%), Enterobacter sp in four cases (25.5%) and Candida tropicalis in one case (6.2%). There was persistent fever, despite antimicrobial treatment, lasting between 2.5 and 30 days, with a median of 18.0 days. On admission leukogram had a wide variety of values for total number of leukocytes (average value of 11,657+7,085 mm 3 ), but with obvious predominance of young neutrophils in all cases if the average values were compared on admission and discharge (p < 0.000) (Table 3). Transthoracic echocardiogram showed endocardiac vegetation in all cases, especially in the tricuspid (25.0%) and mitral (25.0%) valves and at the limits of intraventricular communication (28.6%) (Figure 1). Thirteen (46.4%) children presented concomitant sepsis and three (10.7%) developed nosocomial infections. There was one death (3.6% of cases). Statistical analysis Statistical analysis was performed using the SPSS- CDC Inc for Windows software program (Statistical Package for the Social Sciences of Centers Diseases Control - USA. Release ). Averages were compared using the paired t test or with the Wilcoxon test. Proportions were compared with the Yates corrected Chi-square test, or with Fisher s exact test. Results Data on age, sex, clinical and bacteriological characteristics and the principal echocardiogram findings are shown in Table 2. The previous cardiopathies observed were 12 congenital cardiopathies (85.7%) and two rheumatic cardiopathies (14.3%). The most clinical findings which most often led to a suspicion of Infective endocarditis, and so resulted in the echocardiogram, were: prolonged fever (100%), heart murmur (67.9%), dyspnea (57.1%), hepatomegaly (57.1%), vascular phenomena (32.2%), including small erythematous lesions or painless hemorrhaging on the palms of the hands or soles of the feet (Janeway lesions), splenomegaly Discussion A number of Pediatric Cardiology Units have reported the observation that cases of endocarditis infectious are increasing, primarily among children under two years old, mainly due to the increase in survival rates among children who have had surgery for cardiopathies resulting from the improved care afforded by intensive care units. 4,6 Taking into account the fact that in pediatrics Infective endocarditis is a heterogeneous entity, we must look at all possible criteria, from laboratory findings, echocardiographic and all criteria already described as defining clinical criteria of the disease, 5,7,11 summing up all possible effort in an attempt to achieve a definite diagnosis with urgency, permitting early and adequate treatment, thus reducing the mortality of children with endocarditis. Recent publications demonstrate a significant change in pediatric Infective endocarditis, alterations in prevalence, age distribution and the microorganisms involved as causative agents. 3,4,6 Our results, similar to results reported in literature, demonstrate a changing Infective endocarditis epidemiological profile in our locale too. Fifty percent of cases occurred in newborns and infants, and Staphylococcus aureus was frequently isolated from positive blood cultures. Although blood cultures were only positive in 57.1% of

4 426 Jornal de Pediatria - Vol. 79, Nº5, 2003 Infective endocarditis in children Pereira CAZ et alii Table 2 - Main demographic, clinical, echocardiographic and laboratorial data of 28 cases of infective endocarditis, at HINSG, from 1993 to 2001 Case Age Sex Previous heart Sepsis Murmur Petechiae Hepatomegaly Microorganism Vegetations Evolution (months) disease 1 6 F + C. Cong. + + Entero IVC border discharge 2 41 F + + Staphilo RV end. discharge F + + Staphilo Mitral discharge 4 5 F + C. Cong. + Strepto IVC border discharge 5 6 F + + Entero LV end. discharge 6 5 M + C. Cong. + + Staphilo IVC border discharge F Staphilo Tricuspid discharge M Staphilo Lung discharge F Negative Mitral discharge M + C. Cong Entero IVC border discharge 11 3 M + Entero Tricuspid discharge 12 8 M + C. Cong C.tropic. IVC border discharge M + Negative Mitral discharge M + C. Cong. + Negative Lung discharge M Strepto Mitral discharge M + + Negative Tricúspide discharge M + C. Reum. + + Negative Mitral discharge M Staphilo Mitral discharge M + Staphilo Tricuspid discharge M + C. Cong. + + Staphilo Tricuspid discharge F + + Staphilo RV end. discharge M + Negative Tricuspid discharge F + C. Cong. + Negative IVC border discharge F + C. Reum. + + Negative Mitral discharge M + C. Cong. + Negative IVC border discharge F + C. Cong Negative Tricuspid discharge 27 3 F + C. Cong. + + Negative Lung death M + C. Cong. + Negative IVC border discharge End = endocardium, + present, absent % END = endocardium, IVC = intraventricular communication. Figure Mitral LV End. Tricuspid Limit of IVC Pulmonary RV End. < 24 months > 24 months Location of the lesions observed on the echocardiogram in 28 cases of infective endocarditis cases, the results reinforce the idea of the elevated prevalence of S. aureus as the etiologic agent in acute Infective endocarditis in our environment. In contrast we do not have an adequate explanation for the low frequency of positive blood in this series of cases, bearing in mind that blood samples were collected in a an apparently adequate manner. It is possible that previous antibiotic use is the main factor as many patients arrive at the Children s Hospital having been transferred from other Health Units. The role of transthoracic echocardiograms as a means of diagnosis for children with a clinical suspicion of Infective endocarditis remains controversial and is the cause of disagreement between a number of authors. 5,7,8,11 Some authors consider the method to be of too low a sensitivity to be a method for diagnosing EI in patients with few of the clinical criteria of the disease, 9,12 however others believe

5 Infective endocarditis in children Pereira CAZ et alii Jornal de Pediatria - Vol. 79, Nº5, Table 3 - Comparison of hemoglobin, leukocytes and neutrophils values in rods of 28 cases of infective endocarditis on admission and discharge, HINSG, Statistics Hemoglobin Leukocytes No. of rods Admission Discharge Admission Discharge Admission Discharge Mean ,657 8, Median ,550 9, Standard deviation ,085 2, Range Minimum value , Maximum value ,000 15, p 0.861* 0.192* * paired test Wilcoxon s test (variable without normal distribution). that the use of echocardiography in the evaluation of children with a clinical suspicion of endocarditis has ample applications, primarily because in pediatrics, the transthoracic echo offers an excellent field. 4,11 In the present study characteristic alterations to the results from this examination were one of the inclusion criteria. Nevertheless it is important to remember that cases in which the transthoracic echocardiogram was negative and which did not meet the criteria for a diagnosis of Infective endocarditis could still have had lesions from Infective endocarditis, without obvious evidence, and were treated as sepsis and excluded from the Infective endocarditis group. The microbiology of Infective endocarditis in children has changed considerably as is reported by a number of authors, with a decrease in the number of cases due to infections by Streptococcus viridans and the appearance of new etiological agents which were uncommon in past decades. An important factor in this change is the increased survival rate of children with congenital cardiopathies, and another is the increased incidence of staphylococcal infections. 6,11,12 We too observed this fact and our results demonstrate that Infective endocarditis was frequent among children less than two years old and those with congenital cardiopathies. They also demonstrate that community acquired Staphylococcus aureus was frequently isolated as an infecting microorganism in children with no previous cardiac lesions. Acknowledgements Thanks to Dr. Alba Lília de Almeida Leite, pediatrician at the Infectious Diseases Service at the Nossa Senhora da Glória Children s Hospital, for help with monitoring cases and to Dr. Fausto Edmundo Lima Pereira, Professor and Doctor at the Infectious Diseases Center at the Universidade Federal do Espírito Santo, for help in the final revision of the text and for continuous support for research and scientific production. Thanks also to the staff at the Medical Records Storage Service at HINSG, for their dedication. References 1. Estlow MM. Prevention of infective endocarditis in the pediatric congenital heart population. J Pediatr Nurs 1998;24: Karchmer AW. Endocardite infecciosa. In: Braunwald E, editor. Tratado de Medicina Cardiovascular. 5th ed. São Paulo: Roca; p Mansur AJ, Grinberg M, Cardoso RHA, da Luz PL, Bellotti G, Pileggi F. Determinants of prognosis in 300 episodes of infective endocarditis. Thorac Cardiovasc Surg 1996;44: Foronda A, Foronda G, Camargo LFA. Endocardite Infecciosa. In: Ebaid M, editor. Cardiologia em Pediatria. 1st ed. São Paulo: Roca; p Sable CA, Rome JJ, Martin GR, Patel KM, Karr SS. Indications for echocardiography in the diagnosis of infective endocarditis in children. Am J Cardiol 1995;75: Ashkenazi S, Levy O, Blieden L. Trends of childhood infective endocarditis in Israel with emphasis on children under 2 years of age. Pediatr Cardiol 1997;18: Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994;96: Bayer AS, Bolger AF, Taubert KA, Wilson W, Steckelberg J, Karchmer AW, et al. Diagnosis and management of infective endocarditis and its complications. Circulation 1998;98: Aly AM, Simpson PM, Humes RA. The role of transthoracic echocardiography in the diagnosis of infective endocarditis in children. Arch Pediatr Adolesc Med 1999;153:950-4.

6 428 Jornal de Pediatria - Vol. 79, Nº5, Barreto J, Waderlinder J, Reitich J. Hallarzgos ecocardiográficos y de laboratorio en pacientes pediátricos con endocarditis infecciosa. Bol Hosp Ninos J M de los Rios 1998;34: Li JS, Milazzo-Jr AS. Bacterial endocarditis in infants and children. Clin Infect Dis 2000;30: Heper G, Yorukoglu Y. Clinical, bacteriologic and echocardiographic evaluation of infective endocarditis in Ankara, Turkey. Angiology 2002;53: Infective endocarditis in children Pereira CAZ et alii Corresponding author: Sandra F. Moreira-Silva Rua Natalina Daher Carneiro, 55/302 - Jardim da Penha CEP Vitória, ES, Brazil Tel.: +55 (27) Fax: +55 (27) / sanfag@zaz.com.br