Infective endocarditis is an uncommon condition, but when encountered, it is associated with a high degree of morbidity and mortality. Despite medical advances over the past half century after Osler’s first comprehensive description, its course has remained unchanged, with over four-fifths of patients suffering a serious complication from embolic and immunologic phenomenons.1 In a review made at the turn of the last century,1 the mortality rate remained at approximately one-fifth, and just over one-fifth of patients required emergency surgery. The incidence of infective endocarditis is approximately 2 cases per 100,000 patients per year.2 It occurs less commonly in children, at between 0.8 and 3.3 for each 1000 admissions to hospital,3 but does tend to occur in children with congenital cardiac disease.4, 5
Since the clinical manifestations of infective endocarditis are diverse, and its presentation may vary according to several factors, such as the duration of the illness, the microbiological aetiology, the valve involved, the age of the patient, and the place of acquisition of infection, diagnosis and prediction of outcomes can be very difficult. Recent studies have shown remarkable changes in the spectrum of infective endocarditis. These changes are attributable to changes in the substrate population, the introduction of more accurate diagnostic criterions, better diagnostic facilities, the availability of a range of antibiotics, and aggressive surgical approaches.6
In this report, we describe our own small experience of infective endocarditis in children who presented with different clinical manifestations over the past 2 years, and who were treated surgically.
Patients and methods
We analysed retrospectively the records of all children aged below 16 years who were admitted for surgical treatment of infective endocarditis between May 2003, and March 2005, reviewing the demographic details, clinical presentation, microbiological and echocardiography data, operative findings, and outcome. Investigative work-up in all patients had included assessments of haemogram, total and differential white cell count, acute-phase reactants, liver functions, urine examination, blood cultures, radiological examination, electrocardiography, and echocardiography. Endocarditis was defined according to the modified Duke criterions.7
There were 8 female and 1 male patient. The mean age was 7.8 years, ranging between 4.5 months and 16 years. Congenital cardiac disease was the commonest predisposing factor, encountered in 8 patients, with chronic haemodialysis being present in the other. Prior surgery had been performed in 5 patients, with 2 patients with tetralogy of Fallot and pulmonary atresia undergoing staged unifocalization and closed reconstruction of the right ventricular outflow tract, 1 having closure of a ventricular septal defect, 1 having repair of double outlet right ventricle and pulmonary stenosis, and 1 patient having creation of an arteriovenous fistula for haemodialysis. The other patients, who had not undergone any previous invasive procedures had ventricular septal defect and subaortic shelf in 1, ventricular septal defect, patency of the arterial duct and pulmonary hypertension in 1, and patency of the arterial duct in the last. The demographic, clinical and laboratory data of the patients are presented in Table 1.
Table 1. Clinical data of patients.
The time interval from the first symptoms to the referral ranged between 2 and 6 months. All the patients lived in the vicinity of centers providing health care, albeit that none of them had undergone regular check-ups, even though 4 had undergone prior cardiac surgery. Dyspnoea was the most common presenting feature, seen in all 9 patients, followed by fever in 7 patients, cough in 5 patients, increased cyanosis in 2 patients, and systemic embolization in 1 patient. Non-specific complaints of fatigue, weight loss, myalgia, and loss of appetite or poor feeding were observed in all patients. Infection of a catheter used for haemodialysis in 1, and infection of the lower respiratory tract in 3 patients, were the primary focuses of infection, with no focus identified in the remaining 5 patients.
Among the laboratory parameters, anaemia and raised erythrocytic sedimentation rate were present in all patients, while leucocytosis was present in 7 patients. Various antibiotic treatments had been prescribed for 7 patients prior to their admission with suspected infective endocarditis. Despite hospitalization, usage of antibiotics could not be managed on a regular basis in most patients because of the state of their health care insurance policies, and the socioeconomic state of their families. The duration of antibiotic therapy was irregular, and ranged between 3 weeks and 2 months before referral. Levels of C reactive protein were positive at the time of the first admission to the hospital in 7 patients, but decreased with the antibiotic treatment, which was another reason for the irregular use of antibiotics.
Blood cultures were positive in 3 patients, but remained negative in the other 6 patients, despite repeat blood cultures and serological evaluation. The causative organism was isolated from the graft material in 1 patient. Methicillin resistant Staphylococcus aureus sensitive only to vancomycin was the infecting agent in all of these patients. The duration of postoperative antibiotic therapy was adjusted according to the levels of C reactive protein and clinical improvement, and ranged between 5 weeks and 3 months. Clinical improvement without the C reactive protein becoming negative was accepted as an indication to terminate antibiotic therapy in 1 patient.
A complete cross-sectional and Doppler transthoracic echocardiographic examination was performed in all patients, with detailed examination of all cardiac structures. Transoesophageal echocardiography was performed in 4 patients, with vegetations found in three patients located on the mitral, aortic, and tricuspid valves, respectively (Fig. 1). Obstruction of the right ventricular outflow tract was found in 2 patients with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries. Dehiscence of the patch used to close a ventricular septal defect was detected in 2 patients with signs of congestive heart failure. Radiological examination revealed pulmonary plethora in 4 patients (Fig. 2), and pseudoaneurysmal formation in another two (Figs 3 and 4).
Figure 1. Echocardiogram showing vegetation of mitral valve in patient (patient 1) with renal insufficiency. LA: left atrium; LV: left ventricle; RA: right atrium; RV: right ventricle; K: vegetation.
Figure 2. Chest x-ray showing pulmonary plethora in patient (patient 1) with mitral insufficiency.
Figure 3. Computed tomography scan of patient (patient 6) with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries who had staged unifocalization and closed reconstruction of the right outflow tract, showing pseudoaneursym of the graft.
Figure 4. Pseudoaneursym of the graft on the right ventricular outflow tract in patient (patient 3) with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries who had staged unifocalization and closed reconstruction of the right outflow tract.
The most common indication for surgery was congestive heart failure, seen in 6 patients, dehiscence of a patch in 2 patients, uncontrolled sepsis in 7 patients, dehiscence of a graft and pseudoaneursym of the right ventricular outflow tract in 2 patients, and recurrent endocarditis in 3 patients. Acute cardiorespiratory compromise was encountered in 5 patients, with 1 of these undergoing surgery urgently after cardiopulmonary arrest.
The interval between the previous operations and the surgery for infective endocarditis ranged between 2.5 months and 2 years. All patients were approached through a median sternotomy, under cardiopulmonary bypass, with moderate hypothermia and cardioplegic arrest. The surgical procedures were removal of vegetations and replacement of the mitral valve, removal of vegetations from the tricuspid valve and repair of a ventricular septal defect with a pericardial patch, excision of a pseudoaneursym on the right ventricular outflow tract, revision of the right ventriculotomy, and homograft replacement of right ventricular outflow tract, removal of vegetations from the aortic valve, excision of a discrete subaortic shelf and closure of a ventricular septal defect with a pericardial patch, ligation of the patent arterial duct, and closure of a ventricular septal defect with a pericardial patch accompanied by ligation of the patent arterial duct.
A patient with tetralogy of Fallot and pulmonary atresia, aged 16 years, died in hospital due to uncontrolled sepsis with multiorgan failure after surgery for a pseudoaneursym of the right ventricular outflow tract. Another patient died in the second postoperative month due to cardiac failure after relapse of endocarditis with negative blood cultures following removal of vegetations from the aortic valve, excision of a discrete subaortic shelf, and closure of a ventricular septal defect with a pericardial patch.
Discussion
Infective endocarditis is an uncommon infection in childhood. When encountered, it is found mostly in patients with congenital cardiac malformations.3–5 Although said to be predominant in male populations, in our series there was a female predominance. An aortic valve with two leaflets is said to be the most frequent predisposing condition, followed by ventricular septal defect, patency of the arterial duct, and tetralogy of Fallot.8
The persisting substantial risk associated with infective endocarditis may reflect a continuing lack of pathognomonic diagnostic criterions, a change in the microbial spectrum, or differences in the characteristics of the patients.9 Despite the concurrent introduction of new diagnostic tools, diagnosis of infective endocarditis, with its multiple clinical and morphological manifestations, remains a challenging task.10
Echocardiography is useful in identifying the size, shape, location, and mobility of valvar vegetations, the presence of valvar dysfunction, and cardiac function, and is usually sensitive in up to four-fifths of infected children.11 Although transthoracic echocardiography reveals better images in children than adults, intracardiac vegetations may not be detected if they are smaller than 1 millimetre. Thus, failure to detect vegetations by transthoracic echocardiography does not exclude infective endocarditis.12 Transoesephageal echocardiography has been increasingly used intraoperatively in children, but as far as we know, studies of its value in children with infective endocarditis have yet to be published. It also appears that transoesophageal echocardiography is less valuable for the detection of right-sided vegetations, these be seen more frequently seen in children.13 Furthermore, echocardiographic findings have been most often negative in children with complex cyanotic heart disease.14
Although proper diagnosis and appropriate therapeutic decisions follow positive blood cultures, even repeated blood cultures and serological evaluation may not identify the causative organism. Blood cultures remain negative in up to one-third of all cases of infective endocarditis, a feature which often delays diagnosis and onset of treatment, with profound impact on the clinical outcome.10 Grijalva et al.15 showed that, in over nine-tenths of patients with negative blood cultures, the causative pathogen could be detected using a molecular approach, while all controls remained negative. Two-thirds of our patients had negative blood cultures. Factors that influence the rate of negative cultures include prior use of antibiotics due to systemic infection or suspected diagnosis of a bacterial infection, the microbial agent having no, or limited, proliferation in conventional blood cultures, the microbial agents requiring special conditions for culture, or the infections being caused by fastidious or non-culturable pathogens.10 The clinical, echocardiographic, and radiological findings, therefore, are especially important in patients such as ours with few positive cultures and lack of peripheral signs.
Another important parameter in these patients is the level of C reactive protein. It is usually advised to continue antibiotic therapy until negative results are obtained in patients. Clinical improvement without the C reactive protein reaching negative levels in 1 of our patients, however, persuaded us to terminate the antibiotic therapy at the end of 2 months, and further follow-up of this patient was uneventful.
Many of these patients require surgical treatment, including those with prosthetic valvar endocarditis, antibiotic non-responsiveness, acute infection with rapidly developing heart failure, recurrent embolism, heart block caused by infection, and formation of abscesses.16 The goals of surgery are to eradicate the focus of infection, to repair endocardial destruction and cardiac defects, to prevent the development of complications, and prevent the relapse of infection.17 Combined medical and surgical treatment is generally considered the treatment of choice, especially in patients with staphylococcal endocarditis.12
Since infective endocarditis carries significant morbidity and mortality despite improvements in antimicrobial therapy and diagnosis, primary prevention is very important. Prophylaxis is recommended for all patients with unrepaired congenital heart defects, who have a higher risk for developing infective endocarditis. Patients with a previous history of endocarditis, and those with complex cyanotic heart disease or surgically constructed systemic-to-pulmonary shunts or conduits are at high-risk, and much more likely to develop a severe endocardial infection resulting in morbidity and mortality.14 Because some clinical manifestations may not be demonstrated by echocardiography, it is recommended that prophylaxis should be based on both the clinical and echocardiographic findings.18
Relapse of infective endocarditis usually occurs within 2 months after the end of clinically effective therapy. Infection with staphylococcus aureus, enterococcuses, and gram-negative organisms are associated with a high rate of relapse.19, 20 It is known that patients with symptoms of infective endocarditis of more than 3 months duration prior to treatment are at greater risk for relapse. The significant risk factors for recurrence in children include a previous episode of infective endocarditis, the presence of a prosthetic valve, and congenital cardiac disease.
In conclusion, despite advances in antimicrobial therapy and the diagnosis and treatment of complications, infective endocarditis continues to be responsible for substantial morbidity and mortality.21 Even with appropriate antibiotic prophylaxis, infective endocarditis may develop in individuals with underlying structural cardiac defects. There are few reports describing the epidemiology, clinical findings, modalities for treatment, prognosis of infective endocarditis occurring in children.22 Although now a very rare situation in developed countries, infective endocarditis is still one of the striking problems for cardiac surgeons in the developing world. We believe that our own small collection of patients seen over the past 2 years in which surgical treatment was performed will be helpful in guiding the clinical perspectives for those dealing with children with infective endocarditis. Infective endocarditis, self-evidently, can be devastating for the patients. Once suspected, therefore, patients must be referred immediately to the nearest specialized tertiary centre for health care. In addition, because of the lack of systems for primary health care in the developing countries, it is necessary to improve education of parents of patients who might be at high-risk for developing infective endocarditis due to all the reasons discussed in our review.
