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Archives of cardiovascular diseases
Volume 110, n° 12
pages 676-681 (décembre 2017)
Doi : 10.1016/j.acvd.2016.12.018
Received : 1 November 2016 ;  accepted : 22 December 2016
Clinical features and prognosis of infective endocarditis in children: Insights from a Tunisian multicentre registry
Aspects cliniques et pronostic de l’endocardite infectieuse de l’enfant : aperçu des résultats d’un registre multicentrique tunisien
 

Walid Jomaa a, b, , Imen Ben Ali a, b, Dorra Abid c, Samia Hajri Ernez d, Leila Abid c, Faten Triki c, Samir Kammoun c, Anissa Gharbi d, Oussama Ben Rejeb d, Abdallah Mahdhaoui d, Gouider Jeridi d, Mohamed A. Azaiez a, b, Aymen El Hraiech a, b, Khaldoun Ben Hamda a, b, Faouzi Maatouk a, b
a Cardiology B Department, Fattouma Bourguiba University Hospital, avenue 1er-Juin, 5000 Monastir, Tunisia 
b University of Monastir, Monastir, Tunisia 
c Cardiology Department, Hedi Chaker University Hospital, Sfax, Tunisia 
d Cardiology Department and Reseach Laboratory LR12SP09, Farhat Hached University Hospital, Sousa, Tunisia 

Corresponding author. Cardiology B Department, Fattouma Bourguiba University Hospital, avenue 1er-Juin, 5000 Monastir, Tunisia.
Summary
Background

Infective endocarditis (IE) is a rare condition in the paediatric setting. No data on the epidemiology and prognosis of IE in children are available from North African countries.

Aim

To investigate the epidemiological profile and prognosis of IE in children in Tunisia.

Methods

All patients aged18 years presenting with IE in three Tunisian tertiary care centres between January 1997 and September 2013 were included. Clinical features and 30-day and 6-month mortality rates were studied. Factors predictive of death at 6-month follow-up were determined.

Results

A total of 73 patients were included in the present study. The mean age was 12±4.8 years; 35 (50.7%) patients were male. Rheumatic heart disease (RHD) was the underlying heart disease in 17 (23.3%) cases and IE occurred in a structurally normal heart in 36 (49.3%) cases. Staphylococcus species were isolated in 17 (23.3%) cases. Regarding IE localization, the mitral valve was involved in 28 (38.4%) cases and the aortic valve in 14 (19.2%) cases. Recourse to surgery was reported in 37 (50.7%) cases. Thirty-day and 6-month mortality rates were 13.6% and 19.2%, respectively. Heart failure on admission or during the hospital course, acute renal failure and neurological complications were significantly associated with death at 6-month follow-up in the univariate analysis and after adjustment for age and sex.

Conclusions

In the Tunisian context, IE in children is still characterized by the high prevalence of RHD as an underlying heart disease. Short- and long-term mortality rates remain high. Heart failure, acute renal failure and neurological complications are significantly associated with death at 6-month follow-up.

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Résumé
Contexte

L’endocardite infectieuse (EI) est une affection rare en pathologie pédiatrique. Les données épidémiologiques et pronostiques à propos de l’EI de l’enfant en Afrique du Nord manquent.

Objectif

Le but de ce travail était d’étudier le profil épidémiologique et le pronostic de l’EI de l’enfant en Tunisie.

Méthodes

Tous les patients âgés de 18 ans et moins se présentant pour EI dans trois centres tertiaires tunisiens entre janvier 1997 et septembre 2013 ont été inclus. Les caractéristiques cliniques ainsi que la mortalité à 30jours et à 6 mois ont été étudiées. Les facteurs prédictifs de mortalité à 6 mois ont été déterminés.

Résultats

Au total, 73 patients ont été inclus dans cette étude. L’âge moyen de la population était de 12±4,8 ans et 35 (50,7 %) patients étaient de sexe masculin. Le rhumatisme articulaire aigu (RAA) était la pathologie cardiaque sous-jacente dans 17 (23,3 %) cas et l’EI est survenue sur un cœur structuralement sain dans 36 (49,3 %) cas. Le staphylocoque a été isolé dans 17 (23,3 %) cas. Concernant la localisation de l’EI, la valve mitrale était atteinte dans 28 (38,4 %) cas et la valve aortique dans 14 (19,2 %) cas. Le recours à la chirurgie a été rapporté dans 37 (50,7 %) cas. Les taux de mortalité à 30jours et à 6 mois étaient respectivement de 13,6 % et 19,2 %. En analyse univariée ainsi qu’après ajustement à l’âge et au sexe, l’insuffisance cardiaque à l’admission, l’insuffisance rénale aiguë et les complications neurologiques étaient significativement associés au décès à 6 mois.

Conclusions

Dans le contexte tunisien, l’EI de l’enfant est caractérisée par une prévalence encore élevée du RAA comme cardiopathie sous-jacente. Les taux de mortalité à court et à long-terme restent élevés. L’insuffisance cardiaque, l’insuffisance rénale aiguë et les complications neurologiques sont significativement associées à la mortalité à 6 mois.

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Keywords : Children, Infective endocarditis, Mortality, Rheumatic heart disease

Mots clés : Enfant, Endocardite infectieuse, Mortalité, Rhumatisme articulaire aigu

Abbreviations : CHD, IE, RHD


Background

Infective endocarditis (IE) is a severe heart illness with an established poor prognosis in hospital and long-term [1, 2]. In developed countries, antimicrobial therapeutics and open-heart surgery represent major advances in the field, which have led to a substantial improvement in short- and long-term outcomes. Compared with the adult population, the prevalence of IE remains low in the paediatric setting, and has a quite different epidemiological profile [3, 4]. In this respect, IE in the paediatric setting is characterized nowadays by the emergence of IE in congenital heart disease (CHD), postoperative IE and IE on the structurally normal heart [4, 5]. Studies published on the matter frequently enrolled much fewer cases than studies in the adult population, and studies from North African countries are almost absent. In these countries, characterized by vast rural areas, access to healthcare facilities is somewhat limited, and rheumatic heart disease (RHD), although declining, is still prevalent in current medical practice.

In this study, we sought to describe the clinical profile of IE in children, and to determine its short- and long-term prognosis through a multicentre Tunisian registry.

Methods

The data presented here were collected from three major tertiary-care centres in the centre and south of Tunisia (Fattouma Bourguiba University Hospital, Monastir; Farhat Hached University Hospital, Susa; and Hedi Chaker University Hospital, Sfax). Merging the patient data from the three databases enabled us to establish a multicentre registry. In all centres, clinical data and short- and long-term outcomes were collected in a periodic and retrospective fashion (and updated when necessary) every 1–2 years. The registry enrolled all consecutive patients aged18 years at the time of inclusion, presenting with definite or probable IE according to the modified Duke criteria [6], between January 1997 and September 2013.

Clinical characteristics

Clinical history and demographic data were collected for all patients upon admission. The clinical presentation was reported, including temperature, hemodynamic status, peripheral signs of IE, splenic enlargement, the presence of a new heart murmur or sound and screening for complications on clinical examination. Blood samples were collected from all patients for biological tests upon presentation and at 24hours. According to each centre's protocol, three to six sets of blood cultures were obtained from a peripheral vein before administration of any antibiotic. In some cases, additional blood samples were obtained for immunological tests (i.e. detection of rheumatoid factor and circulating immune complexes). If needed, serological testing was performed for the identification of intracellular microorganisms. Acute renal failure was defined according to the Acute Kidney Injury Network (AKIN) [7].

Transthoracic echocardiography was performed in all patients for diagnostic purposes and for cardiac complication screening. Transoesophageal echocardiography was performed only in patients with poor image quality on transthoracic echocardiography. Echocardiography was repeated on demand when a local, infectious or cardiac complication was suspected during the hospital course. Cerebral imaging was performed each time a neurological complication was suspected; this included any motor or sensitive manifestation or consciousness impairment, but also in cases of non-responsiveness to antimicrobial therapy, defined by persistent fever or biological inflammation after 5–7 days of adequate antibiotic therapy. Other imaging modalities were performed when judged appropriate by the medical staff for identification of other secondary infectious localization (splenic, renal, etc.).

Therapeutics and outcomes

The antibiotic regimens prescribed were summarized. Indications for surgery were reported, as were 30-day and 6-month mortality rates. Surgery was performed on site in one centre and in a regional nearby surgical centre for the two other centres. Factors predictive of death at 6-month follow-up were studied in a univariate analysis.

Statistical analysis

Categorical variables are presented as absolute values and proportions. Continuous variables are presented as means±standard deviations. The univariate analysis was performed using the χ 2 test to identify variables associated with death at 6-month follow-up, with risk estimates and 95% confidence intervals. Ratios for death at 6-month follow-up, adjusted for age and sex, were also determined using binary logistic regression. A P value<0.05 was set for statistical significance. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) for Windows, version 17 (IBM, Armonk, NY, USA).

Results

A total of 73 cases were included in the present registry. Table 1 describes the main demographic and clinical characteristics of the population. The mean age of the study population was 12±4.8 years. Only five patients were aged3 years. A structural underlying CHD was reported in 20 (27.4%) cases; RHD was reported in 17 (23.3%) cases. In 36 (49.3%) children, no underlying heart disease could be identified.

No infectious portal of entry could be identified in 38 (52%) cases and it was predominantly dental in the remaining cases (Table 2). Regarding the microorganisms involved, a germ could be identified in only 31 (42.4%) cases, 17 (23.3%) of which were attributable to Staphylococcus species (Table 2). Negative blood culture IE was reported in the remaining 42 cases.

At clinical examination, a cardiac murmur was reported in 63 (86.3%) cases and heart failure at admission or during the hospital course was diagnosed in 31 (42.5%) cases. Other clinical manifestations are reported in Table 3. The localization of the IE was valvular in 61 (83.5%) cases; the mitral localization was most prevalent, and in six cases the mitral and aortic valves were affected simultaneously. A prosthetic valve was involved in three (4.1%) cases. Echocardiography performed in all cases identified at least one vegetation on a native or prosthetic valve in 62 (84.9%) patients (Table 3).

Fourteen patients presented neurological complications during the hospital course (Table 4). Ischaemic stroke was the most prevalent (n =9). Other peripheral embolizations were diagnosed in 12 (16.4%) patients, with a predominance of renal emboli.

All patients received therapy with at least two antibiotics (Table 5) and surgery was indicated in 37 (50.7%) patients. Hemodynamic indications (n =27) included left- and right-sided heart failure and pulmonary oedema. Six patients underwent surgery for septic indications (four cardiac abscesses and two with persistent fever). At 30-day follow-up, 10 (13.6%) patients had died. The cumulative mortality rate at 6-month follow-up was 19.2%. Among the 14 patients who had died at 6 months, four were solely on medical therapy. In eight patients, death occurred during surgery or the postoperative course. The two remaining patients died from heart failure after discharge. Eleven patients presented heart failure upon admission or during hospital stay, seven had neurological complications and 11 had acute renal failure.

We performed a univariate analysis on the main variables routinely identified as being associated with IE. We identified heart failure on admission or during the hospital course, acute renal failure and neurological complications as the only variables significantly associated with death at 6-month follow-up in the study population (Table 6). After adjustment for age and sex, these factors were still significantly associated with death at 6-month follow-up. Anaemia and recourse to surgery showed a trend towards being associated with death at 6-month follow-up, but statistical significance was not reached.

Discussion

IE in children is a rare entity [3, 8]. By gathering data from three Tunisian tertiary-care centres, this report intended to represent as accurately as possible the epidemiological and prognostic profile of IE in this age group and to highlight the particularities that are specific to our North African region.

The first remarkable finding in the present study was that the prevalence of RHD is still high as an underlying heart condition in children presenting with IE. Our study population was formed by children from urban as well as rural parts of our country. RHD was involved in nearly one quarter of enrolled patients, underscoring the need for more large-scale preventative measures in the paediatric population. In the present era, most developing countries are witnessing a gradual epidemiological transition in IE, characterized by the emergence of IE in CHD, postoperative IE and IE on the structurally normal heart [9, 10]. At the other end of the spectrum, Western series report IE in CHD and on the structurally normal heart as nearly the only aetiological forms in children [11, 12]. In a medical record review of the Mayo Clinic, Johnson et al. reported the disappearance of RHD as the predisposing condition for IE in children between 1980 and 2011 [11]. In the same study, prevalence of CHD was as high as 75% for the same period.

Regarding infectious portal of entry, when it could be identified, findings were not categorically different from those from previous Tunisian IE reports [13, 14]. In our study, predominance of Staphylococcus species in positive cultures is in accordance with other studies from Western and Asian countries [4, 10]. Staphylococcus aureus and coagulase-negative staphylococci are the germs encountered most frequently, especially with the use of indwelling central venous catheters in critically ill children. Likewise, it remains the most prevalent germ in IE on structurally normal hearts. Negative blood culture IE accounted for 57.6% of cases and is largely explained by the liberal prescription of antibiotics in children with febrile states in our current practice.

As in other series of IE in adults [13], mortality rates in children were high in our study. Short- and long-term mortality rates were substantially higher than those reported in Western series. Most American studies report in-hospital mortality rates ranging from 4% to 7% [11, 15]. In a recent nationwide Italian registry [16], albeit including only 47 cases of IE in children, only three deaths were reported in patients with predisposing heart disease. Data from Middle-Eastern countries are very scarce. An old retrospective Lebanese study that enrolled 41 children between 1977 and 1985 reported a 29% overall mortality rate [17] and, to our knowledge, no specific data from North African countries are available. Clinical factors associated with death in our study were determined at 6-month follow-up. Given the small number of enrolled patients, we performed a univariate analysis and adjusted for age and sex. Some other factors not included in the analysis were omitted because of the non-occurrence of the death endpoint in these subgroups. Despite the small number of subjects included in the analysis, we could identify heart failure on admission or during hospital course, acute renal failure and neurological complications as factors significantly associated with death at 6-month follow-up in the univariate analysis and after adjustment for age and sex. Other classical factors reported to be predictive of death in IE did not reach statistical significance in the univariate analysis model because of the small size of the study population.

Study limitations

Although based on a multicentre registry, some limitations to our study have to be highlighted. It was a retrospective study and no randomization or matching was applied, so no firm conclusion could be drawn regarding the efficiency of the therapeutics implemented or their respective prognostic impact. The reduced population size prevented us from performing other prognostic statistical analyses. Finally, much caution should be applied when extrapolating these results to the whole Tunisian paediatric population, especially because of the differences in children's epidemiological profiles and access to healthcare facilities between the different regions of the country.

Conclusions

According to this Tunisian multicentre study, prognosis of IE in children remains relatively poor. Factors predictive of death at 6-month follow-up are dominated by heart failure, acute renal failure and neurological complications. RHD is still highly prevalent as a predisposing factor, with the emergence of IE in CHD and on normal hearts.

Sources of funding

None.

Disclosure of interest

The authors declare that they have no competing interest.

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