Pediatr Cardiol 11:77-81, 1990

Pediatric Cardiology 9 Springer-Verlag New York Inc. 1990

Infectious Endocarditis

in Children

F. Parras, 1 E. Bouza, l J. Romero, 1 L. Buz6n, 1 M. Quero, 2 J. Brito, 2 and D. Vellibre 2 qnfectious Disease Unit and 2Medico-Surgical Unit of Pediatric Cardiology, Hospital Ram6n y Cajal, Madrid, Spain

SUMMARY. With the object of analyzing current characteristics of infectious endocarditis (IE) in children, we carried out a retrospective study of 23 cases of IE in children under 15 years of age seen at the Hospital Ram6n y Cajal in Madrid (Spain) between 1977 and 1985. The incidence was high (1.3 cases per 1000 children admitted). The male/female ratio was 2 : 1. Eight patients were under 2 years of age and 15 over 2 years, the majority being adolescents. The two groups presented marked etiological and prognostic differences. Congenital heart disease was the predisposing factor in 20 of the 23 cases. Streptococcus viridans (nine cases) and Staphylococcus aureus (eight cases) were the most frequent organisms. Fourteen cases were on a native valve and nine were secondary (seven of these on prosthetic patches). In spite of advances in therapy, IE continues to be a severe illness: the mortality rate in our series was 26%. Factors associated with a poor prognosis were: age less than 2 years, Staphylococcus aureus as the causative agent, and the presence of prosthetic material. K E Y WORDS: Infectious endocarditis - - Children

During the last four decades clinical, microbiological and therapeutic characteristics of infectious endocarditis (IE) have changed dramatically as a result of changes in the type of prevalent underlying heart disease, the widespread use of antimicrobial agents, advances in cardiovascular surgery, the increasing use of invasive diagnostic and therapeutic techniques, and the better prospects of survival for patient,s with severe underlying heart disease [1, 4, 9, 12, 13, 15]. The impact of these and other factors are well known in the adult population [9, 15], but information is scant and incomplete both in elderly and young patients. We have carried out a retrospective study of IE occurring during an 8-year period in patients under 15 years of age.

Materials and Methods Our institution, Hospital Ram6n y Cajal, is a 1322-bed general hospital serving a population of approximately 550,000 in Madrid (Spain). The hospital serves as a referral center for pediatric

Address offprint requests to: Dr. F. Parras (present address), Microbiology Department, Hospital Son Dureta, C/Andrea Doria 56, 07104 Palma de Mallorca, Spain.

cardiovascular surgery. During the 8-year period of our study (September 1977 to August 1985), 157,701 patients were hospitalized, of whom 16,404 were in the pediatric age range (under 15 years). Our criteria for IE were those of Pelletier and Petersdorf [8] as modified by Von Reyn et al. [t4], to include data based on echocardiographic findings. Standard methods were employed for obtaining and processing blood cultures, as well as for the identification of microorganism isolates. Antibiotic susceptibility was determined by the agar dilution technique. We considered adequate antimicrobial therapy to be the administration, for a minimum period of 14 days, of one or more antimicrobial agents with in vitro bactericidal activity against the corresponding isolate. We considered as El-related deaths all those which occurred while the patients were under treatment for EI or within 1 week of termination of treatment, unless clear clinical and pathological data suggested otherwise.

Results

During the 8-year period of our study 23 patients fulfilled the previously described diagnostic criteria for IE, an incidence of 1.35/1000 children admitted. Eleven cases were diagnosed as certain, as probable, and one as possible IE. We divided our cases into two groups according to their age: patients under 2 years of age (eight cases) (group 1) and pa-

Pediatric Cardiology Vol. 11, No. 2, 1990

78

Table 3. Clinical findings

Table 1. Underlying heart disease

Congenital heart diseases Ventricular septal defect (complex anomalies) Tetralogy of Fallot Aortic stenosis Pulmonic stenosis Ductus Transposition of the great vessels Others Rheumatic heart diseases None Total

Total

2 years

20 5

8 1

12 4

5 3 3 1 1

3 1 1a 1 1

2 2 2 0 0

2 1 2 23

0 0 0 8

2 1 2 15

No. of patients Mean duration Heart murmur General malaise Fever Heart failure Changing murmur Gross embolism Liver enlargement Spleen enlargement C N S involvement Renal involvement Osteoarticular infections Peripheral signs

Total

2 years

23 27'1 (23) (22) (21) (10) (9) (12) (13) (10) (6) (5) (3) (3)

8 25'3 days 8 8 6 4 4 4 7 4 4 4 1 2

15 28'3 days 15 14 15 6 5 8 6 6 2 1 2 1

Total

2 years

9 8 2 1 1 1 1

1 4b Ic 1 1 1 0

8~ 4 1 0 0 0 1

days 100% 96% 91% 43% 39% 52% 56% 43% 26% 22% 13% 13%

a With single ventricle. C N S , central nervous system.

Table 2. Epidemiology of pediatric infectious endocarditis

Type Native Prosthetic Acquisition Community Nosocomial Site Valvar Left Right Both VSD Patches Origin of sepsis Dental work Pyoderma Catheterization Mediastinitis

Total

2 years

14 9

4 4

10 5

15 8

0 8

15 0

8 5 1 1 7

2 1 0 0 5

6 4 1 1 2

2 1 1 2

0 1 1 2

2 0 0 0

VSD, ventricular septal defect.

tients over 2 years (15 cases) (group 2). There were twice as many males as females. Underlying heart disease (Table 1) was overwhelmingly congenital heart disease (CHD) (20 cases), with only one case of rheumatic heart disease (RHD). Type of endocarditis (native or secondary), place of acquisition, and site and origin of bacteremia are summarized in Table 2. Clinical findings in the two groups of patients are summarized in Table 3. All patients presented as being in a "septic state," although in some children under 2 years the symptoms of the complications (meningitis, cerebral abscesses, major embolisms, etc.) predominated.

Table 4. Responsible microorganisms

S t r e p t o c o c c u s viridans S t a p h y l o c o c c u s aureus S t a p h y l o c o c c u s epidermidis P s e u d o m o n a s aeruginosa Brucella melitensis E. coli + S. fuecalis

Negative culture One case Penicillin R. b One case Methicillin R. c One case Methicillin tolerant.

Causative microorganisms (Table 4) were identified in 22 of the 23 cases. Nineteen patients had persistent positive blood cultures; and in the remaining three cases microorganisms were isolated either from the resected heart valve and/or the emboli. In group 2 IE was almost invariably community acquired and Streptococcus was the most frequent responsible microorganism. All patients in group 1 had nosocomially acquired IE, and in this group Staphylococcus predominated. Echocardiography (M-mode and two-dimensional) was performed in 21 of the 23 patients. In group 2 vegetations were detected in 9 of the 14 cases (all but one occurring on a native valve). In group 1 the echocardiogram proved to be less sensitive, and vegetations were found in only two of seven cases. All but one patient received adequate antimicrobial therapy; another three were considered inadequately treated, since they died during the first week of therapy. Drugs administered and length of

F. Parras et al.: Infectious Endocarditis in Children

79

Table 5. Treatment and evolution No.

Microorganism

Antibiotic

Length

Surgery

Evolution

I 2 3 4 5 6 7 8 9 10 11 12 13 14 15

S. m u t a n s S. viridans S. viridans S. viridans S. aureus S. viridans S. aureus S. aureus S. aureus S. aureus S. aureus Brucella m. E. coli + S. f a e c a l i s Culture ( - ) S. m u t a n s

6d 4w 4w 4w 6w + 2w 6w + 2w 6w + 2w 4w 4d

Yes Yes Yes Yes

Yes Yes Yes Yes

D C C C C C C D D D D C C C C

16 17 18 19

S. a u r e u s (Methi R) S. epidermidis S. viridans S. aureus

No No No No

D C C C

20 21 22 23

P. S. S. S.

P + G P + G P A + G CL + G P + T CZ + G CZ A + G P CZ + G T T + RMP + S A + T P + T P + G V+G V + AK V + RMP A + G CZ + T V CZT + T V + T CZ + G P + S V

No No No No

C C C C

aeruginosa viridans epidermidis viridans

4d 6w 6w 6w 6w 6w 6w + 2w 6w 6w 2w 4w 2w 6w 6w + 3w 2w 4w

No No No No No No No

A, ampicilin; CI, cloxacillin; P, penicillin; V, vancomycin; CZ, cefazolin; G, gentamicin; T, tobramycin; AK, amikacin; S, streptomycin; CZT, ceflazidime; RMP, rifampin; TT, tetracycline; d, days; w, weeks; D, died; C, cured.

treatment are summarized in Table 5. A total of eight patients received surgery as part of the treatment for IE. Of these five had IE on native and three on prosthetic material. The reasons for surgery were: heart failure (six cases), break-through bacteremia (two cases), multiple peripheral embolisms (one case), and difficulty in eradicating the microorganism (Brucella endocarditis). In Table 6 we have analyzed the different prognostic factors. The overall mortality rate in the series was 26%. Analysis of the two age groups shows a mortality in group 2 of only 6.6% (one patient died of heart failure). In group 1 the mortality rate was very high: five of the eight patients died (62.5%). Endocarditis by S. viridans was associated with a mortality rate of 11.1%, while that caused by S. aureus or S. epidermidis had a mortality rate of 50%. In left-sided endocarditis the mortality rate was 25% (2/8), while in right-valve endocarditis the rate was 20% (1/5). Heart failure was related to a poor prognosis, and 40% of these patients died. Embolic phenomena, especially in the central nervous system, in children under 2 years of age, had a very poor prognosis. Surgery did not increase the mor-

Table 6. Mortality rate and related factors Age group Microorganism Site Type

2 years (6.6%) S. aureus (50%) Right (50%) Prosthetic (22.2%)

Values in parentheses represent the mortality rate.

tality rate in either age group. In fact, in group 1 it was lower among those operated on. In spite of the apparent benefits of surgery, various factors prevented its general use in our series; early death in the course of the illness, an extremely poor general state due to extracardiac complications, or technical difficulties of removal of all existing patches.

Discussion The high incidence reported by us, compared with other series [1, 4, 7, 11, 13], may be explained by the high number of children at high risk of getting IE

80

referred to the pediatric medico-surgical cardiology unit of our hospital. While previous reviews of IE have drawn attention to the noteable decrease in the frequency of RHD as a predisposing factor in IE [l, 7, 11-13], our series shows an almost complete disappearance of this entity. Twenty of our 23 patients had CHD (87%), however, as is generally appreciated, not all congenital heart disease carries the same risk as a predisposing factor [1, 4, 10]. Our experience bears out what has previously been described, since the most frequent underlying anomalies were ventricular septal defect (VSD), tetralogy of Fallot (TF), and aortic stenosis (AS). Nine of our patients had endocarditis on prosthetic material (39. I%), seven within 2 months after surgery. Four of these had systemic-pulmonary shunts with Gore-Tex. Only isolated cases of IE on Gore-Tex material have been reported, and the exact risk of infection is unknown [10]. In our hospital the number of Gore-Tex prostheses placed during the period of this study was 721, with an incidence of IE of 0.95% (seven cases). Two children with a Gore-Tex prosthesis were cured without removing the prosthesis. We feel that IE on Gore-Tex is more benign than on valvar prostheses, as has also been stated by others [13]. Cases of IE have been reported as very uncommon under 2 years of age and difficult to diagnose [5, 12]. Our study, like other recent works, does not confirm that impression [13]. The clinical presentation in children of group 1 was characterized by a "septic" state with rapid hemodynamic deterioration and with clinical findings grossly similar to those in older children. The only difference was a higher incidence of systemic embolic phenomena, especially to the CNS in the younger patients. Gram-positive microorganisms are most frequently responsible IE. Also, as in adults, Staphylococcus is now at least as important as Streptococcus as a causative agent. The etiological changes observed in adults in recent decades have also occurred in children [1, 4, 6, 9, 11-13, 15]. Echocardiography is an important tool in locating the infection [2, 13]. Echocardiograms were carried out in 21 of our 23 patients. Although found a noteable difference in the diagnostic sensitivity of echocardiography between our two age groups, these were not related to age but rather to the underlying cardiac disease. Vegetations were recorded in nine of the 15 patients over 2 years, and in only two of the seven under 2 years. It is well known, however, that echocardiography is considerably less sensitive on prosthetic material, which was much more common among the young age group.

Pediatric Cardiology Vol. 11, No. 2, 1990

Antimicrobial therapy in IE depends on the bacteria isolated. In our series all patients who survived long enough were treated for a minimum period of 4 weeks. Cardiac surgery, by prolonging and saving the lives of many children with congenital heart disease, has increased the incidence of IE. Surgery has also a profound impact on the treatment of endocarditis in children. It is indicated in those with severe hemodynamic complications, with multiple systemic emboli, or where adequate antimicrobial treatment has failed to control the disease [6]. Eight of our 23 patients underwent surgery for one or several of these reasons. In spite of the marked improvement in therapy, IE remains a very severe disease with a mortality rate of 26% in our series, which is very similar to that reported in other recent pediatric series [1113]. Our series, demonstrates that there have been important changes in IE among children and that, excluding the differences in underlying disease, endocarditis reflects the same etiological changes, diagnostic problems, and therapeutic expectations that have been exhaustively described in adults.

References 1. Blumental S, Griffihs SP, Morgan RC (1960) Bacterial endocarditis in children with heart disease. A review based on the literature and experience with 58 cases. Pediatrics 26:9931017 2. Dillon T, Meyer RA, Korfhagen JC, Kaplan S, Chung KJ (1980) Management of infective endocarditis using echocardiography. J Pediatr 86:552-558 3. Gersony WM, Hayes GJ (1977) Bacterial endocarditis in patients with pulmonary stenosis, aortic stenosis or ventricular septal defect. Circulation 56(suppl I):84-87 4. Johnson DH, Rosenthal A, Nadas AS (1975) A forty-year review of bacterial endocarditis in infancy and childhood. Circulation 51:581-588 5. Johnson DH, Rosenthal A, Nadas AS (1975) Bacterial endocarditis in children under 2 years of age. Am J Dis Child 129:183-186 6. Karchmer AW, Stinson EB (1980) The role of surgery in infective endocarditis. In: Remington JS, Swartz MN (eds) Current clinical topics in infectious disease/. McGraw-Hill, New York, pp 124-157 7. Kramer HN, Burgeois M, Liersch R, Nebler L , Meyer H, Sievers G (1983) Current clinical aspects of bacterial endocarditis in infancy, childhood and adolescence. Eu J Pediatr 140:253-259 8. Pelletier LL, Petersdorf RG (1977) Infective endocarditis a review of 125 cases from the University of Washington hospital 1963-1972. Medicine (Baltimore) 56:287-318 9. Ravinovich S, Evans J, Smith IM, January LE (1965) A long-term view of bacterial endocarditis. Ann Intern Med 63:185-198 10. Romero J, Bouza E, Buz6n L, Parras F, G6mez R, Villagr~i

F. Parras et al.: Infectious Endocarditis in Children

F, Prrez-Le6n J (1985) Endocarditis on a Gore-Tex tube prosthesis. Pediatric Infect Dis J. May:296-298 11. Schollin J, Bjarke B, Wesstrons G (1985) Infective endocarditis in Swedish children. Acta Paediatr Scand 75:993-1005 12. Stanton BF, Baltimore RS, Clemens JD (1984) Changing spectrum of infective endocarditis in children. Analysis of 26 cases, 1970-1979. A m J Dis Child 138:720-725 13. Van Hare FG, Ben-Shachar G, Liebman J, Boxerbaum B,

81

Reimenschneider TA (1984) Infective endocarditis in infants and children during the past 10 years: a decade of change. A m Heart J 107:1235-1240 14. Von Reyn CF, Levy BS, Arbeit RD, Fredlan G, Chumpaker CS (1981) Infective endocarditis: an analysis based on strict case definition. Ann Intern M e d 94:505-518 15. Watanakunakorn C (1978) Infective endocarditis as a result of medical progress. A m J Med 64:917-919