Archives of Disease in Childhood, 1988, 63, 53-57

Infective endocarditis in neonates

C O'CALLAGHAN AND P MCDOUGALL

Department of Neonatology, Royal Children's Hospital, Melbourne, Australia

SUMMARY Five patients with neonatal infective endocarditis were reviewed, two of whomsurvived. Infection was caused by Staphylococcus aureus in four and by Candida albicans in one.All cases of bacterial endocarditis had clinical signs of septicaemia, positive blood cultures,thrombocytopenia, microscopic haematuria, and heart murmurs. Three developed skin abscessesearly in their illnesses. Three patients had two dimensional echocardiographic studies thatshowed bacterial vegetations. One of these studies was done before the heart murmur could beheard. We suggest that echocardiography in conjunction with the clinical picture described mayhelp in making an early diagnosis of endocarditis in neonates.

Bacterial endocarditis in neonates is a rare andusually fatal disease; the first survivor was reportedin 1983.1 2We became interested in the disease aftertwo patients in our neonatal unit survived. Wetherefore reviewed all five cases of neonatal infec-tive endocarditis seen at this hospital over the past10 years to see if we could find similarities that couldlead to earlier diagnosis and treatment; this is thelargest published series that we know of.

Case reports

CASE 1A boy weighing 1000 g was born by spontaneousvaginal delivery at 28 weeks' gestation. He requiredresuscitation after birth with endotracheal ventila-tion. Sodium bicarbonate and dextrose were giventhrough a catheter in the umbilical vein. His Apgarscores were 1 at one minute and 3 at five minutes.He was transferred to this hospital.

Initial management included mechanical ventila-tion, intravenous fluid replacement, and treatmentwith penicillin and gentamicin. Vascular accesscatheters were inserted in the radial artery and acentral vein. At 7 days of age a patent ductusarteriosus was confirmed by two dimensional echo-cardiography. The heart was structurally normaland the baby was successfully treated with indo-methacin.At 15 days of age he had an abscess over the left

posterior iliac spine; a full blood count showedthrombocytopenia and analysis of the urine showedmicroscopic haematuria. Methicillin resistantStaphylococcus aureus was cultured from pus fromthe abscess, and from the cerebrospinal fluid, blood,

and tracheal aspirates; he was treated with intra-venous vancomycin.At 26 days of age the baby had not improved and

a systolic murmur could be heard. Echocardio-graphy showed vegetation round the mitral valve.Despite the addition of fusidic acid to his treatmenthe continued to deteriorate and died at 28 days.The diagnosis of vegetative bacterial endocarditis

due to methicillin resistant S aureus was confirmedat necropsy, together with lung changes consistentwith bronchopulmonary dysplasia. There were alsoperiventricular cystic changes and a cerebralhaemorrhage.

CASE 2A girl weighing 2800 g was delivered by electivecaesarean section at term. She required resusci-tation with endotracheal ventilation. Sodium bicar-bonate and dextrose were administered through acatheter in the umbilical vein. Her Apgar scoreswere 1 at one minute and 9 at five minutes.

She was slow to begin breast feeding and despitethe early passage of normal meconium she devel-oped progressive abdominal distension. At 4 days ofage she underwent a laparotomy for severe necro-tising enterocolitis of the entire colon. Treatmentincluded penicillin, gentamicin, and metronidazole.Vascular access catheters were inserted in the radialartery and a central vein. No organisms were grownfrom cultures.A systolic murmur accompanied by congestive

cardiac failure was heard postoperatively. An atrio-ventricular canal was diagnosed by two dimensionalechocardiography and she was treated with digoxinand diuretics. At 23 days of age, having received no

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54 Infective endocarditis in neonates

antibiotics for seven days, she showed clinical signsof septicaemia. S aureus was cultured from herblood and she was treated with flucloxacillin andgentamicin. At 25 days of age she developed nodalrhythm and multiple supraventricular and ventri-cular arrhythmias. She died three days later despitefull intensive care.Necropsy showed vegetations on the pulmonary

valve with extension into the main pulmonaryartery, which had ruptured. There was an atrio-ventricular canal and patent ductus arteriosus. Thebowel showed necrotising enterocolitis and therewas an abscess in the loops of small bowel.

CASE 3A boy weighing 3100 g was born at term byspontaneous vaginal delivery following an uncom-plicated pregnancy. His condition at delivery wasgood. He started breast feeding and was dischargedwhen 5 days old.At 21 days he developed a fever, a generalised

rash, and malaise. Cultures of blood, swabs of theskin lesions, and a specimen of urine aspiratedsuprapubically grew S aureus that was sensitive togentamicin. A full blood examination showed aplatelet count of 10 000x 109/l. Despite initial treat-ment with penicillin and gentamicin he failed to

respond. At 27 days of age a swab from a skinpustule grew methicillin resistant S aureus; treat-ment with vancomycin and rifampicin was started.At 28 days a pansystolic murmur was heard and

two dimensional echocardiography showed a mobilevegetation attached to the papillary muscle of themitral valve (fig 1). Fundoscopy showed fourchorioretinal atrophic areas and computed tom-ography of the brain showed several embolic areas.

Antibiotic treatment was continued for six weeks,and echocardiography at 7 weeks of age showed noevidence of vegetations. At discharge he had com-pletely recovered with no obvious sequelae.

CASE 4A boy weighing 800 g was born at 26 weeks'gestation and transferred to this hospital shortlyafter delivery. The mother's membranes had beenruptured for four days before delivery and there hadbeen a small antepartum haemorrhage. Apgarscores at birth were 6 at one minute and 9 at fiveminutes. He was intubated, ventilated at low venti-lator settings, and treatment was started with peni-cillin and gentamicin. Initial cultures showed noevidence of sepsis and his clinical condition wasconsistent with hyaline membrane disease.At 2 days of age an echocardiogram was done

Fig 1 Two dimensional echocardiogram (apicalfour chamber view) showing pedunculated vegetation in left ventricleattached to papillary muscle. RA =right atrium; RV=right ventricle; TV=tricuspid valve; MV=mitral valve; LV=leftventricle; PV=pulmonary valve, and V= vegetation.

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which showed normal cardiac anatomy and noevidence of a patent ductus arteriosus. Methicillinresistant S aureus was cultured from surface swabs.At 8 days he developed persistent metabolic acidosisand methicillin resistant S aureus was isolated fromblood cultures; he was treated with vancomycin, buton day 10 methicillin resistant S aureus was isolatedfrom a pustule on his chest. At 25 days, nine daysafter the vancomycin had been stopped, he againdeveloped metabolic acidosis, his white cell countwas high, platelets were normal and methicillinresistant S aureus was again isolated from bloodcultures. Clotting studies were normal and a chestx-ray picture showed bronchopulmonary dysplasia.Treatment with vancomycin and rifampicin wasstarted. A abscess developed on the left wrist andanother on the upper arm, and methicillin resistantS aureus was isolated from the pus. The cranialultrasound scan was normal. Two dimensionalechocardiography, however, showed a peduncu-lated vegetation in the left atrial appendage (fig 2).The methicillin resistant S aureus isolated from theblood cultures was sensitive to vancomycin, rifam-picin, and fusidic acid, but because of possibleantagonism between vancomycin and rifampicin,rifampicin was replaced by fusidic acid.He was extubated at 7 weeks of age at which time

he became grossly oedematous with a serum albu-min concentration of 19 g/l. This resolved afterinfusion of albumin and restriction of fluids. Anti-

O'Callaghan and McDougall 55

biotics were continued for seven weeks, at whichtime cardiac ultrasound scan showed a slightdecrease in the size of the vegetation. He wasdischarged when 12 weeks of age. When reviewed at12 months of age neurological and developmentalexaminations yielded normal results. A furtherechocardiogram showed that the vegetation haddisappeared.

CASE 5A girl weighing 1500 g was delivered at 37 weeks'gestation by caesarean section because of fallingoestriol concentrations in the mother's urine; shehad had an antepartum haemorrhage at 32 weeks.The infant's Apgar scores were 2 at one minute and5 at five minutes and she responded to three minutesof endotracheal ventilation. At 24 hours of age shedeveloped tachypnoea and became unwell. Culturesof blood and cerebrospinal fluid grew S aureus andshe was treated with flucloxacillin and gentamicin.Her condition deteriorated and she developed dis-seminated intravascular coagulation. An exchangetransfusion was carried out but her condition con-tinued to deteriorate and she required mechanicalventilation. She developed severe cholestatic jaun-dice, and acute hepatic necrosis was suspected.Three further exchange transfusions were carriedout; despite full intensive care she died at 19 days ofage.Necropsy showed peritonitis, pleurisy, peri-

Fig 2 Echocardiogram ofa vegetation in left atrial appendage (long axis view). PV=pulmonary valve; LA =left atrium;RV=right ventricle; MV=mitral valve, and V=vegetation.

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56 Infective endocarditis in neonates

carditis, focal necrotic lesions in the spleen, andhepatic necrosis. There was systemic candidiasiswith lesions in many organs including the brain.Candida pericarditis and myocarditis were presentwith a vegetation on the mitral valve that wasthought to be the origin of the septic foci in the otherorgans.

Discussion

The number of reports of infective endocarditis inchildren have increased during the past 10 years.Symchych et a13 reported an incidence of about 3%among 100 neonatal necropsies carried out in oneyear, but other studies reported lower figures.4 5The true incidence is difficult to determine.There seems to be an increased incidence of

bacterial endocarditis in children who require resus-citation at birth and subsequent intensive care,especially if central venous lines are inserted.' 68Three of our five cases had had central venous linesin place before the endocarditis developed. All fivewere clinically unwell and had blood, cerebrospinalfluid, and urine taken for culture before antibiotictreatment was started.

Previous studies have reported that the der-matological lesions of endocarditis such as Janeway'sspots, Osler's nodes, and Roth's spots are seen inless than 5% of paediatric patients. In our patientsskin abscesses or pustules that were thought to beseedlings of infection from the cardiac vegetationsappeared in three of the four patients with bacterialendocarditis. Two of the five developed petechiaduring their illnesses.The first echocardiographic diagnosis of bacterial

endocarditis was in 1977 by an M mode scan.7 In1983 Kavey et al found that 82% of the children withinfective endocarditis that they examined had echo-cardiographic findings compatible with the diag-nosis.9 Vegetations as small as 1-3 mm could beseen. 10Murmurs or changing murmurs were present in all

four patients later in their illnesses. Thrombocyto-penia and microscopic haematuria were present inall babies at an early stage. In two cases thedevelopment of a murmur led to two dimensionalechocardiographic examination that showed a vege-tation. In one case, with the clinical signs ofsepticaemia, skin pustules, haematuria, and throm-bocytopenia, two dimensional echocardiographyshowed a vegetation in the left atrial appendagebefore a murmur could be detected. Fourteen daysearlier a patient with similar signs was treated withvancomycin for 10 days after methicillin resistant Saureus had been isolated from cultures. Echocardio-

graphy at that stage might have shown a vegetationand resulted in a prolonged course of antibioticswith the hope of preventing further damage. Inter-estingly in older children the mean duration ofsymptoms before the diagnosis of bacterial endocar-ditis is 35 days.With the increasing availability of two dimen-

sional echocardiography neonates with septicaemia,especially if it is prolonged or recurrent, and skinpustules, haematuria, and thrombocytopenia, maywarrant a cardiac scan to search for vegetationsbefore a heart murmur has developed.

Non-bacterial endocarditis is an important predis-posing factor to the development of bacterialendocarditis because it may form a nidus forbacterial superinfection and increase the possibilityof embolisation. In one study of neonates who died10% had evidence of thrombotic endocarditis atnecropsy.3 Eighty per cent of them had had anintracardial central venous catheter inserted. Theinitial event in the development in thrombi isthought to be endocardial damage, presumablytraumatic in these cases.3 8 11 Congenital heartdisease is also an important predisposing factor, andit was present in one of our patients. In addition,one report suggested an association between persis-tent fetal circulation and non-bacterial endocardialthrombosis in neonates.'2

In bacterial endocarditis the bacteraemia isusually low grade and constant, and detectable in77-96% of the first blood cultures. This is increasedto nearly 100% if three blood cultures are taken.'3 Saureus has become an increasingly common cause ofendocarditis since antibiotics have been used, and itis more virulent than other bacterial causes of endo-carditis. The complication rate is higher, congestivecardiac failure occurs more often, and mortality in-creases.13 The treatment of infection by methicillinresistant S aureus with vancomycin alone is usuallysatisfactory. There is some evidence, however, thatthe addition of rifampicin or fusidic acid mayimprove the response, particularly for endocarditisor when skin infection occurs during treatment.Minimum inhibitory concentrations and minimumbactericidal concentrations of any antibiotic used inthe treatment of endocarditis should be routinelytested.'4 15 The serum bactericidal titre should be atleast 1/8-1/16, and preferably higher.

Fungal endocarditis in neonates is rare, and wefound no other case reports. The diagnosis in ourcase was made at necropsy, and there was concur-rent endocarditis and pericarditis. The occurrence ofpericarditis has not been described in neonatalfungal infections, and in neonates with bacterialendocarditis it has only been reported once pre-viously.

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References

Wheeler JG, Weesner KM. Staphylococcus aureus endocarditisand pericarditis in an infant with a central venous catheter. ClinPediatr 1984;23:46-7.

2 Oelburg DG, Fisher DJ, Gross DM, Denson SE, Adcock EW.Endocarditis in high risk neonates. Pediatrics 1983;71:392-9.

3Symchych PS, Krauss AN, Winchester P. Endocarditisfollowing intracardiac placement of umbilical venous cathetersin neonates. J Pediatr 1977;90:287-9.

4 McGuinness GA, Schiekan RM, Maguire GF. Endocarditis inthe newborn. Am J Dis Child 1980;134:577-80.

5Johnson DH, Rosenthal A, Nadas AJ. Bacterial endocarditis inchildren under two years of age. Am J Dis Child 1975;129:183-6.

6 Verhoef J, Fleer A. Staphylococcus epidermidis endocarditisand staphylococcus epidermidis infection in an intensive careunit. Scand J Infect Dis 1982; 41(Suppl):56-63.

7Bender RL, Jaffe RB, McCarthy D, Ruttenburg HD. Echocar-diographic diagnosis of bacterial endocarditis of the mitral valvein a neonate. Am J Dis Child 1977;131:746-9.

8 Favara BE, Franciosi RA, Butterfield LJ. Disseminated intra-vascular and cardiac thrombosis of the neonate. Am J Child1974;127:197-204.

9Kavey RG, Frank DM, Byrum CJ, Blackman MS, SandheimerHM, Bore EL. Two-dimensional echocardiographic assessment

of infective endocarditis in children. Am J Dis Child 1983;137:851-6.

10 Weinburg AG, Laird WP. Group B streptococcal endocarditisdetected by echocardiography. J Pediatr 1978;92:335-9.

l Van Hare GF, Ban-Shaken G, Lieben J, Boxerbann B,Rieneschneider TA. Infective endocarditis in infants and chil-dren during the past ten years: a decade of change. Am Heart J1984;107:1233-40.

12 Morrow WR, Hass JE, Benjamin DR. Non-bacterial endo-cardial thrombosis in neonates: relationship to persistent fetalcirculation. J Pediatr 1982;100: 117-22.

13 Siegal JD. Bacterial endocarditis in infants and children.Incidence and pathogenesis. Pediatr Infect Dis 1983;3:541-3.

14 Strattton CW, Weinster MP, Rellin LB. Correlation of serumbacterial activity with antimicrobial agents level and minimalbacterial correlation. J Infect Dis 1982;145:160-8.

15 Wolfson JS, Swartz MN. Serum bactericidal activity as amonitor of antibiotic therapy. N Engl J Med 1985;312:968-75.

16 Morris GK. Infective endocarditis: a preventable disease? BrMed J 1985;290:1532-3.

Correspondence to Dr C O'Callaghan, University Hospital,Queen's Medical Centre, Nottingham NG2 2UH.

Received 30 July 1987

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