Infective endocarditis (IE) is a rare infection in healthy pediatric population. Most cases of pediatric IE have underlying congenital heart disease (CHD). The overall incidence is rising with an increased proportion of patients that have undergone cardiac surgery. The risk of IE is especially high after surgery for tetralogy of Fallot (ToF) and other complex cyanotic CHD, within 6 months after surgery or below the age of 3 years.1 Mortality of IE is 48% in pediatric patients with ToF and pulmonary atresia.2
IE can be caused by a myriad of microorganisms. Staphylococcus and Streptococcus species are the most common in children either with or without heart disease. Streptococci have been shown to be the most frequent pathogens (32.7%) in pediatric patients with an underlying cardiac condition, followed by Staphylococcus aureus (28.1%).3 Polymicrobial endocarditis is rare, with prevalence of up to 5.9% in adults4; the incidence in pediatric patients varies.
C. burnetii endocarditis can be associated with delayed diagnosis. Reports of Q fever endocarditis in children are scarce. Several months of symptoms before admission have been described.5 The youngest case reported in the literature was 3 years old.6
We report a case of IE after CHD repair, which presented with endocarditis caused by coinfection with C. burnetti and K. kingae.
A 29-month-old boy from a rural area was admitted with fever. He was postnataly diagnosed with ToF with pulmonary atresia. At the age of 13 days, he underwent full repair including ventricular septal defect closure, placement of a 12-mm Contegra pulmonary valved conduit (Medtronic, Minneapolis) and augmentation of the left pulmonary artery.
The boy was first admitted to a pediatric department at another hospital after two weeks of daily fever (up to 40°C) and aphtous stomatitis. He had reduced appetite and weakness for up to a year leading to hospitalization. The parents reported daily contact of the child with cattle, to include contact with saliva, as the cows ate off the child’s hands. He was in proximity to a neighbor’s horse and visited a goat pen, although he did not pet them or have direct contact with their secretions.
On admission, he was pale and tachycardic. Blood tests showed hemoglobin of 8.8 g/dL, 64 × 103/μL platelets, hyponatremia 124 mEq/L and elevated C-reactive protein of 90.5 mg/L. Liver function tests and urinalysis were within normal range throughout the hospitalization. Chest radiograph was normal; the electrocardiogrphy exhibited sinus tachycardia and right bundle branch block. A transthoracic echocardiogram (TTE) showed mild to moderate tricuspid regurgitation, with a peak gradient of 100 mm Hg, indicating suprasystemic right ventricular pressure, and severe right ventricular outflow obstruction, with a peak gradient of 88 mm Hg. No vegetations were identified. Eye examination was negative for Roth spots. Three blood cultures were drawn and he was referred to our tertiary center.
On admission to the intensive care unit, he had a fever of 38°C, tachycardia of 150 bpm, blood pressure of 86/54 mm Hg, desaturations down to 88% and required oxygen supplementation. Hepatosplenomegaly was noted. Laboratory results revealed hemoglobin 7.6 g/dL, thrombocytopenia of 56 × 103/μL, lymphopenia of 0.9 × 103/μL and hypoalbuminemia 2.3 g/dL. He required ionotropic support with dopamine at 5 mcg/kg/min. TTE showed a 70-mm Hg gradient across right ventricular outlet, the right vetricular function was moderately reduced and the ventricle was mildly dilated. A chest radiograph showed a new infiltrate in his right lower lobe. Abdominal and chest ultasonography showed bilateral pleural effusions, mild ascites and hepatosplenomegaly.
Treatment with ceftriaxone (100 mg/kg × 1/day), cloaxacillin (100 mg/kg /day:q6h), gentamicin (7 mg/kg/day:q8h) and doxycycline (4 mg/kg /day:q12h) was initiated for suspected endocarditis. Two cultures that were obtained at the initial admission, prior to antibiotic initiation, grew K. kingae. Monotherapy with ceftriaxone (100 mg/kg/day) was continued. Serologies for C. burnetii, Brucella spp and Bartonella spp were obtained due to his rural origin and clinical course.
He clinically improved and was weaned off hemodynamic support and oxygen supplementation, with concurrent progressive signs of right-sided heart failure, including ascites, hepatosplenmegaly and scrotal edema. Treatment with furosemide and spirinolactone was initiated. With ceftriaxone and diuretics, fever and signs of heart failure improved, inflammatory markers subsided and the thrombocytopenia improved, but did not normalize. On the 17th day of antibiotic treatment, positive serology for C. burnetti, phase 1 IgG 3200, IgM-positive, phase 2 IgG ≥ 3200, IgM-negative, was reported, indicating a chronic infection; serologic testing, and indirect immunofluorescence assays for C. burnetii antibodies were performed at the Israeli Reference Laboratory for Rickettsial Diseases. Serum polymerase chain reaction (PCR) for C. burnetii was negative. Based on the serology, treatment with doxycycline (4 mg/kg/day) and rifampin (20 mg/kg/day) was added, after which he improved clinically and was afebrile with normalization of the thrombocyte count within days.
TTE showed some improvement but still reduced right ventricular function and high gradients across right sided valves (up to 84 mm Hg in the ventricular outlet and time to repetition of 90 mm Hg). As there was no improvement in the right ventricular outflow tract obstruction, and the right ventricle remained suprasystemic, he was referred for surgery after 5 weeks of antibiotics, 8 weeks after initial presentation.
During surgery, the contegra valve was removed (Fig. 1) and a new larger contegra graft was implanted.
Specimen cultures were negative, although PCR was positive for both K. kingae and C. burnetti. A 6-week parenteral treatment with ceftriaxone was completed, and long-term oral treatment with doxycycline (2 mg/kg × 2/day) and rifampin (20 mg/kg × 1/day) was prescribed for at least 24 months.
At a 13-month follow-up, the patient had completely returned to his former state. He exhibited no hepatosplenomegaly, TTE displayed good function of both ventricles, mildly elevated time to repetition and very mild right ventricular outflow tract obstruction across the ventricular outlet with trivial pulmonary regurgitation. Serology results 7 months after initial admission showed phase I IgM-negative, IgG = 3200, phase II IgM-negative, IgG ≥ 1600.
We report a case of polymicrobial endocarditis caused by K. kingae and C. burnetti. Polymicrobial endocarditis is rare, with prevalence of up to 5.9% in adults.4 Prevalence among intravenous drug abusers is well established. Patients with diabetes mellitus, prosthetic and healthcare-related infections are also prone, as shown by a study that surveyed 1195 adult cases. A difference in mortality was not observed when compared with single pathogen infection. The presence of one microorganism creates a niche for other pathogens. The microorganisms most commonly isolated in such infections were coagulase negative staphylococci, enterococci, Gram-negative bacilli, anaerobes and fungi.4,7 Interactions occur within biofilms in additive polymicrobial infections, such have been shown to exist between the Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species (HACEK) group pathogens and other bacteria in endocarditis.8 A study surveying pediatric endocarditis patients in hospitals identified polymicrobial infections in 11% of IE patients.3
Coinfection endocarditis cases with C. burnetii was described by Rovery et al.9 A systematic serology testing in culture negative suspected IE was performed and identified a coinfection in 6.5% of adult IE patients tested.9 They described 4 cases of coinfections that involved Streptococcus gallolyticus, Streptococcus mitis and Enterococcus faecalis, of which only one patient had symptoms suggestive of Q fever. The youngest patient described was 16 years old. Diagnosis of Q fever may have been delayed due to lack of specific signs and symptoms. In our described case, blood cultures did yield a positive result for K. kingae and he met modified Duke criteria for diagnosis of IE. However, because of a history that raised suspicion of Q fever exposure, serologies were obtained and were positive. The 2 rare pathogens were confirmed by postoperative PCR.
Chronic C. burnetii infection in children may manifest as endocarditis or osteomyelitis. In a review from 2002, 4 of 5 patients with Q fever endocarditis had an underlying congenital heart abnormality.5 Our patient may well be the youngest patient reported in the literature. A recent case series reported Q fever endocarditis in pediatric patients with right ventricle to pulmonary artery conduits, 2 of whom had ToF.6 A recent report found a total of 16 children with chronic Q fever infections in the past 20 years in Israel. Endovascular infections were found in 5 of these children (31%).10
The HACEK organisms are rare causes of IE in children. Data are limited for the prevalence of Kingella species in pediatric IE. There are no reports of pediatric endocarditis coinfection with Kingella species.
Our patient’s risk factors, including cyanotic CHD and age of <3 years predisposed him to IE.1
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