Staphylococcus Aureus Endocarditis Associated With Varicella Infection in Children

Varicella infection is a common childhood disease, usually self-limiting and with minimal sequelae. Before the availability of varicella vaccine, there were an estimated 3.9 million cases of varicella each year in the United States.1 Complications of varicella are well-known. Viral-related complications include arthritis, cerebellitis, encephalitis, myocarditis and pneumonia. Bacteria-related complications are a result of superinfections of the skin that can lead to osteomyelitis and pericardial disease.2 On reviewing the medical literature we found no reports of bacterial endocarditis complicating varicella infection. Here we report two cases of Staphylococcus aureus endocarditis complicating varicella infection, both with septic emboli to the brain. Case reports.Case 1. BV was a 5-year-old male transferred to our intensive care unit with a 7-day history of varicella. Two days before admission he had become lethargic and irritable and was minimally arousable on presentation. He had no prior history of medical problems or physical abnormalities. On examination he was febrile (100.3°F rectally), irritable and without nuchal rigidity. The varicella lesions were healing with a few impetiginous lesions. A complete blood count showed a white blood cell count (WBC) of 9600 cells/mm3, 22% neutrophils, 55% band forms and 15% lymphocytes. Other laboratory findings were significant for thrombocytopenia of 104 000/mm3. The cerebrospinal fluid revealed WBC of 277 cells/mm3, 83% neutrophils and 17% lymphocytes. Glucose was 65 mg/dl and protein was 106 mg/dl. Oxacillin, cefotaxime and acyclovir were started. A blood culture grew S. aureus, to penicillin. The cerebrospinal fluid bacterial and viral culture were sterile. The patient improved. Oxacillin was continued for treatment of S. aureus bacteremia and possible meningitis. Throughout the hospital stay our patient had no cardiac murmur. A low grade fever continued until the day of discharge. He was discharged after 7 days, to complete a 14-day antibiotic course. On routine follow-up 3 days after discharge, physical examination demonstrated a murmur and splenomegaly. Echocardiogram showed aortic valve insufficiency with a valvular vegetation. A computerized tomography scan and magnetic resonance imaging of the head showed several focal areas consistent with septic emboli. A repeat lumbar puncture revealed 2 WBC/mm3 and a negative culture. The patient was given digoxin and captopril for heart failure and received a total of 6 weeks of iv oxacillin and rifampin therapy. Repeat echocardiograms showed the valvular vegetation to be resolving; however, the secondary aortic insufficiency continued and a pseudoaneurysm of the left ventricle outflow tract developed. After completion of antibiotic therapy he successfully underwent repair of the pseudoaneurysm, resection of residual valvular endocardial vegetation and aortovalvuloplasty. His aortic insufficiency worsened, requiring surgical correction with a Ross procedure. He tolerated the procedure well and has no neurologic sequelae. Case 2. MF was a 2-year-old white female who presented with altered mental status 7 days after developing varicella. Three days before admission her parents noted her left great toe to have a “cluster of purple lesions.” During the next 2 days she became listless and then had an abrupt change in responsiveness. She had no prior medical history of significant illness. Physical examination was remarkable for a fever of 103°F and depressed mental status with minimal verbal responsiveness. The left first toe had an ecchymotic nonblanching lesion. Laboratory tests were remarkable for a WBC of 4400/mm3, thrombocytopenia of 41 000/mm3 and creatinine phosphokinase of 840. A lumbar puncture showed 17 WBC/mm3, 75% neutrophils, 14% lymphocytes, 11% monocytes, glucose 94 mg/dl and protein 56 mg/dl. She remained obtunded in spite of iv fluids and cefotaxime therapy. The following day a pericardial rub was appreciated, along with hepatosplenomegaly. Acyclovir and oxacillin were added to her treatment. Blood culture from admission yielded S. aureus susceptible to oxacillin. The cerebrospinal fluid culture was negative. Echocardiogram revealed a large pericardial effusion, mild tricuspid regurgitation and two pedunculated and mobile vegetations in the left ventricle, with a third at the aortic valve. During her hospitalization she manifested multiorgan insult secondary to septic emboli. The brain, retina, kidney, knee and toe suffered injury as a result of septic emboli from the left-sided endocarditis. She underwent elective surgery to reduce the risk of further emboli, with pericardectomy and excision of the left ventricular vegetations. An echocardiogram on her 22nd hospital day showed a 3-cm left ventricular aneurysm with a thrombus. A myocardial thallium scan was consistent with infarction of the left ventricular apex. This infarction was believed to be the cause of the aneurysm. The patient underwent successful resection of the aneurysm and thrombus; however, a postoperative echocardiogram showed a new left ventricular pseudoaneurysm immediately beneath the left pulmonary artery. Because of the high risk for rupture, this was repaired. Pathology reports of both types of aneurysms did not find abscesses in either specimen. She received oxacillin for 6 weeks, rifampin for 4 weeks, and gentamicin for 2 weeks. After surgical intervention she has mild residual left ventricular dilatation but good contractility. She has normal development and normal activity and no neurologic sequelae. Discussion. Varicella infection typically has a benign course and outcome. Complications, although uncommon, can be life-threatening.2 Immunocompromised patients are at greater risk for complications. Complications from varicella infection can be a result of direct viral involvement producing pneumonia or encephalitis. Various other complications can occur, including bacterial infections associated with superinfection of skin lesions.3 Soft tissue and skin infections are the most common complications in the pediatric population.4 These include cellulitis, impetigo and adenitis.3 Skin is the primary line of defense against S. aureus infection. When varicella disrupts the skin barrier it allows for bacterial superinfection. One case in the literature reports a transient granulocyte killing defect during varicella infection.5 It is possible that by disrupting the skin barrier and altering cellular immunity, varicella increases the risk of severe bacterial infection. The most common organisms isolated from secondary infected skin lesions are coagulase-positive staphylococci and group A beta-hemolytic streptococci.2,3 Necrotizing fasciitis due to beta-hemolytic streptococci has recently received attention as a serious complication of varicella infection.6 Staphylococcal bacteremia is usually seen with skin or soft tissue infection, but at times the focus may be inapparent.7 In our first case there were areas of mildly impetiginous lesions. In our second case the toe lesion was presumed to be caused by septic emboli secondary to endocarditis. Both cases had cardiac sequelae secondary to varicella infection. Most patients with bacterial endocarditis have a risk factor such as congenital heart disease, cardiac surgery or an indwelling central venous catheter.8 Our cases had no risk factors. The most common cause of bacterial endocarditis occurring in pediatric patients without underlying cardiac abnormalities is S. aureus. Friedland et al.10 recommends considering echocardiography in children with S. aureus bacteremia, as they report clinically silent endocarditis in these patients. Therefore it is not surprising that S. aureus bacteremia could lead to endocarditis in varicella patients. Cardiac complications of varicella are very rare; they are usually manifestations of a viral myocardial involvement.11 Most cases of cardiac complications have been described in adolescents with no known underlying cardiac abnormalities.11-13 A review of the literature found only three cases of pericardial bacterial infection in association with varicella infection in children. Kopec et al.14 describe the case of a 14-year-old male with S. aureus pericarditis as a complication of varicella infection. There was no clinical evidence of bacterial skin infection, and the patient's blood cultures were negative. They hypothesized that an occult cellulitis and transient bacteremia occurred, resulting in pericardial seeding. The article cites two prior cases of young children having S. aureus pericarditis and systemic bacterial infection in association with varicella.15 There have been no published reports of S. aureus endocarditis or myocarditis as a complication of varicella infection. Both of our patients had decreased mental status secondary to septic emboli from their left-sided endocarditis. Initially their abrupt change in mental status was attributed to dehydration and viral encephalitis. Changes in mental status with varicella should also include a consideration of bacterial infection of the brain. When S. aureus bacteremia complicates varicella, it is important to look for serious suppurative complications such as endocarditis, septic emboli to the brain and other organs as well as bacterial meningitis. Use of the recently released varicella vaccine (Varivax®) will greatly decrease the incidence of chickenpox, and in so doing will likely prevent its complications. Acknowledgments. We appreciate the excellent care provided to these patients by the residents, nursing staff, and the pediatric intensive care staff. Lisa C. Gold, M.D.; Stephen D. Barbour, M.D.; Lourdes M. Guerrero-Tiro, M.D.; Ravi Koopot, M.D.; Karen Lewis, M.D.; Mark F. Rudinsky, M.D.; Robert L. Williams, M.D. St. Joseph's Hospital and Medical Center Children's Health Center Phoenix, AZ