Brain Abscesses Complicating Staphylococcus aureus Sepsis in a Premature Infant

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Brain abscess is a rare complication of staphylococcal bacteremia in infants. Here we present a case of a premature infant who developed multiple brain abscesses 12 weeks following an episode of inadequately treated Staphylococcus aureus sepsis. The
  Infection 33 · 2005 · No. 1 © U RBAN  & V OGEL   36 Brain Abscesses Complicating Staphylococcus aureus  Sepsis in a Premature Infant G. Vartzelis, M. Theodoridou, G. L. Daikos, H. Dellagrammaticas, V. P. Syriopoulou  Abstract Brain abscess is a rare complication of staphylococcal bacteremia in infants. Here we present a case of a premature infant who developed multiple brain abscesses 12 weeks following an episode of inadequately treated Staphylococcus aureus  sepsis. The abscess developed in the absence of trauma, prior surgery, cyanotic heart disease, or immune defect. The initial staphylococcal isolate exhibited identical pulsed-field gel electrophoresis pattern with that of the isolate cultured from abscess aspirate. The infant was successfully treated by surgical drainage and adminis-tration of antibiotics for 12 weeks, initially teicoplanin and meropenem followed by trimethoprim/sulfamethoxazole, without neurological or developmental sequelae. Staphylo-coccal bacteremia in neonates should be vigorously treated to prevent life-threatening complications. Infection 2005; 33: 36–38DOI 10.1007/s15010-005-4062-z Introduction Brain abscesses are uncommon complications of bacterial meningitis or sepsis in neonates and young infants[1, 2]. Citrobacter   and Proteus  species are the most commonly reported organisms causing brain abscess during this early stage of life. Although Staphylococcus aureus  is among the causative agents of brain abscess in older children and adults [3, 4], this pathogen rarely causes brain abscess in the first months of life [5–8]. In this report, we present the clinical features, treatment, and outcome of a premature infant with multiple brain abscesses complicating inade-quately treated S. aureus  sepsis. Case Report A premature female was delivered by cesarean section after 33 weeks of gestation with birth weight of 1,590 g, length of 42 cm (< 10th percentile). 15 days after delivery, she became unstable with signs of sepsis; poor responsiveness, grunting, and poor pe-ripheral circulation. Her temperature was 39 °C; heart rate, 140 beats/min; respiratory rate, 50/min and blood pressure, 60/40 mmHg. Laboratory evaluation revealed the following: hemoglo-bin, 8.4 g/dl; white blood cell count, 6,300/mm 3 ; platelets, 115,000/mm 3 ; C-reactive protein was 66 mg/dl. She underwent a full septic screen and she was commenced on empirical treatment with am-picillin (100 mg/kg/day) and gentamicin (5 mg/kg/day). Cerebro-spinal fluid (CSF) examination revealed: no cells, protein of 120 mg/dl, and glucose of 55 mg/dl; Gram stain and cultures were neg-ative. The blood culture grew S. aureus  and Serratia marcescens  and the drainage from the right forearm intravenous catheter site grew S. marcescens . Both organisms were sensitive to gentamicin and resistant to ampicillin. The intravenous catheter was removed and 48 h after initiation of treatment, the bacteremia was cleared and the symptoms relieved. Antibiotics were discontinued after 7 days of treatment. A brain ultrasound, performed on day 18 of life, was unremarkable and the patient was discharged home in excellent condition at the age of 27 days.She remained well until the age of 14 weeks when she was ad-mitted to the hospital with a 3-day history of lethargy and fever of 38 °C. On clinical examination her anterior fontanelle was bulg-ing and her head sutures were widened, while no focal neurologi-cal signs were detected. Her occipitofrontal circumference was 40 cm (75th percentile), birth circumference was 32 cm (3rd percen-tile). Laboratory evaluation revealed the following: hemoglobin, 11.3 g/dl; white blood cell count, 17,300/mm 3 ; platelets, 603,000/mm 3 ; C-reactive protein was 4.2 mg/dl. A full septic screen was performed including a lumbar puncture, and the results from the CSF examination revealed: 8,000 cells/mm 3  (90% neutrophils), protein of 274 mg/dl, and glucose was not detectable. Imaging of the brain with ultrasound and computed tomography (CT) revealed three cerebral abscesses in the left frontal lobe (Fig-ure 1). Cardiac ultrasonography did not reveal any congenital ab-normalities. G. Vartzelis, M. Theodoridou, V. Syriopoulou First Dept. of Pediatrics, Aghia Sophia Children’s Hospital, Athens University, Athens, Greece G. L. Daikos First Dept. of Propaedeutic Medicine, Laiko General Hospital, Athens University, Athens, Greece H. Dellagrammaticas Neonatal Intensive Care Unit, Second Dept. of Pediatrics, Athens University, Aglaia Kyriakou Hospital, Athens, Greece.  V. P. Syriopoulou (corresponding author) First Dept. of Pediatrics, Aghia Sophia Children’s Hospital, Athens University, Thivon and Levadias Streets, GR-115 27 Athens, Greece; Phone: (+30/210) 746 7479, Fax: 775 7211, e-mail: Received: May 3, 2004 • Revision accepted: July 27, 2004 Infection  Case Report  Infection 33 · 2005 · No. 1 © U RBAN  & V OGEL   37 Treatment was initiated with meropenem (120 mg/kg/day) and teicoplanin (20 mg/kg/day) and the largest of the abscesses was drained through a left frontal burr hole. The culture of the as-pirate and CSF grew S. aureus . MICs determined by microdilution method were: oxacillin 0.5 µg/ml, cefotaxime 1 µg/ml, ceftriaxone, 1 µg/ml; imipenem, 0.06 µg/ml, meropenem 0.12 µg/ml, amikacin 1 µg/ml, trimethoprim/sulfamethoxazole 0.5/9.5 µg/ml, vancomy-cin 0.5 µg/ml, teicoplanin 0.5 µg/ml and rifampin 0.008 µg/ml. The Sma I digests of genomic DNA of the staphylococcal isolate from the current infection had identical pulsed-field gel electrophoresis pattern with that of the staphylococcal isolate from the previous hospitalization (Figure 2). Three days after initiation of antibiotic treatment and surgical drainage of the abscesses the patient im-proved significantly. She was discharged home in good condition after completing 8 weeks of intravenous antibiotic therapy with the aforementioned regimen. The child continued treatment with oral administration of trimethoprim/sulfamethoxazole (5/25 mg/kg q 12 h) for 1 additional month.At 3 months following completion of treatment, CT of the brain revealed a porencephalic cyst. At a 6-month follow-up visit, she was well without neurological or developmental sequelae. One year later, the child was doing well without other episodes of infections. A detailed immune workup did not reveal any under-lying immune defect; oxidative killing by neutrophil granulocytes and chemotaxis were normal, C3, C4, and CH50 were: 187 mg/dl, 26.4 mg/dl, and 42 U/ml, respectively; immunoglobulins and IgG subclasses were all within normal range, IgE was 21 IU/ml. The absolute number of CD4 + T cells was 1,833 cells/mm 3  and the CD4/CD8 ratio was 1.1. Discussion Brain abscesses in neonates or young infants are uncom-mon CNS infections and have different characteristics from those in older children [1–3, 9, 10]. They usually occur as complications of bacterial meningitis or bacteremia [1, 2]. The microbial agents that are commonly involved in the pathogenesis of neonatal brain abscesses are gram-nega-tive bacilli [1, 2]. Some microorganisms, such as Citrobacter   and Proteus , are characterized by unusual propensity for causing brain abscesses, whereas others, such as S. aureus , rarely are implicated in the pathogenesis of this infection during the first months of life [1, 2, 5–8]. In older children, congenital cyanotic heart diseases and infections in contig-uous structures such as otitis media, mastoiditis, or sinus-itis are the main etiologies of brain abscesses and the most important pathogens are anaerobic, and microaerophilic organisms, beta-hemolytic streptococci, and S. aureus  [4, 11]. In the case presented here the staphylococcal abscesses developed 12 weeks following an episode of staphylococ-cal bacteremia in the absence of any other predisposing factors.To our knowledge, only a few cases of staphylococcal brain abscesses in young infants have been reported previ-ously in the English literature [5–8]. Among those cases, the etiology of staphylococcal brain abscess was secondary to mastitis in two infants [6, 7], due to bacteremia follow-ing a peripheral vein catheter infection in one neonate [5] and obscure in one infant [8]. Although the case presented herein was diagnosed at 14 weeks of age, the brain most likely was infected by the hematogenous route during the preceding episode of staphylococcal bacteremia at 15 days of life. This is supported by the identical genotypes of the staphylococcal isolates cultured from the blood and the aspirate of the brain abscess of our patient. The hematog-enous dissemination was also favored by the location of the abscess in the frontal lobe. Clinical observations and experimental data have shown that the frontoparietal re-gion is the most favorable site of abscess formation after hematogenous dissemination [12]. Both bacterial and host factors may have played an important role in the pathogenesis of this life-threatening infection in our patient. Neonates have physiologic imma-turity in their immune system and their susceptibility to infections is well established. Furthermore, the right to left shunt that normally may be present in the first days of life, might have facilitated the hematogenous dissemination of bacteria to the brain by bypassing the defense mechanisms G. Vartzelis et al. Brain Abscesses in a Premature Infant Figure 1.  Brain computed tomography of an infant with staphylococ-cal abscesses. A  shows one large and two smaller abscesses with surrounding edema in the left frontal lobe; B  shows a large porencephalic cyst, 3 months following completion of treatment. Figure 2.  Pulsed-field gel electrophoresis of Sma I digests of genomic DNA of S. aureus  isolates. Lanes: L, lamda ladder DNA standard; 1, blood isolate; 2, brain abscess isolate.  G. Vartzelis et al. Brain Abscesses in a Premature Infant 38   Infection 33 · 2005 · No. 1 © U RBAN  & V OGEL of lung macrophages. It is also possible that staphylococci escaped the defense mechanisms of the host and the bac-tericidal effect of the antibiotics by their ability to survive intracellularly [13]. Undoubtedly, the inadequacy of the initial treatment regimen contributed significantly in this complication. Gentamicin cleared the bacteremia, but could not eradicate bacteria seeded in the brain, as this drug does not adequately pass the blood-brain barrier.Neonatal brain abscesses are often recognized late due to insidious onset of symptoms. Of particular interest in the present case was the prolonged (12-week) time interval between the initial episode of bacteremia and the clinical manifestations of the brain abscess. It is worth noting that the clinical presentation of a brain abscess depends mainly on the presence of raised intracranial pressure. In neonates the fontanels and the cranial sutures are still open and an intracranial mass lesion can grow without raising the intra-cranial pressure. This could explain the delayed onset of symptoms in the present case. The infant was brought to the hospital in a lethargic state, just after the rupture of the abscess into the ventricles having caused ventriculitis.Although there have been no controlled studies to draw firm conclusions for optimal therapy of brain abscesses in infants, clinical experience has shown that early surgical intervention combined with administration of specific an-tibiotics is required for a good outcome. Widespread avail-ability of CT scanning has contributed to a reduction in mortality from brain abscess from 30 to 10% [2, 3, 14, 15]. In a series of 30 neonates reported by Renier   et al. [2] four infants died, three from initial illness and one from shunt complications. In the same series, the long-term outcome was not uneventful. In the 17 children followed for more than 2 years, the proportion with an intelligence quotient at or above 80 fell to 24% (four cases). The absence of initial seizures, sterile CSF, normal ventricles on CT scans, and early aspiration of the abscess seem to be factors associated with better prognosis [2]. The presented case illustrates the unusual occurrence of brain abscess complicating staphylococcal sepsis in a premature infant. Prolonged administration of antibiotics along with surgical drainage are the keys to a successful outcome. Staphylococcal bacteremia in neonates should be vigorously treated to prevent metastatic infections and life-threatening complications. References 1. Krajewski R, Stelmasiak Z: Brain abscess in infants Childs Nerv Syst 1992; 8: 279–280.2. Renier D, Flandin C, Hirsch E, Hirsch JF: Brain abscesses in neo-nates. A study of 30 cases. J Neurosurg 1988; 69: 877–882.3. Saez-Llorens XJ, Umana MA, Odio CM, McCracken GH Jr, Nelson JD: Brain abscess in infants and children. Pediatr Infect Dis J 1989; 8: 449–458.4. Lakshmi V, Rao RR, Dinakar I: Bacteriology of brain abscess--ob-servations on 50 cases. J Med Microbiol 1993; 38: 187–190.5. Regev RH, Dolfin TZ, Zamir C: Multiple brain abscesses in a pre-mature infant: complication of Staphylococcus aureus  sepsis. Acta Paediatr 1995; 84: 585–587.6. Manzar S: Brain abscess following mastitis in a 3-month-old infant. J Trop Pediatr 2001; 47: 248–249.7. Mahapatra AK, Pawar SJ, Sharma RR, Lad SD: Brain abscess due to Staphylococcus aureus  following neonatal breast abscess: case report and a brief review of the literature. Annals of Saudi Medicine 2001; 21: 80–83.8. Tsutsumi S, Arai H, Hishii M, Suzuki K, Sato K: A case of neonatal cerebellar abscess. Childs Nerv Syst 2003; 19: 683–685.9. Sutton DL, Ouvrier RA: Cerebral abscess in the under 6 month age group. Arch Dis Child 1983; 58: 901–905.10. Tekkok IH, Erbengi A: Management of brain abscess in children: review of 130 cases over a period of 21 years. Childs Nerv Syst 1992; 8: 411–416.11. Brook I: Microbiology and management of brain abscess in chil-dren J Pediatr Neur 2004; 2: 125–130. Meves SH, Schroder A, Muhs A, Postert T, Federlein J, Buttner T: Distribution of artificially-produced microembolic signals into the cerebral circulation. Ultrasound Med Biol 2001; 27: 285–287.13. Kielian T, Cheung A, Hickey WF: Diminished virulence of an alpha-toxin mutant of Staphylococcus aureus  in experimental brain abscesses. Infect Immun 2001; 69: 6902–6911.14. Jadavji T, Humphreys RP, Prober CG: Brain abscesses in infants and children. Pediatr Infect Dis J 1985; 4: 394–398.15. Mampalam TJ, Rosenblum ML: Trends in the management of bacterial brain abscesses: a review of 102 cases over 17 years. Neurosurgery 1988; 23: 451–458.
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