Published online September 25, 2006
PEDIATRICS Vol. 118 No. 5 November 2006, pp. e1576-e1579 (doi:10.1542/peds.2006-1224)

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EXPERIENCE & REASON

Diffuse Pneumocephalus in Neonatal Citrobacter Meningitis

Joseph N. Alviedo, MD^a, Beena G. Sood, MD, MS, FAAP^a, Jacob V. Aranda, MD, PhD^a and Cristie Becker, MD^b

^a Carman and Ann Adams Department of Pediatrics
^b Department of Pediatric Radiology, Wayne State University, Hutzel Women's Hospital and Children's Hospital of Michigan, Detroit, Michigan

ABSTRACT

Pneumocephalus, intracranial air or gas collection, associated with neonatal meningitis is extremely rare. We report the first case in the United States and the second case in the world of intracranial gas accumulation in a neonate with Citrobacter koseri meningitis. The clinical presentation was acute with pneumocephalus demonstrated by cranial sonography and computed tomography. The clinical course was fatal despite the prompt administration of antibiotics.

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Key Words: neonatal • meningitis • pneumocephalus • Citrobacter • head ultrasound • cranial computed tomography

Abbreviations: CSF, cerebrospinal fluid • CT, computed tomography

Gas within the intracranial cavity commonly results from trauma or is iatrogenic. It is rarely associated with meningitis. Here we report the case of a neonate with diffuse pneumocephalus caused by Citrobacter koseri meningitis in the absence of the predisposing factors noted above or intracranial abscess.

CASE REPORT

The subject of this report is a white male infant delivered at 33 weeks' gestation with a birth weight of 2410 g after an otherwise uncomplicated pregnancy. He was admitted to the NICU for transient tachypnea of the newborn, which was treated with oxygen delivered by hood. Empiric antibiotics (ampicillin and gentamicin) were administered through a peripheral intravenous line and discontinued after 48 hours on documentation of a sterile blood culture. He was discharged well on the ninth day of life. Five days later, he was brought to a local emergency department for poor oral intake and lethargy since the morning of admission. Physical examination was remarkable for hypothermia, lethargy, pallor, and repeated episodes of apnea. Complete blood counts were significant for a total leukocyte count of 2900 cells per mm³ and 18% immature cells. Parenteral antibiotics (ampicillin, gentamicin) were started after obtaining blood culture, and the infant was transferred to a level III NICU within 2 hours of presentation. He required intubation and assisted ventilation for recurrent apneas. He was noted to have a full anterior fontanelle. Cefotaxime was added to the antibiotic regimen, and a spinal tap (performed within 12 hours of admission) revealed turbid cerebrospinal fluid (CSF) with numerous polymorphonuclear cells. Over the next 24 hours he developed seizures, metabolic acidosis, and disseminated intravascular coagulation. The initial blood culture was reported to be positive for C koseri resistant to ampicillin and sensitive to piperacillin. Therefore, ampicillin was discontinued and piperacillin was added to the treatment regimen. A blood culture was repeated at this time. The repeat blood culture and culture of CSF were eventually reported to be positive for C koseri. The patient's clinical condition continued to deteriorate with development of a bulging anterior fontanelle, lack of response to noxious stimuli, hyphema, and fixed dilated pupils. A cranial sonogram was suggestive of extensive intracranial air, and the infant was transferred to the Children's Hospital of Michigan for neurosurgical evaluation. A cranial sonogram at admission confirmed the presence of extensive intracranial air with obscuration of all anatomic detail (Fig 1). Cranial computed tomography (CT) performed 1 day later confirmed the presence of extensive subarachnoid and intraventricular air. It also revealed intraparenchymal, subarachnoid, and subdural blood, protrusion of brain parenchyma, and intracranial air through the widened anterior fontanelle and total loss of gray-white matter differentiation, which are consistent with diffuse cerebral edema/infarct (Figs 2 and 3). Meropenem was added to the treatment regimen because of documented piperacillin resistance on the second set of cultures. The patient's condition continued to deteriorate. Results of an electroencephalogram were severely abnormal with diffuse background attenuation and no response to stimuli. Multiple discussions were subsequently held with the family concerning the infant's devastating central nervous system infection and extremely poor prognosis. They eventually agreed to withdrawal of support, and the infant expired shortly thereafter. Permission for autopsy was refused.

View larger version (105K): [in this window] [in a new window]   FIGURE 1 Midcoronal cranial sonogram demonstrating echogenic foci of air in subarachnoid distribution (arrowheads).

 

View larger version (92K): [in this window] [in a new window]   FIGURE 2 Axial unenhanced cranial CT demonstrating extensive pneumocephalus, subarachnoid hemorrhage in basal cisterns (arrows), and subdural hemorrhage in posterior fossa (star).

 

View larger version (96K): [in this window] [in a new window]   FIGURE 3 Higher scan showing intraparenchymal hemorrhage (star), severe cerebral ischemia/edema, and protrusion of brain parenchyma and intracranial air through the widened anterior fontanelle (arrows).

 

DISCUSSION

Pneumocephalus, the presence of air or gas within the cranial cavity, has been described with central nervous system trauma, surgery, air embolus, brain abscess, or postradiation necrosis of skull appendages.^1–4 The first case of pneumocephalus associated with bacterial meningitis in the absence of predisposing conditions was reported in 1985 in an adult with mixed aerobic-anaerobic infection.⁵ Since then, 10 cases of pneumocephalus have been reported in adults associated with meningitis caused by various aerobic and anaerobic organisms including Streptococcus pneumoniae, Enterobacter cloacae, Klebsiella aerogenes, Enterococcus, Candida albicans, Clostridium perfringens, and Bacteroides fragilis in the absence of other risk factors for pneumocephalus.^6–12 Pneumocephalus associated with meningitis also has been reported in the neonatal and postneonatal period in 5 infants.^8,13–17 All these infants had a fatal outcome. Only 1 case of C koseri meningitis associated with diffuse pneumocephalus has been reported in the literature. We report the second case of neonatal C koseri meningitis, the first from the United States, associated with diffuse pneumocephalus and a fatal outcome.

Intracranial anaerobic and aerobic infections may produce gas by putrefaction of the intracellular protein derived from autolysis and by decomposition of glucose.⁹ Ischemia may also be a contributory factor in that any gas produced may not be absorbed. These factors may act singly or in combination, resulting in pneumocephalus. After the introduction of cranial imaging studies, detection of gas-forming brain abscesses caused by nonclostridial anaerobic or aerobic bacilli has been increasing. In adults, tension pneumocephalus has been described as the "Mount Fuji" sign on CT as bilateral compression, peaking, and separation of the frontal lobes.¹⁸ This appearance was not present in our patient because of patent sutures and anterior fontanelle, through which intracranial air and brain parenchyma were bulging.

Citrobacter spp. are facultative anaerobic Gram-negative enteric bacilli that hydrolyze urea and ferment glucose with the production of gas.¹⁹ This genus includes 11 species, the most commonly identified being Citrobacter freundii, C koseri (formerly Citrobacter diversus), and Citrobacter amalonaticus. Organisms belonging to the genus Citrobacter are widespread in the environment, being found in soil and water. Newborns can acquire colonization at the time of passage through the birth canal of a colonized mother. Onset of diseases beyond the first week of life commonly is related to colonization of the infant in the nursery. Most affected infants are <6 weeks of age, and no cases have been recorded beyond 8 weeks. Approximately one third of the affected patients are <36 weeks' gestational age at birth, suggesting that preterm infants have increased risk for acquiring Citrobacter infection.

The genus Citrobacter accounts for 4% of all cases of neonatal meningitis.^19,20 C koseri, the species isolated in 80% cases, is the most common cause of neonatal brain abscess. This is explained by the ability of Citrobacter spp. to invade, transcytose, and multiply within human brain microvascular endothelial cells in vitro. The case-fatality rate for Citrobacter meningitis is 30%, and at least 75% of the surviving infants have neurologic sequelae.

In the subject of this case report, the C koseri organism initially isolated was resistant to ampicillin but sensitive to piperacillin. However, the organism rapidly developed resistance to piperacillin after 3 days of therapy. This is consistent with the antimicrobial susceptibility patterns described for this organism in the literature. C koseri is usually resistant to ampicillin and sensitive to aminoglycosides and third-generation cephalosporins.¹⁹ Some Citrobacter isolates contain chromosomally mediated group I ß-lactamases that lead to emergence of drug resistance and treatment failure despite initial susceptibility. Carbapenems have been tried in resistant cases, as was done for our patient.

There are several similarities between the subject of this report and the neonate previously reported in the literature with pneumocephalus and C koseri–associated meningitis. Both infants were delivered prematurely, had initial sterile postnatal blood cultures, and presented a few days later with shock, multiorgan failure, meningoencephalitis, and pneumocephalus. Both infants eventually succumbed to the infection and its related multisystem complications within a relatively short period of time. They were brain dead before support was withdrawn. Such a fulminant course of Citrobacter infection despite administration of appropriate antibiotics after identification of the causative organism resulting in death attests to the virulence of the organism. The need for immediate institution of broad-spectrum antibiotics with adequate CSF penetration and appropriate imaging studies may seemingly be futile. However, maximal effort including early suspicion, diagnosis, and appropriate antibiotic therapy, if instituted, may potentially change the poor outcome seen in this disease.

CONCLUSIONS

We add C koseri meningitis to the differential diagnosis of diffuse pneumocephalus found on cranial imaging studies in a neonate. This case emphasizes the value of prompt administration of broad empiric antibiotic treatment (perhaps with piperacillin, gentamicin, and a carbapenem) and brain imaging (cranial sonography and CT) as soon as C koseri is reported in blood or CSF despite potentially adverse outcomes.

FOOTNOTES

Accepted Jun 5, 2006.

Address correspondence to Beena G. Sood, MD, MS, FAAP, Department of Pediatrics, Children's Hospital of Michigan, 3901 Beaubien Blvd, 4H42, Detroit, MI 48201. E-mail: bsood{at}med.wayne.edu

The authors have indicated they have no financial relationships relevant to this article to disclose.

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