Keywords group B streptococcus - neonate - brain abscess - meningitis - otorrhea
Bacterial meningitis has an estimated incidence of 0.1 to 0.4 per 1,000 live births.[1 ] It is a serious condition in neonates having a mortality rate between 8.5 and 15%
with up to 25% of survivors suffering mild to moderate neurological sequelae and 19%
with severe long-term neurological sequelae.[2 ]
[3 ]
[4 ]
Streptococcus agalactiae or group B streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis
worldwide.
GBS is a Gram-positive commensal bacteria that is known to colonize the gastrointestinal
and genitourinary tracts of 15 to 30% of women, which puts neonates at risk for vertical
transmission during the intrapartum period.[5 ] Infection due to GBS can be classified as early-onset (birth to 6 days of life)
which is transmitted vertically and late-onset (7 to 89 days of life) which is often
acquired by horizontal transmission from colonized mothers or household contacts.[6 ] In the past few decades, there has been a progressive decline in the incidence of
bacterial meningitis owing to GBS screening and treatment guidelines for pregnant
women and timely evaluation and treatment of infants with maternal risk factors for
infection.[7 ]
Brain abscess can complicate up to 10% of cases of neonatal meningitis[8 ] and is significantly more common in Gram-negative bacterial meningitis,[9 ] but brain abscess due to GBS infection are extremely rare. We describe the case
of a neonate who presented with the unusual symptom of bilateral otorrhea since birth
and was subsequently found to have a brain abscess caused by GBS, which resulted in
a complicated neurological course.
Case Description
An 8-day-old female infant presented to the emergency room (ER) with a fever of 101.2 F
at home and bilateral otorrhea. On physical examination the infant was noted to be
alert but irritable and thick purulent greenish-yellow discharge was noted from both
ears. Vital signs were normal except for a temperature of 100 F. At home, the infant
was exclusively breast fed with good urine and stool output and she was noted to be
only 3% below birth weight. Due to the infant's age and presentation, a full septic
workup (including blood, urine, and cerebrospinal fluid [CSF] culture and herpes simplex
virus [HSV] studies) was done. Additionally, a bacterial culture of the ear drainage
was also obtained. The infant was started on ampicillin, gentamicin, and acyclovir
and admitted to the neonatal intensive care unit (NICU) for further evaluation and
treatment.
The infant was born at 39 weeks' gestation via spontaneous vaginal delivery to a 21-year-old
gravida 2 para 2 mother. Rupture of membranes was 7 hours prior to delivery and all
maternal serologies including her testing for GBS were negative. Pregnancy was complicated
by maternal anxiety and depression (for which she was on sertraline), pregnancy-induced
hypertension, and intrauterine growth restriction. At delivery, amniotic fluid was
noted to be meconium stained but the infant was not in any distress and Apgar scores
were 8 and 9 at 1 and 5 minutes, respectively. The birth weight was 2,705 g. Mother
was noted to have a fever of 101 F at delivery with evidence of chorioamnionitis and
started on antibiotics. Due to maternal chorioamnionitis, infant was admitted to the
NICU where a screening complete blood cell count showed a white blood cell (WBC) count
of 18,000/μL with 7% banded and 62% segmented neutrophils. A blood culture was also
obtained from the umbilical cord which was eventually negative. The infant otherwise
had normal vital signs and was feeding well during the birth hospitalization, so antibiotics
were not started per recommendations from the neonatal early-onset sepsis calculator[10 ] and she was discharged home at 48 hours of life. However, the mother reported that
she noticed bilateral ear drainage since shortly after birth and the infant failed
her hearing screen bilaterally.
Septic workup obtained in the ER was significant for a grossly abnormal CSF analysis
with low glucose of 20 mg/dL (reference range 40–70 mg/dL), elevated protein of 198
(reference range 15–45 mg/dL), WBC count of 9,825/mm3 (reference range 0–5/mm3 ) with 85% neutrophils, and red blood cell count of 2,525/mm3 (reference range 0/mm3 ) concerning for bacterial meningitis, so antibiotics were switched to vancomycin
and cefepime at meningitic dosing and a pediatric infectious disease specialist was
consulted. Interestingly, bacterial culture of the ear drainage and a screening nasopharyngeal
culture on admission to the NICU were both positive for GBS. However, blood, urine,
and CSF bacterial cultures and HSV polymerase chain reaction studies remained negative.
Soon after admission, the infant was noted to have multiple apneic and bradycardic
events associated with gaze abnormalities (downwards and sideways gaze), concerning
for seizures, so the infant was intubated and placed on mechanical ventilation and
loaded with phenobarbital. An electroencephalogram (EEG) was obtained which confirmed
multiple seizures originating from the left temporocentral region. A screening bedside
head ultrasound was normal but brain magnetic resonance imaging (MRI) with and without
contrast showed a circular lesion demonstrating a partially enhancing rim and adjacent
edema within the left posteroinferior temporal lobe measuring approximately 25 mm
in diameter, concerning for an early abscess. At this point, the neurosurgery team
was consulted who recommended broadening antibiotic coverage by adding metronidazole
for anaerobic coverage. After initiation of phenobarbital the seizures abated so EEG
was discontinued, and the infant was extubated and slowly weaned off all respiratory
support, 4 days after admission. To monitor response to antibiotic treatment, serial
C-reactive protein levels and CSF analyses were also obtained ([Fig. 1 ]). CSF bacterial cultures remained negative throughout the course of treatment.
Fig. 1 Line graphs depicting trends of (A ) C-reactive protein (mg/dL), (B ) serum white blood cell count (103 /μL), (C ) cerebrospinal fluid (CSF) white blood cell count (per mm3 ) on the y -axis and infant age in days of life on the x -axis.
A repeat brain MRI 1 week after admission (day of life 15) showed that the left temporal
lobe abscess had increased in size (30.1 mm × 20.3 mm) and there was purulent material
layering within the lateral ventricles (left greater than right) with increased size
of the ventricular system ([Fig. 2A ]), so decision was made to drain the abscess under ultrasound visualization via a
left temporal burr hole. A right frontal external ventricular drain was also inserted
via a right frontal burr hole ([Fig. 2B ]).
Fig. 2 Serial brain magnetic resonance imaging showing: (A ) Left temporal lobe abscess (30.1 mm × 20.3 mm) and bilateral ventriculomegaly on
day of life 15. (B ) Decompression of the left temporal lobe abscess via a left temporal burr hole and
decreased ventricular size following external ventricular drain placement via a right
frontal burr hole on day of life 16. (C ) Increased size of the trapped temporal horn of left lateral ventricle (36.7 mm × 30.9 mm)
on day of life 69. (D ) Decrease in size of the temporal horn of left lateral ventricle following placement
of left frontal ventriculoperitoneal shunt and revision with placement of a catheter
into the left temporal horn cyst on day of life 104.
Over the next few weeks, the abscess cavity remained decompressed, but the temporal
horn of the left lateral ventricle progressively enlarged, measuring about 36.7 mm × 30.9 mm
on day of life 69 ([Fig. 2C ]), so decision was made to insert a left temporal horn ventricular access device
(VAD) for obstructive hydrocephalus. With multiple and frequent taps of the VAD there
was some initial improvement in the ventricular size but eventually the temporal horn
of the left lateral ventricle continued to enlarge requiring placement of a left frontal
ventriculoperitoneal (VP) shunt. The VP shunt needed revision with placement of a
catheter into the left temporal horn cyst, which eventually led to reduction in size
on day of life 104 ([Fig. 2D ]). In total, the infant received 14 days of intravenous vancomycin, cefepime, and
metronidazole and 10 weeks of intravenous ampicillin monotherapy until discharge.
Discussion
Guidelines for the prevention of perinatal transmission of GBS using intrapartum antibiotic
prophylaxis (IAP) were first published in 1996 by the Center for Disease Control and
Prevention in consensus with the American Academy of Pediatrics and American College
of Obstetrics and Gynecology.[6 ] Since then these recommendations have undergone several iterations and have evolved
from an earlier risk factor-based approach to now universal screening for GBS in pregnant
women at 36 to 37 weeks' gestation.[11 ]
[12 ]
[13 ] The implementation of the universal screening program and the use of IAP has resulted
in an almost eightfold reduction in early-onset GBS sepsis from 1.8 cases per 1,000
live births (1990) to 0.23 cases per 1,000 live births (2015).[14 ] Although a positive prenatal GBS culture increases the likelihood of early-onset
GBS infection in neonates, in the current era of universal screening more than 60%
cases of early-onset disease occur in infants of mothers with a negative prenatal
GBS screen.[15 ]
However, despite the overwhelming success of the screening program, IAP has had no
effect on the incidence of late-onset sepsis.[14 ] This is because maternal prenatal GBS testing does not always accurately predict
the mother's GBS status during the postpartum period and horizontal transmission from
colonized mothers is thought to be the major mechanism implicated in late-onset GBS
disease.[16 ] In a prospective cohort study by Berardi et al, rectovaginal GBS colonization was
found in 64% of mothers at the time of late-onset GBS infection diagnosis in infants
and an additional 6% of mothers had GBS mastitis.[17 ]
In the case we present, the mother's GBS screening was negative but the intrapartum
period was complicated by chorioamnionitis which increases the risk for neonatal infection.[18 ] The infant in our case most likely acquired a focal infection (otitis) by vertical
transmission, as evidenced by the ear discharge reported shortly after birth, but
the overall well appearing status at the time of discharge. This infection then progressed
to GBS meningitis and brain abscess in the days that followed, prior to presentation
to the ER on the 8th day of life. GBS meningitis is seen in only a minority of early-onset
disease but can complicate up to 25 to 30% of late-onset disease.[14 ] It presents with nonspecific symptoms of temperature instability (fever or hypothermia),
irritability or lethargy, respiratory distress or apnea, poor feeding, and seizures.[19 ]
[20 ] Additional complications include the development of hydrocephalus, subdural effusion,
cerebral venous thrombosis, cerebral infarcts, and brain abscess.[21 ]
Brain abscesses are significantly more common with Gram-negative bacteria like Citrobacter , Serratia , Proteus , and Escherichia coli
[9 ] but brain abscess secondary to GBS are extremely rare. In a case reported in 2016,
Giannattasio et al described a 6-week-old presenting with irritability, poor feeding,
and fever who was found to have GBS meningitis and brain abscess. The infant showed
complete resolution of abscess with a 4-week course of meropenem and ampicillin, without
any neurosurgical interventions and had normal neurodevelopmental outcomes. However,
the size of abscess in their case was significantly smaller at 9 × 6 mm compared to
the 25-mm diameter abscess seen in our case.[22 ] In 2009, Pasternak et al reported the case of an 8-week-old who presented with irritability,
projectile vomiting, rapidly increasing head size, and left abducens nerve palsy.
MRI showed a large complex cystic lesion in the left temporo-occipital lobe with mass
effect and signs of obstructive hydrocephalus. Similar to our case, their patient
required neurosurgical drainage and prolonged duration of intravenous ampicillin followed
by intravenous ceftriaxone for a total of 16 weeks until complete resolution of abscess.[23 ] While brain abscesses in the temporal region have been described following otogenic
infections (like chronic otitis media) in children and adults,[24 ] such a presentation has not been described in neonates. It is important to note
that, majority of GBS implicated in neonatal disease is susceptible to beta-lactam
antibiotics and reports of penicillin-binding protein mutations leading to resistance
are extremely rare.[25 ] Thus, due to its narrow spectrum penicillin is considered first-line therapy for
all GBS infections though ampicillin is considered an acceptable alternative[6 ] and both drugs have excellent central nervous system (CNS) penetrance.[26 ]
The imaging modality of choice for diagnosing a brain abscess is a contrast-enhanced
MRI which typically shows a circumscribed area of hypoattenuation with surrounding
contrast enhancing rim.[27 ] Antibiotic therapy alone may be adequate for smaller solitary abscesses (less than
2 cm in diameter), but surgical drainage is often required for larger lesions. Ultrasound
is of value in delineating and accessing the abscess for drainage.[27 ] In a case series of 54 children, majority only needed one aspiration[28 ]; however, those with an increase in size despite drainage and adequate antibiotic
therapy required additional procedures like craniotomy for evacuation of pus and debridement
of surrounding brain parenchyma and placement of ventricular drainage devices for
obstructive hydrocephalus. No prospective studies have been performed to determine
the adequate length of antibiotic therapy for brain abscesses, but experts recommend
at least 4 to 6 weeks of treatment with serial imaging to ensure resolution of abscess.
Longer antibiotic durations may be needed for tubercular brain abscess or in cases
that are slow to resolve.[27 ] Brain abscess in neonates have a grave prognosis with a case series of 30 neonates
describing 4 deaths and an intelligence quotient below 80 at 2 years of age in 76%
of the survivors[21 ].
Conclusion
While exceedingly rare, brain abscess can occur as a sequela of GBS meningitis in
neonates. Otogenic infections require prompt evaluation and treatment in neonates
because of their risk of progression to serious CNS infections like meningitis and
brain abscess. These infections require prolonged antibiotic courses and at times
advanced neurosurgical interventions for treatment and are associated with an unfavorable
prognosis and adverse neurodevelopmental outcomes in neonates.
