SN Comprehensive Clinical Medicine (2020) 2:472–477

https://doi.org/10.1007/s42399-020-00255-7

MEDICINE

Neonatal Group A Streptococcus Meningitis. Case Report

and Literature Review
Tomer Talmy 1,2 & Elad Mazor 1,3 & Ehsan Nasser 1 & Anthony Luder 1,4

Accepted: 10 March 2020 / Published online: 19 March 2020

# Springer Nature Switzerland AG 2020

Abstract
Group A streptococci (GAS) have previously accounted for a large portion of invasive neonatal infections, but differences in the
access to medical care and in the antibiotic used over the last half century has significantly reduced such cases. A literature review
reveals 17 neonatal GAS meningitis reports with positive CSF cultures since 1967, characterized by high morbidity and mortality.
We present a case of a 10-day old well-appearing neonate diagnosed with GAS meningitis, exhibiting an excellent response to
antimicrobial therapy. Epidemiological investigation revealed her mother as the likely source of postnatal transmission of GAS
with an emm1.0 subtype. GAS meningitis is a rare cause of neonatal meningitis associated with high morbidity and mortality
warranting further research assessing potential risk factors, modes of transmission, and therapeutic protocols.

Keywords Neonatal meningitis . Neonatal sepsis . Group a streptococci . Streptococcus pyogenes

Abbreviations Introduction
CDC Centers for disease control and prevention
CSF Cerebrospinal fluid In the early half of the twentieth century, Streptococcus
GAS Group a streptococcus pyogenes (group a streptococcus (GAS)) was considered a
SIADH Syndrome of inappropriate antidiuretic hormone prevalent and important cause of neonatal sepsis and menin-
secretion gitis. However, since the advent and widespread use of anti-
biotics, it has become a rarely reported cause of neonatal sep-
sis [1–3], often accompanied by a rather severe and occasion-
ally fatal disease course [1, 2, 4–6]. Here, we review the clin-
This article is part of the Topical Collection on Medicine ical characteristics of previously reported cases of and present
a case of GAS meningitis in a 10-day old, well appearing
* Tomer Talmy
neonate, most likely resulting from maternal transmission.
ttalmy@gmail.com

Elad Mazor
eladmazor@gmail.com
Ehsan Nasser Materials and Methods
ehsan.n@ziv.health.gov.il
We performed a literature review of PubMed and Google
Anthony Luder
luder.a@ziv.health.gov.il Scholar from 1966 through 2018 to identify documented
cases of neonatal GAS meningitis utilizing the following
1
Department of Pediatrics, Ziv Medical Center, Derech HaRambam, search terms: “Neonatal meningitis,” “Neonatal sepsis,”
Tzfat, 13100 Safed, IL, Israel “Pediatric,” “Children,” “group a streptococcus,” “Group A
2
Faculty of Medicine, Hebrew University Hadassah Medical School, Streptococcal,” “Streptococcus pyogenes,” and “GAS.”
Jerusalem, Israel Articles were reviewed to identify reports describing infants
3
Ben-Gurion University Joyce and Irving Goldman Medical School, ≤28 days of age diagnosed with CSF culture proven GAS
Be’er-Sheva, Israel meningitis. We also carefully considered articles cited in the
4
The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel articles found.
SN Compr. Clin. Med. (2020) 2:472–477
Case Presentation
A 10-day old neonate presented to our pediatric emergency
department with a 2 day history of fever, irritability and loose
stool. She was born to a healthy mother after an uncomplicat-
ed pregnancy by vaginal delivery at 40 weeks of gestation,
with a birth weight of 4250 g. Initial evaluation revealed a
temperature of 39.4 °C with a heart rate of 190/min. Upon
physical examination, the neonate was well appearing without
apparent signs of meningitis or sepsis such as apathy, pallor,
raised fontanelle, prolonged capillary filling or rash. A full
evaluation for serious bacterial infection was performed, in-
cluding culture and laboratory investigations of blood, urine,
and CSF. Lumbar puncture was traumatic and yielded bloody
fluid, sufficient for only a single vial which was sent for cul-
ture. Subsequently, an empirical antibiotic regimen of ampi-
cillin and cefotaxime was instituted.
Initial laboratory results revealed a peripheral blood white-
cell count of 26,800/mm3 with a predominance of neutrophils
(70%) and an elevated C-reactive protein level of 41.3 mg/l
(normal range, 0–5). 24 h after admission, CSF culture re-
vealed growth of gram positive cocci, later confirmed as
S. pyogenes sensitive to ampicillin. Blood and urine cultures
did not reveal bacterial growth. As a result, cefotaxime was
discontinued and treatment with intravenous ampicillin was
continued for a total of 14 days. The child responded well to
antimicrobial therapy and she continued to feed normally with
no unusual clinical signs or events. At discharge, she was
feeding well, with normal vital signs, and laboratory revalua-
tion showed a white-cell count of 10,200/mm3 with a C-
reactive protein level of 1.2 mg/l. Repeat lumbar puncture
and imaging were not performed because of the excellent
clinical response. Follow-up hearing tests conducted after dis-
charge showed normal hearing.
As part of the epidemiological investigation of this case, we
obtained throat, vaginal, and rectal swabs from the parents of
the child after being informed of the neonate’s positive CSF
culture (~48 h from admission). The mother’s throat swab was
positive for GAS and she was advised to start antibiotic ther-
apy with oral penicillin. After being notified of her positive
throat culture, the mother noted throat soreness with
odynophagia. The father’s swabs were negative and no addi-
tional family members were ill according to the mother.
Samples of the microorganism found in the neonate’s CSF
culture as well as the mother’s throat swab were sent for
emm-typing, which revealed that both GAS isolates were of
the same emm1.0 sequence type.
Review of the Literature
A literature review since 1966 reveals 17 documented cases of
neonatal meningitis with CSF cultures positive for group a
473
streptococcus [1, 2, 4, 6–15] (Table 1). The previously pub-
lished reports originated in the following countries: Brazil
(N = 4), USA (N = 3), the UK (N = 3), Morocco (N = 2),
India (N = 1), Israel (N = 1), Saudi Arabia (N = 1),
The Netherlands (N = 1) and Turkey (N = 1).
The clinical characteristics of the 17 neonates mentioned
above as well as the one described in this case are summarized
in Table 2. The majority of previously documented cases was of
late onset (7–28 days) neonatal sepsis (n = 16, 89%). Fever was
the most common presenting symptom, described in 15 cases
(88%). The most common complication of meningitis was sei-
zure, appearing in 11 cases (61%), with only 4 (22%) of the
cases describing no neurologic complications. 5 (28%) of the
cases resulted in a lethal outcome with 9 (50%) cases reporting
full recovery or no neurologic sequelae upon follow-up.
Discussion
While there are fairly few specific reports of neonatal GAS
meningitis in the literature [1, 2, 4, 6–15], centers for disease
control and prevention (CDC) surveillance data suggests that
meningitis constitutes around 3% of invasive GAS infections
in children [16]. Furthermore, a recently published study
found that 45.5% of pediatric meningitis cases occurred in
infants younger than 1 year of age [17]. Therefore, it is plau-
sible that this clinical entity is more common than currently
indicated by the number of published case reports, with cur-
rently limited evidence on modes of transmission, risk factors,
clinical course, and treatment. The case presented here dem-
onstrates an evident mode of transmission with an unusually
benign clinical course, differing from the past reports of neo-
natal GAS meningitis which demonstrated significant morbid-
ity and mortality [1, 2, 4–6].
In the case presented here, we pursued microbiological
clues regarding the mode of transmission by obtaining swabs
from the neonate’s closest contacts. This investigation proved
valuable as we received a positive throat culture from the
neonate’s mother with a matching GAS subtype, hinting that
the late-onset (>7 days of age) GAS meningitis was most
likely caused by postnatal transmission from the mother who
ultimately developed symptoms of pharyngitis in concurrence
with her neonate’s meningitis course.
This suggested mode of transmission, involving an invasive
GAS isolate, raises numerous questions concerning possible
preventive measures in postnatal mothers and neonates’ house-
hold contacts. The management of close contacts to patients
with GAS infections has been discussed in the past [18, 19],
but to the best of our knowledge, not in the setting of neonatal
meningitis. It should be noted that this suggested mode of trans-
mission from a close dweller with symptomatic GAS pharyn-
gitis has been described in two past cases reviewed in this work
[2, 20], but these did not pursue microbiological evidence for
 474

Table 1 Reported cases of CSF culture proven group a streptococcus neonatal meningitis. CSF indicates cerebrospinal fluid, SIADH - syndrome of inappropriate antidiuretic hormone secretion, N/A –
not available

Case Reference Year Country Age Sex Presenting Symptoms Antibiotic Therapy Complications Outcome Culture
(Days)

1 Dillon [10] 1966 UK 6D M Fever, irritability, poor Penicillin + Kanamycin Seizure, keratitis, erysipelas No reported sequelae CSF, blood,
feeding, bulging umbilicus
fontanelle
2 Nelson et al. [11] 1976 USA 17D NA Umbilical discharge, Penicillin None No reported sequelae CSF, umbilicus
meningeal signs
3 Nutman et al. [12] 1979 Israel 3D F Fever, poor feeding, Penicillin Necrotizing fasciitis No reported sequelae CSF, blood, nose,
erythematous facial rash, skin,
apathy, comatose
condition
4 Baumgartner et al. 1983 USA 14D NA N/A Cefotaxime + None No reported sequelae CSF
[13] Ampicillin
5 Murphy [14] 1983 USA 14D F Fever, poor feeding, Penicillin + Gentamycin Seizure, osteomyelitis No reported sequelae CSF, blood, skin
irritability
6 Coulter et al. [4] 1984 UK 13D F Irritability, poor feeding, Penicillin + Cefuroxime Seizure, cellulitis, jaundice Death CSF, blood,
rhinitis, tongue bleeding, umbilicus
transient rash
7 Coulter et al. [4] 1984 UK 26D M Fever, poor feeding, lethargy Cefuroxime + Seizure, porencephalic cyst, Hydrocephalus CSF, umbilicus,
Gentamicin Penicillin communicating hydrocephalus nose, nasogastric
aspirate,
paronchyia
8 Krebs et al. [15] 1998 Brazil 18D F Fever, vomiting, bulging Penicillin + Ceftriaxone, Seizure, SIADH, sagittal sinus Psychomotor retardation, CSF
fontanelle Vancomycin thrombosis microcephaly,
hypertonia
9 Verboon-Maciolek 2000 The 24D M Fever, poor feeding, bulging Penicillin Seizure, brain abscess Death CSF, brain abscess
et al. [5] Netherlands fontanelle
10 Lardhi et al. [1] 2008 Saudi Arabia 28D M Fever, irritability, poor Ceftriaxone + Seizure, brain abscess No reported sequelae CSF
feeding Vancomycin
11 de Almeida Torres 2013 Brazil 23D F Fever, N/A Penicillin + Ceftriaxone Seizure Death CSF
et al. [2]
12 de Almeida Torres 2013 Brazil 26D F Fever, N/A Penicillin + Ceftriaxone Waterhouse-Friderichsen Death CSF
et al. [2] syndrome, toxic shock
syndrome
13 de Almeida Torres 2013 Brazil 21D F Fever, N/A Penicillin + Ceftriaxone Seizure, Waterhouse-Friderichsen Death CSF
et al. [2] syndrome, toxic shock syn-
drome
14 Annagür et al. [7] 2013 Turkey 24D M Fever, poor feeding Penicillin Hydrocephalus Hearing Loss CSF, Blood
15 Hmami et al. [6] 2014 Morocco 22D M Fever, poor feeding, Ceftriaxone + Seizure, cerebral infarcts and Cerebral atrophy, CSF
hypotonia, bulging Gentamicin hemorrhages, portal vein hydrocephalus,
fontanelle thrombosis with portal microcephaly, portal
cavernoma cavernoma
16 Youssi et al. [8] 2015 Morocco 22D M None No reported sequelae CSF
SN Compr. Clin. Med. (2020) 2:472–477
SN Compr. Clin. Med. (2020) 2:472–477 475

this mode of transmission. Moreover, our literature review re-

vealed that 89% of neonatal GAS meningitis cases were of late
onset sepsis, indicating postnatal transmission.

CSF, Blood
In our case, earlier recognition of the mother’s symptoms
Culture

CSF
may have enabled prompt maternal antibiotic treatment and
brought into consideration isolation of the neonate from the
mother. Leonard et al. [21] recently published a study on severe
No reported sequelae GAS infections in mothers and their newborns. In this study of
No sequelae 134 maternal and 21 neonatal invasive GAS infections,
Leonard et al. found that the median onset time for infection
Outcome

was 2 days postpartum for mothers and 12 days postpartum for

neonates. Additionally, 13% of postpartum mothers which suf-
fered from an invasive GAS infection had household contacts
with typical GAS symptoms prior to the mother’s infection. It
should be noted that in 61% of cases the focus of infection in
the mother was the genital tract with only 2% of cases attributed
to maternal respiratory tract GAS infections.
Considering the scarcity of invasive GAS infections in ne-
Complications

onates, screening for the presence of GAS carriers among

prenatal mothers remains unwarranted in the absence of symp-
Seizure

toms. However, this case joined with the previously discussed

None

reports [2, 20, and 21], suggests that close contacts with symp-
tomatic pharyngitis should be promptly tested for GAS, treat-
ed with antibiotics and kept isolated from neonates in order to
Aminoglycoside,
Cephalosporin +
Antibiotic Therapy

prevent transmission. Furthermore, this case demonstrates that

Fever, poor feeding, bulging 3rd Generation

Amoxicillin

Fever, irritability, loose stool Cefotaxime +

cultures obtained from close contacts in the setting of invasive

Ampicillin
Fever, vomiting, irritability, Cefotaxime

neonatal infections may be effective in identifying a probable

source of transmission.
Although strict sterile procedures were followed, we can-
not fully rule out contamination of the CSF specimen and a
CSF white blood cell count may have reinforced the diagnosis
Age Sex Presenting Symptoms

bulging fontanelle

of meningitis, with glucose and protein measurements serving

as potentially supportive laboratory findings. It should be not-
ed that CSF glucose and protein levels may assist the initial
fontanelle

evaluation; they are both insensitive and non-specific in diag-

nosing neonatal meningitis. [22, 23] The diagnosis of GAS
meningitis in our case is further strengthened by the mother’s
positive throat swab which revealed the same GAS subtype as
F

that of the neonate’s CSF culture. Several recently published

(Days)

15D

10D

epidemiological studies [24–26] have revealed that the

emm1.0 subtype identified in our case is the most prevalent
subtype causing invasive GAS infections, and specifically
Year Country

meningitis, in the majority of European and North American

2018 Israel
Panchatcharam [9] 2016 India

countries. Moreover, emm1.0 is associated with death from

invasive GAS infections at all ages. [16] Although CSF con-
tamination does seem to exist, GAS is not considered a con-
taminant organism and an investigation of our microbiological
laboratory’s records did not reveal a single case of GAS con-
Table 1 (continued)

Current Case

tamination in CSF cultures over the last decade.

Case Reference

Due to the rapid clinical improvement in the neonate and

stable disease course, we chose against repeat lumbar punc-
ture to confirm bacterial eradication. Currently, there are no
18
17

guidelines recommending routine repeat lumbar punctures in

476 SN Compr. Clin. Med. (2020) 2:472–477

Table 2 Clinical characteristics of 18 neonatal patients with Authors’ Contributions T.T.: Conceived and drafted the manuscript, per-
cerebrospinal fluid culture proven group a streptococcus meningitis formed literature search and article selection. E.M.: Collected patient
clinical data and aided in article selection and review. E.N.: Collected
Characteristic Cases of neonatal GAS meningitis (n = 18) and analyzed microbiological data presented in the study. A.L.:
Reviewed the manuscript, supervised article selection and review, ap-
Age, median days (IQR) 19.5D (14–23.75) proved final draft of the manuscript.
Sex
Female 9 (56) Funding Information There is no funding source.
Male 7 (44)
Onset Compliance with Ethical Statements
Early (<7D) 2 (11)
Conflict of Interest The authors declare that they have no conflict of
Late Onset (7D-28D) 16 (89)
interest.
Presenting Symptoms
Fever 15 (88) Ethical Approval This article does not contain any studies with human
Poor Feeding 8 (47) participants or animals performed by any of the authors.
Bulging Fontanelle 7 (41)
Irritability 6 (35) Informed Consent Informed consent was obtained from all individual
participants included in the study.
Complications
Seizure 11 (61)
Brain Abscess 2 (11)
Hydrocephalus 2 (11) References
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