++
Group B streptococci has been a common cause of invasive infection
in neonates and young infants for several decades.1 In
recent years, it has been understood that group B streptococci also
is an important cause of maternal obstetrical morbidity and of fetal
loss. Within the past decade, a significant decline in the incidence
of early-onset group B streptococcal neonatal infections has been
observed in association with universal culture-based screening of
pregnant women and administration of intrapartum antibiotic prophylaxis
to women colonized with group B streptococci.
++
Rates of maternal rectal and vaginal colonization with group
B streptococci during pregnancy range from 20% to 30%.
Without interruption of transmission, approximately 50% of
infants delivered of a colonized mother acquire mucous membrane
colonization. The risk for invasive infection among colonized infants
is approximately 1%. This risk is increased when there
is premature onset of labor, maternal chorioamnionitis, a prolonged
interval between rupture of membranes and delivery, twin pregnancy,
or maternal postpartum bacteremia, among other factors. Heavy maternal
colonization also increases the risk for neonatal infection. Fetal
aspiration of infected amniotic fluid can result in the development
of congenital pneumonia with symptoms at or shortly after birth.
++
Group B streptococci are gram-positive cocci that grow readily
as white to gray white colony-forming units with a narrow zone of β-hemolysis
when inoculated on blood agar. Group B streptococci have been classified, based
on capsular polysaccharide antigens, into 8 types. Contemporary
data indicate that types Ia, III, and V predominate in early-onset disease,
accounting for more than three quarters of isolates from infants
with invasive infection.2,3 Together with types
Ib and II, these 5 types account for 99% of isolates from
infant invasive early-onset disease. Among late-onset cases of group
B streptococcal infection, type III strains predominate, accounting
for approximately two thirds of infections. Serotype III strains
also account for approximately 90% of isolates from infants
with meningitis.
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Clinical Manifestations
++
The clinical features of early-onset and later-onset group B
streptococcal infections are shown in Table 286-1.
Risk for early-onset infection is increased in the setting of maternal
obstetric complications but term infants usually present with no risk
factors other than maternal colonization. The three common clinical
presentations for early-onset disease are septicemia without a focus,
pneumonia, and meningitis. In excess of 75% of infants
present with respiratory signs, including tachypnea, grunting, or
cyanosis. Radiographic findings can be suggestive of surfactant
deficiency, transient tachypnea, or congenital pneumonia. Other
signs of early-onset infection are those common to neonatal sepsis,
including temperature or vascular instability, poor feeding, and lethargy.
Clinical signs suggesting meningeal involvement can be unapparent
at the initial presentation, but seizures develop within 24 hours
of presentation in 50% of infants with meningitis.
++
++
The three common presentations for late-onset infection are bacteremia
without a focus of infection, meningitis, and osteoarthritis. The
presentation for bacteremia without a focus can be insidious, with
detection of infection when a sepsis evaluation is undertaken for
an otherwise well-appearing febrile infant. Approximately one third
of infants have a history of upper respiratory tract infection that
heralds the development of bacteremia. For infants with meningitis,
the initial signs of infection include fever, lethargy, irritability,
poor feeding, and tachypnea. Some infants with late-onset meningitis
have a fulminant presentation with seizures, poor perfusion, and
septic shock developing over several hours. These infants have large
numbers of bacteria visible in the cerebrospinal fluid Gram stain.
They usually respond poorly to supportive care and tend to have
a rapidly fatal outcome or, if they survive, to have major neurologic
sequelae.
++
The third clinical presentation for late-onset disease is focal
soft tissue infection or osteomyelitis. Group B streptococcal osteomyelitis
usually has an indolent presentation and is characterized by single-bone involvement, often the
proximal humerus. The signs of infection include swelling, erythema, and
pain overlying the involved bone. Inflammatory signs tend to be
less prominent than those of staphylococcal osteomyelitis, and group
B streptococcal osteomyelitis can be misdiagnosed as Erb palsy.
The hip, knee, or ankle joint is a common site of involvement for
septic arthritis. Monoarticular involvement is the rule. Adenitis
or cellulitis caused by group B streptococci usually is unilateral,
and can involve facial or submandibular sites or the genital or
inguinal region. Infants with cellulitis or adenitis often are bacteremic,
but collections of purulence also yield the organism.
++
The designation late, late-onset infection is appropriate for
infants older than 3 months of age who develop group B streptococcal
sepsis. Late, late-onset infection can account for 20% of
all late-onset disease. Those infants usually have a history of
prematurity and prolonged hospitalization. Bacteremia without a
focus is a common presentation.
++
Isolation of group B streptococci from a normally sterile body
site such as the blood, cerebrospinal fluid, or site of focal infection
such as bone, joint, or abscess fluid is diagnostic. Abnormalities
of the white blood cell count, such as neutropenia or elevation
of the ratio of immature to total neutrophils can be found in association
with group B streptococcal infection, as well as in neonatal sepsis
caused by other bacterial pathogens.
++
Penicillin G is the drug of choice for the treatment of group
B streptococcal infection. Initial therapy for suspected infection
should consist of ampicillin and an aminoglycoside. This combination
is synergistic in vitro and in vivo for killing group B streptococci
and provides broad-spectrum coverage for other potential pathogens
in the newborn infant. When the diagnosis is confirmed, penicillin
G alone should be continued to complete a 10-day course of therapy
for sepsis or pneumonia and a 14-day minimum course of therapy for
meningitis. A 2- to 3-week course of therapy is required for the
treatment of group B streptococcal septic arthritis, and 3 to 4
weeks is required for treatment of osteomyelitis. The dose of penicillin
for the treatment of group B streptococcal sepsis (200,000 U/kg/day)
is lower than that recommended for the treatment of meningitis (400,000–500,000
U/kg/day). This higher dose is given for meningitis because
the inoculum of bacteria in the cerebrospinal fluid can be as high
as 10 million to 100 million colony-forming units per mL, and the
goal of therapy is to exceed the minimal inhibitory concentration
of the infecting isolate by a substantial margin.
++
A blood culture should be performed to document that antimicrobial
therapy has achieved bloodstream sterility for infants with sepsis.
For those with meningitis, a repeat lumbar puncture should be performed
after 24 to 48 hours of therapy and before discontinuing therapy.
The cerebrospinal fluid findings after 14 days of therapy can suggest inadequate
resolution of the inflammatory response as indicated by a proportion
of neutrophils exceeding 25% to 30% of the total,
or a protein level in excess of 200 mg/dL. In this circumstance,
it is advisable to continue antimicrobial therapy for an additional
week and to repeat a lumbar puncture. It is rarely necessary to
continue antibiotic treatment for longer than 3 weeks.
++
For infants with meningitis, an enhanced computed tomographic
scan or magnetic resonance imaging study of the brain should be obtained
before discontinuing antibiotic therapy. Diagnostic imaging gives
additional information regarding the adequacy of resolution of cerebritis
or ventriculitis. On occasion, cerebral imaging can reveal a previously
unsuspected abscess or infarct that will influence the duration
of therapy or prognosis.
++
Supportive care for infants with group B streptococcal infection
includes attention to the details of fluid management, ventilation, and
support of vascular volume. Seizures should be anticipated in infants
with meningitis and controlled to limit brain edema and hypoxia.
For infants with bone or joint infection, open or closed aspiration
can be required to establish the diagnosis and to drain purulent material.
A drainage procedure is required to preserve vascular supply of
the hip or shoulder joints.
+++
Prognosis and Outcomes
++
The mortality rate from group B streptococcal disease has declined
markedly and now stands at 5% to 10% for early-onset
disease. The mortality rate for late-onset disease ranges from 2% to
6%. Term infants surviving sepsis usually have no sequelae
of infection. Premature infants with septic shock and periventricular leukomalacia
can have residual neurologic impairment. There are no current data
for the long-term outcome of term infants recovering from group
B streptococcal meningitis. Approximately one third of infants treated
for meningitis in the 1970s had serious neurologic sequelae. Infection,
including that caused by group B streptococci, in extremely low-birth-weight
infants is associated with poor neurodevelopmental outcomes in early
childhood.4 Infants usually recover fully from
bone or joint infection, but impairment of joint function or bone
growth has occurred.
++
Recognition that intrapartum antibiotic administration could
prevent early-onset neonatal group B streptococcal infection dates
to the 1980s. National standards for intrapartum antibiotic prophylaxis
were first implemented in 1996. These allowed for intervention to
prevent early-onset group B streptococcal infection based on either
maternal risk factors or maternal colonization. A program of active surveillance
for invasive group B streptococcal disease noted a decline in the
incidence of early-onset neonatal infections by 65%, from 1.7
per 1000 live births in 1993 to 0.6 per 1000 live births in 1998.5 Publication
in 2002 of a population-based report finding that routine screening
of all pregnant women at 35 to 37 weeks of gestation and administration
of intrapartum antibiotic prophylaxis to all carriers prevented
more cases of early-onset disease led to the current universal screening recommendations.6 With
this culture-based approach, all pregnant women identified as carriers
of group B streptococci by cultures performed at 35 to 37 weeks’ gestation
should receive intrapartum chemoprophylaxis. The average early-onset
disease incidence in the era of universal culture-based screening
from 2003 to 2005 was 0.33 cases per 1000 live births.7
++
A risk-based method for intrapartum antibiotic prophylaxis is
still recommended for women in whom group B streptococcal colonization
status is not known at the onset of labor or rupture of membranes.
Factors known to increase the risk for early-onset infection, including
onset of labor or rupture of membranes before 37 weeks’ gestation,
rupture of membranes 18 hours or more before delivery, or intrapartum
fever warrant use of intrapartum antibiotic prophylaxis. The current
strategy also targets women with group B streptococcal bacteriuria
during pregnancy, as well as women who have had a previous infant
with invasive group B streptococcal infection.
++
Penicillin G is the antimicrobial of choice and ampicillin an
alternative for intrapartum chemoprophylaxis. Cefazolin is recommended
for women who are allergic to penicillin but at low risk for anaphylaxis.8 Vancomycin
use is reserved for penicillin-allergic women with a high risk for
anaphylaxis for whom the susceptibility pattern of the group B streptococcal
isolate does not permit use of clindamycin. Overall, an 80% decline
in the incidence of early-onset disease has been documented since
guidelines for intrapartum chemoprophylaxis became available.
++
Management of a neonate whose mother received intrapartum antibiotic
prophylaxis is dependent on the infant’s clinical status, the
gestational age of the infant, and the duration of prophylaxis before
delivery.8 Symptomatic infants and those born to
mothers with chorioamnionitis should undergo full diagnostic evaluation
and should receive empiric therapy. A limited evaluation and observation
for at least 48 hours are indicated for asymptomatic infants less
than 35 weeks’ gestation and for those infants whose mothers
received chemoprophylaxis for less than 4 hours before delivery.
Observation alone is indicated for asymptomatic infants of at least 35
weeks’ gestation whose mothers received chemoprophylaxis
at least 4 hours prior to delivery.
++
Intrapartum antibiotic prophylaxis is considered an interim intervention
and its use has not reduced the incidence of late-onset group B
streptococcal infection, which remains 0.3 to 0.4 cases per 1000
live births. A comprehensive program for prevention of group B streptococcal
infection awaits the licensure of protein polysaccharide conjugate
vaccines now under development.