A 2800-g male infant is born at 36 weeks of gestation to a 19-year-old mother
through vaginal delivery. Delivery occurred 19 hours after membrane rupture. The
mother’s pregnancy was uncomplicated, but her prenatal records are not available at delivery. At 6 hours of age he is “breathing hard” and refusing to breastfeed. His respiratory rate is 60 breaths/min with “grunting.” His temperature is
96.5°F (35.8°C), and his blood pressure is lower than normal. You ask the nurses to
obtain a complete blood count (CBC) while you drive to the hospital from home.
Upon arrival you confirm that he is in respiratory distress and that his perfusion
is poor. The CBC demonstrates a white blood cell (WBC) count of 2500 cells/mm3
with 80% bands. His radiograph is shown in the figure below.
CASE 4
» What is the most likely diagnosis?
» What is the best therapy?
Summary: A 2800-g infant born by vaginal delivery at 36 weeks of gestation is
found to have poor feeding, tachypnea, hypothermia, and poor perfusion at 6 hours
of age.
Most likely diagnosis: Group B Streptococcus (GBS) infection.
Best therapy: Intravenous (IV) antibiotics (after addressing “ABCs” of resuscitation [Airway, Breathing, and Circulation]).
ANALYSIS
Objectives
- Understand the common presentations of neonatal sepsis.
- Understand the maternal risk factors for neonatal GBS infection.
- Appreciate the variety of organisms responsible for neonatal infections.
- Learn treatment options for the common neonatal infections.
Considerations
The rapid symptom onset, the low WBC count with left shift, and the chest x-ray
findings are typical for GBS pneumonia. At this point, management would include
rapid application of the ABCs (maintain Airway, control Breathing, and ensure
adequate Circulation) of resuscitation, followed by rapid institution of appropriate
antibiotics once cultures are obtained. Despite these measures, mortality from this
infection is high.
EARLY-ONSET NEONATAL SEPSIS SYNDROME: Neonatal sepsis occurring in the first 6 days of life. The majority of infections (~85%) occur in the first
24 hours of life, an additional 5% by approximately 48 hours, and the remainder
throughout the next 4 days. The infection source usually is microorganism acquisition from the mother’s genitourinary tract.
GROUP B STREPTOCOCCUS (GBS) COLONIZATION: Infection with GBS
limited to mucous membrane sites in a healthy adult; the gastrointestinal (GI) tract
is the most common colonization reservoir.
LATE-ONSET NEONATAL SEPSIS SYNDROME: Neonatal sepsis usually
occurring after approximately 7 days but before approximately 90 days of life. The
infection source often is the caregiver’s environment.
INTRAPARTUM ANTIBIOTIC PROPHYLAXIS: Intravenous penicillin or
ampicillin given during labor to prevent early-onset GBS disease.
CLINICAL APPROACH
Signs and Symptoms of Sepsis
The signs and symptoms of neonatal sepsis can be subtle and nonspecific, often overlapping with findings in other conditions, such as respiratory distress syndrome,
metabolic disorders, intracranial hemorrhages, and traumatic deliveries. Temperature instability, tachypnea, hypotension, and bradycardia are common findings in
sepsis and meningitis. Overwhelming shock is manifested as pallor and poor capillary
refill. Neurologic findings of impaired level of consciousness, coma, seizures, bulging anterior fontanelle, focal cranial nerve signs, and nuchal rigidity are unusual,
but when present hint at meningitis, a condition more commonly seen in late-onset
disease. Examination findings seen frequently with pneumonia (more commonly
seen in early-onset disease) include tachypnea, grunting, nasal flaring, retractions
(costal or substernal), decreased breath sounds, and cyanosis.
Evaluation of the Potentially Septic Child
Some neonatal sepsis laboratory findings can be nonspecific, including hypoglycemia, metabolic acidosis, and jaundice. The CBC often is used to help guide therapy,
although the sensitivity and specificity of this test are low. Evidence of infection on
CBC includes the following:
Markedly elevated or low WBC counts
Increased neutrophil count
Increased immature to total neutrophil (I/T) ratios
Thrombocytopenia with platelet counts less than 100,000/mm
The C-reactive protein (an acute phase protein increased with tissue injury) can
be elevated in septic infants; some use it as an adjunct to assess for neonatal sepsis.
A blood culture is crucial for patients with suspected sepsis. Some argue that the
low meningitis incidence, especially in early-onset disease, does not warrant routine
cerebral spinal fluid testing; rather, the test should be reserved for documented
(positive cultures) or presumed (patients so sick that a full antibiotic course is to
be given regardless of culture results) sepsis. Urine cultures usually are included for
late-onset disease evaluation. Urinary tract infection is uncommon in the first few
days of life, and urinalysis or culture is usually not included in early-onset disease
workup. Chest radiologic findings include segmental, lobar, or diffuse reticulogranular patterns, the latter easily confused with respiratory distress syndrome (lack of
surfactant).
Pathogens
The organisms that commonly cause early-onset sepsis colonize in the mother’s
genitourinary tract and are acquired transplacentally, from an ascending infection
or as the infant passes through the birth canal. Specific organisms include GBS,
Escherichia coli, Haemophilus influenzae, and Listeria monocytogenes. Late-onset disease occurs when the infant becomes infected in the postnatal environment, such as
from the skin, respiratory tract, conjunctivae, GI tract, and umbilicus. For the hospitalized infant, bacteria sources include vascular or urinary catheters or contact
with health care workers. Organisms commonly seen to cause late-onset disease
include coagulase-negative staphylococci, Staphylococcus aureus, E coli, Klebsiella sp,
Pseudomonas sp, Enterobacter sp, Candida, GBS, Serratia sp, Acinetobacter sp, and
anaerobes.
Group B Streptococcus is the most common cause of neonatal sepsis from birth to
3 months. Approximately 80% of cases occur as early-onset disease (septicemia,
pneumonia, and meningitis) resulting from vertical transmission from mother to
infant during labor and delivery. Respiratory signs (apnea, grunting respirations,
tachypnea, or cyanosis) are the initial clinical findings in more than 80% of neonates, regardless of the site of involvement, whereas hypotension is an initial finding in approximately 25% of cases. Other signs are similar to those associated with
other bacterial infections described earlier.
Neonates with GBS meningitis rarely have seizures as a presenting sign, yet
50% develop seizures within 24 hours of infection. The median age at diagnosis of
early-onset GBS infection is 13 hours, earlier than for the other bacterial infections
described previously. Clinical history and findings suggestive of early-onset GBS
disease (rather than of a noninfectious etiology for pulmonary findings) include
prolonged rupture of membranes, apnea, hypotension in the first 24 hours of life,
a 1-minute Apgar score less than 5, and rapid progression of pulmonary disease.
Factors associated with increased risk for early-onset GBS disease are rupture
of membranes more than 18 hours before delivery, chorioamnionitis or intrapartum temperature greater than 100.4°F (38°C), previous infant with GBS infection,
mother younger than 20 years, and low birth weight or prematurity (<37 weeks of
gestation). Mortality because of GBS disease is close to 10%. Major neurologic
sequelae (cortical blindness, spasticity, and global mental retardation) occur in 12%
to 30% of infants who survive meningitis.
The incidence of early-onset GBS infection decreased from 1.7 per 1000 live
births in 1993 to 0.34 to 0.37 per 1000 live births in 2008. The decline is largely
attributed to the widespread use of GBS risk–reduction guidelines. These guidelines recommend screening women at 35 to 37 weeks of gestation and offering intrapartum antibiotic prophylaxis to those with risk factors or positive GBS cultures at
35 to 37 weeks of gestation. Infants born at less than 35 weeks of gestation or born
to women who received inadequate intrapartum prophylaxis sometimes undergo
a limited evaluation that often includes a CBC and blood culture. Intrapartum
antibiotic prophylaxis does not prevent late-onset GBS disease. The association
of early antibiotic use with increased risk of late-onset serious bacterial infections
remains under study.
Late-onset GBS disease is often more subtle in presentation than early-onset
disease. Symptoms often occur between 7 and 30 days of life but can occur up to
3 to 4 months of age. Most commonly, late-onset GBS disease presents as bacteremia
without a focus. Meningitis occurs in 20% to 30% of late-onset GBS cases, and
the presenting symptom may be seizure. Other manifestations of late-onset GBS
disease include focal infections such as pneumonia, septic arthritis, osteomyelitis,
or cellulitis. The major risk factor for late-onset GBS disease is prematurity. Diagnostic testing for late-onset GBS disease should include CBC, blood and urine cultures, as well as CSF culture if the patient has symptoms concerning for meningitis
and for the febrile neonate less than 28 days of life.
Treatment
Initial antibiotic treatment for neonatal sepsis is broad. Antibiotics are directed at
the most common pathogens previously listed, often consisting of a combination
of IV aminoglycosides (such as gentamicin and tobramycin) and penicillin (usually ampicillin). When GBS is identified by culture as the sole causative organism,
antibiotic coverage can be narrowed to penicillin G if the patient has improved
and is clinically stable. Gentamicin may be added to penicillin G for synergy but
is not always required. Other antibiotics often chosen that will also provide coverage for GBS include ampicillin, first- and second-generation cephalosporins, and
vancomycin.
Antibiotics are continued for at least 48 to 72 hours. If cultures are negative and
the patient is well, antibiotics often are stopped. For infants presenting with convincing signs and symptoms of sepsis, antibiotics may be continued even with negative
cultures. For infants with positive cultures, therapy continues for 10 to 21 days
depending on the organism and the infection site. Close observation for signs of
antibiotic toxicity is important for all infants.