Santa Clara Valley Medical Center
Inpatient Pediatric Wards/PICU Rotation
Teaching Module
Ill Neonate
(AAP PREP Self-Assessment, 2007)
You are in the emergency room when a 7-day-old term infant arrives with
respiratory distress, poor perfusion, and lethargy. His temperature is 39.4 C and
physical exam also reveals scleral icterus and hepatosplenomegaly but no skin
lesions. Given his poor perfusion, an IV is placed and a normal saline bolus of 20
mL/kg is given. His respiratory distress worsens and he is intubated. A lumbar
puncture could not be performed.
Lab results include: wbc 2,340/mcL with 32% lymphocytes, 41% neutrophils, 8%
bands, Hb 7.1 g/dL, Hematocrit 21%, platelet count of 40,000/mcL. AST 3,086
units/L, ALT 456 units/L. Total bilirubin 4.4 mg/dL. Coags: PT 41.2 seconds, aPTT
>106 seconds.
CXR shows diffuse interstitial infiltrates bilaterally.
Question 1:
What is the most likely cause of this patient's illness?
A) Adenovirus
B) E. coli
C) Group B Streptococcus
D) Herpes Simplex Virus
E) Listeria monocytogenes
(Answer on next page)
Suzanne Swanson Mendez, MD
Answer to Question 1, Case Two:
D) Herpes Simplex Virus
"Neonates presenting with shock-like symptoms during the first 7 to 10 days after
birth are a diagnostic challenge. The differential diagnosis includes five major
categories: 1) bacterial sepsis, 2) inborn errors of metabolism, 3) ductaldependent complex congenital heart disease, 4) non-accidental trauma, and 5) viral
sepsis. Clinicians must make rapid treatment decisions based on history and
physical examination. The fever, hepatosplenomegaly, leukopenia, and abnormal
findings on chest x-ray suggest infection as the most likely cause. Group B
Streptococcus, E. coli, and Listeria monocytogenes are causes of neonatal septic
shoc, but the interstitial pulmonary involvement and hepatitis reported in this case
make a virus more likely. Although adenoviral infection can have this type of
presentation, the most likely pathogen is herpes simplex.
Neonatal infections with HSV may be due to either HSV-1 (25%) or HSV-2 (75%).
Approximately 80% of mothers of affected infants have no signs or symptoms of
HSV infection prior to delivery. The virus commonly is transmitted to the infant
from the mother because of the large amount of virus present and the prolonged
shedding. If the primary infection affects only the cervix, the mother is usually
asymptomatic. The infants become colonized with HSV at delivery and usually
present with active disease between 5 and 10 days after birth. Neonatal disease
may present as: 1) disease localized to the skin, eye, or mouth (SEM); 2)
disseminated disease involving the liver, lungs, adrenal glands, central nervous
system, and skin; and 3) localized CNS disease. In disseminated disease,
approximately 20% of infants never develop skin lesions. Therefore, the lack of
skin lesions does not eliminate HSV as a potential pathogen for a sick infant."
Question 2:
The diagnosis of HSV can be confirmed by what methods?
A) Viral cultures of skin lesions, the nasopharynx, or CSF
B) Direct fluorescent antibody staining of vesicle scrapings
C) PCR for HSV DNA in the CSF
D) All of the above
(Answer on next page)
Suzanne Swanson Mendez, MD
Answer to Question 2, Case Two:
D) All of the above
A DFA of the skin lesions or a HSV PCR of the CSF is the quickest way to confirm
the diagnosis, although the HSV PCR may be negative early in disease. The Tzanck
preparation from a skin lesion can be helpful but only indicates the presence of a
DNA virus and is not specific for HSV.
From Kimberlin: "When HSV disease is suspected with a sufficiently high index of
suspicion, swabs of the mouth, nasopharynx, conjunctivae, and rectum and
specimens of skin vesicles, blood and CSF should be obtained for culture ("surface
cultures") PCR assay is a sensitive method of detecting HSV DNA and is of
particular value for evaluating CSF specimens from neonates with suspected HSV
CNS disease....although...this test is not infallible. Blood PCR may be of benefit in
the diagnosis of neonatal HSV disease, but its use should not supplant the standard
work-up of such patients (eg, surface cultures and CSF PCR): no data exist to
support use of serial blood PCR testing to monitor response to therapy.....Only half
of all babies with neonatal herpes have CNS involvement, either categoriezed as
CNS disease or disseminated disease with CNS involvement. Thus, negative CSF
PCR results do not rule out neonatal HSV disease since by definition half of all
babies with neonatal herpes would have even have a chance of being PCR-positive
in CSF."
Question 3:
What medications should be given to this infant?
A) Ampicillin and gentamicin
B) Ampicillin, gentamicin, and acyclovir
C) Ampicillin and cefotaxime
D) Acyclovir alone
(Answer on next page)
Suzanne Swanson Mendez, MD
Answer to Question 3 (Case Two):
B) Ampicillin, gentamicin, and acylovir.
Until bacterial sepsis can be ruled out, the safest option would be to cover for GBS,
E. coli, and Listeria as well as HSV.
Which brings up the question: when do you start acyclovir in a neonate? This is a
very controversial topic, and here are two great and relatively short articles, all
from the August 2008 Journal of Pediatrics, which discuss the issue. One author,
Dr. Long, suggests adding acyclovir to the regimen of all neonates under 21 days of
age (see Long SS, "In Defense of Empiric Acyclovir in Certain Neonates," Journal of
Pediatrics, vol. 153, 2:157-8), while the other, Dr. Kimberlin, (see Kimberlin DW,
"When Should You Initiate Acyclovir Therapy in a Neonate?", Journal of Pediatrics
153:2, p. 155-6) suggests that vast majority of infants with HSV do have some
other presenting sign or symptom (such as fever with lethargy, vesicular rash,
respiratory distress with hypothermia, or markedly elevated AST), and acyclovir
should not be started by age criteria with fever alone. But we also need to keep in
mind that HSV disease can cause symptoms without fever as well, particularly if the
infant is in the second week of life.
Overall, I tend to prefer Kimberlin's approach:
"Are there times when parenteral acyclovir should be added empirically to
antibiotics when neonates are admitted for rule-out sepsis? Certainly. Evaluation for
herpes and administering acyclovir is appropriate when there is a clear index of
suspicion because of the presence of skin vesicles, seizures, marked elevation of
hepatic transaminases, a sepsis-like picture (including hypothermia), or simply
when in the clinician's judgment the infant appears more ill than would be
expected. A CSF pleocytosis with a mononuclear cell predominance outside of the
enteroviral season also might be a time when evaluation and initiation of acyclovir
are warranted. The treating physician must gather enough information (surface
cultures, CSF HSV PCR) before the initiation of therapy, however, so that a rational
decision can be made 4 to 5 days later to discontinue acyclovir therapy if the workup is negative. Of course, when the infant is unstable at first evaluation, acyclovir
and antibiotic therapy should be initiated, even when the work-up is not complete."
But when you are at the Valley, you will find that there is not one right answer for
every patient and we are bound to have some interesting discussions! I look
forward to working with you soon.
Suzanne Swanson Mendez, MD
References/Recommended Reading:
Benitz WE et al, "Serial Serum C-Reactive Protein Levels in the Diagnosis of
Neonatal Infection," Pediatrics 1998; 102; e41.
(http://www.pediatrics.org/cgi/content/full/102/4/e41)
Caviness AC et al, "The Prevalence of Neonatal Herpes Simplex Virus Infection
Compared wtih Serious Bacterial Illness in Hospitalized Neonates," Journal of
Pediatrics, vol. 153, no. 2, pp. 164-9.
Ishimine P, "Fever Without Source in Children Ages 0 to 36 Months," Pediatric
Clinics of North America, 53: 167-194, 2006.
http://hsc.unm.edu/emermed/PED/physicians/residents/articles/Fever%20Without
%20a%20Source%20in%20Children%200%20to%2036%20Months%20of%20Age.
pdf
Huppler AR et al, "Performance of Low-Risk Criteria in the Evaluation of Young
Infants with Fever: Review of the Literature," PEDIATRICS Vol. 125 No. 2 February
2010, pp. 228-233.
http://pediatrics.aappublications.org/cgi/content/abstract/125/2/228
Kimberlin DW, "When Should You Initiate Acyclovir Therapy in a Neonate?", Journal
of Pediatrics, vol. 153 no. 2, August 2008, pp. 155-6.
Levine DA, Platt SL, Dayan PS, et al for the Multicenter RSV-SBI Study Group of the
Pediatric Emergency Medicine Collaborative Research Committee of the American
Academy of Pediatrics: Risk of serious bacterial infection in young febrile infants
with respiratory syncytial virus infections. Pediatrics 2004;113:1728-1734.
http://pediatrics.aappublications.org/cgi/content/abstract/113/6/1728
Long SS, "In Defense of Empiric Acyclovir in Certain Neonates," Journal of
Pediatrics, vol. 153, no. 2, August 2008, pp.157-8.
Suzanne Swanson Mendez, MD