Pediatrics and Neonatology (2016) 57, 167e173

Available online at www.sciencedirect.com

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journal homepage: http://www.pediatr-neonatol.com

REVIEW ARTICLE

Bird’s Eye View of a Neonatologist: Clinical

Approach to Emergency Neonatal Infection
Fu-Kuei Huang a,y, Hsiu-Lin Chen b,c,y, Peng-Hong Yang d,
Hung-Chih Lin a,e,*

a
Department of Pediatrics, China Medical University Children Hospital, Taichung, Taiwan
b
Department of Pediatrics of Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
c
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung,
Taiwan
d
Department of Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
e
School of Chinese Medicine, China Medical University, Taichung, Taiwan

Received Mar 18, 2014; received in revised form Apr 21, 2015; accepted Jun 1, 2015
Available online 23 October 2015

Keywords Though the incidence of neonatal infection in term and near-term infants is relatively low, inci-
neonatal sepsis; dence of infection in preterm very low birth weight infants is as high as 20e30% and may result in
antimicrobial neurodevelopmental impairment or mortality. Pediatricians should be familiar with recognition
therapy; and emergency management of life-threatening neonatal infections, such as congenital pneu-
sepsisi screen; monia, early onset sepsis, late onset sepsis, bacterial and fungal meningitis, disseminated
blood culture; neonatal herpes simplex virus (HSV), and HSV meningoencephalitis. For the pediatrician, it is
white blood cell logical to approach the management of these infections by time of onset, i.e., early versus late
count; onset of infection. Perinatal risk factors and simple laboratory tests, such as total white blood-
acute phase reactants cell count, immature/total ratio, and C-reactive protein are helpful in guiding the decision of an-
tibiotics therapy. Successful management of these critical infections depends upon early diag-
nosis and timely administration of adequate antibiotics. Empiric antibiotic therapy must cover
the most likely pathogens according to the risk factors of each individual neonate, and therapy
duration is dependent upon culture results, clinical course, and the microorganism. Future
research may focus on developing a practical neonatal sepsis score system based on risk factors
and common biomarkers, which are readily available at bedside to make early accurate decisions
and achieve better outcomes.
Copyright ª 2015, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/
by-nc-nd/4.0/).

* Corresponding author. China Medical University Children Hospital, Number 2 Yu-Der Road, Taichung, 404, Taiwan.
E-mail address: d0373@mail.cmuh.org.tw (H.-C. Lin).
y
These two authors contributed equally to authorship of this manuscript.

http://dx.doi.org/10.1016/j.pedneo.2015.06.004
1875-9572/Copyright ª 2015, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
168
1. Introduction
Although the incidence of neonatal infections in term and
near-term infants is relatively low, neonatal infections have
a significant impact on medical resource utilization. The
incidence of health care-associated infections in preterm
very low birth weight (PVLBW) infants is as high as 20e30%.1
Furthermore, infection of PVLBW infants can result in death
or neurodevelopmental impairment. Thus, pediatricians
must be aware of the possibility of sepsis or health care-
associated infections in any high-risk infants.
Life-threatening neonatal infections include congenital
pneumonia with the possibility of development into persistent
pulmonary hypertension of the newborn (PPHN) and/or septic
shock and even mortality; early onset sepsis (EOS) in neo-
nates, leading to high mortality rates and adverse neuro-
developmental outcomes in preterm infants; late onset sepsis
(LOS) in neonates, resulting in moderate mortality rates and
adverse neurodevelopmental outcomes in preterm infants.
Bacterial or fungal meningitis is related to adverse neuro-
developmental outcomes, and neonatal disseminated herpes
simplex virus (HSV) infection and HSV meningoencephalitis
can both cause high mortality and high morbidity rates.
For the pediatrician, it is reasonable to approach the
management of these infections by time onset, i.e., early
versus late onset of sepsis, where EOS is defined as infec-
tion occurring within < 3 days usually presenting with
pneumonia or sepsis.
2. Congenital pneumonia
2.1. Pathogenesis
Congenital pneumonias result from intrauterine aspiration
of infected amniotic fluid or aspiration of amniotic fluid
during the birth process. Pediatricians need to be aware
that congenital pneumonias sometimes progress to septic
shock and can be associated with persistent pulmonary
hypertension.
Pneumonia is caused by many of the same pathogens
associated with neonatal sepsis, including EOS and LOS. In
the area of antenatal chemoprophylaxis in developing
countries, the pathogens responsible for congenital pneu-
monia include Escherichia coli, group B streptococcus
(GBS), Staphylococcus aureus, Klebsiella spp, and Strep-
tococcus pneumoniae.2 HSV is the most common viral agent
that causes pneumonia and has a very high mortality
rate.2,3 According to the recommendations of the Centers
for Disease Control and Prevention (CDC), since 1996 early-
onset GBS infection has been reduced by more than 85%
after GBS prophylaxis protocol in the USA.
However, some reports showed that there were more
Escherichia coli infections in neonates or more ampicillin-
resistant organisms, although other reports did not have
similar findings.4
2.2. Diagnostic approach
Any neonates who present with respiratory distress should
be evaluated for pneumonia, with chest X-ray most helpful
F.-K. Huang et al
in its diagnosis and management. Pneumonia caused by GBS
or other pathogens is difficult to distinguish from respira-
tory distress syndrome in the preterm infant. The most
common abnormality identified was dense bilateral alve-
olar infiltrates with air bronchograms.4
2.3. Management
Successful treatment depends upon recognition of risk
factors. Treatments include prompt diagnosis with admin-
istration of antibiotics and supportive therapy, including
surfactant replacement5 and nitric oxide inhalation for
PPHN. Although clinical trials regarding surfactant
replacement for congenital pneumonias are limited, sur-
factant replacement may reduce mortality, especially for
PVLBW infants.6
Ampicillin and gentamicin are commonly used to treat
infants with congenital pneumonias. Since Gram-negative
bacilli rapidly develop resistance to cephalosporins, third-
generation cephalosporins are not recommended routinely
for suspected pneumonia7 except when there is no
improvement after 24 hours of treatment or if S. pneumo-
niae infection is highly suspected.8 Once a specific organ-
ism is identified, therapy is modified according to the
susceptibility pattern.
3. Early onset sepsis
3.1. Pathogenesis
EOS pathogenesis is the same as that of pneumonia. Or-
ganisms responsible for EOS reside in the birth canal and
invade the amniotic cavity through the cervix. Given that
the signs and symptoms of sepsis are also subtle and
nonspecific, identification of infants at risk is critical for
emergency intervention.9 The neonate should be carefully
evaluated for the presence of risk factors, including the
following: intrapartum maternal temperature  38 C
(100.4 F), chorioamnionitis, preterm infants at < 37-
weeks’ gestation, Apgar scores  6 at 5 minutes, evi-
dence of fetal distress, maternal GBS colonization, or
membrane rupture of  18 hours.9 Heart-rate analysis
might also help the early diagnosis of late onset neonatal
sepsis.10
Pneumonia is more common in EOS. If the classic signs of
respiratory distress, including tachypnea, dyspnea, grunt-
ing, and cyanosis present within the first 4e6 hours of life,
pneumonia should be considered.
3.2. Diagnostic approach
Low white blood cells (<5000/mL) (WBC), absolute neutro-
phil count less than 1000/mL (ANC), or proportion of neu-
trophils that are immature greater than 0.6 have been
highly associated with culture-proven early-onset disease.11
Sequential assessment of C-reactive protein (CRP) may
be helpful in guiding the duration of antibiotic therapy in
suspected neonatal bacterial infection,12 however, detailed
physical examination with clinical symptoms is more
important. Elevated procalcitonin (> 0.5 ng/mL) is equally
Emergency neonatal infection
effective as CRP in detecting bacterial infection.13 Serum
calprotectin may be a promising marker of sepsis for pre-
term VLBW infants.14 Studies evaluating serum amyloid A
presented a variable positive predictive value (0.67 and
0.92), but with a high negative predictive value (0.97 and
1.00).15 Apart from expensive biomarkers for the diagnosis
of neonatal sepsis, an objective scoring system according to
risk factors, clinical presentations, and simple tests might
be more practical for neonatal intensive care units.16
3.3. Management
Empiric antibiotic treatment is indicated whenever sepsis is
suspected based on clinical signs or in healthy-appearing
infants born to mothers with chorioamnionitis. Successful
treatment of EOS depends upon the gestational age, early
diagnosis and early intervention with appropriate antibi-
otics, and supportive intensive care. Severely ill PVLBW
infants frequently require respiratory and vasopressor
medical support as soon as possible in order to maintain
adequate oxygenation and perfusion. Ampicillin and
gentamicin are still effective in treating most of the com-
mon pathogens that cause EOS, GBS, and E. coli
infections.17
Cefotaxime may not be appropriate for the treatment of
EOS as shown in retrospective data noting an increase in
mortality rate (4.2% versus 1.9%).18 However, considering
that there is increasing resistance to Gram-negative or-
ganisms, the choice of antibiotics in neonatal sepsis should
depend upon the prevalence of microorganism and antibi-
otic sensitivity in each unit.19 The duration of antibiotic
therapy for culture-proven EOS depends upon the path-
ogen. Usually, 10 days for Gram-positive and 14 days for
Gram-negative microorganisms are adequate.19
In most cases, symptomatic infants with proven sepsis
improve clinically within 48e72 hours. Empiric antibiotic
therapy can generally be discontinued in the infant after 48
hours if blood culture is negative. In a critically ill infant
(with negative cultures), antibiotics should be continued
for 7 days.
Outcomes of GBS neonatal sepsis after the introduction
of intrapartum antibiotic prophylaxis and the routine use of
empirical antibiotic therapy demonstrated an overall mor-
tality rate of between 5% and 10%, with mortality even
lower in term infants with early onset disease ranging from
2% to 3%.20
4. Late onset sepsis
4.1. Pathogenesis
LOS is acquired principally by horizontal transmission from
direct contact with care providers, catheters, or environ-
mental sources, and may occur as early as 3-days of age.
Coagulase-negative staphylococci (CoNS) are the most
common organisms associated with LOS. Other Gram-
positive organisms, including S. aureus, Enterococcus spp,
and GBS, and Gram-negative pathogens, including E. coli,
Klebsiella, Pseudomonas, Enterobacter, and Serratia, were
the most frequent pathogens associated with LOS.1
169
In addition to bacteria, viruses and fungi also cause LOS.
Candida infections have increased in frequency with ad-
vancements in the care of preterm extremely low birth
weight (ELBW) infants. Factors that influence the severity
and type of neonatal Candida infections: gestational age <
32 weeks, Apgar score < 5 at 5 minutes, use of H2 blockers,
shock, prior use of intralipids, parenteral nutrition days,
use of central-venous catheters, intubation, or prolonged
hospital stays.21
4.2. Diagnostic approach
The presentation symptoms and diagnostic approaches are
similar to those for EOS, however, the clinical signs are
more subtle. Any change in vital signs, such as unexplained
tachycardia, hypo- or hyperthermia, apnea, and/or brady-
cardia should be evaluated carefully. Changes in heart-rate
characteristics could constitute physiomarkers for LOS
detection.22
Persistent hyperglycemia and thrombocytopenia are
strongly associated with candidemia and, if present, a
diagnosis of candidemia should be considered.23 Though
Rodwell et al24 developed the hematological scoring system
(HSS) based on the findings of a peripheral blood smear,24
Makkar et al25 noted that the immature poly-
morphonuclear neutrophil (PMN) count was the most sen-
sitive and that the I:M PMN ratio was the most specific
indicator of sepsis. For sepsis and probable sepsis, the I:T
PMN ratio and immature PMN counts have highest sensi-
tivity, whereas the I:T and I:M PMN ratios have highest
specificity. HSS has much higher sensitivity, specificity,
positive predictive value, and negative predictive value in
preterm infants relative to term infants.25
4.3. Management
Successful management of LOS depends upon early diag-
nosis with administration of appropriate antibiotics and
timely cardiopulmonary support. The choice of empiric
antibiotics is dependent upon the most common pathogens
causing LOS in the neonatal intensive care unit, and the
duration of therapy is dependent upon culture results,
clinical course, and organism.
Empirical antibiotics treatment is often combination
therapy with ampicillin and an aminoglycoside or vanco-
mycin with third generation cephalosporin, according to
the most common current pathogen in each unit.26
In symptomatic preterm infants with a central-venous
catheter, the most common isolates are CoNS, with most
CoNS now resistant to oxacillin. In infants with necrotizing
enterocolitis, the same antibiotic coverage may be used,
however, some clinicians add clindamycin or metronidazole
to cover anaerobic organisms. In systemic extended-
spectrum beta-lactamase infections, meropenem is recom-
mended, even without strong evidence of the efficacy or
toxicity for preterm infants.27 Many experts suggest treat-
ment with a beta-lactam antimicrobial agent (beta-lactam or
beta-lactamase inhibitor) combined with an aminoglycoside
for Enterobacter, Serratia, or Pseudomonas sepsis. Cefo-
taxime is commonly reserved for the treatment of infants
with meningitis.
170
Immunotherapeutic interventions, such as intravenous
immunoglobulin (Ig) infusion, IgM-enriched intravenous
immunoglobulin, granulocyte and granulocyte-macrophage
colony-stimulating factor administration, have been eval-
uated, but have not been shown to improve the outcome of
infants with sepsis.26
Pentoxifylline, a synthetic theobromine derivative, is a
nonsteroidal immunomodulating agent with unique hem-
orrheologic effects that has been used in a range of infec-
tious, vascular, and inflammatory conditions in adults and
children. The use of pentoxifylline to modulate inflamma-
tion in neonatal sepsis is controversial. A meta-analysis of
four randomized controlled trials demonstrated that pen-
toxifylline therapy significantly decreased all-cause mor-
tality during hospital stays in infants with sepsis {typical
relative risk, 0.40 [95% confidence interval (CI),
0.20e0.77]; typical risk difference, 0.15 (95% CI,
0.26e0.05); number needed to treat, 7 (95% CI,
4e20)}.28 Subgroup analyses also revealed significant re-
ductions in mortality in preterm infants, infants with
confirmed sepsis, and Gram-negative sepsis.28 However,
these studies were conducted in underdeveloped or
developing countries, therefore, the efficacy of pentox-
ifylline therapy warrants further investigation in large
randomized clinical trials in developed countries.
In addition to its cytokine-suppressing effects, hydro-
cortisone improved myocardial contractility and stroke
volume, increased systemic vascular resistance, and
enhanced urine output. Nonetheless, hydrocortisone has
not been evaluated in prospective randomized clinical trials
for the treatment of neonatal septic shock.29
5. Bacterial meningitis
5.1. Pathogenesis
st
Bacterial meningitis is more common in the 1 month than
at any other time of life, and frequently occurs in infants
with EOS and LOS.30 Although the mortality rate for infant
meningitis has declined from w50% in the 1970s to 10e15%
recently,31 the morbidity rate is relatively unchanged, with
a high prevalence of neurologic sequelae.32
In developed countries, GBS, E. coli, and other Gram-
negative bacilli are the most common organisms causing
neonatal meningitis.30e33 A prospective surveillance dis-
closed that 72% of early sepsis or meningitis was caused by
GBS and E. coli.33 However, Gram-positive organisms
constitute a greater portion of the disease burden among
PVLBW infants.34 Neisseria meningitides is a rare form of
meningitis in newborn infants.35 Additionally, in the
developing world, the microbiology of bacterial meningitis
in neonates varies geographically.36
5.2. Diagnostic approach
The clinical presentation of meningitis is highly variable.
Some infants present with nonspecific signs of sepsis, while
other infants exhibit signs associated with the central
nervous system (CNS), such as irritability, lethargy,
tremors, or seizures. It is suggested that seizures are often
F.-K. Huang et al
the initial manifestation of meningitis resulting from Gram-
negative organisms.37
The decision to perform a lumbar puncture (L-P) in an
infant with suspected sepsis is often difficult. We strongly
suggest that L-P should be performed in any neonate with a
positive blood culture or with clinical and laboratory find-
ings strongly suggestive of sepsis.35e39 Additionally, thor-
ough explanation to the family about the necessity of L-P is
important.
Initial cerebrospinal fluid (CSF) findings are usually suf-
ficient to make the diagnosis of meningitis, however, the
range of normal values for CSF parameters varies according
to gestational age, chronological age, and birth weight. Cell
counts and protein and glucose concentrations in CSF are
highly variable in newborn infants both with and without
meningitis.
WBC counts in CSF exceeding 21 cells/mL have a sensitivity
and specificity of w80% for predicting culture-proven men-
ingitis, however, neonatal meningitis can occasionally occur
with normal CSF parameters.38 A CSF protein concentration
> 150 mg/dL in preterm infants or > 100 mg/dL in term in-
fants is consistent with bacterial meningitis.38 A CSF glucose
concentration < 30 mg/dL (1.7 mmol/L) for term infants or <
20 mg/dL (1.1 mmol/L) for preterm infants is consistent with
neonatal bacterial meningitis.39 Neonates for whom the L-P
is traumatic should be treated presumptively for meningitis
pending results of CSF cultures. Gram-stained smears pro-
vide important information regarding antibiotic selection,
however, w20% of culture-confirmed bacterial meningitis
exhibit negative gram-stained smears. This is especially true
for Listeria monocytogene, the third most common cause of
meningitis in newborns.
5.3. Management
Intensive care with effective control of intracranial hy-
pertension, prevention of fluctuations in cerebral blood
flow, anticonvulsant therapy, maintenance of adequate
oxygenation, and prevention of hypoglycemia are crucial
aspects of managing neonates with bacterial meningitis.
Empiric antimicrobial regimens are identical to those with
for suspected EOS or LOS. However, in infants with sus-
pected meningitis, cefotaxime is preferable to amino-
glycosides. In infants with a suspected shunt infection,
empiric therapy with vancomycin and gentamicin is
appropriate. Meropenem is recommended for treatment of
infections caused by most multidrug-resistant enteric or-
ganisms. Although there are limited data documenting the
optimal dose and toxicity of meropenem in neonates, a
dosage of 20e40 mg/kg every 8e12 hours is recommend.27
A 14-day course is sufficient for neonates with uncom-
plicated GBS meningitis and for other Gram-positive or-
ganisms, while a 21-day course of therapy is required for
neonates with complicated GBS meningitis and Gram-
negative microorganisms. If ventriculitis, abscesses, or
multiple areas of infarction occur, 6e8 weeks of antibiotics
may be required. Administration of dexamethasone does
not significantly improve the mortality or morbidity of
meningitis.40
In the case of neonates with bacteremia and CSF findings
indicative of meningitis with negative CSF culture, we treat
Emergency neonatal infection
as if they have proven bacterial meningitis. For those who
have CSF pleocytosis and negative blood cultures, we
individualize the duration of antimicrobial therapy doses
for meningitis based on other parameters, such as CSF
glucose and protein concentrations.
The L-P should be repeated at 24e48 hours after initi-
ation of antimicrobial therapy to document CSF steriliza-
tion.41 This is important because the first, delayed
sterilization of the CSF is associated with an increased risk
of developing neurologic sequelae and the second, persis-
tent identification of organisms on a gram-stained smear
may be an early indication of inadequacy of antimicrobial
therapy. The duration of antimicrobial therapy is often
determined by the first negative-CSF culture. The persis-
tence of viable organisms more than 48 hours after initia-
tion of antimicrobial therapy may be an indication of need
for diagnostic neuroimaging, which can indicate a purulent
focus (e.g., obstructive ventriculitis, multiple small-vessel
thrombi) that may require additional intervention or pro-
long the duration of antimicrobial therapy.
Cranial sonography is most helpful for assessing ven-
tricular size and the presence of intraventricular hemor-
rhage, ventriculitis, echogenic sulci, abnormal
parenchymal echogenicities, and extracerebral fluid col-
lections in the early course of infection. Magnetic reso-
nance imaging optimizes assessment of injury to white
matter and formation of intracranial abscesses as
compared to contrast-enhanced computerized tomography
scan.42 We believe that neuroimaging study 48e72 hours
before the anticipated end of therapy provides the best
prognostic information.
6. Herpes simplex virus infection
6.1. Pathogenesis
Despite the advances in understanding how HSV is transmitted
to the fetus and neonate, improved molecular methods to
diagnose HSV, and better antiviral treatment strategies,43
neonatal HSV infection remains a clinical challenge.
Most neonatal HSV (NHSV) infections (85%) are acquired
perinatally.44 Factors including maternal primary- or
recurrent-HSV infection, maternal HSV-antibody status,
duration of ruptured membranes, use of fetal scalp moni-
tors, and vaginal delivery affect perinatal transmission.45
Unfortunately, most NHSV disease occurs in mothers
without a history of HSV infection or other identifiable risk
factors.46 Hematogenous spread might result in dissemi-
nated disease in the neonate or retrograde spread from the
nasopharynx and olfactory nerves to the brain.
6.2. Diagnostic approach
Disseminated NHSV infection has an 80% mortality rate if
untreated and often presents in the 1st week of life with
nonspecific signs and symptoms, similar to neonatal
sepsis.46,47 More than 20% of neonates with disseminated
NHSV disease do not have vesicles,44 therefore, diagnosis of
disseminated NHSV infection is often delayed due to wait-
ing for results of possible bacterial sepsis when the clinician
is not alert to HSV infection. Efforts should focus on
171
identifying high-risk neonates with a sepsis-like picture,
progressive pneumonitis, hepatitis, or meningoencephalitis
as methods for HSV screening and determination of early
empiric antiviral therapy.46,48,49
Definitive diagnosis of NHSV infection should be estab-
lished through isolation of HSV in traditional monolayer cell
culture or enhanced cell-culture systems, detection of viral
DNA using polymerase chain reaction (PCR) assays, and
detection of viral antigens using rapid direct immunofluo-
rescence assays or enzyme immunoassays (EIA). Negative
HSV cultures, PCR, and rapid tests do not exclude NHSV,
and the accuracy of EIA tests to diagnose NHSV infection is
unknown. Shell-vial centrifugation fluorescent-foci cultures
and enzyme-linked virus-inducible systems are used in
many clinical laboratories and provide rapid detection of
HSV in clinical systems within 24e48 hours.50
Meningoencephalitis of NHSV usually occurs during the
first 6 weeks of life.51 Nearly 60e70% of infants with NHSV
meningoencephalitis have skin vesicles at some point dur-
ing the disease course,44 however, this may occur without
skin involvement and with or without disseminated disease.
Intractable seizures, low-grade fever, irritability, and poor
feeding are relatively specific for NHSV meningoencepha-
litis.52,53 CSF results may present as normal early in the
course of the illness, but will classically show mononuclear
cell pleocytosis, normal or moderately low glucose con-
centrations, and mild elevated protein concentrations. Red
blood cells are not significantly associated with NHSV
meningoencephalitis.46 Electroencephalogram results are
often abnormal very early in the disease course and may
show focal or multifocal periodic epileptiform discharges.43
The detection of HSV DNA in the CSF of a neonate confirms
the diagnosis of meningoencephalitis and is more sensitive
than viral culture. Nonetheless, the presence of blood or
high protein concentrations in the CSF may interfere with
some PCR assays and produce false-negative results,54 and
> 90% of disseminated NHSV disease may have HSV DNA
detected in CSF by PCR survey.43 Therefore, it is imperative
to include a CSF examination and HSV PCR for CSF in all
neonates with suspected or proven NHSV infection. If initial
CSF PCR is negative, yet HSV meningoencephalitis is
strongly suspected, HSV PCR for CSF should be repeated
during the 1st week of illness.55
6.3. Management
Given that early manifestations of NHSV are frequently
nonspecific and prompt administration improves outcome,
many experts recommend empiric treatment with acyclovir
in all neonates with aseptic meningitis or other signs and
symptoms of meningoencephalitis without an obvious bac-
terial cause.43,44,51,56 A comprehensive laboratory evalua-
tion for NHSV should be performed before initiation of
acyclovir therapy. These evaluations would include com-
plete blood count, liver transaminases, total and direct
bilirubin, ammonia (if clinically indicated), blood urea ni-
trogen, creatinine, urinalysis, CSF cell count and differential
count, glucose, protein, and HSV-DNA PCR with viral culture
of the tracheal aspirate if the infant is intubated.43,51
Because the persistence of HSV DNA in the CSF is asso-
ciated with poor outcomes,57 repeated spinal tap to obtain
172
CSF HSV-DNA for PCR near the end of therapy is necessary
to make sure that HSV-DNA PCR is negative and that CSF
parameters have returned to normal.43,44,58
Intravenous acyclovir (20 mg/kg/dose every 8 hours)
may increase the dosage interval in patients < 34 weeks
postmenstrual age or in patients with significant hepatic or
renal failure. Treatment duration for localized infections is
14 days, however, for disseminated disease or CNS in-
fections, duration of treatment would be 21 days.
Recent evidence disclosed that suppressive therapy
might have favorable outcomes in CNS disease and reduce
cutaneous recurrences.57 Suppressive therapy with oral
acyclovir (300 mg/m2 per dose, 3 times per day for 6
months) immediately following parenteral treatment for all
forms of neonatal HSV disease is highly suggested.43,52,58,59
7. Conclusion
Emergent infections, such as congenital pneumonia, EOS,
LOS, meningitis, and NHSV, still exhibit relatively high
mortality rates and result in severe adverse neuro-
developmental outcomes, especially for PVLBW infants.
Thus, the approach to treating these emergent infections is
critical for the pediatrician. This review provides important
clinical advice for pediatricians. Detailed physical exami-
nations with observation of clinical symptoms are funda-
mentally important. However, we believe a practical
neonatal sepsis scoring system based on risk factors and
common biomarkers is imperative to help pediatricians
predict and diagnose these emergency neonatal infections
more accurately in order to achieve better neuro-
developmental outcomes.
Conflicts of interest
The authors declare on conflicts of interest.
Acknowledgments
This study was supported by China Medical University Hos-
pital (grant DMR99-053). We thank Professor Richard Polin
at the Morgan Presbyterian Stanley Children’s Hospital of
New York, NY, USA for his generous and kind help in the
English editing.
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