Information from 50 infants with neonatal

septicemia from the Louisville General Hospital

during an eight-year period (1964-1972) is
presented. Twenty-five infants had gram-positive
and the other 25 had gram-negative organisms.
E. coli (13 cases), Staphylococcus (10 cases), and
hemolytic Streptococcus non-Group A (7 cases)
were the most common causative microorganisms.
Neonatal Sepsis
Only one of the 25 infants with gram-positive
sepsis died; three with gram-negative sepsis died.
Listeria monocytogenes was demonstrated in three
infants; all had meningitis with no mortality. Early
diagnosis, prompt intensive antibacterial
therapy, and a high index of suspicion are most
helpful for reducing the morbidity and mortal-
ity.

A
Survey of Eight Years
ESPITE the general decline of neonatal Experience at the
mortality caused by sepsis in the United
States to approximately 12.5/1,000 live births Louisville General Hospital
over the past decade, infection still ranks as a

significant cause.1 In recent reports, neonatal

mortality from infection ranges from 13 to
45 per cent. Although newer diagnostic
methods and antimicrobials are available, the
lowest mortality rate for neonatal septicemia
was reported in 1955 as 13 per cent by

Smith, Platou, and Good.~ In contrast, prior

to antibiotics, Dunham reported an 87 per
cent mortality in 1934.3 At the second Euro-
pean Congress on Perinatal Medicine in
April 1970, Nicolopoulos, Zanthou, Arseni,
and Douskas reported a low mortality rate of
Leticia C. Alojipan, M.D.,*
18.8 per cent in 80 cases of neonatal sep-
ticemia for the years 1964 to 1969.~ Because Billy F. Andrews, M.D.
of the high mortality and morbidity, the
status of this problem should be investigated
at least every ten years in various centers
around the world to determine the best
methods for diagnosis, to identify the cur-
rent causative pathogens, to ascertain which

* Assistant Professor of Pediatrics, University of

Louisville School of Medicine, Louisville, Ky. 40202..
** Professor and
Chairman, Department of Pediat-
rics, University of Louisville School of Medicine, Louis-
ville, Ky. 40202.
Supported by General Research Grant FR-5357, De-
partment of Health, Education, and Welfare Grants
04-H-000319-01-0 and MCR 210102-03-0.

181

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 TABLE 1. Categories of Infants zuith
antibiotics most effective against the
are
pathogens, and to establish what supportive
measures are best.
The experience with neonatal septicemia
at the Louisville General Hospital was en-
couraging and may benefit others and stimu-
late them to share their current experiences.
Neonatal septicemia is responsible for 6.36
per cent of the total neonatal deaths in our
center. This is comparable to the experience
of MacGregor ( 1955), who attributed less than
6 per cent of the deaths to infection.~ Arey states
that neonatal infection caused death in 10 to 15
per cent of the infants in his postmortem
study and that infection contributed to death
in 17 per cent..
Cases and Criteria
A retrospective study of all infants admit-
ted to the Newborn Service of Louisville
General Hospital with a Diagnosis of
neonatal septicemia was made for the period
from July 1, 1964 to June 30, 1972. Infants
were categorized into three groups-
&dquo;presumptive,&dquo; &dquo;probable,&dquo; or &dquo;proven&dquo;
septicemia-as depicted in Table 1. Infants
with positive blood culture whose bacterial
growths were deemed contaminants were
excluded. Clinical manifestations considered
for infants with infection included cyanosis,
tachypnea, retractions, apnea, tachycardia,
hypo- or hyperthermia, lethargy, irritability,
TABLE 2. Maturation, Race and Sex
182
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Clinical Sepsis (1964-1972)
seizures, feeding problems, vomiting, diarrhea,
abdominal distention, jaundice, hepatospleno-
megaly, and weight loss. Laboratory evidence
considered to support the diagnosis included:
leukopenia or leukocytosis, thrombocytopenia,
positive tests for C-reactive protein, and positive
tests for C-reactive protein, and positive
cultures from sites other than blood. Proba-
ble relationships to maternal and neonatal
predisposing factors and complications were
also investigated.
Results and Comments
There were 19,121 live births during the
period surveyed. The population was ap-
proximately 60 per cent black. The number
of low birth weight infants (under 2,500 g)
was 2,294. Of 134 infants who were thought
to have neonatal sepsis, only the 50 infants
proven to have sepsis are discussed in this
report. The incidence of neonatal septicemia
was 2.6 per 1,000 live births. Table 2 shows
maturation, race, and sex distribution. The
susceptibility of prematures has been shown
consistently in previous reports. 4,1,1 Al-
though 23 of our 50 cases were males, data
from the literature indicate that a 2:1 male
predominance is a more nearly representa-
tive figure. An almost equal predilection to
develop septicemia by both black and white
infants is demonstrated in our study. None
of the infants with neonatal septicemia
weighed less than 1,000 grams; seven
weighed between 1,000 and 1,499 grams, 17
between 1,500 and 2,500 grams, and 26
were over 2500 grams.
Different reports from the literature indi-
cated the average age of 7.5 to 1I days for
onset of signs and symptoms of neonatal
Septlcernla.2~~3~-11 Our study showed a mean
age of 4.5 days for recognition of symptoms,
although more than 50 per cent of our
infants actually developed manifestations
 TABLE 3. Distribution of the Etiologic Agents in Neonatal Septicemia
during the first 48 hours of life. Early
recognition was attributed to the fact that in
43 cases, infants were still in the nursery
where signs and symptoms were reported by
experienced nurses. These manifestations
may have been impossible for less experi-
enced mothers to recognize.
Table 3 shows the bacteriologic organisms
isolated. In infants with gram-negative sep-
ticemia, E. coli still ranked highest. Klebsiella
r~erobacter, Pseudomonas, Proteus, Klebsiella
pneumoniae and Serratia were among the
gram-negative organisms isolated. The most
common gram-positive organism isolated
was hemolytic Streptococcus non-Group A.
Other gram-positive organisms were coag-
ulase-positive Staphylococcus aureus, Strepto-
coccus viridans, Listeria monocytogenes, and he-
molytic Streptococcus Group ~~.
The most frequent signs and symptoms
associated with a positive diagnosis are de-
picted in Table 4. The presence of several or
a cluster of
signs should be highly sugges-
tive. A few of the patients reported by
Gluck were asymptomatic, yet had positive
cultures.9 Jaundice occurred in 48 per cent
of our cases. Other signs and symptoms such
as poor
feeding, respiratory distress, leth-
argy, fever, seizures, and hepatomegaly
were less frequent.
Table 5 compares signs and symptoms of
infants with gram-negative to those with
gram-positive infections. Although clinical
manifestations were observed more fre-
quently in infants with gram-negative sep-
ticemia, clinical correlation or differences
were not statistically significant. Splenomeg-
aly, reported to be significant in recent
studies, was not often observed in
subjects, though this finding was the
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common prior to availability of antibiotic
therapy.
Laboratory features other than positive
blood cultures were investigated. Twenty-
one (42%) of the group had normal WBC
counts, defined as between 10,000 and 25,
000/mm3. Differential leukocyte counts were
so variable as to be not useful in differentiat-
ing between gram-positive and gram-
negative septicemia; however, 31 of 50 in-
fants exhibited 50 per cent or more seg-
mented neutrophils. Positive C-reactive pro-
tein tests were not diagnostic but may be an
additional aid in diagnosis; of the 11 infants
on which this test was performed, three
infants, two with gram-positive septicemia
and one with gram-negative sepsis, had
positive reactions. A low platelet count was
infrequently found, probably because only
septic infants with hemorrhagic problems
had platelet counts done. One infant, who
died of streptococcal septicemia, showed
persistent HoweII-Jolly bodies and target
cells in the peripheral smear, and had a
large spleen on postmortem examination.
The presence of leukocytes and bacteria in
gastric aspirate has been thought to indicate
amnionitis and to represent an infant who
has increased risk of developing infection. 12
Although such infants may be treated for
presumptive infection, the presence of these
TABLE 4. Signs and Symptoms of Neonatal Septicemia
our
most
183
 TABLE 5. Relationship Betzueen Clinical Features and
Causative Organisms
findings does not establish the diagnosis of
sepsis. Laboratory procedures used by others
to demonstrate inflammatory reaction in the
umbilical cord and/or membranes are not
performed routinely in our center. 13
On the principle that a presumptive diag-
nosis of neonatal sepsis warrants intensive
and broad antibiotictherapy, treatment in
our center was successful in 43 of 50 infants.
No uniform treatment plan was employed,
though only parenteral antibiotics were
used. The combination of penicillin and
kanamycin was used with 44 infants; ampicil-
lin and kanamycin plus colimycin were given
to one infant with Pseudomonas aeroginosa
infection. Neomycin was used orally for one
infant who received penicillin and kanamy-
cin for E. coli septicemia and gastroenteritis.
Changes of antibiotics after onset of therapy
were based on clinical evaluations of
symptoms and probable causative organism
if cultures were not available; when cultures
were available, by the in nitro sensitivity tests.
Treatment periods varied from seven to 14
days; infants with meningitis and urinary
tract infection were treated for longer
periods than those with only positive blood
cultures.
Fortunately, almost all organisms were
sensitive to the antibiotics used initially. No
resistant strains of E. coli or staphylococci were
found in blood cultures taken during the
study period. Carbenicillin, methicillin, and
oxacillin, which are used as secondary drugs
in our center for older patients, were not
given to our neonates.
Newborns whose symptoms began during
the first two days had blood, cerebrospinal
184
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TABLE 6. Factors Predisposing to Neonatal Septicemia
fluid, and urine cultures. Those in whom
sepsis was suspected within the first 30
minutes of life because of predisposing
conditions had cultures taken of fetal and
maternal sides of the placenta, gastric aspi-
rate, external ear, and the umbilical stump.
Infants who had been discharged from the
nurseries and then readmitted for sepsis
similarly had blood, cerebrospinal fluid, and
urine cultures taken. Infants with gastroen-
teritis had stool cultures. The recovery of the
same organism from the blood as well as
from the other sites was thought to confirm
our diagnosis of sepsis.
Of the seven of the 50 infants who died,
six were premature and six harbored gram-
negative organisms.
Analysis of our mortality figures in terms
of etiologic agents revealed the highest mor-
tality rate in infants with Pseudomonas sepsis (2
of 2) and with E. coli (4 of 13). Of 25 infants
with gram-positive infections, only one died.
This infant had a Group B hemolytic strep-
tacoccus. Staphylococcus and Listeria monocyto-
genes recovered from ten and three
were
infants, respectively. Neither organism was
associated with a death.
The most common major complication
observed in our infants was meningitis,
found in eight cases; five had E. coli and
three had Listeria monocytogenes. Only 50 per
cent of our infants with meningitis during
the study period had positive blood cul-
tures. 14 Pneumonia was associated with
three cases, necrotizing enterocolitis and
gastroenteritis with two cases each. One
infant had a urinary tract infection.
The influence of maternal and neonatal
factors in the development of neonatal sep-
ticemia is depicted in Table 6. The frequent
association of prolonged rupture of mater-
nal amniotic membranes, maternal fever and
maternal infection to neonatal sepsis has
been shown by Gluck and others.9 Several
factors may coexist in a given situation. Ten
of our patients had low Apgar scores and
four of these had to be resuscitated by
intubation. Other factors such as difficult or
prolonged delivery and presence of
meconium-stained amniotic fluid were felt to
predispose a few of our infants.
Because of the above findings, we use the
following criteria for initiation of antibiotic
treatment with our newborns at the Louis-
ville General Hospital:
1) Prolonged rupture of membranes
for more than 24 hours prior
ery ; 2) maternal infection at
delivery shortly before it; 3) sig-
or
nificant depression of the infant at birth
requiring intubation or mouth-to-tube
resuscitation, and 4) infants with pro-
In the pres-
gressive respiratory distress.
ence of any of the above factors, we
culture gastric aspirate, ear canal, skin,
oropharynx, and blood before initiation
of appropriate antibiotic therapy.
Many infants in our center are
presumptive sepsis, perhaps too
feel that their survival
we depends upon
early vigorous Follow-up
treatment. results
of these infants in our High Risk Clinic are
gratifying in that no significant difference
has been found when compared with a
control population, with the single exception
of infants with meningitis. We do not have
sufficient data from which to draw broad
conclusions. Others are urged to tabulate
and compare their experiences with ours.
Conclusions
Fifty infants with proven diagnosis of
neonatal septicemia are presented. Pro-
longed rupture of membranes which may be
coexistent with maternal fever, purulent or
foul-smelling amniotic fluid, difficult deliv-
ery, and asphyxia neonatorum have been
associated with the development of neonatal
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sepsis. Icterus is the most common clinical
manifestation of neonatal sepsis, although
poor feeding, gastrointestinal symptoms,
respiratory distress, and lethargy are also
frequent. Although clinical manifestations
are seen more frequently in
gram-negative
septicemia, one cannot differentiate between
gram-negative sepsis versus gram-positive
sepsis on the basis of clinical features. The
presence of positive laboratory evidence for
infection such as leukopenia on leukocytosis,
thrombocytopenia and a positive C-reactive
protein reaction are helpful, but their ab-
sence in the presence of clinical manifesta-
tions does not rule out the diagnosis. Early
and vigorous antibiotic treatment with full
supportive therapy is essential to keep down
morbidity and mortality.
to deliv-
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