Abstract
Objectives: To study incidence, mortality, maternal and neonatal
risk factors and causative microorganisms for neonatal sepsis.
Methods: A total of 60 neonates with sepsis were studied during
the period between January and December 2005.
The clinical presentations, maternal, and neonatal risk factors and the
time of neonatal death were recorded.
Results: Four hundred ninety nine (10.2%) out of 4902 live
neonates were admitted for various reasons to the neonatal intensive care unit
at King Hussein Medical Centre. Sixty
(12.0%) babies had proven sepsis, 28 (46.7%) of these with early onset and 32
(53.3%) with late onset sepsis. Maternal
risk factors associated with neonatal sepsis were: cesarean section in 22
(36.7%) cases, premature rupture of membranes in 4 (6.7%) cases, eclampsia in 4 (6.7%) cases, and maternal
urinary tract infection in 3 (5%). Neonatal risk factors observed were: male
gender in 40 (66.7%) cases, low birth weight in 38 (63.3%) cases, prematurity
in 32 (53.3%) cases, low Apgar score in 10 (16.7%) cases, and mechanical
ventilation in 12 (20.0%) cases. Gram
positive bacteria were isolated in 44 (73.3%) cases of which four died. However gram negative sepsis was associated
with higher morbidity and mortality rates.
Twelve (20%) babies died, seven of them due to Klebsiella sepsis.
Candida sepsis caused three cases of sepsis with one death. Most of deaths occurred out of working hours.
Conclusion: Early recognition and prompt treatment of neonatal
sepsis are of paramount importance particularly in the presence of risk
factors.
Key words: Neonatal
sepsis, Blood culture
JRMS
December 2009; 16(3): 16-19
Introduction
Neonatal sepsis: is a
clinical syndrome resulting from the pathophysiologic effect of local or
systemic infection in the first month of life.
Newborns are immunologically
immature and are ill-suited to defend themselves against the polymicrobial
flora to which they are exposed during and after parturition. Neonatal polymorphonuclear cells demonstrate
decreased chemotaxis, opsonization, phagocytosis, and intracellular bacterial
killing as well as depressed oxidative responses. Neonatal monocytes have decreased chemotaxis
and cytotoxic functions. The most
important risk factors for hospital-acquired sepsis are prolonged use of
intravascular plastic catheters, exposure to antibiotics, prolonged
hospitalization, contaminated respiratory support equipment, and intravascular
or parenteral solutions.
Gram positive organisms may
be introduced from the environment or patient's
skin, while
gram
|
Table I. The organisms isolated from blood cultures
|
Number (n=60)
|
Organism
|
|
Staphylococcus epidermidis
|
40 (67%)
|
|
Klebsiella sp.
|
8 (13%)
|
|
Candida albicans
|
3 (5%)
|
|
Streptococcus viridians
|
3 (5%)
|
|
Staphylococcus aureus
|
2 (3%)
|
|
Enterobacter sp.
|
2 (3%)
|
|
Diphtheroids
|
1 (2%)
|
|
Escherichia coli
|
1 (2%)
|
|
Table II. The organisms isolated in cases of death
|
Number (n=12)
|
Organism
|
|
Klebsiella sp.
|
7 (58.4%)
|
|
Staphylococcus epidermidis
|
4 (33.3%)
|
|
Candida albicans
|
1 (8.3%)
|
|
negative organisms are always derived from patient's
endogenous flora which may have been altered by antecedent antibiotic therapy
or populated by resistant organisms transferred from the hand of health care
workers or contaminated equipments.(1)
Early onset neonatal sepsis
is clinically apparent within six hours of birth in >50% of cases, the great
majority of this presents within the first seven days of life. Late onset neonatal sepsis usually presents
after seven days of age and includes hospital-acquired infections.
The early signs of neonatal
sepsis are nonspecific such as hypoactivity, poor sucking, apnea, bradycardia,
raised temperature, instability, respiratory distress, peri-umbilical erythema,
bulging fontanels, seizures, and coma.
Methods
A prospective study was
conducted from 1st of January to 31st of December 2005.
This study was conducted in a tertiary referral hospital to determine the
frequency of neonatal sepsis, its underlying maternal and neonatal risk
factors, and the time of the day in which the highest mortality occurs. There were total of 60 neonates admitted to
neonatal intensive care unit (NICU) at King Hussein medical Centre, Amman, Jordan
with clinical signs of sepsis as hypoactivity, poor sucking, respiratory
distress, and jaundice, in addition to positive blood culture.
The maternal and neonatal
data were recorded including age of the mother, parity, maternal disease,
method of delivery, time of rupture of membranes, gestational age, birth
weight, sex, Apgar Score at one and ten minutes of life consecutively,
associated diseases including pneumonia and jaundice, need for respirator,
umbilical catheter, and surfactant use.
The duration of
hospitalization was recorded as mean length of hospital stay. Sepsis occurring under seven days was defined
as “Early”, and Sepsis occurring later than seven days was defined as “Late”.
Complete blood count
including erythrocyte sedimentation rate (ESR), blood chemistry including
electrolytes, and C-reactive protein (CRP) were done.
For blood cultures, 1-3 ml
of blood was obtained by standard aseptic methods, and injected directly into
BACTEC PEDS PLUS/F (Becton
Dickinson) blood culture bottle. All
bottles were incubated at 35ºC in BACTEC 9240 system (Becton
Dickinson Diagnostic Instrument Systems).
The system provides continuous incubation and automatic monitoring for
microbial growth using a fluorescent-CO2 sensor. Bottles were inspected by the system every
ten minutes and those with undetected microbial growth were flagged negative
and displayed on the monitor at the end of five days incubation. Bottles with detected microbial growth were
flagged positive and displayed, pulled from the instrument, and Gram
stained. According to the organism
present, subcultures on aerobic and anaerobic bacteriological media, direct
biochemical tests, and direct antimicrobial susceptibility testing were
performed according to the established standard procedures. All subcultures were incubated at 35ºC
in 5% CO2. For confirmatory
purposes, direct identification and susceptibility testing were performed on
the microbial colonies using VITEK 120 system (bioMérieux).
The initial empiric
antibiotic regimen used in the neonatal intensive care unit is ampicillin and
amikacin, and the second line regimen is imipenem and vancomycin.
Results
Out of 499 neonatal
admissions during the study period, a total of 60 (12%) were confirmed neonatal
sepsis. All cases had positive blood
cultures, and the organisms isolated are shown in Table I.
Out of the 60 cases, 12 (20%) neonates died and Table II shows the organisms isolated from their blood cultures.
|
Table III. Maternal risk factors
|
Risk factor
|
Number (n=60)
|
|
Cesarean section
|
22 (36.7%)
|
|
Premature rupture of membranes
>18hr
|
4 (6.7%)
|
|
Pre-eclampsia
|
4 (6.7%)
|
|
Urinary tract infections
|
3 (5%)
|
|
Table IV. Neonatal risk factors
|
Risk factor
|
Number (n=60)
|
|
Male Gender
|
40 (66.7%)
|
|
Low Birth weight
|
38 (63.3%)
|
|
Prematurity
|
32 (53.3%)
|
|
Mechanical-assisted ventilation
|
12 (20%)
|
|
Umbilical catheters
|
11 (18%)
|
|
Low Apgar score
|
10 (16.7%)
|
|
Surfactant
|
8 (13%)
|
|
Total parenteral nutrition
|
8 (13%)
|
|
Gram-positive bacteria were isolated from 44 (73.3%)
cases, of which four died. Thirty-seven
(84%) of the isolated gram positive bacteria were Staphylococcus epidermidis
of which four were proved to be skin contaminants. Gram-negative bacteria were
isolated from 11 (18.3%) neonates, of which seven died.
All mothers were younger
than 30 years old and had antenatal care. Thirty-six (60%) mothers were primipara,
and 22 (36.7%) delivered by cesarean section.
The maternal risk factors are shown in Table III.
Forty neonates (66.7%) were
males and twenty were females.
Thirty-two (53.3%) had a gestational age of <37 weeks. Thirty eight (63.3%) had birth weight <2.5
kg (maximum weight was 5 kg, and minimum weight was 0.750 kg). Ten (16.7%) had Apgar score <7 in first
and ten minutes after birth consecutively.
The neonatal risk factors are shown in Table IV.
Ten premature neonates who
died because of sepsis and other causes, required the use of respirators and
umbilical catheters, and were given surfactant.
Two full-term neonates died, one of them had hyperinsulinemia/
hypoglycemia and needed umbilical catheter.
Early infections were
detected in 28 neonates mainly due to gram-positive organisms, and late
infections were detected in 32 cases mainly due to gram negative organisms.
The twelve neonates who died
due to sepsis were mostly premature with low birth weight, and had late sepsis
due to gram negative bacteria mainly Klebsiella sp. They had leucopoenia, thrombocytopenia,
electrolyte disturbances such as hypocalcaemia, and elevated ESR. CRP was positive in most late infections.
For all the 60 neonates, the
second antibiotic regimen was used and second blood culture was taken.
Discussion
Neonatal sepsis occurs in
0.5-8.0/1000 live births. The highest rates occur in low birth weight newborns,
those with depressed respiratory function at birth, and with maternal prenatal
risk factors.(1) In
our study, neonatal sepsis occurred in 60/4902 (12.2/1000) with similar risk
factors mainly prematurity.
The gram-negative bacteria,
specifically entero-bacteriaceae, have been reported by various authors as the
major cause of neonatal septicemia.(2-4) In our study, gram-negative bacteria were
more common in late onset sepsis and within this group infection with Klebsiella
sp predominated and was associated with the most serious outcome. Similar to our findings, other authors found
that coagulase negative staphylococci were the main cause of late onset sepsis
in NICU.(5,6)
The recovery of an organism
from blood stream should always be considered significant until proven
otherwise. The significance of the
isolate should be determined by establishing close liaison and discussion
between the microbiologist and the clinician.
Although Staphylococcus epidermidis had the highest isolation
rate (40%) in our study, similar to previous studies(7) more
than 94% of these organisms isolated were judged to be contaminants after close
discussions and in the light of clinical picture of the patients. Every clinical microbiology laboratory needs
policies and procedures designed to ensure that blood cultures are collected in
such a way as to minimize contamination.
Whether blood cultures are collected by medical technologists, trained
phlebotomists, nurses, or other health care workers, an ongoing program to
monitor compliance with these policies and procedures is necessary and should
be part of the laboratory quality assurance program. Guidelines for proper blood cultures
collection and reduction of contamination have been recently published.(8)
Some authors recorded that 60% of mothers were primipara, 60% of neonates were premature, and 42%
with body weight less than 2.5kg at birth.(9) These findings are similar to those reported
in other American and European studies.(10-12) Our study showed that 60% of mothers were
primipara, thirty two neonates (53.3%) were premature, and 38 neonates (63.3%) had
a birth weight less than 2.5 kilograms.
In our study a combination
of ampicillin and amikacin was used as initial empiric regimen for early onset
neonatal sepsis, while awaiting blood culture results. However, other regimens were used in other
studies. Clark and colleagues
recommended the use of ampicillin and gentamicin(13) and
Flidel-Rimon and colleagues concluded that piperacillin in combination with
amikacin are microbiologically and clinically efficient and safe in the
treatment of neonatal sepsis.(14)
The increased incidence of
nosocomial infection by methicillin-resistant Staphylococcus aureus in
NICU has led to an increase in the utilization of vancomycin.(15) In our study, a combination of imipenem and
vancomycin was used with good outcome in late onset sepsis.
It was reported that the use
of pentoxifylline, an anti inflammatory drug, resulted in reduction of neonatal
sepsis and its complications.(16) Intraglobulin was given in
combination with the antibiotics to all the neonates in our study. As in other studies,(17) we
demonstrated a high mortality rate in premature babies who required mechanical ventilation
and total parenteral nutrition.
Adequate maternal diagnosis
and treatment are necessary to reduce the neonatal morbidity and mortality
associated with neonatal sepsis. Since
neonatal sepsis may present with non-specific clinical signs and its effect may
be devastating, an early diagnosis and prompt therapy are of paramount
importance. Antibiotics should be used because they are detrimental to the
infant΄s flora in the nursery.
Depending on the laboratory culture method
and rapidity of reporting, almost all bacterial cultures are positive within 72
hours. If negative culture of body fluid
is consistent with the clinical course, antibiotic may be discontinued after 72
hours. Adequate number of nursing staff,
preferably one nurse for every three neonates, is of great importance in the
NICU particularly during night shift.
Strict preventive measures particularly hand washing and isolation
facilities should be adopted.
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