International Journal of Contemporary Pediatrics

Verma P et al. Int J Contemp Pediatr. 2015 Aug;2(3):176-180

http://www.ijpediatrics.com pISSN 2349-3283 | eISSN 2349-3291

DOI: http://dx.doi.org/10.18203/2349-3291.ijcp20150523
Research Article

Neonatal sepsis: epidemiology, clinical spectrum, recent antimicrobial

agents and their antibiotic susceptibility pattern
Pradeep Verma, Pramod Kumar Berwal, Niranjan Nagaraj*,
Sarika Swami, Prathusha Jivaji, Satya Narayan

Department of Peadiatrics, SP Medical College, Bikaner, Rajasthan, India

Received: 05 July 2015

Accepted: 26 July 2015

*Correspondence:
Dr. Niranjan Nagaraj,
E-mail: getniranjan806@yahoo.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Neonatal sepsis is one of the most common causes of neonatal mortality in the developing world. This
study aims to determine the incidence, the bacteriological profile of neonatal septicaemia, their antibacterial
susceptibility pattern.
Methods: It is a prospective study, carried out in the tertiary care NICU of S.P. Medical College, Bikaner, Rajasthan,
from January 2014 to October 2014. Blood culture specimens were collected from neonates, identification of
organisms, their antibiotic susceptibility pattern detection was done.
Results: Gram negative organisms were more common (71.42%) than gram positive (28.57%). Klebsiella was the
most common pathogen (48.21%) in both early and late onset septicemia. In third generation cephalosporins, only one
organism (Strept. faecalis) is sensitive to ceftriaxone but cefoperazone and cefotaxim both have activity against
Klebseilla and coagulase negative Staphylococcus. Ceftazidime showed better results and active against Klebseilla, E.
coli, pseudomonas and unidentified gram negative bacilli. In aminoglycosides amikacin has much better results than
gentamicin. Piperacillin had advantage over ampicillin. All organisms except E. coli showed sensitivity to cefotaxime.
Vancomycin had good activity against gram positive organisms (enterococcus, CONS, MRSA). Neonatal mortality
rate was 23.43%.
Conclusions: Neonatal sepsis is one of the major causes of morbidity and mortality in the newborns. Prematurity, low
birth weight, prolonged rupture of membranes are major risk factors predisposing neonate to sepsis. This study,
showed alarming results of antibiotic sensitivity patterns. The antibiotics which are routinely used like ampicillin and
ceftriaxone showed poor activity against most of the organisms.

Keywords: Neonatal sepsis, Antibiotic susceptibility pattern, Microorganisms, Klebsiella, Bikaner city

INTRODUCTION sepsis according to the data from National Neonatal

Perinatal Database (NNPD, 2002-03) is 30 per 1000 live
Sepsis is the commonest cause of neonatal mortality; it is births. The NNPD network comprising of 18 tertiary care
responsible for about 30-50% of the total neonatal deaths neonatal units across India found sepsis to be one of the
in developing countries.1,2 It is estimated that up to 20% commonest causes of neonatal mortality contributing to
of neonates develop sepsis and approximately 1% die of 19% of all neonatal deaths.3
sepsis related causes.2 Sepsis related mortality is largely
preventable with prevention of sepsis itself. This includes Neonatal sepsis is a clinical syndrome characterized by
timely recognition, rational antimicrobial therapy and signs and symptoms of infection with or without
aggressive supportive care. The incidence of neonatal accompanying bacteremia in the first month of life. It

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encompasses various systemic infections of the newborn suggestive of neonatal sepsis. Detailed history including
such as septicemia, meningitis, pneumonia, arthritis, history regarding maternal risk factors were taken in this
osteomyelitis, and urinary tract infections. Superficial study. Thorough physical examinations were conducted
infections like conjunctivitis and oral thrush are usually with special emphasis on features suggestive of neonatal
not included under neonatal sepsis. Among intramural sepsis. All the babies were examined twice daily to
births, Klebsiella pneumoniae is the most frequently access the progress of disease and development of any
isolated pathogen (32.5%), followed by Staphylococcus new finding till the baby was discharged or expired. All
aureus (13.6%). Among extramural neonates (referred those babies presenting with clinical sepsis were
from community/other hospitals), Klebsiella pneumoniae thoroughly investigated for any evidence of bacterial
is the commonest organism (27%), followed by sepsis and all laboratory investigations were sent within
Staphylococcus aureus (15%) and Pseudomonas (13%). 3 24 hour of admission. The babies had clinical features of
neonatal sepsis and two or more laboratory criteria or
Neonatal sepsis can be classified into two major culture positive were included in the study: Clinical
categories depending on the onset of symptoms,4 Early features: Fever, cold extremities, refusal to feed, sluggish
Onset Sepsis (EOS):It presents within the first 72 hours activity, vomiting, abdominal distension, bleeding,
of life; Late Onset Sepsis (LOS): It usually presents after respiratory distress, grunting, apnea, cyanosis, jaundice,
72 hours of age. The ability of the new born to respond to pallor, lethargy, excessive cry, convulsion, buldging
an infection is limited to identical stereotype response to anterior fontanalle, rash, diarrhea, umbilical discharge,
a variety of insults, thus producing identical clinical pyoderma, oral thrush etc.
picture in a variety of conditions. The new born infant
especially preterm as compared to the older children and Laboratory criteria: 1) Total leucocyte counts (<5000 or
adults has markedly decreased IgM and IgA level at birth. >20000/mm³) 2) Band cell count more than 20% 3) Band
Although IgG may be normal in term infant but it is low cell/Absolute neutrophil counts ratio (>0.2%) 4) Elevated
in preterm infant. The percentage of CD-8 positive T- C-reactive protein (>6 mg/l) 5) Micro ESR (>10 mm in
Lymphocyte (Suppressor) and cytotoxic cells in adults is 1st hour) 6) Blood culture positive. All data were
actually lower in new born infant. The new born infant tabulated and statistically analyzed and appropriate
especially preterm have markedly decreased level of C3, software was used for the analysis of the data.
C5a and properdin and all key element in alternate
pathway of complement. Because of low level of RESULTS
antibodies and complements there is defective generation
of chemotactic factors and abnormalities of opsonisation In this study, incidence of neonatal septicemia was found
leading to life threatening bacterial infections. to be 7.6%.In our study, Klebseilla pneumoniae was the
Considering the meagre resources available in the commonest pathogens, documented in 48.21%, most of
developing countries a reduction in sepsis related them present with early onset sepsis. Amongst the gram
mortality may be possible by identifying high risk positive organisms, Enterococci (16.67%), coagulase
neonates and targeting them for intensive care and negative Staphylococcus (8.92%) were recovered. Micro-
immunotherapy. The purpose of this study is to identify ESR was of limited value in the diagnosis of sepsis. It
the most common symptoms and signs of neonatal revealed positive results (>10 mm in 1 hour) only in
septicaemia in our NICU and the organisms causing these 35.5% cases. Total leukocyte counts revealed better
infections along with their antibiotic sensitivity profiles. results, being positive in 43.09% cases. Band cell:ANC
ratio also showed similar significances (41.4%). However
METHODS C-Reactive Protein (CRP) positive in 56.9% of suspected
sepsis cases. Blood culture was positive in 45.2% of
It is a prospective study, carried out in the tertiary care septicemic neonates. Only one organism (Strept. faecalis)
NICU of S.P. Medical College, Bikaner, Rajasthan, from was found to be sensitive to third generation
January 2014 to October 2014.The study included all cephalosporin namely ceftriaxone, the other agents like
babies who were born in Women’s hospital, S.P. Medical cefoperazone and cefotaxim were sensitive against
College Bikaner, and presented with clinical features Klebseilla and coagulase negative Staphylococcus.

Table 1: Distribution of screening positive cases.

Total No. of live births Screening positive cases

Maturity
Male Female Total Male Female Total
Pre term 618 412 1030 94 45 139 (13.49%)
Full term 1365 735 2100 62 38 100 (4.76%)
Total 1983 1147 3130 156 (65.27%) 83 (34.72%) 239 (7.6%)

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 Verma P et al. Int J Contemp Pediatr. 2015 Aug;2(3):176-180

Table 2: Spectrum of clinical features in suspected showed sensitivity to cefotaxime. Out of 27 Klebseilla
cases of neonatal septicemia. isolates six were resistant to all antibiotics. Citrobactor
was only sensitive to cefotaxim. Vancomycin had good
Age at onset activity against gram positive organisms (Enterococcus,
Clinical features Total CONS, MRSA). Amongst the aminoglycosides, amikacin
Early Late
Refusal to feed 58 50 108 showed better results than gentamicin.
Lethargy 38 53 91
Respiratory distress 76 10 86 Table 3: Distribution of etiological agents according
to age of onset.
Vomiting 43 17 60
Hypothermia 39 13 52 Early Late
Excessive cry 17 20 37 Organisms Total & %
onset onset
Fever 20 32 52 27
Abdominal distension 29 5 34 Klebsiella 18 9
(48.21%)
Circumoral hue 10 7 17 Enterococcus, Streptococcus
Jaundice 15 8 23 7 2 9 (16.07%)
fecalis
Pallor 16 9 25 Coagulase negative Staph.
3 2 5 (8.92%)
Convulsion 21 21 42 aureus
Diarrhoea 10 12 22 Citrobactor 3 2 5 (8.92%)
Apnea 9 2 11 E. coli 1 1 2 (3.57%)
Sclerema 0 6 6 Gram negative bacilli 0 3 3 (5.35%)
MRSA 0 3 3 (5.35%)
Ceftazidime showed better results and found to be Pseudomonas 0 1 1 (1.78%)
sensitive to Klebseilla, E. coli, Pseudomonas and Klebsiella & E. coli 0 1 1 (1.78%)
unidentified gram negative bacilli. Piperacillin had
advantage over ampicillin. All organisms except E. coli

Table 4: Bacterial isolates and their sensitivity to various antibiotics.

Erythromycin

Cefoperazone

all antibiotics
Vancomycin
Clavulanate
Peperacillin

Ceftriaxone

Resistant to
Gentamicin
No. of cases

Cefotaxime
Ceftazidine

Ampicillin
Netilmicin
Organism

Amikacin
Clproflox

Linezolid

Klebsiella 27 - + + - + + - + + - - + - + 6
Streptfaecalis 9 + - - + + - + - _ + + - + - -
Coagulase -ve Staph. 5 + - - - + - + - + - + + + + -
E. coli 2 - - + - - + - - - + - + - + -
Citrobactor 5 - - - - + - - - - - - - - - -
Gram -ve bacilli 3 - + + - + - - - - + - + - - -
MRSA 3 - - - - - - + - - + - - - - -
Psudomonas 1 + - + - - - - - - + - - - - -
Kleb. + E. coli 1 - - - - - - - - - - - - - - -

DISCUSSION was found to be low when compared to study conducted

by Choudhary et al.6 which reported a much higher
Out of 3130 live born babies delivered at Women’s incidence of neonatal septicemia of 11.2% in live births.
Hospital, PBM and Associated Group of Hospitals, The higher incidence of neonatal sepsis was due to the
Bikaner, Rajasthan, from January 2014 to October 2014, fact that their diagnosis of neonatal sepsis was based on
a total of 239 babies developed clinical features clinical features alone. The incidence of male:female was
suggestive of neonatal septicemia were enrolled. The 65.27%:34.72%; male:female ratio was 1.87:1. Neonatal
incidence of neonatal septicemia was found to be 7.6%. septicemia was found to be more common in males. The
Joseph et al.5 observed 7.8% incidence which is almost factors regulating the synthesis of gammaglobulin are
comparable to our study incidence 7.6%. The incidence probably situated on X chromosomes in the male infants

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 Verma P et al. Int J Contemp Pediatr. 2015 Aug;2(3):176-180

thus confers less immunological protection compare to unidentified Gram negative bacilli. In aminoglycosides,
female counterpart.9 In our study, pre term babies had amikacin has much better results than gentamicin.
more sepsis (58.15%) than term babies (41.8%). Khatua Piperacillin had advantage over ampicillin. All organisms
et al.7 observed 63% pre term and 37% term babies. LBW except E. coli showed sensitivity to cefotaxime. Out of 27
infants (both preterm and tern SFD) have low IgG and Klebseilla isolates six were resistant to all antibiotics.
more susceptible to infections. The placental transport of Citrobactor was only sensitive to cefotaxim. Vancomycin
IgG from maternal to fetal circulation increases with had good activity against gram positive organisms
maturity, this transport is hampered in SFD infants who (Enterococcus, CONS, MRSA). The indiscriminate use
are often the products of placental insufficiency. In our of antibiotics with consequent development of resistant
study 60.94% neonates in study group were less than 2.5 strain is cause of drug resistance. Another mechanism
kg. Shitaye et al.8 observed 60% neonates were LBW, is postulated for antibiotic resistance is plasmid theory. The
almost similar to our study. The incidence of early onset common principle that antibiotics must be used only
and late onset sepsis was 69.03% and 30.96% when indicated cannot be over emphasized. It may also
respectively. Our findings were consistent with that of be necessary to rotate the common combinations and first
Choudhary et al.6 In our study most common presenting choice of antibiotics in NICU, so as to change the
features in early onset sepsis were respiratory distress resistance patterns. The unnecessary use of strong
(46.06%), vomiting (26%), hypothermia (23.6%), antibiotics for minor infections and for prophylaxis
abdominal distension (17.5%), while in late onset sepsis should be discouraged. In India, sepsis accounts for one
most common clinical features were lethargy (71.6%), fourth to nearly half of neonatal deaths with a case
refusal to feed (67.5%), fever (43.2%). Convulsion, mortality ranging from 24-69%. The case fatality rate due
diarrhea and excessive cry found in almost equal number to neonatal sepsis in our study was 23.43% (56 deaths in
of neonates in both early and late onset sepsis. The 239 cases). In our observation mortality in early onset
chances of sepsis depend upon the number of maternal septicemia was more (27.77%) while in late onset
risk factors present in any given neonate. As the risk septicemia was 14.86%. In our study, we observed higher
factors increase susceptibility to sepsis increase. Out of mortality rates with culture positive cases (35.71%) than
239 newborns suspected of sepsis PROM was observed culture negative cases (19.67%), though the difference
in 146 babies, out of them (38.3%) were proved as sepsis. was not statistically significant. Higher mortality in
The other important factors predisposing to sepsis were culture positive group was due to invasion of blood
frequent vaginal examination (23.25%), fever in mother stream by larger number of bacteria. In our study, the
(33.33%), and history of foul smelling liquor (24.72%). mortality with Klebsiella was 33.33% and followed by
Streptococcus faecalis (Enterococcus), coagulase
Micro-ESR was of limited value in the diagnosis of negative Staph., Citrobactor and MRSA & pseudomonas.
sepsis. It revealed positive results (>10 mm in 1 hour.) Thus, this study identifies neonatal septicemia, its risk
only in 35.5% cases. Total leukocyte counts revealed factors, incidence, outcome, causative agents and their
better results, being positive in 43.09% cases. Band antimicrobial sensitivity. The results obtained were
cell:ANC ratio also showed similar significances comparable to other studies conducted in our country in
(41.4%). However C-Reactive Protein (CRP) positive in respect to the higher incidence, mortality in pre-term and
56.9% of suspected sepsis cases. Blood culture was low birth weight babies and causative organisms of
positive in 45.2% of septicemic neonates, which is sepsis. While it differed in overall incidence, pattern and
comparable to Shrestha et al.1,9 who observed 42.7% mortality which was low as compared to other studies.
blood culture positive cases.
CONCLUSION
In our study, Klebseilla pneumoniae were the commonest
pathogens, documented in 48.21%, most of them present Septicemia is most frequent and severe disease which
with early onset sepsis. The other gram negative bacilli threatens survival during first few weeks of life.
recovered were Citrobactor, E. coli, while few remained Considering the meager resources available in developing
unlabeled. Amongst the Gram positive organisms, countries a reduction in sepsis related mortality may be
coagulase negative Staphylococcus (8.92%), Enterococci possible by using hygienic measures during and after
(16.67%), were recovered. While MRSA was delivery and identifying high risk neonates and targeting
documented in three cases and Pseudomonas in single them for intensive care and therapy. The changing pattern
new born. Lancefield grouping is not done in our and frequent emergence of resistant bacteria make the
institution. Similar to our study Klebseilla is found most problem more difficult. For best results in infection
common organism in study done by Desai et al.9 management, nurseries should periodically review their
(47.14%), Rathore et al.10 (55.14%), West Peterside et bacterial sensitivity pattern and the antibiotic policy.
al.11 (58.2%). In study in third generation cephalosporins
only one organism (Strept. faecalis) is sensitive to Funding: No funding sources
ceftriaxone but cefoperazone and cefotaxim both have Conflict of interest: None declared
activity against Klebseilla and coagulase negative Ethical approval: The study was approved by the
staphylococcus. Ceftazidime shown better results and institutional ethics committee
active against Klebseilla, E. coli, Pseudomonas and

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 Verma P et al. Int J Contemp Pediatr. 2015 Aug;2(3):176-180

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