Bacterial sensitivity
pattern of neonatal early onset sepsis in a tertiary care hospital in Assam
Devi D1, Gedam DS2
1Dr. Dipti Devi, Ex. Associate Professor,
Pediatrics, Tezpur Medical College, Assam, India, 2Dr. D Sharad
Gedam, Associate Professor, ABV Government autonomous Medical College, Vidisha,
MP, India.
Corresponding address: Dr. D. Sharad Gedam, Associate Professor,
ABV Government Autonomous Medical College, Vidisha, MP, India, Email:
sharad.gedam@gmail.com
Abstract
Introduction: Current trend in Neonatal mortality rate
(NMR) is stagnant for last few decades. Early onset sepsisis one of commonest
causes of NMR. As clinical presentation is often nonspecific, a high degree of suspicion
is required for early initiation of specific therapy. Choice of empiricalantibiotic
is the cornerstone of specific therapy. Depending on the culture report it can
be switched over to appropriate antibiotic. Prevalence of bacterial pathogen
varies in different locality. So, every neonatal care set up should have a
periodical review of the bacteriological profile of the locality. Method: A prospective cohort study
was undertaken in the department of Pediatrics and Obstetrics of Tezpur Medical
College and hospital, Assam to find out the bacteriological profile of culture
proven early onset sepsis (EOS) during July 2016 to June 2017. Results: Out of 5960 hospital born
babies, 298 babies fulfilled the inclusion and exclusion criteria. 15(5.03 %)
babieswere with probable sepsis by clinical criteria and positive sepsis
screen. Out of these, 7(46.66 %) babies were culture positive. Gram negative
organisms were 85.7 % of isolates of which 3(42.8%) were Actinobacterspp
followed by klebseilla, E. Coli and Pseudomonus Aeroginosa. Methicillin
resistant Staph aureus was the only gram-positive organism. There was no growth
of group B streptococcus. Most of the organisms were resistant to common drugs.
One of Actinobacter was resistant to all drugs including meropenam. Conclusion: We conclude that only local
policy of rational antibiotic use can prevent the problem of drug resistance
and reduce NMR due to sepsis.
Key words: Newborn, Early onset sepsis, Drug resistance
Introduction
Neonatal septicaemia is a clinical syndrome characterised by signs and symptoms of infection with or without accompanying bacteraemia in the first month of life [1]. It is classified into early onset sepsis within 72 hour of life and late onset sepsis after 72 hour [1]. The varying microbiological pattern of septicemia and their high antibiotic resistance needs to be studied. Neonatal sepsis is associated with significant morbidity and mortality throughout the world [2]. Though sepsis is a cause of neonatal deaths in the developed countries the scenario is more serious in developing countries, where neonatal sepsis is responsible for 30-50% of neonatal mortality [3]. Incidence of Neonatal septicaemia in India is 30/1000 live births [4]. Neonatal sepsis is one of the commonest causes of neonatal mortality and morbidity specially in developing countries [6]. According to the National Neonatal Perinatal Database (NNPD), it is 30/1000 live birth in India [7]. Globally out of 130 million babies born in a year, 4 million die within one month [5].
Fig-1: Trends of mortality rates in India (SRS statistical report
2000-2012) showing a stagnant status
Early onset sepsis
is defined by infection occurring within 72 hours after birth [1]. The
pathological organism gains access from the mother by transplacental route or ascending
route from the genitourinary tract during delivery. According to NNPD, EOS
contributes to 67% of neonatal sepsis [7].
Early diagnosis and
prompt initiation of appropriate antibiotic is the cornerstone of management.
However clinical presentation is nonspecific and early diagnosis is difficult [8].
Though blood culture is gold standard, it is costly, requires a well-equipped
laboratory, time consuming and success rate is 40% only [8]. Irrational use of
antibiotic results in drug resistance. So, choice of initial antibiotic in
suspected sepsis requires periodic evaluation of local flora. With this
objective, a study was undertaken to find out the bacteriological profile of
proven EOS in a tertiary care hospital. This study was conducted to know the
bacteriological profile of early and late onset neonatal septicaemia along with
the antibiotic susceptibility patterns and thus help the clinician in the
accurate diagnosis and treatment of neonatal septicaemia.
Materials
and methods
A prospective,
observational, cohort study was done in the department of Pediatrics and
Obstetrics of Tezpur Medical College and Hospital, Assam during a period of one
year from July 2016 to June 2017. Hospitalborn newborns with at least 2 of risk
factors likeLBW, preterm, febrile illness in the mother within 2 weeks of
delivery, 3 or more per vaginal examinations after rupture of membrane, foul
smelling liquor, prolonged rupture of membrane, prolonged or difficult delivery
or perinatal asphyxiawere included. Babies born at <28 weeks, with lethal
congenital anomaly or antibiotic to the mother during labor were excluded from
the study. Out of total 5960 babies born, 298(5.03%) babies were selected. The
study was approved by hospital ethical society. Written informed consent was
taken from the parents. Cord blood was collected and sent for sepsis screen
including CRP (>6mg/L), TLC (<5000/cumm), ANC (<1500/cumm) and I/T ratio
(>0.2) regarding abnormal. Neonates were followed for 72 hours. EOS was
suspected in presence of symptoms like respiratory distress, lethargy etc and/ or
positive sepsis screen. Blood culture was sent inoculating in Brain Heart
Infusion Broth at the ratio of 1 in 10. Subcultures were inoculated on
chocolate agar, 5% sheep blood agar and Mac Conkey Agar plates at 24 hrs, third
day and 7th day respectively. No growth in 3 subcultures on 7th
day was reported as culture negative. Broad spectrum antibiotic was started as
per NICU protocol. Data was collected in pretested Performa.
Statistical
analysis- Odds ratio and log odds ratio with chi square test of significance
were used for statistical analysis of data statistical test of significance was
defined as p<0.05.
Results
Out of 298 babies,
15(5.03%) were found with probable sepsis in presence of symptoms and positive
sepsis screen. Of these, 66.6% were male, 53.3% were with LBW, 73.3% were term,
60% of primiparous mother, 53.3% of SVD, 46.7% with ROM 18-24 hrs,46.7% with
>3 VE, 33.3% MSL, 26.7% with prolonged labor, 13.3%with maternal fever and
13.3% with FSL.The most common clinical presentation was respiratory distress (33.3%).
Blood culture was positive in 7(46.66%) cases of probable sepsis(Table 1,
Figure 2)
Table-1: Culture sensitivity pattern
|
Diseased |
Percentage |
Culture positive |
7 |
46.66 |
Culture negative |
8 |
53.33 |
Total |
15 |
100.0 |
Out of 15 patients, 7(46.66%) patients were
culture positive and 8(53.33%) patients were culture negative.
Table 2: Isolated organism
|
Isolates |
No of cases |
Percentage |
1 |
Acinetobacter spp |
3 |
42.8 |
2 |
Klebsiella
pneumoniae |
1 |
14.3 |
3 |
E.Coli |
1 |
14.3 |
4 |
Pseudomonas
aerogenosa |
1 |
14.3 |
5 |
MRSA |
1 |
14.3 |
Table No. 2 shows that
maximum no. isolates shows acinetobacter spp. that is 42.8%, rest organisms
were 14.3% each.
Table 3- showing the sensivity pattern of isolate
|
Acinetobacter spp |
Klebsiella pneumoniae |
E.Coli |
Pseudomonas aerogenosa |
MRSA |
||
Total |
3 |
1 |
1 |
1 |
1 |
||
AK |
NT |
R |
S |
R |
NT |
R |
NT |
GEN |
NT |
NT |
NT |
NT |
NT |
NT |
R |
CX |
NT |
R |
R |
NT |
NT |
NT |
R |
CAZ |
R |
NT |
R |
R |
R |
R |
NT |
CPM |
NT |
R |
NT |
NT |
NT |
NT |
NT |
CXM |
NT |
R |
R |
NT |
NT |
NT |
R |
CIP |
NT |
NT |
S |
S |
S |
MS |
NT |
MRP |
R |
S |
NT |
S |
S |
NT |
NT |
IPM |
R |
NT |
NT |
NT |
R |
NT |
NT |
LE |
NT |
NT |
NT |
NT |
S |
NT |
NT |
LZ |
NT |
NT |
NT |
NT |
NT |
NT |
S |
OX |
NT |
NT |
NT |
NT |
NT |
NT |
R |
CTR |
R |
NT |
NT |
R |
R |
MS |
NT |
PIT |
R |
NT |
NT |
R |
NT |
S |
NT |
VA |
NT |
NT |
NT |
NT |
NT |
NT |
S |
AK-Amikacin, Gen-Gentamycin, Cx-Cefoxitin,
CAZ-Cetazidime, CPM-Cefipime, CXM-Cefuroxime, CP-iprofloxacin, MRP-Meropenam,
IPM- Imipenam, LE- Levofloxacin, LZ-Linezolid, OX-Oxacillin, CTR- Ceftraxone,
PIT-Piperacillin Tazobactum, VA- Vancomycin, NT- Not tested.
Out of 7 isolations, 6 (85.7%) were gram
negative organisms. Among these, acinebacterspp was the commonest organism
(42.8%) followed by E coli, pseudomonas and klebsiella pneumonia.
Staphylococcus aureus (MRSA) was the only gram positive organism. Group B
Streptocococcus, which is common in west, was not found. Among 3 Acinebacterspp, 1 was
resistant to all tested drugs, 1 was sensitive to meropenam and 1 was sensitive
to amikacin and ciprofloxacin.Klebsiella pneumoniae was sensitive to ciprofloxacin and meropenam and was resistant
to amikacin, ceftazidime,
ceftriaxone and piperacillin tazobactum. E. Coli was sensitive to ciprofloxacin, meropenam and levofloxacin and
was resistant to ceftazidime, ceftriaxone and imipenam. Pseudomonasaerogenosa
was sensitive to piperacillin
tazobactum, moderately sensitive to ceftriaxone, and was resistant to amikacin, ceftazidime.MRSA was sensitive to vancomycin and linezolid and was resistant to
gentamycin, cefoxitin,
cefuroxime and oxacillin.
Discussion
Neonatal sepsis is
a serious condition. Prompt treatment is required to reduce mortality and morbidity.
Clinical presentation is nonspecific hindering early diagnosis. High index of
suspicion is needed for early diagnosis and prompt treatment. On the other
hand, increasing drug resistance is an upcoming threat as a result of
irrational use of antibiotics. Periodic analysis of local bacteriological
profile helps initiation of appropriate antibiotic till culture reports are
available. There should be a local evidence-based protocol in every treatment
facility for these sick neonates. It should be updated periodically.
We conducted this
study in all suspected hospital born neonates with EOS. Cord blood sepsis
screen positive and/or in presence of clinical presentation, blood was
collected and sent for C/S and antibiotic was started. Blood culture was
positive in 46.66% of EOS suspected babies which is in concordance with other studies
(Table 4). Gram negative organisms were commonest (85.7%) comparable with other
studies (Table 5). Acinobacterspp was the commonest organism isolated (42.8%). Most
of the organisms were resistant to common drugs. One isolate was resistant to
all antibiotics. This was because of emergence of multidrug resistant
organisms. Irrational use of broad-spectrum antibiotics, overdependence on sepsis
screen results in multidrug resistant bacteria. Antibiotic misuse and microbial
resistance are an ever-increasing problem in the neonatal intensive care units
of our country. Over the years, undisciplined use of broad-spectrum
antibiotics, prolonged courses of antibiotics therapy, overdependence on sepsis
screen for initiating, changing and stopping antibiotics and absence of culture
facilities have resulted in increased incidence of extended spectrum
beta-lactamase (ESBL), methicillin-resistant Staphylococci aureus (MRSA),
vancomycin-resistant Enterococci, carbepenam-resistant
Pseudomonas/Acinetobacter and multi-drug-resistant bacteria [9,10].
Table-4: Showing studies with blood culture
Sl. No |
Studies |
Sepsis positive |
Blood
Culture Positive |
% |
1 |
NNPD 2002[7] |
2219 |
1248 |
56.2% |
2 |
West
et al [9] |
420 |
181 |
43.1% |
3 |
Betty chacko et al[10] |
65 |
28 |
43.1% |
4 |
Twinkle N Gandhi et al[11] |
286 |
130 |
45.5% |
5 |
Jan AZ et al[12] |
700 |
378 |
54% |
6 |
Present study |
15 |
7 |
46.7% |
Table-5: Showing studies with isolates grown
Organism Isolates |
Nepal et al [13] |
Bhat Y et al[14] |
Sucilathangam G. et al[12] |
Twinkle N Gandhi et
al[11] |
Present study |
Acinetobacter spp |
25.7% |
14.4% |
35.7% |
7.69% |
42.8% |
Klebsiella
pneumoniae |
14.3% |
31.4% |
14.3% |
31.5% |
14.3% |
E.Coli |
4.3% |
4.4% |
- |
14.6% |
14.3% |
Pseudomonas
aerogenosa |
2.9% |
33.2% |
7.1% |
16.2% |
14.3% |
MRSA |
38.2% |
9.2% |
14.3% |
11.5% |
14.3% |
EOS is caused
mainly by bacteria transmitted from mothers to neonates during the intrapartum
period, these are the bacteria prevalent either in the maternal genital tract
or in the area of delivery [15]. During
labor, maternal risk factors include prolonged rupture of membranes, fever,
vaginal colonization with group B streptococcus (GBS), and GBS bacteriuria [16].
A history of a previous infant with GBS infection is another identified
maternal risk factor in subsequent pregnancies [17]. In addition, adequacy of
the maternal immune response is an important risk factor for neonatal sepsis.
Maternal serum IgG antibodies against specific capsular polysaccharides of GBS
have been shown to be protective against infection with the relevant GBS strain
in their infants, and an increased risk for GBS EOS has been demonstrated in
infants delivered to mothers with low titers [17]. Infant factors associated
with early-onset sepsis in addition to the factors noted for the mother include
prematurity/low birth weight, congenital anomalies, complicated or
instrument-assisted delivery, and low APGAR scores (score of ≤6 at 5 min).
Immaturity of the premature neonatal immune system, including low
immunoglobulin levels related to decreased transplacental transfer of maternal
IgG, also increases the risk of sepsis in preterm infants [18]. Barrier
function of the skin and mucus membranes is diminished in premature infants and
is additionally compromised in ill premature infants by multiple invasive
procedures, including intravenous (i.v.) access and intubation. Poor or late
prenatal care, low socioeconomic status of the mother, poor maternal nutrition,
maternal substance abuse, male sex, and African American mother (higher rate of
GBS colonization) are additional ethnic and social factors associated with
neonatal sepsis [19].
Neonatal septicemia
remains as an important and challenging problem even with modern and advanced
diagnostics and drug therapy. Hospital data should be generated regularly about
the spectrum of bacteria and their antibiotic susceptibility pattern to enable
accurate diagnosis and empirical treatment.
Conclusion
Our study suggests
that as only 46.66% of suspected EOS was blood culture positive with emergence
of multidrug resistant organisms, periodic local formulation of rational
antibiotic policies is urgently neededin each care facility to reduce multidrug
resistant organisms and hence mortality and morbidity. The susceptibility of
the pathogens to the commonly used antibiotics was low and needs increased
efforts to ensure rational use of antibiotics. A regular antibiotic
susceptibility surveillance and periodic review of the antibiotic policy of the
hospital will reduce the development of antibiotic resistance.
Conflict of interest- none
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