EFFECTS OF ANTIBIOTIC THERAPY ON NEC.

Running head: EFFECTS OF ANTIBIOTIC THERAPY ON NEC 1
The Effects of Antibiotic Therapy on Necrotizing Enterocolitis
Name
Institution

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 2
Problem
AlFaleh and Anabrees (2014) describe necrotizing enterocolitis (henceforth NEC) as an
inflammatory ailment that affects the human intestines and is associated with sepsis. The
researchers explain that in most cases, NEC is complicated by issues such as perforation, and
peritonitis and may result to death. As a consequence, Astrug, and Claud (2018) term NEC as
one of the commonest and devastating conditions among neonates. Similarly, the researchers
demystify that to date, no viable remedies of eradicating NEC have been established. Such
attributes make the study of the effects of antibiotics on NEC a priority for research. Babatunde
et al. (2015) explain that the high degrees of involvement depicted by NEC makes the condition
one of the most acquired in surgical and clinical settings among neonatal and the main cause of
mortality among infants across the globe. The researchers demystify that the rate of morbidity
and mortality resulting from NEC is inversely proportional to the gestational weight and age of
the infant at birth even though it is exacerbated among newborns that require surgery and those
presenting birth weights ranging between 500g and 1500g. Similarly, Albert et al. (2018) reveal
that the condition manifests in about 5% of the hospitalizations related to neonatal care and
among 5% to 10% of newborns who present low birth weights.
Significance of the Study
NEC is characterized by an inflammatory disorder of the gastrointestinal region with a
greater presence among preterm and low birth weight infants. According to (ref), the condition
manifests as an exaggerated and severe ailment in environments that are characterized with
intestinal immaturity; an aspect that increases the susceptibility to the invasion of pathogenic
bacteria. The pathology of NEC extends in severe incidences to present a clinicopathological
syndrome with variable systemic symptoms. (ref 6) explain that NEC has a progressive intensity
resulting from the coagulation of the GIT. Such complications play a n essential role in revealing
the efficacy of the current study.

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 3
The levels of mortality attributed to neonatal sepsis have undergone a significant decline
since the introduction of antibiotics. Despite such developments, Esmaeilizand et al. (2017)
explain that infections still remain the most significant causes of mortality and morbidity among
newborns. Hackam et al. (2018) consider late-onset sepsis as the major cause of death among
preterm infants within the first two weeks of life. The nature of NEC as a multifactorial and
complex condition reveals the significance of the present study. The study seeks to undertake a
critical analysis of prematurity, intestinal colonization and use of formula feeding as the three
causative factors for NEC. However, Gordon et al. (2012) consider prematurity as the most
important factor when studying the pathogenesis of NEC. Currently, physicians consider
antibiotics as the most effective medications in the neonatal unit.
As a consequence AlFaleh and Anabrees (2014) states that most of the infants who
present extremely low birth weights (< 1kg) are exposed to antibiotics in their first postnatal
days. However, the researchers explain that there are tendencies that physicians and caregivers
may overuse antibiotics among neonates despite the presence of a wider range of guidelines and
policy frameworks that explain the appropriate application of antibiotics. According to Reed et
al. (2018), the ineffective use of antibiotics in the neonatal phase of life exposes the child to the
vulnerabilities associated with the disturbance of the microbial colonizing the neonate; a
situation which may result to colonization with the MDR bacteria. Similarly, the scholars reveal
that exposure to antibiotics in the neonatal phase of life is closely related to detrimental
outcomes, allergic conditions, obesity and inflammatory bowel ailments in the adult stages of
life. Therefore, the current study plays an effective role in undertaking a critical appraisal and
synthesis of evidence from previous researches to synthesize evidence from previous scholarly
works revealing a wider range of antibiotic exposures among neonates and the risk of developing
NEC.
PICO Question
In neonates with necrotizing enterocolitis, does antibiotic therapy compared to usual care
lead to clinically significant outcomes?

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 4
Evidence
Search Strategy
The search strategy adopted for the current study was initiated in consultation with a
librarian, a local epidemiologist, a neonatologist and a pediatric pharmacologist. The study
adopted scholarly evidences from databases such as Embase, CINAHL, Cochrane Library,
Excerpta Medica Database, MEDLINE and EBCOhost using the terms adopted in the PICO
question. The authors of the scholarly materials obtained were not contacted to avail
supplementary information regarding their publications. Further, no search was undertaken in the
grey literature.
The search strategy in Embase, CINAHL, Cochrane Library, Excerpta Medica Database,
MEDLINE and EBCOhost databases was as follows: ‘newborns infants’ and ‘antibacterial
agents’ with any of the following outcomes ‘necrotizing, enterocolitis’ or ‘mortality’. The first
search was undertaken by the use of a free text in Embase, CINAHL, Cochrane Library,
Excerpta Medica Database, MEDLINE and EBCOhost through combination of the key words
‘neonatal, low birth weight’ ‘infant, post mature’, ‘premature, infant’ or ‘newborn, infant’ with
the terms ‘antibacterial agents’ or ‘antibiotics’ with ‘necrotizing enterocolitis’. However, the
Embase database adopts certain specific keywords such as ‘newborn’ and ‘antibiotic agent’ the
keywords were combined with the term ‘necrotizing enterocolitis’. Finally, a critical review of
the citations and references lists adopted in the studies and other previous reviews were
incorporated to foster the identification of other eligible studies. The citations were then
combined with the exclusion of duplicates and triplicates.
A Summary of Evidences
The role of microbiome in the development of NEC
All the studies adopted described antibiotics as the most commonly prescribed medical
remedies for necrotizing anterocolitis even though they impose great negative effects on the side

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 5
of the affected infants. Similarly, AlFaleh ,and Anabrees (2014); Astrug, and Claud (2018);
Autmizguine et al. (2015); Babatunde et al. (2015); Esmaeilizand et al. (2017); and Gordon et al.
(2012) revealed that NEC is one of the most devastating conditions that affects about 15% of
neonatal infants. The researchers explain that even though the pathogenesis of NEC remains
unexplained, there are tendencies that the existing defects in the processes that lead to the
development and commensalism of the host microbiome as the most significant contributors. On
the other hand, the studies conducted by Samuels et al. (2016); Staude et al. (2018); Stey et al.
(2016); Bellodas and Kadrofske (2019); and Ting et al. (2016) revealed that the advancement of
NEC is presented by uncontrolled inflammations in the intestinal region that are highly capable
of causing sepsis, tissue necrosis and perforation. Further, Isani et al. (2019) explain that NEC is
associated with increased mortality rates of up to 30% despite the fact that it may depict
substantial long and short term morbidities. McEwen et al. (2018); Seale et al. (2018), Fan et al.
(2018); AlFaleh and Anabrees (2014); Ting et al. (2018); and Albert et al. (2018) identify
prematurity as the greatest risk factor for necrotizing enterocolitis.
The Murine models adopted by Pammi, and Haque (2015) and Hackam et al. (2018)
identify bacterial colonization of the intestines as the most essential factor in fostering the
development of NEC among infants. However, most of the researches incorporated for this study
do not identify a specific bacterial species as the causative agent for NEC. Gordon et al. (2012)
explain that longitudinal analyses of fecal microbiomes obtained from infants based on the
studies conducted by Autmizguine et al. (2015) and Ting et al. (2018) have played an essential
role in shedding light on the existing variations in the colonization patterns and composition of
microbiomes with the ability to develop NEC and those that lack such potentials. For instance,
the study conducted by Esmaeilizand et al. (2017) revealed that the presence of bacterial agents
such as Proteobacteria and Actinobacteria is in great abundance in the fecal matter of infants.
The scholars explain that Proteobacteria and Actinobacteria later develop NEC. On the other
hand, the experimental study conducted by Isani et al. (2019) revealed that the concentration of
bacterial agents such as Bacteriodetes and Bifidobacteria is minimal in the fecal matter of
infants. Similarly, the researchers reveal that fecal dysbiosis is associated with an increase in the
population of microbes of the phyla Firmicutes and Proteobacteria and proceed the advabcemeb
of NEC among neonates.

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 6
The effects of antibiotic therapy
The studies by Gordon et al. (2012); Babatunde et al. (2015); and Reed et al. (2018)
emphasized on the efficacy of prenatal and postnatal exposure to antibiotics as a critical
contributor to the dysbiosis that leads to the presence of NEC. Ting et al. (2018) explain that
prophylactic administration of antibiotics can be applied as a significant procedure in fostering
the prevention of NEC among infants. The scholars explain that the administration of
prophylactic enteral antigiotics such as kenamycin, gentanicin and vancomycin is of critical
essence in fostering great reductions in the rates and symptomatic effects of NEC and a
significant reduction in the number of death related to NEC. However, the aforementioned
studies present several limitations. For instance, the inability of the researchers in these studies to
give a clear account of the diets and feeding schedules adopted by the infants under
consideration, limited adjustments for confounding, and failure to report the possible harmful
effects of the antibiotics adopted reveal their limitations. On the other hand, Gordon et al. (2012)
explain that over the years, NIC units have undergone great changes in terms of upgrade. Such
changes include the adoption of standardized feeding protocols, adoption of donor milk from
humans in the absence of breast milk and the introduction of enteral feeds at an early stage of
life.
On the other hand, Seale et al. (2018) explain that there are tendencies that prolonged
exposure of infants to antibiotics plays a role in increasing the child’s levels of resistance against
the drug. For instance, the scholars demystify that adoption of enteral kenamycin treatments
revealed a positive relationship with the increase in the population of bacteria that are resistant to
antibiotics. Comparatively, the study by Isani et al. (2019) revealed that the use of enteral
vancomycin therapy did not depict a positive relationship with the levels of antibiotic resistance
even though it showed a positive relationship in the levels of microbiota depicting predominant
Gram negative yeast and bacteria. Ideally, predominant Gram negative yeast and bacteria impose
great harmful effects on the side of a premature host.
Over the years, premature neonates have been exposed to broad spectrum antibiotics as a
universal remedy in their first days of life. However, Ting et al. (2016) explain that there are

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 7
tendencies that the neonatal may be exposed to a prolonged course of antibiotic treatments for
culture-negative and/or culture-positive sepsis. The study conducted by Yajamanyam et al.
(2014) revealed that prolonged exposure of antenatal and post natal antibiotics increases the risk
of developing NEC. For instance, Seale et al. (2018) demystify that the administration of
antibiotics suppresses intestinal flora that in turn lead to increased risk of acquiring NEC.
Recommendations
There is need for physicians to undertake a critical analysis of the composition of
antibiotics before administration to infants. As aforementioned, the use of enteral vancomycin
therapy does not depict a positive relationship with the levels of antibiotic resistance even though
it showed a positive relationship in the levels of microbiota depicting predominant Gram
negative yeast and bacteria. However, predominant Gram negative yeast and bacteria impose
great harmful effects on the side of a premature host. Therefore, there is need for provision of
additional information whenever enteral antibiotics are recommended for underdeveloped
neonates with low weight.
While the exposure of infants and their mothers to perinatal and antenatal antibiotics
could lead to negative effects such as the suppression of intestinal flora that play a role in
increasing the risk of NEC, there is need for physicians to prescribe alternative antibiotics such
as ampicilin and gentamycin based on their effectiveness in reducing the effects of NEC.
Translation
The study recommends that physicians should opt for the administration of ampicilin and
gentamycin while seeking for relevant additional information whenever enteral antibiotics are
recommended for underdeveloped neonates with low weight. These recommendations are
feasible and appropriate to the modern day medical practices as they are evidence based.
However, the study preempts that the existing organizational cultures in healthcare institutions
will act as barriers to effective implementation of these recommendations. To foresee the
implementation of the recommendations identified institutional trainings targeting caregivers

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 8
working in neonatal care units on the effects of antibiotic therapy on necrotizing enterocolitis
will be organized. Educational materials on this topic and instructors are the major resources
needed to foresee the implementation of the action plan. On the other hand, surveys and
scorecards will be adopted to evaluate the effectiveness of the proposed changes in clinical
settings. The findings of the proposed changes will be disseminated through publications in
healthcare journals and periodicals.
Measurable goal
To train at least 6 nurses from 15 healthcare institutions in Texas on the effects of antibiotic
therapy on necrotizing enterocolitis by the end of August 2019.
Timeline
Period Activity
April 2019 Prepare study materials on NEC
May 2019 Seek permission from 15 healthcare
institutions in Texas to engage caregivers in
the educational sessions
June- Mid -August 2019 Educate caregivers on the effects of antibiotic
therapy on necrotizing enterocolitis.
Mid-August 2019 –Early September 2019 Administer the survey
Early –Mid September 2019 Publish results

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 9
Conclusion
The study proceeded with the aim of finding answers to the PICO question: In neonates
with necrotizing enterocolitis, does antibiotic therapy compared to usual care lead to clinically
significant outcomes? The study plays an effective role in undertaking a critical appraisal and
synthesis of evidence from previous researches to synthesize evidence from previous scholarly
works revealing a wider range of antibiotic exposures among neonates and the risk of developing
NEC. The study recommends that physicians should opt for the administration of ampicilin and
gentamycin while seeking for relevant additional information whenever enteral antibiotics are
adopted for underdeveloped neonates with low weight.

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 10
References
Albert, J., Kaur, I., Bajwa, G., Touch, S., Souder, E., Long, S., & Bhandari, V. (2018,
November). 175. Implementation of Clinical Practice Guidelines for Care of Neonates
With Necrotizing Enterocolitis Reduces Broad Spectrum Antibiotic Use in the Neonatal
Intensive Care Unit. In Open Forum Infectious Diseases, (Vol. 5, No. suppl_1, pp. S78-
S78). US: Oxford University Press.
Astrug, L., & Claud, E. (2018). Neonatal Necrotizing Enterocolitis. Gastroenterology and
Nutrition: Neonatology Questions and Controversies, 87.
AlFaleh, K., & Anabrees, J. (2014). Probiotics for prevention of necrotizing enterocolitis in
preterm infants. Evidence
‐Based Child Health: A Cochrane Review Journal, 9(3), 584-
671. https://doi.org/10.1002/ebch.1976
Autmizguine, J., Hornik, C. P., Benjamin, D. K., Laughon, M. M., Clark, R. H., Cotten, C. M., ...
& Smith, P. B. (2015). Anaerobic antimicrobial therapy after necrotizing enterocolitis in
VLBW infants. Pediatrics, 135(1), e117-e125. doi: 10.1542/peds.2014-2141
Babatunde, K. A., Irene, A.,Dongo, A. &Sylvester, A. (2015). Advanced necrotizing
enterocolitis with tension pneumoperitoneum in a full-term Nigerian neonate: A case
report. Indian Journal of Basic and Applied Medical Research, 4(3), 86-89. Retrieved
from https://ijbamr.com/pdf/June%202015%2086-89.pdf.pdf
Bellodas S., J., & Kadrofske, M. (2019). Necrotizing enterocolitis. Neurogastroenterology &
Motility, 31(3), e13569.

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 11
Esmaeilizand, R., Shah, P. S., Seshia, M., Yee, W., Yoon, E. W., & Dow, K. (2017). Antibiotic
exposure and development of necrotizing enterocolitis in very preterm
neonates. Paediatrics& child health, 23(4), e56-e61. https://doi.org/10.1093/pch/pxx169
Fan, X., Zhang, L., Tang, J., Chen, C., Chen, J., Qu, Y., & Mu, D. (2018). The initial
prophylactic antibiotic usage and subsequent necrotizing enterocolitis in high-risk
premature infants: a systematic review and meta-analysis. Pediatric surgery
international, 34(1), 35-45.
Gordon, P., Christensen, R., Weitkamp, J. H., & Maheshwari, A. (2012). Mapping the new world
of necrotizing enterocolitis (NEC): review and opinion. The e-journal of neonatology
research, 2(4), 145. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666872/pdf/nihms435179.pdf
Hackam, D. J., Sodhi, C. P., & Good, M. (2018). New insights into necrotizing enterocolitis:
from laboratory observation to personalized prevention and treatment. Journal of
pediatric surgery.
Isani, M. A., Delaplain, P. T., Grishin, A., & Ford, H. R. (2018). Evolving understanding of
neonatal necrotizing enterocolitis. Current opinion in pediatrics, 30(3), 417-423.
McEwen, S. A., Angulo, F. J., Collignon, P. J., & Conly, J. M. (2018). Unintended consequences
associated with national-level restrictions on antimicrobial use in food-producing
animals. The Lancet Planetary Health, 2(7), e279-e282.
Pammi, M., & Haque, K. N. (2015). Pentoxifylline for treatment of sepsis and necrotizing
enterocolitis in neonates. Cochrane Database of Systematic Reviews, (3).
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004205.pub3

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 12
Reed, B. D., Schibler, K. R., Deshmukh, H., Ambalavanan, N., & Morrow, A. L. (2018). The
impact of maternal antibiotics on neonatal disease. The Journal of pediatrics, 197, 97-
103.
Samuels, N., van de Graaf, R., Been, J. V., De Jonge, R. C., Hanff, L. M., Wijnen, R. M., ... &
Vermeulen, M. J. (2016). Necrotising enterocolitis and mortality in preterm infants after
introduction of probiotics: a quasi-experimental study. Scientific reports, 6, 31643.
https://doi.org/10.1038/srep31643
Seale, J. V., Hutchinson, R. A., Fleming, P. F., Sinha, A., Kempley, S. T., Husain, S. M., &
Millar, M. R. (2018). Does antibiotic choice for the treatment of suspected late-onset
sepsis in premature infants determine the risk of developing necrotising enterocolitis? A
systematic review. Early human development, 123, 6-10.
Staude, B., Oehmke, F., Lauer, T., Behnke, J., Göpel, W., Schloter, M., ... & Ehrhardt, H. (2018).
The Microbiome and Preterm Birth: A Change in Paradigm with Profound Implications
for Pathophysiologic Concepts and Novel Therapeutic Strategies. BioMed research
international, 2018.
Stey, A., Barnert, E. S., Tseng, C. H., Keeler, E., Needleman, J., Leng, M., ... & Shew, S. B.
(2015). Outcomes and costs of surgical treatments of necrotizing
enterocolitis. Pediatrics, 135(5), e1190-e1197. doi: 10.1542/peds.2014-1058
Ting, J. Y., Synnes, A., Roberts, A., Deshpandey, A., Dow, K., Yoon, E. W., ... & Shah, P. S.
(2016). Association between antibiotic use and neonatal mortality and morbidities in very
low-birth-weight infants without culture-proven sepsis or necrotizing enterocolitis. JAMA
pediatrics, 170(12), 1181-1187. doi:10.1001/jamapediatrics.2016.2132
Ting, J. Y., Synnes, A., Roberts, A., Deshpandey, A. C., Dow, K., Yang, J., ... & Canadian
Neonatal Network. (2018). Association of antibiotic utilization and neurodevelopmental

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 13
outcomes among extremely low gestational age neonates without proven sepsis or
necrotizing enterocolitis. American journal of perinatology, 35(10), 972-978.
Yajamanyam, P. K., Rasiah, S. V., & Ewer, A. K. (2014). Necrotizing enterocolitis: current
perspectives. Res Rep Neonatol, 4, 31-42. http://dx.doi.org/10.2147/RRN.S36576

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 14
Appendices
Appendix 1: Individual Evidence Summary
EBP QUESTION: What are the effects of antibiotic therapy on necrotizing enterocolitis?
Articl
e #
Author &
Date
Evidence
Type
Sample,
Sample Size,
& Setting
Study findings
that help
answer the
EBP question
Limitation
s
Evidence
Level &
Quality
1 (AlFaleh,
K.,
&Anabrees
, J., 2014)
Quasi-
experime
ntal study
S
Electronic
search of
EMBASE,
MEDLINE,
and Cochrane
databases that
resulted in
extraction of
24 trials
There were
variability in
the enrolment
criteria of the
neonates, as
mentioned in
the trial.
Supplementatio
n of enteral
probiotics
reduced the
NEC incidence
rates and
neonate
mortality rate.
No significant
difference
found in
relation to the
decrease of
nosocomial
There was
a risk of
bias in
several
studies that
were
included in
the review
Level II
Lesser
quality.
Systematic
review of
a
combinati
on of
RCTs and
quasiexper
imental,

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 15
sepsis.
2 (Esmaeiliza
nd et al.,
2017)
Retrospe
ctive
case-
control
study
Conducted
among preterm
neonates born
prior to 29
week gestation
period. 447
controls and
224 cases.
Significant
difference
observed in the
incidence rates
of antibiotic
day number
before NEC
onset, antenatal
steroid
administration,.
High duration
of antibiotic
usage found
among NEC
cases, in
comparison to
control.
Significant
increase in
NEC odds, in
relation to
empiric
treatment of
antibiotics for 5
days or more.
There were
differences
in clinical
practice
modalities
within and
between
centres.
The
researchers
failed to
obtain
detailed
information
on the kind
of feeding
andnumber
or type
ofantibiotic
s used.
Level I1
High
quality
3 (Pammi,
M., &
Haque,
2015)
Systemati
c review
and meta-
analysis
randomised or
quasi‐
randomised
trials assessing
Administration
of
Pentoxifylline
as an adjunct to
Less
number of
studies had
been
II
Good
quality

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 16
conducte
d by
extractin
g quasi‐
randomis
ed or
randomiz
ed trials
from
electronic
databases
the efficacy of
pentoxifylline
as an adjunct
to antibiotics
for treatment
of suspected or
confirmed
sepsis or NEC
in neonates.
other antibiotics
reduced the
rates of all-
cause mortality
among
neonates,
during their
length of
hospitalization.
Pentoxifylline
also decreased
hospital stay.
However, it did
not have any
significant
impact on
retinopathy of
prematurity,
chronic lung
disease,
development of
NEC, or
periventricular
leukomalacia or
severe
intraventricular
haemorrhag, in
neonates
included,
and there
were
methodolog
ical
limitations
in each of
them.
evidence
4 (Samuels et
al., 2016)
Quasi-
experime
ntal study
Preterm
infants
(gestational
Interrupted time
series logistic
regression
Observatio
nal design
prevented
II

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 17
age <32 weeks
or birth weight
<1500 gram)
admitted
before (Jan
2008–Sep
2012; n =
1288) and
after (Oct
2012–Dec
2014; n =
673)
analysis failed
to demonstrate
any noteworthy
difference
between the
death rates or
NEC rates
among the two
infant groups.
General
incidence of
NEC showed a
reduction from
7.8-5.1% (OR
0.63, 95% CI
0.42–0.93, p =
0.02) that was
not statistically
prominent to
the adjusted
models used.
Probiotic
introduction
was allied with
decline in the
NEC or death
or sepsis
adjusted odds
among infant
who were fed
breast milk
random
allocation
of infants.
Confidence
interval
could have
been
narrowed
using a
large
sample
size.
Good
quality
evidence

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 18
(OR 0.43, 95%
CI 0.21–0.93, p
= 0.03)
5 (Ting et al.,
2016)
Retrospe
ctive
cohort
study
conducted
amid VLBW
infants (<1500
g), during Jan
2010-Dec
2014, who had
been admitted
to level
III NICUs.
11 669
(84.9%) infants
were
administered
antibiotics.
Antibiotic use
rates (AURs)
showed
significant
decrease from
0.29-0.25,
concomitant
with a decrease
in late-onset
sepsis (19%-
13.8%). 10%
AUR increase
was allied with
greater odds of
mortality,
primary
composite
outcome, and
stage 3
retinopathy of
prematurity.
Researcher
s failed to
capture
type or
class of
antibiotics
that had
been
administere
d to infants.
Causative
effect of
antibiotics
were not
established.
Inclusion
of infants
with other
infections
might have
also created
bias in the
results.
Effect of
confoundin
g variables
were not
taken into
III
Non-
experimen
tal study
of
moderate
evidence
quality

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 19
considerati
on.
6 (Autmizgui
ne et al.,
2015)
Cohort
study
Total of 1390
infants
exposed to
anaerobic
antimicrobial
therapy were
matched with
1390 infants
not exposed.
that
includedinfants
, who had been
admitted to
348 NICUs
during 1997-
2012.
1390 infants
who had been
subjected to
antimicrobial
anaerobic
therapy were
compared
against similar
number of
infants, not
exposed to any
therapy. Lack
of any
significant
difference
found between
the infants, in
comparison to
death or
strictures. More
prevalence of
strictures, in
relation to
single outcome,
amid anaerobic
antimicrobial
therapy group.
Infants having
surgical NEC
Standardise
d criteria
not
followed
for
diagnosis
of the
infants.
There
might have
been
possible
overlap of
NEC
diagnosis
and/or
spontaneou
s intestinal
perforation.
III
Moderate
level
evidence

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 20
manifested
reduced
mortality rates,
upon being
subjected to
antimicrobial
therapy.
7 (Yajamany
am,
Rasiah&
Ewer,
2014)
Opinion
on the
current
perspecti
ves of
NEC/
Literature
review.
Case
control
study.
The
administration
of antibiotics
generallydepen
d on local
policies that
focus on local
flora. However,
it should
encompass all
potential
pathogens as
well as
anaerobes.
Considering
anaerobic cover
is important if
perforation is
suspected.
Probiotic
administration
will improve
epithelial
function, and
No
potential
limitation
Level III
Case
control
study.

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 21
attenuate
proinflammator
y pathways.
8 (Gordon,
Christensen
,
Weitkamp
&Maheshw
ari, 2012)
Compreh
ensive
review
based on
opinion
of
respected
authoritie
s
Prospective
comparative
Most preterm
infants are
administered
empirical
antibiotics at
birth. Mothers
of the infants
are also
subjected
toantenatal and
perinatal
antibiotic
administration.
These
antibiotics bring
about
suppression of
intestinal flora
that increases
risks of NEC.
Lack of
exposure to
antibiotics also
increases the
likelihood of
suffering from
NEC.
Ampicillin and
No
potential
limitation
Level II
Lesser
quality

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 22
gentamicin are
commonly
administered
and help in
reducing NEC
by as much as
10 times.
9 (Stey et al.,
2015)
Retrospe
ctive
review
study.
Information
was collected
from
California
OSHPD
Linked Birth
File Dataset in
order to
conduct a
financial
evaluation of
in-hospital
costs of 1375
infants who
had been
affected with
NEC from
1999-2007.
Following
propensity
score matching
among 699
infants, $398
173 was the
average costs
for peritoneal
drainage and
laparotomy.
This cost was
higher that only
peritoneal
drainage
(($276 076).
However, the
costs were
similar
tolaparotomy
($341 911).
Rates of
mortality were
almost similar
for laparotomy
Administrat
ive nature
of the
information
prevented
acquiring
information
on disease
severity,
with the
use of ICD-
9 codes. In
addition,
procedure
code billing
governed
the
treatment
group
definition.
Cost
estimates
had low
Level III
Case
control
study

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 23
and peritoneal
drainage.
precision.
10 Babatunde,
K. A.,
Irene,
A.,Dongo,
A.
&Sylvester,
A. (2015).
Case
report
Full term
neonate with
advanced NEC
and tension
pneumoperiton
eum
Respiratory
distress and
abdominal
distension
found in a 6-
day old male
neonate, who
also had
perinatal
asphyxia as
associated
causative
factor.
No
potential
limitations
V
Poor
quality
evidence

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 24
Appendix 2: Synthesis and Recommendations
EBP QUESTION:What are the effects of antibiotic therapy on necrotizing enterocolitis?
Category (Level Type)
*
Total
Number
of
Sources
Overall
Qualit
y
Rating
Synthesis of Findings
Evidence That Answers the EBP Question
Level I
 Experimental study
 Randomized control
trial
 Systematic review of
RCTs with/without
meta-analysis
1 Hig
h
qua
lity
There were variability in the enrolment criteria of
the neonates, as mentioned in the trial.
Supplementation of enteral probiotics reduced the
NEC incidence rates and neonate mortality rate.
No significant difference found in relation to the
decrease of nosocomial sepsis.
Level II
 Quasi-experimental
study
 Systematic review of
combination of
RCTs and quasi-
experimental, or
non-experimental
with/without meta-
analysis
3 Good
quality
Most preterm infants are administered empirical
antibiotics at birth. Mothers of the infants are also
subjected toantenatal and perinatal antibiotic
administration. These antibiotics bring about
suppression of intestinal flora that increases risks
of NEC. Lack of exposure to antibiotics also
increases the likelihood of suffering from NEC.
Ampicillin and gentamicin are commonly
administered and help in reducing NEC by as
much as 10 times.
Level III
 Non-experimental
study
 Systematic review of
4 Good
quality
-11669 (84.9) infants were administered
antibiotics. Antibiotics use rates (AUGs) showed
significant decrease from 0.29-0.25, concomitant
in late-onset sepsis(19%-13.8%). 10% AUR

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 25
combined RCTs,
quasi-experimental,
and non-
experimental studies
only, with/without
meta-analysis
 Qualitative study or
systematic review of
qualitative studies
with/without meta-
synthesis
increases was allied with mortality, primary
composite outcome, and stage 3 retinopathy of
prematurity.
- 1390 infants who had been subjected to
antimicrobial anaerobic therapy were compared
against similar number of infants, not exposed to
any therapy. Lack of any significant difference
found between the infants, in comparison to death
or strictures. More prevalence of strictures, in
relation to single outcome, amid anaerobic
antimicrobial therapy group. Infants having
surgical NEC manifested reduced mortality rates,
upon being subjected to antimicrobial therapy.
-Following propensity score matching among 699
infants, $398 173 was the average costs for
peritoneal drainage and laparotomy. This cost
was higher that only peritoneal drainage (($276
076). However, the costs were similar to
laparotomy ($341 911). Rates of mortality were
almost similar for laparotomy and peritoneal
drainage.
Level IV
 Opinion of respected
authorities and/or
reports of nationally
recognized expert
committees/
consensus panels
based on scientific
1 High
quality
-Most preterm infants are administered empirical
antibiotics at birth. Mothers of the infants are also
subjected toantenatal and perinatal antibiotic
administration. These antibiotics bring about
suppression of intestinal flora that increases risks
of NEC. Lack of exposure to antibiotics also
increases the likelihood of suffering from NEC.
Ampicillin and gentamicin are commonly
administered and help in reducing NEC by as

EFFECTS OF ANTIBIOTIC THERAPY ON NEC 26
evidence much as 10 times.
Level V
 Evidence obtained
from literature
reviews, quality
improvement,
program evaluation,
financial evaluation,
or case reports
 Opinion of
nationally
recognized experts
based on experiential
evidence
1 Poor
quality
-Respiratory distress and abdominal distension
found in a 6-day old male neonate, who also had
perinatal asphyxia as associated causative factor.
Recommendations Based on Evidence Synthesis and Selected Translation Pathway