Antibiotic abuse

MISURATA UNIVERSITY
FACULTY OF MEDICINE
DEPARTMENT OF FAMILY AND COMMUNITY MEDICINE
Study About Antibiotic Abuse in NICU in
Paediatrics Department of MMC
PREPARED BY: Ahmed Gamal Yassin
Altaf Mohammed Patel
Abulaali Abdullah Qamie
UNDER SUPERVISION OF:
Dr.Ibrahim Beitalmal

Antibiotics AbuseCommunity Medicine Dept.
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DEDICATION
These piles of pieces of papers are dedicated to those loving
science for purpose benefiting people with its knowledge away
from material motives. Also we dedicate this work to those who
sacrifice their life and blood for their country and to those who
struggle to upsurge their own knowledge towers, but not ivory
towers, in the middle of hostile materialistic environment seeing
people with money oriented vision. It is also sent to the spirits
of the martyrs who offered their blood and souls for the cause of
freedom and democracy.

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ABSTRACT
An antibiotics is a type of drugs that kill or stop the growth of
bacteria. Examples include penicillin and ciprofloxacin.
The antibiotics uses in form of misuse, overuse/abuse and over prescription
is the most important factor leading to development of antibiotics
resistance.
Antimicrobial resistance (AMR) is the ability of a microbes to resist the
effects of medications previously used to treat them.
Antibiotics resistance nowadays is one of the biggest threats to global
health.
In this study we concentrate on manifestations of antibiotics abuse in ICU
especially neonatal ICU as it known as epicenter of infections &
multidrug resistance (MDR).
MDR is antimicrobial resistance shown by species of microorganism to
multiple antimicrobial drugs.
Severe infections represent the main cause of neonatal mortality accounting
for more than one million neonatal deaths worldwide every year.
Antibiotics are the most commonly prescribed medications in neonatal
intensive care units (NICUs).

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INTRODUCTION
ANTIBIOTICS ABUSE & ANTIBIOTICS
RESISTANCE
An antibiotics is a type of drugs that kill or stop the growth of
bacteria. Examples include penicillin and ciprofloxacin.
Humans developed antimicrobials to destroy disease-causing microbes. The
most commonly known antimicrobials are antibiotics, which target
bacteria. Other forms of antimicrobials are antivirals, antifungals, and
antiparasitics.
Penicillin, the first commercialized antibiotic, was discovered in 1928 by
Alexander Fleming. While it wasn’t distributed among the general public
until 1945, it was widely used in World War II for surgical and wound
infections among the Allied Forces.
Actually, discovery of antibiotics achieve great advances in medicine &
surgery, as once they started to use, then infections that was lethal in the
past became treatable.
But over the last decades, the antibiotics uses in form of misuse,
overuse/abuse and overprescription was the most important factor leading
to development of antibiotics resistance, promising return of pre –
antibiotics discovery era, so we will take interest in this section
"antibiotics abuse" topic.
Common situations in which antibiotics are overused include: treatment of
respiratory infections which apparently are viral in nature (as cold & flu),
use of oral antibiotics instead of local one in treatment of viral otitis media,
also treatment of viral conjunctivitis or viral sinusitis and treatment of
eczema, in addition to massive use of antibiotics in livestock…etc.
Antimicrobial resistance (AMR) is the ability of a microbes to resist the
effects of medications previously used to treat them.

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Antibiotics resistance nowadays is one of the biggest threats to global
health as it can affect anyone, any age, & any country (can spread
globally), also it can leads to higher medical costs, prolonged hospital
stays, and increased mortality. All these because the antibiotics that was
effective in the past, nowadays become not effective, as infections that
caused by resistant bacteria are harder to treat than those caused by non-
resistant bacteria & then requiring alternative medications or higher doses,
both of which may be more expensive or more toxic.
Resistance arises through one of three mechanisms: natural resistance in
certain types of bacteria, genetic mutation (arise spontaneously), or by one
species acquiring resistance from another (vertical or horizontal), and
antibiotics accelerate this process.
All classes of microbes can develop resistance: fungi can develop resistance
against antifungal, virus can develop resistance against antiviral, protozoa
can develop resistance against antiprotozoal & of course bacteria can
develop resistance against antibiotics.
Microbes resistant to multiple antimicrobials are called multidrug
resistant (MDR); or sometimes superbugs.
Therefore, preventive measures include only using antibiotics when needed,
& then stopping misuse of antibiotics or antimicrobials.
How the resistance happen?
As mentioned before, antibiotics resistance either present naturally in
certain types of bacteria, arise spontaneously due to point mutation, or
acquired from other bacteria by genetic materials which carry resistance
genes either vertically via clonal expansion (bacterial multiplication) or
horizontally by mobile genetic elements (MGE)/ plasmids.
Antibiotics overuse will accelerate these processes by selective pressure in
bacterial populations, causing vulnerable bacteria to die; this increases the
percentage of resistant bacteria which continue growing & spreading.

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Antibiotics resistance can spread as following:

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Mechanism by which bacteria can resist antibiotics
There are a number of ways by which microorganisms become resistant
to antimicrobial agents. These include:
• Production of enzymes.
• Alteration in outer membrane permeability.
• Alteration of target sites.
• Efflux pumps.
• Alteration of metabolic pathways.
Therefore we conclude the following:
• Cause of antibiotics resistance: 3 main causes; naturally present, point
mutation (spontaneous) & acquired from other bacteria either vertically or
horizontally
• Key/ accelerating factor: antibiotics abuse
• Mechanism of antibiotics resistance:
o Production of enzymes.
o Alteration in outer membrane permeability.
o Alteration of target sites.
o Efflux pumps.
o Alteration of metabolic pathways.

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List of common antibiotics resistant bacteria:
ICU & ANTIBIOTICS RESISTANCE
In this section, we are going to explain how ICU department play role in
emergence & spread of antibiotics resistance.
As we know, intensive care unit (ICU) is a hospital department for
provision of intensive nursing & medical care of critically ill patients,
characterized by high quantity of continuous nursing & supervision, & by
sophisticated monitoring & resuscitative equipment.

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ICU is known as epicenter of infections (i.e: focal points for the
emergence and spread of antibiotics resistant pathogens) because of:
• Its extremely vulnerable population of critically ill patients (i.e:
highly susceptible to infections).
• Critically ill patients often receive broad – spectrum antimicrobial
therapy during their hospitalization.
• High use of invasive procedures (such as urine catheter, NGT, central
line, peripheral line/ cannula, intubation..etc).
• Several drugs are given, which contribute in infections either by some
drugs that interfere with patients immunity if given in high doses or
for long time, also by drugs that given parenterally for several times
with bad aseptic precautions.
• Transmission of infections in between patients or medical staff.
• Disrespect for correct aseptic techniques.
• Patient who admitted with already community acquired infections.
This patient will act as source of infections to other patients in the
same room.
• Due to the administration of inadequate or inappropriate antimicrobial
treatment.
• Antibiotic abuse/ overuse.
Because of all these causes, then ICU considered as epicenter of infections
that will contribute in emergence of antibiotics resistance strains of bacteria
especially MDR.
Actually, the main reason for taking interest in this section, mainly because
ICU is epicenter of MDR (multidrug resistance).
MDR is antimicrobial resistance shown by species of microorganism to
multiple antimicrobial drugs. MDR is the most threatening form of
antibiotics resistance to public health.
Although ICU account for fewer than 10 percent of total beds in most
hospitals, but more than 20 percent of all nosocomial infections are

10|P A G E
acquired in ICUs, suggesting substantial rates of mortality & morbidity &
then result in a considerable clinical & economic burden for hospitals.
Common MDR organisms:
• Methicillin-Resistant Staphylococcus Aureus (MRSA).
• Vancomycin-Resistant Enterococci (VRE).
• Extended spectrum β-lactamase (ESBLs) producing gram – negative
bacteria.
• Klebsiella Pneumonia Carbapenemase (KPC) producing gram-
negatives.
• MultiDrug-resistant Gram Negative Rods (MDR GNR) MDRGN
bacteria such as Enterobacter species (Enterobacteriaceaes), E.coli,
Klebsiella Pneumonia, Acinetobacter Baumannii, Pseudomonas
aeruginosa.
ANTIBIOTIC USE IN NEONATAL ICU
Severe infections represent the main cause of neonatal mortality
accounting for more than one million neonatal deaths worldwide every year
(Study by National Institutes of Health's National Library of Medicine
published in 2013).
Antibiotics are the most commonly prescribed medications in neonatal
intensive care units (NICUs).
Sepsis has often subtle, nonspecific signs and symptoms and results in
serious consequences ranging from neurodevelopmental deficits to death.
As a result, clinicians frequently administer empirical antibiotics to infants
with first signs of suspected sepsis or infants at high risk of sepsis while
awaiting culture results. However continued use of empiric broad-spectrum
antibiotic treatment in the setting of negative cultures especially in preterm
infants may not be benefit.

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The benefits of antibiotic therapy when indicated are clearly enormous, but
the continued empirical treatment by both broad spectrum antibiotics &
prolonged duration without any microbiological justification is dangerous
and associated with adverse outcomes including invasive candidiasis,
increased antimicrobial resistance, necrotizing enterocolitis, late-onset
sepsis (LOS), and deaths.
Most common neonatal pathogens are susceptible to narrow-spectrum
antibiotics.
The choice of antibiotic and duration of empirical treatment are strongly
associated with center-based rather than with individual patient risk factors,
implying that these choices are modifiable across centers. Thus, clinicians
should aim to treat with short courses of narrow-spectrum antibiotics
whenever possible, choosing the appropriate antibiotics and treatment
duration to balance the risks of potentially untreated sepsis against the
adverse effects of treatment in infants with sterile cultures.
Definitions:
• Neonate: period from birth up to 28 days of life (i.e: first month of
life).
• Low birth weight (LBW): if birth weight less than 2.5 Kg.
• Very low birth weight (VLBW): If birth weight less than 1.5 kg.
• Extremely low birth weight (ELBW): if birth weight less than 1kg.
• Preterm baby: born before 37 weeks of gestational age.
• Neonatal mortality rate (NMR): number of neonatal death per 1000
live births.

12|P A G E
AIM OF STUDY
The purpose of this review is to highlight the inappropriate use of
antibiotics in the NICUs, to exam the impact of antibiotic treatment in
neonates with negative cultures and to summarize existing knowledge
regarding the appropriate choice of antimicrobial agents and optimal
duration of therapy in neonates with suspected or culture-proven sepsis in
order to prevent serious consequences.

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LITERATURE REVIEW
A previous study used multicenter retrospective observational study of
antibiotic use, was performed in 4 tertiary care NICUs in USA to assess
adherence to the guidelines defined by the CDC 12-Step campaign
regarding antibiotic use in NICU . Performed in 2015 by U.S. National
Institutes of Health's National Library of Medicine (NIH/NLM), &
available in PubMed Central (PMC) & published in website of NCBI.
Fifty infants per NICU were identified who received intravenous antibiotics
at greater than 72 hours of age (> 3 days of duration). Antibiotic regimens,
clinical and microbiologic data, and indications for initiation and
continuation of antibiotics (after 72 hours of use) were recorded.
Inappropriate utilization was characterized at initiation, continuation, by
agent, and by CDC 12-Step.
Two hundred neonates received 323 antibiotic courses totaling 3344
antibiotic-days. Ninety (28%) courses and 806 (24%) days were judged to
be nonadherent to a CDC 12-Step. Inappropriate use was more common
with continuation of antibiotics (39%) than with initiation (4%) of therapy.
Vancomycin was the most commonly used drug (n = 895 antibiotic-days)
of which 284 (32%) days were considered inappropriate. Carbapenems
were used less frequently (n = 310 antibiotic-days), and 132 (43%) of these
days were inappropriate. Common reasons for nonadherence at the time of
continuation included failure to narrow antibiotic coverage after
microbiologic results were known and prolonged antibiotic prophylaxis
after surgery with chest tube placement.

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MATERIALS & METHODS
Study design: Observational descriptive retrospective study based on
patients records review.
Study population: Misurata city.
Study area: Misurata Medical Center (MMC), Paediatrics department,
Neonatal ICU.
Study population size: 37 newborn babies.
Study variables: Sex, GA at time of delivery, Mode of delivery, Birth
weight, APGAR score, Sources of infections, Types of AB & duration,
Septic screen, Septic evidence, Duration of stay in hospital, Respiration
Support.
Time of study: the hospital records were reviewed by the researchers
between 1st
of Jan 2018 to 31st
of Feb 2018.
Method of analysis: data are presented in tabular & graphical presentation
using frequency distribution table and multiple bar chart respectively.

15|P A G E
RESULTS
We collect all data about cases which admitted to NICU in paediatrics
department of MMC & treated by antibiotics during period from 1st
of Jan
2018 to 31st
of Feb 2018.
• Total number of cases which treated by antibiotics in this period is 37
cases.
• Types of used antibiotics: benzyl penicillin (penicillin G),
gentamycin, amikacin & meropenem.
• 97.3% cases (36 cases) are treated by penicillin G:
o 77.7% (28 cases) of them are given penicillin G only.
o 22.2% (8 cases) of them are given penicillin G + gentamycin.
o 2.7% (1 case) of them is given amikacin + meropenem after
period of non-response to penicillin G & gentamycin.
o 38.8% (14 cases) of them treated for duration < 3 days.
o 52.7% (19 cases) of them treated for duration 3 – 7 days.
o 11. 1% (4 cases) of them treated for duration > 7 days.
• In almost all cases, evidences of sepsis are investigated only
depending on inflammatory indices (WBC, CRP & ESR) & clinical
data . In 35 cases, results of investigation was suggest sepsis, while
other 2 cases results was normal.
• Only 2 cases (5.4%) of total underwent to real septic workup
(microbiological data).
• In all cases, main causes of admission to NICU & initiation of
antibiotics treatment was not depending on microbiological data for
diagnosis of sepsis (documented sepsis), but mainly depend on
clinically suspected risks for sepsis (suspected sepsis). These risks:
o 54% of cases (20 cases) are preterm babies.
o 72.9% of cases (27 cases) are delivered by caesarean section
(CS). 21 cases (77.7%) of them are delivered by urgent CS.
o 27% of cases (10 cases) are low birth weight (LBW); < 2.5kg.
o APGAR score of 4 cases (10.8%) was record <7.
o 86.5% of cases (32 cases) have sources of infection:
▪ 68.75% (22 cases) of them came after several hours from
rupture of membrane (ROM). 21 cases of them came after

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premature spontaneous ROM (PROM), 19% (4 cases) of
21 cases came after 18 hours from PROM. 1 case of 22
cases came after artificial ROM (AROM).
▪ 15.6% (5 cases) of them came from mother has history of
chorioamnionitis.
▪ 15.6% (5 cases) of them came with breach presentation.
UTI.
per vaginal bleeding.
o 40.5% of total cases (15 cases) was have respiratory distress
symptoms.
o 10.8% (4 cases) was have neonatal jaundice.
o 13.5% (5 cases) kept on CPAP during admission period in
o NICU & 2.7% (1 case) kept on SIMV.

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Total
Meropenem
Amikacin
Gentamycin
PenicillinG
Typesof
antibiotics
35Cases
1Case
1Case
7Cases
34Cases
Suspected
Sepsis
94.6
%
2.8
%
2.8
%
20%
97.1
%
%
2Cases
None
None
1Case
2Cases
Documented
Sepsis
5.4
%
0%
0%
50%
100
%
%
14
Cases
None
None
2
Cases
14
Cases
<3
days
Durationofantibiotics
37.8
%
0%
0%
25%
38.8
%
%
19
Cases
1
Case
1
Case
4
Cases
19
Cases
3–7
days
51.3
%
100
%
100
%
50
%
52.7
%
%
4
Cases
None
None
2
Cases
4
Cases
>7
days
10.8
%
0%
0%
25%
11.1
%
%
37
Cases
1
Case
1
Case
8
Cases
36
Cases
Total
100
%
2.7
%
2.7
%
21.6
%
97.3
%
%
Distributionofantibioticsbynumberofcaseswhichtreatedbythese
antibioticsaftersuspectedsepsis,documentedsepsis&fordifferent
durationsatperiodfrom1st
ofJan2018to31st
ofFeb2018

34
7
11
2
1
00
14
2
00
19
4
11
4
2
00
0
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
PenicillinGGentamycinAmikacinMeropenem
TypesofAntibiotics
Distributionofantibioticsbynumberofcaseswhichtreatedbythese
antibioticsaftersuspectedsepsis,documentedsepsis&fordifferentdurations
atperiodfrom1ofJan2018to31ofFeb2018stst
SuspectedSepsis
DocumentedSepsis
Duration:<3days
Duration:3-7days
Duration:>7days
08|E G A P
Number of Cases
Community Medicine Dept. Antibiotics Abuse

19|P A G E
DISCUSSION
In comparison with study in USA at 2015 that performed by
(NIH/NLM) in which its results was:
• Study done on 200 cases.
• Vancomycin was the most common used antibiotic.
• 50 cases (25%) received antibiotics >3days duration.
• In most of cases, initiation of antibiotics treatment & continuation
with them was not depend on microbiological data, but inappropriate
use was more clear with continuation than initiation because of low
response to antibiotics which lead to lengthening durations of
treatment for >3 days in many cases.
In our study results was :
• Study done on 37 cases.
• Penicillin G was the most common used antibiotic.
• 23 cases (62.1%) received antibiotics >3 days duration. 19 cases (51.3
%) for 3 – 7 days, & 4 cases (10.8%) for >7 days.
• 35 cases (94.6%) received antibiotics independence of
microbiological data & also inappropriate use was more clear with
continuation because of low response to antibiotics which lead to
lengthening durations of treatment for >3 days in many cases.

20|P A G E
CONCLUSION
We conclude in almost all cases admitted in period of study, initiation of
antibiotics treatment was only depend on clinical data (i.e: "Antibiotics
Use" in suspected sepsis), & duration of antibiotics treatment exceed 3
days in most of the cases, which confirm inappropriate use of antibiotics.
All of that because of treatment initiation & continuation was independence
of microbiological data.
Only 2 cases (5.4%) of total cases admitted in period of study, treated by
antibiotics after real septic workup (i.e: "Antibiotics Use" in documented
sepsis).
Most common used antibiotic is benzyl penicillin (penicillin G).

21|P A G E
RECOMMENDATIONS
Although manifestations of antibiotic abuse in paediatrics department is
lesser than other departments in MMC, but we hope to completely avoid
antibiotics abuse by deciding that antibiotics treatment not initiated unless
after establishing diagnosis of sepsis definitively depending on
microbiological data for all patients.

22|P A G E
REFERENCES
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Retrieved January 18, 2018, from
https://www.mayoclinic.org/healthy-lifestyle/consumer-health/in-
depth/antibiotics/art-20045720
• Antibiotic misuse. (2018). In Wikipedia. Retrieved February 8, 2018,
from https://en.wikipedia.org/wiki/Antibiotic_misuse
• Antimicrobial resistance. (2018). In Wikipedia. Retrieved February
17, 2018, from https://en.wikipedia.org/wiki/Antimicrobial_resistance
• Ballani, P., Brown, K., Beall, M. H., Chamberlain, J. R., Bersohn, M.
M., … Verrier, E. D. (2008). Infections in Critically Ill, Current
Diagnosis & Treatment of Critical Care (3rd
ed., pp. 359-396). USA:
McGraw-Hill Companies, Inc.
• Center for Disease Control and Prevention. (2017). About
Antimicrobial Resistance. Retrieved from
https://www.cdc.gov/drugresistance/
• Center for Disease Control and Prevention. (2017). Antibiotic
Resistance Threats In The United States, 2013. Retrieved from
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• Estee Torok, M., Ed Moran, & Cooke, F. J. (2017). Basics of
Antimicrobials, Oxford Handbook of Infectious Diseases and
Microbiology (2nd
ed., pp. 4-29). New York, USA: Oxford University
Press.
• List of antibiotic resistant bacteria. (2018). In Wikipedia. Retrieved
January 26, 2018, from
https://en.wikipedia.org/wiki/List_of_antibiotic_resistant_bacteria
• Scheachter, M., Abedon, S. T., Bower, J. M., Agrios, G. N., Brennan,
P. J., … Spector, M. P. (Eds.). (2009). Antibiotic Resistance In B.
Perichon, & P. Courvalin (Eds.), The Desk Encyclopedia of
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ed., pp. 53-64). UK: Elsevier Inc.

23|P A G E
• Singer, M., & Webb, A. R. (2009). Infection and Inflammation,
Oxford Handbook of Critical Care (3rd
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USA: Oxford Press.
• U.S. National Institutes of Health's National Library of Medicine.
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24|P A G E
Health’ Observational Study on Commensal Coliform from Humans,
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25|P A G E
TABLE OF CONTENTS
1. Title……………………………………………………………… 1
2. Dedication……………………………………………………….. 2
3. Abstract………………………………………………………….. 3
4. Introduction……………………………………………………... 4
4.1. Antibiotics Abuse & Antibiotics Resistance……………………. 4
4.2. How the resistance happen……………………………………… 5
4.3. List of common antibiotics resistant bacteria…………………… 8
4.4. ICU & Antibiotics Resistance…………………………………... 8
4.5. Common MDR organisms………………………………………. 10
4.6. Antibiotic Use In Neonatal ICU………………………………… 10
5. Aim of study…………………………………………………….. 12
6. Literature Review……………………………………………….. 13
7. Materials & Methods……………………………………………. 14
8. Results…………………………………………………………... 15
9. Discussion……………………………………………………….. 19
10. Conclusion………………………………………………………. 20
11. Recommendations……………………………………………..... 21
12. References………………………………………………………. 22
13. Contents………………………………………………………… 25

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