seminar of antibiotic in newborn

1. SEMINAR
Dr. Subhash Sah
Dr. Shorna Rahman

2. Case Scenario
• Son of Eti, 29 weeker, VLBW(1140gm) was a case of congenital
pneumonia. He was getting inj.Cefotaxim and inj. Amakacin. On day
7 baby developed repeated apnoea and desaturation, poor reflex
activity, shock. At that time septic screening was positive. Antibiotic
was changed to Meropenem and Colistin. Blood C/S- Klebsiella
positive only sensitive to Colistin. After few days the baby again
developed features of sepsis & this time antibiotic was changed
from Meropenem to Cefipime, work up was again positive and
blood C/S showed Acinatobacter positive resistant to all
antibiotics.

4. Antibiotic Resistance in
Newborn Infection

5. Contents
• Introduction.
• Magnitude of neonatal sepsis
• Bangladesh scenario
• Definition , classification & site of action of antibiotics
• Classification of bacteria
• Bacterial etiology of neonatal sepsis.
• Choice of antibiotic in NICU, BSMMU.
• Sepsis Prevalence & organism patternSpectrum of antibiotic coverage
• Definition, basis & mechanism of resistance
• How to adress antibiotic resistance.
• Superbugs & it’s prevention
• Prevention of drug resistance
• How to get rid of antibiotic resistance
• Antibiotic Stewardship
• Take home message.

6. Introduction
• Prevalence of infection in newborn is high than any other period of
life due to-
- Physiological & immune system immaturity
- Survival of preterm babies has been increased
• Antibiotic use in the NICU is the 10 times more frequent than in the
rest of the hospital beds.

7. Magnitude of Neonatal Sepsis
• One million deaths per year (10% of all under-five mortality) are due
to neonatal sepsis.
• In settings with very high mortality, neonatal infections are estimated
to cause 40% to 50% of all neonatal deaths.
• Five to 30 % of all neonatal infections are nosocomial infection.
Ref- Goldstein B, Giroir B, Randolph A. Pediatr Crit Care Med. 2005;6:2–8.
Marik PE. Crit Care Med. 2002;30:706–8. The World Health Organization (WHO) estimates
Singh et al.2000; 117:1496-99, Gerbending G. Clin Updates in Infect Dis.2000;5:1-4

8. Bangladesh Scenario
• In a rural setting
sepsis constituted 12% of
direct causes of neonatal
deaths
• A study in Dhaka slums
showed sepsis as a direct
cause of neonatal deaths in
20% cases
Ref:Chowdhury HR, Thompson S, Ali M, Alam N et al. J Health Popul Nutr.2010; 28(4):375-382, Khatun F, Rasheed S, Moran
AC et al. BMC Public Health 2012, 12:84, Liu L, Johnson HL, Cousens S et al. Lancet 2012;379:2151-6, CHERG/WHO/UNICEF
for distribution of causes of neonatal and under-five deaths (published in Liu et al, Lancet 2014)

9. Antibiotics
These are the drugs or chemical substances obtained whether
by synthesizing chemically or from non-pathogenic
microorganism (Actinomycetes, fungi, bacteria) which either
inhibit the growth of pathogenic microorganism or kill them
without injuring the host tissue.

10. History
• On 3rd September 1928, Prof.
Alexander Fleming observed
that one of the staphylococcus
coated glass plate had mould on
it in his laboratory. The mould
was in the shape of ring and the
area around the ring seemed to
be free of the bacteria. The
mould was Penicillium Notatum.
He concluded that Chemical
subastance that came from
mould had killed the bacteria.

11. Classification and Sites Of Antibiotics
Action

12. Classification of Bacteria

13. Cont..

14. Antibiotic Prescription is Common in
NICU: Why?
• Antibiotics are greatly over prescribed in the NICU.
• In a point prevalence study of 29 NICUs, 47% of 827 infants
were receiving at least one antibiotic on the day of the survey.
Reference: Grohskopf L et al.Pediatr Infect Dis J. 2005;24:766-773

15. Antibiotic Prescription is Common in
NICU: Why?
• Suppressed immune system of neonates leads to higher
incidence of infection
• Invasive procedure
• Surgical procedure
Reference: Meyer E et al. Intensive Care Med.2006; 30:1089-96

16. Bacterial Etiology of Neonatal Sepsis
In developed country
• Early Onset Sepsis
– GBS and E coli
– Recently decrease in Gram
positive organisms (GBS)
and increase in Gram
negative organisms
• Late Onset Sepsis
– Coagulase Negative Staph
(CONS)
– GBS
– Staph Aureus
In developing country
• Gram negative organisms
– Klebsiella, Escherichia coli,
– Pseudomonas,Acinetobac
er, Enterobacter,
Citrobacter.
• Gram positive less
common
– Staphylococcus Aureus
– Coagulase negative
staphylococci (CONS)
– Streptococcus
pneumoniae, and
Streptococcus pyogenes

17. Bacterial Etiology of Neonatal Sepsis
In Indian subcontinent
• Almost two third of neonatal sepsis are caused by gram
negative organisms.
• Causative organisms are almost same in Early as well as Late
Onset Sepsis.

18. Choice of Antibiotics in NICU, BSMMU
Antibiotics
1st line Ampicillin+ Gentamicin
2nd line Ceftazidime+ Amikacin
3rd line (Reserve) Meropenem, Ciprofloxacin, Vancomycin,
Cefepime, Clarithromycin, Netilmicin,
Imipenem, Piperacillin+ Tazobactum,
Coloistin
In case of suspected meningitis Cefotaxim+ Amikacin or
Meropenem+ Amikacin

19. Spectrum of antibiotics

20. Sepsis Prevalence & Organism pattern In
NICU,BSMMU(2011-2012)
• A two year (2011-2012) retrospective study showed, out of
948 enrolled newborn, 34% were diagnosed as sepsis. Of
them 21% was culture positive.
• Among them Klebsiella- 18 (27.3%), Acinatobacter- 18
(27.3%), E. coli-12 (18.2%), Pseudomonus- 6 (9.1%),
Salmonella- 6(9.1%), Staphylococcus-2 (3%).
• Klebsiella were the most common organism in EONS while
Acinatobacter were prevalent in LONS.

21. ..
Sensitivity pattern of isolated organism: (2011-2012)
Drugs/
Organisms
[N(%)]
Klebsiella E. coli Acinatobacter Pseudomonus Staph. Salmonella
paratyphi A
Meropenem
20(30%)
06 07 04 02 01 0
Vanco
18(27.3%)
08 04 06 0 01 0
Amikacin
15(22.72%)
07 04 03 0 0 0
Cipro
13(19.7%)
0 01 06 0 0 06
Ampicillin
0(0)
0 0 0 0 0 0
Genta
0(0)
0 0 0 0 0 0

22. • Meropenem was the most sensitive antibiotic against most
of the gram negative and also gram positive organism.
• Vancomycin sensitivity was found against gram positive
organism.
• Ciprofloxacin and amikacin sensitivity were satisfactory
against gram negative organism.
• First line antibiotics were resistant in all culture positive
cases.
• Fifty four percent patients were treated with mero+vanco.

23. Sepsis Prevalence in BSMMU in 2013
• In an outcome based one year study (2013) concluded that,
243 (37%) out of 658 enrolled infant had at least one episode
of sepsis(EONS 42%, LONS 58%).
• Among death cases, 53% patients were diagnosed as sepsis.
• Overall mortality rate was 20%.

24. Title: Bacteriological profiles of blood culture positive sepsis
in newborns and antibiotic susceptibility pattern of the
isolates.
• This prospective study was conducted in the NICU of BSMMU from
October 2014-December 2015 for a period of 14 month. During the
study period, among the admitted patients, (405) blood samples
from patients of clinically suggestive septicemia were evaluated. 48
patients (11.8%) were culture positive.

25. • Among them Acinatobacter- 24 (50%), Klebsiella- 13 (27%), E.
coli-5 (18.2%), Strptococcus-3 (6%) , Staphylococcus-2 (4%),
Gm negative bacilli-1 (2%).
• Here Klebsiella & Acinatobacter both were prevalent in LONS.

26. Sensitivity Pattern of The Common
Isolates,Oct 2014- Dec 2015
Name of antibiotic Acinetobacter Klebsiella E .coli
Ampicillin 0 0 0
Gentamicin 2(8.33%) 0 0
Ceftrazidim 3(12.5%) 0 1
Amikacins 8(33.33%) 3(23.07%) 1
Cefotaxim 3(12.5%) 0 1
Ceftriaxone 2(8.33%) 0 1
Cotrimoxazol 8(33.33%) 1(7.695) 1
Nalidixic Acid 6(25%) 2(15.38%) 1

27. Cont..
Name of antibiotic Acinetobacter Klebsiella E .coli
Ciprofloxacin 11(45.83%) 4(30.76%) 1
Imipenem 10(41.66%) 7(53.84%) 4
Colistin 21(87.5%) 8(61.54%) 3
Netilmycin 12(50%) 2(15.38%) 1
Tazobactum+Pipera
cillin
10(41.66%) 5(38.46%) 3
Polymixin B 3(12.5%) 1(7.69%) Not done
vancomycin Not done Not done Not done
Linezolid Not done Not done Not done

28. • Acinetobacter was the most common organism in late onset
sepsis. Newer drugs like colistin, netilmycin, imipenem,
tazobactum- piperacillin and Ciprofloxacin were effective
rather than Ampicillin and Gentamicin.

29. Data collected from Microbiology Department
of BSMMU September’2016 to April’2017
• Total no. of baby’s having suspected sepsis - 512
• Culture positive baby- 74 (14.4%)
• Klebsiella in- 61(81.3%)
• Acinatobactor-11(14.8%)
• E. coli- 2 (2.7%)
• Citrobacter- 2 (2.7%)

30. Organisms Isolated in Automated Blood Culture
from September’ 16 – April’ 17 in Neonatology
Department of BSMMU
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Klebsiella
Acinatobacter
E.coli

31. January – April’ 2017 in Neonatology
Department, BSMMU
83%
17.00%
Organisms isolated in conventional blood culture
Klebsiella
Acinatobacter

32. Trend of Bacteriological Isolates in Blood Culture Over Last 5
years in NICU, BSMMU
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
Jan 2011-
Dec 2012
Oct 2014-
Dec 2015
Sep 2016-
Apr 2017

33. Name of antibiotics Acinetobacter
n=24
Klebsiella
n=58
E. Coli n=2
Amoxacillin 2(8.33%) 0 0
Gentamicin 9(37.5%) 17(29.31%) 1(50%)
Ceftazidim 8(33.33%) 1(1.72%) 0
Amikacin 9(37.5%) 16(27.58%) 1(50%)
Cefotaxim 2(8.33%) 0 0
Ceftriaxone 5(20.83%) 0 0
Cotrimoxazole 9(37.5%) 3(5.17%) 1(50%)
Nalidixic acid 9(37.5%) 4(6.89%) 1(50%)
Ciprofloxacin 10(41.66%) 6(10.34%) 1(50%)
Meropenem 7(29.16%0 25(43.10%) 1(50%)
Colistin 17(70.83%) 38(65.51%) 1(50%)
Netilmycin 10(41.66%) 16(27.58%) 0
Tozabactum
+piperacilin
8(33.33%) 10(17.24%) 0
Cefipime 1(4.16%) 1(1.72%) 0

34. Organisms Only Sensitive to Colistin in
Last 8 months in NICU, BSMMU
0
1
2
3
4
5
6
7
8
Klebsiella
Acinatobacter
E. coli

35. Antibiotic Resistance
The ability of bacteria and other microorganisms to resist
the effects of an antibiotic to which they were once
sensitive is known as antimicrobial resistance.

37. Basis of drug resistance
1 ) Genetic
a) Chromosomal - spontinous mutation:
Conjugation
Transduction
b)Extrachromosomal- plasmid mediated:
Transduction
Transformation
Transposition
conjugation

38. 2) Nongenetic
-Bacteria can be walled off within an abscess cavity that
drug can’t penetrate effectively.
-Bacteria can be in resting stage, ie, not growing; they are
therefore insensitive to cell wall inhibitors.
-Under certain circumstances, organisms that would be
killed by penicillin can lose there cell wall survive as
protoplasts and be insensitive to drugs
-Presence of foreign body.
-Several artifacts can make it appear that the organisms
are resistant.

39. Mechanism of Drug Resistance
Mechanism Important example Drugs commonly affected
Inactive drug Cleavage by β-lactamase β-lactam drugs such as
penicillin
Modify drug target in bacteria 1. Mutation in penicillin
binding protiens
2. Mutation in protein in 30S
ribosomal subunit
3. Replace alanine with
lactate in peptidoglycan
4. Mutation in DNA gyrase
Penicillin
Aminoglycosides, such as
streptomycin
Vancomycin
Quinolones
Reduce permeability of drug Mutation in porin proteins Penicillin, aminoglycosides
Export of drug from bacteria Mutidrug-resistance pump Tetracyclines, sulfonamides

40. How to Address Antimicrobial Resistance?
• Always take culture prior antibiotic therapy
• Use the narrowest spectrum
• Do not start treatment with 3rd generation cephalosporins
• Develop local antibiotic policy
• Do not believe abnormal result for a nonspecific test
• Try to give antibiotic for appropriate duration
• Treat sepsis, not colonization
• Do your best to treat nosocomial sepsis
Ref: D Isaac Unnatural selection: reducing antibiotic resistance in neonatal unit. Arch dis fetal
neonatal ed 2006; 91: F72-F74.

41. What's a Superbug?
• It's a term coined to describe bacteria that cannot be killed
using multiple antibiotics. "It resonates because it's scary; but
in fairness, there is no real definition. Doctors often use
phrases like "multidrug-resistant bacteria.”
• That's because a superbug isn't necessarily resistant to all
antibiotics. It refers to bacteria that can't be treated using two
or more. Any species of bacteria can turn into a superbug.

42. • Misusing antibiotics (such as taking them when we don't need
them or not finishing all of our medicine) is the "single leading
factor" contributing to this problem, the CDC says. The
concern is that eventually doctors will run out of antibiotics to
treat them.
• The more antibiotics we use & the more encounters have
with the hospital setting, the higher is the superbug risk.

43. Urgent Threat: Carbapenem-Resistant Enterobacteriaceae (CRE)
What is it? It's afamily of bacteria normally found in your gut. But many types of CRE
are resistant to all antibiotics, including carbapenem, which is usually the last
resort. E. coli is an example.
How do you get it? Healthy people usually don't get this type of infection. Most cases
are in people who are in the hospital or a medical care facility, like a nursing home.
The bacteria can be hard to remove from medical tools that are placed into the body,
such as catheters, breathing tubes, or viewing scopes, even after cleaning. That’s
what happened in California, after doctors unknowingly used contaminated
endoscopes on patients.
Why is it a concern? They can cause life-threatening blood infections. "There are no
effective treatments," Coombes says. Some research says that up to 50% of patients
who are sick from CRE die because of it, according to the CDC.
Urgent Threats

44. • Serious Threat: Multidrug-Resistant Acinetobacter
• What is it? It is a bacteria found in soil and water, which can also live on
your skin for days. It doesn't always make you sick. A superbug strain that
doctors worry about is Acinetobacter baumannii.
• How do you get it? People outside the hospital usually don't get sick from
this germ. It's most often seen in people who are already ill and in the
hospital for another reason. Having a breathing tube raises the risk.
• Why is it a concern? We call this a "significant" hospital germ. It "can
develop antibiotic resistance more rapidly than many other bacteria. It can
cause serious illness and can infect the sickest patients." These bacteria
cause dangerous lung, brain, and urinary tract infections, among others.
About 12,000 people get this infection in hospitals every year. Most are
resistant to multiple antibiotics.
• This superbug is considered a "survivor" because it forms a protective
shield against antibiotics. It is tough to treat because it can easily spread
between people.

45. Don’t demand a prescription of antibiotics from your doctor, unless he or she
has diagnosed your affliction as a bacterial infection that requires it.
Take all of the antibiotics as prescribed, even if the symptoms subside.
Never share your antibiotics with friends or family, even if you are 100% sure
that they have the same infection. Let your doctor do the exam and write a
new prescription.
ensuring staff and visitors clean mobile devices with alcohol wipes before
putting them into plastic bags.
3 Tips for Superbug Prevention
.

46. Prevention of drug resistance
• Avoidance of indiscriminate use of antibiotics.
• Use of antibiotic in appropriate dose and for proper duration .
• Use of appropriate antibiotic after culture sensitivity .
• Constant monitoring in resistance cases at hospital or at
community.
• Using of antibiotic combination in appropriate circumstances.
• Limitation of the use of newer antibiotic so long as the
currently used drug are effective.

48. How to Get Rid of Antibiotic Resistance
• Restricted admission of outborn babies.
• Strict isolation of culture positive infected babies.
• Nursing care should be 1:1 in case of babies from whom
organism has been isolated.
• Periodic surveilance of swab culture obtained from NICU
doctors, nurses, equipments.
• Consultation with infectious disease specialist.

49. Cont….
• Implementation of antibiotic stewardship.
• Assigned person to monitor antibiotic utilization, adverse
events related to antibiotic use, bacterial etiology and their
culture and sensitivity pattern.
• Set antibiotic policy according to changing pattern of culture
and sensitivity report
• Empiric use of reserve antibiotics should be avoided.
• Create local evidence.
• Review the policy.

50. Antibiotic Stewardship
• It refers to coordinated intervention designed to improve and
measure the appropriate use of antimicrobial by promoting
the selection of the optimal antimicrobial drug regimen, dose,
duration of therapy and route of administration.

51. Take Home Messages

52. D Isaacs.
Unnatural selection:
reducing antibiotic
resistance in neonatal
unit. Arch dis fetal
neonatal ed 2006; 91:
F72-F74.

54. Because their future is in your
hand !
Thank you