4. CASE SCENARIOs
CASE 1: B/o S CASE 2: B/o M
• 38 wk/ 2.8 Kg/ AFD/ Mch • 34 wk/ 1.2 Kg/ SFD/ Fch
• Day 8 of life • Day 1 of life
• Born in PGI via NVD • Born via NVD at home
• Discharged on D 2 • Brought with
• Brought with 2d history of – Poor feeding
– Episodes of vomiting – Lethargy
– Lethargy – Tachypnea
– Abnormal movements • Examination shows sclerema
• Sepsis screen – POSITIVE • Which antibiotic will you start?
• CSF s/o meningitis
• Which antibiotic will you start?
5. Empirical Antibiotic therapy
Choice of antibiotics
Based on the organisms responsible for the
infection in that region (local data)
Based on the sensitivity patterns of the
organisms in that region (local data)
REVIEW DATA 6 MONTHLY
6. EONS Vs. LONS
• EONS /LONS in the developed world –
Rationale for the concept
• Indian data on EONS and LONS – NNPD
2002-03 Different findings
EONS / LONS division – ARTIFICAL
No difference between EONS and LONS in our settings
7. Organisms causing EOS/LOS
Author / year Isolates Outcome Comments
1. Zaidi et al 3209 isolates – Klebsiella – 25% WHO (Young
PIDJ 2009 1st week of life E.Coli – 15% Infant study)
S. aureus – 18% included
Developing GBS – 7%
countries – 63
studies
(1980 – 2007) 835 isolates – S.Aureus – 14% Home deliveries –
7 to 28 days GBS – 12% 77% Gram -ve
Pneumococci- 12% organisms
Klebsiella – 4%
2. NNPD 2002- 18 Tertiary K.pneumonia-32.5% Intramural births
03 care neonatal S.aureus – 13.6%
Indian data units
K.Pneumonia – 27% Extramural births
S.Aureus – 15%
8.
9.
10. Original Article
Blood Culture Confirmed Bacterial Sepsis in Neonates in a North Indian
Tertiary Care Center: Changes over the Last Decade
Venkataseshan Sundaram, Praveen Kumar*, Sourabh Dutta, Kanya Mukhopadhyay,
Pallab Ray1, Vikas Gautam1, and Anil Narang
Department of Pediatrics and 1Department of Microbiology, Postgraduate Institute of
Medical Education and Research, Chandigarh, India
(Received March 21, 2008. Accepted December 3, 2008 )
SUMMARY: The spectrum of organisms causing sepsis is different in developing countries. Data on the recent
trends of organisms causing sepsis are limited. This study was conducted in a tertiary care neonatal unit in
Northern India. All inborn babies with blood-culture-positive sepsis from 1995 to 2006 were divided into two
epochs, viz. 1995 to 1998 (epoch I) and 2001 to 2006 (epoch II). Organisms were grouped into early (<72 h) and
late onset (≥72 h) sepsis groups. The overall incidence of sepsis, the incidence of sepsis stratified by weight
groups, the organism profile on different days of life, sepsis-related mortality and pathogen-specific case fatal-
ity rate were calculated and compared between the two epochs. Out of 34,362 live births during the study period,
organisms were isolated in 1,491 neonates. Out of these, 89% had bacterial sepsis. The incidence of neonatal
bacterial sepsis increased from epoch I to epoch II (35.8/1,000 versus 40.1/1,000 live births, P < 0.05). The
incidence of early onset sepsis (EOS) did not change between the epochs, but the incidence of late onset sepsis
(LOS) increased from 12 to 16.5 per 1,000 live births (P < 0.001). The incidence of bacterial sepsis decreased
significantly in the 1,000- to 1,999-g birth weight groups. Klebsiella pneumoniae and Enterobacter aerogenes
decreased, whereas Staphylococcus aureus increased in incidence during epoch II. Non-fermenting Gram-negative
bacilli emerged as a newly identified pathogen during epoch II. Sepsis-associated mortality decreased from 42 to
20%. The incidence of bacterial sepsis has decreased significantly in 1,000- to 1,999-g infants, with a significant
reduction in sepsis-related mortality. New organisms have emerged in recent years. The organism profile in
recent years has changed, with a significant overlap of organisms causing EOS and LOS.
of major changes in neonatal care, the study period was
INTRODUCTION
divided into two epochs, viz. 1995 to 1998 (epoch I) and 2001
Neonatal infections are estimated to cause 1.6 million to 2006 (epoch II). Since the changes in peri/neonatal care
deaths every year globally, and 40% of all neonatal deaths were gradual, the intervening period of 1999 - 2000 was
11. Empirical Antibiotics - PGI
• Based on PGIMER NICU data
– Ciprofloxacin / Amikacin : 75% isolates
– Vancomycin/Pip-tazo: 90% isolates
– Vancomycin/Meropenem: 95-100%
AVOID Cefotaxime as empirical
first line antibiotic
Production of ESBLs
Fungal colonization
12. Back to the case scenarios…
CASE 1 B/o S CASE 2 B/o M
• Cefotaxime 200 mg/kg/d • Ciprofloxacin 10
IV in 3 divided doses mg/kg/dose Q12 hourly
slow push IV infusion over 30-60
min
• Amikacin 15 mg/kg/day
• Amikacin 7.5 mg/kg/day
IV Q 24hourly infuse over
1 hour IV Q 24 hourly infuse
over
1 hour
13. Antibiotics
• Timeliness of initiation
– First dose – Important prognostic
factor
– Delay in antibiotics – worsening
outcomes
• Route of administration
– Only Intravenous
– No role for any other route
– Oral therapy – not recommended
14. Dose of Antibiotics
• Always check before every dose- everyday- everytime
• Dependent on postnatal age / weight / gestational age
• Standard source of information
– “The Blue Book” – PGI NICU Handbook of Protocols – 4th
Edition – 2010
– NEOFAX & LEXI COMP – Pediatric & Neonatal drug
dosage handbook
15. Newer drug dose info sources
EPOCRATES – Free android & I pad app
Other applications/ software
Web MD
Drug Handbook
16. CSF penetration of commonly
used antibiotics
ANTIBIOTIC CSF penetration
Ciprofloxacin Good
Cefotaxime Very good
Amikacin Good* (inflamed meninges)
Gentamicin Good* (inflamed meninges)
Vancomycin Good* (inflamed meninges /
continuous infusion of 60 mg/kg/day)
Pip –Tazobactam Poor (Poor penetration into CSF)
Imipenem Good (Propensity for seizures)
Meropenem Good* (higher doses/ infusion)
Amphotericin B Poor (both conventional & Liposomal)
Fluconazole Good
19. Empirical modification of
empirical antibiotic therapy
• Empirical upgradation of
antibiotics if no clinical
improvement within 48-72
hours
• Extremely sick neonate
Even earlier – after discussing
with consultant/ seniors
20. After POSITIVE blood c/s…
• report…
S Narrower spectrum ABx / lower cost
– DOWNGRADE even if neonate was improving
• Use a single sensitive antibiotic
– (Exception: Pseudomonas, S.aureus, E. fecalis, Acinetobacter spp.)
• S Empirical antibiotics but clinical worsening
– Possibility of ‘in vitro’ resistance
– Change antibiotics
• R Empirical antibiotics but clinical improvement
– Do not change antibiotics (exceptions*)
– Possibility of ‘in vivo’ sensitivity
21. Duration of antibiotic therapy
Meningitis (c/s proven) : 21 days
Urinary tract infections : 7-14 days
Proven bone/joint infections : 6 weeks
22. After NEGATIVE blood c/s…
• Asymptomatic neonate: Stop ABx
• Suspected EOS/LOS, neonate improves
but not fully asymptomatic:
– Repeat CRP assay & re-evaluate clinical data
– CRP > 10 antibiotics for 7 days
– CRP: negative & clinical data negative
Stop
• Suspected EOS/LOS, neonate has
worsened clinically:
– Evaluate for causes other than sepsis
– Empirically upgrade antibiotics if sepsis suspected
23.
24. Case 3 B/o K
• 34 wk/ 1.7 kg/ AFD/ F ch
• Seen by you at a primary health centre at
least 300 km away from a tertiary hospital
• Brought with rapid breathing/ poor feeding
• You are unable to establish IV access
• What will you do?
Stabilize ABC and Temperature
Administer first dose of IM Amikacin
Transport with appropriate support
Which other antibiotic can be given IM safely in neonates?
25. Now, tell me this…
Highly protein bound
Displaces bilirubin
Risk of Kernicterus
Ref: Pediatrics 2012; 129: 1006
27. Supportive Care
•Equally important component
of care
•Early recognition of organ
dysfunction
•Development of MODS –
significant rise in mortality
•Watch for SEPTIC SHOCK in
particular
28. What all should you monitor?
CLINICAL
•Temperature MOST IMPORTANT
– Nurse in thermo-neutral environment
– Avoid hypo as well as hyperthermia
•Aggressive nutritional support
– Early enteral feeding
•Rigorous monitoring especially hemodynamic parameters
– Closely watch core-periphery temperature difference
– Capillary refill time/ urine output & others
– Non-invasive BP monitoring
29. What all should you monitor?
LABORATORY
•Monitor pH/ BE/ lactate (ABG/VBG)
•ECG/ CXR/ Echo (if necessary)
•Sugar / Na/ K/ other metabolic parameters
•Conjugated jaundice (sepsis induced)
•Hemoglobin/ platelets / counts
•Coagulation profile / liver function tests
30. Supportive Care
• Mechanical ventilation
• Exogenous surfactant therapy
• Timely volume & vasopressor support
• Anti- convulsants for seizures
• Echocardiography for PDA
• Ultrasonography Head *
32. Case 3: B/o M
• 38 wk/ 3.1 Kg/ AFD/ Mch – D 17 of life
• Brought to PGI Emg. in a state of shock
• History of poor feeding/ lethargy along
with episodes of hypothermia over last 4
days
• You start the baby on Cefotaxime &
Amikacin as per our protocol
• What else would you like to do?
33. Answer
• Would you not like to do a lumbar
puncture?
– YES
• But, if the baby is on multiple ionotropes?
– YES ? NO ?
• In an unstable neonate, the LP can be
deferred until stabilization
Cellular & Biochemical abnormalities persist for 72 hours
Gram positive bacteria clearance occurs in 36 hours
Gram negative bacteria clear in 120 hours
37. International Neonatal Immunotherapy Study
NEJM 2011;365:120111
• Multicentric randomized clinical trial
• 3493 neonates
• Two doses at 500 mg/ kg or matching
placebo 48 hours apart
• No difference in sepsis /mortality
• No difference in long term (2yr) outcome
38. Granulocyte transfusion
• Use justified by reduced number and
abnormal function
• Produced by leukopheresis
✗ The Cochrane Library 2011, Issue 10
39. GCSF & GMCSF
• Glycoprotein
• Deficient in premies; Resistance also described
• Dose 510mcg/kg/day for 3 days
✗ Cochrane Database of Systematic Reviews 2009, Issue 3
44. FOLLOWUP CARE
• Growth monitoring
• Hearing screen – who received Aminoglycosides
• Monitoring organ dysfunction
• Meningitis babies on OPD F/U:
– Weekly OFC
– Neurological examination
– Hearing screen (discharge + 3 months)
– USG Head (1st week/ End of Rx/ Followup)
– Antiepileptics (stop before discharge/ 3 months)
• If proven UTI, start AMOXICILLIN 10 mg/kg OD oral
prophylaxis & plan USG KUB, MCU & DMSA
45. TAKE HOME MESSAGE
• Empirical antibiotics – Start early, choice, in correct
dose, correct mode of administration, check CSF
penetration & side effects
• Collect blood c/s, correlate with clinical picture & modify
therapy as early as possible
• Supportive care & monitoring (clinical & lab) – keeps the
baby alive & buys time for antibiotics to act
• No proven role for any adjunctive therapies at present
• Followup care with focus specific monitoring – also
determines long term outcome
46. Hope we can save
neonates before they reach
this state of NO RETURN
