The Mission Hospital

5/24/2018 The Mission Hospital

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Objectives Antibiotic essentials

Which one? Rationale?

Duration of treatment

Practical applications

Supportive Care

Neonatal septic shock

Adjunctive therapies

Follow up care


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PARENTERAL ANTIBIOTICS

All about antibiotics - Basics


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CASE SCENARIOsCASE 1: B/o S

38 wk/ 2.8 Kg/ AFD/ Mch

Day 8 of life

Born in PGI via NVD

Discharged on D 2

Brought with 2d history of Episodes of vomiting

Lethargy

Abnormal movements

Sepsis screenPOSITIVE

CSF s/o meningitis Which antibiotic will you start?

CASE 2: B/o M

34 wk/ 1.2 Kg/ SFD/ Fch

Day 1 of life

Born via NVD at home

Brought with

Poor feeding Lethargy

Tachypnea

Examination shows sclerema

Which antibiotic will you start?


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Empirical Antibiotic therapy

Choice of antibiotics

Based on the organisms responsible for theinfection in that region (local data)

Based on the sensitivity patterns of theorganisms in that region (local data)

REVIEW DATA 6 MONTHLY


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EONS Vs. LONS

EONS /LONS in the developed worldRationale for the concept

Indian data on EONS and LONSNNPD

2002-03Different findings

EONS / LONS divisionARTIFICAL

No difference between EONS and LONS in our settings


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Organisms causing EOS/LOSAuthor / year Isolates Outcome Comments

1. Zaidi et al

PIDJ 2009

Developing

countries63studies

(19802007)

3209 isolates

1st week of life

Klebsiella25%

E.Coli15%

S. aureus18%

GBS7%

WHO (Young

Infant study)

included

835 isolates

7 to 28 days

S.Aureus14%

GBS12%

Pneumococci- 12%

Klebsiella4%

Home deliveries

77% Gram -ve

organisms

2. NNPD 2002-

03

Indian data

18 Tertiary

care neonatal

units

K.pneumonia-32.5%

S.aureus13.6%

Intramural births

K.Pneumonia27%

S.Aureus15%

Extramural births


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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


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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


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Back to the case scenarios

CASE 1 B/o S Cefotaxime200 mg/kg/d

IV in 3 divided doses

slow push

Amikacin 15 mg/kg/dayIV Q 24hourly infuse over

1 hour

CASE 2 B/o M Ciprofloxacin10

mg/kg/dose Q12 hourly

IV infusion over 30-60

min

Amikacin7.5 mg/kg/day

IV Q 24 hourly infuse

over

1 hour


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Timeliness of initiation

First doseImportant prognostic

factor

Delay in antibioticsworsening

outcomes

Route of administration

Only Intravenous

No role for any other route

Oral therapynot recommended

Antibiotics


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Dose of Antibiotics Always check before every dose- everyday- everytime

Dependent on postnatal age / weight / gestational age

Standard source of information

The Blue BookPGI NICU Handbook of Protocols4th

Edition2010

NEOFAX & LEXI COMPPediatric & Neonatal drug

dosage handbook


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Newer drug dose info sourcesEPOCRATESFree android & I pad app

Other applications/ software

Web MD

Drug Handbook


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CSF penetration of commonly

used antibioticsANTIBIOTIC 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)

PipTazobactam Poor (Poor penetration into CSF)

Imipenem Good (Propensity for seizures)

Meropenem Good* (higher doses/ infusion)

Amphotericin B Poor (both conventional & Liposomal)

Fluconazole Good


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Practical points

ANTIBIOTIC Dose Shelf life

Vial size

Cost

perday

Mode of

admin

Side effects

Cefotaxime 7d: 150-200 mg/kg/day

Q8 hourly

24 hrs

125/250/

500 mg

vials

Rs.3

0

IV slow

push

Blunts AG

peak level

Na contentAmikacin


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Practical points

ANTIBIOTIC Dose Shelf life

Vial size

Cost

per day

Mode of

admin

Side effects

Piperacillin-

Tazobactam

Both dose and

interval depend

on weight and

postnatal age

2.25 gm /

4.5 gm

Rs. 300 IV infuse

30 min

Separate AG

Hypokalemia

Diarrhea/ skin rash

False +ve DCT

LFT/RFT changesMeropenem 20-40

mg/kg/dose Q 8

hourly

Meningitis - 40

500mg/

1gm vial

Rs. 600 IV infuse

4 hours

Modify in

renal/hepatic failure

Ampho B 0.5-1 mg/kg/dse

5-7mg/kg/dose

50 mgvial Rs.300

Rs.2000

IV infuse4 hours NS incompatibleRFT/ K/ Mg/ CBC

LFT/ Anemia/

Tpenia/ chills/ fever

Fluconazole 6 mg/kg/dose 200

mg/100

ml

Rs. 50 IV slow

bolus

Vomiting/ Rashes

Not with Cisapride


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Empirical modification of

empirical antibiotic therapy

Empirical upgradation of

antibiotics if no clinical

improvement within 48-72

hours

Extremely sick neonate

Even earlierafter discussing

with consultant/ seniors


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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.)

SEmpirical antibiotics but clinical worsening

Possibility of in vitroresistance

Change antibiotics

REmpirical antibiotics but clinical improvement

Do not change antibiotics (exceptions*)

Possibility of in vivosensitivity


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Duration of antibiotic therapy

Meningitis (c/s proven) : 21 days

Urinary tract infections : 7-14 days

Proven bone/joint infections : 6 weeks


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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 > 10antibiotics 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


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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?


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Now, tell me this

Highly protein bound

Displaces bilirubin

Risk of Kernicterus

Ref: Pediatrics 2012; 129: 1006


26/46SUPPORTIVE CARE

Management of Organ dysfunction


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Supportive Care

Equally important component

of careEarly recognition of organ

dysfunction

Development of MODS

significant rise in mortalityWatch for SEPTIC SHOCK in

particular


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What all should you monitor?

CLINICAL TemperatureMOST 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


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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


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Supportive Care

Mechanical ventilation Exogenous surfactant therapy

Timely volume & vasopressor support

Anti- convulsants for seizures

Echocardiography for PDA

Ultrasonography Head *


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Early recognitiondetermines survival

Distributive + Cardiogenic Volume support: 1020 ml/kg NS over 20 min

Correct negative ionotropic factors: Ca/ pH/ Sugar

Dopamine 520 mics/kg/min Dobutamine 515 mics/kg/min

Adrenaline 0.050.3 mics/kg/min (inotrope)

0.31 mics/kg/min (vasopressor)

HYDROCORT 1-3 mg/kg Q 8 hourly

(poor response to dopamine)

CLUES to EARLY recognition of shock

Tachycardia / bradycardia in preterms

Cool/ pale skin/ mottling Delayed capillary refill / cold peripheries

Weak peripheral pulses

Narrow pulse pressure (Raised DBP)

Oliguria / Ileus (s/o splanchnic vasoconstriction)

Wide pulse pressure

Lethargy / decreased urine output

Metabolic acidosis

Neonatal Septic Shock


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Case 3: B/o M

38 wk/ 3.1 Kg/ AFD/ MchD 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?


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Answer

Would you not like to do a lumbarpuncture?

YES

But, if the baby is on multiple ionotropes? YES ? NO ?

In an unstable neonate, the LP can be

deferred until stabilizationCellular & Biochemical abnormalities persist for 72 hours

Gram positive bacteria clearance occurs in 36 hours

Gram negative bacteria clear in 120 hours


34/46ADJUNCTIVE THERAPIES

Upcoming modalities

I I l b li


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Level of Evidence No. of Infants Outcomes and Conclusions

Systematic review of therapeutic

RCTs in clinically suspected

infection: all infants

(Cochrane Database of Systematic

Reviews 2010)

10 RCTs and quasi

RCTs

Clinically suspected

infection n=378

Subsequently proven

infection n=262

In clinically suspected infection

group: Mortality reduced

typical RR 0.58 (95% CI; 0.38,

0.89); NNT 10 (95% CI; 6, 33); I2=

0%

In proven infection group

typical RR 0.55 (95% CI; 0.31,

0.98); I2

= 0%

Systematic review of therapeutic

RCTs for sepsis and septic shock:

all infants

(Cochrane Database Syst Rev.

2010)

338 Subgroup analysis of polyclonal

IVIG in neonates showed no

significant reduction in mortality for

standard (n = 174) and IgM-

enriched polyclonal IVIG (n=164)

Systematic review of prophylactic

RCTs in preterm infants

(Cochrane Database of Systematic

Reviews 2010)

4986 Meta-analysis shows 3% reduction

in sepsis but no effect on mortality

No further similar RCTs needed

Intravenous Immunoglobulin


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Intravenous Immunoglobulin

Level of

Evidence

No. of Infants Outcomes and

Conclusions

IVIG (monoclonal)

(The Cochrane

Library 2009)

Systematic review

of prophylactic

RCTs of

antistaphylococcalIgG in

VLBW infants

2701

(two studies of

INH A -21 and one

study ofAltastaph)

No difference

shown in

mortality, sepsis,

or otheradverse outcomes

Use is not

recommended


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International Neonatal Immunotherapy Study

NEJM 2011;365:120111

Multicentric randomized clinical trial

3493 neonates

Two doses at 500 mg/ kg or matchingplacebo 48 hours apart

No difference in sepsis /mortality

No difference in long term (2yr) outcome

G l t t f i


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Granulocyte transfusion

Use justified by reduced number and

abnormal function

Produced by leukopheresis

Level of Evidence No. of

Infants

Outcomes and Conclusions

Systematic review of three

therapeutic RCTs

44 No difference shown in mortality or sepsis: moreRCTs needed

One trial (IVIG Vs. GT) 35 Reduction in all cause mortality of borderlinestatistical significance (RR0.06, 95% CI 0.00 to 1.04;

RD-0.34, 95% CI -0.60 to 0.09; NNT 2.7)

The Cochrane Library 2011, Issue 10


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GCSF & GM-CSF Glycoprotein

Deficient in premies; Resistance also described

Dose 5-10mcg/kg/day for 3 days

Level of Evidence No. of Infants Outcomes and Conclusions

Systematic review of seven

therapeutic RCTs

257 No difference shown in mortality or sepsis:

more RCTs needed

Subgroup analysis of three

therapeutic RCTs

97 ?GM-CSF improves survival in sepsis with

neutropenia: more RCTs needed

Systematic reviews of three

prophylactic RCTs

359 No difference shown in mortality or sepsis:

more RCTs needed

Cochrane Database of Systematic Reviews 2009, Issue 3


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Exchange transfusion

Removal of bacteria, endotoxins &

inflammatory mediators

Improved opsonic & granulocyte activity

Improved O2carrying capacityLevel of Evidence No. of Infants Outcomes and Conclusions

Two therapeutic RCTs 70 Exchange transfusion improves

survival in gram-negative sepsis??

more RCTs needed

Clinics in perinatology,2010


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Pentoxifylline PD inhibitor and reduces TNF

Improves endothelial function and avoids excessivecoagulation


Infants


Four therapeutic

RCTs

227 Significant reduction in all cause mortality

Significant reduction in duration of hospital

stay, mortality in preterm/confirmed

sepsis/gram negative sepsis

The Cochrane Library 2011, Issue 10


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Selenium & Melatonin Free radical scavengers


Infants


Selenium

Systematic review of three

prophylactic RCTs

583 ? Selenium reduces sepsis: more

RCTs needed

Melatonin

No RCTs in newborns

One non randomized trial

10 All babies had lower serum levels

of free radicals and all survived

Clinics in perinatology 2010


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Glutamine

Anabolic for dividing immune and gut cells


Infants


Systematic review of

seven prophylacticRCTs

2365 No difference shown in mortality or

sepsis or disability free survival:More RCTs

Clin Perinatol 37 (2010) 481499


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FOLLOW-UP CARE Growth monitoring

Hearing screenwho received Aminoglycosides Monitoring organ dysfunction

Meningitis babies on OPD F/U:

Weekly OFC

Neurological examination Hearing screen (discharge + 3 months)

USG Head (1stweek/ End of Rx/ Follow-up)

Anti-epileptics (stop before discharge/ 3 months)

If proven UTI, start AMOXICILLIN 10 mg/kg OD oralprophylaxis & plan USG KUB, MCU & DMSA

TAKE HOME MESSAGE


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TAKE HOME MESSAGE Empirical antibioticsStart 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

Follow-up care with focus specific monitoringalso

determines long term outcome


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Hope we can save

neonates before they reach

this state of NO RETURN

The Mission Hospital

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