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AIIMS- NICU protocols 2008

Sepsis in the Newborn

M. Jeeva Sankar, Ramesh Agarwal, Ashok K Deorari, Vinod K Paul

Division of Neonatology, Department of Pediatrics

All India Institute of Medical Sciences

Ansari Nagar, New Delhi 11!"

Address for correspondence

Prof Vinod K Paul

Professor

Department of Pediatrics

All India Institute of Medical SciencesAnsari Nagar, Ne Del!i ""002#

$mail% &inodpaul'neonatal!ealt!(com

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Abstract

Infections are t!e single largest cause of neonatal deat!s glo)all*( According to National Neonatal

Perinatal Data)ase +2002-0, t!e incidence of neonatal sepsis in India as 0 per "000 li&e-)irt!s.

/le)siella pneumoniae and stap!*lococcus aureus ere t!e to most common organisms isolated(

ased on t!e onset, neonatal sepsis is classified into to ma1or categories% earl* onset sepsis !ic!

usuall* presents it! respirator* distress and pneumonia it!in 2 !ours of age and late onset sepsis

t!at usuall* presents it! septicemia and pneumonia after 2 !ours of age( Clinical features of sepsis

are non-specific in neonates and a !ig! inde3 of suspicion is re4uired for timel* diagnosis( Alt!oug!

)lood culture is t!e gold standard for t!e diagnosis of sepsis, culture reports ould )e a&aila)le onl*

after 58-2 !ours( A practical septic screen for t!e diagnosis of sepsis !as )een descri)ed and some

suggestions for anti)iotic use !a&e )een included in t!e protocol(

#ey words: Infections, newborn, sepsis screen, antibiotics.

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!. "n#roduc#ion

Sepsis is t!e commonest cause of neonatal mortalit*. it is responsi)le for a)out 0-607 of t!e total

neonatal deat!s in de&eloping countries",2( It is estimated t!at up to 207 of neonates de&elop sepsis

and appro3imatel* "7 die of sepsis related causes2( Sepsis related mortalit* is largel* pre&enta)le

it! rational antimicro)ial t!erap* and aggressi&e supporti&e care(

$. %pidemiolog& "ndian da#a

!e incidence of neonatal sepsis according to t!e data from National Neonatal Perinatal Data)ase

+NNPD, 2002-0 is 0 per "000 li&e )irt!s( !e data)ase comprising "8 tertiar* care neonatal units

across India found sepsis to )e one of t!e commonest causes of neonatal mortalit* contri)uting to

"#7 of all neonatal deat!s( Septicemia as t!e commonest clinical categor* it! an incidence of 2

per "000 li&e )irt!s !ile t!e incidence of meningitis as reported to )e per "000 li&e )irt!s(

Among intramural )irt!s, 9le)siella pneumoniae as t!e most fre4uentl* isolated pat!ogen +2(67,

folloed )* Stap!*lococcus aureus +"(:7( Among e3tramural neonates +referred from

communit*;ot!er !ospitals, 9le)siella pneumoniae as again t!e commonest organism +27,

folloed )* Stap!*lococcus aureus +"67 and Pseudomonas +"7(

'. Defini#ion

Neonatal sepsis is a clinical s*ndrome c!aracteri

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(. )lassifica#ion of neona#al sepsis

Neonatal sepsis can )e classified into to ma1or categories depending up on t!e onset of s*mptoms5(

$arly onset sepsis %$&S'(It presents it!in t!e first 2 !ours of life( In se&ere cases, t!e neonate

ma* )e s*mptomatic at birth( Infants it! $=S usuall* present it! respirator* distress and

pneumonia( !e source of infection is generall* t!e maternal genital tract( Some maternal ; perinatal

conditions !a&e )een associated it! an increased ris/ of $=S( 9noledge a)out t!ese potential ris/

factors ould !elp in earl* diagnosis of sepsis( ased on t!e studies from India, t!e folloing ris/

factors seem to )e associated it! an increased ris/ of earl* onset sepsis5, 6

"( >o )irt! eig!t +?2600 grams or prematurit*

2( @e)rile illness in t!e mot!er it! e&idence of )acterial infection it!in 2 ee/s prior to

deli&er*(

( @oul smelling and;or meconium stained li4uor(

5( upture of mem)ranes B25 !ours(

6( Single unclean or B sterile &aginal e3amination+s during la)or

:( Prolonged la)or +sum of "stand 2ndstage of la)or B 25 !rs

( Perinatal asp!*3ia +Apgar score ?5 at " minute

Presence of foul smelling li4uor or t!ree of t!e a)o&e mentioned ris/ factors arrant initiation of

anti)iotic treatment( Infants it! to ris/ factors s!ould )e in&estigated and t!en treated accordingl*(

)ate onset sepsis %)&S'( It usuall* presents after 2 !ours of age( !e source of infection in >=S is

eit!er nosocomial +!ospital-ac4uired or communit*-ac4uired and neonates usuall* present it!

septicemia, pneumonia or meningitis:, ( arious factors t!at predispose to an increased ris/ of

nosocomial sepsis include lo )irt! eig!t, prematurit*, admission in intensi&e care unit, mec!anical

&entilation, in&asi&e procedures, administration of parenteral fluids, , and use of stoc/ solutions(

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@actors t!at mig!t increase t!e ris/ of communit*-ac4uired >=S include poor !*giene, poor cord

care, )ottle-feeding, and prelacteal feeds( In contrast, )reastfeeding !elps in pre&ention of infections(

*. )linical fea#ures

*+1 Nonspecific features( !e earliest signs of sepsis are often su)tle and nonspecific. indeed, a !ig!

inde3 of suspicion is needed for earl* diagnosis( Neonates it! sepsis ma* present it! one or more

of t!e folloing s*mptoms and signs +a *pot!ermia or fe&er +former is more common in preterm

lo )irt! eig!t infants +) >et!arg*, poor cr*, refusal to suc/ +c Poor perfusion, prolonged

capillar* refill time +d *potonia, a)sent neonatal refle3es +e rad*;tac!*cardia +f espirator*

distress, apnea and gasping respiration +g *po;!*pergl*cemia +! Meta)olic acidosis(

*+! Specific features related to various systems(

Central ner&ous s*stem +CNS% ulging anterior fontanelle, &acant stare, !ig!-pitc!ed cr*, e3cess

irrita)ilit*, stupor;coma, sei

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+. "nves#iga#ions

Since treatment s!ould )e initiated in a neonate suspected to !a&e sepsis it!out an* dela*, onl*

minimal and rapid in&estigations s!ould )e underta/en8(

+.! lood cul#ureIt is t!e gold standard for diagnosis of septicemia and s!ould )e performed in all

cases of suspected sepsis prior to starting anti)iotics( A positi&e )lood culture it! sensiti&it* of t!e

isolated organism is t!e )est guide to antimicro)ial t!erap*( !erefore it is &er* important to follo

t!e proper procedure for collecting a )lood culture( !e resident doctor;staff s!ould ear sterile

glo&es prior to t!e procedure and prepare a patc! of s/in appro3( 6-cm in diameter o&er t!e proposed

&eni-puncture site( !is area s!ould )e cleansed t!oroug!l* it! alco!ol, folloed )* po&idone-

iodine, and folloed again )* alco!ol( Po&idone-iodine s!ould )e applied in concentric circles

mo&ing outard from t!e centre( !e s/in s!ould )e alloed to dr* for at least " minute )efore t!e

sample is collected( =ne-m> sample of )lood s!ould )e ade4uate for a )lood culture )ottle containing

6-"0 m> of culture media( Since samples collected from indelling lines and cat!eters are li/el* to

)e contaminated, cultures s!ould )e collected onl* from a fres! &eni-puncture site( All )lood cultures

s!ould )e o)ser&ed for at least 2 !ours )efore t!e* are reported as sterile( It is no possi)le to detect

)acterial grot! it!in "2-25 !ours )* using impro&ed )acteriological tec!ni4ues suc! as AC$C

and AC;A>$ )lood culture s*stems( !ese ad&anced tec!ni4ues can detect )acteria at a

concentration of "-2 colon*-forming unit +cfu per m>(

+.$ Sep#ic screen-,! All neonates suspected to !a&e sepsis s!ould !a&e a septic screen to corro)orate

t!e diagnosis( oe&er, t!e decision to start anti)iotics need not )e conditional to t!e sepsis screen

result, if t!ere is a strong clinical suspicion of sepsis( !e &arious components of t!e septic screen

include total leu/oc*te count, a)solute neutrop!il count, immature to total neutrop!il ratio, micro-

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er*t!roc*te sedimentation rate and C reacti&e protein (Table 1)( !e a)solute neutrop!il count &aries

considera)l* in t!e immediate neonatal period and normal reference ranges are a&aila)le from

ManroeFs c!arts""( !e loer limit for normal total neutrop!il counts in t!e ne)orn )egins at

"800;cmm, rises to 200;cmm at "2 !ours of age and t!en declines and persists at "800;cmm after 2

!ours of age( @or &er* lo )irt! eig!t infants, t!e reference ranges are a&aila)le from Mou

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clinical condition sta)ili in urine o)tained )*

cat!eteri

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Pac/ed red cells and fres! fro

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oe&er a mess* e3c!ange transfusion could )e treated it! prop!*lactic anti)iotics( In our unit,

&entilated neonates are treated it! prop!*lactic anti)iotics for 6- da*s(

)hoice of an#i0io#ics $mpirical anti)iotic t!erap* s!ould )e unit-specific and determined )* t!e

pre&alent spectrum of etiological agents and t!eir anti)iotic sensiti&it* pattern( Anti)iotics once

started s!ould )e modified according to t!e sensiti&it* reports( Euidelines for empirical anti)iotic

t!erap* !a&e )een pro&ided in Table (

!e empirical c!oice of anti)iotics is dependent upon t!e pro)a)le source of infection( @or infections

t!at are li/el* to )e communit*-ac4uired !ere resistant strains are unli/el*, a com)ination of

ampicillin or penicillin it! gentamicin ma* )e a good c!oice as a first line t!erap*( @or infections

t!at are ac4uired during !ospital sta*, resistant pat!ogens are li/el* and a com)ination of ampicillin

or clo3acillin it! gentamicin or ami/acin ma* )e instituted( In nurseries !ere t!is com)ination is

ineffecti&e due to t!e presence of multiple resistant strains of /le)siella and ot!er gram-negati&e

)acilli, a com)ination of a t!ird generation cep!alosporin +cefota3ime or cefta

+e3tended spectrum )eta-lactamase positi&e organisms( !erefore it is prefera)le to use anti)iotics

suc! as piperacillin-ta

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stap!*lococcus( Met!icillin resistant stap!*lococcus aureus +MSA s!ould )e treated it! a

com)ination of ciproflo3acin or &ancom*cin it! ami/acin( Ciproflo3acin !as e3cellent acti&it*

against gram-negati&e organisms also. !oe&er, it does not !a&e good CS@ penetration( It ma* )e

used for t!e treatment of resistant gram-negati&e )acteremia after e3cluding meningitis( @or sepsis

due to enterococcus, a com)ination of ampicillin and gentamicin is a good c!oice for initial t!erap*(

ancom*cin s!ould )e used for t!e treatment of enterococcus resistant to t!e first line of t!erap*(

!e dosage, route, and fre4uenc* of commonl* used anti)iotics are gi&en in a)le 6(

Reserve an#i0io#ics Neer anti)iotics li/e a

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References

"( ang A, ang A, actule S, edd* M, Des!mu/! MD( $ffect of !ome-)ased neonatal

care and management of sepsis on neonatal mortalit*% field trial in rural India( >ancet

"###.65%"#66-:"

2( Stoll H( !e glo)al impact of neonatal infection( Clin Perinatol "##.25%"-2"

( eport of t!e National Neonatal Perinatal Data)ase +National Neonatolog* @orum 2002-0(

5( Sing! M, Narang A, !a/oo =N( Predicti&e perinatal score in t!e diagnosis of neonatal

sepsis( H rop Pediatr( "##5 Dec.50+:%:6-8

6( a//ar P, !a/oo =N, Narang A( Scoring s*stem for t!e prediction of earl* neonatal

infections( Indian Pediatr( "#5.""%6#-:00

:( altimore S( Neonatal nosocomial infections( Semin Perinatol "##8.22%26-2

( Golac! ( Neonatal sepsis% pat!ogenesis and supporti&e t!erap*( Semin

Perinatol"##.2"%28-8

8( Eerdes HS, Polin ( $arl* diagnosis and treatment of neonatal sepsis( Indian H Pediatr

"##8.:6%:-8(

#( Polins/i C( !e &alue of !ite )lood cell count and differential in t!e prediction of neonatal

sepsis( Neonatal Net "##:."6%"-2

"0( Da Sil&a =, =!lsson A, 9en*on C( Accurac* of leu/oc*te indices and C-reacti&e protein for

diagnosis of neonatal sepsis% a critical re&ie( Pediatr Infect Dis H "##6."5%:2-:

""( Manroe >, Gein)erg AE, osenfeld C, rone ( !e neonatal )lood count in !ealt! and

disease( I(efernce &alues for neutrop!ilic cells( H Pediatr "##.#6%8#-#8

"2( Mou

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"( Sarff >D, Platt >, McCrac/en E Hr( Cere)rospinal fluid e&aluation in neonates%

Comparison of !ig!-ris/ neonates it! and it!out meningitis( H Pediatr "#:.88%5-

"5( Upad!*a* A, Aggaral , 9apil A, Sing! S, Paul 9, Deorari A9( Profile of neonatal sepsis

in a tertiar* care neonatal unit from India% A retrospecti&e stud*( Hournal of Neonatolog*

200:.20%60-6(

"6( Deorari As!o/ 9( @or t!e In&estigators of t!e National Neonatal Perinatal Data)ase +NNPD(

C!anging pattern of )acteriologic profile in Neonatal Sepsis among intramural )a)ies( Hournal

of Neonatolog* 200:.20%8-"6(

":( aidi A9, us/ins GC, !a&er D, !utta A, A))as , Eoldmann DA(ospital-ac4uired

neonatal infections in de&eloping countries( >ancet 2006.:6%""6-88(

"( Sadana S, Mat!ur N, !a/ur A( $3c!ange transfusion in septic neonates it! sclerema%

effect on immunoglo)ulin and complement le&els( Indian Pediatr "##.5%20-6

"8( Henson , Polloc/ ( !e role of intra&enous immunoglo)ulin for t!e pre&ention and

treatment of neonatal sepsis( Semin Perinatol "##8.22%60-:

"#( Eoldman S, $llis , D!ar , Cairo MS( ationale and potential use of c*to/ines in t!e

pre&ention and treatment of neonatal sepsis( Clin Perinatol "##8.26%:##-"0

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6a0le !. A prac#ical sepsis screen

)omponen#s A0normal value

6o#al leukoce coun#

A0solu#e neu#rophil coun#

"mma#ure:#o#al neu#rophil

Micro8%SR

) reac#ive pro#ein 1)RP2

?6000;mm

>o counts as per Manroe char#""for term

and Mou;inho

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Diagnosis Dura#ion

Meningitis (with or without positive blood!"#$ culture)

%lood culture positive but no meningitis

"ulturenegative,sepsis screen positive and clinical

courseconsistent with sepsis

"ulture and sepsis screennegative, but clinicalcourse

compati.le with sepsis

2" da*s

"5 da*s

-"0 da*s

6( da*s

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6a0le (. %mpirical choice of an#i0io#ics for #rea#men# of neona#al sepsis

)linical si#ua#ion Sep#icemia ? Meningi#is

Pneumonia

@IS >IN$ Penicillin or Ampicillin Add Cefota3ime

Communit*-ac4uired and

+esistant strains unli/el* Eentamicin

S$C=ND >IN$ Ampicillin or Clo3acillin Add Cefota3ime

ospital-ac4uired and

Some strains are li/el* to )e Eentamicin or Ami/acinresistant

ID >IN$ Cefota3ime or

Piperacillin-ai/el* to )e resistant

"onsider &ancomycin if '# is suspected.

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6a0le *. Drugs, rou#e of adminis#ra#ion and doses of common an#i0io#ics used (

Drug Rou#e ir#h @eigh# $g ir#h @eigh# $g

84 d 4 da&s 84 da&s 4 da&s

Ami/acin I;, I;M (6 4"2! (6 48! "0 4"2! "0 48!

Ampicillin'enin*itis I; "00 4"2! "00 48! "00 4 8! "00 4:!

+thers I;, I;M 26 4"2! 26 48! 26 48! 26 4:!

Cefoto3ime

'enin*itis I; 60 4:! 60 4:! 60 4:! 60 4:!

+thers I;M, I; 60 4"2! 60 48! 60 4"2! 60 48!

PiperacillinJ I; 60-"00 4"2! 60-"00 48! 60-"00 4"2! 60-"00 4"2!

a

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Pro#ocol for sepsis

Septic screen J&e

NB. If no response is seen within 48-72 hours of starting treatment, a repeat blood culture should be obtained to determine appropchoice and duration of antibiotic therapy. lumbar puncture should be repeated in gram negati!e meningitis to assess for responto therapy.

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Start antibiotics

2 antenatal risk factors present orClinical features suggestive of

sepsis

Foul smelling liquor orPresence of >3 antenatal riskfactors

Suspected Early OnsetSepsis (EOS)

Suspected Late OnsetSepsis (LOS)

Sepsis screen (if negative, repeatafter 12 hours)

Blood cultureLumbar puncture, chest x-ray (f

re!uired)

Blood cultureLumbar puncture

Blood cultureLumbar puncture

"bdomen x-ray, urine examination (ifre!uired)

#o meningitis $ultures sterile

Screennegative

$linical coursenot


Screennegative

$linical coursecompatible


Screenpositive

$linical coursecompatible

#o meningitis $ultures

positive Screen &

Meningitis + $ultures &

Screen &

Stop antibioticsafter ' days

reat empirically%ith antibiotics fordays

reat empirically%ith antibiotics for-1* days

"ntibiotics acc+ tosensitivity for 1days

"ntibiotics for 21days

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