You are on page 1of 26

Early  Onset  Sepsis  in  term  and  late  

preterm  infants:  a  novel  set  of  
tools  to  improve  care  
Carl  Seashore,  MD  
Professor  of  Pediatrics  
UNC  Newborn  Nursery  

Sepsis  evaluaAon  in  Newborns    
•  Per  current  (2010)  CDC  guidelines,  all  infants  born  to  
mothers  with  chorioamnioniAs  should  get  a  CBC,  blood  
culture  and  48  hours  of  an-bio-cs.  Infants  with  PROM  
or  untreated  GBS  get  CBC/Cx  and/or  prolonged  
hospitalizaAon  for  observaAon  
•  Most  infants  receiving  a  sepsis  evaluaAon  in  NBN  fall  
into  this  category.    
–  Occasionally  a  sepsis  evaluaAon  is  performed  due  to  concern  
for  illness    
–  PosiAve  blood  culture  and  prolonged  treatment  =  RARE!  

CDC  MMWR  December  2010  
hSps://www.cdc.gov/mmwr/preview/mmwrhtml/
rr5910a1.htm?s_cid=rr5910a1_w  

   

CDC  MMWR  December  2010  
hSps://www.cdc.gov/mmwr/preview/mmwrhtml/
rr5910a1.htm?s_cid=rr5910a1_w  

   

BWH Local Algorithm for
EOS Evaluation of
Well-Appearing Infants
Born ≥ 35 weeks
Gestation
Based on CDC 2002
Guidelines

Slide  courtesy  of  Karen  Puoplolo  

Microbiology of Neonatal EOS

Other
GP
12%

Other
GN Listeria
1%
10%
GBS
39%

Other
Strep
15%

•  Mortality from EOS
primarily among preterm
infants
•  Overall 10.8%
•  < 37 weeks: 22.8%
•  ≥ 37 weeks: 1.6%

E. coli
23%

Stoll, et al. Pediatr Infect Dis J 2005;24: 635; Stoll, et al. Pediatrics 2011;127:817
Puopolo KM and Eichenwald EC. Pediatrics 2010;125:e1031; Hyde, et al. Pediatrics. 2002;110:69

Slide  courtesy  of  Karen  Puoplolo  

Kaiser  Sepsis  Calculator  

Infant  parameters  can  be  accessed  using  the  
Epic  SmartPhrase:    
.nbnsepsiscalculator  which  displays  a  
hyperlink  to  the  online  calculator  and  the  
parameters  needed.  
hSps://neonatalsepsiscalculator.kaiserpermanente.org  

Kaiser  Sepsis  Calculator  

Infant  parameters  can  be  accessed  using  the  
Epic  SmartPhrase:    
.nbnsepsiscalculator  which  displays  a  
hyperlink  to  the  online  calculator  and  the  
parameters  needed.  
hSps://neonatalsepsiscalculator.kaiserpermanente.org  

Kaiser  Sepsis  Calculator  

Infant  parameters  can  be  accessed  using  the  
Epic  SmartPhrase:    
.nbnsepsiscalculator  which  displays  a  
hyperlink  to  the  online  calculator  and  the  
parameters  needed.  
hSps://neonatalsepsiscalculator.kaiserpermanente.org  

Rate of EOS by Gestational Age

Slide  courtesy  of  Karen  Puoplolo  

Kaiser  Sepsis  Calculator  

Infant  parameters  can  be  accessed  using  the  
Epic  SmartPhrase:    
.nbnsepsiscalculator  which  displays  a  
hyperlink  to  the  online  calculator  and  the  
parameters  needed.  
hSps://neonatalsepsiscalculator.kaiserpermanente.org  

Rate of EOS by
Highest Maternal Temperature

Slide  courtesy  of  Karen  Puoplolo  

Kaiser  Sepsis  Calculator  

Infant  parameters  can  be  accessed  using  the  
Epic  SmartPhrase:    
.nbnsepsiscalculator  which  displays  a  
hyperlink  to  the  online  calculator  and  the  
parameters  needed.  
hSps://neonatalsepsiscalculator.kaiserpermanente.org  

Rate of EOS by Duration of ROM

Slide  courtesy  of  Karen  Puoplolo  

Kaiser  Sepsis  Calculator  

Infant  parameters  can  be  accessed  using  the  
Epic  SmartPhrase:    
.nbnsepsiscalculator  which  displays  a  
hyperlink  to  the  online  calculator  and  the  
parameters  needed.  
hSps://neonatalsepsiscalculator.kaiserpermanente.org  

UNC Children Hospital Algorithm for Prevention of Early Onset Sepsis (EOS) Among Newborns born ≥34 weeks Gestation
FOOTNOTES:

Signs  of  Neonatal  
Sepsis?  

YES

Full  DiagnosAc  EvaluaAon1  
AnAbioAc  Therapy2  

1. Full diagnostic evaluation includes a blood culture, a complete blood count (CBC)
with differential and platelet counts, chest radiograph (if respiratory distress), and
lumbar puncture (if sepsis suspected and patient is stable enough). 15-38% of infants
with early onset meningitis have sterile blood cultures, so evaluating CSF will
optimize diagnostic sensitivity.

Kaiser  Sepsis  Tool8  

2. Antibiotic therapy should be directed toward the most common causes of neonatal
sepsis, including intravenous ampicillin for GBS and coverage for other organisms.
Start ampicillin and gentamicin. Consider ampicillin and cefotaxime/cefepime if
renal insufficiency is present, cooling protocol in progress, or suspected meningitis
(unless local antibiotic-resistance patterns suggest the need for another combination).

NO

Maternal  
ChorioamnioniAs?3  

YES

Consider  Limited  EvaluaAon4  
Consider  AnAbioAc  Therapy2  

3. Consultation with obstetric providers is important to determine the level of clinical
suspicion for chorioamnionitis. Chorioamnionitis is diagnosed clinically and some of
the signs are nonspecific.

NO
* See Appendix A

GBS  Prophylaxis  
indicated  for  mother?  

NO

RouAne  Clinical  Care5  

* See Appendix A

YES

5. If signs of sepsis develop, a full diagnostic evaluation should be conducted and
antibiotic therapy initiated.
6. Observation may occur at home after 24 hours if all apply: ≥37 weeks gestation,
other discharge criteria have been met, access to medical care is readily available, and
a person who is able to comply fully with instructions for home observation will be
present.

YES

Well-­‐appearing  infant  and  
mother  received  intravenous  for  
≥  4  hours  prior  to  delivery?  

4. Limited evaluation includes blood culture (at birth) and CBC with differential and
platelets (at birth and/or at 6-12 hours of life).

ObservaAon  for  ≥  48  hours5,6  

7. Some experts recommend a CBC with differential and platelets at age 6-12 hours of
life.
8. hSps://neonatalsepsiscalculator.kaiserpermanente.org/  

NO

Well-­‐appearing  infant  and  ≥37  
weeks  AND  membranes  
ruptured  <  18  hours?  

YES

ObservaAon  for  ≥  48  hours5,7  
An-bio-c  dosing:  

NO

Birth  GA  

Well-­‐appearing  infant  and    <37  
weeks  OR  membranes  ruptured  
≥18  hours?  

YES

ObservaAon  for  ≥  48  hours5  
Limited  EvaluaAon4  

Ampicillin  

Gentamicin  

≥35  (weeks)  

100mg/Kg    
q  12  hours  IV  

4mg/Kg  q  24  hours  IV  (give  IM  
if  baby  in  NBN)  

34  (weeks)  

100mg/Kg    
q  12  hours  IV  

4.5mg/Kg  q  36  hours  IV  (give  
IM  if  baby  in  NBN)  

 Appendix  A:  Group  B  Strep  Exposure  and  Disease  in  the  Newborn:  
• 
Group  B  Streptococcus  is  a  major  cause  of  perinatal  bacterial  infecAon,  including    bacteremia,  meningiAs,  endometriAs,  chorioamnioniAs  and  urinary  
tract  infecAons.  Early-­‐onset  disease  usually  occurs  in  the  first  24  hours  of  life  (range  0  –  6  days)  and  is  characterized  by  respiratory  distress,  apnea,  
shock,  pneumonia,  and  meningiAs  (5  –  10%  of  cases).  Late-­‐onset  disease  occurs  aler  the  first  week  of  life,  typically  at  3  to  4  weeks  of  age.  Late-­‐onset  
disease  commonly  presents  as  occult  bacteremia  or  meningiAs.  Late,  late-­‐onset  disease  occurs  aler  89  days  of  age  in  very  preterm  infants  requiring  
prolonged  hospitalizaAon.  
   
• 
The  colonizaAon  rate  in  pregnant  women  ranges  from  15  –  35%.  Since  the  implementaAon  of  widespread  maternal  intrapartum  prophylaxis  the  
incidence  of  early-­‐onset  GBS  has  decreased  by  approximately  80%  from  1-­‐4  cases  per  1000  births  to  0.28  cases  per  1000  live  births.    The  use  of  
intrapartum  chemoprophylaxis  has  had  no  measurable  impact  on  late-­‐onset  GBS  disease.      
   
• 

 

RECOMMENDATIONS  FOR  ALL  PREGNANT  WOMEN  ARE  AS  FOLLOWS:  

All  pregnant  women  should  be  screened  between  35  to  37  weeks’  gestaAon  for  vaginal  and  rectal  GBS  colonizaAon.  
A  paAent  who  presents  with  signs  and  symptoms  of  preterm  labor  (<  35  weeks)  should  be  swabbed  for  vaginal-­‐rectal  GBS  culture  and  started  
on  prophylacAc  anAbioAcs.  If  the  paAent  is  in  true  labor  (meaning  imminent  delivery)  anAbioAcs  should  be  conAnued  unAl  delivery,  if  not  in  
true  labor  (not  delivering  imminently)  may  disconAnue  anAbioAcs  and  obtain  GBS  culture  results.  If  the  results  are  posiAve,  restart  anAbioAcs  
at  onset  of  true  labor.  
– 
Indica-ons  for  intrapartum  an-bio-c  prophylaxis  (IAP):  
•  Previous  infant  born  to  the  mother  with  GBS  disease
•  GBS  bacteriuria  during  any  trimester  of  pregnancy
•  PosiAve  GBS  vaginal-­‐rectal  culture  in  the  preceding  5  weeks  prior  to  true  labor
All newborn infants with signs
•  Unknown  GBS  status,  plus  one  or  more  of  the  following  (for  delivery  ≤  37  weeks  gestaAon):  
suggestive of sepsis should have a
1.  Rupture  of  membranes  ≥18  hours
full diagnostic evaluation.
2.  Intrapartum  temperature  ≥  100.4˚F  (38˚C)
3.  Intrapartum  NAAT  posiAve  for  GBS  (nucleic  acid  amplificaAon  tests)  –  NAAT  test  opAonal  and  may  not  be  available
The  defini-on  of  IAP  has  been  clarified  to  be  AT  LEAST  4  hours  of  penicillin,  ampicillin,  or  cefazolin.  Penicillin  remains  the  agent  of  choice  for  IAP,  and  
ampicillin  is  an  acceptable  alternaAve.    Penicillin-­‐allergic  women  who  do  not  have  a  history  of  anaphylaxis,  angioedema,  respiratory  distress,  or  
urAcaria  aler  administraAon  of  penicillin  or  a  cephalosporin  should  receive  cefazolin.  Penicillin-­‐allergic  women  at  high  risk  of  anaphylaxis  should  
receive  clindamycin  if  their  GBS  isolate  is  suscepAble  or  vancomycin  if  their  GBS  isolate  is  intrinsically  resistant  to  clindamycin.    The  iniAal  intravenous  
dose  of  penicillin  is  5  million  units;  for  ampicillin  and  cefazolin,  the  iniAal  dose  is  2  grams.  All  other  anAbioAcs,  doses,  or  duraAons  are  considered  
inadequate  for  the  purposes  of  neonatal  management  
– 
– 

 

 

 

• 

 

 

 

 

 

References:  
American  Academy  of  Pediatrics,  CommiSee  on  InfecAous  Diseases  and  CommiSee  on  Fetus  and  the  Newborn.  (2011,  September).  
RecommendaAons  for  the  PrevenAon  of  Perinatal  Group  B  Streptococcal  (GBS)  Disease  Pediatrics:  128(3),  pp.  611-­‐616.  
American  Academy  of  Pediatrics.  (2012).  Red  Book:  2012  Report  of  the  Commi4ee  on  Infec8ous  Diseases  (29th  ed.).  Elk  Grove  Village,  IL:  American  Academy  of  Pediatrics.  pp.  680-­‐685.
Adapted  with  permission  from  Centers  for  Disease  Control  and  PrevenAon.  PrevenAon  of  perinatal  group  B  streptococcal  disease:  prevenAon  of  perinatal  group  B  streptococcal  disease  
from  CDC,  2010.  MMWR  Recomm  Rep.  2010;59[RR-­‐10]:1–32.  
Hill,  S.M.,  Bridges,  M.A.,  Knudson,  A.L.,  &  Vezeau,  T.  M.,  (2013).  A  pracAcal  approach  to  implemenAng  new  CBC  GBS  guidelines.  The  Journal  of  Maternal/Child  Nursing,  38(5),  305-­‐310.    

 

Revised  May  2016  –  Lee  /  Peter-­‐Wohl/  Seashore  

 

 

Kaiser  Sepsis  Calculator  
•  In  April  2016,  NBN  began  consistently  using  the  
Kaiser  Neonatal  Early-­‐Onset  Sepsis  Calculator  to  
determine  an  infant’s  individual  risk  of  developing  
sepsis.    
•  The  calculator,  in  conjuncAon  with  clinical  
assessment,  is  used  to  guide  management  of  the  
infant  born  to  a  mother  with  chorioamnioniAs.    
•  Kaiser  sepsis  calculator  was  designed  to  be  used  on  
all  infants,  however  in  our  current  pilot  we  use  only  
on  those  at  higher  risk  for  sepsis.    

Sepsis  SmartPhrase  output  

The  SmartPhrase  returns  the  parameters  needed  to  
complete  the  calculator  as  well  as  a  Hyperlink  that  opens  
the  webpage.  The  red  text  instructs  on  use  of  the  calculator  
and  is  deleted  before  the  note  is  signed.  

hSps://neonatalsepsiscalculator.kaiserpermanente.org  

SRS + Clinical Status =
Posterior Probability of Sepsis
Clinical Status

Sepsis Risk Score
< 0.65

0.65-1.54

> 1.54

Clinical Illness
PP

5.57 (3.73-8.53)

27.10 (11.04-81.56)

NNT

180 (117-268)

37 (12-91)

PP

1.31 (0.93-1.84)

11.07 (5.02-27.74)

NNT

763 (543-1,076)

90 (36-199)

Equivocal

Well-Appearing
PP
NNT

0.11
(0.08-0.13)

1.08
(0.70-1.65)

6.74
(3.09-16.06)

9,370
(7,418-12,073)

923
(605-1,428)

148
(62-323)

Slide  courtesy  of  Karen  Puoplolo  

Process  Change  

Benefits  of  using  the  Kaiser  Sepsis  
Calculator  
•  Avoid  unnecessary  lab  work  for  infants  

–  Pain  of  venipuncture,  cost  of  labs,  angst  for  new  parents  

•  Decrease  anAbioAc  usage  

–  Avoid  unnecessary  exposure  to  IV  anAbioAcs  in  the  first  days  
of  life  and  its  potenAal  effect  on  gut  flora  
–  Decreased  parental  stress  over  needle  sAcks  and  IV  
placement,  perceived  illness  of  their  baby  
–  Less  separaAon  of  mothers  and  babies  

•  Avoid  using  RN  resources  through  less  lab  draws,  IV  
placements  
•  Decrease  pharmacy  resources  by  not  using  anAbioAcs  
unnecessarily  

Resources  
•  UCSF  Caring  Wisely  Sepsis  Guideline  
•  Epic  UGM  Slides  on  IntegraAon  of  the  
calculator