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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

late preterm infants: a novel set of tools to improve care Carl Seashore, MD Professor of

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
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

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

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

Listeria GN 1% 10% Other GP 12% Other Strep 15%
Listeria
GN
1%
10%
Other
GP
12%
Other
Strep
15%

E. coli

23%

GBS

39%

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

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

.nbnsepsiscalculator which displays a hyperlink to the online calculator and the parameters needed.
.nbnsepsiscalculator which displays a
hyperlink to the online calculator and the
parameters needed.

Infant parameters can be accessed using the Epic SmartPhrase:

hSps://neonatalsepsiscalculator.kaiserpermanente.org

Kaiser Sepsis Calculator

.nbnsepsiscalculator which displays a hyperlink to the online calculator and the parameters needed.
.nbnsepsiscalculator which displays a
hyperlink to the online calculator and the
parameters needed.

Infant parameters can be accessed using the Epic SmartPhrase:

hSps://neonatalsepsiscalculator.kaiserpermanente.org

Kaiser Sepsis Calculator

.nbnsepsiscalculator which displays a hyperlink to the online calculator and the parameters needed.
.nbnsepsiscalculator which displays a
hyperlink to the online calculator and the
parameters needed.

Infant parameters can be accessed using the Epic SmartPhrase:

hSps://neonatalsepsiscalculator.kaiserpermanente.org

Rate of EOS by Gestational Age

Rate of EOS by Gestational Age Slide courtesy of Karen Puoplolo

Slide courtesy of Karen Puoplolo

Kaiser Sepsis Calculator

.nbnsepsiscalculator which displays a hyperlink to the online calculator and the parameters needed.
.nbnsepsiscalculator which displays a
hyperlink to the online calculator and the
parameters needed.

Infant parameters can be accessed using the Epic SmartPhrase:

hSps://neonatalsepsiscalculator.kaiserpermanente.org

Rate of EOS by Highest Maternal Temperature

Rate of EOS by Highest Maternal Temperature Slide courtesy of Karen Puoplolo

Slide courtesy of Karen Puoplolo

Kaiser Sepsis Calculator

.nbnsepsiscalculator which displays a hyperlink to the online calculator and the parameters needed.
.nbnsepsiscalculator which displays a
hyperlink to the online calculator and the
parameters needed.

Infant parameters can be accessed using the Epic SmartPhrase:

hSps://neonatalsepsiscalculator.kaiserpermanente.org

Rate of EOS by Duration of ROM

Rate of EOS by Duration of ROM Slide courtesy of Karen Puoplolo

Slide courtesy of Karen Puoplolo

Kaiser Sepsis Calculator

.nbnsepsiscalculator which displays a hyperlink to the online calculator and the parameters needed.
.nbnsepsiscalculator which displays a
hyperlink to the online calculator and the
parameters needed.

Infant parameters can be accessed using the Epic SmartPhrase:

hSps://neonatalsepsiscalculator.kaiserpermanente.org

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

Signs of Neonatal Sepsis?

born ≥ 34 weeks Gestation Signs of Neonatal Sepsis? NO Maternal ChorioamnioniAs? 3 Full DiagnosAc EvaluaAon

NO

Maternal ChorioamnioniAs? 3

Full DiagnosAc EvaluaAon 1 AnAbioAc Therapy 2

Kaiser Sepsis Tool 8

Consider Limited EvaluaAon 4 Consider AnAbioAc Therapy 2

YES

Limited EvaluaAon 4 Consider AnAbioAc Therapy 2 YES Y E S NO   * See Appendix

YES

EvaluaAon 4 Consider AnAbioAc Therapy 2 YES Y E S NO   * See Appendix A

NOEvaluaAon 4 Consider AnAbioAc Therapy 2 YES Y E S   * See Appendix A GBS

 

*

See Appendix A

GBS Prophylaxis

NO

RouAne Clinical Care 5

RouAne Clinical Care 5

indicated for

mother?

 
Care 5 indicated for m o t h e r ?   YES * See Appendix

YES

* See Appendix A

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

received intravenous for ≥ 4 hours prior to delivery? NO Well-appearing infant and ≥37 weeks AND

NO

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

and ≥37 weeks AND membranes ruptured < 18 hours? NO Well-appearing infant and <37 weeks OR

NO

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

YES

and <37 weeks OR membranes ruptured ≥18 hours? YES YES YES ObservaAon for ≥ 48 hours

YES

and <37 weeks OR membranes ruptured ≥18 hours? YES YES YES ObservaAon for ≥ 48 hours

YES

<37 weeks OR membranes ruptured ≥18 hours? YES YES YES ObservaAon for ≥ 48 hours 5

ObservaAon for ≥ 48 hours 5,6

ObservaAon for ≥ 48 hours 5,7

ObservaAon for ≥ 48 hours 5 Limited EvaluaAon 4

FOOTNOTES:

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.

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).

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.

4. Limited evaluation includes blood culture (at birth) and CBC with differential and

platelets (at birth and/or at 6-12 hours of life).

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.

7. Some experts recommend a CBC with differential and platelets at age 6-12 hours of

life.

8. hSps://neonatalsepsiscalculator.kaiserpermanente.org/

An-bio-c dosing:

Birth GA

 

Ampicillin

Gentamicin

≥35 (weeks)

100mg/Kg

4mg/Kg q 24 hours IV (give IM

q

12 hours IV

if baby in NBN)

34 (weeks)

100mg/Kg

4.5mg/Kg q 36 hours IV (give

q

12 hours IV

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 Unknown GBS status, plus one or more of the following (for delivery ≤ 37 weeks gestaAon):

All newborn infants with signs suggestive of sepsis should have a full diagnostic evaluation .

All newborn infants with signs suggestive of sepsis should have a full diagnostic evaluation.

1. Rupture of membranes ≥18 hours

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

Sepsis SmartPhrase output The SmartPhrase returns the parameters needed to complete the calculator as well as

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)
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)
Equivocal
PP
1.31
(0.93-1.84)
11.07 (5.02-27.74)
NNT
763 (543-1,076)
90 (36-199)
Well-Appearing
PP
0.11
1.08
6.74
(0.08-0.13)
(0.70-1.65)
(3.09-16.06)
NNT
9,370
923
148
(605-1,428)
(62-323)
(7,418-12,073)

Slide courtesy of Karen Puoplolo

Process Change
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