Shabnam Zargar, MD, FAAP - PowerPoint Presentation

Slide1

Shabnam Zargar, MD, FAAPAssistant Clinical ProfessorPediatricsUCR School of Medicine

Neonatal Fever Slide2

Neonatal FeverA 15 day old infant presents to the ED with a temperature of 38.4 degrees Celsius (101.4 Fahrenheit). What to do next and why?Slide3

Neonatal feverWhat is neonatal fever?Temperature of 38 degrees Celsius (100.4 Fahrenheit) in infants 0-28 days of life.

Rectal temperature

recommendedSlide4

Neonatal FeverWhy is neonatal fever important?Febrile neonates are at high risk for serious infection (SI) or serious bacterial infection (SBI) because of increased susceptibility to infections, difficulty with clinical examination, and poor outcomes if not diagnosed or treated properlySlide5

Neonatal FeverDifferential Diagnoses:

Meningitis

b

acterial or viral

Bacterial – GBS, E. coli, Listeria

Viral – Enterovirus

HSV infections

localized or disseminated infections

UTI

E. coli, Enterococcus

Bacteremia

SepsisCellulitisAbscessOsteomyelitisSeptic arthritisViralSlide6

Neonatal FeverMost common etiologyViral illness

Viral

Bacterial etiologies:

Most common – UTI

UTI

Followed by:

Meningitis

Bacteremia/Sepsis

Sepsis or bacteremia

Abscess or cellulitisPneumonia Meningitis Approximately 12%-28% of neonates presenting to a pediatric ED with fever have a SBI

- bacteremia, gastroenteritis, cellulitis, osteomyelitis, septic arthritis,

meningitis, pneumonia, and UTI (Cincinnati)Slide7

Neonatal FeverFebrile infants may have few symptoms to guide diagnosis and management

History to obtain

:

Fever? How high?

How was temperature measured?

Last anti-pyretic use?

Change in feeding?

Irritability or lethargy?

Seizures?

Change in cry?

URI symptoms?

Difficulty breathing?

Swelling of joints or skin changes? Sick contacts? Vomiting or diarrhea?Slide8

Neonatal FeverPhysical examGen

:

Mentation?

HEENT

:

Anterior fontanelle – bulging? Eyes –

Cellulitis/conjunctivitis?

Ears – otitis? Nose – congestion? Rhinorrhea? Throat – weak/high pitched cry? Cough?

Neck

:

Swelling? Neck stiffness is a sign in older children

Lungs

: Retractions? Crackles? Ronchi?CVS: Murmur? Tachycardia? Capillary refill? Pulses?Abdomen: Omphalitis? GU: Circumcised?Skin

:

Cellulitis/Abscess? Rash?

MSK: Joint swelling?Neuro: Mentation? Irritable? Lethargic? Slide9

Neonatal FeverDiagnosis

Laboratory:

Full sepsis workup

CBC with manual differential

Blood culture

UA with microanalysis (urethral catheterization)

Urine Culture

CSF studies – tube 1 culture, tube 2 protein and glucose, tube 3 cell count and differential,

tube 4 – HSV PCR if HSV encephalomengitis suggested

If CSF pleocytosis, add enterovirus PCR

CXR if symptomatic

Stool culture if diarrhea present*Ok to delay LP if patient unstable, do administer antibiotics!*Full septic workup still recommended in neonates with

symptoms of bronchiolitisSlide10

Neonatal FeverValuesCBC with manual differential

:

Normal WBC 5,000-15,000 per mm

3

WBC < 5,000 or >15,000 per mm

3

or ANC >10,000 per mm

3

have increased risk of SBI

CSF:

Low risk of meningitis: <20WBC/mm

3High risk of meningitis: >20WBC/mm3Other values: High protein >120mg/dL and low glucose <40mg/dLUrinalysis:WBC < 10/mm

3

, negative LE and nitritesSlide11

Neonatal FeverManagementAdmit

to inpatient pending culture results

IV antibiotics

to cover common organisms – empirical treatment should be given immediately after cultures obtained

Ampicillin and gentamicin

Ampicillin and 3

rd

generation cephalosporin

-Cefotaxime preferred over ceftriaxone

*All neonates should be given a single dose of ampicillin and cefotaxime immediately after cultures are obtainedIV antiviral Acyclovir should be started on all neonates who have pending CSF HSV PCR studies

Clinical prediction models have not been able to accurately predict SBIs in neonates so common practice remains for hospitalization for sepsis evaluation and IV antibiotics (Fielding-Singh et al.)Slide12

Neonatal feverAntibioticsAmpicillin

covers Enterococcus and Listeria, also

Streptococcus/gram

positives

Gentamicin

covers

gram

negatives, crosses blood brain barrier

Cefotaxime

covers

gram

negatives (rising resistance of E. coli to Ampicillin), crosses blood brain barrierSlide13

Neonatal FeverAll febrile neonates ≤ 28 days of age should be hospitalized, undergo a full sepsis evaluation, and receive empirical IV antibioticsSlide14

Neonatal feverPre-treated CSF:Can add real time PCR and DNA sequencing for bacterial rRNA if pleocytosis is present and there is a concern for meningitisSlide15

Neonatal FeverHSV in neonatesComprehensive testing required

Surface swabs sent for HSV culture from

nasopharynx, conjunctivae, and anus

CSF for HSV PCR

Blood for HSV PCR

Vesicle fluid for HSV PCR – if rash present

CBC with differential, BUN, creatinine,

AST and ALT

Nelson Textbook of Pediatrics: Expert ConsultSlide16

Neonatal FeverHSV in neonatesGreatest risk in neonates born vaginally to mothers with risk factors for primary maternal HSV infection

Clinical features

: severe illness, hypothermia, lethargy, seizures, HSM, postnatal HSV contact, vesicular rash,

conjunctivitis,

interstitial pneumonitis

Laboratory features

: Thrombocytopenia, elevated transaminases

, CSF pleocytosis >20 WBC/mm3 with negative gram stain

*If suspicion for HSV infection or HSV PCR performed on CSF, begin acyclovir with empiric antibiotics

Merck Manual Professional VersionSlide17

Neonatal FeverHow long to admit for?Standard length of hospitalization: 48 hours – “48 hour rule out sepsis”

Studies are being performed to determine

if 48 hours of hospitalization is really

needed

Recent studies have also looked at low risk

criteria for treating febrile neonates less

conservatively but concluded that low risk

criteria are not sufficiently reliable to exclude

SBIs in febrile neonatesSlide18

Neonatal FeverOne study from Hospital Pediatrics (Fielding-Singh et al.):

Objective

:

To determine the risk of a positive, pathogenic bacterial culture of blood or CSF in infants ≤ 30 days beyond 24 hours after collection

Methods

:

retrospective review of 1,145 infants ≤ 30 days with blood or CSF cultures drawn at Santa Clara Valley Medical Center in San Jose, CA from 1999-2010. High risk infants had WBC <5,000 or >15,000 per microliter, bands >1,500 per microliter, or abnormal UA

Results

:

1,876 blood and CSF cultures were identified. 79% were hospitalized and of those hospitalized, 45% were for fever without a source. 2.7% had pathogenic cultures and 0.5% had a time to notification >24 hours (not statistically significant), of those 0.5%, all had fever without source and high-risk criteria. No low-risk criteria patient had a time to notification >24 hours. 1.8% of high risk patients had growth 24-48 hours.

Conclusion

:

Low-risk infants hospitalized for fever without source may not need hospitalization for 48 hours to rule out bacteremia or meningitisSlide19

Neonatal feverStudy continued:

Mean and median time to notification 24.5 ± 17.1 and 19 hours for pathogens and 45.3 ± 30.7 and 35.8 hours for contaminants, respectivelySlide20

Neonatal FeverPrevious studies: Time to positivity of blood and CSF cultures in neonates suggest that 48 hours is necessary to identify >95% of cases, however, these studies included infants in the ICU where CoNS and yeast cultured from central lines take time to grow (Fielding et al.)Slide21

Neonatal FeverApproximately 90% of bacterial pathogens are identified within the first 24 hours of incubation (Byington et al.)

Infants 0-6 months of age:

Blood cultures:

Mean time to positivity for true pathogens is ~17.5 hours

Urine and CSF:

Median time to positivity are 16 and 18 hours, respectivelySlide22

Neonatal FeverConsider discharge at 24 hours if bacterial cultures negative and viral studies positive (excluding HSV) AND well-appearingPatients with bronchiolitis or other viral infections are at lower risk of SBI

Seattle Children’s recommends thisSlide23

Neonatal FeverDischarge criteria:Well-appearingTolerating PO

Follow up available within 48-72 hours

Family and primary care team agree with plan

Cultures negativeSlide24

Neonatal FeverIf a neonate presents with fever to your clinic

-Send to the ED

If you receive a call from a mom stating her neonate has a fever

-Send to the ED

If you are working in the ED and have a neonate with fever

-Perform full septic workup, give first dose of ampicillin and cefotaxime, and admit to inpatient

If you are the admitting inpatient team – continue/begin empirical antibiotics, making sure urine, blood, and CSF cultures have been drawn (if LP not successful and patient appears meningitic – do not delay antibiotics), and observe 48 hours pending culturesSlide25

Neonatal FeverSide note:Neonates with meningitis need to be admitted to a hospital with pediatrics ID and PICU

-Complications – seizures, empyema,

elevated ICP

-BAER and ophthalmology examSlide26

Neonatal FeverPossible QI project?Develop a standardization pathway of management of neonatal fever in our institution based on clinical evidence

Standardization improves medical care!Slide27

ReferencesBishop, Julianne, and S. Heath Ackley. Clinical Standard Pathway: Neonatal Fever

. Project Owners, Aug. 2013. Web. 20 July 2015.

https

://

www.seattlechildrens.org/pdf/neonatal-fever-learning-module.pdf

.

Byington, Carrie L., F. Rene Enriquez, Charles Hoff, Richard Tuohy, E. William Taggart, David R. Hillyard, Karen C. Carroll, and John C. Christenson. "Serious Bacterial Infections in Febrile Infants 1 to 90 Days Old With and Without Viral Infections." Pediatrics 113.6 (2004): 1662-666.

Caserta, Mary T. "Neonatal Herpes Simplex Virus (HSV) Infection - Pediatrics."

Merck Manuals Professional Edition

. Merck Sharp & Dohme Corp, May 2013.

http://

www.merckmanuals.com/professional/pediatrics/infections-in-neonates/neonatal-herpes-simplex-virus-hsv-infection

. Accessed 24 July 2015.

Cincinnati

Children's Hospital Medical Center. Evidence-based care guideline for fever of uncertain source in infants 60 days of age or less. October 27, 2010.

http://www.cincinnatichildrens.org/svc/alpha/h/health-policy/ev-based/default.htm. Accessed July 20, 2015

Fielding-Singh, Vikram, David K. Hong, Stephen J. Harris, John R. Hamilton, and Alan R. Schroeder. "Ruling Out Bacteremia and Bacterial Meningitis in Infants Less Than One Month Of Age

: Is 48 Hours of Hospitalization Necessary?" Hospital Pediatrics 3.4 (2013): 355-61. Web.Hamilton, Jennifer L., and Sony P. John. "Evaluation of Fever in Infants and Young Children."

American Family Physician (2013): http://

www.aafp.org/afp/2013/0215/p254.html. Accessed July 20, 2015.Kliegman, Robert M., Bonita M.D. Stanton, Joseph St. Geme, and Nina F. Schor.

Nelson's Textbook of Pediatrics: Expert Consult. 20th ed. Philadelphia: Elsevier, 2016.Jain

, Shabnam, John Cheng, Elizabeth R. Alpern, Cary Thurm, Lisa Schroeder, Kelly Black, Angela M. Ellison, Kimberly Stone, and Evaline A. Alessandrini. "Management of Febrile Neonates in US Pediatric Emergency Departments." Pediatrics 133.2 (2014): 187-95

.