Your first patient of the day

• 1 month old male with 2 days of fussiness

• Decreased stool output for 3 days

• Poor latch during breastfeeding noted at 3AM on day of arrival to the ED

• Started ‘spitting up’ later in the morning

• Was noted to be less alert as well

• Soft spot was ‘hollow’

• He was also ‘breathing real fast’

• He was making a grunting noise which the parents thought was due to him trying to poop

The details

• Birth and past medical history

– G1P1

– Birth weight 8 pounds 5 ounces

– C-section for failure to progress at 41 weeks

– No complications during pregnancy

• GBS and other labs negative

• Maternal health Hx negative

– Unconjugated hyperbilirubinemia required

phototherapy on DOL3

– Regained birth weight by DOL 7

You enter the room

• The infant’s skin is this color

• You suddenly turn this color

First impressions

• ABCDE’s

– He has an airway

– He is breathing fast and making a grunting noise

– He’s skin is a lovely shade of grayish purple

– He appears uncomfortable

Your physical exam

• VS HR205 BP90/65 RR50 T38.8

• GEN grunting, gray skin

• HEENT AF sunken, mmm, + tears

• CV rate >200, no murmurs, 1+ femoral and brachial pulses, cap refill 5 seconds

• PULM tachypneic, CTAB

• ABD firm and distended, tender, no masses, normally positioned anus

• GU nl male

• NEURO irritable, nl tone

One sick baby

• What are his

problems?

• What do you think is

going on?

• What do we need to

do about it?

Goals

• Discuss fever of uncertain source in infants 0 to 60 days

• Focus on the Emergency Department setting

– Clinical assessment

– Diagnostic evaluation

– Treatment strategy

• Discuss use of CCHMC Evidence Based Guidelines

Fever of uncertain source

• FUS is an acute febrile illness with

uncertain etiology after thorough H&P

– No focal infection (eg. otitis media)

• The prevalence of a serious bacterial

infection (SBI) in infants with fever is high

• Clinical exam alone is unable to reliably

predict presence of SBI

Etiology

• SBI include;

– Meningitis, bone and joint infections, soft tissue infections, pneumonia, UTI, sepsis/bacteremia, enteritis

• Most common causes of FUS

#1 systemic viral infections

#2 urinary tract infections

#3 upper and lower respiratory tracts

#4 middle ear

Etiology

• Prevalence is uncertain in the post Hib,

post prevnar era

• <1 month – 8.8-13.7% according to

Bachur, 2001, Kadish, 2001, Baker, 1999

• 1-2 months 5 to 8.7%

• CCHMC data

– <1 month 9%

– 1-2 months 8%

The villains

• Bacteria (Baker, 1999) – E. coli 39%

– Klebsiella 11%

– Group B strep 8%

– Enterococcus 6%

– E. cloacae 6%

– L. monocytogenes 6%

• Viruses – Up to 50% of infants between

Aug-Oct w/ FUS have enterovirus

– HHV-6 in 10% <90 days old

– HSV incidence is 30/100,000, of these only 7-14% present with FUS

Clinical assessment - Fever

• Rectal temperature!

– >38oC or 100.4oF

• Magnitude may not

predict severity

• How accurate is parental

report of fever felt by

touch alone?

– Answer: pretty darn good!

• Sens 82-89%

• Spec 76-86%

Clinical assessment - History

• Low risk for SBI – Rochester criteria – Term birth >37 weeks

– No previous hospitalizations

– No chronic illnesses

– Not hospitalized longer than mother

– Not treated for unexplained hyperbili

– Has not recived antibiotics

– No intrapartum maternal fever, GBS, antibiotics

– No focal bacterial infection on exam • Purulent otitis, skin/soft tissue infection, bone/joint infection

– Negative lab screen

Clinical assessment - Exam

• High risk findings include – Lethargy

– Poor or absent eye contact

– Failure of child to recognize parents, or failure to interact with persons/objects in the environment

– Poor perfusion of the extremities

– Acrocyanosis

– Mottling

– Cap refill >2 seconds in warm ambient environment

– Hyper/hypoventilation

– cyanosis

Per Yale Observation scale <24 months of age

My advice

Be thorough!

Clinical assessment - Exam

• The ‘toxic’ infant

– Lethargy

– Poor perfusion

– Hypo/Hyperventilation

– Cyanosis

Clinical assessment - Labs

• CBC

– Abnormal wbc >15,000 or <5,000

– Bands >1,500

– Note: wbc values do not predict risk of meningitis (Bonsu, 2003)

• Blood Culture

One Unit, Two

Units…

Ah, Ah, Ahhh

Clinical assessment - Labs

• Urinalysis

– Abnormal >10wbc/hpf

– Gram stain for bacteria • Sens 94%

• Spec 92%

• Urine culture

– Catheter! (bagged specimens are useless)

Clinical assessment - Labs

• LP – should be performed in all

<30 days

– You can delay/omit 31-60 days IF

• Low risk via exam AND CBC + U/A

• Reliable follow up <24 hours

• Confident in parents’ ability to recognize changes in condition

• PCP and family agree with plan

• Antibiotic therapy will NOT be initiated

Clinical assessment - Labs

• LP

– Can be performed lying on side or upright

– Most CCHMC MDs and holders prefer upright

– Better success after local infiltration of

anesthetic, and with early stylet removal

– Even if you get a bloody tap still initiate

antibiotic therapy

Clinical assessment - Labs

• CSF studies – Tube 1 – protein and glucose

– Tube 2 – culture and gram stain

– Tube 3 – cell count and differential

– Tube 4 (Wasserman) – extra culture, hold

• Normal values for blood and urine do not rule out meningitis

• Enteroviral meningitis can have a CSF wbc of >1000! – Look for predominance of segs in a high wbc/hpf in bacterial

meningitis

• ‘Normal’ CSF values vary – Boston protocol <10 wbc/hpf

– Philadelphia protocol <8 wbc/hpf

– Rochester criteria <5 wbc/hpf

Cultures

• Try to obtain before giving antibiotics

– Don’t withhold if infant is septic/in shock

• Cultures should be watched for 36 hours at minimum

– Mean time to true positivity for B/C = 17.5 hours

– For blood contaminants = 27.9 hours

– Urine Cx = 16 hours

– CSF Cx = 18 hours

Other adjunctive studies

• Chest XRay

• Stool culture if diarrhea

• Viral studies (+ PCR does NOT rule out SBI)

– Enterovirus PCR of CSF (summer and fall) • Results available in 24 hours

– PCR is more sensitive than viral culture

– HHV-6 PCR

– HSV PCR of CSF (more on HSV later)

Treatment

• Supportive care

– ABCs

– O2 if sats <90%

– Fluid resuscitation w/ NS • Generally 20ml/kg, by if

you suspect heart failure, 10ml/kg may be appropriate

• And, oh yeah… ANTIBIOTICS!

Treatment

• Antibiotics in ALL infants less than 30 days w/ FUS

• NNT with ampicillin to prevent one case of Listeria or enterococcus is 138

AMPICILLIN 50mg/kg IV q6h

q12h <7days old

3rd generation cephalosporin

CEFOTAXIME 50mg/kg IV q8h

q8h bacteremia, q6h meningitis

GENTAMICIN 3mg/kg IV q24h 31-60d - 2.5mg/kg q12h

OR +

If you highly suspect Staph you can

use NAFCILLIN 20-50mg/kg IV q6h

instead of AMPICILLIN

Treatment

• 31-60 days - 3rd generation cephalosporin alone

• If infant is severely ill or UTI suspected add AMPICILLIN

– Listeria, gram + cocci, enterococcus (NNT= 527)

• Don’t give Ceftriaxone if…

– hyperbilirubinemic - since can displace bilirubin from its binding sites

– concurrent administration with intravenous calcium-containing solutions or products (including TPN) – causes potentially fatal precipitation reactions

3rd generation cephalosporin

CEFOTAXIME 50mg/kg IV q8h

q8h bacteremia, q6h meningitis

3rd generation cephalosporin

CEFTRIAXONE 50mg/kg IV q24h for bacteremia

100mg/kg IV q24h for meningitis

OR

Herpes

• What about Herpes?

– Laboratory evaluation

and/or treatment

should be considered

if risk factors are

present

Herpes

• Presentation of infants with neonatal HSV

– 7-14% have FUS

– 61% have no fever

– 95-98% present prior to 22 days of age

– 68% present with a vesicular rash on either the skin or mucous membranes

– 27% have seizures

• Overall incidence of HSV infection is 30/100,000 live births

Which one is due to HSV?

Answer: This is a trick question – neither are.

They are both examples of candidal diaper

dermatitis, which can look like HSV

Herpes

• Highest Risk – Primary maternal HSV infection at delivery

• 2/3 mothers who acquire HSV during pregnancy are symptom free

• Lower Risk Factors – Known exposure to HSV infected persons

• Caregiver with oral/genital herpes

– <37 weeks gestational age

– Fetal scalp electrodes

– Maternal STD Hx or unexplained fever at delivery

– CSF pleocytosis with negative gram stain and negative bact Cx

– Failure of fever to abate within 24-48 hours after starting ABx

– Unexplained CNS signs

Treatment - HSV

• Treatment

• Additional labs/studies recommended – Renal + glucose

– Liver panel

– Head CT

– CSF HSV PCR

– enterococcus PCR (if in season)

– Viral cultures • CSF

• Skin lesions

• Conjunctivae

• NP swab

• Rectal swab

ACYCLOVIR 20mg/kg IV q8h

Treatment - HSV

• The bottom line – treat if… – Mom had HSV at delivery, or infant has been

exposed

– The baby seizes or has worrisome neurologic signs

– There is clinical evidence to suggest that HSV is present

Routine treatment

with Acyclovir is

NOT recommended

Disposition

• <30 days definitely buys you an admission

– Approximately 3% of infants that are ‘low risk’ STILL have SBI

• 31-60 days can be managed at home or inpatient

• Low-risk infants 31-60 days can be D/C home IF

– Baby meets all history and exam findings for ‘LOW RISK’

– Negative labs (LP not necessarily needed)

– They have excellent follow up <24 hours – CALL THE PMD!

– Parents are comfortable

– You can admit without antibiotics if labs are negative but parents are uncomfortable or follow up is lacking

– Some MDs may wish to give IM/IV CEFTRIAXONE and D/C home • If you give antibiotics you SHOULD do an LP too

• Consider PICU or RCNIC if…

– Shock

– Bacterial meningitis suspected

When you are at CCHMC

• In EmSTAT click on the orders tab

Choose the Fever/Sepsis set from the list of ‘Standard Order Panels’

It will take you to a screen

where you can order all of

the requisite labs

Then click

to order the appropriate

antibiotics

Choosing these orders is most appropriate for a 0-30 day old with FUS

Evidence based guidelines

• You can always access the guidelines

You’ll find the guidelines on the Pediatric

Residents tab on CenterLink while

working at CCHMC

Evidence based guidelines

• Choose Guidelines to be taken to the list

Evidence based guidelines

• You can download the pdfs

• When away from CCHMC you can still

access the guidelines

– http://www.cincinnatichildrens.org/svc/alpha/h/

health-policy/ev-based/default.htm

• You can also search for Evidence Based

Care Guidelines after directing your

browser of choice to cincinnatichildrens.org

Case #1

• 3 week old former 39

week infant with temp of

38.4, feeding well, no

respiratory distress,

excellent perfusion

– Labs?

– Antibiotics?

– Disposition?

Case #2

• 5 week old former 35 week old infant

• Fever to 100.7oF rectally at home

• Looks well in the ED

• Can we apply the CCHMC guidelines to this infant?

Case #3

• You are seeing a 7 week old girl at Clinton Memorial

• Former 39 week infant

• Fever to 102 at home for 2 days

• Feeding well

• Crying but consolable

• Defervesces with Tylenol

• Visiting family in Ohio – they live in Chicago

• What are you going to do?

Back to our first patient

• He was clearly quite sick

• We obtained

– CBC, B/C

– U/A, U/C

– CSF labs

– Serum glucose

• We also elected to get

– XRays

– I-STAT

S 72

Bd 9

L 6

M 3

12.4

37.6 760 1.8

7.1 / 69 / -9

U/A 10-15 wbc

+ Leuk Est

no bacteria

CSF Prot, gluc nl

12 rbc

2 wbc

No organisms on gram stain

Back to our first patient

• He was started on Ampicillin and Cefotaxime

• He was intubated for worsening respiratory distress

• Resuscitated w/ 60ml/kg NS – though MAPs still in 50’s started on Dopamine for perfusion

• Admitted to the RCNIC

• Cultures grew E. coli in blood and urine – Dx E. coli urosepsis

• Developed a protracted septic ileus

• D/C after 27 days in the ICU – returned to breast feeding and doing well

Take home point #1

• FUS is an acute febrile illness with uncertain etiology after thorough H&P – Rectal temperature!

– >38oC or 100.4oF

• Clinical exam alone cannot reliably predict presence or absence of SBI – The ‘toxic’ infant

• Lethargy

• Poor perfusion

• Hypo/Hyperventilation

• Cyanosis

Take home point #2

• 30 days or less and FUS

– Blood, Urine, and CSF studies

– Ampiciliin + Cefotaxime OR Gentamicin

– Admission

Remember, bagged

specimens are

USELESS!

Take home point #3

• 31 to 60 days and well appearing

CBC, B/C, U/A, U/C Positive labs

1. Reliable f/u in 12-24 hours

2. Parental education

3. Plan OK w/ PMD and family

1. IV Antibiotics

2. Admit

LP and CSF studies

D/C home

1. f/u in 12-24 hours at PMD

2. If meets low risk criteria consider

D/C w/o antibiotics unless there

are PCP concerns

3. If you do give antibiotics empirically

you SHOULD do an LP

Take home point #4

• HSV – Mom had HSV at delivery, or infant has been

exposed

– The baby seizes or has worrisome neurologic signs

– There is clinical evidence to suggest that HSV is

present

• Treat with Acyclovir – Don’t forget adjunctive labs

Take home point #5

• The CCHMC Evidence based Guidelines

are a Great Resource

• Familiarize yourself with them before your

rotation

• pdfs are always available on the web

– http://www.cincinnatichildrens.org/svc/alpha/h/

health-policy/ev-based/default.htm