Objectives:
1) Discuss the wide variation in management of this patient population
2) Review the low risk criteria for infants deemed safe to be discharged from the emergency room
3) Review the medical evaluation of the febrile neonate and young infant
4) Discuss several difficult clinical situations one may encounter when managing the febrile neonate/young infant (traumatic/dry LP, hyperpyrexia, neonatal mastitis, concomitant viral infection)
5) Answer the question: Can you safely withhold a lumbar puncture from a febrile young infant (4-8 week old)
The Febrile Neonate and Young Infant: An Evidence Based Review
1. NEONATAL FEVER
AN EVIDENCE BASED APPROACH
1
Dan Park, MD
October 30, 2014
MUSC Pediatric Resident Noon Conference
2. 2
A lot of the work in
the ER deals with
managing risk
How comfortable do
you feel sending a
febrile young infant
home from the ER?
3. Our job is to find the
needle in the haystack.
You want to send kids home
who don’t need to be in the
hospital but you also don’t
want to miss that potentially
sick kid
4. The management of febrile
infants and neonates has
been debated since the
4
1980s
Its even tougher in the
emergency room setting
where were are evaluating
these patients in a small
window of time with
relatively limited
information with lots of
other distractions
5. 5
We’ve all been in the ER
when we’ve rolled our eyes at
what we think is super
conservative management by
an attending.
We think to ourselves, there is
no way this kid has meningitis
or bacteremia. Why are we
doing this huge work up?
There’s actually a
phenomenon for this and its
called the
Dunning-Kruger Effect.
The more you practice the
more you’ll see the crazy
cases and build a healthy
respect for the worst case
scenario.
7. 7
You want to have a healthy
respect for the worst case
scenario BUT
8. 8
You don’t want to go
overboard and utilize
precious resources,
waste people’s time,
and potentially hurt the
patient by bring them
into the hospital
unnecessarily
9. 9
And on the other end of the
spectrum, as cool as it looks,
being a cowboy can be very
dangerous from a legal standpoint.
10. 10
OBJECTIVES
Discuss the
variation in care
of febrile
neonates
Review low risk
criteria
Review the
workup of the
febrile
neonate and
young infant
Consider
several specific
difficult clinical
scenarios
1 2 3 4 5
Can we avoid
LP in the 1-2
month old?
12. 12
Variation in Care of Neonatal/Young Infant Fever Within Our Pediatric Emergency Department
Full septic w/u if <8 weeks
*
Full septic w/u if <6 weeks
Full septic w/u if <4 weeks
3 of these attendings will move this to
<4 weeks if there is a viral source
*
n=9
67%
22%
11%
13. 13
Among pediatric emergency departments across the US, does the management of febrile infants <28 days
old vary from recommended clinical guidelines?
Retrospective cohort study; 36 different children’s hospitals
Records reviewed for compliance with recommended testing (blood, urine CSF), treatment (Amp +
Gent/3rd gen ceph), management (labs, treatment, admission)
41,890 neonates evaluated; 2253 had fever
Jain S et al. Pediatrics 2014
14. Percentage of febrile neonates receiving recommended testing, management, and treatment
73%
79%
66%
14 Jain S et al. Pediatrics 2014
received recommended testing
received recommended treatment
received recommended management
3%
269 (12%) diagnosed with SBI
discharged from PED without receiving any recommended testing or treatment
16. Retrospective cohort study of febrile infants < 90 days old
37 Pediatric EDs
Assessed variation in testing, treatment, and disposition for kids in 3 distinct age groups:
<28 days, 29-56, and 57-89 days
35,070 ED visits met inclusion criteria
Aronson PL et al. Pediatrics 2014 16
17. 17
Percentage of febrile neonates/young infants receiving full septic workup
72%
49%
Neonates <28 days
Infants 29-56 days
13%
Infants 57-89 days
Aronson PL et al. Pediatrics 2014
18. This crazy graph just shows you how much variation there is in management of fever in the pediatric ER across 37 centers
Aronson PL et al. Pediatrics 2014 18
20. 20
Part of the reason there is so much variation is that everyone comes at this clinical dilemma with
different levels of knowledge and clinical experience
21. 21
With Hib and Prevnar vaccines and the development of
herd immunity the rate of occult bacteremia in older
infants and children has dropped
23. 23
For kids under 2 months
39%
of meningitis is GBS
32%
of meningitis is gram
negative
What doesn’t Prevnar, Hib and herd
immunity protect against?
Neonates are vulnerable to a whole
different sent of bugs
(GBS, E.coli, Listeria) that they can
catch vertically from mom.
And that’s part of why they’ve been set
aside in a different category when
talking about the work up for fever
24. 24
Incidence of Group B Streptococcal (GBS) disease (1990-2008)
While the rate of invasive strep pneumo has continued to drop with vaccination and herd immunity GBS haven't really changed
recently
25. 25
Prevalence of Serious Bacterial Infection (SBI) by Age
10%
5%
1%
1/5%
1/100%
0-14
14-28
28-60
pre vax
28-60
Percent Chance of SBI
(well appearing febrile neonate/infant)
post vax
>60
26. 26
UTI
Other bacterial infections (gastro, cellulitis, osteo, pneumonia)
Bacteremia
Meningitis
27. 27
Bacterial Infections in Infants < 3 months
67%
33%
Everything else Urinary tract infections
Brown LA. Crit Decis Emerg Med 2000
28. Retrospective study trying to determine rates and etiology of bacterial infection
under 2 months (n=207) during the vaccination era
Children 29-60 days
Morley et al. Pediatric Emergency Care 2012 28
Less than 28 days
2.7%
10.7%
0%
1.5%
8.5%
1.7%
Blood
Blood
Urine
Urine
CSF CSF
30. 30
Clinical scoring systems in neonates and
young infants are
NOT reliable to rule-out
serious bacterial infection (SBI)
2/3 with bacterial infections
“appeared well” to attending
Baker et al. New England Journal of Medicine 1993
31. 31
Sensitivity of Observation, History, and Exam in Detecting Serious Illnesses
McCarthy P. Pediatrics in Review. 1998
32. 474 infants 29-60 days old
Low-risk kids can be managed as outpatients
without antibiotics after a FULL septic workup
Baker et al. New England Journal of Medicine 1993 32
33. 33
Philadelphia
Age 29-60
Exam
Well-appearing
No focal infection
Labs
CSF <8, CSF gram stain neg, WBC < 15,
Band-neutrophil ratio <0.2,
UA <10 WBC/hpf,
CXR neg, Stool neg
High risk Hospitalize + empiric abx
Low risk Home, no abx, f/u within 24 hours
Baker et al. New England Journal of Medicine 1993
34. Sensitivity 98%
Specificity 50%
Positive predictive value 12.3%
Negative predictive value 99.7%
34 Baker et al. New England Journal of Medicine 1993
36. 36
When Thinking About Predictive Value of a Test…
Imagine you are the patient receiving test results of a screening test
If the test is POSITIVE,
How likely is it that you really have the disease?
How worried should you be?
If the test is NEGATIVE,
How likely is it that you really don’t have the disease?
How reassured should you be?
37. 37
64/460= 14%
d
d + c
a
a + c
d
d + b
a
TRUTH
a b
a + b
c
d
Sensitivity Specificity
PPV
NPV
64/65= 98% 286/682= 42%
286/287= 99.7%
38. 38
NPV
Sensitivity
Band:neutrophil
Baker et al. New England Journal of Medicine 1993
39. Looked at 503 febrile infants (1-3 months old)
Gave Rocephin after meeting specific low-risk criteria
Specificity 94.6%
27/503 (5.4%) had SBI
Baskin et al. J Pediatr 1992 39
40. 40
Boston Criteria
Age 28-89 d
Hx
No immunizations in preceding 48 hours
No antibiotics within 48 hours
Exam
Well-appearing
No focal infection
Labs WBC <20, CSF <10, UA <10 WBC/hpf, CXR: no infiltrate
High risk Hospitalize + empiric abx
Low risk Home, Rocephin, F/u within 24 hours
Baskin et al. J Pediatr 1992
42. 42
Looked at 931 well appearing infants <60 days old
Found SBI in 5 of 437 (1%) febrile neonates who
met low-risk criteria had an SBI
Sensitivity 92%, NPV 98.9%
Jaskiewicz JA et al. Pediatrics 1994
43. 43
Rochester
Age <60
Hx
Term
No perinatal abx
No underlying disease
Exam
Well-appearing
No focal infection
Labs
WBC >5000 and <15,000
Absolute band count <1500
UA <10 WBC/hpf
<5 WBC/hpf stool smear
High risk Hospitalize + empiric antibiotics
Low risk Home, no abs, f/u within 24 hours
Jaskiewicz JA et al. Pediatrics 1994
44. 44
NPV
No Rocephin
Jaskiewicz JA et al. Pediatrics 1994
45. 45
Boston Philadelphia Rochester
Age 28-89 d 29-60 <60
Hx
No immunizations in preceding 48 hours
No antibiotics within 48 hours
Term
No perinatal abx
No underlying disease
Exam
Well-appearing
No focal infection
Well-appearing
No focal infection
Well-appearing
No focal infection
Labs
CSF <10
UA <10 WBC/hpf
CXR: no infiltrate
WBC <20,000
CSF <8
CSF gram stain neg
WBC < 15,000
Band-neutrophil ratio <0.2
UA <10 WBC/hpf
CXR neg
Stool neg
WBC >5000 and <15,000
Absolute band count <1500
UA <10 WBC/hpf
<5 WBC/hpf stool smear
High risk Hospitalize + empiric abx Hospitalize + empiric abx Hospitalize + empiric antibiotics
Low risk Home, Rocephin, F/u within 24 hours Home, no abx, f/u within 24 hours Home, no abx, f/u within 24 hours
46. (infants 29-60 days old)
Cincinnati Children’s Evidence-Based Care Guideline 2010 46
47. 8044 infants 1-90 days with fever and normal exam
High-risk patients all admitted: <29 days of age; preterm <37 weeks; chronic conditions; abnormal WBC <5
or >15; UA >10 WBC/hpf
SBI in 9%, 99% with meningitis or bacteremia admitted on first encounter
No cases of missed meningitis
Byington et al. Pediatrics 2012 47
48. Meta-analysis of 21 studies looking at low-risk criteria for febrile infants <90
days old
Rate of SBI in low-risk patients in all studies was 2.23%
The rate of low-risk patients in prospective studies without empiric antibiotics
(variations of Rochester criteria) was significantly different: 0.67%
Huppler et al. Pediatrics 2010 48
50. 50
Estimate your pre-test probability
How likely is it that this kid has a SBI based on
literature and experience?
What are the test’s positive and negative
likelihood ratios?
How good is the test at telling me what I want to
know?
What is your post-test probability?
What is the new estimate that the kid has an
SBI?
51. 51
This is an estimate
Each test has a +/-LR
Use the nomogram
52. LR+ 1-2
USELESS
LR+ 2-10 MOD
LR+ >10 STRONG
LR- 0.5-1
USELESS
LR- 0.1-0.5 MOD
LR- <0.1 STRONG
52
56. Is WBC a good screen for bacteremia in kids 0-90 days old undergoing a full sepsis eval?
No
Bonsu et al. Ann Emerg Med 2003 56
57. Is WBC a good screening tool for febrile kids <90 days who need an LP?
No
Bonsu et al. Ann Emerg Med 2003 57
58. LR- 0.5-1 USELESS
LR- 0.1-0.5 MOD
LR- <0.1 STRONG
234 infants
30 had SBI (12.8%)
For identifying definite and possible serious bacterial infections, a cutoff value of
0.12 ng/mL had a sensitivity of 95.2%, specificity of 25.5%, negative predictive value of 96.1%,
and a negative likelihood ratio of 0.19
All cases of bacteremia were identified accurately with this cutoff value
Maniaci V et al. Pediatrics 2008 58
59. 1112 infants <3 months old
fever without a source
23 cases of SBI (2.1%)
PCT better than CRP in
identifying kids with SBI
LR- 0.5-1 USELESS
LR- 0.1-0.5 MOD
LR- <0.1 STRONG
Gomez B et al. Pediatrics 2012 59
LR+ 1-2 USELESS
LR+ 2-10 MOD
LR+ >10 STRONG
60. LR- 0.5-1 USELESS
LR- 0.1-0.5 MOD
LR- <0.1 STRONG
LR+ 1-2 USELESS
LR+ 2-10 MOD
LR+ >10 STRONG
Bilavsky E et al. Acta Paediatrica 2009 60
64. Everyone gets blood, urine, csf+ abx+
64
admission
Viral URI sx DO NOT count as a fever
source
H&P are UNRELIABLE to rule out SBI
UTI (20%) >>> Bacteremia (3%) >>
Meningitis (<1%)
E. Coli, GBS, HSV >> Listeria,
Salmonella, Staph. aureus
Neonates
Birth to 28 days
65. 65
Neonates will have picked up
bacteria from the birth canal
Herd immunity doesn’t help
against what mom can give you
Immune system sucks
Very little shield between
blood/brain/urine
(membranes are wide open)
Neonates
Birth to 28 days
67. 67
Young Infants
29-60 days
Viral sx MAY count as a fever
source
UTI (15%) >>> bacteremia (1%)
>>> meningitis (0.2-0.4%)
Invasive bacterial infection (IBI)
rate 1/100 to 1/1000
E. coli, GBS, S.pneumo
>>>N.meningitides, H. flu, Staph.
aureus
Classically: Blood, urine, CSF, +/-
antibiotics, +/-admission
68. 68
Older Infants
>60 days
Higher threshold to prompt a
work up >39 C (102.2 F)
Females <24 mo:
UA/UCx
Uncircumcized Males <6 mo:
UA/UCx; consider in <12 mo
Circumcized males:
consider UA/UCx in <6mo
69. 69
Odds are in your favor:
physiology + vaccinations
Occult bacteremia rates
becoming very very low
(<0.5%)
False positive blood
culture rate is higher than
rate of occult bacteremia
Physical exam is useful
Older Infants
>60 days
70. viral syndrome
(documented/suspected)
including bronchiolitis
70
9.5%
6%
0.5%
UTI
Other (gastro, PNA,
AOM, aseptic
meningitis)
Bacteremia
Evaluation of 429 febrile infants 57-180 days old
SBI rate 10.3%
Most of which were UTI and no bacterial meningitis was
diagnosed
No infants, aged 2-3 months had a positive blood culture
This suggests that infants 2-3 months of age perhaps can be
managed less conservatively and be grouped with their older
counterparts
84%
presumed or
documented viral
illness/bronchiolitis
Hsiao AL et al. Pediatrics 2006
71. “CBC+ selective blood culture and treatment using a WBC cutoff of 15 is cost
effective at the current rate (2001) of pneumococcal bacteremia. If the rate of
occult bacteremia falls below 0.5% with widespread use of the conjugate
pneumococcal vaccine, then strategies that use empiric testing and treatment
should be eliminated”
71 Lee GM et al. Pediatrics 2001
72. 72
Looked at rate of occult bacteremia in
8408 well appearing febrile children aged 3 to 36 months:
0.25%
Wilkinson M et al. Acad Emerg Med 2009
73. 73
392 febrile children aged 1-36 months retrospectively reviewed
Occult bacteremia rate 0.34%
Literature review identified 10 relevant studies that showed an overall bacteremia
rate <1% for kids aged 3-36 months
with rates <0.5% in settings with high PCV-7 coverage
Bressan S et al. Acta Paediatrica 2011
74. 74
Blood culture contamination rate is around 2-3% (0.6%-6% range)
Hall KK et al. Clinical Microbiology Reviews 2006
76. 76
Dry or Traumatic Tap
At a minimum, cultures of blood and urine should be
obtained.
If the LP is traumatic, the tube in which the CSF is
clearest should be sent for a cell count.
Two acceptable approaches:
A repeat lumbar puncture after admission, or observing
the infant in the hospital off antibiotics after the cultures
are negative at 48 hours
79. Trautner BW et al. Pediatrics 2006 79
Kids <18 yo with temp >106 (41.1)
Serious bacterial infection
Lab confirmed viral illness
Bacterial/viral coinfection
Children presenting to ED with hyperpyrexia are at high risk for SBI
Equally high risk for a viral illness
Viral symptoms associated with decreased risk of SBI
Diarrhea associated with increased risk of SBI
19%
21%
1%
80. Over 5000 infants younger than 3 months
with fever were retrospectively reviewed
98 patients (1.7%) had temp >40
Prevalence of SBI among febrile infants
>40 C was 38% compared with those with
fever <40 C 8.8%
Stanley R et al. Pediatric Emergency Care 2005 80
81. 81
Lets say a 5 week old full term infant
comes into your ED with this.
Afebrile. No systemic sx.
Well appearing.
What do you do?
Mastitis
83. Admission rates for pustulosis, cellulitis, abscesses were 13%, 84%, and 55%, respectively
83
Retrospective cohort study of patients 0-28 days seen in 2 large PEDs for SSTIs
136 neonates identified, 104 met inclusion criteria
Blood cultures obtained in 13% pustulosis, 96% of cellulitis, 69% of abscesses
No SBI noted
Kharazmi SA et al. Pediatr Emer Care 2012
84. 84
Retrospective case series
Included patients from birth to 120 days
130 patients identified, 94 included in study
No infant with a positive breast culture had
a positive blood, urine, or CSF culture
Recommendations:
No LP in well appearing afebrile infants with mastitis
Consider LP in infants <60 days old with mastitis and fever
Montague EC et al. The Pediatric Infectious Disease Journal 2013
86. 86
844 febrile infants ≤60 days of age who were tested for influenza,
A significantly lower rate of serious bacterial illness (SBI) was noted in the 123 infants who were
influenza-positive compared with the 721 infants who were influenza-negative:
2.5 percent versus 11.7 percent
If the CBC and urinalysis do not suggest bacterial infection, lumbar puncture can be omitted in well-appearing
febrile infants who are older than 28 days of age, have a positive rapid influenza test, and no evidence of
bacterial infection on physical examination.
Mintegi S et al. Pediatric Infectious Disease Journal 2009
87. 705 febrile kids 0-36 months
Lower incidence of bacteremia, UTI, pneumonia, or any SBI in kids
found to have influenza A
10% SBI rate in Flu A + vs. 28% SBI rate in Flu A -
Smitherman HF et al. Pediatrics 2005 87
88. 88
Prospectively looked at 448 febrile infants <3months with and without bronchiolitis
SBI in 30/312 (9.6%) infants without bronchiolitis and 3/136 (2.2%) with bronchiolitis
Bilavsky E et al. Pediatr Infect Dis 2008
90. Retrospective cohort study of febrile
Titus MO et al. Pediatrics 2003 90
infants <8 weeks
174 kids with fever and a positive RSV
test were matched with 174 kids with
fever and a negative RSV test
2 patients in RSV group had SBI (both
UTI) vs. 22 in control group
92. 1248 febrile patients <60 days enrolled into prospective cross-sectional study
7% SBI rate for RSV+ infants vs. 12.5% SBI rate for RSV- infants
Levine DA et al. Pediatrics 2004 92
93. 5.5% of RSV+ infants had UTI
Febrile infants with RSV are less likely to have SBIs
but its probably wise to get a urine culture on these kids
Levine DA et al. Pediatrics 2004 93
95. 95
<28 days >28 days
So what have we learned about who needs a full work up?
Low risk criteria have been studied extensively in the last 20 years
Rochester criteria have been shown to have really good negative predictive value for SBI
We can’t trust kids less than 1 month old: these kids get the full workup no matter what
Older infants >2 months can be treated like older kids
The kids in between, if they have a viral source probably don’t have bacteremia or meningitis
and likely only need a urine culture
96. Algorithm for Managing Fever of Unknown Source in Neonates (0-28 days)
Evidence-Based Care Guideline for Fever of Unknown Source. Cincinnati Children’s Hospital Medical Center 2010
Start
Diagnostic tests
CBC with diff, blood culture
UA, urine culture
CSF
Stool culture (if diarrhea)
CXR (if tachypneic, hypoxemic, etc.)
Focal Infection?
Admit
Antibiotics
(Amp, Gent/Cefotax)
CSF pleocytosis AND
negative CSF gram stain?
Consider CSF HSV PCR and
antiviral therapy
Off the algorithm
Evaluate and treat as appropriate to site and severity
Yes
No
Yes
97. Algorithm for Managing Fever of Unknown Source in Young Infants (29-60 days)
Evidence-Based Care Guideline for Fever of Unknown Source. Cincinnati Children’s Hospital Medical Center 2010
Start
Diagnostic tests
CBC with diff, blood culture
UA, urine culture
Stool culture (if diarrhea)
CXR (if tachypneic, hypoxemic,
etc.)
Focal Infection?
Off the algorithm
Evaluate and treat as appropriate to site and severity
Low-risk criteria met?
CSF
Start antibiotics
Admit
Yes
No
No
Yes
98. Algorithm for Managing Fever of Unknown Source in Young Infants (29-60 days)
Admit for observation until cultures negative
If condition worsens: CSF, antibiotics
No social or family concerns?
Available reliable follow-up in 12-24 hours?
Adequate parental education?
Outpatient plan OK with PCP and family?
Consider outpatient management with
or without antimicrobial therapy
Get CSF if antibiotics will be started
Plan to follow-up in 12-24 hours
Evidence-Based Care Guideline for Fever of Unknown Source. Cincinnati Children’s Hospital Medical Center 2010
Yes
No
99. 99
Variation
in Care
There’s still debate regarding
who gets a full septic work up
Respect the worst case
scenario
How comfortable are you
sending this kid home without a
full workup?
101. 101
The
Workup
Kids < 28 days get a full septic work up
and admission
Kids > 28 days get blood and urine +/-
CXR, stool, RVP
Kids >60 days with a high fever
consider urine
Kids >60 days don’t get routine blood
cultures anymore b/c occult bacteremia
rate is so damn low
Sick looking kids get full septic work
up
102. 102
Difficult
Clinical
Scenarios Dry tap? Admit, re-tap later or follow
cultures if looking well
Traumatic tap? Remember 1:1000
WBC:RBC ratio
Really high fever?
Consider empiric antibiotics if no viral
source
Infant with mastitis?
<1 month full w/u
>1 month blood culture, abx, admit
4-6 week febrile infant with viral source?
Urine is probably enough
then home if low risk
103. 103
Can we avoid LP
in the 1-2 mo?
Yeah, probably.
If low risk and
viral symptoms
you can make a
pretty strong case
to your attending
that you can get
away with no LP
the prevalence of SBI is different in neonates and they are trickier from a physical exam and immune system standpoint
Ultimately its about balancing spending unnecessary resources
The goal of the talk is to discuss the dilemma of what to do with the well-appearing febrile infant in the ER but showing you the most recent evidence
Especially the kids between 4 to 8 weeks of age.
There is little controversy regarding management of sick looking infants with fever.
The debate for the past few decades has been what febrile young infants can we call LOW RISK so we can confidently send home?
Bela Lugosi in Dracula 1931
Neonate <4 weeks
Young infant 4-8 weeks old
My goal for the lecture is to present the most recent evidence to determine when we can avoid an LP in a febrile infant
Prior to the advent of PVC 7 the most likely cause of bacteremia was strep pneumo (80-90%)
The incidence of step pneumo infections has dropped approximately 80%
PVC 13 is kiely to drop the incidence further; this vaccine specifically addresses serotype 19A which had increased in frequency.
We are now seeing only 0.2-0.5% incidence of strep pneumo (2-3% before 2000).
prevalence of SBI changes with age and immunization status
Depending on the study you look at the prevalence of SBI in neonates may be even higher up to 20%
Viral infections are by far the most common cause of febrile illness in infants
approx 90% of young infants and neonates with fever will have a viral source
UTI, bacteremia, and meningitis occur in descending order
the most common SBI with a normal exam
UA normal in 10-20%, always send a culture
Boris Karloff in Frankenstin(1931)
What do we know? We know that physical exam is unreliable in young infants and especially neonates
12-28% of febrile neonates have SBI, and a high rate of missed SBIs exist.
(Ishimine, EM Clinics of N Amer, 2007)
Ill appearing infants or abnormal vital signs make your job easier
Toxic appearance: poor perfusion, poor tone, poor feeding
your ability to rely on the physical exam does get better as the kids get older
If you can’t rely solely on the physical exam in these kids how can we send anyone home and feel good about it?
In the 90s three centers asked this question and developed low risk criteria. These are the Boston, Philly, and Rochester criteria that you keep hearing about.
There are a few ways to figure out how valid your test is, in our case Boston criteria.
Sensitivity—how accurate the screening test is in identifying disease in people who actually have the disease (left hand column)
Specificity gives you the probability that people without the disease will have a negative screening test (right hand column)
A high sensitivity test is reliable when its result is negative, since it rarely misdiagnoses those who have the disease.
Positive predictive value is the probability that people with a positive screening test truly have the disease (true positives/ all positive test results)
Negative predictive value is the probability that people with a negative screening test don’t have the disease (true negatives/all negative test results)
NPV 99.7. Only one false negative
Study showed that their low risk criteria can accurately identify infants unlikely to have SBI. Infants who meet low risk criteria can be carefully observed without administering antibiotics
Boston and Philly excluded kids under 28 days old
A retrospective study applied their low-risk criteria to febrile infants 1-18 days old an showed a negative predictive value of 97% for both protocols
(you’ll miss 3% of febrile neonates <28 days with SBI using these protocols)
without reliance on empiric antibiotic treatment it would be essential to capture all infants at risk of early deterioration in the high-risk group
careful sample collection, as well as meticulous physical examination ,excluded infants with SBIs from the low-risk group
*Key Point- ideally, your goal is to order diagnostic tests that make post-test probability SIGNIFICANTLY HIGHER OR LOWER in order to get closer to definitively ruling in or ruling out a condition.
LR+ of 1-2 represents a diagnostic test that is useless in terms of ruling in a condition.
LR+ of 2-10 represents a diagnostic test that is of moderate value (it helps to increase probability of a condition but often does not definitively rule it in).
LR+ of greater than 10 represents a diagnostic test that of strong value and can often definitively rule in a condition.
LR- of 0.5-1 represents a diagnostic test that is useless in terms of ruling out a condition.
LR- of 0.1-0.5 represents a diagnostic test that is moderately useful in ruling out a condition (it helps to decreases probability of condition but often does not definitively rule it out).
LR- of less than 0.1 represents a diagnostic test that is of strong value and can often definitively rule out a condition.
No
No
Boris Karloff in The Mummy (1932)
high prevalence of SBI in febrile neonate (~10%)
5% in kids between 2-4 weeks of age
+acyclovir for any of the following: elevated WBC in CSF, vesicular lesions, seizures
Stool and CXR if warranted
Immunity changes as a child gets older—infants in the first few months of life have decreased opsonin, macrophage function, and neutrophil activity (pic).
Baby’s immune system IgG crosses placenta but IgM doesn’t come until later
IgA is responsible for mucosal immunity
occult bacteremia= bacteria in the bloodstream without an obvious source
This study looked at kids 2 months to 6 months
No cases of meningitis
5% false positive blood cultures
45% UTI in infants with +viral source
UTI cultures mainly e.coli
this cost effectiveness study in 2001 looked at febrile infants between 3 months to 3 years old
Long Chaney, Jr. in The Wolf Man (1941)
For patients with a peripheral white blood cell (WBC) count that is in the normal range, one rule of thumb is to subtract one WBC for every 500 to 1500 red blood cells.
103,828 visits, 103 kids with hyperpyrexia
largest prospective study of hyperpyrexia in the post-Hib vaccination era.
medical emergency that carries a high risk of SBI
Recommend treatment with antibiotics for all children with hyperpyrexia who don’t have a confirmed viral illness
neonatal mastitis occurs most commonly in full term infants within the first 8 weeks of life; typically with unilateral swelling, erythema, and induration of breast, systemic manifestations are rare
S. aureus is the most common causative organisms
breast hypertrophy from maternal hormones predisposes breast infection
Full work up blood urine csf in kids less than 1 month or any young infant who is ill appearing
this is a topic that has generated a lot of literature in the past 10 years so i’ll spend a few minutes reviewing a few studies
There’s a much lower risk of SBI in febrile kid with documented influenza
123 influenza + kids had a 2.5% serious bacterial infection rate (2.4% UTIs) with no bacteremia or meningitis.
The three infants with SBI in the influenza-positive group all had a urinary tract infection (UTI); none had bacteremia or meningitis.
most of the SBIs were pneumonia
only 1 flu positive kid had bacteremia
no meningitis in kids with flu
findings suggest that it may be reasonable to limit laboratory testing in well-appearing febrile infants older than 28 days of age with bronchiolitis to CBC, blood culture, urinalysis, and urine culture. If the CBC and urinalysis do not suggest bacterial infection, then these children may be managed without antibiotics according to the degree of illness caused by their bronchiolitis.
1779 infants enrolled
retrospective study
looking at rate of SBI in High and Low risk febrile infants with and without viral infections
Kids with documented RSV infection are found to be at lower risk of SBI compared to their RSV-negative counterparts
Take home: if you have a febrile young infant with RSV you probably don’t have to go searching for bacteremia or meningitis. But getting a urine is appropriate.
The best known are from the PECARN network and include kids <60 days. The 269 RSV+ kids had a 7% SBI rate (5.4% UTIs and 1 case of bacteremia- no meningitis). I don't think we have enough patients to guarantee that there is no risk of bacteremia or meningitis, but it is unlikely enough that it is not unreasonable to consider a good discussion with the family and careful follow-up in lieu of LP/ceftriaxone in most cases. Still have to do the urine
There are several studies on patents with viral infections that found they are less likely to have serous bacterial illness but none of the studies are sufficiently powered to exclude meningitis. Levine DA et al. Pediatrics 2004. Showed urinary tract infections in 5.4% and a small amount of bacteremia. The incidence of SBI in patients with RSV did decreased, but the study wasn’t powered for meningitis or bacteremia. All 3 cases of bacteremia (out of 267 patients with RSV) were under 1 month of age and there were no cases of meningitis.
Claude Raines in The Invisible Man (1933)
The bottom line is that a small risk of serious bacterial infection remains for even low-risk patients with a documented viral illness. Know ahead of time what level of risk you are comfortable accepting for your patients. The serious bacterial infection risk for meningitis is very very low.
Low-risk infants over 30 days of age with or without positive viral testing can probably be sent home without a spinal tap. (Cincinnati adapted Rochester criteria for their current guidelines)
There’s still gray area between 4-6 weeks.
But if you have a viral source and a negative urine in a well appearing infant you can feel pretty confident that you’re not sending a sick kid home
