pediatric infectious diseases lecture.1st step to earn

1. Fever Without a Focus in the
Neonate
and Young Infant
BY:
Dr, WALAA SALAH MANAA
CONSULTANT OF PEDIATRIC & INFECTION.
‫الشـيخ‬ ‫كـفر‬ ‫حمـيات‬ ‫مـستشفى‬

4.  For this age-group (0-3 mo), fever
without a focus refers to a rectal
temperature of 38°C (100.4°F) or
greater,
without other presenting signs or
symptoms.

5. The evaluation of these patients can
be challenging because of the difficulty
distinguishing between a serious
infection (bacterial or viral) and a self-
limited viral illness

6. Three age groups are typically
considered:
-neonates 0-28 days,
-young infants 29-90 days,
-children 3-36 mo.

7. Etiology and Epidemiology

8. Serious bacterial infection (SBI)
 occurs in 7% : 13%.
 In this group, the most common SBIs are
-(UTI; 5–13%),
- bacteremia (1–2%)
-meningitis (0.2–0.5%).
.

9.  -the most common organism causing
SBI,
 Escherichia coli
 followed by group B streptococcus (GBS).
 The decrease in GBS infections is related to increased
screening of pregnant women and use of intrapartum antibiotic
prophylaxis.
-Other, less common organisms include
 Klebsiella spp.,
 Enterococcus spp.,
 Streptococcus pneumoniae ,
 Neisseria meningitidis , and
 Staphylococcus aureus.
 Listeria monocytogenes is a rare cause of neonatal
infections,potentially related to changes in public health
education and improvements in food safety

10. Herpes simplex virus (HSV ) infections
should also be considered in febrile
neonates <28 days old.
Neonatal HSV is rare, with a prevalence
of 0.2–0.3% among febrile neonates.
Most of these infections are
caused by HSV type 2, though HSV type
1 can also cause neonatal infection.

11. -Neonates with
disseminated disease and
skin, eye, and mouth
(SEM) disease typically
present at 5-12 days of
life.
Neonates with central
nervous system (CNS)
disease generally
present at 16-19 days.

13. -In febrile infants who appear well, viral illnesses
are much more common than bacterial or serious
viral infections.
The most common viruses include
 respiratory syncytial virus (RSV ),
 enteroviruses ,
 influenza viruses ,
 parainfluenza viruses,
 Human metapneumovirus ,
 adenovirus , parechoviruses
 rhinovirus

14. Clinical Manifestations

15. isolated fever or
nonspecific
symptoms,
 making diagnosis of
serious illnesses
challenging.

16.  signs of systemic illness at presentation,
 including abnormal temperature (hypothermia
<36°C, fever ≥38°C
 abnormal respiratory examination (tachypnea
>60breaths/min, respiratory distress,
apnea),
 abnormal circulatory
examination(tachycardia >180 beats/min,
delayed capillary refill >3 sec, weak or
bounding pulses),
 abnormal abdominal examination,
 abnormal neurologic examination(lethargy,
irritability, alterations in tone),
 abnormal skin examination (rash, petechiae,
cyanosis).

18.  Infants with septic
arthritis or osteomyelitis
may appear
well except for signs
around the involved joint
or bone or may only
manifest with
pseudoparalysis (disuse)
and paradoxical irritability
(pain when attempting to
comfort the child).

19. Diagnosis

20.  Traditionally, all neonates <60 or <90
days of age were hospitalized;
underwent laboratory evaluation of the
blood, urine, and (CSF); and received
empirical antibiotics.
 Additionally, some patients had stool
cultures, chest radiographs, HSV
evaluation, and/or received empirical
antiviral agents

21. Of the 3 widely
used criteria, only
the Rochester
criteria allow
neonates ≤28 days
to be designated as
“low risk” and
 managed outside
the hospital without
antimicrobials.

22. • the Boston and Philadelphia criteria to
neonates, 3–4% of those classified as
low risk had SBI.
• Based on these protocols, all infants
following the Boston or Philadelphia
criteria would undergo lumbar puncture
(LP), whereas low-risk infants following
the Rochester criteria would not.

24. Viral Respiratory
Illness
• Several studies have demonstrated
a decreased risk of SBI in infants
with positive testing for influenza
or RSV, although the risk of UTI
remains significant.
• young febrile infants with
bronchiolitis may not require LP,
particularly if they can be closely
observed or have close follow-up.

25.  Urinary Tract Infection and Bacterial
Meningitis
 Traditionally, infants with abnormal findings on urinalysis (UA)
would undergo complete evaluation for infection, including LP.
 In well-appearing infants >28 days old with an abnormal UA,
some evidence suggests that the risk of bacterial meningitis is
extremely low, <0.5%.
 For neonates 0-28 days, the risk of concomitant bacterial
meningitis with UTI is 1–2%.

26. Laboratory Diagnosis

27. 1-Complete Blood Count
 The (CBC) and differential are frequently obtained when
evaluating febrile neonates and infants. The white blood cell
(WBC) count alone cannot accurately predict SBI risk.
 In one series, isolated use of the WBC cutoffs in the
Rochester criteria, outside 5-15,000 WBCs/mm3 , would
miss at least 33% of infants with bacteremia and 40% of
those with meningitis.
 A prospective study found no increased risk of SBI in
febrile, well-appearing infants with leukopenia (WBC count
<5,000/mm3 ).
 The WBC count combined with other factors may help
determine an infant's risk of SBI, but it should not be used
in isolation to predict infection risk.

28. 2-Blood Culture
 The ability to identify pathogens in the
blood depends on the :
 volume of blood,
 the timing of the blood culture in relation to
antimicrobial administration,
 lesser degree, on the number of blood
cultures obtained.
 A negative blood culture does not eliminate
the risk of bacterial meningitis.

29. 3-Urine analysis
 Traditional UA
consists of dipstic
biochemical analysis
of urine for:
nitrites or
leukocyte esterase
microscopic
examination of the
urine for WBCs and
bacteria.

30. 4-Cerebrospinal Fluid
 CSF evaluation consists of
 culture and
 Gram stain,
 cell count,
 glucose and protein.
 (PCR) testing may also be sent
based on the clinical scenario,
usually for enterovirus or HSV.
 some infants with normal CSF
parameters may have CNS
infections .

31. The interpretation of CSF
can be challenging in the
setting of a traumatic LP,
where the CSF is
contaminated with peripheral
blood.
The formula is:

32.  Treatment with antibiotics prior to LP can
complicate the interpretation of CSF
parameters.
 CSF cultures are negative relatively rapidly after antibiotic
administration, within 2 hr for N. meningitidis and 4-24 hr
for S.pneumoniae.
 In patients with bacterial meningitis, CSF glucose increases
to normal range,usually within 4-24 hr of antibiotic
administration,
 while CSF protein concentrations, despite decreasing,
remain abnormal for >24 hr after antibiotic administration.
 Changes in CSF WBC count and absolute neutrophil count
are minimal in the 1st 24 hr of antibiotic therapy..

33. 5-Herpes Simplex Virus Testing
• Historical and clinical features that should raise concern for
HSV include
 exposure to individuals infected with HSV, particularly
mothers with primary HSV infections or first-time genital
infections,
 seizure or abnormal neurologic examination,
 vesicular rash,
 ill appearance, apnea, hypothermia, petechial rash/excessive
bleeding, or a history of a scalp electrode.
• laboratory studies performed:
-surface cultures of any vesicles;
-CSF PCR (sensitivity:75–100%);
-Blood PCR;
-ALT.

34. 6-Enterovirus Testing
 Enterovirus is a common
and typically benign cause
of fever in febrile
infants.
• Enterovirus PCR testing
of the CSF is a sensitive
and rapid means to
diagnose infection.

35. 7-Other Diagnostic Studies
• Investigations have examined the utility of
inflammatory markers such as (CRP) and serum
procalcitonin (PCT) in the diagnosis of SBI and,
more specifically, IBI (bacteremia and
meningitis).
• One meta-analysis reported that PCT is superior
to WBC count and CRP for the detection of IBI
in children <3 yr old, whereas another found
that PCT was inferior to prediction rules in
identifying SBI in young infants.

36.  Chest radiographs are
unlikely to be clinically
useful in the evaluation
of the febrile infant
without respiratory
symptoms.

37. Treatment

38. Antimicrobials
• Commonly used regimens include
(1) a third-generation cephalosporin (typically cefepime),
(2) a third-generation cephalosporin and ampicillin, or
(3) an aminoglycoside and ampicillin

39.  Ampicillin is the preferred treatment of GBS and
covers L. monocytogenes and many Enterococcus
spp.
 For neonates 0-28 days, options 2 or 3 have been
recommended, given the risk of L. monocytogenes .
• For young infants >28 days, option 1 (third-
generation cephalosporin: ceftriaxone) can be a
reasonable choice.

40.  For ill-appearing infants or those with positive
CSF Gram stains, additional antibiotics may include
vancomycin or broad-spectrum antibiotics such as
carbapenems.
 Neonates with concern for HSV should be
empirically treated with high-dose acyclovir (60
mg/kg/day).
 Treatment duration and route of antimicrobial
administration depend on the infection.

41. Discharge From the Hospital
• Traditionally, infants remained
in the hospital receiving
antimicrobial therapy until
bacterial cultures were negative
for 48 hr or even longer.
 91% of blood cultures were
positive by 24 hr and 96% by
36 hr.
 All positive CSF cultures grew
within 24 hr .
 For blood cultures, 1.3% grew
after 24 hr.
 for urine cultures, 0.9% grew
after 24 hr.

42. Prognosis
 Most well-appearing neonates
and young infants with fever
recover completely and
relatively quickly, depending on
the etiology of the fever.
 The mortality of bacterial
meningitis varies by pathogen,
but ranges from 4–15%.