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Fever
Natt Arayapong, MD
Approach to Acute Febrile Illness
• Definition: Rectal temperature ≥ 38.3°C, < 1 week
• History: Physical examination
• Pattern of fever and Length of illness
• Localizing symptoms
• Immunization status
• Prior use of medication
• Underlying disease
• Travel, contacts, animal and insect exposure
Management of Fever without source
• Infants 0 to 28 days of age
• Infants 29 to 90 days of age
• Infants 3 to 36 months of age
• Children aged 3 years to adulthood
Infants 0 to 28 days of age, Temp ≥ 38oC
• Infants 3 to 28 days old with temp. ≥ 38 oC 254 cases
• 32 (12.6%) had an Serious bacterial illness (SBI)
Arch Pediatr Adolesc Med. 1999 May;153(5):508-11.
Infants 0 to 28 days of age, Temp ≥ 38oC
• Sepsis work up:
• CBC, LFTs, Blood culture
• Urinalysis, Urine culture
• Lumbar puncture:
• HSV PCR if CSF pleocytosis
• Chest X Ray
• Viral study
Infants 0 to 28 days of age, Temp ≥ 38oC
Bacterial pathogens
• group B
streptococcus
• E.coli
• L.monocytogenes
Empirical antibiotics
• Ampicillin plus Gentamicin
• Ampicillin plus Cefotaxime
• Vancomycin
(gram positive on CSF gram
stain or risk for S.aureus)
Empirical acyclovir
• if risk factors for HSV disease
exist
Infants 29 to 90 days of age, Temp ≥ 38oC
Well – appearing Ill – appearing
Infants 29 to 90 days of age, Temp ≥ 38oC
Ill – appearing
Admit & Sepsis work up &
Parenteral antibiotic
Pathogens
• Neonatal pathogens
• H.influenzae, N.meningitides
• S.pneumoniae
Cefotaxime + Ampicillin
Infants 29 to 90 days of age, Temp ≥ 38oC
Well – appearing
Low – risk criteria
Outpatient management
YES
Clinical criteria
• Previously healthy
• No focal bacterial infection
Laboratory criteria
• WBC 5000 to 15000/mm3
• Band < 1500/mm3
• Normal UA
• Normal CSF, Stool exam
• (if obtained)
Infants 29 to 90 days of age, Temp ≥ 38oC
Low risk criteria  Outpatient management
• Blood culture
• Urine culture
• Treat suspected influenza
Option 1
• Lumbar puncture
• Ceftriaxone 50 mg/kg IV/IM
• Reevaluation in 24 hours
Option 2
• No antibiotics
• Reevaluation in 24 hours
Infants 3 to 36 months of age, T ≥ 39oC
Well – appearing Ill – appearing
Infants 3 to 36 months of age, T ≥ 39oC
Ill – appearing
Sepsis work up
• Blood culture
• Urine culture
• Lumbar puncture (meningitis is suspected)
• Chest X Ray
(tachypnia & WBC > 20,000/mm3)
Infants 3 to 36 months of age, T ≥ 39oC
Ill – appearing
Sepsis work up
Parenteral antibiotic
Pathogens
• H.influenzae type B
• N.meningitides
• S.pneumoniae
• S.aureus
Ceftriaxone & Cefotaxime
Infants 3 to 36 months of age, T ≥ 39oC
Well – appearing
Complete
Incomplete
Occult Bacteremia
• Bacteria in the blood
• Well – appearing febrile child
• Absence of an identifiable focal bacterial source
Prevalence of occult bacteremia
1. J Pediatr. 1983 Sep;103(3):352-8.
2. Arch Pediatr Adolesc Med. 1998 Jul;152(7):624-8.
3. Pediatrics. 2000 Sep;106(3):505-11.
4. Arch Pediatr Adolesc Med. 2004 Jul;158(7):671-5.
5. Acad Emerg Med. 2009 Mar;16(3):220-5.
Pathogenic bacteria cultured from patients with occult bacteremia
1. Arch Pediatr Adolesc Med.
1998;152:624-628.
2. Pediatrics. 2000 Sep;106(3):505-11.
Evaluation of febrile young infants
• Boston
• Philadelphia
• Rochester
• Lab-score
• Step by step
Boston protocol
• Prospectively evaluated 503 28- to 89-day-old infants with rectal
temperature greater than 38ºC (100.4ºF)
• Criteria:
• No immunizations or antimicrobials within the preceding 48 hours
• No evidence of dehydration, ear, soft tissue, or bone infection
• Overall well appearance
• Caretaker available by telephone
• The laboratory criteria defining low-risk patients included:
• Peripheral white blood cell (WBC) count less than 20,000/microL
• CSF with WBC <10/microL
• UA <10 WBC per high-powered field
• No infiltrate on chest radiograph if one was obtained
• Ceftriazone 50 mg/kg im, F/U 24 hr
• 27 (5.4%) had SBI
Philadelphia protocol
• 8-year experience with 747 infants 29- to 60-days of age with a rectal
temperature ≥38.2ºC (100.8ºF)
• Low-risk criteria included patients who were well-appearing with:
• WBC <15,000/microL
• Band-neutrophil ratio <0.2
• UA <10 WBC/hpf and a negative urine Gram stain
• CSF <8 WBC/microL and a negative CSF Gram stain
• Chest radiograph lacking an infiltrate if one was obtained
• Stool without blood and few or no WBCs on the smear in infants with
diarrhea
D/C and F/U 24 hr
Sensitivity 98 %(95% CI 92-100); specificity 42 %(95% CI 38-46);
PPV 14 %(95% CI 11-17); NPV 99.7 %(95% CI 98-100)
Rochester protocol
• Identify low-risk febrile infants (defined as a rectal temperature
greater than or equal to 38.0ºC or 100.4ºF) younger than 60 days
• Clinical criteria:
• ≥37 weeks gestation, and hospitalized no longer than the mother
• Infant was previously healthy
• Infant was well-appearing, with no ear, soft tissue, or bone infections
• LAB:
• WBC 5,000 to 15,000/microL with an absolute band count <1,500/microL
• Urinalysis with <10 WBC/hpf and no bacteria seen
• Stool with <5 WBC/hpf if obtained D/C with F/U
Five had SBI, NPV 98.9 %(95% CI 97-100)
Lab score
Step by step
Pediatrics. 2016 Aug;138(2).
• IBI 79.3% (22/26
sepsis, 9/10
meningitis)
• Non IBI 98.5%
Infants 3 to 36 months of age, T ≥ 39oC Well – appearing
Immunization incomplete
WBC ≥ 15,000/mm3  H/C
WBC > 20,000/mm3  CXR
CBC, UA, Urine culture
Infants 3 to 36 months of age, T ≥ 39oC Well – appearing
Immunization incomplete
WBC ≥ 15,000/mm3
CBC, UA, Urine culture
• Ceftriaxone (50 mg/kg/dose) IM
• Outpatient follow up within 24 hrs
• Admit for parenteral antibiotic
Antimicrobial treatment of occult bacteremia: a
multicenter cooperative study.
Children 3 to 36 months, T ≥ 39.5oC without focus of infection
WBC < 15,000/mm3 WBC ≥ 15,000/mm3 WBC ≥ 30,000/mm3
H/C positive 5 of
182, 2.7%
H/C positive 55 of
331, 16.6%
H/C positive 9 of 21,
42.9%
Pediatr Infect Dis J. 1993 Jun;12(6):466-73.
Occult pneumonias: empiric chest radiographs in
febrile children with leukocytosis
CXR were obtained in 225 cases
With respiratory
symptom, 79 case
With leukocytosis ≥
20,000/mm3, 149 cases
Pneumonia, 32 of 79 (40%) Pneumonia, 38 of 146 (26%)
Ann Emerg Med. 1999 Feb;33(2):166-73.
Infants 3 to 36 months of age, T ≥ 39oC Well – appearing
Immunization complete
Sign & Symptoms of UTI
• Girls < 24 mo of age
• Uncircumcised boys < 12 months of age
• Circumcised boys < 6 months of age
UA, Urine culture
NO YES
UTI
Diagnosis
• Urinalysis
• leukocyte esterase, nitrite +Ve
• WBC > 5 cells/HPF
• Uncentrifuge urine G/S > 1 organism/oil field
• Urine C/S
• Suprapubic aspiration: age < 2 yr, phimosis, labial adhesion
• Urethral cath > 104 CFU/mL
• Clean-catch, mid stream void > 105 CFU/mL
• Staphylococcus saprophyticus, Mycobacterium and Candida  correlate with
clinical
coagulase-negative staphylococci (CoNS), novobiocin resistant
Co-trimoxazole, fluoroquinolone
Managment
• ATB
• Upper UTI or fever 7-14 d
• Cystitis 3-7 d
• 1st UTI  U/S KUB, not recommend routine VCUG if U/S normal
• Recurrent UTI  U/S KUB, VCUG if not done before
Antibiotics prophylaxis
• Not recommend routine ATB prophylaxis in 1st UTI
• Consider in patient that has to do VCUG
• High-grade reflux and underlying obstructive/complex uropathies
Renal abscess • Pyelonephrosis
• accumulation of purulent debris and
sediment in the renal pelvis and urinary
collecting system
• Symptoms: severe pyelonephritis,
persistent + signs of hydronephrosis
• ATB + drainage
• Acute focal bacterial nephritis (acute lobar
nephronia)
• intermediate stage between pyelonephritis
and intrarenal abscess
• CT: lobar or wedge-shaped, distribution of
hypointensity lesions
• ATB 14-21 days
• Perinephric or renal abscess
• Hematogenous seeding especially
Staphylococcus aureus BSI or renal
extension of ascending UTIs
• Severe pyelonephritis – fever, flank pain,
leukocytosis, and sometimes BSI
• CT: perirenal fluid or gas, renal distortion
• S. aureus, gram-negative bacilli (GNB)
(especially Escherichia coli and other
enteric GNB)
• Previous abdominal surgery, renal
transplantation, malignancy, and oral or
dental infection  anaerobe
• ATB 2-3 wks + drainage
• Xanthogranulomatous pyelonephritis
• chronic bacterial pyelonephritis and
obstruction
• Age < 8 years, > 40 years
• DDx renal tumor
• Flank pain, fever, chills, and chronic
bacteriuria; vague symptoms such as
malaise, malnutrition, weight loss, and
failure to thrive, usually > 1 mo
• Proteus species, E. coli
• Obstruction is present in 70% to 80% of
children ( congenital genitourinary
anormality, renal calculi)
Children aged 3 years to Adulthood
• The incidence of occult bacteremia decreases after 3 years of
age
Fever of unknown origin
Approach
• History taking
• Symstoms
• Contact, travel, animal exposure
• Medication
• Clinical course
• Physical examination
• Re-evaluate
• Initial investigation
• CBC
• UA
• LFT
• biomarker
• Specific investigation
• H/C
• Serology
• Imaging
• Others: specific disease
Work up
• PHYSICAL EXAMINATION
• Growth chart
• Thorough general examination
• Careful organ-specific examination
• Notation of mouth ulcers, exanthem,
joint abnormalities, lymph nodes
• TESTS
• CBC
• ESR, CRP
• Screening serum chemistry tests (and
uric acid level if prolonged fever)
• Serum quantitative immunoglobulin
levels
• Urinalysis, Urine culture
• Chest plain radiograph (if prolonged
or recurrent fever)
• Other imaging only as directed by
examination/other screening tests
• Blood culture (if prolonged fever)
Etiology
Noninfectious Causes of Fever of Unknown
Origin
• Kawasaki disease
• Autoimmune diseases
• Autoinflammatory disorders
• Inflammatory bowel disease
• Malignancy
• Drugs, other medicinal and
nutritional products
• Munchausen syndrome by proxy
• Dysautonomia
• Central thermoregulatory
disorder
• Diabetes insipidus
• Anhidrotic ectodermal dysplasia
• Hyperthyroidism
• Hematoma in a closed space
• Pulmonary embolus
Etiology
• Infection
• Tropical infection
• Rickettsia, Leptospirosis, Melioidosis,
Enteric fever, Malaria
• Mycobacterial infection: MTB, NTM
• Higher bacteria: Actinomycosis,
Nocardia
• Virus: EBV, CMV, HIV
• Endemic fungus: Histoplamosis
• Zoonosis: Cat scratch, Brucellosis,
• CVS: IE, RF
• RS: OM, sinusitis
• Bone and joint
• Concealed abscess
• Non –infection
• Kawasaki disease
• Autoimmune disease: SoJIA, SLE
• Malignancy
• HLH
• Drug fever
Pathogen Clinical clues Management
EBV Infectious mononucleosis
• (Fever, sore throat, lymphadenopathy),
Hepatomegaly (10%), splenomegaly (50%), rash (3 –
15%)
Primary EBV: not meeting criteria for IM
• CBC: Leukocytosis (>90%), lymphocytes (2/3), AL (20
– 40%), Mild thrombocytopenia (50,000 –
200,000/mm3), Mild elevation of hepatic
transaminase 50%
• Supportive
• Steroid: airway obstruction, massive
splenomegaly, myocarditis, hemolytic
anemia, or HLH
Scrub
typhus
Transmission: expose to chigger mite (6 – 21 days)
1st week: high fever,
• Conjunctival hyperemia (10 - 33%),
lymphadenopathy (30 – 93%), Hepatomegaly (28 –
73%), splenomegaly (20 – 23%) Eschar 46 – 68%
2nd week: recovery or complication from vasculitis
• CBC: Normal WBC (58% – 63%), (>10,000/mm3 4%),
Platelet count < 100,000 (26% – 77%)
• LFT: elevated AST & ALT (31% – 66%)
• Doxycycline 7-14 d
• Azithromycin
IFA titer of > 1:400 or a > 4-fold rise
DDX: CMV, toxo, HIV, adeno, HHV-6,7
Pathogen Clinical clues Management
Murine
typhus
Transmission: expose to flea bite (1 to 2 weeks)
Mild symptom:
• Fever (93% to 100%)
• Rash (20 – 80%): MP rash, lightly pigmented
• No eschar
• Hepatomegaly (24%), splenomegaly (10%)
• Doxycycline 7-14 d
• Fluoroquinolones or chloramphenicol
Melioidosis Transmission: expose to muddy soils or water
1. Multifocal infection with septicemia
• severe, septic shock, pneumonia (most common)
• Multiple metastatic abscess (liver, spleen)
2. Localized infection with septicemia
3. Localized infection
• Parotitis (40%), Pneumonia (8.6 – 45.9%)
• Skin infection (31.4 – 33.9%): skin ulcer or abscess
• Lymphaditis (14.3%)
• No hepatosplenomegaly
• Meropenem, imipenem, or
ceftazidime minimum of 10 to 14
days  trimethoprim-
sulfamethoxazole for 3 to 6 months
• Amoxicillin clavulanate, doxycycline,
ciproploxacin+azithromycin higher
rate of relapse
H/C, IHA,ELISA
Pathogen Clinical clues Management
Leptospirosis Transmission: Exposed to contaminated waters or
infected urine
1st week: High fever, myalgia, conjunctival suffusion,
• Muscle tenderness (calf and lumbar area)
• Less common: lymphadenopathy, splenomegaly,
hepatomegaly
Investigation:
• UA: mild proteinuria, pyuria, with or without
hematuria
2nd weeks: Immune phase: 4 to 30 day
• Jaundice, pulmonary symptoms, aseptic meningitis
• Weil’s disease
Severe
• Penicillin G 7 d (Jarisch-Herxheimer
Reaction)
• Cefotaxime, ceftriaxone, and doxycycline IV
Mild
• oral Doxycycline, Amoxicllin, Azithromycin
Malaria Enter to endemic area 2 weeks to 8 weeks
• High fever, anemia, hepatomegaly, splenomegaly
• CBC: Hct drop, normal WBC, thrombocypenia
(P.falcipalum, P.vivax)
Severe
• Artesunate
• Quinine + Doxy/clinda
Mild
• PF: Dihydroartemisinin-Piperaquine
• PV, PO: Chloroquine+Primaquine
Anicteric leptospirosis Icteric leptospirosis
Weil’s syndrome
(Incubatio
n period 2-
20 days)
Fever
Leptospiremi
c phase
3-7 days
Immune
phase
0-30 days
Leptospiremi
c phase
3-7 days
Immune
phase
0-30 days
Associate
d
symptoms
Myalgia
Headache
Nausea,
Vomiting
Abdominal pain
Conjunctival
suffusion
Meningitis
Uveitis
Rash
Jaundice
Hemorrhage
Acute renal failure
Myocarditis
Hemorrhagic pneumonitis
Meningoencephalitis
Hypotension
Leptospire
s present
in
Blood Blood
CSF CSF
Urine Urine
Microscopic agglutination test (MAT)
Pathogen Clinical clues Managment
Enteric fever
Salmonella
serovars Typhi,
Paratyphi A, and
Paratyphi B
Transmission: expose to contaminated food (7 to 14 days)
Age group: age > 5 year
1st week:
• Fever (pulse – temperature dissociation)
• Diarrhea (peasoup stool) (20%), constipation (20%)
2nd week:
• Rose spots, Rash (<5%)
• Abdominal pain (30%)
3rd week:
• Hepatomegaly (10%), splenomegaly (10%)
• Complication: bowel perforate
Investigations:
• No leukocytosis (leukopenia (> 5000/mm3),
neutrophilia or increased immature neutrophil
• Hct, platelet counts: normal or slightly low
• Elevated serum AST/ ALT 2 to 3 times: very common
• Ceftriazone or Fluoroquinolone iv 14 d
Severe enteric fever (delirium, obtundation,
stupor, coma, or shock)
• Dexamethasone 3 mg/kg iv then 1 mg/kg q 6
h for 48 hr
Chronic carrier (> 1 y)
• ciprofloxacin or norfloxacin 4 wk
• High dose iv ampicillin
• Cholecystectomy (failed ATB)
Culture – Gold standard: Blood, BM
Pathogen Clinical clues Management
IAHS • Etoposide,
glucocorticoid, and
cyclosporine A
Pathogen Clinical clues Management
Cat scratch
Bartonella
hensalae
Typical Cat Scratch disease
• Isolated Lymphadenopathy/Lymphadenitis with fever and no other
symptoms
• Warthin‐starry silver stain
Prolonged Fever/FUO
• Microabscesses in the liver and/or spleen
Ocular Manifestations
• Parinaud oculoglandular syndrome
• Neuroretinitis  mucular star
• Azithromycin 5 days
• Neuroretinitis:
doxycycline +
rifampin 2-4 wk
• Hepatosplenic
disease: rifampicin +
gentamicin
DDX WBC Plt Heptomegaly
/ LFT
Clinical clue
EBV Leukocytosis
AL
Mild AST/ALT
Mild
Infectious mononucleosis
Primary EBV
Dengue Leukopenia D 3 – D7 AST > ALT Hct
Sepsis Leukocytosis DIC SIRS
Melioidosis DIC/No Septicemia, Localized lesion, Liver
abscess
Enteric fever Leukopenia Normal to low AST/ALT
Common
Expose to contaminated food, Age > 5
yr, Diarrhea (20%), Rose spot
Rickettsial Normal 26-77 % AST/ALT
(31 – 66%)
Expose to chigger mite/ Eschar, Conjunctival
hyperemia, lymphadenopathy, splenomegaly
Leptospirosis CBC: Non specific
UA proteinuria, pyuria
Less common Expose to infected urine
1st wk Myalgia, conjunctival suffusion,
LN
2nd wk Jaundice, Weil’s disease
Malaria Anemia Yes AST > ALT Enter into endemic area 2 – 8 wk
Histiocytic necrotizing lymphadenitis
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AFI.pdf

  • 2. Approach to Acute Febrile Illness • Definition: Rectal temperature ≥ 38.3°C, < 1 week • History: Physical examination • Pattern of fever and Length of illness • Localizing symptoms • Immunization status • Prior use of medication • Underlying disease • Travel, contacts, animal and insect exposure
  • 3. Management of Fever without source • Infants 0 to 28 days of age • Infants 29 to 90 days of age • Infants 3 to 36 months of age • Children aged 3 years to adulthood
  • 4. Infants 0 to 28 days of age, Temp ≥ 38oC • Infants 3 to 28 days old with temp. ≥ 38 oC 254 cases • 32 (12.6%) had an Serious bacterial illness (SBI) Arch Pediatr Adolesc Med. 1999 May;153(5):508-11.
  • 5. Infants 0 to 28 days of age, Temp ≥ 38oC • Sepsis work up: • CBC, LFTs, Blood culture • Urinalysis, Urine culture • Lumbar puncture: • HSV PCR if CSF pleocytosis • Chest X Ray • Viral study
  • 6. Infants 0 to 28 days of age, Temp ≥ 38oC Bacterial pathogens • group B streptococcus • E.coli • L.monocytogenes Empirical antibiotics • Ampicillin plus Gentamicin • Ampicillin plus Cefotaxime • Vancomycin (gram positive on CSF gram stain or risk for S.aureus) Empirical acyclovir • if risk factors for HSV disease exist
  • 7. Infants 29 to 90 days of age, Temp ≥ 38oC Well – appearing Ill – appearing
  • 8. Infants 29 to 90 days of age, Temp ≥ 38oC Ill – appearing Admit & Sepsis work up & Parenteral antibiotic Pathogens • Neonatal pathogens • H.influenzae, N.meningitides • S.pneumoniae Cefotaxime + Ampicillin
  • 9. Infants 29 to 90 days of age, Temp ≥ 38oC Well – appearing Low – risk criteria Outpatient management YES Clinical criteria • Previously healthy • No focal bacterial infection Laboratory criteria • WBC 5000 to 15000/mm3 • Band < 1500/mm3 • Normal UA • Normal CSF, Stool exam • (if obtained)
  • 10. Infants 29 to 90 days of age, Temp ≥ 38oC Low risk criteria  Outpatient management • Blood culture • Urine culture • Treat suspected influenza Option 1 • Lumbar puncture • Ceftriaxone 50 mg/kg IV/IM • Reevaluation in 24 hours Option 2 • No antibiotics • Reevaluation in 24 hours
  • 11. Infants 3 to 36 months of age, T ≥ 39oC Well – appearing Ill – appearing
  • 12. Infants 3 to 36 months of age, T ≥ 39oC Ill – appearing Sepsis work up • Blood culture • Urine culture • Lumbar puncture (meningitis is suspected) • Chest X Ray (tachypnia & WBC > 20,000/mm3)
  • 13. Infants 3 to 36 months of age, T ≥ 39oC Ill – appearing Sepsis work up Parenteral antibiotic Pathogens • H.influenzae type B • N.meningitides • S.pneumoniae • S.aureus Ceftriaxone & Cefotaxime
  • 14. Infants 3 to 36 months of age, T ≥ 39oC Well – appearing Complete Incomplete
  • 15. Occult Bacteremia • Bacteria in the blood • Well – appearing febrile child • Absence of an identifiable focal bacterial source
  • 16. Prevalence of occult bacteremia 1. J Pediatr. 1983 Sep;103(3):352-8. 2. Arch Pediatr Adolesc Med. 1998 Jul;152(7):624-8. 3. Pediatrics. 2000 Sep;106(3):505-11. 4. Arch Pediatr Adolesc Med. 2004 Jul;158(7):671-5. 5. Acad Emerg Med. 2009 Mar;16(3):220-5.
  • 17. Pathogenic bacteria cultured from patients with occult bacteremia 1. Arch Pediatr Adolesc Med. 1998;152:624-628. 2. Pediatrics. 2000 Sep;106(3):505-11.
  • 18. Evaluation of febrile young infants • Boston • Philadelphia • Rochester • Lab-score • Step by step
  • 19. Boston protocol • Prospectively evaluated 503 28- to 89-day-old infants with rectal temperature greater than 38ºC (100.4ºF) • Criteria: • No immunizations or antimicrobials within the preceding 48 hours • No evidence of dehydration, ear, soft tissue, or bone infection • Overall well appearance • Caretaker available by telephone • The laboratory criteria defining low-risk patients included: • Peripheral white blood cell (WBC) count less than 20,000/microL • CSF with WBC <10/microL • UA <10 WBC per high-powered field • No infiltrate on chest radiograph if one was obtained • Ceftriazone 50 mg/kg im, F/U 24 hr • 27 (5.4%) had SBI
  • 20. Philadelphia protocol • 8-year experience with 747 infants 29- to 60-days of age with a rectal temperature ≥38.2ºC (100.8ºF) • Low-risk criteria included patients who were well-appearing with: • WBC <15,000/microL • Band-neutrophil ratio <0.2 • UA <10 WBC/hpf and a negative urine Gram stain • CSF <8 WBC/microL and a negative CSF Gram stain • Chest radiograph lacking an infiltrate if one was obtained • Stool without blood and few or no WBCs on the smear in infants with diarrhea D/C and F/U 24 hr Sensitivity 98 %(95% CI 92-100); specificity 42 %(95% CI 38-46); PPV 14 %(95% CI 11-17); NPV 99.7 %(95% CI 98-100)
  • 21. Rochester protocol • Identify low-risk febrile infants (defined as a rectal temperature greater than or equal to 38.0ºC or 100.4ºF) younger than 60 days • Clinical criteria: • ≥37 weeks gestation, and hospitalized no longer than the mother • Infant was previously healthy • Infant was well-appearing, with no ear, soft tissue, or bone infections • LAB: • WBC 5,000 to 15,000/microL with an absolute band count <1,500/microL • Urinalysis with <10 WBC/hpf and no bacteria seen • Stool with <5 WBC/hpf if obtained D/C with F/U Five had SBI, NPV 98.9 %(95% CI 97-100)
  • 23. Step by step Pediatrics. 2016 Aug;138(2).
  • 24. • IBI 79.3% (22/26 sepsis, 9/10 meningitis) • Non IBI 98.5%
  • 25.
  • 26.
  • 27. Infants 3 to 36 months of age, T ≥ 39oC Well – appearing Immunization incomplete WBC ≥ 15,000/mm3  H/C WBC > 20,000/mm3  CXR CBC, UA, Urine culture
  • 28. Infants 3 to 36 months of age, T ≥ 39oC Well – appearing Immunization incomplete WBC ≥ 15,000/mm3 CBC, UA, Urine culture • Ceftriaxone (50 mg/kg/dose) IM • Outpatient follow up within 24 hrs • Admit for parenteral antibiotic
  • 29. Antimicrobial treatment of occult bacteremia: a multicenter cooperative study. Children 3 to 36 months, T ≥ 39.5oC without focus of infection WBC < 15,000/mm3 WBC ≥ 15,000/mm3 WBC ≥ 30,000/mm3 H/C positive 5 of 182, 2.7% H/C positive 55 of 331, 16.6% H/C positive 9 of 21, 42.9% Pediatr Infect Dis J. 1993 Jun;12(6):466-73.
  • 30. Occult pneumonias: empiric chest radiographs in febrile children with leukocytosis CXR were obtained in 225 cases With respiratory symptom, 79 case With leukocytosis ≥ 20,000/mm3, 149 cases Pneumonia, 32 of 79 (40%) Pneumonia, 38 of 146 (26%) Ann Emerg Med. 1999 Feb;33(2):166-73.
  • 31. Infants 3 to 36 months of age, T ≥ 39oC Well – appearing Immunization complete Sign & Symptoms of UTI • Girls < 24 mo of age • Uncircumcised boys < 12 months of age • Circumcised boys < 6 months of age UA, Urine culture NO YES
  • 32. UTI
  • 33. Diagnosis • Urinalysis • leukocyte esterase, nitrite +Ve • WBC > 5 cells/HPF • Uncentrifuge urine G/S > 1 organism/oil field • Urine C/S • Suprapubic aspiration: age < 2 yr, phimosis, labial adhesion • Urethral cath > 104 CFU/mL • Clean-catch, mid stream void > 105 CFU/mL • Staphylococcus saprophyticus, Mycobacterium and Candida  correlate with clinical coagulase-negative staphylococci (CoNS), novobiocin resistant Co-trimoxazole, fluoroquinolone
  • 34. Managment • ATB • Upper UTI or fever 7-14 d • Cystitis 3-7 d • 1st UTI  U/S KUB, not recommend routine VCUG if U/S normal • Recurrent UTI  U/S KUB, VCUG if not done before
  • 35.
  • 36. Antibiotics prophylaxis • Not recommend routine ATB prophylaxis in 1st UTI • Consider in patient that has to do VCUG • High-grade reflux and underlying obstructive/complex uropathies
  • 37. Renal abscess • Pyelonephrosis • accumulation of purulent debris and sediment in the renal pelvis and urinary collecting system • Symptoms: severe pyelonephritis, persistent + signs of hydronephrosis • ATB + drainage • Acute focal bacterial nephritis (acute lobar nephronia) • intermediate stage between pyelonephritis and intrarenal abscess • CT: lobar or wedge-shaped, distribution of hypointensity lesions • ATB 14-21 days
  • 38. • Perinephric or renal abscess • Hematogenous seeding especially Staphylococcus aureus BSI or renal extension of ascending UTIs • Severe pyelonephritis – fever, flank pain, leukocytosis, and sometimes BSI • CT: perirenal fluid or gas, renal distortion • S. aureus, gram-negative bacilli (GNB) (especially Escherichia coli and other enteric GNB) • Previous abdominal surgery, renal transplantation, malignancy, and oral or dental infection  anaerobe • ATB 2-3 wks + drainage • Xanthogranulomatous pyelonephritis • chronic bacterial pyelonephritis and obstruction • Age < 8 years, > 40 years • DDx renal tumor • Flank pain, fever, chills, and chronic bacteriuria; vague symptoms such as malaise, malnutrition, weight loss, and failure to thrive, usually > 1 mo • Proteus species, E. coli • Obstruction is present in 70% to 80% of children ( congenital genitourinary anormality, renal calculi)
  • 39. Children aged 3 years to Adulthood • The incidence of occult bacteremia decreases after 3 years of age
  • 41. Approach • History taking • Symstoms • Contact, travel, animal exposure • Medication • Clinical course • Physical examination • Re-evaluate • Initial investigation • CBC • UA • LFT • biomarker • Specific investigation • H/C • Serology • Imaging • Others: specific disease
  • 42. Work up • PHYSICAL EXAMINATION • Growth chart • Thorough general examination • Careful organ-specific examination • Notation of mouth ulcers, exanthem, joint abnormalities, lymph nodes • TESTS • CBC • ESR, CRP • Screening serum chemistry tests (and uric acid level if prolonged fever) • Serum quantitative immunoglobulin levels • Urinalysis, Urine culture • Chest plain radiograph (if prolonged or recurrent fever) • Other imaging only as directed by examination/other screening tests • Blood culture (if prolonged fever)
  • 44. Noninfectious Causes of Fever of Unknown Origin • Kawasaki disease • Autoimmune diseases • Autoinflammatory disorders • Inflammatory bowel disease • Malignancy • Drugs, other medicinal and nutritional products • Munchausen syndrome by proxy • Dysautonomia • Central thermoregulatory disorder • Diabetes insipidus • Anhidrotic ectodermal dysplasia • Hyperthyroidism • Hematoma in a closed space • Pulmonary embolus
  • 45. Etiology • Infection • Tropical infection • Rickettsia, Leptospirosis, Melioidosis, Enteric fever, Malaria • Mycobacterial infection: MTB, NTM • Higher bacteria: Actinomycosis, Nocardia • Virus: EBV, CMV, HIV • Endemic fungus: Histoplamosis • Zoonosis: Cat scratch, Brucellosis, • CVS: IE, RF • RS: OM, sinusitis • Bone and joint • Concealed abscess • Non –infection • Kawasaki disease • Autoimmune disease: SoJIA, SLE • Malignancy • HLH • Drug fever
  • 46. Pathogen Clinical clues Management EBV Infectious mononucleosis • (Fever, sore throat, lymphadenopathy), Hepatomegaly (10%), splenomegaly (50%), rash (3 – 15%) Primary EBV: not meeting criteria for IM • CBC: Leukocytosis (>90%), lymphocytes (2/3), AL (20 – 40%), Mild thrombocytopenia (50,000 – 200,000/mm3), Mild elevation of hepatic transaminase 50% • Supportive • Steroid: airway obstruction, massive splenomegaly, myocarditis, hemolytic anemia, or HLH Scrub typhus Transmission: expose to chigger mite (6 – 21 days) 1st week: high fever, • Conjunctival hyperemia (10 - 33%), lymphadenopathy (30 – 93%), Hepatomegaly (28 – 73%), splenomegaly (20 – 23%) Eschar 46 – 68% 2nd week: recovery or complication from vasculitis • CBC: Normal WBC (58% – 63%), (>10,000/mm3 4%), Platelet count < 100,000 (26% – 77%) • LFT: elevated AST & ALT (31% – 66%) • Doxycycline 7-14 d • Azithromycin IFA titer of > 1:400 or a > 4-fold rise DDX: CMV, toxo, HIV, adeno, HHV-6,7
  • 47.
  • 48. Pathogen Clinical clues Management Murine typhus Transmission: expose to flea bite (1 to 2 weeks) Mild symptom: • Fever (93% to 100%) • Rash (20 – 80%): MP rash, lightly pigmented • No eschar • Hepatomegaly (24%), splenomegaly (10%) • Doxycycline 7-14 d • Fluoroquinolones or chloramphenicol Melioidosis Transmission: expose to muddy soils or water 1. Multifocal infection with septicemia • severe, septic shock, pneumonia (most common) • Multiple metastatic abscess (liver, spleen) 2. Localized infection with septicemia 3. Localized infection • Parotitis (40%), Pneumonia (8.6 – 45.9%) • Skin infection (31.4 – 33.9%): skin ulcer or abscess • Lymphaditis (14.3%) • No hepatosplenomegaly • Meropenem, imipenem, or ceftazidime minimum of 10 to 14 days  trimethoprim- sulfamethoxazole for 3 to 6 months • Amoxicillin clavulanate, doxycycline, ciproploxacin+azithromycin higher rate of relapse H/C, IHA,ELISA
  • 49. Pathogen Clinical clues Management Leptospirosis Transmission: Exposed to contaminated waters or infected urine 1st week: High fever, myalgia, conjunctival suffusion, • Muscle tenderness (calf and lumbar area) • Less common: lymphadenopathy, splenomegaly, hepatomegaly Investigation: • UA: mild proteinuria, pyuria, with or without hematuria 2nd weeks: Immune phase: 4 to 30 day • Jaundice, pulmonary symptoms, aseptic meningitis • Weil’s disease Severe • Penicillin G 7 d (Jarisch-Herxheimer Reaction) • Cefotaxime, ceftriaxone, and doxycycline IV Mild • oral Doxycycline, Amoxicllin, Azithromycin Malaria Enter to endemic area 2 weeks to 8 weeks • High fever, anemia, hepatomegaly, splenomegaly • CBC: Hct drop, normal WBC, thrombocypenia (P.falcipalum, P.vivax) Severe • Artesunate • Quinine + Doxy/clinda Mild • PF: Dihydroartemisinin-Piperaquine • PV, PO: Chloroquine+Primaquine Anicteric leptospirosis Icteric leptospirosis Weil’s syndrome (Incubatio n period 2- 20 days) Fever Leptospiremi c phase 3-7 days Immune phase 0-30 days Leptospiremi c phase 3-7 days Immune phase 0-30 days Associate d symptoms Myalgia Headache Nausea, Vomiting Abdominal pain Conjunctival suffusion Meningitis Uveitis Rash Jaundice Hemorrhage Acute renal failure Myocarditis Hemorrhagic pneumonitis Meningoencephalitis Hypotension Leptospire s present in Blood Blood CSF CSF Urine Urine Microscopic agglutination test (MAT)
  • 50. Pathogen Clinical clues Managment Enteric fever Salmonella serovars Typhi, Paratyphi A, and Paratyphi B Transmission: expose to contaminated food (7 to 14 days) Age group: age > 5 year 1st week: • Fever (pulse – temperature dissociation) • Diarrhea (peasoup stool) (20%), constipation (20%) 2nd week: • Rose spots, Rash (<5%) • Abdominal pain (30%) 3rd week: • Hepatomegaly (10%), splenomegaly (10%) • Complication: bowel perforate Investigations: • No leukocytosis (leukopenia (> 5000/mm3), neutrophilia or increased immature neutrophil • Hct, platelet counts: normal or slightly low • Elevated serum AST/ ALT 2 to 3 times: very common • Ceftriazone or Fluoroquinolone iv 14 d Severe enteric fever (delirium, obtundation, stupor, coma, or shock) • Dexamethasone 3 mg/kg iv then 1 mg/kg q 6 h for 48 hr Chronic carrier (> 1 y) • ciprofloxacin or norfloxacin 4 wk • High dose iv ampicillin • Cholecystectomy (failed ATB) Culture – Gold standard: Blood, BM
  • 51. Pathogen Clinical clues Management IAHS • Etoposide, glucocorticoid, and cyclosporine A
  • 52. Pathogen Clinical clues Management Cat scratch Bartonella hensalae Typical Cat Scratch disease • Isolated Lymphadenopathy/Lymphadenitis with fever and no other symptoms • Warthin‐starry silver stain Prolonged Fever/FUO • Microabscesses in the liver and/or spleen Ocular Manifestations • Parinaud oculoglandular syndrome • Neuroretinitis  mucular star • Azithromycin 5 days • Neuroretinitis: doxycycline + rifampin 2-4 wk • Hepatosplenic disease: rifampicin + gentamicin
  • 53. DDX WBC Plt Heptomegaly / LFT Clinical clue EBV Leukocytosis AL Mild AST/ALT Mild Infectious mononucleosis Primary EBV Dengue Leukopenia D 3 – D7 AST > ALT Hct Sepsis Leukocytosis DIC SIRS Melioidosis DIC/No Septicemia, Localized lesion, Liver abscess Enteric fever Leukopenia Normal to low AST/ALT Common Expose to contaminated food, Age > 5 yr, Diarrhea (20%), Rose spot Rickettsial Normal 26-77 % AST/ALT (31 – 66%) Expose to chigger mite/ Eschar, Conjunctival hyperemia, lymphadenopathy, splenomegaly Leptospirosis CBC: Non specific UA proteinuria, pyuria Less common Expose to infected urine 1st wk Myalgia, conjunctival suffusion, LN 2nd wk Jaundice, Weil’s disease Malaria Anemia Yes AST > ALT Enter into endemic area 2 – 8 wk
  • 54.
  • 55.