07 - DR Kiki - LAboratory Investigation Panitia-1

ASMP-ID 2018 28-Oct-18
INFORMASI UMUM
• Presentasi ini disampaikan pada kegiatan 1ST ASMP-ID
• Hari / Tanggal : Sabtu - Minggu / 27-28 Oktober 2018
• Tempat : Hotel Novotel Tangerang
• Narasumber : UKK Infeksi dan Penyakit Tropis
• Semua isi dan materi presentasi adalah hak cipta dari

narasumber, digunakan untuk kalangan terbatas dalam
kepentingan edukasi kesehatan di bidang terkait.
Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

In collaboration with 1
Indonesian Pediatric Society (IPS) – Banten Branch
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UKK INFEKSI - IDAI BANTEN 1

CURRICULUM VITAE

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society .

In collaboration with .
Indonesian
Infectious and Tropical Disease Working Group of Pediatric
Indonesian Pediatric Society
Society (IPS) – Banten Branch .
In collaboration with

Harapan ….
Saya berharap penjelasan tentang biomarker
laboratorium ini bisa menolong para dokter untuk:
1. Membedakan antara infeksi bakteria dengan
infeksi virus
2. Menentukan perlunya pemberian Antibiotik
3. Menentukan perubahan dosis dan jenis antibiotik
4. Menentukan penghentian Antibiotik
5. Menentukan perjalanan penyakit
6. Menentukan prognosis

Aplikasi klinis interpretasi

biomarker


Invasi vs bakteriemia vs infeksi vs penyakit infeksi
• INVASI : masuknya bakteri ke dalam tubuh
• BAKTERIEMIA : adanya bakteri dalam darah
• bakteriemia+ respons immune = INFEKSI
• bakteriemia+ respons immune + gejala Klinis
= PENYAKIT INFEKSI

Biomarker Laboratorium
Limmited resources minimal resources
• Haematological parameters
• White blood cell count (WBC) • Serology
• Absolute neutrophil count • IgM Anti dengue… ect
(ANC)
• Absolute band count (ABC) • IgM Salmonella typhi,
• erythrocyte sedimentation Microscopic agglutination
rate (ESR)
• Inflammatory markers test (MAT) of Leptospirosis,
• C-reactive protein (CRP) Rapid antigen detection
• Procalcitonin, test of Streptococcus
• cytokines
• Urine, stool, CSF analysis
antigen,Mannan
• Direct examination antigen,beta-d glukan
antigen,etc
Dr. Debbie L SpA(K), 11st ICTP, 2017



• Anak usia 2 bulan datang dengan keluhan

batuk selama 2 minggu, demam hanya 2
hari pertama
• Malam hari :Batuk hebat, bayi tidak bisa
mengeluarkan lender, sulit bernapas kalau
batuk
• Klinis: Ronchi (-), wheezing (-), slem minimal
Perlu antibiotic ???
Leukosit 30.000 UL, DC: 0-2/2-14/79-3


Diarrhea
A previously healthy 2.5-year-old

girl presented to our hospital
following 2 febrile seizure
( generalized tonic-clonic 1-5 min,
within5 h of each other)
Sebelum ke IGD IGD

-2 day
JOURNAL OF CLINICAL MICROBIOLOGY, Dec. 2011, p. 4382–438

Laboratory analysis of blood obtained while in the

emergency
• white blood cell count: 23,800/l (97% neutrophils)

• hemoglobin, 11.9 g/dl
• Platelet count, 366,000/l
• C-reactive protein, 0.79 mg/dl;
• blood sugar, 121 mg/dl; serum
• sodium,131meq/liter;
• potassium,4.1meq/liter;
• chloride,99meq/liter;
• AST 50 IU/liter; ALT 32 IU/liter;


An hour after arrival at the hospital
The patient experienced two more seizures.

The fourth and final seizure developed into status
epilepticus and was treated with intravenous
diazepam.
As the seizure gradually ended, the electrocardiogram
monitor showed a brief period of ventricular fibrillation
followed by asystole.
Immediate resuscitation attempts were unsuccessful.



A)Hypertrophic (B) Endocardium showing

cardiomyopathy with focal immunohistochemical detection
disorganized myocardial of rotavirus capsid protein
architecture.
.

C) Brain tissue with (D) Brain tissue stained with

hematoxylin-and-eosin staining. anti-VP6 antibody. The brown
The autopsy revealed brain edema color indicates a positive
but no cerebral herniation. reaction.


Leukosit: interpretasi umum bahwa
• Tingginya jumlah leukosit merupakan

biomarker adanya penyakit infeksi bakteri,
• Rendahnya kadar leukosit merupakan

biomarker bahwa infeksi disebabkan oleh
virus,
• BENAR atau MITOS…?

Hsiao AL, Chen L, Baker MD. Incidence and predictors of serious bacterial infections
among 57- to 180-day-old infants. Pediatrics 2006;117:1695-701
105 pasien memiliki jumlah leukosit 11.700 – 15.600/uL,

namun hanya 12 pasien (11,4%) menderita SBI
bila ada 100 anak sakit usia 57 sd 120 hari dengan leukosit
antara 11.700 sd 15.600/uL maka 88 anak tersebut (88.6%)
tidak mengalami infeksi bakteri.


Hsiao AL, Chen L, Baker MD. Incidence and predictors of serious bacterial infections
among 57- to 180-day-old infants. Pediatrics 2006;117:1695-701
102 pasien memiliki jumlah leukosit ≥ 15.700 /uL,

namun hanya 23 pasien (22,5%) menderita SBI
bila ada 100 anak sakit usia 57 sd 120 hari dengan leukosit ≥ 15.700/uL
maka 77 anak tersebut (77.5%) tidak mengalami infeksi bakteri

BMJ 2011;342:d3082 doi:10.1136/bmj.d3082


1. Menilai peran pemeriksaan laboratorium

sederhana dalam memprediksi adanya infeksi
bakteri yang serius
2. The reported outcomes included bacteraemia
(14 studies), sepsis (four), meningitis (13, bacterial
only in eight cases), pneumonia (11), and urinary
tract infection (14), and in some cases additional
infections such as bone or joint infections (eight),
bacterialgastroenteritis (seven), cellulitis (three),
and abscess (three).
3. The age of eligible children also varied among
the studies, with four studies including infants only
(≤3 months) and two studies including older
participants, up to 16 years of age.

Diagnostic value of WBC for serious infection in febrile children
Van den Bruel A,et al. BMJ 2011;342:d3082


Diagnostic value of WBC for serious infection in febrile children

Penelitian metaanalisis dari Bruel dkk
menunjukkan bahwa nilai Leukosit ≥ 15.000/uL

hanya menghasilkan positive likelihood ratio 0.87–
2,43 dan negative likelihood ratio 0,6–1,14
sehingga Leukosit bukanlah biomarker yang baik
dalam membedakan ada atau tidaknya SBI.


Leukosit
• Tingginya jumlah leukosit dipercaya merupakan

biomarker adanya penyakit infeksi bakteri, namun
beberapa infeksi bakteri justru menunjukkan
jumlah leukosit yang lebih rendah dari normal.
Misalnya: demam tifoid dan sepsis bakterialis

Leukosit
• Rendahnya kadar leukosit dipercaya merupakan
biomarker bahwa infeksi disebabkan oleh virus,
namun bukti klinis menunjukkan kasus kasus infeksi
virus yang menunjukkan leukositosis, misalnya :
enterovirus, rotavirus, dan fase awal penyakit
infeksi virus lainnya.


Leukosit
• Sehingga leukosit tidak mampu secara tepat

membedakan apakah infeksi disebabkan
oleh bakteri atau virus.

Bagaimana memanfaatkan biomarker Leukosit ?
1. Gunakan pemeriksaan Leukosit setelah kesimpulan klinis


• Anak usia 2 bulan datang dengan keluhan batuk

selama 2 minggu, demam hanya 2 hari pertama
• Malam hari :Batuk hebat, bayi tidak bisa
mengeluarkan lender, sulit bernapas kalau batuk
• Klinis: Ronchi (-), wheezing (-), slem minimal
Perlu antibiotic ???
Leukosit 30.000 UL, DC: 0-2/2-14/79-3

• video
Leukosit 30.000 UL, DC: 0-2/2-14/79-3


Hitung Jenis Absolute Band Count

(ABC)
• Pemeriksaan hitung jenis ABC umumnya
meningkat pada anak dngan infeksi bakteri,
namun peningkatan ABC ini juga ditemukan
pada 21-29% pasien yang secara kultur virologi
terbukti mengalami infeksi virus.

Penelitian metanalisis oleh Bruel dkk mendapatkan pemeriksaan ABC

tampaknya merupakan biomarker yang baik untuk menentukan adanya SBI,
namun penelitian-penelitian dalam metanalisis ini tidak memiiliki cut off point
ABC yang sama.1,3,4,6


Some guidelines which defining populations of

infants who are at a low risk for bacterial
infection, use band count as part of the low-risk
criteria
• Boston guideline : none

• Philadelphia guideline : less than 0.2 band-to-neutrophil ratio
• Rochester guideline : less than 1,500 ABC
• 1993 Pediatrics : Less than 1,000 ABC

Hitung Jenis: Abolute Netrophyl Count

(ANC)
Pediatr Infect Dis J 2007;26:672-7.


Emergency Departement Pemeriksaan

children younger than 3 years 1. WBC (Leukosit) Serious Bacterial Infection
Kriteria Inklusi 2. ANC (a=absolute Nethrophyl Count) SBI vs no SBI
1. all infants aged 7-days to 3- 3. CRP (C Reactive Protein)
months-old with fever (rectal 4. PCT ( Procalsitonin)
temperature) 38°C; 5. YOS ( Yale Observasional Score)
2. children aged 3–36-months old
ill/toxic-appearing or with fever
(rectal temperature) 39.5°C
Kriteria Eksklusi
1. antibiotic use within the 48 hours before
admission to the hospital,
2. vaccination during the previous 2 days,
3. known immunodeficiencies,
4. any chronic pathology,
5. fever lasting longer than 5 days
Andreola B, Bressan S, Callegaro S, Liverani A, Plebani M, Da Dalt L. Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in
febrile infants and children in the emergency department. Pediatr Infect Dis J 2007;26:672-7.




Emergency Departement children younger than 3

years
Pediatr Infect Dis J 2007;26:672-7.
Kriteria Inklusi
1. all infants aged 7-days to 3-months-old with fever (rectal temperature) 38°C;
2. children aged 3–36-months old ill/toxic-appearing or with fever
(rectal temperature) 39.5°C


PREDIKTOR terbaik ADANYA SBI,

maka pilih LR + TERTINGGI
Prediktor terbaik ADANYA SBI di IGD:

1.PCT >2ng/mL
2. CRP > 80 mg/mL
3.PCT > 1 ng/mL

PREDIKTOR TIDAK ADANYA SBI,

maka pilih LR + TERRENDAH
Prediktor terbaik dalam MENYINGKIRKAN kemungkinan adanya

SBI = NO SBI di IGD adalah:
1.CRP ≤ 20 mg/mL
2.PCT ≤ 0,5 ng/mL






Table 1 Univariate analysis of the clinical and laboratory variables. (RR relative risk, CI 95%)
infants aged 2 weeks-1 year, who

presented during a 1-year-period
with rectal temperature ≥ 380C,
ESR > 50 as predictor for SBI:
RR 6.67; 95%CI 3.03-14.68


BMJ 2011;342:d3082 doi:10.1136/bmj.d3082
infants aged 2 weeks-1 year, who

presented during a 1-year-period
with rectal temperature ≥ 380C,
ESR > 50 as predictor for SBI:
LR + 2.49 (95%CI 1.73 to

3.59)
LR – 0,34 (95%CI 0,17 to

0,65)

Key messages
• Absolute
lymphocytopenia is a
predictor of bacteremia.
• The ratio of neutrophil
and lymphocyte counts:
• higher value in
predicting
bacteremia.
• simple, easily
obtained and
calculated, easy to
integrate into daily
practice and
without extra costs.
de Jager et al. Critical Care 2010, 14:R192


Data from 298 pediatric patients less than 36 months of

age with febrile UTI admitted to Severance Children’s
Hospital from January 2010 to December 2014 were
retrospectively analyzed.
1. a fever of ≥38°C, 1. WBC= lekosit
2. a pyuria (≥5 WBCs per highpower field), 2. Netrophyl
3. a positive urine culture collected from a cleancatch or 3. NLR= Netrophyl
catheterized specimen (defined as growth of a single Lymphocyte Ratio
organism to ≥100,000 colonyforming units/ mL), 4. ESR = LED
4. no previous history of UTI, kidney or bladder disease. 5. CRP
5. Imaging studies, including renal ultrasonography
(USG), dimercaptosuccinic acid (DMSA) scan and
voiding cystourethrogram (VCUG), were performed.
Predict Cortical Renal Defect

Han SY, Lee IR, Park SJ,et al. Usefulness of neutrophil-lymphocyte ratio in young children with febrile urinary tract infection. Korean J
Pediatr 2016;59(3):139-144 http://dx.doi.org/10.3345/kjp.




Clinical and laboratory findings of

common low‐risk criteria
Hui C, et al. Evidence Report/Technology Assessments, No. 205. AHRQ Publication No. 12-E004-EF. 2012


sindroma klinis enteric fever (+)

serologis dan/atau bakteriologi S. typhi (-)
BUKAN DEMAM TIFOID

disertai
serologis dan/atau bakteriologi S. typhi (-) :
(FALSE NEGATIVE)
????????????

Penyebab FALSE NEGATIVE Serologi S.Typhi
Cut off point

serologi
False Negative : pemeriksaan dilakukan terlalu cepat.

Seharusnya:
widal : > hari ke 7 dan diulang selang 7 hari kemudian
IgM serologi (Tubex, typhi-dot M) : ≥ hari ke 5


Penyebab FALSE NEGATIVE Serologi S.Typhi
Cut off point

serologi
SEROLOGI POSITIVE BILA:

widal : hari ke 7 dan diulang selang 7 hari kemudian ADA KENAIKAN
4X
IgM serologi Tubex : ≥ hari ke 5 : (6+)


disertai
serologis dan/atau bakteriologi S. typhi (-) :
(FALSE NEGATIVE)
WHO: DEMAM TIFOID KLINIS/

Clinical Typhoid Fever



serologis dan/atau bakteriologi S. paratyphi (+)
GEJALA DEMAM TIFOID

disertai
serologis dan/atau bakteriologi S. paratyphi (+)
DEMAM PARATIFOID/
MILD ENTERIC FEVER

sindroma klinis enteric fever (-)

Serologis S. typhi (+)
DEMAM TIFOID

disertai
(False Interpretation) positif Serologi

Atau
False negatif sindroma klinis enteric fever


Klinis Demam tifoid dan serologi true positive
MINGGU
I II III
Cut off point

serologi



Serologi di daerah endemis

Cut off point

serologi
SEROLOGI: dinilai kenaikan titer antara 2x

pemeriksaan dengan selang 5-7 hari


DEMAM TIFOID

disertai
Salmonellosis


Bagaimana mengoptimalkan keterbatasan … ?
4T optimalisasi penggunaan biomarker

laboratorium
• Tepat Pemahaman (Memahami kelebihan

dan kekurangan)
• Tepat Waktu
• Tepat Indikasi
• Tepat Interpretasi


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ASMP-ID 2018 28-Oct-18

• Semua isi dan materi presentasi adalah hak cipta dari

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

UKK INFEKSI - IDAI BANTEN 1

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society .

UKK INFEKSI - IDAI BANTEN 2

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

Aplikasi klinis interpretasi

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

UKK INFEKSI - IDAI BANTEN 3

Invasi vs bakteriemia vs infeksi vs penyakit infeksi

• INVASI : masuknya bakteri ke dalam tubuh

• BAKTERIEMIA : adanya bakteri dalam darah

• bakteriemia+ respons immune = INFEKSI

• bakteriemia+ respons immune + gejala Klinis

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

UKK INFEKSI - IDAI BANTEN 4

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

• Anak usia 2 bulan datang dengan keluhan

Leukosit 30.000 UL, DC: 0-2/2-14/79-3

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

UKK INFEKSI - IDAI BANTEN 5

A previously healthy 2.5-year-old

Sebelum ke IGD IGD

JOURNAL OF CLINICAL MICROBIOLOGY, Dec. 2011, p. 4382–438

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

Laboratory analysis of blood obtained while in the

• white blood cell count: 23,800/l (97% neutrophils)

JOURNAL OF CLINICAL MICROBIOLOGY, Dec. 2011, p. 4382–438

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

UKK INFEKSI - IDAI BANTEN 6

An hour after arrival at the hospital

The patient experienced two more seizures.

JOURNAL OF CLINICAL MICROBIOLOGY, Dec. 2011, p. 4382–438

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

JOURNAL OF CLINICAL MICROBIOLOGY, Dec. 2011, p. 4382–438

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

UKK INFEKSI - IDAI BANTEN 7

A)Hypertrophic (B) Endocardium showing

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

C) Brain tissue with (D) Brain tissue stained with

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

UKK INFEKSI - IDAI BANTEN 8

Leukosit: interpretasi umum bahwa

• Tingginya jumlah leukosit merupakan

• Rendahnya kadar leukosit merupakan

• BENAR atau MITOS…?

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

105 pasien memiliki jumlah leukosit 11.700 – 15.600/uL,

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

UKK INFEKSI - IDAI BANTEN 9

102 pasien memiliki jumlah leukosit ≥ 15.700 /uL,

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

BMJ 2011;342:d3082 doi:10.1136/bmj.d3082

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

UKK INFEKSI - IDAI BANTEN 10

1. Menilai peran pemeriksaan laboratorium

Infectious and Tropical Disease Working Group of Indonesian Pediatric Society

Diagnostic value of WBC for serious infection in febrile children

Van den Bruel A,et al. BMJ 2011;342:d3082