Curriculum Vitae

Nama : Dr. Ronald Irwanto Natadidjaja, SpPD – KPTI, FINASIM

Pendidikan :
SMP - SMA : Kolese KANISIUS, lulus 1994
Dokter Umum : FK TRISAKTI, lulus 2002
Spesialis Penyakit Dalam (Internist) : FKUI, lulus 2009
Konsultan / Subspesialis Penyakit Tropik & Infeksi : FKUI / PAPDI, lulus 2013

Pekerjaan :
Bendahara Pengurus Besar Perhimpunan Konsultan Penyakit Tropik dan Infeksi Indonesia (PB PETRI)

SekJen Pengurus Pusat Perhimpunan Pengendalian Infeksi Indonesia (PP. PERDALIN)

Tim Panel Ahli PNPK Sepsis, Kemenkes RI

Anggota Pokja PPI, Kemenkes RI

Kepala Bagian Ilmu Penyakit Dalam, FK TRISAKTI

Ketua PPRA, RS PONDOK INDAH – PURI INDAH dan RS PONDOK INDAH – BINTARO JAYA

Internist - Konsultan, RS PONDOK INDAH – PURI INDAH dan RS PONDOK INDAH – BINTARO JAYA

Tim Pengendalian COVID-19, RS PONDOK INDAH – PURI INDAH dan RS PONDOK INDAH – BINTARO
JAYA
 COVID-19 on the Stage:
Major & Main

Ronald Irwanto
Internist – Infectious Disease (ID) Specialist
Trisakti School of Medicine
Indonesian Society of Tropical Medicine & Infectious Disease
COVID -19 : a gentle reminder for PPE
 Droplet and Airborne
Precaution
Contact ONLY in
Precaution Generating
Red Line Aerosolized

COVID-19 is a respiratory disease that is different from Ebola

virus disease, which is transmitted through infected bodily
fluids. Due to these differences in transmission, the PPE
requirements for COVID-19 are different from those required
for Ebola virus disease. Specifically, coveralls (sometimes called
Ebola PPE) are not required when managing COVID-19 patients.

World Heath Organization. Rational use of personal protective equipment for

coronavirus disease 2019 (COVID-19) : Interim Guidance. 2020
 Standard PPE on COVID-19
• HairCap
• Goggles
• Mask (Surgical / N95)
• Glove
• (Apron)
NOT COVER ALL PPE

World Heath Organization. Rational use of personal protective equipment for

coronavirus disease 2019 (COVID-19) : Interim Guidance. 2020
COVID -19 :The Pathogenesis
 6 Types of Corona Virus

• alphacoronavirus 229E
• alphacoronavirus NL63
• betacoronavirus OC43
• betacoronavirus HKU1
• Severe Acute Respiratory Illness Coronavirus (SARS-CoV),
• Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

Adityo Susilo, C. Martin Rumende, Ceva W Pitoyo et al

Coronavirus Disease 2019: Review of Current Literatures.Jurnal Penyakit Dalam Indonesia |
Vol. 7, No. 1 | Maret 2020

Riedel S, Morse S, Mietzner T, Miller S. Jawetz, Melnick, & Adelberg’s Medical Microbiology.
28th ed. New York: McGraw- Hill Education/Medical; 2019. p.617-22.
 The Rule of 3 on COVID-19
3 Dangerous Predisposition Factor
3 Phase of COVID-19
-High Afinity Receptor Phase 1 (Acute) :
-High Viral Load D1-D7 of Infection
-Co-Morbids No Symptoms-Fever-ILI

3 Sequences of Pathogenesis to Death Phase 2 : (Critical) :

-Alveolar ACE2 –Receptor Bounding > D7- >D 14(H21) of Infection
-Cytokine Storm No Symptoms
-ARDS Mild to ModerateWAITING for Another Update
Severe to ARDS
3 Main Treatment of CoVID-19: Fase III : (Recovery) :
-Obat-obatan sesuai rekomendasi >D 21 of Infection
-Kontrol Gula Darah No Symptoms
-Oksigenasi Well Done Healing
Or
Literature Review / ARDS with Ventilator Dependent
Ronald Irwanto in Asosiasi Dinas Alveolar Fibrotic?
Kesehatan Indonesia (ADINKES)
Symposium, April, 23rd 2020 Ronald Irwanto - Internist Konsultan
 Patogenesis :
COVID-19 - Receptor
COVID-19 - Antibody
Antibody IgM & IgG (Total Antibody)
COVID-19 - Inflamasi
IgM > D7
COVID-19-Receptor IgG > D14

ACE-2 Receptor

Soluble TNF-Alpha-Bounded TNF Alpha

to inflammatory Receptors Alveolar
IL-6 Rules? Apoptosis + ADCC Effect Necrotic Cells
RNA Corona Virus Infected Cells  Antibody + TNF Alpha and other cytokine (IL-6?)
produced (First Phase)Cells Inflammation  Cells Damage  Necrotic Cells
 Hyperinflammatory TNF Alpha and other Cytokine produced (Second Phase)
2 Inflamation Phase Cytokine Storm

Ronald Irwanto - Internist Konsultan

Yufang Shi, Ying Wang, Changshun Shao , et al , COVID-19
infection: the perspectives on immune responses Cell Death &
Differentiationhttps://doi.org/10.1038/s41418-020-0530-3
 COVID-19 to Alveolar Fibrosis

Cytokine Storm Necrotic Fibrosis

Lung Dysfunction
If it is resulting a Ventilator Dependent
What is the Target?

Adityo Susilo, C. Martin Rumende, Ceva W Pitoyo et al

Coronavirus Disease 2019: Review of Current Literatures.Jurnal Penyakit Dalam Indonesia |
Vol. 7, No. 1 | Maret 2020

Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-
nCoV: host-directed therapies should be an option. Lancet. 2020;395(10224):e35-e6.
COVID -19 :The Categories
Slide KemenKes RI
Slide KemenKes RI
Slide KemenKes RI
COVID -19 : Screening & Confirmation
 Confidence Level in Detection

• Culture
• Polymerase Chain Reaction
• Antigen
• Antibody

Press Release : Kewaspadaan Tes Cepat (Rapid Test) CoViD-19 IgM / IgG Berbasis Serologi
Perhimpunan Dokter Spesialis Patologi Klinik Indonesia
9 Maret 2020
 • Corona virus culture : BSL-3 Laboratory (Recommendation?)
• Highest Level of Confident in Confirmation Test : real time
reversetranscroptation-PCR (rRT-PCR)

World Health Organization. Laboratory testing for coronavirus disease 2019 (COVID-19)
in suspected human cases. Geneva : World Health Organization ; 2020

Literature Review /
Ronald Irwanto in Asosiasi Dinas Kesehatan Indonesia (ADINKES) Symposium,
April, 23rd 2020
 Antibody Screening Test

Antibody IgG

Antibody IgM IgM D 40?

IgM Week 12?
Swab PCR + PCR + PCR - PCR -
Terifeksi D7 D14 D21 D28

Literature Review /
Ronald Irwanto in Asosiasi Dinas Kesehatan Indonesia (ADINKES) Symposium,
April, 23rd 2020
 Screening and PCR Interpretation : Daily Practice
PCR IgM IgG Description

+ - - Early Infection < D7 infeksi

+ + - Possible for D7 - D14 (21) of infection

Contagious
+ + + Possible for D14 - D21 of infection phase?
+ - + Possible for > D21 (D40 / W12?) of infection
delay conversion?

- + - Possible for D7 - D14 of infection

dd/ PCR false negative

- + + Possible for D7 – D21 (>H21) of infection

recovery phase dd/ PCR false negative

- - + Possible for > H21 (D40 / W12?) of infection

recovery phase dd/ PCR false negative

- - - Non COVID dd/ false negative

Literature Review /
Ronald Irwanto in Asosiasi Dinas Kesehatan Ronald Irwanto - Internist Konsultan, 2020
Indonesia (ADINKES) Symposium, April, 23rd 2020
Treatment :
No Definitive Treatment
No Adequate Clinical Trial
1. Chloroquine base therapy
Aim : Blocking the ACE-2 Receptor
Side Effect : Prolong QT ECG
Useless in critical phase when alveolar cytokine storm occurred?
Useless in ARDS by cytokine storm?
2. Antiviral base therapy
Oseltamivir  Approve by few Societies
Claimed as Neuraminidase Inhibitor ; CoV No Neuramidase
Indonesian Society of Clinical Pharmacologist ; Press Release 2020

Lopinavir / Ritonavir  Claimed a significant mortality decreasing

CM Chu, VCC Cheng, IFN Hung et al. Role of lopinavir / ritonavirin the treatment of SARS :
Initial virological and clinical findings. Thorax 2004 ; 59 : 252-256.doi : 10.1136 / thorax 2003.012658
 SARS-COV 1 not SARS-COV 2

Redemsvir  USA Claimed ; on Progress? Adequate Clinical Trial ?

3. Anti-Inflammation Base Therapy
Aim : Blocking the inflammation
Hydrocortison 100mg / 24 jam
Protocol tatalaksana COVID-19 ; 2020 . Approved by PDPI, PAPDI, PERKI, PERDATIN, IDAI, 2020

Toclizumab for blocking IL-6

Tocilizumab, as a recombinant humanized antihumanIL-6 receptor monoclonal
antibody, can bind to the IL-6receptor with high affinity, thus preventing IL-6
itself from binding to its receptor, rendering it incapable of immune damage
to target cells, and alleviating the inflammatory responses
Xiaoling Xua, Mingfeng Han, Tiantian Lia et al. Effective treatment of severe COVID-19 patients
with tocilizumab. www.pnas.org/cgi/doi/10.1073/pnas.2005615117

Administered when cytokine storm defined, not for early treatment

Pro & Cons ; Clinical Trial?
4. Plasma Convalescent Therapy
Aim : Fighting COVID with Passive Antibody Therapy : Role of Neutralizing Antibodies
Pro & Cons ; Clinical Trial?

Idea :Inhibiting Penetration Virus to Cells

5. Antibiotics Base Therapy
Azithromycin, Levofloxacin
Aim : off label effect?
Protocol tatalaksana COVID-19 ; Approved by PDPI, PAPDI, PERKI, PERDATIN, IDAI, 2020
Please
Pro beware
& Cons for
; Clinical Antibiotic Misleading
Trial? Used inBUNDLES
Use VENTILATOR COVID-19
when using
Ventilator for patients
Not ANTIBIOTICS unless a bacterial HAP/VAP
Noted!!
RASPRO Indonesia Study Group
It’s a MISLEADING
COVID-19 !! / Fever = Broad Spectrum AB
with shortness of Breath
COVID-19 to Ventilator = Broad Spectrum AB
Warning for Antibiotics Misleading : Selective Pressure
by RASPRO Indonesia Study Group
RASPRO Indonesia Study Group
 Mechanism of Antimicrobial Resistance:
“Selective Pressure” for Antimicrobial-Resistant Strains

Resistant Strains
Rare
Antimicrobial
Exposure

Resistant Strains
Dominant

Campaign to Prevent Antimicrobial Resistance in Healthcare

Settings, CDC 2002
Comparison Gram +ve VS Gram –ve
in Community and Hospital Pola Kepekaan dan Resistensi
Mikroorganisme Aerob pada
  Jumlah   Infeksi Jaringan Lunak Komplikata
  n %   dengan Berbagai Manifestasi Klinisnya
Bakteri gram (+) 54.0% di Tiga IGD Rumah Sakit di Jakarta
Bakteri gram (-) 37.0%
Ronald Irwanto ,Suhendro, Khie Chen, Yeva
Kultur steril 9.0%
Rosana Indonesian Antimicrobial Resistance
Total 100.0%  Watch, 2009

POLA KEPEKAAN DAN RESISTENSI Jumlah

MIKROORGANISME AEROB, PENGGUNAAN n %
ANTIBIOTIKA DAN EFEKTIFITAS KULTUR
PADA INFEKSI KULIT DAN JARINGAN LUNAK Bakteri gram (+) 29 25.7%
KOMPLIKATA DI RUANG RAWAT INAP Bakteri gram (-) 84 74.3%
PENYAKIT DALAM RUMAH SAKIT X
Total 113 100.0%

Ronald Irwanto, Suhendro, Khie Chen, et al 2013

 Comparison Microbial Pattern : Community VS Hospital
Community Hospital

Pola Kepekaan dan Resistensi

Mikroorganisme Aerob pada
Infeksi Jaringan Lunak Komplikata dengan
Berbagai Manifestasi Klinisnya
di Tiga IGD Rumah Sakit di Jakarta

GRAM Positive GRAM Positive

OXA Sensitive S. aureus : 95.5% OXA Sensitive S. aureus : 84.6 %

GRAM NEGATIVE GRAM NEGATIVE

Pseudomonas sp Sensitive to Pseudomonas sp Sensitive to
MEM : 92.3% MEM : 68.2%
IMP : 92.3% IMP : 78.7%
TZP : 92.3% TZP : 50.0%
LVX : 69.2% LVX : 54.5%
AMK : 84.6% AMK : 68.2%
Ronald Irwanto ,Suhendro, Khie Chen, Ronald Irwanto ,Suhendro, Khie Chen,
Yeva Rosana, 2009 et al . Universa Medicina 2013
 Decreasing the Broad Spectrum Antibiotics Unit Sold:
The Prospective Antimicrobial Stewardship of RASPRO Model in
A Private Hospital, Indonesia
Ronald Irwanto Natadidjaja*#, Yuhana Fitra**, Yudianto Budi Saroyo**,
Augustine Matatula**, Rinna Wamila Sundariningrum

J Antimicrobiol Resist & Inf Control. 2019. 8(suppl 1) : P357

Results.
Three months observation and comparison before-after RASPRO-RASAL
flowchart implemented :
0.5g Meropenem unit sold decreased 63.83%, 1g Meropenem decreased 75.42%
while Imipenem showed 100% reduction.
A 93.80% decreasing of Ceftazidime and 70.05% Cefepime unit sold also reported.
Overall, we noted 76.10% broad spectrum reduced before-after RASPRO-RASAL
implemented.
Conclusion.
Decreasing of broad spectrum antibiotics unit sold was reported in 3 months after
RASPRO-RASAL used.
This result might not be a fully improvement of RASPRO-RASAL tools, but in
our experience and opinion, this significant result should be considered as part of
RASPRO-RASAL implementation.
RASPRO Indonesia Study Group
WISMA ATLIT, 22 April 2020, Ronald Irwanto
Ronald Irwanto & Didier Pitet : Father of Hand Hygiene