Curriculum Vitae

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

Pendidikan :
SMP - SMA : Kolese KANISIUS, 1994
Dokter Umum : FK TRISAKTI, 2002
Spesialis Penyakit Dalam (Internist) : FKUI, 2009
Konsultan Penyakit Tropik & Infeksi : FKUI / PAPDI, 2013
Pekerjaan :
Bendahara Pengurus Besar Perhimpunan Konsultan Penyakit Tropik dan Infeksi
Indonesia (PB PETRI)

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

Tim Panel Ahli PNPK Sepsis, Kemenkes RI

Anggota Pokja PPI, Kemenkes RI

Staf Pengajar Ilmu Penyakit Dalam, FK TRISAKTI

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

Wakil Ketua Komite Medik, RS PONDOK INDAH – PURI INDAH

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

BINTARO JAYA
Antibiotic Potency and PK/PD:
The Art of Antibiotic
RONALD IRWANTO

PP. PERDALIN
 Adequate antimicrobial treatment in critically ill patients

Changes to
Empiric Treatment
Pathogen (de-escalation) Timely
Coverage Initiation
(appropriate) (early)

Optimal
Correct
Therapy Correct
Dose Route
(adequate) (adequate)

Increased Survival

Rello J. Eur Respir Rev . 2007;16:33-39.

Optimizing the Antimicrobial Usage
De-escalation strategy
Optimizing the PKPD of antimicrobial
Combination therapy
Short course antimicrobial treatment
Using biomarkers to guide antimicrobial usage
PKPD relationship
 Consideration When Using
an Antibacterial Agent
Outcome
Microbiology
 Clinical efficacy
 Mechanism of action
 Bacterial eradication
 Antibacterial spectrum Concentration
at infection site  Compliance with
Drug dosing regimen
 Tolerability
Pathogen MIC 
PK Rate of resolution
 Prevention of resistance
 Absorption PD
 Distribution

 Time vs. concentration
Metabolism
 Excretion dependent killing
 Optimal dosing  Bactericidal vs. bacteriostatic
regimen activity
 Tissue penetration
(Scaglione, 2002)  Persistence of antibacterial effect
Pharmacodynamic :

MIC Related to Dose

Track / Rute

Pharmacokinetic:
Tissue Penetration
MIC
Parameters of Antimicrobial Activity
• Potency : MIC
MBC
• Time Course of Activity

Persistent effects
Post Antibiotic Effect (PAE)

MIC < MBC < MPC

 MIC-90
Dosis minimal yang dapat digunakan untuk mencegah
pertumbuhan 90% kuman IN VITRO (Standard CLSI )

RESISTENRELATIF

Contoh/
Cut off MIC-90 Resisten betalaktam = 32ug/ml

E.coli dinyatakan RESISTEN terhadap betalaktam apabila diberikan 32ug/ml

Beta Laktam IN VITRO BELUM BISA MENGHAMBAT PERTUMBUHAN 90%

QUESTION :
Bila diberikan AB 34ug/ml36ug/ml 38ug/ml SENSITIF

IN VIVO :
Diberikan 1x2 gram Ceftriaxone Resisten Diberikan 2x2g 3x2gSENSITIF??
ANTIMICROBIAL STEWARDSHIP
PROGRAM

PRE-AUTHORIZATION Post Antibiotic Review

RESTRICTION vs NON RESTRICTION

- Person vs System
- AB Classification vs AB Guidelines
 (A,B,C)
- Hard to do vs Easy to do
GROUP RESTRICTION Based on Spectrum Cut Off

DOSE RESTRICTION Based on Resistant MIC-90 Cut Off

MIC-90 (Based of Drug Restriction) in
Pre Authorization Model

Free RESTRICT
Ceftriaxone 1-2 x2g Ceftriaxone 2x2g
Levofloxacin Levofloxacin
1x500mg 1x750mg / >
Rute
Cunha,2010
 PK/PD parameters affecting antibiotic efficacy in
vivo
Concentration Cmax:MIC
Time dependent
AUC:MIC T>MIC (CEF)
Concentration dependent
Cmax>MIC (AM)
AUC/MIC (FQ)
T>MIC

MIC

PAE
0
Time (hours)
MIC = minimum inhibitory concentration; AUC = area under the curve; T = time;
PAE = post antibiotic effect
Antibiotic Characteristic base on PKPD
Cmax = Peak Concentration Dependent
Cmax / MIC AUC / MIC
Aminoglycosides1,2 Aminoglycosides2
Fluoroquinolones1,2 Fluoroquinolones1,2
Oxazolidanones1,2
Glycopeptides2
Concentration

Lincosamides2
Lipopeptides1,2
Tetracyclines2
Macrolides2

MIC
Penicillins
1

Cephalosporins1 T > MIC

Carbapenems1 Cmin = Trough
Macrolides1,2
Glycopeptides2
Lincosamides2
Time (hours)

1.
Nicolau DP. J Infect Chemother. 2003;9:292-296.
2.
Ambrose PG, et al. Clin Infect Dis. 2007;44:79-86.
Cmax:MIC (aminoglycosides)
Concentration
Target value: Cmax:>8–10 MIC
Cmax:MIC

MIC

0
Time (hours)
Cmax = maximum plasma concentration
T>MIC (β-lactams)
Concentration

MIC
T>MIC
0
Time (hours)
Turnridge. Clin Infect Dis 1998;27:1022; Manduru, et al. Antimicrob Agents Chemother 1997;41:2053–2056;
Tam, et al. J Antimicrob Chemother 2002;50:425–428; Tam, et al. Antimicrob Agents Chemother 2005;49:4920
24 hour Area Under Curve
24 H AUC : cummulative dosage in 24 H
Related to efficacy and drug toxicity
Concentration Target Attaintment : 24 H AUC/MIC : 125
if MIC = 2 24 H AUC : 250
average concentration 250/24 : 10 ug/mL

MIC

0 Time
Time (hours)
Ambrose, et al. Antimicrob Agents Chemother 2001;45:2793–2797;
Forrest, et al. Antimicrob Agents Chemother 1993;37:1073–1081
Conclusion
Antibiotic PK/PD should be known by every clinician
 Antibiotic PK/PD will influence the rational antibiotic
usage
PK is dosed that related to in vivo concentration
PD is in vivo concentration related to effect to
microorganism
PK/PD will determine the potency of antibiotic
Based on the antibiotic potency there are three types
of antibiotic : dose / concentration dependent, time
dependent type II and time dependent type III
Thank You