Post on 29-Dec-2020
Antibiotic Usage Related to Microorganisms Pattern and MIC
DR. Dr. Latre Buntaran Sp.MK(K) Secretary General PERDALIN
Head of Compartment of Infection Control PERSI
Doripenem: Potent Activity Against Enterobacteriaceae
Susceptibility = 100% for all; assuming a break point of 4 μg/mL for doripenem.
*≤ value.
Adapted from Jones RN et al. Antimicrob Agents Chemother. 2004;54:144-154.
* * * *
*
* E. coli K. pneumoniae Enterobacter
spp.
P. mirabilis Citrobacter
spp.
* * * * *
* 0.016
0.032
0.063
0.13
0.25
0.50
1.00
2.00
0
Doripenem Imipenem Meropenem
MIC90
(µg/mL)
Doripenem: More Potent Than Imipenem or Meropenem Against Resistant Enterobacteriaceae
Susceptibility = 100% for all; assuming a break point of 4 μg/mL for doripenem. *≤ value.
Adapted from Jones RN et al. Antimicrob Agents Chemother. 2004;48:3136-3140.
* 0.03
0.06
0.13
0.25
0.50
1.00
2.00
Citrobacter
spp.
(ceftazidime resistant)
E. coli
ESBL
Enterobacter
spp.
(ceftazidime resistant)
K. pneumoniae
ESBL
*
0
Doripenem Imipenem Meropenem
MIC90
(µg/mL)
Doripenem: More Potent Than Imipenem or Meropenem Against Non-fermentative Gram-Negative Bacteria
Adapted from Jones RN et al. Antimicrob Agents Chemother. 2004;54:144-154.
A. baumannii P. aeruginosa
0.5
1.0
2.0
4.0
0
0.5
1.0
2.0
4.0
0
Doripenem Imipenem Meropenem
MIC90
(µg/mL)
MIC50
(µg/mL)
Cumulative % of P aeruginosa isolates inhibited by MIC: Doripenem, Meropenem and Imipenem
100
90
80
70
60
50
40
30
20
10
0
0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 >32
Cu
mu
lati
ve
% o
f is
ola
tes
in
hib
ite
d
MIC (µg/mL)
Meropenem
Doripenem
Imipenem
MIC90
TRUST 11 (2007) surveillance. N=866, all patient isolates of P aeruginosa. In vitro activity does not necessarily correlate with clinical results. Data on file, Ortho-McNeil Janssen Pharmaceuticals, Inc.
Doripenem demonstrated excellent susceptibility vs. P aeruginosa
Doripenem: Low emergency of P. aeruginosa Resistance
0
1
2
3
4
5
6
7
8
Doripenem Meropenem Imipenem
2x MIC 4x MIC 8x MIC
*Out of 8 strains.
Mushtaq S et al. Presented at: 43th ICAAC, Sept 14-17, 2003, Chicago, Illinois. Poster F530.
Number of
Strains
Producing
Mutants*
DORIpenem™: 20-30% masih sensitif terhadap pathogen yang resisten pada Carbapenem lainnya
Assumes a breakpoint of 4 μg/mL for doripenem.
CarbapenemR = resistance to imipenem or meropenem at ≥16 g/mL.
Adapted from Jones RN et al. Antimicrob Agents Chemother. 2004;48:3136-3140.
*In vitro activity does not necessarily
correlate with clinical results.
DORIBAX IS THE ONLY APPROVED CARBAPENEM FOR 1-HOUR
INFUSION AND 4-HOUR EXTENDED INFUSION
DORIBAX Prescribing Information (Malaysia) 2008.
Improved Doripenem Targeting of Higher MICs with 4-hour Infusion
100%
0
20
40
60
80
100
MIC, µg/mL
Target
Attainment,
%
0.06 0.12 0.25 0.5 1 2 4 8 16
Doripenem 500 mg
q8h, 1-h infusion
Doripenem 500 mg
q8h, 4-h infusion
35%
78%
95%
31
Doripenem satu-satunya karbapenem yang FDA Approved untuk penggunaan secara extended infusion 4 jam untuk mengoptimalkan efek bakterisidal
Dose 500 mg 1 h 500 mg 4 h 1500 mg 24 h
Dori
penem
Con
centr
ation
(mg/L
)
Time Since Start of Infusion (h)
MIC = 4
32
16
8
4
2
1
0 6 4 2 8 10 12
31% 49%
1. Data on File, Ortho-McNeil, Inc. Raritan, NJ. 2. Drusano GL. NATURE REVIEWS / MICROBIOLOGY 2004 (April);2:289-300; 3. Craig WA
Clin. Infec. Dis. 1998; 26, 1-12; 4. Zhanel G et al. Drugs. 2007;67:1027-1052.
• Pada Beta Laktam, T>MIC merupakan indikator aktivitas anti bakteri2,3,4
Pada patogen yang cenderung resisten (MIC = 4 mg/l)
pemberian Doribax secara extended infusion 4 jam akan
meningkatkan T>MIC menjadi 49%
Carbapenem hanya memerlukan T>MIC 40%
untuk mencapai aktivitas bakterisidal2,3,4
Stabilitas Doripenem vs Carbapenem lain
Normal Saline = NaCl
32
Synergy of Doripenem with other antibiotics
Time kill synergy studies of doripenem combined with Amikacin and Colistin against 25 isolates of Acinetobacter baumannii.*
Pankuch GA, et al, Harald Seifert, Peter C. Appelbaum. Activity of Doripenem with and without levofloxacin, amikasin, and colistin against Pseudomonas aeruginosa and
Acinetobacter baumannii. Diagnostic Microbiology and Infectious Disease 67 (2010)
Synergy of Doripenem with Amikasin in 100 isolates carbapenem nonsusceptible P. aeruginosa
Number of Pseudomonas aeruginosa with synergy as determined by Etest synergy test
Drugs Combination (n) Synergy or Additive Indifference Antagonis
Doripenem + Amikasin (n= 100) 67 33 0
Doripenem + Colistin (n= 100) 31 69 0
Doripenem + Levofloxacin (n=100) 23 77 0
He W , et al. In vitro Etest synergy of doripenem with amikacin, colistin, and levofloxacin agains Pseudomonas aeruginosa with defined carbapenem resistance mechanisms as determined
by the Etest method. Diagnostic Microbiology and Infectious Disease xxx (2012
Doripenem + terapi kombinasi untuk Acinetobacter baumanii yang resisten
April 13 35