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

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