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 Doripenem Imipenem Meropenem 2.00 1.00 0.50 0.25 MIC 90 (µg/ml) 0.13 0.063 0.032 0.016 0 * * * * * * * * * * * E. coli K. pneumoniae Enterobacter spp. 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. * P. mirabilis Citrobacter spp.
Doripenem: More Potent Than Imipenem or Meropenem Against Resistant Enterobacteriaceae Doripenem Imipenem Meropenem 2.00 1.00 0.50 MIC 90 (µg/ml) 0.25 0.13 0.06 0.03 * * 0 Citrobacter spp. (ceftazidime resistant) E. coli ESBL Enterobacter K. pneumoniae spp. ESBL (ceftazidime resistant) 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.
Doripenem: More Potent Than Imipenem or Meropenem Against Non-fermentative Gram-Negative Bacteria Doripenem Imipenem Meropenem 4.0 4.0 2.0 2.0 MIC 90 (µg/ml) 1.0 MIC 50 (µg/ml) 1.0 0.5 0.5 0 P. aeruginosa 0 A. baumannii Adapted from Jones RN et al. Antimicrob Agents Chemother. 2004;54:144-154.
Doripenem demonstrated excellent susceptibility vs. P aeruginosa Cumulative % of isolates inhibited Cumulative % of P aeruginosa isolates inhibited by MIC: Doripenem, Meropenem and Imipenem 100 90 80 70 60 50 40 30 20 10 0 MIC 90 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 >32 MIC (µg/ml) Doripenem Meropenem Imipenem 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: Low emergency of P. aeruginosa Resistance Number of Strains Producing Mutants * 8 7 6 5 4 3 2 1 0 2x MIC 4x MIC 8x MIC Doripenem Meropenem Imipenem *Out of 8 strains. Mushtaq S et al. Presented at: 43th ICAAC, Sept 14-17, 2003, Chicago, Illinois. Poster F530.
DORIpenem : 20-30% masih sensitif terhadap pathogen yang resisten pada Carbapenem lainnya Assumes a breakpoint of 4 μg/ml for doripenem. Carbapenem R = resistance to imipenem or meropenem at 16 g/ml. *In vitro activity does not necessarily correlate with clinical results. Adapted from Jones RN et al. Antimicrob Agents Chemother. 2004;48:3136-3140.
DORIBAX IS THE ONLY APPROVED CARBAPENEM FOR 1-HOUR INFUSION AND 4-HOUR EXTENDED INFUSION Improved Doripenem Targeting of Higher MICs with 4-hour Infusion 100 100% 95% Target Attainment, % 80 60 40 20 0 Doripenem 500 mg q8h, 1-h infusion Doripenem 500 mg q8h, 4-h infusion 78% 35% 0.06 0.12 0.25 0.5 1 2 4 8 16 MIC, µg/ml DORIBAX Prescribing Information (Malaysia) 2008.
Doripenem Concentration (mg/l) Doripenem satu-satunya karbapenem yang FDA Approved untuk penggunaan secara extended infusion 4 jam untuk mengoptimalkan efek bakterisidal 32 16 8 4 2 31% 49% 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 bakterisidal 2,3,4 MIC = 4 1 0 2 4 6 8 10 12 Time Since Start of Infusion (h) Dose 500 mg 1 h 500 mg 4 h 1500 mg 24 h Pada Beta Laktam, T>MIC merupakan indikator aktivitas anti bakteri 2,3,4 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. 31
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