Eravacycline in vitro activity against clinical isolates obtained from urinary and gastrointestinal sources, including drug-resistant pathogens, from patients in Europe Contact: 1 2 3 3 3 3 Tetraphase Pharmaceuticals Medical Information (TPMI) Matteo Bassetti , Ian Morrissey , Trudy Grossman , Melanie Olesky , Hina Patel , Joyce Sutcliffe Poster P0342 [email protected] 1Santa Maria Misericordia Hospital, Udine, Italy; 2IHMA Europe Sarl, Epalinges, Switzerland; 3Tetraphase Pharmaceuticals, Watertown, MA, USA 617-715-3600 Introduction Results (cont’d) Gram-negative bacteria are common causes of intra-abdominal infections and urinary Table 1. Summary MIC (mg/L) data from eravacycline against isolates from GI (n = 732) Table 3. Antimicrobial activity of eravacycline and comparator agents against Enterobacteriaceae isolates from GI (n = 403) and GU (n = 422) sources. Table 5. Antimicrobial activity of eravacycline and comparator agents against tract infections, and resistance amongst these pathogens is increasing. Eravacycline and GU (n = 678) infections (where n ≥ 10) Gram-positive isolates from GI (n = 186) and GU (n = 161) sources. a is a novel, fully-synthetic fluorocycline antibiotic of the tetracycline class with broad- GI (n) MIC50/90 MIC range GU (n) MIC50/90 MIC range a Organism/Antimicrobial a MIC (mg/L) %S / %I / %R MIC (mg/L) %S / %I / %R Organism/Antimicrobial MIC (mg/L) %S / %I / %R Organism/Antimicrobial Agent (No. Tested) spectrum activity in development for the treatment of serious infections, including Gram-negatives MIC50 MIC90 Range EUCAST Agent (No. Tested) Agent (No. Tested) b Acinetobacter baumannii (45) 0.5/1 0.03-2 Acinetobacter baumannii (25) 0.25/1 0.03-4 MIC50 MIC90 Range EUCAST MIC50 MIC90 Range EUCAST Enterococcus spp. (149) those caused by multidrug-resistant (MDR) pathogens. Eravacycline has been evaluated e Amoxicillin/clavulanate 2 >16 0.25-> 16 52.4 / 1.3 / 46.3 Citrobacter freundii (45) 0.25/0.5 0.12-1 Citrobacter freundii (25) 0.25/0.5 0.12-1 Enterobacteriaceae (825) Klebsiella spp. (137) in phase 3 studies for the treatment of complicated intra-abdominal infections (cIAI) Aztreonam ͠ 0.5 > 16 ͠ 0.5-> 16 78.3 / 3.2 / 18.6 Azithromycin >8 >8 0.25-> 8 -- / -- / -- Citrobacter koseri (10) 0.12/0.25 0.12-0.5 Citrobacter koseri (92) 0.12/0.25 0.12-1 Aztreonam ͠ 0.5 > 16 ͠ 0.5-> 16 75.9 / 1.5 / 22.6 Ceftriaxone >64 >64 1-> 64 -- / -- / -- Cefepime ͠ 0.25 8 ͠ 0.25-> 16 85.8 / 3.8 / 10.4 Cefepime ͠ 0.25 > 16 ͠ 0.25-> 16 78.1 / 3.7 / 18.3 and complicated urinary tract infections (cUTI), including pyelonephritis. The purpose Enterobacter aerogenes (31) 0.5/0.5 0.25-1 Enterobacter aerogenes (52) 0.5/0.5 0.25-2 Daptomycin 4 4 0.25-> 4 -- / -- / -- Ceftazidime ͠ 0.5 > 16 ͠ 0.5-> 16 76.4 / 5.2 / 18.4 Ceftazidime ͠ 0.5 > 16 ͠ 0.5-> 16 78.8 / 3.7 / 17.5 Eravacycline 0.06 0.06 0.015-1 -- / -- / -- of this study was to assess the in vitro activity of eravacycline against recent European Enterobacter cloacae (35) 0.5/2 0.25-4 Enterobacter cloacae (21) 0.5/1 0.5-4 Ceftriaxone ͠ 0.5 > 32 ͠ 0.5-> 32 75.6 / 1.9 / 22.4 Ceftriaxone ͠ 0.5 > 32 ͠ 0.5-> 32 76.6 / 0.7 / 22.6 Levofloxacin >8 >8 0.06-> 8 36.9 / -- / 63.1 Escherichia coli (71) 0.12/0.25 0.06-2 Klebsiella oxytoca (34) 0.25/0.5 0.12-2 Colistin 1 > 4 ͠ 0.12-> 4 62.8 / -- / 37.2 Linezolid 2 2 1-8 99.3 / -- / 0.7 clinical isolates of key pathogens from gastrointestinal (GI) and genitourinary (GU) Colistin 1 1 0.25-> 4 97.8 / -- / 2.2 Minocycline 8 >8 ͠ 0.03-> 8 -- / -- / -- Eravacycline 0.5 2 0.015-16 -- / -- / -- Klebsiella oxytoca (37) 0.25/0.25 0.12-0.5 Morganella morganii (43) 1/2 0.25-8 Eravacycline 0.25 1 0.12-2 -- / -- / -- Penicillin 8 >8 0.5-> 8 -- / -- / -- infections. Gentamicin 1 > 8 ͠ 0.25-> 8 83.8 / 5.5 / 10.8 Klebsiella pneumoniae (63) 0.5/1 0.12-2 Proteus mirabilis (42) 2/2 0.25-4 Gentamicin 0.5 > 8 ͠ 0.25-> 8 89.1 / 0 / 11 Tetracycline 32 >32 0.12->32 -- / -- / -- Imipenem 1 4 ͠ 0.25-> 8 82.4 / 15.9 / 1.7 Tigecycline 0.12 0.25 ͠ 0.015-4 96.6 / 2 / 1.3 Imipenem ͠ 0.25 1 ͠ 0.25-> 8 94.2 / 0.7 / 5.1 Morganella morganii (34) 1/2 0.25-4 Proteus vulgaris (59) 1/1 0.25-2 Levofloxacin ͠ 0.25 > 4 ͠ 0.25-> 4 81.7 / 4.1 / 14.2 Vancomycin 1 >32 0.25-> 32 78.9 / -- / 21.1 Levofloxacin ͠ 0.25 > 4 ͠ 0.25-> 4 81 / 3.7 / 15.3 Proteus mirabilis (35) 1/2 0.5-4 Providencia rettgeri (10) 2/2 0.25-2 Piperacillin/tazobactam 2 32 ͠ 0.5-> 64 83.6 / 3.4 / 13 S. aureus (54) Piperacillin/tazobactam 2 64 ͠ 0.5-> 64 77.4 / 5.8 / 16.8 Amoxicillin/clavulanate 2 >16 0.5-> 16 -- / -- / -- Proteus vulgaris (19) 1/1 0.25-1 Providencia stuartii (25) 1/4 0.5-16 Tetracycline 4 > 8 0.25-> 32 -- / -- / -- Methods Tetracycline 2 > 8 0.5-> 8 -- / -- / -- Azithromycin 1 >8 0.5-> 8 66.7 / 0 / 33.3 Pseudomonas aeruginosa (40) 8/16 1-32 Pseudomonas aeruginosa (13) 8/16 1-16 Tigecycline 1 4 ͠ 0.015-32 70.3 / 18.8 / 10.9 Ceftriaxone 16 >64 1-> 64 -- / -- / -- Tigecycline 0.5 2 0.12-4 89.1 / 8.8 / 2.2 Daptomycin 0.5 1 0.25-1 100 / -- / 0 ! Serratia marcescens (19) 1/4 1-4 Serratia marcescens (15) 1/2 0.5-2 Citrobacter spp.b (172) A total of 732 GI and 678 GU clinical isolates, collected from 2013-2014 from P. mirabilis (77) Eravacycline 0.06 0.25 0.03-1 -- / -- / -- Stenotrophomonas maltophilia (11) 1/1 0.12-2 Stenotrophomonas maltophilia (27) 0.5/1 0.12-2 Aztreonam ͠ 0.5 16 ͠ 0.5-> 16 84.3 / 1.7 / 14 amongst 134 European hospitals, were tested. Aztreonam ͠ 0.5 2 ͠ 0.5-> 16 87 / 11.7 / 1.3 Levofloxacin 0.5 >8 0.25-> 8 57.4 / 0 / 42.6 Cefepime ͠ 0.25 1 ͠ 0.25-> 16 95.9 / 1.2 / 2.9 Linezolid 2 2 2-2 100 / -- / 0 Gram-positives Cefepime ͠ 0.25 4 ͠ 0.25-> 16 85.7 / 5.2 / 9.1 ! Minimum inhibitory concentration (MIC) endpoints were determined by broth Ceftazidime ͠ 0.5 > 16 ͠ 0.5-> 16 83.7 / 2.9 / 13.4 Minocycline 0.12 8 0.06-> 8 85.2 / 0 / 14.8 Enterococcus faecalis (45) 0.06/0.12 0.015-0.5 Enterococcus faecalis (22) 0.06/0.06 0.03-0.12 Ceftriaxone ͠ 0.5 32 ͠ 0.5-> 32 84.9 / 0 / 15.1 Ceftazidime ͠ 0.5 4 ͠ 0.5-> 16 85.7 / 6.5 / 7.8 Penicillin >8 >8 ͠ 0.12-> 8 3.7 / -- / 96.3 microdilution according to CLSI guidelines (1). Ceftriaxone ͠ 0.5 16 ͠ 0.5-> 32 85.7 / 1.3 / 13 Tetracycline 0.5 >32 0.25-> 32 74.1 / 3.7 / 22.2 Enterococcus faecium (58) 0.06/0.06 0.015-1 Enterococcus faecium (24) 0.03/0.06 0.015-0.06 Colistin 0.5 1 ͠ 0.12-4 98.3 / -- / 1.7 Tigecycline 0.12 0.5 0.06-1 94.4 / -- / 5.6 Colistin > 4 > 4 > 4-> 4 0 / -- / 100 ! Quality control testing was performed each day of testing as specified by the Staphylococcus aureus (43) 0.06/0.25 0.03-1 Staphylococcus aureus (11) 0.06/0.12 0.06-1 Eravacycline 0.25 0.5 0.12-1 -- / -- / -- S. haemolyticus (83) Eravacycline 2 2 0.25-4 -- / -- / -- Amoxicillin/clavulanate 2 >16 0.25-> 16 -- / -- / -- Staphylococcus epidermidis (34) 0.12/0.5 0.03-1 Staphylococcus epidermidis (26) 0.25/0.5 0.015-0.5 Gentamicin 0.5 1 ͠ 0.25-> 8 96.5 / 0.6 / 2.9 CLSI using Escherichia coli ATCC 25922, E. coli ATCC 35218, Enterococcus faecalis Imipenem ͠ 0.25 2 ͠ 0.25-> 8 99.4 / 0 / 0.6 Gentamicin 2 > 8 1-> 8 61 / 16.9 / 22.1 Azithromycin >8 >8 0.25-> 8 27.7 / 0 / 72.3 Streptococcus agalactiae (10) 0.03/0.03 0.008-0.03 Staphylococcus haemolyticus (76) 0.12/0.5 0.03-1 Ceftriaxone 64 >64 1-> 64 -- / -- / -- Levofloxacin ͠ 0.25 ͠ 0.25 ͠ 0.25-> 4 97.1 / 1.7 / 1.2 Imipenem 2 8 ͠ 0.25-> 8 53.3 / 45.5 / 1.3 ATCC 29212, Haemophilus influenzae ATCC 49247, H. influenzae ATCC 49766, Streptococcus anginosus (23) 0.008/0.03 ͠ 0.001-0.06 Streptococcus agalactiae (25) 0.015/0.03 0.008-0.06 Daptomycin 0.25 0.5 0.12-1 100 / -- / 0 Piperacillin/tazobactam 2 16 ͠ 0.5-> 64 89.5 / 2.9 / 7.6 Levofloxacin ͠ 0.25 > 4 ͠ 0.25-> 4 75.3 / 9.1 / 15.6 Eravacycline 0.12 0.5 0.03-1 -- / -- / -- Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, and Tetracycline 1 4 0.5-> 8 -- / -- / -- Piperacillin/tazobactam ͠ 0.5 4 ͠ 0.5-> 64 92.2 / 3.9 / 3.9 Levofloxacin 8 >8 0.12-> 8 30.1 / 0 / 69.9 Streptococcus pneumoniae ATCC 49619.