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Home , Eravacycline, Providencia stuartii

Eravacycline in vitro activity against clinical isolates obtained from urinary and gastrointestinal sources, including drug-resistant , 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 are common causes of intra-abdominal 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 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 of the class with broad- GI (n) MIC50/90 MIC range GU (n) MIC50/90 MIC range a a Organism/Antimicrobial MIC (mg/L) %S / %I / %R Organism/Antimicrobial MIC (mg/L) %S / %I / %R Organism/Antimicrobial MIC (mg/L) %S / %I / %R Gram-negatives Agent (No. Tested) spectrum activity in development for the treatment of serious infections, including Agent (No. Tested) Agent (No. Tested) MIC 50 MIC 90 Range EUCAST MIC50 MIC90 Range EUCAST MIC50 MIC90 Range EUCAST Enterococcus spp. b (149) those caused by multidrug-resistant (MDR) pathogens. Eravacycline has been evaluated (45) 0.5/1 0.03-2 Acinetobacter baumannii (25) 0.25/1 0.03-4 e Amoxicillin/clavulanate 2 >16 0.25-> 16 52.4 / 1.3 / 46.3 (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 >8 >8 0.25-> 8 -- / -- / -- (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 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 (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 >8 >8 0.06-> 8 36.9 / -- / 63.1 2 2 1-8 99.3 / -- / 0.7 clinical isolates of key pathogens from gastrointestinal (GI) and genitourinary (GU) (71) 0.12/0.25 0.06-2 (34) 0.25/0.5 0.12-2 1 > 4 ͠ 0.12-> 4 62.8 / -- / 37.2 Colistin 1 1 0.25-> 4 97.8 / -- / 2.2 Eravacycline 0.5 2 0.015-16 -- / -- / -- 8 >8 ͠ 0.03-> 8 -- / -- / -- 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. 1 > 8 ͠ 0.25-> 8 83.8 / 5.5 / 10.8 (63) 0.5/1 0.12-2 (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 Imipenem ͠ 0.25 1 ͠ 0.25-> 8 94.2 / 0.7 / 5.1 0.12 0.25 ͠ 0.015-4 96.6 / 2 / 1.3 Morganella morganii (34) 1/2 0.25-4 (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 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 (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 ! (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 (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 (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 (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) ! Quality control testing was performed each day of testing as specified by the Eravacycline 2 2 0.25-4 -- / -- / -- 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 Amoxicillin/clavulanate 2 >16 0.25-> 16 -- / -- / -- 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, 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 ATCC 49619. Tigecycline 0.5 0.5 ͠ 0.015-2 99.4 / 0.6 / 0 Tetracycline > 8 > 8 1-> 8 -- / -- / -- Linezolid 2 2 ͠ 0.5-2 100 / -- / 0 Minocycline 0.25 0.5 0.06-8 98.8 / 0 / 1.2 Table 2. Cumulative MIC distribution of eravacycline against pertinent organisms by c Tigecycline 4 4 0.5-8 7.8 / 37.7 / 54.6 ! Antibiotic susceptibility was determined using EUCAST 2015 breakpoints (2). Enterobacter spp. (139) Penicillin >8 >8 ͠ 0.12-> 8 16.9 / -- / 83.1 resistance phenotype from GI and GU sources (where n > 5) Aztreonam ͠ 0.5 > 16 ͠ 0.5-> 16 55.4 / 2.2 / 42.5 S. marcescens (34) Tetracycline 1 >32 0.12-> 32 56.6 / 10.8 / 32.5 ! Cefepime ͠ 0.25 4 ͠ 0.25-> 16 79.1 / 11.5 / 9.4 Aztreonam ͠ 0.5 > 16 ͠ 0.5-> 16 79.4 / 5.9 / 14.7 Tigecycline 0.25 0.5 0.06-1 96.4 / -- / 3.6 MDR was defined as resistant to 3 or more of the following antibiotic classes: S. agalactiae (35)

Number of isolates (cumulative %) inhibited at eravacycline MIC (mg/L) of: Ceftazidime ͠ 0.5 > 16 ͠ 0.5-> 16 56.1 / 2.9 / 41 Cefepime ͠ 0.25 16 ͠ 0.25-> 16 82.4 / 2.9 / 14.7 Amoxicillin/clavulanate 0.12 0.25 0.12-0.25 -- / -- / -- cefepime/ceftazidime/ceftriaxone (any one), gentamicin, imipenem, levofloxacin, Organism (n) <0.03 0.03 0.06 0.12 0.25 0.5 1 2 4 8 ͡16 MIC MIC 50 90 Ceftriaxone 1 > 32 ͠ 0.5-> 32 54.7 / 2.2 / 43.2 Ceftazidime ͠ 0.5 4 ͠ 0.5-> 16 85.3 / 8.8 / 5.9 Gram-negatives: Azithromycin 0.12 >2 ͠ 0.03-> 2 80 / 0 / 20 piperacillin-tazobactam or tetracycline. A. baumannii (70) 6 (8.6) 11 (24.3) 8 (35.7) 4 (41.3) 26 (78.6) 13 (97.1) 1 (98.6) 1 (100) 0.5 1 Colistin 0.5 1 0.25-> 4 98.6 / -- / 1.4 Ceftriaxone ͠ 0.5 > 32 ͠ 0.5-> 32 73.5 / 5.9 / 20.6 Ceftriaxone 0.06 0.12 0.06-0.12 -- / -- / -- MDR A. baumannii (38) 1 (2.6) 4 (13.2) 2 (18.4) 19 (68.4) 10 (94.7) 1 (97.4) 1 (100) 0.5 1 Eravacycline 0.5 1 0.25-4 -- / -- / -- Colistin > 4 > 4 1-> 4 5.9 / -- / 94.1 Daptomycin 0.25 0.25 0.06-0.5 100 / -- / 0 CR A. baumannii (40) 1 (2.5) 4 (12.5) 2 (17.5) 21 (70) 10 (95) 1 (97.5) 1 (100) 0.5 1 Gentamicin 0.5 4 ͠ 0.25-> 8 89.2 / 2.2 / 8.6 Eravacycline 0.015 0.03 0.008-0.06 -- / -- / -- C. freundii (70) 11 (15.7) 49 (85.7) 6 (94.3) 4 (100) 0.25 0.5 Eravacycline 1 2 0.5-4 -- / -- / -- Levofloxacin 1 1 0.5-> 8 97.1 / 0 / 2.9 MDR C. freundii (14) 4 (28.6) 7 (78.6) 2 (92.9) 1 (100) 0.25 0.5 Imipenem 1 2 ͠ 0.25-> 8 94.2 / 4.3 / 1.4 Gentamicin 1 > 8 ͠ 0.25-> 8 82.4 / 2.9 / 14.7 Linezolid 2 2 1-2 100 / 0 / 0 C. koseri (102) 52 (51) 42 (92.2) 7 (99) 1 (100) 0.12 0.25 Levofloxacin ͠ 0.25 > 4 ͠ 0.25-> 4 81.3 / 2.9 / 15.8 Imipenem 1 2 0.5-> 8 97.1 / 0 / 2.9 Minocycline >8 >8 0.06-> 8 37.1 / 0 / 62.9 Results E. aerogenes (83) 37 (44.6) 41 (94) 4 (98.8) 1 (100) 0.5 0.5 Penicillin ͠ 0.06 0.12 ͠ 0.06-0.12 100 / -- / 0 MDR E. aerogenes (28) 10 (35.7) 13 (82.1) 4 (96.4) 1 (100) 0.5 1 Piperacillin/tazobactam 4 64 ͠ 0.5-> 64 59.7 / 3.6 / 36.7 Levofloxacin ͠ 0.25 2 ͠ 0.25-> 4 88.2 / 2.9 / 8.8 E. cloacae (56) 4 (7.1) 37 (73.2) 8 (87.5) 3 (92.9) 4 (100) 0.5 2 Tetracycline 2 8 1-> 8 -- / -- / -- Tetracycline >8 >8 0.06-> 8 37.1 / 0 / 62.9 MDR E. cloacae (28) 4 (14.3) 13 (60.7) 6 (82.1) 3 (92.9) 2 (100) 0.5 2 Piperacillin/tazobactam 2 16 ͠ 0.5-> 64 85.3 / 5.9 / 8.8 Tigecycline 0.015 0.03 ͠ 0.008-0.06 100 / 0 / 0 ! The organisms tested were comparably distributed across European countries Tigecycline 1 2 0.25-8 88.5 / 7.9 / 3.6 E. coli (72) 4 (5.6) 48 (72.2) 17 (95.8) 2 (98.6) 1 (100) 0.12 0.25 Tetracycline > 8 > 8 4-> 8 -- / -- / -- S. anginosus (26) with proportions from Germany, France, Italy, Spain and UK being 15%, 9%, 9%, 9% MDR E. coli (21) 1 (4.8) 13 (66.7) 6 (95.2) 1 (100) 0.12 0.25 E. coli (72) Tigecycline 1 2 0.25-4 50 / 41.2 / 8.8 Amoxicillin/clavulanate 0.06 0.25 ͠ 0.015-0.25 -- / -- / -- K. oxytoca (71) 23 (32.4) 39 (87.3) 7 (97.2) 1 (98.6) 1 (100) 0.25 0.5 Azithromycin ͠ 0.03 >2 ͠ 0.03-> 2 -- / -- / -- K. pneumoniae (66) 1 (1.5) 23 (36.4) 23 (71.2) 15 (93.9) 4 (100) 0.5 1 Aztreonam ͠ 0.5 > 16 ͠ 0.5-> 16 59.7 / 1.4 / 38.9 and 6%, respectively. Organisms from Eastern Europe represented 25% of the aCriteria as published by the EUCAST (2015); bIncludes: C. freundii (70 strains) and C. koseri (102 strains); cIncludes: E. aerogenes Ceftriaxone 0.12 0.25 ͠ 0.015-0.25 100/ -- / 0 MDR K. pneumoniae (25) 1 (4) 9 (40) 13 (92) 2 (100) 1 1 Cefepime ͠ 0.25 > 16 ͠ 0.25-> 16 64 / 2.8 / 33.3 CR K. pneumoniae (7) 4 (57.1) 3 (100) - - (83 strains) and E. cloacae (56 strains); dIncludes: M. morganii (77 strains), P. vulgaris (78 strains), P. rettgeri (14 strains), and P. stuartii Daptomycin 0.25 0.5 ͠ 0.03-0.5 -- / -- / -- total (Czech Republic, Hungary, Poland, Romania and Russia). Ceftazidime ͠ 0.5 > 16 ͠ 0.5-> 16 61.1 / 12.5 / 26.4 Eravacycline 0.008 0.03 ̤ 0.001-0.06 -- / -- / -- M. morganii (77) 4 (5.2) 12 (20.8) 36 (67.5) 21 (94.8) 3 (98.7) 1 (100) 1 2 (25 strains); eIncludes: K. oxytoca (71 strains) and K. pneumoniae (66 strains) MDR M. morganii (8) 1 (12.5) 5 (75) 2 (100) - - Ceftriaxone ͠ 0.5 > 32 ͠ 0.5-> 32 62.5 / 0 / 37.5 Levofloxacin 0.5 1 ͠ 0.03-2 -- / -- / -- ! For GI and GU isolates shown in Table 1, the eravacycline MIC was ≤ 2 mg/L “--“ = No breakpoint defined 90 P. mirabilis (77) 1 (1.3) 4 (6.5) 33 (49.4) 36 (96.1) 3 (100) 2 2 Colistin 0.5 1 0.25-> 1 100 / -- / 0 Linezolid 1 1 ͠ 0.12-1 -- / -- / -- MDR P. mirabilis (21) 5 (23.8) 15 (95.2) 1 (100) 2 2 Minocycline 0.06 4 ͠ 0.03-> 8 -- / -- / -- except for Providencia stuartii (GU MIC = 4 mg/L), Pseudomonas aeruginosa (GI Eravacycline 0.12 0.25 0.06-2 -- / -- / -- 90 P. vulgaris (78) 5 (6.4) 24 (37.2) 48 (98.7) 1 (100) 1 1 Table 4. Antimicrobial activity of eravacycline and comparator agents against Penicillin ͠ 0.06 ͠ 0.06 ͠ 0.06-0.5 96.2 / 3.9 / 0 P. rettgeri (14) 1 (7.1) 1 (14.3) 2 (28.6) 10 (100) 2 2 Gentamicin 1 > 8 0.5-> 8 79.2 / 1.4 / 19.4 Tetracycline 0.12 >8 ͠ 0.03-> 8 -- / -- / -- and GU MIC90 = 16 mg/L), and Serratia marcescens (GI MIC90 = 4 mg/L). P. stuartii (25) 5 (20) 8 (52) 8 (84) 2 (92) 2 (100) 1 4 Imipenem ͠ 0.25 0.5 ͠ 0.25-2 100 / 0 / 0 A. baumannii isolates from GI (n = 45) and GU (n = 25) sources. Tigecycline ͠ 0.008 0.015 ͠ 0.008-0.03 -- / -- / -- MDR P. stuartii (11) 2 (18.2) 1 (27.3) 5 (72.7) 1 (81.8) 2 (100) 2 16

! Eravacycline MIC values did not increase in resistant phenotypes (defined as P. aeruginosa (53) 2 (3.8) 2 (7.6) 30 (64.2) 20 (100) 8 16 Levofloxacin ͠ 0.25 > 4 ͠ 0.25-> 4 65.3 / 1.4 / 33.3 a b 90 Organism/Antimicrobial MIC (mg/L) %S / %I / %R Criteria as published by the EUCAST (2015); Includes: E. faecalis (67 strains) and E. faecium (82 strains) MDR P. aeruginosa (17) 5 (29.4) 12 (100) 16 32 Piperacillin/tazobactam 2 32 ͠ 0.5-> 64 81.9 / 4.2 / 13.9 carbapenem-resistant (CR), multidrug-resistant (MDR), vancomycin-resistant Agent (No. Tested) a “--“ = No breakpoint defined CR P. aeruginosa (16) 1(6.3) 4 (31.3) 11 (100) ͡16 ͡16 Tetracycline > 8 > 8 1-> 8 -- / -- / -- MIC 50 MIC 90 Range EUCAST S. marcescens (34) 2 (5.9) 18 (58.8) 11 (91.2) 3 (100) 1 2 (VR), or methicillin-resistant (MR)) for Acinetobacter baumannii, Citrobacter MDR S. marcescens (6) 1 (16.7) 1 (33.3) 2 (66.7) 2 (100) - - Tigecycline 0.25 0.5 0.12-2 98.6 / 1.4 / 0 A. baumannii (70) S. maltophilia (38) 3 (7.9) 10 (34.2) 11 (63.2) 11 (92.1) 3 (100) 0.5 1 d Aztreonam > 16 > 16 1->16 -- / -- / -- freundii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus CR S. maltophilia (38) 3 (7.9) 10 (34.2) 11 (63.2) 11 (92.1) 3 (100) 0.5 1 Indole + Proteeae (194) Cefepime > 16 > 16 ͠ 0.25->16 -- / -- / -- Conclusions Aztreonam ͠ 0.5 1 ͠ 0.5-> 16 94.3 / 3.1 / 2.6 mirabilis, Enterococcus faecium, Staphylococcus epidermidis, and Staphylococcus Gram-positives: Ceftazidime > 16 > 16 ͠ 0.5->16 -- / -- / -- Cefepime ͠ 0.25 0.5 ͠ 0.25-> 16 95.9 / 0.5 / 3.6 haemolyticus (Table 2). E. faecalis (67) 1 (1.5) 15 (23.9) 45 (91) 4 (97) 1 (98.5) 1 (100) 0.06 0.06 Ceftriaxone > 32 > 32 2->32 -- / -- / -- ! Eravacycline showed activity against isolates from gastrointestinal and E. faecium (82) 2 (2.4) 36 (46.3) 41 (96.3) 1 (97.6) 1 (98.8) 1 (100) 0.06 0.06 Ceftazidime ͠ 0.5 8 ͠ 0.5-> 16 83 / 6.2 / 10.8 Colistin 1 2 0.5->4 90 / -- / 10 VRE faecium (22) 1 (4.6) 9 (45.5) 10 (90.9) 1 (95.5) 1 (100) 0.06 0.06 Ceftriaxone ͠ 0.5 4 ͠ 0.5-> 32 83 / 4.6 / 12.4 Eravacycline 0.5 1 0.03-4 -- / -- / -- genitourinary infections, including multidrug-resistant and carbapenem-resistant – Carbapenem-resistant organisms had eravacycline MIC90 values ≤ 2 mg/L, S. aureus (54) 4 (7.4) 34 (70.4) 8 (85.2) 4 (92.6) 2 (96.3) 2 (100) 0.06 0.25 MRSA (29) 1 (3.5) 17 (62.1) 4 (75.9) 3 (86.2) 2 (93.1) 2 (100) 0.06 0.5 Colistin > 4 > 4 0.5-> 4 2.1 / -- / 97.9 Gentamicin > 8 > 8 1->8 30 / -- / 70 isolates from Europe. with the exception of Pseudomonas aeruginosa. S. epidermidis (60) 1 (1.7) 5 (10) 19 (41.7) 5 (50) 12 (70) 15 (95) 3 (100) 0.12 0.5 Eravacycline 1 2 0.25-16 -- / -- / -- Imipenem > 8 > 8 ͠ 0.25->8 38.6 / 4.3 / 57.1 MRSE (39) 1 (2.6) 5 (15.4) 12 (46.2) 2 (51.3) 9 (74.4) 8 (94.9) 2 (100) 0.12 0.5 Gentamicin 2 8 0.5-> 8 75.8 / 13.4 / 10.8 Levofloxacin > 4 > 4 ͠ 0.25->4 21.4 / 0 / 78.6 S. haemolyticus (83) 7 (8.4) 32 (47) 14 (63.9) 18 (85.5) 10 (97.6) 2 (100) 0.12 0.5 – Multidrug-resistant organisms had eravacycline MIC90 values ≤ 2 mg/L, References MDR S. haemolyticus(54) 1 (1.9) 14 (27.8) 11 (48.2) 16 (77.8) 10 (96.3) 2 (100) 0.25 0.5 Imipenem 2 4 ͠ 0.25-> 8 53.1 / 45.9 / 1 Piperacillin/tazobactam > 64 > 64 ͠ 0.5->64 -- / -- / -- S. agalactiae (35) 18 (51.4) 16 (97.1) 1 (100) 0.015 0.03 Tetracycline > 8 > 8 1->8 -- / -- / -- with the exception of Providencia stuartii and Pseudomonas aeruginosa. Levofloxacin ͠ 0.25 > 4 ͠ 0.25-> 4 76.3 / 6.7 / 17 (1) CLSI, 2015. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard- S. anginosus (26) 23 (88.5) 2 (96.2) 1 (100) 0.008 0.03 Tigecycline 1 2 0.06-8 -- / -- / -- Piperacillin/tazobactam ͠ 0.5 2 ͠ 0.5-> 64 96.9 / 1 / 2.1 Eighth Edition M07-A10. Clinical and Laboratory Standards Institute (CLSI), Wayne, PA 19087-1898 USA. ! Based on MIC values in certain pathogens represented in Tables 3-5, the S. pneumoniae (7) 7 (100) - - 90 S. pyogenes (9) 9 (100) - - Tetracycline 8 > 8 1-> 8 -- / -- / -- aCriteria as published by the EUCAST (2015) (2) The European Committee on Antimicrobial Susceptibility testing, 2015. Breakpoint tables for interpretation of MICs and potency of eravacycline was generally 2-fold greater than that of tigecycline. Tigecycline 2 4 0.5-32 36.1 / 44.9 / 19.1 Red text = MIC90; Underlined = MIC50; “-“ = MIC50 or MIC90 not applicable for species with isolates of N < 10; CR = carbapenem-resistant “--“ = No breakpoint defined zone diameters. Version 5.0 http://www.eucast.org

Presented at the 26th ECCMID, April 9 - 12, 2016, Amsterdam, Netherlands