Plazomicin Poster 35X74.Indd 1 100 4/3/17 9:57 AM Organisms (Number of Isolates) 90 Enterobacteriaceae (742) 80 CRE (20) 70 ESBL-Phenotype Non-CRE (105) 60 P

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Contact Information: Mariana Castanheira, Ph.D. Activity of Plazomicin and Comparator Agents Tested against Recent Clinical Isolates Collected in Asia-Pacific, JMI Laboratories ECCMID 2017 345 Beaver Kreek Centre, Suite A Europe, and Latin America North Liberty, IA 52317 Poster #P1280 Phone: (319) 665-3370 M Castanheira, JM Streit, LM Deshpande, RE Mendes, RK Flamm Fax: (319) 665-3371 JMI Laboratories, North Liberty, Iowa, USA Email: [email protected]

• Plazomicin is very active against Enterobacteriaceae, some Pseudomonas • The majority of CRE isolates carried blaKPC (94 isolates, 52 blaKPC-2, and 42 blaKPC-3; Figure 1 Activity of plazomicin against main organism groups for geographic Figure 2 Distribution of CREs and carbapenemase genes by region aeruginosa, and Staphylococcus spp., including methicillin-resistant (MRSA) isolates Figure 2) and plazomicin (MIC , 0.25/128 mg/L) displayed greater activity against regions evaluated Amended Abstract 50/90 130 these isolates when compared to amikacin (MIC , 16/>32 mg/L), gentamicin 125 • In this study, we evaluated the activity of plazomicin tested against a collection of 50/90 120 Region Background: Plazomicin is a next-generation aminoglycoside that was developed (MIC , 2/>8 mg/L) or tobramycin (MIC , >8/>8 mg/L; Table 2) A. All regions D. Latin America Asia-Pacific 3,830 clinical isolates collected in Asia-Pacific, Europe, and Latin America during 50/90 50/90 to overcome common aminoglycoside resistance mechanisms and is under 50 Europe 2015 that comprised 3,375 Enterobacteriaceae, including molecular characterized • A total of 30 isolates from Europe harboured bla , 41 isolates carried bla , 100 100 42 42 Latin America development for the treatment of patients with serious bacterial infections due to OXA-48 NDM-1 Organisms (number of isolates) 40 Organisms (number of isolates) 90 90 30 carbapenem-resistant (CRE) isolates, 252 gram-positive cocci, 101 P. aeruginosa, 7 harboured bla , and bla was detected in 1 isolate (Figure 2) 27 MDR Enterobacteriaceae, including ESBL-producing and carbapenem-resistant OXA-232 VIM-1 A. All regions Enterobacteriaceae (3,375) D. 30Latin America Enterobacteriaceae (501) 80 CRE (187) 80 20 20 21 CRE (42) and 102 Acinetobacter spp. 20 15 Enterobacteriaceae (CRE). We evaluated the activity of plazomicin and comparators • The activity of plazomicin and all other aminoglycosides (Table 2) was limited against 70 70 11

ESBL-phenotype non-CRE (663) Number of isolates by ESBL-phenotype non-CRE (130) 100 10100 5 5 5 5 tested against 3,830 clinical isolates collected in hospitals from the Asia-Pacific 60 OrganismsP. aeruginosa (number (101) of isolates) 60 0 0 2 0 0 OrganismsP. aeruginosa0 (number0 (24)1 of0 isolates) 0 NDM-1-producing organisms, but plazomicin (MIC50/90, 0.25/128 mg/L) was more 90 phenotypic/genotypic groups 0 90 50 StaphylococcusEnterobacteriaceae spp. (129)(3,375) 50 CRE KPC-2 KPC-3 NDM-1 OXA-232 OXA-48StaphylococcusEnterobacteriaceaeVIM-1 spp. (31) (501)Carbapenemase (APAC) region, Europe, and Latin America (LATAM) during 2015. active against OXA-48-producers when compared to amikacin (MIC , 4/>32 mg/L) A. All80 regions D. Latin80 America 50/90 40 CRE (187) 40 Organism CRE (42) negative

or gentamicin (MIC , >8/>8 mg/L) inhibition (%) 70 inhibition (%) 70 50/90 30 ESBL-phenotype non-CRE (663) 30 Mexico ESBL-phenotype non-CRE (130) Materials/methods: A total of 3,375 Enterobacteriaceae, 252 gram-positive cocci, Materials and Methods 10060 P. aeruginosa (101) 10060 P. aeruginosa (24) Plazomicin cumulative 20 Organisms (number of isolates) Plazomicin cumulative 20 Organisms (number of isolates) 101 Pseudomonas aeruginosa (PSA), and 102 Acinetobacter spp. were collected • Plazomicin (MIC50/90, 4/8 mg/L) activity was similar to the activity of amikacin (MIC50/90, 5090 Staphylococcus spp. (129) Table 1 50Activity90 of plazomicin and comparator agents against mainStaphylococcus bacterial spp. (31) 10 Enterobacteriaceae (3,375) 10 EnterobacteriaceaeBrazil (501) • A total of 3,830 bacterial isolates deemed cause of infection limited to 1 per patient 2/16 mg/L) and four-fold lower than that of gentamicin (MIC , 1/8 mg/L) against 80 80 in hospitals in APAC (n=851), Europe (n=2,365), and LATAM (n=614). Isolates 50/90 40 CRE (187) species40 analyzed CREChile (42)

inhibition (%) 0 inhibition (%) 0 were susceptibility (S) tested using the reference broth microdilution method. CLSI episode were included in the study P. aeruginosa isolates 30700 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 ESBL-phenotype non-CRE (663) 30700 0.06 0.12 0.25 0.5 1 2 4 8 16 32Region64 128(no. >128tested) MexicoESBL-phenotype non-CRE (130) Organism Argentina Plazomicin cumulative 60 MIC (mg/L) P. aeruginosa (101) Plazomicin cumulative 60 MIC (mg/L) P. aeruginosa (24) 20 20 MIC50/90 (mg/L) and EUCAST interpretive criteria were applied. CRE isolates were screened for Staphylococcus spp. (129) antimicrobial agent Staphylococcus spp. (31) • Isolates were collected during 2015 from 59 hospitals in Asia-Pacific (n=851), Europe • Plazomicin demonstrated activity against Staphylococcus spp. isolates (MIC50/90, 1050 1050 Overall Asia-Pacific Europe BrazilLatin America carbapenemase encoding genes by PCR/sequencing. (n=2,365), and Latin America (n=614) and included 3,375 Enterobacteriaceae, 252 40 Enterobacteriaceae40 3,375 742 2,132 Chile 501 0.5/1 mg/L; Figure 1), including coagulase-negative staphylococci (MIC50/90, 0 0 inhibition (%) 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 inhibition (%) 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 gram-positive cocci, 101 Pseudomonas aeruginosa, and 102 Acinetobacter spp. B. Asia-Pacific30 Plazomicin30 0.5 / 1 0.5 / 1 0.5 /Mexico 1 0.5 / 2 Results: Overall, plazomicin (MIC , 0.5/1 mg/L) inhibited 90.9% and 95.8% of 0.25/0.5 mg/L) and S. aureus (MIC50/90, 0.5/1 mg/L; data not shown) MIC (mg/L) Amikacin 2 / 4 MIC (mg/L) 2 / 4 2 / 8 Argentina2 / 8 50/90 Plazomicin cumulative 20 Plazomicin cumulative 20 Gentamicin 0.5 / >8 0.5 / >8 0.5 / >8 0.5 / >8 Enterobacteriaceae at ≤1 and ≤2 mg/L, respectively. Plazomicin displayed good • Species identification was confirmed when necessary by matrix-assisted laser • The activity of plazomicin was limited against Acinetobacter spp. (MIC , 10010 10 Brazil 50/90 Organisms (number of isolates) Tobramycin 0.5 / >8 0.5 / 8 0.5 / >8 1 / >8 activity against the main Enterobacteriaceae species, including E. coli (MIC , desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) 900 Ceftazidime0 0.25 / >32 0.12 / 32 0.25 / >32 Chile 0.25 / >32 50/90 8/>128 mg/L), Enterococcus spp. (MIC50/90, 32/64 mg/L), and S. pneumoniae 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 Enterobacteriaceae (742) 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 B. Asia-Pacific80 CRE (20) Meropenem 0.03 / 0.06 0.03 / 0.06 0.03 / 0.12 0.03 / 1 0.5/1 mg/L), K. pneumoniae (MIC50/90, 0.25/0.5 mg/L), and E. cloacae (MIC50/90, (MIC , 32/64 mg/L) isolates (data not shown) MIC (mg/L) MIC (mg/L) Argentina • Isolates were susceptibility tested against plazomicin and comparator agents using 50/90 70 ESBL-phenotype non-CRE (105) Piperacillin-tazobactam 2 / 128 2 / 16 2 / 128 2 / >128 0.25/0.5 mg/L). Against ESBL-phenotype isolates that were not CRE (MIC50/90, 100 Colistin 0.12 / >8 0.12 / >8 0.12 / >8 0.12 / >8 the reference broth microdilution method as described by the Clinical and Laboratory 60 OrganismsP. aeruginosa (number (25) of isolates) 0.25/1 mg/L), plazomicin inhibited 94.1% at ≤1 mg/L and 95.8% at ≤2 mg/L. 5090 Staphylococcus spp. (30) Tigecycline 0.25 / 1 0.25 / 0.5 0.25 / 1 0.25 / 1 Standards Institute (CLSI) Enterobacteriaceae (742) ESBL non-CRE 663 105 428 130 Among 187 CRE isolates, 52 carried bla , 42 bla , 41 bla , 37 bla - B. Asia-Pacific4080 KPC-2 KPC-3 NDM-1 OXA-48 CRE (20) Korea Plazomicin 0.25 / 1 0.5 / 1 0.25 / 1 0.5 / 1 inhibition (%) 70 like, and 1 bla . Plazomicin (MIC , 0.25/>128 mg/L for CRE) inhibited 83/94 • Quality control (QC) was performed according to CLSI guidelines (M100-S27) and all 30 ESBL-phenotype non-CRE (105) Amikacin 2 / 8 2 / 8 2 / 8 2 / 8 VIM-1 50/90 100 Taiwan

Conclusions Plazomicin cumulative 60 P. aeruginosaMalaysia (25) QC MIC results were within acceptable ranges as published in CLSI documents 20 ThailandOrganisms (number of isolates) Gentamicin 1 / >8 1 / >8 1 / >8 >8 / >8 isolates carrying blaKPC, 32/30 isolates carrying blaOXA-48-like, and 11/42 isolates 90 Staphylococcus spp. (30) 1050 SingaporeEnterobacteriaceae (742) Tobramycin 8 / >8 4 / >8 8 / >8 >8 / >8 carrying metallo-beta-lactamase genes. The activity of plazomicin (MIC50/90, 4/8 • Categorical interpretations for all comparator agents were those found in CLSI 4080 Ceftazidime 32 / >32 16 / >32 32 / >32 32 / >32 • Plazomicin was active against Enterobacteriaceae isolates, including resistance 0 CRE (20) Korea mg/L) against PSA was similar to the activity of amikacin (MIC , 2/16 mg/L) and inhibition (%) 30700 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 ESBL-phenotypeAustralia non-CRE (105) Meropenem 0.03 / 0.12 0.03 / 0.06 0.03 / 0.12 0.03 / 0.5 50/90 criteria in M100-S27 (2017), EUCAST breakpoint tables (version 7.0, January 2017), groups such as cephalosporin-resistant isolates (ESBL non-CRE) and CRE Taiwan MIC (mg/L) New Zealand Piperacillin-tazobactam 8 / >128 8 / >128 8 / >128 8 / >128 Plazomicin cumulative 2060 ThailandP. aeruginosaMalaysia (25) lower than the activity of gentamicin (MIC50/90, 1/8 mg/L) against these isolates. or United States Food and Drug Administration (US FDA) package insert (tigecycline) Colistin 0.12 / 0.25 0.12 / 0.25 0.12 / 0.25 0.12 / 1 • The in vitro activity of plazomicin was greater compared to the activity of 50 SingaporeStaphylococcus spp. (30) Plazomicin demonstrated good activity against coagulase-negative staphylococci 10 Tigecycline 0.25 / 1 0.25 / 1 0.25 / 1 0.25 / 1 40 • ESBL-phenotype criterion was applied for Escherichia coli, Klebsiella pneumoniae, aminoglycosides against cephalosporin-resistant isolates and CRE, including 0 Korea CRE 187 20 125 42 (CoNS; MIC , 0.25/0.5 mg/L) and S. aureus (MIC , 0.5/1 mg/L). Plazomicin C. inhibition (%) Europe0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 50/90 50/90 30 Australia Plazomicin 0.25 / >128 0.25 / 1 0.25 / >128 0.25 / >128 K. oxytoca, and P. mirabilis displaying an MIC value ≥2 mg/L for ceftriaxone, isolates producing KPC or OXA-48 Taiwan MIC (mg/L) New Zealand Amikacin 16 / >32 4 / 16 16 / >32 16 / >32 activity was limited against Acinetobacter spp. (MIC50/90, 8/>128 mg/L), Enterococcus Plazomicin cumulative 20 Thailand Malaysia ceftazidime, or aztreonam (M100-S27) 100 Gentamicin >8 / >8 0.5 / >8 >8 / >8 >8 / >8 spp. (MIC , 32/64 mg/L), and S. pneumoniae (MIC , 32/64 mg/L). The activity • Plazomicin displayed activity against Staphylococcus spp. and some P. 10 OrganismsSingapore (number of isolates) 50/90 50/90 90 Tobramycin >8 / >8 8 / >8 >8 / >8 >8 / >8 Enterobacteriaceae (2,132) of plazomicin and other aminoglycosides displayed slight variability according to • Carbapenem-resistant Enterobacteriaceae (CRE) was defined as any isolate aeruginosa, but its activity was limited against Acinetobacter spp., Enterococcus 800 Ceftazidime >32 / >32 >32 / >32 >32 / >32 >32 / >32 C. Europe0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 CRE (125) Australia exhibiting doripenem, imipenem, and/or meropenem MIC values at ≥2 mg/L Meropenem 32 / >32 16 / >32 32 / >32 32 / >32 geographic region (Table). spp., and S. pneumoniae 70 MIC (mg/L) ESBL-phenotype non-CRENew (428) Zealand Piperacillin-tazobactam >128 / >128 >128 / >128 >128 / >128 >128 / >128 10060 P. aeruginosa (52) -- Proteus mirabilis and indole-positive Proteeae were categorized as CRE if • Plazomicin seems to be a valuable option for the treatment of infections caused by Organisms (number of isolates) Colistin 0.25 / >8 0.12 / >8 0.25 / >8 0.25 / >8 Conclusions: Plazomicin was active against Enterobacteriaceae isolates, including 5090 Staphylococcus spp. (68) Enterobacteriaceae (2,132) Tigecycline 0.5 / 2 0.25 / 0.5 0.5 / 2 0.5 / 2 meropenem or doripenem MIC values at ≥2 mg/L due to intrinsically elevated Enterobacteriaceae isolates, including isolates that may produce ESBLs and those 4080 isolates displaying an ESBL phenotype and carrying genes encoding serine- C. Europe CRESweden (125)Czech Republic P. aeruginosa 101 25 52 24 imipenem MIC values carrying serine-carbapenemases inhibition (%) 3070 Plazomicin 4 / 8 4 / 8 4 / 8 4 / 16 carbapenemases. These data support the current development plan for plazomicin United GermanyESBL-phenotypePoland non-CRE (428) Kingdom Plazomicin cumulative 1002060 P. aeruginosaBelarus (52) Russia Amikacin 2 / 16 4 / 4 2 / 16 4 / 16 to treat serious infections caused by resistant Enterobacteriaceae where treatment • CRE were screened for acquired carbapenemase encoding genes by PCR using IrelandOrganisms (numberSlovenia of isolates) Gentamicin 1 / 8 1 / 4 1 / >8 1 / >8 105090 France StaphylococcusHungary spp. (68) Enterobacteriaceae (2,132) Tobramycin 0.5 / 4 0.5 / 1 0.5 / 8 0.5 / >8 options are limited. custom primers 40800 Portugal Turkey CRESweden (125) Czech Republic Ceftazidime 2 / 16 2 / >32 2 / 16 2 / 16 inhibition (%) 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 Israel 3070 - Amplicons were sequenced on both strands and nucleotide sequences obtained UnitedSpainGermanyESBL-phenotypeItaly RomaniaPoland non-CRE (428) Meropenem 0.5 / 16 0.25 / 8 0.25 / 16 0.5 / 16 MIC (mg/L) Kingdom Plazomicin cumulative 2060 BelgiumP. aeruginosaGreece Belarus (52) Russia Piperacillin-tazobactam 4 / >64 4 / >64 4 / >64 4 / 64 Ireland Slovenia MIC50/MIC90 in mg/L were analyzed using the Lasergene® software package (DNAStar; Madison, 1050 France StaphylococcusHungary spp. (68) Colistin ≤0.5 / 1 1 / 1 ≤0.5 / 1 ≤0.5 / 1 Asia-Pacific Europe Latin America Organism/Group Wisconsin, USA) and compared to available sequences via NCBI BLAST search Acknowledgements 400 Portugal Turkey Sweden Czech Republic (no. tested) PLZ AMK GEN PLZ AMK GEN PLZ AMK GEN inhibition (%) 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 Israel (http://www.ncbi.nlm.nih.gov/blast/) 30 Poland Table 2 Activity of plazomicin and comparator agents against main carbapenemase Enterobacteriaceae United SpainGermanyItaly Romania MIC (mg/L) Kingdom Plazomicin cumulative 20 Belgium Greece Belarus Russia (3,375) 0.5/1 2/4 0.5/>8 0.5/1 2/8 0.5/>8 0.5/2 2/8 0.5/>8 This study was performed by JMI Laboratories and supported by Achaogen, which Ireland Slovenia groups ESBL-phenotype included funding for services related to preparing this poster. 10 France Hungary Region (no. tested) non-CRE (663) 0.5/1 2/8 1/>8 0.25/1 2/8 1/>8 0.5/1 2/8 >8/>8 Portugal Organism 0 Turkey MIC (mg/L) CRE (187) 0.25/1 4/16 0.5/>8 0.25/>128 16/>32 >8/>8 0.25/>128 16/>32 >8/>8 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 Israel antimicrobial agent 50/90 MIC (mg/L) Spain Italy Romania Overall Asia-Pacific Europe Latin America P. aeruginosa (101) 4/8 4/4 1/4 4/8 2/16 1/>8 4/16 4/16 1/>8 Results Belgium Greece KPC producers 94 5 62 27 S. aureus (65) 0.5/1 — ≤1/>8 0.5/1 — ≤1/≤1 0.5/0.5 — ≤1/>8 Plazomicin 0.25 / 128 0.5 / 0.25 / 2 0.25 / >128 CoNS (64) 0.25/0.5 — ≤1/>8 0.25/0.5 — ≤1/>8 0.25/0.5 — 8/>8 Amikacin 16 / >32 2 / 32 / >32 4 / >32 • Plazomicin (MIC50/90, 0.5/1 mg/L) inhibited 95.8% at ≤2 mg/L and 97.7% at ≤4 mg/L of PLZ, plazomicin; AMK, amikacin; GEN, gentamicin Gentamicin 2 / >8 0.5 / 1 / >8 >8 / >8 3,375 Enterobacteriaceae isolates collected in all regions (Figure 1) References Tobramycin >8 / >8 0.5 / >8 / >8 >8 / >8 Meropenem >32 / >32 >32 / >32 / >32 >32 / >32 • The activity of plazomicin was similar in all 3 regions, MIC values were 0.5 mg/L Piperacillin-tazobactam >128 / >128 >128 / >128 / >128 >128 / >128 50 Clinical and Laboratory Standards Institute (2017). M100-S27. Performance standards Colistin 0.5 / >8 0.25 / 0.25 / >8 8 / >8 for all 3 regions, and MIC values were 1 mg/L (Asia-Pacific and Europe) or 2 mg/L 90 for A.antimicrobial All regions susceptibility testing: 27th informational supplement. Wayne, PA: CLSI. D. Latin America Tigecycline 0.5 / 2 0.5 / 0.5 / 2 0.5 / 1 (Latin America; Figure 1) OXA-48-producers 30 0 30 0 Introduction Plazomicin 0.25 / 128 0.25 / 128 EUCAST100 (2017). Breakpoint tables for interpretation of MICs and zone diameters. 100 • Against Enterobacteriaceae, plazomicin (MIC , 1 mg/L) was more active than Organisms (number of isolates) Organisms (number of isolates) Amikacin 4 / >32 4 / >32 90 90 90 Gentamicin >8 / >8 >8 / >8 • Aminoglycosides are broad spectrum antimicrobial agents that bind to the 16S Version 7.0, January 2017. Available at http://www.eucast.org/clinical_breakpoints/.Enterobacteriaceae (3,375) Enterobacteriaceae (501) amikacin (MIC , 4 mg/L), gentamicin (MIC , >8 mg/L), and tobramycin (MIC , Tobramycin >8 / >8 >8 / >8 ribosomal RNA leading to inhibition of polypeptide synthesis and subsequent cell death 90 90 90 80 CRE (187) 80 CRE (42) >8 mg/L; Table 1) Accessed January 2017. Meropenem 16 / 32 16 / 32 70 ESBL-phenotype non-CRE (663) 70 ESBL-phenotype non-CRE (130) Piperacillin-tazobactam >128 / >128 >128 / >128 • Resistance to aminoglycosides may occur due to a variety of different resistance 60 P. aeruginosa (101) 60 P. aeruginosa (24) Colistin 1 / >8 1 / >8 • Plazomicin was very active against ESBL-phenotype isolates, displaying no Walkty A, Adam H, Baxter M, et al. (2014). In vitro activity of plazomicin against 5,015 50 Staphylococcus spp. (129) 50 Staphylococcus spp. (31) Tigecycline 0.5 / 1 0.5 / 1 mechanisms gram-negative and gram-positive clinical isolates obtained from patients in Canadian NDM producers 41 5 21 15 resistance to the carbapenems (ESBL non-CRE; MIC50/90, 0.25/1 mg/L) and inhibiting 40 40 Plazomicin 128 / >128 0.25 / >128 / >128 128 / >128 hospitalsinhibition (%) as part of the CANWARD study, 2011-2012. Antimicrob Agents Chemother 58: inhibition (%) • The main mechanism in gram-positive and -negative bacteria is the enzymatic 95.8% and 96.8% at ≤2 and ≤4 mg/L, respectively (Figure 1) 30 30 Mexico Amikacin >32 / >32 16 / >32 / >32 >32 / >32

modification and inactivation of the aminoglycosides, mediated by aminoglycoside 2554-2563.Plazomicin cumulative 20 Plazomicin cumulative 20 Gentamicin >8 / >8 1 / >8 / >8 >8 / >8 • A total of 187 CRE isolates were observed in this collection and plazomicin (MIC , Tobramycin >8 / >8 >8 / >8 / >8 >8 / >8 50/90 10 10 Brazil modifying enzymes (AME) Meropenem 32 / >32 >32 / >32 / >32 32 / >32 0.25/>128 mg/L) was considerably more active against these isolates when Zhanel GG,0 Lawson CD, Zelenitsky S, et al. (2012). Comparison of the next-generation 0 Chile 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 Piperacillin-tazobactam >128 / >128 >128 / >128 / >128 >128 / >128 • Plazomicin is a semi-synthetic aminoglycoside derived from sisomicin and contains compared to amikacin (MIC , 16/>32 mg/L), gentamicin, or tobramycin (MIC , aminoglycoside plazomicin to gentamicin, tobramycin and amikacin. Expert Rev Anti Colistin 0.12 / >8 0.12 / 0.12 / 0.5 0.25 / >8 50/90 50/90 Argentina structural modifications that allow it to retain activity in the presence of AMEs >8/>8 mg/L for both; Table 1) Infect Ther 10: 459-473. MIC (mg/L) MIC (mg/L) Tigecycline 0.5 / 2 0.5 / 0.5 / 2 1 / 2

B. Asia-Pacific

Plazomicin poster_35x74.indd 1 100 4/3/17 9:57 AM Organisms (number of isolates) 90 Enterobacteriaceae (742) 80 CRE (20) 70 ESBL-phenotype non-CRE (105) 60 P. aeruginosa (25) 50 Staphylococcus spp. (30) 40 Korea inhibition (%) 30 Taiwan

Plazomicin cumulative 20 Thailand Malaysia 10 Singapore 0 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 Australia MIC (mg/L) New Zealand

C. Europe

100 Organisms (number of isolates) 90 Enterobacteriaceae (2,132) 80 CRE (125) 70 ESBL-phenotype non-CRE (428) 60 P. aeruginosa (52) 50 Staphylococcus spp. (68) 40 Sweden Czech Republic inhibition (%) 30 United Germany Poland Kingdom Plazomicin cumulative 20 Belarus Russia Ireland Slovenia 10 France Hungary 0 Portugal Turkey 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 Israel MIC (mg/L) Spain Italy Romania Belgium Greece