In Vitro Evaluation of Delafloxacin Activity When Tested Against Contemporary ABSSSI Isolates Dee Shortridge, Ph.D

Contact Information: In vitro Evaluation of Delafloxacin Activity When Tested against Contemporary ABSSSI Isolates Dee Shortridge, Ph.D. JMI Laboratories ASM Microbe 2017 345 Beaver Kreek Centre, Suite A from the United States (2014–2016): Results from the SENTRY Antimicrobial Surveillance Program North Liberty, IA 52317 Sunday - 4 D Shortridge, JM Streit, MD Huband, P Rhomberg, RK Flamm Phone: (319) 665-3370 Fax: (319) 665-3371 JMI Laboratories, North Liberty, Iowa, USA Email: [email protected]

− Other drugs tested against Gram-positive isolates included: levofloxacin (LVX), moxifloxacin • For β-haemolytic streptococci, Streptococcus pyogenes and S. dysgalactiae were inhibited by Table 2 Activities of delafloxacin and comparators against the main organism groups isolated from acute bacterial skin and skin structure infections (SENTRY 2014–2016) (tested in 2016 only), clindamycin, daptomycin, doxycycline (tested in 2016 only), erythromycin, ≤0.06 µg/mL of DLX, while S. agalactiae were inhibited by 1 µg/mL of DLX (Table 1) CLSIa EUCASTa CLSIa EUCASTa MIC MIC MIC MIC Amended Abstract linezolid, oxacillin, tetracycline, trimethoprim-sulfamethoxazole, and vancomycin Organism / antimicrobial agent 50 90 %S %R %S %R Organism / antimicrobial agent 50 90 %S %R %S %R Oxacillin 0.5 >2 61.8 38.2 61.8 38.2 − All BHS had a DLX MIC50/90 of 0.015/0.03 µg/mL and 99.3% were S to LVX (Table 2) Staphylococcus aureus (n=3,163) − Other drugs tested against Gram-negative isolates included: levofloxacin, ciprofloxacin, Delafloxacin 0.008 0.25 Tetracycline ≤0.5 >8 86.4 12.7 85.5 13.6 • Against viridans group streptococci, DLX was very active (MIC 0.008/0.03 µg/mL) (Table 1) Tigecycline 0.06 0.12 100 0 : Delafloxacin (DLX) is a broad-spectrum fluoroquinolone (FQ) antibacterial that has 50/90 Levofloxacin 0.25 >4 65.8 32.8 65.8 34.2 Background moxifloxacin (tested in 2016 only), amikacin, cefepime, ceftazidime, ceftriaxone, colistin, Ciprofloxacin >128 >128 0 100 0 100 Trimethoprim-sulfamethoxazole ≤0.5 4 81.6 18.4 81.6 8.3 completed clinical development (oral and intravenous formulations) with the new drug application doxycycline (tested in 2016 only), gentamicin, meropenem, piperacillin-tazobactam, tigecycline, • Against E. faecalis, DLX inhibited 94.5% of isolates at ≤1.0 µg/mL and 71.5% were S to LVX Moxifloxacin ≤0.06 2 67.5 16.7 66.8 33.2 Vancomycin 1 2 100 0 100 0 Clindamycin ≤0.25 >2 88.7 11.1 88.6 11.3 MS-CoNS (n=141) under FDA review for treating acute bacterial skin and skin structure infections (ABSSSI). trimethoprim-sulfamethoxazole, and ampicillin-sulbactam (tested in 2014 and 2015) (Tables 1 and 2) Daptomycin 0.25 0.5 >99.9 >99.9 <0.1 Delafloxacin 0.015 0.015 Delafloxacin has potent activity against Staphylococcus aureus (SA), both methicillin- (MRSA) Doxycycline ≤0.06 0.12 99 <0.1 97.4 2.1 Levofloxacin 0.25 0.25 95 5 95 5 − DLX inhibited 100% of VRE from skin infections at an MIC ≤ 1 µg/mL (n=8) Erythromycin >8 >8 42.4 52.6 43.1 54.7 Moxifloxacin ≤0.06 0.12 95.9 4.1 95.9 4.1 and FQ-resistant (FQRSA); β-haemolytic streptococci (BHS); viridans group streptococci (VGS); Linezolid 1 1 100 0 100 0 Clindamycin ≤0.25 0.5 90.1 9.2 88.7 9.9 Enterococcus faecalis (EF); Enterobacteriaceae (ENT); and Pseudomonas aeruginosa (PSA). • DLX inhibited 82.9% of Enterobacteriaceae and 78.6% of P. aeruginosa at ≤1.0 µg/mL, 87.4% and Oxacillin 1 >2 54.6 45.4 54.6 45.4 Daptomycin 0.25 0.5 100 100 0 81.2% were S to LVX, respectively (Tables 1 and 2) Tetracycline ≤0.5 ≤0.5 95.2 3.7 93.6 5.9 Doxycycline ≤0.06 0.25 98 0 95.9 2 The table shows in vitro susceptibility results for DLX and comparator agents tested against Tigecycline 0.06 0.12 100 b 100 0 Erythromycin ≤0.12 >8 83 17 83 17 ABSSSI clinical isolates collected from patients in 81 US medical centers participating in the Results Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 98.5 1.5 98.5 1.4 Linezolid 0.5 0.5 100 0 100 0 Vancomycin 0.5 1 100 0 100 0 Oxacillin 0.5 1 100 0 100 0 SENTRY surveillance program during 2014–2016. MSSA (n=1,726) Tetracycline ≤0.5 ≤0.5 91.5 7.1 91.5 8.5 • The most frequently isolated species are shown in Figure 1 Delafloxacin 0.008 0.25 Tigecycline 0.03 0.12 100 0 Methods: A total of 3,391 staphylococci, 967 BHS, 133 VGS, 235 EF, 1,325 ENT, and 230 PSA Table 1 MIC distribution of delafloxacin tested against the main organisms Levofloxacin 0.25 >4 65.8 32.8 65.8 34.2 Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 95.7 4.3 95.7 2.8 isolates from patients with ABSSSI were collected during 2014–2016 and included only 1 isolate/ −− S. aureus was the most common pathogen Ciprofloxacin >128 >128 0 100 0 100 Vancomycin 0.5 1 100 0 100 0 and organism groups in this study MIC (µg/mL) Moxifloxacin ≤0.06 2 67.5 16.7 66.8 33.2 MR-CoNS (n=67) patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility − MRSA made up 45% of S. aureus isolates (1,437 of 3,163) Clindamycin ≤0.25 >2 88.7 11.1 88.6 11.3 Delafloxacin 0.12 1 Organism / organism group No. of isolates at MIC (µg/mL; cumulative %) Levofloxacin 4 >4 48.3 50.6 48.3 51.7 MIC MIC Daptomycin 0.25 0.5 >99.9 >99.9 <0.1 testing was performed according to CLSI reference broth microdilution methodology, and results 50 90 • DLX demonstrated potent in vitro activity against S. aureus (MIC 0.008/0.25 µg/mL) and (no. of isolates) 0.004 0.008 0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 > Doxycycline ≤0.06 0.12 99 <0.1 97.4 2.1 Moxifloxacin 1 >4 47.5 40 42.5 57.5 50/90 Staphylococcus aureus 1,404 593 80 41 168 365 284 84 52 51 38 3 were interpreted per CLSI (2017) breakpoints. Other drugs tested included levofloxacin (LVX). 0.008 0.25 Erythromycin >8 >8 42.4 52.6 43.1 54.7 Clindamycin ≤0.25 >2 58.6 39.1 56.3 41.4 coagulase-negative staphylococci (CoNS; MIC50/90 0.015/0.5 µg/mL) where LVX susceptibility (S) (3,163) 44.4 63.1 65.7 67.0 72.3 83.8 92.8 95.4 97.1 98.7 99.9 100.0 Linezolid 1 1 100 0 100 0 Daptomycin 0.5 0.5 100 100 0 MSSA Staphylococcus 1,087 395 52 11 26 67 58 14 8 4 3 1 Results: DLX demonstrated potent in vitro activity against SA (MIC 0.008/0.25 µg/mL) and was 65.8% and 77.2%, respectively (Tables 1 and 2) ≤0.004 0.06 Oxacillin 1 >2 54.6 45.4 54.6 45.4 Doxycycline 0.25 4 95 2.5 77.5 15 50/90 aureus (1,726) 63.0 85.9 88.9 89.5 91.0 94.9 98.3 99.1 99.5 99.8 99.9 100.0 Tetracycline ≤0.5 ≤0.5 95.2 3.7 93.6 5.9 Erythromycin >8 >8 14.9 83.9 14.9 85.1 MRSA Staphylococcus 317 198 28 30 142 298 226 70 44 47 35 2 coagulase-negative staphylococci (CoNS; MIC 0.015/0.5 µg/mL) where LVX susceptibility 0.12 0.5 Tigecycline 0.06 0.12 100 b 100 0 Linezolid 0.5 1 100 0 100 0 50/90 − DLX was highly active against MRSA, with 94.2% of isolates inhibited by ≤1.0 µg/mL (MIC50/90 aureus (1,437) 22.1 35.8 37.8 39.9 49.8 70.5 86.2 91.1 94.2 97.4 99.9 100.0 Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 98.5 1.5 98.5 1.4 Oxacillin >2 >2 0 100 0 100 (S) was 65.8% and 77.2%, respectively. DLX was highly active against MRSA, with 94.2% Coagulase-negative 61 47 62 6 1 5 13 14 14 5 0.12/0.5 mg/mL) and against MR-CoNS (MIC50/90 0.12/1 µg/mL) where LVX S was 38.0% and 0.015 0.5 Vancomycin 0.5 1 100 0 100 0 Tetracycline ≤0.5 >8 78.2 21.8 75.9 21.8 staphylococci (228) 26.8 47.4 74.6 77.2 77.6 79.8 85.5 91.7 97.8 100.0 MRSA (n=1,437) Tigecycline 0.12 0.25 100 0 of isolates inhibited by ≤1.0 µg/mL (MIC50/90 0.12/0.5 µg/mL) and against MR-CoNS (MIC50/90 48.3%, respectively MS-CoNS coagulase-nega- 39 29 61 5 0 1 2 1 3 0.015 0.015 Trimethoprim-sulfamethoxazole 1 >4 58.6 41.4 58.6 17.2 0.12/1 µg/mL) where LVX %S was 38.0% and 48.3%, respectively. For 856 FQ-R MRSA, 90.2% tive staphylococci (141) 27.7 48.2 91.5 95.0 95.0 95.7 97.2 97.9 100.0 Delafloxacin 0.12 0.5 Levofloxacin 4 >4 38 59.6 38 62 Vancomycin 1 2 100 0 100 0 − For 856 LVX-R MRSA, 90.2% had a DLX MIC ≤1.0 µg/mL (MIC 0.12/1 µg/mL) as shown in MR-CoNS coagulase-nega- 22 18 1 1 1 4 11 13 11 5 d had a DLX MIC ≤1.0 µg/mL (MIC 0.12/1 µg/mL). For 44 FQ-R MR-CoNS, 88.6% had a DLX 50/90 0.12 1 Moxifloxacin 1 >4 39.8 31.2 38.7 61.3 Beta-haemolytic streptococci (n=967) 50/90 Table 2 and Figure 2 tive staphylococci (87) 25.3 46.0 47.1 48.3 49.4 54.0 66.7 81.6 94.3 100.0 Delafloxacin 0.015 0.03 Staphylococcus 26 19 2 0 1 4 12 3 11 3 Clindamycin ≤0.25 >2 80.2 19.5 80.2 19.8 MIC ≤1.0 µg/mL. BHS were inhibited by low levels of DLX (MIC 0.015/0.0.03 µg/mL), 99.3% 0.008 1 Levofloxacin 0.5 1 99.3 0.7 99.3 0.7 50/90 epidermidis (81) 32.1 55.6 58.0 58.0 59.3 64.2 79.0 82.7 96.3 100.0 Daptomycin 0.25 0.5 99.9 99.9 0.1 Moxifloxacin ≤0.12 0.25 99.3 0.7 were S to LVX. Against VGS, DLX was very active (MIC 0.008/0.03 µg/mL). Against EF, DLX Staphylococcus hominis 7 1 0 0 0 0 0 1 0 2 Doxycycline ≤0.06 0.25 98.4 0 95.8 3.3 50/90 ≤0.004 >1 Amoxicillin-clavulanic acid ≤1 ≤1 100 100 0 (11) 63.6 72.7 72.7 72.7 72.7 72.7 72.7 81.8 81.8 100.0 Erythromycin >8 >8 13.1 84.1 13.4 85.6 inhibited 94.5% of isolates at ≤1.0 µg/mL. DLX inhibited 82.9% of ENT and 78.6% of PSA at Ceftriaxone ≤0.06 ≤0.06 100 100 0 Staphylococcus 4 21 58 5 0 1 0 0 1 Linezolid 1 1 100 0 100 0 0.015 0.015 Clindamycin ≤0.25 >2 86 13.5 86.5 13.5 ≤1.0 µg/mL. lugdunensis (90) 4.4 27.8 92.2 97.8 97.8 98.9 98.9 98.9 100.0 Oxacillin >2 >2 0 100 0 100 Erythromycin ≤0.12 >4 73.9 25.1 73.9 25.1 Staphylococcus simulans 6 1 0 0 0 0 0 2 Tetracycline ≤0.5 ≤0.5 94.2 5 92.6 6.5 Figure 1 Most common species isolated from acute bacterial skin and skin structure ≤0.004 b Meropenem ≤0.015 0.06 100 100 0 Conclusions: Delafloxacin demonstrated potent in vitro antibacterial activity against ABSSSI (9) 66.7 77.8 77.8 77.8 77.8 77.8 77.8 100.0 Tigecycline 0.06 0.12 100 100 0 Staphylococcus 2 2 0 0 0 0 1 8 2 Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 97.6 2.4 97.6 2.2 Penicillin ≤0.06 ≤0.06 100 100 0 infections in US (species with more than 200 isolates) 0.5 1 isolates, including MRSA and FQ-R MRSA, MR-CoNS, BHS, EF, and some ENT. These data haemolyticus (15) 13.3 26.7 26.7 26.7 26.7 26.7 33.3 86.7 100.0 Vancomycin 0.5 1 100 0 100 0 Tetracycline ≤0.5 >8 63.9 34.2 62.9 36.1 Other CoNS MR-CoNS 16 3 2 1 Levofloxacin-R SA (n=1,036) Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 support DLX as a potential treatment for ABSSSI. ≤0.004 0.015 (22) 72.7 86.4 95.5 100.0 Delafloxacin 0.12 1 Vancomycin 0.25 0.5 100 100 0 58 255 241 82 6 Levofloxacin 4 >4 0 100 0 100 Enterococcus faecalis (n=235) Streptococcus agalactiae (217) Streptococcus pyogenes (642) 0.015 0.03 DLX MIC (µg/mL) LVX MIC (µg/mL) 9.0 48.8 86.3 99.1 100.0 Moxifloxacin 2 >4 0.6 53 0.2 99.8 Delafloxacin 0.12 1 b Streptococcus agalactiae 10 50 111 40 2 0 1 2 1 Clindamycin ≤0.25 >2 73.5 26.2 73.4 26.5 Levofloxacin 1 >4 71.5 28.1 71.9 28.1 Organism No. tested MIC50 MIC90 MIC50 MIC90 %S 0.015 0.03 Pseudomonas aeruginosa (224) (217) 4.6 27.6 78.8 97.2 98.2 98.2 98.6 99.5 100.0 Moxifloxacin 0.25 >4 SA 3,163 0.008 0.25 0.25 >4 65.8 Daptomycin 0.5 0.5 99.9 99.9 0.1 Streptococcus dysgalactiae 11 55 34 4 Ampicillin 1 2 100 0 99.6 0 MRSA 1,437 0.12 0.5 4 >4 38.0 0.008 0.015 Doxycycline ≤0.06 0.5 98.5 0 95.3 3.3 (104) 10.6 63.5 96.2 100.0 Clindamycin >2 >2 CoNS 228 0.015 0.5 0.25 >4 77.2 Enterococcus faecalis (235) Erythromycin >8 >8 15.4 81.1 15.7 83 Viridans group streptococci 42 37 29 18 4 3 Daptomycin 1 2 100 MR-CoNS 87 0.12 1 4 >4 48.3 5% 0.008 0.03 Linezolid 1 1 100 0 100 0 (133) 31.6 59.4 81.2 94.7 97.7 100.0 Erythromycin >16 >16 6 54.3 BHS 967 0.015 0.03 0.5 1 99.3 5% Oxacillin >2 >2 17.4 82.6 17.4 82.6 Streptococcus anginosus 24 19 5 Linezolid 1 1 100 0 100 0 VGS 133 0.008 0.03 0.5 1 99.2 Escherichia coli (243) 5% MSSA (1,726) ≤0.004 0.015 Tetracycline ≤0.5 1 93.4 6 92 6.9 (48) 50.0 89.6 100.0 Tigecycline 0.06 0.12 100 b 100 0 Teicoplanin ≤2 ≤2 97 3 96.6 3.4 EF 235 0.12 1 1 >4 71.5 Streptococcus constellatus 6 4 2 Tetracycline >8 >8 23.8 75.3 ≤0.004 0.015 Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 95.9 4.1 95.9 3.9 ENT 1,325 0.12 2 ≤0.12 >4 87.4 5% (12) 50.0 83.3 100.0 Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 PSA 224 0.5 4 0.5 >4 81.2 Vancomycin 0.5 1 100 0 100 0 37% Streptococcus intermedius 6 7 2 Coagulase-negative staphylococcic (n=228) Vancomycin 1 2 96.6 3.4 96.6 3.4 0.008 0.015 e (15) 40.0 86.7 100.0 Delafloxacin 0.015 0.5 Enterobacteriaceae (n=1,325) 0 1 0 14 75 69 18 14 31 13 Enterococcus faecalis (235) 0.12 1 Levofloxacin 0.25 >4 77.2 22.4 77.2 22.8 Delafloxacin 0.12 2 14% 0.0 0.4 0.4 6.4 38.3 67.7 75.3 81.3 94.5 100.0 Moxifloxacin 0.12 4 74.2 20.2 71.9 28.1 Levofloxacin ≤0.12 >4 87.4 11.2 83.4 14.3 0 7 56 236 359 216 91 57 77 97 59 70 Streptococcus pyogenes (642) Enterobacteriaceae (1325) 0.12 2 Clindamycin ≤0.25 >2 78.1 20.6 76.3 21.9 Ciprofloxacin ≤0.03 >4 85.8 12.4 82.7 15.5 0.0 0.5 4.8 22.6 49.7 66.0 72.8 77.1 82.9 90.3 94.7 100.0 Daptomycin 0.25 0.5 100 100 0 Moxifloxacin ≤0.25 >4 73.8 26.2 0 3 27 84 26 12 8 3 10 23 24 23 Escherichia coli (243) 0.06 4 Doxycycline ≤0.06 2 96.6 1.1 87.6 7.9 Amikacin 2 4 99.3 0.5 98.8 0.7 0.0 1.2 12.3 46.9 57.6 62.6 65.8 67.1 71.2 80.7 90.5 100.0 b Erythromycin ≤0.12 >8 57 42.5 57 43 Cefepime ≤0.5 ≤0.5 93.6 4.8 92.3 5.4 Non-ESBL-phenotype 0 3 25 82 25 10 7 3 6 13 14 10 30% 0.03 4 Linezolid 0.5 1 100 0 100 0 Ceftazidime 0.25 4 90.6 8.3 86.6 9.4 Introduction Escherichia coli (198) 0.0 1.5 14.1 55.6 68.2 73.2 76.8 78.3 81.3 87.9 94.9 100.0 Ceftriaxone 0.12 >8 84.8 13.9 84.8 13.9 ESBL-phenotype Esche- 0 2 2 1 2 1 0 4 10 10 13 4 >4 Colistin 0.25 >8 69.8 30.2 richia coli (45) 0.0 4.4 8.9 11.1 15.6 17.8 17.8 26.7 48.9 71.1 100.0 Doxycycline 2 >8 66.7 25.5 0 1 14 95 55 18 7 4 5 8 14 • Delafloxacin (DLX) is a broad spectrum fluoroquinolone (FQ) antibacterial that has completed Klebsiella spp. (221) 0.12 2 Gentamicin ≤1 ≤1 94 5.5 93.1 6 0.0 0.5 6.8 49.8 74.7 82.8 86.0 87.8 90.0 93.7 100.0 Meropenem 0.03 0.06 98.9 0.9 99.1 0.5 0 1 9 61 38 11 5 4 4 8 14 clinical development (oral and intravenous formulations) with the new drug application under FDA Klebsiella pneumoniae (155) 0.12 4 Piperacillin-tazobactam 2 8 93.9 3.3 91.9 6.1 MRSA (1,437) 0.0 0.6 6.5 45.8 70.3 77.4 80.6 83.2 85.8 91.0 100.0 Conclusions c Tigecycline 0.25 2 97.5 0.0 89.3 2.5 review for treating acute bacterial skin and skin structure infections (ABSSSI) Non-ESBL-phenotype 0 1 9 60 35 10 4 2 2 1 0.06 0.25 Trimethoprim-sulfamethoxazole ≤0.5 >4 82.9 17.1 82.9 16.8 Klebsiella pneumoniae (124) 0.0 0.8 8.1 56.5 84.7 92.7 96.0 97.6 99.2 100.0 Ampicillin-sulbactam 8 >32 51.7 28.2 51.7 48.3 • DLX has potent activity against ABSSSI pathogens, including methicillin-resistant (MRSA) and ESBL-phenotype Klebsiella 0 1 3 1 1 2 2 7 14 4 >4 • Delafloxacin demonstrated potent in vitro antibacterial activity against ABSSSI isolates, Pseudomonas aeruginosa (n=224) pneumoniae (31) 0.0 3.2 12.9 16.1 19.4 25.8 32.3 54.8 100.0 FQ-resistant (FQRSA) Staphylococcus aureus. Delafloxacin 0.5 4 0 5 33 16 7 1 0 1 including MRSA, MR-CoNS, BHS, EF, and some ENT Klebsiella oxytoca (63) 0.06 0.25 Levofloxacin 0.5 >4 81.2 11.6 72.8 27.2 − DLX is more active than levofloxacin (LVX) against β-haemolytic streptococci (BHS), viridans 0.0 7.9 60.3 85.7 96.8 98.4 98.4 100.0 Non-ESBL-phenotype 0 5 31 15 6 1 • For FQR-SA (LVX-R), DLX was an excellent inhibitor with ≥90% inhibited by an MIC of ≤1 µg/mL Ciprofloxacin 0.12 2 85.3 9.8 81.7 18.3 0.06 0.25 group streptococci (VGS), and Enterococcus faecalis (EF), Figure 2 MIC distribution for delafloxacin tested against levofloxacin-resistant Klebsiella oxytoca (58) 0.0 8.6 62.1 87.9 98.3 100.0 Moxifloxacin 1 >4 ESBL-phenotype Klebsiella 0 2 1 1 0 0 1 Amikacin 4 8 99.6 0.4 97.8 0.4 0.12 • These data support the potential of DLX as an IV or oral therapy for the treatment of ABSSSI. • DLX activity is similar to other FQs against Enterobacteriaceae (ENT) and Pseudomonas MRSA (n=856) and MSSA (n=180) oxytoca (5) 0.0 40.0 60.0 80.0 80.0 80.0 100.0 Cefepime 2 8 90.2 1.8 90.2 9.8 0 1 4 22 111 89 28 5 5 7 5 6 Ceftazidime 2 16 84.8 8.9 84.8 15.2 Enterobacter (283) 0.12 0.25 aeruginosa (PSA) 0.0 0.4 1.8 9.5 48.8 80.2 90.1 91.9 93.6 96.1 97.9 100.0 Ceftriaxone >8 >8 E. cloacae species complex 0 1 1 21 96 71 13 4 4 7 4 4 1 Colistin 1 2 99.1 0.9 99.1 0.9 350 0.06 0.5 • In vitro susceptibility was determined for DLX and comparator agents against ABSSSI clinical (227) 0.0 0.4 0.9 10.1 52.4 83.7 89.4 91.2 93.0 96.0 97.8 99.6 100.0 Gentamicin ≤1 4 94.2 2.2 94.2 5.8 0 3 1 15 18 15 1 1 0 1 1 Meropenem 0.5 8 83 12.1 83 5.8 isolates collected from patients in 81 US medical centers participating in the SENTRY surveillance E. aerogenes (56) 0.12 0.25 300 287 0.0 5.4 7.1 33.9 66.1 92.9 94.6 96.4 96.4 98.2 100.0 Piperacillin-tazobactam 4 64 82.1 7.2 82.1 17.9 MRSA 0 3 10 37 33 4 5 5 12 9 2 2 4 a program during 2014–2016 Citrobacter (126) 0.06 2 Acknowledgements Criteria as published by CLSI [2017] and EUCAST [2017] 0.0 2.4 10.3 39.7 65.9 69.0 73.0 77.0 86.5 93.7 95.2 96.8 100.0 b FDA breakpoints MSSA 0 3 9 28 9 0 0 0 2 c Organisms include: Staphylococcus capitis (8), S. caprae (3), S. epidermidis (81), S. haemolyticus (15), S. hominis (11), S. intermedius (2), S. lugdunensis (90), S. pseudintermedius C. koseri (51) 0.03 0.06 250 225 0.0 5.9 23.5 78.4 96.1 96.1 96.1 96.1 100.0 (1), S. pseudintermedius / intermedius / delphini (3), S. schleiferi (3), S. simulans (9), S. warneri (2) Melinta Therapeutics sponsored this study. d Organisms include: Streptococcus agalactiae (217), S. canis (4), S. dysgalactiae (104), S. pyogenes (642) C. freundii species complex 0 1 9 21 3 5 5 10 9 2 2 4 e 0.25 4 Organisms include: Citrobacter amalonaticus (2), C. braakii (4), C. farmeri (2), C. freundii (44), C. freundii species complex (22), C. koseri (51), C. youngae (1), Enterobacter aero- (71) 0.0 1.4 14.1 43.7 47.9 54.9 62.0 76.1 88.7 91.5 94.4 100.0 genes (56), E. cloacae (118), E. cloacae species complex (109), Escherichia coli (243), Klebsiella oxytoca (63), K. pneumoniae (155), K. variicola (3), Kluyvera ascorbata (2), Leclercia 200 0 7 55 68 8 3 5 8 27 8 1 adecarboxylata (1), Morganella morganii (80), Pantoea calida (1), Pluralibacter gergoviae (1), Proteus mirabilis (190), P. penneri (5), P. vulgaris (32), P. vulgaris group (9), Providencia Proteus mirabilis (190) 0.06 2 Materials and Methods 0.0 3.7 32.6 68.4 72.6 74.2 76.8 81.1 95.3 99.5 100.0 rettgeri (17), P. stuartii (16), Raoultella ornithinolytica (3), Serratia fonticola (1), S. liquefaciens (5), S. marcescens (85), unspeciated Providencia (3), unspeciated Raoultella (1) ESBL-phenotype Proteus 0 1 1 0 0 1 1 4 2 150 2 4 124 mirabilis (10) 0.0 10.0 20.0 20.0 20.0 30.0 40.0 80.0 100.0 References Non-ESBL-phenotype Pro- 0 7 54 67 8 3 4 7 23 6 1 • A total of 6,488 isolates composed of 3,391 staphylococci, 967 BHS, 133 VGS, 235 EF, 1,325 0.06 2 ENT, and 230 PSA were isolated from patients with ABSSSI and collected during 2014–2016 teus mirabilis (180) 0.0 3.9 33.9 71.1 75.6 77.2 79.4 83.3 96.1 99.4 100.0 Number of isolates 0 5 21 19 43 18 10 12 11 9 9 100 Indole-positive Proteeae (157) 0.12 4 63 70 0.0 3.2 16.6 28.7 56.1 67.5 73.9 81.5 88.5 94.3 100.0 Clinical and Laboratory Standards Institute (2015). M07-A10. Methods for dilution antimicrobial susceptibility − Only 1 isolate/patient/infection episode was included 58 0 2 2 11 22 26 15 3 10 44 47 Serratia (91) 1 >4 tests for bacteria that grow aerobically; approved standard: tenth edition. Wayne, PA: CLSI. 50 35 0.0 2.2 4.4 16.5 40.7 69.2 85.7 89.0 100.0 • JMI Laboratories confirmed isolate identifications using matrix-assisted laser desorption 20 0 2 3 5 3 0 0 0 0 0 1 19 14 Other Enterobacteriaceae (14) 0.06 0.12 Clinical and Laboratory Standards Institute (2017). M100-S27. Performance standards for antimicrobial 2 4 7 7 4 3 2 1 0.0 14.3 35.7 71.4 92.9 92.9 92.9 92.9 92.9 92.9 100.0 ionization-time of flight mass spectrometry and DNA sequencing, when required Pseudomonas aeruginosa 1 0 0 1 4 30 75 45 20 18 11 19 susceptibility testing: 27th informational supplement. Wayne, PA: CLSI. 0 0.5 4 ≤0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 (224) 0.4 0.4 0.4 0.9 2.7 16.1 49.6 69.6 78.6 86.6 91.5 100.0 • Susceptibility testing was performed according to CLSI reference broth microdilution methodology, Acinetobacter baumannii- 0 1 5 10 13 3 8 3 8 2 19 EUCAST (2017). Breakpoint tables for interpretation of MICs and zone diameters. Version 7.0, January 2017. https://www.jmilabs.com/data/posters/ASMMicrobe17 0.5 >4 and results were interpreted per CLSI (2017) and EUCAST (2017) breakpoints DLX MIC (µg/mL) calcoaceticus (72) 0.0 1.4 8.3 22.2 40.3 44.4 55.6 59.7 70.8 73.6 100.0 Available at: http://www.eucast.org/clinical_breakpoints/. Accessed January 2017. -delafloxacin-ABSSSI-US.pdf