Tedizolid Phosphate Vs Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections: the ESTABLISH-1 Randomized Trial

Supplementary Online Content

Prokocimer P, De Anda C, Fang E, Mehra P, Das A. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA. doi:10.1001/jama.2013.241

eTable 1. Enrollment by clinical study site

eTable 2. Bacterial pathogens isolated from the primary ABSSSI site or blood culture

eTable 3. Tedizolid susceptibility of bacterial pathogens isolated from the primary ABSSSI site or blood culture

eTable 4. Linezolid susceptibility of bacterial pathogens isolated from the primary ABSSSI site or blood culture

eTable 5. Investigator assessment of clinical success at the post-treatment evaluation visit by baseline pathogen (MITT analysis set)

eMethods. Microbiology

This supplementary material has been provided by the authors to give readers additional information about their work.

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eTable 1. Enrollment by Clinical Study Site

Site N Principal Investigator Site, City, State/Province, Postal Code Country No. 101 49 Jeffery Kingsley, DO SE Regional Research Group US Columbus, GA 31904 102 15 Maria Mascolo, MD Southeast Regional Research Group US Savannah, GA 31406 103 85 Purvi Mehra, MD eStudySite US Chula Vista, CA 91911 104 24 Paul J. Manos, DO eStudy Site US Oceanside, CA 92056 105 99 Sinikka Green, MD eStudySite US La Mesa, CA 91942 106 3 Barry Heller, MD Novellus Research Sites US Long Beach, CA 90813 107 5 Jose Vazquez, MD Henry Ford Hospital US Detroit, MI 48202 111 1 Paz Eilat, MD Devise Research, Inc US Torrance, CA 90501 112 5 Hubert Reyes, MD MediSphere Medical Research Center, LLC US Evansville, IN 47714 113 9 Augusto Focil, MD Private Practice US Oxnard, CA 93030 114 5 Luis Jauregui-Peredo, MD ID Clinical Research, Ltd US Toledo, OH 43608 115 12 Christopher Lucasti, DO South Jersey Infectious Disease US Somers Point, NJ 08244 116 2 Kathleen Mullane, DO University of Chicago US Chicago, IL 60637 118 61 Richard Keech, MD Physician Alliance Research Center US Anaheim, CA 92804 120 5 Alan Nolasco, MD Mercury Clinical Research US Houston, TX 77005 121 5 Alan Nolasco, MD Mercury Clinical Research US Houston, TX 77093 122 8 Jennifer Johnson-Caldwell, Mercury Clinical Research US MD Houston, TX 77002 125 1 Arturo Velasquez, MD Futura Research Inc US Norwalk, CA 90650 126 8 Robert Cockrell, MD Novellus Research Sites, Inc US Fountain Valley, CA 128 29 Wade Sears, MD eStudySite US Las Vegas, NV 89109 129 37 James Chen, MD Southbay Pharma Research US Buena Park, CA 90620 130 44 Vladimir Samonte, MD Quality of Life Medical Center, LLC US Anaheim, CA 92804 132 5 Stanley Klein, MD Harbor-UCLA Medical Center US Torrance, CA 90502 133 5 John Pullman, MD Mercury Street Medical Group US Butte, MT 59701

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Site N Principal Investigator Site, City, State/Province, Postal Code Country No. 135 6 Farid Marquez, MD Palm Springs Research Institute US Hialeah, FL 33012 173 5 Doria Grimard, MD Centre de Sante et de Services Sociaux de Chicoutimi Canada Chicoutimi, QC, G7H 5H6 175 5 Andre Poirier, MD Centre Hospitalier Regional de Trois-Rivierès Canada Trois-Rivierès, QC 200 1 Jochen Utikal, MD University Medical Center Mannheim Germany 68167 Mannheim 201 1 Wolfgram Sterry, MD Humboldt University, Germany 10117 Berlin 202 1 Hans Ockenfels, MD Klinikum Stadt Hanau Germany 63450 Hanau 235 5 Jan Roháč, MD Hospital Melnik Czech Republic Melnik 276 01 240 15 Lajos Kemény, MD University of Szeged Albert Szent-Györgyi Clinical Hungary Center Szeged H-6721 241 1 Éva Remenyik, MD University of Debrecen Medical and Health Science Hungary Center Debrecen H-4032. 242 15 Iván Péter, MD Komló Health Center Hungary Komló H-7300 250 6 Dušan Mištuna, MD, PhD. University Hospital Martin Slovakia Martin 036 59 251 2 Slavomir Urbanček, MD, PhD University Hospital of F.D. Roosevelt Slovakia Banská Bystrica 975 17 255 14 Janis Gardovskis, MD P. Stradius Clinical University Hospital Latvia Riga LV-1002 256 3 Maris Nalivaiko, MD Liepajas Regional Hospital Latvia Liepaja LV-3414 257 5 Edgars Zarembo, MD Rezekne Hospital Latvia Rezekne, LV-4600 258 5 Viktors Lovcinovskis, MD Public Hospital Latvia Daugavpils, LV-5417 260 6 Oleksii Datsenko, MD, PhD Kharkiv City Clinical Hospital #2 Ukraine Kharkiv 61037 261 4 Borys Bezrodnyy, MD, PhD Kyiv City Clinical Hospital #4 Ukraine Kyiv 03110 262 5 Sergiy Shapoval, MD, PhD Zaporizhzhya City Clinical Hospital #3 Ukraine Zaporizhzhya 69032 265 1 Oleksandra Stasyshyn, MD, Academy of Medical Sciences of Ukraine Ukraine PhD Lviv 79044 268 4 Ihor Herych, MD, PhD Lviv National Medical University at Municipal City Ukraine Clinical Emergency Hospital, Lviv 79059 269 6 Oleksandr Pyptiuk, MD, PhD Central City Clinical Hospital Ukraine Ivano-Frankivsk 76014 270 3 Ihor Hospodarky, MD, PhD Ternopil University Hospital Ukraine Ternopil 46002 271 5 Valeriy Chernyak, MD, PhD Cherkasy Regional Hospital Ukraine Cherkasy 18009 300 1 German Ambasch, MD Sanatorio Mayo Privado S.A. Argentina Cordoba 5000

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Site N Principal Investigator Site, City, State/Province, Postal Code Country No. 307 5 Analia Mykietiuk, MD Sanatorio Profesor Itoiz Argentina Avellaneda, Buenos Aires 1870 321 1 Fernando Rubio, MD, PhD Hospital de Base de Sao Jose do Rio Preto Brazil São José do Rio Preto 15090-000 341 9 Cristhian Vasquez, MD Centro de Investigaciones Medicas-Hospital Maria Peru Auxiliadora, Lima 29 342 2 Manuel Espichan, MD Hospital Central de la Fuerza Aerea del Peru Peru Lima 18 343 3 Jaime Medina, MD Hospital Nacional Dos de Mayo Peru Lima 01 N, number of patients enrolled and randomized (Intent-to-treat Analysis Set)

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eTable 2. Bacterial Pathogens Isolated from the Primary ABSSSI Site or Blood Culture

Number (%) of Isolates Tedizolid Phosphate Linezolid Species (N=209) (N=209) Gram-positive aerobes 207 (99.0) 205 (98.1) Staphylococcus aureus 171 (81.8) 175 (83.7) MRSA 88 (42.1) 90 (43.1) MSSA 83 (39.7) 87 (41.6) PVL Staphylococcus aureus 97 (46.4) 102 (48.8) Streptococcus pyogenes 8 (3.8) 4 (1.9) Streptococcus anginosus-milleri group 15 (7.2) 15 (7.2) Streptococcus anginosus 4 (1.9) 3 (1.4) Streptococcus intermedius 3 (1.4) 4 (1.9) Streptococcus constellatus 8 (3.8) 8 (3.8) Enterococcus faecalis 5 (2.4) 0 Enterococcus faecium 1 (0.5) 2 (1.0) Enterococcus gallinarum 1 (0.5) 0 Mycobacterium fortuitum 1 (0.5) 0 Staphylococcus haemolyticus 4 (1.9) 3 (1.4) Staphylococcus lugdunensis 3 (1.4) 2 (1.0) Streptococcus Group C 1 (0.5) 0 Streptococcus agalactiae 9 (4.3) 5 (2.4) Streptococcus dysgalactiae 1 (0.5) 0 Streptococcus mitis 0 5 (2.4) Streptococcus mutans 1 (0.5) 1 (0.5) Streptococcus oralis 1 (0.5) 0 Streptococcus salivarius 2 (1.0) 2 (1.0) Streptococcus sanguis 3 (1.4) 2 (1.0) Streptococcus viridans group 3 (1.4) 3 (1.4) Gram-positive anaerobes 3 (1.4) 8 (3.8) Actinomyces israelii 0 1 (0.5) Actinomyces odontolyticus 0 1 (0.5) Clostridium perfringens 1 (0.5) 1 (0.5) Clostridium septicum 0 1 (0.5) Finegoldia magna 1 (0.5) 2 (1.0) Gemella morbillorum 0 1 (0.5) Peptostreptococcus anaerobius 1 (0.5) 0 Peptostreptococcus asaccharolyticus 0 1 (0.5) Peptostreptococcus micros 0 1 (0.5) Peptostreptococcus prevotii 0 1 (0.5)

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Number (%) of Isolates Tedizolid Phosphate Linezolid Species (N=209) (N=209) Gram-negative aerobes 6 (2.9) 6 (2.9) Acinetobacter baumannii 1 (0.5) 0 Eikenella corrodens 2 (1.0) 1 (0.5) Enterobacter amnigenus 0 1 (0.5) Enterobacter cloacae 1 (0.5) 0 Escherichia coli 1 (0.5) 1 (0.5) Klebsiella oxytoca 1 (0.5) 2 (1.0) Klebsiella pneumoniae 1 (0.5) 1 (0.5) Proteus mirabilis 1 (0.5) 0 Pseudomonas aeruginosa 0 1 (0.5) Gram-negative anaerobes 0 1 (0.5) Prevotella denticola 0 1 (0.5) Prevotella intermedia 0 1 (0.5) Abbreviations: ABSSSI, acute bacterial skin and skin structure infection; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive S aureus; N=number of patients in the microbiological intent-to-treat analysis set; n=number of patients in the specific category; PVL, Panton-Valentine Leukocidin. Patients with the same pathogen isolated from multiple specimens are counted only once for that pathogen. Patients with the same pathogen identified from both the blood and primary ABSSSI are counted only once. Patients with both MRSA and MSSA are counted only once in the overall S. aureus row, and untyped S aureus isolates are counted only once in the overall S aureus row.

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eTable 3. Tedizolid Susceptibility of Bacterial Pathogens Isolated from the Primary ABSSSI Site or Blood Culture Treatment Group Tedizolid Tedizolid Phosphate Linezolid Combined Tedizolid Baseline Pathogen MIC (N=209) (N=209) (N=418) MIC90 (µg/mL) n (%) n (%) n (%) (µg/mL) Gram-positive aerobes Staphylococcus aureus, N1 168 173 341 0.5 0.12 5 (3.0) 6 (3.5) 11 (3.2) 0.25 138 (82.1) 138 (79.8) 276 (80.9) 0.5 25 (14.9) 29 (16.8) 54 (15.8) MRSA, N1 86 88 174 0.25 0.12 5 (5.8) 6 (6.8) 11(6.3) 0.25 79 (91.9) 76 (86.4) 155 (89.1) 0.5 2 (2.3) 6 (6.8) 8 (4.6) MSSA, N1 82 85 167 0.5 0.25 59 (72.0) 62 (72.9) 121 (72.5) 0.5 23 (28.0) 23 (27.1) 46 (27.5) Streptococcus pyogenes, N1 8 4 12 0.25 0.12 3 (37.5) 1 (25.0) 4 (33.3) 0.25 5 (62.5) 3 (75.0) 8 (66.7) Streptococcus agalactiae, N1 8 4 12 0.25 0.12 2 (25.0) 2 (50.0) 4 (33.3) 0.25 6 (75.0) 2 (50.0) 8 (66.7) Streptococcus anginosus-milleri group, N1 14 15 29 0.25 ≤0.015 2 (14.3) 2 (13.3) 4 (13.8) 0.03 0 4 (26.7) 4 (13.8) 0.06 1 (7.1) 2 (13.3) 3 (10.3) 0.12 7 (50.0) 6 (40.0) 13 (44.8) 0.25 4 (28.6) 1 (6.7) 5 (17.2) Streptococcus anginosus, N1 4 3 7 ND 0.12 3 (75.0) 3 (100) 6 (85.7) 0.25 1 (25.0) 0 1 (14.3) Streptococcus intermedius, N1 3 4 7 ND ≤0.015 1 (33.3) 1 (25.0) 2 (28.6) 0.03 0 1 (25.0) 1 (14.3) 0.06 1 (33.3) 1 (25.0) 2 (28.6) 0.12 1 (33.3) 1 (25.0) 2 (28.6) Streptococcus constellatus, N1 7 8 15 0.25 ≤0.015 1 (14.3) 1 (12.5) 2 (13.3) 0.03 0 3 (37.5) 3 (20.0) 0.06 0 1 (12.5) 1 (6.7) 0.12 3 (42.9) 2 (25.0) 5 (33.3) 0.25 3 (42.9) 1 (12.5) 4 (26.7) Staphylococcus haemolyticus, N1 4 3 7 ND 0.12 2 (50.0) 1 (33.3) 3 (42.9) 0.25 2 (50.0) 2 (66.7) 4 (57.1)

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Treatment Group Tedizolid Tedizolid Phosphate Linezolid Combined Tedizolid Baseline Pathogen MIC (N=209) (N=209) (N=418) MIC90 (µg/mL) n (%) n (%) n (%) (µg/mL) Staphylococcus lugdunensis, N1 3 2 5 ND 0.12 2 (66.7) 1 (50.0) 3 (60.0) 0.25 1 (33.3) 1 (50.0) 2 (40.0) Enterococcus faecalis, N1 3 0 3 ND 0.25 2 (66.7) 0 2 (66.7) 0.5 1 (33.3) 0 1 (33.0) Enterococcus faecium, N1 1 1 2 ND 0.25 1 (100) 1 (100) 2 (100) Enterococcus gallinarum, N1 1 0 1 ND 0.5 1 (100) 0 1 (100) Streptococcus Group C, N1 1 0 1 ND 0.12 1 (100) 0 1 (100) Streptococcus mitis, N1 0 5 5 ND 0.03 0 1 (20.0) 1 (20.0) 0.06 0 1 (20.0) 1 (20.0) 0.12 0 2 (40.0) 2 (40.0) 0.25 0 1 (20.0) 1 (20.0) Streptococcus mutans, N1 1 1 2 ND 0.12 0 1 (100) 1 (50.0) 0.25 1 (100) 0 1 (50.0) Streptococcus oralis, N1 1 0 1 ND 0.25 1 (100) 0 1 (100) Streptococcus salivarius, N1 2 2 4 ND 0.06 0 1 (50.0) 1 (25.0) 0.12 2 (100) 0 2 (50.0) 0.25 0 1 (50.0) 1 (25.0) Streptococcus sanguis, N1 3 2 5 ND 0.12 3 (100) 2 (100) 5 (100) Streptococcus viridans group, N1 2 4 6 ND 0.12 1 (50.0) 1 (25.0) 2 (33.3) 0.25 1 (50.0) 3 (75.0) 4 (66.7) Gram-positive anaerobes Actinomyces israelii, N1 0 1 1 ND 0.12 0 1 (100) 1 (100) Gemella morbillorum, N1 0 1 1 ND 0.06 0 1 (100) 1 (100) Gram-negative anaerobes Eikenella corrodens, N1 1 0 1 ND 0.12 1 (100) 0 1 (100) Enterobacter amnigenus, N1 0 1 1 ND 0.5 0 1 (100) 1 (100) Abbreviations: ABSSSI, acute bacterial skin and skin structure infection; MIC, minimum inhibitory concentration to inhibit growth in vitro; MIC90, MIC required to inhibit growth of 90% of isolates; MRSA, methicillin-resistant Staphylococcus aureus;

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MSSA, methicillin-sensitive S aureus; N, number of patients in the microbiological intent-to-treat analysis set; N1, number of with pathogen isolated; n, number of patients in the specific category; ND, not determined; PVL, Panton-Valentine Leukocidin. Percentages are calculated as 100*n/N1. For patients with multiple specimens of the same type having the same baseline pathogen tested, the specimen with the highest MIC is used. For patients with ABSSSI and blood specimens having the same baseline pathogen tested, each specimen is counted separately. For patients with both MRSA and MSSA, both isolates are counted separately in the S aureus row.

MIC90 is not determined if N1<10 for the treatment groups combined.

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eTable 4. Linezolid Susceptibility of Bacterial Pathogens Isolated from the Primary ABSSSI Site or Blood Culture Treatment Group Tedizolid Linezolid Phosphate Linezolid Combined Linezolid Baseline Pathogen MIC (N=209) (N=209) (N=418) MIC90 (µg/mL) n (%) n (%) n (%) (μg/mL) Gram-positive organisms (aerobes) Staphylococcus aureus, N1 168 173 341 2 1 27 (16.1) 30 (17.3) 57 (16.7) 2 129 (76.8) 130 (75.1) 259 (76.0) 4 12 (7.1) 13 (7.5) 25 (7.3) MRSA, N1 86 88 174 2 1 22 (25.6) 20 (22.7) 42 (24.1) 2 64 (74.4) 66 (75.0) 130 (74.7) 4 0 2 (2.3) 2 (1.1) MSSA, N1 82 85 167 4 1 5 (6.1) 10 (11.8) 15 (9.0) 2 65 (79.3) 64 (75.3) 129 (77.2) 4 12 (14.6) 11 (12.9) 23 (13.8) Streptococcus pyogenes, N1 8 4 12 1 0.5 4 (50.0) 2 (50.0) 6 (50.0) 1 4 (50.0) 2 (50.0) 6 (50.0) Streptococcus agalactiae, N1 8 4 12 1 0.5 2 (25.0) 3 (75.0) 5 (41.7) 1 6 (75.0) 1 (25.0) 7 (58.3) Streptococcus anginosus-milleri group, N1 14 15 29 1 ≤0.06 0 3 (20.0) 3 (10.3) 0.12 2 (14.3) 3 (20.0) 5 (17.2) 0.25 2 (14.3) 3 (20.0) 5 (17.2) 0.5 6 (42.9) 1 (6.7) 7 (24.1) 1 4 (28.6) 5 (33.3) 9 (31.0) Streptococcus anginosus, N1 4 3 7 ND 0.25 1 (25.0) 1 (33.3) 2 (28.6) 0.5 2 (50.0) 1 (33.3) 3 (42.9) 1 1 (25.0) 1 (33.3) 2 (28.6) Streptococcus intermedius, N1 3 4 7 ND ≤0.06 0 1 (25.0) 1 (14.3) 0.12 1 (33.3) 2 (50.0) 3 (42.9) 0.25 1 (33.3) 0 1 (14.3) 0.5 1 (33.3) 0 1 (14.3) 1 0 1 (25.0) 1 (14.3) Streptococcus constellatus, N1 7 8 15 1 ≤0.06 0 2 (25.0) 2 (13.3) 0.12 1 (14.3) 1 (12.5) 2 (13.3) 0.25 0 2 (25.0) 2 (13.3) 0.5 3 (42.9) 0 3 (20.0) 1 3 (42.9) 3 (37.5) 6 (40.0)

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Treatment Group Tedizolid Linezolid Phosphate Linezolid Combined Linezolid Baseline Pathogen MIC (N=209) (N=209) (N=418) MIC90 (µg/mL) n (%) n (%) n (%) (μg/mL) Staphylococcus haemolyticus, N1 4 3 7 ND 0.5 1 (25.0) 0 1 (14.3) 1 3 (75.0) 3 (100) 6 (85.7) Staphylococcus lugdunensis, N1 3 2 5 ND 0.5 1 (33.3) 1 (50.0) 2 (40.0) 1 2 (66.7) 1 (50.0) 3 (60.0) Enterococcus faecalis, N1 3 0 3 ND 1 2 (66.7) 0 2 (66.7) 2 1 (33.3) 0 1 (33.3) Enterococcus faecium, N1 1 1 2 ND 2 1 (100) 1 (100) 2 (100) Enterococcus gallinarum, N1 1 0 1 ND 2 1 (100) 0 1 (100) Streptococcus Group C, N1 1 0 1 ND 0.5 1 (100) 0 1 (100) Streptococcus mitis, N1 0 5 5 ND 0.25 0 2 (40.0) 2 (40.0) 0.5 0 2 (40.0) 2 (40.0) 1 0 1 (20.0) 1 (20.0) Streptococcus mutans, N1 1 1 1 ND 0.5 0 1 (100) 1 (50.0) 1 1 (100) 0 1 (50.0) Streptococcus oralis, N1 1 0 1 ND 1 1 (100) 0 1 (100) Streptococcus salivarius, N1 2 2 4 ND ≤0.06 0 1 (50.0) 1 (25.0) 0.5 2 (100) 0 2 (50.0) 1 0 1 (50.0) 1 (25.0) Streptococcus sanguis, N1 3 2 5 ND 0.5 3 (100) 2 (100) 5 (100) Streptococcus viridans group, N1 2 4 6 ND 0.25 1 (50.0) 0 1 (16.7) 0.5 0 1 (25.0) 1 (16.7) 1 1 (50.0) 3 (75.0) 4 (66.7) Gram-positive anaerobes Actinomyces israelii, N1 0 1 1 ND 0.12 0 1 (100) 1 (100) Gemella morbillorum, N1 0 1 1 ND 0.25 0 1 (100) 1 (100) Gram-negative aerobes Eikenella corrodens, N1 1 0 1 ND 0.5 1 (100) 0 1 (100)

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Treatment Group Tedizolid Linezolid Phosphate Linezolid Combined Linezolid Baseline Pathogen MIC (N=209) (N=209) (N=418) MIC90 (µg/mL) n (%) n (%) n (%) (μg/mL) Enterobacter amnigenus, N1 0 1 1 ND 2 0 1 (100) 1 (100) Abbreviations: ABSSSI, acute bacterial skin and skin structure infection; MIC, minimum inhibitory concentration to inhibit growth in vitro; MIC90, MIC required to inhibit growth of 90% of isolates; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive S aureus; N, number of patients in the microbiological intent-to-treat analysis set; N1, number of patients with pathogen isolated; n, number of patients in the specific category; ND, not determined; PVL, Panton-Valentine Leukocidin. Percentages are calculated as 100*n/N1. For patients with multiple specimens of the same type having the same baseline pathogen tested, the specimen with the highest MIC is used. For patients with ABSSSI and blood specimens having the same baseline pathogen tested, each specimen is counted separately. For patients with both MRSA and MSSA, both isolates are counted separately in the S aureus row. MIC90 is not determined if N1<10 for the treatment groups combined.

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eTable 5. Investigator Assessment of Clinical Success at the Post-treatment Evaluation Visit by Baseline Pathogen (MITT Analysis Set) Tedizolid Phosphate Linezolid (N=209) (N=209) Clinical Success Clinical Success Baseline Pathogen N1 n (%) N1 n (%) Gram-positive aerobes 207 176 (85.0) 205 179 (87.3) Staphylococcus aureus 171 148 (86.5) 175 157 (89.7) MRSA 88 75 (85.2) 90 77 (85.6) MSSA 83 73 (88.0) 87 82 (94.3) PVL Staphylococcus aureus 97 83 (85.6) 102 86 (84.3) Streptococcus pyogenes 8 7 (87.5) 4 4 (100) Streptococcus anginosus-milleri group 15 11 (73.3) 15 12 (80.0) Streptococcus anginosus 4 3 (75.0) 3 3 (100) Streptococcus intermedius 3 3 (100) 4 3 (75.0) Streptococcus constellatus 8 5 (62.5) 8 6 (75.0) Enterococcus faecalis 5 3 (60.0) 0 NA Enterococcus faecium 1 0 2 2 (100) Enterococcus gallinarum 1 0 0 NA Mycobacterium fortuitum 1 0 0 NA Staphylococcus haemolyticus 4 4 (100) 3 3 (100) Staphylococcus lugdunensis 3 3 (100) 2 1 (50.0) Streptococcus Group C 1 1 (100) 0 NA Streptococcus agalactiae 9 8 (88.9) 5 3 (60.0) Streptococcus dysgalactiae 1 1 (100) 0 NA Streptococcus mitis 0 NA 5 4 (80.0) Streptococcus mutans 1 1 (100) 1 1 (100) Streptococcus oralis 1 1 (100) 0 NA Streptococcus salivarius 2 1 (50.0) 2 2 (100) Streptococcus sanguis 3 1 (33.3) 2 0 Streptococcus viridans group 3 2 (66.7) 3 1 (33.3) Gram-positive anaerobes 3 2 (66.7) 8 4 (50.0) Actinomyces israelii 0 NA 1 0 Actinomyces odontolyticus 0 NA 1 1 (100) Clostridium perfringens 1 1 (100) 1 0 Clostridium septicum 0 NA 1 1 (100) Finegoldia magna 1 0 2 0 Gemella morbillorum 0 NA 1 0 Peptostreptococcus anaerobius 1 1 (100) 0 NA Peptostreptococcus asaccharolyticus 0 NA 1 1 (100) Peptostreptococcus micros 0 NA 1 1 (100) Peptostreptococcus prevotii 0 NA 1 1 (100)

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Tedizolid Phosphate Linezolid (N=209) (N=209) Clinical Success Clinical Success Baseline Pathogen N1 n (%) N1 n (%) Gram-negative aerobes 6 3 (50.0) 6 5 (83.3) Acinetobacter baumannii 1 1 (100) 0 NA Eikenella corrodens 2 1 (50.0) 1 1 (100) Enterobacter amnigenus 0 NA 1 1 (100) Enterobacter cloacae 1 0 0 NA Escherichia coli 1 0 1 1 (100) Klebsiella oxytoca 1 0 2 2 (100) Klebsiella pneumoniae 1 NA 1 0 Proteus mirabilis 1 1 (100) 0 NA Pseudomonas aeruginosa 0 NA 1 1 (100) Gram-negative anaerobes 0 NA 1 0 Prevotella denticola 0 NA 1 0 Prevotella intermedia 0 NA 1 0 Abbreviations: ABSSSI, acute bacterial skin and skin structure infection; MITT, microbiological intent-to-treat analysis set; MRSA, methicillin-resisitant Staphylococcus aureus; MSSA, methicillin-sensitive S aureus; N, number of patients in the MITT analysis set; N1, number of patients in the MITT analysis set with the baseline pathogen; n, number of patients with investigator-assessed clinical success at the post-treatment evaluation; NA, not applicable. Clinical success is defined as resolution of most disease-specific signs and symptoms, including systemic signs of infection, present at baseline, and no new signs, symptoms, or complications attributable to the ABSSSI such that further antibiotic therapy is required to treat the primary lesion. Percentages are calculated as 100*n/N1. Patients with the same pathogen isolated from multiple specimens are counted only once for that pathogen. Patients with both MRSA and MSSA are counted only once in the overall S aureus row, and untyped S aureus pathogens are counted only once in the S aureus row.

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eMethods. Microbiology

Baseline microbiological samples for culture were collected as aspirates, biopsies, incisions, deep swabs, or other appropriate methods; superficial swabs were not acceptable. Blood samples were also collected.

Gram stain and culturing were performed on isolates at the local laboratory using standard microbiological procedures. All unique organisms from the ABSSSI primary site and/or blood were sent to one of two central laboratories, Eurofins Medinet (Chantilly, VA, for US, Canada, and South America; and Breda, Netherlands, for Europe), for confirmation of identification and for susceptibility testing using agar dilution with tedizolid (0.03-32 μg/mL) and linezolid (0.03-32 μg/mL). Staphylococcus aureus isolates were also tested for the presence of Panton-Valentine leukocidin.

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