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Susceptibility

Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, against Hospital and Community Pathogens

J. A. Sutcliffe, W. O'Brien, C. Fyfe, T. H. Grossman
J. A. Sutcliffe
Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA
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W. O'Brien
Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA
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C. Fyfe
Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA
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T. H. Grossman
Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA
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DOI: 10.1128/AAC.01288-13
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    Fig 1

    Chemical structure of eravacycline (TP-434).

Tables

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  • Table 1

    Susceptibilities of Gram-negative aerobic bacteria to eravacycline and comparatorsa

    OrganismMIC50/90 (μg/ml), MIC range (μg/ml), and no. of isolates
    ERVTETTGCCARBAG3rd GCFQCSTPTZ
    Acinetobacter baumannii0.25/18/>320.5/42/328/>32>16/>32>2/>20.5/2>64/>128
    0.016–8≤0.25–>32≤0.016–80.13–>32≤0.25–>320.13–>640.016–>320.13–>4≤0.5–>128
    188159188188188128188155128
    Acinetobacter baumannii CARB-I/R,b FQ-R,d AG-R0.5/2>8/>322/8>8/>32>8/>32>32/>32>4/160.5/1>64/>128
    ≤0.016–42–>320.13–8>8–>32>8–>32>16–>32>2–>320.13–>464–>128
    524352525237524344
    Acinetobacter baumannii TET-R0.5/2>8/>322/4>8/>32>8/>32>32/>32>4/320.5/1>64/>128
    0.06–2>8–>320.25–8≤0.25–>32≤0.25–>324–>64≤0.25–>320.13–>44–>128
    696969696939696856
    Acinetobacter lwoffii0.13/0.251/20.13/0.5≤1/4≤0.25/11/16≤0.25/≤0.250.25/>2≤0.5/8
    0.03–0.25≤0.25–>80.06–0.5≤0.25–>8≤0.25–>8≤0.5–>64≤0.25–2≤0.13–4≤0.5–16
    343434343434343434
    Burkholderia cenocepacia8/32>32/>328/3232/>32>32/>3216/324/8>32/>3216/>128
    0.13–3216–>320.25–>321–>32>32–>322–>320.5–>32>32–>320.5–>128
    101010101010101010
    Citrobacter freundii0.25/11/>80.5/20.5/20.5/>81/32<0.25/>20.5/14/>128
    0.06–20.5–>80.13–80.004–>32≤0.25–>320.06–>640.008–>40.25–>20.25–>128
    1156511510311511511564115
    Citrobacter freundii 3rd-GC-I/Rc0.5/12/81/21/160.5/>32>16/>641/>40.25/1>64/>128
    0.13–21–>80.25–80.25–>32≤0.25–>324–>640.016–>40.25–>22–>128
    421642394242421642
    Enterobacter cloacae0.5/22/>80.5/20.5/20.5/82/>64≤0.25/>40.5/>44/>64
    0.03–40.5–>320.06–80.03–>32≤0.25–>320.03–>640.008–>32≤0.13–>320.5–>128
    270218270270270246270178220
    Enterobacter cloacae 3rd-GC-I/R0.5/24/>81/40.5/40.5/16>32/>640.25/>40.25/>2>64/>128
    0.03–41–>320.06–80.03–>32≤0.25–>322–>640.008–>32≤0.13–>322–>128
    1229312212212212212281107
    Enterobacter cloacae CARB-I/R0.5/24/>320.5/42/161/>32>32/>64≤0.25/>40.25/>4>64/>128
    0.25–42–>320.13–4≤0.016–>32≤0.25–>320.13–>640.03–>32≤0.13–>321–>128
    343134343426342121
    Enterobacter cloacae FQ-R2/48/>322/40.5/81/>32>32/>64>4/320.25/1>64/>128
    0.25–42–>320.25–8≤0.016–>32≤0.25–>320.5–>64>2–>32≤0.13–>42–>128
    362936363635362127
    Enterobacter cloacae AG-R0.5/28/>321/40.5/1616/>32>32/>64>2/>40.25/1>64/>128
    0.25–41–>320.25–80.13–>32>8–>320.25–>64≤0.016–>32≤0.13–12–>128
    262026262626261522
    Enterobacter cloacae TET-R2/4>8/>321/40.25/21/>3232/>644/160.25/>416/>64
    0.25–4>8–>320.25–80.03–>32≤0.25–>320.13–>640.03–>32≤0.13–>322–>128
    252525252525252116
    Enterobacter aerogenes0.25/12/80.5/2≤1/1≤0.25/0.5≤0.5/>32≤0.25/≤0.250.25/0.54/>64
    0.13–20.5–>80.25–4≤0.25–8≤0.25–8≤0.5–>64≤0.25–>4≤0.13–>4≤0.5–>64
    777777777777777777
    Enterobacter aerogenes 3rd-GC-I/R0.25/12/80.5/20.5/1≤0.25/132/>32≤0.25/>40.25/164/>64
    0.13–21–>80.25–4≤0.25–8≤0.25–24–>64≤0.25–>4≤0.13–18–>64
    272727272727272727
    Escherichia coli0.25/0.54/>320.25/0.50.25/0.51/>8≤0.5/>32≤0.25/>40.5/0.52/>64
    ≤0.016–40.25–>640.06–>8≤0.002–>32≤0.25–>32≤0.016–>64≤0.25–>32≤0.13–4≤0.5–>128
    445390445445445445445216359
    Escherichia coli 3rd-GC-I/R0.25/0.5>8/>320.25/10.06/0.52/>32>32/>64>4/320.25/0.58/128
    ≤0.016–10.5–>320.03–>8≤1–>32≤0.25–>322–>64≤0.25–>32≤0.13–4≤0.5–>128
    1271131271271271271276993
    Escherichia coli FQ-R0.25/0.5>8/>320.25/0.50.13/≤0.54/>32>16/>64>4/320.25/0.58/>64
    ≤0.016–40.25–>320.06–>8≤1–>320.25–>320.06–>64>2–>32≤0.13–41–>128
    14311814314314314314372142
    Escherichia coli AG-R0.25/0.5>8/>320.25/0.50.063/≤0.5>8/>3232/>64>4/320.25/0.58/>64
    ≤0.016–10.25–>320.063–>8≤1–>32>8–>320.06–>64≤0.25–>32≤0.13–0.5≤0.5–>128
    796979797979794478
    Escherichia coli AG-R, FQ-R, 3rd-GC-I/R0.25/0.5>8/>320.25/0.50.063/0.5>32/>32>32/>64>4/320.25/0.58/>128
    ≤0.016–10.5–>320.063–>8≤1–>32>8–>324–>64>2–>32≤0.12–0.51–>128
    403540404040402140
    Escherichia coli TET-R0.25/0.516/>320.25/0.50.063/≤0.52/>84/>321/320.25/0.54/>64
    ≤0.016–2>8–>640.06–4≤1–>32≤0.25–>320.06–>64≤0.25–>32≤0.13–4≤0.5–>128
    15715715715715715715794148
    Haemophilus influenzae0.13/0.250.5/10.13/0.251/2ND<0.03/0.130.016/0.03NDND
    ≤0.016–0.5≤0.06–16≤0.016–10.06–8ND≤0.016–0.50.004–0.13NDND
    114114114101ND114114NDND
    Klebsiella pneumoniae0.5/24/>320.5/20.25/>80.5/>88/>320.5/>320.5/18/>128
    0.03–16≤0.25–>640.13–16≤0.002–>32≤0.25–>32≤0.016–>64≤0.25–>64≤0.13–>16≤0.5–>128
    394339394394223394394209394
    Klebsiella pneumoniae 3rd-GC-I/R0.5/28/>321/41/164/16>32/64>4/>320.5/4>64/>128
    0.03–161–>640.13–16≤1–>320.25–>324–>64≤0.25–>64≤0.13–>160.5–>128
    21018721021082210210110209
    Klebsiella pneumoniae CARB-I/R0.5/28/>321/2>8/>324/>8>32/>32>4/>320.5/>4>64/>128
    0.13–161–>320.25–162–>320.25–>321–>640.06–>640.13–>164–>128
    908190905090905790
    Klebsiella pneumoniae FQ-R0.5/28/>321/21/324/32>32/>32>4/>320.5/>4>64/>128
    0.13–161–>320.13–16≤1–>32≤0.25–>320.25–>64>2–>640.13–>164–>128
    1561341561568215615678156
    Klebsiella pneumoniae AG-R0.5/28/>321/40.5/32>8/>32>32/>64>4/>320.5/1>64/>128
    0.06–161–>320.13–16≤1–>32>8–>320.25–>64≤0.25–>64≤0.13–>162–>128
    1191061191195911911961118
    Klebsiella pneumoniae AG-R, FQ-R, 3rd-GC-I/R0.5/28/>321/41/32>8/>32>32/>328/>320.5/1>64/>128
    0.13–162–>320.13–16≤1–>32>8–>328–>64>2–>640.13- >164–>128
    746674743574743674
    Klebsiella pneumoniae AG-R, FQ-R, CARB-I/R0.5/28/>321/2>8/>32>8/>32>32/>32>4/>320.5/>4>128/>128
    0.13–164–>320.25–162–>32>8–>32>16–>64>2–>640.13–>16>64–>128
    373337372137372137
    Klebsiella oxytoca0.5/11/>320.5/2≤1/≤10.5/>32≤0.5/>32≤0.25/4≤0.13/0.132/16
    0.03–20.5–>320.06–40.004–1≤0.13–>32≤0.016–>320.03–>320.03–>2≤0.5–>64
    484848484848484148
    Klebsiella oxytoca 3rd-GC-I/R0.5/1>32/>320.25/0.50.06/0.25>32/>32>32/>320.5/>320.13/0.138/>32
    0.03–10.5–>320.06–10.03–10.5–>324–>320.03–>320.03–0.130.5–>32
    111111111111111111
    Legionella pneumophila1/24/8NDNDNDNDNDNDND
    0.016–20.5–8NDNDNDNDNDNDND
    7070NDNDNDNDNDNDND
    Moraxella catarrhalis0.03/0.06≤0.25/0.50.06/0.13≤0.25/≤0.25≤0.25/≤0.25≤0.5/≤0.5≤0.25/≤0.251/1≤0.5/≤0.5
    ≤0.016–0.06≤0.06–>32≤0.016–0.13≤0.25–≤0.25≤0.06–0.25≤0.5–2≤0.25–≤0.250.5–2≤0.5–2
    929292787878922828
    Morganella morganii1/22/>82/4≤1/21/>8≤0.5/8≤0.25/4>2/>4≤0.5/2
    0.5–40.5–>80.25–80.008–4≤0.25–>8≤0.016–>160.03–>4>2–>4≤0.5–>64
    434343434343433943
    Proteus mirabilis1/2>8/324/82/41/>8≤0.5/1≤0.25/>4>2/>4≤0.5/2
    0.25–162–>640.5–160.008–>32≤0.25–>64≤0.016–>640.016–>64>2–>4≤0.016–64
    16611116616616616616695157
    Proteus mirabilis 3rd-GC-I/R1/4>8/644/84/88/168/>32>2/8ND2/4
    0.5–8>8–641–160.25–320.5–>644–>64≤0.25–16>2–>4≤0.5–64
    21152121212121919
    Proteus mirabilis CARB-R1/4>8/324/82/81/>8≤0.5/2≤0.25/>4>2/>4≤0.5/2
    0.25–162–>641–160.06–>32≤0.25–>64≤0.016–>640.016–>64>2–>4≤0.06–>64
    1368113613613613613667127
    Proteus mirabilis FQ-R2/4>8/644/84/82/16≤0.5/16>4/16>2/>41/2
    0.5–16>8–>641–160.25–32≤0.25–>64≤0.016–>64>2–>64>2–>4≤0.13–64
    432643434343431938
    Proteus mirabilis AG-R2/4>8/>324/82/8>8/>64≤0.5/32>2/>4>2/>40.5/4
    0.5–8>8–642–80.25–32>8–>64≤0.016–>640.016–32>2–>4≤0.13–8
    241624242424241223
    Proteus mirabilis TET-R1/2>8/324/82/81/>8≤0.5/1≤0.25/>4>2/>4≤0.5/2
    0.25–16>8–>640.5–160.008–>32≤0.25–>64≤0.015–>640.03–>64>2–>4≤0.5–>64
    10910910910910910910993100
    Proteus vulgaris0.5/18/>82/4≤1/21/4≤0.5/32≤0.25/0.5>2/>2≤0.5/1
    0.25–21–>80.5–8≤0.5–4≤0.25–>8≤0.03–>64≤0.25–4>2–>4≤0.5–4
    555555555555555555
    Providencia stuartii1/2>8/>82/42/44/32<0.5/16>2/>4>2/>24/64
    0.13–8<0.25–>80.06–160.25–16≤0.25–>32≤0.016–>640.016–>4>2–>4≤0.13–>128
    1015110110110110110151101
    Pseudomonas aeruginosa8/32>8/6416/322/>82/>8>16/>321/>41/28/>128
    1–>328–641–>320.13–>320.13–>321–>640.06–>320.25–4>64–>128
    1459314514514514514585145
    Salmonella spp.0.25/0.251/>80.25/0.5≤1/≤10.5/1≤0.5/≤0.5≤0.25/≤0.25≤0.13/0.52/4
    0.13–0.50.5–>80.13–1≤1–8≤0.25–>8≤0.5–≤0.5≤0.25–>4≤0.13–21–64
    303030303030303030
    Serratia marcescens1/1>8/>81/20.5/10.5/1≤0.5/1≤0.25/1>2/>42/4
    0.25–82–>80.5–4≤0.25–2≤0.25–8≤0.5–>64≤0.25–>40.25–>4≤0.5–>64
    112112112112112112112112112
    Shigella spp.0.13/0.5>8/>80.25/0.5≤1/≤11/1≤0.5/≤0.5≤0.25/0.5≤0.13/≤0.132/2
    0.06–1≤0.25–>80.13–1≤1–≤1≤0.25–>8≤0.5–2≤0.25–1≤0.13–≤0.13≤0.5–4
    303030303030303030
    Stenotrophomonas maltophilia0.5/2>8/320.5/4>8/>32>8/>32>32/>321/>4>2/>32>64/>128
    ≤0.016–80.5–>320.03–82–>32≤0.25–>321–>640.13–32≤0.13–>328–>128
    105105105105105105105104105
    • ↵a CARB, carbapenem (imipenem, meropenem, or ertapenem); AG, aminoglycoside (gentamicin or tobramycin); 3rd-GC, third-generation cephalosporin (ceftazidime, cefotaxime, or ceftriaxone); FQ, fluoroquinolone (levofloxacin or ciprofloxacin); ERV, eravacycline; TET, tetracycline; TGC, tigecycline; CST, colistin; PTZ, piperacillin-tazobactam; ND, not determined.

    • ↵b For Enterobacteriaceae, carbapenem-I/R isolates were defined as having an imipenem/meropenem MIC of ≥2 μg/ml or an ertapenem MIC of ≥1 μg/ml, and for Acinetobacter, carbapenem-I/R isolates were defined as having an imipenem/meropenem MIC of ≥16 μg/ml.

    • ↵c Third-generation cephalosporin-I/R isolates were defined as having a ceftazidime MIC of ≥8 μg/ml and a cefotaxime/ceftriaxone MIC of ≥2 μg/ml.

    • ↵d Fluoroquinolone-resistant (FQ-R) isolates were defined as having a levofloxacin MIC of ≥8 μg/ml or a ciprofloxacin MIC of ≥4 μg/ml.

  • Table 2

    Susceptibilities of Gram-positive aerobic bacteria to eravacycline and comparatorsa

    OrganismMIC50/90 (μg/ml), MIC range (μg/ml), and no. of isolates
    ERVTETTGCDAPLZDVANLEVMACRO
    Enterococcus faecalis0.06/0.1332/>320.13/0.252/42/22/>64>8/>32>8/>8
    ≤0.016–0.130.13–>32≤0.016–0.50.13–8≤0.5–320.5–>640.25–>32≤0.13–>8
    1949819419419415019459
    Enterococcus faecalis VSE0.06/0.1332/>320.13/0.252/42/21/22/>32>4/>8
    ≤0.016–0.130.13–>32≤0.016–0.50.13–8≤0.5–320.5–40.25–>32≤0.13–>8
    121701211211219212138
    Enterococcus faecalis VRE0.06/0.1332/>320.13/0.252/42/2>64/>64>32/>32>8/>8
    ≤0.016–0.131–>320.03–0.250.13–81–8>16–>640.25–>322–>8
    7328737373587321
    Enterococcus faecalis FQ-R0.06/0.1332/>320.13/0.252/42/2>64/>64>32/>32>8/>8
    ≤0.016–0.130.13–>32≤0.016–0.5≤0.5–81–321–>64>4–>32≤0.13–32
    111481111111118711134
    Enterococcus faecium0.06/0.06≤2/>320.06/0.134/82/42/>64>32/>32>8/>8
    ≤0.016–0.50.25–>32≤0.016–0.51–16≤0.5–32≤0.5–>640.25–>320.25–>8
    1535915315315310815356
    Enterococcus faecium VSE0.06/0.131/>320.06/0.134/82/21/1>8/>32>8/>8
    0.03–0.50.25–>320.03–0.251–81–4≤0.5–40.25–>320.25–>8
    8433848484588433
    Enterococcus faecium VRE0.06/0.0632/>320.06/0.134/82/4>64/>64>32/>32>8/>8
    ≤0.016–0.250.25–>320.03–0.51–16≤0.5–32>16–>641–>328–>8
    6926696969496924
    Enterococcus faecium FQ-R0.06/0.062/>320.06/0.124/82/432/>64>32/>32>8/>8
    ≤0.016–0.50.25–>32≤0.016–0.51–16≤0.5–32≤0.5–>64>4–>32>4–>8
    127481271271278812745
    Enterococcus faecium DAP-NS0.06/0.06ND0.06/0.138/164/4>64/>64>32/>32ND
    ≤0.016–0.5ND0.03–0.258–161–320.5–>642–>32ND
    44ND4444444444ND
    Enterococcus spp.0.03/0.060.5/320.13/0.130.5/22/2ND1/>80.5/>8
    ≤0.016–0.13≤0.06–>32≤0.016–0.250.25–41–2ND≤0.13–>8≤0.13–>8
    2929292929ND2929
    Staphylococcus aureus0.06/0.250.25/320.13/0.251/12/41/11/32>8/>32
    ≤0.016–40.06–>64≤0.016–160.063–41–640.5–80.06–>640.13–>64
    408245408407407258399237
    MRSA0.06/0.130.25/320.13/0.251/12/41/18/>32>8/>32
    0.016–40.063–>64≤0.016–10.063–41–640.5–80.06–>640.13–>64
    284177284283283202275169
    MRSA PVL+0.03/0.030.25/0.250.13/0.130.5/11/21/10.25/>2>4/>4
    ≤0.016–0.030.13–0.250.06–0.130.5–11–21–10.25–>21–>4
    3030303030303030
    Staphylococcus aureus MACRO-Rb0.06/0.250.25/320.13/0.250.5/12/41/18/32>8/>32
    ≤0.016–40.06–>64≤0.016–160.13–41–640.5–80.06–>64>4–>64
    13213213213113170132132
    Staphylococcus aureus FQ-R0.06/0.130.25/320.12/0.251/12/41/1>8/>32>8/>32
    ≤0.016–20.06–>64≤0.016–160.125–21–640.5–8>2–>640.25–>64
    178109178178178126174105
    Staphylococcus aureus MACRO-R, FQ-R0.06/0.250.25/>320.13/0.250.5/12/41/2>8/32>8/>32
    ≤0.016–20.06–>64≤0.016–160.13–21–640.5–8>2–>64>4–>64
    8383838383458383
    MSSA0.13/0.250.5/10.13/0.251/14/41/10.25/11/>8
    0.03–0.250.25–320.06–0.250.25–12–40.5–20.13–>320.25–>8
    124681241241245612468
    Coagulase-negative staphylococci0.06/0.50.25/320.25/11/12/21/20.5/>320.5/>8
    ≤0.016–2≤0.06–>320.03–20.25–2≤0.5–40.5–20.13–>32≤0.13–>8
    1655916516516511116559
    Coagulase-negative staphylococci, methicillin sensitive0.06/0.50.25/320.25/11/12/21/20.25/>80.25/>8
    ≤0.016–1≤0.06–>320.03–20.25–2≤0.5–40.5–20.13–>32≤0.13–>8
    8937898989548937
    Coagulase-negative staphylococci, methicillin resistant0.06/0.50.25/>320.13/0.51/11/21/28/>32>4/>8
    0.03–20.25–>320.06–10.25–2≤0.5–20.5–20.13–>320.25–>8
    7622767676577622
    Streptococcus pneumoniae0.016/0.0160.25/>80.016/0.03≤0.03/0.50.5/10.25/0.51/12/>2
    ≤0.008–0.03≤0.03–>8≤0.008–0.06≤0.03–2≤0.13–20.13–0.5≤0.03–>8≤0.03–>2
    18210018218218282182100
    Streptococcus pneumoniae penicillin resistantc0.016/0.016>8/>80.016/0.03≤0.03/0.50.5/10.25/0.251/1>2/>2
    ≤0.008–0.030.13–>8≤0.008–0.03≤0.03–0.50.25–10.13–0.50.5–>8≤0.03–>2
    6033606060276033
    Streptococcus pneumoniae MACRO-Rd≤0.008/0.016>8/>80.016/0.03≤0.03/≤0.030.5/0.5ND1/1>2/>2
    ≤0.008–0.016≤0.03–>8≤0.008–0.03≤0.03–0.130.25–1ND0.5–>82–>2
    5353535353ND5353
    Streptococcus pneumoniae penicillin resistant, MACRO-R≤0.008/0.016>8/<80.016/0.03≤0.03/≤0.030.5/0.5ND1/1>2/>2
    ≤0.008–0.0160.13–>8≤0.008–0.03≤0.03–≤0.030.25–0.5ND0.5–>82–>2
    2929292929ND2929
    Streptococcus pneumoniae TET-R≤0.008/0.016>8/>80.016/0.03≤0.03/≤0.030.5/0.5ND1/1>2/>2
    ≤0.008–0.016>8–>8≤0.008–0.03≤0.03–0.060.25–0.5ND0.5–>22–>2
    3434343434ND3434
    Streptococcus pyogenes0.03/0.030.25/0.250.03/0.060.13/0.131/2ND0.5/10.06/0.06
    0.015–0.130.13–>8≤0.016–0.13≤0.03–0.250.5–2ND0.25–2≤0.03–0.13
    7420747474ND7420
    Streptococcus agalactiae0.03/0.06>8/>80.03/0.060.06/0.51/20.5/0.50.5/10.06/>4
    0.016–0.060.25–>80.016–0.13≤0.03–10.5–20.25–0.50.5–2≤0.03–>4
    123791231231234812379
    Streptococcus anginosus0.016/0.0310.5/>160.016/0.060.25/0.51/20.5/10.5/10.03/>0.5
    ≤0.008–0.13≤0.06–>16≤0.008–0.25≤0.03–0.5≤0.25–2≤0.008–1≤0.25–2≤0.016–>2
    4747472547462525
    Streptococcus intermedius0.016/0.060.25/>40.03/0.130.5/11/10.5/0.51/20.06/>0.5
    ≤0.008–0.06≤0.06–>4≤0.008–0.25≤0.03–>1≤0.25–1≤0.06–0.5≤0.25–>4≤0.016–>0.5
    3131313131313031
    Streptococcus mitis0.016/0.060.5/>40.03/0.130.5/11/10.5/0.51/2>0.5/>0.5
    ≤0.008–0.060.13–>8≤0.008–0.250.06–>10.5–1≤0.06–10.5–>4≤0.016–>2
    3232323232313232
    Streptococcus spp.0.016/0.131/>80.03/0.130.13/10.5/10.5/11/20.06/>2
    ≤0.008–0.25≤0.06–>8≤0.008–0.25≤0.03–1≤0.25–2≤0.06–1≤0.25–2≤0.016–>2
    6262626262216262
    • ↵a MACRO, macrolide (erythromycin, azithromycin, or clarithromycin); ND, not determined; ERV, eravacycline; TET, tetracycline; TGC, tigecycline; DAP, daptomycin; LZD, linezolid; VAN, vancomycin; LEV, levofloxacin; DAP-NS, daptomycin nonsusceptible; PVL+, Panton-Valentine leukocidin positive.

    • ↵b Macrolide-resistant staphylococci were defined as having an erythromycin/azithromycin/clarithromycin MIC of ≥8 μg/ml.

    • ↵c Penicillin-resistant streptococcal isolates were defined as having an MIC of ≥2 μg/ml for the oral penicillin breakpoint.

    • ↵d Macrolide-resistant streptococcal isolates were defined as having an erythromycin/clarithromycin MIC of ≥1 μg/ml and an azithromycin MIC of ≥2 μg/ml.

  • Table 3

    Susceptibilities of anaerobic bacteria to eravacycline and comparatorsa

    OrganismMIC50/90 (μg/ml), MIC range (μg/ml), and no. of isolates
    ERVTGCCARBMTZVAN
    Actinomyces spp.NDNDNDNDND
    0.25–0.250.25–0.5ND4–>16ND
    55ND5ND
    Anaerococcus spp.0.13/0.130.13/0.25ND2/2ND
    0.03–0.250.06–0.25ND0.5–4ND
    1010ND10ND
    Bacteroides fragilis0.5/10.5/40.25/11/1>16/>16
    0.06–20.13–80.13–40.25–>1616–>16
    3636163111
    B. fragilis cefinase positive0.5/11/4ND1/1ND
    0.13–20.25–8ND0.25–1ND
    2020ND20ND
    Bacteroides ovatus1/40.5/160.25/0.251/2>16/>16
    0.016–80.06–320.03–10.13–>168–>16
    1111111010
    Bacteroides thetaiotaomicron1/48/160.5/21/2>16/>16
    0.13–40.25–160.13–40.5–>1616–>16
    1111111010
    Bacteroides vulgatus0.25/0.250.5/0.50.25/10.5/1>16/>16
    0.13–10.13–40.25–10.5–116–>16
    1212121010
    Bifidobacterium spp.NDNDNDNDND
    0.13–0.50.25–0.5ND2–>16ND
    77ND6ND
    Clostridium difficile0.06/0.130.13/0.134/81/11/2
    0.03–0.250.06–0.50.25–80.5–20.5–4
    1111111111
    Clostridium perfringens1/21/40.13/0.54/161/>16
    0.06–40.13–80.06–12–>160.5–>16
    1111111010
    Eggerthella lenta0.25/0.250.5/0.5ND0.5/0.5ND
    0.25–0.250.25–0.5ND0.25–0.5ND
    1212ND12ND
    Finegoldia magna0.25/0.50.25/0.25ND0.5/1ND
    0.13–0.50.13–0.25ND≤0.13–1ND
    1010ND10ND
    Fusobacterium spp.0.13/0.250.13/0.5ND≤0.13/0.25ND
    0.03–0.250.06–0.5ND≤0.13–0.25ND
    2121ND21ND
    Lactobacillus spp.0.25/0.50.5/0.5ND>16/>16ND
    0.25–10.25–1ND>16–>16ND
    77ND7ND
    Parabacteroides distasonis0.5/11/2ND1/1ND
    0.25–10.25–4ND0.5–1ND
    1010ND10ND
    Peptoniphilus asaccharolyticus0.06/0.130.13/0.25ND1/2ND
    0.03–0.130.06–0.25ND0.5–2ND
    1010ND10ND
    Peptostreptococcus anaerobius0.06/0.250.06/0.250.06/11/20.5/2
    0.016–0.250.016–0.50.03–10.25–20.5–>16
    1010101010
    Peptostreptococcus micros0.016/0.250.03/0.250.016/0.030.25/>161/1
    0.016–0.50.016–1≤0.008–0.03≤0.008–>160.5–2
    1010101010
    Porphyromonas asaccharolytica0.03/0.060.06/0.060.016/0.031/20.25/0.5
    0.016–0.130.03–0.13≤0.008–0.060.5–40.13–1
    1010101010
    Prevotella bivia1/11/2ND1/4ND
    0.13–10.03–2ND0.5–4ND
    1313ND13ND
    Prevotella buccae0.06/0.130.13/0.13ND0.5/1ND
    0.03–0.130.06–0.25ND0.25–1ND
    1010ND10ND
    Prevotella disiens0.13/0.250.25/0.5ND1/1ND
    0.06–0.250.13–0.5ND0.5–2ND
    1212ND12ND
    Prevotella intermedia0.06/0.130.25/0.25ND0.5/0.5ND
    0.03–0.130.13–0.25ND0.25–1ND
    1010ND10ND
    Prevotella melaninogenica0.13/10.5/1ND0.25/1ND
    0.06–10.06–4ND≤0.008–>161–>16
    1313ND138
    Prevotella spp.NDNDNDNDND
    0.03–10.06–0.5ND0.25–>16ND
    77ND7ND
    Propionibacterium acnesNDNDNDNDND
    0.13–0.130.13–0.13ND>16–>16ND
    55ND5ND
    • ↵a ERV, eravacycline; TGC, tigecycline; MTZ, metronidazole; VAN, vancomycin; CARB, ertapenem or imipenem; ND, not determined.

  • Table 4

    Distribution of tigecycline/eravacycline MIC ratiosa for individual isolates

    TGC/ERV MIC ratioNo. of isolates with TGC/ERV ratio
    A. baumanniiE. coliE. cloacaeK. pneumoniaeP. mirabilisB. fragilis
    322
    16143
    83974451
    480272135826
    2441061341406521
    12021195185138
    0.548615270
    0.25211
    Total18844527039416636
    • ↵a For each isolate within a given organism panel, the ratio of the tigecycline MIC to the eravacycline MIC (TGC/ERV MIC) was calculated.

  • Table 5

    Activity of eravacycline against S. aureus strains expressing NorA or MepA efflux pumps

    CompoundMIC (μg/ml)
    SA981 (parent)SA982 (norA)SA983 (parent)SA984 (mepA)
    Eravacycline0.0040.0040.0040.016
    Tigecycline0.0630.130.0161
    Tetracycline0.50.50.50.5
    Ciprofloxacin0.51624
    Meropenem0.250.130.130.13
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Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, against Hospital and Community Pathogens
J. A. Sutcliffe, W. O'Brien, C. Fyfe, T. H. Grossman
Antimicrobial Agents and Chemotherapy Oct 2013, 57 (11) 5548-5558; DOI: 10.1128/AAC.01288-13

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Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, against Hospital and Community Pathogens
J. A. Sutcliffe, W. O'Brien, C. Fyfe, T. H. Grossman
Antimicrobial Agents and Chemotherapy Oct 2013, 57 (11) 5548-5558; DOI: 10.1128/AAC.01288-13
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