DOI: 10.1128/AAC.02206-17
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- TABLE 1
In vitro activities of eravacycline and comparator antibiotics against 335 Gram-negative anaerobic clinical isolates
Organism (n) Antimicrobial agent MIC (μg/ml) % resistant by guidelinea Range MIC50 MIC90 CLSI/FDA EUCAST Bacteroides fragilis group (286) Eravacycline 0.03 to 4 0.25 1 NA NA Tigecycline 0.12 to 16 1 8 3.1 NA Minocycline ≤0.25 to 64 8 16 NA NA Imipenem ≤0.12 to 4 0.25 1 0 0 Meropenem ≤0.12 to 16 0.25 2 1.0 1.0 Piperacillin-tazobactam ≤0.5 to 256 4 32 0.7 10.8 Ampicillin-sulbactam ≤0.5 to >128 2 16 4.9 22.7 Moxifloxacin ≤0.5 to 64 2 32 38.8 NA Linezolid ≤1 to >16 2 4 NA NA Clindamycin ≤0.5 to >128 4 >128 43.7 43.7 Metronidazole ≤1 to 2 ≤1 2 0 0 Bacteroides fragilis (110) Eravacycline 0.03 to 4 0.25 1 NA NA Tigecycline 0.12 to 16 1 8 4.5 NA Minocycline ≤0.25 to 64 8 16 NA NA Imipenem ≤0.12 to 4 0.25 1 0 0 Meropenem ≤0.12 to 16 0.25 2 1.8 1.8 Piperacillin-tazobactam ≤0.5 to 128 1 8 0.9 1.8 Ampicillin-sulbactam 1 to 32 2 16 1.8 17.3 Moxifloxacin ≤0.5 to 32 2 16 36.4 NA Linezolid 2 to >16 2 4 NA NA Clindamycin ≤0.5 to >128 1 >128 30.0 30.0 Metronidazole ≤1 to 2 ≤1 2 0 0 Non-B. fragilis (176) Eravacycline 0.06 to 4 0.25 1 NA NA Tigecycline 0.12 to 16 1 8 2.3 NA Minocycline ≤0.25 to 32 4 16 NA NA Imipenem ≤0.12 to 4 0.5 1 0 0 Meropenem ≤0.12 to 16 0.25 2 0.6 0.6 Piperacillin-tazobactam ≤0.5 to 256 8 32 0.6 16.5 Ampicillin-sulbactam ≤0.5 to >128 4 16 6.8 26.1 Moxifloxacin ≤0.5 to 64 4 32 40.3 NA Linezolid ≤1 to >16 2 4 NA NA Clindamycin ≤0.5 to >128 8 >128 52.3 52.3 Metronidazole ≤1 to 2 ≤1 2 0 0 Bacteroides caccae (10) Eravacycline 0.12 to 0.5 0.5 0.5 NA NA Tigecycline 0.5 to 4 1 4 0 NA Minocycline 4 to 16 8 16 NA NA Imipenem ≤0.12 to 1 0.25 0.5 0 0 Meropenem ≤0.12 to 4 0.25 1 0 0 Piperacillin-tazobactam ≤0.5 to 4 2 4 0 0 Ampicillin-sulbactam 1 to 8 2 8 0 0 Moxifloxacin ≤0.5 to 64 4 32 50.0 NA Linezolid All 2 2 2 NA NA Clindamycin 4 to >128 >128 >128 90.0 90.0 Metronidazole ≤1 to 2 ≤1 2 0 0 Bacteroides ovatus (30) Eravacycline 0.06 to 1 0.25 1 NA NA Tigecycline 0.25 to 8 1 8 0 NA Minocycline ≤0.25 to 16 4 8 NA NA Imipenem ≤0.12 to 2 0.25 0.5 0 0 Meropenem ≤0.12 to 8 0.25 2 0 0 Piperacillin-tazobactam ≤0.5 to 32 4 32 0 13.3 Ampicillin-sulbactam ≤0.5 to 32 2 16 3.3 20.0 Moxifloxacin ≤0.5 to 32 4 8 20.0 NA Linezolid ≤1 to 8 2 4 NA NA Clindamycin ≤0.5 to >128 8 >128 53.3 53.3 Metronidazole ≤1 to 2 ≤1 2 0 0 Bacteroides thetaiotaomicron (70) Eravacycline 0.06 to 4 0.25 1 NA NA Tigecycline 0.12 to 16 1 8 4.3 NA Minocycline ≤0.25 to 16 4 8 NA NA Imipenem ≤0.12 to 1 0.5 1 0 0 Meropenem ≤0.12 to 2 0.25 1 0 0 Piperacillin-tazobactam 1 to 64 16 32 0 20.0 Ampicillin-sulbactam 1 to 64 2 16 4.3 18.6 Moxifloxacin ≤0.5 to 64 2 32 35.7 NA Linezolid 2 to 4 4 4 NA NA Clindamycin ≤0.5 to >128 8 >128 51.4 51.4 Metronidazole ≤1 to 2 ≤1 2 0 0 Parabacteroides distasonis (26) Eravacycline 0.12 to 4 0.25 1 NA NA Tigecycline 0.5 to 16 1 8 3.8 NA Minocycline ≤0.25 to 32 4 16 NA NA Imipenem 0.25 to 2 0.5 2 0 0 Meropenem ≤0.12 to 4 0.5 4 0 0 Piperacillin-tazobactam 1 to 64 8 32 0 26.9 Ampicillin-sulbactam 2 to 64 8 32 15.4 38.5 Moxifloxacin ≤0.5 to 64 2 32 46.2 NA Linezolid 2 to 4 2 4 NA NA Clindamycin ≤0.5 to >128 4 >128 38.5 38.5 Metronidazole ≤1 to 2 ≤1 2 0 0 Bacteroides uniformis (15) Eravacycline 0.06 to 1 0.25 1 NA NA Tigecycline 0.25 to 8 1 4 0 NA Minocycline ≤0.25 to 32 8 16 NA NA Imipenem ≤0.12 to 2 0.25 1 0 0 Meropenem ≤0.12 to 4 0.25 2 0 0 Piperacillin-tazobactam ≤0.5 to 32 4 32 0 13.3 Ampicillin-sulbactam ≤0.5 to 16 2 16 0 20.0 Moxifloxacin ≤0.5 to 64 8 32 53.3 NA Linezolid 2 to 4 2 4 NA NA Clindamycin ≤0.5 to >128 >128 >128 60.0 60.0 Metronidazole ≤1 to 2 ≤1 2 0 0 Bacteroides vulgatus (18) Eravacycline 0.06 to 0.5 0.12 0.5 NA NA Tigecycline 0.12 to 8 0.5 8 0 NA Minocycline ≤0.25 to 16 8 16 NA NA Imipenem 0.25 to 4 0.5 2 0 0 Meropenem 0.25 to 16 0.5 4 5.6 5.6 Piperacillin-tazobactam 2 to 256 4 32 5.6 11.1 Ampicillin-sulbactam 2 to 64 16 64 16.7 61.1 Moxifloxacin 1 to 64 32 64 72.2 NA Linezolid 2 to >16 2 4 NA NA Clindamycin ≤0.5 to >128 >128 >128 55.6 55.6 Metronidazole ≤1 to 2 ≤1 ≤1 0 0 Other Parabacteroides/Bacteroides spp. (7)b Eravacycline 0.06 to 1 Tigecycline 0.5 to 8 Minocycline ≤0.25 to 32 Imipenem ≤0.12 to 1 Meropenem 0.25 to 1 Piperacillin-tazobactam ≤0.5 to 16 Ampicillin-sulbactam 2 to >128 Moxifloxacin ≤0.5 to 8 Linezolid 2 to 4 Clindamycin ≤0.5 to >128 Metronidazole ≤1 to 2 Prevotella spp. (29) Eravacycline ≤0.015 to 0.5 0.25 0.5 NA NA Tigecycline ≤0.06 to 1 0.5 1 0 NA Minocycline ≤0.25 to 32 4 32 NA NA Imipenem ≤0.12 to 2 ≤0.12 2 0 0 Meropenem ≤0.12 to 8 ≤0.12 2 0 0 Piperacillin-tazobactam ≤0.5 to 128 ≤0.5 8 3.4 3.4 Ampicillin-sulbactam ≤0.5 to 32 1 4 3.4 3.4 Moxifloxacin ≤0.5 to >64 1 16 10.3 NA Linezolid ≤1 to 4 2 4 NA NA Clindamycin ≤0.5 to >128 ≤0.5 >128 27.6 27.6 Metronidazole ≤1 to >16 ≤1 2 3.4 3.4 Fusobacterium spp. (20) Eravacycline ≤0.015 to 0.5 0.03 0.12 NA NA Tigecycline ≤0.06 to 1 0.12 0.5 0 NA Minocycline ≤0.25 to 0.5 ≤0.25 0.5 NA NA Imipenem ≤0.12 to 0.5 ≤0.12 0.5 0 0 Meropenem ≤0.12 to 0.5 0.25 0.25 0 0 Piperacillin-tazobactam ≤0.5 to 2 1 2 0 0 Ampicillin-sulbactam ≤0.5 to 2 1 2 0 0 Moxifloxacin ≤0.5 to 2 ≤0.5 1 0 NA Linezolid ≤1 to 2 ≤1 ≤1 NA NA Clindamycin All ≤0.5 ≤0.5 ≤0.5 0 0 Metronidazole All ≤1 ≤1 ≤1 0 0 - TABLE 2
In vitro activities of eravacycline and comparator antibiotics against 205 Gram-positive anaerobic clinical isolates
Species (n) Antimicrobial agent MIC (μg/ml) % resistant by guidelinea Range MIC50 MIC90 CLSI/FDA EUCAST Clostridium perfringens (15) Eravacycline 0.03 to 1 0.12 1 NA NA Tigecycline 0.12 to 2 0.5 2 0 NA Minocycline ≤0.25 to 8 0.5 8 NA NA Imipenem ≤0.12 to 1 0.25 0.5 0 0 Meropenem ≤0.12 to 1 ≤0.12 0.25 0 0 Piperacillin-tazobactam ≤0.5 to 1 ≤0.5 1 0 0 Ampicillin-sulbactam ≤0.5 to 2 ≤0.5 1 0 0 Moxifloxacin ≤0.5 to 4 1 4 0 NA Linezolid ≤1 to 2 2 2 NA NA Clindamycin ≤0.5 to 128 1 64 13.3 13.3 Metronidazole ≤1 to 2 ≤1 2 0 0 Vancomycin 0.5 to 64 1 32 NA 20.0 Clostridium difficile (76) Eravacycline ≤0.015 to 0.25 0.06 0.12 NA NA Tigecycline ≤0.06 to 1 0.12 0.25 0 6.6 Minocycline ≤0.25 to 16 ≤0.25 4 NA NA Imipenem ≤0.12 to 16 4 8 6.6 NA Meropenem ≤0.12 to 8 2 4 0 NA Piperacillin-tazobactam ≤0.5 to 64 8 16 0 NA Ampicillin-sulbactam ≤0.5 to 16 2 4 0 NA Moxifloxacin ≤0.5 to 32 2 16 18.4 18.4 Linezolid ≤1 to 8 2 2 NA NA Clindamycin ≤0.5 to >128 4 128 28.9 NA Metronidazole ≤1 to 4 ≤1 ≤1 0 1.3 Vancomycin ≤0.5 to 4 1 2 NA 2.6 Other Clostridium spp. (22) Eravacycline ≤0.015 to 0.5 0.03 0.12 NA NA Tigecycline ≤0.06 to 1 0.12 0.5 0 NA Minocycline ≤0.25 to 16 ≤0.25 4 NA NA Imipenem ≤0.12 to 4 1 4 0 0 Meropenem ≤0.12 to 2 1 2 0 0 Piperacillin-tazobactam ≤0.5 to 32 2 16 0 9.1 Ampicillin-sulbactam ≤0.5 to 2 ≤0.5 2 0 0 Moxifloxacin ≤0.5 to >64 2 4 9.1 NA Linezolid ≤1 to 8 2 4 NA NA Clindamycin ≤0.5 to >128 4 128 40.9 40.9 Metronidazole ≤1 to >16 ≤1 ≤1 4.5 4.5 Vancomycin ≤0.25 to 16 2 16 NA 31.8 Peptostreptococcus spp. (53) Eravacycline 0.03 to 0.25 0.12 0.25 NA NA Tigecycline ≤0.06 to 1 0.25 0.25 0 NA Minocycline ≤0.25 to 16 0.5 8 NA NA Imipenem ≤0.12 to 0.5 ≤0.12 ≤0.12 0 0 Meropenem ≤0.12 to 0.5 ≤0.12 ≤0.12 0 0 Piperacillin-tazobactam ≤0.5 to 4 ≤0.5 ≤0.5 0 0 Ampicillin-sulbactam ≤0.5 to 2 ≤0.5 1 0 0 Moxifloxacin ≤0.5 to 16 ≤0.5 4 9.4 NA Linezolid ≤1 to 2 ≤1 2 NA NA Clindamycin ≤0.5 to >128 ≤0.5 64 11.3 11.3 Metronidazole ≤1 to >16 ≤1 ≤1 5.7 5.7 Vancomycin ≤0.25 to 4 0.5 1 NA 5.7 Propionibacterium spp./Cutibacterium acnes (13) Eravacycline ≤0.015 to 1 0.06 0.25 NA NA Tigecycline 0.12 to 2 0.12 0.5 0 NA Minocycline ≤0.25 to 8 0.5 2 NA NA Imipenem ≤0.12 to 0.5 ≤0.12 ≤0.12 0 0 Meropenem ≤0.12 to 0.25 ≤0.12 0.25 0 0 Piperacillin-tazobactam ≤0.5 to 1 ≤0.5 ≤0.5 0 0 Ampicillin-sulbactam ≤0.5 to 4 ≤0.5 1 0 0 Moxifloxacin ≤0.5 to 4 ≤0.5 1 0 NA Linezolid ≤1 to 2 ≤1 ≤1 NA NA Clindamycin ≤0.5 to 64 1 64 23.1 23.1 Metronidazole ≤1 to >16 >16 >16 92.3 92.3 Vancomycin 0.5 to 32 1 8 NA 23.1 Bifidobacterium spp. (15) Eravacycline 0.12 to 0.5 0.25 0.5 NA NA Tigecycline 0.12 to 1 0.5 1 0 NA Minocycline 0.5 to 64 1 32 NA NA Imipenem ≤0.12 to 2 0.5 2 0 0 Meropenem ≤0.12 to 8 0.5 4 0 0 Piperacillin-tazobactam 1 to 16 2 8 0 0 Ampicillin-sulbactam 1 to 16 1 2 0 6.7 Moxifloxacin 1 to 64 1 32 13.3 NA Linezolid ≤1 to 2 ≤1 2 NA NA Clindamycin ≤0.5 to >128 ≤0.5 >128 13.3 13.3 Metronidazole 4 to >16 >16 >16 93.3 93.3 Vancomycin 0.5 to 32 1 4 NA 13.3 Eggerthella lenta (6)b Eravacycline 0.03 to 0.12 Tigecycline ≤0.06 to 0.5 Minocycline 1 to 32 Imipenem ≤0.12 to 0.5 Meropenem ≤0.12 to 0.5 Piperacillin-tazobactam ≤0.5 to 64 Ampicillin-sulbactam ≤0.5 to 8 Moxifloxacin ≤0.5 to >64 Linezolid ≤1 to 4 Clindamycin ≤0.5 to 16 Metronidazole All ≤1 Vancomycin 1 to 4 Lactobacillus spp. (5)b Eravacycline 0.06 to 0.5 Tigecycline 0.25 to 1 Minocycline ≤0.25 to 4 Imipenem ≤0.12 to 2 Meropenem ≤0.12 to 8 Piperacillin-tazobactam ≤0.5 to 4 Ampicillin-sulbactam ≤0.5 to 2 Moxifloxacin ≤0.5 to 2 Linezolid ≤1 to 4 Clindamycin All ≤0.5 Metronidazole All >16 Vancomycin 0.5 to >64 - TABLE 3
In vitro activities of eravacycline and comparator tetracyclines against 27 Bacteroides fragilis clinical isolates characterized for tetracycline resistance determinants
No. of strains Presence of tetracycline resistance determinanta MIC range (μg/ml)b tet(Q) tet(X)2 tet(X2)2 tet(X1)3 tet(M) ERV TIG MIN 4 − − − − − 0.12–0.5 0.5–2 ≤0.25 18 +4 − − − − 0.06–4 0.25–16 0.5–32 3 +4 − + + − 0.25–1 2–8 2–16 2 + + − − − 0.5–1 2–8 4–32 ↵a tet(X) was distinguished from tet(X2) by generating PCR products with universal tet(X) primers, sequencing with primers specific to both tet(X) and tet(X2), and identifying sequences specific to either tet(X) or tet(X2). tet(X1) was identified by generating PCR products with primers specific to tet(X1) and sequencing with the same primer set to verify tet(X1)-specific sequences. The tet(Q) gene in special studies laboratory strain numbers 28441 and 27741, with MIN MICs of 0.5 and 2 μg/ml, respectively, were sequenced and shown to encode amino acid sequences identical to each other and to 74 Tet(Q) proteins in the UniProtKB database (http://www.uniprot.org/help/uniprotkb, released on 15 March 2017), indicating that the genes encoded a common variant of Tet(Q).
↵b MIC determined by agar dilution method; ERV, eravacycline; TIG, tigecycline; MIN, minocycline.
