Tedizolid’s anaerobic activity is unappreciated. In this study, it was active against all 332 anaerobic isolates tested at ≤2 μg/ml except Bilophila wadsworthia and was more active than linezolid against Bacteroides fragilis group species (MIC90, 1 μg/ml versus 2 to 4 μg/ml). Tedizolid was active against Gram-positive anaerobes (MIC90 for clostridia, 0.25 to 1 μg/ml; MIC90 for anaerobic cocci, ≤0.
KEYWORDS: Bacteroides fragilis, Prevotella spp., Veillonella spp., anaerobes, linezolid, tedizolid
ABSTRACT
Tedizolid’s anaerobic activity is unappreciated. In this study, it was active against all 332 anaerobic isolates tested at ≤2 μg/ml except Bilophila wadsworthia and was more active than linezolid against Bacteroides fragilis group species (MIC90, 1 μg/ml versus 2 to 4 μg/ml). Tedizolid was active against Gram-positive anaerobes (MIC90 for clostridia, 0.25 to 1 μg/ml; MIC90 for anaerobic cocci, ≤0.06 to 0.25 μg/ml). Our data coupled with clinical reports indicate that clinicians should consider its use in mixed infections where Staphylococcus aureus and anaerobes are involved.
INTRODUCTION
Oxazolidinones are primarily thought of as active against Gram-positive aerobes (1, 2). Tedizolid, the newest oxazolidinone, is approved for use in acute bacterial skin and skin structure infections (ABSSSIs) and offers potential advantages of once-a-day dosing, as well as potential decreased toxicities and has activity against linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA) (3–5). There is a paucity of data about the susceptibility of anaerobic bacteria in general, including susceptibility to tedizolid (6, 7). However, the successful clinical use of linezolid in patients with ABSSSIs due to resistant anaerobic bacteria and cases of resistant Bacteroides fragilis wound sepsis has been reported (8, 9). We evaluated the comparative activity of tedizolid against a broad range of clinically isolated anaerobic pathogens, including Fusobacterium, Prevotella, and Veillonella spp.
Organisms tested were recovered from clinical samples (generally obtained from 2015 to 2017) from human infections, identified by standard methods (10, 11), and stored at −70°C. Susceptibility testing was performed using supplemented brucella blood agar dilution according to CLSI methods (12).
The antimicrobial agents tested were tedizolid, linezolid, moxifloxacin, ampicillin-sulbactam, piperacillin-tazobactam, clindamycin, and metronidazole. Drugs were reconstituted according to the manufacturers’ instructions or the guidelines in CLSI document M11-A9 (12). Piperacillin-tazobactam was tested from 128 μg/ml to 0.06 μg/ml with tazobactam constant at 4 μg/ml; tedizolid was tested at 32 to 0.03 μg/ml and the remainder at 32 to 0.06 μg/ml.
Quality control (QC) strains included Bacteroides fragilis ATCC 25285 and Clostridioides difficile ATCC 700057. After 36 to 48 h of incubation in the anaerobic chamber at 36°C, the plates were examined for growth. The MIC was defined as the concentration of drug that completely inhibited growth or resulted in a marked reduction relative to the drug-free growth control. Breakpoints were interpreted according to CLSI document M100-S30 (13).
The comparative in vitro activity (MICs) of tedizolid against 332 anaerobes is presented in Table 1. Tedizolid was active against all 332 anaerobic isolates at ≤2 μg/ml, except for Bilophila wadsworthia (MIC90, 16 μg/ml), which was also resistant to linezolid (MIC90, 16 μg/ml), ampicillin-sulbactam, and piperacillin-tazobactam (MIC90, >64 μg/ml) but susceptible to moxifloxacin (MIC90, 0.5 μg/ml) and metronidazole (MIC90, 1 μg/ml). Tedizolid was generally one to four dilutions more active than linezolid, including against B. fragilis group species (MIC90, 1 μg/ml versus 2 to 4 μg/ml) and most other Gram-negative anaerobes tested. It was active at <2 μg/ml against 13 B. fragilis strains, 8 Bacteroides thetaiotaomicron strains, 2 Bacteroides ovatus strains, and 1 Bacteroides uniformis strain with piperacillin-tazobactam MICs of >16 μg/ml. Clindamycin resistance was common at ∼50% or more for B. fragilis, B. uniformis, and B. ovatus isolates and ∼30% for Bacteroides caccae, B. thetaiotaomicron, and B. vulgatus isolates. Tedizolid was especially active against Gram-positive anaerobes (MIC90 for clostridia, 0.25 to 1 μg/ml; MIC90 for cocci, ≤0.06 to 0.25 μg/ml). Moxifloxacin resistance was found in 44% of B. fragilis group isolates, including 10% of B. fragilis isolates, ∼30% of B. caccae and B. thetaiotaomicron isolates, and ∼55% of B. vulgatus isolates.
TABLE 1.
Comparative in vitro activity of tedizolid compared to linezolid and 5 other agents against 332 anaerobic isolates, including Bacteroides fragilis group species
| Organism (no. of isolates) and agent | MIC (μg/ml) |
||
|---|---|---|---|
| Range | 50% | 90% | |
| Bacteroides caccae (11) | |||
| Tedizolid | 0.25–1 | 1 | 1 |
| Linezolid | 1–4 | 2 | 4 |
| Ampicillin-sulbactam | 0.5–8 | 1 | 4 |
| Piperacillin-tazobactam | 0.5–8 | 2 | 8 |
| Moxifloxacin | 0.25–16 | 2 | 16 |
| Clindamycin | ≤0.06–>32 | 1 | >32 |
| Metronidazole | 0.25–1 | 0.5 | 1 |
| Bacteroides fragilis (46) | |||
| Tedizolid | 0.5–2 | 1 | 1 |
| Linezolid | 2–16 | 4 | 4 |
| Ampicillin-sulbactam | 0.5–>64 | 16 | 64 |
| Piperacillin-tazobactam | ≤0.03–>64 | 4 | >64 |
| Moxifloxacin | 0.125–>16 | 0.5 | 8 |
| Clindamycin | ≤0.06–>32 | 0.5 | >32 |
| Metronidazole | 0.25–32 | 1 | 1 |
| Bacteroides ovatus (11) | |||
| Tedizolid | 1–2 | 1 | 1 |
| Linezolid | 2–4 | 2 | 2 |
| Ampicillin-sulbactam | 1–32 | 4 | 16 |
| Piperacillin-tazobactam | 2–>64 | 4 | 32 |
| Moxifloxacin | 0.5–>16 | 1 | 8 |
| Clindamycin | 0.125–>32 | 2 | >32 |
| Metronidazole | 0.25–2 | 1 | 1 |
| Bacteroides thetaiotaomicron (14) | |||
| Tedizolid | 1–1 | 1 | 1 |
| Linezolid | 2–4 | 2 | 4 |
| Ampicillin-sulbactam | 1–32 | 4 | 16 |
| Piperacillin-tazobactam | 8–>64 | 16 | >64 |
| Moxifloxacin | 0.5–16 | 1 | 16 |
| Clindamycin | 0.25–>32 | 4 | >32 |
| Metronidazole | 0.25–2 | 0.5 | 1 |
| Bacteroides uniformis (11) | |||
| Tedizolid | 0.5–1 | 0.5 | 1 |
| Linezolid | 1–2 | 2 | 2 |
| Ampicillin-sulbactam | 1–32 | 8 | 16 |
| Piperacillin-tazobactam | 0.5–>64 | 2 | 4 |
| Moxifloxacin | 0.25–>16 | 4 | 16 |
| Clindamycin | ≤0.06–>32 | >32 | >32 |
| Metronidazole | 0.25–1 | 0.5 | 1 |
| Bacteroides vulgatus (15) | |||
| Tedizolid | 0.25–2 | 1 | 1 |
| Linezolid | 1–2 | 2 | 2 |
| Ampicillin-sulbactam | 0.5–16 | 4 | 16 |
| Piperacillin-tazobactam | 0.125–4 | 4 | 4 |
| Moxifloxacin | 0.125–>16 | 16 | >16 |
| Clindamycin | ≤0.06–>32 | >32 | >32 |
| Metronidazole | 0.125–2 | 0.5 | 2 |
| Bilophila wadsworthia (11) | |||
| Tedizolid | >16–>16 | >16 | >16 |
| Linezolid | 4–16 | 16 | 16 |
| Ampicillin-sulbactam | 2–>64 | 64 | >64 |
| Piperacillin-tazobactam | 4–>64 | >64 | >64 |
| Moxifloxacin | 0.25–0.5 | 0.5 | 0.5 |
| Clindamycin | 0.25–>32 | 0.25 | 1 |
| Metronidazole | ≤0.06–≤0.06 | ≤0.06 | ≤0.06 |
| Parabacteroides distasonis (11) | |||
| Tedizolid | 1–2 | 2 | 2 |
| Linezolid | 2–4 | 4 | 4 |
| Ampicillin-sulbactam | 4–64 | 4 | 32 |
| Piperacillin-tazobactam | 4–>64 | 8 | 64 |
| Moxifloxacin | 0.25–16 | 0.5 | 8 |
| Clindamycin | 0.25–>32 | 2 | >32 |
| Metronidazole | 0.5–1 | 1 | 1 |
| Parabacteroides goldsteinii (10) | |||
| Tedizolid | 0.5–2 | 1 | 2 |
| Linezolid | 1–4 | 4 | 4 |
| Ampicillin-sulbactam | 2–32 | 8 | 32 |
| Piperacillin-tazobactam | 4–64 | 8 | 64 |
| Moxifloxacin | 0.25–16 | 0.5 | 8 |
| Clindamycin | ≤0.06–>32 | 4 | >32 |
| Metronidazole | 0.5–1 | 0.5 | 1 |
| Parabacteroides merdae (10) | |||
| Tedizolid | 0.25–2 | 1 | 2 |
| Linezolid | 1–4 | 4 | 4 |
| Ampicillin-sulbactam | 1–64 | 8 | 16 |
| Piperacillin-tazobactam | ≤0.03–>64 | 6 | 64 |
| Moxifloxacin | 0.125–8 | 1.25 | 8 |
| Clindamycin | ≤0.06–>32 | 0.25 | >32 |
| Metronidazole | 0.25–2 | 0.5 | 1 |
| Fusobacterium necrophorum (10) | |||
| Tedizolid | ≤0.06–0.125 | ≤0.06 | ≤0.06 |
| Linezolid | 0.5–1 | 0.5 | 1 |
| Ampicillin-sulbactam | ≤0.06–0.125 | 0.125 | 0.125 |
| Piperacillin-tazobactam | ≤0.03 | ≤0.03 | ≤0.03 |
| Moxifloxacin | 1–2 | 1 | 2 |
| Clindamycin | ≤0.06–>64 | ≤0.06 | >64 |
| Metronidazole | 0.125–0.5 | 0.25 | 0.5 |
| Fusobacterium varium (10) | |||
| Tedizolid | ≤0.06–0.25 | 0.125 | 0.125 |
| Linezolid | 0.25–2 | 0.5 | 0.5 |
| Ampicillin-sulbactam | 0.5–1 | 1 | 1 |
| Piperacillin-tazobactam | 1–4 | 2 | 4 |
| Moxifloxacin | 0.25–>16 | 4 | >16 |
| Clindamycin | 0.125–>32 | 2 | >32 |
| Metronidazole | 0.25–1 | 0.5 | 1 |
| Fusobacterium spp. (10)a | |||
| Tedizolid | ≤0.06–0.125 | ≤0.06 | ≤0.06 |
| Linezolid | 0.25–0.5 | 0.5 | 0.5 |
| Ampicillin-sulbactam | ≤0.06–0.25 | ≤0.06 | ≤0.06 |
| Piperacillin-tazobactam | ≤0.03–0.06 | ≤0.03 | ≤0.03 |
| Moxifloxacin | 0.125–2 | 0.25 | 2 |
| Clindamycin | ≤0.06 = 1 | ≤0.06 | 1 |
| Metronidazole | ≤0.06 = 0.25 | ≤0.06 | 0.125 |
| Porphyromonas spp. (10)b | |||
| Tedizolid | ≤0.06–1 | 0.125 | 0.25 |
| Linezolid | 0.5–4 | 1 | 2 |
| Ampicillin-sulbactam | ≤0.06–2 | ≤0.06 | 0.5 |
| Piperacillin-tazobactam | ≤0.03–2 | ≤0.03 | ≤0.03 |
| Moxifloxacin | 0.125–2 | 0.5 | 1 |
| Clindamycin | ≤0.06–>64 | ≤0.06 | >64 |
| Metronidazole | ≤0.06–2 | 0.125 | 0.5 |
| Prevotella bivia (10) | |||
| Tedizolid | 0.25–4 | 2 | 4 |
| Linezolid | 2–8 | 4 | 4 |
| Ampicillin-sulbactam | 0.125–2 | 1 | 2 |
| Piperacillin-tazobactam | ≤0.03–0.06 | ≤0.03 | ≤0.03 |
| Moxifloxacin | 0.125–8 | 4 | 4 |
| Clindamycin | ≤0.06 = >32 | ≤0.06 | >32 |
| Metronidazole | 0.25–8 | 1 | 8 |
| Prevotella buccae (10) | |||
| Tedizolid | 0.5–1 | 1 | 1 |
| Linezolid | 2–2 | 2 | 2 |
| Ampicillin-sulbactam | 0.125–1 | 1 | 1 |
| Piperacillin-tazobactam | ≤0.03 | ≤0.03 | ≤0.03 |
| Moxifloxacin | 0.5–>16 | 0.5 | >16 |
| Clindamycin | ≤0.06–>32 | >32 | >32 |
| Metronidazole | 0.25–0.5 | 0.5 | 0.5 |
| Prevotella melaninogenica (10) | |||
| Tedizolid | 0.5–1 | 1 | 1 |
| Linezolid | 2–4 | 2 | 4 |
| Ampicillin-sulbactam | 0.25–2 | 1 | 2 |
| Piperacillin-tazobactam | ≤0.03 | ≤0.03 | ≤0.03 |
| Moxifloxacin | 0.5–>16 | 1 | 16 |
| Clindamycin | ≤0.06–>64 | ≤0.03 | >64 |
| Metronidazole | 0.25–1 | 0.5 | 0.5 |
| Prevotella oralis (10) | |||
| Tedizolid | 0.125–1 | 0.25 | 0.25 |
| Linezolid | 0.5–4 | 2 | 2 |
| Ampicillin-sulbactam | ≤0.06–1 | ≤0.06 | 0.5 |
| Piperacillin-tazobactam | ≤0.03 | ≤0.03 | ≤0.03 |
| Moxifloxacin | 0.5–16 | 1 | 8 |
| Clindamycin | ≤0.06–>32 | ≤0.06 | >32 |
| Metronidazole | ≤0.06–1 | ≤0.06 | 0.25 |
| Veillonella spp. (10)c | |||
| Tedizolid | 1–2 | 2 | 2 |
| Linezolid | 2–8 | 2 | 4 |
| Ampicillin-sulbactam | 0.125–16 | 0.5 | 4 |
| Piperacillin-tazobactam | 0.125 = 64 | 8 | 64 |
| Moxifloxacin | 0.125–8 | 4 | 8 |
| Clindamycin | ≤0.06–64 | ≤0.06 | 4 |
| Metronidazole | 0.5–4 | 2 | 4 |
| Clostridioides difficile (10) | |||
| Tedizolid | 0.25–0.5 | 0.25 | 0.25 |
| Linezolid | 2–2 | 2 | 2 |
| Ampicillin-sulbactam | 1–4 | 2 | 2 |
| Piperacillin-tazobactam | 8–64 | 8 | 16 |
| Moxifloxacin | 1–16 | 1 | 2 |
| Clindamycin | 4–16 | 4 | 8 |
| Metronidazole | 0.25–0.5 | 0.5 | 0.5 |
| Clostridium clostridioforme group (10)d | |||
| Tedizolid | 0.125–0.2 | 0.25 | 0.25 |
| Linezolid | 2–16 | 4 | 16 |
| Ampicillin-sulbactam | 0.5–16 | 1 | 1 |
| Piperacillin-tazobactam | 0.125–>64 | 4 | 8 |
| Moxifloxacin | 4–16 | 8 | 16 |
| Clindamycin | 0.25–>32 | 1 | >32 |
| Metronidazole | ≤0.06–0.25 | ≤0.06 | 0.25 |
| Clostridium innocuum (10) | |||
| Tedizolid | 0.5–1 | 0.5 | 1 |
| Linezolid | 2–>16 | 4 | 4 |
| Ampicillin-sulbactam | 0.125–0.5 | 0.25 | 0.5 |
| Piperacillin-tazobactam | 0.5–2 | 1 | 2 |
| Moxifloxacin | 1–16 | 2 | 2 |
| Clindamycin | 0.25–>32 | 0.5 | >32 |
| Metronidazole | 0.5–0.5 | 0.5 | 0.5 |
| Clostridium perfringens (10) | |||
| Tedizolid | 0.125–0.25 | 0.125 | 0.25 |
| Linezolid | 1–16 | 2 | 2 |
| Ampicillin-sulbactam | ≤0.06–0.5 | 0.125 | 0.25 |
| Piperacillin-tazobactam | ≤0.03–1 | 0.25 | 1 |
| Moxifloxacin | 0.25–0.5 | 0.5 | 0.5 |
| Clindamycin | ≤0.06–>32 | 0.25 | 1 |
| Metronidazole | 0.25–2 | 0.5 | 1 |
| Clostridium ramosum (10) | |||
| Tedizolid | 0.5–0.5 | 0.5 | 0.5 |
| Linezolid | 8–16 | 8 | 8 |
| Ampicillin-sulbactam | ≤0.06–0.25 | 0.125 | 0.125 |
| Piperacillin-tazobactam | 0.06–0.5 | 0.06 | 0.25 |
| Moxifloxacin | 2–>16 | 2 | >16 |
| Clindamycin | 0.5–>32 | 2 | 4 |
| Metronidazole | 0.5–8 | 1 | 1 |
| Eggerthella lenta (10) | |||
| Tedizolid | 0.25–0.25 | 0.25 | 0.25 |
| Linezolid | 1–2 | 1 | 2 |
| Ampicillin-sulbactam | 1–2 | 1 | 2 |
| Piperacillin-tazobactam | 16–32 | 16 | 32 |
| Moxifloxacin | 0.125–>16 | 0.25 | 4 |
| Clindamycin | ≤0.06–32 | 0.125 | 16 |
| Metronidazole | 0.125–0.25 | 0.25 | 0.25 |
| Finegoldia magna (10) | |||
| Tedizolid | 0.125–0.25 | 0.25 | 0.25 |
| Linezolid | 1–2 | 2 | 2 |
| Ampicillin-sulbactam | ≤0.06–0.25 | 0.125 | 0.125 |
| Piperacillin-tazobactam | 0.06–0.125 | 0.06 | 0.125 |
| Moxifloxacin | 0.06–8 | 0.125 | 8 |
| Clindamycin | ≤0.06–>32 | 0.25 | 1 |
| Metronidazole | ≤0.06–0.5 | 0.25 | 0.5 |
| Parvimonas micra (10) | |||
| Tedizolid | ≤0.06 | ≤0.06 | ≤0.06 |
| Linezolid | 0.5–1 | 0.5 | 1 |
| Ampicillin-sulbactam | ≤0.06–≥0.06 | ≤0.06 | ≤0.06 |
| Piperacillin-tazobactam | ≤0.03 | ≤0.03 | ≤0.03 |
| Moxifloxacin | 0.25–2 | 0.25 | 2 |
| Clindamycin | ≤0.06–8 | ≤0.06 | 0.125 |
| Metronidazole | ≤0.06–0.125 | 0.125 | 0.125 |
| Peptostreptococcus anaerobius (10) | |||
| Tedizolid | ≤0.06–0.125 | ≤0.06 | 0.125 |
| Linezolid | 0.5–1 | 0.5 | 0.5 |
| Ampicillin-sulbactam | 0.125–8 | 0.125 | 0.25 |
| Piperacillin-tazobactam | 0.125–16 | 0.25 | 2 |
| Moxifloxacin | 0.125–8 | 0.125 | 8 |
| Clindamycin | ≤0.06–0.5 | 0.125 | 0.25 |
| Metronidazole | 0.25–1 | 0.5 | 0.5 |
Fusobacterium nucleatum (6 isolates), F. nucleatum subsp. animalis (2), F. nucleatum subsp. funduliforme (1), and F. nucleatum subsp. vincentii (1).
Porphyromonas asaccharolytica (4 isolates), Porphyromonas somerae (3), Porphyromonas species (3).
Veillonella species (7 isolates), Veillonella parvula (3).
Clostridium aldenense (4 isolates), Clostridium bolteae (3), Clostridium clostridioforme (2), and Clostridium hathewayi (1).
Against Parabacteroides distasonis, P. goldsteinii, P. merdae, and Veillonella spp., the tedizolid MIC90 was 2 μg/ml. Tedizolid was also active against a variety of Fusobacterium spp. (MIC90, ≤0.125 μg/ml) as well as Porphyromonas and Prevotella (MIC90, ≤1 μg/ml, except for P. bivia [MIC90, 4 μg/ml]).
Tedizolid is FDA approved for use in ABSSSIs and is active in vitro against clindamycin-, tetracycline-, levofloxacin-, daptomycin-, and tigecycline-resistant MRSA isolates (14–16).
Six days of tedizolid therapy was noninferior to 10 days of linezolid, including an early clinical response at 48 to 72 h (5). A study of 433 patients with diabetic foot infections (DFIs), a subset of ABSSSIs, showed that 83% were polymicrobial and 46% involved anaerobes with 2.7 anaerobic isolates per specimen (17). Gram-positive anaerobic cocci, especially Finegoldia magna (22.1%), accounted for 48.2% of the anaerobic isolates along with clostridia (4.4%). B. fragilis group species were the most common Gram-negative anaerobes (12.1%) isolated.
Zurenko et al. (18) found variable linezolid activity against 4 strains of B. fragilis group species (MIC range, 2 to 16 μg/ml) and 2 strains of Prevotella spp. (MIC, 1 μg/ml). Wybo et al. (19) found a linezolid MIC90 of 4 μg/ml for Bacteroides spp. and Parabacteroides spp., while fusobacteria had an MIC90 of 1 μg/ml. We previously noted that linezolid had activity against many anaerobic Gram-positive organisms, including F. magna, Peptostreptococcus anaerobius, Parvimonas micra (MIC90, 2 μg/ml; range, 2 to 4 μg/ml), and Peptoniphilus asaccharolyticus (MIC90, 1 μg/ml) (20).
Lee et al. (16) found that tedizolid had MICs 4- to 8-fold lower than those of linezolid. Similarly, Schaadt et al. (21) reported that tedizolid had up to 4-fold better activity than linezolid against Bacteroides spp. (MIC90 range, 2 to 8 μg/ml).
Previously (7), tedizolid’s in vitro activity against B. fragilis was found to be equivalent to (B. fragilis, B. ovatus, and B. vulgatus) to 2- to 4-fold greater (B. thetaiotaomicron) than linezolid’s. Our study confirms the improved comparative in vitro activity of tedizolid versus linezolid against a broader range of anaerobes with improved activity against Gram-negative anaerobes, including Fusobacterium spp., Prevotella spp., and Veillonella spp. Prevotella bivia had an MIC90 of 4 μg/ml, which was higher than that of other Prevotella spp. (MIC 90, 1 μg/ml). Schaadt et al. (21) found Prevotella to have an MIC90 of 4 μg/ml (range, ≤0.016 to 16 μg/ml). Veillonella spp., emerging pathogens which are not often tested, had a tedizolid MIC90 of 1 μg/ml.
A U.S. soldier in Afghanistan injured by an improvised explosive device (IED) developed B. fragilis sepsis and a leg infection resistant to all usual anaerobic agents but was treated and cured with a combination of linezolid and moxifloxacin (7). A case of B. fragilis sepsis resistant to metronidazole, beta-lactam–beta-lactamase inhibitors, and carbapenems was successfully treated with linezolid (8). These cases suggest a possible clinical use of tedizolid for infections with mixed Gram-positive aerobic and anaerobic bacteria, resistant infections with anaerobic bacteria, and/or infections in patients with multiple drug allergies.
The marrow toxicity of longer-duration oxazolidinone therapy has been of clinical concern; however, a recent retrospective study of patients who received tedizolid for a median duration of 28 days (interquartile range, 14 to 59 days), including patients with prosthetic joint infections and osteomyelitis, found it to be well tolerated and showed only an 8.7% discontinuation rate (22).
Tedizolid has good and underappreciated in vitro activity against a wide variety of anaerobes, including those typically isolated from ABSSSIs, such as diabetic foot infections. Clinicians might consider its use as a potential therapeutic partner in mixed infections where S. aureus and anaerobes are involved.
ACKNOWLEDGMENTS
This study was partially supported by an educational grant from the Bayer Corp., Leverkusen, Germany.
We thank Eliza Leoncio for technical help.
REFERENCES
- 1.Kisgen JJ, Mansour H, Unger NR, Childs LM. 2014. Tedizolid: a new oxazolidinone antimicrobial. Am J Health Syst Pharm 71:621–633. doi: 10.2146/ajhp130482. [DOI] [PubMed] [Google Scholar]
- 2.FDA. 2016. FDA tedizolid package insert. https://www.iodine.com/drug/sivextro/fda-package-insert#S1. Accessed 4 May 2020.
- 3.Stevens DL, Bisno AL, Chambers HF, Dellinger P, Goldstein EJC, Gorbach SL, Hirschmann JV, Kaplan S, Montoya JG, Wade JC. 2014. Practice guidelines for the diagnosis and management of skin and soft-tissue nfections; 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 59:e10–e52. doi: 10.1093/cid/ciu444. [DOI] [PubMed] [Google Scholar]
- 4.Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. 2014. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin structure infections (ESTABLISH-2): a randomized, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis 14:696–705. doi: 10.1016/S1473-3099(14)70737-6. [DOI] [PubMed] [Google Scholar]
- 5.Prokocimer P, De Anda C, Fang E, Mehra P, Das A. 2013. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA 309:559–569. doi: 10.1001/jama.2013.241. [DOI] [PubMed] [Google Scholar]
- 6.Goldstein EJC, Citron DM, Goldman PJ, Goldman RJ. 2008. National hospital survey of anaerobic culture and susceptibility methods III. Anaerobe 14:68–72. doi: 10.1016/j.anaerobe.2008.01.001. [DOI] [PubMed] [Google Scholar]
- 7.Goldstein EJC, Citron DM, Tyrrell KL, Leoncio ES, Merriam CV. 2017. The underappreciated in vitro activity of tedizolid against Bacteroides fragilis species, including strains resistant to carbapenems. Anaerobe 43:1–3. doi: 10.1016/j.anaerobe.2016.09.008. [DOI] [PubMed] [Google Scholar]
- 8.Sherwood JE, Fraser S, Citron D, Wexler H, Blakely G, Jobling K, Patrick S. 2011. Multi-drug resistant Bacteroides fragilis recovered from blood and severe leg wounds caused by an improvised explosive device (IED) in Afghanistan. Anaerobe 17:152–155. doi: 10.1016/j.anaerobe.2011.02.007. [DOI] [PubMed] [Google Scholar]
- 9.Wareham DW, Wilks M, Ahmed D, Brazier JS, Millar M. 2005. Anaerobic sepsis due to multi-resistant Bacteroides fragilis: cure and clinical response with linezolid therapy. Clin Infect Dis 40:e67-68–e68. doi: 10.1086/428623. [DOI] [PubMed] [Google Scholar]
- 10.Jousimies-Somer HR, Summanen P, Citron DM, Baron EJ, Wexler HM, Finegold SM. 2002. Wadsworth-KTL anaerobic bacteriology manual. Star Publishing, Belmont, CA. [Google Scholar]
- 11.Versalovic J, Carroll KC, Jorgensen JG, Funke G, Landry ML, Warnock DW (ed). 2011. Manual of clinical microbiology, 10th ed, vol 2 ASM Press, Washington, DC. [Google Scholar]
- 12.CLSI. 2018. Methods for antimicrobial susceptibility of anaerobic bacteria. Approved standard, 9th ed CLSI document M11-A9 CLSI, Wayne, PA. [Google Scholar]
- 13.CLSI. 2020. Performance standards for antimicrobial susceptibility testing, 30th ed CLSI supplement M100 CLSI, Wayne, PA. [Google Scholar]
- 14.Moellering RC. 2014. Tedizolid: a novel oxazolidinone for Gram-positive infections. Clin Infect Dis 58(Suppl 1):S1–S3. doi: 10.1093/cid/cit658. [DOI] [PubMed] [Google Scholar]
- 15.Thomson KS, Goering RV. 2013. Activity of tedizolid (TR-700) against well-characterized methicillin-resistant Staphylococcus aureus strains of diverse epidemiological origins. Antimicrob Agents Chemother 57:2892–2895. doi: 10.1128/AAC.00274-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Lee Y, Hong SK, Choi S, Im W, Yong D, Lee K. 2015. In vitro activity of tedizolid against gram-positive bacteria in patients with skin and skin structure infections and hospital-acquired pneumonia: a Korean multicenter study. Ann Lab Med 35:523–530. doi: 10.3343/alm.2015.35.5.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Citron DM, Goldstein EJC, Merriam CV, Lipsky B, Abramson MA. 2007. Bacteriology of moderate to severe diabetic foot infections and in vitro activity of antimicrobial agents. J Clin Microbiol 45:2819–2828. doi: 10.1128/JCM.00551-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Zurenko GE, Yagi BH, Schaadt RD, Allison JW, Kilburn JO, Glickman SE, Hutchinson DK, Barbachyn MR, Brickner SJ. 1996. In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob Agents Chemother 40:839–845. doi: 10.1128/AAC.40.4.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Wybo I, Van den Bossche D, Soetens O, Vekens E, Vandoorslaer K, Claeys G, Glupczynski Y, Ieven M, Melin P, Nonhoff C, Rodriguez-Villalobos H, Verhaegen J, Piérard D. 2014. Fourth Belgian multicentre survey of antibiotic susceptibility of anaerobic bacteria. J Antimicrob Chemother 69:155–161. doi: 10.1093/jac/dkt344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Citron DM, Merriam CV, Tyrrell KL, Warren YA, Fernandez H, Goldstein EJC. 2003. Comparative in vitro activity of ramoplanin, teichoplanin, vancomycin, linezolid, bacitracin, and four other antimicrobials against intestinal anaerobic bacteria. 2003. Antimicrob Agents Chemother 47:2334–2338. doi: 10.1128/AAC.47.7.2334-2338.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Schaadt R, Sweeney D, Shinabarger D, Zurenko G. 2009. In vitro activity of TR-700, the active ingredient of the antibacterial prodrug TR-701, a novel oxazolidinone antibacterial agent. Antimicrob Agents Chemother 53:3236–3239. doi: 10.1128/AAC.00228-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Mensa Vendrell M, Tasias Pitarch M, Salavert Lletí M, Calabuig Muñoz E, Morata Ruiz L, Castells Lao G, López Suñé E, Mensa Pueyo J, Oltra Sempere MR, Pedro-Botet Montoya ML, Isernia V, Reynaga Sosa EA, Moreno Nuñez L, Pasquau Liaño J, Sequera Arquelladas S, Yuste Ara JR, Soriano Viladomiu A. 2020. Safety and tolerability of more than 6 days of tedizolid treatment. Antimicrob Agents Chemother 64:e00356-20. doi: 10.1128/AAC.00356-20. [DOI] [PMC free article] [PubMed] [Google Scholar]