Contezolid, a new oxazolidinone antibacterial agent currently in development for the treatment of skin and skin structure infections, was susceptibility tested against Gram-positive clinical isolates (n = 1,211). Contezolid demonstrated potent activity against Staphylococcus aureus (MIC50/90, 0.5/1 mg/liter), coagulase-negative Staphylococcus (MIC50/90, 0.25/0.5 mg/liter), Enterococcus spp.
KEYWORDS: Staphylococcus aureus, MRSA, Enterococcus, streptococci, Streptococcus spp., antibiotics
ABSTRACT
Contezolid, a new oxazolidinone antibacterial agent currently in development for the treatment of skin and skin structure infections, was susceptibility tested against Gram-positive clinical isolates (n = 1,211). Contezolid demonstrated potent activity against Staphylococcus aureus (MIC50/90, 0.5/1 mg/liter), coagulase-negative Staphylococcus (MIC50/90, 0.25/0.5 mg/liter), Enterococcus spp. (MIC50/90, 0.5/1 mg/liter), and streptococci (MIC50/90, 1/1 mg/liter). Moreover, methicillin-resistant S. aureus and vancomycin-resistant Enterococcus faecium isolates were all inhibited by contezolid at ≤1 mg/liter. These results support the clinical development of contezolid.
TEXT
Antimicrobial resistance in Gram-positive pathogens remains a significant health challenge across the world. Staphylococcus aureus and Enterococcus spp. are among the most difficult-to-treat Gram-positive pathogens commonly isolated as causes of serious health care-associated infections, such as bloodstream infections, pneumonia, sepsis, and complicated skin and soft tissue infections (1, 2). These pathogens have demonstrated the formidable ability to acquire resistance to most clinically relevant antimicrobial agents. Additionally, Streptococcus pneumoniae, beta-hemolytic streptococci (BHS), and Viridans group streptococci (VGS) are important pathogens frequently recovered from community-acquired infections, which makes their spread even more difficult to identify and contain. S. pneumoniae is the most common cause of community-acquired bacterial pneumonia worldwide (1, 3). Furthermore, BHS and VGS may cause serious infections, such as complicated skin and soft tissue infections, necrotizing fasciitis, infective endocarditis, and streptococcal toxic shock syndrome (3).
The high prevalence of methicillin-resistant S. aureus (MRSA), penicillin-resistant S. pneumoniae, and vancomycin-resistant enterococci (VRE) in many regions narrows the selection of appropriate empirical and definitive antimicrobial treatments (4–6). Rapid introduction of appropriate antimicrobial therapy is crucial to improve patient outcomes, but very few agents remain active against these organisms in some regions. As a result, several studies have demonstrated high mortality rates attributable to the severe infections caused by these MDR organisms (7, 8).
Contezolid (MRX-I) is a new ortho-fluorophenyl dihydropyridine oxazolidinone that has shown potent in vitro antibacterial activity against resistant Gram-positive pathogens, including MRSA, penicillin-resistant S. pneumoniae, and VRE isolates (9). Contezolid is in development for the treatment of acute bacterial skin and skin structure infections (10). The objective of this study was to evaluate the in vitro activity and spectrum of contezolid against a large collection of Gram-positive clinical isolates from U.S. and European medical centers.
A total of 1,211 Gram-positive organisms were selected randomly from bacterial isolates collected in the United States and Europe in 2015 through the SENTRY Antimicrobial Surveillance Program. The bacterial collection included 606 S. aureus (398 methicillin-susceptible [MSSA] and 208 MRSA strains), 100 coagulase-negative staphylococci (CoNS, 35 methicillin-susceptible and 65 methicillin-resistant isolates), 52 Enterococcus faecalis, 51 Enterococcus faecium (25 vancomycin-susceptible and 26 vancomycin-resistant strains), 201 S. pneumoniae, 102 BHS, and 99 VGS isolates.
Only one bacterial isolate per infection episode determined to be significant by local criteria as the reported probable cause of an infection was included in this investigation. Species identification was confirmed when necessary by matrix-assisted laser desorption ionization–time of flight mass spectrometry using the Bruker Daltonics MALDI Biotyper (Billerica, MA) by following the manufacturer’s instructions.
Antimicrobial susceptibility testing was performed by reference broth microdilution methods conducted according to CLSI procedures (11). Broth microdilution frozen-form panels were produced by JMI Laboratories (North Liberty, IA). These panels included two media types: cation-adjusted Mueller-Hinton broth (CA-MHB) and CA-MHB supplemented with 2.5% to 5% lysed horse blood. Contezolid powder was provided by MicuRx Pharmaceuticals, Inc. (Hayward, CA). Concurrent quality control (QC) testing was performed to ensure proper test conditions and procedures. QC strains included S. aureus ATCC 29213, E. faecalis ATCC 29212, and S. pneumoniae ATCC 49619. CLSI and EUCAST susceptibility interpretive criteria were used to determine susceptibility/resistance rates for comparator agents (12, 13).
Contezolid demonstrated potent in vitro activity against S. aureus isolates overall (MIC50/90, 0.5/1 mg/liter) and inhibited all isolates at ≤2 mg/liter, which is below the linezolid susceptibility breakpoint for staphylococci (≤4 mg/liter, CLSI and EUCAST criteria). Contezolid activity against MRSA strains (MIC50/90, 0.5/1 mg/liter; highest MIC, 1 mg/liter) was equivalent to that observed against MSSA strains (MIC50/90, 0.5/1 mg/liter; highest MIC, 2 mg/liter) (Table 1). In addition, the activity of contezolid was similar to the activity of linezolid (MIC50/90, 1/1 mg/liter; 100% susceptible) against all S. aureus isolates (Fig. 1). Notably, the only comparator agents active against >90% of S. aureus isolates were doxycycline (MIC50/90, 0.06/0.12 mg/liter; 99.2% and 97.2% susceptible per CLSI and EUCAST, respectively), trimethoprim-sulfamethoxazole (MIC50/90, ≤0.12/≤0.12 mg/liter; 99.2% susceptible), and vancomycin (MIC50/90, 0.5/1 mg/liter; 100.0% susceptible) (Table 2). Susceptibilities of S. aureus isolates to erythromycin (MIC50/90, 0.5/>8 mg/liter), levofloxacin (MIC50/90, 0.25/>8 mg/liter), and clindamycin (MIC50/90, ≤0.06/>4 mg/liter) were 50.3%, 69.1%, and 87.0%, respectively, by CLSI criteria (Table 2). The most potent agents against CoNS were contezolid (MIC50/90, 0.25/0.5 mg/liter), linezolid (MIC50/90, 0.5/1 mg/liter; 100% susceptible), doxycycline (MIC50/90, 0.12/0.5 mg/liter; 100% and 96.0% susceptible per CLSI and EUCAST, respectively), and vancomycin (MIC50/90, 1/2 mg/liter; 100% susceptible) (Table 2).
TABLE 1.
Summary of contezolid (MRX-I) and linezolid activity when tested against 1,211 Gram-positive clinical isolates
| Organism/antimicrobial agent | No. of isolates (cumulative %) inhibited at MIC (mg/liter) of: |
MIC (mg/liter) |
|||||
|---|---|---|---|---|---|---|---|
| 0.12 | 0.25 | 0.5 | 1 | 2 | MIC50 | MIC90 | |
| S. aureus (n = 606) | |||||||
| Contezolid | 2 (0.3) | 54 (9.2) | 406 (76.2) | 142 (99.7) | 2 (100.0) | 0.5 | 1 |
| Linezolid | 1 (0.2) | 10 (1.8) | 270 (46.4) | 322 (99.5) | 3 (100.0) | 1 | 1 |
| MSSA (n = 398) | |||||||
| Contezolid | 2 (0.5) | 21 (5.8) | 260 (71.1) | 113 (99.5) | 2 (100.0) | 0.5 | 1 |
| Linezolid | 1 (0.3) | 4 (1.3) | 152 (39.4) | 238 (99.2) | 3 (100.0) | 1 | 1 |
| MRSA (n = 208) | |||||||
| Contezolid | 33 (15.9) | 146 (86.1) | 29 (100.0) | 0.5 | 1 | ||
| Linezolid | 6 (2.9) | 118 (59.6) | 84 (100.0) | 0.5 | 1 | ||
| CoNS (n = 100) | |||||||
| Contezolid | 12 (12.0) | 53 (65.0) | 32 (97.0) | 3 (100.0) | 0.25 | 0.5 | |
| Linezolid | 4 (4.0) | 39 (43.0) | 44 (87.0) | 13 (100.0) | 0.5 | 1 | |
| E. faecalis (n = 52) | |||||||
| Contezolid | 4 (7.7) | 29 (63.5) | 15 (92.3) | 4 (100.0) | 0.5 | 1 | |
| Linezolid | 4 (7.7) | 27 (59.6) | 16 (90.4) | 5 (100.0) | 0.5 | 1 | |
| E. faecium (n = 51) | |||||||
| Contezolid | 2 (3.9) | 30 (62.7) | 17 (96.1) | 2 (100.0) | 0.5 | 1 | |
| Linezolid | 2 (3.9) | 28 (58.8) | 19 (96.1) | 2 (100.0) | 0.5 | 1 | |
| Vancomycin susceptible (n = 25) | |||||||
| Contezolid | 1 (4.0) | 12 (52.0) | 10 (92.0) | 2 (100.0) | 0.5 | 1 | |
| Linezolid | 1 (4.0) | 11 (48.0) | 11 (92.0) | 2 (100.0) | 1 | 1 | |
| Vancomycin resistant (n = 26) | |||||||
| Contezolid | 1 (3.8) | 18 (73.1) | 7 (100.0) | 0.5 | 1 | ||
| Linezolid | 1 (3.8) | 17 (69.2) | 8 (100.0) | 0.5 | 1 | ||
| S. pneumoniae (n = 201) | |||||||
| Contezolid | 2 (1.0) | 35 (18.4) | 160 (98.0) | 4 (100.0) | 1 | 1 | |
| Linezolid | 2 (1.0) | 34 (17.9) | 161 (98.0) | 4 (100.0) | 1 | 1 | |
| Beta-hemolytic streptococci (n = 102) | |||||||
| Contezolid | 4 (3.9) | 95 (97.1) | 3 (100.0) | 1 | 1 | ||
| Linezolid | 3 (2.9) | 97 (98.0) | 2 (100.0) | 1 | 1 | ||
| Viridans group streptococci (n = 99) | |||||||
| Contezolid | 1 (1.0) | 4 (5.1) | 29 (34.3) | 64 (99.0) | 1 (100.0) | 1 | 1 |
| Linezolid | 5 (5.1) | 28 (33.3) | 65 (99.0) | 1 (100.0) | 1 | 1 | |
FIG 1.
Contezolid (MRX-I) and linezolid activity when tested against Staphylococcus aureus clinical isolates.
TABLE 2.
Activity of contezolid (MRX-1) and comparator antimicrobial agents when tested against Gram-positive organisms from U.S. and European medical centers
| Organism/antimicrobial agent | MIC (mg/liter) |
Susceptibility (%) according toa
: |
||||
|---|---|---|---|---|---|---|
| CLSI |
EUCAST |
|||||
| MIC50 | MIC90 | S | R | S | R | |
| S. aureus (n = 606) | ||||||
| Contezolid | 0.5 | 1 | –c | – | – | – |
| Linezolid | 1 | 1 | 100.0 | 0.0 | 100.0 | 0.0 |
| Oxacillin | 0.5 | >4 | 65.7 | 34.3 | 65.7 | 34.3 |
| Doxycycline | 0.06 | 0.12 | 99.2 | 0.3 | 97.2 | 2.1 |
| Erythromycin | 0.5 | >8 | 50.3 | 45.9 | 52.5 | 47.4 |
| Clindamycin | ≤0.06 | >4 | 87.0 | 12.9 | 86.8 | 13.0 |
| Levofloxacin | 0.25 | >8 | 69.1 | 30.9 | 69.1 | 30.9 |
| TMP-SMXb | ≤0.12 | ≤0.12 | 99.2 | 0.8 | 99.2 | 0.5 |
| Vancomycin | 0.5 | 1 | 100.0 | 0.0 | 100.0 | 0.0 |
| MRSA (n = 208) | ||||||
| Contezolid | 0.5 | 1 | – | – | – | – |
| Linezolid | 0.5 | 1 | 100.0 | 0.0 | 100.0 | 0.0 |
| Doxycycline | 0.06 | 0.25 | 98.6 | 0.5 | 96.2 | 2.9 |
| Erythromycin | >8 | >8 | 11.1 | 87.5 | 11.5 | 88.5 |
| Clindamycin | ≤0.06 | >4 | 66.8 | 33.2 | 66.8 | 33.2 |
| Levofloxacin | 8 | >8 | 20.7 | 79.3 | 20.7 | 79.3 |
| TMP-SMX | ≤0.12 | ≤0.12 | 98.1 | 1.9 | 98.1 | 1.0 |
| Vancomycin | 0.5 | 1 | 100.0 | 0.0 | 100.0 | 0.0 |
| CoNS (n = 100) | ||||||
| Contezolid | 0.25 | 0.5 | – | – | – | – |
| Linezolid | 0.5 | 1 | 100.0 | 0.0 | 100.0 | 0.0 |
| Oxacillin | 4 | >4 | 35.0 | 65.0 | 35.0 | 65.0 |
| Doxycycline | 0.12 | 0.5 | 100.0 | 0.0 | 96.0 | 1.0 |
| Erythromycin | >8 | >8 | 43.0 | 56.0 | 44.0 | 56.0 |
| Clindamycin | ≤0.06 | >4 | 71.0 | 27.0 | 70.0 | 29.0 |
| Levofloxacin | 0.5 | >8 | 54.0 | 40.0 | 54.0 | 40.0 |
| TMP-SMX | ≤0.12 | >4 | 69.0 | 31.0 | 69.0 | 18.0 |
| Vancomycin | 1 | 2 | 100.0 | 0.0 | 100.0 | 0.0 |
| E. faecalis (n = 52) | ||||||
| Contezolid | 0.5 | 1 | – | – | – | – |
| Linezolid | 0.5 | 1 | 100.0 | 0.0 | 100.0 | 0.0 |
| Levofloxacin | 1 | >8 | 75.0 | 25.0 | 75.0 | 25.0d |
| Vancomycin | 1 | 2 | 98.1 | 1.9 | 98.1 | 1.9 |
| E. faecium (n = 51) | ||||||
| Contezolid | 0.5 | 1 | – | – | – | – |
| Linezolid | 0.5 | 1 | 100.0 | 0.0 | 100.0 | 0.0 |
| Levofloxacin | >8 | >8 | 5.9 | 92.2 | 7.8 | 92.2d |
| Vancomycin | >16 | >16 | 49.0 | 51.0 | 49.0 | 51.0 |
| Vancomycin resistant (n = 26) | ||||||
| Contezolid | 0.5 | 1 | – | – | – | – |
| Linezolid | 0.5 | 1 | 100.0 | 0.0 | 100.0 | 0.0 |
| Levofloxacin | >8 | >8 | 0.0 | 100.0 | 0.0 | 100.0d |
| Vancomycin | >16 | >16 | 0.0 | 100.0 | 0.0 | 100.0 |
| S. pneumoniae (n = 201) | ||||||
| Contezolid | 1 | 1 | – | – | – | – |
| Linezolid | 1 | 1 | 100.0 | – | 100.0 | 0.0 |
| Ceftriaxone | 0.03 | 1 | 90.0 | 2.5e | 90.0 | 0.5 |
| 97.5 | 0.5f | – | – | |||
| Erythromycin | 0.12 | >8 | 66.2 | 33.3 | 66.2 | 33.3 |
| Doxycycline | 0.12 | 8 | 76.1 | 23.4 | 77.1 | 22.4 |
| Clindamycin | ≤0.06 | >4 | 83.1 | 16.4 | 83.6 | 16.4 |
| Levofloxacin | 1 | 1 | 100.0 | 0.0 | 100.0 | 0.0 |
| Penicillin | ≤0.06 | 2 | 95.5 | 0.0g | 63.5 | 4.5f |
| TMP-SMX | 0.25 | >4 | 69.2 | 16.4 | 75.6 | 16.4 |
| Vancomycin | 0.25 | 0.25 | 100.0 | – | 100.0 | 0.0 |
| Beta-hemolytic streptococci (n = 102) | ||||||
| Contezolid | 1 | 1 | – | – | – | – |
| Linezolid | 1 | 1 | 100.0 | – | – | – |
| Ceftriaxone | 0.03 | 0.06 | 100.0 | – | 100.0 | 0.0 |
| Erythromycin | 0.12 | >8 | 72.5 | 27.5 | 72.5 | 27.5 |
| Doxycycline | 0.12 | 16 | – | – | 57.8 | 42.2 |
| Clindamycin | ≤0.06 | >4 | 82.4 | 17.6 | 82.4 | 17.6 |
| Levofloxacin | 0.5 | 2 | 98.0 | 0.0 | 88.2 | 2.0 |
| TMP-SMX | ≤0.12 | ≤0.12 | – | – | 99.0 | 1.0 |
| Vancomycin | 0.25 | 0.5 | 100.0 | – | 100.0 | 0.0 |
| Viridans group streptococci (n = 99) | ||||||
| Contezolid | 1 | 1 | – | – | – | – |
| Linezolid | 1 | 1 | 100.0 | – | – | – |
| Ceftriaxone | 0.12 | 0.5 | 94.9 | 4.0 | 93.9 | 6.1 |
| Erythromycin | 2 | >8 | 47.5 | 52.5 | – | – |
| Clindamycin | ≤0.06 | >4 | 84.8 | 13.1 | 86.9 | 13.1 |
| Levofloxacin | 1 | 2 | 93.9 | 4.0 | – | – |
| Vancomycin | 0.5 | 0.5 | 100.0 | – | 100.0 | 0.0 |
TMP-SMX, trimethoprim-sulfamethoxazole.
–, no breakpoint has been established.
Uncomplicated urinary tract infections only.
Using meningitis breakpoints.
Using nonmeningitis breakpoints.
Using parenteral, nonmeningitis breakpoints.
All Enterococcus spp. isolates were inhibited by contezolid at ≤2 mg/liter (susceptibility breakpoint for linezolid per CLSI; EUCAST susceptibility breakpoint, ≤4 mg/liter). Contezolid displayed equivalent activity against E. faecalis (MIC50/90, 0.5/1 mg/liter) and E. faecium (MIC50/90, 0.5/1 mg/liter) isolates (Table 1). Moreover, contezolid remained active against the vancomycin-resistant E. faecium subset (MIC50/90, 0.5/1 mg/liter). Contezolid and linezolid showed similar MIC distributions against E. faecalis and E. faecium isolates, regardless of the vancomycin phenotype (Table 1).
All S. pneumoniae isolates were susceptible to linezolid (MIC50/90, 1/1 mg/liter), levofloxacin (MIC50/90, 1/1 mg/liter), and vancomycin (MIC50/90, 0.25/0.25 mg/liter); likewise, 97.5% and 90.0% were susceptible to ceftriaxone (MIC50/90, 0.03/1 mg/liter) according to CLSI and EUCAST breakpoints, respectively (Table 2). Penicillin-nonsusceptible MIC values were obtained in 4.5% and 36.8% of S. pneumoniae isolates when applying CLSI (parenteral, nonmeningitis) and EUCAST (nonmeningitis) breakpoints, respectively. Contezolid (MIC50/90, 1/1 mg/liter) inhibited all S. pneumoniae isolates at the linezolid susceptibility breakpoint (≤2 mg/liter, CLSI and EUCAST criteria) (Table 1). In addition, all BHS and VGS isolates displayed susceptibilities of >90% to linezolid, ceftriaxone, and vancomycin per CLSI and EUCAST criteria (Table 2), and contezolid showed good activity against these organisms (MIC50/90, 1/1 mg/liter). The highest contezolid MIC value was 2 mg/liter for both VGS and BHS, which is the current linezolid susceptibility breakpoint per CLSI criteria. Levofloxacin showed coverage of 98.0% and 93.9% of BHS and VGS isolates, respectively, per CLSI criteria, but only 88.2% of BHS isolates were susceptible to levofloxacin per EUCAST criteria. Clindamycin and erythromycin inhibited <87% of BHS and VGS isolates per CLSI and EUCAST criteria (Table 2).
Invasive infections frequently are caused by Gram-positive bacteria in community and health care settings (14). Whereas surveillance studies have pointed to a reduction in the proportion of important resistant Gram-positive pathogens in the past decade, S. aureus and Enterococcus spp. are still among the five most common causes of bacteremia worldwide (4, 14). Furthermore, MRSA, VRE, and penicillin-resistant S. pneumoniae are on the list of pathogens considered serious threats by CDC. These bacterial species frequently challenge empirical and targeted antimicrobial therapy by forcing clinicians to seek alternative treatments for patients with serious infections (1, 2).
Oxazolidinones are a class of antimicrobial agents with broad activity against Gram-positive pathogens, differentiated from many other antibacterials by exceedingly low bacterial resistance, as illustrated by the global surveillance data for linezolid (2, 4), which are consistent with the MIC results presented in this article. Linezolid was the first oxazolidinone approved for clinical use by the U.S. Food and Drug Administration (FDA) in 2000; a second compound from this promising class of antimicrobial agents, tedizolid, was approved in 2014 (15, 16). The development of oxazolidinones is challenged by the balance between their antimicrobial activity and safety profile (17). Oxazolidinones inhibit the elongation of the polypeptide chain during protein synthesis by binding to the A site of bacterial ribosomes. Their mechanism of action is unique, and no cross-resistance between oxazolidinones and other protein synthesis inhibitors has been reported (18). However, safety concerns impaired the clinical development of many oxazolidinone compounds because of the homology between the 23S ribosomal target and the closely related mitochondrial protein synthesis machinery in mammals, resulting in adverse effects such as myelosuppression (19). Contezolid is a new representative of the oxazolidinone class in clinical development and is differentiated from linezolid and tedizolid by adjustments to the B-ring, C-ring, and C-5 domain that markedly reduce the potential for myelosuppression and monoamine oxidase inhibition and seem to improve contezolid activity (19).
Notably, contezolid displayed potent activity (MIC50/90, 0.25 to 1/0.5 to 1 mg/liter) against this entire collection of Gram-positive clinical isolates (>1,200 isolates) from the United States and Europe. Contezolid activity was similar to or slightly higher (staphylococci showed a single dilution lower MIC50 value, not significantly different) than that observed by linezolid. These results are consistent with previous in vitro and in vivo contezolid data reported for a smaller collection of staphylococci, enterococci, and streptococci isolates and infection models (9). Moreover, the contezolid activity against resistant subsets (MRSA MIC50/90, 0.5/1 mg/liter; vancomycin-resistant E. faecium MIC50/90, 0.5/1 mg/liter) was equivalent to that observed for contezolid against MSSA (MIC50/90, 0.5/1 mg/liter) and vancomycin-susceptible E. faecium subsets (MIC50/90, 0.5/1 mg/liter). No linezolid-resistant isolate was observed in this randomly selected collection of Gram-positive cocci. Oxazolidinone resistance rarely occurs in clinical isolates, and surveillance studies showed that after nearly 20 years of clinical use, linezolid resistance rates are as low as 0.1%, 0.0%, 0.5%, and 0.0% for S. aureus, E. faecalis, E. faecium, and streptococcal isolates, respectively (2, 4, 20). Although uncommon, ∼1.5% of clinical isolates of methicillin-resistant CoNS may exhibit resistance to linezolid (MIC, ≥8 μg/ml), mainly among Staphylococcus epidermidis isolates (21). Of concern, cross-resistance between oxazolidinone compounds, linezolid, and tedizolid was observed previously in Staphylococcus spp. and Enterococcus spp. isolates exhibiting mutations in 23S rRNA (22, 23). The current study did not include any isolate with acquired resistance to linezolid and/or tedizolid; however, it is important to note that decreased susceptibility to contezolid was observed in MRSA and MSSA mutants obtained by in vitro serial passage experiments (24). In addition to mutations on 23S rRNA and ribosomal protein-encoding genes, linezolid resistance can develop after acquisition of the resistance genes optrA and poxtA and variants of the cfr gene. Further studies are required to evaluate the activity of contezolid against linezolid-resistant isolates harboring these resistance mechanisms.
Recently, the results of a phase 2 study comparing contezolid acefosamil (MRX-4), the prodrug of the active antimicrobial metabolite contezolid (MRX-I), with linezolid for the treatment of acute bacterial skin and skin structure infections were released (25). MRSA was the most commonly identified pathogen, and efficacy outcomes in patients with MRSA infections were similar between the two study arms. Overall, the safety and efficacy of contezolid acefosamil (intravenous and oral formulations) for 10 to 14 days of therapy were comparable to those results for linezolid (25). In addition, contezolid was demonstrated to be noninferior to linezolid for the treatment of complicated skin and skin structure infections in a phase 3 study conducted in China (26).
In summary, contezolid demonstrated potent in vitro activity against a large collection of Gram-positive clinical isolates from U.S. and European medical centers. The results of this investigation indicate that contezolid may be a valuable option to treat S. aureus, CoNS, Enterococcus spp., and Streptococcus spp. infections, including those infections caused by MRSA and VRE. Furthermore, contezolid may exhibit increased potency against certain clinically important pathogens compared with linezolid. These findings support the clinical development of contezolid to treat infections caused by Gram-positive organisms.
ACKNOWLEDGMENTS
We thank all participants of the SENTRY Antimicrobial Surveillance Program for providing bacterial isolates.
This study was supported by MicuRx Pharmaceuticals, Inc. (Hayward, CA).
MicuRx was involved in the design and decision to present these results, and JMI Laboratories received compensation fees for services in relation to preparing the manuscript. MicuRx had no involvement in the collection, analysis, or interpretation of data.
JMI Laboratories was contracted to perform services in 2019 for Achaogen, Inc., Albany College of Pharmacy and Health Sciences, Allecra Therapeutics, Allergan, AmpliPhi Biosciences Corp., Amicrobe Advanced Biomaterials, Amplyx, Antabio, American Proficiency Institute, Arietis Corp., Arixa Pharmaceuticals, Inc., Astellas Pharma, Inc., Athelas, Basilea Pharmaceutica Ltd., Bayer AG, Becton, Dickinson and Company, bioMérieux SA, Boston Pharmaceuticals, Bugworks Research, Inc., CEM-102 Pharmaceuticals, Cepheid, Cidara Therapeutics, Inc., CorMedix, Inc., DePuy Synthes, Destiny Pharma, Discuva Ltd., Falk Pharma GmbH, Emery Pharma, Entasis Therapeutics, Eurofarma Laboratorios SA, FDA, Fox Chase Chemical Diversity Center, Inc., Gateway Pharmaceutical LLC, GenePOC, Inc., Geom Therapeutics, Inc., GlaxoSmithKline plc, Harvard University, Helperby, HiMedia Laboratories, F. Hoffmann-La Roche Ltd., ICON plc, Idorsia Pharmaceuticals Ltd., Iterum Therapeutics plc, Laboratory Specialists, Inc., Melinta Therapeutics, Inc., Merck & Co., Inc., Microchem Laboratory, Micromyx, MicuRx Pharmaceuticals, Inc., Mutabilis Co., Nabriva Therapeutics plc, NAEJA-RGM, Novartis AG, Oxoid Ltd., Paratek Pharmaceuticals, Inc., Pfizer, Inc., Polyphor Ltd., Pharmaceutical Product Development, LLC, Prokaryotics, Inc., Qpex Biopharma, Inc., Roivant Sciences, Ltd., Safeguard Biosystems, Scynexis, Inc., SeLux Diagnostics, Inc., Shionogi and Co., Ltd., SinSa Labs, Spero Therapeutics, Summit Pharmaceuticals International Corp., Synlogic, T2 Biosystems, Inc., Taisho Pharmaceutical Co., Ltd., TenNor Therapeutics Ltd., Tetraphase Pharmaceuticals, Theravance Biopharma, University of Colorado, University of Southern California-San Diego, University of North Texas Health Science Center, VenatoRx Pharmaceuticals, Inc., Viosera Therapeutics, Vyome Therapeutics, Inc., Wockhardt, Yukon Pharmaceuticals, Inc., Zai Lab, Zavante Therapeutics, Inc.
We have no speakers’ bureaus or stock options to declare.
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