scholarly journals In Vitro Activity of Imipenem-Relebactam against Clinical Isolates of Gram-Negative Bacilli Isolated in Hospital Laboratories in the United States as Part of the SMART 2016 Program

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
James A. Karlowsky ◽  
Sibylle H. Lob ◽  
Krystyna M. Kazmierczak ◽  
Katherine Young ◽  
Mary R. Motyl ◽  
...  
Keyword(s):  
The United States ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Content Type ◽  
Microdilution Method ◽  
Smart Study ◽  
Fixed Concentration ◽  
Broth Microdilution Method ◽  
Further Development

ABSTRACT Relebactam is a non-β-lactam, bicyclic diazabicyclooctane β-lactamase inhibitor of class A and class C β-lactamases, including Klebsiella pneumoniae carbapenemases (KPCs). It is in phase 3 clinical development in combination with imipenem/cilastatin. The in vitro activities of imipenem-relebactam, imipenem, and comparators were determined using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method for isolates of Enterobacteriaceae ( n = 3,419) and Pseudomonas aeruginosa ( n = 896) collected in 2016 by 21 U.S. hospital laboratories participating in the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Relebactam was tested at a fixed concentration of 4 μg/ml. Imipenem-relebactam MICs were interpreted using CLSI breakpoints for imipenem. Rates of susceptibility to imipenem-relebactam and imipenem for non- Proteeae Enterobacteriaceae ( n = 3,143) and P. aeruginosa were 99.1% (3,115/3,143) and 95.9% (3,013/3,143) and were 94.4% (846/896) and 74.7% (669/896), respectively. Relebactam restored imipenem susceptibility to 78.5% (102/130) of imipenem-nonsusceptible non- Proteeae Enterobacteriaceae and to 78.0% (177/227) of imipenem-nonsusceptible P. aeruginosa isolates. Susceptibility to imipenem-relebactam was 98.2% (444/452) and 82.2% (217/264) for multidrug-resistant (MDR) non- Proteeae Enterobacteriaceae and MDR P. aeruginosa , respectively. Given the ability of relebactam to restore susceptibility to imipenem in nonsusceptible isolates of both non- Proteeae Enterobacteriaceae and P. aeruginosa and to demonstrate potent activity against current MDR isolates of both non- Proteeae Enterobacteriaceae and P. aeruginosa , further development of imipenem-relebactam appears warranted.

scholarly journals Arbekacin Activity against Contemporary Clinical Bacteria Isolated from Patients Hospitalized with Pneumonia

2015 ◽  
Vol 59 (6) ◽  
pp. 3263-3270 ◽  
Author(s):  
Helio S. Sader ◽  
Paul R. Rhomberg ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
The United States ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Content Type ◽  
Microdilution Method ◽  
Medical Centers ◽  
Broth Microdilution Method ◽  
Mrsa Strains ◽  
Infection Types

ABSTRACTArbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States. We evaluated the occurrence of organisms isolated from pneumonias in U.S. hospitalized patients (PHP), including ventilator-associated pneumonia (VAP), and thein vitroactivity of arbekacin. Organism frequency was evaluated from a collection of 2,203 bacterial isolates (339 from VAP) consecutively collected from 25 medical centers in 2012 through the SENTRY Antimicrobial Surveillance Program. Arbekacin activity was tested against 904 isolates from PHP collected in 2012 from 62 U.S. medical centers and 303 multidrug-resistant (MDR) organisms collected worldwide in 2009 and 2010 from various infection types. Susceptibility to arbekacin and comparator agents was evaluated by the reference broth microdilution method. The four most common organisms from PHP wereStaphylococcus aureus,Pseudomonas aeruginosa,Klebsiellaspp., andEnterobacterspp. The highest arbekacin MIC amongS. aureusisolates from PHP (43% methicillin-resistantS. aureus[MRSA]) was 4 μg/ml. AmongP. aeruginosaisolates from PHP, only one had an arbekacin MIC of >16 μg/ml (MIC50and MIC90, 1 and 4 μg/ml), and susceptibility rates for gentamicin, tobramycin, and amikacin were 88.0, 90.0, and 98.0%, respectively. Arbekacin (MIC50, 2 μg/ml) and tobramycin (MIC50, 4 μg/ml) were the most potent aminoglycosides tested againstAcinetobacter baumannii. AgainstEnterobacteriaceaefrom PHP, arbekacin and gentamicin (MIC50and MIC90, 0.25 to 1 and 1 to 8 μg/ml for both compounds) were generally more potent than tobramycin (MIC50and MIC90, 0.25 to 2 and 1 to 32 μg/ml) and amikacin (MIC50and MIC90, 1 to 2 and 2 to 32 μg/ml). Arbekacin also demonstrated potentin vitroactivity against a worldwide collection of well-characterized MDR Gram-negative and MRSA strains.

scholarly journals Ceftolozane-Tazobactam Activity against Pseudomonas aeruginosa Clinical Isolates from U.S. Hospitals: Report from the PACTS Antimicrobial Surveillance Program, 2012 to 2015

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Dee Shortridge ◽  
Mariana Castanheira ◽  
Michael A. Pfaller ◽  
Robert K. Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Drug Resistant ◽  
Content Type ◽  
Microdilution Method ◽  
Antimicrobial Surveillance ◽  
Broth Microdilution Method

ABSTRACT The activity of ceftolozane-tazobactam was compared to the activities of 7 antimicrobials against 3,851 Pseudomonas aeruginosa isolates collected from 32 U.S. hospitals in the Program to Assess Ceftolozane-Tazobactam Susceptibility from 2012 to 2015. Ceftolozane-tazobactam and comparator susceptibilities were determined using the CLSI broth microdilution method at a central monitoring laboratory. For ceftolozane-tazobactam, 97.0% of the isolates were susceptible. Susceptibilities of the other antibacterials tested were: amikacin, 96.9%; cefepime, 85.9%; ceftazidime, 85.1%; colistin, 99.2%; levofloxacin, 76.6%; meropenem, 81.8%; and piperacillin-tazobactam, 80.4%. Of the 699 (18.1%) meropenem-nonsusceptible P. aeruginosa isolates, 87.6% were susceptible to ceftolozane-tazobactam. Six hundred seven isolates (15.8%) were classified as multidrug resistant (MDR), and 363 (9.4%) were classified as extensively drug resistant (XDR). Only 1 isolate was considered pandrug resistant, which was resistant to all tested agents, including colistin. Of the 607 MDR isolates, 84.9% were ceftolozane-tazobactam susceptible, and 76.9% of XDR isolates were ceftolozane-tazobactam susceptible. In vitro activity against drug-resistant P. aeruginosa indicates ceftolozane-tazobactam may be an important agent in treating serious bacterial infections.

scholarly journals In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Latin American Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
James A. Karlowsky ◽  
Krystyna M. Kazmierczak ◽  
Samuel K. Bouchillon ◽  
Boudewijn L. M. de Jonge ◽  
Gregory G. Stone ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin American ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Latin American Countries

ABSTRACT The International Network for Optimal Resistance Monitoring (INFORM) global surveillance program collected clinical isolates of Enterobacteriaceae (n = 7,665) and Pseudomonas aeruginosa (n = 1,794) from 26 medical centers in six Latin American countries from 2012 to 2015. The in vitro activity of ceftazidime-avibactam and comparators was determined for the isolates using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method. Enterobacteriaceae were highly susceptible (99.7%) to ceftazidime-avibactam, including 99.9% of metallo-β-lactamase (MBL)-negative isolates; 87.4% of all P. aeruginosa isolates and 92.8% of MBL-negative isolates were susceptible to ceftazidime-avibactam. Susceptibility to ceftazidime-avibactam ranged from 99.4% to 100% for Enterobacteriaceae and from 79.1% to 94.7% for P. aeruginosa when isolates were analyzed by country of origin. Ceftazidime-avibactam inhibited 99.6% to 100% of Enterobacteriaceae isolates that carried serine β-lactamases, including extended-spectrum β-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases (KPC and OXA-48-like) as well as 99.7%, 99.6%, 99.5%, and 99.2% of MBL-negative isolates demonstrating ceftazidime-nonsusceptible, multidrug-resistant (MDR), meropenem-nonsusceptible, and colistin-resistant phenotypes, respectively. Among carbapenem-nonsusceptible isolates of P. aeruginosa (n = 750), 14.7% carried MBLs with or without additional acquired serine β-lactamases, while in the majority of isolates (70.0%), no acquired β-lactamase was identified. Ceftazidime-avibactam inhibited 89.5% of carbapenem-nonsusceptible P. aeruginosa isolates in which no acquired β-lactamase was detected. Overall, clinical isolates of Enterobacteriaceae collected in Latin America from 2012 to 2015 were highly susceptible to ceftazidime-avibactam, including isolates that exhibited resistance to ceftazidime, meropenem, colistin, or an MDR phenotype. Country-specific variations were noted in the susceptibility of P. aeruginosa isolates to ceftazidime-avibactam.

scholarly journals In Vitro Activity of Meropenem-Vaborbactam against Clinical Isolates of KPC-Positive Enterobacteriaceae

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Meredith A. Hackel ◽  
Olga Lomovskaya ◽  
Michael N. Dudley ◽  
James A. Karlowsky ◽  
Daniel F. Sahm
Keyword(s):  
Clinical Isolates ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Content Type ◽  
Class A ◽  
Microdilution Method ◽  
Fixed Concentration ◽  
Broth Microdilution Method ◽  
The U.S

ABSTRACT Vaborbactam (formerly RPX7009) is a novel inhibitor of serine β-lactamases, including Ambler class A carbapenemases, such as KPCs. The current study evaluated the in vitro activity of the combination agent meropenem-vaborbactam against a global collection of 991 isolates of KPC-positive Enterobacteriaceae collected in 2014 and 2015 using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. The MIC90 of meropenem (when tested with a fixed concentration of 8 μg/ml of vaborbactam) for isolates of KPC-positive Enterobacteriaceae was 1 μg/ml, and MIC values ranged from ≤0.03 to >32 μg/ml; 99.0% (981/991) of isolates had meropenem-vaborbactam MICs of ≤4 μg/ml, the U.S. FDA-approved MIC breakpoint for susceptibility to meropenem-vaborbactam (Vabomere). Vaborbactam lowered the meropenem MIC50 from 32 to 0.06 μg/ml and the MIC90 from >32 to 1 μg/ml. There were no differences in the activity of meropenem-vaborbactam when the isolates were stratified by KPC variant type. We conclude that meropenem-vaborbactam demonstrates potent in vitro activity against a worldwide collection of clinical isolates of KPC-positive Enterobacteriaceae collected in 2014 and 2015.

scholarly journals Antimicrobial Activity of Ceftolozane-Tazobactam Tested against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2011-2012)

2013 ◽  
Vol 57 (12) ◽  
pp. 6305-6310 ◽  
Author(s):  
David J. Farrell ◽  
Robert K. Flamm ◽  
Helio S. Sader ◽  
Ronald N. Jones
Keyword(s):  
Pseudomonas Aeruginosa ◽  
The United States ◽  
Multidrug Resistant ◽  
High Rate ◽  
Drug Resistant ◽  
Good Activity ◽  
Content Type ◽  
Microdilution Method ◽  
Medical Centers ◽  
Broth Microdilution Method

ABSTRACTCeftolozane/tazobactam, a novel antimicrobial agent with activity againstPseudomonas aeruginosa(including drug-resistant strains) and other common Gram-negative pathogens (including most extended-spectrum-β-lactamase [ESBL]-producingEnterobacteriaceaestrains), and comparator agents were susceptibility tested by a reference broth microdilution method against 7,071Enterobacteriaceaeand 1,971P. aeruginosaisolates. Isolates were collected consecutively from patients in 32 medical centers across the United States during 2011 to 2012. Overall, 15.7% and 8.9% ofP. aeruginosaisolates were classified as multidrug resistant (MDR) and extensively drug resistant (XDR), and 8.4% and 1.2% ofEnterobacteriaceaewere classified as MDR and XDR. No pandrug-resistant (PDR)Enterobacteriaceaeisolates and only one PDRP. aeruginosaisolate were detected. Ceftolozane/tazobactam was the most potent (MIC50/90, 0.5/2 μg/ml) agent tested againstP. aeruginosaand demonstrated good activity against 310 MDR strains (MIC50/90, 2/8 μg/ml) and 175 XDR strains (MIC50/90, 4/16 μg/ml). Ceftolozane/tazobactam exhibited high overall activity (MIC50/90, 0.25/1 μg/ml) againstEnterobacteriaceaeand retained activity (MIC50/90, 4/>32 μg/ml) against many 601 MDR strains but not against the 86 XDR strains (MIC50, >32 μg/ml). Ceftolozane/tazobactam was highly potent (MIC50/90, 0.25/0.5 μg/ml) against 2,691Escherichia coliisolates and retained good activity against most ESBL-phenotypeE. coliisolates (MIC50/90, 0.5/4 μg/ml), but activity was low against ESBL-phenotypeKlebsiella pneumoniaeisolates (MIC50/90, 32/>32 μg/ml), explained by the high rate (39.8%) of meropenem coresistance observed in this species phenotype. In summary, ceftolozane/tazobactam demonstrated high potency and broad-spectrum activity against many contemporaryEnterobacteriaceaeandP. aeruginosaisolates collected in U.S. medical centers. Importantly, ceftolozane/tazobactam retained potency against many MDR and XDR strains.

scholarly journals In Vitro Susceptibility Testing of Tedizolid against Isolates of Nocardia

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Barbara A. Brown-Elliott ◽  
Richard J. Wallace
Keyword(s):  
Common Species ◽  
Multidrug Resistant ◽  
In Vitro Susceptibility ◽  
Content Type ◽  
Nocardia Brasiliensis ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Clinically Significant

ABSTRACT There is a paucity of efficacious antimicrobials (especially oral) against clinically relevant species of Nocardia. To date, all species of Nocardia have been susceptible to linezolid, the first commercially available oxazolidinone. Tedizolid is a new oxazolidinone with previously reported improved in vitro and in vivo (intracellular) potency against multidrug-resistant strains of Mycobacterium sp. and Nocardia brasiliensis. Using the current Clinical and Laboratory Standards Institute-recommended broth microdilution method, 101 isolates of Nocardia spp., including 29 Nocardia cyriacigeorgica, 17 Nocardia farcinica, 13 Nocardia nova complex, 21 Nocardia brasiliensis, 5 Nocardia pseudobrasiliensis, and 5 Nocardia wallacei isolates and 11 isolates of less common species, were tested for susceptibility to tedizolid and linezolid. For the most common clinically significant species of Nocardia, tedizolid MIC50 values were 0.25 μg/ml for N. nova complex, N. brasiliensis, N. pseudobrasiliensis, and N. wallacei, compared to linezolid MIC50 values of 1, 2, 0.5, and 1 μg/ml, respectively. Tedizolid and linezolid MIC90 values were 2 μg/ml for N. nova complex and N. brasiliensis. Tedizolid MIC50 and MIC90 values for both N. cyriacigeorgica and N. farcinica were 0.5 μg/ml and 1 μg/ml, respectively, compared to linezolid MIC50 and MIC90 values of 2 and 4 μg/ml, respectively. Based on MIC90 values, this study showed that tedizolid was 2- to 3-fold more active than linezolid in vitro against most common species of Nocardia, with the exception of the N. nova complex and N. brasiliensis, for which values were the same. These results may warrant evaluation of tedizolid as a potential treatment option for Nocardia infections.

scholarly journals In VitroActivity of Plazomicin against Gram-Negative and Gram-Positive Bacterial Pathogens Isolated from Patients in Canadian Hospitals from 2013 to 2017 as Part of the CANWARD Surveillance Study

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Andrew Walkty ◽  
James A. Karlowsky ◽  
Melanie R. Baxter ◽  
Heather J. Adam ◽  
George G. Zhanel
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Pathogens ◽  
Multidrug Resistant ◽  
Surveillance Study ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method

ABSTRACTThe Clinical and Laboratory Standards Institute (CLSI) broth microdilution method was used to evaluate thein vitroactivities of plazomicin and comparator antimicrobial agents against 7,712 Gram-negative and 4,481 Gram-positive bacterial pathogens obtained from 2013 to 2017 from patients in Canadian hospitals as part of the CANWARD Surveillance Study. Plazomicin demonstrated potentin vitroactivity againstEnterobacteriaceae(MIC90≤ 1 µg/ml for all species tested exceptProteus mirabilisandMorganella morganii), including aminoglycoside-nonsusceptible, extended-spectrum β-lactamase (ESBL)-positive, and multidrug-resistant (MDR) isolates. Plazomicin was equally active against methicillin-susceptible and methicillin-resistant isolates ofStaphylococcus aureus.

scholarly journals Antimicrobial Activity of Ceftaroline Tested against Staphylococci with Reduced Susceptibility to Linezolid, Daptomycin, or Vancomycin from U.S. Hospitals, 2008 to 2011

2013 ◽  
Vol 57 (7) ◽  
pp. 3178-3181 ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Microdilution Method ◽  
Medical Centers ◽  
Broth Microdilution Method ◽  
Valuable Treatment

ABSTRACTVancomycin, linezolid, and daptomycin are very active against staphylococci, but isolates with decreased susceptibility to these antimicrobial agents are isolated sporadically. A total of 19,350Staphylococcus aureusisolates (51% methicillin resistant [MRSA]) and 3,270 coagulase-negative staphylococci (CoNS) were collected consecutively from 82 U.S. medical centers from January 2008 to December 2011 and tested for susceptibility against ceftaroline and comparator agents by the reference broth microdilution method. AmongS. aureusstrains, 14 isolates (0.07%) exhibited decreased susceptibility to linezolid (MIC, ≥8 μg/ml), 18 (0.09%) to daptomycin (MIC, ≥2 μg/ml), and 369 (1.9%) to vancomycin (MIC, ≥2 μg/ml; 368 isolates at 2 μg/ml and 1 at 4 μg/ml). Fifty-one (1.6%) CoNS were linezolid resistant (MIC, ≥8 μg/ml), and four (0.12%) were daptomycin nonsusceptible (MIC, ≥2 μg/ml). Ceftaroline was very active againstS. aureusoverall (MIC50/90, 0.5/1 μg/ml; 98.5% susceptible), including MRSA (MIC50/90, 0.5/1 μg/ml; 97.2% susceptible). All daptomycin-nonsusceptible and 85.7% of linezolid-resistantS. aureusisolates were susceptible to ceftaroline. AgainstS. aureusisolates with a vancomycin MIC of ≥2 μg/ml, 91.9, 96.2, and 98.9% were susceptible to ceftaroline, daptomycin, and linezolid, respectively. CoNS strains were susceptible to ceftaroline (MIC50/90, 0.25/0.5 μg/ml; 99.1% inhibited at ≤1 μg/ml), including methicillin-resistant (MIC50/90, 0.25/0.5 μg/ml), linezolid-resistant (MIC50/90, 0.5/0.5 μg/ml), and daptomycin-nonsusceptible (4 isolates; MIC range, 0.03 to 0.12 μg/ml) strains. In conclusion, ceftaroline demonstrated potentin vitroactivity against staphylococci with reduced susceptibility to linezolid, daptomycin, or vancomycin, and it may represent a valuable treatment option for infections caused by these multidrug-resistant staphylococci.

scholarly journals In Vitro Activity of WCK 5222 (Cefepime-Zidebactam) against Worldwide Collected Gram-Negative Bacilli Not Susceptible to Carbapenems

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
James A. Karlowsky ◽  
Meredith A. Hackel ◽  
Samuel K. Bouchillon ◽  
Daniel F. Sahm
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Limiting Factor ◽  
Gram Negative ◽  
Content Type ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method ◽  
Universal Stability

ABSTRACT WCK 5222 (cefepime-zidebactam, 2 g + 1g, every 8 h [q8h]) is in clinical development for the treatment of infections caused by carbapenem-resistant and multidrug-resistant (MDR) Gram-negative bacilli. We determined the in vitro susceptibility of 1,385 clinical isolates of non-carbapenem-susceptible Enterobacterales, MDR Pseudomonas aeruginosa (also non-carbapenem susceptible), Stenotrophomonas maltophilia, and Burkholderia spp. collected worldwide (49 countries) from 2014 to 2016 to cefepime-zidebactam (1:1 ratio), ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, and colistin using the CLSI broth microdilution method. Cefepime-zidebactam inhibited 98.5% of non-carbapenem-susceptible Enterobacterales (n = 1,018) at ≤8 μg/ml (provisional cefepime-zidebactam-susceptible MIC breakpoint). Against the subset of metallo-β-lactamase (MBL)-positive Enterobacterales (n = 214), cefepime-zidebactam inhibited 94.9% of isolates at ≤8 μg/ml. Further, it inhibited 99.6% of MDR P. aeruginosa (n = 262) isolates at ≤32 μg/ml (proposed cefepime-zidebactam-susceptible pharmacokinetic/pharmacodynamic MIC breakpoint), including all MBL-positive isolates (n = 94). Moreover, cefepime-zidebactam was active against the majority of isolates of Enterobacterales (≥95%) and P. aeruginosa (99%) that were not susceptible to ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, and colistin. Most isolates (99%) of S. maltophilia (n = 101; MIC50, 8 μg/ml; MIC90, 32 μg/ml) and Burkholderia spp. (n = 4; MIC range, 16 to 32 μg/ml) were also inhibited by cefepime-zidebactam at ≤32 μg/ml. The activity of cefepime-zidebactam against carbapenem-resistant Gram-negative bacteria is ascribed to its β-lactam enhancer mechanism of action (i.e., zidebactam binding to penicillin binding protein 2 [PBP2] and its universal stability to both serine β-lactamases and MBLs). The results from this study support the continued development of cefepime-zidebactam as a potential therapy for infections caused by Enterobacterales, P. aeruginosa, and other nonfermentative Gram-negative bacilli where resistance to marketed antimicrobial agents is a limiting factor.

scholarly journals In Vitro Activity of Omadacycline, a New Tetracycline Analog, and Comparators against Clostridioides difficile

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Khurshida Begum ◽  
Eugénie Bassères ◽  
Julie Miranda ◽  
Chris Lancaster ◽  
Anne J. Gonzales-Luna ◽  
...  
Keyword(s):  
Large Scale ◽  
Anaerobic Bacteria ◽  
Oral Antibiotic ◽  
Content Type ◽  
Microdilution Method ◽  
Clostridioides Difficile ◽  
Broth Microdilution Method ◽  
Time Kill ◽  
Further Development

ABSTRACT Omadacycline is a potent aminomethylcycline with in vitro activity against Gram-positive, Gram-negative, and anaerobic bacteria. Preliminary data demonstrated that omadacycline has in vitro activity against Clostridioides difficile; however, large-scale in vitro studies have not been done. The purpose of this study was to assess the in vitro susceptibility of omadacycline and comparators on a large biobank of clinical C. difficile isolates. In vitro C. difficile susceptibility to omadacycline and comparators (fidaxomicin, metronidazole, and vancomycin) was assessed using the broth microdilution method. Minimum bactericidal concentrations (MBCs) and time-kill assays were assessed for pharmacodynamics analysis, and whole-genome sequencing was performed in a subset of isolates to assess distribution of MICs and resistance determinants. Two hundred fifty clinical C. difficile isolates collected between 2015 and 2018 were tested for in vitro susceptibility of omadacycline and comparators. Ribotypes included F001 (n = 5), F002 (n = 56), F014-020 (n = 66), F017 (n = 8), F027 (n = 53), F106 (n = 45), and F255 (n = 17). Omadacycline demonstrated potent in vitro activity with an MIC range of 0.016 to 0.13 μg/ml, an MIC50 of 0.031 μg/ml, and an MIC90 of 0.031 μg/ml. No difference was observed for omadacycline MIC50 and MIC90 values stratified by ribotype, disease severity, or vancomycin susceptibility. Bactericidal activity was confirmed in time-kill studies. No difference was observed in MIC based on C. difficile phylogeny. Further development of omadacycline as an intravenous and oral antibiotic directed toward C. difficile infection is warranted.

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