scholarly journals New β-Lactamase Inhibitors Nacubactam and Zidebactam Improve the In Vitro Activity of β-Lactam Antibiotics Against Mycobacterium abscessus Complex Clinical Isolates

2019 ◽  
Author(s):  
Amit Kaushik ◽  
Nicole C. Ammerman ◽  
Nicole M. Parrish ◽  
Eric L. Nuermberger
Keyword(s):  
Mycobacterium Abscessus ◽  
Clinical Development ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Mycobacterium Abscessus Complex

AbstractThe new diazabicyclooctane-based β-lactamase inhibitors avibactam and relebactam improve the in vitro activity of β-lactam antibiotics against Mycobacterium abscessus complex (MABC). Here, we evaluated the in vitro activity of two newer diazabicyclooctane-based β-lactamase inhibitors in clinical development, nacubactam and zidebactam, with β-lactams against clinical isolates of MABC. Both inhibitors lowered the MICs of their partner β-lactams, meropenem (eight-fold) and cefepime (two-fold), and those of other β-lactams, similar to prior results with avibactam and relebactam.

scholarly journals New β-Lactamase Inhibitors Nacubactam and Zidebactam Improve the In Vitro Activity of β-Lactam Antibiotics against Mycobacterium abscessus Complex Clinical Isolates

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Amit Kaushik ◽  
Nicole C. Ammerman ◽  
Nicole M. Parrish ◽  
Eric L. Nuermberger
Keyword(s):  
Mycobacterium Abscessus ◽  
Clinical Development ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Content Type ◽  
Mycobacterium Abscessus Complex

ABSTRACT The new diazabicyclooctane-based β-lactamase inhibitors avibactam and relebactam improve the in vitro activity of β-lactam antibiotics against bacteria of the Mycobacterium abscessus complex (MABC). Here, we evaluated the in vitro activities of two newer diazabicyclooctane-based β-lactamase inhibitors in clinical development, nacubactam and zidebactam, with β-lactams against clinical isolates of MABC. Both inhibitors lowered the MICs of their partner β-lactams, meropenem (8-fold) and cefepime (2-fold), respectively, and those of other β-lactams, similar to prior results with avibactam and relebactam.

scholarly journals In vitro activity of the new β-lactamase inhibitors relebactam and vaborbactam in combination with β-lactams against Mycobacterium abscessus complex clinical isolates

2018 ◽  
Author(s):  
Amit Kaushik ◽  
Nicole C. Ammerman ◽  
Jin Lee ◽  
Olumide Martins ◽  
Barry N Kreiswirth ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Phase Iii ◽  
In Vitro Activity ◽  
Intrinsic Resistance ◽  
Phase Iii Trials ◽  
Lactamase Inhibitor

Pulmonary disease due to infection with Mycobacterium abscessus complex (MABC) is notoriously difficult to treat, in large part due to MABC’s intrinsic resistance to most antibiotics, including β-lactams. MABC organisms express a broad-spectrum β-lactamase that is resistant to traditional β-lactam-based β-lactamase inhibitors but inhibited by a newer non-β-lactam-based β-lactamase inhibitor, avibactam. Consequently, the susceptibility of MABC to some β-lactams is increased in the presence of avibactam. Therefore, we hypothesized that two new non-β-lactam-based β-lactamase inhibitors, relebactam and vaborbactam, would also increase susceptibility of MABC to β-lactams. The objective of the present study was to evaluate the in vitro activity of various marketed β-lactams alone and in combination with either relebactam or vaborbactam against multidrug-resistant MABC clinical isolates. Our data demonstrate that both β-lactamase inhibitors significantly improved the anti-MABC activity of many carbapenems (including imipenem and meropenem) and cephalosporins (including cefepime, ceftaroline, and cefuroxime). As a meropenem/vaborbactam combination is now marketed and an imipenem/relebactam combination is currently in phase III trials, these fixed combinations may become the β-lactams of choice for the treatment of MABC infections. Furthermore, given the evolving interest in dual β-lactam regimens, our results identify select cephalosporins, such as cefuroxime, with superior activity in the presence of a β-lactamase inhibitor, deserving of further evaluation in combination with these carbapenem/β-lactamase inhibitor products.

scholarly journals In vitro activity of cefoxitin and imipenem against Mycobacterium abscessus complex

2014 ◽  
Vol 20 (5) ◽  
pp. O297-O300 ◽  
Author(s):  
M. Lavollay ◽  
V. Dubée ◽  
B. Heym ◽  
J.-L. Herrmann ◽  
J.-L. Gaillard ◽  
...  
Keyword(s):  
Mycobacterium Abscessus ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Mycobacterium Abscessus Complex

scholarly journals In Vitro Activity of Bedaquiline and Delamanid against Nontuberculous Mycobacteria, Including Macrolide-Resistant Clinical Isolates

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Dae Hun Kim ◽  
Byung Woo Jhun ◽  
Seong Mi Moon ◽  
Su-Young Kim ◽  
Kyeongman Jeon ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Abscessus ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Mycobacterium Kansasii ◽  
Antimicrobial Drugs ◽  
Content Type

ABSTRACT We evaluated the in vitro activities of the antimicrobial drugs bedaquiline and delamanid against the major pathogenic nontuberculous mycobacteria (NTM). Delamanid showed high MIC values for all NTM except Mycobacterium kansasii. However, bedaquiline showed low MIC values for the major pathogenic NTM, including Mycobacterium avium complex, Mycobacterium abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. kansasii. Bedaquiline also had low MIC values with macrolide-resistant NTM strains and warrants further investigation as a potential antibiotic for NTM treatment.

scholarly journals In Vitro Activity of Mirincamycin (U24729A) against Plasmodium falciparum Isolates from Gabon

2009 ◽  
Vol 54 (1) ◽  
pp. 540-542 ◽  
Author(s):  
Jana Held ◽  
Richard Westerman ◽  
Peter G. Kremsner ◽  
Benjamin Mordmüller
Keyword(s):  
Plasmodium Falciparum ◽  
Immunosorbent Assay ◽  
Incubation Time ◽  
Clinical Development ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Activity ◽  
Prolonged Incubation

ABSTRACT We assessed the in vitro activity of mirincamycin, a lincosamide antibiotic, against Plasmodium falciparum clinical isolates from Gabon. Growth was determined by HRP2 enzyme-linked immunosorbent assay using an adapted protocol with a prolonged incubation time (6 days) to account for antibiotic-induced delayed death. Mirincamycin's cis and trans isomers are more active (median 50% inhibitory concentrations [IC50s], 3.2 nM and 2.6 nM) than the comparator drugs clindamycin (IC50, 12 nM) and doxycycline (IC50, 720 nM), and therefore, further clinical development is promising.

In vitro activity of tedizolid against the Mycobacterium abscessus complex

2018 ◽  
Vol 90 (3) ◽  
pp. 186-189 ◽  
Author(s):  
Fabrice Compain ◽  
Daria Soroka ◽  
Beate Heym ◽  
Jean-Louis Gaillard ◽  
Jean-Louis Herrmann ◽  
...  
Keyword(s):  
Mycobacterium Abscessus ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Mycobacterium Abscessus Complex

scholarly journals 1280. In-Vitro Activity of Cefiderocol, Imipenem/Relebactam, & Ceftazidime/Avibactam in Ceftolozane/Tazobactam Resistant Strains of Multidrug Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S655-S655
Author(s):  
Daniel Navas ◽  
Angela Charles ◽  
Amy Carr ◽  
Jose Alexander
Keyword(s):  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Resistance Testing ◽  
Clinical Samples ◽  
In Vitro Activity ◽  
Carbapenemase Gene ◽  
Resistant Strains

Abstract Background The activity of imipenem/relebactam (I/R), ceftazidime/avibactam (CZA) and cefiderocol (FDC) were evaluated against clinical isolates of multidrug resistant (MDR) strains of P. aeruginosa which was resistant to ceftolozane/tazobactam (C/T). The recent increase of MDR P. aeruginosa strains isolated from clinical samples has prompted research and development of new antimicrobials that can withstand its multiple resistance mechanisms. C/T is an effective option for treatment of MDR P. aeruginosa in our facility with only 10% of resistance in MDR strains, but the emergence of resistance may occur due to the presence of a carbapenemase gene or an ampC mutation. Methods Antimicrobial susceptibility testing for C/T Etest® (bioMérieux, Inc.) were performed on all MDR strains initially screened by the VITEK2® (bioMérieux, Inc.). 10% (n=20) of all MDR isolates were resistant to C/T by the CLSI 2019 breakpoints. These resistant isolates were tested for presence of a carbapenemase gene using the GeneXpert CARBA-R (Cepheid®) PCR and against CZA Etest® (bioMérieux, Inc.) I/R gradient strips (Liofilchem®) and FDC broth microdilution (Thermo Scientific™ Sensititre™). Results A total of 20 clinical isolates of MDR P. aeruginosa resistant to C/T were tested following standardized CLSI protocols and techniques. All 20 isolates were screened for the presence of a carbapenemase gene (blaVIM, blaNDM, blaKPC, blaOXA-48, blaIMP). A blaVIM gene was detected in 6 (30%) out of 20 isolates. FDC demonstrated the greatest activity with 85% (n=17) of susceptible isolates (CLSI MIC <4µg/dL). CZA (CLSI MIC <8µg/dL) and I/R (FDA MIC <2µg/dL) showed 15% (n=3) and 10% (n=2) of susceptible isolates respectively. FDC was active against all 6 blaVIM isolates, where all 6 strains were resistant to CZA and I/R as expected. 3 isolates tested non-susceptible against FDC; additional characterization was not performed at this time. Conclusion Based on these results, FDC demonstrated the greatest in-vitro activity against C/T resistant strains of MDR P. aeruginosa. FDC also demonstrated activity against all 6 MDR P. aeruginosa carrying blaVIM gene. FDC is a strong option to consider on MDR P. aeruginosa strains based on a resistance testing algorithm and a cost/effective protocol. Disclosures All Authors: No reported disclosures

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