scholarly journals In vitro efficacy of relebactam versus avibactam against Mycobacterium abscessus complex

2021 ◽  
pp. 100064
Author(s):  
James Harrison ◽  
John A. Weaver ◽  
Maya Desai ◽  
Jonathan A.G. Cox
Keyword(s):  
Mycobacterium Abscessus ◽  
Mycobacterium Abscessus Complex

scholarly journals 1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S488-S489
Author(s):  
Joy Yong ◽  
Ka Lip Chew ◽  
Paul Tambyah
Keyword(s):  
Active Agent ◽  
Liver Function Tests ◽  
Mycobacterium Abscessus ◽  
Prolonged Treatment ◽  
Attractive Alternative ◽  
In Vitro Susceptibility ◽  
Treatment Regimens ◽  
Drug Intolerance ◽  
Mycobacterium Abscessus Complex

Abstract Background Infections caused by the multi-drug-resistant Mycobacterium abscessus complex (MabsC) are challenging to treat and often require multiple antimicrobials for a prolonged treatment course and still have poor outcomes. Clofazimine, an oral anti-leprosy drug, has demonstrated good in vitro susceptibility and is being increasingly employed in treatment regimens for MabsC infections. We performed a drug-use-evaluation of clofazimine in the treatment of MabsC infections. Methods A retrospective review was performed for all patients with MabsC infections treated with clofazimine-containing regimens from January 2014 to June 2017. Results Twenty-nine patients were included. Twelve patients had pulmonary MabsC infections and seventeen had extrapulmonary infections. All isolates had clofazimine minimum-inhibitory-concentration of ≤0.5 mg/L as tested by broth microdilution. Clofazimine was prescribed at initiation of therapy in 31.0% (9/29), as a companion drug during maintenance therapy after initial intravenous therapy in 44.8% (13/29) and as part of salvage therapy due to disease progression or drug intolerance in 24.1% (7/29) of patients. Dosing of clofazimine for the pediatric patients was prescribed at 1–2 mg/kg/day while the adult patients received a range of 50–200 mg/day. Clofazimine was given for a median duration of 148.5 days (range: 14–1212) and most commonly in combination with clarithromycin (82.8%), amikacin (58.6%), and cefoxitin (24.1%). Twelve patients had documented adverse reactions attributable to clofazimine: skin hyperpigmentation (66.7%), abnormal liver function tests (16.7%), and gastrointestinal disturbance (16.7%). Table 1 describes the patients who had clofazimine ceased due to an adverse effect. Nine patients with pulmonary MabsC infections and 16 with extrapulmonary MabsC infections had documented improvement in symptoms. Conclusion Clofazimine as a companion drug in the treatment of MabsC infections was reasonably tolerated over a prolonged period of time. Its availability as an oral active agent makes it an attractive alternative to IV companion drugs and potentially improves compliance to the protracted treatment courses for patients with MabsC infections. Disclosures All authors: No reported disclosures.

In vitro susceptibility of Mycobacterium abscessus complex and feasibility of standardizing treatment regimens

2020 ◽  
Author(s):  
Ka Lip Chew ◽  
Sophie Octavia ◽  
Joelle Go ◽  
Sally Ng ◽  
Yit Er Tang ◽  
...  
Keyword(s):  
Retrospective Review ◽  
Susceptibility Testing ◽  
Mycobacterium Abscessus ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Treatment Regimens ◽  
Mycobacterium Abscessus Complex ◽  
Additional Testing

Abstract Objectives To determine the in vitro susceptibility of members of the Mycobacterium abscessus complex to routinely tested antibiotics and to an extended antibiotic panel. Methods Non-duplicate isolates for which susceptibility testing results were available were included in this study. Retrospective laboratory records were reviewed, including tigecycline susceptibility results, and testing was performed with additional drugs, including vancomycin, dalbavancin, telavancin, oritavancin, rifabutin, delafloxacin, eravacycline, clofazimine and bedaquiline using broth microdilution (Sensititre, Thermo Fisher). Results A total of 218 M. abscessus complex isolates were included for retrospective review, of which 151 were respiratory isolates. Of these 218 isolates, 211 were available for additional testing with the extended antibiotic panel. Of these, 146 were respiratory isolates. One isolate had a vancomycin MIC of 2 mg/L and MICs of all other isolates were >8 mg/L. All isolates had MICs of >8 mg/L for oritavancin, dalbavancin and telavancin. One isolate had a delafloxacin MIC of 4 mg/L and MICs of all other isolates were >8 mg/L. The MIC50/MIC90s of rifabutin, tigecycline, eravacycline, clofazimine and bedaquiline were 16/32, 0.5/1, 0.12/0.25, 0.12/0.25 and 0.06/0.12 mg/L, respectively. Conclusions In vitro activity was demonstrated for clofazimine, bedaquiline and eravacycline, indicating potential for inclusion as standardized therapy for M. abscessus complex infections.

scholarly journals Evaluation of Ceftaroline-Avibactam Activity in vitro and ex vivo Against Mycobacterium abscessus Complex

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S675-S675 ◽  
Author(s):  
Ruchi Pandey ◽  
Liang Chen ◽  
Elena Shashkina ◽  
Claudia Manca ◽  
Robert A Bonomo ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Mycobacterium Abscessus ◽  
Mycobacterium Abscessus Complex

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 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 Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Mycobacterium abscessus Complex

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Aristine Cheng ◽  
Yi-Tzu Tsai ◽  
Shu-Yuan Chang ◽  
Hsin-Yun Sun ◽  
Un-In Wu ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Mycobacterium Abscessus ◽  
First Line ◽  
Content Type ◽  
Mycobacterium Abscessus Complex ◽  
Potential Synergy ◽  
Resistant Strains ◽  
Reference Strains

ABSTRACT Infections caused by the difficult-to-treat bacterium Mycobacterium abscessus are increasing in frequency. Rifabutin, in contrast to rifampin, appears to be active in vitro against M. abscessus, especially against clarithromycin-resistant strains. However, explorations for potential synergy between rifabutin and available antimicrobials are currently limited. In vitro synergism between rifabutin and 10 antimicrobials was evaluated in 31 mycobacterial strains by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for each rifabutin-based combination. The colony morphology was recorded. Molecular methods for determination of the M. abscessus subspecies and analysis of macrolide resistance were performed by sequencing of the secA1, rpoB, hsp65, erm(41), and rrl genes. Rifabutin yielded an MIC50 of 16 mg/liter (range, 2 to 32 mg/liter) against 26 clinical M. abscessus isolates (comprising 13 M. abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates) and 5 reference strains, including M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii BCRC 16915, M. abscessus subsp. massiliense BCRC 16916, M. chelonae ATCC 35752, and M. peregrinum ATCC 700686. Significant synergism, classified by an FICI of ≤0.5, was demonstrated for the combinations of rifabutin and imipenem in 100% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates, and significant synergism for rifabutin and tigecycline was demonstrated in 77% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates. Among the 6 clarithromycin-resistant (MICs ≥ 8 mg/liter) M. abscessus subsp. abscessus isolates, the combination of rifabutin and clarithromycin was 100% synergistic. Rifabutin showed promising in vitro synergism with first-line anti-M. abscessus agents, especially for macrolide-resistant M. abscessus subsp. abscessus isolates.

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.

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