Abstract:
:Mycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases. As it is intrinsically resistant to most conventional antibiotics, there is an unmet medical need for effective treatments. Repurposing of clinically validated pharmaceuticals represents an attractive option for the development of chemotherapeutic alternatives against M. abscessus infections. In this context, rifabutin (RFB) has been shown to be active against M. abscessus and has raised renewed interest in using rifamycins for the treatment of M. abscessus pulmonary diseases. Here, we compared the in vitro and in vivo activity of RFB against the smooth and rough variants of M. abscessus, differing in their susceptibility profiles to several drugs and physiopathologial characteristics. While the activity of RFB is greater against rough strains than in smooth strains in vitro, suggesting a role of the glycopeptidolipid layer in susceptibility to RFB, both variants were equally susceptible to RFB inside human macrophages. RFB treatment also led to a reduction in the number and size of intracellular and extracellular mycobacterial cords. Furthermore, RFB was highly effective in a zebrafish model of infection and protected the infected larvae from M. abscessus-induced killing. This was corroborated by a significant reduction in the overall bacterial burden, as well as decreased numbers of abscesses and cords, two major pathophysiological traits in infected zebrafish. This study indicates that RFB is active against M. abscessus both in vitro and in vivo, further supporting its potential usefulness as part of combination regimens targeting this difficult-to-treat mycobacterium.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Johansen MD,Daher W,Roquet-Banères F,Raynaud C,Alcaraz M,Maurer FP,Kremer Ldoi
10.1128/AAC.00363-20subject
Has Abstractpub_date
2020-10-20 00:00:00issue
11eissn
0066-4804issn
1098-6596pii
AAC.00363-20journal_volume
64pub_type
杂志文章abstract::Chloramphenicol acetyltransferases specified by fi(-) (F fertility-noninhibiting) R factors were compared with those specified by the fi(+) R factors R1, 222, and R6-S. Three classes of enzyme were distinguished: class I was determined by group N fi(-) R factors and was indistinguishable from the enzyme determined by ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.1.99
更新日期:1973-01-01 00:00:00
abstract::Eighty-nine clinical isolates of Staphylococcus aureus that were resistant to both ciprofloxacin (MIC, greater than or equal to 3.13 micrograms/ml) and methicillin (MIC, greater than or equal to 12.5 micrograms/ml) were divided into two groups with respect to their susceptibilities to AT-4140. Most isolates that were ...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.34.6.1123
更新日期:1990-06-01 00:00:00
abstract::Piperacillin and vancomycin were used as initial empirical therapy for 211 febrile episodes in cancer patients. The response rate in 95 episodes of documented infection was 72%. The response of bacteremias, soft tissue infections, and pneumonias was 78, 71, and 38%, respectively. The response in infections caused by g...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.3.295
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.01909-19
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.43.7.1669
更新日期:1999-07-01 00:00:00
abstract::Small unilamellar amphotericin B liposomes can reduce the toxicity of amphotericin B. In this study, we compared the physical, antifungal, pharmocokinetic, and toxic properties of two liposomal amphotericin B products, AmBisome and Anfogen, that have the same chemical composition but are manufactured differently. In v...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00870-07
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.12.2781
更新日期:1996-12-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01801-18
更新日期:2018-12-21 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.1.33
更新日期:1988-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.5.634
更新日期:1985-11-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.3.528
更新日期:1994-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00451-06
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
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更新日期:2013-11-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.38.9.1930
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05566-11
更新日期:2012-04-01 00:00:00
abstract::The inactivation of virus-contaminated nonporous inanimate surfaces was investigated using adenovirus type 8, a common cause of epidemic keratoconjunctivitis. A 10-microl inoculum of adenovirus was placed onto each stainless steel disk (1-cm diameter), and the inoculum was allowed to air dry for 40 min. Twenty-one dif...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.4.1419-1424.2006
更新日期:2006-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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abstract::We conducted time-kill studies to evaluate the inhibitory activities of either cefotaxime or minocycline alone and the two drugs in combination against a clinical strain of Vibrio vulnificus. The MICs of cefotaxime and minocycline were 0.03 and 0.06 microg/ml, respectively. When approximately 5 x 10(5) CFU of V. vulni...
journal_title:Antimicrobial agents and chemotherapy
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