scholarly journals In Vitro Activity of Clofazimine against Nontuberculous Mycobacteria Isolated in Beijing, China

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Jingjing Luo ◽  
Xia Yu ◽  
Guanglu Jiang ◽  
Yuhong Fu ◽  
Fengmin Huo ◽  
...  
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Clinical Isolates ◽  
Natural Resistance ◽  
Cross Resistance ◽  
Mycobacterium Fortuitum ◽  
Strong Activity ◽  
Content Type ◽  
Beijing China ◽  
Reference Strains

ABSTRACT Due to the natural resistance of nontuberculous mycobacteria (NTM) to many antibiotics, the treatment of diseases caused by NTM is often long-term but unsuccessful. The main goal of this study was to evaluate the in vitro susceptibilities to clofazimine of 209 isolates consisting of different NTM species isolated in Beijing, China. Furthermore, 47 reference strains were also tested, including 30 rapidly growing mycobacterium (RGM) species and 17 slowly growing mycobacterium (SGM) species. The potential molecular mechanism contributing to clofazimine resistance of NTM was investigated as well. Clofazimine exhibited excellent activity against both reference strains and clinical isolates of different SGM species, and most of the strains had MICs far below 1 μg/ml. Although the majority of the clinical isolates of Mycobacterium abscessus and Mycobacterium fortuitum had MICs higher than 2 μg/ml, 17 out of the 30 reference strains of different RGM species had MICs below 1 μg/ml in vitro . According to the MIC distributions, the tentative epidemiological cutoff (ECOFF) values for Mycobacterium kansasii , Mycobacterium avium , and Mycobacterium intracellulare were defined at 0.5 μg/ml, 1 μg/ml, and 2 μg/ml, respectively. Intriguingly, single-direction cross-resistance between bedaquiline- and clofazimine (Cfz)-resistant isolates was observed among the tested NTM species. This study demonstrates that clofazimine had strong activity against most SGM species in vitro , as well as some RGM species. The data provide important insights into the possible clinical application of Cfz to treat NTM infections.

scholarly journals In Vitro Activities of Bedaquiline and Delamanid against Nontuberculous Mycobacteria Isolated in Beijing, China

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Xia Yu ◽  
XiaoPan Gao ◽  
Chenghai Li ◽  
Jingjing Luo ◽  
Shuan Wen ◽  
...  
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Antimicrobial Activities ◽  
Clinical Isolates ◽  
Natural Resistance ◽  
Pharmacokinetic Data ◽  
Moderate Activity ◽  
Content Type ◽  
Long Course ◽  
Reference Strains

ABSTRACT Due to the natural resistance of nontuberculous mycobacteria (NTM) against multiple antibiotics, treatment of infections caused by them is often long-course and less successful. The main objective of our study was the evaluation of in vitro susceptibility of 209 isolates consisting of different NTM species against bedaquiline and delamanid. Furthermore, reference strains of 33 rapidly growing mycobacterium (RGM) species and 19 slowly growing mycobacterium (SGM) species were also tested. Bedaquiline exhibited strong in vitro activity against both reference strains and clinical isolates of different SGM species, as the majority of the strains demonstrated MICs far below 1 μg/ml. Bedaquiline (Bdq) also exhibited potent activity against the recruited RGM species. A total of 29 out of 33 reference RGM strains had MICs lower than 1 μg/ml. According to the MIC distributions, the tentative epidemiological cutoff (ECOFF) values, and the pharmacokinetic data, a uniform breakpoint of 2 μg/ml was temporarily proposed for NTM’s Bdq susceptibility testing. Although delamanid (Dlm) was not active against most of the tested reference strains and clinical isolates of RGM species, it exhibited highly variable antimicrobial activities against the 19 tested SGM species. Eleven species had MICs lower than 0.25 μg/ml, and 7 species had MICs greater than 32 μg/ml. Large numbers of M. kansasii (39/45) and M. gordonae (6/10) clinical isolates had MICs of ≤0.125 μg/ml. This study demonstrated that bedaquiline had potent activity against different NTM species in vitro, and delamanid had moderate activity against certain species of SGM. The data provided important insights on the possible clinical application of Bdq and Dlm to treat NTM infections.

scholarly journals In VitroAntimicrobial Activity of Razupenem (SMP-601, PTZ601) against Anaerobic Bacteria

2011 ◽  
Vol 55 (5) ◽  
pp. 2398-2402 ◽  
Author(s):  
Chau Minh Tran ◽  
Kaori Tanaka ◽  
Yuka Yamagishi ◽  
Takatsugu Goto ◽  
Hiroshige Mikamo ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Anaerobic Bacteria ◽  
Clinical Isolates ◽  
Strong Activity ◽  
Content Type ◽  
Spectrum Activity ◽  
Reference Strains ◽  
Gram Positive Cocci ◽  
Broad Spectrum Activity

ABSTRACTWe evaluated thein vitroantianaerobic activity of razupenem (SMP-601, PTZ601), a new parenterally administered carbapenem, against 70 reference strains and 323 clinical isolates. Razupenem exhibited broad-spectrum activity against anaerobes, inhibiting most of the reference strains when used at a concentration of ≤1 μg/ml. Furthermore, it exhibited strong activity, comparable to those of other carbapenems (meropenem and doripenem), against clinically isolated non-fragilis Bacteroidesspp. (MIC90s of 2 μg/ml), with MIC90values of 0.06, 0.03, and 0.5 μg/ml againstPrevotellaspp.,Porphyromonasspp., andFusobacteriumspp., respectively. Clinical isolates of anaerobic Gram-positive cocci,Eggerthellaspp., andClostridiumspp. were highly susceptible to razupenem (MIC90s, 0.03 to 1 μg/ml).

scholarly journals In Vitro Activity of Rifamycin Derivatives against Nontuberculous Mycobacteria, Including Macrolide- and Amikacin-Resistant Clinical Isolates

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Dae Hun Kim ◽  
Su-Young Kim ◽  
Hee Jae Huh ◽  
Nam Yong Lee ◽  
Won-Jung Koh ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Therapeutic Option ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Content Type ◽  
Resistant Disease

ABSTRACT We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii. Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease.

scholarly journals In VitroActivity of AZD5847 against Geographically Diverse Clinical Isolates of Mycobacterium tuberculosis

2014 ◽  
Vol 58 (7) ◽  
pp. 4222-4223 ◽  
Author(s):  
Jim Werngren ◽  
Maria Wijkander ◽  
Nasrin Perskvist ◽  
V. Balasubramanian ◽  
Vasan K. Sambandamurthy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Lavage Fluid ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Drug Candidate ◽  
Content Type ◽  
Geographical Regions ◽  
Lung Biopsies

ABSTRACTThe MIC of the novel antituberculosis (anti-TB) drug AZD5847 was determined against 146 clinical isolates from diverse geographical regions, including eastern Europe, North America, Africa, and Asia, using the automated Bactec Mycobacterial Growth Indicator Tube (MGIT) 960 system. These isolates originated from specimen sources such as sputum, bronchial alveolar lavage fluid, pleural fluid, abscess material, lung biopsies, and feces. The overall MIC90was 1.0 mg/liter (range, 0.125 to 4 mg/liter). The MICs of AZD5847 for isolates ofMycobacterium tuberculosiswere similar among drug-sensitive strains, multidrug-resistant (MDR) strains, and extensively drug resistant (XDR) strains. The goodin vitroactivity of AZD5847 againstM. tuberculosisand the lack of cross-resistance make this agent a promising anti-TB drug candidate.

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 VitroActivity of Delafloxacin against Clinical Neisseria gonorrhoeae Isolates and Selection of Gonococcal Delafloxacin Resistance

2016 ◽  
Vol 60 (5) ◽  
pp. 3106-3111 ◽  
Author(s):  
Olusegun O. Soge ◽  
Stephen J. Salipante ◽  
David No ◽  
Erin Duffy ◽  
Marilyn C. Roberts
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Spontaneous Mutation ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Content Type ◽  
Resistant Mutants ◽  
Reference Strains ◽  
Selection Of

ABSTRACTWe evaluated thein vitroactivity of delafloxacin against a panel of 117Neisseria gonorrhoeaestrains, including 110 clinical isolates collected from 2012 to 2015 and seven reference strains, compared with the activities of seven antimicrobials currently or previously recommended for treatment of gonorrhea. We examined the potential for delafloxacin to select for resistant mutants in ciprofloxacin-susceptible and ciprofloxacin-resistantN. gonorrhoeae. We characterized mutations in thegyrA,gyrB,parC, andparEgenes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) by PCR and sequencing and by whole-genome sequencing. The MIC50, MIC90, and MIC ranges of delafloxacin were 0.06 μg/ml, 0.125 μg/ml, and ≤0.001 to 0.25 μg/ml, respectively. The frequency of spontaneous mutation ranged from 10−7to <10−9. The multistep delafloxacin resistance selection of 30 daily passages resulted in stable resistant mutants. There was no obvious cross-resistance to nonfluoroquinolone comparator antimicrobials. A mutant with reduced susceptibility to ciprofloxacin (MIC, 0.25 μg/ml) obtained from the ciprofloxacin-susceptible parental strain had a novel Ser91Tyr alteration in thegyrAgene. We also identified new mutations in thegyrAand/orparCandparEgenes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) of two mutant strains with elevated delafloxacin MICs of 1 μg/ml. Although delafloxacin exhibited potentin vitroactivity againstN. gonorrhoeaeisolates and reference strains with diverse antimicrobial resistance profiles and demonstrated a low tendency to select for spontaneous mutants, it is important to establish the correlation between these excellentin vitrodata and treatment outcomes through appropriate randomized controlled clinical trials.

scholarly journals In Vitro Selection oframRandsoxRMutants Overexpressing Efflux Systems by Fluoroquinolones as Well as Cefoxitin in Klebsiella pneumoniae

2011 ◽  
Vol 55 (6) ◽  
pp. 2795-2802 ◽  
Author(s):  
Suzanne Bialek-Davenet ◽  
Estelle Marcon ◽  
Véronique Leflon-Guibout ◽  
Jean-Philippe Lavigne ◽  
Frédéric Bert ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
In Vitro Selection ◽  
Efflux Pump ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Efflux System ◽  
Content Type ◽  
New Antibiotics ◽  
Regulator Genes

ABSTRACTThe relationship between efflux system overexpression and cross-resistance to cefoxitin, quinolones, and chloramphenicol has recently been reported inKlebsiella pneumoniae. In 3 previously published clinical isolates and 17in vitromutants selected with cefoxitin or fluoroquinolones, mutations in the potential regulator genes of the AcrAB efflux pump (acrR,ramR,ramA,marR,marA,soxR,soxS, androb) were searched, and their impacts on efflux-related antibiotic cross-resistance were assessed. All mutants but 1, and 2 clinical isolates, overexpressedacrB. No mutation was detected in the regulator genes studied among the clinical isolates and 8 of the mutants. For the 9 remaining mutants, a mutation was found in theramRgene in 8 of them and in thesoxRgene in the last one, resulting in overexpression oframAandsoxS, respectively. Transformation of theramRmutants and thesoxRmutant with the wild-typeramRandsoxRgenes, respectively, abolished overexpression ofacrBandramAin theramRmutants and ofsoxSin thesoxRmutant, as well as antibiotic cross-resistance. Resistance due to efflux system overexpression was demonstrated for 4 new antibiotics: cefuroxime, cefotaxime, ceftazidime, and ertapenem. This study shows that theramRandsoxRgenes control the expression of efflux systems inK. pneumoniaeand suggests the existence of efflux pumps other than AcrAB and of other loci involved in the regulation of AcrAB expression.

scholarly journals In Vitro Efficacy Comparison of Linezolid, Tedizolid, Sutezolid and Delpazolid Against Rapid Growing Mycobacteria Isolated in Beijing, China

2021 ◽  
Author(s):  
Shuan Wen ◽  
Xiaopan Gao ◽  
Weijie Zhao ◽  
Fengmin Huo ◽  
Guanglu Jiang ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Clinical Application ◽  
Rapid Growth ◽  
Inhibitory Activity ◽  
Natural Resistance ◽  
Protein Alignment ◽  
Beijing China ◽  
Reference Strains ◽  
Multiple Antibiotics

Abstract The natural resistance of rapid growth Mycobacterium (RGM) against multiple antibiotics renders the treatment of caused infections less successful and time consuming. Therefore, new effective agents are urgently needed. The aim of this study was to evaluate the in vitro susceptibility of 115 isolates, constituting different RGM species, to four oxazolidinones i.e. delpazolid, sutezolid, tedizolid and linezolid. Additionally, 32 reference strains of different RGM species were also tested. The four oxazolidinones exhibited potent in vitro activity against the recruited RGM reference strains, 24 out of 32 RGM species had MICs ≤ 8 µg/mL against all four oxazolidinones whereas tedizolid and delpazolid generally presented lower MICs than linezolid or sutezolid. Tedizolid showed the strongest activity against clinical isolates of M. abscessus with MIC50 = 1 µg/mL and MIC90 = 2 µg/mL. MIC values for tedizolid were usually 4- to 8-fold less than the MICs of linezolid for M. abscessus subsp. abscessus. The MIC distributions of sutezolid and linezolid were similar, while delpazolid showed 2-fold lower MIC as compared with linezolid. Linezolid was not active against most of the tested M. fortuitum isolates, since 22 out of the 25 M. fortuitum were resistant against linezolid. However, delpazolid exhibited better antimicrobial activity against these isolates with 4-fold lower MIC values, in contrast with linezolid. In addition, the protein alignment of RplC and RplD and structure based analysis showed that there may be no correlation between oxazolidinones resistance and mutations in rplC ,rplD and 23srRNA genes in tested RGM. This study showed tedizolid harbors the strongest inhibitory activity against M. abscessus in vitro, while delpazolid presented the best activity against M. fortuitum, which provided important insights on the potential clinical application of oxazolidinones to treat RGM infections.

scholarly journals In Vitro efficacy comparison of linezolid, tedizolid, sutezolid and delpazolid against rapid growing Mycobacteria isolated in Beijing, China

2020 ◽  
Author(s):  
Shuan Wen ◽  
Xiaopan Gao ◽  
Weijie Zhao ◽  
Fengmin Huo ◽  
Guanglu Jiang ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Clinical Application ◽  
Rapid Growth ◽  
Inhibitory Activity ◽  
Natural Resistance ◽  
Protein Alignment ◽  
Beijing China ◽  
Reference Strains ◽  
Multiple Antibiotics

ABSTRACTThe natural resistance of rapid growth Mycobacterium (RGM) against multiple antibiotics renders the treatment of caused infections less successful and time consuming. Therefore, new effective agents are urgently needed. The aim of this study was to evaluate the in vitro susceptibility of 115 isolates, constituting different RGM species, against four oxazolidinones i.e. delpazolid, sutezolid, tedizolid and linezolid. Additionally, 32 reference strains of different RGM species were also tested. The four oxazolidinones exhibited potent in vitro activity against the recruited RGM reference strains, 24 out of 32 RGM species had MICs ≤ 8 μg/mL against all four oxazolidinones whereas tedizolid and delpazolid generally presented lower MICs than linezolid or sutezolid. Tedizolid showed the strongest activity against clinical isolates of M. abscessus with MIC50=1μg/mL and MIC90=2μg/mL. MIC values for tedizolid were usually 4- to 8-fold less than the MICs of linezolid for M. abscessus subsp. abscessus. The MIC distributions of sutezolid and linezolid were similar, while delpazolid showed 2-fold lower MIC as compared with linezolid. Linezolid was not active against most of the tested M. fortuitum isolates, 22 out of the 25 M. fortuitum were resistant against linezolid. However, delpazolid exhibited better antimicrobial activity against these isolates with 4-fold lower MIC values, in contrast with linezolid. In addition, the protein alignment of RplC and RplD and structure based analysis showed that there may be no correlation between oxazolidinones resistance and mutations in rplC, rplD and 23 srRNAgenes in tested RGM. This study showed tedizolid harbors the strongest inhibitory activity against M. abscessus in vitro, while delpazolid presented the best activity against M. fortuitum, which provided important insights on the potential clinical application of oxazolidinones to treat RGM infections.

scholarly journals In Vitro Susceptibility to Closthioamide among Clinical and Reference Strains of Neisseria gonorrhoeae

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Victoria F. Miari ◽  
Priya Solanki ◽  
Yonek Hleba ◽  
Richard A. Stabler ◽  
John T. Heap
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Related Species ◽  
Cross Resistance ◽  
Drug Resistant ◽  
In Vitro Susceptibility ◽  
Content Type ◽  
Reference Strains ◽  
Species Cross

ABSTRACT Neisseria gonorrhoeae is one of the leading antimicrobial resistance threats worldwide. This study determined the MICs of closthioamide to be 0.008 to 0.5 mg/liter for clinical N. gonorrhoeae strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant N. gonorrhoeae.

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