scholarly journals In Vitro Activities of the Novel Oxazolidinones DA-7867 and DA-7157 against Rapidly and Slowly Growing Mycobacteria

2006 ◽  
Vol 50 (12) ◽  
pp. 4027-4029 ◽  
Author(s):  
Lucio Vera-Cabrera ◽  
Barbara A. Brown-Elliott ◽  
Richard J. Wallace ◽  
Jorge Ocampo-Candiani ◽  
Oliverio Welsh ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Isolates ◽  
Nontuberculous Mycobacterium ◽  
The Novel ◽  
Broth Microdilution ◽  
Reference Species ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Aerobic Actinomycetes

ABSTRACT DA-7867 and DA-7157 are oxazolidinones active against pathogenic aerobic actinomycetes including Nocardia spp. and Mycobacterium tuberculosis. However, the activity of these drugs against nontuberculous mycobacterium (NTM) species is not known. In this work, we compared the susceptibilities of 122 clinical isolates and 29 reference species of both rapidly growing and slowly growing mycobacteria to linezolid, DA-7867, and DA-7157 by the broth microdilution method. The MICs for 50 and 90% of the strains tested (MIC50s and MIC90s, respectively) of DA-7867 and DA-7157 were lower than those of linezolid. In all of the cases, a MIC90 of <8 μg/ml was observed for all of the species tested in both groups of NTM. For M. kansasii and M. marinum isolates, the MIC90s of both DA-7867 and DA-7157 were less than 0.5 μg/ml. These results demonstrate the potential of these compounds to treat NTM infections.

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 In Vitro Evaluation of the activity of Ceftazidime-avibactam and Aztreonam-Avibactam against 76 Stenotrophomonas maltophilia isolates from a teaching hospital in Chongqing

2020 ◽  
Author(s):  
Qiuxia Lin ◽  
Hua Zou ◽  
Xian Chen ◽  
Menglu Wu ◽  
Deyu Ma ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Combined Therapy ◽  
Treatment Options ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Medical University ◽  
Selection Of

Abstract Background: Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime-avibactam (CAZ-AVI) and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011-2018. Methods: We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011-2018, a collection of 76 isolates of which were available for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM) and aztreonam-avibactam (ATM-AVI) were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more effective in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” with CAZ or ATM alone to “Susceptible” or “Intermediate” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 2-fold lower than the MIC of CAZ or ATM alone. Results: For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03-64, 1-1024, 0.016-64, and 0.06-64 μg/mL, respectively. In combined therapy, AVI was effective at restoring the susceptibility of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs.56.58%, P<0.001), MIC50 (2μg/mL vs. 8μg/mL, P<0.05), and MIC distribution (P<0.001) when compared to CAZ. According to our definition, CAZ-AVI was more effective in vitro than CAZ alone for 84.21% of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79%vs. 10.53%, P<0.001), MIC50 (2μg/mL vs. 64μg/mL, P<0.001), and MIC distribution (P<0.001) when compared to ATM. According to our definition, ATM-AVI was also more effective in vitro than ATM alone for 97.37% of the isolates. Conclusions: AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

scholarly journals Comparison of In Vitro Activities of ABT-773 and Telithromycin against Macrolide-Susceptible and -Resistant Streptococci and Staphylococci

2002 ◽  
Vol 46 (3) ◽  
pp. 783-786 ◽  
Author(s):  
Virginia D. Shortridge ◽  
Ping Zhong ◽  
Zhensheng Cao ◽  
Jill M. Beyer ◽  
Laurel S. Almer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Ribosomal Protein ◽  
Streptococcus Pyogenes ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
Minimum Inhibitory Concentrations ◽  
Microdilution Method ◽  
Broth Microdilution Method

ABSTRACT The activity of a new ketolide, ABT-773, was compared to the activity of the ketolide telithromycin (HMR-3647) against over 600 gram-positive clinical isolates, including 356 Streptococcus pneumoniae, 167 Staphylococcus aureus, and 136 Streptococcus pyogenes isolates. Macrolide-susceptible isolates as well as macrolide-resistant isolates with ribosomal methylase (Erm), macrolide efflux (Mef), and ribosomal mutations were tested using the NCCLS reference broth microdilution method. Both compounds were extremely active against macrolide-susceptible isolates, with the minimum inhibitory concentrations at which 90% of the isolates tested were inhibited (MIC90s) for susceptible streptococci and staphylococci ranging from 0.002 to 0.03 μg/ml for ABT-773 and 0.008 to 0.06 μg/ml for telithromycin. ABT-773 had increased activities against macrolide-resistant S. pneumoniae (Erm MIC90, 0.015 μg/ml; Mef MIC90, 0.12 μg/ml) compared to those of telithromycin (Erm MIC90, 0.12 μg/ml; Mef MIC90, 1 μg/ml). Both compounds were active against strains with rRNA or ribosomal protein mutations (MIC90, 0.12 μg/ml). ABT-773 was also more active against macrolide-resistant S. pyogenes (ABT-773 Erm MIC90, 0.5 μg/ml; ABT-773 Mef MIC90, 0.12 μg/ml; telithromycin Erm MIC90, >8 μg/ml; telithromycin Mef MIC90, 1.0 μg/ml). Both compounds lacked activity against constitutive macrolide-resistant Staphylococcus aureus but had good activities against inducibly resistant Staphylococcus aureus (ABT-773 MIC90, 0.06 μg/ml; telithromycin MIC90, 0.5 μg/ml). ABT-773 has superior activity against macrolide-resistant streptococci compared to that of telithromycin.

In vitro activities of acetylmidecamycin and other antimicrobials against human macrolide-resistant Mycoplasma pneumoniae isolates

2020 ◽  
Vol 75 (6) ◽  
pp. 1513-1517 ◽  
Author(s):  
Na Wang ◽  
Yunheng Zhou ◽  
Hong Zhang ◽  
Yang Liu
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Antimicrobial Agents ◽  
Mycoplasma Hominis ◽  
Clinical Isolates ◽  
Mycoplasma Species ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Ureaplasma Spp

Abstract Objectives To assess the in vitro activities of acetylmidecamycin, a 16-membered macrolide, and 11 other antimicrobial agents against human mycoplasmas. Methods A total of 187 clinical isolates, Mycoplasma pneumoniae (n = 110), Mycoplasma hominis (n = 26) and Ureaplasma species (n = 51), were included in this study. The MICs of 12 antimicrobial agents, including acetylmidecamycin, thiamphenicol, chloramphenicol and some other macrolides, fluoroquinolones and tetracyclines, for these clinical isolates were determined by the broth microdilution method. Results For M. pneumoniae, the MIC90 values of the tested macrolides were: acetylmidecamycin (1 mg/L)&lt;josamycin (4 mg/L)&lt;midecamycin (8 mg/L)&lt;azithromycin (16 mg/L)&lt;erythromycin (&gt;128 mg/L). Thiamphenicol and chloramphenicol had the same MIC90 (2 mg/L). For Ureaplasma species, the MIC90 values were: acetylmidecamycin (0.25 mg/L)&lt;josamycin (0.5 mg/L)=midecamycin&lt;azithromycin (1 mg/L)=erythromycin. Chloramphenicol had a lower MIC90 (2 mg/L) than that of thiamphenicol (4 mg/L). For M. hominis, the MIC90 values were: acetylmidecamycin (0.25 mg/L)&lt;josamycin (0.5 mg/L)&lt;midecamycin (2 mg/L)&lt;azithromycin (&gt;128 mg/L)=erythromycin. The MIC90 values of chloramphenicol and thiamphenicol were 2 and 4 mg/L, respectively. Conclusions The results indicated that acetylmidecamycin and thiamphenicol are active in vitro against the most common mycoplasma species infecting humans, including those resistant to macrolides and fluoroquinolones. Acetylmidecamycin and thiamphenicol might be a promising option for clinicians to treat infections caused by Mycoplasma and Ureaplasma spp., particularly macrolide-resistant M. pneumoniae in paediatrics and fluoroquinolone-resistant M. hominis in adults. Further investigation of their clinical roles in treating infections caused by these organisms is warranted.

scholarly journals Avibactam potentiated the activity of both ceftazidime and aztreonam against S. maltophilia clinical isolates in vitro

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiuxia Lin ◽  
Hua Zou ◽  
Xian Chen ◽  
Menglu Wu ◽  
Deyu Ma ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Combined Therapy ◽  
Treatment Options ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Medical University ◽  
Selection Of

Abstract Background Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM), and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011–2018. Methods We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011–2018, a collection of 76 isolates were selected for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of CAZ, CAZ-AVI, ATM and ATM-AVI were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more active in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” or “Intermediate” with CAZ or ATM alone to “Susceptible” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 4-fold lower than the MIC of CAZ or ATM alone. Results For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03–64, 1–1024, 0.016–64, and 0.06–64 μg/mL, respectively. In combined therapy, AVI was active at restoring the activity of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs. 56.58%, P < 0.001), and MIC50 (2 μg/mL vs. 8 μg/mL, P < 0.05) when compared to CAZ. According to our definition, CAZ-AVI was more active in vitro than CAZ alone for 81.58% (62/76) of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79% vs.10.53%, P < 0.001) and MIC50 (2 μg/mL vs. 64 μg/mL, P < 0.001) when compared to ATM. According to our definition, ATM-AVI was also more active in vitro than ATM alone for 94.74% (72/76) of the isolates. Conclusions AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

scholarly journals Effect of Polysorbate 80 on Oritavancin Binding to Plastic Surfaces: Implications for Susceptibility Testing

2008 ◽  
Vol 52 (5) ◽  
pp. 1597-1603 ◽  
Author(s):  
Francis F. Arhin ◽  
Ingrid Sarmiento ◽  
Adam Belley ◽  
Geoffrey A. McKay ◽  
Deborah C. Draghi ◽  
...  
Keyword(s):  
Clinical Isolates ◽  
Polysorbate 80 ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Drug Concentrations ◽  
Broth Microdilution Method ◽  
Horse Blood ◽  
Lysed Horse Blood ◽  
Susceptibility Assay

ABSTRACT Oritavancin, a semisynthetic lipoglycopeptide with activity against gram-positive bacteria, has multiple mechanisms of action, including the inhibition of cell wall synthesis and the perturbation of the membrane potential. Approved guidelines for broth microdilution MIC assays with dalbavancin, another lipoglycopeptide, require inclusion of 0.002% polysorbate 80. To investigate the potential impact of polysorbate 80 on oritavancin susceptibility assays, we quantified the recovery of [14C]oritavancin from susceptibility assay plates with and without polysorbate 80 and examined the effect of the presence of polysorbate 80 on the oritavancin MICs for 301 clinical isolates from the genera Staphylococcus, Enterococcus, and Streptococcus. In the absence of polysorbate 80, [14C]oritavancin was rapidly lost from solution in susceptibility assay test plates: 9% of the input drug was recovered in broth at 1 h when [14C]oritavancin was tested at 1 μg/ml. Furthermore, proportionately greater losses were observed at lower oritavancin concentrations, suggesting saturable binding of oritavancin to surfaces. The inclusion of 0.002% polysorbate 80 or 2% lysed horse blood permitted the recovery of 80 to 100% [14C]oritavancin at 24 h for all drug concentrations tested. Concordantly, oritavancin MIC90s for streptococcal isolates, as determined in medium containing 2% lysed horse blood, were identical with and without polysorbate 80. In stark contrast, polysorbate 80 reduced the oritavancin MIC90s by 16- to 32-fold for clinical isolates of enterococci and staphylococci, which are typically cultured without blood. The results presented here provide evidence that the MIC data for oritavancin in the current literature significantly underestimate the potency of oritavancin in vitro. Moreover, the combination of data from MIC and [14C]oritavancin recovery studies supports the revision of the oritavancin broth microdilution method to include polysorbate 80 throughout the assay.

scholarly journals In Vitro Evaluation of The Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam Against 76 Stenotrophomonas Maltophilia Isolates From A Teaching Hospital in Chongqing

2020 ◽  
Author(s):  
Qiuxia Lin ◽  
Hua Zou ◽  
Xian Chen ◽  
Menglu Wu ◽  
Deyu Ma ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Combined Therapy ◽  
Treatment Options ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Medical University ◽  
Selection Of

Abstract Background: Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime-avibactam (CAZ-AVI) and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011-2018.Methods: We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011-2018, a collection of 76 isolates of which were available for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM) and aztreonam-avibactam (ATM-AVI) were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more effective in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” with CAZ or ATM alone to “Susceptible” or “Intermediate” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 2-fold lower than the MIC of CAZ or ATM alone.Results: For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03-64, 1-1024, 0.016-64, and 0.06-64 μg/mL, respectively. In combined therapy, AVI was effective at restoring the susceptibility of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs.56.58%, P<0.001), MIC50 (2μg/mL vs. 8μg/mL, P<0.05), and MIC distribution (P<0.001) when compared to CAZ. According to our definition, CAZ-AVI was more effective in vitro than CAZ alone for 84.21% of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79%vs. 10.53%, P<0.001), MIC50 (2μg/mL vs. 64μg/mL, P<0.001), and MIC distribution (P<0.001) when compared to ATM. According to our definition, ATM-AVI was also more effective in vitro than ATM alone for 97.37% of the isolates.Conclusions: AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

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