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 ◽  
...  

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.

2021 ◽  
Vol 23 (1) ◽  
pp. 92-99
Author(s):  
Nataly V. Ivanchik ◽  
Мarina V. Sukhorukova ◽  
Аida N. Chagaryan ◽  
Ivan V. Trushin ◽  
Andrey V. Dekhnich ◽  
...  

Objective. To determine in vitro activity of thiamphenicol and other clinically available antimicrobials against clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. Materials and Methods. We included in the study 875 clinical isolates from 20 Russian cities during 2018–2019. Among tested strains, 126 were H. influenzae, 389 – S. pneumoniae, 360 – S. pyogenes. Antimicrobial susceptibility testing was performed using broth microdilution method according to ISO 20776-1:2006. AST results were interpreted according to EUCAST v.11.0 clinical breakpoints. Results. The minimum inhibitory concentrations (MICs) of thiamphenicol did not exceed 2 mg/L for 94.4% of H. influenzae strains (MIC50 and MIC90 were 0.5 and 1 mg/L, respectively). Thiamphenicol was active against 76.9% of ampicillin-resistant H. influenzae strains (MIC of thiamphenicol < 2 mg/L). The MIC of thiamphenicol was in the range of 0.06–2 mg/L for 96.7% of S. pneumoniae strains (MIC50 and MIC90 were 0.5 and 2 mg/L, respectively). The MIC of thiamphenicol for 90.6% of S. pneumoniae strains with reduced susceptibility to penicillin (MIC of penicillin > 0.06 mg/L) did not exceed 2 mg/L. A total of 88.1% of S. pneumoniae strains resistant to erythromycin were highly susceptible to thiamphenicol (MIC < 2 mg/L). The MIC of thiamphenicol did not exceed 8 mg/L for 96.1% of S. pyogenes strains (MIC50 and MIC90 were 2 and 4 mg/L, respectively). Conclusions. Thiamphenicol was characterized by relatively high in vitro activity, comparable to that of chloramphenicol, against tested strains of H. influenzae, S. pneumoniae and S. pyogenes, including S. pneumoniae isolates with reduced susceptibility to penicillin.


2006 ◽  
Vol 50 (12) ◽  
pp. 4027-4029 ◽  
Author(s):  
Lucio Vera-Cabrera ◽  
Barbara A. Brown-Elliott ◽  
Richard J. Wallace ◽  
Jorge Ocampo-Candiani ◽  
Oliverio Welsh ◽  
...  

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.


2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Meredith A. Hackel ◽  
Olga Lomovskaya ◽  
Michael N. Dudley ◽  
James A. Karlowsky ◽  
Daniel F. Sahm

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.


2020 ◽  
Author(s):  
Qiuxia Lin ◽  
Hua Zou ◽  
Xian Chen ◽  
Menglu Wu ◽  
Deyu Ma ◽  
...  

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.


2001 ◽  
Vol 45 (6) ◽  
pp. 1860-1867 ◽  
Author(s):  
David M. Livermore ◽  
Michael W. Carter ◽  
Simone Bagel ◽  
Bernd Wiedemann ◽  
Fernando Baquero ◽  
...  

ABSTRACT Ertapenem (MK-0826, L-749,345) is a 1-β-methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the familyEnterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC90s) of ≤1 μg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC90s for these groups remained ≤0.5 μg/ml.Acinetobacter spp. and Pseudomonas aeruginosawere also much less susceptible to ertapenem than imipenem, and mostEnterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of ≥16 μg/ml, was seen in only 3 of 1,611 strains of the familyEnterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of ≤2 μg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 μg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 μg/ml and one required an MIC of 4 μg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 μg/ml. These streptococci also had diminished susceptibilities to other β-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.


2020 ◽  
Vol 75 (6) ◽  
pp. 1513-1517 ◽  
Author(s):  
Na Wang ◽  
Yunheng Zhou ◽  
Hong Zhang ◽  
Yang Liu

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.


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