In Vitro Activities of the Novel Ketolide Telithromycin (HMR 3647) against Erythromycin-Resistant StreptococcusSpecies

ABSTRACT The in vitro susceptibilities of 184 erythromycin-resistant streptococci to a novel ketolide, telithromycin (HMR 3647), were tested. These clinical isolates included 111 Streptococcus pyogenes, 18 group C streptococcus, 18 group G streptococcus, and 37 Streptococcus pneumoniae strains. The MICs for all but eight S. pyogenes strains were ≤0.5 μg/ml, indicating that telithromycin is active in vitro against erythromycin-resistant Streptococcus strains. All strains for which MICs were ≥1 μg/ml had an erm(B) resistance gene and six strains for which MICs were ≥4 μg/ml had a constitutiveerm(B) gene (MIC range, 4 to 64 μg/ml). Interestingly, for S. pneumoniae strains with a constitutiveerm(B) gene, MICs were ≤0.25 μg/ml (MIC range, ≤0.008 to 0.25 μg/ml). Our in vitro data show that for S. pyogenes strains which constitutively express theerm(B) methylase gene, MICs are so high that the strains might be clinically resistant to telithromycin.

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In vitro activity of telithromycin (HMR 3647) against Greek Streptococcus pyogenes and Streptococcus pneumoniae clinical isolates with different macrolide susceptibilities

Clinical Microbiology and Infection ◽

10.1046/j.1469-0691.2003.00572.x ◽

2003 ◽

Vol 9 (7) ◽

pp. 704-707 ◽

Cited By ~ 14

Author(s):

S. Ioannidou ◽

P.T. Tassios ◽

L. Zachariadou ◽

Z. Salem ◽

M. Kanelopoulou ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Streptococcus Pyogenes ◽

Vitro Activity ◽

Clinical Isolates ◽

In Vitro Activity

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In Vitro Activities of DX-619 and Comparison Quinolones against Gram-Positive Cocci

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00011-06 ◽

2006 ◽

Vol 50 (6) ◽

pp. 2255-2257 ◽

Cited By ~ 4

Author(s):

Paul A. Wickman ◽

Jennifer A. Black ◽

Ellen Smith Moland ◽

Kenneth S. Thomson

Keyword(s):

Staphylococcus Aureus ◽

Streptococcus Pneumoniae ◽

Streptococcus Pyogenes ◽

Vitro Activity ◽

The Novel ◽

In Vitro Activity ◽

Coagulase Negative Staphylococci ◽

Gram Positive ◽

Gram Positive Cocci

ABSTRACT The in vitro activity of the novel quinolone DX-619 was compared to those of currently available quinolones against U.S. clinical isolates of Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp., Streptococcus pyogenes, and Streptococcus pneumoniae. DX-619 was the most potent quinolone overall, indicating possible utility as an anti-gram-positive quinolone.

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In vitro activity of thiamphenicol against Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes clinical isolates

Clinical Microbiology and Antimicrobial Chemotherapy ◽

10.36488/cmac.2021.1.92-99 ◽

2021 ◽

Vol 23 (1) ◽

pp. 92-99

Author(s):

Nataly V. Ivanchik ◽

Мarina V. Sukhorukova ◽

Аida N. Chagaryan ◽

Ivan V. Trushin ◽

Andrey V. Dekhnich ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Haemophilus Influenzae ◽

Streptococcus Pyogenes ◽

Vitro Activity ◽

Clinical Isolates ◽

In Vitro Activity ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Clinical Breakpoints

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.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.3.783-786.2002 ◽

2002 ◽

Vol 46 (3) ◽

pp. 783-786 ◽

Cited By ~ 51

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.

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Development of a New Experimental Model of Penicillin-ResistantStreptococcus pneumoniae Pneumonia and Amoxicillin Treatment by Reproducing Human Pharmacokinetics

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.10.2484 ◽

1999 ◽

Vol 43 (10) ◽

pp. 2484-2492 ◽

Cited By ~ 38

Author(s):

Lionel Piroth ◽

Laurent Martin ◽

Alexis Coulon ◽

Catherine Lequeu ◽

Michel Duong ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Animal Models ◽

Antibacterial Agents ◽

Human Pharmacokinetics ◽

Bacterial Clearance ◽

Cumulative Survival ◽

Microbiological Criteria ◽

Vitro Data ◽

In Vitro Data

ABSTRACT The increase of penicillin-resistant Streptococcus pneumoniae (PRSP) pneumonia results in a greater risk of antibiotic treatment failure. In vitro data are not sufficient predictors of clinical efficacy, and animal models may be insufficiently contributive, since they often use immunocompromised animals and do not always respect the human pharmacokinetics of antibiotics. We developed an experimental PRSP pneumonia model in immunocompetent rabbits, by using intrabronchial instillation of PRSP (MIC = 4 mg/liter), without any adjuvant. This reproducible model was used to assess amoxicillin efficacy by reproducing human serum pharmacokinetics following 1-g oral or intravenous administrations of amoxicillin every 8 h. Evaluation was performed by using clinical, CT scan, macroscopic, histopathologic, and microbiological criteria. Experimental pneumonia in untreated rabbits was similar to untreated severe human bacteremic untreated pneumonia; in both rabbits and humans, (i) cumulative survival was close to 50%, (ii) red or gray lung congestion and pleuritis were observed, and (iii) lung and spleen concentrations reached 5 and 4 log10 CFU/g. A 48-h treatment resulted in a significant bacterial clearance in the lungs (1.53 versus 5.07 log10 CFU/ml, P < 0.001) and spleen (1.00 versus 4.40 log10 CFU/ml,P < 10−6) and a significant decrease in mortality (0% versus 50%, P = 0.02) in treated versus untreated rabbits. No difference was observed on macroscopic and histopathologic lesions between treated and untreated rabbits (P = 0.36 and 0.78, respectively). Similar results were obtained by using a fully penicillin-susceptible S. pneumoniae strain (MIC = 0.01 mg/liter). Our findings suggest that (i) this new model can be contributive in the evaluation of antibacterial agents and (ii) 1 g of amoxicillin three times a day may be sufficient to treat PRSP pneumonia in immunocompetent humans.

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In Vitro Data Reveals Potential Novel Mechanism of Action of Teriflunomide on CNS Microglia and Astrocytes

10.26226/morressier.59a3eda8d462b8028d8951bb ◽

2017 ◽

Author(s):

Andrea Edling

Keyword(s):

Mechanism Of Action ◽

Vitro Data ◽

In Vitro Data

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Faculty Opinions recommendation of Simulation and prediction of in vivo drug metabolism in human populations from in vitro data.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1091007.544382 ◽

2007 ◽

Author(s):

Marival Bermejo

Keyword(s):

Drug Metabolism ◽

Human Populations ◽

In Vivo Drug Metabolism ◽

Vitro Data ◽

In Vitro Data

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Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

Alternatives to Laboratory Animals ◽

10.1177/026119299302100209 ◽

1993 ◽

Vol 21 (2) ◽

pp. 173-180

Author(s):

Gunnar Johanson

Keyword(s):

Risk Assessment ◽

Whole Body ◽

External Exposure ◽

Target Dose ◽

Toxic Response ◽

Route Of Exposure ◽

Vitro Data ◽

In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

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Lymphocutaneous spread of Mycobacterium elephantis in an immunocompetent individual: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x211034913 ◽

2021 ◽

Vol 9 ◽

pp. 2050313X2110349

Author(s):

Brett D Edwards ◽

Ranjani Somayaji ◽

Dina Fisher ◽

Justin C Chia

Keyword(s):

Case Report ◽

Chronic Lung Disease ◽

Contaminated Soil ◽

Lung Abscess ◽

Immunocompetent Individual ◽

First Case ◽

Antimycobacterial Agents ◽

Vitro Data ◽

In Vitro Data

Mycobacterium elephantis was first described when isolated from an elephant that succumbed to lung abscess. However, despite this namesake, it is not associated with animals and has been described most often as a probable colonizer rather than pathogen in humans with chronic lung disease. In this report, we describe the first case of lymphocutaneous infection from M. elephantis, likely as a result of cutaneous inoculation with contaminated soil. This offers further evidence to its capabilities as a pathogen. We provide a review of the limited prior reports of M. elephantis and outline the available in vitro data on efficacy of various antimycobacterial agents.

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