Biomaterial Database

CEM-101 activity against Gram-positive organisms. 2010

Leah N Woosley, and Mariana Castanheira, and Ronald N Jones

JMI Laboratories, North Liberty, IA 52317, USA.

The in vitro activity of CEM-101, a new fluoroketolide, was determined against Gram-positive organisms with various macrolide susceptibility profiles. Experiments for determination of the MICs and minimum bactericidal concentrations (MBCs), timed killing, single-step and multistep mutation rates, the erythromycin induction of resistance, postantibiotic effect (PAE), and drug interactions were performed for CEM-101; and the results were compared to those obtained with telithromycin, macrolides, and lincosamides. The MBCs of CEM-101 remained lower overall than those of telithromycin, and CEM-101 displayed a 2-fold greater potency than the ketolide. Timed-killing curve testing showed that CEM-101 had greater bactericidal activity than telithromycin (a >or=3-log(10)-CFU/ml decrease in the initial inoculum at 24 h) against the staphylococcal isolates tested. The propensity of CEM-101 to cause resistance was low, as determined from the rates of resistance determined in single-step mutational studies (<10(-8) or 10(-9)). In multipassaging studies, mutants of two strains (both of which were USA300 isolates) resistant to CEM-101 emerged. That number was comparable to the number resistant to clindamycin but less than the number resistant to telithromycin. Erythromycin induced CEM-101 resistance in Staphylococcus aureus and Streptococcus pneumoniae, similar to telithromycin; however, in seven of eight beta-hemolytic streptococci, CEM-101 resistance induction was not observed. CEM-101 showed a significant concentration- and exposure-dependent PAE against the strains tested, with the values ranging from 2.3 to 6.1 h for Gram-positive organisms (these times were longer than those for telithromycin). No antagonism was found in synergy analyses, with enhanced inhibition being most noted for combinations with CEM-101 and ceftriaxone, gentamicin, and trimethoprim-sulfamethoxazole. Overall, this new antimicrobial agent (CEM-101) showed good antimicrobial characteristics compared with those of the agents in its class and exhibited measured parameter values similar or superior to those of utilized comparators, indicating that CEM-101 warrants further clinical evaluation.

UI	MeSH Term	Description	Entries
D008826	Microbial Sensitivity Tests	Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).	Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D002443	Ceftriaxone	A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears.	Benaxona,Cefatriaxone,Cefaxona,Ceftrex,Ceftriaxon,Ceftriaxon Curamed,Ceftriaxon Hexal,Ceftriaxona Andreu,Ceftriaxona LDP Torlan,Ceftriaxone Irex,Ceftriaxone Sodium,Ceftriaxone Sodium, Anhydrous,Ceftriaxone, Disodium Salt,Ceftriaxone, Disodium Salt, Hemiheptahydrate,Lendacin,Longacef,Longaceph,Ro 13-9904,Ro-13-9904,Ro13-9904,Rocefalin,Rocefin,Rocephin,Rocephine,Tacex,Terbac,Anhydrous Ceftriaxone Sodium,Ro 13 9904,Ro 139904,Ro13 9904,Ro139904
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004917	Erythromycin	A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins.	Erycette,Erymax,Erythromycin A,Erythromycin C,Erythromycin Lactate,Erythromycin Phosphate,Ilotycin,T-Stat,Lactate, Erythromycin,Phosphate, Erythromycin,T Stat,TStat
D005839	Gentamicins	A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.	Gentamicin Sulfate (USP),Gentamycin,G-Myticin,Garamycin,Gentacycol,Gentamicin,Gentamicin Sulfate,Gentamycins,Gentavet,Genticin,G Myticin,GMyticin,Sulfate, Gentamicin
D006094	Gram-Positive Bacteria	Bacteria which retain the crystal violet stain when treated by Gram's method.	Gram Positive Bacteria
D000900	Anti-Bacterial Agents	Substances that inhibit the growth or reproduction of BACTERIA.	Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D013211	Staphylococcus aureus	Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
D013212	Staphylococcus epidermidis	A species of STAPHYLOCOCCUS that is a spherical, non-motile, gram-positive, chemoorganotrophic, facultative anaerobe. Mainly found on the skin and mucous membrane of warm-blooded animals, it can be primary pathogen or secondary invader.
D013296	Streptococcus pneumoniae	A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.	Diplococcus pneumoniae,Pneumococcus