Time-kill kinetics of antibiotics active against rapidly growing mycobacteria.

The Journal of antimicrobial chemotherapy (2014-10-27)
Beatriz E Ferro, Jakko van Ingen, Melanie Wattenberg, Dick van Soolingen, Johan W Mouton
RESUMO

This study was conducted to generate basic pharmacodynamic information on the relationship between antibiotic concentrations and the growth of rapidly growing mycobacteria (RGM), and thereby contribute to a better understanding of current and future drug regimens for diseases caused by RGM. Type strains of Mycobacterium abscessus and Mycobacterium fortuitum were used; the MICs of cefoxitin, amikacin, moxifloxacin, linezolid and clarithromycin were determined by broth microdilution. Time-kill assays were performed, exposing the bacteria to 2-fold concentrations from 0.25 to 32 times the MIC at 30°C for 120 h. The sigmoid maximum effect (Emax) model was fitted to the time-kill curves data. The highest killing of M. abscessus was observed between 24 and 72 h; amikacin had the highest Emax (0.0427 h(-1)), followed by clarithromycin (0.0231 h(-1)) and cefoxitin (0.0142 h(-1)). For M. fortuitum, between 3 and 24 h, amikacin also showed the highest Emax (0.1933 h(-1)). There were no significant differences between the Hill's slopes determined for all the antibiotics tested against M. abscessus or M. fortuitum (P = 0.2213 and P = 0.2696, respectively). The total effect observed for all antibiotics was low and primarily determined by the Emax and not by the Hill's slope. The limited activity detected fits well with the poor outcome of antibiotic treatment for disease caused by RGM, particularly for M. abscessus. An evaluation of drug combinations will be the next step in understanding and improving current treatment standards.

MATERIAIS
Número do produto
Marca
Descrição do produto

Sigma-Aldrich
D-(+)-Glucose, ≥99.5% (GC)
Sigma-Aldrich
Oleic acid, ≥99% (GC)
Sigma-Aldrich
D-(+)-Glucose, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.5%
Sigma-Aldrich
Oleic acid, technical grade, 90%
Sigma-Aldrich
Dextrose, meets EP, BP, JP, USP testing specifications, anhydrous
Sigma-Aldrich
D-(+)-Glucose, ACS reagent
Supelco
Dextrose, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
D-(+)-Glucose, BioXtra, ≥99.5% (GC)
Sigma-Aldrich
Oleic acid, suitable for cell culture, BioReagent
Supelco
Oleic acid, analytical standard
Sigma-Aldrich
Oleic acid, natural, FCC
Sigma-Aldrich
D-(+)-Glucose, BioUltra, anhydrous, ≥99.5% (sum of enantiomers, HPLC)
Supelco
D-(+)-Glucose, analytical standard
Supelco
Clarithromycin, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
D-(+)-Glucose, suitable for mouse embryo cell culture, ≥99.5% (GC)
Sigma-Aldrich
Clarithromycin, ≥95% (HPLC)
Sigma-Aldrich
Oleic acid, meets analytical specification of Ph, Eur., 65.0-88.0% (GC)
Sigma-Aldrich
D-(+)-Glucose, tested according to Ph. Eur.
Sigma-Aldrich
D-(+)-Glucose, Hybri-Max, powder, BioReagent, suitable for hybridoma
Sigma-Aldrich
Clarithromycin, 96.0-102.0% (HPLC)
Clarithromycin for peak identification, European Pharmacopoeia (EP) Reference Standard
Clarithromycin, European Pharmacopoeia (EP) Reference Standard
Supelco
Oleic acid, Selectophore, ≥99.0%
Oleic acid, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
D-Glucose-12C6, 16O6, 99.9 atom % 16O, 99.9 atom % 12C