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Chemotherapy. 2008;54(5):404-11. doi: 10.1159/000153314. Epub 2008 Sep 5.

Evaluation of killing kinetics of anti-tuberculosis drugs on Mycobacterium tuberculosis using a bacteriophage-based assay.

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1
AstraZeneca India Private Limited, Bangalore, India.

Abstract

BACKGROUND:

Killing kinetics studies on Mycobacterium tuberculosis are labour intensive and time consuming since it takes nearly 6-7 weeks to get the data from an experiment. A modified protocol is required to increase the throughput and expedite the results.

METHODS:

The killing kinetics of frontline drugs used for the treatment of tuberculosis was studied using 24-well plates and 2 methods of enumeration of survivors of M. tuberculosis following drug exposure, namely conventional plating (CFU) and a phage-based assay (plaque-forming units) using mycobacteriophage D29.

RESULTS:

The use of 24-well plates enabled in reducing the volume of the compound required for the studies and the phage-based enumeration speeded up the readout and compared well with the CFU-based enumeration.

CONCLUSION:

These results were in agreement with the earlier findings reported with respect to rifampicin, isoniazid and moxifloxacin. Also, this study shows for the first time the concentration-dependent killing of streptomycin, the time-dependent killing of ethambutol and the profiling of an experimental anti-mycobacterial compound by these 2 methods.

PMID:
18772589
DOI:
10.1159/000153314
[Indexed for MEDLINE]

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