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Clin Infect Dis. 2015 Apr 15;60(8):1186-95. doi: 10.1093/cid/ciu1153. Epub 2014 Dec 23.

Clinical evaluation of tuberculosis viability microscopy for assessing treatment response.

Author information

1
Innovation for Health and Development (IFHAD), Laboratory for Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru Infectious Diseases and Immunity and Wellcome Trust Centre for global Health Research, Imperial College London, United Kingdom.
2
Innovation for Health and Development (IFHAD), Laboratory for Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru Innovacion por la Salud y el Desarollo (IPSYD), Asociación Benéfica Prisma, Lima, Peru.
3
Infectious Diseases and Immunity and Wellcome Trust Centre for global Health Research, Imperial College London, United Kingdom.
4
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Abstract

BACKGROUND:

It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis.

METHODS:

To assess treatment response, sputum samples (n=124) from unselected patients (n=35) with sputum microscopy-positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate.

RESULTS:

Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS=0.85; P<.0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P<.001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P=.4) or quantitative culture (P=.6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P<.001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P=.6).

CONCLUSIONS:

Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy.

KEYWORDS:

early bactericidal activity; fluorescein diacetate; multidrug-resistant tuberculosis; viability stain; vital stain tuberculosis

PMID:
25537870
PMCID:
PMC4370166
DOI:
10.1093/cid/ciu1153
[Indexed for MEDLINE]
Free PMC Article

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