European Society of Mycobacteriology - Instituto Nacional de Saúde ...

PP-109
PREVALENCE OF EFFLUX-MEDIATED RIFAMPICIN RESISTANCE
IN Mycobacterium tuberculosis CLINICAL ISOLATES
Carrie K. W. Au-Yeang, T. K. Au, Edward W. C. Chan, Raphael C. Y. Chan
Department of Microbiology, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, New Territories, Hong Kong
Rifampicin is one major ingredient in the cocktail-regimen used in treatment of Mycobacterium tuberculosis (MTB) infection.
Although mutations in the rpoB gene are considered the basis of rifampicin resistance, we noted that a significant
proportion of local resistant cases could not be attributed to mutations. Alternative mechanisms such as drug efflux
have been proposed. In order to evaluate the role of drug efflux mechanisms in mediating rifampicin resistance in MTB,
we examined the prevalence of efflux activities in rifampicin resistant isolates using three efflux inhibitors: reserpine,
carbonyl cyanide chlorophenylhydrazone and verapamil. Forty-two rifampicin resistant and nine drug susceptible MTB
clinical isolates were studied. The minimum inhibitory concentration (MIC) values for rifampicin were determined in the
presence and absence of efflux inhibitors. The magnitude of MIC reduction for each efflux inhibitor and the prevalence
of efflux-mediated resistance were examined. We found that among the three efflux inhibitors tested, significant MIC
reduction, ≥ 2-fold MIC decrease, was observed only for verapamil. 61% (31/51) of the test isolates had an MIC reduction
between 2 to 8-fold in the presence of verapamil. This verapamil-sensitive efflux-mediated MIC reduction effect
was much more apparent in rifampicin resistant isolates than the drug susceptible controls: 71% (30/42) versus 11%
(1/9). Likewise, this phenomenon was more prevalent in isolates resistant to 3 - 5 anti-tuberculosis drugs than isolates
resistant to 1 - 2 drugs: 77% (24/31) versus 55% (6/11). This data support the notion that drug efflux systems contribute
significantly to rifampicin resistance in MTB clinical isolates and highlight the need for determining the extent by which
these systems contribute to resistance to other anti-tuberculosis drugs.
This study is supported by a grant (08070292) from Research Fund for the Control of Infectious Diseases.
European Society of Mycobacteriology | 30 th Annual Congress | July 2009 | Porto - Portugal
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