High rates of ofloxacin resistance in Mycobacterium tuberculosis among both new and previously treated patients in Tamil Nadu, South India.

N Selvakumar,Vanaja Kumar,Puneet Dewan,Soumya Swaminathan,S Balaji,S Prabuseenivasan,R Radhakrishnan,S Arunagiri,Gomathi Sekar,Aleyamma Thomas,V Chandrasekaran,T Kannan,Anil Kumar Tyagi

doi:10.1371/journal.pone.0117421

Abstract

Periodic drug resistance surveillance provides useful information on trends of drug resistance and effectiveness of tuberculosis (TB) control measures. The present study determines the prevalence of drug resistance among new sputum smear positive (NSP) and previously treated (PT) pulmonary TB patients, diagnosed at public sector designated microscopy centers (DMCs) in the state of Tamil Nadu, India. In this single-stage cluster-sampling prevalence survey, 70 of 700 DMCs were randomly selected using a probability-proportional to size method. A cluster size of 24 for NSP and a varying size of 0 to 99 for PT cases were fixed for each selected DMC. Culture and drug susceptibility testing was done on Lowenstein-Jensen medium using the economic variant of proportion sensitivity test for isoniazid (INH), rifampicin (RMP), ofloxacin (OFX) and kanamycin (KAN). Human Immunodeficiency Virus (HIV) status was collected from patient records. From June 2011 to August 2012, 1524 NSP and 901 PT patients were enrolled. Any RMP resistance and any INH resistance were observed in 2.6% and 15.1%, and in 10.4% and 30% respectively in NSP and PT cases. Among PT patients, multi drug resistant TB (MDR-TB) was highest in the treatment failure (35%) group, followed by relapse (13%) and treatment after default (10%) groups. Extensively drug resistant TB (XDRTB) was seen in 4.3% of MDR-TB cases. Any OFX resistance was seen in 10.4% of NSP, 13.9% of PT and 29% of PT MDR-TB patients. The HIV status of the patient had no impact on drug resistance levels. RMP resistance was present in 2.6% of new and 15.1% of previously treated patients in Tamil Nadu. Rates of OFX resistance were high among NSP and PT patients, especially among those with MDR-TB, a matter of concern for development of new treatment regimens for TB.

Highlights

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a major public health issue in most of developing countries, despite scaling up interventions to achieve global control [1]
Of the total 2425 patients enrolled in the study, 1524 were new smear positive TB (NSP) and 901 were previously treated cases (PT) cases
Our findings provide reassurance that multi drug resistant TB (MDR-TB) rates have remained stable in this region, but highlight the high rates of OFX resistance and ‘pre-XDR-TB’, due most likely to the widespread misuse of fluoroquinolones

Summary

Introduction

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a major public health issue in most of developing countries, despite scaling up interventions to achieve global control [1]. In 2011, there were an estimated 8.7 million new cases of TB (13% co-infected with HIV) and 1.4 million TB deaths, including one million deaths among HIV-negative patients and 0.43 million among HIV-positive patients [4]. Emergence of multi drug resistant TB (MDR-TB: organism resistant to isoniazid [INH] and rifampicin [RMP]) is a major hurdle for TB control programs especially in developing countries like India. The global report on drug resistance surveillance by the World Health Organization (WHO) estimated that 3.6% of new smear positive TB (NSP) cases and 20% of previously treated cases (PT) have MDR-TB [5]. A regular national drug resistance surveillance programme is imperative to monitor the levels of drug resistance among NSP and PT cases, and to assess the performance of national TB control programmes [6]

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