Treatment of Tuberculosis in a Region with High Drug Resistance: Outcomes, Drug Resistance Amplification and Re-Infection

Maryline Bonnet,Juliet Melzer,Heinz Rinder,Mike Barer,Stefan Niemann,Francesco Checchi,Lanfranco Fattorini,Peter W Andrew,Germano Orrù,Manuela Pardini,Graziella Orefici,Francesca Meacci,Sabine Rüsch-Gerdes,Hasan Yesilkaya,Marco Rinaldo Oggioni,Thierry Jarosz,Francis Varaine

doi:10.1371/journal.pone.0023081

Abstract

IntroductionEmerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries.MethodsWe combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment.ResultsAt baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome.ConclusionIn Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals.

Highlights

Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries
Antituberculosis drug resistance is a serious threat to the achievement of the goal of the Stop TB partnership to eliminate tuberculosis (TB) as a public health problem by 2050 [1]
All non MDR-TB patients presenting with a Mycobacterium tuberculosis (MTB) resistance to at least H or R were given an adapted treatment regimen (Table 1)

Summary

Introduction

Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Antituberculosis drug resistance is a serious threat to the achievement of the goal of the Stop TB partnership to eliminate tuberculosis (TB) as a public health problem by 2050 [1]. Multidrug-resistance (MDR-TB) is defined as resistance to isoniazid (H) and rifampicin (R). Extensive drug-resistance (XDR-TB) is defined as MDR-TB plus resistance to a fluoroquinolone and any one of the second-line injectable drugs (capreomycin, amikacin or kanamycin). There are very few reports on treatment outcomes of regimens for mono- or poly-drug resistant TB. MDR-TB is associated with much poorer treatment outcomes compared with drug susceptible TB [4,5,6,7,8]

Methods

Results

Conclusion