Eur J Clin Microbiol Infect Dis (2005) 24: 202–206 DOI 10.1007/s10096-005-1284-z
ARTICLE
O. S. Toungoussova · A. O. Mariandyshev · G. Bjune · D. A. Caugant · P. Sandven
Resistance of multidrug-resistant strains of Mycobacterium tuberculosis from the Archangel oblast, Russia, to second-line anti-tuberculosis drugs Published online: 2 March 2005 C Springer-Verlag 2005
Abstract Multidrug-resistant tuberculosis has become common all over the world, necessitating the inclusion of second-line drugs in treatment regimens. In the present study, the susceptibility of a selection of multidrugresistant strains of Mycobacterium tuberculosis isolated in the Archangel oblast, Russia, to second-line antituberculosis drugs was analysed. Susceptibility testing of 77 Mycobacterium tuberculosis strains was performed by the Bactec method using the following recommended drug concentrations: capreomycin 1.25 µg/ml; ethionamide 1.25 µg/ml; kanamycin 5 µg/ml; and ofloxacin 2 µg/ml. The majority of strains (92.2%) were resistant to ethionamide. High rates of drug resistance were also found for capreomycin (42.9%) and kanamycin (41.6%), while nearly all strains (98.7%) were susceptible to ofloxacin. The high rates of resistance to ethionamide, capreomycin, and kanamycin show the real burden of drug resistance in the region and pose a serious problem for the treatment of patients with multidrug-resistant tuberculosis.
O. S. Toungoussova () · G. Bjune Department of General Practice and Community Medicine, Faculty of Medicine, University of Oslo, P.O. Box 1130, Blindern, 0317 Oslo, Norway e-mail:
[email protected] Fax: +47-22850672 A. O. Mariandyshev Department of Phthisiopulmonology, Northern State Medical University, Troitsky Avenue 51, 163000 Archangel, Russia O. S. Toungoussova · D. A. Caugant · P. Sandven Division of Infectious Disease Control, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, 0403 Oslo, Norway
Introduction Multidrug-resistant (MDR) tuberculosis, i.e. tuberculosis resistant to at least isoniazid and rifampin [1], the most effective anti-tuberculosis drugs, is a serious health problem in many geographical settings of the world [2]. According to an estimation of the World Health Organization (WHO), nearly 50 million people worldwide are infected with MDR tuberculosis [3], and about 273,000 new cases of MDR tuberculosis occurred in the year 2000 [4]. In 1999–2002, the prevalence of MDR in the world varied from 0% to 14.2% [2]. Strains of MDR Mycobacterium tuberculosis are also frequently resistant to the other first-line anti-tuberculosis drugs, ethambutol and streptomycin [5]. Second-line drugs may be used as an alternative treatment regimen, but many of these drugs are not very effective. They are also expensive and have toxic side effects [6, 7]. Treatment of patients with MDR tuberculosis with second-line anti-tuberculosis drugs should preferably be based on the results of susceptibility testing. Reliable results of susceptibility testing to second line-drugs are the basic requirement of the directly observed treatment short course (DOTS)-Plus strategy [8], as they support sound clinical decision-making, which in turn can help prevent the emergence of resistance to additional drugs. Susceptibility testing of M. tuberculosis to second-line drugs is difficult, expensive, and not well standardised. An alternative is, therefore, to perform susceptibility testing of a sample of MDR strains in a region and to base the treatment of MDR tuberculosis on these results [7, 9]. An increasing demand for testing the susceptibility of M. tuberculosis strains to second-line drugs raises important methodological issues. Unfortunately, data on critical concentrations of second-line drugs are fragmentary or lacking altogether [10]. The WHO developed guidelines for drug susceptibility testing for second-line anti-tuberculosis drugs on the basis of culture on L¨owenstein-Jensen medium and the proportion method [9]. In 1999, Inderlied and Pfyffer [11] developed a basic protocol that defined appropriate critical concentrations of second-line drugs, allowing reliable susceptibility testing using the Bactec method [10].
203
Recommendations from that study have been accepted internationally. We have shown that the resurgence of tuberculosis in the Archangel oblast, located in the northwestern part of Russia, was accompanied by a rise in drug resistance of M. tuberculosis [5, 12]. The rates of MDR tuberculosis in the Archangel community among new (13.5%) and previously treated (60%) cases were higher than those described for other oblasts of Russia. The situation was worse in prison settings, where 34% of new cases of tuberculosis were caused by MDR strains. Thus, the implementation of alternative treatment regimens with second-line anti-tuberculosis drugs is imperative. The objective of the present study was to analyse M. tuberculosis resistance to second-line anti-tuberculosis drugs in the Archangel oblast by testing a selection of MDR strains obtained from patients in the community and in prisons. Materials and methods Mycobacterium tuberculosis strains The study was performed using a collection of clinical M. tuberculosis strains isolated from patients with pulmonary tuberculosis in the Archangel oblast during the period 1998–2002 [5, 12]. The collection was composed of strains isolated from patients prior to initiation of treatment with anti-tuberculosis drugs. The strains were isolated from all consecutively diagnosed patients during fixed time periods [5, 12], according to WHO guidelines [1]. For the present study, all 77 MDR strains, i.e. those resistant to at least isoniazid and rifampin [1], isolated from community patients (n=47; 61%) and prison patients (n=30; 39%) were selected. All strains were divided into two groups according to the case categories “new” or “previously treated” patients. New patients were defined as patients who had never received anti-tuberculosis drugs or had received them for less than 1 month prior to inclusion in the study [7, 13]. Previously treated patients included those who relapsed, those in whom treatment failed, and those who returned after default. Relapse was defined as recurrence of disease in a patient previously treated for tuberculosis who had been declared cured or who had completed treatment prior to becoming smear positive again [13, 14]. Failure was defined as a sputum-positive finding in a patient who had been receiving treatment for at least 5 months [13, 14]. Return after default was defined as the return of a patient who had interrupted treatment for more than 2 months before returning to the health facilities and being found sputum positive [13, 14]. According to our previously published studies [5, 15], 63 of the 77 (81.8%) strains included in the present study belonged to the W-Beijing genotype. The majority of these (84.4%) W-Beijing isolates were part of a cluster, whereas only 15.6% of the other isolates were clustered (p
