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To the Editor: Drug-resistant tuberculosis (TB) has been identified as a major problem in the former Soviet Union, and was recently surveyed in the Aral Sea regions of Dashoguz (Turkmenistan) and Karakalpakstan (Uzbekistan) (1). However, few data are available for the Caucasian region and published reports have focused mainly on prisons (2,3). We report a drug resistance survey for first- and second-line anti-TB drugs conducted in Abkhazia, a Caucasian region of 8,600 km2 with approximately 250,000 inhabitants, at the western end of Georgia on the Black Sea. The collapse of the Soviet Union lead to disruption of TB control activities in all Eastern bloc regions (4). In Abkhazia, the shortage and poor quality of drugs, self-medication, and poor adherence to the therapy became even more evident during the war with Georgia in 1993 and the international embargo that followed. A TB program based on the World Health Organization/International Union against Tuberculosis and Lung Disease (WHO/IUATLD) recommendations was initiated in Abkhazia with the support of Medecins Sans Frontieres (MSF) in 1999. In 2000, monitoring of drug resistance was started for new cases and previously treated case-patients. The study was performed in collaboration with the Guliripchi TB Hospital, MSF, and the Istituto Superiore di Sanita (ISS), a WHO/IUATLD Supranational Reference Laboratory for anti-TB drug resistance. Sputa were collected from all patients attending Guliripchi TB Hospital in Sukhumi, the capital of Abkhazia, from September 2000 to April 2004. Patients were either referred by their practitioners or came spontaneously because TB was suspected. Diagnosis, treatment, and hospitalization were provided free. Samples were treated as previously described (5). Of 489 sputa collected from individual patients, 447 were culture positive (246 from new case-patients and 201 from previously treated case-patients) and 42 were culture negative; of these, >90% showed a negative, doubtful, or 1+ smear result. Susceptibility to first-line (streptomycin, isoniazid, rifampin, and ethambutol) and second-line (kanamycin, ethionamide, capreomycin, cycloserine, p-aminosalicylic acid, and ofloxacin) drugs was determined by the proportion method on Middlebrook 7H10 agar. The critical concentrations used were streptomycin, 2 µg/mL; isoniazid, 0.2 µg/mL; rifampin, 1 µg/mL; ethambutol, 5 µg/mL; kanamycin, 5 µg/mL; ethionamide, 5 µg/mL; capreomycin, 10 µg/mL; p-aminosalicylic acid, 2 µg/mL; and ofloxacin, 2 µg/mL (6–8). Cycloserine was used at a concentration of 30 µg/mL (9). If a strain was resistant to >1 first-line drugs, the susceptibility to all second-line drugs was determined. Data on resistance to the first- and second-line drugs are given in the Table. The strains isolated from 35.8% of the new cases and 57.2% of the previously treated case-patients were resistant to >1 first-line drugs. The highest monoresistance was seen for isoniazid and streptomycin in both new and previously treated case-patients, while monoresistance to rifampin and ethambutol was low ( 1 second-line drugs. Table First-line and second line antituberculosis drug resistance in 447 Mycobacterium tuberculosis strains collected in Abkhazia from September 2000 to April 2004* Few data have been reported on drug resistance to first- and second-line drugs in the former Soviet Union and in the Caucasian region (1–4). Overall, in Abkhazia, monoresistance to isoniazid was higher than in Karakalpakstan and Dashoguz (1), while monoresistance to streptomycin was lower. MDR-TB in new and previously treated case-patients showed levels intermediate between these 2 regions. Resistance to kanamycin and ethionamide was 14.3% and 12.8%, respectively, while resistance to ofloxacin was low (1.5%). Fluoroquinolones have not been commonly used in Abkhazia and former regions of the Soviet Union. Currently, regimens for the treatment of MDR-TB in Abkhazia combine an intensive phase for a minimum of 6 months with at least 4 drugs to which the MTB strain is susceptible, including 1 parenteral agent and 1 fluoroquinolone (ofloxacin), followed by a continuation phase of at least 15 months with >3 drugs. This is the first survey reporting drug susceptibility data for MTB within the Caucasus. It indicates that the prevalence of MDR strains is similar to that in other central Asia regions (1). Our results are representative of the present situation in Abkhazia since sampling systematically covered all TB cases for the period examined. The Guliripchi TB Hospital of Sukhumi is the only TB treatment center in the region, and all cases were included in the study. Overall, our data show that second-line drug resistance is present in Abkhazia, particularly among cases with MDR, and suggest the adoption of strategies for access and correct use of second-line drugs (10).

The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, i.e. strains resistant at least to isoniazid (INH) and rifampin (RMP), the two most powerful first-line drugs for the treatment of tuberculosis (TB), represents a worldwide health care problem. Patients with MDR strains should receive therapy based on individual drug susceptibility testing (DST) 1 including residual first-line (streptomycin, SM; ethambutol, EMB; and pyrazinamide, PZA) and second-line (ofloxacin, kanamycin, capreomycin, ethionamide, p-aminosalicylic acid, cycloserine) anti-TB drugs.

The ability of fluorescence resonance energy transfer, molecular-beacon, and TaqMan probes to detect single nucleotide polymorphism (SNP) in the presence of a wild-type allele was evaluated using drug resistance-conferring SNPs in mixed Mycobacterium tuberculosis DNA. It was found that both the absolute quantity and the ratio of alleles determine the detection sensitivity of the probe systems.

Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. Out of 366 patients, 60.4% were resistant to any first-line drugs and 21% had MDR-TB. Overall, 25% of all strains belong to the Beijing genotype, which was found to be strongly associated with the risk of MDR-TB (OR 25.9, 95% CI 10.2-66.0) and transmission (OR 2.8, 95% CI 1.6-5.0). One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community.