A Report on Drug Resistance Patterns of Mycobacterium tuberculosis Isolates in Northern Iran.

BACKGROUND: There are limited data on the Mycobacterium tuberculosis (MTB) drug resistance in regions located at the proximity of the Caspian Sea. We aimed to assess the drug resistance patterns of the MTB isolates to anti-tuberculosis drugs in patients from four northern provinces of Iran between April 2013 and March 2019. METHODS: Drug susceptibility testing (DST) was performed by culturing MTB isolates on the Lowenstein-Jensen medium using the proportion method. RESULTS: Out of 963 MTB isolates, 927 (96.3%) were recovered from Iranian cases and 36 (3.7%) were from Afghan immigrants. Based on DST, 59 (6.1%) showed any drug resistance pattern, while 18 patients (1.9%) were multidrug-resistant (MDR) or rifampicin-resistant (RR). Resistance to streptomycin (STR), isoniazid (INZ), rifampicin (RIN), and ethambutol (ETL) was reported in 33 (3.4%), 28 (2.9%), 18 (1.9%), and 12 isolates (1.2%), respectively. CONCLUSION: The rate of MDR/RR in four northern provinces of Iran was in line with previous reports from the World Health Organization. Due to proximity to the former Soviet Union, which had a high rate of MDR/RR isolates, the establishment of cross-border tuberculosis (TB) control strategies is recommended to reduce the possibility of MDR-TB transmission. Moreover, DST for all TB cases is recommended as an effective diagnostic tool for optimal monitoring and control of drug resistance in these areas. Future studies with a molecular epidemiology approach will be needed to evaluate the transmission dynamics of MTB in these regions.

Evaluation of the Xpert MTB/RIF test accuracy for diagnosis of tuberculosis in areas with a moderate tuberculosis burden.

The Xpert MTB/RIF assay (Xpert) is a molecular assay used for direct detection of Mycobacterium tuberculosis (MTB) in clinical specimens. In this study, we aimed to assess the accuracy of the Xpert assay for the diagnosis of tuberculosis (TB) in TB suspected patients from the northern region of Iran. The obtained results were compared with the culture method. The sputum specimens were examined using the Xpert assay, smear microscopy, and solid culture media as a reference diagnostic tool. Among 293 presumptive TB cases, 92 (31.4%) were positive according to the culture method. The Xpert method detected 88 (95.7%) cases that were positive according to the culture method, compared with 78 (84.8%) positive cases according to smear microscopy. The overall sensitivity and specificity of the Xpert method for TB diagnosis were 95.7% and 99%, respectively. Also, the sensitivity and specificity for smear microscopy were 84.8% and 97.5%, respectively. The Xpert assay showed high overall sensitivity and specificity; thus, it can be effectively used for the early and accurate diagnosis of MTB in TB endemic areas. In addition, the agreement between semi-quantitative results of Xpert and smear microscopy assays could be helpful in evaluating transmission potential in TB patients.

Spoligotype and Drug Susceptibility Profiles of Mycobacterium tuberculosis Complex Isolates in Golestan Province, North Iran.

INTRODUCTION: Despite the moderate incidence of tuberculosis (TB) in many parts of Iran, Golestan province had a permanently higher TB incidence rate than the national average. Moreover, Golestan province receives immigrants, mainly from TB-endemic areas of Iran and neighbor countries. Here, we aimed to characterize the circulating Mycobacterium tuberculosis complex (MTBC) isolates in terms of the spoligotype and drug resistance patterns, across Golestan province. MATERIALS AND METHODS: A set of 166 MTBC isolates was collected during July 2014 to July 2015 and subjected to drug susceptibility testing for first- and second-line anti-TB drugs and spoligotyping. RESULTS: Of 166 MTBC isolates, 139 (83.7%) isolates were assigned to 28 spoligotype international types (SITs). The most frequent SITs were SIT127/Ural-2 (n=25, 15.1%), followed by SIT1/Beijing (n=21, 12.7%) and SIT3427/Ural-2 (n=18, 10.8%). The set of 18 isolates (10.8%) showed resistance to at least one drug, which mainly belonged to SIT1/Beijing (n=7, 38.9%), orphan patterns (n=4, 22.2%) and SIT357/CAS1-Delhi (n=3, 16.7%). In addition, four isolates (2.4%) were resistant to pyrazinamide. The analysis of mutation corresponded to resistance to rifampin and isoniazid showed that two isolates had Ser531Leu substitution in rpoB, four isolates had Ser315Thr substitution in katG and one isolate had [C(-15)T] in inhA locus. CONCLUSION: High diversity in spoligotypes of the MTBC isolates and lack of dominant genotype might be due to residence of immigrants in this region and consequent reactivation of latent infection. In addition, due to the presence of extensively drug-resistant (XDR) isolates in Golestan province, it is important to conduct future studies to determine transmission pattern of drug-resistant isolates in this region.

Genetic diversity of Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in the capital of Iran.

OBJECTIVES: Evaluation of the genetic diversity of Mycobacterium tuberculosis (M.tb) and determining if the association between a specific genotype and the site of infection is crucial. Accordingly, the current study aimed at comparing predominant M.tb genotypes in pulmonary (PTB) and extrapulmonary tuberculosis (EPTB) isolates circulating in the capital of Iran. METHODS: The genetic diversity of culture-confirmed PTB and EPTB isolates were evaluated by Spoligotyping and MIRU-VNTR (mycobacterial interspersed repetitive-unit-variable-number tandem-repeat) typing methods. Genotyping data were analyzed with SITVIT, MIRU-VNTRplus, and TBminer databases. To assess adjusted associations, chi-square/the Fisher exact test and multiple logistic regression model were applied. RESULTS: URAL2 (NEW-1) (28/88; 31.8%) and CAS1-DELHI (25/84; 29.8%) genotypes were predominant in EPTB and PTB strains, respectively. Based on MIRU-VNTR typing, 158 different MIRU-VNTR patterns were identified. Clustering rate and minimum estimate of the proportion of TB caused by recent transmission was 4.1% and 8.1%, respectively. CONCLUSIONS: The current study provided new insight into circulating genotypes of M.tb in PTB and EPTB patients in Tehran, Iran. This low percentage of TB transmission rate, demonstrated that mode of TB transmission was mainly associated with reactivation of latent TB rather than recently transmitted infection in this region. There was no significant difference in the association between the genotypes of M.tb strains and the site of the disease.

Genetic diversity of Mycobacterium tuberculosis complex isolates circulating in an area with high tuberculosis incidence: Using 24-locus MIRU-VNTR method.

We aimed to determine the genetic diversity, phylogenetic relationship and transmission dynamics of Mycobacterium tuberculosis complex (MTBC) genotypes in an area with high tuberculosis (TB) incidence. A set of 164 MTBC isolates from new TB patients of Golestan province, Iran, were subjected to genotyping using the standard 24-locus MIRU-VNTR method. Recent TB transmission was evaluated and phylogenetic relationships were analysed by minimum spanning tree and cluster-graph methods. Among the 164 isolates, 132 distinct patterns were detected. The 48 clustered isolates (29.3%) were distributed into 16 clusters ranging in size from 2 to 12 isolates. The most frequent genotype was Central Asian Strain/Delhi (CAS/Delhi) (n = 67, 40.8%), followed by NEW-1 (n = 53, 32.3%) and Beijing (n = 19, 11.6%) genotypes. Thirty five (72.9%) of NEW-1 isolates were recovered from immigrant patients and 84.2% (n = 16) of Beijing genotypes recovered from native cases. Statistically significant association was found between clustering and smoking (p = 0.047), drug addiction (p = 0.01) and prison history (p = 0.003). The estimated proportion of recent transmission was 19.5%. Presence of highly diverse MTBC isolates circulating in this province without a dominant genotype might be a consequence of importation of various genotypes in this area.

Mycobacterium tuberculosis Complex Drug Resistance in a High Tuberculosis Incidence Area from the WHO Eastern Mediterranean Region.

PURPOSE: The incidence of tuberculosis (TB) in Golestan province of Iran has been ranked 10th among countries of World Health Organization (WHO) Eastern Mediterranean Region. The province is residence of ethnically heterogeneous groups. However, there are limited data on Mycobacterium tuberculosis drug resistance in this province. The main aim of this study was to determine the resistance profile of M. tuberculosis complex (MTBC) isolates to first-line anti-TB drugs. METHODS: The clinical specimens were collected from 11807 cases diagnosed during this study. MTBC isolates were tested for susceptibility to first-line anti-TB drugs. RESULTS: A total of 176 new cases were diagnosed as culture positive for MTBC. There was one case that had multidrug-resistant (MDR) isolate and 18 (10.2%) had isolates that were resistant to at least one drug (any drug resistant). Resistance to streptomycin and isoniazid was noted in 15 (8.5%) and 5 isolates (2.8%), respectively. Also, a statistically significant association was observed between age groups and any drug resistance pattern (p = 0.022): 1-24 years vs. 25-45 years (p = 0.033), 25-45 years vs. >65 years (p = 0.010), 46-65 years vs. >65 years (p = 0.050). One third of any drug resistant isolates were obtained from TB patients of Persian ethnic group. CONCLUSION: Despite the high incidence of TB, the rate of MDR-TB in Golestan province was similar to those reported by WHO for Iranian new cases from other regions. One-tenth of the studied isolates showed any drug resistance pattern. This rate of any drug resistance implies the possibility of initial resistance of MTBC isolates circulating in this region.

Emergence of rifampicin, tigecycline, and colistin-resistant Acinetobacter baumannii in Iran; spreading of MDR strains of novel International Clone variants.

Multidrug-resistant Acinetobacter baumannii infections are serious challenges for clinicians because of A. baumannii propensity to acquire resistance to a wide spectrum of antimicrobial agents. In this study, 91 A. baumannii isolates from patients in tertiary intensive care units of three university hospitals in the north, central, and south of Iran were selected and tested for susceptibility to 22 antimicrobials; amplified restriction fragment polymorphism and multiplex polymerase chain reaction methods were used to determine genetic relationships and International Clone (IC) of A. baumannii isolates, respectively. Twenty-four genotypes were identified in A. baumannii isolates. About 91.2% of isolates categorized into 4 distinct clusters; one was more heterogeneous and observed across the three locations. A considerable number of the isolates (27.5%) belonged to the novel IC variant, sequence group 7 (SG7), which was geographically widespread in three locations. The drug resistance pattern showed that 14.2%, 20%, and 77% of the A. baumannii isolates were resistant to colistin, tigecycline, and rifampicin, respectively. Nine percent of isolates (8) showed simultaneous resistance to colistin, rifampicin, and tigecycline. Interestingly, all of them were susceptible to ampicillin-sulbactam and/or tobramycin. According to our results, SG7 could be considered as a pan-Iranian clone.