ABSTRACT
A fluoroquinolone (FQ) resistance rate of 5.9% is reported in 205 Mycobacterium tuberculosis isolates from patients presenting to field clinics in Karachi, Pakistan (2006 to 2009). FQ resistance among multidrug-resistant (MDR) strains was 11.1% (5/45), and it was 4.9% (5/103) in M. tuberculosis strains susceptible to all first-line agents. Spoligotyping of resistant strains did not show dominance of one strain type. Our data reflect considerable FQ-resistant M. tuberculosis isolates and the need to consider inclusion of FQ within first-line sensitivity testing in such settings.
Subject(s)
Antitubercular Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Fluoroquinolones/pharmacology , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/epidemiology , Ambulatory Care Facilities/statistics & numerical data , Bacterial Typing Techniques , Drug Resistance, Multiple, Bacterial/genetics , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/genetics , Oligonucleotides/analysis , Pakistan/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/microbiology , Urban PopulationABSTRACT
Frequency of extensively drug-resistant tuberculosis in Pakistan increased from 1.5% in 2006 to 4.5% in 2009 (p<0.01). To understand the epidemiology, we genotyped selected strains by using spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats, and IS6110 restriction fragment length polymorphism analysis.
Subject(s)
Extensively Drug-Resistant Tuberculosis/epidemiology , Extensively Drug-Resistant Tuberculosis/microbiology , Mycobacterium tuberculosis/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Base Sequence , DNA Primers/genetics , DNA Transposable Elements , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Drug Resistance, Multiple, Bacterial/genetics , Female , Genotype , Humans , Interspersed Repetitive Sequences , Male , Middle Aged , Minisatellite Repeats , Molecular Epidemiology , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Pakistan/epidemiology , Polymorphism, Restriction Fragment Length , Young AdultABSTRACT
INTRODUCTION: Central Asian Strain 1 (CAS1) is the predominant Mycobacterium tuberculosis genotype in Pakistan. The occurrence of deletions in regions of differences (RDs) among CAS1 and other predominant genogroups in the country were investigated. METHODOLOGY: Using stratified random sampling, 235 M. tuberculosis (185 pulmonary; 50 extrapulmonary) strains were selected from 926 previously spoligotyped isolates, including 171 CAS strains (133 CAS1 (ST26), 38 CAS subfamily), 8 Beijing isolates, 47 isolates belonging to other previously defined ("Other") clusters, and 9 previously undefined Unique isolates. Commonly reported RD deletions, RD1, RD750, RD207, RD149, RD152, RD105, RD150, RD142 and RD181, were investigated using a PCR-based method. RESULTS: Deletions in RDs 750, 149 and 152 were identified among CAS strains, and in RDs 207, 149, 152, 105, 150, 142 and 181 in Beijing isolates. CAS1 strains showed more frequent RD149 deletions compared with CAS subfamily strains (p = 0.036), and more frequent RD152 deletions compared with "Other" clusters (p = 0.003). RD149 and RD152 deletions were more frequent in Beijing isolates compared with CAS1 strains (p < 0.001). Concurrent RD149 and RD152 deletions were more frequent in CAS1 compared with "Other" clusters (p < 0.001) and in Beijing strains compared with CAS1 (p < 0.001). No significant difference was detected in RD deletion patterns between pulmonary and extra pulmonary isolates. CONCLUSION: Higher frequencies of RD149 and RD152 deletions and of concurrent RD149 and RD152 deletions were found in CAS1 and Beijing strains compared with CAS subfamilies, "Other" clusters and Unique strains. No association between these deletions and disease presentation, pulmonary or extrapulmonary tuberculosis, was observed.