Extensively Drug‐Resistant<i>Mycobacterium tuberculosis</i>during a Trend of Decreasing Drug Resistance from 2000 through 2006 at a Medical Center in Taiwan

Chiu

Antimicrob Agents Chemother

et al. 2016

In order to correlate the mutations inside the entire gyrA and gyrB genes with the level of resistance to ofloxacin (OFX) and moxifloxacin (MFX) in isolates of multidrug-resistant Mycobacterium tuberculosis (MDR-TB), a total of 111 isolates were categorized into OFX-susceptible (MIC, <2 g/ml) and low-level (MIC, 4 to 8 g/ml) and high-level (MIC, >16 g/ml) OFX-resistant isolates and MFX-susceptible (MIC, <0.5 g/ml) and low-level (MIC, 1 to 2 g/ml) and high-level (MIC, >4 g/ml) MFXresistant isolates. Resistance-associated mutations inside the gyrA gene were found in 30.2% of OFX-susceptible and 72.5% and 72.2% of low-level and high-level OFX-resistant isolates and in 28.6% of MFX-susceptible and 58.1% and 83.9% of low-level and high-level MFX-resistant isolates. Compared with OFX-susceptible isolates, low-level and high-level OFX-resistant isolates had a significantly higher prevalence of mutations at gyrA codons 88 to 94 (17.0%, 65.0%, and 72.2%, respectively; P < 0.001) and a higher prevalence of the gyrB G512R mutation (0.0%, 2.5%, and 16.7%, respectively; P ‫؍‬ 0.006). Similarly, compared with MFXsusceptible isolates, low-level and high-level MFX-resistant isolates had a significantly higher prevalence of mutations at gyrA codons 88 to 94 (14.3%, 51.6%, and 80.6%, respectively; P < 0.001) as well as a higher prevalence of the gyrB G512R mutation (0.0%, 0.0%, and 12.9%, respectively; P ‫؍‬ 0.011). D94G and D94N mutations in gyrA and the G512R mutation in gyrB were correlated with high-level MFX resistance, while the D94A mutation was associated with low-level MFX resistance. The prevalence of mutations at gyrA codons 88 to 94 and the gyrB G512R mutation were higher among fluoroquinolone (FQ)-susceptible East Asian (Beijing) and Indo-Oceanic strains than they were among Euro-American strains, implying that molecular techniques to detect FQ resistance may be less specific in areas with a high prevalence of East Asian (Beijing) and Indo-Oceanic strains. F luoroquinolones (FQs) are used as second-line drugs for the treatment of tuberculosis (TB). These broad-spectrum antibacterial agents with bactericidal activity against Mycobacterium tuberculosis exert their bactericidal effects by inhibiting mycobacterial DNA gyrase activity, which prevents bacterial DNA from unwinding and replicating (1-3).Moxifloxacin (MFX), a "fourth-generation" FQ, has been shown to have better activity against M. tuberculosis than ofloxacin (OFX) and is recommended by the World Health Organization (WHO) for the treatment of multidrug-resistant TB (MDR-TB; defined as resistant to at least two of the most effective antituberculosis drugs, isoniazid and rifampin) (2, 3). Unfortunately, the widespread use of FQs to treat bacterial infections has led to the emergence of FQ-resistant MDR-TB and extensively drug-resistant TB (XDR-TB; defined as MDR-TB resistant to any FQ and a second-line injectable drug) (4, 5), thereby complicating patient care.Mutations in genes encoding DNA gyrase subunits gyrA and gyrB are the most common mechanism conveying ...

Section: Selection Of Isolatesmentioning

confidence: 99%

“…Unfortunately, the widespread use of FQs to treat bacterial infections has led to the emergence of FQ-resistant MDR-TB and extensively drug-resistant TB (XDR-TB; defined as MDR-TB resistant to any FQ and a second-line injectable drug) (4,5), thereby complicating patient care.…”

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confidence: 99%

Mutations in gyrA and gyrB among Fluoroquinolone- and Multidrug-Resistant Mycobacterium tuberculosis Isolates

Chiu

Antimicrob Agents Chemother

et al. 2016

European Respiratory Journal

“…First-line drugs were reported to be available in all studies, and the vast majority of cohorts had access to all second-line drugs [9][10][11][12][16][17][18][19][20][21][22][23][24]. Linezolid was reported to be available in only three XDR-TB MANAGEMENT G. SOTGIU ET AL. …”

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confidence: 99%

Epidemiology and clinical management of XDR-TB: a systematic review by TBNET

Sotgiu¹,

Ferrara²,

Matteelli³

et al. 2009

162

132

Extensively drug-resistant tuberculosis (XDR-TB) is present in all regions and poses serious challenges for public health and clinical management. Laboratory diagnosis is difficult and little evidence exists to guide clinicians in treating people with XDR-TB effectively. To summarise the available data on diagnosis and treatment, the current authors performed a systematic review on 13 recent studies of the epidemiology and clinical management of XDR-TB.Studies that met inclusion criteria were reviewed, in order to assess methodology, treatment regimens and treatment outcomes.Meta-analysis of currently available data is not possible because of inconsistent definitions and methodologies. Data show that XDR-TB can be successfully treated in up to 65% of patients, particularly those who are not co-infected with HIV. However, treatment duration is longer and outcomes are in general poorer than for non-XDR TB patients.To strengthen the evidence for extensively drug-resistant tuberculosis diagnosis, treatment and prevention, future studies should: 1) be prospective in design; 2) adopt standardised, internationally accepted definitions; 3) use quality-assured laboratory testing for all first-and second-line drugs; and 4) collect data on an agreed-upon set of standard variables, allowing for comparisons across studies. Early diagnosis and aggressive management of extensively drugresistant tuberculosis provide the best chance of positive outcome, but prevention is still paramount.KEYWORDS: Extensively drug-resistant tuberculosis, microbiological diagnosis, outcomes, systematic review, treatment efficacy A ccording to the latest World Health Organization (WHO) estimates, approximately 9.2 million new cases of tuberculosis (TB) and 1.5 million TB-related deaths occurred in 2006. TB remains a global emergency [1]. TB treatment requires multiple antibiotics over 6 months or more to achieve cure but, for decades, no new and better drugs have been developed and licensed. In addition, drug-resistant strains of Mycobacterium tuberculosis have emerged as a serious problem. The prevalence of multidrugresistant (MDR) M. tuberculosis (defined as in vitro resistance to isoniazid and rifampicin, the two most potent first-line drugs for TB treatment) is now widely reported [2,3]. MDR strains are currently found in more than 15% of all new cases of TB in some areas of the former Soviet Union (Azerbaijan, Moldova, Ukraine and Tomsk Oblast (Russian Federation)), and in more than 10% in parts of China and other areas of the former Soviet Union (Latvia, Estonia, Kazakhstan, Uzbekistan, and Ivanovo and Mari El (both Russian Federation)) [4][5][6].Strains of M. tuberculosis resistant to second-line drugs are also emerging. Cases of extensively drug-resistant (XDR)-TB (defined as in vitro drug resistance to isoniazid and rifampicin plus any fluoroquinolone and at least one of the injectable drugs (capreomycin, kanamycin or amikacin)) have been described around the globe [7,8] Despite the growing amount of public awareness about TB dru...

European Respiratory Journal

“…However, the first reports of XDR-TB were in non-HIV-infected individuals from Europe, demonstrating higher risk of death and a longer time required for culture conversion [5,6]. Multiple convenience sample studies from Spain, Iran, Taiwan, and South Korea have been reported, which included treatment outcome data with subnational denominators [7][8][9][10][11][12][13][14]. Population-based MDR-TB and XDR-TB incidence data are now available from the United States [15], as well as from South Korea, Estonia, Peru and Tomsk (Russia), although the proportion of persons with TB infected with HIV in these locations was very low [12][13][14][16][17][18].…”

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confidence: 99%

Treatment outcome of multidrug/extensively drug-resistant tuberculosis in Latvia, 2000-2004

Leimane¹,

Dravniece²,

Riekstiņa³

et al. 2010

In the present study, we characterised drug-resistance patterns, compared treatment outcome between extensively and nonextensively drug-resistant tuberculosis (non-XDR-TB) cases, and assessed risk factors for poor outcome in a high-prevalence country that screens all TB patients for first-line anti-TB drug resistance.We reviewed drug susceptibility test results among all pulmonary TB cases in Latvia diagnosed from 2000-2004, as well as demographic and clinical characteristics, drug-resistance patterns, and treatment outcomes.During the 5-yr period, 1,027 multidrug-resistant tuberculosis (MDR-TB) cases initiated treatment. Among all cases, the proportion that experienced an outcome of cure or completion increased from 66.2 to 70.2% (p50.06 for linear trend). Among the 48 (4.7%) XDR-TB cases, 18 (38%) were cured, four (8%) died, three (6%) defaulted, and treatment failed in 23 (48%). In proportional-hazards analysis, characteristics significantly associated with poor outcome included XDR-TB, being retired, presence of bilateral cavitation, and previous MDR-TB treatment history for those aged o55 yrs.Overall, treatment success among all MDR-TB cases increased over time. Strategies to prevent transmission of XDR-TB and to further improve treatment outcome are crucial for the future of TB control in Latvia.