Epidemiology and Treatment of Multidrug Resistant Tuberculosis

Abstract

Multidrug resistant tuberculosis is now thought to afflict between 1 and 2 million patients annually. Although significant regional variability in the distribution of disease has been recorded, surveillance data are limited by several factors. The true burden of disease is likely underestimated. Nevertheless, the estimated burden is substantial enough to warrant concerted action. A range of approaches is possible, but all appropriate interventions require scale-up of laboratories and early treatment with regimens containing a sufficient number of second-line drugs. Ambulatory treatment for most patients, and improved infection control, can facilitate scale-up with decreased risk of nosocomial transmission. Several obstacles have been considered to preclude worldwide scale-up of treatment, mostly attributable to inadequate human, drug, and financial resources. Further delays in scale-up, however, risk continued generation and transmission of resistant tuberculosis, as well as associated morbidity and mortality. KeywordsTuberculosis; drug resistance; surveillance; management; epidemiology An estimated 489,139, or nearly 5% of all new cases of tuberculosis (TB) diagnosed in 2006 were multidrug resistant (MDR), that is resistant to isoniazid and rifampicin, the two most effective anti-TB agents. This represents an increase of 12% since 2004 and 56% since 2000. 1 An additional 1 to 1.5 million prevalent cases of MDR-TB were estimated in 2006, resulting in as many as 2 million people with active disease. 2 The successful treatment of MDR-TB requires the use of second-line drugs, which historically presented an insurmountable cost barrier in resource-poor settings. To alleviate this gap, the World Health Organization (WHO) established the Green Light Committee (GLC) in 2000 to facilitate access to and strictly supervise the use of second-line agents for TB control.Even with the inception of the GLC and a significant reduction in cost of second-line drugs, drug resistant TB continues to grow and challenge the current capacity in most settings. Recognition of the magnitude of the MDR-TB problem and its associated morbidity and mortality has motivated recent calls for increased research and scaled-up treatment. 3,4 Several recent, excellent articles have reviewed the molecular mechanisms of resistance, risk factors for drug resistant TB (DR-TB), DR-TB and HIV, and global epidemiology of TB. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] This article highlights the gaps in knowledge of the global epidemiology of MDR-TB, illustrates EPIDEMIOLOGY OF MDR-TB Drug Resistance and Multidrug TherapyDR-TB is defined as tuberculosis caused by a strain of Mycobacterium tuberculosis that grows, in vitro, in the presence of one or more antimycobacterial drugs. Spontaneous mutations leading to resistance occur at random in large populations of M. tuberculosis at a rate per cell division of 10 −10 for rifampin (RIF), 10 −8 for isoniazid (INH) and streptomycin, 10 −6 to 10 −8 for fluoroquinolones, 10 −7 for etham...

Rapid Detection of rpoB Gene Mutations Conferring Rifampin Resistance in Mycobacterium tuberculosis

“…Rates of MDR TB have been estimated to be 4.8% of the 9.8 million TB infections (42), but rates as high as 55% have been observed for previously treated patients (4). TB can be treated effectively if properly identified (28,29). However, delayed initiation of appropriate treatment in suspected MDR TB cases is associated with excess morbidity and nosocomial transmission (39).…”

Rolling Circle Amplification for Direct Detection of rpoB Gene Mutations in Mycobacterium tuberculosis Isolates from Clinical Specimens

“…The two most important drugs used to treat TB are isoniazid (INH) and rifampin (RIF). Inadequate or inappropriate therapy, together with long and costly treatment courses, often result in the emergence of drug resistance (2). Multidrug-resistant (MDR) Mycobacterium tuberculosis strains-defined as bacillary resistance to at least INH and RIF-have spread rapidly and become a global health emergency (3).…”

Role of fluoroquinolones in the treatment of tuberculosis

“…This is also apparent from the fact that development of resistance of MDR-TB strains to FQs is associated with poor treatment outcome. Additional development of resistance of MDR-TB strains to FQs is also one of two key defining conditions of XDR-TB [12][13][14][53][54][55]. Although initial studies were carried out with OFX-containing regimens, some studies and clinical trials involving MDR-TB patients in developed countries have also used LFX in treatment regimens.…”

“…Overall, ~440,000 cases of MDR-TB occurred in 2008, resulting in 150,000 deaths [12]. The MDR-TB is a major threat to global public health as it is more difficult to treat than drug-susceptible TB and often results in relapse or treatment failure [13][14][15][16]. It is also a risk factor for the emergence of extensively drug-resistant (XDR) TB (defined as infection with MDR-TB strains additionally resist-ant to a fluoroquinolone and an injectable anti-TB agent such as kanamycin, amikacin, capreomycin or viomycin) [12,17].…”

“…The FQs, particularly new generation FQs such as LFX, MFX and GFX due to their potent bactericidal activity and lack of cross-resistance with existing anti-TB drugs, have also been used extensively for the treatment of drug-resistant TB and are now regarded as one of the two most important second-line agents for the treatment of MDR-TB [22,28,31,36,51,52]. Several studies have shown that inclusion of a FQ (particularly mFQs) and an injectable aminoglycoside (kanamycin or amikacin) or cyclic peptide (capreomycin and viomycin) in multidrug treatment regimens has the maximum effect for a more favorable outcome in the treatment of MDR-TB [12][13][14][51][52][53][54]. This is also apparent from the fact that development of resistance of MDR-TB strains to FQs is associated with poor treatment outcome.…”