A high prevalence of resistance in new tuberculosis cases of midwestern Brazil

Review: The Molecular Basis of Resistance in <i>Mycobaterium tuberculosis</i>

“…The mode of action of INH has been the subject of intensive studies, but it is known to generate a range of highly reactive compounds, including reactive oxygen species (ROS) such as superoxide, peroxide and hydroxyl radical [18], nitric oxide [19], reactive organic species such as isonicotinic-acyl radical or anion [20], and certain electrophilic species [21], which then attack multiple targets in M. tuberculosis. This attack results in pleiotropic effects like the inhibition of protein and nucleic acid synthesis [3,22]. Additionally, INH inhibits InhA, a nicotinamide adenine dinucleotide (NADH)-specific enoylacyl carries protein (ACP) reductase involved in fatty acid synthesis, resulting in loss of acid-fastness, probably as a result of the inhibition of the synthesis of mycolic acids, the long-chained found in the cell wall [23,24].…”

“…There are still many unexplained points concerning the action of INH on M. tuberculosis. Although there are still about 10% to 25% of INH-resistant strains in which neither of the known genes are affected by genetic modifications, it is known the most part of INH resistance is controlled by a complex genetic system that involves genes such as katG, inhA, ahpC, kasA, and ndh [3,26]. However, mutations in at least 16 other genes have been reported to be associated with INH resistance in clinical isolates [27].…”

“…Although TB is a curable disease, some factors have been identified as reasons for a mounting global TB burden, such as inadequate detection, cure rates, and Aids, resulting in individuals more susceptible to development of TB [1,2]. A steady increase in the frequency of Mycobacterium tuberculosis strains resistant to one or more agents commonly used to treat TB including isoniazid (INH), rifampin (RMP), streptomycin (STR), ethambutol (EMB), or pyrazinamide (PZA), components of the first-line multidrug therapy, is also of concern [3].…”

“…Treating TB in these patients is difficult, as they carry strains resistant to the two most efficient anti-TB drugs. These strains require treatment with second-line drugs that have limited treatment efficacy with more toxicity [3]. Additionally, in the last two decades, with the misuse of other drugs with anti-TB action, in particular the fluoroquinolones (FQs), the most effective among the second-line drugs, resistance has broadened to extensively drug-resistant TB (XDR-TB defined as MDR-TB with additional bacillary resistance to FQs and at least one second-line injectable drug) [9].…”

“…MDR-TB is a great concern in the antibiotic resistance pandemic due to the high risk of death, because patients can remain infected for months or years, and due to the high risk of contracting XDR-TB [3,11]. The Anti-tuberculosis Drug Resistance Surveillance Global Project published by the WHO and the International Union Against Tuberculosis and Lung Disease [9], reviewing the global status of TB, have pointed to an increasing incidence of drug-resistance TB in several countries in the world.…”