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Molecular mechanisms and clinical management of drug-resistant tuberculosis: An invincible enemy?

Abstract:

Drug-resistant tuberculosis is a global public health problem and is one of the main obstacles to reach the control objectives set worldwide, causing worse clinical results such as a lower cure rate and higher mortality. This can be classified as: multidrug-resistant TBC when it is resistant to isoniazid and rifampicin, the main first-line drugs that are used in therapeutic regimens; and extensively resistant TBC, which also has resistance to fluoroquinolones and injectable drugs. Currently, the molecular mechanisms behind this pharmacological resistance are known, being caused by polymorphisms of a single nucleotide, multinucleotides, insertions or deletions (indels) and rearrangement of chromosomal genes of prodrug activating enzymes, target proteins of drugs or pumps efflux, which has allowed the entry of new management strategies. Although the diagnosis initially was based on determining the phenotypic susceptibility by culture, its results are late and delay the adequate treatment, for this reason the molecular tests have been implemented that allow to make the diagnosis in hours, as well as to determine the pharmacological susceptibility in hours for Rifampicine or days for the other drugs, which allows to initiate an optimal therapeutic strategy. On the other hand, new drugs are already in clinical phases and other drugs approved for other pathologies have been repurposed to be used with tuberculosis. All these steps are being carried out to confront this old and apparent invincible enemy, so in the next few years its clinical and epidemiological implications will be known.