Moralism and antibiotic resistance (22/01/22 13:43:51)
"The drug rifampicin (Rif) was initially developed in the 1960s, through modification of the natural isolate rifamycin B1. This novel, orally available, semi-synthetic agent, was shown to block the DNA-dependent RNA polymerase transcription initiation complex1, which confers its bactericidal activity. Since its discovery, Rif has become part of the backbone treatment for mycobacterial tuberculosis (TB) and leprosy infections and remains their most effective therapeutic available today2,3. The introduction of Rif to the TB multi-drug regimen reduced treatment time from 18 to 9 months4, which was further shortened to 6 months through introduction of pyrazinamide5. Inclusion of Rif as part of the multi-drug therapy regimen for leprosy in the mid-80 s reduced initial disease incidence from over 5 million to less than 200,000 cases in the two following decades6. Clinically, Rif is also reserved as a last line drug in multi-drug resistant (MDR) infections from Staphylococcus aureus (methicillin-resistant S. aureus; MRSA)7 and Pseudomonas aeruginosa8, among other infections7.
Following its introduction, resistance in the mycobacteria M. tuberculosis and M. leprae has developed as a direct result of evolutionary purging upon extended Rif exposure, primarily through missense mutations in drug targets or activating enzymes9. This phenomenon affected over half a million tuberculosis cases in 2018, of which, 78% were also classified as MDR-TB2."
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