In-vitro activity of rifabutin against rifampicin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations

Abstract

The relationship between resistance to rifampicin and rifabutin and genetic alterations in the rpoB gene of 41 rifampicin-resistant isolates of Mycobacterium tuberculosis was evaluated. Although 35 isolates with rifampicin MICs > or = 32 mg/L were also rifabutin-resistant, six isolates with rifampicin MICs of 2-16 mg/L were susceptible to rifabutin (MIC < or = 0.5 mg/L). Mutations Asp516Val, Asp516Tyr, Leu533Pro and the double mutation Met515Ile and Leu533Pro influenced susceptibility to rifampicin, but not to rifabutin. All mutations at codons 531 and 526, except one isolate with a His526Cys mutation, correlated with resistance to both compounds.

Rapid Whole-Genome Sequencing of Mycobacterium tuberculosis Isolates Directly from Clinical Samples

“…The isolate from patient 5 was also phenotypically sensitive to rifampin, notwithstanding the presence of a L452P (codon 533 in E. coli) mutation in the rpoB gene. This mutation has also been associated with both high and low levels of rifampin resistance in the literature (26). A M. tuberculosis strain isolated from this patient in the past had been found to be rifampin resis- tant, suggesting either that this mutation results in a borderline phenotype or, alternatively, that a mixture of rifampin-resistant and -sensitive strains could have been present in this patient, although this was not detected in the sequencing data obtained from either the sputum or culture.…”

The Beginning of therpoBGene in Addition to the Rifampin Resistance Determination Region Might Be Needed for Identifying Rifampin/Rifabutin Cross-Resistance in Multidrug-Resistant Mycobacterium tuberculosis Isolates from Southern China

“…Among all incident TB cases globally, 3.6% are estimated to have MDR-TB (19), so a series of new drugs or alternatives for treatment of MDR-TB has been recommended by WHO since 2008 (20). Rifabutin (Rfb) has been one of the most efficacious drugs and the first-line oral agent recommended by WHO for MDR-TB, but Rfb sometimes has cross-resistance to rifampin (RIF) (2,4,15), which implies that the characterization of rpoB mutations in Rfb-resistant (Rfb r ) isolates is not completely the same as that of rpoB mutations in RIF-resistant (RIF r ) isolates. There have been few data supporting this conjecture to this day because of a lack of characterization of rpoB mutations in Rfb r clinical Mycobacterium tuberculosis isolates, so it is very hard to identify the Rfb r isolates from RIF r isolates, even though so many molecular assays for prediction of rifampin susceptibility have been established (8,1,13,3,5).…”

Rapid Detection of Mycobacterium tuberculosis Strains Resistant to Isoniazid and/or Rifampicin: Standardization of Multiplex Polymerase Chain Reaction Analysis

“…8,33,34 However, some studies have also reported other uncommon mutations inside and outside of the "hot-spot" region that were regularly or even systematically missed by standard, World Health Organization-endorsed DST methods. 35,36 The most sensitive limit of detection theoretically possible is three copies per PCR reaction, assuming a Poisson distribution. 37 The analytical sensitivity is defined as the concentration that can be detected with reasonable certainty (95% probability is commonly used) with a given analytical procedure.…”