1.17. TB - the superbug Flashcards
M. tuberculosis complex description
- Nonmotile, nonsporing, noncapsulated, straight or slightly curved rods about 3 ×0.3μm in size.
- In sputum and other clinical specimens, may occur singly or in small clumps
- In liquid cultures, often grow as twisted rope-like colonies termedserpentine cords
- Slow generation time –divides once every 24 hours
- Optimal growth temp: 35-37°C, obligate aerobe
- Facultative intracellular pathogen
Cell wall -mycolic acids
- Long chain fatty acids
- Unique to mycobacteria
- Form a thick, waxy layer that is difficult to penetrate –resistance to acids and alkalis
- Aids in formation of biofilms
- Immune system: Specifically modulate immune response
- Aids in resistance to antibiotics
- Resistance to attack via osmotic lysis
- Lysozyme resistance
- Forms the “outer membrane”
M. tuberculosis complex: Acid fast bacteria
•Not classified as gram positive or gram negative (stains very weakly, or not at all)
•DNA-based molecular taxonomy groups mycobacteria with gram positive bacteria BUT distinctions between the mycobacterial cell wall and the standard gram-positive cell wall
•Acid fast staining procedure (ZiehlNeelsenstain): to promote uptake of dye
1. Primary stain: carbolfuchsin. By applying heat, allows penetration of the stain through the cell wall
2. De-stain with acid alcohol: mycolic acid residues retain the primary stain even after exposure to acid-alcohol –Thisresistance to decolorizationis required for an organism to be termed acid fast
3. Counterstain with methylene blue to highlight the background for easier microscopic recognition
Resistance to antibiotics
•Mycobacteria are inherently resistant to numerous antibiotics: attributable to the cell wall -low rate of diffusion through the cell wall
•Acquired resistance: almost exclusively through chromosomal mutations in genes required for antibiotic action
-Genes encoding the protein targets of the drugs
- Enzymes required for prodrug activation
•Egrifampicin resistance: single-nucleotide substitution mutations in small region of rpoB, the gene encoding the β-subunit of the DNA-dependent RNA polymerase
Rifampicin resistance in MTB complex: rifampicin resistance determining region (RRDR)
•Around 96% of mutations conferring rifampicin resistance are confined within an 81 base pair region of the rpoBgene
Molecular technologies to diagnose TB and provide rifampicin susceptibility: XpertMTB/RIFand MTBDRplus(binding probes extend across the RRDR
Drug-resistant tuberculosis (DR-TB)
active tuberculosis disease caused by Mycobacterium tuberculosis complex that are resistant to one or more anti-TB drugs.
Mono-resistant TB
Resistance to only one anti-TB drug, without resistance to other drugs
Poly-drug resistant TB
Resistance to more than one anti-TB drug, other than both isoniazid and rifampicin
Multidrug-resistant TB (MDR-TB)
Resistance to isoniazid and rifampicin with or without resistance to other anti-TB drugs
Rifampicin resistant TB (RR-TB)
Resistance to at least rifampicin, with or without resistance to other drugs. This category includes MDR-TB, rifampicin mono-resistant TB, pre-XDR-TB and XDR-TB.
Extensively drug-resistant TB (XDR-TB)
MDR-TB with resistance to any fluoroquinolone as well as one or more of the three second-line injectable drugs (amikacin, kanamycin or capreomycin). Given that South Africa is moving away from the routine use of the injectable agents, this term may have limited clinical relevance. When possible, resistance to individual medications used in the newly recommended regimens should be specified, including resistance to bedaquiline, clofazimine, delamanidand/or linezolid
Pre-XDR-TB
MDR-TB with additional resistance to either a second-line injectable agent or a fluoroquinolone. More appropriate to refer instead to fluoroquinolone-resistant RR-TB. However, pre-XDR TB with injectable resistance is still an exclusion criterion for the shorter regimen. This is because even though the injection is no longer used, resistance to it may be a marker for resistance to other medications in the shorter regimen.
