Sometimes drug-resistant TB occurs when bacteria become resistant to the drugs used to treat TB. This means that the drug can no longer kill the TB bacteria. Drug-resistant TB (DR TB) is spread the same way that drug-susceptible TB is spread. TB is spread through the air from one person to another.
How does drug resistance happen? Resistance to anti-TB drugs can occur when these drugs are misused or mismanaged. Examples include when patients do not complete their full course of treatment; when health-care providers prescribe the wrong treatment, the wrong dose, or length of time for taking the drugs; when the supply of drugs is not always available; or when the drugs …
Depending on the drugs concerned, resistance sometimes develops if the patient was receiving the functional equivalent of two drugs. For example, pyrazinamide is not considered a good companion drug to prevent resistance (1, 9). If a patient was functionally receiving only rifampicin and pyrazinamide in the initial phase (because of resistance to isoniazid and ethambutol), …
Jul 02, 2014 · Drug resistance in TB remains a man-made phenomenon. It emerges as a result of spontaneous gene mutations in M. tuberculosis that render the bacteria resistant to the most commonly used anti-TB drugs. Among the reasons for this, the non-compliance with the treatment regimens is signaled as the first cause.
Drug resistance in TB remains a man-made phenomenon. It emerges as a result of spontaneous gene mutations in M. tuberculosis that render the bacteria resistant to the most commonly used anti-TB drugs. Among the reasons for this, the non-compliance with the treatment regimens is signaled as the first cause.
Factors such as inadequate chemotherapy, poor drug quality, poor adherence to treatment, treatment failure, prior treatment, cavity pulmonary TB, HIV infection and diabetes accounted for the development of drug resistance in TB10,11.
Resistance to anti-TB drugs is caused mainly by mutations in drug target genes [4], the impermeability of M. tuberculosis cell wall, and the activity of efflux pumps [5, 6]. The presence of mutations in the target genes of antibiotics is considered the most important resistance mechanism in this bacterium [7].May 2, 2019
How is XDR TB spread? Drug-susceptible TB and XDR TB are spread the same way. TB bacteria are put into the air when a person with TB disease of the lungs or throat coughs, sneezes, shouts, or sings. These bacteria can float in the air for several hours, depending on the environment.
Listen to pronunciation. (... reh-ZIH-stunts) When cancer cells or microorganisms, such as bacteria or viruses, don't respond to a drug that is usually able to kill or weaken them.
Bacteria, not humans or animals, become antibiotic-resistant. These bacteria may infect humans and animals, and the infections they cause are harder to treat than those caused by non-resistant bacteria. Antibiotic resistance leads to higher medical costs, prolonged hospital stays, and increased mortality.Jul 31, 2020
Bacterial resistance to rifampin is caused by mutations leading to a change in the structure of the beta subunit of RNA polymerase. Such resistance is not an all-or-nothing phenomenon; rather, a large number of RNA polymerases with various degrees of sensitivity to rifampin have been found.
It's because taking them regularly until the prescription is complete helps ensure that all of the illness-causing bacteria are killed or prevented from multiplying. Even if your symptoms go away, the bacteria may still be present in your body.Oct 2, 2016
Antibiotic resistance evolves naturally via natural selection through random mutation, but it could also be engineered by applying an evolutionary stress on a population. Once such a gene is generated, bacteria can then transfer the genetic information in a horizontal fashion (between individuals) by plasmid exchange.
Multidrug resistance in bacteria occurs by the accumulation, on resistance (R) plasmids or transposons, of genes, with each coding for resistance to a specific agent, and/or by the action of multidrug efflux pumps, each of which can pump out more than one drug type.
Table 3Pattern of Drug ResistanceSuggested RegimenMinimum Duration of Treatment (mo)Rifampin and ethambutol (±streptomycin)Isoniazid, pyrazinamide, fluoroquinolone, plus an injectable agent for at least the first 2–3 mo Or a fully oral MDR-TB regimen per WHO guidelines187 more rows
Tuberculosis (TB)(https://www.cdc.gov/tb/publications/factsheets/general/tb.htm) is a disease caused by bacteria that are spread from person to per...
Multidrug-resistant TB (MDR TB) is caused by an organism that is resistant to at least isoniazid and rifampin, the two most potent TB drugs. These...
Extensively drug resistant TB (XDR TB) is a rare type of MDR TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least...
Resistance to anti-TB drugs can occur when these drugs are misused or mismanaged. Examples include when patients do not complete their full course...
Drug resistance is more common in people who: 1. Do not take their TB medicine regularly 2. Do not take all of their TB medicine as told by their d...
The most important thing a person can do to prevent the spread of MDR TB is to take all of their medications exactly as prescribed by their health...
Yes, there is a vaccine for TB disease called Bacille Calmette-Guérin (BCG)(https://www.cdc.gov/tb/publications/factsheets/prevention/bcg.htm). It...
If you think you have been exposed to someone with TB disease, you should contact your doctor or local health department about getting a TB skin te...
The general symptoms of TB disease include feelings of sickness or weakness, weight loss, fever, and night sweats. The symptoms of TB disease of th...
Because XDR TB is resistant to the most potent TB drugs, patients are left with treatment options that are much less effective. XDR TB is of special concern for persons with HIV infection or other conditions that can weaken the immune system.
Another way to prevent getting MDR TB is to avoid exposure to known MDR TB patients in closed or crowded places such as hospitals, prisons, or homeless shelters. If you work in hospitals or health-care settings where TB patients are likely to be seen, you should consult infection control or occupational health experts.
What is multidrug-resistant tuberculosis (MDR TB)? Multidrug-resistant TB (MDR TB) is caused by an organism that is resistant to at least isoniazid and rifampin, the two most potent TB drugs. These drugs are used to treat all persons with TB disease.
The symptoms of TB disease of the lungs may also include coughing, chest pain, and coughing up blood. Symptoms of TB disease in other parts of the body depend on the area affected. If you have these symptoms, you should contact your doctor or local health department.
If you think you have been exposed to someone with TB disease, you should contact your doctor or local health department about getting a TB skin test or TB blood test. And tell the doctor or nurse when you spent time with this person.
These bacteria can float in the air for several hours, depending on the environment. Persons who breathe in the air containing these TB bacteria can become infected. TB is not spread by. Shaking someone’s hand. Sharing food or drink. Touching bed linens or toilet seats. Sharing toothbrushes.
Examples include when patients do not complete their full course of treatment; when health-care providers prescribe the wrong treatment, the wrong dose, or length of time for taking the drugs; when the supply of drugs is not always available; or when the drugs are of poor quality.
Para-Amino Salicylic Acid. Although it was one of the first anti-tuberculosis drugs used in the treatment of the disease, together with isoniazid and streptomycin, para-amino salicylic acid or PAS is now considered as a second-line drug part of the treatment regimen for MDR-TB.
3.5. Cycloserine. Cycloserine is an oral bacteriostatic second-line anti-tuberculosis drug used in MDR-TB treatment regimens. It is an analog of d-alanine that by blocking the activity of d-alanine: d-alanine ligase inhibits the synthesis of peptidoglycan.
Mutations in the gene pncAremain as the most common finding in pyrazinamide resistant strains. These mutations, however, are scattered throughout the gene but most occur in a 561-bp region in the open reading frame or in an 82-bp region of its putative promoter [60,61].
The mode of action of bedaquiline is by inhibiting the ATP synthase of M. tuberculosis, which was a completely new target of action for an antimycobacterial drug. This mode of action was discovered by analyzing M. tuberculosisand M. smegmatismutants resistant to bedaquiline.
Kanamycin and amikacin inhibit protein synthesis by alteration at the level of 16S rRNA. The most common mutations found in kanamycin-resistant strains are at position 1400 and 1401 of the rrsgene, conferring high-level resistance to kanamycin and amikacin.
Tuberculosis (TB) remains as an important infectious disease and public health concern worldwide. According to the latest World Health Organization (WHO) report, there were an estimated 8.6 million incident cases of TB in 2012 and 1.3 million deaths were attributed to the disease.
MDR-TB is caused by strains of Mycobacterium tuberculosisthat are resistant to at least rifampicin and isoniazid, two key drugs in the treatment of the disease. Since 2006, it has been recognized the presence of even more resistant strains of M. tuberculosislabelled as extensively drug resistant (XDR)-TB [2,3,4].
For example, ABCC2 and ABCC3 can transport many chemotherapeutic drugs, including cisplatin, doxorubicin, and etoposide, and their overexpression results in multidrug resistance [ 62-65]. Mutations and overexpression of ABC transporters directly influence tumor sensitivity and drugs’ anticancer efficacy.
Acquired resistance can be a result of: (1) activation of second proto-oncogene that becomes the newly emerged driver gene; (2) mutations or altered expression levels of the drug targets; (3) changes in tumor microenvironment (TME) after treatment.
TERF1 protein is an inhibitor of telomerase, and decreased expression of TER F1 would result in increased telomerase activity and resistance to chemotherapy. Therefore, the exchange of exosomic miRNAs between tumor cells and stromal cells in TME can promote drug resistance.
Researchers found that exosomes, which are released by cancer cells and carry certain miRNAs were used by cancer cells and tumor-associated macrophages (TAMs) in the TME to communicate with each other [ 38].
Many chemotherapy drugs, like cisplatin and 5-fluorouracil (5-FU), kill cancer cells by inducing DNA damage. The DNA damage response (DDR) of affected cells to the anti-cancer drugs may result in reduced efficacy of the drugs by DNA lesion repairs, leading to drug resistance [ 80].
Compared to traditional chemotherapies which kill cancer cells by disrupting rapid cell proliferation and may affect normal dividing cells, targeted therapies can block the growth of cancer cells by inhibiting the activity of specific target proteins involved in tumor development, thus being more selective and effective to cancer cells and less harmful to normal cells. However, targeted therapy may also develop the problem of resistance, resulting from alteration of drug targets. The alteration of drug targets may be either a secondary mutation in the target protein or changes in expression levels due to epigenetic alterations.
Intrinsic resistance is usually defined as the innate resistance that exists before the patient is administered with (exposed to) drugs, which usually causes reduced efficacy of the drug treatment . Intrinsic resistance can be caused by: (1) pre-existing (inherent) genetic mutations in a majority of tumors that result in decreased responsiveness of cancer cells, such as triple negative breast cancer cells, to both chemo and target drugs; (2) heterogeneity of tumors in which pre-existed insensitive subpopulations, including cancer stem cells, will be selected upon drug treatment thus leading to relapse in later stages of therapeutic treatment; (3) activation of intrinsic pathways used as defense against environmental toxins (such as anticancer drugs).
These mechanisms include enzymatic modification of the drug, modification of the antimicrobial target, and prevention of drug penetration or accumulation.
These include the overuse and misuse of antimicrobials, inappropriate use of antimicrobials, subtherapeutic dosing, and patient noncompliance with the recommended course of treatment.
Resistance genes may code for enzymes that chemically modify an antimicrobial, thereby inactivating it, or destroy an antimicrobial through hydrolysis. Resistance to many types of antimicrobials occurs through this mechanism. For example, aminoglycoside resistance can occur through enzymatic transfer of chemical groups to the drug molecule, impairing the binding of the drug to its bacterial target. For β-lactams, bacterial resistance can involve the enzymatic hydrolysis of the β-lactam bond within the β-lactam ring of the drug molecule. Once the β-lactam bond is broken, the drug loses its antibacterial activity. This mechanism of resistance is mediated by β-lactamases, which are the most common mechanism of β-lactam resistance. Inactivation of rifampin commonly occurs through glycosylation, phosphorylation, or adenosine diphosphate (ADP) ribosylation, and resistance to macrolides and lincosamides can also occur due to enzymatic inactivation of the drug or modification.
Because antimicrobial drugs have very specific targets, structural changes to those targets can prevent drug binding, rendering the drug ineffective. Through spontaneous mutations in the genes encoding antibacterial drug targets, bacteria have an evolutionary advantage that allows them to develop resistance to drugs.
Antimicrobial resistance is on the rise and is the result of selection of drug-resistant strains in clinical environments, the overuse and misuse of antibacterials, the use of subtherapeutic doses of antibacterial drugs, and poor patient compliance with antibacterial drug therapies.
In nature, microbes are constantly evolving in order to overcome the antimicrobial compounds produced by other microorganisms. Human development of antimicrobial drugs and their widespread clinical use has simply provided another selective pressure that promotes further evolution. Several important factors can accelerate the evolution ...
Exposure of a pathogen to an antimicrobial compound can select for chromosomal mutations conferring resistance, which can be transferred vertically to subsequent microbial generations and eventually become predominant in a microbial population that is repeatedly exposed to the anti microbial.
The TB bacteria has natural defenses against some drugs, and can acquire drug resistance through genetic mutations. The bacteria does not have the ability to transfer genes for resistance between organisms through plasmids ( see horizontal transfer ). Some mechanisms of drug resistance include:
Some mechanisms of drug resistance include: Cell wall: The cell wall of M. tuberculosis (TB) contains complex lipid molecules which act as a barrier to stop drugs from entering the cell. Drug modifying & inactivating enzymes: The TB genome codes for enzymes ( proteins) that inactivate drug molecules.
MDR-TB most commonly develops in the course of TB treatment, and is most commonly due to doctors giving inappropriate treatment, or patients missing doses or failing to complete their treatment. Because MDR tuberculosis is an airborne pathogen, persons with active, pulmonary tuberculosis caused by a multidrug-resistant strain can transmit the disease if they are alive and coughing. TB strains are often less fit and less transmissible, and outbreaks occur more readily in people with weakened immune systems (e.g., patients with HIV ). Outbreaks among non immunocompromised healthy people do occur, but are less common.
Specialty. Infectious disease. Multidrug-resistant tuberculosis ( MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs), isoniazid and rifampin. Some forms of TB are also resistant to second-line medications, ...
One of the so-called "hot-spots" of drug-resistant tuberculosis is within the Russian prison system. Infectious disease researchers Nachega & Chaisson report that 10% of the one million prisoners within the system have active TB. One of their studies found that 75% of newly diagnosed inmates with TB are resistant to at least one drug; 40% of new cases are multidrug-resistant. In 1997, TB accounted for almost half of all Russian prison deaths, and as Bobrik et al. point out in their public health study, the 90% reduction in TB incidence contributed to a consequential fall in the prisoner death rate in the years following 1997. Baussano et al. articulate that concerning statistics like these are especially worrisome because spikes in TB incidence in prisons are linked to corresponding outbreaks in surrounding communities. Additionally, rising rates of incarceration, especially in Central Asian and Eastern European countries like Russia, have been correlated with higher TB rates in civilian populations. Even as the DOTS program is expanded throughout Russian prisons, researchers such as Shin et al. have noted that wide-scale interventions have not had their desired effect, especially with regard to the spread of drug-resistant strains of TB.
MDR-TB can become resistant to the major second-line TB drug groups: fluoroquinolones ( moxifloxacin, ofloxacin) and injectable aminoglycoside or polypeptide drugs ( amikacin, capreomycin, kanamycin ). When MDR-TB is resistant to at least one drug from each group, it is classified as extensively drug-resistant tuberculosis (XDR-TB).
MDR-TB caused an estimated 600,000 new TB cases and 240,000 deaths in 2016 and MDR-TB accounts for 4.1% of all new TB cases and 19% of previously treated cases worldwide. Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.