The need for multidrug and long-term therapy stems from two different drug resistance mechanisms. MTB can exhibit genetic resistance that is heritable and fixed, as well as phenotypic, reversible resistance to administered antibiotics.
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Why is long-term therapy required to cure tuberculosis?
Why is long-term therapy required to cure tuberculosis? The authors argue that understanding and countering general bacterial mechanisms of phenotypic antibiotic resistance may hold the key to reducing the duration of treatment of all recalcitrant bacterial infections, including tuberculosis.
Does duration of antibiotic therapy correlate with bacterial burden in tuberculosis?
In this article, we consider general versus MTB-specific models of phenotypic antibiotic resistance (see Glossary) in light of our review of human TB treatment data. These data suggest that the duration of therapy required for cure correlates with overall bacterial burden.
How long do you have to take antibiotics for TB?
Patients with TB typically have to take 4 antibiotics for 2 months and then continue 2 of these antibiotics for an additional 4 months. Why is such long treatment needed?
How effective is streptomycin in the treatment of tuberculosis (TB)?
Soon after the discovery of streptomycin it became clear that while many patients with TB treated with this drug initially improved dramatically, most developed streptomycin-resistant strains so that there was little improvement in mortality over untreated patients.
Why is long term and regular treatment necessary in TB?
A fundamental problem in the treatment of tuberculosis (TB) is the long duration of therapy required for cure. The recalcitrance of Mycobacterium tuberculosis (MTB) to eradication is thought to result from its achieving a nonreplicating (dormant) state in the host.
Why mycobacterial infections have to be treated for 6 months or longer?
If treatment is not continued for a long enough duration, the surviving bacteria may cause the patient to become ill and infectious again, potentially with drug-resistant disease.
Why does antibiotic treatment of TB takes a long time?
Because virtually all types of antibiotics act only on replicating bacteria, the dormant state of TB is thought to render it resistant to treatment.
Why does tuberculosis have long term effects?
If TB of the lung is not treated early or if treatment isn't followed, long-lasting (permanent) lung damage can result. TB can also cause infection of the bones, spine, brain and spinal cord, lymph glands, and other parts of the body.
Why do TB patients stop their medication early?
The main reason treatments fail is that people do not take their medications properly. Medicines given to people with TB disease usually stop them from spreading TB bacteria within a few weeks. Most TB patients live at home and can continue normal activities if they take their medicine.
Why is Mycobacterium treated with multiple drug regimen?
Currently, treatment of tuberculosis requires administration of multiple bactericidal and sterilizing drugs for prolonged periods to ensure elimination of active M. tuberculosis and preventing the development of antibiotic resistance in surviving bacteria [6].
Why are mycobacterial infections often persistent?
In addition to sequestration from the immune system and antibiotics, another factor contributing to persistent infection is the ability of bacteria to adopt an altered physiologic state against which current antibiotics that predominantly target replicating cells are less efficacious.
Why has it become more difficult to treat TB over time?
This is because there are many bacteria to be killed. Taking multiple drugs also helps to prevent the bacteria from becoming drug resistant and, thus, much more difficult to cure. If you have TB of the lungs, or pulmonary TB, you are probably infectious.
What is the total time of treatment for tuberculosis TB multidrug therapy?
RIPE regimens for treating TB disease have an intensive phase of 2 months, followed by a continuation phase of either 4 or 7 months (total of 6 to 9 months for treatment).
How does Mycobacterium tuberculosis affect the lungs?
TB is caused by the bacterium M tuberculosis. The infection destroys patients' lung tissue, causing them to cough up the bacteria, which then spread through the air and can be inhaled by others. The mechanism behind this lung damage is poorly understood.
How can you prevent Mycobacterium tuberculosis?
The BCG vaccination It is one of the most widely used vaccines worldwide, yet we still see around 9 million new cases of TB annually – a testament to the BCG's limited effectiveness. The BCG is: 80% effective in preventing TB for 15 years. more effective against complex forms of TB in children.
What disease is caused by Mycobacterium tuberculosis?
Tuberculosis (TB) is a contagious disease caused by infection with Mycobacterium tuberculosis (Mtb) bacteria. It is spread through the air when a person with TB disease of the lungs or throat coughs, speaks or sings, and people nearby breathe in these bacteria and become infected.
Why is TB a fundamental problem?
A fundamental problem in the treatment of tuberculosis (TB) is the long duration of therapy required for cure. The recalcitrance of Mycobacterium tuberculosis (MTB) to eradication is thought to result from its achieving a nonreplicating (dormant) state in the host. Because virtually all classes of antibiotics require bacterial replication ...
What is the term for a nonreplicating state of infection in which the host is resistant to both host immune
Latency: Clinically asymptomatic infection with M. tuberculosis.
What is phenotypic antibiotic resistance?
Phenotypic antibiotic resistance: A general term for the phenomenon by which genetically homogeneous, antibiotic-susceptible bacterial populations (or subpopulations) become transiently insensitive to antibiotic killing. The need for multidrug and long-term therapy stems from two different drug resistance mechanisms.
What is the subtype of phenotypic resistance to antibiotics?
Antibiotic indifference: A subtype of phenotypic resistance to antibiotics due to decreased or absent bacterial growth of the entire bacterial population, generally in response to adverse environmental conditions, such as host defense reactions.
Is MTB genetic or phenotypic?
MTB can exhibit genetic resistance that is heritable and fixed, as well as phenotypic, reversible resistance to administered antibiotics. The presence of genetic drug resistance in some or all of the infecting bacteria dictates ...
Does TB have a correlation with time to cure?
This correlation between bacterial burden and time to cure is not unique to TB, as it has been found in other bacterial infections, both acute and chronic. High bacterial burden infections, in turn, are associated with an increased frequency ...
Do pathogenic bacteria have drug resistance?
Yet, it is also known that many other pathogenic bacteria display phenotypic drug resistance in vivo, accounting for the need for longer durations of antibiotic therapy than would be predicted from the time required for in vitro bacterial killing.
Why is mycobacterium abscessus so difficult to treat?
Mycobacterium abscessus infections are challenging to treat because multidrug resistance necessitates prolonged intravenous (IV) therapy and side effects are perceived to be common. For the best chance of pulmonary disease cure, guidelines from the American Thoracic Society/Infectious Diseases Society of America ...
Why was antimicrobial therapy discontinued?
Among patients with pulmonary infection, antimicrobial drug therapy was completely discontinued for 4 because of side effects. No patients with extrapulmonary disease completely stopped therapy because of side effects. Overall, > 54 medication changes among 30 patients were made because of side effects or intolerance.
Is amikacin therapy stopped?
Amikacin, the most commonly used IV agent, was associated with multiple side effects; amikacin therapy was stopped or adjusted for 51% of patients.
Is Mycobacterium abscessus resistant to antimicrobials?
Mycobacterium abscessus is often resistant to multiple antimicrobial drugs , and data supporting effective drugs or dosing regimens are limited. To better identify treatment approaches and associated toxicities, we collected a series of case reports from the Emerging Infections Network.
How long does it take for TB to relapse?
Mycobacterium tuberculosis (Mtb) is extremely recalcitrant to antimicrobial chemotherapy requiring 6 months to treat drug-sensitive tuberculosis (TB). Despite this, 4–10% of cured patients will develop recurrent disease within 12 months after completing therapy. Reasons for relapse in cured TB patients remains speculative, attributed to both pathogen and host factors. Populations of dormant bacilli are hypothesized to cause relapse in initially cured TB patients however, development of tests to convincingly demonstrate their presence at the end of anti-TB treatment has been challenging. Previous studies have indicated the utility of culture filtrate supplemented media (CFSM) to detect differentially culturable tubercle bacilli (DCTB). Here, we show that 3/22 of clinically cured patients retained DCTB in induced sputum and bronchoalveolar lavage fluid (BALF), with one DCTB positive patient relapsing within the first year of completing therapy. We also show a correlation of DCTB status with “unresolved” end of treatment FDG PET-CT imaging. Additionally, 19 end of treatment induced sputum samples from patients not undergoing bronchoscopy were assessed for DCTB, identifying a further relapse case with DCTB. We further show that induced sputum is a less reliable source for the DCTB assay at the end of treatment, limiting the utility of this assay in a clinical setting. We next investigated the host proteome at the site of disease (BALF) using multiplexed proteomic analysis and compared these to active TB cases to identify host-specific factors indicative of cure. Distinct signatures stratified active from cured TB patients into distinct groups, with a DCTB positive, subsequently relapsing, end of treatment patient showing a proteomic signature closer to active TB disease than cure. This exploratory study offers evidence of live Mtb, undetectable with conventional culture methods, at the end of clinically successful treatment and putative host protein biomarkers of active disease and cure. These findings have implications for the assessment of true sterilizing cure in TB patients and opens new avenues for targeted approaches to monitor treatment response.
What are persisters in bacteria?
Antibiotic persisters (persister cells) are believed to be among the factors that make these infections challenging. Persisters are subpopulations of bacteria which survive treatment with bactericidal antibiotics in otherwise antibiotic-sensitive cultures and were extensively studied in a hope to discover the mechanisms that cause treatment failures in chronically infected patients; however, most of these studies were conducted in the test tube. Research into antibiotic persistence has uncovered large intrapopulation heterogeneity of bacterial growth and regrowth but has not identified essential, dedicated molecular mechanisms of antibiotic persistence. Diverse factors and stresses that inhibit bacterial growth reduce killing of the bulk population and may also increase the persister subpopulation, implying that an array of mechanisms are present. Hopefully, further studies under conditions that simulate the key aspects of persistent infections will lead to identifying target mechanisms for effective therapeutic solutions.
How long do you have to take antibiotics for TB?
advertisement. Patients with TB typically have to take 4 antibiotics for 2 months and then continue 2 of these antibiotics for an additional 4 months. Why is such long treatment needed? Lalita Ramakrishnan (University of Washington) and colleagues say that traditionally the answer was thought to lie in the fact that the tuberculosis microbe ...
Why is TB resistant to antibiotics?
Because virtually all types of antibiotics act only on replicating bacteria, the dormant state of TB is thought to render it resistant to treatment. But the authors now challenge this traditional view.
Is TB a non-replicating disease?
In the light of data on treating human TB and other bacterial infections, they suggest that the non-replicating state is not TB-specific and that the number of non- replicating bacteria correlates with total bacterial burden rather than TB-specific pathology.
