Mycobacteria and Tuberculosis Quiz

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Questions and Answers

Match the risk groups for Tuberculosis with their descriptions:

Close contacts with TB patients = Individuals who are frequently around TB patients Immunosuppressed = People with weakened immune systems People from countries with high incidence of TB = Individuals from regions where TB is common Injecting drug users = Individuals who use drugs through injections and are at higher risk

Match the factors that increase the risk of developing active TB with their descriptions:

HIV+ = Individuals with HIV infection Organ transplantation = Patients who have received an organ transplant Chronic renal failure = Those undergoing regular dialysis treatments Silicosis = Chronic lung disease caused by silica exposure

Match the therapeutic problems associated with Tuberculosis with their descriptions:

Patients compliance = Challenges in ensuring patients follow treatment regimens Intracellular location of mycobacteria = Difficulty accessing bacteria hiding in cells Slow growth of organism = Long periods needed for culture and treatment response Resistant strains = Bacteria that have adapted to resist anti-TB drugs

Match the mechanism of action of Isoniazid with its effects:

Activated by KatG = Isoniazid's activation process Inhibits InhA = Interfering with acyl carrier protein synthesis Disrupts mycolic acid synthesis = Prevents formation of cell wall components Chromosomal mutations = Changes in DNA leading to drug resistance Signup and view all the answers

Match the aspects of Isoniazid resistance with their details:

Mutation of KatG = Loss of function in the enzyme that activates Isoniazid Overexpression of InhA = Increased levels leading to reduced drug efficacy Varying mutations of acyl carrier proteins = Changes in protein structure affecting drug action Cross-resistance = Resistance to multiple anti-TB medications Signup and view all the answers

Match the following mycobacterial infections with their primary characteristics:

Mycobacterium tuberculosis = Causes pulmonary tuberculosis Mycobacterium leprae = Causes leprosy Nontuberculosis mycobacteria (NTM) = Increasing infections affecting immunocompromised Mycobacterium avium-intracellulare = Common NTM infection Signup and view all the answers

Match the following drug resistance strategies with their purposes:

Multidrug therapy = Prevents emergence of drug-resistant bacteria Isoniazid = First-line treatment for tuberculosis Aminoglycosides = Second-line treatment for MDR-TB Fluoroquinolone = Target multi-drug resistant strains Signup and view all the answers

Match the following tuberculosis characteristics with their descriptions:

Pulmonary TB = 90% of initial infections are asymptomatic Extrapulmonary TB = Spreads outside the lungs Latent TB = May become chronic with scarring Infection in children = More common in immunocompromised individuals Signup and view all the answers

Match the following first-line drugs for tuberculosis with their roles:

Isoniazid = Inhibits mycobacterial cell wall synthesis Rifampin = Inhibits RNA synthesis in bacteria Ethambutol = Inhibits cell wall formation Pyrazinamide = Disrupts the mycobacterial membrane potential Signup and view all the answers

Match the following types of mycobacterial drug resistance with their definitions:

MDR-TB = Resistant to isoniazid and rifampin XDR-TB = Resistant to isoniazid, rifampin, and fluoroquinolones First-line drugs = Primary treatments for non-resistant TB Second-line drugs = Used when first-line treatments fail Signup and view all the answers

Match the following characteristics of Mycobacteria with their implications:

Intracellular pathogens = Survive inside macrophages Lipid-rich cell wall = Causes resistance to antibiotics Slow cell division = Makes treatment more challenging Asymptomatic initial infections = Complicates early diagnosis Signup and view all the answers

Match the following terms related to TB with their meanings:

Pulmonary tuberculosis = Affects lungs primarily Latent tuberculosis = No symptoms but infection present Acid-fast bacilli = Characteristic of mycobacteria Cavitary lesions = Cavities in lungs caused by TB Signup and view all the answers

Match the following drugs with their potential substitutes in treatment regimens:

Rifampin = Can be replaced by rifabutin Streptomycin = An example of an aminoglycoside Levofloxacin = A type of fluoroquinolone Ethionamide = Part of second-line therapy options Signup and view all the answers

Match the following adverse effects with their corresponding medications:

Isoniazid = Convulsions in prone patients Rifampin = Nausea and vomiting Rifabutin = Risk of hepatic dysfunction when combined with isoniazid Signup and view all the answers

Match the following pharmacokinetic properties with their respective drugs:

Isoniazid = Excretion: Glomerular filtration and secretion Rifampin = Well oral absorption and distribution Signup and view all the answers

Match the following mechanisms of action with the respective medications:

Isoniazid = Inhibits metabolism of carbamazepine Rifampin = Blocks RNA transcription Rifabutin = Targets extra and intracellular mycobacteria Signup and view all the answers

Match the following statements about drug resistance with the corresponding drugs:

Isoniazid = Potentiates effects of phenytoin Rifampin = Mutations of RNA polymerase gene Rifapentine = Not given as a single agent due to resistance Signup and view all the answers

Match the following vitamin deficiencies with their related medications:

Isoniazid = Can be corrected by pyridoxine supplementation Rifampin = None Rifabutin = None Signup and view all the answers

Match the following patient scenarios with the appropriate medication caution:

Isoniazid = Dose adjustment in slow acetylators Rifampin = May cause orange-red coloration in body fluids Signup and view all the answers

Match the following common side effects with the respective drugs:

Isoniazid = Hepatitis and toxic metabolites Rifampin = Flu-like syndrome with intermittent dosing Rifabutin = Nausea and vomiting Signup and view all the answers

Match the following information about bacterial activity with the specific drug:

Isoniazid = Bactericidal for active infections Rifampin = Mycobacterium leprae Rifabutin = Broader spectrum than isoniazid Signup and view all the answers

Match the following second-line treatments for TB with their descriptions:

Streptomycin = Against extracellular organisms, resistant organisms may be treated with kanamycin or amikacin Para-aminosalicylic acid (PAS) = 18 months standard regimen to treat MDR-TB Capreomycin = Inhibits protein synthesis, reserved for MDR-TB Cycloserine = Disrupts d-alanine incorporation into the cell wall, distributes well in CSF Signup and view all the answers

Match the following features of rifamycins with their characteristics:

Rifampin = Potent inducer of drug metabolism Rifabutin = 40% less potent inducer, used in HIV co-infected patients Rifapentine = Long half-life, used with isoniazid for LTBI Pyrazinamide = Active in acidic lesions, can cause liver toxicity Signup and view all the answers

Match the following adverse effects with the respective drugs:

Rifabutin = Causes uveitis and skin hyperpigmentation Ethambutol = Optic neuritis and decreased uric acid excretion Pyrazinamide = Liver toxicity and uric acid retention Capreomycin = Monitored for nephrotoxicity and ototoxicity Signup and view all the answers

Match each drug with its specific role in TB treatment:

Streptomycin = Used against extracellular organisms Ethionamide = Analog of isoniazid, disrupts mycolic acid synthesis Kanamycin = Used for streptomycin-resistant organisms Amikacin = Alternative for treatment of resistant mycobacterial infections Signup and view all the answers

Match the following tuberculosis drugs with what they primarily target:

Rifampin = Mycolic acid synthesis Ethambutol = Cell wall synthesis inhibition Pyrazinamide = Acidic environment within macrophages Isoniazid = Inhibition of mycolic acid synthesis Signup and view all the answers

Match the following terms related to drug interactions with their implications:

Higher dosages for coadministered drugs = Increased risk of adverse effects Switching to drugs less affected by rifampin = Mitigating drug interactions Monitoring renal impairment patients = Reducing optic neuritis risk with Ethambutol Uric acid retention = Potential gouty attacks due to Pyrazinamide Signup and view all the answers

Match the following conditions associated with certain TB medications:

Rifabutin = Preferred for patients receiving protease inhibitors Ethambutol = Risk of visual impairment at higher doses Pyrazinamide = Rarely precipitates gouty attacks Capreomycin = Reserved for multi-drug resistant TB Signup and view all the answers

Match each drug to its unique characteristic:

Rifapentine = May be used once weekly in select HIV-negative patients Cycloserine = Well distributed including CNS Para-aminosalicylic acid (PAS) = Standard infection regimen from the 1950s Capreomycin = Requires TDM due to toxicity risks Signup and view all the answers

Match the following anti-leprosy drugs with their mechanism of action:

Dapsone = Inhibits dihydropteroate synthetase Clofazimine = Binds to DNA to block synthesis Rifampicin = Inhibits RNA polymerase Ofloxacin = Inhibits DNA gyrase Signup and view all the answers

Match the following side effects with their corresponding drugs:

Dapsone = Haemolysis in G6PD patients Clofazimine = Skin discoloration Azithromycin = Potential for gastrointestinal upset Levofloxacin = Nausea and vomiting Signup and view all the answers

Match the following tuberculosis treatment regimens with their type:

Multibacillary leprosy = Rifampicin and Clofazimine Paucibacillary leprosy = Rifampicin and Dapsone Single Skin Lesion PB leprosy = Rifampicin and Ofloxacin MDR-TB = Moxifloxacin and levofloxacin Signup and view all the answers

Match the following adverse reactions to their drug class:

Fluoroquinolones = Hepatotoxicity Macrolides = CYP 450 interactions Anti-leprosy drugs = Peripheral neuropathy Clofazimine = Cytotoxic oxygen radicals Signup and view all the answers

Match the following tuberculosis treatment drugs with their dosing frequency:

Rifampicin = Once a month in MB leprosy Dapsone = Daily in MB and PB leprosy Clofazimine = Once a month in MB leprosy Minocycline = Single dose in Single Skin Lesion PB Signup and view all the answers

Match the following drugs with their primary use:

Azithromycin = Pneumocystis jirovecii pneumonia Ofloxacin = Single Skin Lesion Paucibacillary leprosy Clofazimine = Leprosy and tuberculosis Moxifloxacin = MDR-TB treatment Signup and view all the answers

Match the following symptoms with their drug association:

Hypothyroidism = Clofazimine CNS effects = Dapsone Gynecomastia = Dapsone Impotence = Moxifloxacin Signup and view all the answers

Match the following treatment duration with their regimen:

12 months = Multibacillary leprosy regimens 6 months = Paucibacillary leprosy regimens Single dose = Single Skin Lesion Paucibacillary leprosy Varies = MDR-TB treatment Signup and view all the answers

Study Notes

Mycobacteria

Intracellular pathogens that can survive inside macrophages
Resistant to most antibiotics due to lipid-rich cell walls and slow cell division (18-24 hours)
Humans are mainly affected by Mycobacterium tuberculosis and Mycobacterium leprae (leprosy).
Nontuberculosis mycobactera (NTM) infections are increasing (M.avium-intracellulare, M. kansasii)

Pulmonary Tuberculosis

Most initial infections are asymptomatic (latent tuberculosis)
It can become a chronic illness causing extensive scarring in the upper lobes of the lungs
Early lung lesions heal without residual changes, except occasional calcification in the pulmonary or tracheobronchial lymph nodes
Extrapulmonary infection spreads outside the lungs.
More prevalent in immunocompromised individuals and children.

Strategies to overcome drug resistance

Multidrug therapy is essential to reduce the bacterial population rapidly and prevent drug resistance.
First-line drugs: isoniazid, rifampin, ethambutol, pyrazinamide
Second-line drugs for MDR-TB (resistant to isoniazid and rifampin): aminoglycosides (streptomycin, kanamycin, or amikacin) or capreomycin, fluoroquinolone (levofloxacin or moxifloxacin), remaining active first-line drugs, cycloserine, ethionamide, or p-aminosalicylic acid

Tuberculosis Risk Groups

Close contacts with TB patients.
Immunocompromised people.
Individuals from countries with a high incidence of TB.

Factors increasing the risk of developing active TB:

HIV+ individuals
Injecting drug users
Organ transplant recipients
Individuals with hematological malignancies (leukemia and lymphomas)
Individuals with chronic renal failure or receiving hemodialysis
People with silicosis (chronic lung disease caused by inhaling silica particles leading to lung function loss)

Tuberculosis Therapeutic Problems

Patient compliance
Intracellular location of mycobacteria.
Slow growth rate of the organism: difficult to culture and the response to chemotherapy is slow (treatment lasts 6 months to 2 years).
Resistant strains: particularly in patients who received prior therapy or failed to adhere to treatment.

Isoniazid (INH)

The most potent anti-TB drug for prophylaxis and treatment.
Mechanism of action: activated by mycobacterial catalase–peroxidase (KatG) which inhibits enzymes acyl carrier protein reductase (InhA) and β-ketoacyl-ACP synthase (KasA), disrupting mycolic acid synthesis.
Antibacterial spectrum: specific for M. tuberculosis, most non-tuberculosis mycobacteria are resistant to isoniazid.
Effective against rapidly growing bacilli and intracellular organisms

Isoniazid (INH) Resistance

Chromosomal mutations: mutation or deletion of KatG, varying mutations of acyl carrier proteins, overexpression of InhA
Cross-resistance may occur between isoniazid and other anti-TB drugs.
Pharmacokinetics: readily absorbed orally (avoid high-fat meals), distributed to all body fluids, cells, and caseous material (necrotic tissue resembling cheese produced in tuberculous lesions).
Undergoes N-acetylation and hydrolysis to produce inactive products: fast acetylators (T1/2 = 90 mins), slow acetylators (T1/2 = 3-4 hours).
Excretion: glomerular filtration and secretion.

Isoniazid (INH) Adverse Effects

Peripheral neuritis (most common): paresthesias of the hands and feet due to pyridoxine (vitamin B6) deficiency (supplementation of 25-50 mg per day of pyridoxine corrects this).
Hepatitis (most severe side effect): caused by a toxic metabolite of monoacetyl hydrazine. Incidence rises with age, in patients taking rifampin, or those who drink alcohol daily.
Convulsions in patients prone to seizures.
Hypersensitivity reactions including rashes and fever.
Drug potentiation (isoniazid inhibits the metabolism of carbamazepine and phenytoin causing nystagmus and ataxia). Slow acetylators are particularly at risk.

Rifamycins: Rifampin, Rifabutin, and Rifapentine

Rifampin: broader spectrum than isoniazid (never administer as a single agent). Blocks RNA transcription by interacting with the β subunit of mycobacterial DNA-dependent RNA polymerase. Bactericidal (targets extra and intracellular mycobacteria). Prophylaxis for individuals exposed to meningitis caused by meningococci or Haemophilus influenzae. Highly active against M. Leprae.
Resistance: mutations in the RNA polymerase gene (decreased drug affinity).
Rifampin (PK): well absorbed orally, distributed well (including CSF). CYP450 inducer. Elimination: mainly bile and feces, and urine (urine, feces, and secretions have orange-red color, tears can also stain soft contact lenses).

Rifampin Adverse Effects

Nausea, vomiting, and rash (most common).
Increased risk of hepatic dysfunction when combined with isoniazid.
Intermittent dosing (≥ 1.2 g): flu-like syndrome, fever, chills, myalgia. Can extend to acute renal failure, hemolytic anemia, and shock.
Drug interactions: patients receiving higher dosages for coadministered drugs need to switch to drugs that are less affected by rifampin.

Rifabutin

Used for TB patients co-infected with HIV who are receiving protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs).
40% less potent inducer than Rifampin.
Adverse effects similar to rifampin (can also cause uveitis, skin hyperpigmentation, and neutropenia).

Rifapentine

More active than rifampin
Long half-life
In combination with isoniazid, it can be used once weekly in patients with latent TB infection and select HIV-negative patients with minimal pulmonary TB.

Pyrazinamide

Short course oral agent (first 2 months).
Unknown mechanism of action.
Active against tuberculosis bacilli in acidic lesions and macrophages.
Bacteria pyrazinamidase converts pyrazinamide to pyrazinoic acid (the active drug).
Well distributed including CSF.
Can cause liver toxicity and uric acid retention (rarely precipitates a gouty attack).

Ethambutol

Bacteriostatic (specific for mycobacteria)
Inhibits arabinosyl transferase (cell wall synthesis).
Well distributed, low penetration into CNS.
Excreted in the urine.
Adverse effects: optic neuritis (decreased visual acuity and loss of red/green discrimination). Risk increases with higher doses and in patients with renal impairment. Decreased uric acid excretion (monitor gout patients).

Second-line Treatment for TB

Less effective and more toxic than first-line agents.

Streptomycin

Active against extracellular organisms
Streptomycin-resistant organisms may be treated with kanamycin or amikacin.

Para-aminosalicylic acid (PAS)

Standard 18-month regimen from the 1950s-1960s
Used to treat MDR-TB.

Capreomycin (Avoid with streptomycin)

Inhibits protein synthesis
Reserved for MDR-TB
Therapeutic drug monitoring (TDM) is needed to monitor nephrotoxicity and ototoxicity

Cycloserine

Disrupts d-alanine incorporation into the bacterial cell wall
Well distributed including CSF.

Ethionamide

Analog of INH
Disrupts mycolic acid synthesis in a different pathway from INH
Wide distribution including CSF
Metabolized in the liver to both active and inactive metabolites
Nausea, vomiting, and hepatotoxicity (common)
May cause hypothyroidism, gynecomastia, alopecia, impotence, and CNS effects

Fluoroquinolones: Moxifloxacin and levofloxacin

Used for MDR-TB

Macrolides:

Azithromycin is preferred to avoid drug interactions (clarithromycin is both a substrate and inhibitor of CYP 450).

Leprosy

Anti-Leprosy Drug: Dapsone

Inhibits dihydropteroate synthetase in the folate synthesis pathway (bacteriostatic).
Treats Pneumocystis jirovecii pneumonia in immunosuppressed patients.
Well absorbed and distributed orally (concentrate in the skin).
Parent drug undergoes hepatic acetylation.
Parent drug and metabolites are eliminated in the urine.
Adverse reactions: hemolysis (especially in G6PD patients), methemoglobinemia, peripheral neuropathy.

Anti-Leprosy Drug: Clofazimine

Binds to, and blocks DNA synthesis.
May generate cytotoxic oxygen radicals to kill bacteria.
Also effective against M. tuberculosis and NTM.
Well absorbed orally and distributed (not into CNS).
Accumulates in tissues (allowing intermittent therapy).
T1/2= 70 days
Possesses anti-inflammatory properties to control Type II lepra reaction (erythema nodosum leprosum).
Side effects: pink to brownish-black discoloration of the skin.

WHO Recommended Multidrug Treatment Regimen (Free of charge by WHO)

Multibacillary (MB) leprosy
- Adults: Rifampicin (600 mg once a month), Dapsone (100 mg daily), Clofazimine (300 mg once a month, 50 mg daily)
- Duration: 12 months
Paucibacillary (PB) leprosy
- Adults: Rifampicin (600 mg once a month), Dapsone (100 mg daily)
- Duration: 6 months
Single Skin Lesion Paucibacillary leprosy
- Adults: Rifampicin (600 mg), Ofloxacin (400 mg), Minocycline (100 mg)
- Single dose

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Test your knowledge on mycobacteria, focusing on their characteristics, the impact of pulmonary tuberculosis, and strategies to combat drug resistance. This quiz covers essential information about Mycobacterium tuberculosis and associated infections, as well as treatment approaches. Challenge yourself to learn more about these intracellular pathogens and their implications for human health.