tuberculosis antimycobacterial therapy
DESCRIPTION
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Tuberculosis
ANTI-MYCOBACTERIALS
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DIAGNOSIS OF TB
The recognition of an active TB case:
Symptomatic due to lesions caused by Mycobacterium tuberculosis.
Confirmed by microbiologic studies to harbor M.tuberculosis
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The diagnosis of tuberculosis (TB) refers to the recognition of an active TB case: the identification of a patient who is symptomatic due to lesions caused by Mycobacterium tuberculosis. A TB case is a patient confirmed (by microbiologic studies) to harbor the organism Mycobacterium tuberculosis. Infrequently, a case of TB may also be one where microbiologic work-up is negative but other data support or suggest the presence of the organism.
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The Gold Standard
TB Culture
with Drug Susceptibility Testing Because of the increased sensitivity of TB culture to detect TB cases compared to sputum microscopy alone, international standards recommend that all adults suspected to have pulmonary tuberculosis should have TB culture in addition to sputum microscopy where resources permit.
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Classification of TB Cases
WHO Case Definitions: Latent TB Active TB
Pulmonary Smear (-) Smear (+)
Extra Pulmonary Smear (-) Smear (+)
Latent TB: TB infection but no evidence of the disease A Clinically Active TB is classified as either Pulmonary
or Extrapulmonary, smear (-) or smear (+)
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TB Symptomatic
Cough > 2weeks
Unexplained fever and chills
Night sweats
Weight loss
Anorexia
Chest pain
Fatigue and Body malaise
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When should one suspect that a patient may have PTB?
In the Philippines, cough of two weeks or more should make the physician and/or other healthcare workers suspect the possibility of pulmonary tuberculosis. Cough with or without the following: night sweats, weight loss, anorexia, unexplained fever and chills, chest pain, fatigue and body malaise, is suggestive of TB.
A patient exhibiting cough of two weeks or more with or without accompanying symptoms will be referred to as a TB Symptomatic.
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TB Symptomatic : work up
Sputum microscopy for AFB Chest radiography (CXR) Tuberculin Skin Testing (PPD) Sputum TB culture and
Drug Susceptibility Testing Blood or serum tests Note: Other diagnostic modalities for TB
symptomatics with negative smears and cases of Extrapulmonary TB shall not be discussed in the interest of time and because these are beyond the scope of the subject matter and therefore for further discussion elsewhere.
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Sputum microscopy for AFB
Preferably 3, at least 2
The most efficient way to ID TB cases
Easy to collect
Readily available, accessible, affordable, results rapidly available
Correlates well with infectiousness
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The initial work-up of choice for a TB symptomatic is the sputum microscopy for Acid Fast Bacilli. All patients who present with cough of two weeks or more should preferably have three, but at the least two sputum specimens sent for sputum microscopy for Acid Fast Bacilli (AFB).
Sputum microscopy is still the most efficient way of identifying cases of tuberculosis.
Sputum collected first thing in the morning for three consecutive days is recommended.
How should results of sputum microscopy be interpreted? Results of sputum microscopy are interpreted and reported as follows: SMEAR POSITIVE if at least two sputum specimens are AFB (+). SMEAR NEGATIVE if none of the specimens are AFB (+). DOUBTFUL When only one of the 3 sputum specimens is (+). When results are doubtful, a second set of three must be collected
again. If at least one of the second three is (+), the diagnosis is SMEAR
POSITIVE. If all of the second three are (-), the diagnosis is SMEAR NEGATIVE.
Sputum smear for AFB is available, accessible, affordable, with results rapidly available, correlates well with infectiousness.
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TB Symptomatic : work up
Chest radiography (CXR)
Tuberculin Skin Testing (PPD)
Sputum TB culture and Drug Susceptibility Testing
Blood or serum tests
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Chest radiographs are not routinely necessary in the management of a TB symptomatic patient who is smear positive.A chest radiograph in smear positive TB symptomatics may be helpful if other concomitant diseases or life-threatening conditions are being considered.
The tuberculin skin testing (TST), more popularly known as PPD (for purified protein derivative), will not add additional information if the patient is smear (+). But: TB symptomatic, smear (-) patients will benefit from Chest radiography, & Sputum TB culture and Drug susceptibility testing.To further strengthen the diagnosis. In the Philippines where resources are limited and laboratory capability for
sputum culture is still being strengthened, sputum TB culture with DST is primarily recommended for patients who are at risk for drug resistance and should be done in the following smear positive patients:
o All cases of retreatment/ o All cases of treatment failure/o All other cases of smear (+) patients suspected to have one or multi- drug resistant TB (MDR-TB)
Certain blood or serum tests may be taken when specific risks for possible adverse events during treatment are present
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Classification of TB based on
Location & Sputum Smear
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Location Smear Definition of Terms
Pulmonary TB
(+) 1. A patient w/ at least 2 sputum specimens (+) for AFB, w/ or w/o CXR abnormalities consistent with active TB or
2. A patient w/ 1 sputum specimen (+) for AFB & w/ CXR abnormalities consistent with active TB as determined by a clinician, or
3. A patient w/ sputum specimen (+) for AFB with sputum culture (+) for M. tb.
(-) A patient with at least 3 sputum specimens (-) for AFB with CXR abnormalities consistent with active TB, and there has been no response to a course of antibiotics and/or symptomatic medications, and the Medical Officer decides treatment with anti-TB drugs.
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Location Definition of Terms
Extra- Pulmonary TB
1. A patient w/ at least 1 mycobacterial smear / culture (+) from an extra-pulmonary site (organs other than the lungs: pleura, lymph nodes, genito-urinary tract, skin, joints and bones, meninges, intestines, peritoneum and pericardium, among others), or
1. A patient with histiological and / or
clinical evidence consistent with active TB and there is a decision by a Medical Officer to treat the patient with anti-TB drugs.
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Categories of TB Cases according to Previous Treatment Received by the
Patient
Once the diagnosis of active TB is made, a case is also categorized according to
previous treatment received. Thus, cases are either New, Relapse, Return to treatment after default, Failures,
Transferred-in, and Others
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Category Definition
New Patient who has never had tx for TB or Patient who has taken anti-TB meds for < four weeks.
Relapse Patient declared cured of any form of TB in the past by a physician after one full course of anti-TB meds and now has become sputum smear (+)
Return to treatment after default
Patient stops taking his medications for two months or more and comes back to the clinic smear (+).
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Category Definition
Failure Patient while on tx, remained or became smear (+) again at the 5th month of anti-TB tx or later; or Patient smear (-) at the start of treatment and becomes smear (+) at the 2nd month.
Transfer-in Patient whose mx was started from another area and now transferred to a new clinic
Chronic Case Patient who became or remained smear (+) after completing fully a supervised re-treatment regimen
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Once the diagnosis of active TB is made, a case is also categorized according to previous treatment received. Thus, cases are either New, Relapse, Return to treatment after default, Failures, Transferred-in, and Others. This table provides definitions of TB cases according to previous treatment received. This categorization helps guide the health provider on the recommended treatment regimens for that particular patient.
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Treatment
Drug Therapy aims to: Cure
Prevent death
Prevent relapse
Prevent drug resistance
Decrease transmission
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Drug therapy of TB aims to achieve the following objectives:
Cure by rapidly eliminating most of the bacilli. Prevent death from active TB or its late effects.
Prevent relapse of TB by eliminating the dormant bacilli. Prevent the development of drug resistance by using a combination of drugs. Decrease the transmission to others.
The need for multiple drugs and prolonged duration of therapy = because naturally occurring drug resistant mutants are present within large bacterial populations even before chemotherapy is started. In addition, mycobacteria replicate slowly, can remain dormant for prolonged periods and can be eradicated only during replication.Finally, bacilli live in several sites within the host, and each site contains organisms with a different population size, metabolic activity and replication rate.
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Treatment
Therapeutic Principles
Treatment of disease must contain multiple drugs to which organisms are susceptible.
Drugs must be taken regularly.
Therapy must continue for a sufficient length of time.
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Multiple drugs are given simultaneously: Since mutant organisms naturally resistant to multiple drugs are extremely rare, this strategy decreases the likelihood of selecting out drug-resistant organisms and prevents the emergence of resistance.
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Treatment
2 Phases of Treatment Intensive Phase
kills actively replicating bacilli
Continuation Phase kills slowly dividing bacilli
Intensive phase: initial, consisting of more than 2 drugs promotes efficient killing of actively dividing organisms and leads to the rapid reduction of large bacillary populations; provides relief of symptoms, terminates transmission and prevents the emergence of drug resistance.
Continuation phase: uses fewer drugs, kills slowly or irregularly dividing bacilli, sterilizes lesions, prevents relapse
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Treatment Regimens
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TB Patient To Be Given Tx Drugs /TxDuration
I New PTB smear (+) cases New seriously ill PTB smear (-) cases w/ extensive parenchymal involvement New severely ill Extra-Pulmonary TB
cases
2HRZE / 4HR
II Failure cases Relapse cases Return after default smear(+) Others smear (+)
2HRZES/1HREZ/ 5HRE
III New smear (-) but minimal PTB on CXR as confirmed by Medical officer New Extra-Pulmonary TB (not
serious)
2HRZ / 4HR
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Take s of drugs used for Intensive and Continuation phases For Regimens I & II For Patients >50kg BW: add 1 tab each INH 100mg, PZA 500mg, Ethambutol 400mg before initiation of treatment. For Regimen III For Patients >50kg BW: add 1 tab each INH 100 mg, PZA 500mg before initiation of treatment. Category IV (not present in the 2001 NTP manual: Chronic and multidrug-resistant TB (smear positive after supervised retreatment). Multidrug-resistant or individualized regimen per country protocol. Given if there is resistance and/or decreased tolerance to 1st line drugs, Amikacin and Quinolone are the only 2nd line drugs in Philippines
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Outcomes of Treatment
Cure
Treatment Completed
Died
Treatment Failure
Defaulter Failure
Transfer Out
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Cure: sputum smear (+) patient who has completed tx and is sputum smear (-) in the last month of tx and on at least one previous occasion.
Treatment completed: a patient who has completed tx but does not meet the criteria to be classified as cure or failure. This group includes:
(1)a sputum smear-positive patient initially who has completed treatment without follow-up sputum examinations during the treatment, or with only one negative smear during the treatment, or without sputum in the last month of treatment; and
(2)a sputum smear (-) patient who has completed treatment Died - A patient who dies for any reason during the course of treatment Failure: A patient who is smear(+)at five months or later during treatment
or a sputum smear (-) patient initially before starting tx and becomes smear (+) during the treatment.
A defaulter is one whose treatment was interrupted for 2 consecutive months or more
Transfer out: A patient who has been transferred to another facility with proper referral/transfer slips for continuation of treatment.
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Issues Unique to the Infant and Child
with Tuberculosis
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How and from whom do infants and children acquire Tuberculosis? A. playmates & classmates B. yaya/driver/parents/grandparent C. house pet D. ingestion of cows milk
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How?: airborne route/transmission Childhood TB arises most often as a result of the inhalation of droplet nuclei approximately 1-5 microns containing M.tuberculosis bacilli expectorated by a sputum smear positive adult with pulmonary TB. TB infected infants and postpubertal adolescents are at increased risk for progression to TB disease and children aged less than 4 yrs are at increased risk for disseminated disease. From whom?: yaya/driver or parents/grandparent - by close contact with adults who are TB(+) TB is not a zoonotic disease so children cant get TB from their pets Filipinos are not fond of drinking fresh milk(mycobacterium bovis), besides, most fresh milk is pasteurized.
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Spectrum of TB
TB exposure: child in close contact with a source case
(-) Signs & symptoms presumptive of TB
(-) Tuberculin Skin Test (TST)
TB infection: child is found to have
(-) Signs & symptoms presumptive of TB
(+)Tuberculin Skin Test
(-) radiologic/laboratory evidence suggestive of TB
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Spectrum of TB
TB disease:
(+) signs & symptoms presumptive of TB
(+) Tuberculin Skin Test and/or
(+) radiologic/laboratory evidence suggestive of TB
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Diagnosis of TB in Children
GOLD STANDARD
a positive culture with or without a positive AFB smear for Mycobacterium tuberculosis
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Why is the diagnosis of Tuberculosis in a child so difficult?
the diagnosis of childhood
tuberculosis (TB) is especially difficult compared to that of an adult in the absence of a gold
standard in many cases because of the following reasons:
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Diagnosis of TB in Children
The occurrence of asymptomatic infection (latent TB infection) and early disease in childhood.
The poor bacteriologic yield.
The difficulty of collecting specimen in the young.
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The occurrence of asymptomatic infection (latent TB infection) and early disease in childhood,
The poor bacteriologic yield brought about by the paucibacillary character of TB in the young.
The difficulty of collecting specimen in the young: i.e. children
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Diagnosis of TB in Children
Demonstration of acidfast bacilli on microscopy and histologic changes on biopsy can only provide presumptive diagnosis in the absence of a positive culture.
Radiologic evidence is often equivocal: it requires consensus among radiologists.
The Tuberculin Skin Test has logistic limitations on top of high false negative findings even under ideal settings.
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Demonstration of acid-fast bacilli on microscopy and histologic changes on biopsy can only provide presumptive diagnosis in the absence of a positive culture.
Radiologic evidence is often equivocal: it requires consensus among radiologists for a clear-cut set of criteria.
The Tuberculin skin test has logistic limitations on top of high false negative findings even under ideal settings.
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Diagnosis of TB in Children
In the absence of bacteriologic evidence, a child is presumed to have active TB if 3 or more of the following criteria are present:
Epidemiologic
Clinical
Immunologic
Radiologic
Laboratory
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Epidemiologic
Exposure to an adult/adolescent with active TB disease
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Clinical: TB symptomatic
cough or wheezing of >2wks
unexplained fever of >2wks
loss of appetite, wt. loss, failure to gain wt.
failure to respond to 2wks of AB tx for LRTI
failure to regain previous state of health after 2
wks of viral infection or exanthema (measles)
fatigue, reduced playfulness, lethargy, loss of normal energy
TB symptomatic: 3 or more of the following signs and symptoms suggestive of TB
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Immunologic
(+) Tuberculin Skin Test
>5mm induration
Hx: close contact with known or suspected case of TB
Clinical findings suggestive of TB
Chest X-ray suggestive of TB
Immunocompromised condition
>10mm induration
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2008 PPS Evidence Based Clinical Practice Guidelines for Childhood TB recommendation statement: After intradermal administration of 0.1ml of 5 TU PPD purified protein derivative, the mantoux test is read at 48-72hours, regardless of BCG status, an induration of >5 mm is considered positive in the presence of any of the following:history of close contact with a known or suspected infectious case of TB, clinical findings suggestive of TB, chest x-ray suggestive of TB, immunocompromised condition. Otherwise, an induration >10mm is considered positive.
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Radiologic
No pathognomonic radiologic findings
Most suggestive of PTB:
hilar/paratracheal adenopathy
parenchymal changes
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Laboratory
Laboratory findings suggestive of TB
Histologic
Cytologic
Biochemical
Immunologic
Molecular
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Classification: TB Disease in Children
Pulmonary TB
Latent Infection
Primary TB
Progressive Primary TB
Extra-Pulmonary TB
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Latent Infection : infection associated with tuberculin hypersensitivity and a positive tuberculin skin test but with no striking clinical or roentgenographic manifestations. Occasionally, low grade fever is found , usually by chance. Primary TB: Infection among infants more frequently results in disease with local progression and dissemination: the younger the patient, the greater the risk of progressive disease until the age of 5 yrs. When disease occurs it is usually the childhood type of pulmonary TB referred to as Primary TB. A radiographic correlate is the demonstration of the Ghon complex: the primary focus, lymphangitis, regional lymphadenitis. Progressive Primary disease: latent primary infection and primary disease can progress into an area of advancing pneumonia. The pulmonary focus enlarges and develops a large caseous center, instead of resolving or calcifying. Persistent fever or cough, with malaise and weight loss with lung findings suggestive of cavitation occur. Crepitant rales and/or diminution of breath sounds over the affected area may be appreciated. Extrapulmonary Tuberculosis: TB of organs other than the lungs. Signs and symptoms are referable to the site of lesion.
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The First-Line Anti-TB Drugs
INH
Rifampicin
Pyrazinamide
Ethambutol
Streptomycin
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First line drugs have superior efficacy and acceptable toxicity
Second-line drugs haave less efficacy, greater toxicity or both. These are used as alternatives when there is either resistance, toxicity or hypersensitivity to first-line drugs, in cases of failure of clincal response to first line drugs and when expert guidance is available.
Unfortunately, none of the secon-line drugs are widely available locally.a
Except for ethambutol, all first-line drugs are bactericidal agents.
The ATS, IDSA, and CDC no longer consider streptomycin as a first-line drug
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INH MOA
Bactericidal for actively growing bacilli
Acts on extra/intracellular populations
Inhibit biosynthesis of mycolic acid (cell wall component)
The INH prodrug is activated by KatG, mycobacterial catalase peroxidase. Once activated, forms a covalent complex that blocks mycolic acid synthesis.
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INH
Pharmacokinetics
Absorption Readily absorbed fr GIT
Distribution Diffuses to all body fluids and tissues
CSF concn 20-100% of serum
Metabolism genetically determined
Rapid acetylators T/2 1hr; achieves subtherapeutic levels if given once/wk
Slow acetylators T/2 3hrs
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Absroption is decreased by aluminum hydroxide
Excreted in urine
Drug interactions may reduce the metabolism of pheynytoin, carbamazepine and ethosuximide
Routine monitoring of transaminases not believed necessary for children
Protect drug from light.
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INH
Adverse Reactions
Hepatotoxicity INH induced hepatitis
most frequent major toxic effect
d/c INH if (+) sx or if transaminases increase >3.5 x upper limits of normal
Fever and rash hypersensitivity rxns
Peripheral neuropathy
due to increased pyridoxine excretion
Supplement 10mg B6 daily if with sz/malnut
Seizures in high doses
Optic neuritis, toxic psychosis
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Rifampicin
Bactericidal / acts on extra and intracellular bacillary populations
MOA: binds strongly to subunit of bacterial DNA-dependent RNA polymerase inhibits RNA synthesis.
Pharmacokinetics
Well absorbed orally, enterohepatic circulation
Well distributed in tissues, body fluids with therapeutic levels in CSF
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Rifampicin
Pharmacokinetics
Metabolism even deacetylated form (metabolized form) has antibacterial activity
Excreted mainly through liver into bile and urine (deacylated form)
Drug interactions:
Potentiate microsomal Cytochrome P450 mediated enzymatic activities causing increased metabolism of digoxin, phenytoin, chloramphenicol,coumadin, ketoconazole, prednisone, theophyline
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Rifampicin
Adverse Effects
GI intolerance may be severe
Produce reddish coloration of body fluids - urine, tears, saliva
Cholestatic jaundice/hepatitis
Hypersensitivity: flushing, fever, pruritus, flu-like sx
Increases risk of hepatotoxicity if used with INH (adjust doses)
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Rifampicin
Other clinical uses
Leprosy in combination with other drugs
For chemoprophylaxis- household contacts of meningococcal and H.flu dis.
MRSA
In combination with Vancomycin or Ceftriaxone for meningitis
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Pyrazinamide Weakly bactericidal but with potent sterilizing activity
within macrophages and areas of acute inflammation, vs residual intracellular organisms that may cause relapse.
MOA
Converted to active pyrazinoic acid (unknown drug target and MOA)
Pharmacokinetics Well absorbed from GIT
Widely distributed to body tissues and inflammed meninges
T/2 8-11hrs
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Pyrazinamide
Adverse Effects Most hepatotoxic of all TB agents
GI sx
Photosensitivity and rash
Hyperuricemia due to decreased urate excretion
Arthralgia, esp of shoulders
If patient is diabetic: monitor glucose levels
Protect from light.
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Ethambutol
Bacteriostatic in macrophages, but with some cidal action at higher doses.
Acts on extra and intracellular bacillary populations, active vs bacilli in cavities.
MOA
Inhibitor of mycobacterial arabinosyl transferases leading to inhibition of polymerization of arabinoglycan, an essential component of the mycobacterial cell wall.
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Ethambutol
Pharmacokinetics
Well absorbed from the gut
CSF concn increases with inflammed meninges = 4-64% of serum levels
50% of dose is excreted in the urine unchanged
20% excreted in feces
Reduce dose by half if Cr clearance is
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Ethambutol
Adverse Effects
Retrobulbar neuritis
Reduced visual acuity
contraction of visual fields
green-red color blindness
Not usually seen at recommended doses
Hypersensitivity reactions rare
Should not be given to children
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Streptomycin
Bactericidal aminoglycoside vs M.tb in vitro but inactive vs intracellular bacilli limited activity to suppression, activity limited to extracellular bacteria.
MOA
Binds to 30S ribosomal subunit and interferes with initiation of protein synthesis by fixing the 30S-50S ribosomal complex at the start codon (AUG) of mRNA.
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Streptomycin
Pharmacokinetics
Poorly absorbed orally
Must be given parenterally
Poor CSF penetration, unless meninges inflammed
Elimination renal reduce dose if with decreased UO or if (+) casts/albumin in urine
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Streptomycin
Adverse Effects
Ototoxicity
Nephrotoxicity
Vertigo and hearing loss most common side effects
Sterile abscess
Lupoid reactions rare
Do not give with other nephrotoxic and ototoxic drugs
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Adverse Reactions
What are the recommendations in case the patient develops these adverse drug reactions?
GI intolerance
Mild skin reactions
Orange-red colored urine
Pain at the injection site
Burning sensation in the feet (periph neuropathy)
Arthralgia due to hyperuricemia
Flu-like sx
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Side Effects Drug Responsible
What to Do
GI intolerance Rifampicin Give medication at bedtime
Mild skin reactions
Any kind Give anti-histamines
Orange-red colored urine
Rifampicin Reassure the patient
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Side Effects Drug Responsible
What to Do
Burning sensation feet
INH Give vit B6
Arthralgia hyper-uricemia
PZA Give NSAID
Flu-like sx Rifampicin Give anti-pyretics
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Side Effects Drug Responsible
What to Do
severe rash hyper- sensitivity
Any kind esp streptomycin
d/c anti TB drugs, refer to MD
Jaundice -hepatitis
Any kind esp INH,Rifampicin PZA
d/c anti TB refer, resume tx if sx gone
Impaired visual acuity/color
vision-optic neuritis
Ethambutol d/c etham, refer to ophtha
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Side Effects Drug Responsible
What to Do
Hearing impairmnt, tinnitus CN8
Streptomycin d/c anti-TB drugs and refer to MD
Oliguria/albuminuria Renal dis.
Streptomycin Rifampicin
Psychosis and convulsion
INH
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Clinical Form Intensive Phase
Continuation Phase
TB Exposure < 5 yrs 5 yrs
3H to be modified based on follow up TST result
Latent TB PPD conversion within past 1-2 yrs (-)Cxray
9H
Latent TB PPD(+) with stable healed lesion (-) previous Tx
9H
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Clinical Form Intensive Phase
Continuation Phase
Latent TB PPD(+),stable/healed lesion, previous tx(+) At risk for reactivation due to measles/pertussis
1-2 H
Latent TB PPD(+),stable/healed lesion, previous tx(+) At risk for reactivation due to immunosuppression
H for the duration immuno-suppression
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Clinical Form Intensive Phase
Continuation Phase
Active TB disease New, smear(-) pulmonary TB
2HRZ 4HR or 6HE
Active TB disease Less severe form extrapulmonary TB
2HRZ 4HR or 6HE
Active TB disease New, smear(+) pulmonary TB
2HRZE(S) 4HR or 6HE
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Clinical Form Intensive Phase
Continuation Phase
Active TB Disease New smear (-) pulmonary TB with extensive parenchymal involvement
2HRZE(S)
4HR or 6HE
Active TB Disease Severe forms of extrapulmonary TB (other than TB meningitis)
2HRZE(S)
4HR or 6HE
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Clinical Form Intensive Phase
Continuation Phase
Active TB Disease TB Meningitis
2HRZS 4HR
Active TB Disease Miliary TB Bone & Joint TB
2HRZS 7-10HR
Active TB Disease previously treated smear(+)Pulmo TB, Relapse tx after interruption tx failure
2HRZES/ 1HRZE
5HRE
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TB & Pregnancy
TB in pregnancy should be treated without delay.
H,R,Z,E have no known teratogenic effects
2HRZE then 4HR
Pyridoxine 25mg/day
Streptomycin - contraindicated
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Tuberculosis in pregnancy should be treated without delay. Untreated TB will cause more harm than adverse events associated with treatment of pregnant women and babies. Infants born to women with untreated TB have higher risks of having fetal growth retardation, small for gestational age,
low APGAR scores, low birth weight and rarely congenital TB. Isoniazid, rifampicin, pyrazinamide, and ethambutol have no known teratogenic effects and are considered safe for pregnant patients with TB. Although the safety of PZA is not yet well established, the WHO recommends the use of PZA for 2 months. The standard short- course chemotherapy consisting of an initial
phase using HRZE for two months followed by HR for four months is recommended if the probability of TB is moderate to high.
Pregnant women taking isoniazid should be given pyridoxine (Vitamin B6) at 25 mg/day because isoniazid may cause demyelination in the patient and in the fetus.
Streptomycin may cause ototoxicity in fetuses and should not be used in the treatment of pregnant patients with TB. [Grade B]
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TB and Breastfeeding
Lactating women being treated for TB with the first-line anti-TB drugs may continue to breastfeed.
The small concentrations of anti-TB drugs in breast milk do not produce toxicity in nursing newborns.
Drugs in breast milk should not be considered as an effective treatment for active TB or latent TB infection in a nursing infant. Drug levels in breast milk are not sufficient for Treatment of TB in the infant.
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Review
Mechanisms of Action of first line & second line anti-TB drugs
Pharmacokinetics
Adverse Drug Reactions
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INH inhibits mycolic acid synthesis (cell wall synthesis)-Cidal Rifampicin inhibits RNA synthesis by binding to RNA polymerase and
penetrates phagocytic cells Cidal PZA Intracellular drug (macrophage) and works within the lysosome
MOA unknown Cidal/ not for longterm tx bec. Dormant bacilli resistant to PZA
Ethambutol inhibits mycolic acid synthesis by inhibiting transferases involved polymerization of cell wall components Static
Streptomycin inhibits protein synthesis So INH/Ethambutol inhibit mycobacterial cell wall synthesis/ While
Rifampicin inhibits RNA synthesis/Streptomycin inhibitsProtein synthesis PZA MOA unknown. Adverse Drug Reactions: INH hepatitis, peripheral neuropathy, seizures Rifampicin- orange color of body fluids, cholestatic jaundice PZA most hepatotoxic, gout hyperuricemia Ethambutol retrobulbar neuritis, difficult to administer to