_____ causes tuberculosis in humans.
_____ are obligately aerobic, non-motile, slightly curved or straight bacilli.
MTB retains _____ dye when decolorized with acid-ethanol by the _____ method (acid fastness).
MTB Survival Strategies
1. prevention of acidification of phagosomes 2. neutralization of the effects of reactive oxygen intermediates by the mycobacterial cell wall 3. inhibition of plasma membrane repair 4. inhibition of phagosome-lysosomal fusion through secretion of SapM (acid phosphatase)
Key Risk Factors for TB
smear (+) household contact < 5 y.o. immunodeficiency
inhalation of droplet nuclei (5-200 bacilli)
TB Incubation Period
_____ is the condition in which a child is in close contact with a contagious host but without any signs and symptoms, with (-) TST and (-) CXR and laboratory findings.
_____ is the condition in which a child has no signs or symptoms, (-) CXR and laboratory findings but has (+) TST.
TB Infection Latent TB Infection (LTBI)
_____ is presumptive TB with (+) CXR and/or TST.
_____ TB has biological specimen which is positive by sear microscopy, culture or rapid diagnostic tests.
_____ TB does not fulfill the criteria for bacteriological confirmation but has been diagnosed with active TB.
_____ is a case of tuberculosis involving lung parenchyma and tracheobronchial tree ± other sites of the body.
Pulmonary TB (PTB)
_____ is a case of TB involving orgens outside the pulmonary system.
Extrapulmonary TB (EPTB)
Laryngeal TB is considered as _____.
_____ is the initial stage in children who inhale MTB.
Primary PTB Disease Components
Ghon focus lymphadenitis lymphangitis
95% of primary PTB disease heals by _____.
fibrosis and/or calcification
Primary TB in children is asymptomatic up to _____ of patients.
Fever in primary Tb is usually _____ and lasts for _____.
low-grade 14-21 days
_____ is the condition which develops when initial TB infection fails to heal and continues to progress for months or years.
Progressive Primary TB
_____ is the condition which represents reactivation of an old, possibly subclinical TB infection.
Secondary (Reactivation) TB
Secondary TB occurs in _____ of the cases of primary infection.
Secondary TB is more common on _____.
Clinical Manifestations of Secondary TB
chronic or persistent cough prolonged fever chest pain hemoptysis supraclavicular adenitis
_____ is the clinical disease resulting from the hematogenous dissemination of MTB.
_____ is the most common clinically significant form of disseminated TB.
_____ is now used to denote all forms of progressive widely disseminated hematogenous TB.
The most common extrapulmonary sites of Miliary TB include the _____.
lymphatic system bones joints liver
_____ are more common in childhood TB than in adults.
peripheral lymphadenopathy hepatomegaly
Peritonitis is found in _____ of patients with advanced Miliary TB.
_____ can be a complication of primary TB which results in enlargement of peribronchial lymph nodes with subsequent compression or nodal extension into the bronchus.
Compression from Endobronchial TB cam cause _____.
asphyxia obstructive emphysema atelectasis
The _____ is more vulnerable to Endobronchial TB due to its anatomy and drainage.
R middle lobe
Endobronchial TB can cause _____ which could be mistaken for pertussis or bronchial asthma.
crepitant rales wheezes
_____ is the most common form of extrapulmonary TB and probably the most common cause of chronic lymphadenitis in children.
Tuberculous Lymphadenitis (Scrofula)
TB Lymphadenitis occurs most frequently in the _____ age group.
The most common location for TB Lymphadenitis is the _____, followed by the _____ areas.
anterior cervical space (49.4%) axillary and supraclaavicular areas
The most common presentation of TB Lymphadenitis is _____.
unilateral or multiple slow-growing nontender lymphadenopathies
The involved lymph node in TB Lymphadenitis is usually described as _____.
firm painless ruberry discrete matted fixed overlying skin induration
Fistula formation is seen in _____ of TB Lymphadenitis cases.
The use of _____ can improve the diagnosis of TB Lymphadenitis.
FNAB with rapid molecular diagnostic tests
_____ is the most severe form of extrapulmonary TB.
TB Meningitis occurs most commonly in children _____ but uncommon in infants _____.
< 6 y.o., < 4 mos.
TB Meningitis usually appears within _____ after initial infection.
TB Meningitis usually accompanies Miliary TN in _____ of cases.
TB Meningitis Stages: personality changes, irritability, anorexia, listlessness, fever
TB Meningitis Stages: increased ICP, cerebral damage, drowsiness, stiff neck, CN palsies, anisocoria, vomiting, tâche cérébrale, absence of abdominal reflexes, seizures
TB Meningitis Stages: coma, irregular HR and RR, rising fever
TB Meningitis CSF Findings
↑ WBC 50-500 WBC/mm3 PMNS - early Lymphocytes - late ↓ glucose ↑ protein
TB Meningitis Neuroimaging Triad
Hydrocephalus (80%) Basal Meningeal Enhancement (75%) Arteritis (cerebral infarcts)
_____ are enlarged granulomatous foci within the brain parenchyma.
Tuberculous brain abscesses lack _____ associated with tuberculomas.
giant cells granulomatous reaction
Tuberculomas occur most often in children _____.
< 10 y.o.
Tuberculomas are often located at the_____.
infratentorial area cerebellar area
The most common areas affected by TB spinal meningitis are _____.
dorsal cord (most common) lumbar region cervical region
TB osteomyelitis and arthritis account for _____ of EPTB and only _____ of all cases of TB.
TB osteomyelitis and arthritis can be cause by _____ spread from an initial infection.
Younger children are more vulnerable to TB osteomyelitis and arthritis due to the _____
increased blood flow to growing bones
TB osteomyelitis usually starts as an area of endarteritis in the _____ of long bone where blood supply is more abundant.
The most common skeletal sites affected by TB are _____.
spine (most common) hip knee
The most common sites affected by Pott's Disease are _____.
upper lumbar lower thoracic lumbosacral
In Pott's Disease, there is destruction of the intervertebral disk space and adjacent vertebral bodies, collapse of spinal elements and anterior wedging leading to _____.
angulation gibbus kyphosis
_____ is the most frequent symptom of Pott's Disease.
Duration of Pott's Disease ranges from _____.
TB arthritis is _____ in children and is usually _____.
_____ is an aseptic reactive polyarthritis caused by TB..
_____ is second to PTB in frequency.
The most common forms of abdominal TB are _____.
nodal involvement peritonitis intestinal involvement liver (6.1%) ileum (1.5%) perineum (1..5%) spleen (1.5%)
Ingested of sputum infected with MTB is the most important suggested cause of _____.
TB Enteritis usually affects the _____.
ileocecal area mesenteric LN peritoneum
Enlarged caseous and calcified meseneric LNs also known as _____ are often seen as densities on abdominal x-ray.
_____ is commonly due to rupture of a caseous abdominal LN and less frequently from a focus in the intestine or fallopian tube.
_____ TB Peritonitis is less common and is characterized by tender abdominal masses and a doughy abdomen.
_____ TB Peritonitis presents with ascitis and classic signs of peritonitis.
TB Peritonitis Peritoneal Fluid Analysis
exudative lymphocytic predominance serum ascitic fluid albumin gradient < 1.1 g/dl ↑ protein content (> 25 g/L)
_____ is referred to as primary miliary TB of the liver.
Hepatobiliary TB Types
diffuse hepatic involvement with PTB or miliary TB diffuse hepatic involvement without PTB focal tuberculoma or abscess
The overall incidence of isolated liver TB is _____.
Hepatic TB lesions that are larger than 2 mm are called _____.
macronodular TB pseudotumoral TB
Cutaneous TB Classification: tuberculous chancre
Cutaneous TB Classification: miliary tuberculosis
Cutaneous TB Classification: lupus vulgaris
Cutaneous TB Classification: scrofuloderma
Cutaneous TB Classification: tuberculous verrucosa cutis
Cutaneous TB Classification: tuberculous gumma (metastatic abscess)
Cutaneous TB Classification: orificial tuberculosis
Cutaneous TB Classification: micropapular lichen
Cutaneous TB Classification: scrofuloderma
Cutaneous TB Classification: papular-papulonectrotic
Cutaneous TB Classification: nodular (erythema induratum)
Cutaneous TB Classification: Primary
tuberculous chancre miliary TB
Cutaneous TB Classification: Secondary
lupus vulgaris scrofuloderma tuberculous verrucosa cutis tuberculous gumma (metastatic abscess) orofocial TB
Cutaneous TB Classification: Tuberculids
micropapular lichen scrofuloderma papular-papulonecrotic nodular (erythema induratum)
_____ are hypersensitivity reactions to MTB.
_____ is the most common form of childhood cutaneous TB.
Cutaneous TB Manifestations
inoculation from an exogenous source or BCG hematogenous dissemination erythema nodosum
Ocular TB frequently involves the conjunctivae and the cornea in the form of _____.
Phlyctenular Keratoconjunctivitis is considered a hypersensitivity reaction to _____.
Phlyctenular Keratoconjunctivitis presents as _____.
1-3 mm grey to yellow colored jelly-like nodules
Renal TB is an uncommon complication of primary TB which occurs _____ after primary infection.
Genitourinary TB is usually seen in children _____.
> 7 y.o.
_____ spread could cause tubercles in the glomeruli with caseating sloughing lesions.
Children whose urine reveal presence of MTB are considered highly infectious and should be isolated until _____.
their urine is sterile
The most common sites for genital TB in females are _____.
fallopian tubes (90-100%) endometrium (50%) ovaries (20-30%) cervix (2-4%)
_____ should be highly suspected in the presence of painless otorrhea unresponsive to conventional treatment ina patient with TB.
Pathophysiology of Perinatal TB
hematogenous spread from umbilical vein → ingestion of infected amniotic fluid or postpartum inhalation
Criteria for Congenital TB
1. 1st week of life 2. primary hepatic complex or caseating hepatic granuloma 3. TB infected placenta or endometrium
Effects of Maternal TB
infertility poor reproductive performance recurrent abortions stillbirth PROM preterm labor
Spectrum of TB: (+) exposure (-) signs and symptoms (-) TST (-) CXR (-) sputum smear (-) other diagnostics
Spectrum of TB: (+) exposure (-) signs and symptoms (+) TST (-) CXR (-) sputum smear (±) other diagnostics
Spectrum of TB: (+) exposure (+) signs and symptoms (+) TST (±) CXR (±) sputum smear (±) other diagnostics
Classification of TB Disease is based on _____.
bacteriological status anatomical site history of previous treatment HIV status drug susceptibility
Those who can expectorate sputum may be classified into PTB, _____.
sputum smear positive or negative
TB Classification: a patient who has never had treatment for TB or who has taken anti-TB drugs for < 1 mo. Isoniazid Preventive Therapy (IPT) or other preventive regimens are not considered.
TB Classification: a patient who has been previously treated with anti-TB drugs for ≥ 1 mo.
TB Classification: a case of TB who has a (-) HIV result at the time of diagnosis
HIV (-) Patient
TB Classification: a case of TB who has a (+) HIV result at the time of diagnosis
HIV (+) Patient
TB Classification: resistant to 1 first-line anti-TB drug
TB Classification: resistant to > 1 first-line anti-TB drug (other than Isoniazid or Rifampicin)
TB Classification: resistance to at least both Isoniazid and Rifampicin
Multidrug-Resistant TB (MDR-TB)
TB Classification: resistance to any fluoroquinolone and to at least 1 of 3 second-line injectable drugs (capreomycin, kanamycin, amikacin)
Extensively Drug-Resistant TB (XDR-TB)
TB Classification: resistance to Rifampicin, detected using phenotypic or genotypic methods, ± resistance to other anti-TB drugs.
Rifampicin-Resistant TB (RR-TB)
A child is presumed to have active TB if ≥ 3 of the following criteria are met:
exposure to host with active TB (Epidemiologic) signs and symptoms (Clinical) (+) TST (Immunologic) (+) CXR findings (Radiologic) (+) laboratory findings (Laboratory)
_____ refers to any person with signs and/or symptoms suggestive of TB or those with CXR findings suggestive of TB.
Children who are ≥ 15 y.o. with cough of ≥ 2 weeks are presumed to have TB if they have any of the ff.:
weight loss fever hemoptysis chest or back pains easy fatigueability malaise night sweats shortness of breath difficulty of breathing
Children who are ≥ 15 y.o. with unexplained cough of any duration are presumed to have TB if they have _____.
close contact to host with active TB immunocompromised state
A child < 15 y.o. is presumed to have active TB if ≥ 3 of the following criteria are met:
coughing/wheezing x 2 weeks unexplained fever x 2 weeks weight loss failure to thrive loss of appetite failure to respond to 2 weeks of antibiotics failure to regain previous state of health 2 weeks after viral infection fatigue reduced playfulness lethargy
A child < 15 y.o. and has had _____ is presumed to have TB if at least 1 of the clinical criteria are met.
close contact to a known case of active TB
A child is presumed to have EPTB if the any of the ff. are present:
gibbus non-painful enlarged cervical lymphadenopathy with or without fistula nuchal rigidity pleural effusion pericardial effusion distended abdomen with ascites non-painful enlarged joint tuberculin hypersensitivity
Treatment for active TB should be done if the child has ≥ 3 of the ff.:
exposure (+) TST signs &amp;amp; symptoms (+) CXR (+) laboratory tests
_____ is the most important diagnostic tool in TB.
Reaction to TST starts after _____ and reaches its peak at _____.
5-6 hours, 48-72 hours
The current standard for TST is the _____.
The Mantoux Test is done with _____ of solution containing _____ of purified protein derivative (PPD).
0.1 ml, 0.1 μg
PPD for Mantoux Test
5 tuberculin units of PPD-S 2 tuberculin units of PPD-RT 23 with Tween 80
Immunologic-based testing for TB is done with _____.
Interferon-Gamma Release Assay (IGRA)
The delayed hypersensitivity reaction is manifested as a _____ immune response mediated by _____ and is characterized by an indurated response to the intradermal injection from the cell wall of the MTB.
Type IV, sensiitized T-Lymphocytes
Administration of Mantoux Test
2 in. below elbow in the volar aspect of the forearm g.25-27 short bevel needle (1/4-1/2 in.) 0.1 ml of PPD intradermal - wheal of 6-10 mm
TST should be read within _____.
(+) TST reactions can be read accurately for up to _____.
(-) TST reactions can be read accurately for up to _____.
False (+) TST
infection with non-tuberculous mycobacteria previous BCG vaccination (≤ 5 years) incorrect TST administration incorrect measurement or interpretation incorrect strength of antigen
False (-) TST: Host Factors
infections live attenuated virus vaccinations (measles, mumps, polio, varicella) metabolic derangements nutritional factors lymphoid organ diseases coricosteroids immunosuppressive agents age (newborns, elderly) advanced TB infection stress complete anergy
False (-) TST: Tuberculin Factors
improper storage (light, heat) improper dilution chemical denaturation contamination adsorption into syringe (controlled with Tween 80)
False (-) TST: Administration Factors
too little antigen delayed administration after drawing into syringe too deep
False (-) TST: Reading and Recording Factors
inexperienced reader conscious or unconscious bias error in recording
The tuberculin solution must be stored at _____.
(+) TST: populations with no risk factors
≥ 15 mm
(+) TST: high risk populations
≥ 10 mm
(+) TST: ≥ 5 mm
HIV (+) close contact CXR with untreated TB organ transplant immunosuppression
_____ is the inability to react to a TST because of a weakened immune system.
_____ is the change from a (-) to a (+) TST result.
Skin Test Conversion
_____ can distinguish latent TB from previous BCG vaccination.
_____ is preferred for childern < 5 y.o.
IGRA is preferred for children who _____.
have receivedd BCG are unlikely to return for reading
IGRA results are available within _____.
IGRA blood samples should be processed within _____.
_____ of blood is needed to perform IGRA.
The only finding that may be highly suggestive of TB infants and children is the _____ found in miliary TB.
uniform stippling of both lungs
Gastric AFB is only (+) in _____ of cases.
Primary Complex CXR Findings
parenchymal involvement (primary focus) lymphangitis localized pleural effusion regional lymphadenitis
_____ is the most common CXR finding in children with TB.
Proper Exposure for CXR
PTB CT Scan Findings
< 1 cm LN calcified nodes ring enhancement granuloma peribronchial, axillary, hilar, paricardiac nodes
PTB CXR Findings
Ghon Complex (64%) parenchymal infiltrates (78%) air-space opacities (63%) atelectasis (22%) cavitary lesions (21%) bronchial and tracheal compression (12%) miliary pattern (10%)
The parenchymal reaction to TB is typically _____.
acinar consolidation (homogenous with ill-defined borders)
PTB predominantly affects the _____ with preferential location between _____.
upper lobes anterior-posterior segments right-left segments
Atelectasis in TB usually affects the _____
R upper and middle lobes *bronchial compression by enlarged LN
Progression from Ghon focus and lymohadenopathy occur in children _____.
< 5 y.o. > 10 y.o.
Radiographic clearing of TB usually occurs within _____ after therapy.
6 mos. - 2 years
Chronic PTB tends to localize in the _____.
apical and posterior segments of the upper lobes R > L
Chronic PTB CXR Findings
Local Exudative TB Local Fibroproductive TB Cavitation Tuberculoma
_____ is the radiolodic hallmark of reactivation TB.
Tuberculomas are usually found in the _____.
upper lobe R > L
In advanced Miliary TB, stippling in the lungs coalesce and produce a richly stippled patter called the _____.
Radiographic Improvement of Miliary TB starts at _____ and complete clearing is seen in _____.
5 weeks 7-22 mos. (mean 16 weeks)
Bronchiectasis from TB is 2x more frequent in patients with _____.
Pott's Disease begins with deposition of MTD through end arterioles into the _____.
anterior part of the vertebral body adjacent to the end plate.
_____ bone loss from TB is needed before changes are manifested on x-ray.
X-ray Triad of TB Arthritis
Phemister Triad juxtaarticular osteoporosis peripherally located osseous erosions narrowing of the interosseous space
the Phemister Triad is characteristic of _____.
The most specific CT Scan finding in TB Meningitis is _____.
basal cistern enhancement
The majority of infarcts caused by TB Meningitis are located at the _____.
basal ganglia internal capsule
The _____ are the most commonly affected regions of Tuberculoma.
frontal and parietal lobes
If the caseous core of a tuberculoma liquefies, it results in a _____.
Tuberculomas are usually _____ while TB Abscesses are usually _____.
multiple (tuberculoma) solitary (abscess)
Spinal TB MRI Findings
CSF loculation obliteration of he spinal subarachnoid space loss of outline of the spinal cord (cervicothoracic) matting of nerve roots (lumbar)
Routes of Abdominal TB
ingestion of infected sputum hematogenous spread local spread
_____ is the most common radiographic manifestation of abdominal TB.
Lymphadenopathy (55-66%) *mesenteric, omental, peripancreatic
_____ is the most common clinical manifestation of abdominal TB.
_____ involvement is seen in 80-90% of abdominal TB cases.
The wide gaping of the ileocecal valve with narrowing of he terminal ileum is called the _____.
The earliest radiographic abnormality seen in Renal TB is _____ due to erosion.
Genital TB in males is usually confined to _____.
seminal vesicles prostate gland
The primary sign of TB Pericarditis is pericardial thickening _____ on CT scan.
> 3 mm
Most patients with TB Pericarditis have distention of the inferior vena cava to a diameter _____.
> 3 cm
_____ microscopy is the easiest, least expensive and most rapid (1 hour) procedure in diagnosing TB.
Fluorescence Microscopy uses _____ which causes the acid-fast bacilli to fluoresce against a dark background.
Traditional TB culture methods used solid culture media like _____.
Solid TB culture requires _____ to isolate organisms and another _____ for sensitivity testing.
4-6 weeks, 2-4 weeks
Mycobacterial culture with the use of _____ are more rapid and sensitive.
broth-based culture media
Liquid TB culture provides results in ____.
Specimen Collection: _____ is recommended for infants and children who are unable to produce sputum even with aerosol inhalation.
Specimen Collection: _____ of gastric content should be aspirated for gastric AFB.
5-10 ml (max 15 ml)
Specimen Collection: For gastric lavage, _____ of sterile distilled water is injected through a stomach tube.
Specimen Collection: Gastric AFB should be done once daily for _____.
3 consecutive days
Specimen Collection: If transfer of gastric AFB is delayed for more than 1 hour, it must be neutralized with _____ and stored at _____>
sodium carbonate, room temperature
Specimen Collection: For older children who can expectorate, a series of _____ should be collected in _____ before start of therapy.
2 sputum specimens 2 different days
Specimen Collection: Sputum AFB
1. clean and thorough rinse of mouth with water 2. breathe deeply 3 times 3. after 3rd breath, cough hard and bring sputum from deep in the lungs. 4. expectorate the sputum into a sterile container.
Specimen Collection: _____ of sputum should be collected for AFB.
3 ml (1 tsp.)
Specimen Collection: If a sputum AFB sample is delayed for more than 1 hour, it should be _____.
Specimen Collection: The minimum amount for a respiratory aspirate AFB sample is _____.
Specimen Collection: If respiratory aspirate AFB sample is delayed for more than 1 hour, it should be _____.
Specimen Collection: The minimum amount for a CSF AFB sample is _____.
Specimen Collection: If a CSF AFB sample is delayed for more than 1 hour, it should be _____.
kept at room temperature
Specimen Collection: CSF AFB samples should be _____ if for PCR testing.
refrigerated or frozen
Specimen Collection: Tissue AFB samples should have _____ added for transport.
2-3 ml sterile saline
Specimen Collection: If a tissue AFB sample is delayed for more than 1 hour, it should be _____.
Specimen Collection: If an exudate or abscess AFB sample is delayed for more than 1 hour, it should be _____.
Specimen Collection: Exudate AFB swabs should have _____ added for transport.
2-3 ml sterile saline *ideally 7H9 broth
Specimen Collection: _____ of blood should be taken for TB culture.
Specimen Collection: Blood for TB culture must be placed in a _____.
yellow top vial (sodium polyanetholsulfonate, SPS) green top vial (heparin)
Specimen Collection: Blood for TB culture must be transported at _____.
Specimen Collection: BMA AFB specimen should be placed in a _____.
yellow top vial (sodium polyanetholsulfonate, SPS)
Specimen Collection: _____ of first morning urine should be collected for _____ for urine AFB testing.
40 ml (min. 10-15 ml) 3 consecutive days q8-24 hours
Specimen Collection: Stool AFB is not recommended except in patients with _____.
When MTB antigen load is small and the degree of tissue sensitivity is high, granuloma formation results from _____.
organization of lymphocytes, macrophages, Langerhans giant cells and fibroblasts
_____ utilize techniques to amplify nucleic acid regions specific to the MTB complex.
Nucleic Acid Amplification Tests (NAATs)
The most common target of NAATs is the _____ followed by the _____.
Line probe assays are recommended for _____ specimen only.
The _____ is the first fully automated, cartridge-based NAAT for TB which simplifies molecular testing by integrating and automating sample preparation, amplification and detection.
Gene Xpert MTB/RIF Assay
The _____ is a time-PCR-based molecular test that can simultaneously detect TB and Rifampicin resistance.
Gene Xpert MTB/RIF Assay
The Gene Xpert MTB/RIF Assay will show results within _____.
The _____ is recommended by the WHO as a replacement for conventional microscopy, culture and drug susceptibility testing as the initial diagnostic test for TB.
Gene Xpert MTB/RIF Assay
T-Lymphocytes from an infected host release _____ as a marker of infection or active TB.
Interferon Gamma (IFN-g)
Drug Efficacy TB Groups
1. actively growing MTB in open cavities (bactericidal drugs) 2. slowly multiplying MTB in caseous lesions (sterilizing drugs) 3. intracellular MTB in acidic compartments of macrophagesor acidic lung lesions (sterilizing drugs 4. TB persisters in hypoxic environments which are unresponsive to most anti-TB medication
Children have fewer mycobacterial organisms and are thus less likely to develop _____.
secondary drug resistance
EPTB is more common in _____.
_____ involves direct observation of anti-TB medication intake.
Direct Observed Treatment Short Course (DOTS)
3 Properties of Anti-TB Drugs
bactericidal activity sterilizing activity ability to prevent resistance
Properties of Anti-TB Drugs: killing of bacteria in a log-phase growth
Properties of Anti-TB Drugs: kill slowly growing or intermittently replicating bacilli
_____ is the most potent sterilizing anti-TB drug.
_____ is only active in the acidic intracellular environment of macrophages and in areas of acute inflammation.
_____ is bactericidal against rapidly multiplying MTB in an environment with high oxygen tension and neutral pH.
_____ is used together with other drugs to prevent emergence of resistant bacilli.
First-Line Anti-TB Drugs
Isoniazid Rifampicin Pyrazinamide Ethambutol
Second-Line Anti-TB Drugs: Injectables
Aminoglycosides (Streptomycin, Kanamycin, Amikacin) Polypeptides (Capreomycin)
Second-Line Anti-TB Drugs: Fluoroquinlones
Levofloxacin Moxifloxacin Ofloxacin
Second-Line Anti-TB Drugs: Rifampicin Analogs
Second-Line Anti-TB Drugs: Oral Bacteriostatic Agents
Para-Aminosalicylic Acid Cycloserine Terizidone Ethionamide Prothionamide
_____, formerly a first-line anti-TB drug, is now classified as a second-line drug due to the increasing resistance and its IM route.
In cases of _____, Streptomycin may still be used as part of the initial treatment
meningitis liver disease
_____ and _____ have recently been approved as anti-TB drugs as they have been proven to be effective in culture conversion.
Bedaquiline (hastens conversion) Delamanid (increasing conversion rates after 8 weeks of treatment)
Children should be given the adult dose of anti-TB drugs once they reach _____.
children - 10 (10-15 mkday) adults - 5 (4-6 mkday) *max. 300 mg/day
Isoniazid: Mechanism of Action
bactericidal against actively growing MTB inhibits mycolic acid synthesis inhibits catalase-peroxidase enzyme
Isoniazid: Adverse Reactions
hepatitis, peripheral neuropathy, allergic sken reactiong, possible hemolysis in G6PD, inhibits drug-metabolizing enzymes (DME) leading to increased risk of phenytoin, ethosuximide and carbamazepine toxicity
First-Line Anti-TB Drugs: bactericidal against actively growing MTB inhibits mycolic acid synthesis inhibits catalase-peroxidase enzyme
First-Line Anti-TB Drugs: hepatitis, peripheral neuropathy, allergic sken reactiong, possible hemolysis in G6PD, inhibits drug-metabolizing enzymes (DME) leading to increased risk of phenytoin, ethosuximide and carbamazepine toxicity
Plasma half-life of Isoniazid varies from _____ to _____.
< 1 hour (fast acetylators) > 3 hours (slow acetylators)
Discontinue Isoniazid, Rifampicin and Pyrazinamide if AST and/or ALT are _____.
> 3-5x normal values
For Isoniazid and Rifampicin, there is _____ for renal dysfunction.
no dose adjustment
Isoniazid and Rifampicin are best absorbed on an _____.
When co-administering Isoniazid and Rifampicin, Isoniazid must not exceed _____.
children - 15 (10-20 mkday) adults - 10 (8-12 mkday) *max. 600 mg/day
Rifampicin: Mechanism of Action
inhibits DNA-dependent RNA polymerase
Rifampicin: Adverse Reactions
hepatitis, hypersensitivity reactions, flu-like symptoms, thrombocytopenia, orange discoloration of body fluids, induces drug-metabolizing enzymes (DME) resulting in decreased plasma levels of AEDs, antibiotics, hormonal therapy agents and corticosteroids
First-Line Anti-TB Drugs: inhibits DNA-dependent RNA polymerase
First-Line Anti-TB Drugs: hepatitis, hypersensitivity reactions, flu-like symptoms, thrombocytopenia, orange discoloration of body fluids, induces drug-metabolizing enzymes (DME) resulting in decreased plasma levels of AEDs, antibiotics, hormonal therapy agents and corticosteroids
children - 30 (20-40 mkday) adults - (20-30 mkday) *max. 2 g/day
Pyrazinamide: Mechanism of Action
disruption of membrane energy metabolism
Pyrazinamide: Adverse Reactions
nausea, vomiting, most common cause of hepatotoxicity, hypersensitivity reactions, polyarthralgia
First-Line Anti-TB Drugs: disruption of membrane energy metabolism
First-Line Anti-TB Drugs: nausea, vomiting, most common cause of hepatotoxicity, hypersensitivity reactions, polyarthralgia
Pyrazinamide requires dose modification in _____.
children - 20 (15-25 mkday) adults - 15 (15-20 mkday) *max. 1.2 g/day
Ethambutol: Mechanism of Action
inhibits transferase enzymes involved in cell wall synthesis
Ethambutol: Adverse Reactions
peripheral neuropathy, retrobulbar optic neuritis (impairment of visual acuity and red-green color vision)
First-Line Anti-TB Drugs: inhibits transferase enzymes involved in cell wall synthesis
First-Line Anti-TB Drugs: peripheral neuropathy, retrobulbar optic neuritis (impairment of visual acuity and red-green color vision)
_____ was previously omitted from anti-TB regimens in children < 6 y.o. due to difficulty monitoring optic neuritis.
No anti-TB drug is effective against _____.
non-replicating or dormant MTB
_____ has the best bactericidal activity against rapidly multiplying MTB.
Rifabutin's advantages are _____.
reduced induction of hepatic metabolism used in patients also receiving antiretroviral therapt for HIV
______ was developed for once-weekly anti-TB therapy because it was more potent and longer-acting.
children - 15-30 mkday IM/IV adults - 15 mkday IM/IV *max. 1 g/day
children - 15-30 mkday IM/IV adults - 15 mkday IM/IV *max. 1 g/day
children - 20-40 mkday IM adults - 15 mkday IM *max. 1 g/day
Aminoglycosides: Mechanism of Action
bactericidal inhibits protein synthesis
Aminoglycosides: Adverse Reactions
nephrotoxicity, electrolyte disorders, CN VIII damage (ototoxicity), neuromuscular blockade
Second-Line Anti-TB Drugs: bactericidal inhibits protein synthesis
Second-Line Anti-TB Drugs: nephrotoxicity, electrolyte disorders, CN VIII damage (ototoxicity), neuromuscular blockade
Aminoglycosides are contraindicated in _____.
Aminoglycosides need dose adjustment in _____.
children - 15-30 mkday IM adults - 15 mkday IM *max. 1g
Capreomycin: Mechanism of Action
bactericidal inhibits protein synthesis
Capreomycin: Adverse Reactions
personality changes, psychosis, depression, seizures
Second-Line Anti-TB Drugs: personality changes, psychosis, depression, seizures
≤ 5 y.o. - 15-20 mkday PO BID > 5 y.o. - 10-15 mkday PO OD adults - 10-15 mkday PO OD
children - 7.5-10 mkday PO adults - 10-15 mkday PO *max. 740 mg/day
children - 7.5-10 mkday PO adults - 10-15 mkday PO *max. 400 mg/day
Fluoroquinolones: Mechanism of Action
bactericidal inhibits DNA gyrase
Fluoroquinolones: Adverse Reactions
nausea, bloating, headache, dizziness, insomnia, tremulousness, tendon rupture, arthralgia, QTc prolongation, hypoglycemia
Second-Line Anti-TB Drugs: bactericidal inhibits DNA gyrase
Second-Line Anti-TB Drugs: nausea, bloating, headache, dizziness, insomnia, tremulousness, tendon rupture, arthralgia, QTc prolongation, hypoglycemia
Fluoroquinolones are avoided during _____ due to concerns for arthropathy.
pregnancy < 18 y.o.
Fluoroquinolones need dose adjustment in _____.
Later-generation quinolones such as _____ are recommended instead of Ofloxacin since they are more potent.
Children _____ metabolize Levofloxacin faster.
< 5 y.o.
children - 15-20 mkday BID or TID adults 15-20 mkday OD or BID (500 or 750 mg/day) *max. 1 g/day
Prothionamide: Mechanism of Action
weakly bactericidal blocks mycolic acid synthesis
Prothionamide: Adverse Reactions
GI upset, anorexia, metallic taste, hepatotoxicity, endocrine disorders, gynecomastia, hair loss, acne, impotence, menstrual irregularity, reversible hypothyroidism
Second-Line Anti-TB Drugs: weakly bactericidal blocks mycolic acid synthesis
Second-Line Anti-TB Drugs: GI upset, anorexia, metallic taste, hepatotoxicity, endocrine disorders, gynecomastia, hair loss, acne, impotence, menstrual irregularity, reversible hypothyroidism
GI symptoms caused by Prothionamide can be minimized by _____.
food bedtime intake
_____ is recommended while on Prothionamide.
15-20 mkday PO *max. 750 mg/day
Ethionamide: Mechanism of Action
bactericidal inhibits cell wall (mycolic acid) synthesis
Ethionamide: Adverse Reactions
GI upset, hepatotoxicity, hypothyroidism
Second-Line Anti-TB Drugs: bactericidal inhibits cell wall (mycolic acid) synthesis
Second-Line Anti-TB Drugs: GI upset, hepatotoxicity, hypothyroidism
Ethionamide should be given at a _____ initially and if there is no adverse GI events then it can be given OD.
Ethionamide is contraindicated in pregnancy due to its _____.
children - 10-20 mkday q12 adults - 10-15 mkday OD or BID (500 or 750 mg/day) *max. 1 g/day
Cycloserine: Mechanism of Action
bacteriostatic inhibits cell wall synthesis
Cycloserine: Adverse Reactions
CNS toxicity, inability to concentrate, lethargy, personality changes, peripheral neuropathy, skin problems, lichenoid eruptions, SJS
Second-Line Anti-TB Drugs: bacteriostatic inhibits cell wall synthesis
Second-Line Anti-TB Drugs: CNS toxicity, inability to concentrate, lethargy, personality changes, peripheral neuropathy, skin problems, lichenoid eruptions, SJS
Cycloserine should be used with caution in patients with pre-existing _____.
mental health issues
Cycloserine may be associated with severe _____ adverse reactions.
Cycloserine should be avoided in patients with a history of _____.
_____ is recommended while on Cycloserine.
Para-Aminosalicylic Acid (PAS): Dose
150 mkday PO OD *max. 12 g/day
Para-Aminosalicylic Acid (PAS): Mechanism of Action
bacteriostatic inhibits folic acid synthesis inhibits iron metabolism
Para-Aminosalicylic Acid (PAS): Adverse Reactions
GI upset, hypothyroidism, hypersensitivity, crystallization in urine
Second-Line Anti-TB Drugs: bacteriostatic inhibits folic acid synthesis inhibits iron metabolism
Para-Aminosalicylic Acid (PAS)
Second-Line Anti-TB Drugs: GI upset, hypothyroidism, hypersensitivity, crystallization in urine
Para-Aminosalicylic Acid (PAS)
Advantages of Fixed-Dose Combination (FDC) Tablets
prescription errors are less likely less tablets to ingest the patient cannot be selective about which drugs to take
Fixed-Dose Combination (FDC) Tablets Preparations
H 50 mg + R 75 mg + Z 150 mg H 50 mg + R 75 mg
Fixed-Dose Combination (FDC) Tablets: 4-7 kg, Intensive Phase (HRZ)
Fixed-Dose Combination (FDC) Tablets: 8-11 kg, Intensive Phase (HRZ)
Fixed-Dose Combination (FDC) Tablets: 12-15 kg, Intensive Phase (HRZ)
Fixed-Dose Combination (FDC) Tablets: 16-24 kg, Intensive Phase (HRZ)
Fixed-Dose Combination (FDC) Tablets: 25+ kg, Intensive Phase (HRZ)
Fixed-Dose Combination (FDC) Tablets: 4-7 kg, Continuation Phase (HR)
Fixed-Dose Combination (FDC) Tablets: 8-11 kg, Continuation Phase (HR)
Fixed-Dose Combination (FDC) Tablets: 12-15 kg, Continuation Phase (HR)
Fixed-Dose Combination (FDC) Tablets: 16-24 kg, Continuation Phase (HR)
Fixed-Dose Combination (FDC) Tablets: 25+ kg, Continuation Phase (HR)
_____ should be added in the intensive phase for children with extensive disease or living in settings where the prevalence of HIV or of Isoniazaid resistance is high.
TB Registration Groups: a patient who has never had treatment for TB or who has taken anti-TB drugs for <1 mo.
TB Registration Groups: a patient previously treated for TB who has been declared cured or completed treatment in their most recent treatment episode, and is presently diagnosed with bacterioloically-confirmed or clinically diagnosed TB
TB Registration Groups: a patient who has been previously treated for TB and whose treatment failed at the end of their most recent course
Treatment After Failure (Retreatment)
TB Registration Groups: a patient whose sputum smear or culture is (+) at 5 mos. or later during treatment
Treatment After Failure (Retreatment)
TB Registration Groups: a clinically diagnosed patient for whom sputum examination cannot be done and who does not show clinical improvement anytime during treatment
Treatment After Failure (Retreatment)
TB Registration Groups: a patient who was previously treated for TB but was lost to follow-up for ≥ 2 mos. in their most recent course of treatment, and is currently diagnosed with either bacteriologically-confirmed or clinically-diagnosed TB
Treatment After Lost to Follow-up (TALF) (Retreatment)
TB Registration Groups: a patient who has been previously treated for TB but whose outcome after their most recent course of treatment is unknown or undocumented
Previous Treatment Outcome Unknown (PTOU)
TB Registration Groups: a patient who does not fit into any of the other groups
TB Categories: new PTB or EPTB (except CNS/bones/joints)
TB Categories: new EPTB (CNS/bones/joints)
TB Categories: previously treated drug-susceptible PTB or EPTB (except CNS/bones/joints)
TB Categories: previously treated drug-susceptible EPTB (CNS/bones/joints)
TB Treatment: Category I
2 HRZE / 4 HR
TB Treatment: Category Ia
2 HRZE / 10 HR
TB Treatment: Category II
2 HRZES / 1 HRZE / 5 HRE
TB Treatment: Category IIa
2 HRZES / 1 HRZE / 9 HRE
TB prophylaxis is recommended for _____.
children < 5 y.o. HIV (+) immunosuppressed individuals
Isoniazid Preventive Therapy (IPT) Dose
_____ is a case of TB, usually PTB, excreting bacilli which are resistant to one or more anti-TB drugs.
_____ is the bacterial resistance present in patients who have not received prior treatment with anti-TB drugs.
_____ is the bacterial resistance in patients with some record of previous treatment.
_____ is defined as clinical evidence of TB together with the detection of MTB from a specimen collected from the subject with genotypic or phenotypic resistance to at least Rifampicin.
_____ is defined as clinical evidence of TB and with positive clinical response to MDR-TB treatment or with immunological evidence of TB and documented exposure to a source case of MDR-TB.
TB is said to be cured when _____.
treatment is completed as recommended by the national policy without evidence of failure and ≥ 3 consecutive cultures taken at least 30 days apart are (-) after the intensive phase
The outcome when TB treatment is completed as recommended by the national policy without evidence of failure but no record that ≥ 3 consecutive cultures taken at least 30 days apart are (-) after the intensive phase is _____.
Risk Factors for Drug Resistance
failure to adhere to the appropriate regimen previous inappropriate treatment contact with DRTB host immigration from an area withhigh incidence of DRTB HIV (+)
Treatment Strategies for DRTB
Standardized Empirical Individualized
Treatment Strategies for DRTB: drug resistance and susceptibility (DRS) data from representative patient populations are used to base regimen design in the absence of individual drug susceptibility testing, and all patients in a defined group or category receive the same regimen
Treatment Strategies for DRTB: each regimen is individually designed based in the patient's previous history of anti-TB treatment and with consideration of drug resistance and susceptibility (DRS) data from the representative patient population
Treatment Strategies for DRTB: each regimen is individually designed based in the patient's previous history of anti-TB treatment and individual drug susceptibility testing results
TB Treatment: focuses on sputum culture conversion
TB Treatment: focuses on ensuring sterilization
Anti-TB Drug Groups: Group 1
First-Line Oral Agents (HRZE)
Anti-TB Drug Groups: Group 2
Injectable Agents (Kanamycin, Amikacin, Capreomycin, Streptomycin)
Anti-TB Drug Groups: Group 3
Fluoroquinolones (Moxifloxacin, Levofloxacin, Ofloxacin)
Anti-TB Drug Groups: Group 4
Oral Bacteriostatic Second-Line Agents (Ethionamide, Prothionamide, Cycloserine, Terizidone, PAS)
Anti-TB Drug Groups: Group 5
Agents with Unclear Efficacy (Clofazimine, Linezolid, Amoxicillin-Clavulanic Acid, Thioacetazone, Imipenem, Cilastatin, Clarithromycin, High Dose Isoniazid - 16-20 mkday)
use any Group 1 agents use an injectable agent to which the strain is susceptible and consider an extended duration of use if resistant to all injectable agents, use one which has not yet been given use later-generation fluoroquinolones use all Group 4 agents that have not been used extensively in a previous regimen use ≥ 2 agents from Group 5 consider low dose H treatment if with low-level resistance adjuvant surgery for local disease strong infection control measures treat HIV comprehensive monitoring and full adherence support
BCG Vaccine Storage
lyophilized powder (heat and light sensitive) refrigerated (2-8°C)
Once reconstituted, BCG must be refrigerated and used within _____.
Contraindications for BCG
HIV (+) Immunosuppression
_____ are intended to be used on newborns and young infants to replace or amplify BCG early in life and on older children who have not yet been exposed or infected.
Pre-Exposure TB Vaccines
_____ are given post-infancy and to older age groups to reduce progression of latent TB.
Post-Exposure TB Vaccines
_____ are given to those with active TB in conjunction with anti-TB treatment to shorten the duration of drug therapy or reduce relapses after completion of treatment
Algorithm for Preventive Therapy of Childhood Tuberculosis
Diagnostic Algorithm for TB
Screening of Pediatric Drug-Susceptible Household Contacts of TB