ROADMAP TO ROADMAP TO DIAGNOSIS & DIAGNOSIS &

TREATMENT OF TREATMENT OF EXTRAPULMONARY EXTRAPULMONARY

TBTB

DR. LIZA D. MARIPOSQUEDR. LIZA D. MARIPOSQUE

OCTOBER 23, 2008OCTOBER 23, 2008

MOST COMMON MOST COMMON EXTRAPULMONARY SITES FOR EXTRAPULMONARY SITES FOR

TBTB►Lymph nodesLymph nodes►PleuraPleura►Genitourinary tractGenitourinary tract►Bones & jointsBones & joints►MeningesMeninges►PeritoneumPeritoneum►pericardiumpericardium

LYMPADENITISLYMPADENITIS

►>40% associated with pulmonary >40% associated with pulmonary cases.cases.

►Presents as painless swelling of the LN Presents as painless swelling of the LN most commonly at posterior cervical & most commonly at posterior cervical & supraclavicular sites. (supraclavicular sites. (scrofula)scrofula)

►Discrete & nontender LN in early stage Discrete & nontender LN in early stage but may be inflamed and have a but may be inflamed and have a fistulous tract draining caseous fistulous tract draining caseous material.material.

►Dx: FNAB or Surgical BxDx: FNAB or Surgical Bx►50% AFB (+)50% AFB (+)►70-80% culture (+)70-80% culture (+)►Histologic exam shows granulomatous Histologic exam shows granulomatous

lesions but usually not seen in HIV Pt.lesions but usually not seen in HIV Pt.►DDx: neoplastic dses such as DDx: neoplastic dses such as

lymphomas or metastatic CA ; rarely lymphomas or metastatic CA ; rarely Kikuchi dse (necrotizing histiocytic Kikuchi dse (necrotizing histiocytic lymphadenitis)lymphadenitis)

PLEURAL TEBERCULOSISPLEURAL TEBERCULOSIS

►̴H̴H20% extrapulmonary TB in the US.20% extrapulmonary TB in the US.►Common in primary TB & may be due Common in primary TB & may be due

to either contiguous spread of to either contiguous spread of parenchymal inflammation or parenchymal inflammation or penetration of the tubercle to the penetration of the tubercle to the pleural space.pleural space.

►S/Sx: pleural effusion, fever, pleuritic S/Sx: pleural effusion, fever, pleuritic chest pain & dyspnea; tuberculous chest pain & dyspnea; tuberculous empyema is less commonempyema is less common

►Pleural fluid: straw colored and Pleural fluid: straw colored and sometimes hgic, exudative w/ a CHON sometimes hgic, exudative w/ a CHON conc.>50% (conc.>50% ( H 4-6g/dl), normal-low H 4-6g/dl), normal-low glucose conc., pH H 7.3 (<7.2), WBC glucose conc., pH H 7.3 (<7.2), WBC 500-6000/µL.500-6000/µL.

►> neutrophils in the early stage & > neutrophils in the early stage & mononuclear cells are the typical findings mononuclear cells are the typical findings later.later.

►AFB smear 10-25% & AFB culture 25-75%.AFB smear 10-25% & AFB culture 25-75%.►Adenosine deaminase (ADA) det.of the Adenosine deaminase (ADA) det.of the

pleural fluid is useful screening test.pleural fluid is useful screening test.

►FNAB- Dx, (+) granulomaFNAB- Dx, (+) granuloma►Culture (+) 80%Culture (+) 80%►Responds well to chemotherapy & may Responds well to chemotherapy & may

resolve spontaneously.resolve spontaneously.►Glucocortecoid?Glucocortecoid?

Tuberculous empyemaTuberculous empyema – – less common Cx. less common Cx.►Usually the result of the rupture of a Usually the result of the rupture of a

cavity & spillage of of organism to pleural cavity & spillage of of organism to pleural space.space.

►CXR – Hydropneumothorax w/ an air fluid CXR – Hydropneumothorax w/ an air fluid levellevel

►Pleural fluid is purulent & thick w/ inc. Pleural fluid is purulent & thick w/ inc. lymphocytes.lymphocytes.

►AFB & Culture (+)AFB & Culture (+)►Rx: surgical drainage, chemotx, Rx: surgical drainage, chemotx,

decorticationdecortication

Tuberculosis of the Upper Tuberculosis of the Upper AirwaysAirways

►Always a complication of cavitary Always a complication of cavitary tuberculosis.tuberculosis.

► Involve the larynx, pharyns & epiglottis.Involve the larynx, pharyns & epiglottis.►S/Sx: hoarseness, dysphonia, dysphagia, S/Sx: hoarseness, dysphonia, dysphagia,

chronic productive cough.chronic productive cough.►Laryngoscopy: (+) ulcerationLaryngoscopy: (+) ulceration►AFB sputum (+)AFB sputum (+)►Biopsy- to R/O laryngeal CABiopsy- to R/O laryngeal CA

GENITOURINARY GENITOURINARY TUBERCULOSISTUBERCULOSIS

►~~15% of cases in the US.15% of cases in the US.► Involved any portion of the GUT and 1/3 Involved any portion of the GUT and 1/3

have concomitant pulmonary disease.have concomitant pulmonary disease.►S/Sx: inc. urinary freq., dysuria, nocturia, S/Sx: inc. urinary freq., dysuria, nocturia,

hematuria and flank pain or abdominal hematuria and flank pain or abdominal pain.pain.

►Pt may be asymptomatic & the dse Pt may be asymptomatic & the dse discovered only after severe destructive discovered only after severe destructive lesion of the kidneys dev.lesion of the kidneys dev.

►>female, affects fallopian tubes, >female, affects fallopian tubes, endometrium – infertility, pelvic pain & endometrium – infertility, pelvic pain & menstrual abnormality.menstrual abnormality.

►Dx: Bx & cultureDx: Bx & culture►U/A: 90% abnormal; pyuria & hematuria.U/A: 90% abnormal; pyuria & hematuria.►Culture-negative pyuria in acidic urine Culture-negative pyuria in acidic urine

raises the suspicion.raises the suspicion.► IVP, CT/MRI: deformities, obstruction, IVP, CT/MRI: deformities, obstruction,

calcifications & ureteral strictures.calcifications & ureteral strictures.►Culture of 3 morning urine specimens Culture of 3 morning urine specimens

yields definitive Dx (90%).yields definitive Dx (90%).

►Male: >epididymis – tenderMale: >epididymis – tender

orchitis, prostatitis, UTIorchitis, prostatitis, UTI►Responds well to chemo.Responds well to chemo.

SKELETAL TUBERCULOSISSKELETAL TUBERCULOSIS

►~10% of the cases involves bones & ~10% of the cases involves bones & joints in the US.joints in the US.

►Pathogenesis: reactivation of Pathogenesis: reactivation of hematogenous foci or to spread from hematogenous foci or to spread from adjacent paravertebral LN.adjacent paravertebral LN.

Weight-bearing joints are most Weight-bearing joints are most commonly affected.commonly affected.

► Spine (Pott’s dse) = Spine (Pott’s dse) = 40%40%

► Hips = 30%Hips = 30%► Knees = 10%Knees = 10%

► Involves 2 or more Involves 2 or more adjacent vertebral adjacent vertebral bodies.bodies.

► Upper thoracic Upper thoracic spine is the most spine is the most common site in common site in children.children.

► Lower thoracic & Lower thoracic & lumbar vertebra are lumbar vertebra are common in adults. common in adults.

►Dx: CT/MRI; Aspiration of abscess & Dx: CT/MRI; Aspiration of abscess & bone Bx confirmsbone Bx confirms

synovial fluid – culture (+); thick synovial fluid – culture (+); thick in appearance w/ high protein content in appearance w/ high protein content & variable cell ct.& variable cell ct.

►Respond well to chemo but in severe Respond well to chemo but in severe cases may require surgery.cases may require surgery.

TUBERCULOUS MENINGITIS TUBERCULOUS MENINGITIS & TUBERCULOMA& TUBERCULOMA

►~5% CNS TB in the US.~5% CNS TB in the US.►Most often seen in adults, esp. HIV Most often seen in adults, esp. HIV

infected.infected.►Pathogenesis: hematogenous spread of Pathogenesis: hematogenous spread of

primary or postprimary pulmonary dse or primary or postprimary pulmonary dse or from the rupture of a subependymal from the rupture of a subependymal tubercle into the subarachnoid space.tubercle into the subarachnoid space.

►CXR: (+) old pulmonary lesion or miliary CXR: (+) old pulmonary lesion or miliary pattern pattern

►S/Sx: often presents subtly as HA, S/Sx: often presents subtly as HA, slight mental changes after a slight mental changes after a prodrome of wks of low-grade fever, prodrome of wks of low-grade fever, malaise, anorexia & irritability malaise, anorexia & irritability severe HA, confusion, lethargy, altered severe HA, confusion, lethargy, altered sensorium & neck rigidity.sensorium & neck rigidity.

►Typically, the disease evolves over 1-2 Typically, the disease evolves over 1-2 wks, a course longer than that of wks, a course longer than that of bacterial meningitis.bacterial meningitis.

►Paresis of CN (ocular) is a frequent Paresis of CN (ocular) is a frequent findings.findings.

►Cerebral art. Focal ischimia comaCerebral art. Focal ischimia coma►Dx: Dx: Lumbar punctureLumbar puncture

- CSF – high leukocyte ct. (up to - CSF – high leukocyte ct. (up to 1000/1000/µL)µL) but sometimes with increase but sometimes with increase neutrophils in the early stage.neutrophils in the early stage.

- CHON 1-8g/L (100-800mg/dl)- CHON 1-8g/L (100-800mg/dl)- low glucose conc.- low glucose conc.

AFB OF CSF – (+) 1/3 of cases.AFB OF CSF – (+) 1/3 of cases.Culture of CSF – gold standard, 80%Culture of CSF – gold standard, 80%PCR – 80% sensitive, 10% false (+)PCR – 80% sensitive, 10% false (+)

GASTROINTESTINAL TBGASTROINTESTINAL TB► Uncommon, 3.5% in the USUncommon, 3.5% in the US► MOT: swallowing of sputum w/ direct MOT: swallowing of sputum w/ direct

seeding, hematogenous spread, ingestion of seeding, hematogenous spread, ingestion of infected milk.infected milk.

► Most commonly affected are terminal ileum Most commonly affected are terminal ileum & the cecum.& the cecum.

► Mimic appendicitis.Mimic appendicitis.► Surgery is required in most cases.Surgery is required in most cases.► Dx: histopath & culture of specimes Dx: histopath & culture of specimes

obtained intraoperatively.obtained intraoperatively.

Tuberculous peritonitisTuberculous peritonitis►Ff either the direct spread of tubercle Ff either the direct spread of tubercle

bacilli fr ruptured LN & intraabdominal bacilli fr ruptured LN & intraabdominal organs or hematogenous seeding.organs or hematogenous seeding.

►S/Sx: nonspecific abdominal pain, S/Sx: nonspecific abdominal pain, fever & ascitesfever & ascites

►Paracentesis: exudative fluid w/ a high Paracentesis: exudative fluid w/ a high CHON content & leukocytosis, CHON content & leukocytosis, sometimes occ. Neutrophils sometimes occ. Neutrophils predominatepredominate

► Gram stain & culture.Gram stain & culture.

PERICARDIAL TB PERICARDIAL TB (TUBERCULOUS (TUBERCULOUS PERICARDITIS)PERICARDITIS)

►Pathogenesis: Pathogenesis:

1.Direct progression of a primary focus 1.Direct progression of a primary focus w/n the pericardium.w/n the pericardium.

2. Reactivation of the latent focus.2. Reactivation of the latent focus.

3. Rupture of an adjacent subcarinal LN3. Rupture of an adjacent subcarinal LN►Case-fatality rate of 40%.Case-fatality rate of 40%.

►S/Sx: dysnea, fever, dull retrosternal S/Sx: dysnea, fever, dull retrosternal pain, pericardial friction rub, pericardial pain, pericardial friction rub, pericardial effusion, cardiac tamponade.effusion, cardiac tamponade.

►Dx: Dx: pericardiocentesis under pericardiocentesis under echocardiographic guidance – echocardiographic guidance – definitive.definitive.

►Pericardial fluidPericardial fluid for biochemical, for biochemical, cytologic, microbiologic study.cytologic, microbiologic study.

►Exudative, leukocytosis, frequently hgic.Exudative, leukocytosis, frequently hgic.►Smear rarely (+) & culture 2/3Smear rarely (+) & culture 2/3►BxBx

MILIARY OR DISSEMINATED MILIARY OR DISSEMINATED TBTB

►Pathogenesis: hematogenous spreadPathogenesis: hematogenous spread►Consequence of primary infxn in child’n.Consequence of primary infxn in child’n.►Recent infxn or reactivation of old Recent infxn or reactivation of old

disseminated foci in adult.disseminated foci in adult.►S/Sx: fever, night sweats, anorexia, S/Sx: fever, night sweats, anorexia,

weakness, wt. loss, respiratory & weakness, wt. loss, respiratory & abdominal Sx.abdominal Sx.

►Choroidal tubercleChoroidal tubercle – pathognomonic, – pathognomonic, 30%30%

►CXR: miliary reticulonodular patternCXR: miliary reticulonodular pattern►Sputum smear: 80% negativeSputum smear: 80% negative►Hematologic abnormalities: anemia w/ Hematologic abnormalities: anemia w/

leukopenia, lymphopenia, neutrophilic leukopenia, lymphopenia, neutrophilic leukocytosis & leukomoid rxn, and leukocytosis & leukomoid rxn, and polycythemia.polycythemia.

►Bronchoalveolar lavage & Bronchoalveolar lavage & transbronchial Bx – provide transbronchial Bx – provide bacteriologic confirmation.bacteriologic confirmation.

►Bone marrow Bx – granuloma (+)Bone marrow Bx – granuloma (+)►Glucocortecoid – not proven beneficialGlucocortecoid – not proven beneficial

►Cryptic miliary TB – Cryptic miliary TB – rare, chronic type rare, chronic type characterize by mild intermittent characterize by mild intermittent fever, anemia meningeal fever, anemia meningeal involvement death.involvement death.

►Nonreactive miliary TB – Nonreactive miliary TB – very rarely, very rarely, due to massive hematogenous due to massive hematogenous disseminationdissemination

Less Common Less Common Extrapulmonary TBExtrapulmonary TB►Tuberculous otitisTuberculous otitis – hearing loss, – hearing loss,

otorrhea, tympanic membrane otorrhea, tympanic membrane perforationperforation

►Adrenal TBAdrenal TB – Mx of disseminated dse, – Mx of disseminated dse, manifest as adrenal insufficiency.manifest as adrenal insufficiency.

►Congenital TBCongenital TB – transplacental spread – transplacental spread or from ingestion of contaminated or from ingestion of contaminated amniotic fluid.amniotic fluid.

HIV-ASSOCIATED HIV-ASSOCIATED TUBERCULOSISTUBERCULOSIS

►One of the most common diseases One of the most common diseases among HIV-infected person worldwide.among HIV-infected person worldwide.

►HIV w/ TST (+) = 3-13% annual risk of HIV w/ TST (+) = 3-13% annual risk of developing active TB.developing active TB.

►A new TB infxn acquired by an infected A new TB infxn acquired by an infected HIV individual may evolve to active HIV individual may evolve to active dse in a matter of wks.dse in a matter of wks.

► It appear in any stage of HIV and it It appear in any stage of HIV and it varies the presentation.varies the presentation.

►Late stage of HIV: a primary TB-like Late stage of HIV: a primary TB-like pattern, w/ diffuse interstitial or miliary pattern, w/ diffuse interstitial or miliary infiltrates, little or no cavitation, & infiltrates, little or no cavitation, & intrathoracic lymphadenopathy, is intrathoracic lymphadenopathy, is more common.more common.

►Mycobacteremia & meningitis are also Mycobacteremia & meningitis are also frequent.frequent.

►Sputum smear negativ 40%Sputum smear negativ 40%

DIAGNOSIS OF TBDIAGNOSIS OF TB

►AFB SmearAFB Smear►Mycobacterial cultureMycobacterial culture►Nucleic acid amplificationNucleic acid amplification►Drug susceptibility testingDrug susceptibility testing►Radiographic proceduresRadiographic procedures►Tuberculin skin testingTuberculin skin testing► IFN-y Release assay (IGRAs)IFN-y Release assay (IGRAs)

AFB MicroscopyAFB Microscopy►Used as presumptive Dx.Used as presumptive Dx.►40-60% sensitivity40-60% sensitivity►Traditional method: light microscopy Traditional method: light microscopy

of specimens stained w/ Kinyoun or of specimens stained w/ Kinyoun or Ziehl-Neelsen basic fuchsin dyes.Ziehl-Neelsen basic fuchsin dyes.

►Modern method: auramine-rhodamine Modern method: auramine-rhodamine staining & fluorescence microscopy.staining & fluorescence microscopy.

►Early morning collection w/ no Early morning collection w/ no formaldehyde.formaldehyde.

MYCOBACTERIAL MYCOBACTERIAL CULTURECULTURE

► Definitive diagnosis.Definitive diagnosis.► Specimen inoculated into egg or agar-based Specimen inoculated into egg or agar-based

medium (Lmedium (LÖwenstein-Jensen or Middlebrook Öwenstein-Jensen or Middlebrook 7H10) & incubated @ 37C (under 5% CO2 for 7H10) & incubated @ 37C (under 5% CO2 for Middlebrook medium.Middlebrook medium.

► M. tuberculosis grow slowly for 4-8 wks.M. tuberculosis grow slowly for 4-8 wks.► The use of broth-based culture for isolation & The use of broth-based culture for isolation &

speciation by molecular methods or high-speciation by molecular methods or high-pressure liquid chromatography of mycolic pressure liquid chromatography of mycolic acids to decreased the time required for acids to decreased the time required for bacteriologic confirmation to 2-3 wks.bacteriologic confirmation to 2-3 wks.

NUCLEIC ACID NUCLEIC ACID AMPLIFICATIONAMPLIFICATION

►Definitive Dx: identification of specific Definitive Dx: identification of specific sequences of DNA.sequences of DNA.

► it takes few hrs only with high it takes few hrs only with high specificity & sensitivity.specificity & sensitivity.

►Most useful than culture & for those Most useful than culture & for those AFB-negative. AFB-negative.

DRUGDRUG SUSCEPTIBILITY SUSCEPTIBILITY TESTINGTESTING

► Initial Isolate: INH, rifampin, ethambutolInitial Isolate: INH, rifampin, ethambutol►Expanded susceptibility testing is Expanded susceptibility testing is

mandatory when resistance to 1 or more mandatory when resistance to 1 or more of these drugs or either patient fails to of these drugs or either patient fails to respond to initial therapy or has a respond to initial therapy or has a relapse after the completion Tx.relapse after the completion Tx.

►Conducted directly (w/ clinical Conducted directly (w/ clinical specimens) or indirectly (w/ specimens) or indirectly (w/ mycobacterial cultures).mycobacterial cultures).

►Direct testing on liquid medium – 3 wksDirect testing on liquid medium – 3 wks►Direct testing on solid medium - Direct testing on solid medium - ≥8 wks.≥8 wks.

►CLASSIC PICTURE: (+) infiltrates & CLASSIC PICTURE: (+) infiltrates & cavities on the upper lobe.cavities on the upper lobe.

► AIDS Pt have no radiographic pattern that AIDS Pt have no radiographic pattern that can be pathognomonic.can be pathognomonic.

►CT-scan may be useful in interpreting CT-scan may be useful in interpreting questionable CXR & to diagnose questionable CXR & to diagnose extrapulmonary TB.extrapulmonary TB.

►MRI is useful in the Dx of intracranial TB.MRI is useful in the Dx of intracranial TB.

RADIOGRAPHIC RADIOGRAPHIC PROCEDURESPROCEDURES

Tuberculin Rxn SizeTuberculin Rxn Size

RISK GROUPRISK GROUP TUBERCULIN Rxn TUBERCULIN Rxn SIZE, mmSIZE, mm

HIV-infected person or HIV-infected person or persons receiving persons receiving immunosupressive Tximmunosupressive Tx

≥≥55

Close contacts of TB Close contacts of TB pt.pt.

≥≥55aa

Persons w/ fibrotic Persons w/ fibrotic lesions on CXRlesions on CXR

≥≥55

Recently infected Recently infected person (person (≤≤2yrs)2yrs)

≥≥1010

RISK GROUPRISK GROUP TUBERCULIN Rxn TUBERCULIN Rxn SIZE, mmSIZE, mm

Persons w/ high-risk Persons w/ high-risk medical conditionsmedical conditionsbb

≥≥1010

Low risk personsLow risk personscc ≥≥1515

►a- a- Tuberculin-negative contacts, esp. Tuberculin-negative contacts, esp. child. Should receive prohylaxis for 2-3 child. Should receive prohylaxis for 2-3 months after contact ends & should months after contact ends & should then be retested w/ PPD. Those whose then be retested w/ PPD. Those whose result remain negative should result remain negative should discontinue prophylaxis.discontinue prophylaxis.

►HIV infected contacts should receive a HIV infected contacts should receive a full course of Tx regardsless of PPD full course of Tx regardsless of PPD results.results.

FIRST-LINE AGENTSFIRST-LINE AGENTS

►RIFAMPIN- RIFAMPIN- Most important & potent anti-Most important & potent anti-TB agent.TB agent.

- - 600mg/d. 600mg/d. - distributes well throughout the body - distributes well throughout the body

tissues including inflamed meninges.tissues including inflamed meninges.- cause GI upset & hepatitis because - cause GI upset & hepatitis because

it is a potent inducer of hepatic it is a potent inducer of hepatic microsomal Enz.microsomal Enz.

Rifabutin – Rifabutin – closely related to Rifampin agent closely related to Rifampin agent w/c have fewer side effects.w/c have fewer side effects.

ISONIAZIDE (INH)ISONIAZIDE (INH)

►Best agent 2Best agent 2ndnd to Rifampin. to Rifampin.►300 mg/d or 900mg 2 or 3x per wk.300 mg/d or 900mg 2 or 3x per wk.►Distributed well throughout the body, Distributed well throughout the body,

infected tissues, CSF & caseous infected tissues, CSF & caseous granuloma.granuloma.

►Hepatotoxicity & peripheral Hepatotoxicity & peripheral neuropathy.neuropathy.

►Pyridoxine 25-50mg/dPyridoxine 25-50mg/d

►PYRAZINAMIDE (PZA)PYRAZINAMIDE (PZA)►25mg/kg daily25mg/kg daily►Less hepatotoxic, hyperuricemiaLess hepatotoxic, hyperuricemia

►ETHAMBUTOLETHAMBUTOL- Less potentLess potent- 15mg/kg/day15mg/kg/day- At higher doses – retrobulbar optic At higher doses – retrobulbar optic

neuritis causing central scotoma & neuritis causing central scotoma & impairing both visual acuity & ability impairing both visual acuity & ability to see reen.to see reen.

INITIAL PHASEINITIAL PHASE

INDICATIONINDICATION DURATION DURATION (month)(month)

DRUGSDRUGS

New smear New smear or culture or culture (+)(+)

2 mos.2 mos. HRZEHRZEa,ba,b

New New culture(-)culture(-)

2 mos.2 mos. HRZEHRZEaa

pregnantpregnant 2 mos.2 mos. HREHREee

INITIAL PHASEINITIAL PHASE

INDICATIONINDICATION DURATION DURATION (month)(month)

DRUGSDRUGS

Failure & Failure & relapserelapseff

Resistance Resistance or or intolerance intolerance to Hto H

Throughout Throughout 6 mos.6 mos.

RZERZEgg

Resistance Resistance to H + Rto H + R

18-24 mos.18-24 mos. ZEQ + SZEQ + S

INITIAL PHASEINITIAL PHASE

INDICATIONINDICATION DURATION DURATION (month)(month)

DRUGSDRUGS

Resistance Resistance to all 1to all 1stst-line -line drugsdrugs

24 mos.24 mos. 1 IV1 IVh h + 3 of + 3 of these 4: these 4: ethionamideethionamide, , cycloserine, cycloserine, Q, PASQ, PAS

StandardizeStandardized re-tx d re-tx (susceptibilit(susceptibility testing y testing unavailable)unavailable)

3 mos.3 mos. HRZESHRZESii

INITIAL PHASEINITIAL PHASE

INDICATIONINDICATION DURATION DURATION (month)(month)

DRUGSDRUGS

Drug Drug intolerance intolerance to Rto R

12 mos.12 mos. HZEHZE

Drug Drug intolerance intolerance to Zto Z

2 mos.2 mos. HREHRE

CONTINUATION PHASECONTINUATION PHASE

INDICATIONINDICATION DURATION DURATION (months)(months)

DRUGSDRUGS

New smear New smear or culture or culture (+)(+)

4 mos.4 mos. HRHRa,c,da,c,d

New New culture(-)culture(-)

2 mos.2 mos. HRHRaa

PregnantPregnant 7 mos.7 mos. HRHR

Failure & Failure & relapserelapseff

CONTINUATION PHASECONTINUATION PHASE

INDICATIOINDICATIONN

DURATION DURATION (months)(months)

DRUGSDRUGS

StandardizStandardized re-tx ed re-tx (susceptibil(susceptibility testing ity testing unavailableunavailable))

5 mos.5 mos. HREHRE

Drug Drug intolerance intolerance to Zto Z

7 mos.7 mos. HRHR

Footnotes:Footnotes:►b- b- striptomycin can be used in place of striptomycin can be used in place of

EthambutolEthambutol►c- c- continuation phase should be continuation phase should be

extended to 7 mos.for pt.w/ cavitary extended to 7 mos.for pt.w/ cavitary lesion who remain sputum culture (+) lesion who remain sputum culture (+) after the initial phase of tx.after the initial phase of tx.

►dd- HIV-negative pt.w/ noncavitary - HIV-negative pt.w/ noncavitary lesion & AFB sputum (-) after initial lesion & AFB sputum (-) after initial phase of tx can be given weekly phase of tx can be given weekly Rifapentine/INH in the continuation Rifapentine/INH in the continuation phase.phase.

►e- e- PZA is safe to pregnant for 6 mos. If PZA is safe to pregnant for 6 mos. If PZA is not included in the initial tx PZA is not included in the initial tx regimen, the minimum duration of regimen, the minimum duration of therapy is 9 mos.therapy is 9 mos.

► f- f- regimen is tailored according to the regimen is tailored according to the results of susceptibility tests.results of susceptibility tests.

►g-g- Q ( Q (Fluoroquinolone) may strengthen Fluoroquinolone) may strengthen the regimen for pt w/ extensive dse.the regimen for pt w/ extensive dse.

►h- Amikacin, kanamycin or capreomycin h- Amikacin, kanamycin or capreomycin should be d/c after 2-6 mos.should be d/c after 2-6 mos.

► i- i- Streptomycin should be d/c after 2 mos. Streptomycin should be d/c after 2 mos. Because it is less effective for tx failure.Because it is less effective for tx failure.

► j- j- Streptomycin for initial 2 mos.or a Streptomycin for initial 2 mos.or a Fluroquinolone might strengthen the Fluroquinolone might strengthen the regimen for extensive dse.regimen for extensive dse.

►PASPAS – – para-aminosalicylic acid.para-aminosalicylic acid.►FluroquinolonesFluroquinolones: Levofloxacin, : Levofloxacin,

ciprofloxacin, moxifloxacin, ciprofloxacin, moxifloxacin, gatifloxacin have a good, broad gatifloxacin have a good, broad antimycobacterial activity.antimycobacterial activity.

RECOMMENDED DOSAGE FOR INITIAL RECOMMENDED DOSAGE FOR INITIAL Rx OF TB IN ADULTRx OF TB IN ADULT

DOSAGEDOSAGE

DRUGDRUG DAILY DOSEDAILY DOSE TRICE-TRICE-WKLYWKLY

INHINH 5mg/kg, max 5mg/kg, max 300mg300mg

15mg/kg, 15mg/kg, max 900mgmax 900mg

RifampinRifampin 10mg/kg, 10mg/kg, max 600mgmax 600mg

10mg/kg, 10mg/kg, max 600mgmax 600mg

PZAPZA 20-25mg/kg, 20-25mg/kg, max 2Gmax 2G

30-40mg/kg, 30-40mg/kg, max 3Gmax 3G

EthambutolEthambutol 15-20mg/kg15-20mg/kg 25-30mg/kg25-30mg/kg

►StreptomycinStreptomycin – usual adult dose is 0.5- – usual adult dose is 0.5-1.0g IM OD or 5x per wk.1.0g IM OD or 5x per wk.

- less nephrotoxic; ototoxic- less nephrotoxic; ototoxic

►Bacteriologic evaluation is the prefereed Bacteriologic evaluation is the prefereed method of monitoring response to tx.method of monitoring response to tx.

►All pts. Have negative sputum culture by All pts. Have negative sputum culture by the end of 2-3 mos.of tx.the end of 2-3 mos.of tx.

► If the culture remains (+), tx failure & If the culture remains (+), tx failure & drug resistance should be suspected.drug resistance should be suspected.

Drug ResistanceDrug Resistance

►Primary – infection caused by a strain Primary – infection caused by a strain resistant prior to therapy.resistant prior to therapy.

►Acquired – resistance arising during tx Acquired – resistance arising during tx because of an inadequate regimen.because of an inadequate regimen.

►Noncompliance.Noncompliance.