2. Objectives
Become familiar with the first and second line anti-
tuberculosis antibiotics and the standard treatment
regimes.
Identify the common adverse effects and drug
interactions associated with these antibiotics.
Describe problem-solving techniques that are
used to help identify and manage common
adverse effects.
3. Outline
Review the first line agents
Discuss duration of therapy
Review common side effects and
management
Review treatment of TB in special populations
Short talk about drug resistance and second
line agents
4. The scope of the problem
A 2 cm cavity contains 108 organisms.
There are naturally occurring mutations to all our TB
drugs.
Use of monotherapy allows the selective growth of
the resistant organisms and gives rise to drug
resistance.
A prolonged course of antibiotics is required to kill the
semi-dormant and dormant organisms.
5. In order to treat TB you must
Take into consideration:
Known or suspected drug resistance
• Hx of prior TB treatment
Location of disease
• Standard tx is 6 months
• TB meningitis: 9-12 months
Likelihood of adherence and/or adverse
reactions
Co morbidities and host immune status
6. Category I
•New (untreated)smear positive pulmonary TB
•New smear negative pulmonary TB
•New cases of severe forms of extrapulmonary TB
( meningitis,spinal,intestinal,genitourinary TB).
Category II
These are smear positive failure, relapse and
Interrupted treatment cases
Patient catogories
7. Category III
These are new cases of smear negative pulmonary TB
With less severe form of extrapulmonary TB, (skin
Bone,peripheral joint TB).
Category IV
These are chronic cases who have become smear
Positive after completing fully supervised retreatment.
These are mostly MDR cases.(multi drug resistant)
8. TB Category Initial phase Continuation
phase
Total duration
I 2 HRZE (S) 4 HR/ 4 H3R3
Or 6 HE
6
8
II 2 HRZES + 1 HRZE 5 HRE or 5H3R3E3 8
8
III 2 HRZ 4 HR/ 4 H3R3 0r 6
HE
6
8
IV Chronic case
9. Standard treatment regime
Intensive phase
Goal is to quickly kill the rapidly dividing
organism to control disease
render patient non-infectious
prevent emergence of drug resistance
Continuation phase
Sterilize the lungs by killing dormant and
semi-dormant organisms to prevent
relapse
10. Give all meds together as a
single dose unless:
Profound nausea, vomiting
Swallowing issues
11. Antituberculosis drugs (by group)
Group Description Drug Abbreviation
1. First-line oral antituberculosis drugs isoniazid
rifampicin
ethambutol
pyrazinamide
rifabutin
H
R
E
Z
Rfb
2. Injectable antituberculosis drugs kanamycin
amikacin
capreomycin
streptomycin
Km
Amk
Cm
S
3. Fluoroquinolones levofloxacin
moxifloxacin
ofloxacin
Lfx
Mfx
Ofx
4. Oral bacteriostatic second-line
antituberculosis drugs
ethionamide
protionamide
cycloserine
terizidone
p-aminosalicylic acid
Eto
Pto
Cs
Trd
PAS
5. Antituberculosis drugs with unclear efficacy
or unclear role in MDR-TB treatment (not
recommended by WHO for routine use in MDR-
TB patients)
clofazimine
linezolid
amoxicillin/clavulanate
thioacetazone
clarithromycin
imipenem
Cfz
Lzd
Amx/Clv
Thz
Clr
Ipm
13. 2HREZ/4HR
In intensive phase
H,R: kill rapidly dividing TB
Z: works to kill semi dormant TB in the acidic
environment of the cavity or in macrophages
E: used to prevent the emergence of RIF
resistance when primary resistance to INH may be
present
In continuation phase
H,R: kill any remaining rapidly dividing cells as
well as sterilizing fibrotic areas
14. 14
Rifampin
Binds to DNA-dependent RNA polymerase
The most important drug we use
Bactericidal against rapidly dividing agents, and
penetrates into fibrotic areas to kill semidormant
organisms
Without rifampin treatment course is 12-18 months
Usual dose 10 mg/kg max 600mg
15. Rifampin side effects
Change in colour of urine, sweat
Pruritis with or without rash: 6%
Hepatotoxicity
Significant transaminase elevation: rare
Can be seen as part of hypersensitivity rx
Dose dependent interference with bilirubin
uptake causing unconjugated hyperbilirubinemia
or jaundice without LFT abnormalities
Thrombocytopenia
Hypersensitivity rx in 0.07-0.3%
18. 18
Isoniazid side effects
Peripheral neuropathy
Dose related side effect
Vit B6 supplements to prevent
Rare: seizures
+ANA antibodies in 20%, less than 1%
develop lupus
*
19. INH Hepatotoxicity
Hepatitis
Incidence increases with age
Generally occurs within weeks to months rather
than days
Takes weeks to regress, recovery is complete in
most following drug cessation
20. 20
INH Drug Interactions
INH inhibits cytochrome P450 system
Increase concentrations of:
carbamazepine, phenytoin, cycloserine,
theophylline, warfarin
These effects are offset with rifampin
Check levels
21. 21
Pyrazinamide
Active against dormant and semi-
dormant TB within macrophages or in
acidic environments
No PZA → minimum of 9 months of tx
Dose is 25 mg/kg, requires renal dosing
22. 22
Pyrazinamide side effects
Hepatotoxicity
Actual incidence hard to predict as PZA always
used with other TB meds, in one study
hepatotoxicity attributed to PZA in 1%
Rash
Non gouty arthralgia
Seen in up to 40% of patients on daily Z
23. 23
Ethambutol
Inhibits arabinosyl transferase (synthesis of
TB cell wall component), (This may
increase penetration of other drugs into
the organisms).
Suppresses growth (static)
Less bactericidal compared to INH or RIF
Dose: 15 mg/kg
Requires renal dosing
24. 24
Ethambutol side effects
retrobulbar neuritis
• Manifests as decreased visual acuity or decreased
red-green colour discrimination in one or both eyes
• Risk higher in pts with renal failure
Rarely used in children due to an inability to
monitor for symptoms
25. 1) In case of resistance to first line agents;
2) In case of failure of clinical response to conventional
therapy.
3) In case of serious treatment limiting adverse drug
reactions.
4) When expert guidance is available to deal with the
toxic effects, because the dosage, emergence of
resistance & long-term toxicity have not been fully
established.
Second Line / Alternate Anti T.B Drugs:
27. Streptomycin
Aminoglycoside antibiotic.
First line Anti TB drug, given by injection.
Given I/M or I/V as Streptomycin sulfate.
Crosses BBB & achieves therapeutic conc. if meninges
are inflamed.
28. Clinical Uses
Mycobacterium TB Infections:
Used when an injectable drug is required in severe ,life
threatening form of infection:
• Disseminated Tuberculosis
• Tuberculous Meningitis
• Infections resistant to other drugs.
Dose: 1 g / (15mg/kg/day) I/M or I/V daily.
20-40mg/kg/day for children-not to exceed
1-1.5 G/d.
Given in combination with other drugs to delay /
prevent emergence of resistance.
29. Adverse Effects
Main toxic effects are:
Ototoxicity—vertigo & hearing loss ,may be permanent.
Nephrotoxicity—dose related ,more in elderly.
Dosage adjustment according to Creatinine CL.
Toxicity can be reduced by limiting the therapy for 6
months.
30. Antibiotic derived from Rifamycin & is related to Rifampin.
Less potent inducer of cytochrome P450 less D/I.
Active against Myco. TB & Atypical mycobacteria.
Rifabutin
31. Uses: For treatment of mycobacterial TB infection in
place of Rifampin in HIV-infected patients receiving Anti-
viral treatment.
In AIDS patients.
Prevention of T.B: alone for 6 months or with
pyrazinamide for 2 months
Prevention and treatment of disseminated atypical
mycobacterial infection.
Dose: 300mg/day orally.--- 150mg/day with protease
inhibitor.
450mg/day with Efavirenz ( also an inducer of p450
enzymes)
32. Analog of Rifampin.
Cross resistance with Rifampin
Potent inducer of cytochrome P450 like Rifampin
, so similar drug interactions.
Active against Myco .TB & Atypical mycobacteria.
Rifapentine
33. Therapeutic uses:
For ttt of Rifampin susceptible strains during
continuation phase. 600mg / week orally.
C/I: HIV infected patients --- high relapse rate with
Rifampin resistant Mycobacteria.
34. Activates macrophages to kill Myco. T.B
Given by Aerosol to the lungs of patients with
multidrug resistant TB.
There is wide pulmonary distribution &
enhanced local immune stimulation.
Interferon-γ
35. Kanamycin (Km)
Aminoglycoside
Interferes with protein
synthesis through disruption of
ribosome
Dose: 1 g IM/IV (15-20 mg/kg)
Side effects:
Nephrotoxicity
Ototoxicity
Electrolyte wasting
Adjust dose for renal failure
36. Amikacin (Amk)
Aminoglycoside
Highly similar to kanamycin (can
be essentially considered the
same drug)
Dose: 1 g IM/IV (15-20 mg/kg)
daily
Side effects:
Same as kanamycin; renal
failure and ototoxicity
High cross-resistance with
kanamycin
Adjust dose in renal failure
(same as kanamycin)
37. Capreomycin (Cm)
Structurally and
functionally similar to
aminoglycosides
Dose: 1 g IM/IV (15-20
mg/kg) daily
Side effects
same as Km/Amk
Some cross-resistance
with Km/Amk
Adjust dose for renal failure
38. Ofloxacin (Ofx)
Inhibits DNA-gyrase
Dose: 800 mg daily
Side effects
Generally well-tolerated
GI upset, rash, CNS
disturbance
Avoid antacids around time of
ingestion (reduces
absorption)
Near complete cross-resistance
with other fluoroquinolones
39. Levofloxacin (Lfx)
Dose: 750 mg daily for
<50 kg (1000 mg daily
for > 75kg)
A higher dose for
tuberculosis is used than
for other infections
Side effects
Generally well-tolerated
GI upset, rash, CNS
disturbance
Adjust dose in renal failure
40. Moxifloxacin (Mfx)
May be more active than earlier
generation quinolones
Dose: 400 mg daily
Near complete cross-resistance
with other fluoroquinolones
No dose adjustment in renal
failure
Hepatically cleared
41. Ethionamide (Eto)
Derivative of isonicotinic acid
(same family as isoniazid)
Dose: 500-1000 mg daily in
divided doses
Side effects
GI upset, hypothyroidism,
peripheral neuropathy
Partial cross-resistance with
isoniazid, complete with
prothionamide
Hepatically excreted
Co-administer vitamin B6
42. Prothionamide (Pto)
Structurally similar to
ethionamide
Dose: 500-1000 mg daily
in divided doses
Overall side effect profile
similar to ethionamide
Slightly less GI side
effects
Complete cross-resistance
with ethionamide
44. Terizidone (Trd)
Structure is composed of two connected molecules
of cycloserine
Commonly used in South Africa in place of
cycloserine
Dose: 500-1000 mg daily in divided doses
Possibly less side effects than cycloserine
Not yet recommended by the WHO
45. Para-aminosalicylic acid (PAS)
Various formulations; delayed-
release microcapsules best
tolerated
Dose of PASER is 4 g (1 sachet)
twice daily
Side effects
GI upset, hypothyroidism
Hepatitis, electrolyte abnormalities
Hepatic metabolism, renal
excretion
Administer with acidic food or
drink
46. Group 5: Possible reinforcing agents
Minimal clinical data to support use in MDR-TB
therapy.
Should only be used in cases of extreme drug
resistance (XDR-TB):
Amoxicillin/clavulanic acid
Clofazamine
Linezolid
High dose isoniazid
Imipenem
47. Amoxicillin-clavulanic acid (AMX-CLV)
GROUP 5
Beta-lactam antibiotic with
beta-lactamase inhibitor
Dose
1000/250 mg twice daily or
875/125mg twice daily
Side effects
GI upset, rash
Contraindicated: Penicillin
allergy
48. Clofazimine (CFZ)
GROUP 5
Substituted
iminophenazine
Usual adult dose is 100
mg daily
Side effects
Bronzing of skin
Malabsorption
Abdominal pain (can
be severe)
49. Linezolid (LZD)
GROUP 5
Oxazolidinone: inhibits protein synthesis,
interacting with ribosomal RNA
Dosing
Coated tablets: 400 and 600 mg
Intravenous solution: 2 mg/ml; 100, 200, or
300 mg bags
Usual dose: 600 mg twice daily.
Some case series have successfully used daily
half dosing (600 mg once daily) to decrease
toxicity and maintain efficacy
50. Linezolid (LZD) (Continued)
Side effects
Generally well tolerated for treatment courses ≤28
days.
Common: diarrhea, nausea, headache, insomnia, and
rash.
More serious:
• myelosuppression (generally reversible with discontinuation of
the drug)
• optic neuropathy (usually resolved over time with drug
discontinuation)
• peripheral neuropathy (possibly irreversible).
Rare: hypertension, lactic acidosis, pancreatitis
51. Linezolid (LZD) (Continued)
Monitoring
CBC weekly during the initial period, then monthly, and then as
needed based on symptoms.
Visual function should be monitored in all patients taking linezolid
for extended periods (≥3 months) and in all patients reporting new
visual symptoms regardless of length of therapy.
Alerting symptoms:
Black, tarry stools or severe diarrhea
Unusual bleeding or bruising
Extreme tiredness or weakness
Numbness, tingling, or burning pain in your hands, arms, legs, or
feet
Change in visual acuity, vision blurring, or visual field defect
Headache, nausea, or vomiting
52. High-dose isoniazid (H)
GROUP 5 (AT HIGH
DOSES)
Dosing
16 to 18 mg/kg per day,
typically 600 mg to 1200
mg per week
Some clinicians give it
three times a week
instead of daily at the 16
to 18 mg/kg dosing
53. Imipenem/Cilastin
GROUP 5—BETA-LACTAM/CARBAPENEM
In vitro activity—very limited clinical experience
Dosing
Adults: 1000 mg IV every 12 hours
In children, meropenem preferred: 20-40 mg/kg/dose
IV every 8 hours up to 2 grams per day (high rates of
seizures were seen in children treated with imipenem
for TB meningitis
Side effects
Diarrhea, nausea, vomiting
Seizure noted in CNS infections
54. Management of patients with adverse drug
reactions to Anti-tubercular drugs:
Minor A/E ---- managed symptomatically without altering
medication.
Severe A/E ---- stop the offending drug if possible isoniazid ,
rifampin should be continued or re-introduced after the
reaction has subsided.
Never re-introduce in case haemolysis, thrombocytopenia or
renal failure.
55. Monitoring for side effects during
therapy
Clinical
Screen for common side effects
Microbiological response
Sputum at 2 months
Sputum at completion of therapy
Laboratory response
First 2 weeks: twice weekly
At 1 month then monthly
Check: AST, ALT, Bilirubin, CBC
56. Common problems during therapy
Nausea and vomiting
Abnormal LFTs
Drowsiness
Rash/puritis
Missed doses
57. SYMPTOM MANAGEMENT
Drowsiness:
HS dosing
Nausea:
Have light food 30 – 60 minutes prior to DOT
Antiemetic 30 minutes prior to DOT
Stronger antiemetic/ranitidine/PPI
Rash/Itch:
Minor itch continue meds with antihistamine (usually
RMP)
Major rash drug challenge after rest
– RMP/INH/EMB/PZA (usually PZA)
58. Hepatotoxicity
Asymptomatic increases in LFTs occur in
20% of pts on tx for TB
Most common serious side effect
Defined as AST >5xULN or >3xULN with
symptoms
Incidence depends on
Age
Pre-existing liver disease
ETOH: appears to more than double risk of INH
hepatotoxiticity
INH more hepatotoxic than rifampin
59. What to do if a patient develops
abnormal LFTs on therapy?
AST/ALT 5X ULN asymptomatic or
AST/ALT 3X ULN symptomatic or
Jaundice
→ HOLD TB Meds
Once ALT returns to <2x ULN then
• Restart rifampin alone or with ethambutol, repeat ALT on
day 3
• IF ALT <2x ULN then add in INH and repeat ALT in 3
days
• Rechallenge with PZA may be hazardous and consider
D/C and extending tx to 9 months
61. Re-introduction of TB drugs (1)
LFTs normal or AST/ALT <2x upper limit
If LFTs due to EtOH (or not due to TB drugs)
restart RHZ together
If bilirubin and ALP
rifampicin most likely
start HE
add Z 1 week later if OK
If OK, use S (+Fq)
62. Re-introduction of TB drugs (2)
ATS : R RH RHE (2RHE/7RH)
Common: H RH RHE (2RHE/7RH)
NYBTC: E ER REZ (2REZ/7RE)
• If R the problem, 2SHEZ/10HE
• If H the problem, 2REZ/7RE
• If Z the problem, 2SHE(Fq)/10HE
63. Rash
If minor, consisting of mainly puritis or
affecting limited area
→ trial antihistamines
Petechial rash
Check platelet count
Generalized rash especially with fever or
involving mucocutaneous areas
→ hold all TB meds
Once rash subsides: restart drugs one by one
Rif → INH→ethambutol or PZA. If no rash with 3rd
drug then assume it is the 4th drug that is the
cause
65. Paradoxical Reactions
Worsening of TB adenitis with
development of new lymph nodes,
increasing lymph node size or sinus
drainage
Seen in up to 20% of patients
Median time to onset: 1.5 months
Can present with new pleural effusions
during trt for Pulm TB
66. Mgmt of Paradoxical Reactions
Rule out drug resistant TB
Aspiration of lymph nodes, effusions
Corticosteroids
Unproven benefit
NSAIDS
67. Treatment of patients in special
populations
Hepatic Disease
Epilepsy
Renal insufficiency/ESRD
HIV infection
Pregnancy/breastfeeding
68. Treatment in patients with pre-existing
liver disease
Remember ↑ AST/ALT may be secondary to
TB
If ALT more than 3xULN not related to TB
Avoid PZA
IF patient has cirrhosis
Rifampin + ethambutol + fluoroquinolone
69. Severe liver disease with encephalopathy
Ethambutol, fluoroquinolone, aminoglycoside (or
capreomycin), cycloserine
recommended regimens are;
2SHRE/6HR OR 2SHE/10HE
70. INH may be associated with an increased
risk of seizures.
Pyridoxine 10 mg daily should be given to
all epileptics taking INH.
There is no evidence that INH causes
seizures in patients who are not epileptic.
Epilepsy
71. TB treatment involves numerous drug
interactions with anti-epileptic drugs
and serum drug levels should be
closely monitored.
There are serious interactions between
rifampicin and carbamazepine,
rifampicin and phenytoin, and
rifampicin and sodium valproate.
72. Renal insufficiency/ESRD:
Dose adjust Z and E if CrCl<30ml/min or on
PD or HD
Intensive:
INH/RMP OD post HD
PZA/EMB 3X per week post HD
Continuation
INH/RMP 3X per week post HD
No data on peritoneal dialysis
2HRZ/4HR
73. Antituberculosis drugs in
hemodialysis patients
Confusion exists regarding regimen,
duration etc however,
Treatment duration should follow NICE
guidelines (UK) namely,
6 months for most cases of fully sensitive
disease, with the exception of
TB involving the CNS when treatment
should be for 1 year
75. For patients on haemodialysis, dosing
intervals should be increased to three times
weekly to reduce the risk of drug
accumulation and toxicity
pryazinamide Variable doses of 25-30 mg/kg
three times weekly or 40 mg/kg three times
weekly have been recommended
76. Treatment can be given immediately after
haemodialysis to avoid premature drug removal
With this strategy there is a possible risk of raised drug
levels of ethambutol and pyrazinamide between dialysis
sessions. Alternatively, Treatment can be given 4-6 h before
dialysis, increasing the possibility of premature drug removal
but reducing possible ethambutol or pyrazinamide toxicity
Both rifampicin and isoniazid may be given in their usual
daily doses.
77. HIV infection:
CD4 count <200
OD 7/7 X 2 months for intensive phase
3X per week for continuation phase
Protease inhibitor interaction with Rifampin
Rifabutin in consultation with HIV pharmacist
Starting of ART (on new HIV DX)
Dependent on CD4 count
78. 78
TB and HIV Drug Interactions
Rifampin and Protease inhibitors (PI)
Effect: Decreased PI serum levels
Substitute Rifampin with Rifabutin 150 mg po thrice
weekly (may need to increase to 300 mg thrice
weekly or 150 mg po daily)
Rifampin and Efavirenz
Effect: Decreased efavirenz levels
Increase efavirenz dose to 800 mg po daily (usual
600 mg daily)
Rifampin and Raltegravir
Effect: Decreased raltegravir levels
Increase raltegravir to 800 mg po BID (usual dose
400 mg po BID and continue higher dose for at least
2 weeks post completion of Rifampin)
79. Initial phase for 2 months
Continuation phase for 7- 10months (total 9-12 M)
In resistant cases up to 18 months
T.B in AIDs patients
80. Pregnancy
TB not an indication for pregnancy
termination
First line drugs safe in pregnancy (H,E,R)
PZA: limited data with respect to teratogenic
effects. Recommended by WHO and IUATLD
Fluoroquinolones and aminoglycosides
contraindicated while pregnant
81. Breastfeeding Moms
1st line drugs
Very small concentrations in breast milk
Encourage breast feeding
Have not shown to produce toxic effects in newborn
Mum should be on pyridoxine supplements
Drugs level in breast milk not sufficiently high to be
considered effective tx for infant
Certain 2nd line drugs not recommended - data
unknown
82. Concerns re poor absorption
Consider if significant malnutrition, diabetic
gastroparesis, HIV, underlying GI disease, treatment
failure
INH/RMP serum levels:
Usually 2 hours (+/- 6 hours) post oral drug adminstration
Available IV drugs include INH, RIF,
fluoroquinolones, aminoglycocides
Recommendations-Parental route (delays discharge)
Only select drugs via Home Care/Mount Carmel Clinic/Lions
Place in WRHA
83. Drug resistance
Primary versus acquired
PZA resistance: treat for 9 months
INH monoresistance
6 month R,Z,E
12 months of 2RZE/10RE
MDR= resistance to INH and RIF
86. Management of MDR-TB
Injectable: used daily for first 2-6 months then
can be stepped down to 3x/week, ideally for
>6 months
Must have daily directly observed therapy for
the duration of therapy
Duration: 18-24 months after sputum
conversion
87. Treatment Monitoring
Sputum smear microscopy for AFB at 2 months
and 6 months
If positive at two months, repeat at 3
If still smear positive at 3 months, continuation
phase (4HR) is still started while awaiting DST
results
Continue drug-susceptibility tests if smear-
positive after 3 months of treatment
88. Monitoring during treatment of DR-TB
Monitoring evaluation Recommended frequency
Evaluation by clinician At baseline, and at least monthly until conversion, then
every 2–3 months
Screening by DOT worker At every DOT encounter
Sputum smears and
cultures
Monitor smears and cultures monthly throughout treatment. (Note:
programmes with limited resources may choose to do smears monthly
but cultures only every other month)
Weight At baseline and then monthly
Drug susceptibility At baseline in programmes doing individualized treatment
Chest radiograph At baseline, and then every 6 months
Serum creatinine At baseline, then monthly if possible while receiving an
injectable drug. Every 1–3 weeks in HIV-infected patients,
diabetics and other high-risk patients
Serum potassium Monthly while receiving an injectable agent. Every 1–3
weeks in HIV-infected patients, diabetics and other high-risk
patients
89. Monitoring evaluation Recommended frequency
Thyroid stimulating hormone
(TSH)
Every 6 months if receiving ethionamide/protionamide
hormone and/or PAS; and monitor monthly for
signs/symptoms of hypothyroidism. TSH is sufficient for screening for
hypothyroidism; it is not necessary to measure hormone thyroid levels
Liver serum enzymes Periodic monitoring (every 1–3 months) in patients
receiving pyrazinamide for extended periods or for patients
at risk for or with symptoms of hepatitis. For HIV-infected
patients, do monthly monitoring
HIV screening At baseline, and repeat if clinically indicated
Pregnancy tests At baseline for women of childbearing age, and repeat if
indicated
Haemoglobin and
white blood count
If on linezolid, monitor weekly at first, then monthly or as
needed based on symptoms; there is little clinical experience
with prolonged use
For HIV-positive patients on an ART regimen that includes AZT,
monitor monthly initially and then as needed based on symptoms
Lipase Indicated for work up of abdominal pain to rule out
pancreatitis in patients on linezolid, D4T, ddI, ddc.
Lactic acidosis Indicated for work up of lactic acidosis in patients on linezolid or ART
Serum glucose If receiving gatifloxacin, monitor glucose frequently (weekly) and educate patient on
signs and symptoms of hypoglycaemia and hyperglcycaemia
90. Mode of action & Recommended dose mg/kg
Twice/wk3times/wkDaily dose
mg/kg
Mode of
action
Essential anti-
tuberculosis drug
15105bactericidalINH
101010bactericidalRifampicin
503525bactericidalpyrazinamide
151515bactericidalstreptomyicin
453015bacteriostaticEthambutol
92. Cross-resistance
Aminoglycosides
Minimal cross resistance between SM and
other aminoglycosides
KM and AM have almost complete cross
resistance
Cross resistance between CM and KM
and/or AM has been documented
Fluoroquinolones
Mutations that confer resistance to one
fluoroquinolone will confer some degree of
93. It is the practice of treating latent infection to prevent
progression to active disease
Indications:
1. In close contacts of active pulmonary TB patients
2. Immunosuppressed / HIV infection & AIDS pts , Diabetes
Mellitus
3. Recent converters.
4. Neonate of tubercular mother.
Chemoprophylaxis/Prevention of TB
94. Isoniazid: DOC
300 mg (10mg/kg in children daily for 6-12 months) with
pyridoxine.
Rifampin: (10 mg/kg) alone for 4 months.
Pyrazinamide: With rifampin for 2 months.
For multidrug resistant mycobacteria with fluroquinolones /
Rifabutin
In pregnancy prophylaxis should be delayed untill delivery.
Drugs Used for chemoprophylaxis:
95. Initial intensive phase is longer (3 months)
5 drugs for 2 months & 4 drugs for 1 months
Continuation phase is longer i.e. 5 months
Use alternate drugs if mycobacteria are resistant to first line
drugs.
Treatment of Previously
treated / failure / default / relapse cases:
96. a) In seriously ill patients (miliary or severe pulmonary TB) to
buy time for drugs to act.
b) When hypersensitivity reactions occur to antitubercular
drugs.
c) In meningeal or renal TB or pleural effusion – to reduce
exudation and prevent its organisation, strictures etc.
d) In AIDS patients with severe manifestations of T.B
Role of corticosteroids in tubercular patients:
97. Contraindication: Intestinal T.B --- silent perforation can
occur.
Precaution: Corticosteroids, if given, should be
gradually withdrawn when the general condition of the
patient improves.
98. Take home points
Duration of tx depends on results of 2 month
cultures and the inclusion of PZA
Treatment completion depends on the
number of doses taken not duration of tx
Many side effects do not require
discontinuation of tx
99. Take home points-cont
Beware of drug-drug interactions
Hepatotoxicity is the most common serious
side effect requiring discontinuation of drug
Introduce Rif then INH once LFTs return to normal