TREATMENT OF

TB IN SPECIAL
SITUATIONS
Module 7 - Treatment of TB in Special Situations

Learning Outcomes

At the end of this session, participants will be

able to:
Administer appropriate treatment regimen to DSTB and
LEARNING OBJECTIVE
DRTB patients with unconventional situations.

• Children • Renal Failure

• Pregnancy • Seizure Disorder
• Psychiatric Disorder
• Breastfeeding
• HIV
• Contraception
• Substance
• Diabetes Mellitus Dependence
• Liver Disorder
Children
Module 7 - Treatment of TB in Special Situations

DRTB

Regimen should consist of 4-5 drugs given for the entire

treatment duration.
▪ Regimen and dosages should be presented to the TB
MAC prior to initiation of treatment
CHILDREN
▪ Avoid injectable drugs to avoid hearing loss

Regimen 6 Regimen 7
Age
FQ susceptible MDR TB FQ resistant MDR TB

7a. Lzd-Cfz-Cs-PAS
<3 y.o 6a. Lfx-Lzd-Cfz-Cs (PAS/Eto)
(Eto/Dlm )

6b. Lfx-Lzd-Cfz-Cs 7b. Lzd-Cfz-Cs-Dlm

3-6 y.o
(Dlm/PAS) (PAS/Eto)

7c. Bdq-Lzd-Cfz-Cs
> 6 y.o 6c. Bdq-Lfx-Lzd-Cfz (Cs/Dlm)
(Dlm/PAS)

Determine the severity of the disease based on the presence

of any (1) one of the following:
▪ Positive TB bacteriology (smear microscopy, Xpert
MTB/Rif Test, TB culture)
▪ Cavities or bilateral disease on chest radiography
▪ Extrapulmonary forms of disease other than
lymphadenopathy (peripheral nodes or isolated
mediastinal mass without compression)
▪ Presence of co morbid condition or disease such as
severe malnutrition or advanced immunosuppression
Module 7 - Treatment of TB in Special Situations

Treatment duration based on severity

▪ 9-12 months for non-severe disease depending on
the clinical progress as assessed by physician
▪ 15-18 months for severe or extensive disease

Monitoring of treatment

For children with no bacteriologic confirmation at baseline,

monitor clinically:
▪ Resolution of TB signs and symptoms
▪ Monthly weight gain and growth (weight and height
chart for children < 5 y.o.)
▪ Baseline CXR and follow-up CXR at month 6 to check
resolution of lesions in case of pulmonary TB
▪ Healing of other EPTB lesions (e.g. cold abscess)
For children who have bacteriologic confirmation at
baseline:
▪ Monitor clinically as above
▪ Follow bacteriological monitoring schedule for
sputum and culture tests (as in adults)
Pregnancy
Module 7 - Treatment of TB in Special Situations

• Female patients of child bearing age should be assessed

for pregnancy upon initial evaluation
▪ Obtain OB History especially LMP
▪ Do pregnancy test (part of baseline)

PREGNANCY
• Avoid pregnancy during treatment

• Encourage family planning and offer effective and

appropriate method of contraception .

• Most first line drugs for TB are safe for pregnant women

• Advise a pregnant woman that successful treatment of

TB with the standardized treatment regimen
(2HRZE/4HR) is important for a successful outcome of
pregnancy.

• Pregnant women taking Isoniazid (H) should be given

pyridoxine (Vitamin B6) at 25 mg/day.

• If a TB patient becomes pregnant during the treatment -

follow-up the newborn for 12 months post natal to check
for congenital anomalies.
Module 7 - Treatment of TB in Special Situations

• For MDRTB, determine initiation of treatment and

management of pregnant patients according to the
severity of TB disease.
Consider the following:
▪ If clinically stable with minimal radiological
disease, treatment may be deferred until the 2nd
trimester with close clinical follow-up
▪ If clinically unstable, MDR-TB treatment that is
effective and safe for the mother and baby should
be initiated immediately
▪ Avoid drugs with potential teratogenic effects
(SLIs/Pto)
▪ Delamanid - potentially teratogenic in animal
studies, and should be avoided until more data is
available
▪ Bedaquiline - demonstrated to be safe in animal
studies and may be considered for pregnant
patients weighing risks and benefits

What are possible consequences of not treating?

▪ higher rates of complications of pregnancy such
as pre-eclampsia, vaginal hemorrhage and fetal
loss

What is the DRTB regimen for pregnant patient?

▪ Includes three to four oral medicines deemed to
be effective but exclude the following:
▪ Injectable agents
▪ Prothionamide
Module 7 - Treatment of TB in Special Situations

Safety of Anti-TB Drugs in Pregnancy according

to US FDA Classification

Safety
Safety Class Interpretation Anti-TB Drug
Class
Safety established using human ---
A
studies
Presumed safety based on animal E, Meropenem
B studies, no human studies Amoxcycillin/Clavul
anate, Bedaquiline
Uncertain safety, no human studies, H, R, Z, FQs, Cm,
animal studies show an adverse Eth/Pto, Cs, PAS,
C
effect Cfz, Lzd, Lfx/Mfx,
Ipm-cln
Unsafe , evidence of risk that may Am, S
be justifiable under certain clinical
D
circumstances

Department of Health – National TB Control Program

Module 7 - Treatment of TB in Special Situations

Breastfeeding
• A breastfeeding woman afflicted with TB should receive a full
course of TB treatment.
• Timely and properly applied treatment is the best way to prevent
transmission of the tubercle bacilli to the baby.
• Drugs in breastmilk:
BREASTFEEDING
▪ Most anti-tuberculosis drugs will be found in the breast
milk in concentrations equal to only a small fraction of the
therapeutic dose used in infants.
▪ Effects of such exposure on infants have not been
established.
▪ It is recommended that lactating mothers feed their infants
before taking medications.
• Mothers who are breastfeeding and are sputum positive should
discontinue breastfeeding.
• If their regimen contains Bdq and Dlm:
▪ Bdq and Dlm are excreted in breastmilk in animal studies.
▪ Decide whether to discontinue the drug or breastfeeding as
an alternative weighing benefits and risks with clinical
considerations.
• Exposure
▪ If the mother is not undergoing appropriate treatment or
still has positive cultures, contacts between mother and
child should be limited for the well being of the child.
▪ Contact should occur in an open-air space if possible, with
the mother wearing a surgical mask or N95 respirator.
• Supplemental pyridoxine (i.e Vitamin B6) should be given to the
infant whose breastfeeding mother is taking INH
Module 7 - Treatment of TB in Special Situations

Contraception
• Birth control is strongly recommended for all non-pregnant
sexually active women receiving therapy for drug-resistant
TB

• There is no contraindication to the use of oral contraceptives

with non rifamycin containing regimens. Advise a woman
receiving oral contraceptives while on Rifampicin treatment
that she has the following options:

▪ Use an oral contraceptive pill containing higher dose

of estrogen (50 μg); or
▪ Use another form of contraception
Module 7 - Treatment of TB in Special Situations

Diabetes Mellitus
• Diabetes mellitus may multiply the adverse effects of anti-TB
medicines, especially renal dysfunction and peripheral
neuropathy.
DIABETES MELLITUS
• Use modern insulin or insulin analogues especially in the
early phase of TB to achieve optimal blood glucose control
with strict glycemic control.

• Cautions to consider when managing patients with diabetes

▪ use of nephrotoxic agents such as aminoglycosides

▪ use of neurotoxic agents such as Lzd
▪ co-administration of Bdq and hypoglycemic agents
such as sulfonylureas and glinides since these agents
function by inhibiting ATP-dependent potassium
channels thus delaying repolarization which leads to
QTc prolongation co-administration of Bdq and
potentially hepatotoxic hypoglycemic agents such as
thiazolidinediones
Module 7 - Treatment of TB in Special Situations

Liver Disorder
• Mild elevation of liver enzymes at baseline may be due to
disseminated TB itself.

• Isoniazid, Rifampicin and Pyrazinamide are associated with

hepatitis. Rifampicin is least likely to cause hepatocellular
damage although it is associated with cholestatic jaundice.
Pyrazinamide is the most hepatotoxic.

• Treatment should be interrupted and modified or alternative

regimen used for the following:

▪ ALT elevation >3x the upper limit of normal (ULN) in

the presence of hepatitis and/or jaundice.
▪ ALT is elevated 5x the ULN, in the absence of
symptoms.

• Wait for the liver function tests to revert to normal and

clinical symptoms (e.g. nausea, abdominal pain) to resolve
before reintroducing the anti-tb drugs.

• If liver function tests cannot be done, it is advisable to wait

an extra 2 weeks after resolution of jaundice and upper
abdominal tenderness before restarting TB treatment.

• Once drug-induced hepatitis has resolved, the drugs are

reintroduced one at a time beginning with R. After 3-7 days,
H maybe reintroduced. In patients who have experienced
jaundice but tolerate the reintroduction of R and H. It is
advisable to avoid Z, If symptoms recur or liver function tests
become abnormal as the drugs are reintroduced, the last
drug added should be stopped.
Module 7 - Treatment of TB in Special Situations

• Patients with chronic liver disease should not receive Z.

Alternative regimens are 2SHRE/6HR, 9RE, or 2SHE/10HE
• For acute viral hepatitis, defer treatment until the acute
hepatitis has been resolve. When it is necessary to treat TB,
the safest option is:
▪ SE x 3 months and once hepatitis has resolved,
follow with continuation phase of 6 months of HR
(3SE/6HR)
▪ If the hepatitis has not been resolved, SE should be
continued for a total of 12 months (i.e., 12SE)

• Bdq and Dlm are not contraindicated in case of mild to

moderate hepatitis.
• In severe hepatitis, Bdq and Dlm may be used with caution
Module 7 - Treatment of TB in Special Situations

Renal Failure
• Renal failure maybe due to any of the following:
▪ concomitant renal problem
▪ Result of previous DRTB treatment with SLI
▪ disseminated TB with renal involvement

Recommended dose and frequency for patients

who have creatinine clearance <30 ml/min and
those having renal dialysis (unless otherwise
indicated dose after dialysis)

Isoniazid No adjustment necessary

Rifampicin No adjustment necessary
15-25 mg/kg per dose 3 times per week (not daily
Ethambutol
dose)
25-35 mg/kg per dose 3 times per week (not daily
Pyrazinamide
dose)
Normal dose can be used, if possible monitor drug
Rifabutin
concentration level to avoid toxicity

Rifapentine No adjustment necessary

Levofloxacin 750-1000 mg per day 3 times per week (not daily)
Moxifloxacin No adjustment necessary

Etionamide/Prothi
No adjustment necessary
onamide

250 mg once daily or (500 mg per day 3 time per

Cycloserine
week – not daily)

PAS 4 G/dose, twice daily maximum dose

Module 7 - Treatment of TB in Special Situations

No adjustment necessary in mild to moderate

Bedaquiline renal impairment, no established dosage in
severe renal impairment, use with caution

No adjustment necessary in mild to moderate

Delamanid renal impairment, no established dosage in severe
renal impairment, use with caution
Clofazimine No adjustment necessary
Linezolid No adjustment necessary
Creatine Clearance 10-30 ml/min, 1000 mg twice
daily for Amoxicillin component
Amox/Clv
Creatinine clearance <10 ml/min, 1000 mg once
daily for Amoxicillin component
High dose
Recommended dosage not available
isoniazid
12-15 mg/kg per dose two-three times per week
Streptomycin
(not daily)
12-15 mg/kg per dose two-three times per week
Amikacin
(not daily)

Creatine Clearance <20-40 ml/min: 500 mg every 8

Imipenem/Cilasta hours daily
tin Creatine Clearance <20 ml/min: 500 mg every 12
hours daily

Creatine Clearance <20-40 ml/min: 750 mg every

12 hours daily
Meropenem
Creatine Clearance <20 ml/min: 500 mg every 12
hours daily
Module 7 - Treatment of TB in Special Situations

Creatinine Clearance Computation

Calculation of Creatinine Clearance

(Estimated Glomerular Filtration Rate)

Crea Cl = Weight (kg) x (140 – Age) x constant

Serum creatinine (µmol/L)

Constant: for Male = 1.23; for Female = 1.04

If Serum Creatinine value is given in mg/dl, it can be
converted to umol/l by multiplying by 88.4.
___________________________________________________________
IOS and Android App: Qx Calculate
(Nephrology > eGFR > Cockcfoft Gault Equation)

-AGE -WEIGHT
-SEX -CREATININE LEVEL
Module 7 - Treatment of TB in Special Situations

• For Regimen I,
▪ Intensive phase - give a 4-drug FDC (HRZE) 3 x a week
(i.e. M-W-F)and then give a 2-drug FDC (HR) for the rest
of the week (i.e. T-Th-S-Su)
▪ Continuation phase - give 4HR.
▪ Otherwise, another safe option is 2HRZ/4HR.

• It is recommended that anti-TB medications be taken after

hemodialysis.

• Bdq and Dlm are not contraindicated for mild to moderate

renal insufficiency.
▪ In severe renal insufficiency, these drugs may be used
with caution.

• Dosing of drugs should be adjusted per patients’ creatinine

clearance (EGFR)
Module 7 - Treatment of TB in Special Situations

HIV Co-infection
• The likelihood of dying from TB greatly increases if PLHIV
with TB is not supported by ART

HIV CO-INFECTION
• Proper coordination between the treatment hub/health care
provider and TB facility to discuss potential drug-drug
interactions

• In patients with HIV-related TB, the priority is to treat TB,

especially bacteriologically confirmed PTB to stop
transmission.

• Patients with HIV-related TB can have Antiretroviral Therapy

(ART) and anti-TB treatment at the same time, if managed
carefully. Careful evaluation is necessary in judging when to
start Anti–Retroviral Therapy.

DRTB/DSTB
▪ Within 8 wks from TB treatment
▪ If CD4<50 cells/mm3 – within 2 weeks

• Patients with TB/HIV co-infection should also receive co-

trimoxazole as prophylaxis for other infections.

• Persons with HIV infection who, after careful evaluation, do

not have active tuberculosis should be treated for
presumed latent tuberculosis infection with isoniazid
preventive therapy
Module 7 - Treatment of TB in Special Situations

Co-administration of Bdq and antiretroviral drugs:

• Replace EFV with Nevirapine (NVP) if the virus is still

susceptible and patient has no toxicity to NVP, because EFV
decreases Bdq blood concentration level by 52%. Allow 5
days wash-out if EFV is to be replaced with NVP (i.e.
Substitute NVP on Day 1 and start MDR TB treatment 5 days
later). However, if patient is critically ill, start MDR TB
treatment immediately, no need to wait for wash-out period.

• Potential risk of additive adverse event when using with

Linezolid containing treatment regimen :
▪ HIV related neuropathy when co-administered with
Stavudine
▪ Bone marrow dysfunction, particularly anaemia when
co-administered with Zidovudine .

• Dolutegravir, which is now becoming widely used globally

in first line ART has no significant interactions with Bdq, Dlm
or Lzd
Module 7 - Treatment of TB in Special Situations

Psychiatric Disorder
• DRTB patients have high rates of depression and anxiety due
to chronicity of the disease and socioeconomic stressors.

• Special caution should be considered in using Cycloserine but

this is not absolutely contraindicated.

• Patients with psychiatric disorder should undergo psychiatric

evaluation prior to start of treatment.

• Family members or significant others should be educated

about Cycloserine toxicity and instructed to contact health
care provider for any changes in patient’s behavior.

• Individual or group therapy session and treatment with

psychiatric medication may be necessary to manage patients
with psychiatric condition or neurotoxicity brought about by
DR-TB treatment.

• Pyridoxine (Vitamin B6) 50 mg is indicated for every 250 mg

of Cs
Module 7 - Treatment of TB in Special Situations

SEIZURE DISORDER
• Cycloserine and high dose H can cause seizures

• Avoid Cycloserine and high dose H in patients with active

SEIZURE
seizure disorders that are not well controlled with
medication.

• In cases where Cycloserine or high dose H is a crucial

component of the treatment regimen, it can be given and the
seizure medication adjusted as needed.

• Prophylactic use of oral pyridoxine (Vit. B6)

▪ 10 – 25 mg/day for at-risk patients on isoniazid
▪ 25 – 50 mg for every 250 mg of cycloserine
▪ 10 – 50 mg/day for pediatric patients at risk for
neurological sequella
Module 7 - Treatment of TB in Special Situations

Substance Dependence
• Patients with substance-dependence disorders should be
referred for therapy in specialized institutions.

• Special caution should be considered in patients taking

Cycloserine
SUBSTANCE DEPENDENCE
CAGE Questionnaire for Assessing Alcohol Use

1. Have you ever felt you should Cut down on your

drinking?
2. Have people Annoyed you by criticizing your drinking?
3. Have you ever felt bad or Guilty about your drinking?
4. Have you ever had a drink first thing in the morning to
steady your nerves or to get rid of a hangover (Eye
opener?)

Scoring:

No – 0
Yes – 1

A total score of 2 or greater is considered

clinically significant.