Management of TB in Special Situations

TREATMENT OF TB IN
SPECIAL SITUATIONS
ncroffice.doh.gov.ph
LEARNING OBJECTIVES
Administer appropriate treatment regimen to

DSTB and DRTB patients with unconventional
situations.
DOH Center for Health Development

Metro Manila 2
TREATMENT CONSIDERATION IN SPECIAL POPULATION
• Children
• Pregnancy
• Breastfeeding
• Contraception
• Diabetes Mellitus
• Liver Disorder
• Renal Failure
•
Seizure Disorder Metro Manila

3
CHILDREN
⮚ Assess the newborn. If the newborn is not well, refer it to a

specialist/pediatrician.
⮚ If the newborn is well (absence of any signs or symptoms

presumptive of TB), do not give BCG first. Instead give TB
preventive treatment. Give Pyridoxine at 5–10 mg/day.
⮚ Preventive treatment is not necessary if the mother has

received more than two months of anti-TB treatment and is
not considered infectious.

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CHILDREN
⮚ At the end of treatment, perform TST. If TST is negative

or not available, give BCG.
⮚ If the mother is taking anti-TB drugs, she can safely

continue to breastfeed. Mother and baby should stay
together and the baby may be breastfed while on TB
preventive treatment.

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TREATMENT OF TB IN CHILDREN
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

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⮚ 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

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DSTB
• isoniazid (H) 10 mg/kg (range 7–15 mg/kg);

maximum dose 300 mg/ day
• rifampicin (R) 15 mg/kg (range 10–20 mg/kg);
maximum dose 600 mg/ day
• pyrazinamide (Z) 35 mg/kg (range 30–40 mg/kg)
• ethambutol (E) 20 mg/kg (range 15–25 mg/kg)
Treatment duration 2 HRZE/ 4HR

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DRTB
▪ Bedaquiline and Delamanid is now recommended by WHO for the

treatment of MDR/RR-TB in adults and children of ALL ages
▪ CTR FQ – susceptible
Bdq - Lfx - Lzd - Cfz (Cs/Dlm)
▪ CTR FQ- Resistant
Bdq - Lzd - Cfz - Cs (Dlm/PAS)
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
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MONITORING OF TREATMENT IN CHILDREN
BACTERIOLOGICALLY CONFIRMED (BC)
▪ Monitor clinically
▪ Follow bacteriological monitoring schedule for

sputum and culture tests (as in adults)

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MONITORING OF TREATMENT IN CHILDREN
CLINICALLY DIAGNOSED (CD)

Monitor clinically for:
▪ 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)

Metro Manila
PREGNANCY
● 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)
● Avoid pregnancy during treatment
● Encourage family planning and offer effective and appropriate
method of contraception .
● For pregnant women with HIV who are already on ART, defer
preventive treatment until three months post-partum.

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PREGNANT
Drug susceptible TB Drug Resistant TB

Most first line drugs for TB are safe for Women who are pregnant or breastfeeding
pregnant women should be assessed for eligibility to SSOR with
Lzd.
(If not eligible, refer to TBMAC for ITR.)
Successful treatment of TB with the Determine initiation of treatment and management

standardized treatment of pregnant patients according to the severity o
regimen (2HRZE/4HR) is important for a
successful outcome of pregnancy. 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
Pregnant women taking Isoniazid (H) should be for

DOH Center Avoid drugs with potential teratogenic effects
Health Development
given pyridoxine (Vitamin B6) at 25 mg/dayMetro Manila

(SLIs/Pto) 13
PREGNANT
The use of bedaquiline in pregnancy has

been associated with infants born with a
lower mean birth weight than infants
whose mothers did not take bedaquiline.
However, when infants were followed up
over time, no evidence of late adverse
impacts were found.

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Safety of Anti-TB Drugs in Pregnancy according to
US FDA Classification
Safety Class Safety Class Interpretation Anti-TB Drug
A Safety established using human studies ---

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

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BREASTFEEDING
o A breastfeeding woman afflicted with TB should receive a full

course of TB treatment.
o Timely and properly applied treatment is the best way to

prevent transmission of the tubercle bacilli to the baby.

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BREASTFEEDING
o Drugs in breastmilk:
o 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.
o Effects of such exposure on infants have not been established.
o It is recommended that lactating mothers feed their infants before
taking medications.
Pregnant or breastfeeding patients shall be referred to TBMAC for

evaluation of
eligibility to Lzd–containing SSOR or ITR
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BREASTFEEDING
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
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CONTRACEPTION
• Birth control is strongly recommended for all non-pregnant

sexually active women receiving therapy for drug-resistant TB
• Rifampicin and rifapentine interact with oral contraceptive

medications with a risk of decreased protective efficacy against
pregnancy.

Metro Manila
CONTRACEPTION
• Advise a woman receiving oral contraceptives while on rifampicin or rifapentine that she
has the following options:
1) take an oral contraceptive pill containing a higher dose of estrogen (50u),

following consultation with a clinician;
2) use another form of contraception.
Patients who vomit directly after taking an oral contraceptive can be at risk of decreased
absorption and therefore of decreased efficacy, and should be advised to use a barrier
method of contraception

Metro Manila
DIABETES MELLITUS
o Diabetes mellitus may multiply the adverse effects of
anti-TB medicines, especially renal dysfunction and
peripheral neuropathy.
o Use modern insulin or insulin analogues especially in

the early phase of TB to achieve optimal blood glucose
control with strict glycemic control.

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DIABETES MELLITUS
o Cautions to consider when managing patients with diabetes
▪ use of nephrotoxic agents such as aminoglycosides
▪ use of neurotoxic agents such as Lzd

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DIABETES MELLITUS
⮚ 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

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LIVER DISORDER
POSSIBLE ANTI-TB DRUG CAUSES:
Z, H, Pa, Bdq, Pto/Eto, Cs,/Trd, PAS
• 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.

Metro Manila
LIVER DISORDER
POSSIBLE ANTI-TB DRUG CAUSES:
Z, H, Pa, Bdq, Pto/Eto, Cs,/Trd, PAS
• 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.

Metro Manila
LIVER DISORDER
• 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.

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LIVER DISORDER
• 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

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LIVER DISORDER
• Bdq and Dlm are not contraindicated in case of mild

to moderate hepatitis
• In severe hepatitis, Bdq and Dlm may be used

with caution

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RENAL FAILURE
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.

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RENAL FAILURE
DSTB DRTB
⮚ Intensive phase - give a 4- Renal dosing is applicable to
drug FDC (HRZE) 3 x a week other regimens except
(i.e. M-W-F)and then give a 2- BPaLM/BPaL
drug FDC (HR) for the rest of
the week (i.e. T-Th-S-Su) Bdq and Dlm are not
contraindicated for mild to
⮚ Continuation phase - give moderate renal insufficiency.
4HR
In severe renal insufficiency,
⮚ Otherwise, another safe these drugs may be used with
option is 2HRZ/4HR caution.
⮚ It is recommended that anti-
TB medications be taken after
hemodialysis Metro Manila 30
HIV CO- INFECTION
• The likelihood of dying from TB greatly increases

if PLHIV with TB is not supported by ART
• Proper coordination between the treatment

hub/health care provider and TB facility to
discuss potential drug-drug interactions

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HIV CO- INFECTION
• 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
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MDR-TB AND RR-TB TREATMENT IN
HIV CO-INFECTED
▪ Antiretroviral treatment (ART) should be started in all MDR-TB
patients living with HIV, regardless of CD4 cell count.
▪ TB treatment should be initiated first, followed by ART as soon

as possible within the first eight weeks of treatment.
▪ If with profound immunosuppression (e.g. CD4 counts less than

50 cells/mm3), HIV-positive MDR-TB patients should receive
ART within the first two weeks of initiating treatment
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HIV CO- INFECTION
▪ For those who are suspected to have TB meningitis for whom
ART initiation should be deferred due to the risk of developing
potentially fatal immune reconstitution inflammatory syndrome
▪ Patients with TB/HIV co-infection should also receive
cotrimoxazole 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 TB Preventive Treatment

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CO-ADMINISTRATION OF BEDAQUILINE AND
ANTIRETROVIRAL DRUGS (ARVS);
o Replace efavirenz (EFV) with nevirapine (NVP) if still susceptible

EFV decreases Bdq blood concentration level by 52%.
o Allow five days for washout (i.e. substitute NVP then start MDR-TB
treatment five days later).
o If patient is critically ill, no need to wait for a washout period just start
MDR-TB treatment immediately.

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CO-ADMINISTRATION OF BEDAQUILINE AND
ANTIRETROVIRAL DRUGS (ARVS);
o Use Bdq with iopinavir/ritonavir (LPV/r) only when other options
are not available
LPV/r increases Bdq concentration threefold.
o The better option is to substitute with raltegravir or dolutegravir

together with dual nucleoside reverse-transcriptase.25,26
o If the co-administration of Bdq and LPV/r is really needed, use

with extreme caution and closely monitor ECG every two weeks.
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CO-ADMINISTRATION OF LINEZOLID AND
ANTIRETROVIRAL DRUGS (ARVS)
o Be aware of potential risk of an additive adverse

event when using with linezolid-containing treatment
regimen
o HIV-related neuropathy when co-administered with

stavudine

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CO-ADMINISTRATION OF LINEZOLID AND
ANTIRETROVIRAL DRUGS (ARVS)
o Bone marrow dysfunction, particularly anemia
when co-administered with zidovudine
o Dolutegravir, which is now becoming widely used

globally in first-line ART, has no significant
interactions with Bdq, Dlm or Lzd.

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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.

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• 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.

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• 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

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SEIZURE
• Cycloserine and high dose H can cause
seizures
• Avoid Cycloserine and high dose H in
patients with active 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.

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SEIZURE
• 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 sequala

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SUBSTANCE DEPENDENCE
• Patients with substance-dependence disorders should

be referred for therapy in specialized institutions.
• Special caution should be considered in patients taking

Cycloserine

Metro Manila
Maraming Salamat po!

Metro Manila

Management of TB in Special Situations

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TREATMENT OF TB IN

Administer appropriate treatment regimen to

DOH Center for Health Development

Seizure Disorder Metro Manila

⮚ Assess the newborn. If the newborn is not well, refer it to a

⮚ If the newborn is well (absence of any signs or symptoms

⮚ Preventive treatment is not necessary if the mother has

DOH Center for Health Development

⮚ At the end of treatment, perform TST. If TST is negative

⮚ If the mother is taking anti-TB drugs, she can safely

DOH Center for Health Development

⮚ Positive TB bacteriology (smear microscopy, Xpert

⮚ Cavities or bilateral disease on chest radiography

DOH Center for Health Development

⮚ Extrapulmonary forms of disease other than

⮚ Presence of co morbid condition or disease such as

DOH Center for Health Development

• isoniazid (H) 10 mg/kg (range 7–15 mg/kg);

Treatment duration 2 HRZE/ 4HR

▪ Bedaquiline and Delamanid is now recommended by WHO for the

BACTERIOLOGICALLY CONFIRMED (BC)

▪ Follow bacteriological monitoring schedule for

DOH Center for Health Development

CLINICALLY DIAGNOSED (CD)

DOH Center for Health Development

● Do pregnancy test (part of baseline)

● Avoid pregnancy during treatment

● Encourage family planning and offer effective and appropriate

DOH Center for Health Development

Drug susceptible TB Drug Resistant TB

Successful treatment of TB with the Determine initiation of treatment and management

If clinically unstable, MDR-TB treatment that is

Pregnant women taking Isoniazid (H) should be for

given pyridoxine (Vitamin B6) at 25 mg/dayMetro Manila

The use of bedaquiline in pregnancy has

DOH Center for Health Development

A Safety established using human studies ---

DOH Center for Health Development

o A breastfeeding woman afflicted with TB should receive a full

o Timely and properly applied treatment is the best way to

DOH Center for Health Development

Pregnant or breastfeeding patients shall be referred to TBMAC for

Supplemental pyridoxine (i.e. Vitamin B6) should be given to the

• Birth control is strongly recommended for all non-pregnant

• Rifampicin and rifapentine interact with oral contraceptive

DOH Center for Health Development

1) take an oral contraceptive pill containing a higher dose of estrogen (50u),

2) use another form of contraception.

DOH Center for Health Development

o Use modern insulin or insulin analogues especially in

DOH Center for Health Development

o Cautions to consider when managing patients with diabetes

▪ use of nephrotoxic agents such as aminoglycosides

▪ use of neurotoxic agents such as Lzd

DOH Center for Health Development

⮚co-administration of Bdq and potentially hepatotoxic

DOH Center for Health Development