NTP MOP 6th Edition Pocket Guide PDF

Pocket Guide
TB (DS & DR) and Latent TB

Screening, Diagnosis and
Management
The primary users of this pocket guide are health service
providers (physicians, nurses, medical technologists, midwives,
and community volunteers) who are providing TB and MDR TB care services.
Contents of the pocket guide were adapted from

the 6th edition of the Manual of Procedures (MOP)
of the Department of Health-National Tuberculosis Control Program (DOH-NTP).
CONTENTS
Screening and Diagnosis of TB Disease 4

Systematic Screening for PTB in Adults ≥15 years old with Unknown HIV Infection Status 4
Screening for Active Pulmonary TB among Children <15 years old 5
TB Diagnostic Algorithm for Children <15 years old 6
Systematic Screening for Diagnosis of Active Pulmonary TB Disease in PLHIV 7
Screening among Health Care Workers 8
Screening of PTB in Targeted Community/Workplace and Congregate Setting 9
Instructions on Proper Sputum Collection 10
TB Diagnostic Test Interpretation 11-12
Interpretation of Xpert MTB/RIF Results & Treatment Decisions 11
Interpretation of LPA Result and Treatment Decision 12
TB Case Classification/Definition 13
TB Treatment and Management 14
Treatment Regimen & Treatment Monitoring for Adults and Children with DS-TB 14
Standard Regimens for DSTB: Dosing for Adults 15
Standard Regimen for DS-TB: Drug Dose for Children Using Single Dose Formulations 16
Second Line Anti-TB Drugs Grouping 17
MDR-TB Treatment Regimens Algorithm 18
Eligibility Criteria for Different MDR/RR-TB Regimens 19
Decision Guide on Appropriate Treatment Regimen Based on LPA Results 20
MDR/RR-TB Regimens for Children 21
Dosing of Medicine Used in Second Line MDR-TB Regimens by Weight Band in Patients <15 Years Old 22-23
Dosing of Medicine Used in Second Line MDR-TB Regimens by Weight Band in Patients >15 Years Old 24
Dose Adjustment of Anti-TB Drugs in Patients with Renal Insufficiency 25
Preparation and Administration of Imipenem 26
TB Treatment Monitoring 27-28
Schedule of Baseline and follow-up Clinical and Laboratory Examination for Patients on Standard Short Treatment
Regimen (SSOR/ SSTR) 27
Schedule of Baseline and follow-up Clinical and Laboratory Examination for Patients on 18-20-Month Regimens 28
Management of Adverse Events 29-51
• Ancillary Diagnostic Tests 29-39
1. Electrocardiography 29-33
2. How to calculate Creatinine Clearance 34
3. Audiometry Reading and Interpretation 35
4. Snellen’s Test 36-38
5. Ishihara Colour Vision Test 39
• Adverse Events Management Algorithm 40-52
Monitoring and Management of Adverse Events Related to Linezolid 40
Management of Depression 41
1
Management of Dyspepsia 42
Management of Headache 43
Management of Hemoptysis 44
Management of Hepatotoxicity 45
Management of Joint Pains 46
Management of Myelosuppression 47
Management of Nausea and Vomiting 48
Management of Nephrotoxicity 49
Management of Peripheral Neuropathy 50
Management of Psychosis 51
Management of Prolonged QTc 52
Indication to Consult with Physician or TB MAC 53
Indication for Referral to Hospital 54
Active Drug Safety Monitoring (aDSM) 55-61
Severity Grading of Adverse Event 55-59
Checklist to Monitor Clinical Condition and Adverse Events by Treatment Supporter 60-61
Description of Some Important Drug Side Effects for the Treatment Supporter 62-63
Ancillary Drugs used in Managing Adverse Event 64-68
Definition of DS-TB & MDR/RR-TB Treatment Outcomes 69-71
Tuberculosis Infection Prevention and Control 72-84
• Prevention of TB Transmission in Health Care Settings 72-73
• TB Preventive Treatment 74
Checking eligibility of different risk groups for TB Preventive Treatment using TST 75
LTBI Algorithm in HIV-negative child contacts <5 years old 76
LTBI Algorithm in HIV-negative at-risk individuals ≥5 years old 77
LTBI Algorithm in adults and children with HIV aged 1-4 years 78
LTBI Algorithm in adults and children with HIV ≥5 years old 79
Selection of preventive treatment regimens 80
Dosing for 6H, 4R and 3HR in children 81
Dosing for 3-month weekly rifapentine and isoniazid in adults and children ≥2 years old 82
Dosing for TPT Regimen by Using Tablets and Fixed-Dose Combination 83
Definition of TPT Treatment outcome 84
2
ABBREVIATIONS, ACRONYMS and SYMBOLS
ADR Adverse Drug Reaction IPC Infection Prevention and Control

AE Adverse Event IV Intravenous
AIDS Acquired Immune Deficiency Syndrome Km Kanamycin
ALT Alanine aminotransferase Lfx Levofloxacin
Am Amikacin LLN Lower Limit of Normal
Amx/Clv Amoxicillin/Clavulanate LPA Line Probe Assay
ART Antiretroviral treatment/therapy LTBI Latent TB Infection
ARV Antiretroviral Lzd Linezolid
AST Aspartate aminotransferase MDR-TB Multidrug Resistant TB
Bdq Bedaquiline Mfx Moxifloxacin
BID Twice daily MGIT Mycobacterial growth indicator tube
CBC Complete Blood Count Mpm Meropenem
Cfz Clofazimine NTRL National TB Reference Laboratory
Cm Capreomycin OD Once a day
CP Continuation Phase PAS Para-aminosalicylic Acid
CrCl Creatinine Clearance p.o. by mouth
Cs Cycloserine PRN as needed
CSF Cerebrospinal Fluid PTB Pulmonary Tuberculosis
CXR Chest X-ray Pto Prothionamide
Dlm Delamanid Q Every
DOT Directly Observed Treatment R Rifampicin
DR-TB Drug-Resistant Tuberculosis S Streptomycin
DST Drug Susceptibility Testing S/S Signs and Symptoms
DS-TB Drug-Susceptible Tuberculosis SLI Secondline Injectables
E Ethambutol SLD Second line drug
ECG Electrocardiogram SL-LPA Second Line-Line Probe Assay
EP Extrapulmonary SM Smear Microscopy
FL-LPA First Line LPA SSTR Standard Short Treatment Regimen
FQ Fluoroquinolones TB Tuberculosis
GI Gastrointestinal TB-LAMP Loop-mediated isothermal amplification
Gx GeneXpert TBC TB Culture
H Isoniazid TB MAC TB Medical Advisory Commitee
Hct Hematocrit TID Three times a day
HdH High dose Isoniazid TNF Tumor Necrosis Factor
Hgb Hemoglobin TSH Thyroid Stimulating Hormone
HIV Human Immunodeficiency Virus ULN Upper Limits of Normal
Imp Imipenem WBC White blood cells
IM Intramuscular WHO World Health Organization
IP Intensive Phase Z Pyrazinamide
3
Diagnosis of TB
Screening and
Disease
Screening and Diagnosis of TB Disease
A. Systematic Screening for Active Pulmonary TB in Adults

≥15 years old with Unknown HIV Infection Status in Health Facilities
With the following signs and symptoms for ≥ 2 weeks:

• Cough
• Unexplained fever
• Unexplained weight loss
• Night sweat
NO YES in at least 1
Request for CXR
CXR - suggestive of TB
NO YES Presumptive TB
Collect spot sputum sample
Request Xpert MTB/RIF Test

ASSESS for
or (SM/ TB LAMP if Xpert
other diseases
not available)
4
B. Screening for Active Pulmonary TB among
Children <15 years old
Presence of at least one of the following signs and symptoms for 2 weeks:
Unexplained cough/ wheezing (e.g., not responding to antibiotic or bronchodilators)
Unexplained fever after ruling out other causes such as malaria or pneumonia
Unexplained weight loss or failure to thrive and no response to nutrition therapy
(check FNRI weight for age)
Among pediatric TB contacts, even without above S/S, presence of >2 weeks
fatigue, decreased activity and playfulness and poor appetite is already
considered as Presumptive TB
With available CXR that is suggestive of TB
Collect sputum and/or extra pulmonary sample

(especially in children >8 years old)
Sample available Sample not available
Do Xpert MTB/RIF Test Do CXR
Follow TB Diagnostic Algorithm

(p.6) for further decision
FNRI - Food and Nutrition Research Institute
5
C. TB Diagnostic Algorithm for Children <15 Years Old
Presumptive TB with/without Risk Factors#
Presumptive PTB Presumptive EP-TB
Ask to expectorate sputum sample Collect (if possible) pus/tissue/fluid

especially from ages >8 years old samples for Xpert MTB/RIF
OR (keep EP samples for culture and DST)
Collect gastric aspirate sample (if possible)
Do Xpert MTB/RIFπ Refer to specialist for further investigation

if sample cannot be collected.
MTB Detected with or MTB not Detected /cannot

without Rif Resistance expectorate
Do CXR (if not yet done)
May give broad spectrum

Strongly suggestive of TB* antibiotic for 1 week/
Normal or uncertain
with clinical S/S observe for 2 weeks
Initiate treatment Persistence of S/S

(Refer to pp 12, 14-21)
*CXR finding strongly suggestive of TB in children = markedly Contact of active TB Case: Not a Contact of TB Case:
enlarged hilar lymph nodes (>2 cm in size) with or without Treat as CD TB Do TST
opacification, miliary mottling, massive pleural effusion (>1/3
of pleural cavity), apical opacification with cavitation
#
Risk factors = < 5 years old, HIV, severe malnutrition, Positive TST: Negative TST
measles, on Immune-suppressing drugs Treat as CD TB or TST unavailable:
π
For Xpert MTB/RIF results and treatment for RR TB,
refer to page 11.
Refer to a specialist
• If clinically unstable (respiratory distress, S/S
of TB Meningitis) or have risk factors for TB:
may TREAT as CD TB
• If clinically stable, follow up after 2-4 weeks
6
D. Systematic Screening for the Diagnosis of Active Pulmonary
TB Disease among PLHIV
At the time of diagnosis of HIV and annually Every Visit (if not on TB Treatment)
Screen for TB S/S* Screen for TB S/S*
+
(of any duration) (of any duration)
• Cough • Cough
CXR
• Fever • Fever
• Weight loss • Weight loss
• Night sweat • Night sweat
Yes in at least 1 AND/OR Suggestive of TB Yes in at least 1
Collect one sputum sample
Request for Xpert MTB/RIF Test

(SM/ TB LAMP only when Xpert test is not available)
7
E. Screening Among Healthcare Workers
Baseline screening when TB symptoms screening

staff is recruited + CXR
TB symptoms screening:
Any of the following signs and
symptoms > 2weeks:
Follow-up screening
Cough and symptoms • Cough
TB symptoms screening
surveillance • Unexplained fever
• Unexplained weight loss
• Night sweat
Follow-up screening TB symptoms screening

annually + CXR
If any symptoms
and/ or Collect a spot sputum specimen for
any abnormality Xpert MTB/RIF
compatible with (or SM/ TB LAMP) Test
TB on CXR
8
F. Screening of Active Pulmonary TB in Targeted Community/
Workplace and Congregate Setting
DO CXR Screening
Annually
Suggestive of TB Not Suggestive of TB
Presumptive TB End of evaluation
Do sputum Xpert
MTB/RIF test
9
Sundan ang mga sumusunod na hakbang sa pagkuha ng maayos na
sampol ng plema para sa eksaminasyon para sa TB
1 Pumunta sa sputum collection area.
2
Magmumog ng tubig at siguraduhin na walang tirang pagkain
o iba pang laman ang bibig.
3
Huminga nang malalim ng tatlong (3) beses at siguraduhing malakas
ang pagbuga ng hangin palabas sa baga.
4 Idahak ang plema mula sa iyong baga.
5
Buksan ang takip ng lagayan ng plema, ilapit sa iyong mga labi
at maingat na idura ang iyong plema sa loob ng lalagyan.
6
Siguraduhing may isang (1) kutsarita ang nakolekta mong plema.
Isarang mabuti ang lalagyan.
7 Dalhin ang sampol ng iyong plema sa tagapangasiwa ng iyong kalusugan.
8 Siguraduhing maghugas ng iyong mga kamay.
10
TB DIAGNOSTIC TEST INTERPRETATION
Interpretation of Xpert MTB/RIF Results and Treatment Decisions
MTB detected, MTB detected, MTB detected, MTB not

RIF Resistance Rif Resistance Rif Resistance Error/Invalid detected
not detected detected indeterminate (I) (N)
(T) (RR) (TI)
Reassess patient
Low DR-TB • Collect new
Treat with DS- TB High DR-TB •Take CXR if not
Risk specimen
Regimen Risk taken before
•Investigate for EP
• Repeat test • Repeat test
TB or other
disease
• Antibiotic trial if
not given before
• Collect baseline sputum Follow the second • If not TB, give
samples for TBC & DST, result and treat TPT if contacts
LPA-1st & 2ndline drugs DST accordingly of BC DS-TB case
• Check Eligibility Criteria to (if final result is TI,
Standard Treatment Regimens treat as DS-TB)
• Revise regimen based on

DST (LPA & Phenotypic) results
• Refer to TB MAC as necessary
TBC & DST = TB culture and phenotypic DST
11
Interpretation of LPA Result and Treatment Decision
Classification/
Definition
TB Case
Meaning and
Mutation* Treatment regimen
resistance caused
InhA Low level H resistance and

confers resistance to Pto Treat with the
First-line LPA result regimen for
High level H resistance and confers H-resistant TB
KatG
resistance to high dose H
Rifampicin resistance Treat with MDR-TB

RpoB
with and without H resistance regimen
Treatment with FQ Resistant

MDR-TB Regimen
GyrA, GyrB FQ resistance (Ofx, Lfx, Mfx) If GyrA and D94A mutation is
absent, high dose Mfx may
still be effective
Second-line LPA result
(all RR-TB cases) High level injectable (Am, Km, Cm)
rrs Treat with MDR-TB
resistance
regimen
If eis mutation is present, Am
low level resistance to Km,
may still be effective
eis susceptibility or low level to Am & Cm
• This is not provided in the official result but can be requested by TB MAC members from the LPA Laboratory
to assist physicians in designing individualized regimens for DR-TB.
12
TB Case Classification/Definition
History of TB Drug resistant pattern

Bacteriologic Anatomical sites
treatment
Presence of
Positive in any drug resistance
of the following tests: Type
Pulmonary New
• Xpert MTB/Rif H R FQ SLI
• SM
• TB LAMP Bacteriologically Lungs +/- Never treated for DS-TB
• TB Culture Confirmed other organs TB or < 1 month
of TB treatment Isoniazid
R
resistant TB
If the above tests cannot
confirm TB, check RR TB R
• Clinical S/S Extra
Pulmonary Retreatment
MDR-TB R R
• CXR
• Other imaging test
(ultrasound, CT Scan) PreXDR-TB
R R R
• Histology Other organs (FQ/SLI)
Previous TB
• Biochemistry, etc treatment for ≥ 1
R R R
(e.g. lymph nodes,
month regardless
meninges, bone/ XDR-TB R R R R
of TB treatment
Phycisian’s discretion Clinically joints)
completion
to treat as TB Diagnosed
R Resistance to drug/s
13
TB Treatment and Management
Treatment Regimen Eligible TB Patients

PTB or EPTB (except CNS, bones, joints) whether new or retreatment,
with final Xpert result:
MTB, Rif sensitive
Regimen 1 MTB, Rif indeterminate
2HRZE/4HR New PTB or New EPTB (except CNS, bones, joints), with positive
SM/TB LAMP or clinically diagnosed, and:
and Management
Xpert not done
TB Treatment
Xpert result is MTB not detected
EPTB of CNS, bones, joints whether new or retreatment, with final

Xpert result:
MTB, Rif sensitive
Regimen 2 MTB, Rif indeterminate
2HRZE/10HR
New EPTB of CNS, bones, joints, with positive SM/TB LAMP
or clinically diagnosed, and:
Xpert not done
Xpert result is MTB not detected
Schedule of Sputum follow-up examinations (SM)* for Pulmonary TB on DS-TB Regimen
Type of PTB Ff-up 1 Ff-up 2 Ff-up 3

New, CDTB End of Intensive ONLY IF positive at end of Intensive Phase
Phase**
(2nd month) End of 5th month End of Treatment
(6th month)
New, BCTB End of Intensive End of 5th month End of Treatment
Retreatment Phase (6th month)
(2nd month)
*Xpert MTB/Rif test is not used for follow-up examination to monitor treatment because current-generation PCR-based tests
are unable to determine Mycobacterium tuberculosis viability and may test positive even with nonviable or dead bacilli
**for New CDTB, only one (1) follow-up examination is needed if result of this follow-up is negative.
• Do Xpert MTB/Rif if SM (+) at the end of intensive phase (month 2)
• Repeat Xpert MTB/Rif if SM (+) at 5th or 6th month of treatment
Once the NTP laboratory network has capacity for rapid molecular tests for first line drug-susceptibility (e.g., LPA), a request for FL-LPA
should be done for non-converters of DSTB regimens (Regimen 1 and 2) who are still Rifampicin susceptible on Xpert MTB/RIF.
14
Dosing for Drug Sensitive TB Treatment for Adults and Children
Table 1. Standard Regimens for DS-TB: Dosing for Adults
Weight Band (Kg) Intensive Phase Continuation Phase

(2 months HRZE) Regimen 1: 4 months HR
150/75/400/275 Regimen 2: 10 months HR
150/75
Number of Tablets per day
25-37 2 2
38-54 3 3
55-70 4 4
>70 5 5
Table 2. Standard Regimens for DS-TB: Dosing for Children using FDC*
Weight band (Kg) Number of tablets

Intensive phase Continuation Phase
2 months RHZ Regimen 1: 4 months HR
75/50/150* Regimen 2: 10 months HR
75/50
4-7 1 1
8-11 2 2
12-15 3 3
16-24 4 4
25+ Adult dosages recommended
*compute for Ethambutol based on Table 3, in page 16
15
Table 3. Standard Regimen for DS-TB:
Dosing for Children using Single Dose Formulations
Isoniazid Rifampicin Pyrazinamide Ethambutol (100

Body (200mg/5ml) (200mg/5ml (250mg/5ml) or 400 mg/tab)
Weight 10mg/kg 15mg/kg 30mg/kg 20mg/kg
(kgs.)
ml ml ml tablet
3 0.75 1.00 1.75 50mg
4 1.00 1.50 2.50
5 1.25 2.00 3.00
100mg
6 1.50 2.25 3.50
7 1.75 2.50 4.25
8 2.00 3.00 4.75
9 2.25 3.50 5.50
10 2.50 3.75 6.00 200mg
11 2.75 4.00 6.50
12 3.00 4.50 7.25
13 3.25 5.00 7.75
14 3.50 5.25 8.50
15 3.75 5.50 9.00
16 4.00 6.00 9.50 300mg
17 4.25 6.50 10.25
18 4.50 6.75 10.75
19 4.75 7.00 11.50
20 5.00 7.50 12.00
21 5.25 8.00 12.50
22 5.50 8.25 13.25 400mg
23 5.75 8.50 13.75
24 6.00 9.00 14.50
16
Second Line Anti-TB Drugs Grouping
Drug Group Drugs
Group A: Levofloxacin (Lfx) or Moxifloxacin (Mfx)

Include all three medicines
(unless they cannot be used) Bedaquiline (BDQ)
Linezolid (Lzd)
Group B: Clofazimine (Cfz)

Add one or both medicines
(unless cannot be used) Cycloserine (Cs)
Group C: Ethambutol (E)

Add to complete the regimen when
medicines from Groups A and B Delamanid (Dlm)
cannot be used
Pyrazinamide (Z)
Imipenem-Cilastatin (Imp/Cln) or
Meropenem (Mpm)
Amikacin (Am) or Streptomycin (S)
Prothionamide (Pto)
P-aminosalicylic acid (PAS)
17
Type of MDR/RR-TB treatment regimens
Regimen Name Type of DRTB Regimen Remarks

Regimen 3: MDR/RR-TB 4-6 months: Bdq is given for 6
Standard Short all Oral eligible to SSOR Lfx-Bdq(6)-Cfz-Pto-E-Z-HdH months
Regimen (SSOR)
5 months:
Lfx-Cfz-Z-E
Regimen 4: MDR/RR-TB eligible to 6 Months: Request for “Off Label”

Standard Long all SLOR Lfx-Bdq-Lzd-Cfz use from TB MAC for
Oral Regimen for FQ (no FQ resistance; extended use of Bdq
Susceptible when SSOR is not 12-14 months (beyond 6 months)
(SLOR FQ-S) eligible - e.g. Lfx-Lzd-Cfz
disseminated MDR TB)
Regimen 5: MDR/RR-TB eligible to 6 Months: Request for “Off Label”

Standard Long all Oral SLOR (with FQ Lzd-Bdq-Dlm-Cfz-Cs and extended use of
Regimen for FQ resistance) Bdq and/ or Dlm from
Resistance 12-14 months: TB MAC
(SLOR FQ-R) Lzd-Cfz-Cs
Individual Treatment Retreatment Design a regimen with at Present the case to TB

Regimen (ITR) MDR/RRTB cases least 4-5 likely effective MAC and follow the
(not eligible to SSOR drugs recommended
nor SLOR) regimen
Note: For SSOR and SLOR FQ-S shifted to SLOR FQ-R due to confirmed resistance to FQ, check presence of resistance to SLI.
If without SLI resistance, use the same registration number. If with SLI resistance (confirmed XDR-TB), outcome is “Excluded”,
classify patient as BC XDR-TB and assign a new registration number.
18
Eligibility Criteria for Different MDR/RR-TB Regimens for ADULT, NON-PREGNANT,
and NOT a CONTACT of PATIENT who FAILED on MDR-TB TREATMENT
1 Check exclusion criteria for Standard Short All Oral Regimen (SSOR), (if YES to any of the following,
DO NOT GIVE SSOR)
1. Disseminated/ extensive TB or severe/intractable extrapulmonary (EP) TB (e.g., TB Meningitis, Bone/Joint TB)
2. Confirmed resistance to fluoroquinolone (Moxifloxacin/Levofloxacin)
3. Exposure to Moxifloxacin/Levofloxacin, Bedaquiline, Clofazimine, Prothionamide for >1 month
4. Risk of toxicity or intolerance to any drugs in SSOR as manifested by:
History of heart disease (heart failure, myocardial infarction, cardiac conduction abnormality, arrythmia)
QTcF >500 ms
History of chronic active hepatitis (AST/ALT >5 times elevated)
History of chronic renal insufficiency (Creatinine Clearance <20 ml/min)
If eligible, give SSOR. if not, check eligibility to SLOR FQ-S.
2 Check eligiblity criteria for Standard Long All Oral Regimen (SLOR) for fluoroquinolone susceptible
(FQ-S), (if YES to any of the following, DO NOT GIVE SLOR FQ-S)
1. Confirmed resistance to fluoroquinolone (Moxifloxacin/Levofloxacin)

2. Exposure to Moxifloxacin/Levofloxacin, Bedaquiline, Clofazimine, Linezolid for >1 month
3. Risk of toxicity or intolerance to any drugs in SLOR as manifested by:
QTcF >500 ms
Severe anemia (Hgb <8 g/dL)
If eligible, give SLOR FQ-S. If not, check eligibility to SLOR FQ-R.
3 Check eligiblity criteria for Standard Long All Oral Regimen (SLOR) for fluoroquinolone Resistant
(FQ-R), (if YES to any of the following, DO NOT GIVE SLOR FQ-R)
1. Exposure to Bedaquiline, Clofazimine, Linezolid, Cycloserine, and Delamanid for >1 month
2. Risk of toxicity or intolerance to any drugs in SLOR as manifested by:
QTcF >500 ms
Severe anemia (Hgb <8 g/dL)
If eligible, give SLOR FQ-R. If not, consult R-TB MAC for ITR.
19
Decision Guide on Appropriate Treatment Regimen
Based on LPA Results
Initial Regimen Baseline LPA Result

FQ High Dose Clinical and
Pto
Resistance H (HdH) Programmatic
Resistance
Detected Resistance Action
Detected
Detected
- - - Continue SSOR
- + - Continue SSOR
- - + Continue SSOR
Shift to SLOR FQ-S
SSOR Continue dose count if within
- + +
1 month from treatment
initiation
Shift to SLOR FQ-R
+ +/- +/-
Restart dose count
- +/- +/- Continue SLOR FQ-S
SLOR FQ-S Shift to SLOR FQ-R
+ +/- +/- Restart dose count
SLOR FQ-R +/- +/- +/- Continue SLOR FQ-R
Review initial regimen
ITR +/- +/- +/- and revise if needed in
consultation with R-TB MAC
Legend: (-) Resistance NOT Detected; (+) Resistance Detected
20
MDR/RR TB Regimen for children
DRTB Treatment regimens for children
Age Regimen 6 Regimen 7

FQ susceptible MDR TB FQ resistant MDR TB
<3 years (6a) Lfx-Lzd-Cfz-Cs (PAS/Pto) (7a) Lzd-Cfz-Cs-PAS (Pto/Dlm)
3-6 Years (6b) Lfx-Lzd-Cfz-Cs (Dlm/PAS) (7b) Lzd-Cfz-Cs-Dlm (PAS/Pto)
>6 years (6c) Bdq-Lfx-Lzd-Cfz (Cs/Dlm) (7c) Bdq-Lzd-Cfz-Cs (Dlm/PAS)
Treatment Duration:
9-12 months for non-severe disease depending on physician’s assessment
on patient’s clinical progress
15-18 months for severe or extensive disease
Determine the severity of the disease.
Severity of TB in children is usually defined by the presence of any of the following:
positive TB bacteriology (smear, Xpert MTB/RIF, culture)
cavities or bilateral disease on chest radiography or smear-positivity
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.
21
Dosing of Medicine Used in Second line MDR-TB
Regimens by Weight Band in Patients <15 Years Old
Weight bands for patients not yet 15 years old Usual

Group Medicine Weight-based Formulation Upper
daily dose Daily Remarks
5-6 kg 7-9 kg 10-15 kg 16-23 kg 24-30 kg 31-34 kg >34 kg Dose
Fluoroquinolones 15-20 100 mg dt 1 1.5 2 or 3 3 or 4 (≥14 y) (≥14 y) (≥14 y) 1.5 g
Levofloxacin mg/kg
250 mg tab 0.5 0.5 1-1.5 1.5-2 2 3 (≥14 y) 1.5 g
Moxifloxacin 10–15 400 mg tab 0.8 1.5 2 3 4 (≥14 y) (≥14 y) 400 mg
mg/kg Use 10 mg/kg in <6
400 mg tabc 2ml 3ml 5ml 0.5 or 0.75 1 (≥14 y) (≥14y) 400mg months
A Bedaquiline 100 mg tab 2 tabs OD for 2 4 tabs OD for 2 Only in patients >5 years old
weeks; then 1 tab weeks; then2 tabs - (lower dosefrom 15-29 kg;
OD M/W/F OD M/W/F higher dose from >29 kg
for 22 weeks for 22 weeks
Linezolid 15 mg/kg OD 20 mg/ml
in < 16 kg susp 4ml 6ml 8ml 11ml 14ml 15ml 20ml 600mg
10-12mg/kg 600 mg tabc 0.75
OD in >15 kg 0.25 0.25 0.25 0.25 0.5 0.5
Clofazimine 2-5 mg/kg 50 mg cap 1 alt days 1 alt days 1 alt days 1 2 2 (≥14 y) 100mg Give on alternate days if dose
100 mg cap M/W/F M/W/F 1 alt days 1 alt days 1 (≥14 y) (≥14 y) 100mg in mg/kg/day is too high
B 125 mg mini 1 1 2 3 4 (≥14 y) (≥14 y)
Cycloserine 15-20 mg/kg
cap
250 mg capc 4 to 5 mlc 5 to 6 mlc 7 to 10 mlc 2 2 2 (≥14 y) 1g
Ethambutol 15-25 mg/kg 100 mg dt 1 2 3 4 - - (≥14 y)
400 mg tabc 3 mlc 4 mlc 6 mlc 1 1 or 1.5 2 (≥14 y)
Delamanid 50 mg tab - - - - 1 bid 1 bid 2 bid 200 mg Only in patients >2 years old
(25 mg BID in 3-5 yrs, 50 mg
BID in 6-11 yrs; 100mg BID in
12-17 yrs)
Pyrazinamide 30 40 mg/kg 150 mg tab 1 2 3 4 or 5 - - (≥14 y)
500 mg tab 0.5 0.5 0.75 or 1 1.5 2 2.5 (≥14 y)
Imipinem - 0.5 g + 0.5 g Not used in patients <15 years
Cilastatin vial Use Meropenem
Meropenem
20-40mg/kg 1g vial 2 ml 4 ml 6 ml 8-9 ml 11 ml ≥14 y ≥14 y To be used with clavulanic acid
IV q 8 hrs (20ml)
C
Amikacin 15-20 mg/kg 500 0.4 0.6 0.8-1.0 1.2-1.5 2.0 ≥14 y ≥14 y 1g
mg/2ml vial ml ml ml ml ml
Streptomycin 20-40 mg/kg 1 gm vial Calculate according to the dilution used ≥14 y ≥14 y 1g
Prothionamide 15-20 250 mg
mg/kg tab 0.5 0.5 0.75 or 1 1.5 2 2.5 ≥14 y 1g
22
p-aminosalicylic 200-300. PAS acid (4g) 0.5-0.75 0.75-1 1-2 2-3 3-3.5 (>14 y) (>14 y) - Full dose can be given
acid mg/kg in 2 sachet g bid g bid g bid g bid g bid
divided doses once daily if tolerated
C PAS sodium salt 0.5-0.75 0.75-1 1-2 2-3 3-3.5 (>14 y) (>14 y)
(4g) sachet g bid g bid g bid g bid g bid
PAS sodium salt 1.5 2-3 3-4 4 or 6 6 or 8 8-12 8-12 -
60% (9.2g) sachet g bid g bid g bid g bid g bid g bid g bid
Isoniazid 15-20 50mg/5 ml 8-10 ml 15 ml 20 ml - - - - 300 mg isoniazid tablet can

mg/kg soln be used in patients >20 kg
(high.dose) Pyridoxine is always given
with high-dose isoniazid in
100 mg 1 1.5 2 3 4 4 (>14 y) children (12.5 mg od in <5 y
Others
tab olds and 25 mg od in >4 y

olds)
Clavulanic - 250 mg Only be used with

acid amoxicillin/ 2 ml 3 ml 5 ml 8 ml 10 ml (>14 y) (>14 y)
62.5 mg bid bid bid bid bid carbapenems
clavulanic
acid/5 ml
suspension
(>14 y) = follow the separate dose for patients older than14 years of age, alt = alternate, bid = two times a day,
dt = dispersible tablet, g = grams, im = intramuscular, iv = intravenous, kg = kilogram, ml = milligram, M/W/F =
Monday, Wednesday, Friday, OD = once a day, soln = solution, tab = tablet
c
Dissolving in 10 ml distilled water may facilitate administration in patients in lower weight bands & avoids
fractioning of solid formulation although biolavailability is uncertain (use of dispersible tablet is perferred if
available)
23
Dosing of Medicine Used In Second line MDR-TB Regimens
by Weight Band in Patients >15 Years Old
Group Medicine Weight-base Formulation Weight bands for patients older than 14 years old Usual
d daily dose Upper Comments
30-35 kg 36-45 kg 46-55kg 56-70kg >70kg Daily Dose
Fluoroquinolones 250 mg tab 3 3 4 4 4
500 mg tab 1.5 1.5 2 2 2 1.5
Levofloxacin
750 mg tab 1 1 1.5 1.5 1.5
A
Moxifloxacin Standard dose 400 mg tab 1 1 1 1 1 400 mg As used in the standardized shorter
High dose 400 mg tab 1 or 1.5 1 or 1.5 1.5 or 2 2 2 800 mg MDR-TB Regimen
Bedaquiline 100 mg tab 4 tabs OD for 2 weeks; then 2 tabs OD 400 mg
M/W/F for 22 weeks
Linezolid 600 mg tab (<15y) (<15y) 1 1 1 1.2 g
Clofazimine 50 mg cap 2 2 2 2 2 100 mg

100 mg cap 1 1 1 1 1 100 mg
B
Cycloserine or 2 2 3 3 3 1g
Terizidone 10-15 mg/kg 250 mg cap
Ethambutol 15-25 mg/kg 400 mg tab 2 2 3 3 3
Delamanid 50 mg tab 2 bid 2 bid 2 bid 2 bid 2 bid 200 mg

400 mg tab 3 4 4 4 5
Pyrazinamide 20-30 mg/kg
500 mg tab 2 3 3 3 4
Imipinem - 0.5 g + To be used with clavulanic acid
Cilastatin 0.5g vial 2 vials (1g + 1g) bid
Meropenem 1g vial (20ml) 1 vials 3x/day or 2 vials bid To be used with clavulanic acid
C Amikacin 15-20 mg/kg 500 mg/2ml 2.5 ml 3 ml 3 to 4 ml 4 ml 4 ml 1g
vial
Streptomycin 12-18 mg/kg 1 gm vial Calculate according to the dilution used 1g
Ethionamide or 15-20mg/kg 250 mg tab 2 2 3 3 4 1g Once daily dose advised but can start with
Prothionamide 2 divided doses until tolerance improves
p-aminosalicylic 8-12 g/day PAS Na Salt 1 bid 1 bid 1 bid 1 bid 1 to 1.5 12 g
acid in 2 to 3 (4gm) sachet bid
divided
PAS Acid
doses 1 bid 1 bid 1 bid 1 bid 1 to 1.5
(4gm) sachet
bid
Isoniazid Standard 100 mg isoniazid tablet can facilitate the
dose: 4-6 300 mg tab 2/3 1 1 1 1 administration of certain dosages
Others
mg/kg Pyridoxine is given with isoniazid in

High dose: patients at risk (such as dose with HIV and
10-15 mg/kg 300 mg tab 1.5 1.5 2 2 2
malnutrition)
Clavulanic 125 mg tab 1 bid 1 bid 1 bid 1 bid 1 bid To be used only with carbapenems
acid (such as imipenem and meropenem)
24
Dose Adjustment of Anti-TB Drugs in Patients with Renal Insufficiency
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
Ethambutol 15-25 mg/kg per dose 3 times per week (not daily dose)
Pyrazinamide 25-35 mg/kg per dose 3 times per week (not daily dose)
Rifabutin Normal dose can be used, if possible monitor drug 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/Prothionamide No adjustment necessary
Cycloserine 250 mg once daily or (500 mg per day 3 time per week – not daily)
PAS 4 G/dose, twice daily maximum dose
Bedaquiline No adjustment necessary in mild to moderate renal impairment, no established dosage
in severe renal impairment, use with caution
Delamanid No adjustment necessary in mild to moderate renal impairment, no established dosage
in severe renal impairment, use with caution
Clofazamine No adjustment necessary
Linezolid No adjustment necessary
Amoxicillin/ Clavulanate Acid Creatinine Clearance 10-30 ml/min, 1000 mg twice daily for Amoxicillin component
Creatinine clearance <10 ml/min, 1000 mg once daily for Amoxicillin component
High Dose Isoniazid Recommended dosage not available
Streptomycin 12-15 mg/kg per dose two-three times per week (not daily)
Amikacin 12-15 mg/kg per dose two-three times per week (not daily)
Imipinem/Cilastatin Creatinine Clearance <20-40 ml/min: 500 mg every 8 hours daily
Creatinine Clearance <20 ml/min: 500 mg every 12 hours daily
Meropenem Creatinine Clearance <20-40 ml/min: 750 mg every 12 hours daily
Creatinine Clearance <20 ml/min: 500 mg every 12 hours daily
25
PREPARATION AND ADMINISTRATION OF IMIPENEM
Prepare a 100ml vial of 0.9 NaCl solution and aspirate 10ml of the solution to dilute each of the imipenem 500mg vial.
Shake the combined solutions of Imipenem and 0.9 NaCl well and return them to the 100ml vial of NaCl. Shake well
again.
Imipenem is administered twice daily (q 12 hrs) and infusion can be given for 40 to 60 minutes, depending on
preferred rate of infusion. There is always the risk of phlebitis, obstruction or inflammation at the injection site. Advise
the patient on proper care of the injection site.
Prior to the infusion of the imipenem/cilastatin solution, give 1 tab of Co Amoxicav 875mg /125mg tab 30 minutes
before the procedure. For the second infusion, instruct the patient to take 1 tab of Co Amoxicav 875mg /125mg
tab 30 minutes before the procedure. Imipenem/cilastatin would only work with the addition of the beta-lactam
formulation in AmxClv. Always use AmxClv with Imipenem.
The use of lmp is expected to last until the end of treatment.
Implantable venous access system port-a-cath will be used for long term IV Imipenem Administration.
26
RR/MDR-TB Treatment Monitoring
1. Schedule of baseline and follow-up clinical, laboratory and bacteriologic examination

for patients on standard short treatment regimen (SSOR/ SSTR)
Intensive Phase: 4 months, Post-Treatment

Continuation Phase: 5 months
may be extended'up to 6 months Follow-up
Test/Examination Baseline M1 M2 M3 M4 M5 M6 M7 M8 M9 P6 P12
Clinical Evaluation by the PMDT

Physician including weight for all
and height for children
Mycobacteriological Tests
Smear Microscopy
TB Culture(TBC)
Drug Susceptibility Testing (DST)

If culture remains positive at month 4 of treatment, in case of culture reversion or culture positive
First-line and Second-line Line during post-treatment follow-up
Probe Assay (LPA)
Diagnostic Tests
Chest X-ray (CXR)
Electrocardiogram (ECG)
Visual Acuity and Color Vision
Brief Peripheral Neuropathy

Screening (BPNS)
Monthly if regimen contains Cycloserine (Patient Health Questionnaire-9 or

Mental health screening
short screening tool may be used)
Audiometry Monthly while on injectable (SSTR)
Blood Chemistry/Hematology/Immunological Tests

Alanine and Aspartate
Transaminase (ALT/AST) *
Complete Blood Count (CBC) Monthly if regimen contains Linezolid

Urea Nitrogen, Creatinine,
Fasting Blood Sugar (FBS),
Potassium (K),
Thyroid Stimulating Hormone

(TSH)
HIV Rapid Antibody Test
Pregnancy Test
*If ALT and AST are higher than upper limit of normal value, consider doing total bilirubin test.
27
2. Schedule of baseline and follow-up Clinical, Laboratory and Bacteriologic Examinations
for Patients on 18-20 months treatment regimens
Post-Treatment
Intensive Phase: 6 months Continuation Phase: 12-14 months Follow-up
Test/ Base- M1
Examination line M2 M3 M4 M5 M6 M7 M8 M9 M10 M11 M12 M13 M14 M15 M16 M17 M18 M19 M20 P6 P12
Clinical
Evaluation
Mycobacteriology Tests
Smear Microscopy
TB Culture(TBC)
DST If culture remains positive at month 4 of treatment, in case of culture reversion or culture positive
LPA during post-treatment follow-up
Diagnostic Tests
CXR
ECG Monthly if regimen contains Bedaquiline, Delamanid, Clofazimine and/or Moxifloxacin

Visual Acuity
Monthly if regimen contains Linezolid and/or Ethambutol
and Color Vision
BPNS Monthly if regimen contains Linezolid, Cycloserine and/or High Dose Isoniazid
Audiometry Baseline and Monthly if regimen contains Amikacin or Streptomycin
Mental health
screening Baseline and Monthly if regimen contains Cycloserine (Patient Health Questionnaire-9 or short screening tool may be used)
Blood Chemistry/Hematology/Immunological Tests
ALT/AST* Monthly if regimen contains Bedaquiline and/or Pyrazinamide
CBC Monthly if regimen contains Linezolid
FBS,
Urea Nitrogen,
Creatinine, K Monthly if regimen contains Amikacin or Streptomycin
Every 6 months if regimen contains Prothionamide or Para-aminosalicylic Acid (PAS)

TSH
Every 3 months if regimen contains both Prothionamide and Para-aminosalicylic Acid (PAS)
Albumin Baseline if regimen contains Delamanid
HIV Rapid
Antibody Test
Pregnancy Test
* If ALT and AST are higher than upper limit of normal value, consider doing total bilirubin test. If regimen contain Bdq+Dlm and/ or
Mfx+Cfz, more frequent ECG monitoring, every other week for initial 3 months is recommended.
28
Management of Adverse Event: Ancillary Diagnostic Tests
1. Electrocardiography
a. ECG Machine Calibration
The ECG machine should be calibrated to ensure that
the following voltage and speeds apply:
One large 5 mm x 5 mm box One small 1 mm x 1 mm block

1 mV (10 mm high) represents 0.2 seconds (200 ms) represents 40 ms time
reference pulse time and 0.5 mV amplitude and 0.1 mV amplitude
Amplitude
Time
29
b. Normal Heart Rhythm & QTc
ID: X-97 10-Oct-2016 15:21:21
25 Years Vent. rate 87 bpm Normal sinus rhythm (sinus rate 60-100/min)
Female PR Interval 116 ms Normal ECG
QRS duration 90 ms
QTc = 445 mc
P duration 90 ms
RR interval 689 ms
P-R-T axes 62 55 43
Regular Heart rate Regular Heart rate
Cardiac dysrhythmia/arrythmia:.
• Hospitalize patient
• Withhold BDQ and all other QT prolonging drugs.
Irregular Heart rate
30
c. Calculation of QTc by using Fredericia Formula
QRS
Complex
R
QTc = Q T/ 3√ RR
QTc = the corrected QT interval
QT = the time between the start of the QRS
complex and the end of the T wave
Auto-reporting from the machine may not be
programmed with Fredericia formula.
Read at lead II or V5
QT: no of small squares x 40
QT
(e.g 9x40=360ms)
PR Segment
T HR: 1500/no of small squares b/t RR
P Segment
(e.g., 1500/17= 88)
Can use calculator app that can be downloaded as

PR Interval
Q per below link:
S https://www.thecalculator.co/health/QTc-Calculator
-385.html
QT Interval http://www.qxmd.com/apps/calculate-by-qxmd
QT in milliseconds (ms)
and RR interval in
seconds (s).
31
d. Automated QTc value and manual calculation
ID: X-97 10-Oct-2016 15:21:21

25 Years Vent. rate 87 bpm Normal sinus rhythm (sinus rate 60-100/min)
Female PR Interval 116 ms Normal ECG
QRS duration 90 ms
QT/QTc 370/445 ms
P duration 90 ms AUTOMATED REPORT
RR interval 689 ms
P-R-T axes 62 55 43
Step 1:
RR = 17 squares
= 17 x 0.04 = 0.68 sec
HR = 1500/17 = 88
Step 2:
QT = 9 squares x 40
= 360 ms
Step 3:
QTc= 360/3√0.68
= 360/0.88 = 409 ms
Management of
Adverse Events
If the two values are <50 ms
difference, the machine is
more likely to be programmed
with Fredericia formula.
32
Use of Nomogram to get QTcF (QT 420, HR 70, QTcF read as 442)
Heart Rate
(beats per minute)
45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 135 140 145 150
R-R interval(sec) 1.33 1.20 1.09 1.00 0.92 0.86 0.80 0.75 0.71 0.67 0.63 0.60 0.57 0.55 0.52 0.50 0.48 0.46 0.44 0.43 0.41 0.40
300 273 282 291 300 308 316 323 330 337 343 350 356 362 367 373 378 383 388 393 398 403 407
310 282 292 301 310 318 326 334 341 348 355 361 368 374 379 385 391 396 401 406 411 416 421
320 291 301 311 320 329 337 345 352 359 366 373 379 386 392 397 403 409 414 419 424 429 434
330 300 311 321 330 339 347 355 363 371 378 385 391 398 404 410 416 421 427 432 438 443 448
340 309 320 330 340 349 358 366 374 382 389 396 403 410 416 422 428 434 440 446 451 456 461
350 318 329 340 350 359 368 377 385 393 401 408 415 422 428 435 441 447 453 459 464 470 475
360 327 339 350 360 370 379 388 396 404 412 420 427 434 441 447 454 460 466 472 477 483 489
370 336 348 360 370 380 390 399 407 416 424 431 439 446 453 460 466 473 479 485 491 497 502
380 345 358 370 380 390 400 409 418 427 435 443 451 458 465 472 479 485 492 498 504 510 516
390 354 367 379 390 401 411 420 429 438 446 455 462 470 477 484 491 498 505 511 517 523 529
400 363 376 389 400 411 421 431 440 449 458 466 474 482 490 497 504 511 518 524 531 537 543
410 373 386 399 410 421 432 442 451 460 469 478 486 494 502 509 517 524 531 537 544 550 556
QT Interval (msec)
420 382 395 408 420 431 442 452 462 472 481 490 498 506 514 522 529 536 543 550 557 564 570
430 391 405 418 430 442 453 463 473 483 492 501 510 518 526 534 542 549 556 563 570 577 584
440 400 414 427 440 452 463 474 484 494 504 513 522 530 539 547 554 562 569 577 584 590 597
450 409 423 437 450 462 474 485 495 505 515 524 534 542 551 559 567 575 582 590 597 604 611
460 418 433 447 460 472 484 496 506 517 527 536 545 554 563 571 580 588 595 603 610 617 624
470 427 442 457 470 483 495 506 517 528 538 548 557 566 575 584 592 600 608 616 623 631 638
480 436 452 466 480 493 505 517 528 539 549 559 569 578 587 596 605 613 621 629 637 644 651
490 445 461 476 490 503 516 528 539 550 561 571 581 590 600 609 617 626 634 642 650 658 665
500 454 471 486 500 514 526 539 550 562 572 583 593 603 612 621 630 639 647 655 663 671 679
510 463 480 495 510 524 537 549 561 573 584 594 605 615 624 634 643 651 660 668 676 684 692
520 472 489 505 520 534 547 560 572 584 595 606 617 627 636 646 655 664 673 681 690 698 706
530 482 499 515 530 544 558 571 583 595 607 618 628 639 649 658 668 677 686 694 703 711 719
540 491 508 525 540 555 568 582 594 606 618 629 640 651 661 671 680 690 699 708 716 725 733
550 500 518 534 550 565 579 592 605 618 630 641 652 663 673 683 693 702 712 721 729 738 746
560 509 527 544 560 575 590 603 616 629 641 653 664 675 685 696 706 715 725 734 743 751 760
570 518 536 554 570 585 600 614 627 640 652 664 676 687 698 708 718 728 738 747 756 765 774
580 527 546 563 580 596 611 625 638 651 664 676 688 699 710 720 731 741 751 760 769 778 787
590 536 555 573 590 606 621 636 649 663 675 688 700 711 722 733 743 754 763 773 783 792 801
600 545 565 583 600 616 632 646 660 674 687 699 711 723 724 745 756 766 776 786 796 805 814
33
2. How to calculate Creatinine Clearance:
Calculation of Creatinine Clearance

(Estimated Glomerular Filtration Rate)
Constant
weight (kg) x (140 – age) X
Serum Creatinine (umol/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.
Normal Value: Male = 60-110 umol/L; Female: 45-90umol/L
34
3. Audiometry Reading and Interpretation
AUDIOGRAM KEY
Right Ear UNMASKED MASKED
Left Ear
-10 -10
0
AIR 0
10 10
20 Normal 20
30 30
Audiogram
Loudness (dB)
Loudness (dB)
40 40
50
60
25db 50
60
70 70
80 80
90 90
100 100
110 110
120 120
250 500 1000 2000 4000 6000 8000 250 500 1000 2000 4000 6000 8000
Frequencies (Hz) Frequencies (Hz)
Right Ear Interpretation Left Ear Interpretation
Hearing loss was detected. Please consult Hearing loss was detected. Please consult
an audiologist. Threshhold (Hz:dB): an audiologist. Threshhold (Hz:dB):
1K:45, 2K:50, 3K:65, 4K:60, 6K:55, 8K:50 1K:45, 2K:50, 3K:55, 4K:55, 6K:45, 8K:45
Results from the test indicate that hearing Results from the test: indicate that hearing
loss was present at these frequencies: loss was present at these frequencies:
1K, 2K, 3K, 4K, 6K, 8K 1K, 2K, 3K, 4K, 6K, 8K
35
4. How to perform Snellen’s Test
Equipment
• Multi-letter Snellen chart

• E or C Snellen chart or a chart with illustrations for patients
who cannot read or speak
• Plain occluder (not essential)
• Pinhole occluder
• Torch or flashlight
• Patient's documentation
A multi-letter Snellen chart (left) and a chart with illustrations
36
Procedure
• Ensure good natural light or illumination on the chart
• Explain the procedure to the patient
• Wash and dry the occluder and pinhole. If no plain occluder is available, ask the
patient to wash his/her hands as they will use a hand to cover one eye at a time
• Test each eye separately – the ‘bad’ eye first
• Position the patient, sitting or standing, at a distance of 6 metres from the chart
• Ask the patient to wear any current distance spectacles, to cover one eye with
his/her hand (or with a plain occluder), and to start reading from the top of the chart
• The smallest line he/she can read (the VA) will be expressed as a fraction, e.g. 6/18
or 6/24 (usually written on the chart). The upper number refers to the distance the
chart is from the patient (6 metres) and the lower number is the distance in metres
at which a person with no impairment should be able to see the chart
• In the patient's documentation, record the VA for each eye, stating whether it is
with or without correction (spectacles), for example:
Right VA = 6/18 with correction Left VA = 6/24 with correction

• If the patient cannot read the largest (top) letter at 6 metres, move him/her closer,
one metre at a time, until the top letter can be seen – the VA will then be recorded
as 5/60 or 4/60, etc.
• If the top letter cannot be read at 1 metre (1/60), hold up your fingers at varying
distances of less than 1 metre and check whether the patient can count them.
This is recorded as counting fingers (CF). Record as: VA = CF
• If the patient cannot count fingers, wave your hand and check if he/she can see
this. This is recorded as hand movements (HM). Record as: VA = HM
• If the patient cannot see hand movements, shine a flashlight toward his/her eye
from four directions of a quadrant. Record this in the documentation, in the relevant
quadrant, as perception of light (PL or √), or no perception of light (NPL or X).
Record as:
Right VA = NPL NPL Left VA = PL NPL

NPL NPL PL NPL
Right VA = X X Left VA = √ NPL

X X √ NPL
37
• If 6/6 (normal vision) is not achieved, test one eye at a time with a pinhole occluder
(plus any current spectacles) and repeat the above procedure at 6 metres only.
The use of the pinhole enables assessment of central vision
• If the vision improves, it indicates the visual impairment is due to a refractive error,
which is correctable with spectacles or a new prescription
• Repeat the whole procedure for the second eye
• Summarize the VA of both eyes in the documentation, for example:
Right VA = 6/24 with specs, 6/6 with pinhole Left VA = NPL
If using the E or C chart:
• Point to each letter on each line and ask the patient to point in the direction toward
which the open end of the letter is facing
• Follow the same procedure and recording methods as above.
Source: https://www.ncbi.nlm.nih/gov/PMC2040251/
38
5. For Ishihara Colour Vision Test, please refer to:
1 https://www.colour-blindness.com/colour-blindness-tests/ishihara- colour-test-plates/
2 or get the hard copy of Ishihara Colour Vision Test Book
39
Adverse Events Management Algorithm
Monitoring and Management of Adverse Events

Related to Linezolid
Clinical:
Ask for peripheral neuropathy signs and symptoms (S/S) at every visit and assess severity by using Brief
Peripheral Neuropathy Score (BPNS) - see below if there is any complaint of S/S.
Ask for any change in vision.
Do color vison test and visual acuity test every visit.
Examine signs and symptoms of anemia.
Pale lips/sclera/palms, easy fatigability, weakness, palpitations.
Lab:
Do complete blood cell counts monthly and if clinically indicated.
Education to patients and family:

Educate on the above clinical signs and symptoms.
Advise patients and family to proactively report any experience of the adverse events.
Brief Peripheral Neuropathy Screening Tool (BPNS)

Assess Symptoms and Ask Patient to Score Severity Level Left Right
a. Pain, aching, or burning in feet, legs
b. "Pins and needles" in feet, legs
c. Numbness (lack of feeling) in feet, legs
Total Score
Normal Mild ----------------------------------------------------------------------------- Severe

00 1 2 3 4 5 6 7 8 9 10
Use the single highest severity score above to obtain a total subjective sensory neuropathy score for severity grading.
Severity Grading of Total Score:

Grade 0 = 00 Grade 1 = 01-03 Grde 2 = 04-06 Grde 3 = 07-10
Management of Adverse Events related to Lzd
• Peripheral neuropathy (refer to page 50):
• Grade 1 : STOP and consider reintroduction if symptoms resolved
• Grade ≥ 2 : STOP Lzd, NEVER re-introduce
• Visual acuity:
• REFER to ophthalmologist to check for optic neuritis, abnormal color vision test or change in visual acuity
• STOP Lzd immediately and NEVER reintroduce if there is optic neuritis of any grade (color blindness
and/or visual acuity deterioration in the affected eye)
• Myelosuppression (refer to page 47)
• Grade 1 (Hgb 9.5 to 10.5 g/dl, ANC <1,500 mm3, Platelet <100,000 mm3 ): DECREASE dose of Lzd to
300mg
• Grade ≥ 2: stop Lzd (Hgb <9.5.g/dl, ANC <1,000 mm3, Platelet <75,000 mm3), STOP Lzd immediately
and MANAGE myelosuppression. Lzd may be REINTRODUCED if severity grade is reduced to Grade 1
40
Management of Depression
(Possible causative anti-TB Drugs: Cs, Lfx, Mfx, H, Pto)
Administer Patient Health Questionnaire-9 (PHQ-9)

Over the last 2 weeks, how often More than Nearly
have you been bothered by any Not Several half the every
of the following problems? at all days days day
1. Little interest or pleasure in 0 1 2 3
doing things
2. Feeling down, depressed, or
hopeless 0 1 2 3
3. Trouble falling or staying

0 1 2 3
asleep, or sleeping too much
4. Feeling tired or having little

0 1 2 3
energy
5. Poor appetite or overeating 0 1 2 3
Severity Grading Scale
6. Feeling bad about yourself -
or that you are a failure or
0 1 2 3
have let yourself or your
family down
7. Trouble concentrating on
things, such as reading the PHQ-9 Depression
0 1 2 3 Score Severity Proposed Treatment Action
newspaper or watching
television
9. Moving or speaking so slowly 0-4 None-minimal None
that other people could have 5-9 Mild Watchful waiting; repeat PHQ-9
noticed. Or the opposite - at follow up
being fidgety or restless that 0 1 2 3
you have been moving a lot 10-14 Moderate Treatment plan, consider
more than usual counseling, follow up and
10. Thoughts that you would be 15-19 pharmacotherapy
better off dead, or of hurting Moderately Severe Active treatment with
yourself in some way 0 1 2 3
pharmacotherapy and/or
(Suicidal ideation or attempt)
psychotherapy
20-27 Severe Immediate initiation of
For office coding 0 + + + psychotherapy and, if severe
= Total Score: impairment or poor response to
If you checked off any problems, how difficult have these problems made therapy, expedited referral to a
it for you to do your work, take care of things at home, or get along with
mental health specialist for
other people?
psychotherapy and/or
Not difficult Somewhat Very Extremely
at all difficult difficult difficult collaborative management
PHQ9 - Patient Health Quality 9

Developed by Drs. Robert L. Spitzer, Janet B. Williams, Kurt Kroenke and
colleagues, with an educational grant from Pfizer Inc. No permission
required to reproduce, translate, display or distribute.
Consult with TB MAC for

WARNING! possible dose adjustment,
Patients with suicidal ideation must be assessed discontinuation or
immediately for possible hospitalization. replacement of causative
anti TB drug.
(Exclude hypothyroidism & manage accordingly)
41
Management of Dyspepsia
Possible Causative anti-TB Drugs: PAS, Pto, Cfz, FQs, H, E, Z
DYSPEPSIA
(epigastric fullness, nausea,
vomiting, heartburn)
• Hepatitis (fatigue, abdominal pain,
ictericia)
• GI Bleeding or other organic pathology
• H. pylori positive
• Small frequent meals

• Avoid NSAIDS, food and drink1 YES
that trigger symptoms
• Relaxation and/ or distraction
Manage Accordingly
techniques
NO
Resolved? Give proton pump
inhibitor2 for 8 weeks
Follow-up after two weeks

YES
Continue clinical monitoring

Better Not better
Continue Refer to TB MAC for dose adjustment

Protopump or discontinuation and replacement
Inhibitors until of causative anti TB drug or for introduction
8 weeks of additional ancillary drugs (i.e tricyclic
antidepressant3 and prokinetic drugs4)
1
Food and drinks that may cause & aggravate dyspepsia:
Alcohol, caffeine, soda and acidic drinks
Spicy and high fat food
2
Proton pump inhibitor
Lanzoprazole 30 mg/tab 30mins before breakfast
Pantoprazole 20-40 mg/tab with or without food (normal release), 1hr before meal
(controlled-release)
Omeprazole 20-40 mg/tab 30 mins before breakfast
3
Tricyclic anti-depressant
Amitriptyline HCl 50-75 mg at bed time
4
Prokinetic Drug
Domperidone 10 mg po q8 (use with caution in patients with cardiac pathology)
42
Management of Headache
(Possible causative anti-TB Drugs: Cs, Bdq, Lfx)
Although headache is one of the side effects of anti-TB treatment, it is important to rule
out other causes such as meningitis, migraine and cluster headaches.
Headache is accompanied by:

• nuchal rigidity YES EMERGENCY!
• photophobia for hospitalization for
• fever possible MENINGITIS
• confusion
• somnolence
NO
• (a) with prior history of

pulsating headache with
nausea, vomiting & vision • Manage for possible
YES
change migraine headache or
(b) discrete episodes • Corrective lenses for the
lasting hours, relieved by error of refraction
darkness and sleep
• blurring of vision
NO
Hydrate patient
• exposure to extreme YES Instruct patient to avoid
temperature/ heat exhaustion exposure to extreme heat
• dehydration (use of umbrella, increase
intake of water, etc)
NO
May give:
if with Cs, may increase
pyridoxine to 200mg daily
Paracetamol
NSAIDs (use with caution YES Refer to TB MAC for
recurrent headache
among patients with GI possible dose adjustment,
and already affecting
and Renal pathology) discontinuation or
adherence?
counseling & replacement of causative
psychosocial support to anti TB drug
address emotional NO
component
Continue clinical surveillance
43
Management of Hemoptysis
Hemoptysis is expectoration of blood originating from the lower airways. It is important to quantify the
blood loss and the period over which the loss occurred. Blood pressure, heart rate and respiratory
rate, as well as blood type should be obtained and documented.
Does the blood exit from the nose YES May be due to epistaxis.
and not the mouth? Manage accordingly
NO
YES
Is the patient vomiting blood? Probable GI Bleeding
Send patient to Emergency
Room
NO
LIKELY HEMOPTYSIS
• Quantity of blood >200 ml (3/4 cups) MASSIVE HEMOPTYSIS!

YES
• Total Quantitiy in 48 hrs >600ml SEND PATIENT TO
(2 1/2 cups) EMERGENCY ROOM FOR
TERTIARY MANAGEMENT
NO
¤ Bed Rest
¤ Monitor Patient Closely
¤ Avoid NSAIDS and Aspirin
¤ If with evidence of respiratory
superinfection, initiate antibiotic
¤ Tranexamic acid 500 mg cap q 8
¤ Butamirate citrate tab q8 or q12
to suppress cough
Close Clinical Surveillance
44
Management of Hepatotoxicity
Possible Causative anti-TB Drugs: Z, H, R, Pto/ Eto, PAS, Bdq, Cfz, Dlm
Presence of Hepatitis S/S:

(nausea,vomiting, abdominal pain, dark urine, jaundice, pale stool, anorexia)
and/ or
ALT/ AST done on regular follow up
Check AST, ALT
Normal • >3x ULN • >3x ULN • >5x ULN

• NO Hepatitis S/S • WITH Hepatitis S/S • WITH/NO Hepatitis S/S
PRESENCE
Continue monthly of other liver
monitoring Investigate for other causes and DO Laboratory tests
1 disease Refer to
and diagnostics2 Gastroenterologist for
co-management
• CONTINUE anti-TB drugs
• DO Weekly LFTs
• DO Total Bilirunin
• STOP all anti TB drugs

Normal ALT/ AST • AST/ALT >3x ULN • REPEAT LFTs after 1 week
• Total Bilirunin >2x ULN • CONSULT TB MAC
Continue monthly
AST/ALT >3x ULN repeatedly
monitoring Normal/decreasing ALT/ AST
after 2 weeks
• RESUME 3 not/ least hepatotoxic LED3s

• REPEAT AST/ALT after 1 week
• CONSULT with TB MAC
Normal/decreasing AST/ALT >3x ULN

AST/ AST
• REINTRODUCE4 possible culprit drugs if • REFER to TB MAC

still vital in the regimen • Refer to specialists for co-management
• MONITOR ALT/AST q 3 days
• Discontinue culprit drug if AST/ ALT increases
• REFER to TB MAC
1
Alcoholic and Non Alcoholic liver disease, viral hepatitis
2
Serology tests for Hep A, Hep B (HbsAg, antiHBC) and Hep C, Hepatobiliary ultrasound, etc.
3
LED - Likely Effective Drugs
4
Most hepatotoxic (H,Z,R) drugs will be reintroduced using incremental dose starting with the least culprit drug for 3 days.
Repeat AST/ALT q3 days prior to adding another drug.
45
Management of Joint Pains
(Possible causative anti-TB Drugs: Z, Lfx/Mfx, Pto, Bdq)
Joint pains (in large joints)

(May use Pain Severity Scale (0-10)
to measure pain)
GIVE paracetamol or NSAIDS1

NO light massage exercise
signs of acute swelling, erythema,
dietary modification Rule out other
and warmth at the site of joint
causes and manage
and muscle pain?
accordingly
NO Refer to TB MAC
YES Resolved? for possible dose
adjustment,
discontinuation or
replacement of
Continue clinical surveillance causative anti TB
drug
• elevated blood NO Determine History

uric acid and with other causes of trauma?
tophi, podagra?
• involvement of big
YES
joints ?
YES Manage accordingly/

refer for appropriate management
Pharmacologic Management: NO
NSAIDS1 Resolved?
Colchicine2
Allopurinol3
Dietary Management: YES
avoid high purine diet4
1
Non-steroidal Anti-inflammatory Drugs (NSAIDS), (has to be given with caution in patients with GI, renal and cardiac pathology)
Mefenamic Acid 500 mg/cap, 1 cap every 8 hrs as needed for pain after meals
Indomethacin 25 mg tab, 1 -2 tabs every 12 hrs with meals as needed for pain
Celecoxib 100-200 mg cap every 12 hrs as needed for pain
2
Colchicine - has to be given within 36 hrs of onset of acute attacks initially at 1.2 mg followed by 0.6 mg after an hour ( given
for acute attacks may also cause GI symptoms such as diarrhea)
3
Allopurinol - 100 mg/day and may be increased to 200 mg/day after a week to lower blood uric acid levels, hence, reducing
symptoms (watch out for Steven Johnson's disease) Not to be used during acute attacks
4
Food High in Purine
sardines, innards, mussels, anchovies, trout and salmon, bacon, alcoholic drinks, etc
46
Management of Myelosuppression
(Possible causative anti-TB Drug: Lzd)
Presence of any and combination of

the following:
• ANEMIA NO
• LEUKOPENIA Continue monthly
• THROMBOCYTOPENIA CBC monitoring
YES
Determine the Grade

Investigate for other possible causes: of Myelosuppression
• nutritional deficiencies
• viral infections
• advanced HIV/AIDS
• chronic renal insufficiency GRADE 1 GRADE 2 and above
• occult blood loss • Hgb 9.5 to 10.5 g/dl • Hgb <9.5.g/dl
• intestinal parasitism • ANC <1,500 mm3 • ANC <1,000 mm3
• medications other than anti-TB • Platelet <100,000 mm3 • Platelet <75,000 mm3
medications (e.g. Azidothymidine,
Zidovudine, cotrimoxazole)
• other causes of myelosuppression
• DECREASE Lzd to 300 mg daily • STOP Lzd immediately
• MONITOR CBC weekly • GIVE erythropoietin with caution (see page 68)
• GIVE blood transfusion*
Manage Accordingly • MONITOR CBC weekly
(clinical assessment and
laboratory examinations
such as BUN, Crea, CBC improved or normalized? NO Severity reduced to Grade 1?
Fecalysis with occult
blood, etc) YES YES
• CONTINUE Lzd at 300 mg daily • REINTRODUCE Lzd at 300 mg daily
• MONITOR CBC monthly • MONITOR CBC weekly for 2 weeks
REFER to TB MAC for further

management and change in regimen CBC improved or normalized?
NO YES
• STOP Lzd completely • CONTINUE Lzd at 300 mg daily

• REPLACE with any of the ff: • MONITOR CBC monthly
Dlm, Cs, Pto, injectable
*Given to severity GRADE 4 (Hb of <6.5 g/dL, ANC <500/mm3 or and/or platelet count of <20,000/mm3)
Note: Absolute Neutrophilic Count (ANC) =10 x WBC count in 1000s x (% PMNs + bands)
The following web application may be used to compute for ANC: Calculate by QxMD; MDCalc Medical Calc; Medscape App
47
Management of Nausea and Vomiting
Possible causative anti-TB Drugs: Pto, PAS, Cfz, H, Bdq, Dlm, E, Z
Patient has nausea and vomiting
pregnant; with comorbidities (gastrointestinal

bleeding, gastritis/dyspepsia, renal, liver
disease, meningitis, vestibular disturbance);
psychological (conditional/association)
Signs of dehydration?
(thirst, dry mouth, sunken eyes, low blood YES
pressure, orthostasis, weakness)
Manage accordingly
NO YES
REFER to Emergency Room

Classify severity of for AGGRESSIVE
Nausea and Vomiting HYDRATION In SSTR/SSOR, replace Pto
with Cs in case of repeated
nausea and vomiting even
if it is mild or induced.
Mild Moderate to severe
• Take light meal before intake

• Give oral anti emetics1
of anti TB Drugs
• May give benzodiazepines2
• May give ice chips
if with anxiety or psychological
• Adjust drug administration or
aspects of vomiting
split dose of medications
NO
NO Give IV/IM anti emetics1 if
Resolved?
Resolved? setting permits
YES
Resolved?
YES YES
Continue clinical monitoring NO
1
Anti-emetics:
(1) Metoclopromide 10 mg, 30 mins before intake of anti TB meds, q 8 hrs thereafter
Refer to TB MAC for possible
(2) Ondansetron 8 mg, 30 mins before intake of anti TB meds, q 8 hrs thereafter dose adjustment,
(not to be given in patients on Bdq and Dlm) discontinuation or replacement
(3) Combination of Metoclopromide and Ondansetron. Watch out for concomitant of causative anti
cardiac pathology prior to use.
Both anti- emetics may be given as oral, IV or IM
2
Benzodiazepines
(1) Diazepam 5 mg/tab OD
48
Management of Nephrotoxicity
Possible Causative anti-TB Drugs: S, Km, Am, Cm
Patient presents with diminished urine

Patient has elevated BUN and/or production (< 0.5ml/kg/hr or < 30ml/hr)?
Creatinine on routine follow up
Edema or anasarca? malaise? nausea?
Increased difficulty of breathing
DECREASED Creatinine Clearance

compared to baseline EMERGENCY
HOSPITALIZATION
Check BUN, Creatinine
and Urinalysis
Investigate for other causes1 (1) Check the weight base dosing
of renal insufficiency and of the injectable agent and
manage co morbidity correct the dose as necessary
(2) In consultation with TB MAC, Elevated BUN and/or Creatinine
may replace injectable with Lzd Creatinine Clearance < 30ml/min
YES
• Discontinue nephrotoxic medication

• Refer to TB MAC for possible change in regimen
• Determine and manage other causes of renal failure
Patient renal profile stabilized

and overall status?
YES

Refer back to TB MAC for updates
Other causes of renal insufficiency

1
Calculation of Creatinine Clearance (Estimated Glomerular Filtration Rate)
(1) diabetes Constant
(2) dehydration weight (kg) x (140 – age) x
Serum Creatinine (umol/L)
(3) congestive heart failure
(4) urinary obstruction Constant: for Male = 1.23, for Female = 1.04
(5) urinary tract infection If Serum Creatinine value is given in mg/dl, it can be converted to umol/l by
(6) prostatic hypertrophy multiplying by 88.4.
49
Management of Peripheral Neuropathy
(Possible causative anti-TB Drugs: Lzd, H, Cs, S, Am, Lfx, Mfx)
• burning sensation, "pins and

needles?"
• numbness of both fingers and NO
toes/feet; worse at night or Continue clinical
when walking? surveillance
• leg weakness when walking?
• leg cramps or pain?
YES
Investigate for the following conditions: Assess according to severity GRADING

• Diabetes (using BPNS Tool, See page 40 )
• Alcoholism
• Vitamin Deficiencies
YES
• HIV
• Hypothyroidism
• Uremia
• taking drugs other than anti-TB? GRADE 1: GRADES 2 and 3:
BPNS Score 1-3 BPNS Score ≥4
STOP Lzd, Hhd, and Cs

Manage Accordingly MONITOR BPNS weekly
(clinical assessment and
laboratory examinations
such as fasting blood Symptoms Symptoms
improved? NO improved?
sugar, HbAIC, thyroid
function tests, etc)
YES YES
• Consider restarting Lzd (300 • Consider restarting Cs and Hhd

mg daily) , Cs and Hhd • DO NOT reintroduce Lzd
• INCREASE pyridoxine to 200 • INCREASE pyridoxine to 200 mg daily
mg daily • May PROVIDE other ancillary drugs*
with caution
REFER to TB MAC for further

management and change in regimen
*Other ancillary drugs

• Gabapentin 300 mg daily
• Amitriptyline 25 mg at bedtime (for adult only; use with caution if with cardiac, hepatic, renal and thyroid pathology;
avoid concomitant use with Lzd due to concern of Serotonin Syndrome)
Note: Peripheral neuropathy may be irreversible. However, many patients experience improvement when offending
drugs are suspended, especially if the symptoms are mild.
50
Management of Psychosis
(Possible causative anti-TB Drugs: Cs, Lfx, Mfx, H, Pto)
Does the patient see or hear things

that the others do not perceive? Continue clinical observation.
Have unintelligible thoughts or NO If there are other behavioral
speech? abnormalities, consider
Exhibit bizzare behavior? DEPRESSION and manage
accordingly
YES
LIKELY PSYCHOSIS
Refer to Psychiatrist
Is the patient at risk of harming With any of the May give haloperidol
him/her self or others? NO following conditions 0.5-5 mg PO 2x/day with
NO
Does the patient express the (illicit drug use, precaution
desire to harm or kill him/her self seizure, alcohol Increase pyridoxine to a
or others? withdrawal, etc) maximum of 200 mg/day
Refer to TB MAC for
YES possible dose
YES adjustment,
discontinuation or
replacement of causative
anti TB drug
EMERGENCY
Consider hospitalization
Close surveillance to ensure
safety of patient and others
51
Management of Prolonged QTc
(Possible causative anti-TB Drugs: Bdq,Cfz,Dlm,FQ)
Presence of :
• ABNORMAL QTc
OR
• > 60 ms increased from the NO
baseline QTc Continue monthly ECG clinical
OR symptoms3
• CARDIAC SYMPTOMS3
YES
Investigate for other possible

Determine the Grade of QTc Prolongation
causes such as:
• hypothyroidism
• electrolyte imbalance
• hypoglycemia
• Other cardiac pathologies* GRADEs 1 and 2
• other QT prolonging drugs** GRADE 3 and above
• >450 ms - <500 ms)
• QTc of >500 ms
• >60 ms increased from the baseline1
Manage Accordingly (clinical
assessment and include laboratory • CONTINUE anti TB Treatment
tests such as (i.e. thyroid function • MONITOR ECG weekly
tests, serum electrolytes, FBS/RBS,
2D echo, etc)
NO • STOP ALL QT prolonging drugs immediately
QTc and ECG normalized/back to • REFER and HOSPITALIZE patient for close
baseline values cardiac monitoring2
AND
Absence of Cardiac Symptoms?
YES QTc and ECG NO

normalized/back to baseline REFER to TB MAC for
CONTINUE anti TB Treatment values? change in regimen
MONITOR ECG monthly or as
necessary (when cardiac
symptom occurs) YES
CONSIDER REINTRODUCTION of QT
prolonging drugs if considered critical to
the regimen in coordination with TB MAC
1
QTc on at least 2 separate ECGs done after reassuring patients to relax after 10-15 minutes
2
Repeat ECG every 2-3 days until within normal limits
3
syncopal attacks, dizziness, weakness, chest pains, difficulty of breathing, agitation
* ventricular arrythmias,severe coronary artery disease, genetic conditions, valvular heart disease, rheumatic heart disease, etc
** Ondansetron, Macrolides (e.g. azithromycin), antifungals (e.g. fluconazole), domperidone, neuropsychiatric drugs (e.g. quetiapine,
haloperidol, etc), antiretroviral (e.g. efavirenz), antimalarial (e.g hydroxychloroquine)
52
Indication to Consult with Physician or TB MAC
• Repeated or induced vomiting, abdominal pain/gastritis

• Severe joint pain not responding to NSAID
• Hearing loss
• Change of vision
• Tinnitus/vertigo/dizziness
• Tingling, burning sensation on feet/hands not
responding to 1 week with high dose of pyridoxine
• Depression
• Psychosis
• AST/ALT: >3 ULN
• CrCl: <50 ml/min (or) > 2 times of ULN
• K+: <3.5 mmol/L
• QTc >500ms or 60ms increase from baseline
53
Indication for Referral to Hospital
• Seizure
• Arrythmia (fast/slow and irregular heart beat)
• Severe renal toxicity (Oliguria or Creatinine
Clearance <30 ml/min).
• Severe hepatotoxicity (Jaundice, AST/ALT: >5 times
of ULN, Total Billirubin >3 times of ULN)
• Severe electrolyte imbalance (K+ <2.5 mmol/l,
Mg+ <1.4 mmol/l)
• Severe anemia (Hb<8g/dl)
• Acute psychotic crisis
• Severe depression
• Any other clinical condition that warrants further
evaluation and management
In the referral note, INDICATE patient’s anti-TB drugs and other ancillary drugs
54
ACTIVE DRUG SAFETY MONITORING and
Management (aDSM)
An active and systematic clinical and laboratory assessment of patients while on treatment.
It applies to patients on treatment with (a) new and repurposed anti-TB drugs, (b) novel
MDR-TB regimens, and (c) regimens for extensively drug resistant TB (XDR-TB).
Serious Adverse Events (SAE) refers to any untoward medical

occurrence that at any dose:
• Results in death
• ls life threatening
• Requires inpatient hospitalization or results in prolongation of existing hospitalization
• Results in persistent disability/incapacity
• ls a congenital anomaly/birth defect
• SAE that do not immediately result in one of the above outcomes, but which
require an intervention to prevent a serious outcome are included
Adverse Events of Special Interests (AESI)
AESI refers to adverse event documented to have occurred during clinical trials and for
which the monitoring programme is specifically sensitized to report regardless of its
seriousness, severity or causal relationship to the TB treatment.
These are the following:
• Acute kidney injury
• Hepatitis
• Hypokalemia
• Myelosuppression (Anemia, Leukopenia, Thrombocytopenia: any or all of these)
• Optic Nerve Disorder
• Ototoxicity (hearing impairment, hearing loss)
• Pancreatitis
• Peripheral Neuropathy
• Prolonged QT interval (using Fridericia Formula)
• Psychiatric Disorders and CNS toxicity
55
Severity Grading of Adverse Event (AE)
Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

Adverse event Mild Moderate Severe Life threatening Death
Asymptomatic or Minimal, local or Medically
mild symptoms; non-invasive significant but not Urgent
clinical or intervention immediately intervention
diagnostic indicated; limiting life-threatening; indicated
observations only; age-appropriate hospitalization or
intervention not instrumental prolongation of
indicated activities of daily hospitalization
living (ADL)* indicated;
disabling; limiting
selfcare ADL*
(All AEs from grade 3 to 5 are to be reported electronically/manually to FDA/PD. Some grade 3 and all grade 4 are to be
managed at hospital level. For the purpose of managing AEs at peripheral health facilities level, only 3 levels of grading for AEs
are illustrated below.)
Adverse Event Grade 1 (Mild) Grade 2 (Moderate) Grade 3 (Severe)

Rash, Allergy, Anaphylaxis
Allergic Transient flushing or rash, drug Intervention or infusion Prolonged (e.g., not rapidly responsive
reaction fever <38 degrees C (<100.4 interruption indicated; responds to symptomatic medication and/or brief
degrees F); intervention not promptly to symptomatic interruption of infusion); recurrence of
indicated treatment (e.g., antihistamines, symptoms following initial improvement;
NSAIDS, narcotics); prophylactic hospitalization indicated for clinical
medications indicated for ≤24 hrs sequelae (e.g., renal impairment,
pulmonary infiltrates)
Anaphylaxis Symptomatic bronchospasm, with or

without urticaria; parenteral intervention
indicated; allergy-related
edema/angioedema; hypotension
56
GASTROINTESTINAL
Grade 1 (MILD) Grade 2 (MODERATE) Grade 3 (SEVERE)

Abdominal Moderate pain; limiting
Mild pain Severe pain; limiting selfcare ADL
Pain instrumental ADL
ALT (SGPT) >ULN - 3.0 x ULN >3.0 - 5.0 x ULN >5.0 - 20.0 x ULN
AST (SGOT) >ULN - 3.0 x ULN >3.0 - 5.0 x ULN >5.0 - 20.0 x ULN
Bilirubin (Total) >ULN - 1.5 x ULN >1.5 - 3.0 x ULN >3.0 - 10.0 x ULN
Increase of >7 stools per day over

Increase of <4 stools per Increase of 4 - 6 stools per baseline; incontinence;
day over baseline; mild day over baseline; hospitalization indicated; severe
Diarrhea increase in ostomy output moderate increase in increase in ostomy output
compared to baseline ostomy output compared to baseline; limiting
compared to baseline selfcare ADL
Asymptomatic; clinical or Symptomatic; altered GI Severely altered eating or gastric

Gastritis diagnostic observations function; medical function; TPN or
only; intervention not intervention indicated hospitalization indicated
indicated
Oral intake decreased Inadequate oral caloric or fluid

Nausea Loss of appetite without without significant weight intake; tube feeding, TPN, or
alteration in eating habits loss, dehydration or hospitalization indicated
malnutrition
1 - 2 episodes (separated >6 episodes (separated by 5

3 - 5 episodes (separated
Vomiting by 5 mins) in 24 hrs minutes) in 24 hrs; tube feeding,
by 5 minutes) in 24 hrs
TPN or hospitalization indicated
57
MUSCULOSKELETAL
Moderate pain; limiting
Arthralgia Mild pain Severe pain; limiting selfcare ADL
instrumental ADL
ELECTROLYTE ABNORMALITIES
<LLN - 3.0 mmol/L; <3.0 - 2.5 mmol/L; hospitalization
Hypokalemia <LLN - 3.0 mmol/L symptomatic; intervention indicated
indicated
Hypomagnesaemia <1.4 - 1.2 mmol/L <1.1 - 0.9 mmol/L <0.8 - 0.6 mmol/L
RENAL
Creatinine level increase of
Acute Kidney Creatinine >3 x baseline or >4.0 mg/dL;
>0.3 mg/dL; creatinine 1.5 Creatinine 2-3 x above baseline
Injury hospitalization indicated
- 2.0 x above baseline
NEUROLOGICAL
Moderate depressive symptoms; Severe depressive symptoms; limiting self
Depression Mild depressive symptoms
limiting instrumental ADL care ADL; hospitalization not indicated
Moderate pain; limiting
Headache Mild pain Severe pain; limiting self -care ADL
instrumental ADL
Hearing Impaired Adults (on a 1, 2, 3, 4, 6 Adults (on a 1, 2, 3, 4, 6 and 8 Adults (on a 1, 2, 3, 4, 6 and 8 kHz
and 8 kHz audiogram): kHz audiogram): Threshold shift audiogram): Threshold shift of >25 dB
Threshold shift of 15 - 25 of >25 dB averaged at 2 averaged at 3 contiguous test
dB averaged at 2 contiguous test frequencies in at frequencies in at least one ear;
contiguous test least one ear. therapeutic intervention indicated.
frequencies in at least one Adults (if by clinical monitoring)): Adults (if by clinical monitoring):
ear. Adults (if by clinical hearing loss but hearing aid or hearing loss with hearing aid or
monitoring): subjective intervention not indicated; intervention indicated; limiting self
change in hearing in the limiting instrumental ADL. care ADL.
absence of documented Pediatric (on a 1, 2, 3, 4, 6 and 8 Pediatric (on a 1, 2, 3, 4, 6 and 8 kHz
hearing loss. kHz audiogram): Threshold shift audiogram): hearing loss sufficient to
Pediatric (on a 1, 2, 3, 4, 6 >20 dB at 4 kHz and above in at indicate therapeutic intervention,
and 8 kHz audiogram): least one ear. including hearing aids; threshold shift
Threshold shift >20 dB at >20 dB at 3 kHz and above in at least
8 kHz in at least one ear. one ear; additional speech-language
related services indicated
58
Asymptomatic; clinical or Limiting vision of the affected eye Limiting vision in the affected eye (worse
Optic Neuritis
diagnostic observations only (20/40 or better) than 20/40 but better than 20/200)
Peripheral Sensory Asymptomatic; loss of deep Moderate symptoms; limiting

Severe symptoms; limiting self care ADL**
Neuropathy tendon reflexes or paresthesia instrumental ADL
Moderate psychotic symptoms Severe psychotic symptoms (e.g.,

Psychosis Mild psychotic symptoms (e.g., disorganized speech; paranoid; extreme disorganization);
impaired reality testing) hospitalization not indicated
Brief partial seizure; no loss of Multiple seizures despite medical

Seizure Brief generalized seizure
Consciousness intervention
ENDOCRINE
Asymptomatic; clinical or Symptomatic; thyroid
Hypothyroidism Severe symptoms; limiting selfcare ADL;
diagnostic observations only; replacement indicated; limiting
hospitalization Indicated
intervention not indicated instrumental ADL
METABOLIC
Asymptomatic or mild Moderate; minimal, local or Severe or medically significant but not
symptoms; clinical or non-invasive intervention immediately life-threatening;
Lactic Acidosis hospitalization or prolongation of
diagnostic observations only; indicated; limiting age
intervention not indicated appropriate instrumental ADL existing hospitalization indicated;
disabling; limiting selfcare ADL
CARDIOVASCULAR
Prolonged QTc QTc ≥ 501 ms on at least
QTc 450 - 480 ms QTc 481 - 500 ms
(ECG) two separate ECGs
HEMATOLOGICAL
Anemia 10.5 - 9.5 g/dL 9.4 - 8.0 g/dL 7.9 - 6.5 g/dL
Platelet Count
75,000 – 99,999 /mm³ 50,000 – 74,999 /mm³ 20,000 – 49,999 /mm³
Decreased
Absolute
neutrophil count 1500 - 1000/mm3 999 - 750/mm3 749 - 500/mm3
low
** ADL - Activities of Daily Living
59
Checklist to Monitor Clinical Condition
and Adverse Events by Treatment Supporter
ENGLISH
Observe and ask the followings signs and symptoms. tick ( ) in Yes or No column. If yes, refer
Yes No
patient/report to heath center.
Fever
Cough
Cough with blood
Shortness of breath
Yellow discoloration of skin and/or eyes
Pale lips and/or fingers & palms
Checking for Adverse Events
Have you had any nausea?
Have you had vomiting?
Have you had abdominal pain?
Have you noticed yellowing of your eyes or your skin?
Have you had diarrhea?
Have you had pain or burning sensation in your legs?
Have you had any change in vision?
Have you had any hearing loss?
Have you had any dizziness, vertigo or tinnitus?
Have you had leg cramping?
Do you feel weaker than before?
Do you easily get tired than before?
Have you had any fainting or light-headedness?
Do you have any chest pain?
Do you feel pounding/racing or slowness of heartbeat/fluttering in chest?
Do you have any headache?
Do you feel sad?
Have you had loss of sleep or sleep disturbance?
Do you have thoughts of life not worth living?
Do you feel anxious or agitated?
Do you hear voices or see things that may not be there?
Have you had any convulsion/seizures?
Do you have any rashes?
Do you have any pain in the joints?
60
FILIPINO
Obserbahan at tanungin kung mayroon ang pasyente ng mga sumusunod na sintomas. Lagyan ng
tsek ( ) ang kahon katapat ng meron o wala ayon sa sagot ng pasyente. I-refer ang pasyente sa
doctor o sa pinakamalapit na health center kapag mayroon isa sa mga sintomas na nabanggit. Oo Hindi
Lagnat
Ubo
Ubo o pag-ubo na may kasamang dugo
Hirap sa paghinga
Paninilaw ng balat at mata
Pamumutla ng labi, palad at mga daliri
Mayroon ka bang nararamdaman kagaya ng mga sumusunod:
Pakiramdam na nasusuka?
Pagsusuka?
Pananakit ng tyan o sikmura?
Paninilaw ng mata at balat?
Pagtatae?
Pananakit o pamamanhid ng binti?
Pagbabago sa paningin o panlalabo ng paningin?
Paghina ng pandinig? Ugong sa loob ng tainga?
Pagkahilo?
Pamumulikat?
Mas mahina ba ang pakiramdam mo ngayon?
Mas madali ka bang mapagod ngayon?
Nawawalan ka ba ng malay o nakararamdam ka ba ng panghihilo?
Paninikip at pagkabog ng dibdib?
Nakararamdam ka ba ng mabilis o mahinang pagtibok ng puso?
Pananakit ng ulo?
Malulungkutin?
Pagkabalisa o kulang sa tulog?
Walang ganang mabuhay?
Pagka-aburido o pagkabalisa?
May naririnig ka bang boses na di naririnig ng iba?
Kumbulsyun o pangingisay?
Pangangati at pamamantal ng balat?
Pananakit ng kasukasuan?
Note: This page can be reproduced for Health Care worker’s and patient’s use.
61
Description of Some Important Drug Side Effects
for the TREATMENT SUPPORTER
Drug Side Effect Signs and Symptoms
Arrythmia • QTc prolongation (>500 ms) in ECG recording

(irregular pulse or heartbeat) • If symptomatic: fainting attack, chest pain, sweating,
light-headedness or dizziness, shortness of breath, fluttering in
chest, feeling of racing or slow heart rate
Peripheral Neuropathy • A nerve problem that can cause weakness, tingling sensation and
numbness, most often in fingers, toes, arms and legs
• More severe cases can cause a person to have difficulty walking
or using hands
• More common in patients with diabetes or alcoholism
Psychotic Symptoms • Person sees or hears voices or noises that are not real
• Person hears voices telling them to hurt themselves or other
people
• Person becomes obsessed about something (for example:
religion) or about a person
• Confusion, aggression, serious difficulty in sleeping
62
Description of Some Important Drug Side Effects
for the TREATMENT SUPPORTER
Drug Side Effect Signs and Symptoms
Depression • Difficulty concentrating

• Too much sleeping, not able to sleep
• Loss of appetite or increase in appetite
• Feeling hopeless about life or helpless to change their lives
Hypothyroidism The thyroid gland is not producing enough thyroid hormone

Feeling of tiredness or low energy and weight gain
Hepatitis When the liver becomes swollen and does not work as well as it
should. With symptoms of loss of appetite, nausea, stomach pain,
severe vomiting, dark urine, pail stool and yellowish discoloration
of skin and sclerae
Kidney failure The kidneys are unable to produce urine and these wastes remain
in the body, nausea, loss of appetite, weakness, confusion, muscle
cramp
Electrolyte disturbance An imbalance of chemicals in the body that can cause the patient
to feel weak, have cramps and in serious cases, can cause heart
problems
63
Ancillary Drugs used in Managing Adverse Event
ADVERSE EVENT ANCILLARY DRUG DOSAGE
Gastrointestinal Drugs
Nausea, vomiting, upset Metoclopramide 10 mg/tab/IV/IM 30 minutes before taking anti TB
stomach Drugs; can be given 3-4x/day as needed for
vomiting
Renal Dose:
CrCl <40 ml/min: decrease dose by 50%
CrCl <10 ml/min: decrease dose by 75%
For Anticipatory Ondansetron (and other serotonin 4-8 mg p.o. 30 minutes before taking anti TB
Vomiting 5-HT3 receptor antagonist) drugs, repeated q 8 hours
Diazepam 2-10 mg 30-60 minutes prior to taking anti TB

Drugs (watch out for dependence and addiction)
Heartburn, acid H2-blockers

indigestion, sour Ranitidine 300 mg/tab p.o. at bedtime
stomach, ulcer Famotidine 40 mg/tab p.o. at bedtime
Proton Pump Inhibitors

Omeprazole 20 mg/tab p.o. at bedtime
Lansoprazole 15 mg/tab p.o. at bedtime
*Avoid antacids because they can
decrease absorption of fluoroquinolone
Diarrhea Loperamide 4 mg initially; 2 mg after each loose stool max of

16 mgs for 24 hrs
64
Neuropsychiatric Drugs
Depression Sertraline Start 25-50 mg p.o. daily, usual effective dose
50-200 mg/day, maximum dose 200 mg/day
Insomnia Diphenhydramine 25-50 mg p.o. at bed time

Zolpidem 10 mg/tab p.o. at bed time
Psychosis Haloperidol Start 0.5 to 5.0 mg p.o. 2 or 3 times a day.

Usual effective dose 2-10 mg/day (note: include
biperiden to address extrapyramidal symptoms)
Quetiapine Fumarate Immediate Release:

Initially at 25 mg p.o. q 12 hr, increased daily in
increments of 25-50 mg q 8-12 hr to 300-400
mg/day at intervals of > 2 days
Prophylaxis of Pyridoxine (vitamin B6) At least 50 mg for every 250 mg of Cycloserine

neurological
complications of
cycloserine and
isoniazid
Peripheral neuropathy Gabapentin 300mg/tab p.o. q 8hrs
Pregabalin* 50mg/tab p.o. q 8 hrs
Note: Use ancillary drugs that are included in the latest Philippine National Formulary Essential Medicine List.
*Not in the Essential Medicine List but may be considered as an alternative drug
65
Seizures Diazepam (for active seizure) 0.2-0.4 mg/kg up to 5-30 mg IV
Phenytoin Intravenous load: 10-20 mg/kg (1,000 mg in typical

adult) IV, not faster than 50 mg/min
Oral load: 400 mg initially, then 300 mg in two hours
and four hours
Maintenance: 5 mg/kg or 100 mg p.o. three times a
day
Carbamazepine 200-400 mg p.o. two or four times a day
Valproic acid Start 15 mg/kg p.o. daily or divided in two daily doses,
maximum 60 mg/kg
Phenobarbital Intravenous load: 15-20 mg/kg up to 300-800 mg IV at

25-50 mg/min
Maintenance: 60 mg p.o. two or three times a day
66
Vestibular symptoms Meclizine 25 mg/tab p.o. q 6 hrs
Musculoskeletal pain, Ibuprofen 200 mg/tab p.o. q 8 hrs PRN in full stomach
arthralgia, headaches Mefenamic Acid 500 mg/tab p.o. q 8 hrs PRN in full stomach
Paracetamol 500 mg/tab p.o. q 4 hrs PRN
Celecoxib 100-200 mg/cap p.o. BID
Cutaneous reactions, Hydrocortisone cream 1-2% apply to affected area 3-4x/day PRN
itching
Calamine/zinc oxide ointment* Apply to affected area, 3-4x/day
Systemic hypersensitivity Antihistamines

reactions Diphenhydramine 25-50 mg/cap p.o. q 6-8 hrs
Cetirizine 10 mg/tab p.o. once a day
Corticosteroids
prednisone 1-2 mg/kg/day and decrease dose at 5-10mg daily
dexamethasone 4-8 mg/tab q 8hrs daily
Bronchospasm Inhaled beta-agonists

Salbutamol and terbutaline 1 nebule every 4-6 hrs as needed
Inhaled Corticosteroids
Budesonide 1 nebule every 12 hours
Fluticasone
Oral Steroids
Prednisone 1-2 mg/kg/day and decrease dose at 5-10mg daily
Injectable steroids
Dexamethasone 4-8 mg/IVq 8hrs
Note: Use ancillary drugs that are included in the latest Philippine National Formulary Essential Medicine List
*Not in the Essential Medicine List but may be considered as an alternative drug
67
Hypothyroidism Levothyroxine • Young healthy adults: start at 75 to 100 mcg daily

• Older patients: start at 50 mcg daily
• Patients with significant cardiovascular disease: start at
25 mcg daily
• Children (4-15 years): 4 mcg/kg/day (maximum dose
is 200 mcg)
• Infants (1-3 years): 10-15 mcg/kg/day (maximum dose
is 200 mcg)
Electrolyte wasting Potassium Chloride 3.3-3.5: 40 mEq PO daily

2.9-3.2: 60-80 mEq p.o. daily
2.7-2.8: 60 mEq p.o. three times a day
2.4-2.6: 80 mEq p.o. every eight hours
< 2.4: 10 mEq/hr IV and 80 mEq p.o. every 6 to 8 hours
Magnesium gluconate 1.5–1.9: 1,000 mg-1,200 mg

1.0–1.4: 2,000 mg/IV or IM
< 1.0: 3,000 mg-6,000 mg/IV or IM
Calcium replacement therapy 500 mg tab p.o. 3x/day

Note: K and Mg replacement must be given 2
hours before or four hours after intake of FQ
Myelosuppression Iron Supplementation, decrease

dose of Lzd
Erythropoietin Epoetin alfa prefilled syringes of 10 000 UI or 40 000 IU/ml

to be stored in cold chain (2°C to 8°C).
Dosing Epoetin alfa: 150 IU/Kg three times a week or 450
IU/Kg once a week SQ or IV (to be used with caution in
patients with epilepsy, thrombocytosis, chronic liver failure,
hyperkalemia and hypertension)
Blood transfusion
68
Treatment Outcome Definition for Drug Sensitive Tuberculosis
TREATMENT OUTCOME DEFINITION
Cured A patient with bacteriologically confirmed TB at the beginning of treatment and who was smear-
or culture-negative in the last month of treatment and on at least one previous occasion in the
continuation phase
Treatment Completed BC at start of treatment with smear (-) or culture (-) in the last month of treatment and on at least one
occasion in the continuation phase
BC at start of treatment
completed the recommended course of treatment without evidence of failure
without any record of negative smear and culture results in the last month of treatment
and on at least one occasion in the continuation phase
CD who completed the recommended course of treatment
Treatment Failed Smear or culture positive at 5th month of treatment or later during treatment
Treatment terminated due to evidence of additional acquired resistance (e.g., Rif-Res on Xpert at 2nd
month of treatment)
A patient for whom follow-up sputum examination was not done (e.g., child or EPTB) and who does
not show clinical improvement anytime during treatment
Severe uncontrolled adverse drug reaction
Died Patient died for any reason during TB treatment
Lost to Follow up Interrupted treatment for at least 2 consecutive months

A patient diagnosed with active TB but was not started on treatment
Not Evaluated A patient for whom no treatment outcome is assigned

This includes patients transferred to another facility for continuation of treatment, but the final
outcome was not determined
69
Treatment Outcome Definition for Drug Resistant Tuberculosis treated
with Standard Short All Oral Regimen (SSOR)
Cured BC at start of treatment

Completed the recommended duration of treatment without evidence of failure
At least 3 consecutive negative cultures after the intensive phase (at least 30 days apart)
Treatment Completed Completed the recommended duration of treatment

No record of 3 consecutive cultures after intensive phase
No evidence of clinical deterioration
Treatment Failed Presence of any of the following:

Treatment terminated or need for permanent regimen change
Lack of evidence of at least two* consecutive negative cultures (and not followed by a positive culture)
by the end of an extended intensive phase (6 months) of the shorter regimen
Positive sputum smear (confirmed by two consecutive samples) after > 6 months of treatment
Culture reversion** in the continuation phase after conversion to negative
Evidence of additional acquired resistance to a FQ or a SLI,
Adverse drug reaction resulting to switching to a new regimen
Lost to Follow up*** Interrupted treatment for at least 2 consecutive months
Not Evaluated A patient for whom no treatment outcome is assigned.

This includes patients transferred to another facility for continuation of treatment but the final
outcome was not determined.
Treatment Outcomes
*Perform culture from two specimens every month during the intensive phase or do culture after 4, 6, 8, 12 and 16 weeks of
treatment
MDR/RR-TB
** Culture reversion (to positive) after an initial conversion; two consecutive cultures taken at least 30 days apart, are found to be
DS-TB &
positive during continuation phase.
Remark: In all other situations when failure is suspected, the possible causes, patient management strategy and registration of
outcome will be discussed by the expert committee
*** If a patient has received the SSTR/SSOR for more than a month and returns for treatment after an interruption of 2 consecutive
months or more, he is not restarted on the SSTR/SSOR but on a longer MDR-TB regimen which is individualized based on the
medicines most like to be effective. If the interruption is less than 2 months, e.g., medical indication in case of adverse events (AE),
or patient’s decision, then the SSTR/SSOR can be continued and the missed doses added to the rest of the treatment.
70
Treatment Outcome Definition for Drug Resistant Tuberculosis
treated with Standard Long Oral Regimen (SLOR)
and Individualized Treatment Regimen (ITR)
Cured BC at start of treatment

Completed the recommended duration of treatment without evidence of failure
At least 3 consecutive negative cultures after the intensive phase (at least 30 days apart)
Treatment Completed Completed the recommended duration of treatment

No record of 3 consecutive cultures after intensive phase
No evidence of clinical deterioration
Treatment Failed Treatment terminated or need for permanent regimen change of at least two anti-TB drugs because of:
Lack of conversion by the end of 8 month from the start of treatment or
Bacteriological reversion after the conversion to negative in the initial 8 month of treatment or
Evidence of additional acquired resistance to fluoroquinolones or other second-line drugs in
the regimen
Adverse drug reaction that needed to completely stop MDR/RR-TB treatment
Lost to Follow up*** Interrupted treatment for at least 2 consecutive months
Not Evaluated A patient for whom no treatment outcome is assigned

This includes patients transferred to another facility for continuation of treatment, but the final
outcome was not determined
Culture conversion (to negative); two consecutive cultures taken at least 30 days apart, are found to be negative, the specimen
collection date of the 1st culture is taken as culture conversion date
Culture reversion (to positive) after an initial conversion; two consecutive cultures taken at least 30 days apart, are found to be positive,
for the purpose of defining “Treatment Failed”, culture reversion is considered only when it occurs after 8 months of treatment
71
TB Infection Prevention & Control
Prevention of Transmission of TB in Health Care Settings
STEP Action Description
Designate health care worker (Triage) to screen patients with

1 Screen prolonged cough immediately after they arrive at the facility.
Separate patients with symptoms of TB and patients on treatment
from other patients
Instruct all patients with cough on cough hygiene

2 Educate (i.e. covering the nose and mouth when coughing or sneezing)
Educate on safe sputum disposal
Keep patients with symptoms of TB and patients on treatment away

from other patients and allow them to stay in a well-ventilated
3 Separate waiting area
If possible, provide face masks or tissue to cover their mouths and
noses while waiting
Investigate for TB Perform recommended TB diagnostic tests or collect and send

4
or refer to TB Clinic specimen to TB diagnostic facility
5 Monitor and evaluate Monitor and evaluate the TB prevention plan
Infection Prevention
Tuberculosis
and Control
72
Prevention of TB Transmission in Healthcare Settings
Screen Educate Separate Investigate

Designate of health care Instruct all patients with Segregate patients with TB or refer
worker (Triage) to screen cough on cough hygiene symptoms and patients on
Perform recommended TB
patients with prolonged (i.e. covering the nose TB treatment from other
diagnostic tests or collect
cough immediately after and mouth when patients and allow them to
and send specimen to TB
they arrive at the facility. coughing or sneezing stay in a well ventilated
diagnostic facility
Separate patients with Educate on safe sputum waiting area
symptoms of TB and disposal If possible, provide face
patients on treatment from masks or tissue to cover
other patients their mouths and noses
while waiting
Reference:
Guidelines on Infection Control for Tuberculosis and Other Airborne Infectious Diseases in Healthcare Facilities
and Congregate Settings and Households, Department of Health, Manila, 2011
73
TB Preventive Treatment
Population groups to receive TB preventive treatment after

exclusion of active TB disease
• All household contacts of bacteriologically-confirmed pulmonary TB

• Children less than 5 years old who are household contacts of clinically
diagnosed pulmonary TB
• Close contact of bacteriologically-confirmed pulmonary TB
(outside the household)
• People living with HIV
• Other risk groups
• Patients receiving dialysis
• Patients preparing for an organ or hematological transplantation
• Patients initiating anti-TNF treatment
• Patients with silicosis
74
Checking eligibility of different risk groups for TB Preventive Treatment
using TST
TST NOT REQUIRED TST REQUIRED NOT ELIGIBLE*

(Eligible for TPT) (Eligible if positive)
<5yo, BC TB index <5yo, CD TB index ---
HH contacts ≥5yo, BC TB index ≥5yo, BC TB index, ≥5yo, CD TB index

with TB risk no TB risk
Close contacts --- All ages, BC TB index All ages, CD TB index
Age <1yo
PLHIV Ages ≥1yo
(If not contact of a TB case)
--- Patient receiving dialysis, ---

Patients preparing for an
organ or hematological
Other Risk transplantation
Groups Patients initiating
anti-TNF treatment
Patients with silicosis
Individuals in jails or
prisons
* TB Risk - PLHIV, diabetes, smokers, those with immune-suppressive medical conditions,

malnourished, with multiple people with TB in same household
75
LTBI algorithm in HIV-negative child contacts<5 years old
< 5 y/o household or close contact

of patient with TB
Presence of any of the

*CXR is not required following symptoms:
• Cough
prior to giving • Fever
preventive treatment • Anorexia/poor oral intake
• Weight loss/failure to thrive
• Fatigue
• Reduced playfulness/activity
No YES, for < 2 weeks YES, for ≥2 weeks
Follow up and check

for persistence of PRESUMPTIVE TB
symptoms
YES NO
WELL Resolved? • Follow the TB diagnostic algorithm.
• Reevaluate for preventive treatment
once active TB is excluded.
Household or close
contact of Household or close
BACTERIOLOGICALLY contact of CLINICALLY
CONFIRMED PTB DIAGNOSED PTB
• Educate about TB
Give preventive treatment Perform TST • Advise to seek care if
Positive Negative or TST TB symptoms occur
is not available
76
LTBI algorithm in HIV-negative at-risk individuals ≥ 5 years old
Follow Screening
Algorithm for Active TB
• NO TB Symptoms • NO TB Symptoms
• CXR, not done yet • Normal CXR
TST TST
Positive or Not Required* Negative or Not Available Positive or Not Required*
Do CXR • Educate about TB Treat for LTBI

• Advise to seek care if TB
symptoms occur
Suggestive of TB?
YES NO
Do further investigation
Treat for LTBI
to rule out active TB
With Active TB NO Active TB
*TST is not required in individuals aged 5 years and older with TB risk factors
Treat According to
(i.e., PLHIV, diabetes, smokers, those with immune-suppressive medical
NTP Protocol
conditions, malnourished, with multiple TB cases in same household) and who
are household contacts of bacteriologically confirmed pulmonary TB.
77
LTBI algorithm in children with HIV aged 1-4 years
Children (1-4 y/o) with HIV
Presence of any of the following: *CXR is not required

• Poor weight gain prior to giving
• Fever
• Current cough
preventive treatment
• History of contact with person with TB
NO YES
Do further investigation to rule out active TB
NO Active TB With Active TB
Treat for LTBI unless Treat

contraindicated According to
NTP Protocol
78
LTBI algorithm in adults and children ( ≥ 5 yo) with HIV
Adults and children (≥5 y/o) living with HIV
Presence of any of the following:

• Current cough
• Fever
• Weight loss
• Night sweats
NO YES
Do CXR Do further investigation

to rule out active TB
Suggestive
of TB?
NO Active TB With Active TB

YES NO
Do further investigation Treat for LTBI, Treat According to

to rule out active TB unless contraindicated NTP Protocol
With Active TB NO Active TB
Treat According to
NTP Protocol
79
Selection of TB preventive treatment regimens
TB Preventive Treatment Regimen Indications
3HP (Isoniazid, Rifapentine - weekly) Weekly dosing for 3 months

Contraindicated in pregnant and <2 yo
3 HR (Isoniazid, Rifampicin - daily) Preferred for children if 3HP not available
4R (Rifampicin- daily) Preferred for adults if 3HP not available
6H (Isoniazid – daily) Currently available under the program
80
Dosing for 6H, 4R and 3HR in children
Dosage (in ml)

Body Weigth (kg) isoniazid 200mg/ 5ml Rifampicin 200mg/ 5ml
(at 10mg/kg) (at least 15mg/kg)
2.1-3 0.75 1.0
3.1-4 1.0 1.5
4.1-5 1.25 2.0
5.1-6 1.5 2.25
6.1-7 1.75 2.5
7.1-8 2.0 3.0
8.1-9 2.25 3.5
9.1-10 2.5 3.75
10.1-11 2.75 4.0
11.1-12 3.0 4.5
12.1-13 3.25 5.0
13.1-14 3.5 5.25
14.1-15 3.75 5.5
15.1-16 4.0 6.0
16.1-17 4.25 6.5
17.1-18 4.5 6.75
18.1-19 4.75 7.0
19.1-20 5.0 7.5
20.1-21 5.25 8.0
21.1-22 5.5 8.25
22.1-23 5.75 8.5
23.1-24 6.0 9.0
24.1-25 6.25 9.5
25.1-26 6.5 9.75
26.1-27 6.75 10.0
27.1-28 7.0 10.5
28.1-29 7.25 11.0
29.1-30 7.5 11.25
81
Dosing for 3-month weekly rifapentine and isoniazid
in adults and children ≥ 2 years old
Age >2 yo 2-11 yo >12yo
Rifapentine Isoniazid 200mg/5ml Isoniazid 200mg/5ml
Body Weight (in kgs)
150mg/tab (at 25mg/kg) (at 15mg/kg)
No. of tablets in ml in ml
10-12 1 tab 7.5ml --
12.1-14 2 8.75 --
14.1-16 3 10.0 --
16.1-18 3 11.0 --
18.1-20 3 12.0 --
20.1-22 3 13.0 --
22.1-24 3 14.5 --
24.1-25 3 15.0 --
25.1-27 4 17.0 10.0
27.1-30 4 18.5 11.0
30.1-32 4 20.0 12.0
32.1-35 5 21.0 13.0
35.1-37 5 14.0
37.1-40 5 15.0
40.1-42 5 16.0
42.1-45 5 17.0
45.1-50 5 22.5 18.0
50.1-55 6 20.0
55.1-58 6 21.0
≥58.1 6 22.5
Dosing for 6H and 4R in adults
Drug Dosing in Adults
Isoniazid (H) 5 mg/kg (range: 4-6 mg/kg
Not to exceed 400mg daily)
Rifampicin (R) 5 mg/kg (range: 8-12 mg/kg
Not to exceed 600mg daily)
*Tablet or FDC formulation may be used when available
82
Dosing for TPT regimens by using tablets and fixed
dose formulations
Regimen Dose by age and weight band

6 or 9 months of daily isoniazid Age 10 years & older: 5 mg/kg/day
monotherapy (6H, 9H) Age <10 years: 10 mg/kg/day (range, 7–15 mg)
Four months of Age 10 years & older: 10 mg/kg/day
daily rifampicin (4R) Age <10 years: 15 mg/kg/day (range, 10–20 mg)
Three months of daily rifampicin plus Isoniazid:

isoniazid (3HR) Age 10 years & older: 5 mg/kg/day
Age <10 years: 10 mg/kg/day (range, 7–15 mg)
Rifampicin:
Age 10 years & older: 10 mg/kg/day
Age <10 years: 15 mg/kg/day (range, 10–20 mg)
Weight
4–7 kg 8–11 kg 12–15 kg 16–24 kg >25 kg
band
RH 75/50 Use adult
1 2 3 4
mg (FDC) formulations
Three months of rifapentine plus high Age 2-14 years

dose isoniazid weekly (12 doses) Medicine,
10–15 kg 16–23 kg 24–30 kg 31–34 kg >34 kg
(3HP) Formulation
Isoniazid 100 3 5 6 7 7
mga
Rifapentine
2 3 4 5 5
150 mg
Isoniazid +
rifapentine
FDC 2 3 4 5 5
(150 mg/150
mg)b
Age >14 years

Medicine, 30–35 kg 36–45 kg 46–55 kg 56–70 kg >70 kg
Formulation
Isoniazid 300 3 3 3 3 3
mg
Rifapentine
6 6 6 6 6
150 mg
Isoniazid +
Rifapentine
FDC 3 3 3 3 3
(300 mg/300
mg)b
a
300 mg formulation can be used to reduce the pill burden
b
use when available
83
Definition of LTBI treatment outcomes
Completed - an individual who has completed the prescribed

duration of treatment and remains well or asymptomatic during the
entire period.
Lost to follow-up - an individual who interrupted TB preventive

treatment for two (2) consecutive months or more.
Died - an individual who dies for any reason during the course of
therapy.
Failed - an individual who developed active TB disease anytime

while on TB preventive treatment.
Not Evaluated - an individual who has been transferred to another

health facility with proper referral slip for continuation of TB
preventive treatment and whose treatment outcome is not known;
include here discontinued by physician because patient cannot
tolerate (e.g. severe ADR) or refused to continue.
84
Further Reading:
Companion handbook to the WHO guidelines for the programmatic management of drug-resistant
tuberculosis, 2014.
https://www.who.int/tb/publications/pmdt_companionhandbook/en/
Diagnosis and management of latent tuberculosis infection in Asia: Review of current status
and challenges, N.I. Paton et al., International Journal of Infectious Diseases 87 (2019) 21–29
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected
Version 2.1; July 2017; Division of AIDS National Institute of Allergy and Infectious Diseases, National
Institutes of Health, US Department of Health and Human Services
endTB Clinical and Programmatic Guide for Patient Management withNew TB Drugs. Version 4.0;
January 2018.
http://www.endtb.org/sites/default/files/2016-07
Frequently Asked Questions on the WHO Rapid Communication 2019: Key changes to the treatment
of drug-resistant TB Version: 2.0
https://www.who.int/tb/publications/2018/MDR_RR-TB-TaskForce-FAQs-Updated-June2019.pdf
Frequently Asked Questions: Updated and consolidated guidelines for programmatic management
of LTBI: a critical action to achieve the WHO End TB Strategy targets.
https://www.who.int/tb/publications/2018/ltbi_faqs.pdf
GLI model TB diagnostic algorithms Revised June 2018. Geneva, Stop TB Partnership,
http://stoptb.org/wg/gli/assets/documents/GLI_algorithms.pdf
Guidance for national tuberculosis programmes on the management of tuberculosis in children 2nd ed.,
WHO, 2014
https://www.who.int/tb/publications/childtb_guidelines/en/
Guidelines for Establishing DOTS-Plus Pilot Projects for the Management of Multidrug-Resistant
Tuberculosis (MDR-TB), World Health Organization, 2000;
https://www.who.int/tb/publications/dotsplus-mdrtb-guidelines/en/
Guidelines for the treatment of drug-susceptible tuberculosis and patient care, 2017 update.
(WHO/HTM/TB/2017.5). Geneva, World Health Organization, 2017.
http://apps.who.int/iris/bitstream/10665/255052/1/9789241550000-eng.pdf
Guidelines on Infection Control for Tuberculosis and Other Airborne Infectious Diseases in Healthcare
Facilities, Congregate Settings and Households, Department of Health, Manila, 2011
Implementing tuberculosis diagnostics: a policy framework (WHO/HTM/TB/2015.11). Geneva, World

Health Organization, 2015.
http://apps.who.int/iris/bitstream/10665/162712/1/9789241508612_eng.pdf
Latent TB Infection: Updated and consolidated guidelines for programmatic management.

(WHO/CDS/TB/2018.4). Geneva, World Health Organization. 2018.
http://apps.who.int/iris/bitstream/handle/10665/260233/9789241550239-eng.pdf
85
Line probe assays for drug resistant tuberculosis detection Interpretation and reporting guide
for laboratory staff and clinicians.
http://www.stoptb.org/wg/gli/assets/documents/LPA_test_web_ready.pdf
Management of drug-resistant tuberculosis, Christoph Lange, et.al, Lancet 2019; 394: 953–66
Medscape app; https://www.medscape.com/public/medscapeapp
MIMS App; https://www.mims.com/philippines/CustomContent/HTML/download_mims_app
Rapid communication: key changes to treatment of multidrug- and rifampicin-resistant tuberculosis

(MDR/RRTB) (WHO/CDS/TB/2018.18). Geneva, World Health Organization, 2018.
http://www.who.int/tb/publications/2018/WHO_RapidCommunicationMDRTB.pdf
Rapid Communication: Key changes to the treatment of drug-resistant tuberculosis December 2019
https://www.who.int/tb/publications/2019/WHO_RapidCommunicationMDR_TB2019.pdf
Rapid Communication on forthcoming changes to the programmatic management of tuberculosis

preventive treatment. February 2020.
https://www.who.int/tb/features_archive/New-guidance-on-TB-preventive-treatment/en/
MANAGEMENT OF TUBERCULOSIS: A Guide to Essential Practice, Seventh Edition International

Union Against Tuberculosis and Lung Disease (The Union) 68 Boulevard Saint-Michel, 75006 Paris,
France, October 2019
https://www.theunion.org/what-we-do/publications/technical/management-of-tuberculosis-a-guide-to-
essential-practice
The PIH Guide to the Medical Management of Multidrug-Resistant Tuberculosis, 2nd Edition.
Partners in Health. Boston, USA. USAID TB CARE II. 2013
The use of molecular Line Probe Assays for the detection of resistance to second-line anti-tuberculosis
drugs. Policy guidance. (WHO/HTM/TB/2016.07). Geneva, World Health Organization, 2016.
http://www.who.int/tb/publications/lpa-mdr-diagnostics/en/
WHO consolidated guideline on drug-resistant tuberculosis treatment. (WHO/CDS/TB/2019.4).

Geneva, World Health Organization, 2019
https://apps.who.int/iris/bitstream/handle/10665/311389/9789241550529-eng.pdf
WHO operational handbook on tuberculosis. Module 1: prevention - tuberculosis preventive treatment,

2020
https://www.who.int/publications-detail/who-operational-handbook-on-tuberculosis-module-1-preventi
on-tuberculosis-preventive-treatment
WHO treatment guidelines for drug resistant tuberculosis 2016 update OCTOBER 2016 REVISION
https://apps.who.int/iris/bitstream/handle/10665/250125/9789241549639-eng.pdf
86
NOTES
87
NOTES
88
NOTES
NOTES
NOTES

NTP MOP 6th Edition Pocket Guide PDF

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NTP MOP 6th Edition Pocket Guide PDF

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Pocket Guide

TB (DS & DR) and Latent TB

Contents of the pocket guide were adapted from

Screening and Diagnosis of TB Disease 4

ADR Adverse Drug Reaction IPC Infection Prevention and Control

A. Systematic Screening for Active Pulmonary TB in Adults

With the following signs and symptoms for ≥ 2 weeks:

Request for CXR

Collect spot sputum sample

Request Xpert MTB/RIF Test

Collect sputum and/or extra pulmonary sample

Sample available Sample not available

Do Xpert MTB/RIF Test Do CXR

Follow TB Diagnostic Algorithm

FNRI - Food and Nutrition Research Institute

Presumptive TB with/without Risk Factors#

Presumptive PTB Presumptive EP-TB

Ask to expectorate sputum sample Collect (if possible) pus/tissue/fluid

Do Xpert MTB/RIFπ Refer to specialist for further investigation

MTB Detected with or MTB not Detected /cannot

Do CXR (if not yet done)

May give broad spectrum

Initiate treatment Persistence of S/S

Screen for TB S/S* Screen for TB S/S*

Yes in at least 1 AND/OR Suggestive of TB Yes in at least 1

Collect one sputum sample

Request for Xpert MTB/RIF Test

Baseline screening when TB symptoms screening

Follow-up screening TB symptoms screening

Suggestive of TB Not Suggestive of TB

Presumptive TB End of evaluation

1 Pumunta sa sputum collection area.

4 Idahak ang plema mula sa iyong baga.

7 Dalhin ang sampol ng iyong plema sa tagapangasiwa ng iyong kalusugan.

8 Siguraduhing maghugas ng iyong mga kamay.

Interpretation of Xpert MTB/RIF Results and Treatment Decisions

MTB detected, MTB detected, MTB detected, MTB not

• Revise regimen based on

TBC & DST = TB culture and phenotypic DST

InhA Low level H resistance and

Rifampicin resistance Treat with MDR-TB

Treatment with FQ Resistant

History of TB Drug resistant pattern

Treatment Regimen Eligible TB Patients

EPTB of CNS, bones, joints whether new or retreatment, with final

Type of PTB Ff-up 1 Ff-up 2 Ff-up 3

Table 1. Standard Regimens for DS-TB: Dosing for Adults

Weight Band (Kg) Intensive Phase Continuation Phase

Weight band (Kg) Number of tablets

Isoniazid Rifampicin Pyrazinamide Ethambutol (100

Drug Group Drugs

Group A: Levofloxacin (Lfx) or Moxifloxacin (Mfx)

Group B: Clofazimine (Cfz)

Group C: Ethambutol (E)

Amikacin (Am) or Streptomycin (S)

P-aminosalicylic acid (PAS)

Regimen Name Type of DRTB Regimen Remarks

Regimen 4: MDR/RR-TB eligible to 6 Months: Request for “Off Label”

Regimen 5: MDR/RR-TB eligible to 6 Months: Request for “Off Label”

Individual Treatment Retreatment Design a regimen with at Present the case to TB

If eligible, give SSOR. if not, check eligibility to SLOR FQ-S.

1. Confirmed resistance to fluoroquinolone (Moxifloxacin/Levofloxacin)

If eligible, give SLOR FQ-S. If not, check eligibility to SLOR FQ-R.