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
• Ancillary Diagnostic Tests
1. Electrocardiography
2. How to calculate Creatinine Clearance
3. Audiometry Reading and Interpretation
4. Snellen’s Test
5. Ishihara Colour Vision Test
• Adverse Events Management Algorithm
Monitoring and Management of Adverse Events Related to Linezolid
Management of Depression
1
29-51
29-39
29-33
34
35
36-38
39
40-52
40
41
Management of Dyspepsia
Management of Headache
Management of Hemoptysis
Management of Hepatotoxicity
Management of Joint Pains
Management of Myelosuppression
Management of Nausea and Vomiting
Management of Nephrotoxicity
Management of Peripheral Neuropathy
Management of Psychosis
Management of Prolonged QTc
Indication to Consult with Physician or TB MAC
Indication for Referral to Hospital
Active Drug Safety Monitoring (aDSM)
Severity Grading of Adverse Event
Checklist to Monitor Clinical Condition and Adverse Events by Treatment Supporter
Description of Some Important Drug Side Effects for the Treatment Supporter
Ancillary Drugs used in Managing Adverse Event
Definition of DS-TB & MDR/RR-TB Treatment Outcomes
Tuberculosis Infection Prevention and Control
• Prevention of TB Transmission in Health Care Settings
• TB Preventive Treatment
Checking eligibility of different risk groups for TB Preventive Treatment using TST
LTBI Algorithm in HIV-negative child contacts <5 years old
LTBI Algorithm in HIV-negative at-risk individuals ≥5 years old
LTBI Algorithm in adults and children with HIV aged 1-4 years
LTBI Algorithm in adults and children with HIV ≥5 years old
Selection of preventive treatment regimens
Dosing for 6H, 4R and 3HR in children
Dosing for 3-month weekly rifapentine and isoniazid in adults and children ≥2 years old
Dosing for TPT Regimen by Using Tablets and Fixed-Dose Combination
Definition of TPT Treatment outcome
2
42
43
44
45
46
47
48
49
50
51
52
53
54
55-61
55-59
60-61
62-63
64-68
69-71
72-84
72-73
74
75
76
77
78
79
80
81
82
83
84
ABBREVIATIONS, ACRONYMS and SYMBOLS
ADR
AE
AIDS
ALT
Am
Amx/Clv
ART
ARV
AST
Bdq
BID
CBC
Cfz
Cm
CP
CrCl
Cs
CSF
CXR
Dlm
DOT
DR-TB
DST
DS-TB
E
ECG
EP
FL-LPA
FQ
GI
Gx
H
Hct
HdH
Hgb
HIV
Imp
IM
IP
IPC
IV
Km
Lfx
LLN
LPA
LTBI
Lzd
MDR-TB
Mfx
MGIT
Mpm
NTRL
OD
PAS
p.o.
PRN
PTB
Pto
Q
R
S
S/S
SLI
SLD
SL-LPA
SM
SSTR
TB
TB-LAMP
TBC
TB MAC
TID
TNF
TSH
ULN
WBC
WHO
Z
Adverse Drug Reaction
Adverse Event
Acquired Immune Deficiency Syndrome
Alanine aminotransferase
Amikacin
Amoxicillin/Clavulanate
Antiretroviral treatment/therapy
Antiretroviral
Aspartate aminotransferase
Bedaquiline
Twice daily
Complete Blood Count
Clofazimine
Capreomycin
Continuation Phase
Creatinine Clearance
Cycloserine
Cerebrospinal Fluid
Chest X-ray
Delamanid
Directly Observed Treatment
Drug-Resistant Tuberculosis
Drug Susceptibility Testing
Drug-Susceptible Tuberculosis
Ethambutol
Electrocardiogram
Extrapulmonary
First Line LPA
Fluoroquinolones
Gastrointestinal
GeneXpert
Isoniazid
Hematocrit
High dose Isoniazid
Hemoglobin
Human Immunodeficiency Virus
Imipenem
Intramuscular
Intensive Phase
3
Infection Prevention and Control
Intravenous
Kanamycin
Levofloxacin
Lower Limit of Normal
Line Probe Assay
Latent TB Infection
Linezolid
Multidrug Resistant TB
Moxifloxacin
Mycobacterial growth indicator tube
Meropenem
National TB Reference Laboratory
Once a day
Para-aminosalicylic Acid
by mouth
as needed
Pulmonary Tuberculosis
Prothionamide
Every
Rifampicin
Streptomycin
Signs and Symptoms
Secondline Injectables
Second line drug
Second Line-Line Probe Assay
Smear Microscopy
Standard Short Treatment Regimen
Tuberculosis
Loop-mediated isothermal amplification
TB Culture
TB Medical Advisory Commitee
Three times a day
Tumor Necrosis Factor
Thyroid Stimulating Hormone
Upper Limits of Normal
White blood cells
World Health Organization
Pyrazinamide
Screening and
Diagnosis of TB
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
or (SM/ TB LAMP if Xpert
not available)
ASSESS for
other diseases
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
especially from ages >8 years old
OR
Collect gastric aspirate sample (if possible)
Collect (if possible) pus/tissue/fluid
samples for Xpert MTB/RIF
(keep EP samples for culture and DST)
Refer to specialist for further investigation
if sample cannot be collected.
Do Xpert MTB/RIFπ
MTB Detected with or
without Rif Resistance
MTB not Detected /cannot
expectorate
Do CXR (if not yet done)
Strongly suggestive of TB*
with clinical S/S
Persistence of S/S
Initiate treatment
(Refer to pp 12, 14-21)
*CXR finding strongly suggestive of TB in children = markedly
enlarged hilar lymph nodes (>2 cm in size) with or without
opacification, miliary mottling, massive pleural effusion (>1/3
of pleural cavity), apical opacification with cavitation
#
Risk factors = < 5 years old, HIV, severe malnutrition,
measles, on Immune-suppressing drugs
π
For Xpert MTB/RIF results and treatment for RR TB,
refer to page 11.
May give broad spectrum
antibiotic for 1 week/
observe for 2 weeks
Normal or uncertain
Contact of active TB Case:
Treat as CD TB
Not a Contact of TB Case:
Do TST
Positive TST:
Treat as CD TB
Negative TST
or TST unavailable:
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
Screen for TB S/S*
(of any duration)
• Cough
• Fever
• Weight loss
• Night sweat
+
Every Visit (if not on TB Treatment)
Screen for TB S/S*
(of any duration)
• Cough
• Fever
• Weight loss
• Night sweat
CXR
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
staff is recruited
TB symptoms screening
+ CXR
TB symptoms screening:
Any of the following signs and
symptoms > 2weeks:
Follow-up screening
Cough and symptoms
surveillance
TB symptoms screening
Follow-up screening
annually
TB symptoms screening
+ CXR
If any symptoms
and/ or
any abnormality
compatible with
TB on CXR
8
• Cough
• Unexplained fever
• Unexplained weight loss
• Night sweat
Collect a spot sputum specimen for
Xpert MTB/RIF
(or SM/ TB LAMP) Test
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,
RIF Resistance
not detected
(T)
Treat with DS- TB
Regimen
MTB detected,
Rif Resistance
detected
(RR)
MTB detected,
Rif Resistance
indeterminate
(TI)
Error/Invalid
(I)
Low DR-TB
Risk
• Collect new
specimen
• Repeat test
• Repeat test
High DR-TB
Risk
• Collect baseline sputum
samples for TBC & DST,
LPA-1st & 2ndline drugs DST
• Check Eligibility Criteria to
Standard Treatment Regimens
Follow the second
result and treat
accordingly
(if final result is TI,
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
MTB not
detected
(N)
Reassess patient
•Take CXR if not
taken before
•Investigate for EP
TB or other
disease
• Antibiotic trial if
not given before
• If not TB, give
TPT if contacts
of BC DS-TB case
Meaning and
resistance caused
Mutation*
InhA
Low level H resistance and
confers resistance to Pto
KatG
High level H resistance and confers
resistance to high dose H
First-line LPA result
RpoB
Second-line LPA result
(all RR-TB cases)
Rifampicin resistance
with and without H resistance
GyrA, GyrB
FQ resistance (Ofx, Lfx, Mfx)
rrs
High level injectable (Am, Km, Cm)
resistance
eis
low level resistance to Km,
susceptibility or low level to Am & Cm
Treatment regimen
Treat with the
regimen for
H-resistant TB
Treat with MDR-TB
regimen
Treatment with FQ Resistant
MDR-TB Regimen
If GyrA and D94A mutation is
absent, high dose Mfx may
still be effective
Treat with MDR-TB
regimen
If eis mutation is present, Am
may still be effective
• 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
Interpretation of LPA Result and Treatment Decision
TB Case Classification/Definition
Bacteriologic
Anatomical sites
Positive in any
of the following tests:
• Xpert MTB/Rif
• SM
Bacteriologically
• TB LAMP
Confirmed
• TB Culture
History of TB
treatment
Pulmonary
New
Lungs +/other organs
Never treated for
TB or < 1 month
of TB treatment
If the above tests cannot
confirm TB, check
Presence of
drug resistance
Type
H
Extra
Pulmonary
Other organs
Clinically
Diagnosed
(e.g. lymph nodes,
meninges, bone/
joints)
13
Retreatment
Previous TB
treatment for ≥ 1
month regardless
of TB treatment
completion
R
FQ SLI
DS-TB
Isoniazid
resistant TB
R
R
RR TB
• Clinical S/S
• CXR
• Other imaging test
(ultrasound, CT Scan)
• Histology
• Biochemistry, etc
Phycisian’s discretion
to treat as TB
Drug resistant pattern
MDR-TB
PreXDR-TB
(FQ/SLI)
XDR-TB
R
R
R
R
R
R
R
R
R
R
R
R
Resistance to drug/s
R
TB Treatment and Management
Eligible TB Patients
Treatment Regimen
Regimen 2
2HRZE/10HR
New PTB or New EPTB (except CNS, bones, joints), with positive
SM/TB LAMP or clinically diagnosed, and:
Xpert not done
Xpert result is MTB not detected
EPTB of CNS, bones, joints whether new or retreatment, with final
Xpert result:
MTB, Rif sensitive
MTB, Rif indeterminate
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
New, CDTB
New, BCTB
Retreatment
Ff-up 1
Ff-up 2
Ff-up 3
ONLY IF positive at end of Intensive Phase
End of Intensive
Phase**
(2nd month)
End of Intensive
Phase
(2nd month)
End of 5th month
End of Treatment
(6th month)
End of 5th month
End of Treatment
(6th 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
TB Treatment
and Management
Regimen 1
2HRZE/4HR
PTB or EPTB (except CNS, bones, joints) whether new or retreatment,
with final Xpert result:
MTB, Rif sensitive
MTB, Rif indeterminate
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
(2 months HRZE)
150/75/400/275
Continuation Phase
Regimen 1: 4 months HR
Regimen 2: 10 months HR
150/75
Number of Tablets per day
2
3
4
2
3
4
25-37
38-54
55-70
5
5
>70
Table 2. Standard Regimens for DS-TB: Dosing for Children using FDC*
Weight band (Kg)
Number of tablets
Intensive phase
2 months RHZ
75/50/150*
Continuation Phase
Regimen 1: 4 months HR
Regimen 2: 10 months HR
75/50
4-7
1
1
8-11
2
2
12-15
16-24
3
4
3
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
Body
Weight
(kgs.)
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Isoniazid
(200mg/5ml)
10mg/kg
Rifampicin
(200mg/5ml
15mg/kg
ml
ml
0.75
1.00
1.25
1.50
1.75
2.00
2.25
2.50
2.75
3.00
3.25
3.50
3.75
4.00
4.25
4.50
4.75
5.00
5.25
5.50
5.75
6.00
1.00
1.50
2.00
2.25
2.50
3.00
3.50
3.75
4.00
4.50
5.00
5.25
5.50
6.00
6.50
6.75
7.00
7.50
8.00
8.25
8.50
9.00
Pyrazinamide
(250mg/5ml)
30mg/kg
ml
16
1.75
2.50
3.00
3.50
4.25
4.75
5.50
6.00
6.50
7.25
7.75
8.50
9.00
9.50
10.25
10.75
11.50
12.00
12.50
13.25
13.75
14.50
Ethambutol (100
or 400 mg/tab)
20mg/kg
tablet
50mg
100mg
200mg
300mg
400mg
Second Line Anti-TB Drugs Grouping
Drugs
Drug Group
Group A:
Include all three medicines
(unless they cannot be used)
Levofloxacin (Lfx) or Moxifloxacin (Mfx)
Bedaquiline (BDQ)
Linezolid (Lzd)
Group B:
Add one or both medicines
(unless cannot be used)
Group C:
Add to complete the regimen when
medicines from Groups A and B
cannot be used
Clofazimine (Cfz)
Cycloserine (Cs)
Ethambutol (E)
Delamanid (Dlm)
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
4-6 months:
Lfx-Bdq(6)-Cfz-Pto-E-Z-HdH
Regimen 3:
Standard Short all Oral
Regimen (SSOR)
MDR/RR-TB
eligible to SSOR
Regimen 4:
Standard Long all
Oral Regimen for FQ
Susceptible
(SLOR FQ-S)
MDR/RR-TB eligible to
SLOR
(no FQ resistance;
when SSOR is not
eligible - e.g.
disseminated MDR TB)
6 Months:
Lfx-Bdq-Lzd-Cfz
Regimen 5:
Standard Long all Oral
Regimen for FQ
Resistance
(SLOR FQ-R)
MDR/RR-TB eligible to
SLOR (with FQ
resistance)
6 Months:
Lzd-Bdq-Dlm-Cfz-Cs
Individual Treatment
Regimen (ITR)
Retreatment
MDR/RRTB cases
(not eligible to SSOR
nor SLOR)
Design a regimen with at
least 4-5 likely effective
drugs
Remarks
Bdq is given for 6
months
5 months:
Lfx-Cfz-Z-E
12-14 months
Lfx-Lzd-Cfz
12-14 months:
Lzd-Cfz-Cs
Request for “Off Label”
use from TB MAC for
extended use of Bdq
(beyond 6 months)
Request for “Off Label”
and extended use of
Bdq and/ or Dlm from
TB MAC
Present the case to TB
MAC and follow the
recommended
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
1.
2.
3.
4.
2
Check exclusion criteria for Standard Short All Oral Regimen (SSOR), (if YES to any of the following,
DO NOT GIVE SSOR)
Disseminated/ extensive TB or severe/intractable extrapulmonary (EP) TB (e.g., TB Meningitis, Bone/Joint TB)
Confirmed resistance to fluoroquinolone (Moxifloxacin/Levofloxacin)
Exposure to Moxifloxacin/Levofloxacin, Bedaquiline, Clofazimine, Prothionamide for >1 month
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.
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:
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)
Severe anemia (Hgb <8 g/dL)
3
If eligible, give SLOR FQ-S. If not, check eligibility to SLOR FQ-R.
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:
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)
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
Resistance
Detected
-
High Dose
H (HdH)
Resistance
Detected
Pto
Resistance
Detected
Clinical and
Programmatic
Action
+
-
+
-
+
+
Shift to SLOR FQ-S
Continue dose count if within
1 month from treatment
initiation
+
+/-
+/-
-
+/-
+/-
Shift to SLOR FQ-R
Restart dose count
+
+/-
+/-
SLOR FQ-R
+/-
+/-
+/-
ITR
+/-
+/-
+/-
SSOR
SLOR FQ-S
Legend: (-) Resistance NOT Detected; (+) Resistance Detected
20
Continue SSOR
Continue SSOR
Continue SSOR
Continue SLOR FQ-S
Shift to SLOR FQ-R
Restart dose count
Continue SLOR FQ-R
Review initial regimen
and revise if needed in
consultation with R-TB MAC
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
Group
A
Medicine
Fluoroquinolones
Levofloxacin
15-20
mg/kg
Moxifloxacin
10–15
mg/kg
Clofazimine
Ethambutol
C
Meropenem
Amikacin
10-15 kg 16-23 kg 24-30 kg 31-34 kg >34 kg
1
1.5
2 or 3
3 or 4
(≥14 y)
(≥14 y)
(≥14 y)
1.5 g
0.5
0.5
1-1.5
1.5-2
2
3
(≥14 y)
1.5 g
400 mg tab
0.8
1.5
2
3
4
(≥14 y)
400 mg tabc
2ml
3ml
5ml
0.5 or 0.75
4ml
6ml
8ml
11ml
14ml
15ml
0.25
0.25
10-12mg/kg
OD in >15 kg
600 mg tabc
2-5 mg/kg
50 mg cap
15-20 mg/kg
15-25 mg/kg
30 40 mg/kg
1 alt days 1 alt days
M/W/F
M/W/F
125 mg mini
1
1
cap
250 mg capc 4 to 5 mlc 5 to 6 mlc
Use 10 mg/kg in <6
months
1
(≥14 y) (≥14y) 400mg
4 tabs OD for 2
2 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
20ml
0.25
0.25
0.5
0.5
0.75
1 alt days
1
2
2
(≥14 y)
1 alt days
1 alt days
2
3
1
4
(≥14 y)
(≥14 y)
(≥14 y)
(≥14 y)
7 to 10 mlc
2
1 or 1.5
1 bid
2
2
1 bid
(≥14 y)
(≥14 y)
600mg
100mg Give on alternate days if dose
100mg in mg/kg/day is too high
1g
2
4 mlc
3
6 mlc
50 mg tab
-
-
-
2
4
1
-
150 mg tab
500 mg tab
0.5 g + 0.5 g
vial
1
0.5
2
0.5
3
0.75 or 1
4 or 5
1.5
2
2.5
-
(≥14 y)
(≥14 y)
2 ml
4 ml
6 ml
8-9 ml
11 ml
≥14 y
≥14 y
≥14 y
≥14 y
1g
≥14 y
≥14 y
1g
2.5
≥14 y
1g
1g vial
(20ml)
500
15-20 mg/kg
mg/2ml vial
20-40mg/kg
IV q 8 hrs
Streptomycin 20-40 mg/kg 1 gm vial
Prothionamide
15-20
250 mg
mg/kg
tab
-
0.6
0.8-1.0
1.2-1.5
2.0
0.4
ml
ml
ml
ml
ml
Calculate according to the dilution used
0.5
0.5
0.75 or 1
22
Remarks
(≥14 y) 400 mg
1
3 mlc
100 mg dt
400 mg tabc
Imipinem Cilastatin
7-9 kg
100 mg dt
15 mg/kg OD 20 mg/ml
in < 16 kg
susp
Delamanid
Pyrazinamide
5-6 kg
Usual
Upper
Daily
Dose
250 mg tab
100 mg cap
Cycloserine
Weight bands for patients not yet 15 years old
100 mg tab
Bedaquiline
Linezolid
B
Weight-based Formulation
daily dose
1.5
2
(≥14 y)
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)
Not used in patients <15 years
Use Meropenem
To be used with clavulanic acid
C
PAS acid (4g)
p-aminosalicylic 200-300.
mg/kg in 2
sachet
acid
divided doses
0.5-0.75
g bid
0.75-1
g bid
1-2
g bid
2-3
g bid
3-3.5
g bid
(>14 y)
(>14 y)
PAS sodium salt
(4g) sachet
0.5-0.75
g bid
1.5
g bid
0.75-1
g bid
2-3
g bid
1-2
g bid
3-4
g bid
2-3
g bid
4 or 6
g bid
3-3.5
g bid
6 or 8
g bid
(>14 y)
(>14 y)
8-12
g bid
8-12
g bid
50mg/5 ml 8-10 ml
soln
15 ml
20 ml
-
-
-
-
1
1.5
2
3
4
4
(>14 y)
2 ml
bid
3 ml
bid
5 ml
bid
8 ml
bid
10 ml
bid
(>14 y)
(>14 y)
PAS sodium salt
60% (9.2g) sachet
Isoniazid
15-20
mg/kg
(high.dose)
Others
100 mg
tab
Clavulanic
acid
-
250 mg
amoxicillin/
62.5 mg
clavulanic
acid/5 ml
suspension
-
Full dose can be given
once daily if tolerated
300 mg isoniazid tablet can
be used in patients >20 kg
Pyridoxine is always given
with high-dose isoniazid in
children (12.5 mg od in <5 y
olds and 25 mg od in >4 y
olds)
Only be used with
carbapenems
(>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
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)
c
23
Dosing of Medicine Used In Second line MDR-TB Regimens
by Weight Band in Patients >15 Years Old
Group
Medicine
Fluoroquinolones
Levofloxacin
A
Moxifloxacin
Weight-base Formulation Weight bands for patients older than 14 years old Usual
Upper
d daily dose
30-35 kg 36-45 kg 46-55kg 56-70kg >70kg Daily Dose
250 mg tab
500 mg tab
750 mg tab
Standard dose 400 mg tab
4
2
1.5
1
4
2
1.5
1
4
2
1.5
1
1.5
400 mg
800 mg
400 mg
Bedaquiline
Linezolid
600 mg tab (<15y)
1
1
1
1.2 g
Clofazimine
50 mg cap
2
2
2
2
2
100 mg
100 mg cap
Cycloserine or
10-15 mg/kg 250 mg cap
Terizidone
1
1
1
1
1
100 mg
2
2
3
3
3
1g
Ethambutol
2
2
3
3
3
50 mg tab
2 bid
2 bid
2 bid
2 bid
2 bid
3
2
4
3
4
3
4
3
5
4
Imipinem Cilastatin
400 mg tab
500 mg tab
0.5 g +
0.5g vial
Meropenem
1g vial (20ml)
15-25 mg/kg 400 mg tab
Delamanid
Pyrazinamide
C
3
1.5
1
1
400 mg tab 1 or 1.5 1 or 1.5 1.5 or 2
2
2
100 mg tab
4 tabs OD for 2 weeks; then 2 tabs OD
M/W/F for 22 weeks
High dose
B
3
1.5
1
1
20-30 mg/kg
Amikacin
15-20 mg/kg 500 mg/2ml
vial
Streptomycin
12-18 mg/kg 1 gm vial
Ethionamide or 15-20mg/kg 250 mg tab
Prothionamide
p-aminosalicylic
acid
Others
Isoniazid
Clavulanic
acid
(<15y)
To be used with clavulanic acid
2 vials (1g + 1g) bid
3 ml
3 to 4 ml
To be used with clavulanic acid
4 ml
4 ml
Calculate according to the dilution used
1g
1g
2
2
3
3
4
1g
PAS Na Salt
(4gm) sachet
1 bid
1 bid
1 bid
1 bid
1 to 1.5
bid
12 g
PAS Acid
(4gm) sachet
1 bid
1 bid
1 bid
1 bid
1 to 1.5
bid
300 mg tab
2/3
1
1
1
1
High dose:
10-15 mg/kg 300 mg tab
1.5
1.5
2
2
2
1 bid
1 bid
1 bid
1 bid
1 bid
8-12 g/day
in 2 to 3
divided
doses
Standard
dose: 4-6
mg/kg
125 mg tab
24
As used in the standardized shorter
MDR-TB Regimen
200 mg
1 vials 3x/day or 2 vials bid
2.5 ml
Comments
Once daily dose advised but can start with
2 divided doses until tolerance improves
100 mg isoniazid tablet can facilitate the
administration of certain dosages
Pyridoxine is given with isoniazid in
patients at risk (such as dose with HIV and
malnutrition)
To be used only with carbapenems
(such as imipenem and meropenem)
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,
may be extended'up to 6 months
Test/Examination
Baseline
M1
M2
M3
M4
Post-Treatment
Follow-up
Continuation Phase: 5 months
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)
First-line and Second-line Line
Probe Assay (LPA)
If culture remains positive at month 4 of treatment, in case of culture reversion or culture positive
during post-treatment follow-up
Diagnostic Tests
Chest X-ray (CXR)
Electrocardiogram (ECG)
Visual Acuity and Color Vision
Brief Peripheral Neuropathy
Screening (BPNS)
Mental health screening
Monthly if regimen contains Cycloserine (Patient Health Questionnaire-9 or
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
Intensive Phase: 6 months
Test/
Base- M1
line
Examination
Clinical
Evaluation
Mycobacteriology Tests
M2
M3
M4
M5
M6
Continuation Phase: 12-14 months
M7
M8
Post-Treatment
Follow-up
M9 M10 M11 M12 M13 M14 M15 M16 M17 M18 M19 M20 P6
Smear Microscopy
TB Culture(TBC)
DST
If culture remains positive at month 4 of treatment, in case of culture reversion or culture positive
during post-treatment follow-up
LPA
Diagnostic Tests
CXR
ECG
Monthly if regimen contains Bedaquiline, Delamanid, Clofazimine and/or Moxifloxacin
Visual Acuity
and Color Vision
Monthly if regimen contains Linezolid and/or Ethambutol
BPNS
Audiometry
Mental health
screening
Monthly if regimen contains Linezolid, Cycloserine and/or High Dose Isoniazid
Baseline and Monthly if regimen contains Amikacin or Streptomycin
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*
CBC
Monthly if regimen contains Bedaquiline and/or Pyrazinamide
Monthly if regimen contains Linezolid
FBS,
Urea Nitrogen,
Creatinine, K
Monthly if regimen contains Amikacin or Streptomycin
TSH
Every 6 months if regimen contains Prothionamide or Para-aminosalicylic Acid (PAS)
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
P12
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
represents 0.2 seconds (200 ms)
time and 0.5 mV amplitude
1 mV (10 mm high)
reference pulse
Amplitude
Time
29
One small 1 mm x 1 mm block
represents 40 ms time
and 0.1 mV amplitude
b. Normal Heart Rhythm & QTc
25 Years
Female
ID: X-97
Vent. rate
87 bpm
PR Interval
116 ms
QRS duration 90 ms
QTc
=
445 mc
P duration
90 ms
RR interval
689 ms
P-R-T axes
62 55 43
10-Oct-2016
15:21:21
Normal sinus rhythm (sinus rate 60-100/min)
Normal ECG
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
P
QT
Segment
PR
Segment
PR Interval
Q
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
(e.g 9x40=360ms)
HR: 1500/no of small squares b/t RR
(e.g., 1500/17= 88)
T
Can use calculator app that can be downloaded as
per below link:
S
https://www.thecalculator.co/health/QTc-Calculator
-385.html
http://www.qxmd.com/apps/calculate-by-qxmd
QT Interval
QT in milliseconds (ms)
and RR interval in
seconds (s).
31
d. Automated QTc value and manual calculation
ID: X-97
Vent. rate
87 bpm
PR Interval
116 ms
QRS duration 90 ms
QT/QTc
370/445 ms
P duration
90 ms
RR interval
689 ms
P-R-T axes
62 55 43
10-Oct-2016
15:21:21
Normal sinus rhythm (sinus rate 60-100/min)
Normal ECG
AUTOMATED REPORT
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
If the two values are <50 ms
difference, the machine is
more likely to be programmed
with Fredericia formula.
32
Management of
Adverse Events
25 Years
Female
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
QT Interval (msec)
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
310
320
330
340
350
360
370
380
390
400
410
420
430
440
450
460
470
480
490
500
510
520
530
540
550
560
570
580
590
600
273
282
291
300
309
318
327
336
345
354
363
373
382
391
400
409
418
427
436
445
454
463
472
482
491
500
509
518
527
536
545
282
292
301
311
320
329
339
348
358
367
376
386
395
405
414
423
433
442
452
461
471
480
489
499
508
518
527
536
546
555
565
291
301
311
321
330
340
350
360
370
379
389
399
408
418
427
437
447
457
466
476
486
495
505
515
525
534
544
554
563
573
583
300
310
320
330
340
350
360
370
380
390
400
410
420
430
440
450
460
470
480
490
500
510
520
530
540
550
560
570
580
590
600
308
318
329
339
349
359
370
380
390
401
411
421
431
442
452
462
472
483
493
503
514
524
534
544
555
565
575
585
596
606
616
316
326
337
347
358
368
379
390
400
411
421
432
442
453
463
474
484
495
505
516
526
537
547
558
568
579
590
600
611
621
632
323
334
345
355
366
377
388
399
409
420
431
442
452
463
474
485
496
506
517
528
539
549
560
571
582
592
603
614
625
636
646
330
341
352
363
374
385
396
407
418
429
440
451
462
473
484
495
506
517
528
539
550
561
572
583
594
605
616
627
638
649
660
337
348
359
371
382
393
404
416
427
438
449
460
472
483
494
505
517
528
539
550
562
573
584
595
606
618
629
640
651
663
674
343
355
366
378
389
401
412
424
435
446
458
469
481
492
504
515
527
538
549
561
572
584
595
607
618
630
641
652
664
675
687
33
350
361
373
385
396
408
420
431
443
455
466
478
490
501
513
524
536
548
559
571
583
594
606
618
629
641
653
664
676
688
699
356
368
379
391
403
415
427
439
451
462
474
486
498
510
522
534
545
557
569
581
593
605
617
628
640
652
664
676
688
700
711
362
374
386
398
410
422
434
446
458
470
482
494
506
518
530
542
554
566
578
590
603
615
627
639
651
663
675
687
699
711
723
367
379
392
404
416
428
441
453
465
477
490
502
514
526
539
551
563
575
587
600
612
624
636
649
661
673
685
698
710
722
724
373
385
397
410
422
435
447
460
472
484
497
509
522
534
547
559
571
584
596
609
621
634
646
658
671
683
696
708
720
733
745
378
391
403
416
428
441
454
466
479
491
504
517
529
542
554
567
580
592
605
617
630
643
655
668
680
693
706
718
731
743
756
383
396
409
421
434
447
460
473
485
498
511
524
536
549
562
575
588
600
613
626
639
651
664
677
690
702
715
728
741
754
766
388
401
414
427
440
453
466
479
492
505
518
531
543
556
569
582
595
608
621
634
647
660
673
686
699
712
725
738
751
763
776
393
406
419
432
446
459
472
485
498
511
524
537
550
563
577
590
603
616
629
642
655
668
681
694
708
721
734
747
760
773
786
398
411
424
438
451
464
477
491
504
517
531
544
557
570
584
597
610
623
637
650
663
676
690
703
716
729
743
756
769
783
796
403
416
429
443
456
470
483
497
510
523
537
550
564
577
590
604
617
631
644
658
671
684
698
711
725
738
751
765
778
792
805
407
421
434
448
461
475
489
502
516
529
543
556
570
584
597
611
624
638
651
665
679
692
706
719
733
746
760
774
787
801
814
2. How to calculate Creatinine Clearance:
Calculation of Creatinine Clearance
(Estimated Glomerular Filtration Rate)
weight (kg) x (140 – age)
Constant
Serum Creatinine (umol/L)
X
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
UNMASKED
MASKED
-10
0
10
20
30
40
50
60
70
80
90
100
110
120
250
Left Ear
-10
0
10
20
30
40
50
60
70
80
90
100
110
120
AIR
Normal
Audiogram
25db
500
1000
2000
4000
6000
250
8000
Frequencies (Hz)
500
1000
2000
4000
6000
8000
Frequencies (Hz)
Left Ear Interpretation
Right Ear Interpretation
Hearing loss was detected. Please consult
an audiologist. Threshhold (Hz:dB):
1K:45, 2K:50, 3K:65, 4K:60, 6K:55, 8K:50
Hearing loss was detected. Please consult
an audiologist. Threshhold (Hz:dB):
1K:45, 2K:50, 3K:55, 4K:55, 6K:45, 8K:45
Results from the test indicate that hearing
loss was present at these frequencies:
1K, 2K, 3K, 4K, 6K, 8K
Results from the test: indicate that hearing
loss was present at these frequencies:
1K, 2K, 3K, 4K, 6K, 8K
Note: This is a sample automated audiogram results from digital audiometry app used
for monitoring of hearing loss due to secondline injectable (Am,S). An audiometry may
need to be repeated by an audiologist for confirmation. Persistence and/or worsening
of hearing impairment/loss after discontinuation of injectables (S, Am) may warrant
further evaluation by an ENT (ears, nose and throat) specialist.
35
Loudness (dB)
Loudness (dB)
Right Ear
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
NPL NPL
Right VA =
X
X
X
X
Left VA =
PL
PL
NPL
NPL
Left VA =
√
√
NPL
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
00
Mild ----------------------------------------------------------------------------- Severe
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
have you been bothered by any
Not
of the following problems?
at all
Several
days
More than
half the
days
Nearly
every
day
1. Little interest or pleasure in
doing things
0
1
2
3
2. Feeling down, depressed, or
hopeless
0
1
2
3
3. Trouble falling or staying
asleep, or sleeping too much
0
1
2
3
4. Feeling tired or having little
energy
0
1
2
3
5. Poor appetite or overeating
0
1
2
3
6. Feeling bad about yourself or that you are a failure or
have let yourself or your
family down
0
1
2
3
7. Trouble concentrating on
things, such as reading the
newspaper or watching
television
0
1
2
3
PHQ-9
Score
0-4
9. Moving or speaking so slowly
that other people could have
noticed. Or the opposite being fidgety or restless that
you have been moving a lot
more than usual
0
10. Thoughts that you would be
better off dead, or of hurting
yourself in some way
(Suicidal ideation or attempt)
0
For office coding
Severity Grading Scale
1
2
3
0
+
2
Mild
10-14
Moderate
+
3
20-27
+
= Total Score:
If you checked off any problems, how difficult have these problems made
it for you to do your work, take care of things at home, or get along with
other people?
Not difficult
at all
Somewhat
difficult
Very
difficult
Extremely
difficult
Proposed Treatment Action
None-minimal
5-9
15-19
1
Depression
Severity
None
Watchful waiting; repeat PHQ-9
at follow up
Treatment plan, consider
counseling, follow up and
Moderately Severe
Severe
pharmacotherapy
Active treatment with
pharmacotherapy and/or
psychotherapy
Immediate initiation of
psychotherapy and, if severe
impairment or poor response to
therapy, expedited referral to a
mental health specialist for
psychotherapy and/or
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.
WARNING!
Patients with suicidal ideation must be assessed
immediately for possible hospitalization.
(Exclude hypothyroidism & manage accordingly)
41
Consult with TB MAC for
possible dose adjustment,
discontinuation or
replacement of causative
anti TB drug.
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
that trigger symptoms
• Relaxation and/ or distraction
techniques
Resolved?
YES
Manage Accordingly
NO
Give proton pump
inhibitor2 for 8 weeks
Follow-up after two weeks
YES
Continue clinical monitoring
Better
Continue
Protopump
Inhibitors until
8 weeks
Not better
Refer to TB MAC for dose adjustment
or discontinuation and replacement
of causative anti TB drug or for introduction
of additional ancillary drugs (i.e tricyclic
antidepressant3 and prokinetic drugs4)
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)
1
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
• photophobia
• fever
• confusion
• somnolence
YES
EMERGENCY!
for hospitalization for
possible MENINGITIS
YES
• Manage for possible
migraine headache or
• Corrective lenses for the
error of refraction
NO
• (a) with prior history of
pulsating headache with
nausea, vomiting & vision
change
(b) discrete episodes
lasting hours, relieved by
darkness and sleep
• blurring of vision
NO
• exposure to extreme
temperature/ heat exhaustion
• dehydration
YES
Hydrate patient
Instruct patient to avoid
exposure to extreme heat
(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
among patients with GI
and Renal pathology)
counseling &
psychosocial support to
address emotional
component
recurrent headache
and already affecting
adherence?
NO
Continue clinical surveillance
43
YES
Refer to TB MAC for
possible dose adjustment,
discontinuation or
replacement of causative
anti TB drug
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
and not the mouth?
YES
May be due to epistaxis.
Manage accordingly
NO
Is the patient vomiting blood?
YES
NO
Probable GI Bleeding
Send patient to Emergency
Room
LIKELY HEMOPTYSIS
• Quantity of blood >200 ml (3/4 cups)
YES
• Total Quantitiy in 48 hrs >600ml
(2 1/2 cups)
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
MASSIVE HEMOPTYSIS!
SEND PATIENT TO
EMERGENCY ROOM FOR
TERTIARY MANAGEMENT
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
• NO Hepatitis S/S
Continue monthly
monitoring
• >3x ULN
• WITH Hepatitis S/S
• >5x ULN
• WITH/NO Hepatitis S/S
Investigate for other causes and DO Laboratory tests
and diagnostics2
1
PRESENCE
of other liver
disease
Refer to
Gastroenterologist for
co-management
• CONTINUE anti-TB drugs
• DO Weekly LFTs
• DO Total Bilirunin
Normal ALT/ AST
Continue monthly
monitoring
• AST/ALT >3x ULN
• Total Bilirunin >2x ULN
• STOP all anti TB drugs
• REPEAT LFTs after 1 week
• CONSULT TB MAC
Normal/decreasing ALT/ AST
AST/ALT >3x ULN repeatedly
after 2 weeks
• RESUME 3 not/ least hepatotoxic LED3s
• REPEAT AST/ALT after 1 week
• CONSULT with TB MAC
Normal/decreasing
AST/ AST
AST/ALT >3x ULN
• REINTRODUCE4 possible culprit drugs if
still vital in the regimen
• MONITOR ALT/AST q 3 days
• Discontinue culprit drug if AST/ ALT increases
• REFER to TB MAC
• REFER to TB MAC
• Refer to specialists for co-management
Alcoholic and Non Alcoholic liver disease, viral hepatitis
Serology tests for Hep A, Hep B (HbsAg, antiHBC) and Hep C, Hepatobiliary ultrasound, etc.
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.
1
2
3
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)
signs of acute swelling, erythema,
and warmth at the site of joint
and muscle pain?
GIVE paracetamol or NSAIDS1
light massage exercise
dietary modification
NO
YES
Resolved?
Rule out other
causes and manage
accordingly
Refer to TB MAC
for possible dose
adjustment,
discontinuation or
replacement of
causative anti TB
drug
NO
Continue clinical surveillance
• elevated blood
uric acid and with
tophi, podagra?
• involvement of big
joints ?
YES
NO
Determine
other causes
History
of trauma?
YES
Manage accordingly/
refer for appropriate management
Pharmacologic Management:
NSAIDS1
Colchicine2
Allopurinol3
Dietary Management:
avoid high purine diet4
Resolved?
NO
YES
Continue clinical surveillance
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
1
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)
2
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
3
Food High in Purine
sardines, innards, mussels, anchovies, trout and salmon, bacon, alcoholic drinks, etc
4
46
Management of Myelosuppression
(Possible causative anti-TB Drug: Lzd)
Presence of any and combination of
the following:
• ANEMIA
• LEUKOPENIA
• THROMBOCYTOPENIA
NO
Continue monthly
CBC monitoring
YES
Investigate for other possible causes:
• nutritional deficiencies
• viral infections
• advanced HIV/AIDS
• chronic renal insufficiency
• occult blood loss
• intestinal parasitism
• medications other than anti-TB
medications (e.g. Azidothymidine,
Zidovudine, cotrimoxazole)
• other causes of myelosuppression
Manage Accordingly
(clinical assessment and
laboratory examinations
such as BUN, Crea,
Fecalysis with occult
blood, etc)
Determine the Grade
of Myelosuppression
GRADE 1
• Hgb 9.5 to 10.5 g/dl
• ANC <1,500 mm3
• Platelet <100,000 mm3
GRADE 2 and above
• Hgb <9.5.g/dl
• ANC <1,000 mm3
• Platelet <75,000 mm3
• DECREASE Lzd to 300 mg daily
• MONITOR CBC weekly
• STOP Lzd immediately
• GIVE erythropoietin with caution (see page 68)
• GIVE blood transfusion*
• MONITOR CBC weekly
NO
CBC improved or normalized?
Severity reduced to Grade 1?
YES
YES
• CONTINUE Lzd at 300 mg daily
• MONITOR CBC monthly
• REINTRODUCE Lzd at 300 mg daily
• MONITOR CBC weekly for 2 weeks
REFER to TB MAC for further
management and change in regimen
CBC improved or normalized?
NO
• STOP Lzd completely
• REPLACE with any of the ff:
Dlm, Cs, Pto, injectable
YES
• CONTINUE Lzd at 300 mg daily
• MONITOR CBC monthly
*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
pressure, orthostasis, weakness)
NO
Manage accordingly
YES
REFER to Emergency Room
for AGGRESSIVE
HYDRATION
Classify severity of
Nausea and Vomiting
In SSTR/SSOR, replace Pto
with Cs in case of repeated
nausea and vomiting even
if it is mild or induced.
Moderate to severe
Mild
• Take light meal before intake
of anti TB Drugs
• May give ice chips
• Adjust drug administration or
split dose of medications
Resolved?
YES
• Give oral anti emetics1
• May give benzodiazepines2
if with anxiety or psychological
aspects of vomiting
NO
Resolved?
NO
YES
Continue clinical monitoring
YES
YES
Give IV/IM anti emetics1 if
setting permits
Resolved?
NO
Anti-emetics:
(1) Metoclopromide 10 mg, 30 mins before intake of anti TB meds, q 8 hrs thereafter
(2) Ondansetron 8 mg, 30 mins before intake of anti TB meds, q 8 hrs thereafter
(not to be given in patients on Bdq and Dlm)
(3) Combination of Metoclopromide and Ondansetron. Watch out for concomitant
cardiac pathology prior to use.
Both anti- emetics may be given as oral, IV or IM
2
Benzodiazepines
(1) Diazepam 5 mg/tab OD
1
48
Refer to TB MAC for possible
dose adjustment,
discontinuation or replacement
of causative anti
Management of Nephrotoxicity
Possible Causative anti-TB Drugs: S, Km, Am, Cm
Patient presents with diminished urine
production (< 0.5ml/kg/hr or < 30ml/hr)?
Patient has elevated BUN and/or
Creatinine on routine follow up
Edema or anasarca? malaise? nausea?
Increased difficulty of breathing
DECREASED Creatinine Clearance
compared to baseline
Investigate for other causes1
of renal insufficiency and
manage co morbidity
EMERGENCY
HOSPITALIZATION
Check BUN, Creatinine
and Urinalysis
(1) Check the weight base dosing
of the injectable agent and
correct the dose as necessary
(2) In consultation with TB MAC,
may replace injectable with Lzd
Elevated BUN and/or Creatinine
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
Continue clinical surveillance
Refer back to TB MAC for updates
Other causes of renal insufficiency
(1) diabetes
(2) dehydration
(3) congestive heart failure
(4) urinary obstruction
(5) urinary tract infection
(6) prostatic hypertrophy
1
Calculation of Creatinine Clearance (Estimated Glomerular Filtration Rate)
weight (kg) x (140 – age)
x
Constant
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.
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
toes/feet; worse at night or
when walking?
• leg weakness when walking?
• leg cramps or pain?
NO
Continue clinical
surveillance
YES
Investigate for the following conditions:
• Diabetes
• Alcoholism
• Vitamin Deficiencies
• HIV
• Hypothyroidism
• Uremia
• taking drugs other than anti-TB?
Manage Accordingly
(clinical assessment and
laboratory examinations
such as fasting blood
sugar, HbAIC, thyroid
function tests, etc)
Assess according to severity GRADING
(using BPNS Tool, See page 40 )
YES
GRADE 1:
BPNS Score 1-3
GRADES 2 and 3:
BPNS Score ≥4
STOP Lzd, Hhd, and Cs
MONITOR BPNS weekly
Symptoms
improved?
Symptoms
improved?
NO
YES
YES
• Consider restarting Lzd (300
mg daily) , Cs and Hhd
• INCREASE pyridoxine to 200
mg daily
• Consider restarting Cs and Hhd
• DO NOT reintroduce Lzd
• INCREASE pyridoxine to 200 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?
Have unintelligible thoughts or
speech?
Exhibit bizzare behavior?
NO
Continue clinical observation.
If there are other behavioral
abnormalities, consider
DEPRESSION and manage
accordingly
YES
LIKELY PSYCHOSIS
Is the patient at risk of harming
him/her self or others?
Does the patient express the
desire to harm or kill him/her self
or others?
YES
NO
With any of the
following conditions
(illicit drug use,
seizure, alcohol
withdrawal, etc)
YES
EMERGENCY
Consider hospitalization
Close surveillance to ensure
safety of patient and others
51
NO
Refer to Psychiatrist
May give haloperidol
0.5-5 mg PO 2x/day with
precaution
Increase pyridoxine to a
maximum of 200 mg/day
Refer to TB MAC for
possible dose
adjustment,
discontinuation or
replacement of causative
anti TB drug
Management of Prolonged QTc
(Possible causative anti-TB Drugs: Bdq,Cfz,Dlm,FQ)
Presence of :
• ABNORMAL QTc
OR
• > 60 ms increased from the
baseline QTc
OR
• CARDIAC SYMPTOMS3
NO
Continue monthly ECG clinical
symptoms3
YES
Investigate for other possible
causes such as:
• hypothyroidism
• electrolyte imbalance
• hypoglycemia
• Other cardiac pathologies*
• other QT prolonging drugs**
Determine the Grade of QTc Prolongation
GRADEs 1 and 2
• >450 ms - <500 ms)
Manage Accordingly (clinical
assessment and include laboratory
tests such as (i.e. thyroid function
tests, serum electrolytes, FBS/RBS,
2D echo, etc)
GRADE 3 and above
• QTc of >500 ms
• >60 ms increased from the baseline1
• CONTINUE anti TB Treatment
• MONITOR ECG weekly
QTc and ECG normalized/back to
baseline values
AND
Absence of Cardiac Symptoms?
NO
YES
CONTINUE anti TB Treatment
MONITOR ECG monthly or as
necessary (when cardiac
symptom occurs)
• STOP ALL QT prolonging drugs immediately
• REFER and HOSPITALIZE patient for close
cardiac monitoring2
QTc and ECG
normalized/back to baseline
values?
NO
REFER to TB MAC for
change in regimen
YES
CONSIDER REINTRODUCTION of QT
prolonging drugs if considered critical to
the regimen in coordination with TB MAC
QTc on at least 2 separate ECGs done after reassuring patients to relax after 10-15 minutes
Repeat ECG every 2-3 days until within normal limits
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)
1
2
3
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)
Adverse event
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Mild
Moderate
Severe
Life threatening
Death
Asymptomatic or
mild symptoms;
clinical or
diagnostic
observations only;
intervention not
indicated
Minimal, local or
non-invasive
intervention
indicated; limiting
age-appropriate
instrumental
activities of daily
living (ADL)*
Medically
significant but not
immediately
life-threatening;
hospitalization or
prolongation of
hospitalization
indicated;
disabling; limiting
selfcare ADL*
Urgent
intervention
indicated
(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)
Intervention or infusion
interruption indicated; responds
promptly to symptomatic
treatment (e.g., antihistamines,
NSAIDS, narcotics); prophylactic
medications indicated for ≤24 hrs
Prolonged (e.g., not rapidly responsive
to symptomatic medication and/or brief
interruption of infusion); recurrence of
symptoms following initial improvement;
hospitalization indicated for clinical
sequelae (e.g., renal impairment,
pulmonary infiltrates)
Rash, Allergy, Anaphylaxis
Allergic
reaction
Transient flushing or rash, drug
fever <38 degrees C (<100.4
degrees F); intervention not
indicated
Symptomatic bronchospasm, with or
without urticaria; parenteral intervention
indicated; allergy-related
edema/angioedema; hypotension
Anaphylaxis
56
GASTROINTESTINAL
Abdominal
Pain
Grade 1 (MILD)
Grade 2 (MODERATE)
Grade 3 (SEVERE)
Mild pain
Moderate pain; limiting
instrumental ADL
Severe pain; limiting selfcare 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 4 - 6 stools per
day over baseline;
moderate increase in
ostomy output
compared to baseline
Increase of >7 stools per day over
baseline; incontinence;
hospitalization indicated; severe
increase in ostomy output
compared to baseline; limiting
selfcare ADL
Diarrhea
Increase of <4 stools per
day over baseline; mild
increase in ostomy output
compared to baseline
Gastritis
Asymptomatic; clinical or
diagnostic observations
only; intervention not
indicated
Symptomatic; altered GI
function; medical
intervention indicated
Severely altered eating or gastric
function; TPN or
hospitalization indicated
Nausea
Loss of appetite without
alteration in eating habits
Oral intake decreased
without significant weight
loss, dehydration or
malnutrition
Inadequate oral caloric or fluid
intake; tube feeding, TPN, or
hospitalization indicated
Vomiting
1 - 2 episodes (separated
by 5 mins) in 24 hrs
3 - 5 episodes (separated
by 5 minutes) in 24 hrs
57
>6 episodes (separated by 5
minutes) in 24 hrs; tube feeding,
TPN or hospitalization indicated
Grade 1 (MILD)
Grade 2 (MODERATE)
Grade 3 (SEVERE)
Mild pain
Moderate pain; limiting
instrumental ADL
Severe pain; limiting selfcare ADL
<LLN - 3.0 mmol/L
<LLN - 3.0 mmol/L;
symptomatic; intervention
indicated
<3.0 - 2.5 mmol/L; hospitalization
indicated
<1.4 - 1.2 mmol/L
<1.1 - 0.9 mmol/L
<0.8 - 0.6 mmol/L
MUSCULOSKELETAL
Arthralgia
ELECTROLYTE ABNORMALITIES
Hypokalemia
Hypomagnesaemia
RENAL
Acute Kidney
Injury
NEUROLOGICAL
Depression
Headache
Hearing Impaired
Creatinine level increase of
>0.3 mg/dL; creatinine 1.5
- 2.0 x above baseline
Mild depressive symptoms
Mild pain
Adults (on a 1, 2, 3, 4, 6
and 8 kHz audiogram):
Threshold shift of 15 - 25
dB averaged at 2
contiguous test
frequencies in at least one
ear. Adults (if by clinical
monitoring): subjective
change in hearing in the
absence of documented
hearing loss.
Pediatric (on a 1, 2, 3, 4, 6
and 8 kHz audiogram):
Threshold shift >20 dB at
8 kHz in at least one ear.
Creatinine 2-3 x above baseline
Creatinine >3 x baseline or >4.0 mg/dL;
hospitalization indicated
Moderate depressive symptoms;
limiting instrumental ADL
Moderate pain; limiting
instrumental ADL
Severe depressive symptoms; limiting self
care ADL; hospitalization not indicated
Adults (on a 1, 2, 3, 4, 6 and 8
kHz audiogram): Threshold shift
of >25 dB averaged at 2
contiguous test frequencies in at
least one ear.
Adults (if by clinical monitoring)):
hearing loss but hearing aid or
intervention not indicated;
limiting instrumental ADL.
Pediatric (on a 1, 2, 3, 4, 6 and 8
kHz audiogram): Threshold shift
>20 dB at 4 kHz and above in at
least one ear.
Adults (on a 1, 2, 3, 4, 6 and 8 kHz
audiogram): Threshold shift of >25 dB
averaged at 3 contiguous test
frequencies in at least one ear;
therapeutic intervention indicated.
Adults (if by clinical monitoring):
hearing loss with hearing aid or
intervention indicated; limiting self
care ADL.
Pediatric (on a 1, 2, 3, 4, 6 and 8 kHz
audiogram): hearing loss sufficient to
indicate therapeutic intervention,
including hearing aids; threshold shift
>20 dB at 3 kHz and above in at least
one ear; additional speech-language
related services indicated
58
Severe pain; limiting self -care ADL
Optic Neuritis
Grade 1 (MILD)
Grade 2 (MODERATE)
Grade 3 (SEVERE)
Asymptomatic; clinical or
diagnostic observations only
Limiting vision of the affected eye
(20/40 or better)
Limiting vision in the affected eye (worse
than 20/40 but better than 20/200)
Moderate symptoms; limiting
instrumental ADL
Severe symptoms; limiting self care ADL**
Peripheral Sensory Asymptomatic; loss of deep
tendon reflexes or paresthesia
Neuropathy
Psychosis
Mild psychotic symptoms
Moderate psychotic symptoms
(e.g., disorganized speech;
impaired reality testing)
Severe psychotic symptoms (e.g.,
paranoid; extreme disorganization);
hospitalization not indicated
Seizure
Brief partial seizure; no loss of
Consciousness
Brief generalized seizure
Multiple seizures despite medical
intervention
Asymptomatic; clinical or
diagnostic observations only;
intervention not indicated
Symptomatic; thyroid
replacement indicated; limiting
instrumental ADL
Severe symptoms; limiting selfcare ADL;
hospitalization Indicated
Asymptomatic or mild
symptoms; clinical or
diagnostic observations only;
intervention not indicated
Moderate; minimal, local or
non-invasive intervention
indicated; limiting age
appropriate instrumental ADL
Severe or medically significant but not
immediately life-threatening;
hospitalization or prolongation of
existing hospitalization indicated;
disabling; limiting selfcare ADL
QTc 450 - 480 ms
QTc 481 - 500 ms
QTc ≥ 501 ms on at least
two separate ECGs
10.5 - 9.5 g/dL
9.4 - 8.0 g/dL
7.9 - 6.5 g/dL
75,000 – 99,999 /mm³
50,000 – 74,999 /mm³
20,000 – 49,999 /mm³
1500 - 1000/mm3
999 - 750/mm3
749 - 500/mm3
ENDOCRINE
Hypothyroidism
METABOLIC
Lactic Acidosis
CARDIOVASCULAR
Prolonged QTc
(ECG)
HEMATOLOGICAL
Anemia
Platelet Count
Decreased
Absolute
neutrophil count
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
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
Yes
No
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.
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
Oo
Hindi
Description of Some Important Drug Side Effects
for the TREATMENT SUPPORTER
Drug Side Effect
Signs and Symptoms
Arrythmia
(irregular pulse or heartbeat)
• QTc prolongation (>500 ms) in ECG recording
• 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
stomach
Metoclopramide
10 mg/tab/IV/IM 30 minutes before taking anti TB
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
Vomiting
Ondansetron (and other serotonin
5-HT3 receptor antagonist)
4-8 mg p.o. 30 minutes before taking anti TB
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
indigestion, sour
stomach, ulcer
H2-blockers
Ranitidine
Famotidine
300 mg/tab p.o. at bedtime
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
4 mg initially; 2 mg after each loose stool max of
16 mgs for 24 hrs
Loperamide
64
Ancillary Drugs used in Managing Adverse Event
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
Zolpidem
25-50 mg p.o. at bed time
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
neurological
complications of
cycloserine and
isoniazid
Pyridoxine (vitamin B6)
At least 50 mg for every 250 mg of Cycloserine
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
Ancillary Drugs used in Managing Adverse Event
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
Ancillary Drugs used in Managing Adverse Event
Vestibular symptoms
Meclizine
25 mg/tab p.o. q 6 hrs
Musculoskeletal pain,
arthralgia, headaches
Ibuprofen
200 mg/tab p.o. q 8 hrs PRN in full stomach
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
Cutaneous reactions,
itching
Systemic hypersensitivity
reactions
Bronchospasm
100-200 mg/cap p.o. BID
Hydrocortisone cream
1-2% apply to affected area 3-4x/day PRN
Calamine/zinc oxide ointment*
Apply to affected area, 3-4x/day
Antihistamines
Diphenhydramine
Cetirizine
25-50 mg/cap p.o. q 6-8 hrs
10 mg/tab p.o. once a day
Corticosteroids
prednisone
dexamethasone
1-2 mg/kg/day and decrease dose at 5-10mg daily
4-8 mg/tab q 8hrs daily
Inhaled beta-agonists
Salbutamol and terbutaline
1 nebule every 4-6 hrs as needed
Inhaled Corticosteroids
Budesonide
Fluticasone
1 nebule every 12 hours
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
Ancillary Drugs used in Managing Adverse Event
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
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)
Erythropoietin
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 smearor 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)
DEFINITION
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
Died
Patient died for any reason during 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.
*Perform culture from two specimens every month during the intensive phase or do culture after 4, 6, 8, 12 and 16 weeks of
treatment
** Culture reversion (to positive) after an initial conversion; two consecutive cultures taken at least 30 days apart, are found to be
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
DS-TB &
MDR/RR-TB
Treatment Outcomes
TREATMENT OUTCOME
Cured
Treatment Outcome Definition for Drug Resistant Tuberculosis
treated with Standard Long Oral Regimen (SLOR)
and Individualized Treatment Regimen (ITR)
TREATMENT OUTCOME
DEFINITION
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:
Died
Patient died for any reason during 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
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
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
1
Screen
Designate health care worker (Triage) to screen patients with
prolonged cough immediately after they arrive at the facility.
Separate patients with symptoms of TB and patients on treatment
from other patients
2
Educate
Instruct all patients with cough on cough hygiene
(i.e. covering the nose and mouth when coughing or sneezing)
Educate on safe sputum disposal
3
Separate
Keep patients with symptoms of TB and patients on treatment away
from other patients and allow them to stay in a well-ventilated
waiting area
If possible, provide face masks or tissue to cover their mouths and
noses while waiting
4
Investigate for TB
or refer to TB Clinic
5
Monitor and evaluate
Perform recommended TB diagnostic tests or collect and send
specimen to TB diagnostic facility
72
Tuberculosis
Infection Prevention
and Control
Monitor and evaluate the TB prevention plan
Prevention of TB Transmission in Healthcare Settings
Screen
Educate
Separate
Designate of health care
worker (Triage) to screen
patients with 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
(i.e. covering the nose
and mouth when
coughing or sneezing
Educate on safe sputum
disposal
Segregate patients with TB
symptoms and patients on
TB treatment from other
patients and allow them to
stay in a well ventilated
waiting area
If possible, provide face
masks or tissue to cover
their mouths and noses
while waiting
Investigate
or refer
Perform recommended TB
diagnostic tests or collect
and send specimen to TB
diagnostic facility
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
(Eligible for TPT)
TST REQUIRED
(Eligible if positive)
<5yo, BC TB index
<5yo, CD TB index
HH contacts
≥5yo, BC TB index
with TB risk
≥5yo, BC TB index,
no TB risk
Close contacts
---
PLHIV
Ages ≥1yo
---
Other Risk
Groups
All ages, BC TB index
NOT ELIGIBLE*
--≥5yo, CD TB index
All ages, CD TB index
Age <1yo
(If not contact of a TB case)
Patient receiving dialysis,
Patients preparing for an
organ or hematological
transplantation
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
following symptoms:
• Cough
• Fever
• Anorexia/poor oral intake
• Weight loss/failure to thrive
• Fatigue
• Reduced playfulness/activity
*CXR is not required
prior to giving
preventive treatment
No
YES
WELL
YES, for < 2 weeks
YES, for ≥2 weeks
Follow up and check
for persistence of
symptoms
PRESUMPTIVE TB
Resolved?
Household or close
contact of
BACTERIOLOGICALLY
CONFIRMED PTB
Household or close
contact of CLINICALLY
DIAGNOSED PTB
Give preventive treatment
Perform TST
Positive
76
NO
• Follow the TB diagnostic algorithm.
• Reevaluate for preventive treatment
once active TB is excluded.
Negative or TST
is not available
• Educate about TB
• Advise to seek care if
TB symptoms occur
LTBI algorithm in HIV-negative at-risk individuals ≥ 5 years old
Follow Screening
Algorithm for Active TB
• NO TB Symptoms
• CXR, not done yet
• NO TB Symptoms
• Normal CXR
TST
TST
Positive or Not Required*
Do CXR
Negative or Not Available
• Educate about TB
• Advise to seek care if TB
symptoms occur
Positive or Not Required*
Treat for LTBI
Suggestive of TB?
NO
YES
Do further investigation
to rule out active TB
With Active TB
Treat According to
NTP Protocol
Treat for LTBI
NO Active TB
*TST is not required in individuals aged 5 years and older with TB risk factors
(i.e., PLHIV, diabetes, smokers, those with immune-suppressive medical
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
*CXR is not required
prior to giving
preventive treatment
Presence of any of the following:
• Poor weight gain
• Fever
• Current cough
• 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
contraindicated
Treat
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?
Do further investigation
to rule out active TB
With Active TB
NO Active TB
NO
YES
Treat for LTBI,
unless contraindicated
NO Active TB
Treat According to
NTP Protocol
79
With Active TB
Treat According to
NTP Protocol
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)
2.1-3
3.1-4
4.1-5
5.1-6
6.1-7
7.1-8
8.1-9
9.1-10
10.1-11
11.1-12
12.1-13
13.1-14
14.1-15
15.1-16
16.1-17
17.1-18
18.1-19
19.1-20
20.1-21
21.1-22
22.1-23
23.1-24
24.1-25
25.1-26
26.1-27
27.1-28
28.1-29
29.1-30
isoniazid 200mg/ 5ml
(at 10mg/kg)
0.75
1.0
1.25
1.5
1.75
2.0
2.25
2.5
2.75
3.0
3.25
3.5
3.75
4.0
4.25
4.5
4.75
5.0
5.25
5.5
5.75
6.0
6.25
6.5
6.75
7.0
7.25
7.5
81
Rifampicin 200mg/ 5ml
(at least 15mg/kg)
1.0
1.5
2.0
2.25
2.5
3.0
3.5
3.75
4.0
4.5
5.0
5.25
5.5
6.0
6.5
6.75
7.0
7.5
8.0
8.25
8.5
9.0
9.5
9.75
10.0
10.5
11.0
11.25
Dosing for 3-month weekly rifapentine and isoniazid
in adults and children ≥ 2 years old
>2 yo
Rifapentine
Body Weight (in kgs)
150mg/tab
No. of tablets
1 tab
10-12
2
12.1-14
3
14.1-16
3
16.1-18
3
18.1-20
3
20.1-22
3
22.1-24
3
24.1-25
4
25.1-27
4
27.1-30
4
30.1-32
5
32.1-35
5
35.1-37
5
37.1-40
5
40.1-42
5
42.1-45
5
45.1-50
6
50.1-55
6
55.1-58
6
≥58.1
Dosing for 6H and 4R in adults
Drug
Dosing in Adults
Age
2-11 yo
>12yo
Isoniazid 200mg/5ml Isoniazid 200mg/5ml
(at 25mg/kg)
(at 15mg/kg)
in ml
in ml
7.5ml
-8.75
-10.0
-11.0
-12.0
-13.0
-14.5
-15.0
-17.0
10.0
18.5
11.0
20.0
12.0
21.0
13.0
14.0
15.0
16.0
17.0
22.5
18.0
20.0
21.0
22.5
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
6 or 9 months of daily isoniazid
monotherapy (6H, 9H)
Four months of
daily rifampicin (4R)
Three months of daily rifampicin plus
isoniazid (3HR)
Dose by age and weight band
Age 10 years & older: 5 mg/kg/day
Age <10 years: 10 mg/kg/day (range, 7–15 mg)
Age 10 years & older: 10 mg/kg/day
Age <10 years: 15 mg/kg/day (range, 10–20 mg)
Isoniazid:
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
band
RH 75/50
mg (FDC)
Three months of rifapentine plus high
dose isoniazid weekly (12 doses)
(3HP)
4–7 kg
8–11 kg
1
2
Age 2-14 years
Medicine,
10–15 kg
Formulation
Isoniazid 100
3
mga
Rifapentine
150 mg
Isoniazid +
rifapentine
FDC
(150 mg/150
mg)b
a
b
3
4
>25 kg
Use adult
formulations
24–30 kg
31–34 kg
5
6
7
7
2
3
4
5
5
2
3
4
5
5
36–45 kg
46–55 kg
56–70 kg
3
3
3
3
6
6
6
6
6
3
3
3
3
3
300 mg formulation can be used to reduce the pill burden
use when available
83
16–24 kg
16–23 kg
Age >14 years
Medicine,
30–35 kg
Formulation
Isoniazid 300
3
mg
Rifapentine
150 mg
Isoniazid +
Rifapentine
FDC
(300 mg/300
mg)b
12–15 kg
>34 kg
>70 kg
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-toessential-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