TB Flashcards
What ARV to start in HIV/TB coinfection?
Tdf/ftc plus EFV - most studied
ABC/3TC also ok but Iris and drug hypersensitivity both common may be hard to tell between the 2
RAL or DTG suitable 3rd agents but less data
Rifabutin instead of rifampicin if needing booster - only ritonavir not to use cobi with rifabutin or rifampicin
Dose of RAL if using with rifampicin?
800mg BD - REFLATE TB2 study ral 400mg bd ‘not non inferior’ to EFV
Dose of DTG if used with rifampicin
50mg BD - switch to OD 2 weeks after stopping rifampicin
Can doravirine be used in context of tb coinfection?
Possible with rifabutin only and at 100mg BD - to
Continue this for 2 weeks after dropping rifabutin
What tb treatment
To give if patient already suppressed on ARVs?
If on EFV, dtg or RAL plus 2 nucs then rifampicin and double dose dtg and ral
If on a boosted PI to use rifabutin instead
If on cobi rifabutin would need to be 150mg 3x week
Steroid DDI
Accelerated by rifamycins - increase steroid dose
Also with PI - risk of adrenal suppression
Methadone DDI tb tx
Reduced plasma levels and increased elimination with rifampicin - may need close monitoring and side effects on cessation rifampicin
What if patient has hep C and TB at same time?
Majority of patients - treat TB first then Hep C as DAA contraindicated with rifampicin
Definition of DILI
AST or ALT >3x ULN in presence of symptoms or
AST or ALT >5x ULN in absence of symptoms
Management of DILI
Consider stopping all potentially hepatotoxic drugs immediately - isoniazid, rifampicin, pyrazinamide, septrin - continue ART unless likely to cause hepatotoxicity
Check hep A, B, C serology
Ask about exposure to other hepatotoxic eg alcohol
Until cause identified treat with two or more anti tv drugs without risk of hepatotoxicity eg ethambutol, streptomycin, levo
Once ALT/AST drops below 2x ULN reintroduce as per table
Which drugs have highest risk of hepatotoxicity in pre existing liver disease
Pyrazinamide followed by isoniazid then rifampicin
What to do if hepatotoxicity occurs in individual with pre existing liver disease? (Rise of 2-3x abnormal baseline lfts)
Avoid pyrazinamide and treat with isoniazid and rifampicin for 9/12 adding ethambutol for first 8 weeks
Or avoid isoniazid and tx with rifampicin ethambutol pyrazinamide and levo for 6/12
Monitor bloods at least 2 weekly and patient to report any anorexia, nausea, vomiting, jaundice
GI side effects of TB treatment
Epigastric pain, nausea, vomiting are common especially in first 2 weeks
Try anti emetics
Can take with food (except rifampicin doses under 600mg), change timings, could switch to a regime without food restrictions if needed
Peripheral neuropathy
Occurs with isoniazid so pyridoxine co administered. can increase pyridoxine to 50mg od if peripheral neuropathy occurs.
Second line drugs need higher dose pyridoxine
Rash (as tx SE)
Most often caused by ethambutol
Occurs in first 2/12 tx
Widespread or worsening rash with systemic symptoms - stop all drugs and careful reintroduction as per table
Reintroduction of tb drugs after Dili or rash
Reintroduce all at once
If reaction occurs to all at once sequentially introduce as per table
If reaction severe or occurs again after reintroduction start with 1/10th first day dose of each drug
Definition of paradoxical TB IRIS
One major or two minor clinical criteria - no alternative explanation for deterioration
Major - new/enlarging LNs, cold abscesses, focal tissue involvement. New or worsening radiological features. New or worsening CNS TB. New or worsening serositis.
Minor - new or worsening constitutional symptoms, new or worsening resp symptoms, new or worsening abdo pain, in retrospect resolution of clinical or radiological findings without having made a change in tb tx
Definition unmasking IRIS
Major and one of two minor criteria must be met
Major - not receiving treatment when ART is started and presents with tb within 3 months of starting att
Minor - heightened intensity of clinical manifestations, once established on tb tx a clinical course that is complicated by a paradoxical reaction
When does TB IRIS occur?
Within 60 days
Median 15 days
Most individuals had advanced HIV
When to start ARVs in tb/hiv co infection
SAPIT trial
If CD4 <50 start within 2 weeks
Otherwise as soon as practically possible but within 4 weeks
Delay until 8 weeks for CNS TB
Symptoms of TB IRIS
Fever and increased or new lymphadenopathy
Dusky red skin overkykng
Need to exclude - tx failure, drug hypersensitivity, OI, malignancy
Management TB IRIS
Corticosteroids - prednisolone or methylpred 1-1.5mg/kg with gradual reduction after 1-2 weeks
Rifampicin will reduce steroid effect
Management of TB in pregnancy
Usual drugs at usual doses - no data to suggest teratogenic effect. Isoniazid not teratogenic even if used in first 4/12.
Increased risk peripheral neuropathy with isoniazid so increase pyridoxine
Tx latent tb in pregnancy
Isoniazid recommended for pregnant women who are likely to have acquired tb recently and therefore at a higher risk of disease progression. If less risk then can be deferred until after delivery.
Risks for babies born to mothers tx for tb in pregnancy
May be LBW
Need review by drs for congenital TB
Screening of household contact of mother should be completed before baby born
Contact tracing for TB
CXR for asymptomatic close contacts over 65
Don’t routinely assess social contacts unless for laryngeal tb - index case has already infected someone else, social contacts immunosuppressed
Diagnosis active TB
Microscopy for AFB plus culture and sensitivity
Molecular testing - XPERT MTB/RIF ULTRA - rapid confirmation TB, differentiates silent mutations from resistance conferring ones
All specimens still need full culture - liquid culture 7-28 days
Symptoms of TB meningitis
Fever, headache, vomitting, gradual onset duration. Meningism, behavioural changes, alterations in consciousness
CSF findings for TB meningitis
Mononuclear fell lymphocytic predominant pleocytosis in 60-85%
In advanced HIV CSF can be acellular
Low glucose (<2.5) high protein (1-5) suggestive of TBM
Culture is gold standard - AFB ZN stain - requires 6ml CSF
WHO recommends using PCR but neg result doesn’t rule out still need culture
Classic TB histology findings
Epithelioid cell granulomas with or without longhand cells and cassation, necrosis and AFB
FUNGAL STAINING must always be undertaken to exclude mycosis
MDR TB definition
Resistance to at least isoniazid and rifampicin
XDR TB definition
Resistance to isoniazid, rifampicin and quinolones and at least one of the second line injectables eg amikacin
How to detect drug resistant TB?
Routine use of whole genome sequencing of culture isolates
Routine use of PCR also
High proportion with rifampicin resistance also have isoniazid resistance so tx as MDR
High TB incidence
> 151/100000
Medium TB incidence 40-150/100000 person years
To diagnose latent tb
People from medium to high incidence countries - IGRA and CXR
Also those from low incidence countries but with other risk factors
What to do if IGRA result borderline
Repeat within 4 weeks
What to do if IGRA pos
CXR and if negative tx for LTBI and if not then for tb investigations
Treatment for LTBI
Daily isoniazid with pyridoxine for 6/12
Daily isoniazid with pyridoxine and rifampicin for 3/12
In certain circumstances isoniazid and rifampicin with pyridoxine twice weekly for 3/12
Balance benefit of tx against risk of hepatotoxicity of isoniazid in those with risk factors
What should patients given isoniazid be aware of?
Risk of hepatotoxicity
Look out for anorexia, nausea, vomiting, abdo pain, persistent fatigue , dark coloured urine, pale stools, jaundice. Contact us urgently.
TB treatment
4 drugs for 2 months, 2 drugs for 4 months
Isoniazid 5mg/kg/day 6 months
Rifampicin 10mg/kg/day 6 months
Pyrazinamide 25-35mh/kg 2/12
Ethambutol 15-20mg/kg
TB meningitis treatment
Up to 12 months
Also reducing course dexamethasone IV for first 4 weeks then 4 weeks oral therapy
Tb treatment interruption during intensive phase
<14 days continue and complete planned number of doses
>14 days restart tx from beginning
Tb treatment interruption rules continuation phase
> 80% doses and and sputum AFB negative on initial testing - further therapy may not be necessary
80% doses and sputum was AFB pos or disease was extra pulmonary - complete course
<80% and <3/12 lapse / continue all doses until therapy completed unless consecutive lapse >2/12 and can’t be completed within 9 months then needs to restart from beginning
<80% doses and lapse >3/12 - restart from beginning
Pre treatment testing - TB
Hiv cd4 and VL, lfts, u+e, fbc, how b and c, visual acuity with Snellen chart and colour vision with ishihara plates before starting ethambutol
After how long on treatment will there be clinical improvement and negative cultures?
3/12
Causes of treatment failure or relapse
Suboptimal prescription of or adherence to appropriate tb tx.
Presence or development of drug resistance, use of intermittent tb therapy, malabsorption of tb drugs,
If treatment failure or relapse is diagnosed what tests should be done?
Drug susceptibility testing and rapid resistance testing
If too unwell to wait for result use rapid rifampicin resistance result and prev result to start a new regime
What should patient with isoniazid mono resistant isolates be treated with?
Rifampicin, ethambutol, levofloxazin, pyrazinamide
Treatment for MDR-TB
At least 4 active drugs all oral where possible
DOT/VOT if needed
Bedaquiline - 24 weeks - first line. Qt prolongation so caution in cardiac patients and not to use other qt prolonging drugs for 6/12 after dropping
