TB / Atypical Mycobacteria Flashcards
How many people with latent TB go on to have active disease
5-10%
In HIV its 10% per year
When is a 5mm on PPD mantoux test positive? Who is 10mm? 15mm?
-HIV-positive or immunosuppressed patients
-Recent contacts of TB case
-fibrotic changes on chest radiograph consistent with old healed TB
10mm - pepeople with some risk factor eg immigrants
- work in healthcare
15mm - no risk factors and healthy
Why use Quantiferon-TB to test for latent infection
Zero cross-reactivity with BCG
latent TB rx? in HIV? Alternative?
6 months isoniazid daily (WHO)
9 months in HIV
Rifampicin for 4 months alternative
What % Tb is pulmonary? What if HIV positive ?
85%
In HIV
- PULMONARY– 40%
- EXTRAPULMONARY AND SYSTEMIC 30-40%
- PULMONARY PLUS EXTRAPULMONARY– 20-30%
Which TB usually causes GI TB infection? from?
Bovine TB
Consumption of milk
How much TB do you need for a positive AFB in sputum
Requires 10,000 organisms/ml
-Often takes 5 months of infection
Best quick way to test for TB
Molecular (Xpert MTB/RIF assay) - most specific and tells if rifampicin resistant
Pleural TB best dx if no Xpert MTB/RIF assay
Biopsy more sensitive than effusion
Pleural TB best dx if no Xpert MTB/RIF assay
Culture effusion - much more sensitive than biosy
Where 90% of TB lymphadenitis? Key Sx
Neck and head
Often Systemicall well - With NO fever
3 types of cutaneous TB
- Primary cutaneous (exogenous source)
-More like an ulcer - Secondary Acute hematogenous papules and pustules
* Lupus vulgaris: Multiple nodules and plaques
on face and neck - Tuberculids
-Allergic reaction without AFB in the skin
-Commonly with erythema nodosum
Most common presentation of GU TB
“Aseptic” pyuria (50-80%) i
Who has very high rates of developing tb meningitis as their presenting feature in 10%
children <1
Pulmonary disease 30-40%
TB meningitis or miliary disease 10%
Prevention of tb in children
BCG at birth
Logistic reasons sputum samples are poor for TB diagnosis
Smear only analyses 0.1ml
Requires cold chain transportation
Lack of well trained lab technicians
How to improve sensitivity of sputum collection for TB
Early morning
Centrifuge
Well trained staff
Fluorescence (auramine) microscopy
Why is fluorescence (auramine) microscpy better than ZN
Cheaper
Takes less time
More sensitive
[BUT microscope is much more expensive]
Culture for TB done on?
Lowenstein-jensen medium
Culture for TB done on?
Lowenstein-jensen medium
ZHeill-neilson stain what do cultured TB look like
Cording (like a purple star)
TB Drug sennsitiviy testing is usually using a …. medium? Eg?
Liquid - MGIT (Mycobacteria Growth Indicator Tube)
Solid - Eg Lowenstein-Jensen medium
-Add different abx to various tubes
Which is fastest diagnosis of TB
Xpert MTB/Rif - also works for csf
Which TB molecular test is read with a naked eye key issue?
LAMP - Can do multiple samples at once
Does NOT give any drug resistance
Who could you use a TB urine test for
LF-LAM test - Only patients with active disease
HIV positive with CD4 <100
Results in <30mins
Low sensitivities 50% if not above population
Which population is the XpertMTB ultra especially better in? Issue with all xpertmtb vs LAMP or PCR?
Hiv positive
If power goes out loose sample unlike pcr - also a bit less robust eg to dust / temperature
Which tb test for rapid screening of big populations eg prison
LAMP - Does16 tests at once
TB rx
RIPE
RI 6m
PE 2m only
Mono-resistance:
* Poly-resistance:
* Multidrug-Resistant ( MDR-TB): r
* Pre-XDR :
* Extensively Drug Resistant (XDR-TB):
Mono-resistance: One single drug
- Poly-resistance: Multiple drugs but not MDR/RR-TB
- Multidrug-Resistant ( MDR-TB): At least resistant to INH and Rif
- Rifampin resistant (RR-TB): Rifampin resistant tuberculosis. Consider equivalent as MDR ~90%.
- Pre-XDR : MDR/RR-TB + resistant to any fluoroquinolone
- Extensively Drug Resistant (XDR-TB): MDR/RR-TB + resistant to any fluoroquinolone + one additional Group A drug
which of the 1st line TB drugs is has the highest bacteriocidal activity
Isoniazid
Which RIPE TB drug has the best sterilising activity
Pyrazinamide
- Kills inactive bacteria in macrophages - > prevents relapse
TB where means you need to extend therapy to 12 months
CNS
Bone and joints
To 12 months
[Disseminated only 6months]
In TB meningitis and new diagnosis HIV when start ARV?
Not until end of the intensive phase (within 4-8weeks)
Start ARV within 2 weeks if CD4 <50 and prophylactic abx in resource rich setting
Most common acute complications TB meningitis
SIADH / cerebral salt wasting - HypoNa in 50%
Vasculitis/stroke ~60% Eg Hemiparesis
Tuburculomas
TB meningitis how to prevent vasculitis
Aspirin
Which TB course can be 4 months
Rifapentine / INH /PZA / Moxifloxacin
Protrusion of back with bruising clinical name [in Potts]
Gibus
What part of vertebrae does pots start on?
Lytic destruction of anterior portion of the vertebral body
50% of MDRTB from
India
Russia
China
rifampicin-susceptible and isoniazid-resistant
tuberculosis rx? Exemptions?
rifampicin, ethambutol, pyrazinamide
and levofloxacin for 6 (or 9) months§
in cases where resistance to rifampicin cannot be
excluded (i.e. unknown susceptibility to rifampicin;
indeterminate/error results on Xpert MTB/RIF);
* known or suspected resistance to levofloxacin;
* known intolerance to fluoroquinolones;
* known or suspected risk for prolonged QT-interval;
MDR TB short course rx
BPaLM is 6 months
bedaquiline, pretomanid, linezolid, moxifloxacin
BPaL is 9 months (I’ll B your PaL for longer)
How to make long regime for xdr TB
Group A Pick 3
Levofloxacin/Moxifloxacin
Bedaquiline
Linezolid
Add 2 of: Group B
Clofazimine
Cycloserine or
Terizidone
If still don’t have 4 drugs…Add from Group C
Ethambutol
Delamanid
Pyrazinamide
Amikacin
Ethionamide/Prothionamide
Imipenem-cilastatin
Meropenem
PAS
Key side effects linezolid
Myelosuppression, peripheral and optic neuropathy
TB resistant to Rif/Isoniazid, fluoro/aminoglycoside =? rx?
XDR TB
Individualised long regime
-At least 4 drugs in the intensive phase
-At least 3 drugs when bedaquiline stopped (as max 6m)
-Treat for 15m following culture conversion
Surgery if localised disease
Treatment in hospital
When must you treat TB in a hospital?
XDR TB
Household contact rx of MDR TB
Moxifloxacin 6 months
Who should get screened for TB in HIV
Any 1 of 4 symptoms
current cough, fever, weight loss or night sweats
Who should get screened for TB in HIV
Any of 4 symptoms
-current cough, fever, weight loss or night sweats
Crp>5
Benefits of LAM urine POC testing in HIV
Picks up most cases of those who would die soon
Cheap test
Rx of TB in HIV? When start ARV?
Same as normal RIPE
Start early ARV during TB rx
ALWAYS within 2 weeks if CD4 <50
Or within 8 weeks otherwise
Only side effect of starting ART within 2 weeks of TB therapy
Immune reconstruction syndrome (no increase in mortality)
When might you delay ARV slightly in TB-HIV coinfection
TB meningitis - wait 4-8 weeks
Best ARV combo for HIV TB? What extra consideration?
2 NRTIs
-Tenofovir (TDF)
-Emtricitabine (FTC)
Intergrase inhibitor
-Dolutegravir (DTG)
Double dose as interaction with rifampicin
[Double D]
How do kids present differently with TB
More variable - Still mostly pulmonary
Lymphadenitis in 40%
Failure to thrive
[Also higher proportion of disseminated/extrapulmonary]
Rx TB in kids who are a contact of positive case
6 months isoniazid (other options to….)
Key indicator a kid has TB
Failure to thrive
Especially static weight /weight loss
Joint disease in paediatric TB is usually
1 joint - usually large Eg Hip/knee
What sample can you use in Xpert for kids TB
Sputum, gastric aspirate, stool
Tb Rx kids? Dosing? When adult doses?
Same as adulits
Dosing based on weight - often needs re dosed monthly
Adult dosing when >25kg
Key indicator of improvement in kids on TB rx
Weight gain
When start ART in kids with TB? Other key considerations?
ART within 2-8 weeks of starting TB Rx
Cotrimoxazole preventive therapy
Pyridoxine supplement
Nutritional support - eg continue breast feeding until 2yrs (with solid food introduction at 6m)
TB drug side effects in kids
Rare
[Be aware of hepatotoxicity]
When can congenital TB be diagnosed
Proven TB in the infant + one of the following:
Lesions in 1st week of life
primary hepatic complex
maternal genital tract or placental tuberculosis
exclusion of postnatal transmission by thorough investigation of contacts
Neonatal TB / congenital TB Rx?
RIPE for 6 months and for mother
When BCG contraindicated in babies
preterm <34weeks
weight <2kg
Which tb drug may cause thrombocytopenia
Rifampicin
Which tb drug may cause CN VIII damage and ototoxicitiy
Streptomycin
Unilateral chain of matted lymph nodes with occasionaly ulcerate =?
Tb lymphadenitis
Who needs latent TB testing if ASx
Household contacts, HIV
2 options for screening test for LTBI? if positive?
TST / IFGRA
CXR
If neg - treat for latent TB
If positive - screen for active TB
If prev BCG + positive PPD …?
Treat as positive result
Key thing to do with follow up of TB rx
Smear test +/- XR after 2 months
[Ideally fluroscopy]
Fully suseptible RIPE TB. Positive smear after 2 months plan?
Suspicion of Drug resistant - switch to second line regime
Not suspicious [eg pt cliically improved]- c§arry on and switch to continuation phase
Pregnant women with TB rx? Which commonly used drug (not in RIPE) is contraindicated? Management of baby?
RIPE as normal
with pyridoxine supplement
Sreptomycin is contraindicated - congenital deafness in 17%
Rule out TB (gastric aspirate) in baby then 6 months Isoniazid
Differentials of Potts’
Brucella
Staph aureus
Salmonella
Bar TB meningitis what other TB infection should you use steroids
Pericarditis
Key thing to exclude in new maculopapular rash starting drug therapy Eg RIPE? When would you re challenge pt
Oral / mucosal lesions - SJS
Re challenge if only maculopapular rash
DO NOT re challenge if blisters/bullae/urticaria
LFTS to stop TB strugs and re challnge
AST/ALT >3x upper limit with Sx
or 5x Upper limit
Which TB drug is most common for hepatitis if if <2weeks? >1m of therapy
Rifampicin
Pyrazinamide
What is the rpoB gene
RNA polymerase B sub unit
Mutations = rifampicin resistance
What is GenoTypeMTBDR plus ? Benefit over geneXpert ? Issue?
Manual PCR test for TB
Gives Rifampicin and Isoniazid resistance
Needs to be sent to regional centre - Biosecuirty level 3
Which gene Xpert gives more than rifampicin resistance testing
Xpert MTB/XDR
Isoniazid, fluoroquinolones, streptomycin, amikacin, ethambutol..
katG and inhA are?
Genes that confer isoniazid resistance
[inhA - less resistance but still some]
rpoB and katG gene mutations in TB means? Rx?
Rifampicin and isoniazid resistance
=MDR TB rx
BPaLM - bedaquiline, pretomanid, linezolid, moxifloxacin
for 6 months
2 main risk factors of having MDR TB
Previous Rx
Household contact of MDR-TB
Bedaquiline and pretomanid class?
Bedaquiline - ATP synthase inhibitor
-Bactericidal and sterilising activity
Pretomanid - Nitroimidazole
- Prevents bedaquiline resistance
-Bacteriocidal and sterilising activity
What type of TB - Isoniazid, Rifapmpicin and a fluoroquinolone resistance is? rx?
Pre-XDR TB
BPaL
Who is BPaL not recommended for in MDR TB
CNS / Bone/joint / milliary disease as poor penetration
CD4<50
“Swimming pool” or “fish tank granuloma”
M. marinum
– Optimal growth temp. 30 C
Middle age male smokers, often heavy alcohol users. Upper lobe cavitary disease; resembles M. tuberculosis disease
MAI, M. kansasii
Older nonsmoking females, no apparent underlying disease
RML, lingular bronchiectasis (Lady Windermere Syndrome).
Which non TB mycobacteria?
MAI, M. abscessus
what am I
Rice bodies
Due to granuloma formation in tendon sheaths
-Often mycobacteria (eg MAC) or fungal (eg sporotrichosis)
HIV uncontrolled with anaemia neutropenia diarrhoea weight loss
BM biopsy -
Globi associated with disseminated MAC (BM biopsy
-All the red is MAC
Mycobacterium kansasii rx
RIPE
What am I if not TB? rx?
Scrofula: M scrofulaceum
Rifampin + clary + ethambutol
immunocompromised. What do you Suspect in situation of recurrent positive AFB smear and negative routine AFB culture?
Mycobacterium hemophilum
[Cipro+ rifabutin+ clarithromycin]
Contact with fish tanks at home or work prior to infection.
papulonodular lesion on finger or hand remained confined to the skin and lymphatics resembling sporotrichosis =? rx?
Mycobacterium marinum
Clary(or rifampin) + Ethambutol
+ debridement if possible
[Marinum = sea = CE]
MAC rx
Azithromycin
Ethambutol
Rifampin
[Minimum 12 months]
Rx M abscessus/chelonae
clarithromycin (l00%)
+linezolid (90%)
[tobramycin (l00%) only IV]
Most common finding CT TB meningitis?
Normal
Most common abnormal - hydrocephalus
How many ml of csf for tb gene expert?
Need 6ml =120 drops for good sensitivity
Define congenital TB
hematogenous spread - umbilical cord or aspiration/ingestion AF at birth
Define neonatal TB
TB acquired from infectious contact after birth
How specific is TB LAM
100%
Ie if its positive, you’ve got TB
MDR TB CNS rx?
CNS penetrating group A
Levo/moxi, linezolid
B - None penetrate
C - meropenem + co-amox
Amikacin
Requirements for an anti-TB drug
Ability to prevent emergence of resistance in the companion drug, early bactericidal activity, and sterilizing activity
Define early bactericidal activity
The fall in log (10) colony forming units of mycobacterium tuberculosis per ml sputum per day during the first 2 days of treatment
Define sterilizing activity
The ability to kill either these non-replicating bacteria or dormant bacteria under hypoxic conditions
When do you use corticosteroids in TB
As an adjunct when treating TB meningitis and DR TB has been ruled out
Who is the 4-month TB rx regimen recommended for?
People who are 12 yrs and older
Weight > 40 kg
HIV, CD4 > 100 who are on or planning to be on efavirenz
No contraindications to this regiment
People who have a negative sputum culture, considered to have paucibacillary disease
XDR TB additional non-medication treatment
Surgery if localized dz
Treat in hospital
Treat HIV
Comprehensive monitoring with full social support to enable adherence
Who should receive LTBI treatment for 36 months
Adults and adolescents living with HIV, in settings with high TB incidence and transmission who are unknown or have a positive TST
How long should pregnant women (at high risk) and children receive treatment for LTBI
9 months, daily or twice weekly
What are the alternative treatments for LTBI
*Just learn isoniazid 6 months
Rifampicin + INH x3 months
Rifapentine + INH weekly x3 months
Rifampicin x3-4 months
What are the adverse effects of INH
Hepatitis, neuropathy, hypersensitivity, and lupus like syndrome
What are the adverse effects of rifampin
maculopapular rash, flushing, hepatitis, GI upset, thrombocytopenia, drug interactions (p450 cytochrome interaction)
What are the adverse effects of pyrazinamide
athralgia, hyperuricemia, GI upset, (late) hepatitits
what are the adverse effects of ethambutol
retro-bulbar neuritis, rash (rare)
what are the adverse effects of streptomycin
ototoxicity, dermatological reactions (DRESS, SJS, mouth ulcers)
Linezolid adverse effects
Myelosuppression, peripheral and optic neuropathy
BPaL/BPaLM adverse effects
Myelosuppression, peripheral and optic neuropathy (LNZ)
Hepatotoxicity, lactic acidosis, QT prolongation (>500), and pancreatitis
Which mycobacteria is wound, skin and soft tissue infections, disseminated and pulmonary infections, particularly in immunocomprosed hosts and a rapid grower?
Rx?
M chelonae
Clarithromycin + linezolid
Why is sputum in miliary TB often negative
It’s interstitial rather than intraalveolar
Multi bacillary cutaneous TB - name 3
-primary-inoculation TB or tuberculous chancre (by direct inoculation)
-(scrofula) by extension from underlying tissue
-TB periorificialis (by extension)
-acute military TB
-gumma (by hematogenous dissemination).
What are the molecular tests for TB
Gen Xpert (high sensitivity/Specificity)
TrueNAT (high sensitivity/Specificity)
LAMP (not ideal for high HIV prevalence settings, due to poor sensitivity in smear negative patients, but ideal for mass screenings in low HIV settings)
Line probe Assay ( Hain TEST MTBDR _ resistance to Rif and INH)
TB treatment length is extended when?
Drug combo for a 4 month course in pulm tb?
Bone / joint / CNS - 9-12 months
Rifapentin / INH / Pyrazidamide / Moxifloxacin
Who can get a 4-month regime for TB
[Rifapentin / ING / Pyrazidamide / Moxifloxacin]
People who are 12 years and older / Weight > 40 Kg /
People with HIV with CD4 >100 cells, on/planning efavirenz
No interactions between antituberculosis and antiretroviral medications
People who have no contraindications to this regimen
People with a negative sp§utum culture who are considered to have a paucibacillary disease
Which of the molecular tests do not cover INH resistance? What does this mean?
Gene Xpert or TruNAT alone will miss INH-resistant mycobacteria.
So ideally a Hain test (line probe assay combine for early detection)
What is the LAM urine test looking for?
lipoarabinomanam
Name the group B drugs for TB
Clofazimine
Cycloserine OR terizodone
INHA confers resistance to?
INH and ethionamide
Which molecular TB test not favourited in HIV positive
LAMP not favorable due to poor sensitivity in smear neg
