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Transcript
RespNET clinic aide memoire: TB. Oct 2016
Tuberculosis
Notifiable tuberculosis infections are caused by M. Tuberculosis complex organisms (M. tuberculosis, M.
africanum, and M. bovis)
Initial infection is pulmonary and is acquired by droplet infection. In some cases infection is completely
cleared by immune system, but in the majority, a small number of viable mycobacteria remain in a
dormant state. This is latent TB and is, by definition asymptomatic. The risk of progression to Post-primary
TB is around 10% (reduced by ~60% with chemoprophylaxis). It results from re-activation of the latent
focus and can occur months to decades after the initial infection.
History and Examination
Pulmonary TB (commonly post-primary in adults)
 Chronic cough
 Intermittent fever and drenching night sweats
 Weight loss
 Haemoptysys
 Chest pain (relatively uncommon)
 Breathlessness is usually a late feature when a large amount of lung is destroyed or there is a large
effusion. (But note dyspnoea/hypoxia is more common in miliary TB – associated with ALI/ARDS)
 On examination, classically upper lobe chest signs
o In primary TB may also be:
 erythema nodosum
 phylectenular conjunctivitis
 focal lung collapse or wheeze due to mediastinal node enlargement and bronchial
narrowing/ obstruction
 History must include exposure history and risk factors for TB:
o NB: In adults, >50% cases result from re-activation of endogenous latent tuberculosis, rather
than a recent infection from someone else
o Close contacts of infectious cases
o Those who have lived in or (extensively) travelled to places where TB is very common
o Those living in ethnic minorities where TB is very common
o Immunusuprresion eg HIV, other significant major conditions (also very young and very old)
o Malnutrition or poor health from homelessness, drug addiction or alcoholism
o Those living in overcrowded or poor conditions, e.g. hostels
Extrapulmonary TB
Site
Lymph node
Spinal
Bone
Features
Classical ‘cold abscess’ is firm discrete
swelling without redness and warmth
Pain. Extradural abscess/spinal collapse can
cause motor/sensory symptoms including
cord/ cauda compression, e.g. sphincter
disturbance.
Paraspinal abscess may present as loin mass,
or psoas abscess causing psoas spasm + hip
flexion. Compression of nerve roots can
mimic abdominal pathology
Occasionally, symptoms of a mono-arthritis
Investigations
LN aspirate of pus. Trucut biopsy.
Excision biopsy.
MRI
Biopsy if location amenable
Joint aspiration
RespNET clinic aide memoire: TB. Oct 2016
GI
Acute abdomen (RIF pain or mass, or
symptoms of intestinal obstruction).
Can mimic Crohns (ileocaecal TB)
Sometimes PR bleeding from colonic disease
GU
Dysuria, haematuria, nocturia, loin or anterior
abdominal pain.
Testicular mass if testes involved
Infertility/menorrhagia in female genital tract
Miliary/disseminated Fever, weight loss, malaise, headache,
dyspnoea, hypoxaemia
Abdo/pelvis CT
Endoscopy +/- biopsy
CNS
CT, MRI
LP
Skin
Pericardial
Anorexia, malaise, headache, vomiting,
altered behaviour, irritability, drowsiness,
seizures, focal neurological signs, cerebellar
signs, extrapyradimal movement disorders
Usually sinus formation discharging from
lymph node, bone, or urogenital tract
(“scrofuloderma”).
Focal skin lesions: lupus vulgaris, panniculitis,
erythema induratum.
Fever, malaise, night sweats, cough
Hypotension, peripheral oedema, raised JVP,
pulsus paradoxus, abdominal distension,
breathlessness (if tamponade)
EMUs
USS (testicular/transvaginal)
Uretoscopy/cystoscopy/hysteroscopy
Biopsy
Biopsy
ECHO
Paracentesis (low diagnostic yield)
Investigations
 Chest X-Ray
o Note radiological features of old TB, e.g. calcified granulomata can be considered as latent
TB infection
 Bloods: FBC (lymphopaenia), elevated ESR, elevated globulins and reduced albumin, renal function,
LFTs (important to know baseline as may need refinement of anti-TB therapy or monitoring through
treatment if abnormal).
 3 sputum samples (at least one should be an early morning sample, and several hours apart – can
be kept in fridge and brought to lab the following day) – for smear (Ziehl-Nielson or Auramine
stain), and culture (can take up to 6 weeks)
 CT chest:
o Primary TB
 consolidation, esp lower lobes, RML and lingula, and anterior segments of upper
lobes
 mediastinal lymphadenopathy (note this is conspicuously absent in post-primary
disease, unless associated with HIV)
 pleural effusions (also seen in post-primary TB)
 bronchiectasis
o Post-primary TB
 calcified granulomas. Previous fibrotic changes (evidence of original primary
infection)
 tree-in bud appearance of lung parenchyma
 Patchy or confluent upper lobe (or apical lower lobe) shadowing
 Cavitatory opacities upper lobes
 Pleural effusions
RespNET clinic aide memoire: TB. Oct 2016
o Miliary TB
 miliary shadowing (haematogenously disseminated miliary TB)

CT brain/ MRI spine
o If neurological deficit to look for evidence of meningeal/ spinal disease
 Lumbar puncture (if meningeal TB suspected)
o High (mononuclear) cell count 10-1000/mm3, low CSF glucose (< 1/2 plasma), high protein (15g/L)
 bronchoscopy
o lavage for TB bacteriology and cytology
o Transbronchial needle aspiration (TBNA) esp. of subcarinal lymph nodes for cytology
o Occasionally biopsy of nodal tissue eroding into endobronchial wall
 tissue/lymph node aspirate (FNA) for bacteriology
 tissue/lymph node aspirate (FNA) for histology/cytology:
o non-caseating granulomata
o Langhans Giant cells
o Note in HIV +ve patients, granuloma formation may not occur if CD4 <200, however AFB
more likely to be seen in tissue
o PCR of tissue where AFB seen – may help differentiate between MTB and MAI.
 Pleural fluid analysis and biopsy
o Lymphocytic exudative pleural effusion – protein usually very high >50g/L, pH usually 7.37.4
o Pleural biopsy (Abrams needle) for histology/ bacteriology
o Auramine deaminase in pleural fluid – elevated in TB
 Early morning urines, only useful if renal disease (e.g with sterile pyuria) or miliary disease
suspected
 Vitamin D level. Vitamin D deficiency has adverse consequences on the immune response to TB.
Check serum 25-OH-D3 levels. Replace if deficient with 250mcg (10,000IU) calciferol daily for 8
weeks.
 HIV testing – all individuals diagnosed with TB should be offered and recommended an HIV test.
Rates of co-infection in London are 17-25%
 PCR/ molecular probes
o Can be used on cultured mycobacteria for species confirmation (e.g. prior to an extensive
contact tracing initiative)
o Can be used on cultured mycobacteria for rifampicin resistance testing (if risk factors for
MDR-TB present) – rifampicicn resistance is commonly associated with isoniazid resistance,
and therefore is a marker of MDR-TB
o Can be used to identify TB in smear negative fluid samples
 But note significant false negative rate in pleural fluid and CSF
o Can be used on formalin-fixed biopsy samples when AFB are seen on microscopy
 Mantoux (Tuberculin) test
- intradermal injection of 0.1ml (2Tuberculin Units) Tuberculin. Measurement at 48-72h of diameter of
skin lesion.
 < 6mm – negative
 6-15mm – if history of previous BCG vaccination – negative


≥ 6mm – if no history of previous BCG vaccination – positive
≥ 15mm – if history of previous BCG vaccination – positive (if no history of previous
BCG vaccination, said to be strongly positive)
RespNET clinic aide memoire: TB. Oct 2016
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o A positive test should indicate latent or active TB. But note:
- False +ves can occur with: prior BCG vaccination, opportunistic
environmental mycobacteria
- False –ves can occur with: co-infection with HIV, cytotoxics,
immunosuppressive therapy (e.g. methotrexate), extensive TB (pulmonary or
miliary)
o The main role for these tests is in screening for latent disease. They cannot differentiate
between latent and active TB infection, but a positive test may be supporting evidence for
the diagnosis of TB, where tuberculosis has not been proven histologically/microbiologically.
Similarly a negative test may be supporting evidence to help exclude TB
Interferon-gamma release assays (IGRA): more specific and sensitive than tuberculin skin tests.
They measure interferon gamma release from T cells in response to early tuberculosis antigens:
ESAT-6 and CFP-10. These antigens are not present in BCG or most environmental mycobacteria.
Note that false negatives are less common than in Mantoux, but can still occur in profound
immunosuppression/ T cell unresponsiveness.
o QuantiFERON-TB Gold: measures IFN-gamma release from whole blood incubated with
ESAT-6 and CFP-10
o T-SPOT: measures (quantitatively) interferon-gamma producing T cells amongst peripheral
blood mononuclear cells (isolated from whole blood) incubated with ESAT-6 and CFP-10
o The main role for these tests is in screening for latent disease. They cannot differentiate
between latent and active TB infection, but a positive test may be supporting evidence for
the diagnosis of TB, where tuberculosis has not been proven histologically/microbiologically.
Similarly a negative test may be supporting evidence to help exclude TB.
prior to ethambutol use: testing of visual acuity with Snellen chart and colour vision with Ishihara
plates.
BCG scar inspection – to determine if previously vaccinated
Response to TB therapy – note that in many cases diagnosis is based on supporting but inconclusive
evidence from a range of sources. Clinical improvement on antituberculous therapy adds additional
confirmatory evidence of TB.
Contact tracing (by TB nurses - please see algorithm in NICE quick reference guide, for investigation
of household/close contacts who are children)
o Household contacts and close contacts (e.g. girlfriend) of patient with TB at any site
 If age <35, test for latent TB (Mantoux, then IGRA if positive) and active TB (Chest XRay). Treat latent and active disease where present. If no active or latent disease and
no BCG vaccination, consider vaccination.
 If age >35, look for any evidence of active disease on chest-X-ray. Investigate and
treat where appropriate.
o Casual contacts – no need to investigate unless index case very infectious or contact very
vulnerable.
o Contacts of smear-positive TB who are HIV +ve – Mantoux may be unreliable – consider
treating for latent TB once active TB excluded
New entrants to UK screening
o Chest X-ray (unless age <11 or pregnant) – investigate as appropriate anyone with an
abnormal chest X-ray
o Risk assess for HIV and consider testing
o Mantoux test if <16 or age 16-35 and from sub-Saharan Africa or country with high
incidence of TB
RespNET clinic aide memoire: TB. Oct 2016
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o Interferon gamma test if Mantoux positive (unvaccinated person) or strongly positive
(vaccinated person). Positive test means latent or active TB
o Assess individuals with positive interferon gamma test for active TB (chest X-ray and clinical
features)
o Treat active TB. Treat latent TB in individuals below age 35
o Consider BCG vaccination if unvaccinated and Mantoux negative, and from high risk country
and age 35 or below
New NHS employee screening
o Documentary evidence of TB testing/ BCG scar inspection by occupational health physician
o Mantoux (within last 5 years if available) if no evidence of prior BCG
o If Mantoux is positive, follow with Chest X-ray to look for active disease. Treat active and
latent infection
o Offer BCG to unvaccinated Mantoux-negative staff (risk assess for HIV first)
Evaluation of possible latent TB prior to immunosuppressive therapy (e.g TNF-alpha)
o 2005 BTS guidelines advocate the following:
 CXR in all. If history, clinical features, or X-ray features suggest active TB, 6 months of
standard TB chemotherapy should be given. Anti-TNF therapy can begin 2 months
into this.
 If the patient has had TB in the past and had an adequate full course of treatment,
no further action other than monitoring for symptoms/signs of TB is required. This
should include a chest X-ray 3 months into therapy, and culture of sputum if it
develops.
 Those with radiological features of old TB (untreated) on the X-ray or in
extrapulmonary sites who have never been treated should be considered to have
“high risk” latent TB. They should generally all receive chemoprophylaxis before
anti-TNF therapy is started.
 Those with a normal chest-X-ray not on immunosuppressive therapy (will be a
minority) should have a Mantoux test. This should be interpreted in light of their
previous BCG vaccination history. ≥ 6mm is positive if no prior BCG. ≥ 15mm is
positive if they have previously had BCG. Treat latent TB in those where the risk of
acquiring TB will outweigh the risk of TB-drug associated hepatotoxicity (black
Africans over the age of 15, south Asians born outside the UK and patients from
other ethnic groups who have been resident in the UK for less than 5yr). If the risk
of hepatitis is greater, the patient should be monitored regularly on anti-TNF therapy
and any symptoms suggestive of TB promptly investigated. TNF therapy can be
started concurrently with anti-TNF therapy.
 Those with a normal chest X-ray on immunosuppressive therapy cannot have a
Mantoux test, as it will be unreliable. These cases could be assumed to have latent
TB (although see IGRA testing below). Chemoprophylaxis should be given where the
risk of acquiring TB is considered greater than the risk of TB-drug associated
hepatotoxicity (black Africans over the age of 15, south Asians born outside the UK
and patients from other ethnic groups who have been resident in the UK for less
than 5yr). If the risk of hepatitis is greater, the patient should be monitored regularly
and any symptoms suggestive of TB promptly investigated.
o In practice, the HPA recommends that an IGRA test may be useful to look for latent disease
in BCG-vaccinated individuals (IGRA should not be affected to the same extent by
immunosuppressants). In those individuals with positive IGRAs, active disease should be
excluded and latent disease should be treated as above (where the risk of acquiring TB is
RespNET clinic aide memoire: TB. Oct 2016
greater than risk of TB-drug-associated hepatotoxicity). TNF therapy can start concurrently
with chemoprophylaxis.
Treatment
Notification – within 72hr diagnosis/start of treatment
Contact tracing (see above)
Compliance
 Always enquire about this
 Pill counts / spot urine examination (red if taking rifampicin) / Directly Observed Therapy
Vitamin B6
 People who have alcohol dependence, HIV+, pregnant or malnourished, should be given
pyridoxine (vit. B6) 10mg od throughout their use of isoniazid to prevent isoniazid-induced
neuropathy
Standard regime
 4-drug 6-month regime: pyrazinamide (Z), rifampicin (R), isoniazid (H); plus ethambutol (E) or
streptomycin (S) for first 2 months, then rifampicin and isoniazid for a further 4 months.
 Combination formulations improve compliance and prevent monotherapy (=resistance)
 Usually daily schedule. Can be 3x weekly (DOT)
 Note side effects:
o pyrazinamide, rifampicin – hepatotoxicity
o isoniazid – peripheral neuropathy
o ethambutol – ocular and nephrotoxicity
Initiation phase
Rifater® [rifampicin, isoniazid,
and pyrazinamide]
Ethambutol
Continuation phase
Rifinah®[rifampicin and isoniazid]
<40kg adult
40-49kg
50-64kg
>65kg
15mg/kg/day
3 tablets a day
4 tablets a day
5 tablets a day
6 tablets a day
<50kg use 150/100
>50kg use 300/150
3 tablets a day
2 tablets a day
BNF pages: http://www.evidence.nhs.uk/formulary/bnf/current/5-infections/51-antibacterial-drugs/519antituberculosis-drugs
Active meningeal TB regime
 12 months of treatment
 rifampicin (R), isoniazid (H), prrazimanide (Z) plus a fourth drug: ethambutol (E) or streptomycin (S)
for 1st 2 months
 isoniazid (H) plus rifampicin (R) for remainder of treatment
 20-40mg/day prednisolone, with withdrawal starting 2-3 weeks after initiation
Spinal TB
 Generally should be the standard 6 month regime, unless evidence of spinal cord involvement
(neurological symptoms or CT/MRI features) when 12 month regime (as for meningeal TB) should
be used (with prednisolone)
 Need input from spinal surgeons. Occasionally anterior spinal fusion required if spine unstable, or
cord is compressed
RespNET clinic aide memoire: TB. Oct 2016
Pericardial TB
 Standard 6 month regime plus
 Prednisolone 60mg daily, with withdrawal starting 2-3 weeks after initiation
Disseminated (miliary) TB
 Normal 6 month regime, even if baseline liver function abnormal.
 May need to change therapy if LFTs deteriorate significantly
 Consider looking for CNS involvement by CT/MRI or lumbar puncture – if found, regime should be
as for meningeal TB
Chemoprophylaxis
 6 months of isoniazid (6H)
 Or 3 months of isoniazid and rifampicin (3HR)
 Or rifampicin alone for 4-6 months (4-6R)
Directly Observed Therapy
 Consider for people with likely or established low adherence to treatment regimes
Criteria for DOT:
Known/suspected MDRTB
Previous treatment for TB
Known alcohol/substance abuse/dependence
No fixed address
Under 16 yrs
3 x a week DOT regime:
Isoniazid (H)
Rifampicin (R)
Pyrazinamide (Z)
Ethambutol (E)
Treatment breakdown/unable to adhere
Confusion/memory loss
Learning difficulties
Significant mental health problems
Severe communication difficulties
15mg/kg
600-900mg
<50kg
>50kg
30mg/kg
Max 900mg
2g
2.5g
Pregnancy and breast feeding
Standard regime can be given in pregnancy and breast feeding. Avoid streptomycin in pregnancy.
Drug-resistant TB
 Molecular tests for rifampicin resistance (on smear or culture-positive material) should be
considered for those at high risk of resistant TB. These will provide information on possible much
earlier than the standard waiting for drug susceptibilities of isolates.
Risk factors are:
History of prior TB drug treatment; prior treatment failure
Contact with a known case of drug-resistant TB
Birth in a high-incidence country
Male gender

HIV infection
Residence in London
Age profile, highest rates between 25 & 44
MDR-TB is resistance to at least 2 standard 1st line anti_TB drugs (RHZES), usually rifampicin and
isoniazid (RH) (note streptomycin and isoniazid dual resistance doesn’t count as MDR-TB)
RespNET clinic aide memoire: TB. Oct 2016
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Treatment modifications for isolated drug resistances (N.B. stop drug which to which isolate is
resistant):
o Streptomycin resistance
 No change to standard regime – use ethambutol where possible
o Isoniazid resistance
 If known before treatment commences
 Rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months, then
 Rifampicin and ethambutol for a further 7 months
 If not known before treatment commences
 Stop isoniazid
 Ethambutol, pyrazinamide, Rifampicin for 2 months, then
 Ethambutol and rifampicin for 10 months
o Pyrazinamide resistance
 Usually due to infection with M. Bovis (still requires treatment)
 Use ethambutol, isoniazid and rifampicin for 2 months, then
 Isoniazid and rifampicin for 7 months
o Ethambutol resistance (uncommon)
 Isoniazid, Rifampicin, Pyrazinamide for 2 months, then
 Isoniazid and rifampicin for 4 months
o Rifampicin resistance
 If detected by molecular probe, or drug susceptibility testing, patient should be
isolated, and treated as MDR-TB until full profile of susceptibilities of isolates to 1st
line drugs is available. In 90% of cases rifampicin resistance is not isolated and is a
marker or MDR-TB
 If isolated rifampicin resistance:
 Ethambutol, isoniazid, pyrazinamide for 2 months then
 Isoniazid and ethambutol for a further 16 months
Combined streptomycin and isoniazid resistance (does not class as MDR-TB)
o Use regime as for isolated isoniazid resistance:
 Ethambutol, pyrazinamide, Rifampicin for 2 months, then
 Ethambutol and rifampicin for 10 months
Review response to treatment and repeat cultures in high risk groups. Positive cultures after four
months is treatment failure
Multi-drug resistant TB
 Refer cases of multi-drug resistant TB to a specialist unit
o Treatment principles:
 Use at least 4 drugs to which the isolate is likely to be susceptible to, often more if
extensive or bilateral pulmonary disease
 An injectable agent should be used for at least 6 months, and at least 4 months post
culture conversion (defined by at least 2 consecutive negative cultures)
 Minimal length of treatment is 18 months after culture conversion
 Close monitoring essential (consider DOT) throughout
 Refine regime based on intolerances and culture susceptibilities
 Designing a treatment regime (progress stepwise until ≥ 4 drugs in regime):
1. Start with 1st line oral agents (unless resistance or intolerance): pyrazinamide,
ethambutol
2. Add injectable agent: kanamycin, capreomycin, streptomycin
3. Add fluoroquinolone: levofloxacin, moxifloxacin, ofloxacin
RespNET clinic aide memoire: TB. Oct 2016
4. Add a 2nd line oral bacteriostatic drug: p-aminosalicylic acid, cycloserine, or
ethionamide/ protionamide
5. Consider addition of: clofazimine, linezolid, co-amoxiclav, thioacetazone (not
if co-infected with HIV), imipenem/cilasatin, high-dose isoniazid,
clarithromycin

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
Note if MDR is admitted to hospital, it must be in a negative-pressure room with staff wearing FFP3
masks
Chemoprophylaxis for close contacts of MDR-TB should include at least drugs to which the
organism is sensitive for at least 6 months. Alternative is regular follow-up if organism highly
resistant
XDR-TB is extremely drug resistant TB which is resistant to Rifampicin, Isoniazid, Fluoroquinolones
plus injectable agents above.
Post-treatment follow up
 Not generally necessary, except drug resistant TB – follow up after 12 months, MDR-TB – consider
prolonged follow-up
Liver dysfunction
 If it is imperative to continue antituberculous therapy (e.g. respiratory failure secondary to
suspected (miliary) TB), aminoglycosides, ethambutol, quinolones (not moxifloxacin), and
cycloserine are possible options as part of a multi-drug regime.
 Patients with chronic liver disease should have LFTs monitoring weekly for 1 st 2 weeks then at 2
weekly intervals on starting TB drugs
 LFT should also be checked urgently in anyone with nausea/ vomiting or jaundice
 If AST/ALT rise to greater than 5x normal or bilirubin increases, rifampicin, isoniazid and
pyrazinamide and ethambutol should be stopped until LFTs have normalised (rationale to stop
ethambutol as well is that although it is not itself hepatotoxic, monotherapy might risk resistance).
Drugs should then be restarted stepwise (possibly as an inpatient):
o normal dose ethambutol plus isoniazid 50mg/day, increasing afer 2-3 days to 300mg/day if
no reaction
o rifampicin at 75mg/day, increasing to 300mg/day after 2-3 days if no reaction, and then to
maximal dose
o pyrazinamide 250mg/day, increasing to 1g/day after 2-3 days, and then to maximum dose
o Monitor LFTs daily and continue treatment if no recurrent adverse effects/ toxicity
o If toxicity to one of the drugs occurs, exclude this from the regime and treat as for isolated
resistance, e.g. if pyrazinamide toxicity, use rifampicin, isoniazid and ethambutol for 2
months, then rifampicin and isoniazid for a further 7 months.
Non-tuberculous mycobacterial treatment
 M. avium complex (MAI), M kansasii, M. Malmoense, M. Xenopi most important
 Can cause pulmonary infections in elderly, immunocompromised, or structural lung disease
(including old TB)
 May be subacute illness with weight loss, fever, productive cough.
 Diagnosis requires multiple/repeated microbiologal isolates plus clinical/radiological evidence of
disease
 No need to notify or contact trace.
 Treatment:
o M. kansasii – progresses without treatment
 Rifampicin plus ethambutol for ≥ 9 months
RespNET clinic aide memoire: TB. Oct 2016
o M. avium complex – rifampicin, ethambutol ± isoniazid for 2 years (can also use
clarithromycin)
o M. malmoense – ethambutol and rifampicin for 18-24 months
o M. xenopi – often resistant – ethambutol, isoniazid and rifampicin for ≥ 2 years
Tuberculosis in renal patients
 For stage IV and V CKD (GFR <30ml/min) use a 3x weekly regime for ethambutol, pyrazinamide, and
aminoglycosides. Rifampicin and isoniazid can be given in their usual daily dosage.
 For patients on haemodialysis, use a 3x weekly regime of all standard drugs, immediately after
dialysis.
 For patients on continuous RRT (on ICU) can use standard regime
 For transplant patients, aim to use a standard regime, but note:
o Dose of corticosteroids needs to be doubled if rifampicin being started
o Rifampicin may interact with mycophenolate, tacrolimus, and ciclosporin. Doses of these
agents need monitoring and adjusting.
Tuberculosis and HIV co-infection
 Wherever possible use standard TB regime, containing rifampicin and isoniazid
 Generally large choice of antiretroviral drugs, so choose HIV drugs which are tolerated, to which
there is no resistance, and which do not interact with TB drugs.
 Only change TB regime where the above is not possible
 Baseline investigations in an HIV patient newly diagnosed with TB:
CD4 count and percentage
serum AST or ALT, bilirubin and ALP
serum creatinine and estimated GFR
platelet count
hepatitis B and C serology
Snellen chart & Ishihara plates
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Use a rifamycin-based TB regime if at all possible (generally rifampicin or rifabutin)
Rifampicin is a potent CYP450 inducer and interacts with protease inhibitors, NNRTIs, CCR5
inhibitors, and antimicrobials such as fluconazole. Consider rifabutin (a less potent inducer) as an
alternative (especially when boosted PIs are required).
o (See British HIV association guidelines for interaction of (and solutions to) rifamycin-type
drugs with NNRTIs, protease inhibitors, integrase inhibitors and entry inhibitors)
Note side effects of rifabutin: bone marrow suppression, uveiitis, and arthralgia
Generally better to start HIV treatment after 6 months of TB therapy is complete (if CD4 count >
200) - because of interactions, or risk of Immune Reconstitution Syndrome (IRIS). However if:
o CD4 count <200 – could start HAART if practical but may defer until 2 months into TB
therapy
o CD4 count <100 – should start HAART as soon as practical after starting TB therapy
Consider IGRA rather than tuberculin test (Mantoux) if needing to evaluate possibility of latent TB
Patients on TB therapy who continue to have a productive cough after 2 months of initial therapy
should have a repeat sputum culture
Patients with cavitatory pulmonary TB who remain culture positive after 2 months of treatment,
should have a TB therapy continuation phase of 7 months rather than 4 months (total 9 months)
Interruptions to TB treatment (common due to side effects, and interactions) in initial phase (1st 2
months)
 If > 14 days, restart from beginning
 If < 14 days, extend initial phase until normal expected number of doses have been
given
RespNET clinic aide memoire: TB. Oct 2016
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

In treatment failure (+ve cultures after 4 months), never add a single drug to a failing regime. Add 2
or preferably 3 drugs to which the patient has not been exposed.
Consider resistant organisms in cases of relapse after completion of TB therapy, particularly if:
o A rifamycin-based regime was not used or DOT was not used
o There were treatment interruptions
o Relapse is with life-threatening features
o In such cases consider treating with standard 4-drug regime plus 3 additional agents
Immune Reconstitution Inflammatory Syndrome (IRIS)
o Apparent flare of TB symptoms often with fever and lymphadenopathy, on TB therapy,
usually after starting HAART (within 60 days) but also seen in patients without HIV during TB
therapy
o Must exclude TB treatment failure, drug hypersensitivity, opportunistic infection, or
malignancy to explain symptoms
o Treat with prednisolone 1-1.5mg/kg then wean from 1-2 weeks
Typical appointment schedule for TB treatment & relevant issues
(based on Prof Graham Bothamley’s proforma)
4weekly outpatient review (can be nurse-led for uncomplicated TB)
Time
Decisions
Day 0
Day 7/14
2 months
6 months
DOT risk assessment
Ishihara & Snellen charts (Ethambutol)
LFTs at baseline +/- hepatitis serology/autoantibodies
Renal function at baseline (? reduce S & E)
Drug interactions (OCP, warfarin, methadone etc)
Steroids? (pericarditis, meningitis, ureteric obstruction etc)
HIV test
Vit B6 (pyridoxine 10mg)? EtOH, pregnant, malnutrition etc
Weight (calculate drug doses)
Side effects? 10%
If any symptoms check LFTs
Weight (adjust drug doses)
Urine for rifampicin compliance
Sputum
Result of Rifampicin PCR - ?MDRTB
Weight (adjust drug doses)
Urine for rifampicin compliance
Antibiotics sensitivities - ? switch to continuation phase
CXR
Sputum
If no improvement consider: MDRTB, HIV, non-adherence
HIV test result
Check TB nurse has visited & pt knows name/contact no.
CXR
Sputum (if any)
HIV tested – check
Follow-up?
S+ PTB
PTB
C+
EPTB
Other
-
-
-
-
-
-
all
all
Y
Y
Y
all
Y
Y
Y
Y/?
all
Y
Y
Y
Y
all
consider
RespNET clinic aide memoire: TB. Oct 2016
Typical appointment schedule for chemoprophylaxis, & relevant issues
(based on Prof Graham Bothamley’s proforma)
Time
First visit
Decisions
Check info correct (no symptoms, age)
Note additional risk factors (pregnancy, EtOH, HIV) & details of index case (?MDR)
Examination (exclude sterile pyuria, LNTB)
Renal function at baseline (? reduce S & E)
Other bloods: FBC, LFT, CRP (? Hepatitis serology)
Weight
HIV test
Explain reason for treatment and choice of regime:
 1.68% PPD+ develop TB in 5yrs, 10% lifetime risk
 0.28% PPD+ develop TB with preventive treatment
Explain potential side effects:
 hepatitis 0.05% children (1 in 2000), 0.3% age 20-34 (3 in 1000), 1.2% age 35-49.
Give 4/52 supply of drugs, and appt for 2/52
Second visit
Weight (increase may suggest active TB)
(wk 2)
Urine for rifampicin compliance
Repeat LFTs if any symptoms, or known chronic liver disease
Explain any SE, record in notes and letter ? continue treatment / add antihistamine /
change to CXR follow-up only (at 3/12 and 1 year post-exposure)
Give apt for end of treatment (3RH) or 10 weeks (6H). TB nurses see every 4/52.
Third visit (wk Complete 3RH
13)
If 6H book apt for end of treatment
Can do LFTs routinely at d0, d14, and d28/42.
With thanks to Dr Robin Johns for the original version of this clinic aide memoire. Rewritten and updated by LJ Smith.
For more information see: http://www.tbdrugmonographs.co.uk/