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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 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 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 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 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 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 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/