Tuberculosis — Written Clinical Reasoning

SAQ 1 — Integrated Management (25 marks, 35 minutes)

Prompt: Outline your integrated management plan for this patient, addressing the problem list, infection control, the standard anti-tuberculous regimen and its modifications, the anticipated drug interactions, the management of comorbidities, public health responsibilities, and the surveillance plan. Justify each decision with reference to evidence and guidelines. ^[1]

Model Answer

Problem list (3 marks):

1. Smear-positive drug-susceptible pulmonary tuberculosis with cavitary disease — high infectivity.
2. Hepatitis B co-infection — high baseline risk of drug-induced hepatotoxicity.
3. Type 2 diabetes with poor control — worsens TB outcomes and is itself worsened by TB and rifampicin.
4. Stage 4 chronic kidney disease (eGFR 22) — requires dose adjustment of ethambutol and pyrazinamide.
5. Atrial fibrillation on warfarin — clinically significant rifampicin-warfarin interaction anticipated.
6. Smoker (35 pack-years) and cachexia — malnutrition, smoking cessation, and aspiration of supratherapeutic anticoagulation (haemoptysis).
7. Household and community contacts at risk — public health notification and contact tracing. ^[1]

Immediate infection control (3 marks):

• Place the patient in airborne isolation in a negative-pressure ventilation room (6 to 12 air changes per hour) with the door closed; healthcare workers and visitors wear a fit-tested N95 or P2 particulate respirator, not a surgical mask (droplet nuclei are smaller than 5 micrometres and pass through a surgical mask).
• Notify the TB service, microbiology, public health unit and infection control immediately.
• Airborne precautions continue until the patient is on effective therapy, clinically improving, and has three consecutive negative sputum smears on separate days (including one early morning) — typically 2 to 3 weeks for drug-susceptible disease (Lewinsohn et al, 2017, PMID 28052967). ^[1]

Confirming the diagnosis and resistance pattern (2 marks):

• The GeneXpert-positive sputum with no rifampicin resistance is sufficient to start standard therapy, but mycobacterial culture and full phenotypic drug susceptibility testing are still required because Xpert detects only the commonest rpoB mutations and does not test isoniazid, pyrazinamide or ethambutol. Liquid culture (MGIT) plus solid (LJ) in parallel; susceptibilities expected in 4 to 8 weeks.
• Line-probe assay (GenoType MTBdrplus) on smear-positive sputum can also rapidly detect isoniazid resistance and is performed in parallel. ^[1]

Standard anti-tuberculous regimen (3 marks): The patient has drug-susceptible pulmonary TB and starts the standard RIPE regimen (Nahid et al, 2016, PMID 27516382):

• Intensive phase (8 weeks): rifampicin 600 mg orally daily, isoniazid 300 mg orally daily (with pyridoxine 25 mg daily because of the diabetic/CKD/hepatitis B risk of neuropathy), pyrazinamide (renal-dose adjusted, see below), ethambutol (renal-dose adjusted, see below).
• Continuation phase (16 weeks): rifampicin 600 mg daily plus isoniazid 300 mg daily with pyridoxine.
• Total duration 6 months. Because he has cavitary disease, the 2-month sputum culture must be checked; if positive at 2 months the continuation phase is extended to 7 months for a total of 9 months. ^[1]

Renal dose adjustment (2 marks): With eGFR 22 mL per min per 1.73 m squared:

• Ethambutol is renally cleared and requires dose reduction (typically 15 mg/kg three times weekly after the first 2 weeks) with monthly visual acuity and colour vision monitoring; baseline Ishihara plates are essential and the patient must be educated to stop immediately and report any visual change.
• Pyrazinamide is hepatically metabolised but its metabolites are renally cleared; the daily dose is generally maintained but some guidelines reduce to 25 mg/kg three times weekly in advanced CKD.
• Rifampicin and isoniazid do not require dose adjustment in CKD. ^[1]

Rifampicin-warfarin interaction (3 marks): Rifampicin is a potent inducer of hepatic CYP2C9 and will markedly accelerate warfarin metabolism. The INR is expected to fall within 1 to 2 weeks of starting therapy. Management options:

• Continue warfarin and substantially increase the dose (often double or triple) with INR monitored twice weekly during rifampicin therapy, or
• Switch to therapeutic-dose low-molecular-weight heparin (weight-based enoxaparin, reduced for eGFR) for the duration of TB therapy. In this patient, with stage 4 CKD and the complexity of dose adjustment, the preference in ANZ is usually to continue warfarin with intensive twice-weekly INR monitoring and close liaison with the anticoagulation clinic; LMWH in severe CKD accumulates and is harder to manage. The patient must be counselled that the OCP would also be ineffective (not relevant here) and that any concomitant drug (statin, beta-blocker, sulfonylurea, corticosteroid) may have reduced effect. ^[1]

Rifampicin-sulfonylurea and diabetes interaction (2 marks): Rifampicin induces metabolism of sulfonylureas (gliclazide) and may reduce their hypoglycaemic effect. More importantly, active TB worsens glycaemic control and rifampicin alters drug levels. In the acute phase, the patient is usually started on a sliding-scale insulin regimen in hospital with the diabetes team; oral hypoglycaemics can be re-introduced once TB therapy is established and glycaemia is stable. Target HbA1c is relaxed in the acute illness (under 64 mmol per mol is reasonable) to avoid hypoglycaemia in a cachectic patient with reduced intake. ^[1]

Hepatitis B co-infection and hepatotoxicity monitoring (2 marks): The shared hepatotoxicity of isoniazid, rifampicin and pyrazinamide is significantly amplified by chronic hepatitis B. Baseline LFTs are normal; check hepatitis B DNA and refer to hepatology. LFTs are monitored monthly and immediately for any symptoms of hepatitis (nausea, vomiting, abdominal pain, jaundice). The action threshold for stopping therapy is ALT greater than 3 times ULN with symptoms, or greater than 5 times ULN without symptoms. If drug-induced hepatitis develops, all four drugs are stopped, other causes excluded, and drugs reintroduced sequentially (rifampicin first, then isoniazid, then pyrazinamide) with LFTs at each step. Consider antiviral prophylaxis for hepatitis B (entecavir or tenofovir) if the patient is at high risk of HBV reactivation during immunosuppression or chemotherapy; this is discussed with hepatology. ^[1]

Public health and contact tracing (2 marks):

• Notify the case to the public health unit under the relevant Public Health Act (mandatory in all ANZ jurisdictions).
• Initiate a concentric (stone-on-stone) contact investigation: highest priority to the household (wife and two adult children), who are screened with a symptom screen, IGRA or TST (8 to 10 weeks after last exposure), and chest radiograph. Close social and workplace contacts are screened next.
• The patient is educated about cough hygiene, the importance of adherence, and the support available (social work, transport, language interpreter). ^[1]

Surveillance and follow-up (3 marks):

• Monthly clinical review: weight, symptoms, adherence, side effects (especially visual symptoms on ethambutol and hepatitis symptoms).
• LFTs monthly (hepatitis B risk) and PRN; renal function monthly; INR twice weekly during rifampicin titration then weekly.
• Visual acuity and colour vision monthly while on ethambutol.
• Sputum smear and culture at 2, 5, and 6 months; if the 2-month culture is positive in cavitary disease, extend to 9 months.
• Chest radiograph at end of therapy for documentation (does not in itself determine cure; culture negativity does).
• Smoking cessation, nutritional support, pneumococcal and influenza vaccination (defer BCG-related workups; the patient is an adult with established infection).
• Hepatology follow-up for hepatitis B; endocrinology/diabetes team for glycaemic stabilisation. ^[1]