A 65-year-old man with diabetes presents with a non-healing foot ulcer for 3 months. X-ray shows osteolytic changes in the underlying bone. MRI confirms osteomyelitis. What is the most appropriate treatment duration for antibiotics?

4-6 weeks IV followed by 2-6 weeks oral

A 35-year-old man with HIV infection (CD4 count 80 cells/mm³, viral load 125,000 copies/mL, not on antiretroviral therapy) presents with a 4-week history of headache, fever, and confusion. CT head shows basal meningeal enhancement and multiple small nodules. Lumbar puncture shows: opening pressure 32 cmH2O, CSF white cells 45/mm³ (80% lymphocytes), protein 1.2 g/L, glucose 1.9 mmol/L (serum glucose 5.4 mmol/L). India ink stain is positive. Cryptococcal antigen is positive in both CSF and serum at titres of 1:2048 and 1:1024 respectively. He is started on liposomal amphotericin B and flucytosine. Which one of the following additional interventions has been shown to improve survival in this patient?

Performing daily therapeutic lumbar punctures until opening pressure normalizes

Commencing antiretroviral therapy immediately alongside antifungal treatment

Adding adjunctive dexamethasone 0.4 mg/kg daily for 6 weeks

Adding adjunctive interferon-gamma to enhance immune response

Inserting a ventriculoperitoneal shunt to manage hydrocephalus

A 48-year-old woman from Kazakhstan is diagnosed with pulmonary tuberculosis. Initial molecular testing (GeneXpert MTB/RIF) detects Mycobacterium tuberculosis with rifampicin resistance. Subsequent culture and phenotypic drug susceptibility testing confirms resistance to rifampicin and isoniazid, but the isolate is sensitive to pyrazinamide, ethambutol, fluoroquinolones, bedaquiline, and linezolid. She has a history of seizures controlled with carbamazepine and is otherwise well. Which one of the following represents the most significant drug interaction that needs to be considered when designing her MDR-TB treatment regimen?

Carbamazepine induces cytochrome P450 enzymes which will reduce levels of bedaquiline and fluoroquinolones

Linezolid may reduce seizure threshold and interact with carbamazepine

Bedaquiline requires dose adjustment due to carbamazepine-induced enzyme induction

Moxifloxacin may prolong QT interval which is exacerbated by carbamazepine

Clofazimine absorption is significantly reduced by carbamazepine

A 28-year-old previously healthy man is admitted with suspected bacterial meningitis. He is treated empirically with IV ceftriaxone 2 g twice daily and IV dexamethasone 10 mg four times daily. Lumbar puncture performed before antibiotics shows: CSF white cells 2,100/mm³ (90% neutrophils), protein 2.3 g/L, glucose 1.5 mmol/L (serum glucose 6.0 mmol/L). Blood and CSF cultures taken on admission subsequently grow Streptococcus pneumoniae fully sensitive to penicillin (penicillin MIC 0.06 mg/L). He improves clinically over 48 hours. Which one of the following represents the most appropriate modification to his antimicrobial therapy at this stage?

Switch to benzylpenicillin 2.4 g four-hourly and stop dexamethasone

Continue ceftriaxone 2 g twice daily and stop dexamethasone

Switch to benzylpenicillin 2.4 g four-hourly and continue dexamethasone

Switch to amoxicillin 2 g four-hourly and continue dexamethasone

Continue ceftriaxone 2 g twice daily and continue dexamethasone for the full 10-day course

A 56-year-old man with end-stage renal failure on haemodialysis three times per week is diagnosed with fully drug-sensitive pulmonary tuberculosis. He weighs 70 kg. His renal function shows: creatinine 680 micromol/L, eGFR <10 mL/min/1.73m². Which one of the following represents the most appropriate dosing regimen for the intensive phase of treatment?

Rifampicin 600 mg once daily, isoniazid 300 mg once daily, pyrazinamide 1.5 g three times per week post-dialysis, ethambutol 600 mg three times per week post-dialysis

Rifampicin 450 mg once daily, isoniazid 200 mg once daily, pyrazinamide 1 g once daily, ethambutol 800 mg three times per week post-dialysis

Rifampicin 600 mg three times per week post-dialysis, isoniazid 300 mg three times per week post-dialysis, pyrazinamide 25 mg/kg three times per week post-dialysis, ethambutol 15 mg/kg three times per week post-dialysis

Rifampicin 600 mg once daily, isoniazid 300 mg three times per week post-dialysis, pyrazinamide 25 mg/kg three times per week post-dialysis, ethambutol 15 mg/kg three times per week post-dialysis

Rifampicin 600 mg once daily, isoniazid 300 mg once daily, pyrazinamide 500 mg once daily, ethambutol 400 mg once daily

Tuberculosis for UKMLA AKT: High-Yield Infectious Diseases Lessons

Quick Overview

Tuberculosis (TB) is a notifiable infectious disease caused by Mycobacterium tuberculosis, affecting primarily the lungs (pulmonary TB) but can involve any organ system (extrapulmonary TB). NICE NG33 provides comprehensive guidance on diagnosis, treatment, and contact tracing. Key priorities include identifying active disease early, managing latent TB infection (LTBI), and recognizing drug-resistant TB to prevent transmission and complications.

Core Facts & Concepts

Diagnostic Criteria (NICE NG33)

Active pulmonary TB: Clinical symptoms + microbiological confirmation (culture/PCR) OR radiological evidence + clinical response to treatment
Latent TB: Positive interferon-gamma release assay (IGRA) or tuberculin skin test (TST ≥6mm if BCG vaccinated, ≥5mm if not) WITHOUT active disease
Microbiological confirmation: Sputum smear (Ziehl-Neelsen stain), culture (gold standard, 2-6 weeks), or nucleic acid amplification test (NAAT, results in 24-48 hours)

Figure 1: Chest X-ray showing upper lobe cavitation and patchy consolidation

First-Line Treatment Regimens

Standard 6-month regimen (drug-sensitive TB):
- Intensive phase (2 months): RIPE daily
  - Rifampicin 10mg/kg (max 600mg)
  - Isoniazid 5mg/kg (max 300mg) + pyridoxine 10mg
  - Pyrazinamide 25mg/kg (max 2g if <50kg, 2.5g if ≥50kg)
  - Ethambutol 15mg/kg
- Continuation phase (4 months): RI daily
CNS/bone/joint TB: Extend continuation phase to 10 months (12 months total)
Pyridoxine supplementation: Mandatory with isoniazid (prevents peripheral neuropathy)

Drug-Resistant TB Recognition

Risk factors: Previous TB treatment, contact with drug-resistant case, birth/residence in high-prevalence area
Send rapid molecular testing (e.g., GeneXpert for rifampicin resistance)
MDR-TB: Resistant to rifampicin + isoniazid (requires specialist management, 18-24 month regimens)

Problem-Solving Approach

Step-by-Step Diagnostic Pathway

Clinical suspicion: Persistent cough >3 weeks, fever, night sweats, weight loss, haemoptysis
Initial investigations:
- Chest X-ray (upper lobe infiltrates, cavitation, lymphadenopathy)
- Three sputum samples (early morning) for smear, culture, and NAAT
- HIV test (mandatory in all TB cases)
Extrapulmonary TB: Sample appropriate site (pleural fluid, CSF, lymph node biopsy)
LTBI screening indications:
- Close contacts of active TB cases
- Immunosuppression planned (anti-TNF, transplant)
- Healthcare workers, migrants from high-prevalence countries

Figure 2: Ziehl-Neelsen stain showing acid-fast bacilli

🚩 Red Flags Requiring Urgent Action

Smear-positive pulmonary TB → respiratory isolation immediately
CNS TB → dexamethasone 0.4mg/kg daily (reduces mortality)
Drug-resistant TB suspected → specialist referral same day
HIV co-infection → start ART within 2-8 weeks of TB treatment

Analysis Framework

Feature	Active TB	Latent TB
Symptoms	Present (cough, fever, weight loss)	Absent
Chest X-ray	Abnormal	Normal
Sputum/culture	Positive	Negative
IGRA/TST	Usually positive	Positive
Treatment duration	6-12 months (RIPE → RI)	3 months (rifampicin + isoniazid) OR 6 months (isoniazid alone)
Infectivity	Contagious (if pulmonary, smear-positive)	Non-infectious

Contact Tracing Protocol (NICE NG33)

Close contacts: Screen with IGRA/TST and chest X-ray
Timing: Test at initial contact; if negative and immunocompetent, repeat at 8 weeks
Offer LTBI treatment if positive screening and active TB excluded

Visual Aid

Key Points Summary

✓ Standard treatment: 2 months RIPE (rifampicin 10mg/kg, isoniazid 5mg/kg + pyridoxine, pyrazinamide 25mg/kg, ethambutol 15mg/kg) → 4 months RI

✓ Extend to 12 months total for CNS, bone, or joint TB

✓ LTBI treatment: 3 months rifampicin + isoniazid OR 6 months isoniazid alone (prevents progression to active disease in 60-90%)

✓ Drug-resistant TB risk factors: Previous treatment, contact with resistant case, high-prevalence country origin → send rapid molecular testing

✓ Contact tracing: Screen close contacts with IGRA/TST + chest X-ray; repeat at 8 weeks if initially negative

✓ Mandatory notifications: Report all TB cases (active and LTBI treated) to local Health Protection Team within 3 days

✓ Directly observed therapy (DOT): Consider for non-adherence risk, homelessness, substance misuse, MDR-TB

⚠️ Warning: Never use monotherapy (risks resistance development). Always check HIV status and ensure pyridoxine supplementation with isoniazid.

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Tuberculosis