Serious & Notifiable Infections — MCQs
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A 48-year-old man with recently diagnosed smear-positive pulmonary tuberculosis has been on standard four-drug therapy (rifampicin, isoniazid, pyrazinamide, ethambutol) for 10 days. He now presents with sudden onset severe left-sided pleuritic chest pain. Chest X-ray shows a large left-sided pneumothorax. What is the most likely explanation for this complication?
A 2-year-old girl is brought to the emergency department with a 3-hour history of fever, lethargy, and a non-blanching purpuric rash on her legs. She is tachycardic with a capillary refill time of 4 seconds. Blood pressure is 85/50 mmHg. After initial fluid resuscitation and blood cultures, which antibiotic should be administered immediately?
A 36-year-old man from Vietnam presents with a 6-week history of malaise, weight loss, and back pain. He reports no respiratory symptoms. Examination reveals tenderness over the L2-L3 vertebrae and reduced straight leg raise bilaterally. MRI spine shows destruction of L2-L3 vertebral bodies with a paravertebral abscess. Which investigation is most likely to establish the diagnosis?
A 6-year-old boy presents with fever, headache and vomiting. Lumbar puncture is performed. CSF analysis shows: glucose 3.2 mmol/L (plasma glucose 5.8 mmol/L), protein 0.6 g/L, white cell count 180 cells/mm³ (90% lymphocytes). Gram stain is negative. What is the most appropriate initial antimicrobial therapy?
A 41-year-old man from India who moved to the UK 6 months ago presents with a 10-week history of progressive headache, low-grade fever, and confusion. He has lost 8 kg in weight. CT head shows basal meningeal enhancement and hydrocephalus. Lumbar puncture reveals: opening pressure 32 cmH₂O, CSF glucose 1.2 mmol/L (serum 5.6 mmol/L), protein 3.2 g/L, white cells 240/mm³ (70% lymphocytes). Ziehl-Neelsen stain and TB PCR of CSF are negative. What is the most appropriate next step in management?
A 29-year-old woman presents with headache, fever, and photophobia. Lumbar puncture shows: opening pressure 18 cmH₂O, CSF glucose 3.1 mmol/L (serum 5.4 mmol/L), protein 0.65 g/L, white cells 580/mm³ (85% lymphocytes), red cells 15/mm³. Gram stain is negative. CSF PCR for enterovirus is positive. She is currently 10 weeks pregnant. What is the most appropriate management?
A 38-year-old man with cavitating pulmonary tuberculosis has been on treatment for 3 weeks with rifampicin, isoniazid, pyrazinamide, and ethambutol. His baseline liver function tests were normal. He now presents with jaundice. Blood tests show: bilirubin 156 μmol/L, ALT 420 U/L, AST 385 U/L, ALP 178 U/L. What is the most appropriate management approach?
A 8-month-old infant is brought to the emergency department with a 12-hour history of fever of 39.8°C, irritability, and poor feeding. There is no rash. Lumbar puncture is performed: CSF glucose 1.4 mmol/L (blood glucose 4.8 mmol/L), protein 2.8 g/L, white cells 1200/mm³ (90% polymorphs). Gram stain shows Gram-negative coccobacilli. Intravenous ceftriaxone is commenced. Which organism is most likely responsible for this presentation?
A 62-year-old woman with end-stage renal failure on haemodialysis presents with a 4-week history of fever, night sweats, and cough. Chest X-ray shows bilateral miliary shadowing. Sputum is positive for acid-fast bacilli and culture confirms Mycobacterium tuberculosis fully sensitive to first-line agents. She weighs 65 kg. What is the most appropriate dosing regimen for the intensive phase of treatment?
A 52-year-old man with HIV infection (CD4 count 180 cells/mm³, viral load undetectable on antiretroviral therapy) presents with a 3-week history of headache and fever. CT head with contrast shows multiple ring-enhancing lesions in the basal ganglia and thalamus. Lumbar puncture shows: opening pressure 24 cmH₂O, CSF glucose 2.6 mmol/L (serum 5.8 mmol/L), protein 0.85 g/L, white cells 45/mm³ (80% lymphocytes). India ink stain is positive. What is the most appropriate initial management?
Serious & Notifiable Infections UK Medical PG Practice Questions and MCQs
Question 201: A 48-year-old man with recently diagnosed smear-positive pulmonary tuberculosis has been on standard four-drug therapy (rifampicin, isoniazid, pyrazinamide, ethambutol) for 10 days. He now presents with sudden onset severe left-sided pleuritic chest pain. Chest X-ray shows a large left-sided pneumothorax. What is the most likely explanation for this complication?
- A. Paradoxical reaction to anti-tuberculous therapy
- B. Rupture of a subpleural tuberculous cavity (Correct Answer)
- C. Drug-induced pulmonary toxicity from rifampicin
- D. Secondary spontaneous pneumothorax from underlying emphysema
- E. Hospital-acquired pneumonia with necrotising infection
Explanation: ***Rupture of a subpleural tuberculous cavity*** - Pneumothorax is a recognized complication of pulmonary **tuberculosis (TB)**, occurring most commonly due to the rupture of a **subpleural cavity** or necrotic focus into the pleural space. - In smear-positive patients with cavitary disease, this rupture creates a **bronchopleural fistula**, leading to acute **secondary spontaneous pneumothorax** early in the treatment course. *Paradoxical reaction to anti-tuberculous therapy* - A paradoxical reaction involves the **transient worsening** of symptoms or new inflammatory lesions (like lymphadenopathy) despite effective treatment. - While it reflects an **immune reconstitution**, it typically presents as fever or enlarging masses rather than an acute mechanical event like a large **pneumothorax**. *Drug-induced pulmonary toxicity from rifampicin* - **Rifampicin** is primarily associated with **hepatotoxicity** and various drug-drug interactions involving the P450 system. - It is not known to cause acute structural lung changes or **pleural complications** like pneumothorax. *Secondary spontaneous pneumothorax from underlying emphysema* - Although emphysema is a major cause of **secondary spontaneous pneumothorax**, the patient has a confirmed, active **smear-positive TB** infection. - The acute complication in the setting of active TB is statistically and clinically more likely to be due to **tuberculous cavitation** than incidental emphysema. *Hospital-acquired pneumonia with necrotising infection* - While **necrotizing pneumonia** can lead to pneumothorax, it typically presents with new-onset sepsis, purulent sputum, and distinct **infiltrates** on imaging. - The short duration of therapy (10 days) and the baseline diagnosis of **cavitary TB** point toward the TB itself as the primary cause of the pleural air.
Question 202: A 2-year-old girl is brought to the emergency department with a 3-hour history of fever, lethargy, and a non-blanching purpuric rash on her legs. She is tachycardic with a capillary refill time of 4 seconds. Blood pressure is 85/50 mmHg. After initial fluid resuscitation and blood cultures, which antibiotic should be administered immediately?
- A. Intravenous ceftriaxone 80 mg/kg
- B. Intravenous benzylpenicillin 300 mg
- C. Intravenous cefotaxime 50 mg/kg and amoxicillin 50 mg/kg (Correct Answer)
- D. Intramuscular benzylpenicillin 300 mg
- E. Intravenous vancomycin 15 mg/kg
Explanation: ***Intravenous cefotaxime 50 mg/kg and amoxicillin 50 mg/kg*** - This combination is the standard empirical treatment for suspected **bacterial meningitis** or **septicaemia** in children under **3 years of age** because it provides coverage against common pathogens like **Neisseria meningitidis**, **Streptococcus pneumoniae** (cefotaxime), and crucially, **Listeria monocytogenes** (amoxicillin). - The clinical presentation of fever, lethargy, **non-blanching purpuric rash**, and signs of **shock** (tachycardia, prolonged capillary refill, hypotension) is highly suggestive of severe invasive bacterial disease requiring immediate broad-spectrum intravenous antibiotics. *Intravenous ceftriaxone 80 mg/kg* - While **ceftriaxone** is a potent third-generation cephalosporin effective against **Neisseria meningitidis** and **Streptococcus pneumoniae**, used as monotherapy it lacks coverage for **Listeria monocytogenes**. - **Listeria** is an important pathogen to empirically cover in children, particularly those under **3 months** of age, and often extended to under 3 years or based on local guidelines for suspected meningitis/sepsis. *Intravenous benzylpenicillin 300 mg* - **Intravenous benzylpenicillin** alone is not sufficient for comprehensive empirical treatment in a hospital setting for suspected sepsis with a purpuric rash, as it lacks broad-spectrum coverage against many common gram-negative organisms beyond **Neisseria meningitidis**. - Its primary appropriate use in this context is as an **emergency pre-hospital administration** by paramedics or GPs to patients with suspected meningococcal disease to improve outcomes before hospital arrival. *Intramuscular benzylpenicillin 300 mg* - **Intramuscular administration** of benzylpenicillin is specifically recommended for **pre-hospital emergency use** when intravenous access is difficult or delayed, typically in the community setting by a GP or paramedic. - Once the patient has arrived in the **Emergency Department** and IV access is established, the standard of care requires switching to a broad-spectrum intravenous antibiotic regimen. *Intravenous vancomycin 15 mg/kg* - **Vancomycin** is primarily used for infections involving **methicillin-resistant Staphylococcus aureus (MRSA)** or **penicillin-resistant Streptococcus pneumoniae**, or in patients with severe beta-lactam allergies. - It is not the first-line empirical antibiotic for suspected **meningococcal sepsis** and does not provide adequate sole coverage against **Neisseria meningitidis** or other potential gram-negative pathogens in this clinical scenario.
Question 203: A 36-year-old man from Vietnam presents with a 6-week history of malaise, weight loss, and back pain. He reports no respiratory symptoms. Examination reveals tenderness over the L2-L3 vertebrae and reduced straight leg raise bilaterally. MRI spine shows destruction of L2-L3 vertebral bodies with a paravertebral abscess. Which investigation is most likely to establish the diagnosis?
- A. Blood cultures for Mycobacterium tuberculosis
- B. Three early morning sputum samples for acid-fast bacilli
- C. CT-guided biopsy of the affected vertebra (Correct Answer)
- D. Mantoux tuberculin skin test
- E. Interferon-gamma release assay (IGRA)
Explanation: ***CT-guided biopsy of the affected vertebra*** - This investigation is the **gold standard** for diagnosing **extrapulmonary tuberculosis**, specifically **Pott's disease** (spinal TB), as it allows for direct tissue sampling. - The biopsy enables **histopathological examination** (identifying **caseating granulomas**), **culture for *Mycobacterium tuberculosis***, and **molecular tests (e.g., PCR)**, providing definitive diagnosis and crucial **drug sensitivity testing**. *Blood cultures for Mycobacterium tuberculosis* - **Mycobacterium tuberculosis** is rarely isolated from blood cultures, especially in immunocompetent individuals with localized disease, making its **diagnostic yield very low**. - This test is primarily useful in cases of **disseminated (miliary) TB**, often seen in severely immunocompromised patients. *Three early morning sputum samples for acid-fast bacilli* - The patient reports **no respiratory symptoms**, indicating that **pulmonary involvement** is unlikely to be the primary site or a source for diagnosis in this case of isolated spinal disease. - Sputum samples are highly improbable to yield **acid-fast bacilli** in **Pott's disease** without co-existing active lung lesions. *Mantoux tuberculin skin test* - A **positive Mantoux test** only indicates **prior exposure** to *M. tuberculosis* or latent infection, and cannot differentiate between **latent and active tuberculosis**. - In individuals from endemic regions like Vietnam, prior **BCG vaccination** often leads to **false-positive results**, limiting its utility for diagnosing active disease. *Interferon-gamma release assay (IGRA)* - **IGRA** detects sensitization to *M. tuberculosis* antigens, indicating infection, but it cannot distinguish between **active disease** and **latent TB infection**. - This test provides no information regarding the **specific site of infection** or **antibiotic sensitivities**, which are essential for managing a complex case of vertebral destruction.
Question 204: A 6-year-old boy presents with fever, headache and vomiting. Lumbar puncture is performed. CSF analysis shows: glucose 3.2 mmol/L (plasma glucose 5.8 mmol/L), protein 0.6 g/L, white cell count 180 cells/mm³ (90% lymphocytes). Gram stain is negative. What is the most appropriate initial antimicrobial therapy?
- A. Intravenous ceftriaxone and aciclovir (Correct Answer)
- B. Intravenous benzylpenicillin and gentamicin
- C. Intravenous ceftriaxone alone
- D. Intravenous vancomycin and ceftriaxone
- E. Oral amoxicillin
Explanation: ***Intravenous ceftriaxone and aciclovir***- The CSF analysis reveals a **lymphocytic pleocytosis** (90% lymphocytes) and near-normal glucose, which can represent **viral meningitis** or early/partially treated **bacterial meningitis**.- Empirical management must cover common bacterial pathogens with **ceftriaxone** while adding **aciclovir** to cover potential **herpes simplex virus (HSV)** encephalitis until cultures and PCR results are available.*Intravenous benzylpenicillin and gentamicin*- This regimen is typically used for **neonatal meningitis** to cover *Group B Streptococcus* and *Listeria*, but is not standard for a 6-year-old child.- In this age group, **ceftriaxone** is preferred for its superior coverage of *Streptococcus pneumoniae* and *Neisseria meningitidis*.*Intravenous ceftriaxone alone*- While ceftriaxone provides excellent coverage for **bacterial meningitis**, it lacks activity against viral pathogens like **HSV** or **VZV**.- Given the **lymphocytic predominance** in the CSF, viral encephalitis remains a critical differential that requires the addition of **aciclovir** for patient safety.*Intravenous vancomycin and ceftriaxone*- This combination is often used empirically in regions with high rates of **penicillin-resistant pneumococcus**, but it still fails to address the **viral** differential indicated by the 90% lymphocytes.- **Aciclovir** is specifically required because the clinical presentation and CSF profile are highly suggestive of a **viral etiology**.*Oral amoxicillin*- Oral antibiotics are inappropriate for suspected meningitis as they cannot achieve reliable **cerebrospinal fluid penetration** or therapeutic levels quickly enough.- **Intravenous therapy** is mandatory for any child suspected of having a serious **central nervous system infection** to prevent rapid neurological deterioration.
Question 205: A 41-year-old man from India who moved to the UK 6 months ago presents with a 10-week history of progressive headache, low-grade fever, and confusion. He has lost 8 kg in weight. CT head shows basal meningeal enhancement and hydrocephalus. Lumbar puncture reveals: opening pressure 32 cmH₂O, CSF glucose 1.2 mmol/L (serum 5.6 mmol/L), protein 3.2 g/L, white cells 240/mm³ (70% lymphocytes). Ziehl-Neelsen stain and TB PCR of CSF are negative. What is the most appropriate next step in management?
- A. Repeat lumbar puncture to obtain larger CSF volume for TB culture and commence anti-tuberculosis therapy (Correct Answer)
- B. Perform CT chest and commence four-drug anti-tuberculosis therapy empirically
- C. Arrange brain MRI and neurosurgical assessment for possible ventriculoperitoneal shunt insertion before starting treatment
- D. Request CSF cryptococcal antigen test and commence liposomal amphotericin B
- E. Commence intravenous ceftriaxone and aciclovir pending further investigation results
Explanation: ***Repeat lumbar puncture to obtain larger CSF volume for TB culture and commence anti-tuberculosis therapy*** - This patient presents with classic features of **tuberculous (TB) meningitis**, including a subacute progressive course, **basal meningeal enhancement**, **lymphocytic pleocytosis**, and very **low CSF glucose**. The epidemiological link to an endemic area (India) further strengthens the diagnosis. - Given the low sensitivity of **CSF Ziehl-Neelsen stain and PCR** in TBM, empiric **anti-tuberculosis therapy** must be started immediately to prevent high mortality and morbidity, while concurrently obtaining a larger CSF volume for the more sensitive **TB culture**. *Perform CT chest and commence four-drug anti-tuberculosis therapy empirically* - While a **CT chest** may show evidence of active pulmonary TB in approximately 50% of TBM cases, it is not the most crucial immediate diagnostic step for the neurological infection itself. The priority remains confirming and optimally culturing the CNS pathogen. - Although empiric therapy is correct, obtaining a high-volume CSF sample for culture is paramount for definitive diagnosis and sensitivity testing, which this option does not prioritize as the immediate next step. *Arrange brain MRI and neurosurgical assessment for possible ventriculoperitoneal shunt insertion before starting treatment* - The elevated **intracranial pressure** (32 cmH₂O) and **hydrocephalus** indicate a need for monitoring and potential intervention; however, **delaying specific anti-tuberculosis therapy** for a neurosurgical assessment is inappropriate and carries a high risk of worsening outcomes. - The immediate priority is to initiate **anti-tuberculosis therapy** and corticosteroids to address the underlying inflammatory process causing the hydrocephalus and prevent further neurological damage. *Request CSF cryptococcal antigen test and commence liposomal amphotericin B* - **Cryptococcal meningitis** can present with similar CSF findings (lymphocytic pleocytosis, low glucose) and elevated ICP, especially in immunocompromised individuals. However, the patient's background and the characteristic **basal meningeal enhancement** on CT make **tuberculosis** significantly more likely. - Without explicit evidence of immunocompromise or other risk factors for fungal infection, empirically treating for cryptococcosis is less appropriate than for TB, given the strong clinical and epidemiological indicators for the latter. *Commence intravenous ceftriaxone and aciclovir pending further investigation results* - These medications target **acute bacterial meningitis** (ceftriaxone) and **herpes simplex encephalitis** (aciclovir). The patient's 10-week history of progressive symptoms clearly points to a **subacute or chronic process**, not an acute infection typically managed by these drugs. - The profound **lymphocytic pleocytosis** and extremely **low CSF glucose** are inconsistent with typical acute bacterial meningitis (usually neutrophilic predominance) and are more suggestive of a granulomatous infection like TB rather than a viral encephalitis where glucose is often normal.
Question 206: A 29-year-old woman presents with headache, fever, and photophobia. Lumbar puncture shows: opening pressure 18 cmH₂O, CSF glucose 3.1 mmol/L (serum 5.4 mmol/L), protein 0.65 g/L, white cells 580/mm³ (85% lymphocytes), red cells 15/mm³. Gram stain is negative. CSF PCR for enterovirus is positive. She is currently 10 weeks pregnant. What is the most appropriate management?
- A. Commence intravenous aciclovir 10 mg/kg three times daily for 14 days
- B. Commence oral pleconaril 400 mg three times daily for 7 days
- C. Supportive management only with analgesia, antiemetics, and intravenous fluids (Correct Answer)
- D. Commence intravenous immunoglobulin 0.4 g/kg daily for 5 days
- E. Commence intravenous ceftriaxone 2 g twice daily until bacterial culture results confirmed negative
Explanation: ***Supportive management only with analgesia, antiemetics, and intravenous fluids*** - This patient presents with characteristic CSF findings for **viral meningitis**, including a **lymphocytic pleocytosis**, normal CSF glucose (CSF:blood glucose ratio 3.1/5.4 > 0.5), and moderately elevated protein. The diagnosis is confirmed by a **positive CSF PCR for enterovirus**. - **Enteroviral meningitis** in an immunocompetent individual, even during pregnancy, is typically a **self-limiting** illness that resolves within 7-10 days, making supportive care the most appropriate management. *Commence intravenous aciclovir 10 mg/kg three times daily for 14 days* - **Aciclovir** is an antiviral drug specifically active against **herpes simplex virus (HSV)** and **varicella-zoster virus (VZV)**, not enteroviruses. - The definitive diagnosis of enteroviral meningitis by PCR renders aciclovir therapy inappropriate and ineffective in this case. *Commence oral pleconaril 400 mg three times daily for 7 days* - **Pleconaril** is an investigational antiviral with activity against enteroviruses but is **not licensed or recommended** for routine clinical use due to concerns about efficacy and drug interactions. - Given that enteroviral meningitis usually resolves spontaneously, standard practice does not involve the use of unapproved antiviral agents. *Commence intravenous immunoglobulin 0.4 g/kg daily for 5 days* - **Intravenous immunoglobulin (IVIG)** is reserved for severe or chronic enteroviral infections, primarily in **immunocompromised patients** (e.g., those with B-cell deficiencies). - This patient is described as immunocompetent and presenting with typical, self-limiting viral meningitis, making IVIG unnecessary. *Commence intravenous ceftriaxone 2 g twice daily until bacterial culture results confirmed negative* - **Ceftriaxone** is an appropriate empirical antibiotic for suspected **bacterial meningitis**, but this diagnosis has been ruled out. - The **negative Gram stain**, **lymphocytic predominance** in the CSF, and especially the **positive enterovirus PCR** confirm a viral etiology, negating the need for antibiotic treatment.
Question 207: A 38-year-old man with cavitating pulmonary tuberculosis has been on treatment for 3 weeks with rifampicin, isoniazid, pyrazinamide, and ethambutol. His baseline liver function tests were normal. He now presents with jaundice. Blood tests show: bilirubin 156 μmol/L, ALT 420 U/L, AST 385 U/L, ALP 178 U/L. What is the most appropriate management approach?
- A. Continue all four drugs and add ursodeoxycholic acid for hepatoprotection
- B. Stop all anti-tuberculosis drugs until liver function normalizes, then reintroduce sequentially (Correct Answer)
- C. Stop pyrazinamide only and continue with the other three drugs
- D. Switch to a non-hepatotoxic regimen with streptomycin, ethambutol, and moxifloxacin
- E. Reduce the doses of all anti-tuberculosis drugs by 50% and recheck liver function in 1 week
Explanation: ***Stop all anti-tuberculosis drugs until liver function normalizes, then reintroduce sequentially***- This patient is experiencing severe **drug-induced hepatotoxicity** characterized by **clinical jaundice** (bilirubin 156 μmol/L) and markedly elevated **transaminases** (ALT 420 U/L, AST 385 U/L, which are >5 times the upper limit of normal).- The immediate and most appropriate action is to **discontinue all hepatotoxic anti-tuberculosis drugs** (isoniazid, rifampicin, pyrazinamide) to prevent progression to **acute liver failure**. Once liver function normalizes, drugs can be carefully reintroduced one by one.*Continue all four drugs and add ursodeoxycholic acid for hepatoprotection*- Continuing the current **hepatotoxic regimen** in the presence of significant **jaundice** and elevated **transaminases** is extremely dangerous and could lead to irreversible liver damage or death.- **Ursodeoxycholic acid** is primarily used for cholestatic liver diseases and has no established role in the acute management or reversal of **anti-tuberculosis drug-induced hepatocellular injury**.*Stop pyrazinamide only and continue with the other three drugs*- While **pyrazinamide** is known for its high hepatotoxic potential, both **isoniazid** and **rifampicin** also contribute significantly to **liver injury** and must be stopped during severe hepatotoxicity.- Selective discontinuation is typically reserved for milder, asymptomatic elevations of liver enzymes, not for cases with overt **jaundice**.*Switch to a non-hepatotoxic regimen with streptomycin, ethambutol, and moxifloxacin*- While a **non-hepatotoxic regimen** might be considered, the primary and immediate management for severe DILI in a stable patient is to completely **withdraw the offending drugs** to allow liver recovery.- This alternative regimen is usually reserved as a temporary measure for critically ill patients or those with highly infectious disease needing continuous therapy, while awaiting liver function normalization and potential reintroduction of first-line drugs.*Reduce the doses of all anti-tuberculosis drugs by 50% and recheck liver function in 1 week*- **Dose reduction** is insufficient and unsafe when a patient presents with **clinical jaundice** and significantly elevated liver enzymes, as it continues the hepatotoxic insult.- Furthermore, using sub-therapeutic doses risks promoting the development of **drug-resistant tuberculosis**, which would complicate future treatment.
Question 208: A 8-month-old infant is brought to the emergency department with a 12-hour history of fever of 39.8°C, irritability, and poor feeding. There is no rash. Lumbar puncture is performed: CSF glucose 1.4 mmol/L (blood glucose 4.8 mmol/L), protein 2.8 g/L, white cells 1200/mm³ (90% polymorphs). Gram stain shows Gram-negative coccobacilli. Intravenous ceftriaxone is commenced. Which organism is most likely responsible for this presentation?
- A. Neisseria meningitidis
- B. Streptococcus pneumoniae
- C. Haemophilus influenzae type b (Correct Answer)
- D. Listeria monocytogenes
- E. Group B Streptococcus
Explanation: ***Haemophilus influenzae type b*** - The presence of **Gram-negative coccobacilli** on Gram stain is the classic morphological description for *Haemophilus influenzae*. - The **CSF findings** (low glucose, high protein, high white cells with neutrophil predominance) confirm bacterial meningitis, which historically *H. influenzae type b* was a leading cause of in infants aged 3 months to 5 years. *Neisseria meningitidis* - While a major cause of meningitis, *Neisseria meningitidis* typically appears as **Gram-negative diplococci** (kidney-bean shaped), not coccobacilli. - It is frequently associated with a **purpuric or petechial rash**, which was specifically noted as absent in this patient. *Streptococcus pneumoniae* - This organism is a common cause of bacterial meningitis in children but would appear as **Gram-positive diplococci** (lancet-shaped). - The Gram stain showing Gram-negative coccobacilli definitively rules out *Streptococcus pneumoniae*. *Listeria monocytogenes* - This pathogen is characterized as a **Gram-positive bacillus** (rod-shaped) and typically affects neonates (under 3 months), the elderly, or immunocompromised individuals. - The Gram stain result of Gram-negative coccobacilli is inconsistent with *Listeria monocytogenes*. *Group B Streptococcus* - *Group B Streptococcus* appears as **Gram-positive cocci in chains** on microscopic examination. - It is the leading cause of **neonatal meningitis** but is rarely a cause of meningitis beyond 3-4 months of age.
Question 209: A 62-year-old woman with end-stage renal failure on haemodialysis presents with a 4-week history of fever, night sweats, and cough. Chest X-ray shows bilateral miliary shadowing. Sputum is positive for acid-fast bacilli and culture confirms Mycobacterium tuberculosis fully sensitive to first-line agents. She weighs 65 kg. What is the most appropriate dosing regimen for the intensive phase of treatment?
- A. Rifampicin 600 mg, isoniazid 300 mg, pyrazinamide 1500 mg, ethambutol 800 mg - all given daily
- B. Rifampicin 600 mg, isoniazid 300 mg, ethambutol 800 mg - given three times weekly post-dialysis, omit pyrazinamide
- C. Rifampicin 450 mg, isoniazid 200 mg, pyrazinamide 1000 mg, ethambutol 600 mg - given three times weekly post-dialysis
- D. Rifampicin 600 mg and isoniazid 300 mg given daily, pyrazinamide 1500 mg and ethambutol 1200 mg given three times weekly post-dialysis (Correct Answer)
- E. Rifampicin 600 mg, isoniazid 300 mg given daily, omit pyrazinamide and ethambutol due to renal impairment
Explanation: ***Rifampicin 600 mg and isoniazid 300 mg given daily, pyrazinamide 1500 mg and ethambutol 1200 mg given three times weekly post-dialysis*** - **Rifampicin** and **isoniazid** are predominantly metabolized by the **liver**, so their standard daily doses do not require adjustment for **end-stage renal disease (ESRD)**. - **Pyrazinamide** and **ethambutol** are primarily renally excreted and are significantly dialyzable; thus, they should be given **three times weekly post-dialysis** to prevent accumulation and reduce the risk of toxicity. *Rifampicin 600 mg, isoniazid 300 mg, pyrazinamide 1500 mg, ethambutol 800 mg - all given daily* - Administering **pyrazinamide** and **ethambutol** daily in a patient with **ESRD** on haemodialysis would lead to severe drug accumulation and an increased risk of dose-dependent toxicities, such as **hepatotoxicity** and **optic neuritis**. - This regimen is only appropriate for patients with **normal renal function**, as ESRD necessitates significant dose adjustments for renally cleared medications. *Rifampicin 600 mg, isoniazid 300 mg, ethambutol 800 mg - given three times weekly post-dialysis, omit pyrazinamide* - **Rifampicin** and **isoniazid** are hepatically cleared and should be given daily; reducing their frequency to three times weekly risks **subtherapeutic levels** and the development of drug resistance. - **Pyrazinamide** is a critical component of the standard four-drug intensive phase for tuberculosis treatment and should not be omitted unless there is a specific contraindication. *Rifampicin 450 mg, isoniazid 200 mg, pyrazinamide 1000 mg, ethambutol 600 mg - given three times weekly post-dialysis* - This option provides **subtherapeutic doses** for rifampicin (target 600 mg) and isoniazid (target 300 mg) for a 65 kg patient, which could lead to **treatment failure** and the development of drug resistance. - Rifampicin and isoniazid, being **hepatically cleared**, do not require reduction in frequency to three times weekly; they should be administered daily to maintain effective drug concentrations. *Rifampicin 600 mg, isoniazid 300 mg given daily, omit pyrazinamide and ethambutol due to renal impairment* - Omitting two essential drugs (**pyrazinamide** and **ethambutol**) from the intensive phase of anti-TB treatment significantly reduces treatment efficacy, especially for **miliary tuberculosis**. - While these drugs require dose adjustment in **renal impairment**, the correct approach is to modify their **dosing interval** and administer them post-dialysis, not to omit them entirely.
Question 210: A 52-year-old man with HIV infection (CD4 count 180 cells/mm³, viral load undetectable on antiretroviral therapy) presents with a 3-week history of headache and fever. CT head with contrast shows multiple ring-enhancing lesions in the basal ganglia and thalamus. Lumbar puncture shows: opening pressure 24 cmH₂O, CSF glucose 2.6 mmol/L (serum 5.8 mmol/L), protein 0.85 g/L, white cells 45/mm³ (80% lymphocytes). India ink stain is positive. What is the most appropriate initial management?
- A. Commence liposomal amphotericin B and flucytosine for 2 weeks followed by fluconazole (Correct Answer)
- B. Commence high-dose fluconazole 1200 mg daily for 10 weeks
- C. Commence pyrimethamine, sulfadiazine, and folinic acid for presumed toxoplasmosis
- D. Commence tuberculosis therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol
- E. Arrange urgent neurosurgical referral for stereotactic biopsy
Explanation: ***Commence liposomal amphotericin B and flucytosine for 2 weeks followed by fluconazole*** - The positive **India ink stain** in an HIV-positive patient definitively diagnoses **Cryptococcal meningitis**, despite the atypical presentation of **ring-enhancing lesions** (cryptococcomas). - The recommended initial management for cryptococcal meningitis is a 2-week induction phase with **liposomal amphotericin B** and **flucytosine**, followed by **fluconazole** for consolidation and maintenance. *Commence high-dose fluconazole 1200 mg daily for 10 weeks* - **High-dose fluconazole monotherapy** is not the standard induction therapy for cryptococcal meningitis, as it has a slower fungicidal effect and is associated with higher treatment failure rates and mortality compared to amphotericin-based regimens. - Fluconazole is primarily reserved for the **consolidation** and **maintenance** phases of cryptococcal meningitis treatment, after the initial induction phase with amphotericin B and flucytosine. *Commence pyrimethamine, sulfadiazine, and folinic acid for presumed toxoplasmosis* - Although **multiple ring-enhancing lesions** in the basal ganglia and thalamus are classic for **cerebral toxoplasmosis** in HIV patients, the definitive **positive India ink stain** specifically identifies *Cryptococcus neoformans* as the causative agent. - Toxoplasmosis would not result in a positive India ink stain, and initiating anti-toxoplasma therapy would delay appropriate treatment for the confirmed cryptococcal infection. *Commence tuberculosis therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol* - While **tuberculous meningitis** can present with headache, fever, lymphocytic pleocytosis, low CSF glucose, and sometimes ring-enhancing lesions, the definitive finding of a **positive India ink stain** specifically indicates **Cryptococcus**, not *Mycobacterium tuberculosis*. - The microbiological evidence directly points to a fungal infection, making empiric anti-tuberculosis therapy inappropriate as the initial management in this case. *Arrange urgent neurosurgical referral for stereotactic biopsy* - A **brain biopsy** is an invasive procedure that is not necessary when a clear diagnosis of **cryptococcal meningitis** has been established through less invasive means like CSF microscopy with **India ink stain**. - Biopsy is typically reserved for cases where the diagnosis remains unclear despite extensive non-invasive investigations, or if the patient fails to respond to appropriate empiric therapy.
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