{"title": "Chapter 10: Infectious Diseases", "flashcards": [{"q": "Define Sepsis-3 and the SOFA score threshold.", "a": "Sepsis-3 (2016): life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction defined by SOFA score increase of ≥2 points from baseline. Septic shock: subset with circulatory and cellular/metabolic dysfunction sufficient to substantially increase mortality — vasopressor needed to maintain MAP ≥65 mmHg AND serum lactate >2 mmol/L despite adequate fluid resuscitation."}, {"q": "What are the Surviving Sepsis Campaign Hour-1 Bundle elements?", "a": "(1) Measure lactate; repeat if initial >2 mmol/L; (2) Blood cultures before antibiotics; (3) Broad-spectrum antibiotics; (4) IV crystalloids 30 mL/kg if hypotension or lactate ≥4 mmol/L; (5) Vasopressors if hypotensive during/after fluids to maintain MAP ≥65 mmHg. All five should be initiated within 1 hour of sepsis recognition."}, {"q": "Name the CURB-65 score components and thresholds for hospital admission.", "a": "Confusion (AMTS ≤8), Urea >7 mmol/L, Respiratory rate ≥30/min, Blood pressure <90 systolic or ≤60 diastolic, age ≥65. Each = 1 point. Score 0–1: low risk, home; Score 2: intermediate, consider admission; Score ≥3: high risk, hospital admission (ICU if ≥4–5). BTS guidelines for CAP."}, {"q": "What are the WHO staging criteria for HIV disease and CD4 thresholds?", "a": "WHO Stage 1: asymptomatic/PGL. Stage 2: mild symptoms (seborrhoeic dermatitis, herpes zoster, minor mucosal disease). Stage 3: moderate (oral candidiasis, TB pulmonary, unexplained anaemia). Stage 4 (AIDS): CD4 <200/µL or AIDS-defining illness (PCP, cryptococcal meningitis, CMV retinitis, cerebral toxoplasmosis, Kaposi's sarcoma, MAC, CNS lymphoma)."}, {"q": "What is the mechanism of resistance of MRSA to beta-lactam antibiotics?", "a": "MRSA expresses mecA gene-encoded penicillin-binding protein PBP2a, which has very low affinity for all beta-lactams (penicillins, cephalosporins, carbapenems). Beta-lactams cannot inhibit cell wall synthesis via PBP2a, rendering them ineffective. Treatment: vancomycin or teicoplanin (glycopeptides); linezolid; daptomycin; ceftaroline (anti-MRSA cephalosporin)."}, {"q": "Name three AIDS-defining opportunistic infections and their CD4 thresholds.", "a": "PCP (Pneumocystis jirovecii pneumonia): CD4 <200/µL; Toxoplasma encephalitis: CD4 <100/µL; CMV retinitis: CD4 <50/µL; Cryptococcal meningitis: CD4 <100/µL; MAC (Mycobacterium avium complex): CD4 <50/µL; cerebral lymphoma: CD4 <50/µL. Each threshold guides prophylaxis initiation in HIV management."}, {"q": "What is the mechanism of action of nucleoside reverse transcriptase inhibitors (NRTIs) in HIV treatment?", "a": "NRTIs (tenofovir, emtricitabine, abacavir, lamivudine) are prodrugs that undergo intracellular phosphorylation to triphosphate form. They competitively inhibit HIV reverse transcriptase and act as chain terminators — lacking a 3'-OH group needed for DNA chain elongation. NRTIs form the 'backbone' of all current first-line ART regimens."}, {"q": "What is the empirical antibiotic treatment for community-acquired pneumonia requiring hospitalisation (non-ICU)?", "a": "Co-amoxiclav (amoxicillin-clavulanate) + clarithromycin, OR amoxicillin (for low severity) + clarithromycin for atypical coverage. Doxycycline as alternative to clarithromycin. For severe CAP: IV co-amoxiclav + IV clarithromycin, or pip-tazo + clarithromycin if HAP features. Duration: 5 days for low-moderate severity; 7–10 days if Legionella or severe. De-escalate based on culture results."}, {"q": "Name three vector-borne infections seen in returning travellers and their vectors.", "a": "Malaria (Plasmodium spp.) — Anopheles mosquito (Africa, South/Southeast Asia, Central America). Dengue fever — Aedes mosquito (tropical/subtropical). Chikungunya — Aedes mosquito. Yellow fever — Aedes mosquito (sub-Saharan Africa, South America). Leishmaniasis — sandfly. Lyme disease — Ixodes tick. Rickettsia — ticks."}, {"q": "What is the Weil-Felix test and why is it no longer preferred?", "a": "Weil-Felix test detects antibodies against Proteus OX antigens in suspected rickettsial infection — based on cross-reactivity. It has low sensitivity (~50–70%) and poor specificity (false positives in urinary tract infections, liver disease). IFA (indirect immunofluorescence assay) or PCR from skin biopsy are now preferred for diagnosis of rickettsial diseases (Rocky Mountain spotted fever, typhus)."}], "quiz": [{"q": "What is the most appropriate antibiotic regimen for suspected meningococcal meningitis before LP results?", "opts": ["Aciclovir IV", "IV ceftriaxone 2 g immediately (before LP if it would delay treatment by >1 hour) + dexamethasone 0.15 mg/kg QDS for 4 days", "Oral amoxicillin", "IV vancomycin alone"], "ans": 1, "exp": "IV ceftriaxone should be given immediately in suspected bacterial meningitis — do NOT delay for LP if it cannot be performed within 1 hour. Dexamethasone reduces neurological complications in pneumococcal meningitis. Add dexamethasone before or with first antibiotic dose. If CT indicated before LP, do not delay antibiotics for CT either."}, {"q": "Which HIV antiretroviral class acts by preventing viral integration into host DNA?", "opts": ["NRTIs", "Integrase strand transfer inhibitors (INSTIs — dolutegravir, bictegravir, raltegravir)", "Protease inhibitors", "CCR5 antagonists"], "ans": 1, "exp": "INSTIs inhibit HIV integrase enzyme, which catalyses the integration of viral dsDNA into the host genome. Without integration, viral replication cannot proceed. INSTIs (dolutegravir, bictegravir) are now first-line in most guidelines due to high efficacy, tolerability, and high genetic barrier to resistance."}, {"q": "What is the treatment for falciparum malaria in a non-immune adult?", "opts": ["Chloroquine", "Artemisinin-based combination therapy (ACT) — e.g. artemether-lumefantrine (Riamet) or artesunate IV for severe malaria", "Mefloquine alone", "Doxycycline alone"], "ans": 1, "exp": "Uncomplicated falciparum malaria: artemether-lumefantrine (Riamet) or dihydroartemisinin-piperaquine first-line (UK and most areas). Severe malaria (impaired consciousness, ARDS, AKI, parasitaemia >2%): IV artesunate is superior to quinine. Confirm against current PHE/WHO guidance. Chloroquine resistance is widespread in P. falciparum."}, {"q": "What is the most specific diagnostic test for Clostridioides difficile infection?", "opts": ["Stool culture", "Stool PCR (NAAT) for C. difficile toxin genes, or toxin ELISA — used in a two-step algorithm", "Colonoscopy showing pseudomembranes", "WBC count >15,000"], "ans": 1, "exp": "IDSA/SHEA recommend a two-step algorithm: GDH (glutamate dehydrogenase) antigen as initial screen, confirmed by toxin ELISA or PCR if GDH positive. PCR alone can over-diagnose CDI (detects colonisation). Clinical correlation is essential — a positive test alone without diarrhoea (≥3 unformed stools/day) does not confirm CDI."}, {"q": "What complication of infective endocarditis requires immediate surgical consultation?", "opts": ["New mild mitral regurgitation", "Heart failure from valvular destruction, perivalvular abscess, or uncontrolled infection despite appropriate antibiotics", "Single embolic event", "Positive blood cultures at 48 hours"], "ans": 1, "exp": "Indications for urgent surgery in IE: (1) heart failure from valve destruction; (2) uncontrolled infection (perivalvular abscess, fistula, enlarging vegetation on therapy); (3) prevention of embolism (vegetation >10 mm on LVOT or after embolic event). Duke criteria guide diagnosis; surgery in 40–50% of IE cases."}, {"q": "What is the recommended treatment for latent tuberculosis infection (LTBI) in a 35-year-old with positive IGRA and HIV?", "opts": ["No treatment required if asymptomatic", "6 months isoniazid (6H) or 3 months rifampicin + isoniazid (3RH) as per NICE NG33, plus pyridoxine (vitamin B6) to prevent peripheral neuropathy", "12 months rifampicin alone", "4-drug therapy for active TB"], "ans": 1, "exp": "NICE NG33 recommends treatment of LTBI in IGRA/Mantoux positive individuals with risk factors including HIV, recent conversion, or contacts of smear-positive TB. Options: 6 months isoniazid (6H), or 3RH (3 months rifampicin + isoniazid) — both equally effective. Pyridoxine 10–25 mg/day prevents isoniazid-induced peripheral neuropathy. Rule out active TB before LTBI treatment."}, {"q": "What is post-exposure prophylaxis (PEP) for HIV and when must it be started?", "opts": ["Within 72 hours — ideally as soon as possible after exposure", "Within 1 week", "Only after a confirmed positive test", "Only for healthcare workers"], "ans": 0, "exp": "HIV PEP (tenofovir/emtricitabine + raltegravir or dolutegravir) must be started as soon as possible — ideally within 24 hours of high-risk exposure (unprotected sex with HIV+ individual, needlestick injury) and no later than 72 hours. Efficacy falls rapidly beyond 72 hours. Duration: 28 days. Available free via sexual health clinics and A&E in the UK."}, {"q": "Which antibiotic class is preferred for treating Legionella pneumophila pneumonia?", "opts": ["Aminoglycosides", "Fluoroquinolones (levofloxacin, moxifloxacin) or macrolides (azithromycin, clarithromycin)", "Penicillins", "Metronidazole"], "ans": 1, "exp": "Legionella is an intracellular organism that requires antibiotics with good intracellular penetration. Fluoroquinolones (levofloxacin) are preferred for severe Legionella pneumonia; macrolides (azithromycin) for mild-moderate disease. Urinary Legionella antigen (detects serogroup 1 — responsible for 80–90% of cases) is the rapid diagnostic test of choice."}, {"q": "What is the mechanism of carbapenem resistance in Gram-negative bacteria?", "opts": ["Beta-lactamase that only inactivates carbapenems at low concentrations", "Production of carbapenemases (e.g. KPC, NDM-1, OXA-48) that hydrolyse the beta-lactam ring of carbapenems, conferring resistance to all beta-lactams", "Altered porin channels only", "Efflux pumps alone"], "ans": 1, "exp": "Carbapenem-resistant Enterobacterales (CRE) resist all beta-lactams via carbapenemase production. KPC (Klebsiella pneumoniae carbapenemase) — serine carbapenemase; NDM-1 (New Delhi metallo-beta-lactamase) — zinc-dependent metalloprotease. Treatment options: ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, or cefiderocol — choice depends on carbapenemase type. Infection control measures are critical."}, {"q": "What is the recommended prophylaxis against Pneumocystis jirovecii pneumonia in HIV patients?", "opts": ["Fluconazole 150 mg weekly", "Co-trimoxazole (trimethoprim-sulfamethoxazole) 960 mg OD or 480 mg OD when CD4 <200 cells/µL", "Atovaquone only", "Dapsone only"], "ans": 1, "exp": "PJP prophylaxis is indicated when CD4 <200 cells/µL. First-line: co-trimoxazole 960 mg OD (or 480 mg OD three times/week). Alternatives if sulfa allergy: dapsone 100 mg OD, atovaquone 750 mg BD, or nebulised pentamidine monthly. Prophylaxis can be discontinued when CD4 >200 for ≥3 months on effective ART."}, {"q": "What is the mechanism of action of vancomycin?", "opts": ["Inhibits DNA gyrase", "Binds D-Ala–D-Ala terminus of lipid-linked peptidoglycan precursors, preventing cross-linking of bacterial cell wall; active against Gram-positive organisms only (cannot penetrate Gram-negative outer membrane)", "Inhibits protein synthesis at 30S ribosomal subunit", "Disrupts cell membrane integrity"], "ans": 1, "exp": "Vancomycin binds to D-alanyl-D-alanine termini of peptidoglycan precursors on the cell wall surface, preventing transglycosylation and transpeptidation required for cell wall synthesis. It requires IV administration for systemic infection (oral is not absorbed — only for C. difficile colitis treatment). Monitoring: trough-based or AUC/MIC-based TDM to optimise efficacy and minimise nephrotoxicity."}, {"q": "What is the treatment for Lyme disease with erythema migrans?", "opts": ["IV ceftriaxone for all cases", "Oral doxycycline 100 mg BD for 14–21 days (first-line) or amoxicillin 500 mg TDS for 14 days; IV ceftriaxone reserved for neurological Lyme (neuroborreliosis — meningitis, cranial nerve palsy, radiculopathy) or cardiac involvement", "No treatment required for isolated rash", "Azithromycin as first-line"], "ans": 1, "exp": "Lyme disease (Borrelia burgdorferi sensu lato — UK predominantly B. afzelii/B. garinii) presents with erythema migrans (expanding ring-like rash at tick bite site). Early localised disease: oral doxycycline 14–21 days. Disseminated Lyme with neurological/cardiac involvement: IV ceftriaxone 2 g OD for 14–28 days. ELISA + Western blot (two-tier testing) confirms diagnosis in patients with clinical features; serology unreliable in early disease."}, {"q": "Which antibiotic class causes C. difficile infection most commonly?", "opts": ["Macrolides", "Fluoroquinolones, cephalosporins, clindamycin, and broad-spectrum penicillins — all disrupt normal gut microbiota, allowing C. difficile overgrowth and toxin production", "Aminoglycosides", "Antifungals"], "ans": 1, "exp": "Fluoroquinolones (ciprofloxacin, levofloxacin) and cephalosporins are the most strongly associated with CDI in recent epidemiology (particularly the hypervirulent NAP1/ribotype 027 strain). Clindamycin was historically most implicated. Antibiotic stewardship — restricting CDI-associated antibiotics — is the primary prevention strategy. Risk also increases with PPIs, age >65, and immunosuppression."}, {"q": "What is the mechanism of resistance of ESBL-producing Enterobacterales?", "opts": ["Reduced cell permeability only", "Production of extended-spectrum beta-lactamases (enzymes hydrolysing the beta-lactam ring of penicillins, cephalosporins, and aztreonam, but NOT carbapenems); encoded by plasmid-borne genes (CTX-M most common globally)", "Cell wall thickening", "Efflux pump only"], "ans": 1, "exp": "ESBL-producing organisms (Klebsiella, E. coli, Enterobacter) produce plasmid-encoded beta-lactamases that hydrolyse oxyimino-cephalosporins (cefotaxime, ceftriaxone, ceftazidime) and broad-spectrum penicillins. They are NOT hydrolysed by carbapenems. Treatment of ESBL bacteraemia: meropenem or ertapenem. Piperacillin-tazobactam should be avoided (inoculum effect). Oral step-down: nitrofurantoin or trimethoprim for UTI if susceptible."}, {"q": "What is the recommended first-line antiretroviral regimen for treatment-naive HIV in adults?", "opts": ["Dual NRTI backbone alone", "Bictegravir/tenofovir alafenamide/emtricitabine (Biktarvy — single tablet regimen) or dolutegravir + tenofovir alafenamide/emtricitabine (Dovato/TLD) — INSTIs + NRTIs", "Protease inhibitor + two NRTIs", "NNRTI monotherapy"], "ans": 1, "exp": "BHIVA 2023 guidelines: integrase strand transfer inhibitor (INSTI) + two NRTIs as preferred first-line ART. Preferred regimens: bictegravir/TAF/FTC (Biktarvy) or dolutegravir-based dual/triple therapy. High genetic barrier to resistance, excellent tolerability, one-tablet once daily. Dolutegravir is WHO-recommended globally for resource-limited settings. Avoid efavirenz (CNS side effects) and boosted PI (drug interactions) as first-line in most patients."}, {"q": "What is the blood test profile of acute viral hepatitis A?", "opts": ["Positive HBsAg, elevated ALT", "Positive anti-HAV IgM (acute marker), markedly elevated ALT (hepatocellular pattern), normal or mildly elevated ALP, elevated bilirubin — prodromal phase has flu-like symptoms before jaundice develops", "Anti-HCV positive", "Positive anti-HAV IgG (past infection/immunity)"], "ans": 1, "exp": "Acute HAV: anti-HAV IgM appears at symptom onset (highly sensitive and specific for acute infection; persists ~3–6 months). Anti-HAV IgG indicates past infection or vaccination (lifelong immunity). ALT rises markedly (often >1000 IU/L — hepatocellular pattern). HAV RNA can be detected by PCR in early infection. HAV is self-limiting in adults; fulminant hepatic failure rare (<0.5%) but mortality higher in elderly and those with chronic liver disease."}, {"q": "What is the empirical antibiotic regimen for healthcare-associated pneumonia (HCAP) at high risk of Pseudomonas?", "opts": ["Amoxicillin alone", "Piperacillin-tazobactam (or ceftazidime) ± aminoglycoside (gentamicin) ± anti-MRSA agent (vancomycin) — based on local antibiogram and risk factors for resistant organisms", "Oral clarithromycin", "Co-amoxiclav alone"], "ans": 1, "exp": "HCAP (contact with healthcare settings, recent hospitalisation, immunosuppression, broad-spectrum antibiotic use) carries risk of resistant Gram-negative organisms including Pseudomonas. Anti-pseudomonal coverage: piperacillin-tazobactam, ceftazidime, or cefepime. MRSA risk: add vancomycin or linezolid. De-escalate at 48–72h based on culture/sensitivity results. Duration: 7 days for HAP; 8 days for VAP (no benefit from longer courses in most patients)."}, {"q": "What is the most sensitive test for active pulmonary tuberculosis?", "opts": ["Ziehl-Neelsen smear of sputum", "Mycobacterium tuberculosis nucleic acid amplification test (NAAT — e.g. Xpert MTB/RIF) on respiratory sample — faster than culture (result in 2 hours), detects rifampicin resistance simultaneously; culture remains gold standard for drug susceptibility testing", "Tuberculin skin test (Mantoux)", "CXR showing cavitation"], "ans": 1, "exp": "GeneXpert MTB/RIF (WHO-endorsed NAAT) has sensitivity ~90% vs smear microscopy (~60–80% for smear-positive, ~40–60% for smear-negative disease). Results in 2 hours. Also identifies rifampicin resistance (surrogate for MDR-TB). Culture (Löwenstein-Jensen or liquid MGIT) remains gold standard for full drug susceptibility testing but takes 2–8 weeks. WHO recommends NAAT as the initial diagnostic test for presumptive pulmonary TB."}, {"q": "What prophylaxis reduces risk of spontaneous bacterial peritonitis (SBP) recurrence in cirrhosis?", "opts": ["No prophylaxis is effective", "Long-term oral norfloxacin 400 mg OD or ciprofloxacin 500 mg OD (primary prophylaxis in high-risk cirrhosis: protein <15 g/L ascites, Child-Pugh >9, bilirubin >45 µmol/L, AKI, hyponatraemia; secondary prophylaxis after SBP episode)", "IV antibiotics monthly", "Rifaximin for SBP prophylaxis specifically"], "ans": 1, "exp": "Secondary SBP prophylaxis: norfloxacin 400 mg OD (or ciprofloxacin 500 mg OD) reduces recurrence from ~70% to ~20% at 1 year. Primary prophylaxis is indicated in high-risk cirrhotic ascites (protein <15 g/L + Child-Pugh ≥9 or bilirubin ≥45 µmol/L) or after GI bleed (norfloxacin or IV ceftriaxone for 7 days). Prophylaxis should be continued until ascites resolves or transplantation."}, {"q": "What is the mechanism of action of azithromycin?", "opts": ["Inhibits cell wall synthesis", "Binds 50S ribosomal subunit, inhibiting translocation and peptide chain elongation — macrolide antibiotic with prolonged intracellular half-life (~68 hours), excellent tissue penetration, and 5-day treatment courses for most indications", "Inhibits DNA gyrase", "Disrupts cell membrane"], "ans": 1, "exp": "Azithromycin (azalide subclass of macrolides) achieves high intracellular concentrations in phagocytes (leukocytes carry it to sites of infection), explaining efficacy against intracellular organisms (Legionella, Chlamydia, Mycoplasma, Campylobacter) and the prolonged post-antibiotic effect. 5-day course provides ~10 days of tissue-level activity. QT prolongation risk — avoid with other QT-prolonging drugs."}]}