Master Infectious Diseases
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Core Concepts
Infectious diseases result from the invasion of a host by pathogenic microorganisms (bacteria, viruses, fungi, parasites) leading to illness. Key principles include antimicrobial stewardship (right drug, dose, duration, indication), understanding resistance mechanisms (e.g., beta-lactamases, efflux pumps), and host factors (immunocompromised states like neutropenia, HIV, organ transplant). Healthcare-associated infections (HAIs) are a significant concern. Vaccines are crucial for prevention. Epidemiology distinguishes between community-acquired and nosocomial infections, with understanding of transmission routes (droplet, airborne, contact, vector-borne).
Clinical Presentation
- Sepsis/Septic Shock: Life-threatening organ dysfunction caused by a dysregulated host response to infection. High qSOFA score (respiratory rate ≥22, altered mentation, systolic BP ≤100 mmHg) or SOFA score increase is critical.
- Fever of Unknown Origin (FUO): Fever >38.3°C on several occasions over >3 weeks, no diagnosis despite 1 week of investigation. Common causes: infections (abscesses, TB, endocarditis), malignancy, autoimmune.
- Meningitis/Encephalitis:
- Meningitis: Headache, fever, neck stiffness, photophobia. CSF analysis differentiates bacterial (high protein, low glucose, high neutrophils) from viral (normal/mildly elevated protein, normal glucose, high lymphocytes) and fungal.
- Encephalitis: Altered mental status, seizures, focal neurological deficits.
- Endocarditis: Fever, new murmur, embolic phenomena, heart failure. Duke criteria for diagnosis (TTE/TOE, blood cultures). HACEK organisms are slow-growing.
- Urinary Tract Infections (UTIs): Dysuria, frequency, urgency. Pyelonephritis presents with fever, flank pain. Complicated UTIs involve structural/functional abnormalities or immunocompromise.
- Respiratory Tract Infections:
- Community-Acquired Pneumonia (CAP): CURB-65 for severity assessment.
- Healthcare-Associated Pneumonia (HAP)/Ventilator-Associated Pneumonia (VAP): Different pathogen spectrum.
- TB: Chronic cough, weight loss, night sweats, haemoptysis.
- Gastrointestinal Infections: Diarrhea, abdominal pain, vomiting. Specific pathogens (e.g., C. difficile, Salmonella, Shigella, Campylobacter, E. coli O157).
- Skin & Soft Tissue Infections: Cellulitis, erysipelas (superficial), necrotizing fasciitis (severe, rapid progression, crepitus, disproportionate pain).
- Opportunistic Infections in Immunocompromised Hosts: e.g., PCP, CMV, Cryptococcus, Toxoplasma.
Diagnosis (Gold Standard)
Diagnosis typically relies on isolating the pathogen or detecting its components/immune response.
- Cultures: Blood, urine, CSF, sputum, wound swabs. Essential for pathogen identification and antimicrobial susceptibility testing.
- Molecular Methods (PCR): Rapid detection for viruses (HIV viral load, CMV, EBV), atypical bacteria (Mycoplasma, Chlamydia), C. difficile toxin genes, TB.
- Serology: Detects antibodies or antigens. Used for viral hepatitis (HBV, HCV), HIV, syphilis, Lyme disease, specific fungal infections, and some parasitic infections (e.g., Toxoplasma). Paired acute and convalescent titres can show rising antibodies.
- Microscopy: Gram stain (bacteria), Ziehl-Neelsen stain (TB), India ink (Cryptococcus), wet mounts (parasites).
- Imaging: Chest X-ray/CT (pneumonia, TB), MRI brain (encephalitis, abscesses), Echocardiography (TTE/TOE for endocarditis), CT abdomen (intra-abdominal abscesses).
- CSF Analysis: Differentiates types of meningitis/encephalitis based on cell count, protein, glucose, and culture/PCR.
- Biomarkers: CRP and Procalcitonin can support bacterial infection suspicion, though non-specific.
Management (First Line)
Management involves timely initiation of appropriate antimicrobials, source control, and supportive care.
- Sepsis: "Sepsis six" – oxygen, cultures, IV fluids, broad-spectrum IV antibiotics, lactate, urine output. Source control (drainage of abscess, debridement).
- Bacterial Meningitis: Empiric IV antibiotics (e.g., Ceftriaxone + Vancomycin, +/- Ampicillin for Listeria in elderly/immunocompromised) immediately after CSF collection (or before if delay). Dexamethasone reduces neurological sequelae in adults with pneumococcal meningitis.
- Endocarditis: Prolonged IV antibiotics (e.g., Penicillin/Gentamicin for Strep. viridans, Vancomycin/Gentamicin for Staph. aureus), often guided by susceptibility. Surgery for severe valvular damage, persistent infection, or embolic risk.
- Community-Acquired Pneumonia: Amoxicillin or Doxycycline/Macrolide (clarithromycin) for mild-moderate; Ceftriaxone/Cefotaxime + Macrolide for severe.
- Urinary Tract Infections: Uncomplicated cystitis: Nitrofurantoin or Trimethoprim. Pyelonephritis/Complicated UTI: Ciprofloxacin or Co-amoxiclav (oral); IV Ceftriaxone or Gentamicin for severe.
- Clostridioides difficile Infection (CDI): Oral Vancomycin or Fidaxomicin. Metronidazole for mild/non-severe cases if vancomycin unavailable.
- HIV: Antiretroviral Therapy (ART) with combination drugs (HAART). Prophylaxis against opportunistic infections (e.g., Trimethoprim-sulfamethoxazole for PCP when CD4 count <200 cells/mm³).
- Tuberculosis: First-line therapy is a 6-month regimen: 2 months of Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RIPE), followed by 4 months of Rifampicin and Isoniazid.
- Malaria: Artemisinin-based combination therapies (ACTs) are first-line for uncomplicated P. falciparum malaria. IV Artesunate for severe malaria.
Exam Red Flags
- Sepsis with organ dysfunction: Clinical emergency requiring immediate management (Sepsis Six).
- Neutropenic fever: Broad-spectrum antibiotics immediately, prior to culture results, due to high mortality risk.
- Necrotizing fasciitis: Suspect with severe pain, crepitus, skin changes. Surgical emergency for debridement.
- Acute Meningococcal Disease: Rapid progression, non-blanching rash. Public health emergency.
- Tuberculosis: Especially drug-resistant forms, high index of suspicion in at-risk groups.
- Antimicrobial resistance: Awareness of MRSA, ESBLs, CRE and their appropriate management.
- Drug toxicities: E.g., Rifampicin (liver), Isoniazid (peripheral neuropathy - give pyridoxine), Aminoglycosides (nephro-/ototoxicity), Vancomycin (Red Man Syndrome, nephrotoxicity).
- Immunocompromised host: Atypical presentations, unusual pathogens, higher mortality.
- Notifiable diseases: Meningitis, TB, HIV, Salmonella, Shigella, Viral Haemorrhagic Fevers.
Sample Practice Questions
An 82-year-old man presents with a 6-week history of unexplained fever, night sweats, and a 5 kg weight loss. He has a history of COPD and prostate cancer, currently in remission. Physical examination is unremarkable except for mild cachexia. Laboratory tests reveal an ESR of 105 mm/hr and CRP of 150 mg/L. Initial blood cultures, urinalysis, and chest X-ray are normal.
A 45-year-old woman presents with a 2-day history of fever (39°C), rigors, nausea, and severe right flank pain radiating to the groin. She also reports dysuria and increased urinary frequency for the past week. Urinalysis shows leukocyte esterase, nitrites, and numerous white blood cells. Which of the following is the most appropriate initial management for this patient?
A 45-year-old man with a known history of HIV infection, who has been non-adherent with his antiretroviral therapy (ART) for the past two years, presents with a 3-week history of progressive shortness of breath, dry cough, and low-grade fever. On examination, he is tachypnoeic, saturating 88% on room air, and has bilateral fine inspiratory crackles. Chest X-ray shows diffuse bilateral interstitial infiltrates, predominantly in the perihilar regions. His CD4 count is 75 cells/µL.
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