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Infectious Diseases: Clinical Features, Diagnosis & Management
Based on Harrison's Principles of Internal Medicine, 21st Edition
OVERVIEW & DIAGNOSTIC PRINCIPLES
Diagnosis of infectious disease requires integration of:
- Clinical history and physical examination
- Epidemiological context (exposure, travel, immunocompromised state)
- Microbiological specimens (blood, urine, CSF, sputum, tissue)
- Laboratory science (cultures, PCR, serology, sensitivity testing)
- Pharmacokinetic principles for antibiotic dosing
(Harrison's 21e, p. 3; Guide to Microbiology Lab Utilization, p. 3)
I. BACTERIAL INFECTIONS
1. COMMUNITY-ACQUIRED PNEUMONIA (CAP)
Pathogens: S. pneumoniae (most common), H. influenzae, Mycoplasma pneumoniae, Legionella, Chlamydophila pneumoniae
Clinical Features:
- Fever, chills, productive cough (rusty sputum in pneumococcal)
- Pleuritic chest pain, dyspnea
- Lobar consolidation on exam (dullness, bronchial breathing, egophony)
- Atypicals: dry cough, headache, myalgia, extrapulmonary features
Diagnosis:
- Chest X-ray: lobar/segmental consolidation
- Sputum Gram stain and culture
- Blood cultures (2 sets before antibiotics)
- Urinary antigen for Legionella and S. pneumoniae
- PCT, CRP, CBC with differential
- CURB-65 or PSI scoring for severity
Management & Drug Dosages:
| Setting | Regimen | Dose & Timing |
|---|---|---|
| Outpatient (no comorbidities) | Amoxicillin | 1 g PO TID × 5 days |
| Outpatient (comorbidities/prior antibiotics) | Amoxicillin-clavulanate + Azithromycin | 875/125 mg PO BID + 500 mg PO OD × 5 days |
| Outpatient (alternative) | Respiratory fluoroquinolone (Levofloxacin) | 750 mg PO OD × 5 days |
| Inpatient (non-ICU) | Beta-lactam + Macrolide OR Respiratory FQ | Ceftriaxone 1–2 g IV OD + Azithromycin 500 mg IV/PO OD |
| ICU (severe CAP) | Beta-lactam + Azithromycin OR Beta-lactam + FQ | Ceftriaxone 2 g IV OD + Azithromycin 500 mg IV OD |
| Atypical (Mycoplasma, Chlamydia) | Azithromycin or Doxycycline | Azithromycin 500 mg day 1, then 250 mg OD × 4 days; OR Doxycycline 100 mg PO BID × 5 days |
| Legionella | Azithromycin or Levofloxacin | Azithromycin 500 mg IV/PO OD × 7–10 days; Levofloxacin 750 mg OD × 5–7 days |
2. HOSPITAL-ACQUIRED / VENTILATOR-ASSOCIATED PNEUMONIA (HAP/VAP)
Pathogens: Pseudomonas aeruginosa, MRSA, Klebsiella, Acinetobacter
Clinical Features: New or progressive pulmonary infiltrate + fever + leukocytosis + purulent secretions (≥48h after admission)
Diagnosis:
- BAL / endotracheal aspirate culture (quantitative)
- Blood cultures
- CPIS scoring
Management:
| Pathogen | Drug | Dose & Timing |
|---|---|---|
| Empiric (no MDR risk) | Piperacillin-tazobactam | 4.5 g IV q6h |
| Pseudomonas coverage | Cefepime or Meropenem | Cefepime 2 g IV q8h; Meropenem 1–2 g IV q8h |
| MRSA (add if risk factors) | Vancomycin or Linezolid | Vancomycin 15–20 mg/kg IV q8–12h (target AUC 400–600); Linezolid 600 mg IV/PO BID |
| Acinetobacter | Carbapenem ± Colistin | Meropenem 2 g IV q8h; Colistin 5 mg/kg/day in 2–4 divided doses |
3. TUBERCULOSIS (TB)
Pathogen: Mycobacterium tuberculosis
Clinical Features:
- Primary TB: Often asymptomatic or mild; Ghon complex on CXR
- Post-primary/Reactivation TB:
- Chronic productive cough (hemoptysis), fever, drenching night sweats, weight loss, fatigue
- Apical/upper lobe infiltrates, cavitation on CXR
- Extrapulmonary TB: Lymphadenitis, pleural effusion, miliary TB, TB meningitis, skeletal TB (Pott's disease), genitourinary TB
Diagnosis:
- Sputum AFB smear × 3 (morning specimens)
- Sputum MGIT/LJ culture (gold standard; 2–8 weeks)
- GeneXpert MTB/RIF (rapid PCR: detects TB + rifampicin resistance in ~2h)
- Tuberculin Skin Test (TST) / IGRA (QUANTIFERON-TB Gold)
- CXR: cavitation, upper lobe infiltrates, hilar adenopathy
- ADA level in pleural/CSF fluid
Management — Standard Regimen (Drug-Sensitive TB):
| Phase | Drugs (HRZE) | Dose | Duration |
|---|---|---|---|
| Intensive | Isoniazid (H) | 5 mg/kg/day (max 300 mg) PO OD | 2 months |
| Intensive | Rifampicin (R) | 10 mg/kg/day (max 600 mg) PO OD | 2 months |
| Intensive | Pyrazinamide (Z) | 25 mg/kg/day (max 2 g) PO OD | 2 months |
| Intensive | Ethambutol (E) | 15–20 mg/kg/day PO OD | 2 months |
| Continuation | Isoniazid + Rifampicin (HR) | Same doses | 4 months |
| Total Duration | 6 months |
- Add Pyridoxine (B6) 25–50 mg/day with INH to prevent neuropathy
- MDR-TB: Bedaquiline 400 mg OD × 2 weeks, then 200 mg 3×/week × 22 weeks + Linezolid + Levofloxacin
- TB Meningitis: HRZE × 2 months + HR × 10 months + Dexamethasone 0.3–0.4 mg/kg/day tapered over 6–8 weeks
- Latent TB: INH 300 mg/day × 9 months OR INH+Rifapentine once-weekly × 12 weeks (3HP regimen)
4. INFECTIVE ENDOCARDITIS (IE)
Pathogens: S. aureus (most common, acute), viridans streptococci (subacute), HACEK organisms, Enterococcus, CoNS
Clinical Features (Duke Criteria):
- Fever, new/changing murmur, embolic phenomena
- Osler nodes (painful, finger pulps), Janeway lesions (painless, palmar)
- Roth spots (retinal), splinter hemorrhages
- Splenomegaly, clubbing (chronic)
Diagnosis:
- Blood cultures × 3 (from different sites, before antibiotics) — major criterion
- Echocardiography (TEE > TTE for sensitivity) — vegetations, abscess
- Modified Duke criteria (2 major OR 1 major + 3 minor OR 5 minor)
Management:
| Organism | Drug | Dose & Duration |
|---|---|---|
| Viridans Strep (PCN-sensitive MIC ≤0.12) | Penicillin G | 12–18 MU/day IV continuously or in 4–6 divided doses × 4 weeks |
| Viridans Strep (PCN-sensitive) alternative | Ceftriaxone | 2 g IV OD × 4 weeks |
| Enterococcus (PCN-sensitive) | Ampicillin + Gentamicin | Ampicillin 12 g/day IV in 6 divided doses + Gentamicin 1 mg/kg IV q8h × 4–6 weeks |
| S. aureus (MSSA) — native valve | Nafcillin or Oxacillin | 12 g/day IV in 4–6 divided doses × 6 weeks |
| S. aureus (MRSA) | Vancomycin | 15–20 mg/kg IV q8–12h (target AUC 400–600) × 6 weeks |
| S. aureus (MRSA) alternative | Daptomycin | 8–10 mg/kg IV OD × 6 weeks |
| Prosthetic valve (MRSA) | Vancomycin + Rifampicin + Gentamicin | Vanco + Rifampicin 300 mg PO/IV BID × ≥6 weeks + Gentamicin × 2 weeks |
| HACEK organisms | Ceftriaxone | 2 g IV OD × 4 weeks |
5. MENINGITIS
A. Bacterial Meningitis
Pathogens: N. meningitidis, S. pneumoniae, L. monocytogenes (elderly/immunocompromised), Group B Strep (neonates), E. coli (neonates)
Clinical Features:
- Classic triad: fever + neck stiffness + altered sensorium (present in only 44%)
- Kernig's sign, Brudzinski's sign
- Petechial/purpuric rash (N. meningitidis)
- Photophobia, phonophobia, headache
- Papilledema (raised ICP), focal neurological deficits
Diagnosis:
- Lumbar puncture (LP) — key investigation:
- Bacterial: turbid CSF, WBC >1000/μL (neutrophils), glucose <45 mg/dL, protein >150 mg/dL
- CSF Gram stain, culture + sensitivity
- CT head before LP if: papilledema, focal neuro deficit, immunocompromised, new-onset seizures
- Blood cultures before antibiotics
- CRP, PCT, CBC
Management:
| Age/Setting | Empirical Antibiotics | Dose |
|---|---|---|
| Adults (16–50 y) | Ceftriaxone | 2 g IV q12h |
| >50 y or immunocompromised (add Listeria cover) | Ceftriaxone + Ampicillin | Ceftriaxone 2 g IV q12h + Ampicillin 2 g IV q4h |
| MRSA suspected | Add Vancomycin | 15–20 mg/kg IV q8–12h |
| Neonates | Ampicillin + Gentamicin or Cefotaxime | Ampicillin 200–300 mg/kg/day ÷ q6h + Gentamicin 2.5 mg/kg IV q8–12h |
| PCN allergy | Chloramphenicol + TMP-SMX | — |
| Adjunct | Dexamethasone 0.15 mg/kg IV q6h × 4 days | Start before/with first antibiotic dose; reduces mortality and neurologic sequelae |
- Duration: N. meningitidis 7 days, S. pneumoniae 10–14 days, Listeria 21 days, Gram-negative 21 days
B. Neonatal GBS Meningitis (Harrison's 21e, p. 4479)
- Penicillin G: ≤7 days: 250,000–450,000 units/kg/day IV ÷ TID; >7 days: 450,000–500,000 units/kg/day ÷ QID
- Treat ≥14 days
6. TYPHOID FEVER (Enteric Fever)
Pathogen: Salmonella typhi / S. paratyphi
Clinical Features:
- Week 1: Step-ladder fever, relative bradycardia (Faget's sign), headache, dry cough
- Week 2: Rose spots (chest/abdomen), splenomegaly, hepatomegaly, "pea soup" diarrhea
- Week 3: Intestinal perforation, hemorrhage, encephalopathy
- Week 4: Gradual defervescence or complications
Diagnosis:
- Blood culture (gold standard; highest yield Week 1)
- Widal test (limited sensitivity/specificity; titer >1:160 significant)
- Bone marrow culture (most sensitive)
- Typhidot / TUBEX (rapid serology)
- CBC: Leukopenia, thrombocytopenia, elevated LFTs
Management:
| Drug | Dose | Duration | Notes |
|---|---|---|---|
| Ceftriaxone (drug of choice) | 2 g IV OD (adults); 75 mg/kg/day IV (children) | 10–14 days | Preferred for severe disease |
| Azithromycin | 1 g PO day 1, then 500 mg OD (adults); 20 mg/kg OD (children) | 7 days | Preferred for uncomplicated; excellent oral bioavailability |
| Ciprofloxacin | 500 mg PO BID or 400 mg IV BID | 10–14 days | Avoid if fluoroquinolone-resistant (common in South Asia) |
| Chloramphenicol | 50–75 mg/kg/day PO/IV ÷ QID | 14 days | Cheap, effective; bone marrow toxicity risk |
| Ampicillin | 2 g IV q6h | 14 days | Alternative |
| TMP-SMX | 160/800 mg PO BID | 14 days | Alternative (resistance common) |
| Dexamethasone | 3 mg/kg IV then 1 mg/kg q6h × 8 doses | — | Severe typhoid with encephalopathy |
| Carriers | Ciprofloxacin 750 mg BID | 4 weeks | Eradication of biliary carriage |
7. CHOLERA
Pathogen: Vibrio cholerae O1 / O139
Clinical Features:
- Sudden onset profuse watery diarrhea ("rice-water stools"), vomiting
- Severe dehydration: sunken eyes, loss of skin turgor, reduced urine output
- Electrolyte imbalance: hypokalemia, metabolic acidosis
- No fever (toxin-mediated)
Diagnosis:
- Stool dark-field microscopy: "shooting star" motility
- Stool culture on TCBS agar
- Rapid antigen test (RDT)
Management:
- ORS (cornerstone): WHO low-osmolarity ORS 75 mL/kg over 4 hours
- IV Ringer's Lactate for severe dehydration: 100 mL/kg over 3h (adults), 6h (children)
- Antibiotics (reduce duration/volume):
| Drug | Adult Dose | Pediatric Dose | Duration |
|---|---|---|---|
| Doxycycline (first-line) | 300 mg PO single dose | Not recommended <8y | Single dose |
| Azithromycin | 1 g PO single dose | 20 mg/kg single dose | Single dose |
| Ciprofloxacin | 1 g PO single dose | 20 mg/kg | Single dose |
| TMP-SMX | 160/800 mg BID | 5 mg/kg TMP BID | 3 days |
8. URINARY TRACT INFECTION (UTI)
Pathogens: E. coli (80%), Klebsiella, Proteus, Enterococcus, S. saprophyticus (young women)
Clinical Features:
- Cystitis: Dysuria, frequency, urgency, suprapubic pain, cloudy/foul-smelling urine
- Pyelonephritis: Fever, rigors, flank pain (CVA tenderness), nausea/vomiting + cystitis symptoms
- Urethritis: Dysuria + urethral discharge
Diagnosis:
- Urine dipstick: Nitrites + leukocyte esterase
- Urine microscopy: >5 WBC/HPF, bacteria
- Urine culture and sensitivity (gold standard): ≥10⁵ CFU/mL
- Blood cultures for pyelonephritis/sepsis
Management:
| Condition | Drug | Dose | Duration |
|---|---|---|---|
| Uncomplicated cystitis (women) | Nitrofurantoin | 100 mg PO BID (modified release) | 5 days |
| Uncomplicated cystitis | TMP-SMX | 160/800 mg PO BID | 3 days |
| Uncomplicated cystitis | Fosfomycin | 3 g PO single dose | Single dose |
| Uncomplicated cystitis | Ciprofloxacin | 250 mg PO BID | 3 days |
| Mild-moderate pyelonephritis | Ciprofloxacin | 500 mg PO BID or 400 mg IV BID | 7 days |
| Moderate-severe pyelonephritis | Ceftriaxone | 1–2 g IV OD | 10–14 days |
| Complicated UTI / ESBL | Ertapenem or Meropenem | Ertapenem 1 g IV OD; Meropenem 500 mg IV q8h | 10–14 days |
| Catheter-associated UTI | Based on culture sensitivity | — | 7–14 days |
| UTI in pregnancy | Cephalexin or Nitrofurantoin (avoid at term) | Cephalexin 500 mg QID × 7 days | 7 days |
9. SEPSIS & SEPTIC SHOCK
Definition (Sepsis-3): Life-threatening organ dysfunction due to dysregulated host response to infection (SOFA score increase ≥2)
Clinical Features:
- Fever >38°C or hypothermia <36°C
- Tachycardia (HR >90), tachypnea (RR >20)
- Altered mental status, oliguria, hypotension (MAP <65 mmHg in septic shock)
- Organ dysfunction: AKI, ARDS, DIC, hepatic dysfunction
Diagnosis:
- Blood cultures × 2 (before antibiotics)
- PCT, Lactate (>2 mmol/L = poor prognosis; >4 = septic shock)
- SOFA scoring, qSOFA (RR≥22, AMS, SBP≤100)
Management (Hour-1 Bundle — Surviving Sepsis Campaign 2021):
- Measure lactate; remeasure if >2 mmol/L
- Blood cultures before antibiotics
- Broad-spectrum antibiotics within 1 hour
- 30 mL/kg IV crystalloid for hypotension or lactate ≥4
- Vasopressors if MAP <65 despite fluids
Antibiotic Regimens:
| Source | Empirical Regimen | Dose |
|---|---|---|
| Unknown source | Piperacillin-tazobactam + Vancomycin | Pip-Tazo 4.5 g IV q6h + Vanco 15–20 mg/kg q8–12h |
| Abdominal | Meropenem ± Metronidazole | Meropenem 1 g IV q8h + Metronidazole 500 mg IV q8h |
| Urinary | Ceftriaxone or Ciprofloxacin | Ceftriaxone 2 g IV OD |
| Lung (CAP-sepsis) | Ceftriaxone + Azithromycin | See CAP section |
| MRSA suspected | Vancomycin or Daptomycin | As above |
| Fungal sepsis (Candida) | Micafungin | 100 mg IV OD |
| Vasopressors | Norepinephrine (first-line) | 0.01–3 mcg/kg/min IV |
| Adjunct (refractory) | Vasopressin | 0.03 units/min IV |
| Adjunct | Hydrocortisone (if refractory shock) | 200 mg/day IV continuous infusion |
II. VIRAL INFECTIONS
10. INFLUENZA
Clinical Features:
- Abrupt onset: high fever, severe myalgia, headache, dry cough
- Sore throat, rhinorrhea, prostration
- Complications: primary viral pneumonia, secondary bacterial pneumonia, myocarditis, encephalitis
Diagnosis:
- Rapid Influenza Diagnostic Test (RIDT): nasopharyngeal swab
- RT-PCR (gold standard)
Management:
| Drug | Dose | Duration | Notes |
|---|---|---|---|
| Oseltamivir (Tamiflu) | 75 mg PO BID (adults); weight-based in children | 5 days | Start within 48h of symptoms |
| Zanamivir | 2 inhalations (10 mg) BID | 5 days | Inhaled; not for COPD/asthma |
| Baloxavir marboxil | 40 mg single dose (<80 kg) or 80 mg (>80 kg) | Single dose | Cap-dependent endonuclease inhibitor |
| IV Peramivir | 600 mg IV single dose | Single dose | Severe/hospitalized cases |
| IV Zanamivir | 600 mg IV BID | 5–10 days | Resistant or critically ill |
11. HIV/AIDS
Clinical Features:
- Acute HIV (2–4 weeks post-exposure): Mononucleosis-like syndrome: fever, pharyngitis, lymphadenopathy, rash, myalgia
- Chronic HIV: Asymptomatic for years; progressive immunodeficiency
- AIDS (CD4 <200/μL): Opportunistic infections (PCP, toxoplasmosis, CMV, MAC, cryptococcal meningitis), AIDS-defining malignancies (Kaposi sarcoma, NHL, cervical cancer)
Diagnosis:
- 4th-generation HIV Ag/Ab combo assay (detects HIV-1/2 Ab + HIV-1 p24 Ag)
- HIV RNA PCR (viral load) — confirms and quantifies
- CD4 count — staging and OI prophylaxis threshold
- Genotypic resistance testing before ART initiation
Management — Antiretroviral Therapy (ART):
Preferred first-line regimen (2023/2024):
| Regimen | Drugs | Dose |
|---|---|---|
| Preferred (INSTI-based) | Bictegravir/Tenofovir alafenamide/Emtricitabine (BIC/TAF/FTC) | 1 tablet PO OD |
| Alternative | Dolutegravir/Abacavir/Lamivudine (DTG/ABC/3TC) — if HLA-B*57:01 negative | 1 tablet PO OD |
| Alternative | Dolutegravir + Tenofovir/Emtricitabine | DTG 50 mg OD + TDF/FTC 1 tab OD |
| 2-drug regimen | Dolutegravir/Lamivudine | 1 tablet PO OD (if viral load <500,000; no HBV co-infection) |
| Pregnancy | Dolutegravir + Tenofovir/Emtricitabine | Preferred |
OI Prophylaxis:
| CD4 Count | Infection to Prevent | Drug | Dose |
|---|---|---|---|
| <200/μL | PCP | TMP-SMX | 1 DS tablet PO OD |
| <100/μL | Toxoplasmosis | TMP-SMX (same as PCP dose) | — |
| <50/μL | MAC | Azithromycin | 1,200 mg PO weekly |
| Any | Tuberculosis (LTBI) | INH + Pyridoxine | 300 mg OD × 9 months |
PCP Treatment:
- TMP-SMX 15–20 mg/kg/day (TMP component) IV or PO ÷ TID-QID × 21 days
- Add Prednisone 40 mg BID × 5 days, then taper if PaO₂ <70 mmHg
12. DENGUE FEVER
Pathogen: Dengue virus (DENV 1–4), Flavivirus
Clinical Features:
- Dengue fever (DF): Sudden high fever, severe headache, retro-orbital pain, myalgia/arthralgia ("breakbone fever"), maculopapular rash, mild hemorrhagic manifestations
- Dengue Hemorrhagic Fever (DHF): Plasma leakage (hematocrit rise ≥20%), thrombocytopenia (<100,000), hemorrhagic manifestations
- Dengue Shock Syndrome (DSS): Signs of DHF + circulatory failure
Warning Signs: Abdominal pain, persistent vomiting, rapid breathing, bleeding, fatigue, restlessness, liver enlargement, ↑hematocrit with rapid ↓platelet
Diagnosis:
- NS1 antigen (Days 1–5): highly sensitive in early disease
- IgM/IgG ELISA (Days 5 onwards)
- RT-PCR (first 5 days)
- CBC: Leukopenia + thrombocytopenia (hallmark)
Management (No specific antiviral):
| Severity | Management |
|---|---|
| Dengue without warning signs | Oral hydration, paracetamol (max 4 g/day); avoid NSAIDs/aspirin |
| Dengue with warning signs | IV isotonic crystalloids 5–10 mL/kg/h; monitor closely |
| Severe dengue/DSS | IV fluid resuscitation 10–20 mL/kg bolus; colloids if needed; platelet transfusion if <10,000 or active bleeding |
13. MALARIA
Pathogen: Plasmodium falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi
Clinical Features:
- Periodic fever (tertian — 48h for P. vivax/ovale/falciparum; quartan — 72h for P. malariae)
- Cold stage (rigors) → Hot stage (fever 40–41°C) → Sweating stage
- Anemia, splenomegaly, hepatomegaly
- Severe malaria (P. falciparum): Cerebral malaria (coma, seizures), ARDS, AKI, blackwater fever (hemoglobinuria), severe anemia (Hb <7 g/dL), hypoglycemia, DIC
Diagnosis:
- Peripheral blood smear (thick + thin): gold standard
- Rapid Diagnostic Test (RDT) — HRP2 antigen for P. falciparum
- PCR (most sensitive)
Management:
| Type | Drug | Dose |
|---|---|---|
| Uncomplicated P. falciparum (1st line) | Artemether-Lumefantrine (AL) | 4 tabs PO BID × 3 days (adult: 20/120 mg/tab) |
| Uncomplicated P. falciparum (alternative) | Artesunate-Amodiaquine or Artesunate-Mefloquine | Per weight-based dosing × 3 days |
| Uncomplicated P. vivax (chloroquine-sensitive) | Chloroquine | 1000 mg base (600 mg base) stat, then 500 mg at 6h, 24h, 48h |
| P. vivax radical cure (prevent relapse) | Primaquine | 0.5 mg/kg/day × 14 days (check G6PD first!) |
| Uncomplicated P. vivax (CQ-resistant) | AL or Artesunate-based | As above |
| Severe/Cerebral Malaria | IV Artesunate (FIRST-LINE) | 2.4 mg/kg IV at 0, 12, 24h, then OD until able to take oral |
| Severe malaria (if artesunate unavailable) | IV Quinine + Doxycycline | Quinine 20 mg/kg loading dose over 4h, then 10 mg/kg q8h; Doxycycline 100 mg BID × 7 days |
| Chemoprophylaxis | Mefloquine or Atovaquone-Proguanil or Doxycycline | Mefloquine 250 mg weekly; Atovaquone-proguanil 1 tab OD; Doxycycline 100 mg OD |
III. FUNGAL INFECTIONS
14. CANDIDIASIS
Clinical Features:
- Oropharyngeal: white plaques on erythematous base (thrush)
- Esophageal: dysphagia, odynophagia (AIDS-defining)
- Vulvovaginal: pruritus, thick white "cottage cheese" discharge
- Candidemia: persistent fever despite broad-spectrum antibiotics in ICU
Diagnosis:
- Clinical (oropharyngeal); KOH wet mount (pseudohyphae)
- Blood culture (sensitivity ~50% for invasive disease)
- Beta-D-glucan (>80 pg/mL suggestive)
- Candida PCR/T2 Candida assay
Management:
| Condition | Drug | Dose | Duration |
|---|---|---|---|
| Oropharyngeal | Fluconazole | 200 mg PO day 1, then 100 mg OD | 7–14 days |
| Esophageal | Fluconazole | 400 mg PO/IV OD | 14–21 days |
| Vulvovaginal (uncomplicated) | Fluconazole | 150 mg PO single dose | Single dose |
| Candidemia (non-neutropenic) | Echinocandin (Micafungin/Caspofungin) | Micafungin 100 mg IV OD; Caspofungin 70 mg load → 50 mg IV OD | ≥14 days after last positive culture |
| Candidemia (stable, fluconazole-sensitive) | Fluconazole | 800 mg loading, then 400 mg IV/PO OD | ≥14 days |
| Fluconazole-resistant (C. glabrata) | Echinocandin | As above | — |
| CNS candidiasis | Liposomal AmB + Flucytosine | L-AmB 5 mg/kg/day + 5-FC 25 mg/kg QID | Induction then fluconazole |
15. CRYPTOCOCCAL MENINGITIS
Clinical Features:
- Subacute headache, fever, nausea
- Altered mental status, seizures
- Papilledema (raised ICP — major cause of morbidity)
- Predominantly in HIV (CD4 <100), transplant recipients
Diagnosis:
- CSF India ink stain: encapsulated yeast
- CSF cryptococcal antigen (CrAg): highly sensitive
- Serum CrAg (screening in HIV CD4 <100)
- Culture (gold standard)
Management (WHO 2022):
| Phase | Regimen | Dose | Duration |
|---|---|---|---|
| Induction | Liposomal AmB + Flucytosine | L-AmB 3 mg/kg/day IV + 5-FC 25 mg/kg PO QID | 1 week |
| Consolidation | Fluconazole | 400–800 mg PO OD | 8 weeks |
| Maintenance | Fluconazole | 200 mg PO OD | ≥1 year (until CD4 >100 on ART) |
| ICP management | Therapeutic LP | Remove 20–30 mL CSF if opening pressure >25 cmH₂O | Daily until stable |
IV. PARASITIC INFECTIONS
16. AMOEBIASIS
Pathogen: Entamoeba histolytica
Clinical Features:
- Intestinal: Amoebic dysentery (blood + mucus in stool, colicky pain, tenesmus)
- Extraintestinal: Amoebic liver abscess (right-sided fever, tender hepatomegaly, "anchovy sauce" pus)
Diagnosis:
- Stool microscopy: trophozoites with ingested RBCs (E. histolytica specific)
- Stool antigen ELISA (high sensitivity)
- Serology (for liver abscess)
- Ultrasound/CT: hypoechoic lesion right lobe of liver
Management:
| Condition | Drug | Dose | Duration |
|---|---|---|---|
| Amoebic colitis | Metronidazole | 750 mg PO/IV TID | 7–10 days |
| Amoebic liver abscess | Metronidazole | 750 mg PO TID OR 500 mg IV TID | 7–10 days |
| Luminal eradication (after metronidazole) | Paromomycin | 25–35 mg/kg/day PO ÷ TID | 7 days |
| Alternative luminal agent | Diloxanide furoate | 500 mg PO TID | 10 days |
17. GIARDIASIS
Pathogen: Giardia lamblia (G. intestinalis)
Clinical Features:
- Explosive watery diarrhea → steatorrhea (fatty, foul-smelling, floating stools)
- Bloating, flatulence, abdominal cramps
- Nausea, weight loss
- No blood/mucus in stool (non-invasive)
Diagnosis:
- Stool microscopy: cysts (diagnostic)
- Stool antigen ELISA (most sensitive)
- Duodenal biopsy (recalcitrant cases)
Management:
| Drug | Dose | Duration |
|---|---|---|
| Metronidazole | 400 mg PO TID | 5–7 days |
| Tinidazole (first choice) | 2 g PO single dose | Single dose |
| Albendazole | 400 mg PO OD | 5 days |
| Nitazoxanide | 500 mg PO BID | 3 days |
18. LEISHMANIASIS
Clinical Features:
- Visceral (Kala-azar): Prolonged fever, massive splenomegaly, hepatomegaly, lymphadenopathy, anemia, wasting, pancytopenia
- Cutaneous: Painless nodule → ulcer with raised indurated border
- Mucocutaneous: Destructive lesions of nose, palate, pharynx
Diagnosis:
- Splenic aspirate (most sensitive), bone marrow aspirate
- rK39 rapid test (visceral — high sensitivity in India)
- PCR
Management:
| Form | Drug | Dose | Duration |
|---|---|---|---|
| Visceral (South Asia) | Liposomal AmB | 3 mg/kg IV OD days 1–5, 14, 21 (total 21 mg/kg) | 21 days |
| Visceral (Africa) | Sodium stibogluconate + Paromomycin | SSG 20 mg/kg/day IM + Paromomycin 15 mg/kg/day IM | 17 days |
| Visceral (alternative) | Miltefosine | 2.5 mg/kg/day PO (max 150 mg) | 28 days |
| Cutaneous | Meglumine antimoniate (Glucantime) | 20 mg/kg/day IM | 20–28 days |
| Cutaneous (simple) | Local intralesional antimonials or topical therapy | — | — |
19. HELMINTHS (WORM INFECTIONS)
Common Intestinal Helminths
| Helminth | Drug | Dose | Notes |
|---|---|---|---|
| Ascariasis (A. lumbricoides) | Albendazole | 400 mg PO single dose | Or Mebendazole 500 mg single dose |
| Hookworm (Ancylostoma/Necator) | Albendazole | 400 mg PO single dose | |
| Trichuriasis (T. trichiura) | Mebendazole | 100 mg PO BID × 3 days | |
| Strongyloidiasis | Ivermectin | 200 mcg/kg/day PO × 2 days | Drug of choice |
| Tapeworm (T. solium, T. saginata) | Praziquantel | 5–10 mg/kg PO single dose | |
| Neurocysticercosis | Albendazole + Praziquantel | Albendazole 15 mg/kg/day ÷ BID; Praziquantel 50 mg/kg/day ÷ TID | 8–30 days + steroids |
| Echinococcosis (Hydatid) | Albendazole | 400 mg PO BID × 28 days on/14 days off | PAIR procedure + surgical |
| Filariasis (LF) | DEC + Albendazole | DEC 6 mg/kg single dose + Albendazole 400 mg | Annual MDA |
| Onchocerciasis | Ivermectin | 150 mcg/kg PO | Annually × 10–15 years |
| Schistosomiasis | Praziquantel | 40 mg/kg/day PO ÷ BID (S. mansoni); 60 mg/kg ÷ TID (S. japonicum) | Single day |
V. SEXUALLY TRANSMITTED INFECTIONS (STIs)
20. STI SUMMARY TABLE
| STI | Pathogen | Clinical Features | Diagnosis | Treatment | Dose & Duration |
|---|---|---|---|---|---|
| Gonorrhea | N. gonorrhoeae | Urethral/cervical discharge, dysuria, PID, epididymo-orchitis | NAAT (most sensitive); Gram stain (urethral discharge) | Ceftriaxone | 500 mg IM single dose (or 1 g if >150 kg) |
| Chlamydia | C. trachomatis | Urethritis, cervicitis, PID (often asymptomatic) | NAAT | Doxycycline | 100 mg PO BID × 7 days |
| Syphilis (Primary) | T. pallidum | Painless chancre at inoculation site | VDRL/RPR (screening) + TPHA/FTA-ABS (confirmatory); Dark-field microscopy | Benzathine PCN G | 2.4 MU IM single dose |
| Syphilis (Secondary) | — | Maculopapular rash (palms+soles), condylomata lata, lymphadenopathy | VDRL/RPR (high titers) | Benzathine PCN G | 2.4 MU IM single dose |
| Syphilis (Tertiary/Late Latent) | — | Gummas, cardiovascular syphilis, neurosyphilis | As above | Benzathine PCN G | 2.4 MU IM weekly × 3 doses |
| Neurosyphilis | — | Tabes dorsalis, Argyll Robertson pupil, dementia | CSF VDRL, FTA-ABS | Aqueous PCN G | 3–4 MU IV q4h × 10–14 days |
| Genital Herpes | HSV-2 (>HSV-1) | Painful vesicles/ulcers, dysuria, LAD | Clinical; PCR; viral culture | Acyclovir / Valacyclovir | Acyclovir 400 mg TID × 7–10 days (primary); Valacyclovir 500 mg BID × 3 days (recurrent) |
| Chancroid | H. ducreyi | Painful soft ulcer + tender inguinal LAD (bubo) | Clinical; culture | Azithromycin | 1 g PO single dose OR Ceftriaxone 250 mg IM |
| Trichomoniasis | T. vaginalis | Frothy yellow-green vaginal discharge, pruritus | Wet mount (motile trichomonads); NAAT | Metronidazole | 2 g PO single dose OR 500 mg BID × 7 days |
| BV | Gardnerella vaginalis | Thin gray discharge, fishy odor, clue cells | Amsel's criteria; Whiff test; Clue cells | Metronidazole | 500 mg PO BID × 7 days OR 0.75% gel intravaginal OD × 5 days |
VI. VECTOR-BORNE & RICKETTSIAL INFECTIONS
21. RICKETTSIAL INFECTIONS
| Disease | Organism | Vector | Clinical Features | Treatment | Dose |
|---|---|---|---|---|---|
| Rocky Mountain Spotted Fever | R. rickettsii | Tick | Fever + rash (centripetal spread, involves palms/soles) + eschar | Doxycycline | 100 mg PO/IV BID × 7 days (treat empirically; don't wait for confirmation) |
| Typhus (Epidemic) | R. prowazekii | Louse | Fever, headache, maculopapular rash (trunk → extremities) | Doxycycline | 200 mg PO single dose |
| Murine Typhus | R. typhi | Flea | Similar to epidemic but milder | Doxycycline | 100 mg BID × 7 days |
| Scrub Typhus | O. tsutsugamushi | Mite (chigger) | Eschar + fever + lymphadenopathy + rash | Doxycycline | 100 mg PO BID × 7 days (or Azithromycin if pregnant/children) |
| Q Fever (acute) | Coxiella burnetii | Aerosol (no vector) | Fever, hepatitis, pneumonia | Doxycycline | 100 mg PO BID × 14–21 days |
| Ehrlichiosis/Anaplasmosis | Ehrlichia/Anaplasma | Tick | Fever, leukopenia, thrombocytopenia, elevated LFTs ("spotless" rickettsia) | Doxycycline | 100 mg PO BID × 5–10 days |
22. LEPTOSPIROSIS
Clinical Features:
- Phase I (Leptospiremic, days 1–7): Fever, headache, myalgia (especially calf muscles), conjunctival suffusion, rash
- Phase II (Immune/Weil's disease): Jaundice + AKI + bleeding tendency (Weil's disease); uveitis; aseptic meningitis
Diagnosis:
- Blood/urine culture (first week/second week)
- Serology (MAT — gold standard; ELISA for screening)
- PCR
Management:
| Severity | Drug | Dose | Duration |
|---|---|---|---|
| Mild | Doxycycline | 100 mg PO BID | 7 days |
| Mild alternative | Amoxicillin | 500 mg PO TID | 7 days |
| Severe (Weil's) | Penicillin G | 1.5 MU IV q6h | 7 days |
| Severe alternative | Ceftriaxone | 1 g IV OD | 7 days |
| Prophylaxis | Doxycycline | 200 mg PO weekly | During exposure |
VII. IMPORTANT MULTI-SYSTEM INFECTIONS
23. BRUCELLOSIS
Clinical Features: Undulant fever, night sweats, arthralgia, hepatosplenomegaly; complications: spondylitis (Brucella spondylitis), endocarditis, neurobrucellosis
Diagnosis: Blood culture (gold standard); RBPT + serology (SAT titer ≥1:160)
Management:
| Regimen | Drugs | Dose | Duration |
|---|---|---|---|
| Standard (WHO) | Doxycycline + Rifampicin | Doxy 100 mg PO BID + Rifampicin 600–900 mg OD | 6 weeks |
| Alternative (preferred for complicated) | Doxycycline + Streptomycin | Doxy 100 mg BID × 6 weeks + Streptomycin 1 g IM OD × 2–3 weeks | — |
| Spondylitis/endocarditis | Triple therapy: Doxy + Rifampicin + Aminoglycoside | As above + aminoglycoside | 3–6 months |
| Children (<8y) | TMP-SMX + Rifampicin | TMP 10 mg/kg/day ÷ BID + Rifampicin 15–20 mg/kg OD | 6 weeks |
24. TETANUS
Pathogen: Clostridium tetani (tetanospasmin toxin)
Clinical Features:
- Trismus (lockjaw), risus sardonicus
- Opisthotonus (board-like rigidity)
- Laryngospasm, autonomic dysfunction (BP fluctuations, arrhythmias)
- Spasms triggered by noise/light/touch
Management:
| Intervention | Drug/Action | Dose |
|---|---|---|
| Wound care | Debridement | — |
| Neutralize toxin | Human Tetanus Immune Globulin (HTIG) | 3,000–6,000 IU IM (infiltrate around wound) |
| Antimicrobial | Metronidazole | 500 mg IV q6h × 10 days |
| Alternative | PCN G | 10–12 MU/day IV |
| Muscle relaxation | Diazepam | 10–40 mg IV q1–8h (titrated); up to 500 mg/day |
| Severe spasms | Midazolam infusion or Baclofen (intrathecal) | Midazolam 5–15 mg/h IV |
| Autonomic | Labetalol or Magnesium sulfate | Magnesium 40 mg/kg loading, then 2 g/h infusion |
| Vaccination (post-recovery) | Tetanus toxoid | Complete immunization series |
25. RABIES
Clinical Features:
- Prodrome (2–10 days): fever, paresthesia/pain at wound site, anxiety
- Neurological (Encephalitic/Furious): hydrophobia, aerophobia, hypersalivation, agitation, seizures
- Paralytic: ascending flaccid paralysis (Guillain-Barré-like)
- Once symptomatic: almost uniformly fatal
Diagnosis (ante-mortem): DFA on skin biopsy (nuchal); CSF PCR; Negri bodies (post-mortem)
Post-Exposure Prophylaxis (PEP):
| Component | Drug | Schedule | Notes |
|---|---|---|---|
| Wound care | Soap + water wash × 15 min | Immediate | Most effective single intervention |
| Rabies Immune Globulin (RIG) | Human RIG (HRIG) | 20 IU/kg — infiltrate around wound; remainder IM | Give on Day 0 only; if not available give within 7 days |
| Vaccine (unvaccinated) | Rabies vaccine (PCECV/HDCV) | Days 0, 3, 7, 14 (IM deltoid) | 4-dose Essen regimen |
| Vaccine (previously vaccinated) | Rabies vaccine | Days 0 and 3 only | No RIG needed |
VIII. COMMON DRUG DOSAGE QUICK REFERENCE
| Drug | Standard Adult Dose | Route | Frequency |
|---|---|---|---|
| Amoxicillin | 500 mg–1 g | PO | TID |
| Amoxicillin-clavulanate | 875/125 mg | PO | BID |
| Ampicillin | 1–2 g | IV | q4–6h |
| Piperacillin-tazobactam | 4.5 g | IV | q6h (or q8h extended infusion) |
| Ceftriaxone | 1–2 g | IV/IM | OD–BID |
| Cefepime | 2 g | IV | q8h |
| Meropenem | 1–2 g | IV | q8h |
| Ertapenem | 1 g | IV/IM | OD |
| Vancomycin | 15–20 mg/kg | IV | q8–12h (AUC-guided) |
| Linezolid | 600 mg | IV/PO | BID |
| Daptomycin | 6–10 mg/kg | IV | OD |
| Metronidazole | 500 mg | IV/PO | TID (q8h) |
| Ciprofloxacin | 400 mg IV / 500 mg PO | IV/PO | BID |
| Levofloxacin | 750 mg | IV/PO | OD |
| Azithromycin | 500 mg | IV/PO | OD |
| Doxycycline | 100 mg | PO/IV | BID |
| TMP-SMX (DS) | 160/800 mg | PO | BID (varies) |
| Fluconazole | 400–800 mg loading, 200–400 mg maintenance | PO/IV | OD |
| Micafungin | 100 mg | IV | OD |
| Caspofungin | 70 mg loading → 50 mg | IV | OD |
| Liposomal AmB | 3–5 mg/kg | IV | OD |
| Acyclovir (severe HSV) | 10 mg/kg | IV | q8h |
| Oseltamivir | 75 mg | PO | BID × 5 days |
| Isoniazid | 5 mg/kg (max 300 mg) | PO | OD |
| Rifampicin | 10 mg/kg (max 600 mg) | PO | OD |
KEY CLINICAL PEARLS (Harrison's 21e)
- Start antibiotics within 1 hour in septic shock — every hour of delay increases mortality by ~7%
- Never delay antibiotics for LP in suspected bacterial meningitis if CT is needed first — give dexamethasone + ceftriaxone immediately
- IV Artesunate is now the definitive first-line for severe malaria (superior to IV quinine — AQUAMAT & SEAQUAMAT trials)
- Doxycycline is the drug of choice for nearly all rickettsial diseases — never withhold for fear of tooth discoloration in short courses even in children
- Check G6PD before primaquine in vivax malaria — can precipitate life-threatening hemolysis
- Treat both partners in STIs; test-of-cure for gonorrhea (increasing resistance)
- ART should be started in all HIV patients regardless of CD4 count (START trial)
- Rifampicin reduces levels of many drugs (oral contraceptives, warfarin, antiretrovirals) — always check interactions
- Echinocandins are preferred over fluconazole for empirical candidemia in ICU patients
- Rabies PEP works if given promptly — the key is thorough wound washing immediately after exposure
This synthesis is based on Harrison's Principles of Internal Medicine, 21st Edition, supplemented by WHO treatment guidelines, CDC recommendations, and Infectious Diseases Society of America (IDSA) guidelines. For pediatric dosing, renal/hepatic adjustments, and specific patient populations, always consult the full prescribing information and institutional protocols.
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