from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.lib import colors
from reportlab.platypus import SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable, PageBreak
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY

doc = SimpleDocTemplate(
    "/home/daytona/workspace/hospital-infection-control/Hospital_Infection_Control_B1_to_B7.pdf",
    pagesize=A4,
    rightMargin=2*cm, leftMargin=2*cm,
    topMargin=2*cm, bottomMargin=2*cm
)

styles = getSampleStyleSheet()

# Custom styles
title_style = ParagraphStyle('Title', parent=styles['Title'],
    fontSize=16, spaceAfter=10, textColor=colors.HexColor('#1a3a5c'), alignment=TA_CENTER)

subtitle_style = ParagraphStyle('Subtitle', parent=styles['Normal'],
    fontSize=11, spaceAfter=6, textColor=colors.HexColor('#555555'), alignment=TA_CENTER)

h1_style = ParagraphStyle('H1', parent=styles['Heading1'],
    fontSize=14, spaceBefore=14, spaceAfter=6,
    textColor=colors.HexColor('#1a3a5c'),
    borderPad=4)

h2_style = ParagraphStyle('H2', parent=styles['Heading2'],
    fontSize=12, spaceBefore=10, spaceAfter=4,
    textColor=colors.HexColor('#2e6da4'))

h3_style = ParagraphStyle('H3', parent=styles['Heading3'],
    fontSize=11, spaceBefore=8, spaceAfter=3,
    textColor=colors.HexColor('#444444'))

body_style = ParagraphStyle('Body', parent=styles['Normal'],
    fontSize=10, spaceAfter=5, leading=15, alignment=TA_JUSTIFY)

bullet_style = ParagraphStyle('Bullet', parent=styles['Normal'],
    fontSize=10, spaceAfter=3, leading=14,
    leftIndent=18, bulletIndent=6)

bullet2_style = ParagraphStyle('Bullet2', parent=styles['Normal'],
    fontSize=10, spaceAfter=2, leading=13,
    leftIndent=36, bulletIndent=18)

def h1(text): return Paragraph(text, h1_style)
def h2(text): return Paragraph(text, h2_style)
def h3(text): return Paragraph(text, h3_style)
def body(text): return Paragraph(text, body_style)
def bullet(text): return Paragraph(f"• {text}", bullet_style)
def bullet2(text): return Paragraph(f"◦ {text}", bullet2_style)
def sp(n=6): return Spacer(1, n)
def hr(): return HRFlowable(width="100%", thickness=0.5, color=colors.HexColor('#aaaaaa'), spaceAfter=4, spaceBefore=4)

def make_table(headers, rows, col_widths=None):
    data = [headers] + rows
    if col_widths is None:
        col_widths = [16*cm/len(headers)] * len(headers)
    t = Table(data, colWidths=col_widths)
    t.setStyle(TableStyle([
        ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#1a3a5c')),
        ('TEXTCOLOR', (0,0), (-1,0), colors.white),
        ('FONTNAME', (0,0), (-1,0), 'Helvetica-Bold'),
        ('FONTSIZE', (0,0), (-1,0), 9),
        ('FONTSIZE', (0,1), (-1,-1), 9),
        ('ROWBACKGROUNDS', (0,1), (-1,-1), [colors.HexColor('#f5f8ff'), colors.white]),
        ('GRID', (0,0), (-1,-1), 0.4, colors.HexColor('#cccccc')),
        ('VALIGN', (0,0), (-1,-1), 'TOP'),
        ('TOPPADDING', (0,0), (-1,-1), 4),
        ('BOTTOMPADDING', (0,0), (-1,-1), 4),
        ('LEFTPADDING', (0,0), (-1,-1), 5),
        ('RIGHTPADDING', (0,0), (-1,-1), 5),
        ('WORDWRAP', (0,0), (-1,-1), True),
    ]))
    return t

# ─── BUILD CONTENT ──────────────────────────────────────────────────────────
story = []

# Cover
story += [
    sp(30),
    Paragraph("HOSPITAL INFECTION CONTROL", title_style),
    sp(6),
    Paragraph("Part B — Modified Essay Questions", subtitle_style),
    Paragraph("Questions 1 – 7 | Comprehensive Answers", subtitle_style),
    sp(4),
    hr(),
    sp(4),
    Paragraph("Based on standard MBBS Microbiology textbooks", subtitle_style),
    Paragraph("Sherris & Ryan's Medical Microbiology • Harrison's Principles of Internal Medicine", subtitle_style),
    Paragraph("Barash's Clinical Anesthesia • Goldman-Cecil Medicine • Park's Preventive Medicine", subtitle_style),
    PageBreak(),
]

# ══════════════════════════════════════════════════════════
# B1 — HAND HYGIENE
# ══════════════════════════════════════════════════════════
story += [
    h1("B1. Hand Hygiene Methods, Steps, Products & WHO Five Moments"),
    hr(),
    h2("Introduction"),
    body("Hand hygiene is the single most important measure in preventing healthcare-associated infections. Ignaz Semmelweis (1847) demonstrated that handwashing with chlorinated lime solution reduced puerperal fever mortality from 15% to 2%. Despite this, compliance rates remain only ~40% globally."),
    sp(),
    h2("1. Methods of Hand Hygiene"),
    h3("A. Handwashing with Plain Soap and Water"),
    body("Indicated when hands are <b>visibly soiled</b> with blood/body fluids or after contact with <i>Clostridium difficile</i> or <i>Bacillus anthracis</i> (spores not removed by alcohol). Mechanism: detergent action + mechanical friction removes transient flora and dirt."),
    sp(),
    body("<b>WHO 6-Step Technique (Duration: 40–60 seconds):</b>"),
    bullet("Wet hands; apply enough soap to cover all surfaces"),
    bullet("Rub palms together"),
    bullet("Rub back of each hand with the palm of the other, fingers interlaced"),
    bullet("Rub palm to palm with fingers interlaced"),
    bullet("Rub backs of fingers to opposing palms with fingers interlocked"),
    bullet("Rotational rubbing of each thumb clasped in opposite hand"),
    bullet("Rotational rubbing backwards/forwards with clasped fingers in opposite palm"),
    bullet("Rinse hands with water; dry thoroughly with single-use towel"),
    bullet("Use towel to turn off the tap"),
    sp(),
    h3("B. Alcohol-Based Hand Rub (ABHR) — Preferred method when hands not visibly soiled"),
    body("Mechanism: denatures proteins of microorganisms. Ethanol (60–95%) preferred over isopropanol for better antiviral activity. Requires only ~25% of the time compared to soap/water."),
    sp(),
    body("<b>Effective against:</b> Gram-positive bacteria, gram-negative bacteria, fungi, lipophilic viruses (HIV, influenza, HSV, RSV)."),
    body("<b>NOT effective against:</b> Bacterial spores, <i>C. difficile</i>, <i>B. anthracis</i>, non-lipid viruses (norovirus, Hep A)."),
    sp(),
    body("<b>Steps (Duration: 20–30 seconds):</b>"),
    bullet("Apply a palmful of product in a cupped hand"),
    bullet("Follow same 7-step rubbing technique as handwashing"),
    bullet("Allow to dry completely — do NOT wipe off"),
    sp(),
    h3("C. Surgical Hand Antisepsis (Surgical Scrub)"),
    body("Used before performing surgical procedures. Removes transient flora AND reduces resident flora. Preferred product: Chlorhexidine gluconate 4% (better residual activity >6 hours) or Povidone-iodine scrub. Technique: Scrub hands and forearms to elbows for 2–5 minutes using sterile brush for nails."),
    sp(),
    h2("2. Products Used in Hand Hygiene"),
]

story.append(make_table(
    ["Product", "Mechanism", "Spectrum", "Notes"],
    [
        ["Plain soap", "Mechanical/detergent", "Removes transient flora", "Least effective; best for spores/soiling"],
        ["Alcohol (60–95%)", "Protein denaturation", "Bacteria, fungi, lipophilic viruses", "Fastest; no residual activity"],
        ["Chlorhexidine gluconate (2–4%)", "Disrupts cell membrane", "Broad-spectrum, gram+/gram-", "Best residual activity (>6h); surgical scrub"],
        ["Povidone-iodine", "Iodination/oxidation", "Broad spectrum", "Less residual than CHG"],
        ["Triclosan", "Inhibits fatty acid synthesis", "Broad spectrum", "Some resistance concerns"],
        ["PCMX", "Disrupts cell wall/enzymes", "Gram+ve, some gram-ve", "Used in antiseptic soaps"],
    ],
    col_widths=[3.5*cm, 3.5*cm, 4*cm, 5.5*cm]
))

story += [
    sp(),
    h2("3. WHO Five Moments for Hand Hygiene"),
    body("Based on the WHO 'Clean Care is Safer Care' initiative (2009), hand hygiene must be performed at these five critical moments:"),
    sp(),
    bullet("<b>Moment 1 — BEFORE touching a patient:</b> Protect patient from harmful germs on HCW hands"),
    bullet("<b>Moment 2 — BEFORE a clean/aseptic procedure:</b> Protect patient during IV insertion, catheterization, wound dressing"),
    bullet("<b>Moment 3 — AFTER body fluid exposure risk:</b> Protect HCW after blood draw, urine handling, sputum collection"),
    bullet("<b>Moment 4 — AFTER touching a patient:</b> Protect HCW and environment from patient's germs"),
    bullet("<b>Moment 5 — AFTER touching patient surroundings:</b> Protect HCW even if patient not directly touched (bed rails, monitors, call bell)"),
    sp(),
    body("Barriers to compliance include: skin irritation, inaccessibility of dispensers, time constraints, workload. Emollient-containing ABHR reduces skin irritation and improves compliance by 50%."),
    PageBreak(),
]

# ══════════════════════════════════════════════════════════
# B2 — HAIs + CAUTI
# ══════════════════════════════════════════════════════════
story += [
    h1("B2. Major Types of HAIs; CAUTI — Definition, Etiopathogenesis, Risk Factors, Lab Diagnosis, Treatment"),
    hr(),
    h2("Definition of HAI"),
    body("Healthcare-Associated Infections (HAIs) / Nosocomial Infections = infections acquired during hospital care that are <b>NOT present or incubating at the time of admission</b>. Typically manifest <b>&gt;48 hours after admission</b> (or within 30 days for SSI; 1 year for implant-related SSI)."),
    sp(),
    h2("Major Types of HAIs"),
]

story.append(make_table(
    ["HAI Type", "Abbreviation", "Approximate %", "Common Organisms"],
    [
        ["Catheter-Associated UTI", "CAUTI", "35–40% (most common)", "E. coli, Klebsiella, Enterococcus, Candida"],
        ["Surgical Site Infection", "SSI", "~20%", "S. aureus, CoNS, E. coli"],
        ["Ventilator-Associated Pneumonia", "VAP", "~15%", "P. aeruginosa, Acinetobacter, MRSA"],
        ["Catheter-Related BSI", "CRBSI/CLABSI", "~15%", "CoNS, S. aureus, Candida"],
        ["Others (skin, GI, ENT)", "—", "~10%", "Variable"],
    ],
    col_widths=[4.5*cm, 3*cm, 3.5*cm, 5.5*cm]
))

story += [
    sp(),
    body("<b>Organisms implicated in HAIs (ESKAPE pathogens):</b> Enterococcus faecium, Staphylococcus aureus (MRSA), Klebsiella pneumoniae (ESBL/CRE), Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. Also: Candida spp., Clostridioides difficile."),
    sp(),
    h2("CAUTI — Definition"),
    body("Catheter-Associated Urinary Tract Infection (CAUTI) = presence of symptoms of UTI (fever, localising urinary symptoms) PLUS pyuria AND bacteriuria (<b>≥10³ CFU/mL</b>) in a patient with an indwelling urinary catheter (present within 48 hours), with no other identifiable source of infection."),
    sp(),
    h2("Etiopathogenesis of CAUTI"),
    h3("Route of Infection"),
    bullet("<b>Extraluminal route (~66%, most common):</b> Microorganisms migrate along the outer catheter surface from the perineum/meatus — occurs continuously during catheterization"),
    bullet("<b>Intraluminal route (~34%):</b> Organisms enter via catheter lumen through contamination of drainage bag or breaks in the closed drainage system"),
    sp(),
    h3("Biofilm Formation"),
    body("Organisms adhere to catheter surface and form a glycocalyx biofilm that: protects from antibiotics and host immune defenses; serves as a persistent reservoir; facilitates ascending infection to kidney and bloodstream."),
    sp(),
    body("<b>Organisms (frequency order):</b> Escherichia coli (most common) → Klebsiella pneumoniae → Enterococcus spp. → Candida spp. (ICU, prolonged catheterization) → Pseudomonas aeruginosa → Proteus mirabilis → Staphylococcus aureus"),
    sp(),
    h2("Risk Factors for CAUTI"),
    h3("Patient-Related"),
    bullet("Female sex (shorter urethra)"),
    bullet("Advanced age, diabetes mellitus, immunocompromised state"),
    bullet("Severe underlying illness, colonization of meatus/rectum"),
    h3("Catheter-Related"),
    bullet("<b>Duration of catheterization</b> — single most important risk factor (risk increases ~3–7% per day)"),
    bullet("Breaks in aseptic technique during insertion"),
    bullet("Disconnection of closed drainage system; urine reflux from drainage bag"),
    bullet("Catheter material (latex > silicone for encrustation)"),
    sp(),
    h2("Laboratory Diagnosis of CAUTI"),
    bullet("<b>Urinalysis (dipstick):</b> Leukocyte esterase (+), nitrite (+); sensitivity ~75%, specificity ~82%"),
    bullet("<b>Microscopy:</b> Pyuria (>10 WBC/mm³); bacteriuria on Gram stain"),
    bullet("<b>Urine culture (gold standard):</b> Catheter specimen urine; threshold ≥10³ CFU/mL; culture on CLED + MacConkey; mandatory AST"),
    bullet("<b>Blood cultures:</b> 2 sets from peripheral veins if systemic sepsis suspected"),
    sp(),
    h2("Treatment of CAUTI"),
    body("Key principle: <b>Remove or change catheter</b> if possible. Treat only symptomatic CAUTI (not asymptomatic bacteriuria, except pre-procedure)."),
    sp(),
]

story.append(make_table(
    ["Severity", "Drug of Choice"],
    [
        ["Mild-moderate", "Nitrofurantoin / TMP-SMX / Ciprofloxacin (oral)"],
        ["Moderate-severe", "Ciprofloxacin / Levofloxacin (oral or IV)"],
        ["Severe/ICU/ESBL suspected", "Piperacillin-tazobactam or Carbapenem (Meropenem/Imipenem)"],
        ["Candida CAUTI", "Fluconazole (C. albicans); Micafungin/Caspofungin (resistant species)"],
    ],
    col_widths=[5*cm, 11.5*cm]
))

story += [
    sp(),
    body("Duration: 7 days (mild); 10–14 days (severe). De-escalate based on culture/sensitivity results."),
    PageBreak(),
]

# ══════════════════════════════════════════════════════════
# B3 — VAP
# ══════════════════════════════════════════════════════════
story += [
    h1("B3. VAP — Risk Factors, Pathogenesis, Laboratory Diagnosis, Treatment"),
    hr(),
    h2("Definition"),
    body("Ventilator-Associated Pneumonia (VAP) = pneumonia occurring <b>&gt;48 hours after endotracheal intubation and mechanical ventilation</b>, not present at time of intubation."),
    bullet("<b>Early-onset VAP (&lt;5 days):</b> Antibiotic-sensitive organisms — MSSA, H. influenzae, S. pneumoniae"),
    bullet("<b>Late-onset VAP (&gt;5 days):</b> MDR organisms — P. aeruginosa, MRSA, Acinetobacter, Enterobacteriaceae"),
    body("Prevalence: 6–52 per 100 ventilated patients; risk increases 1% per day; up to 70% cumulative by day 30."),
    sp(),
    h2("Causative Organisms"),
]

story.append(make_table(
    ["Non-MDR (Core Pathogens)", "MDR Pathogens"],
    [
        ["Streptococcus pneumoniae", "Pseudomonas aeruginosa"],
        ["Haemophilus influenzae", "MRSA (Methicillin-resistant S. aureus)"],
        ["MSSA, other Streptococcus spp.", "Acinetobacter spp."],
        ["E. coli, Klebsiella pneumoniae", "ESBL-producing Enterobacteriaceae"],
        ["Proteus, Enterobacter, Serratia", "Carbapenem-resistant strains, Legionella"],
    ],
    col_widths=[8*cm, 8.5*cm]
))

story += [
    sp(),
    h2("Risk Factors"),
    h3("Patient-Related"),
    bullet("Severe underlying illness (high APACHE II score), immunosuppression, malnutrition"),
    bullet("<b>Prior antibiotic exposure</b> — greatest risk (selects MDR organisms like P. aeruginosa)"),
    bullet("Impaired consciousness, trauma, burns, ARDS, advanced age, COPD"),
    h3("Device-Related"),
    bullet("<b>Endotracheal tube</b> — main risk factor; bypasses natural mechanical defenses"),
    bullet("Duration of mechanical ventilation (1% per day; cumulative up to 70% by day 30)"),
    bullet("Nasogastric tube (promotes aspiration), reintubation"),
    h3("Procedure-Related"),
    bullet("Supine position, sedation and neuromuscular blockade"),
    bullet("Frequent ventilator circuit changes, inadequate hand hygiene"),
    sp(),
    h2("Pathogenesis"),
    body("Three critical factors in VAP pathogenesis (Harrison's Principles):"),
    bullet("<b>1. Oropharyngeal colonisation with pathogens:</b> Normal oral flora replaced by gram-negative pathogens/MRSA due to antibiotic pressure, cross-infection, severe illness, malnutrition. Antibiotic exposure is the greatest risk by far."),
    bullet("<b>2. Aspiration into lower respiratory tract:</b> Microaspiration of secretions pooling above the endotracheal tube cuff occurs in virtually all intubated patients. ETT bypasses epiglottis and cough reflex. Bacteria form biofilm on inner ETT surface; fragments dislodged during suctioning reseed the trachea."),
    bullet("<b>3. Compromise of host defenses:</b> Severely ill/septic patients develop 'immunoparalysis' days after ICU admission. Hyperglycemia and frequent transfusions further impair immune response. Colony counts rise to overwhelming levels before clinical VAP manifests."),
    sp(),
    h2("Laboratory Diagnosis"),
    h3("Clinical Criteria"),
    bullet("New/progressive infiltrate on CXR or CT chest"),
    bullet("Fever (&gt;38°C) or hypothermia, leucocytosis or leucopenia"),
    bullet("Purulent tracheal secretions, worsening oxygenation (PaO₂/FiO₂ ratio)"),
    sp(),
    h3("Microbiological Methods"),
]

story.append(make_table(
    ["Method", "Threshold", "Sensitivity/Specificity", "Comment"],
    [
        ["Endotracheal aspirate (ETA)", "≥10⁵ CFU/mL", "High sens / Low spec", "Simple; non-invasive; colonisation confounds"],
        ["Bronchoalveolar lavage (BAL)", "≥10⁴ CFU/mL", "High sens + spec", "Gold standard; needs bronchoscopy"],
        ["Protected specimen brush (PSB)", "≥10³ CFU/mL", "Best specificity", "Used when BAL not possible"],
        ["Blind/Mini-BAL", "≥10⁴ CFU/mL", "Intermediate", "Non-bronchoscopic; useful if bronchoscopy unavailable"],
        ["Blood cultures", "Any growth", "Positive in 10–20%", "Useful if positive; not sensitive for VAP"],
    ],
    col_widths=[3.8*cm, 3*cm, 3.8*cm, 5.9*cm]
))

story += [
    sp(),
    body("Gram stain of respiratory secretions provides rapid (within hours) guidance for initial therapy."),
    sp(),
    h2("Treatment of VAP"),
    h3("Empirical Therapy"),
    bullet("<b>Non-MDR/Early-onset VAP:</b> Ceftriaxone OR Piperacillin-tazobactam OR Levofloxacin/Moxifloxacin"),
    bullet("<b>Late-onset/MDR risk VAP:</b>"),
    bullet2("Anti-pseudomonal beta-lactam (Pip-tazo OR Cefepime OR Imipenem/Meropenem)"),
    bullet2("PLUS anti-pseudomonal fluoroquinolone (Ciprofloxacin) OR aminoglycoside (Amikacin/Tobramycin)"),
    bullet2("PLUS if MRSA risk: Vancomycin OR Linezolid"),
    bullet("<b>Duration:</b> 7–8 days for most VAP (reduces MDR selection); 14–21 days for Pseudomonas/Acinetobacter"),
    sp(),
    h3("VAP Prevention Bundle"),
    bullet("A — Assess sedation daily; spontaneous breathing trials"),
    bullet("B — Bed head elevation 30–45°"),
    bullet("C — Chlorhexidine oral decontamination twice daily"),
    bullet("D — Drainage of subglottic secretions (specialised ETT)"),
    bullet("E — Enteral feeding; maintain normoglycemia"),
    bullet("Ventilator circuits changed only when soiled (not routinely)"),
    PageBreak(),
]

# ══════════════════════════════════════════════════════════
# B4 — Sterilisation / Autoclave
# ══════════════════════════════════════════════════════════
story += [
    h1("B4. Sterilisation and Disinfection; Steam Steriliser (Autoclave)"),
    hr(),
    h2("Definitions"),
    bullet("<b>Sterilisation:</b> Complete killing or removal of ALL living organisms (including bacterial spores) from a material or surface. An absolute term. Methods: incineration, moist heat (autoclave), dry heat, ethylene oxide, ionising radiation, filtration, plasma sterilisation."),
    bullet("<b>Disinfection:</b> Destruction of pathogenic microorganisms but NOT necessarily all spores. Less precise than sterilisation. Types: High-level (kills all except high spore numbers), Intermediate-level (kills mycobacteria, vegetative bacteria, most viruses), Low-level (kills most vegetative bacteria, some fungi/viruses)."),
    bullet("<b>Antiseptic:</b> Disinfecting agent safe to use on living body surfaces (skin, mucous membranes)."),
    bullet("<b>Asepsis:</b> Working systems designed to prevent microorganisms from reaching a protected environment."),
    sp(),
    h2("Steam Steriliser (Autoclave)"),
    h3("Principle"),
    body("The autoclave uses <b>moist heat under pressure</b> (saturated steam) to sterilise materials. Steam under pressure achieves temperatures above 100°C. Protein denaturation and coagulation kills all microorganisms including spores. The latent heat of vaporisation of steam makes it far more effective than dry heat at the same temperature — when steam contacts cooler objects, it condenses and releases large amounts of heat, rapidly raising temperature."),
    sp(),
    h3("Operating Parameters"),
]

story.append(make_table(
    ["Mode", "Temperature", "Pressure", "Holding Time"],
    [
        ["Gravity displacement", "121°C", "15 psi (103 kPa)", "15–20 minutes"],
        ["Gravity displacement (faster)", "126°C", "20 psi", "10 minutes"],
        ["High-vacuum (pre-vacuum)", "134°C", "30 psi", "3–5 minutes"],
    ],
    col_widths=[4.5*cm, 3.5*cm, 4*cm, 4.5*cm]
))

story += [
    sp(),
    h3("Diagram — Key Components of Autoclave"),
    body("The autoclave consists of the following key parts:"),
    bullet("<b>Outer cylindrical pressure vessel:</b> Withstands high pressure"),
    bullet("<b>Inner sterilisation chamber:</b> Holds the load/items to be sterilised"),
    bullet("<b>Steam inlet:</b> Admits steam from boiler or self-generated steam"),
    bullet("<b>Pressure gauge:</b> Monitors chamber pressure"),
    bullet("<b>Safety valve (pressure relief valve):</b> Prevents over-pressurisation"),
    bullet("<b>Thermometer:</b> Monitors chamber temperature"),
    bullet("<b>Air exhaust valve / drain:</b> Air (heavier than steam) sinks and escapes through bottom drain — critical for complete air removal"),
    bullet("<b>Door:</b> Heavy, airtight door with locking mechanism and rubber gasket"),
    bullet("<b>Jacket (modern autoclaves):</b> Surrounding steam jacket maintains temperature and speeds drying"),
    sp(),
    h3("Process"),
    bullet("Load materials (wrapped instruments, linen, culture media) into chamber"),
    bullet("Seal door (airtight)"),
    bullet("Admit steam from above/sides; air (heavier) sinks and escapes through bottom drain"),
    bullet("Chamber reaches desired temperature and pressure"),
    bullet("Maintain holding time (15–20 min at 121°C)"),
    bullet("Release steam; vacuum drying cycle removes moisture from load"),
    bullet("Cool; door opened; materials retrieved"),
    sp(),
    h3("Uses"),
    bullet("Surgical instruments, drapes, gowns, linen, gloves"),
    bullet("Culture media preparation (autoclaving at 121°C/15 min)"),
    bullet("Dressings, bandages, suture materials"),
    bullet("Pharmaceutical preparations (heat-stable)"),
    bullet("Hollow instruments (with appropriate cycle)"),
    sp(),
    h3("Advantages"),
    bullet("Most reliable and effective method of sterilisation — gold standard"),
    bullet("No toxic residues; economical; reproducible"),
    bullet("Penetrates packaging well"),
    bullet("Fast cycle (15–20 minutes at 121°C)"),
    bullet("Can sterilise liquids (culture media, aqueous solutions)"),
    bullet("Widely available and validated"),
    sp(),
    h3("Disadvantages"),
    bullet("Cannot sterilise heat-labile materials: plastics, rubber, electronic equipment, optical instruments, certain drugs"),
    bullet("May cause rust/corrosion of carbon steel instruments"),
    bullet("Wet load if drying cycle inadequate ('wet packs')"),
    bullet("Air pockets (if not adequately evacuated) prevent steam penetration → sterilisation failure"),
    bullet("Complex monitoring required (chemical indicators, biological indicators, mechanical records)"),
    PageBreak(),
]

# ══════════════════════════════════════════════════════════
# B5 — Chemical Sterilants
# ══════════════════════════════════════════════════════════
story += [
    h1("B5. Classification of Chemical Sterilants and Their Application in Healthcare"),
    hr(),
    h2("Classification"),
    h3("Level 1 — High-Level Disinfectants / Chemical Sterilants"),
    body("Can achieve sterilisation with prolonged contact; kill all microorganisms including bacterial spores."),
    sp(),
]

story.append(make_table(
    ["Agent", "Mechanism", "Spectrum", "Healthcare Application"],
    [
        ["Glutaraldehyde (2%)", "Alkylation of proteins/nucleic acids", "All organisms + spores (prolonged contact)", "Endoscopes, heat-labile instruments; 20–45 min HLD; 10h sterilisation"],
        ["Orthophthalaldehyde (OPA) 0.55%", "Alkylation", "All organisms; better mycobactericidal than Glut", "Endoscopes; less irritating, faster than glutaraldehyde"],
        ["H₂O₂ (6–7.5%)", "Oxidative damage to cell components", "Broad including spores", "Contact lenses, surfaces; inactivated by organic matter"],
        ["Peracetic acid (0.2–0.35%)", "Oxidation", "Very broad, including spores", "Endoscopes in automated reprocessors (Steris)"],
        ["Chlorine/hypochlorite (1000 ppm)", "Oxidation", "Broad, including spores at high concentrations", "Blood spills (10,000 ppm), environmental surfaces"],
    ],
    col_widths=[3.5*cm, 3.5*cm, 3.5*cm, 6*cm]
))

story += [
    sp(),
    h3("Level 2 — Intermediate-Level Disinfectants"),
]

story.append(make_table(
    ["Agent", "Mechanism", "Spectrum", "Application"],
    [
        ["Alcohols (70–90% ethanol/isopropanol)", "Protein denaturation", "Vegetative bacteria, fungi, lipophilic viruses; NOT spores", "Skin antisepsis, surface/equipment disinfection, thermometers"],
        ["Iodophors (Povidone-iodine)", "Oxidation/iodination", "Broad: bacteria, viruses, fungi, mycobacteria", "Skin prep before surgery/venipuncture; wound antisepsis"],
        ["Phenolics", "Protein denaturation, membrane disruption", "Vegetative bacteria, mycobacteria, fungi", "Floors, furniture, non-critical environmental surfaces"],
    ],
    col_widths=[4*cm, 3.5*cm, 4.5*cm, 4.5*cm]
))

story += [
    sp(),
    h3("Level 3 — Low-Level Disinfectants"),
]

story.append(make_table(
    ["Agent", "Mechanism", "Spectrum", "Application"],
    [
        ["Quaternary Ammonium Compounds (QACs)", "Membrane disruption", "Gram+ve bacteria, limited gram-ve, fungi; NOT mycobacteria/spores", "Floors, furniture, non-critical items, general housekeeping"],
        ["Chlorhexidine (0.5–4%)", "Membrane disruption", "Gram+ve, gram-ve, some viruses; residual activity", "Skin antisepsis, hand hygiene, oral hygiene (0.2%)"],
    ],
    col_widths=[4.5*cm, 3.5*cm, 4.5*cm, 4*cm]
))

story += [
    sp(),
    h3("Gaseous Chemical Sterilants"),
    bullet("<b>Ethylene oxide (ETO):</b> Alkylating agent; sterilises heat/moisture-labile items at low temperature; toxic, explosive, requires long aeration (10–12 hours); used for medical devices, plastics, rubber, catheters"),
    bullet("<b>Formaldehyde gas:</b> Alkylating agent; used for OT fumigation, cabinet sterilisation; highly toxic and carcinogenic; being replaced by H₂O₂ vapor"),
    bullet("<b>Hydrogen peroxide vapor/plasma:</b> Oxidative; non-toxic; rapid; for heat-labile items (STERRAD system)"),
    sp(),
    h2("Applications in Healthcare Settings"),
    bullet("<b>Surgical site skin preparation:</b> Chlorhexidine-alcohol (preferred); Povidone-iodine-alcohol"),
    bullet("<b>Hand hygiene:</b> ABHR (alcohol-based); CHG 4% for surgical scrub"),
    bullet("<b>Endoscope HLD/sterilisation:</b> Glutaraldehyde 2%, OPA 0.55%, peracetic acid (automated reprocessors)"),
    bullet("<b>Blood spills:</b> 1% sodium hypochlorite (10,000 ppm available chlorine)"),
    bullet("<b>Environmental surface disinfection:</b> Phenolics, QACs, H₂O₂, alcohols"),
    bullet("<b>Drinking water disinfection:</b> Chlorination (0.2–0.5 ppm free residual chlorine)"),
    bullet("<b>Non-critical medical devices:</b> 70% alcohol or QACs (wipe-down)"),
    bullet("<b>Heat-labile instruments/implants:</b> ETO gas or plasma sterilisation"),
    bullet("<b>OT fumigation:</b> Formaldehyde gas OR hydrogen peroxide vapor (preferred, safer)"),
    PageBreak(),
]

# ══════════════════════════════════════════════════════════
# B6 — BIOMEDICAL WASTE
# ══════════════════════════════════════════════════════════
story += [
    h1("B6. Biomedical Waste — Definition, Segregation, Treatment and Disposal"),
    hr(),
    h2("Definition"),
    body("Biomedical Waste (BMW) = any waste generated during the <b>diagnosis, treatment, or immunisation</b> of human beings or animals, or during research pertaining thereto, or in the production or testing of biological products. Governed in India by the <b>Biomedical Waste (Management and Handling) Rules, 1998 (amended 2016)</b> under the Environment Protection Act."),
    sp(),
    h2("Segregation of Biomedical Waste (Colour-Coded System)"),
]

story.append(make_table(
    ["Category", "Type of Waste", "Container/Colour", "Treatment & Disposal"],
    [
        ["Cat 1", "Human anatomical waste (body parts, organs, tissues, foetus)", "Yellow bag", "Incineration / Deep burial"],
        ["Cat 2", "Animal waste (from veterinary hospitals)", "Yellow bag", "Incineration / Deep burial"],
        ["Cat 3", "Microbiology & biotechnology waste (cultures, stocks, vaccines, specimens)", "Yellow/Red bag", "Autoclave/Microwave → Incineration"],
        ["Cat 4", "Sharps waste (needles, syringes with needles, blades, scalpels, broken glass)", "White translucent puncture-proof container", "Autoclave → Shredding → Secure landfill"],
        ["Cat 5", "Discarded medicines & cytotoxic drugs", "Yellow bag (separate)", "Incineration"],
        ["Cat 6", "Solid waste contaminated with blood/body fluids (dressings, tubing, soiled cotton, plaster)", "Red bag", "Autoclave/Microwave → Municipal landfill"],
        ["Cat 7", "Liquid waste (blood, secretions from ICU/labs)", "Liquid drain to ETP", "Chemical disinfection (hypochlorite) → drain to ETP"],
        ["Cat 8", "Incineration ash", "Black bag", "Secure landfill"],
        ["Cat 9", "Chemical waste (disinfectants, mercury, solvents)", "Blue/White container", "Chemical treatment/secure landfill"],
    ],
    col_widths=[1.5*cm, 5*cm, 3.5*cm, 6.5*cm]
))

story += [
    sp(),
    h2("Treatment and Disposal Methods"),
    h3("1. Incineration"),
    body("High-temperature combustion (800–1000°C) completely destroys waste. Used for anatomical waste, cytotoxics, animal waste, pathological waste. Type: double-chamber pyrolytic incinerators. Produces ash (safe for landfill) and flue gases (filtered before release)."),
    sp(),
    h3("2. Autoclave/Microwave Disinfection"),
    body("Autoclave at 121°C/15 psi for 30–60 minutes OR microwave at 95°C. Used for microbiology waste, sharps (post-disinfection). After treatment, waste sent to landfill. Autoclave must be validated and monitored with biological indicators."),
    sp(),
    h3("3. Chemical Disinfection"),
    body("For liquid wastes: blood, body fluids. Use 1% hypochlorite. Treated liquid drained to Effluent Treatment Plant (ETP). Also 2% glutaraldehyde for reusable equipment sterilisation."),
    sp(),
    h3("4. Deep Burial"),
    body("For anatomical waste when incineration unavailable (rural/remote areas). Pit lined with lime, covered with at least 50 cm soil. Only permitted with prior written approval."),
    sp(),
    h3("5. Shredding/Mutilation"),
    body("For sharps after autoclaving — destroys to prevent reuse and repackaging. Mutilated sharps sent to secure landfill."),
    sp(),
    h3("6. Secure Landfill"),
    body("For non-recyclable, treated solid waste. Lined pits with leachate collection system."),
    sp(),
    body("<b>Transportation:</b> BMW transported in dedicated labelled vehicles with manifest system (tracking from generation site to final disposal site)."),
    body("<b>Documentation:</b> All BMW generation, transport, and disposal must be recorded and submitted to the Pollution Control Board."),
    PageBreak(),
]

# ══════════════════════════════════════════════════════════
# B7 — AMSP
# ══════════════════════════════════════════════════════════
story += [
    h1("B7. Antimicrobial Stewardship Program (AMSP)"),
    hr(),
    h2("Definition"),
    body("Antimicrobial Stewardship Program (ASP) = a coordinated program that promotes the <b>appropriate use of antimicrobials</b> (antibiotics, antifungals, antivirals, antiparasitics) to improve patient outcomes, reduce microbial resistance, and decrease the spread of infections caused by multidrug-resistant organisms."),
    sp(),
    h2("Need for AMSP in Healthcare Settings"),
    bullet("<b>Growing antimicrobial resistance (AMR):</b> Overuse/misuse of antibiotics selects for resistant organisms (MRSA, ESBL, CRE, VRE). The CDC states that AMR causes &gt;2.8 million infections/year in the USA. A 'post-antibiotic world' is approaching."),
    bullet("<b>Pharmaceutical costs:</b> Antibiotics are the largest and fastest-growing drug expenditure in hospitals. Stewardship programmes control costs by formulary management and appropriate use."),
    bullet("<b>Adverse effects:</b> Antibiotic-associated diarrhoea, Clostridioides difficile colitis, allergic reactions (anaphylaxis), nephrotoxicity (aminoglycosides), hepatotoxicity (isoniazid), QT prolongation (fluoroquinolones, azithromycin)."),
    bullet("<b>Ecological impact:</b> Broad-spectrum antibiotics disrupt normal flora, promote emergence of resistant organisms and Candida overgrowth."),
    bullet("<b>Inadequate empirical therapy:</b> Incorrect antibiotic choice or dosing increases mortality in severe sepsis and septic shock."),
    bullet("<b>Limited new antibiotic pipeline:</b> Only a few truly new antibiotics are in development, making preservation of existing agents critical."),
    sp(),
    h2("Strategies of Antimicrobial Stewardship Program"),
    h3("A. Administrative Strategies (CDC Core Elements)"),
]

story.append(make_table(
    ["Core Element", "Description"],
    [
        ["1. Leadership Commitment", "Hospital administration dedicates human, financial, and IT resources to the programme"],
        ["2. Accountability", "Appoint a physician (infectious diseases/microbiologist) as programme leader; co-lead with clinical pharmacist"],
        ["3. Pharmacy Expertise", "Pharmacist co-leads implementation; expertise in PK/PD, drug interactions, dose optimisation"],
        ["4. Action", "Implement interventions: prospective audit & feedback OR preauthorisation"],
        ["5. Tracking", "Monitor antibiotic use (DDD/DOT per 1000 patient-days); track C. difficile rates, resistance patterns"],
        ["6. Reporting", "Regular reports on antibiotic use and resistance to prescribers, nurses, pharmacists, and leadership"],
        ["7. Education", "Educate prescribers, pharmacists, nurses on adverse reactions, resistance, and optimal prescribing"],
    ],
    col_widths=[4*cm, 12.5*cm]
))

story += [
    sp(),
    h3("B. Interventional Strategies"),
    bullet("<b>1. Preauthorisation (Formulary restriction):</b> Certain broad-spectrum antibiotics (carbapenems, linezolid, daptomycin, antifungals) require approval from ID physician/microbiologist before dispensing. Most immediately effective strategy for reducing inappropriate use."),
    bullet("<b>2. Prospective audit and feedback:</b> Review of ongoing antibiotic prescriptions by the stewardship team; feedback to prescribers with recommendations for de-escalation, dose optimisation, IV-to-oral switch. Best evidence-based strategy for sustained improvement."),
    bullet("<b>3. De-escalation:</b> Narrow antibiotic spectrum once culture/sensitivity results available (48–72 hours). Switch from broad-spectrum to targeted agent. 'Start smart, then focus.'"),
    bullet("<b>4. Duration of therapy guidelines:</b> Standardised treatment durations for common infections to avoid unnecessarily prolonged courses."),
    bullet("<b>5. Dose optimisation:</b> Correct dosing based on PK/PD principles (e.g., time-dependent vs concentration-dependent killing), renal/hepatic function, therapeutic drug monitoring (vancomycin AUC/MIC, aminoglycoside peak/trough)."),
    bullet("<b>6. IV-to-oral (IV-to-PO) switch:</b> Convert to equivalent oral agents as soon as clinical condition permits. Reduces length of stay, costs, and IV-related complications (phlebitis, CRBSI)."),
    bullet("<b>7. Antibiotic time-out:</b> Reassess antibiotic prescription at 48–72 hours; confirm indication, correct drug/dose/duration."),
    sp(),
    h3("C. Monitoring and Reporting"),
    bullet("Track antibiotic use: DDD (Defined Daily Doses) and DOT (Days of Therapy) per 1000 patient-days"),
    bullet("Monitor resistance patterns, C. difficile rates, MDR organism rates"),
    bullet("Annual Hospital Antibiogram: Cumulative susceptibility data from own patient population — guides empirical therapy"),
    bullet("Benchmarking with regional/national data"),
    sp(),
    h3("D. Education and Training"),
    bullet("Regular CME/training sessions on antibiotic resistance, appropriate use, adverse effects"),
    bullet("Case-based learning for prescribers and pharmacists"),
    bullet("Disseminate guidelines and antibiogram to all clinical staff"),
    sp(),
    body("<b>Outcomes of Effective AMSP:</b> Reduced AMR rates, reduced C. difficile infections, reduced adverse drug reactions, decreased antibiotic costs, shorter length of stay, improved patient outcomes."),
    sp(10),
    hr(),
    Paragraph("Sources: Sherris & Ryan's Medical Microbiology 8th Ed | Harrison's Principles of Internal Medicine 22nd Ed | Barash's Clinical Anesthesia 9th Ed | Goldman-Cecil Medicine | Park's Textbook of Preventive and Social Medicine", subtitle_style),
]

# BUILD PDF
doc.build(story)
print("PDF generated successfully!")