UTI in pregnancy

UTI in pregnancy

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"urinary tract infection" AND "pregnancy"

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Why Pregnant Women Are at Higher Risk

Pregnancy creates a perfect storm for urinary tract infections through several overlapping mechanisms:

Anatomic changes:

The gravid uterus compresses the ureters at the pelvic brim, causing significant ureteral dilation and hydro-ureter - especially from the second trimester onward
Mild right-sided hydronephrosis occurs in ~75% of women by mid-pregnancy; left-sided in ~33% (dextrorotation of uterus by the sigmoid colon causes right-sided predominance)
The bladder is displaced superiorly/anteriorly, with decreased tone, increased capacity, and incomplete emptying - promoting vesicoureteric reflux

Physiologic/biochemical changes:

Progesterone reduces ureteral and bladder smooth muscle tone, slowing urine flow and causing stasis
GFR increases 30-50%, but urinary stasis counteracts the "washout" benefit
Urinary pH rises (due to increased bicarbonate excretion) - favoring bacterial growth
Glycosuria accelerates bacterial multiplication
Increased urinary estrogen excretion may accelerate growth of uropathogenic E. coli
Creasy & Resnik's Maternal-Fetal Medicine, p. 1124-1125
Smith & Tanagho's General Urology, 19th Ed., p. 234

Classification and Clinical Spectrum

1. Asymptomatic Bacteriuria (ASB)

Prevalence: 5-10% of pregnant women (similar to non-pregnant women of comparable age)
Most common between 9-17 weeks of gestation
Risk factors: advancing age, increasing parity, diabetes, sickle cell disease, structural urinary tract abnormalities
Critically important: in non-pregnant women ASB rarely progresses, but in pregnancy, untreated ASB progresses to pyelonephritis in 20-40% of cases
All pregnant women should be screened at the first antenatal visit by urine culture; a positive leukocyte esterase or urinary nitrite on dipstick warrants culture confirmation and treatment

2. Acute Cystitis

Symptomatic lower UTI: dysuria, frequency, urgency, suprapubic discomfort
No fever or systemic features
Causative organisms: E. coli (75%), Klebsiella pneumoniae, Proteus, Group B Streptococcus

3. Acute Pyelonephritis

Occurs in 2-4% of pregnant women overall; 60-70% of cases occur in the 2nd and 3rd trimesters when stasis is greatest
Right-sided in at least 75% of cases (due to uterine dextrorotation)
Presentation: high fever (>38.5°C), rigors, costovertebral angle tenderness, nausea/vomiting, dysuria, frequency
Lab findings: pyuria, bacteriuria, WBC casts (highly predictive), positive urine culture; blood cultures in 10-20% of cases are positive
10-20% of patients develop recurrent episodes before delivery
Creasy & Resnik's, p. 1125-1127; Tintinalli's Emergency Medicine, p. 667

Microbiology

Organism	Frequency
Escherichia coli	70-80%
Klebsiella pneumoniae	3-7%
Proteus mirabilis	2%
Staphylococcus aureus	~7%
Group B Streptococcus	~10%

Complications

Fetal/obstetric:

Preterm labor (pyelonephritis is one of the most common identifiable causes)
Low birth weight
Increased perinatal mortality (if untreated pyelonephritis)

Maternal:

Up to 20% of pregnant women with acute pyelonephritis develop multiorgan involvement from endotoxemia/sepsis
Complications include: hemolytic anemia, ARDS (2-8%), DIC, septic shock
Transient renal dysfunction occurs in ~7% with aggressive fluid resuscitation (vs ~20% without)
Pyelonephritis is one of the most common causes of septic shock in pregnancy

ARDS predictors in antepartum pyelonephritis: maternal HR >110 bpm, use of tocolytics, temperature ≥103°F in first 24 hrs, fluid overload, ampicillin as sole antibiotic.

Creasy & Resnik's, p. 1126-1127

Treatment

Safe Antibiotics in Pregnancy

Drug	Status	Notes
Penicillins (amoxicillin, ampicillin)	Safe	First-line for cystitis/ASB
Cephalosporins (cephalexin, cefazolin)	Safe	First-line; preferred for pyelonephritis
β-lactamase inhibitors (amox-clavulanate)	Safe	Use when indicated
Nitrofurantoin	Safe in 1st-2nd trimester	Avoid in 3rd trimester (hemolysis risk, especially G6PD); also avoid at term
Azithromycin	Safe

Antibiotics to Avoid

Drug	Reason to Avoid
Fluoroquinolones	Interfere with cartilage formation
Tetracyclines	Dysplasia and discoloration of teeth/bones
Trimethoprim	Folate antagonist - interferes with neural tube development (especially 1st trimester)
Sulfonamides	Kernicterus (avoid in 3rd trimester)
Aminoglycosides	Nerve damage (ototoxicity/nephrotoxicity)

Smith & Tanagho's, p. 235

Treatment Regimens

ASB and uncomplicated cystitis:

Amoxicillin 500 mg PO 2-3x/day for 3-7 days, OR
Cephalexin 500 mg PO 2-4x/day for 3-7 days
Follow-up urine culture 1-2 weeks after treatment to confirm cure
Suppressive therapy (e.g., cephalexin 250-500 mg at bedtime) for recurrent infections

Acute pyelonephritis:

Hospital admission is recommended (outpatient management may be considered only in selected, low-risk patients after careful evaluation)
IV antibiotics: cephalosporins (e.g., cefazolin 1-2 g IV q8h) or ampicillin + gentamicin (with caution given nephrotoxicity risk); transition to oral therapy once afebrile for 24-48 hours
Aggressive IV fluid resuscitation is a critical component - reduces rate of renal dysfunction from 20% to 7%
Total treatment duration: 10-14 days
Suppressive antibiotic therapy for the remainder of pregnancy after pyelonephritis to prevent recurrence (in 10-20% recurrence rate)
Monitor closely for preterm labor contractions

Screening and Prevention

Universal screening: urine culture at the first prenatal visit (ideally 12-16 weeks) is the standard of care
Treat all cases of ASB to prevent progression to pyelonephritis and reduce rates of low birth weight
Follow-up urine cultures after treatment and periodically throughout pregnancy
Adequate hydration; voiding before and after intercourse
Avoid catheterization unless essential

Key Points Summary

UTI in pregnancy is classified as ASB, cystitis, or pyelonephritis - all require treatment
ASB must be screened for and treated (unlike in non-pregnant adults)
E. coli is the dominant pathogen (~75%)
Pyelonephritis predominantly affects the right side and peaks in the 2nd-3rd trimester
Pyelonephritis in pregnancy carries serious risk of preterm labor, ARDS, and septic shock
Penicillins and cephalosporins are the safest antibiotic classes
Avoid fluoroquinolones, tetracyclines, and trimethoprim (especially 1st trimester) throughout pregnancy

Create a treatment protocol guide for UTI management in pregnancy

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~/uti_protocol/generate_pdf.py

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import cm, mm
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, PageBreak, KeepTogether
)
from reportlab.platypus.flowables import HRFlowable
from reportlab.graphics.shapes import Drawing, Rect, String, Line, Polygon
from reportlab.graphics import renderPDF
from reportlab.platypus import Flowable
import os

OUTPUT_PATH = "/tmp/workspace/uti_protocol/UTI_in_Pregnancy_Protocol.pdf"
os.makedirs(os.path.dirname(OUTPUT_PATH), exist_ok=True)

# ── Colour palette ──────────────────────────────────────────────────
NAVY     = colors.HexColor("#1A3A5C")
TEAL     = colors.HexColor("#1D7A8C")
MINT     = colors.HexColor("#E8F7F9")
AMBER    = colors.HexColor("#E8A020")
AMBER_BG = colors.HexColor("#FFF8EC")
RED      = colors.HexColor("#C0392B")
RED_BG   = colors.HexColor("#FDEEEC")
GREEN    = colors.HexColor("#1E8449")
GREEN_BG = colors.HexColor("#EAF7EE")
GREY     = colors.HexColor("#5D6D7E")
LGREY    = colors.HexColor("#F2F3F4")
WHITE    = colors.white

# ── Document setup ──────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT_PATH,
    pagesize=A4,
    leftMargin=1.8*cm, rightMargin=1.8*cm,
    topMargin=2.2*cm,  bottomMargin=2.2*cm,
    title="UTI in Pregnancy – Treatment Protocol",
    author="Orris Medical Education",
)

W = A4[0] - 3.6*cm   # usable page width

# ── Styles ──────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def S(name, **kw):
    """Quick ParagraphStyle factory."""
    return ParagraphStyle(name, **kw)

cover_title = S("CoverTitle", fontSize=28, textColor=WHITE,
                fontName="Helvetica-Bold", leading=34, alignment=TA_CENTER)
cover_sub   = S("CoverSub",   fontSize=14, textColor=colors.HexColor("#BEE6F0"),
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cover_meta  = S("CoverMeta",  fontSize=10, textColor=colors.HexColor("#A0C8D8"),
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sec_head    = S("SecHead",    fontSize=13, textColor=WHITE,
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                leftIndent=6, spaceBefore=0, spaceAfter=0)
sub_head    = S("SubHead",    fontSize=11, textColor=NAVY,
                fontName="Helvetica-Bold", leading=14,
                spaceBefore=8, spaceAfter=4)
body        = S("Body",       fontSize=9,  textColor=colors.HexColor("#2C3E50"),
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                spaceBefore=2, spaceAfter=2)
body_bold   = S("BodyBold",   fontSize=9,  textColor=colors.HexColor("#2C3E50"),
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small       = S("Small",      fontSize=8,  textColor=GREY,
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table_hdr   = S("TblHdr",     fontSize=9,  textColor=WHITE,
                fontName="Helvetica-Bold", leading=12, alignment=TA_CENTER)
table_cell  = S("TblCell",    fontSize=8.5,textColor=colors.HexColor("#2C3E50"),
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table_cell_b= S("TblCellB",   fontSize=8.5,textColor=colors.HexColor("#2C3E50"),
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warn_style  = S("Warn",       fontSize=9,  textColor=RED,
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note_style  = S("Note",       fontSize=8.5,textColor=colors.HexColor("#5D4037"),
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bullet      = S("Bullet",     fontSize=9,  textColor=colors.HexColor("#2C3E50"),
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                leftIndent=14, firstLineIndent=-8,
                spaceBefore=1, spaceAfter=1)

# ── Helper Flowables ────────────────────────────────────────────────
def section_banner(text, bg=NAVY):
    data = [[Paragraph(text, sec_head)]]
    t = Table(data, colWidths=[W])
    t.setStyle(TableStyle([
        ("BACKGROUND",  (0,0), (-1,-1), bg),
        ("TOPPADDING",  (0,0), (-1,-1), 7),
        ("BOTTOMPADDING",(0,0),(-1,-1), 7),
        ("LEFTPADDING", (0,0), (-1,-1), 10),
        ("RIGHTPADDING",(0,0), (-1,-1), 10),
        ("ROUNDEDCORNERS", [4]),
    ]))
    return t

def colored_box(paragraphs, bg=MINT, border=TEAL, radius=4):
    data = [[p] for p in paragraphs]
    # flatten to single cell
    inner = [p for p in paragraphs]
    container_data = [[inner[0]] if len(inner)==1 else inner]
    # Use a 1-cell table with stacked paragraphs
    combined = [p for p in paragraphs]
    t = Table([[combined[0]]] if len(combined)==1 else [[combined[0]]],
              colWidths=[W])
    # Better: put all in one cell using KeepTogether
    cell_content = paragraphs
    t2 = Table([cell_content], colWidths=[W])
    t2.setStyle(TableStyle([
        ("BACKGROUND",  (0,0),(-1,-1), bg),
        ("BOX",         (0,0),(-1,-1), 1.2, border),
        ("TOPPADDING",  (0,0),(-1,-1), 8),
        ("BOTTOMPADDING",(0,0),(-1,-1), 8),
        ("LEFTPADDING", (0,0),(-1,-1), 10),
        ("RIGHTPADDING",(0,0),(-1,-1), 10),
    ]))
    return t2

def info_box(title, items, bg=MINT, border=TEAL):
    """Titled box with bullet items."""
    rows = []
    rows.append(Paragraph(f"<b>{title}</b>", S("IB", fontSize=9.5, textColor=border,
                fontName="Helvetica-Bold", leading=13)))
    for item in items:
        rows.append(Paragraph(f"• {item}", bullet))
    data = [[r] for r in rows]
    t = Table(data, colWidths=[W])
    t.setStyle(TableStyle([
        ("BACKGROUND",  (0,0),(-1,-1), bg),
        ("BOX",         (0,0),(-1,-1), 1.5, border),
        ("TOPPADDING",  (0,0),(-1,-1), 5),
        ("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING", (0,0),(-1,-1), 10),
        ("RIGHTPADDING",(0,0),(-1,-1), 10),
    ]))
    return t

def spacer(h=6):
    return Spacer(1, h)

def hr(color=TEAL, thickness=0.8):
    return HRFlowable(width="100%", thickness=thickness, color=color,
                      spaceAfter=4, spaceBefore=4)

# ── COVER PAGE ──────────────────────────────────────────────────────
def build_cover():
    elements = []

    # Big header band
    header_data = [
        [Paragraph("UTI IN PREGNANCY", cover_title)],
        [Spacer(1, 6)],
        [Paragraph("Treatment Protocol Guide", cover_sub)],
        [Spacer(1, 4)],
        [Paragraph("For Medical Students", cover_meta)],
        [Spacer(1, 4)],
        [Paragraph("Based on Creasy &amp; Resnik's Maternal-Fetal Medicine | Smith &amp; Tanagho's Urology | Tintinalli's Emergency Medicine", cover_meta)],
    ]
    cover_table = Table(header_data, colWidths=[W])
    cover_table.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), NAVY),
        ("TOPPADDING",    (0,0),(-1,-1), 28),
        ("BOTTOMPADDING", (0,0),(-1,-1), 28),
        ("LEFTPADDING",   (0,0),(-1,-1), 20),
        ("RIGHTPADDING",  (0,0),(-1,-1), 20),
        ("ROUNDEDCORNERS",[6]),
    ]))
    elements.append(cover_table)
    elements.append(spacer(14))

    # 3-column quick-facts
    qf_style = S("QF", fontSize=8.5, textColor=NAVY, fontName="Helvetica",
                 leading=13, alignment=TA_CENTER)
    qf_num   = S("QFN", fontSize=22, textColor=TEAL, fontName="Helvetica-Bold",
                 leading=26, alignment=TA_CENTER, spaceBefore=4)

    def qf_cell(num, label):
        return [Paragraph(num, qf_num), Paragraph(label, qf_style)]

    qf_data = [
        [qf_cell("5–10%", "Prevalence of\nAsymptomatic Bacteriuria"),
         qf_cell("2–4%",  "Pregnant women\ndevelop Pyelonephritis"),
         qf_cell("75%",   "Pyelonephritis cases\nare Right-sided")]
    ]
    qf_t = Table(qf_data, colWidths=[W/3]*3)
    qf_t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), MINT),
        ("BOX",           (0,0),(-1,-1), 1.5, TEAL),
        ("INNERGRID",     (0,0),(-1,-1), 0.5, TEAL),
        ("TOPPADDING",    (0,0),(-1,-1), 14),
        ("BOTTOMPADDING", (0,0),(-1,-1), 14),
        ("ALIGN",         (0,0),(-1,-1), "CENTER"),
        ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
    ]))
    elements.append(qf_t)
    elements.append(spacer(12))

    # TOC / overview
    toc_items = [
        ("01", "Pathophysiology", "Why pregnancy increases UTI risk"),
        ("02", "Classification",  "ASB · Cystitis · Pyelonephritis"),
        ("03", "Microbiology",    "Common organisms"),
        ("04", "Diagnosis",       "Screening & investigations"),
        ("05", "Safe Antibiotics","What to use & what to avoid"),
        ("06", "Treatment",       "Regimens by category"),
        ("07", "Complications",   "Maternal & fetal risks"),
        ("08", "Prevention",      "Suppression & follow-up"),
    ]
    toc_data = []
    for num, title_t, desc in toc_items:
        toc_data.append([
            Paragraph(f"<b>{num}</b>", S("TN", fontSize=10, textColor=TEAL,
                       fontName="Helvetica-Bold", leading=13, alignment=TA_CENTER)),
            Paragraph(f"<b>{title_t}</b>", S("TT", fontSize=9.5, textColor=NAVY,
                       fontName="Helvetica-Bold", leading=13)),
            Paragraph(desc, S("TD", fontSize=9, textColor=GREY,
                       fontName="Helvetica", leading=13)),
        ])

    toc_t = Table(toc_data, colWidths=[1.2*cm, 5*cm, W - 6.2*cm])
    toc_t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), LGREY),
        ("ROWBACKGROUNDS",(0,0),(-1,-1), [LGREY, WHITE]),
        ("BOX",           (0,0),(-1,-1), 1, TEAL),
        ("LINEBEFORE",    (0,0),(0,-1),  3, TEAL),
        ("TOPPADDING",    (0,0),(-1,-1), 6),
        ("BOTTOMPADDING", (0,0),(-1,-1), 6),
        ("LEFTPADDING",   (0,0),(-1,-1), 8),
        ("RIGHTPADDING",  (0,0),(-1,-1), 8),
        ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
    ]))
    elements.append(toc_t)
    elements.append(spacer(12))

    # Footer note
    elements.append(Paragraph(
        "⚠ This guide is intended for educational purposes. Always consult current institutional guidelines and senior clinicians for patient management.",
        S("FootNote", fontSize=7.5, textColor=GREY, fontName="Helvetica-Oblique",
          leading=11, alignment=TA_CENTER)
    ))
    elements.append(PageBreak())
    return elements

# ── PAGE 2: PATHOPHYSIOLOGY + CLASSIFICATION ────────────────────────
def build_page2():
    e = []
    e.append(section_banner("01  |  PATHOPHYSIOLOGY OF UTI IN PREGNANCY"))
    e.append(spacer(8))

    # Two-column layout: anatomic vs physiologic
    col1 = [
        Paragraph("<b>Anatomic Changes</b>", sub_head),
        Paragraph("• Gravid uterus compresses ureters at the pelvic brim", bullet),
        Paragraph("• Significant ureteral dilation → hydro-ureter (2nd–3rd trimester)", bullet),
        Paragraph("• Renal length increases ~1 cm (↑ vascular/interstitial volume)", bullet),
        Paragraph("• Bladder displaced superiorly/anteriorly; incomplete emptying", bullet),
        Paragraph("• Mild right hydronephrosis: 75% of women by mid-pregnancy", bullet),
        Paragraph("• Mild left hydronephrosis: ~33%", bullet),
    ]
    col2 = [
        Paragraph("<b>Physiologic Changes</b>", sub_head),
        Paragraph("• Progesterone reduces ureteral + bladder smooth muscle tone", bullet),
        Paragraph("• GFR increases 30–50% (↑ cardiac output)", bullet),
        Paragraph("• Urinary pH rises (↑ bicarbonate excretion) → ↑ bacterial growth", bullet),
        Paragraph("• Glycosuria is common → accelerates bacterial multiplication", bullet),
        Paragraph("• ↑ Urinary estrogen excretion → accelerates uropathogenic E. coli growth", bullet),
        Paragraph("• Vesicoureteric reflux risk ↑ (↓ bladder tone, ↑ capacity)", bullet),
    ]

    tbl = Table([[col1, col2]], colWidths=[W/2 - 4, W/2 - 4])
    tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(0,-1), MINT),
        ("BACKGROUND", (1,0),(1,-1), colors.HexColor("#F0F9FF")),
        ("BOX",        (0,0),(0,-1), 1, TEAL),
        ("BOX",        (1,0),(1,-1), 1, TEAL),
        ("TOPPADDING",    (0,0),(-1,-1), 8),
        ("BOTTOMPADDING", (0,0),(-1,-1), 8),
        ("LEFTPADDING",   (0,0),(-1,-1), 10),
        ("RIGHTPADDING",  (0,0),(-1,-1), 10),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    e.append(tbl)
    e.append(spacer(12))

    e.append(section_banner("02  |  CLASSIFICATION", bg=TEAL))
    e.append(spacer(8))

    # Classification table
    cls_header = [
        Paragraph("Category", table_hdr),
        Paragraph("Definition", table_hdr),
        Paragraph("Symptoms", table_hdr),
        Paragraph("Timing / Prevalence", table_hdr),
    ]
    cls_rows = [
        ["Asymptomatic\nBacteriuria (ASB)",
         "≥10⁵ CFU/mL on 2 consecutive cultures without symptoms",
         "None",
         "5–10% of pregnant women\nPeak: 9–17 weeks gestation"],
        ["Acute Cystitis",
         "Symptomatic lower UTI",
         "Dysuria, frequency,\nurgency, suprapubic pain\nNo fever",
         "1–2% of pregnancies\nAny trimester"],
        ["Acute\nPyelonephritis",
         "Upper UTI involving renal parenchyma",
         "Fever >38.5°C, rigors, CVA\ntenderness, N&V, dysuria\nFrequency",
         "2–4% of pregnancies\n60–70% in 2nd–3rd trimester"],
    ]
    cls_colors = [MINT, colors.HexColor("#FFF5E6"), RED_BG]
    cls_borders = [TEAL, AMBER, RED]

    cls_data = [cls_header]
    for row in cls_rows:
        cls_data.append([Paragraph(str(c), table_cell) for c in row])

    cls_t = Table(cls_data, colWidths=[3.2*cm, 5.5*cm, 4.2*cm, W-12.9*cm])
    style_cmds = [
        ("BACKGROUND",    (0,0),(-1,0),  NAVY),
        ("TEXTCOLOR",     (0,0),(-1,0),  WHITE),
        ("FONTNAME",      (0,0),(-1,0),  "Helvetica-Bold"),
        ("FONTSIZE",      (0,0),(-1,0),  9),
        ("ALIGN",         (0,0),(-1,-1), "LEFT"),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("GRID",          (0,0),(-1,-1), 0.4, colors.HexColor("#BDC3C7")),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [MINT, colors.HexColor("#FFF5E6"), RED_BG]),
        ("TOPPADDING",    (0,0),(-1,-1), 6),
        ("BOTTOMPADDING", (0,0),(-1,-1), 6),
        ("LEFTPADDING",   (0,0),(-1,-1), 7),
        ("RIGHTPADDING",  (0,0),(-1,-1), 7),
        ("FONTNAME",      (0,1),(0,-1),  "Helvetica-Bold"),
        ("TEXTCOLOR",     (0,1),(0,1),   TEAL),
        ("TEXTCOLOR",     (0,2),(0,2),   AMBER),
        ("TEXTCOLOR",     (0,3),(0,3),   RED),
    ]
    cls_t.setStyle(TableStyle(style_cmds))
    e.append(cls_t)
    e.append(spacer(12))

    e.append(PageBreak())
    return e

# ── PAGE 3: MICROBIOLOGY + DIAGNOSIS ────────────────────────────────
def build_page3():
    e = []
    e.append(section_banner("03  |  MICROBIOLOGY"))
    e.append(spacer(8))

    micro_header = [Paragraph(h, table_hdr) for h in ["Organism", "Frequency", "Notes"]]
    micro_rows = [
        ["Escherichia coli",          "70–80%",  "Dominant pathogen; P fimbriae mediate adherence to uroepithelium"],
        ["Group B Streptococcus (GBS)","~10%",   "Also screened at 35–37 weeks; important in neonatal sepsis"],
        ["Klebsiella pneumoniae",      "3–7%",   "Second most common gram-negative"],
        ["Staphylococcus aureus",      "~7%",    "Less common; consider in bacteremia"],
        ["Proteus mirabilis",          "~2%",    "Urease-producing; associated with struvite stones"],
        ["Enterobacter spp.",          "~2%",    "Gram-negative; less frequent"],
    ]
    micro_data = [micro_header] + [[Paragraph(c, table_cell if i>0 else S("OrgName", fontSize=8.5,
                  fontName="Helvetica-Oblique" if i==0 else "Helvetica",
                  textColor=NAVY, leading=12)) for i, c in enumerate(row)]
                  for row in micro_rows]

    micro_t = Table(micro_data, colWidths=[4.5*cm, 2.5*cm, W-7*cm])
    micro_t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0),  TEAL),
        ("TEXTCOLOR",     (0,0),(-1,0),  WHITE),
        ("FONTNAME",      (0,0),(-1,0),  "Helvetica-Bold"),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [LGREY, WHITE]),
        ("GRID",          (0,0),(-1,-1), 0.4, colors.HexColor("#BDC3C7")),
        ("TOPPADDING",    (0,0),(-1,-1), 6),
        ("BOTTOMPADDING", (0,0),(-1,-1), 6),
        ("LEFTPADDING",   (0,0),(-1,-1), 8),
        ("RIGHTPADDING",  (0,0),(-1,-1), 8),
        ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
        ("FONTNAME",      (0,1),(-1,-1), "Helvetica"),
        ("FONTSIZE",      (0,1),(-1,-1), 8.5),
    ]))
    e.append(micro_t)
    e.append(spacer(12))

    e.append(section_banner("04  |  DIAGNOSIS & SCREENING", bg=TEAL))
    e.append(spacer(8))

    # Two-column: screening vs investigations
    col_l = [
        Paragraph("<b>Screening (All Pregnant Women)</b>", sub_head),
        Paragraph("• Universal urine culture at <b>first antenatal visit</b> (ideally 12–16 weeks)", bullet),
        Paragraph("• Dipstick: positive leukocyte esterase or nitrite → send culture", bullet),
        Paragraph("• A negative dipstick does not rule out ASB — culture remains gold standard", bullet),
        Paragraph("• Repeat culture after treatment to confirm cure (1–2 weeks post-treatment)", bullet),
        Paragraph("• Periodic re-screening in high-risk patients (DM, recurrent UTI, structural anomalies)", bullet),
        spacer(6),
        Paragraph("<b>Diagnostic Thresholds</b>", sub_head),
        Paragraph("• ASB: ≥10⁵ CFU/mL on 2 consecutive midstream clean-catch cultures (no symptoms)", bullet),
        Paragraph("• Symptomatic UTI: ≥10² CFU/mL with compatible symptoms", bullet),
        Paragraph("• Catheter specimen: ≥10² CFU/mL", bullet),
    ]
    col_r = [
        Paragraph("<b>Investigations in Pyelonephritis</b>", sub_head),
        Paragraph("• Urinalysis: pyuria, bacteriuria, WBC casts (highly predictive of pyelonephritis)", bullet),
        Paragraph("• Urine culture + sensitivities: always obtain before antibiotics", bullet),
        Paragraph("• FBC: leukocytosis, may show anaemia (haemolysis in severe cases)", bullet),
        Paragraph("• U&E/Creatinine: 7–20% develop transient renal dysfunction", bullet),
        Paragraph("• Blood cultures: obtain if febrile or systemically unwell (bacteraemia in 10–20%)", bullet),
        Paragraph("• Renal USS: if no improvement in 48–72 hrs (exclude obstruction, abscess)", bullet),
        Paragraph("• LFTs, coagulation: if DIC suspected", bullet),
        Paragraph("• CTG / fetal monitoring: pyelonephritis can precipitate preterm labour", bullet),
    ]
    diag_tbl = Table([[col_l, col_r]], colWidths=[W/2-4, W/2-4])
    diag_tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(0,-1), colors.HexColor("#F0F9FF")),
        ("BACKGROUND", (1,0),(1,-1), MINT),
        ("BOX",        (0,0),(0,-1), 1, TEAL),
        ("BOX",        (1,0),(1,-1), 1, TEAL),
        ("TOPPADDING",    (0,0),(-1,-1), 8),
        ("BOTTOMPADDING", (0,0),(-1,-1), 8),
        ("LEFTPADDING",   (0,0),(-1,-1), 8),
        ("RIGHTPADDING",  (0,0),(-1,-1), 8),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    e.append(diag_tbl)
    e.append(PageBreak())
    return e

# ── PAGE 4: ANTIBIOTIC SAFETY ────────────────────────────────────────
def build_page4():
    e = []
    e.append(section_banner("05  |  ANTIBIOTIC SAFETY IN PREGNANCY"))
    e.append(spacer(8))

    ab_header = [Paragraph(h, table_hdr) for h in
                 ["Antibiotic", "Trimester Safety", "Fetal/Neonatal Risk", "Use in UTI"]]
    ab_rows = [
        ["Penicillins\n(amoxicillin,\nampicillin)", "✔ All trimesters", "None known — SAFE", "1st-line cystitis/ASB\nIV ampicillin for pyelonephritis"],
        ["Cephalosporins\n(cephalexin,\ncefazolin,\nceftriaxone)", "✔ All trimesters", "None known — SAFE", "1st-line for all UTI categories\nCefazolin 1–2 g IV preferred for pyelonephritis"],
        ["Nitrofurantoin", "✔ 1st–2nd trimester\n✖ 3rd trimester / term", "3rd trimester: haemolysis\n(G6PD deficiency)\nAvoid at term (neonatal haemolysis)", "Lower UTI only\nNOT for pyelonephritis\n(poor tissue penetration)"],
        ["Trimethoprim", "⚠ Avoid 1st trimester\n✔ 2nd trimester only", "Folate antagonist →\nneural tube defects (1st trimester)\nAcceptable 2nd trimester", "Avoid if alternatives available"],
        ["Sulfonamides\n(TMP-SMX)", "✔ 1st–2nd trimester\n✖ 3rd trimester", "3rd trimester: kernicterus\n(displaces bilirubin from albumin)", "Use with caution; avoid 3rd trimester"],
        ["Fluoroquinolones\n(ciprofloxacin,\nnorfloxacin)", "✖ ALL trimesters\n(relative contraindication)", "Cartilage formation defects;\narthropathy in animal studies", "AVOID throughout pregnancy"],
        ["Tetracyclines", "✖ ALL trimesters", "Dysplasia + discolouration\nof teeth and bones", "AVOID throughout pregnancy"],
        ["Aminoglycosides\n(gentamicin)", "⚠ Use with extreme caution", "Fetal ototoxicity;\nnephrotoxicity", "Reserve for severe pyelonephritis +\nresistant organisms only"],
    ]
    ab_bg = [GREEN_BG, GREEN_BG, AMBER_BG, AMBER_BG, AMBER_BG, RED_BG, RED_BG, AMBER_BG]
    ab_data = [ab_header]
    for i, row in enumerate(ab_rows):
        ab_data.append([Paragraph(str(c), table_cell) for c in row])

    ab_t = Table(ab_data, colWidths=[3.5*cm, 3.2*cm, 4.5*cm, W-11.2*cm])
    style = [
        ("BACKGROUND",    (0,0),(-1,0),  NAVY),
        ("TEXTCOLOR",     (0,0),(-1,0),  WHITE),
        ("FONTNAME",      (0,0),(-1,0),  "Helvetica-Bold"),
        ("GRID",          (0,0),(-1,-1), 0.4, colors.HexColor("#BDC3C7")),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("TOPPADDING",    (0,0),(-1,-1), 6),
        ("BOTTOMPADDING", (0,0),(-1,-1), 6),
        ("LEFTPADDING",   (0,0),(-1,-1), 7),
        ("RIGHTPADDING",  (0,0),(-1,-1), 7),
        ("FONTNAME",      (0,1),(-1,-1), "Helvetica"),
        ("FONTSIZE",      (0,1),(-1,-1), 8),
    ]
    for i, bg in enumerate(ab_bg):
        style.append(("BACKGROUND", (0, i+1), (-1, i+1), bg))
    ab_t.setStyle(TableStyle(style))
    e.append(ab_t)
    e.append(spacer(10))

    # Legend
    leg_data = [[
        Paragraph("✔ SAFE", S("L", fontSize=8, fontName="Helvetica-Bold", textColor=GREEN, leading=11)),
        Paragraph("⚠ CAUTION", S("L2", fontSize=8, fontName="Helvetica-Bold", textColor=AMBER, leading=11)),
        Paragraph("✖ AVOID", S("L3", fontSize=8, fontName="Helvetica-Bold", textColor=RED, leading=11)),
        Paragraph("Green = safe | Amber = caution / trimester-dependent | Red = contraindicated",
                  S("L4", fontSize=7.5, fontName="Helvetica", textColor=GREY, leading=11)),
    ]]
    leg_t = Table(leg_data, colWidths=[2*cm, 2.5*cm, 2*cm, W-6.5*cm])
    leg_t.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(-1,-1), LGREY),
        ("TOPPADDING", (0,0),(-1,-1), 5),
        ("BOTTOMPADDING", (0,0),(-1,-1), 5),
        ("LEFTPADDING", (0,0),(-1,-1), 8),
        ("RIGHTPADDING", (0,0),(-1,-1), 8),
        ("VALIGN", (0,0),(-1,-1), "MIDDLE"),
    ]))
    e.append(leg_t)
    e.append(PageBreak())
    return e

# ── PAGE 5: TREATMENT REGIMENS ───────────────────────────────────────
def build_page5():
    e = []
    e.append(section_banner("06  |  TREATMENT REGIMENS"))
    e.append(spacer(8))

    # ─ ASB ─
    e.append(Table([[Paragraph("A.  ASYMPTOMATIC BACTERIURIA (ASB)", S("SH2",
              fontSize=10.5, textColor=TEAL, fontName="Helvetica-Bold", leading=13))]],
              colWidths=[W], style=[("BACKGROUND",(0,0),(-1,-1),MINT),
              ("LEFTPADDING",(0,0),(-1,-1),10),("TOPPADDING",(0,0),(-1,-1),6),
              ("BOTTOMPADDING",(0,0),(-1,-1),6)]))
    e.append(spacer(5))

    asb_data = [
        [Paragraph("<b>Drug</b>", table_hdr), Paragraph("<b>Dose / Frequency</b>", table_hdr),
         Paragraph("<b>Duration</b>", table_hdr), Paragraph("<b>Notes</b>", table_hdr)],
        [Paragraph("Cephalexin", table_cell_b), Paragraph("500 mg PO 2–4× daily", table_cell),
         Paragraph("3–7 days", table_cell), Paragraph("Preferred 1st-line", table_cell)],
        [Paragraph("Amoxicillin", table_cell_b), Paragraph("500 mg PO 2–3× daily", table_cell),
         Paragraph("3–7 days", table_cell), Paragraph("If susceptibility confirmed", table_cell)],
        [Paragraph("Amoxicillin-Clavulanate", table_cell_b), Paragraph("625 mg PO 3× daily", table_cell),
         Paragraph("3–7 days", table_cell), Paragraph("Use if resistant organism", table_cell)],
        [Paragraph("Nitrofurantoin", table_cell_b), Paragraph("100 mg MR PO twice daily", table_cell),
         Paragraph("5–7 days", table_cell), Paragraph("1st–2nd trimester ONLY; NOT in 3rd trimester", table_cell)],
    ]
    asb_t = Table(asb_data, colWidths=[3.8*cm, 4.2*cm, 2.5*cm, W-10.5*cm])
    asb_t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0),  TEAL),
        ("TEXTCOLOR",     (0,0),(-1,0),  WHITE),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [WHITE, LGREY]),
        ("GRID",          (0,0),(-1,-1), 0.4, colors.HexColor("#BDC3C7")),
        ("TOPPADDING",    (0,0),(-1,-1), 5), ("BOTTOMPADDING",(0,0),(-1,-1), 5),
        ("LEFTPADDING",   (0,0),(-1,-1), 7), ("RIGHTPADDING",  (0,0),(-1,-1), 7),
        ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
    ]))
    e.append(asb_t)
    e.append(spacer(4))
    e.append(Paragraph("→ Follow-up urine culture 1–2 weeks after completing treatment. Treat each recurrence; consider suppressive therapy.", note_style))
    e.append(spacer(10))

    # ─ Cystitis ─
    e.append(Table([[Paragraph("B.  ACUTE CYSTITIS", S("SH3",
              fontSize=10.5, textColor=AMBER, fontName="Helvetica-Bold", leading=13))]],
              colWidths=[W], style=[("BACKGROUND",(0,0),(-1,-1),AMBER_BG),
              ("LEFTPADDING",(0,0),(-1,-1),10),("TOPPADDING",(0,0),(-1,-1),6),
              ("BOTTOMPADDING",(0,0),(-1,-1),6)]))
    e.append(spacer(5))
    e.append(Paragraph("Use same agents as for ASB above. Confirm sensitivity pattern. Duration: <b>5–7 days</b> (longer than non-pregnant). Follow-up culture mandatory.", body))
    e.append(spacer(10))

    # ─ Pyelonephritis ─
    e.append(Table([[Paragraph("C.  ACUTE PYELONEPHRITIS", S("SH4",
              fontSize=10.5, textColor=RED, fontName="Helvetica-Bold", leading=13))]],
              colWidths=[W], style=[("BACKGROUND",(0,0),(-1,-1),RED_BG),
              ("LEFTPADDING",(0,0),(-1,-1),10),("TOPPADDING",(0,0),(-1,-1),6),
              ("BOTTOMPADDING",(0,0),(-1,-1),6)]))
    e.append(spacer(5))

    pye_data = [
        [Paragraph("<b>Setting</b>", table_hdr), Paragraph("<b>Drug</b>", table_hdr),
         Paragraph("<b>Dose</b>", table_hdr), Paragraph("<b>Duration</b>", table_hdr)],
        [Paragraph("IV (hospital)\n1st-line", table_cell_b),
         Paragraph("Cefazolin", table_cell_b),
         Paragraph("1–2 g IV every 8 hours", table_cell),
         Paragraph("IV until afebrile 24–48 hrs;\nthen oral ×10–14 days total", table_cell)],
        [Paragraph("IV (hospital)\nalternative", table_cell_b),
         Paragraph("Ampicillin\n+ Gentamicin", table_cell),
         Paragraph("Ampicillin 2 g IV q6h\nGentamicin 5 mg/kg IV once daily", table_cell),
         Paragraph("Caution with gentamicin\n(monitor renal function)", table_cell)],
        [Paragraph("Oral step-down\n(after IV)", table_cell_b),
         Paragraph("Cephalexin\nor Amoxicillin-Clav", table_cell),
         Paragraph("500 mg PO 4× daily\nor 625 mg PO 3× daily", table_cell),
         Paragraph("Complete 10–14 days total", table_cell)],
    ]
    pye_t = Table(pye_data, colWidths=[3.5*cm, 3.8*cm, 5*cm, W-12.3*cm])
    pye_t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,0),  colors.HexColor("#8B1A1A")),
        ("TEXTCOLOR",     (0,0),(-1,0),  WHITE),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [RED_BG, colors.HexColor("#FDF0EF"), RED_BG]),
        ("GRID",          (0,0),(-1,-1), 0.4, colors.HexColor("#BDC3C7")),
        ("TOPPADDING",    (0,0),(-1,-1), 6), ("BOTTOMPADDING",(0,0),(-1,-1), 6),
        ("LEFTPADDING",   (0,0),(-1,-1), 7), ("RIGHTPADDING",  (0,0),(-1,-1), 7),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    e.append(pye_t)
    e.append(spacer(6))

    # Pyelonephritis management steps
    pye_mgmt = [
        "Hospital admission is strongly recommended for all cases of pyelonephritis in pregnancy",
        "Aggressive IV fluid resuscitation — reduces rate of transient renal dysfunction from ~20% to ~7%",
        "Urine culture + sensitivities before first antibiotic dose",
        "Blood cultures if systemically unwell or bacteraemia suspected",
        "Regular monitoring: temperature, HR, RR, O₂ saturation, urine output, fetal CTG",
        "If no improvement in 48–72 hrs → renal USS to exclude obstruction/abscess",
        "Watch for ARDS (2–8%): dyspnoea, tachypnoea, hypoxia, pulmonary oedema on CXR",
        "Suppressive antibiotics for the remainder of pregnancy after an episode of pyelonephritis",
    ]
    e.append(info_box("Pyelonephritis Management Checklist", pye_mgmt, bg=RED_BG, border=RED))
    e.append(PageBreak())
    return e

# ── PAGE 6: COMPLICATIONS + PREVENTION ──────────────────────────────
def build_page6():
    e = []
    e.append(section_banner("07  |  COMPLICATIONS"))
    e.append(spacer(8))

    col_mat = [
        Paragraph("<b>Maternal Complications</b>", S("CH", fontSize=10, textColor=RED,
                   fontName="Helvetica-Bold", leading=13)),
        Paragraph("• Septic shock — pyelonephritis is one of the most common causes in pregnancy", bullet),
        Paragraph("• ARDS in 2–8% of pyelonephritis cases (cytokine-mediated endothelial injury)", bullet),
        Paragraph("• Multiorgan dysfunction: up to 20% of pyelonephritis patients", bullet),
        Paragraph("• Haemolytic anaemia, DIC (severe sepsis)", bullet),
        Paragraph("• Transient renal dysfunction: ~7% with aggressive fluids; ~20% without", bullet),
        Paragraph("• Recurrent pyelonephritis in 10–20% before delivery", bullet),
        spacer(4),
        Paragraph("<b>ARDS Risk Predictors in Pyelonephritis:</b>", body_bold),
        Paragraph("• Maternal HR >110 bpm", bullet),
        Paragraph("• Temp ≥103°F (39.4°C) within first 24 hrs", bullet),
        Paragraph("• Tocolytic agent use", bullet),
        Paragraph("• Ampicillin as sole antibiotic", bullet),
        Paragraph("• Fluid overload", bullet),
    ]
    col_fet = [
        Paragraph("<b>Fetal / Obstetric Complications</b>", S("CH2", fontSize=10, textColor=AMBER,
                   fontName="Helvetica-Bold", leading=13)),
        Paragraph("• Preterm labour — pyelonephritis is one of the most common identifiable causes\n(cytokine-mediated uterine contractions)", bullet),
        Paragraph("• Low birth weight", bullet),
        Paragraph("• Increased perinatal mortality (with untreated pyelonephritis)", bullet),
        Paragraph("• Risk of neonatal sepsis (GBS bacteriuria warrants intrapartum prophylaxis)", bullet),
        spacer(4),
        Paragraph("<b>Consequences of Untreated ASB:</b>", body_bold),
        Paragraph("• Progresses to pyelonephritis in 20–40% (vs <2% in non-pregnant women)", bullet),
        Paragraph("• Associated with low birth weight and preterm delivery", bullet),
        Paragraph("• This is why screening + treatment of ASB is mandatory in pregnancy", bullet),
        spacer(4),
        Paragraph("<b>Reflux Nephropathy (if present):</b>", body_bold),
        Paragraph("• Increases risk of sudden escalating hypertension", bullet),
        Paragraph("• Risk of worsening renal function during pregnancy", bullet),
    ]
    comp_tbl = Table([[col_mat, col_fet]], colWidths=[W/2-4, W/2-4])
    comp_tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(0,-1), RED_BG),
        ("BACKGROUND", (1,0),(1,-1), AMBER_BG),
        ("BOX",        (0,0),(0,-1), 1.5, RED),
        ("BOX",        (1,0),(1,-1), 1.5, AMBER),
        ("TOPPADDING",    (0,0),(-1,-1), 8),
        ("BOTTOMPADDING", (0,0),(-1,-1), 8),
        ("LEFTPADDING",   (0,0),(-1,-1), 10),
        ("RIGHTPADDING",  (0,0),(-1,-1), 10),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    e.append(comp_tbl)
    e.append(spacer(12))

    e.append(section_banner("08  |  PREVENTION & FOLLOW-UP", bg=GREEN))
    e.append(spacer(8))

    prev_col1 = [
        Paragraph("<b>Suppressive Antibiotic Therapy</b>", sub_head),
        Paragraph("Indications:", body_bold),
        Paragraph("• ≥2 UTIs during pregnancy", bullet),
        Paragraph("• After an episode of pyelonephritis", bullet),
        Paragraph("• Structural urinary tract abnormality", bullet),
        Paragraph("• Reflux nephropathy", bullet),
        spacer(4),
        Paragraph("Agents for nightly suppression:", body_bold),
        Paragraph("• Cephalexin 250–500 mg at bedtime", bullet),
        Paragraph("• Nitrofurantoin 50–100 mg at bedtime (1st–2nd trimester only)", bullet),
        Paragraph("• Amoxicillin 250 mg at bedtime (if susceptible)", bullet),
        spacer(4),
        Paragraph("<b>Duration:</b> Until 4–6 weeks postpartum, then reassess with urine culture.", body),
    ]
    prev_col2 = [
        Paragraph("<b>General Prevention Measures</b>", sub_head),
        Paragraph("• Adequate hydration (8+ glasses of water/day)", bullet),
        Paragraph("• Void frequently — avoid prolonged bladder distension", bullet),
        Paragraph("• Void before and after intercourse", bullet),
        Paragraph("• Wipe front-to-back after toileting", bullet),
        Paragraph("• Avoid catheterisation unless essential", bullet),
        spacer(4),
        Paragraph("<b>Monitoring Schedule</b>", body_bold),
        Paragraph("• Urine culture at first antenatal visit (12–16 weeks)", bullet),
        Paragraph("• Culture 1–2 weeks after completing any UTI treatment", bullet),
        Paragraph("• Culture each trimester in high-risk patients (DM, sickle cell, structural abnormality)", bullet),
        Paragraph("• Postnatal urine culture at 6-week check", bullet),
        Paragraph("• Renal imaging postpartum if recurrent UTI or structural concern", bullet),
    ]
    prev_tbl = Table([[prev_col1, prev_col2]], colWidths=[W/2-4, W/2-4])
    prev_tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(0,-1), GREEN_BG),
        ("BACKGROUND", (1,0),(1,-1), colors.HexColor("#F0FFF4")),
        ("BOX",        (0,0),(0,-1), 1.5, GREEN),
        ("BOX",        (1,0),(1,-1), 1.5, GREEN),
        ("TOPPADDING",    (0,0),(-1,-1), 8),
        ("BOTTOMPADDING", (0,0),(-1,-1), 8),
        ("LEFTPADDING",   (0,0),(-1,-1), 10),
        ("RIGHTPADDING",  (0,0),(-1,-1), 10),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]))
    e.append(prev_tbl)
    e.append(spacer(10))

    # References
    e.append(hr(color=GREY, thickness=0.5))
    e.append(spacer(4))
    e.append(Paragraph("<b>Sources:</b>", S("RefHdr", fontSize=8, fontName="Helvetica-Bold",
              textColor=GREY, leading=11)))
    refs = [
        "Creasy &amp; Resnik's Maternal-Fetal Medicine: Principles and Practice (9780323828499), Chapters on UTI and Pyelonephritis in Pregnancy, pp. 1124–1130",
        "Smith and Tanagho's General Urology, 19th Edition (9781259834332), Chapter 14: UTI Related to Pregnancy, p. 234–235",
        "Tintinalli's Emergency Medicine: A Comprehensive Study Guide (9781260019933), Chapter 99: Asymptomatic Bacteriuria, Cystitis and Pyelonephritis, pp. 667–668",
        "Comprehensive Clinical Nephrology, 7th Edition (9780323825924), Chapter: Kidney Disease in Pregnancy",
        "ACOG Practice Bulletin No. 91: Treatment of Urinary Tract Infections During Pregnancy",
    ]
    for r in refs:
        e.append(Paragraph(f"• {r}", S("Ref", fontSize=7.5, fontName="Helvetica",
                  textColor=GREY, leading=11, leftIndent=10, firstLineIndent=-8,
                  spaceBefore=2)))
    return e

# ── Page number canvas callback ─────────────────────────────────────
def on_page(canvas, doc):
    canvas.saveState()
    canvas.setFont("Helvetica", 8)
    canvas.setFillColor(GREY)
    w, h = A4
    canvas.drawRightString(w - 1.8*cm, 1.3*cm, f"Page {doc.page}")
    canvas.drawString(1.8*cm, 1.3*cm, "UTI in Pregnancy – Treatment Protocol  |  Orris Medical Education")
    canvas.setStrokeColor(TEAL)
    canvas.setLineWidth(0.5)
    canvas.line(1.8*cm, 1.6*cm, w - 1.8*cm, 1.6*cm)
    canvas.restoreState()

# ── Build ────────────────────────────────────────────────────────────
story = []
story += build_cover()
story += build_page2()
story += build_page3()
story += build_page4()
story += build_page5()
story += build_page6()

doc.build(story, onFirstPage=on_page, onLaterPages=on_page)
print(f"PDF created: {OUTPUT_PATH}")

Running Command

cd /tmp/workspace/uti_protocol && python generate_pdf.py 2>&1

Running Command

ls -lh /tmp/workspace/uti_protocol/UTI_in_Pregnancy_Protocol.pdf

Your protocol guide is ready. Download it here:

UTI in Pregnancy Protocol

PDF Document · PDF

What's inside the 6-page guide:

Section	Content
Cover	Title banner, quick-stats panel (5-10% ASB prevalence, 2-4% pyelonephritis, 75% right-sided), visual table of contents
01 - Pathophysiology	Two-column layout: anatomic changes vs physiologic changes during pregnancy
02 - Classification	Colour-coded table: ASB / Acute Cystitis / Acute Pyelonephritis with definitions, symptoms, timing
03 - Microbiology	Organism frequency table with clinical notes (E. coli dominant at 70-80%)
04 - Diagnosis	Screening protocol + investigation checklist for pyelonephritis
05 - Antibiotic Safety	Full colour-coded table: safe (green) / caution (amber) / avoid (red) for each antibiotic class by trimester
06 - Treatment Regimens	Specific dose tables for ASB, cystitis, and IV/oral pyelonephritis; management checklist
07 - Complications	Maternal (ARDS, septic shock, renal dysfunction) and fetal (preterm labour, low birth weight) risks
08 - Prevention	Suppressive therapy indications + agents; monitoring schedule throughout pregnancy

Sources: Creasy & Resnik's Maternal-Fetal Medicine, Smith & Tanagho's General Urology, Tintinalli's Emergency Medicine, and Comprehensive Clinical Nephrology.

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