from reportlab.lib import colors
from reportlab.lib.enums import TA_CENTER, TA_LEFT
from reportlab.lib.pagesizes import letter
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import inch
from reportlab.platypus import SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, PageBreak, KeepTogether
from reportlab.pdfbase.ttfonts import TTFont
from reportlab.pdfbase import pdfmetrics
from reportlab.lib.colors import HexColor

OUT='/tmp/workspace/pulmonary-reviewer/output/Opportunistic_Pulmonary_Mycoses_Exam_Reviewer.pdf'
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def P(text, style='Bodyx'): return Paragraph(text, styles[style])
def bullets(items, style='Bodyx'):
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def section(title): return [P(title,'H1x')]
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    canvas.drawString(.55*inch,.32*inch,'Murray & Nadel, 7th ed., Ch. 57, pp. 763-778 | High-yield exam review')
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doc=SimpleDocTemplate(OUT,pagesize=letter,rightMargin=.52*inch,leftMargin=.52*inch,topMargin=.52*inch,bottomMargin=.62*inch)
story=[]
story += [Spacer(1,.18*inch), P('OPPORTUNISTIC PULMONARY MYCOSES','Title2'),P('Pulmonary Fellowship Rapid Reviewer | Based on Murray & Nadel’s Textbook of Respiratory Medicine, 7th ed., Chapter 57, pp. 763-778','Sub')]
story += [P('<b>Scope:</b> antifungal pharmacology, cryptococcosis, candidiasis, aspergillosis, mucormycosis, and uncommon hyaline/dematiaceous molds. This is a recall-focused synthesis of the supplied pages, not a prescribing protocol.','Callout')]
story += section('1. First-pass framework')
story += bullets([
'<b>Host + morphology + syndrome</b> is the fastest diagnostic scaffold. Ask: Is there neutropenia, transplant, hematologic malignancy, advanced HIV, corticosteroid/targeted immunomodulator exposure, diabetes/acidosis, chronic structural lung disease, or ICU viral pneumonia?',
'<b>Yeasts:</b> <i>Candida</i> and <i>Cryptococcus</i>. <b>Molds:</b> septate hyaline molds (including <i>Aspergillus</i>), septate dematiaceous molds, and broad aseptate/sparsely septate Mucorales.',
'<b>Invasive mold disease</b> is often angioinvasive: expect thrombosis, infarction, necrosis, pleuritic pain, hemoptysis, and rapidly progressive illness in neutropenia.',
'<b>Do not equate a respiratory culture with disease.</b> Colonization is common with Candida and environmental molds. Establish compatible host factors, imaging, mycology, and where feasible tissue invasion.'
])
story += [P('Morphology that wins questions','H2x'), table(['Organism group','Tissue / microscopy clue','Exam implication'],[
['<i>Aspergillus</i>','Narrow 3-6 µm, septate hyphae; acute-angle (~45°) branching','Culture needed to distinguish from other hyaline molds.'],
['Mucorales','Broad 10-20 µm, ribbon-like, irregular, aseptate or sparsely septate hyphae','GM and beta-D-glucan are not useful. Think diabetes/acidosis.'],
['Dematiaceous molds','Septate hyphae with brown pigment from melanin','Phaeohyphomycosis; can cause pulmonary/CNS disease.'],
['<i>Cryptococcus</i>','Encapsulated yeast; inhalational acquisition','Lung is common entry site; CNS is common dissemination site.']
],[1.25*inch,2.45*inch,3.05*inch])]
story += [P('<b>Memory hook:</b> “<b>45 = Aspergillus; broad ribbon = Mucor</b>.”','Callout')]
story.append(PageBreak())

story += section('2. Antifungal pharmacology: practical exam matrix')
story += [table(['Class / agent','Best recall uses from source','Major liabilities / monitoring'],[
['Polyenes: amphotericin B (deoxycholate or lipid formulations)','Broad: Aspergillus (but <i>A. terreus</i> resistant), Candida, Cryptococcus, Mucorales, endemic fungi, dematiaceous molds. Lipid products reduce nephrotoxicity.','IV only. Infusion reactions, nephrotoxicity, hypokalemia/hypomagnesemia, anemia. Hydration helps.'],
['Fluconazole','Cryptococcus; Candida when susceptible; some endemic mycosis activity.','Renal dose adjustment; hepatotoxicity, QT prolongation; CYP2C9/3A4 inhibition. <i>C. krusei</i> intrinsically resistant; <i>C. glabrata</i> variable.'],
['Itraconazole','Aspergillus, Cryptococcus, endemic fungi, dematiaceous molds.','TDM for systemic disease: after >=2 weeks, random HPLC goal >=1.0 µg/mL (itraconazole + hydroxy-itraconazole). Capsules need food/acid and have reduced absorption with PPIs/H2 blockers; solution empty stomach. Avoid in CHF/ventricular dysfunction.'],
['Voriconazole','Preferred primary therapy for IPA in this chapter; active against Aspergillus.','TDM recommended. Hepatotoxicity, visual/neurologic effects, photosensitivity, QT prolongation, major CYP interactions. No Mucorales activity.'],
['Posaconazole / isavuconazole','Mold-active azoles. Isavuconazole has activity against some Mucorales; posaconazole used in mold settings.','TDM important for posaconazole (especially variable absorption formulations); interactions matter. Isavuconazole shortens QT.'],
['Echinocandins','Candida; Aspergillus salvage/combination role.','IV. Minimal CYP interactions; not active against Cryptococcus or Mucorales.'],
['Flucytosine','Combination partner with amphotericin B for Cryptococcus; severe Candida CNS/endocarditis.','Use only in combination. Monitor levels/toxicity: marrow suppression, hepatotoxicity, GI effects.']
],[1.3*inch,3.15*inch,2.3*inch], 'Tiny')]
story += [P('<b>High-yield interaction rule:</b> azoles are interaction-heavy. Before starting, review QT risk, hepatic function, calcineurin/mTOR inhibitors, chemotherapy, and CYP substrates.','Callout')]
story += section('3. Cryptococcosis')
story += bullets([
'<b>Species and ecology:</b> <i>C. neoformans</i> is global and associated with soil/bird excreta. <i>C. gattii</i> classically tropical/subtropical but recognized in Vancouver and the Pacific Northwest; it can affect immunocompetent hosts.',
'<b>Who gets severe disease?</b> Advanced HIV, malignancy, solid-organ transplant, and other cellular immune deficits. Anti-GM-CSF autoantibodies predispose to <i>C. gattii</i> infection.',
'<b>Clinical/radiology:</b> Immunocompetent hosts may have asymptomatic nodules or mild pneumonia. Immunocompromised patients can progress to respiratory failure/ARDS. CT: nodules, patchy consolidation, cavitation, masses/cryptococcomas, GGO, effusions, or adenopathy. Cryptococcomas are more common with <i>C. gattii</i>.',
'<b>Dissemination:</b> CNS is the most common site. A pulmonary diagnosis in an immunocompromised patient should trigger evaluation for extrapulmonary, particularly CNS, disease.'
])
story.append(PageBreak())

story += section('4. Cryptococcosis: diagnostic and treatment logic')
story += [P('Diagnostic approach','H2x')]
story += bullets([
'Obtain respiratory specimen for microscopy/culture and serum cryptococcal antigen (CrAg). Serum CrAg may be negative in isolated pulmonary disease, especially in immunocompetent hosts.',
'Perform lumbar puncture when dissemination/CNS disease is suspected, in immunocompromised hosts, or when serum CrAg is positive or high. Check opening pressure, CSF CrAg, fungal culture, and routine CSF studies.',
'India ink is insensitive. Histology can demonstrate encapsulated yeast; mucicarmine highlights capsule. Culture remains important for identification and susceptibility when needed.'
])
story += [P('Treatment: severity and CNS status drive therapy','H2x'), table(['Syndrome','Core approach'],[
['Mild-to-moderate, isolated pulmonary disease in immunocompetent host','Fluconazole is typical therapy. Confirm no CNS/disseminated disease and follow clinical/radiographic response.'],
['Severe pulmonary disease, disseminated infection, or CNS infection','Induction with amphotericin B plus flucytosine, then azole consolidation and maintenance. Manage raised intracranial pressure with serial therapeutic LPs when present.'],
['Transplant / profound immunosuppression','Assess CNS and dissemination aggressively. Reduce immunosuppression thoughtfully with transplant/ID input to avoid immune reconstitution phenomena or graft compromise.']
],[2.5*inch,4.25*inch])]
story += [P('<b>Exam pearl:</b> Pulmonary cryptococcosis is not automatically “lung-only.” Determine whether the patient has CNS disease before choosing a limited pulmonary regimen.','Callout')]
story += section('5. Candidiasis in pulmonary practice')
story += bullets([
'<b>Candida in sputum/BAL almost always means colonization</b>, not Candida pneumonia. True primary Candida pneumonia is rare and requires histopathologic evidence of invasion.',
'Candida can cause invasive disease in critically ill, neutropenic, transplant, or device-exposed patients. Think candidemia with hematogenous lung lesions rather than treating a positive airway culture alone.',
'<b>Management principle:</b> obtain blood cultures and source-control evaluation when invasive candidiasis is suspected. Echinocandins are foundational initial therapy for many invasive Candida syndromes; tailor to species/susceptibility and clinical stability.',
'<b>Resistance traps:</b> <i>C. krusei</i> is intrinsically fluconazole-resistant; <i>C. glabrata</i> has variable fluconazole susceptibility; <i>C. auris</i> may have high fluconazole resistance.'
])
story += section('6. Invasive pulmonary aspergillosis (IPA)')
story += bullets([
'<b>Major hosts:</b> prolonged neutropenia/AML, HCT (early neutropenia and later GVHD), SOT especially lung transplant, advanced HIV, CGD, high-dose steroids/immunomodulators including ibrutinib. ICU risk also occurs with renal failure, diabetes, COPD, cirrhosis, and severe influenza.',
'<b>Presentation:</b> fever, cough, pleuritic chest pain, and hemoptysis. In neutropenia, deterioration can occur in hours to days.',
'<b>Pathobiology:</b> angioinvasion leads to thrombosis, infarction, and coagulative necrosis. This explains the halo sign and hemoptysis.'
])
story.append(PageBreak())

story += section('7. IPA: diagnosis, imaging, treatment')
story += [P('CT and mycology','H2x'), table(['Tool','How to use it / limitation'],[
['Chest CT','Nodules, halo sign, wedge-shaped infarct-like lesions, consolidation, cavitation/air-crescent later. A normal chest radiograph does not exclude early IPA.'],
['Serum galactomannan (GM)','Most useful in high-risk neutropenic/hematologic patients. Reduced sensitivity with mold-active prophylaxis and in non-neutropenic hosts. False positives occur.'],
['BAL GM','Useful when bronchoscopy is feasible; interpret with clinical context. Send fungal culture, microscopy, GM, and other relevant testing.'],
['Beta-D-glucan','Supportive, not Aspergillus-specific. Not useful for Mucorales.'],
['Culture / histology','Culture identifies species and supports susceptibility testing. Tissue showing hyphal invasion provides strongest evidence; do not delay treatment in unstable high-probability disease.']
],[1.25*inch,5.5*inch])]
story += [P('Treatment and decision points','H2x')]
story += bullets([
'<b>First-line IPA:</b> voriconazole in this source. Isavuconazole is an alternative mold-active azole. Start promptly when probable disease is present; correct neutropenia or reduce immunosuppression if feasible.',
'<b>Therapeutic drug monitoring:</b> important with voriconazole and other variable-exposure triazoles. Check hepatic tests, QT effects, neuro/visual adverse effects, and interactions.',
'<b>Duration:</b> individualized by immune recovery and response. The source notes minimum 4-6 months for chronic pulmonary aspergillosis, with prolonged or indefinite therapy in responders often necessary.',
'<b>Species trap:</b> <i>A. terreus</i> has intrinsic amphotericin B resistance. Breakthrough mold infection during azole prophylaxis requires species identification and reassessment of resistance/exposure.'
])
story += section('8. Chronic pulmonary aspergillosis (CPA)')
story += bullets([
'Occurs in chronic structural lung disease or residual cavities. Phenotypes include chronic cavitary, fibrosing, and nodular disease; an aspergilloma is fungus within a pre-existing cavity.',
'Consider with chronic symptoms, weight loss/fatigue, hemoptysis, progressive cavities or pericavitary infiltrates over months, and Aspergillus-specific IgG/microbiology support.',
'Long-term oral triazole therapy is standard when active disease is present; hemoptysis may require bronchial artery embolization and selected surgery. Monitor resistance, toxicity, interactions, and drug levels.'
])
story += [P('<b>Differentiate:</b> IPA = acute invasive disease in impaired host defenses. CPA = months-long destructive disease in structurally abnormal lungs. ABPA = allergic, noninvasive disease and is not the focus of these pages.','Callout')]
story.append(PageBreak())

story += section('9. Pulmonary mucormycosis')
story += [P('Recognize early','H2x')]
story += bullets([
'<b>Who?</b> Poorly controlled diabetes, especially hyperglycemia/acidosis; hematologic malignancy and neutropenia; HCT; transplant. Free iron promotes Mucorales growth, and phagocyte dysfunction is central.',
'<b>Clinical:</b> acute severe fever, cough, dyspnea, pleuritic pain, and hemoptysis in neutropenia. Diabetes can produce a more subacute course. Vascular invasion can cause catastrophic hemoptysis and mediastinal/chest-wall extension.',
'<b>CT clues:</b> nodules, masses, GGO, consolidation, cavities. >=10 nodules and pleural effusion favor mucormycosis over IPA. Reversed halo is more common in mucormycosis, though not exclusive.',
'<b>Diagnostic trap:</b> serum GM and beta-D-glucan are not helpful because Mucorales lack substantial quantities of those cell-wall components.'
])
story += [P('Urgent management','H2x'), table(['Action','Why it matters'],[
['Get tissue / direct microscopy and culture quickly','Broad ribbon-like 10-20 µm irregular hyphae in BAL/sputum can be a clue; tissue establishes invasion and culture enables identification.'],
['Start liposomal amphotericin B promptly','Treatment delay increases mortality. Do not use voriconazole as treatment for Mucorales.'],
['Source control and reverse predisposition','Surgical debridement/resection when feasible; correct hyperglycemia/acidosis, reduce immunosuppression if possible, address neutropenia.'],
['Step-down / salvage','Isavuconazole or posaconazole are options in appropriate settings, guided by species, response, tolerability, and expertise.']
],[2.05*inch,4.7*inch])]
story += [P('<b>Board-style contrast:</b> IPA: GM may help, acute-angle septate hyphae, voriconazole. Mucor: GM/BDG do not help, broad ribbon-like hyphae, liposomal amphotericin B plus surgery.','Callout')]
story += section('10. Uncommon molds')
story += [table(['Group','High-yield clue','Management implication'],[
['Non-Aspergillus hyaline molds: Fusarium, Scedosporium/Lomentospora, Purpureocillium, Acremonium, Trichoderma','Can colonize airways. Invasive disease in impaired immunity; adventitious sporulation can cause fungemia. Fusarium disseminated disease has fungemia in >50% in source. Near-drowning is a classic Scedosporium risk for CNS/sinopulmonary infection.','Species-level ID and susceptibility are essential. Some are resistant to amphotericin B and/or azoles. Lomentospora is particularly difficult; seek expert input.'],
['Dematiaceous (melanized) molds','Melanin gives brown-pigmented septate hyphae. Can cause pulmonary, sinus, cutaneous, and CNS disease.','Often managed with extended-spectrum azoles; surgery/source control may be needed. Identify species.']
],[1.65*inch,2.55*inch,2.55*inch], 'Tiny')]
story.append(PageBreak())

story += section('11. 60-second exam algorithm')
story += [table(['If this is the scenario...','Think / do this next'],[
['Neutropenic AML/HCT patient + fever + pleuritic pain/hemoptysis + CT nodules/halo','Probable IPA. CT, serum/BAL GM as appropriate, BAL/culture, start mold-active therapy promptly.'],
['Diabetes/acidosis or breakthrough on voriconazole + multiple nodules/effusion/reversed halo','Mucormycosis until excluded. Biopsy/direct exam/culture; liposomal amphotericin B and surgical evaluation. Do not be reassured by negative GM/BDG.'],
['Pulmonary nodule/consolidation + positive CrAg or immunocompromised host','Cryptococcosis. Assess CNS/dissemination, including LP when indicated; therapy depends on severity/CNS involvement.'],
['Candida recovered from BAL/sputum only','Usually colonization. Do not diagnose Candida pneumonia without tissue invasion; look for another cause or candidemia/source.'],
['Chronic cavities + hemoptysis + Aspergillus IgG in prior TB/bronchiectasis/structural lung disease','CPA. Define phenotype, assess progression, long-term triazole plan and hemoptysis control.'],
['Mold in culture during azole prophylaxis','Breakthrough infection: verify exposure/adherence/TDM, identify species, evaluate azole resistance, reconsider Mucorales or rare molds.']
],[2.6*inch,4.15*inch])]
story += section('12. Rapid-fire self-test')
qs=[
('1. Which fungal biomarkers are usually unhelpful in mucormycosis?', '<b>Answer:</b> Serum galactomannan and beta-D-glucan.'),
('2. What is the microscopic contrast between Aspergillus and Mucorales?', '<b>Answer:</b> Aspergillus has narrow septate hyphae with acute-angle branching; Mucorales have broad ribbon-like, irregular, aseptate/sparsely septate hyphae.'),
('3. What should a positive respiratory Candida culture usually mean?', '<b>Answer:</b> Colonization, unless invasive pneumonia is established histopathologically.'),
('4. Which two events make a pulmonary cryptococcal finding more urgent?', '<b>Answer:</b> Immunocompromise and concern for CNS/disseminated disease, prompting assessment including LP when indicated.'),
('5. Which Aspergillus species has intrinsic amphotericin B resistance?', '<b>Answer:</b> <i>Aspergillus terreus</i>.'),
('6. What CT pattern favors mucormycosis over IPA, while remaining non-specific?', '<b>Answer:</b> Numerous nodules with pleural effusions and a reversed halo sign.'),
('7. In what setting is Scedosporium a classic concern even without baseline immunodeficiency?', '<b>Answer:</b> Near-drowning, with sinopulmonary and CNS infection risk.'),
('8. What is the central first-line treatment principle for suspected pulmonary mucormycosis?', '<b>Answer:</b> Do not delay liposomal amphotericin B, pursue tissue diagnosis, and obtain surgical/source-control evaluation.'),
]
for q,a in qs: story += [P(q,'Q'),P(a,'A')]
story += [Spacer(1,8), P('Source note','H2x'),P('Prepared solely from the supplied excerpt: <i>Murray & Nadel’s Textbook of Respiratory Medicine</i>, 7th edition, Chapter 57 “Fungal Infections: Opportunistic,” pp. 763-778 (PDF pages supplied). Drug selection and dosing must be checked against current institutional protocols, susceptibility data, and updated guidelines before clinical use.','Small')]
doc.build(story,onFirstPage=footer,onLaterPages=footer)
print(OUT)