What are the key concepts and management strategies in various medical specialties, including cardiology, pulmonology, infectious diseases, nephrology, neurology, gastroenterology, endocrinology, allergology, oncology, hematology, and rheumatology?

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COMPREHENSIVE MEDICAL CONSULTANT ROUNDS: KEY CONCEPTS ACROSS SPECIALTIES

CARDIOLOGY

Heart Failure Classification

Heart failure is classified by ejection fraction (EF) into three categories: HFrEF (EF ≤40%), HFmrEF (EF 41-49%), and HFpEF (EF ≥50%).

  • HFrEF (Heart Failure with Reduced Ejection Fraction): EF ≤40% - systolic dysfunction predominates 1
  • HFmrEF (Heart Failure with Mildly Reduced Ejection Fraction): EF 41-49% - intermediate category 1
  • HFpEF (Heart Failure with Preserved Ejection Fraction): EF ≥50% - diastolic dysfunction predominates 1

Additional classification systems include:

  • NYHA Functional Classification: Class I (no limitation), Class II (slight limitation), Class III (marked limitation), Class IV (symptoms at rest) 1
  • ACC/AHA Stages: Stage A (at risk), Stage B (structural disease, no symptoms), Stage C (structural disease with symptoms), Stage D (refractory/end-stage) 1

The 4 Pillars of Heart Failure (HFrEF) Management

The four pillars of HFrEF management are: ACE inhibitors/ARBs/ARNI, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors.

  1. ACE Inhibitors/ARBs/ARNI (Angiotensin Receptor-Neprilysin Inhibitor): Reduce mortality and hospitalization; ARNI preferred over ACE-I when tolerated 1

  2. Beta-Blockers: Carvedilol, metoprolol succinate, or bisoprolol reduce mortality and improve symptoms 1

  3. Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone or eplerenone reduce mortality in NYHA Class II-IV 1

  4. SGLT2 Inhibitors: Dapagliflozin or empagliflozin reduce cardiovascular death and HF hospitalization regardless of diabetes status 2

All four pillars should be initiated and uptitrated as tolerated to achieve guideline-directed medical therapy (GDMT). 1

Causes of High Output Cardiac Failure

High output heart failure occurs when cardiac output is elevated but insufficient to meet tissue demands, commonly caused by severe anemia, thyrotoxicosis, arteriovenous fistulas, beriberi (thiamine deficiency), and Paget's disease.

  • Severe Anemia: Hemoglobin <7 g/dL increases cardiac output to maintain oxygen delivery 1
  • Thyrotoxicosis: Excess thyroid hormone increases metabolic rate and cardiac demand 1
  • Arteriovenous Fistulas: Large shunts (dialysis access, traumatic, congenital) reduce systemic vascular resistance 1
  • Beriberi (Thiamine Deficiency): Wet beriberi causes peripheral vasodilation and increased cardiac output 1
  • Paget's Disease: Extensive bone involvement creates arteriovenous shunting 1
  • Pregnancy: Physiologic increase in cardiac output may unmask underlying cardiac dysfunction 1

Differentiating Stable Angina from Acute Coronary Syndrome

Stable angina is predictable, exertional chest pain relieved by rest or nitroglycerin within 5 minutes, while ACS presents with prolonged (>20 minutes), severe chest pain at rest or with minimal exertion, often with associated symptoms.

Stable Angina Characteristics: 1

  • Predictable pattern triggered by exertion, emotional stress, or cold exposure
  • Duration typically 2-5 minutes
  • Relieved by rest or sublingual nitroglycerin within 5 minutes
  • No ECG changes at rest (may show changes during stress testing)
  • Normal cardiac biomarkers

Acute Coronary Syndrome (ACS) Characteristics: 1

  • Prolonged chest pain (>20 minutes) at rest or with minimal exertion
  • New onset severe angina or crescendo pattern (increasing frequency/severity)
  • Associated symptoms: diaphoresis, nausea, dyspnea, radiation to jaw/arm
  • ECG changes: ST elevation, ST depression, T-wave inversion, or new Q waves
  • Elevated cardiac biomarkers (troponin)

Red flags for ACS: Pain lasting >20 minutes, pain at rest, pain waking patient from sleep, associated autonomic symptoms, new ECG changes 1

Differentiating the Different Acute Coronary Syndromes

ACS is classified into three categories based on ECG findings and troponin levels: STEMI (ST elevation with troponin elevation), NSTEMI (no ST elevation but troponin elevation), and unstable angina (no ST elevation, normal troponin).

STEMI (ST-Elevation Myocardial Infarction): 1

  • ST elevation ≥1 mm in two contiguous leads OR new LBBB
  • Elevated troponin (confirms myocardial necrosis)
  • Requires immediate reperfusion therapy (PCI or fibrinolysis)
  • Represents complete coronary occlusion

NSTEMI (Non-ST-Elevation Myocardial Infarction): 1

  • No ST elevation (may have ST depression or T-wave inversion)
  • Elevated troponin (confirms myocardial necrosis)
  • Represents partial coronary occlusion or distal embolization
  • Managed with antiplatelet therapy, anticoagulation, and early invasive strategy

Unstable Angina: 1

  • No ST elevation
  • Normal troponin (no myocardial necrosis)
  • Prolonged or rest angina with ECG changes (ST depression, T-wave inversion)
  • Managed similarly to NSTEMI but lower risk

Key differentiator: Troponin elevation distinguishes MI (STEMI/NSTEMI) from unstable angina; ST elevation distinguishes STEMI from NSTEMI 1

Why Nitrates are Contraindicated in Right Ventricular Infarction

Nitrates are contraindicated in RV infarction because they cause venodilation and reduce preload, which critically compromises RV filling and cardiac output in a preload-dependent right ventricle.

Pathophysiology: 1

  • RV infarction (usually with inferior STEMI) causes RV systolic dysfunction
  • The failing RV becomes highly preload-dependent to maintain cardiac output
  • Adequate RV filling pressure is essential to maintain LV preload via the pulmonary circulation
  • Nitrates cause systemic venodilation, reducing venous return and RV preload
  • This precipitates severe hypotension and cardiogenic shock

Clinical Recognition: 1

  • Suspect RV infarction with inferior STEMI (ST elevation in II, III, aVF)
  • Confirm with right-sided ECG leads: ST elevation ≥1 mm in V4R
  • Classic triad: hypotension, clear lung fields, elevated JVP
  • Kussmaul's sign (JVP rises with inspiration) may be present

Management: 1

  • Avoid nitrates, diuretics, and other preload-reducing agents
  • Aggressive IV fluid resuscitation (1-2 L normal saline)
  • Maintain AV synchrony (avoid bradycardia)
  • Early reperfusion therapy

The 3 Different Reperfusion Strategies

The three reperfusion strategies for STEMI are: primary PCI (preferred), fibrinolytic therapy (when PCI unavailable), and rescue PCI (after failed fibrinolysis).

1. Primary PCI (Percutaneous Coronary Intervention): 1

  • Preferred strategy when available within appropriate time windows
  • Mechanical opening of occluded artery with balloon angioplasty and stent placement
  • Superior to fibrinolysis: higher patency rates, lower mortality, less bleeding, less reinfarction
  • Indicated for all STEMI patients when timely access available

2. Fibrinolytic Therapy: 1

  • Pharmacologic reperfusion using thrombolytic agents (alteplase, tenecteplase, reteplase)
  • Indicated when primary PCI cannot be performed within 120 minutes of first medical contact
  • Most effective when given within 3 hours of symptom onset (up to 12 hours acceptable)
  • Contraindications: prior intracranial hemorrhage, ischemic stroke within 3 months, active bleeding, suspected aortic dissection

3. Rescue PCI: 1

  • Performed after failed fibrinolysis (persistent chest pain, <50% ST resolution at 60-90 minutes)
  • Also called "facilitated PCI" when planned after fibrinolysis
  • Higher complication rates than primary PCI but necessary for failed reperfusion

Selection depends on: Time from symptom onset, time to PCI capability, contraindications to fibrinolysis, patient risk factors 1

Recommended Time Targets in STEMI Management

Door-to-ECG should be ≤10 minutes; door-to-needle (fibrinolysis) ≤30 minutes; door-to-balloon (primary PCI) ≤90 minutes at PCI-capable hospitals or ≤120 minutes total ischemic time at non-PCI-capable hospitals.

Door-to-ECG Time: 1

  • Target: ≤10 minutes from hospital arrival
  • Critical for rapid STEMI diagnosis and triage
  • Should be performed immediately upon arrival for chest pain patients

Door-to-Needle Time (Fibrinolytic Therapy): 1

  • Target: ≤30 minutes from hospital arrival to fibrinolytic administration
  • Applies when fibrinolysis is the chosen reperfusion strategy
  • Every minute delay increases mortality

Door-to-Balloon Time (Primary PCI): 1

  • PCI-capable hospital: ≤90 minutes from first medical contact to balloon inflation
  • Non-PCI-capable hospital: ≤120 minutes total ischemic time (first medical contact to balloon inflation)
  • If transfer time from non-PCI hospital exceeds these targets, fibrinolysis preferred

First Medical Contact to Device Time: 1

  • Preferred metric: ≤90 minutes regardless of first contact location (EMS or hospital)
  • Emphasizes system-wide coordination

Transfer Decision: If anticipated door-to-balloon time at PCI center exceeds 120 minutes, administer fibrinolysis at presenting hospital 1

The 4 Malignant Arrhythmias and Shockable vs Non-Shockable Rhythms

The four malignant arrhythmias are ventricular fibrillation (VF), pulseless ventricular tachycardia (pVT), pulseless electrical activity (PEA), and asystole; VF and pVT are shockable, while PEA and asystole are non-shockable.

Malignant Arrhythmias (Cardiac Arrest Rhythms): 1

  1. Ventricular Fibrillation (VF): Chaotic, disorganized ventricular electrical activity with no effective cardiac output
  2. Pulseless Ventricular Tachycardia (pVT): Rapid ventricular rhythm without effective cardiac output
  3. Pulseless Electrical Activity (PEA): Organized electrical activity on ECG but no palpable pulse
  4. Asystole: Complete absence of ventricular electrical activity (flat line)

Shockable Rhythms (Defibrillation Indicated): 1

  • Ventricular Fibrillation (VF)
  • Pulseless Ventricular Tachycardia (pVT)
  • Immediate defibrillation is priority treatment
  • Better prognosis than non-shockable rhythms
  • Defibrillation dose: 120-200J biphasic (360J monophasic)

Non-Shockable Rhythms (Defibrillation NOT Indicated): 1

  • Pulseless Electrical Activity (PEA)
  • Asystole
  • Focus on high-quality CPR and identifying/treating reversible causes
  • Worse prognosis than shockable rhythms
  • Treat reversible causes (H's and T's): Hypovolemia, Hypoxia, Hydrogen ion (acidosis), Hypo/hyperkalemia, Hypothermia, Tension pneumothorax, Tamponade, Toxins, Thrombosis (coronary/pulmonary)

Drug of Choice and Dose for Stable vs Unstable SVT

For stable SVT, adenosine 6 mg IV rapid push (followed by 12 mg if needed) is first-line; for unstable SVT with hemodynamic compromise, immediate synchronized cardioversion at 50-100J is indicated.

Stable SVT (Hemodynamically Stable): 1

First-Line: Adenosine

  • Dose: 6 mg IV rapid push followed immediately by 20 mL saline flush
  • If no response after 1-2 minutes: 12 mg IV rapid push
  • If still no response: 12 mg IV rapid push (second dose)
  • Must be given as rapid push (<2 seconds) followed by saline flush
  • Transient asystole expected (warn patient of impending "doom" sensation)
  • Contraindications: asthma/COPD (may cause bronchospasm), second/third-degree AV block

Alternative Agents (if adenosine fails or contraindicated):

  • Diltiazem: 0.25 mg/kg IV over 2 minutes (typically 15-20 mg), may repeat 0.35 mg/kg
  • Metoprolol: 5 mg IV over 2 minutes, repeat every 5 minutes up to 15 mg total
  • Verapamil: 2.5-5 mg IV over 2 minutes, may repeat 5-10 mg

Unstable SVT (Hemodynamically Unstable): 1

  • Immediate synchronized cardioversion is indicated
  • Signs of instability: hypotension, altered mental status, chest pain, acute heart failure
  • Initial energy: 50-100J synchronized
  • Sedate if conscious (unless immediately life-threatening)
  • Increase energy if initial shock fails: 100J → 200J → 300J → 360J

Drug of Choice for Symptomatic Bradycardia

Atropine 0.5 mg IV push (repeat every 3-5 minutes to maximum 3 mg) is the first-line drug for symptomatic bradycardia; if ineffective, transcutaneous pacing or epinephrine/dopamine infusion should be initiated.

First-Line: Atropine 1

  • Dose: 0.5 mg IV push
  • Repeat: Every 3-5 minutes as needed
  • Maximum total dose: 3 mg
  • Increases heart rate by blocking vagal effects on SA and AV nodes
  • Most effective for sinus bradycardia and AV block at the AV node level (Mobitz I)
  • Caution: May worsen ischemia in acute MI by increasing myocardial oxygen demand
  • Avoid: In high-degree AV block (Mobitz II, third-degree) or wide-complex bradycardia (may paradoxically worsen)

Second-Line Options (if atropine ineffective): 1

Transcutaneous Pacing:

  • Preferred for high-degree AV block or atropine-refractory bradycardia
  • Immediate temporary measure while arranging transvenous pacing

Epinephrine Infusion:

  • Dose: 2-10 mcg/min IV infusion
  • Titrate to adequate heart rate and blood pressure

Dopamine Infusion:

  • Dose: 5-20 mcg/kg/min IV infusion
  • Chronotropic effects at higher doses

Symptomatic bradycardia defined as: Heart rate <50 bpm with hypotension, altered mental status, chest pain, acute heart failure, or shock 1

How Heart Murmurs are Graded

Heart murmurs are graded on a scale of 1 to 6 based on intensity: Grade 1 (barely audible), Grade 2 (soft but easily heard), Grade 3 (moderately loud), Grade 4 (loud with palpable thrill), Grade 5 (very loud, heard with stethoscope partially off chest), and Grade 6 (heard without stethoscope).

Levine Grading Scale (1-6): 1

  • Grade 1/6: Barely audible, heard only with special effort in a quiet room
  • Grade 2/6: Soft murmur but easily heard with stethoscope on chest
  • Grade 3/6: Moderately loud murmur, no thrill
  • Grade 4/6: Loud murmur with palpable thrill (vibration felt on chest wall)
  • Grade 5/6: Very loud murmur, heard with stethoscope partially off the chest, thrill present
  • Grade 6/6: Extremely loud murmur, heard with stethoscope entirely off the chest (or without stethoscope), thrill present

Additional Murmur Characteristics to Document: 1

  • Timing: Systolic, diastolic, or continuous
  • Location: Where best heard (aortic, pulmonic, tricuspid, mitral areas)
  • Radiation: Where sound travels (carotids, axilla, back)
  • Quality: Harsh, blowing, rumbling, musical
  • Pitch: High, medium, or low frequency
  • Configuration: Crescendo, decrescendo, crescendo-decrescendo, plateau

Clinical Significance: Grades 4-6 indicate significant hemodynamic abnormality; grades 1-2 may be physiologic 1

How JVP is Measured

JVP is measured by identifying the highest point of internal jugular venous pulsation with the patient at 45 degrees, measuring the vertical distance from the sternal angle (angle of Louis) to this point, and adding 5 cm (the distance from sternal angle to right atrium); normal JVP is ≤8 cm H2O.

Technique: 1

  1. Patient Positioning: Position patient at 45-degree angle (adjust between 30-60 degrees to optimize visualization)

  2. Identify Internal Jugular Vein: Located between the two heads of the sternocleidomastoid muscle, medial to the carotid artery

  3. Distinguish Venous from Arterial Pulsation:

    • Venous: biphasic pulsation, varies with respiration, non-palpable, obliterated by light pressure
    • Arterial: single pulsation, does not vary with respiration, palpable

  4. Measure Vertical Height: Identify the highest point of venous pulsation, measure vertical distance from sternal angle (angle of Louis) to this point

  5. Calculate JVP: Add 5 cm to the measured height (sternal angle is approximately 5 cm above right atrium)

Normal JVP: ≤8 cm H2O (≤3 cm above sternal angle) 1

Elevated JVP Causes: Right heart failure, tricuspid regurgitation, pericardial disease, volume overload, pulmonary hypertension 1

Kussmaul's Sign: Paradoxical rise in JVP with inspiration (seen in constrictive pericarditis, RV infarction, restrictive cardiomyopathy) 1

How Cardiac Tamponade is Diagnosed

Cardiac tamponade is diagnosed clinically by Beck's triad (hypotension, elevated JVP, muffled heart sounds) plus pulsus paradoxus >10 mmHg, confirmed by echocardiography showing pericardial effusion with right atrial/ventricular diastolic collapse.

Clinical Diagnosis: 1

Beck's Triad (Classic but present in only 30% of cases):

  1. Hypotension (decreased cardiac output)
  2. Elevated jugular venous pressure (JVP)
  3. Muffled/distant heart sounds

Additional Clinical Findings:

  • Pulsus paradoxus: Systolic BP drop >10 mmHg with inspiration (exaggerated normal physiology)
  • Tachycardia (compensatory response)
  • Tachypnea and dyspnea
  • Narrow pulse pressure
  • Cool extremities (poor perfusion)

ECG Findings: 1

  • Low voltage QRS complexes (fluid dampens electrical signals)
  • Electrical alternans (beat-to-beat variation in QRS amplitude due to heart swinging in fluid)
  • Sinus tachycardia

Chest X-ray: 1

  • Enlarged cardiac silhouette ("water bottle" heart) if >250 mL fluid
  • May be normal in acute tamponade

Echocardiography (Diagnostic Gold Standard): 1

  • Pericardial effusion (circumferential fluid)
  • Right atrial collapse in diastole (early, sensitive sign)
  • Right ventricular diastolic collapse (more specific sign)
  • Dilated inferior vena cava with <50% inspiratory collapse
  • Exaggerated respiratory variation in mitral/tricuspid inflow velocities

Immediate Treatment: Pericardiocentesis (needle drainage) or surgical pericardial window; IV fluids temporize 1

What Comprises Beck's Triad

Beck's triad consists of three clinical findings in cardiac tamponade: hypotension, elevated jugular venous pressure (JVP), and muffled heart sounds.

Beck's Triad Components: 1

  1. Hypotension: Decreased cardiac output due to impaired ventricular filling from pericardial fluid compression

  2. Elevated Jugular Venous Pressure (JVP): Increased systemic venous pressure from impaired right heart filling

  3. Muffled/Distant Heart Sounds: Pericardial fluid dampens sound transmission from heart to chest wall

Clinical Context: 1

  • Described by Claude Beck in 1935 for acute cardiac tamponade
  • Present in only 30% of tamponade cases (more common in acute than subacute/chronic)
  • More likely with rapid fluid accumulation (trauma, aortic dissection, post-MI rupture)
  • Chronic effusions may not present with complete triad due to compensatory mechanisms

Additional Findings Often Present: 1

  • Pulsus paradoxus (>10 mmHg drop in systolic BP with inspiration)
  • Tachycardia
  • Narrow pulse pressure
  • Cool, clammy extremities

Diagnosis requires high clinical suspicion and echocardiographic confirmation 1

Difference Between Dihydropyridine and Non-Dihydropyridine CCBs

Dihydropyridine CCBs (e.g., amlodipine, nifedipine) are potent peripheral vasodilators with minimal cardiac effects, while non-dihydropyridine CCBs (e.g., diltiazem, verapamil) have significant cardiac effects including heart rate reduction and negative inotropy.

Dihydropyridine CCBs: 1

Mechanism:

  • Selective for vascular smooth muscle L-type calcium channels
  • Minimal effect on cardiac tissue (SA node, AV node, myocardium)

Effects:

  • Potent peripheral arterial vasodilation (reduce afterload)
  • Minimal to no effect on heart rate or AV conduction
  • No negative inotropic effect
  • Reflex tachycardia may occur (especially with short-acting agents)

Examples:

  • Amlodipine (long-acting, once daily)
  • Nifedipine (short-acting causes reflex tachycardia; extended-release preferred)
  • Felodipine, nicardipine, clevidipine

Indications: Hypertension, vasospastic angina, Raynaud's phenomenon 1

Non-Dihydropyridine CCBs: 1

Mechanism:

  • Act on both vascular smooth muscle AND cardiac tissue
  • Significant effects on SA node, AV node, and myocardium

Effects:

  • Moderate peripheral vasodilation
  • Decrease heart rate (negative chronotropy)
  • Slow AV conduction (negative dromotropy)
  • Negative inotropic effect (reduce contractility)

Examples:

  • Diltiazem (preferred for rate control in atrial fibrillation)
  • Verapamil (most potent negative inotrope)

Indications: Hypertension, rate control (atrial fibrillation/flutter), supraventricular tachycardia 1

Contraindications: Heart failure with reduced EF, second/third-degree AV block, sick sinus syndrome, concurrent beta-blocker use (increased risk of bradycardia/heart block) 1

Key Clinical Distinction: Use dihydropyridines for pure vasodilation; use non-dihydropyridines for rate control 1

Criteria for Sinus Rhythm

Sinus rhythm requires: P waves present and upright in leads I, II, aVF; each P wave followed by a QRS complex; consistent PR interval 0.12-0.20 seconds; heart rate 60-100 bpm; and P wave morphology consistent across beats.

Criteria for Normal Sinus Rhythm: 1

  1. P Wave Present Before Each QRS: Every QRS complex must be preceded by a P wave

  2. P Wave Morphology:

    • Upright in leads I, II, aVF (positive in inferior leads indicates atrial depolarization from SA node)
    • Inverted in aVR
    • Consistent morphology across all beats

  3. PR Interval:

    • 0.12-0.20 seconds (3-5 small boxes)
    • Consistent from beat to beat

  4. Heart Rate:

    • 60-100 beats per minute
    • <60 bpm = sinus bradycardia

    • 100 bpm = sinus tachycardia

  5. Regular Rhythm:

    • R-R intervals consistent (slight variation with respiration is normal = sinus arrhythmia)

  6. QRS Complex:

    • Follows each P wave
    • Normal duration <0.12 seconds (narrow complex)

Sinus Arrhythmia: Phasic variation in heart rate with respiration (rate increases with inspiration, decreases with expiration); all other criteria for sinus rhythm met; common in young, healthy individuals 1

PULMONOLOGY

The 4 Types of Respiratory Failure

The four types of respiratory failure are: Type I (hypoxemic, PaO2 <60 mmHg with normal/low PaCO2), Type II (hypercapnic, PaCO2 >50 mmHg), Type III (perioperative atelectasis), and Type IV (shock with inadequate tissue perfusion).

Type I: Hypoxemic Respiratory Failure 1

  • Definition: PaO2 <60 mmHg on room air with normal or low PaCO2
  • Mechanism: V/Q mismatch, shunt, diffusion impairment
  • Causes: Pneumonia, ARDS, pulmonary edema, pulmonary embolism, interstitial lung disease
  • Treatment: Supplemental oxygen, treat underlying cause, may require mechanical ventilation

Type II: Hypercapnic (Ventilatory) Respiratory Failure 1

  • Definition: PaCO2 >50 mmHg (may have concurrent hypoxemia)
  • Mechanism: Alveolar hypoventilation (inadequate minute ventilation)
  • Causes: COPD exacerbation, neuromuscular disease, CNS depression (drugs, stroke), chest wall disorders, severe asthma
  • Treatment: Non-invasive ventilation (BiPAP) or mechanical ventilation, treat underlying cause

Type III: Perioperative (Atelectatic) Respiratory Failure 1

  • Definition: Respiratory failure due to atelectasis in perioperative period
  • Mechanism: Lung collapse from anesthesia, pain limiting deep breathing, immobility
  • Causes: Post-operative state, especially after abdominal or thoracic surgery
  • Treatment: Incentive spirometry, early mobilization, adequate analgesia, CPAP/BiPAP

Type IV: Shock-Related Respiratory Failure 1

  • Definition: Respiratory failure in patients with shock and inadequate tissue perfusion
  • Mechanism: Increased work of breathing in shock states leads to respiratory muscle fatigue
  • Causes: Septic shock, cardiogenic shock, hypovolemic shock
  • Treatment: Mechanical ventilation to reduce work of breathing, treat underlying shock

Criteria for ARDS Diagnosis and Classification

ARDS is diagnosed by the Berlin criteria: acute onset (<1 week), bilateral infiltrates on imaging, PaO2/FiO2 ratio ≤300 mmHg with PEEP ≥5 cm H2O, and respiratory failure not fully explained by cardiac failure or fluid overload; classified as mild (P/F 201-300), moderate (P/F 101-200), or severe (P/F ≤100).

Berlin Definition of ARDS (2012): 1

Diagnostic Criteria (All Must Be Present):

  1. Timing: Acute onset within 1 week of known clinical insult or new/worsening respiratory symptoms

  2. Chest Imaging: Bilateral opacities on chest X-ray or CT not fully explained by effusions, lobar/lung collapse, or nodules

  3. Origin of Edema: Respiratory failure not fully explained by cardiac failure or fluid overload

    • Objective assessment (echocardiography) needed if no risk factor present

  4. Oxygenation Impairment: PaO2/FiO2 ratio ≤300 mmHg with PEEP or CPAP ≥5 cm H2O

ARDS Severity Classification (Based on P/F Ratio with PEEP ≥5): 1

  • Mild ARDS: PaO2/FiO2 201-300 mmHg
  • Moderate ARDS: PaO2/FiO2 101-200 mmHg
  • Severe ARDS: PaO2/FiO2 ≤100 mmHg

Common ARDS Risk Factors: 1

  • Direct lung injury: Pneumonia, aspiration, inhalation injury, pulmonary contusion, near-drowning
  • Indirect lung injury: Sepsis, severe trauma, pancreatitis, massive transfusion, drug overdose

How to Compute PF Ratio and Desired FiO2

The PF ratio (PaO2/FiO2) is calculated by dividing arterial PaO2 (mmHg) by FiO2 (expressed as decimal); to compute desired FiO2, use the formula: Desired FiO2 = (Target PaO2 × Current FiO2) / Current PaO2.

PF Ratio Calculation: 1

Formula: PF Ratio = PaO2 / FiO2

Example:

  • Patient on 60% oxygen (FiO2 = 0.60)
  • ABG shows PaO2 = 80 mmHg
  • PF Ratio = 80 / 0.60 = 133 mmHg (indicates moderate ARDS)

Interpretation:

  • Normal: >400 mmHg
  • Mild ARDS: 201-300 mmHg
  • Moderate ARDS: 101-200 mmHg
  • Severe ARDS: ≤100 mmHg

Desired FiO2 Calculation: 1

Formula: Desired FiO2 = (Target PaO2 × Current FiO2) / Current PaO2

Example:

  • Current: FiO2 0.60, PaO2 80 mmHg
  • Target PaO2: 90 mmHg
  • Desired FiO2 = (90 × 0.60) / 80 = 54 / 80 = 0.675 or 67.5%

Clinical Application:

  • Target PaO2 typically 55-80 mmHg (SpO2 88-95%) in ARDS to minimize oxygen toxicity
  • Adjust FiO2 in increments of 5-10%
  • Reassess ABG 30 minutes after FiO2 change
  • Prioritize PEEP optimization over high FiO2 (FiO2 >60% increases risk of oxygen toxicity)

FiO2 Reference Values: 1

  • Room air: 0.21 (21%)
  • Nasal cannula 1-6 L/min: approximately 0.24-0.44
  • Simple face mask: 0.35-0.50
  • Non-rebreather mask: 0.60-0.95
  • Mechanical ventilation: 0.21-1.0 (precisely controlled)

Causes of Exudative vs Transudative Pleural Effusion

Transudative effusions result from altered hydrostatic/oncotic pressures (heart failure, cirrhosis, nephrotic syndrome) with protein-poor fluid, while exudative effusions result from increased capillary permeability or impaired lymphatic drainage (pneumonia, malignancy, pulmonary embolism) with protein-rich fluid.

Transudative Pleural Effusion (Altered Starling Forces): 1

Mechanism:

  • Increased hydrostatic pressure OR decreased oncotic pressure
  • Intact capillary membranes (protein-poor fluid)
  • Normal pleural surfaces

Common Causes:

  • Heart failure (most common cause overall) - increased hydrostatic pressure
  • Cirrhosis with ascites - decreased oncotic pressure, ascitic fluid transudation
  • Nephrotic syndrome - decreased oncotic pressure from hypoalbuminemia
  • Hypoalbuminemia (any cause) - decreased oncotic pressure
  • Peritoneal dialysis - fluid transudation
  • Superior vena cava obstruction - increased hydrostatic pressure
  • Atelectasis - increased negative pleural pressure

Exudative Pleural Effusion (Increased Permeability/Impaired Drainage): 1

Mechanism:

  • Increased capillary permeability (inflammation, infection, malignancy)
  • Impaired lymphatic drainage
  • Damaged pleural surfaces (protein-rich fluid)

Common Causes:

  • Parapneumonic effusion/empyema - bacterial pneumonia with pleural inflammation
  • Malignancy - lung cancer, metastases, mesothelioma, lymphoma
  • Pulmonary embolism - pleural inflammation from infarction
  • Tuberculosis - granulomatous inflammation
  • Viral infections - pleural inflammation
  • Autoimmune diseases - SLE, rheumatoid arthritis (RA pleuritis)
  • Pancreatitis - enzyme-mediated inflammation
  • Esophageal rupture - chemical pleuritis
  • Post-cardiac injury syndrome (Dressler's) - autoimmune inflammation
  • Chylothorax - lymphatic obstruction/injury (thoracic duct)
  • Hemothorax - trauma, malignancy, anticoagulation

Differentiation requires pleural fluid analysis using Light's criteria 1

How to Interpret Pleural Fluid Analysis Using Light's Criteria

Light's criteria classify pleural effusions as exudative if ANY of the following are met: pleural fluid protein/serum protein >0.5, pleural fluid LDH/serum LDH >0.6, or pleural fluid LDH >2/3 upper limit of normal serum LDH; if none are met, the effusion is transudative.

Light's Criteria (Exudate if ≥1 criterion met): 1

  1. Pleural fluid protein / Serum protein ratio >0.5

  2. Pleural fluid LDH / Serum LDH ratio >0.6

  3. Pleural fluid LDH >2/3 upper limit of normal serum LDH

Interpretation:

  • Exudate: ≥1 criterion positive (sensitivity 98%, specificity 80%)
  • Transudate: All 3 criteria negative

Additional Pleural Fluid Tests: 1

Appearance:

  • Clear/straw-colored: transudate or early exudate
  • Turbid/cloudy: infection, high cell count
  • Bloody: malignancy, trauma, pulmonary embolism
  • Milky: chylothorax (triglycerides >110 mg/dL)
  • Purulent: empyema
  • Food particles: esophageal rupture

Cell Count and Differential:

  • Neutrophil predominance (>50%): parapneumonic, pulmonary embolism, pancreatitis
  • Lymphocyte predominance (>50%): tuberculosis, malignancy, lymphoma
  • Eosinophilia (>10%): drug reaction, parasites, asbestos, pneumothorax

Glucose:

  • <60 mg/dL: parapneumonic effusion, empyema, rheumatoid arthritis, tuberculosis, malignancy, esophageal rupture

pH:

  • <7.20: empyema, complicated parapneumonic effusion (requires drainage)
  • <7.30: consider drainage

Microbiology:

  • Gram stain and culture: bacterial infection
  • AFB stain and culture: tuberculosis (low sensitivity, culture takes weeks)
  • Adenosine deaminase (ADA) >40 U/L: suggests tuberculosis

Cytology:

  • Malignant cells: sensitivity 60% (first tap), increases to 80-90% with repeat taps

Amylase:

  • Elevated: pancreatitis, esophageal rupture, malignancy

Triglycerides:

  • 110 mg/dL: chylothorax (lymphatic obstruction)

Clinical Pitfall: Light's criteria may misclassify 20-25% of transudates as exudates (especially in diuretic-treated heart failure patients); if clinical suspicion for transudate is high despite positive Light's criteria, check serum-pleural fluid albumin gradient >1.2 g/dL (suggests transudate) 1

How to Diagnose and Manage Pulmonary Tuberculosis

Pulmonary TB is diagnosed by identifying Mycobacterium tuberculosis in sputum via AFB smear (rapid but low sensitivity) and culture (gold standard, takes 2-8 weeks), or by nucleic acid amplification tests (NAAT); treatment requires 6-9 months of multi-drug therapy with initial intensive phase (2 months of rifampin, isoniazid, pyrazinamide, ethambutol) followed by continuation phase (4-7 months of rifampin and isoniazid).

Diagnosis of Pulmonary TB: 1

Clinical Presentation:

  • Chronic cough >3 weeks (often productive, may be hemoptysis)
  • Fever, night sweats, weight loss
  • Upper lobe infiltrates, cavitation on chest X-ray

Diagnostic Tests:

  1. AFB Smear (Acid-Fast Bacilli):

    • 3 sputum samples (early morning specimens preferred)
    • Rapid results (24 hours)
    • Low sensitivity (50-60% for first smear, 70-80% for 3 smears)
    • Cannot distinguish M. tuberculosis from non-tuberculous mycobacteria

  2. Mycobacterial Culture (Gold Standard):

    • Liquid media (MGIT): 10-14 days
    • Solid media (Lowenstein-Jensen): 3-8 weeks
    • Allows drug susceptibility testing
    • Confirms diagnosis definitively

  3. Nucleic Acid Amplification Test (NAAT/GeneXpert MTB/RIF):

    • Rapid molecular test (2 hours)
    • High sensitivity (90-95%) and specificity (>95%)
    • Detects rifampin resistance
    • Recommended by WHO as initial diagnostic test

  4. Tuberculin Skin Test (TST) or Interferon-Gamma Release Assay (IGRA):

    • Screens for latent TB infection (LTBI)
    • Cannot distinguish active from latent TB
    • Positive in prior BCG vaccination (TST only)

  5. Chest Imaging:

    • Upper lobe infiltrates, cavitation (reactivation TB)
    • Hilar/mediastinal lymphadenopathy (primary TB)
    • Miliary pattern (disseminated TB)

Treatment of Active Pulmonary TB: 1

Standard Regimen (Drug-Susceptible TB):

Intensive Phase (2 months):

  • Rifampin (R): 10 mg/kg/day (max 600 mg)
  • Isoniazid (H): 5 mg/kg/day (max 300 mg) + pyridoxine (vitamin B6) 25-50 mg/day
  • Pyrazinamide (Z): 25 mg/kg/day (max 2000 mg)
  • Ethambutol (E): 15-20 mg/kg/day (max 1600 mg)

Continuation Phase (4 months):

  • Rifampin (R): 10 mg/kg/day
  • Isoniazid (H): 5 mg/kg/day + pyridoxine

Total Duration: 6 months (can extend to 9 months if cavitary disease and positive culture at 2 months)

Monitoring:

  • Baseline: LFTs, CBC, creatinine, visual acuity (ethambutol)
  • Monthly: clinical assessment, adherence, adverse effects
  • Sputum culture at 2 months (should be negative)
  • LFTs if symptomatic or baseline abnormalities

Directly Observed Therapy (DOT): Recommended for all patients to ensure adherence 1

Drug-Resistant TB:

  • MDR-TB (resistant to rifampin + isoniazid): requires 18-24 months of second-line drugs
  • XDR-TB (MDR + fluoroquinolone + injectable resistance): requires individualized regimens

Isolation: Airborne precautions until 3 consecutive negative sputum smears (usually 2-4 weeks of treatment) 1

Classification and Antibiotic Options for Community-Acquired Pneumonia

Community-acquired pneumonia (CAP) is classified by severity into outpatient, inpatient non-ICU, and inpatient ICU categories; outpatient treatment uses amoxicillin or doxycycline (or macrolide if local resistance <25%), inpatient non-ICU uses beta-lactam plus macrolide or respiratory fluoroquinolone, and ICU uses beta-lactam plus macrolide or fluoroquinolone with consideration for anti-MRSA and anti-Pseudomonal coverage if risk factors present.

CAP Severity Classification: 1

Outpatient (Low Risk):

  • No criteria for hospitalization
  • CURB-65 score 0-1 or PSI class I-II

Inpatient Non-ICU (Moderate Risk):

  • CURB-65 score ≥2 or PSI class III-IV
  • Requires hospitalization but not ICU

Inpatient ICU (Severe/High Risk):

  • Meets ≥1 major criterion OR ≥3 minor criteria for severe CAP
  • Major criteria: Septic shock requiring vasopressors, respiratory failure requiring mechanical ventilation
  • Minor criteria: RR ≥30, PaO2/FiO2 ≤250, multilobar infiltrates, confusion, uremia (BUN ≥20), leukopenia (WBC <4000), thrombocytopenia (platelets <100,000), hypothermia (temp <36°C), hypotension requiring aggressive fluid resuscitation

Antibiotic Options by Severity: 1

Outpatient (Previously Healthy, No Antibiotic Use in Past 3 Months):

First-Line:

  • Amoxicillin 1 g PO TID for 5-7 days
  • Doxycycline 100 mg PO BID for 5-7 days

Alternative (if local pneumococcal macrolide resistance <25%):

  • Azithromycin 500 mg PO day 1, then 250 mg daily days 2-5
  • Clarithromycin 500 mg PO BID for 5-7 days

Outpatient (Comorbidities or Recent Antibiotic Use):

  • Amoxicillin-clavulanate 875/125 mg PO BID PLUS macrolide
  • Cephalosporin (cefpodoxime, cefuroxime) PLUS macrolide
  • Respiratory fluoroquinolone alone: levofloxacin 750 mg daily or moxifloxacin 400 mg daily

Inpatient Non-ICU:

Preferred:

  • Beta-lactam (ceftriaxone 1-2 g IV daily, cefotaxime 1-2 g IV q8h, or ampicillin-sulbactam 1.5-3 g IV q6h) PLUS macrolide (azithromycin 500 mg IV/PO daily)

Alternative:

  • Respiratory fluoroquinolone alone: levofloxacin 750 mg IV/PO daily or moxifloxacin 400 mg IV/PO daily

Inpatient ICU:

Standard Severe CAP:

  • Beta-lactam (ceftriaxone 2 g IV daily or cefotaxime 2 g IV q8h) PLUS either:
    • Azithromycin 500 mg IV daily, OR
    • Respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily)

If Risk Factors for Pseudomonas (structural lung disease, recent hospitalization, recent broad-spectrum antibiotics):

  • Anti-pseudomonal beta-lactam (piperacillin-tazobactam 4.5 g IV q6h, cefepime 2 g IV q8h, imipenem 500 mg IV q6h, or meropenem 1 g IV q8h) PLUS either:
    • Ciprofloxacin 400 mg IV q8h, OR
    • Levofloxacin 750 mg IV daily PLUS azithromycin 500 mg IV daily

If Risk Factors for MRSA (prior MRSA infection, recent hospitalization, IV drug use):

  • ADD vancomycin 15-20 mg/kg IV q8-12h (target trough 15-20 mcg/mL) OR linezolid 600 mg IV q12h

Duration: 5-7 days for most patients (longer if slow clinical response, complications, or extrapulmonary infection) 1

Most Common Cause of Community-Acquired Pneumonia

Streptococcus pneumoniae (pneumococcus) is the most common bacterial cause of community-acquired pneumonia across all age groups and severity levels, accounting for approximately 30-50% of cases requiring hospitalization.

Streptococcus pneumoniae (Pneumococcus): 1

  • Most common bacterial pathogen in CAP
  • Gram-positive diplococci
  • Accounts for 30-50% of hospitalized CAP cases
  • Classic presentation: abrupt onset, high fever, productive cough with rust-colored sputum, pleuritic chest pain
  • Chest X-ray: lobar consolidation (classic)
  • Risk factors: age >65, chronic lung disease, immunosuppression, asplenia, alcoholism
  • Complications: bacteremia, empyema, meningitis
  • Treatment: beta-lactams (penicillin, amoxicillin, ceftriaxone) remain effective despite increasing resistance

Other Common CAP Pathogens: 1

Atypical Pathogens (20-40% of cases):

  • Mycoplasma pneumoniae: young adults, gradual onset, dry cough, extrapulmonary manifestations
  • Chlamydophila pneumoniae: similar to Mycoplasma, hoarseness common
  • Legionella pneumophila: severe CAP, hyponatremia, diarrhea, confusion, exposure to water sources

Viral Pathogens (10-30% of cases):

  • Influenza: seasonal, rapid onset, myalgias
  • SARS-CoV-2 (COVID-19): pandemic pathogen
  • Respiratory syncytial virus (RSV): elderly, immunocompromised

Other Bacterial Pathogens:

  • Haemophilus influenzae: COPD patients, smokers
  • Staphylococcus aureus: post-influenza, IV drug users, severe necrotizing pneumonia
  • Moraxella catarrhalis: COPD patients

Aspiration Pneumonia:

  • Anaerobes: altered consciousness, dysphagia, poor dentition

Empiric therapy must cover S. pneumoniae and atypical pathogens 1

Diagnosis and Empiric Antibiotics for Hospital-Acquired Pneumonia

Hospital-acquired pneumonia (HAP) is diagnosed by new lung infiltrate on imaging plus ≥2 clinical criteria (fever, leukocytosis, purulent sputum) occurring ≥48 hours after hospital admission; empiric antibiotics should cover Pseudomonas and MRSA with regimens like piperacillin-tazobactam or cefepime PLUS vancomycin or linezolid, de-escalated based on cultures.

Definition of HAP: 1

  • Pneumonia occurring ≥48 hours after hospital admission
  • Excludes pneumonia incubating at time of admission
  • Distinct from ventilator-associated pneumonia (VAP)

Diagnostic Criteria (All Required): 1

  1. New or progressive lung infiltrate on chest imaging (X-ray or CT)

  2. Plus ≥2 of the following clinical criteria:

    • Fever >38°C or hypothermia <36°C
    • Leukocytosis (WBC >10,000) or leukopenia (WBC <4,000)
    • Purulent respiratory secretions
    • Decline in oxygenation (increased O2 requirement, decreased PaO2/FiO2)

Diagnostic Testing: 1

  • Lower respiratory tract sampling: Sputum culture, endotracheal aspirate, bronchoalveolar lavage (BAL)
  • Blood cultures: Before antibiotic initiation
  • Procalcitonin: May help guide antibiotic duration
  • Legionella and pneumococcal urinary antigens: If epidemiologically indicated

Risk Stratification for Multidrug-Resistant (MDR) Pathogens: 1

High Risk for MDR Pathogens (Pseudomonas, MRSA, ESBL):

  • Prior IV antibiotics within 90 days
  • Hospitalization ≥5 days
  • High local prevalence of MDR pathogens
  • Immunosuppression
  • Septic shock at presentation

Empiric Antibiotic Regimens: 1

Standard HAP (No Risk Factors for MDR):

  • Piperacillin-tazobactam 4.5 g IV q6h, OR
  • Cefepime 2 g IV q8h, OR
  • Levofloxacin 750 mg IV daily, OR
  • Imipenem 500 mg IV q6h OR meropenem 1 g IV q8h

HAP with Risk Factors for MDR Pathogens:

Anti-Pseudomonal Coverage (Choose ONE):

  • Piperacillin-tazobactam 4.5 g IV q6h (extended infusion preferred)
  • Cefepime 2 g IV q8h
  • Ceftazidime 2 g IV q8h
  • Imipenem 500 mg IV q6h OR meropenem 1 g IV q8h
  • Aztreonam 2 g IV q8h (if beta-lactam allergy)

PLUS Anti-MRSA Coverage (Choose ONE):

  • Vancomycin 15-20 mg/kg IV q8-12h (target trough 15-20 mcg/mL)
  • Linezolid 600 mg IV q12h

Consider Adding Second Anti-Pseudomonal Agent if:

  • Septic shock
  • High risk of mortality
  • High local Pseudomonas resistance rates
  • Options: Add aminoglycoside (gentamicin, tobramycin, amikacin) OR fluoroquinolone (ciprofloxacin, levofloxacin)

De-escalation: 1

  • Narrow antibiotics based on culture results and susceptibilities within 48-72 hours
  • Discontinue MRSA coverage if MRSA-negative cultures and low clinical suspicion
  • Shorten duration if good clinical response

Duration: 7 days for most patients (may extend to 14 days if slow response, complications, or non-fermenting gram-negative bacilli) 1

Definition of Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is pneumonia that develops ≥48 hours after endotracheal intubation and mechanical ventilation, diagnosed by new or progressive lung infiltrate plus ≥2 clinical criteria (fever, leukocytosis, purulent secretions, worsening oxygenation).

Definition: 1

  • Pneumonia occurring ≥48 hours after endotracheal intubation and initiation of mechanical ventilation
  • Excludes pneumonia present at time of intubation
  • Subset of hospital-acquired pneumonia (HAP)

Diagnostic Criteria (Similar to HAP): 1

  1. New or progressive lung infiltrate on chest imaging

  2. Plus ≥2 clinical criteria:

    • Fever >38°C or hypothermia <36°C
    • Leukocytosis (WBC >10,000) or leukopenia (WBC <4,000)
    • Purulent endotracheal secretions
    • Worsening oxygenation (increased FiO2 or PEEP requirements)

Risk Factors for VAP: 1

  • Duration of mechanical ventilation (risk increases 1-3% per day)
  • Supine positioning (vs. semi-recumbent 30-45 degrees)
  • Reintubation
  • Witnessed aspiration
  • Gastric overdistension
  • Transport out of ICU
  • Prior antibiotic exposure
  • Immunosuppression
  • ARDS
  • Neuromuscular blockade

Common VAP Pathogens: 1

  • Early VAP (<5 days): Similar to CAP pathogens (S. pneumoniae, H. influenzae, MSSA)
  • Late VAP (≥5 days): MDR pathogens (Pseudomonas aeruginosa, MRSA, Acinetobacter, ESBL-producing Enterobacteriaceae)

Prevention Strategies (VAP Bundle): 1

  • Elevate head of bed 30-45 degrees
  • Daily sedation vacation and spontaneous breathing trials
  • Oral care with chlorhexidine
  • Subglottic suctioning (if available)
  • Avoid unnecessary reintubation
  • Stress ulcer prophylaxis only when indicated
  • DVT prophylaxis

Empiric Treatment: Same as HAP with MDR risk factors (anti-pseudomonal beta-lactam PLUS anti-MRSA coverage) 1

Lung Protective Strategies in Intubated Patients

Lung protective ventilation strategies include: low tidal volume (6 mL/kg ideal body weight), plateau pressure <30 cm H2O, adequate PEEP (typically 5-15 cm H2O), permissive hypercapnia (pH ≥7.20), FiO2 titrated to SpO2 88-95%, and prone positioning for severe ARDS (P/F <150).

Low Tidal Volume Ventilation: 1

  • Target: 6 mL/kg ideal body weight (IBW), NOT actual body weight
  • Rationale: Reduces volutrauma and mortality in ARDS
  • IBW calculation:
    • Males: 50 + 2.3 × (height in inches - 60)
    • Females: 45.5 + 2.3 × (height in inches - 60)
  • Never exceed: 8 mL/kg IBW

Plateau Pressure Limitation: 1

  • Target: Plateau pressure (Pplat) <30 cm H2O
  • Measured during inspiratory hold (reflects alveolar pressure)
  • Reduces barotrauma and ventilator-induced lung injury (VILI)
  • If Pplat >30, further reduce tidal volume (minimum 4 mL/kg IBW)

Adequate PEEP (Positive End-Expiratory Pressure): 1

  • Target: 5-15 cm H2O (individualized based on oxygenation and compliance)
  • Prevents alveolar collapse (atelectrauma)
  • Improves oxygenation by recruiting collapsed alveoli
  • Use PEEP/FiO2 tables to optimize balance
  • Higher PEEP (10-15) for moderate-severe ARDS

Permissive Hypercapnia: 1

  • Accept: PaCO2 >45 mmHg and pH ≥7.20
  • Allows lower tidal volumes without excessive respiratory rate
  • Contraindications: increased intracranial pressure, severe pulmonary hypertension

Oxygenation Targets: 1

  • Target SpO2: 88-95% (avoid hyperoxia)
  • Target PaO2: 55-80 mmHg
  • Minimize FiO2 to reduce oxygen toxicity (goal FiO2 <0.60)

Driving Pressure Minimization: 1

  • Driving pressure = Plateau pressure - PEEP
  • Target: <15 cm H2O
  • Strong predictor of mortality (lower is better)

Prone Positioning: 1

  • Indication: Severe ARDS (PaO2/FiO2 <150) despite optimization
  • Duration: 16-18 hours per day
  • Improves oxygenation and reduces mortality
  • Requires experienced team

Neuromuscular Blockade: 1

  • Consider for severe ARDS (P/F <150) with ventilator dyssynchrony
  • Duration: 48 hours maximum (continuous infusion)
  • Improves oxygenation, may reduce mortality
  • Monitor with train-of-four

Fluid Management: 1

  • Conservative fluid strategy after initial resuscitation
  • Target neutral to negative fluid balance
  • Reduces pulmonary edema and ventilator days

Avoid: High tidal volumes, high plateau pressures, excessive FiO2, prolonged deep sedation, routine neuromuscular blockade 1

FEV1, FVC, and FEV1/FVC in Obstructive vs Restrictive Lung Disease

In obstructive lung disease, FEV1 is reduced, FVC is normal or reduced, and FEV1/FVC ratio is <0.70; in restrictive lung disease, both FEV1 and FVC are proportionally reduced, but FEV1/FVC ratio is normal (≥0.70) or increased.

Normal Spirometry Values: 1

  • FEV1 (Forced Expiratory Volume in 1 second): >80% predicted
  • FVC (Forced Vital Capacity): >80% predicted
  • FEV1/FVC ratio: ≥0.70 (or ≥70%)

Obstructive Lung Disease: 1

Pattern:

  • FEV1: Reduced (<80% predicted)
  • FVC: Normal or reduced (less than FEV1 reduction)
  • FEV1/FVC ratio: <0.70 (diagnostic hallmark)

Pathophysiology:

  • Airflow limitation due to airway narrowing or loss of elastic recoil
  • Air trapping and prolonged expiration

Examples:

  • COPD (chronic bronchitis, emphysema)
  • Asthma
  • Bronchiectasis
  • Cystic fibrosis
  • Bronchiolitis obliterans

Severity Classification (Based on FEV1 % predicted):

  • Mild: FEV1 ≥80%
  • Moderate: FEV1 50-79%
  • Severe: FEV1 30-49%
  • Very severe: FEV1 <30%

Restrictive Lung Disease: 1

Pattern:

  • FEV1: Reduced (<80% predicted)
  • FVC: Reduced (<80% predicted) - proportionally more than FEV1
  • FEV1/FVC ratio: ≥0.70 or increased (normal or supranormal)

Pathophysiology:

  • Reduced lung volumes due to:
    • Intrinsic lung disease (parenchymal restriction)
    • Extrinsic factors (chest wall, pleural, neuromuscular)

Examples:

Intrinsic (Parenchymal):

  • Interstitial lung disease (IPF, sarcoidosis, hypersensitivity pneumonitis)
  • Pneumoconiosis (asbestosis, silicosis)
  • Drug-induced lung disease (amiodarone, bleomycin, methotrexate)

Extrinsic:

  • Chest wall disorders: Kyphoscoliosis, obesity
  • Pleural disease: Pleural effusion, pleural thickening
  • Neuromuscular disease: Myasthenia gravis, ALS, muscular dystrophy
  • Diaphragm weakness

Confirmation: Total lung capacity (TLC) <80% predicted on full pulmonary function testing 1

Mixed Pattern: Both FEV1/FVC <0.70 AND reduced TLC (e.g., COPD with pulmonary fibrosis) 1

INFECTIOUS DISEASES

The 1-Hour Bundle of Care in Septic Shock

The 1-hour sepsis bundle includes: measure lactate, obtain blood cultures before antibiotics, administer broad-spectrum antibiotics, begin rapid fluid resuscitation with 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L, and apply vasopressors if hypotension persists after initial fluid resuscitation.

Surviving Sepsis Campaign 1-Hour Bundle (All Within 1 Hour of Recognition): 1

  1. Measure Lactate Level

    • Repeat if initial lactate ≥2 mmol/L
    • Lactate clearance guides resuscitation

  2. Obtain Blood Cultures Before Antibiotics

    • At least 2 sets (aerobic and anaerobic) from different sites
    • Do NOT delay antibiotics >45 minutes for cultures

  3. Administer Broad-Spectrum Antibiotics

    • Within 1 hour of sepsis recognition
    • Empiric coverage based on suspected source
    • Each hour delay increases mortality by 7.6%

  4. Begin Rapid Fluid Resuscitation

    • 30 mL/kg crystalloid (normal saline or lactated Ringer's) for:
      • Hypotension (SBP <90 mmHg or MAP <65 mmHg), OR
      • Lactate ≥4 mmol/L
    • Administer within first 3 hours
    • Reassess volume status frequently

  5. Apply Vasopressors if Hypotension Persists

    • If MAP <65 mmHg despite initial fluid resuscitation
    • Norepinephrine is first-line vasopressor
    • Target MAP ≥65 mmHg

Additional Early Management (Within 6 Hours): 1

  • Remeasure lactate if initial lactate elevated (goal: normalize)
  • Reassess volume status and tissue perfusion
  • Document reassessment of volume status
  • Consider invasive monitoring if not responding

Rationale: Early recognition and aggressive treatment within 1 hour significantly reduces mortality in sepsis and septic shock 1

What Comprises qSOFA

qSOFA (quick Sequential Organ Failure Assessment) consists of three criteria: respiratory rate ≥22/min, altered mentation (GCS <15), and systolic blood pressure ≤100 mmHg; a score ≥2 suggests higher risk of poor outcomes and prompts further evaluation for sepsis.

qSOFA Criteria (1 point each): 1

  1. Respiratory Rate ≥22 breaths per minute

  2. Altered Mentation (Glasgow Coma Scale <15)

  3. Systolic Blood Pressure ≤100 mmHg

Interpretation: 1

  • qSOFA ≥2: Suggests higher risk of death or prolonged ICU stay
  • Prompts clinician to further investigate for organ dysfunction and sepsis
  • Should trigger full SOFA score calculation and sepsis workup

Clinical Application: 1

  • Bedside screening tool for suspected infection outside ICU
  • Does NOT define sepsis (requires SOFA score ≥2)
  • More specific but less sensitive than SIRS criteria
  • Identifies patients who need closer monitoring and aggressive management

Limitations: 1

  • Not a diagnostic tool for sepsis
  • Less sensitive than SOFA score
  • Should not replace clinical judgment
  • Not validated in all patient populations (e.g., immunocompromised)

qSOFA vs SIRS: 1

  • qSOFA is more specific for adverse outcomes
  • SIRS is more sensitive but less specific
  • qSOFA preferred for rapid bedside assessment

Latest Definition of Sepsis and Septic Shock

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection (SOFA score increase ≥2 points); septic shock is sepsis with persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg AND lactate >2 mmol/L despite adequate fluid resuscitation.

Sepsis-3 Definitions (2016): 1

Sepsis:

  • Life-threatening organ dysfunction caused by a dysregulated host response to infection
  • Operationalized as: Suspected or documented infection PLUS acute increase in SOFA score ≥2 points
  • Baseline SOFA assumed to be zero in patients without known organ dysfunction
  • Associated with in-hospital mortality >10%

SOFA Score Components (0-4 points each, max 24): 1

  • Respiration: PaO2/FiO2 ratio
  • Coagulation: Platelet count
  • Liver: Bilirubin level
  • Cardiovascular: MAP or vasopressor requirement
  • CNS: Glasgow Coma Scale
  • Renal: Creatinine or urine output

Septic Shock:

  • Subset of sepsis with profound circulatory, cellular, and metabolic abnormalities
  • Clinical criteria (BOTH required):
    1. Persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg, AND
    2. Lactate >2 mmol/L (>18 mg/dL)
  • Despite adequate fluid resuscitation (typically 30 mL/kg crystalloid)
  • Associated with in-hospital mortality >40%

Key Changes from Previous Definitions: 1

  • Removed SIRS criteria (too sensitive, not specific)
  • Emphasizes organ dysfunction (SOFA score) rather than inflammation
  • Septic shock requires both vasopressor need AND hyperlactatemia
  • Recognizes sepsis as organ dysfunction, not just infection + SIRS

Clinical Application: 1

  • Suspected infection + qSOFA ≥2 → Calculate full SOFA score
  • SOFA increase ≥2 → Diagnose sepsis, initiate sepsis bundle
  • Persistent hypotension + lactate >2 despite fluids → Diagnose septic shock, escalate care

Difference Between Prophylactic, Empiric, and Definitive Antibiotics

Prophylactic antibiotics prevent infection in high-risk situations (e.g., surgical prophylaxis, endocarditis prophylaxis); empiric antibiotics treat suspected infection before culture results using broad-spectrum coverage; definitive antibiotics are narrow-spectrum therapy targeted to identified pathogen based on culture and susceptibility results.

Prophylactic Antibiotics: 1

Definition:

  • Antibiotics given to prevent infection in patients at high risk
  • Administered before infection occurs

Examples:

  • Surgical prophylaxis: Single dose pre-operatively (e.g., cefazolin before clean surgery)
  • Endocarditis prophylaxis: Before dental procedures in high-risk cardiac patients (e.g., amoxicillin)
  • PCP prophylaxis: Trimethoprim-sulfamethoxazole in HIV patients with CD4 <200
  • MAC prophylaxis: Azithromycin in HIV patients with CD4 <50
  • Meningococcal prophylaxis: Rifampin for close contacts of meningitis case
  • Post-exposure prophylaxis: After HIV exposure, rabies exposure

Key Principle: Short duration, specific indication, prevent infection in defined high-risk scenario 1

Empiric Antibiotics: 1

Definition:

  • Antibiotics given to treat suspected infection before pathogen identification
  • Broad-spectrum coverage based on:
    • Most likely pathogens
    • Local resistance patterns
    • Patient risk factors
    • Infection source

Examples:

  • Sepsis: Broad-spectrum (e.g., piperacillin-tazobactam + vancomycin) before culture results
  • CAP: Beta-lactam + macrolide before sputum culture
  • Meningitis: Ceftriaxone + vancomycin + ampicillin (if >50 years) before CSF culture
  • Febrile neutropenia: Anti-pseudomonal beta-lactam before blood culture results

Key Principle: Start immediately (within 1 hour for sepsis), broad coverage, de-escalate when cultures available 1

Definitive (Targeted) Antibiotics: 1

Definition:

  • Antibiotics tailored to identified pathogen based on culture and susceptibility testing
  • Narrow-spectrum therapy targeting specific organism
  • De-escalation from empiric therapy

Examples:

  • MSSA bacteremia: Switch from vancomycin to nafcillin/cefazolin
  • E. coli UTI: Switch from piperacillin-tazobactam to ceftriaxone (if susceptible)
  • Streptococcus pneumoniae pneumonia: Switch from broad-spectrum to penicillin (if susceptible)
  • Pseudomonas pneumonia: Continue anti-pseudomonal beta-lactam, discontinue MRSA coverage

Key Principle: Narrow spectrum, pathogen-directed, optimize efficacy and minimize resistance 1

Clinical Workflow: Prophylactic (prevent) → Empiric (treat suspected) → Definitive (treat confirmed) 1

Antibiotics with Anti-Pseudomonal Coverage, ESBL Drug of Choice, and MRSA Drug of Choice

Anti-pseudomonal antibiotics include piperacillin-tazobactam, cefepime, ceftazidime, carbapenems (meropenem, imipenem), aztreonam, and fluoroquinolones (ciprofloxacin, levofloxacin); carbapenems (meropenem, imipenem, ertapenem) are first-line for ESBL-producing organisms; vancomycin or linezolid are first-line for MRSA.

Anti-Pseudomonal Antibiotics: 1

Beta-Lactams:

  • Piperacillin-tazobactam 4.5 g IV q6h (extended infusion preferred)
  • Cefepime 2 g IV q8h
  • Ceftazidime 2 g IV q8h (less gram-positive coverage than cefepime)
  • Ceftazidime-avibactam 2.5 g IV q8h (for resistant Pseudomonas, including some carbapenem-resistant)
  • Ceftolozane-tazobactam 1.5 g IV q8h (excellent anti-pseudomonal activity)

Carbapenems:

  • Meropenem 1 g IV q8h (or 2 g IV q8h for severe infections)
  • Imipenem-cilastatin 500 mg IV q6h
  • Doripenem 500 mg IV q8h
  • Note: Ertapenem has NO anti-pseudomonal activity

Monobactams:

  • Aztreonam 2 g IV q8h (beta-lactam alternative for beta-lactam allergic patients)

Fluoroquinolones:

  • Ciprofloxacin 400 mg IV q8h (best anti-pseudomonal fluoroquinolone)
  • Levofloxacin 750 mg IV daily (less active than ciprofloxacin against Pseudomonas)

Aminoglycosides:

  • Gentamicin 5-7 mg/kg IV daily
  • Tobramycin 5-7 mg/kg IV daily
  • Amikacin 15-20 mg/kg IV daily
  • Note: Used as adjunctive therapy, not monotherapy

Polymyxins (Last Resort):

  • Colistin (polymyxin E) for multidrug-resistant Pseudomonas

Drug of Choice for ESBL (Extended-Spectrum Beta-Lactamase) Producers: 1

First-Line:

  • Carbapenems (preferred):
    • Meropenem 1 g IV q8h
    • Imipenem-cilastatin 500 mg IV q6h
    • Ertapenem 1 g IV daily (if not Pseudomonas)
    • Doripenem 500 mg IV q8h

Alternatives (if carbapenem-sparing desired):

  • Cefepime (may be effective for some ESBL strains with low MIC)
  • Piperacillin-tazobactam (controversial, higher failure rates than carbapenems)
  • Ceftazidime-avibactam 2.5 g IV q8h
  • Ceftolozane-tazobactam 1.5 g IV q8h

Oral Options (for uncomplicated UTI only):

  • Fosfomycin 3 g PO single dose
  • Nitrofurantoin 100 mg PO BID (if susceptible, not for pyelonephritis)

Drug of Choice for MRSA (Methicillin-Resistant Staphylococcus aureus): 1

First-Line (Serious Infections):

  • Vancomycin 15-20 mg/kg IV q8-12h
    • Target trough 15-20 mcg/mL for bacteremia, endocarditis, meningitis, pneumonia
    • Target trough 10-15 mcg/mL for skin/soft tissue infections
    • Monitor renal function and trough levels

Alternative First-Line:

  • Daptomycin 6-10 mg/kg IV daily
    • Preferred for bacteremia, endocarditis (dose 8-10 mg/kg)
    • NOT for pneumonia (inactivated by surfactant)
    • Monitor CPK weekly (risk of myopathy)

Other Options:

  • Linezolid 600 mg IV/PO q12h

    • Excellent for pneumonia (100% lung penetration)
    • Oral bioavailability 100%
    • Avoid prolonged use (>14 days) due to myelosuppression, neuropathy

  • Ceftaroline 600 mg IV q12h

    • Fifth-generation cephalosporin with MRSA activity
    • Good for skin/soft tissue infections and pneumonia

  • Telavancin 10 mg/kg IV daily

    • For complicated skin infections and hospital-acquired pneumonia

Oral Options (for uncomplicated skin infections):

  • Trimethoprim-sulfamethoxazole 1-2 DS tablets PO BID
  • Doxycycline 100 mg PO BID
  • Clindamycin 300-450 mg PO TID (if susceptible, check D-test)
  • Linezolid 600 mg PO BID

Drug of Choice for VRSA

Linezolid 600 mg IV/PO q12h is the first-line drug for VRSA (vancomycin-resistant Staphylococcus aureus); alternatives include daptomycin (8-10 mg/kg IV daily), quinupristin-dalfopristin, or tigecycline, with treatment guided by susceptibility testing and infectious disease consultation.

VRSA (Vancomycin-Resistant Staphylococcus aureus): 1

  • Extremely rare (MIC >16 mcg/mL)
  • Distinct from VISA (vancomycin-intermediate, MIC 4-8 mcg/mL)
  • Requires infectious disease consultation
  • Treatment based on susceptibility testing

First-Line Options: 1

Linezolid:

  • Dose: 600 mg IV or PO q12h
  • Excellent tissue penetration
  • 100% oral bioavailability
  • Effective for pneumonia, bacteremia, skin/soft tissue infections
  • Limitations: Myelosuppression (thrombocytopenia, anemia), peripheral neuropathy, optic neuropathy with prolonged use (>14 days), serotonin syndrome risk with SSRIs

Daptomycin:

  • Dose: 8-10 mg/kg IV daily (higher doses for serious infections)
  • Preferred for bacteremia, endocarditis
  • NOT for pneumonia (inactivated by pulmonary surfactant)
  • Monitor CPK weekly (myopathy risk)

Alternative Options: 1

Quinupristin-Dalfopristin (Synercid):

  • Dose: 7.5 mg/kg IV q8h
  • Streptogramin combination
  • Significant side effects: myalgias, arthralgias, phlebitis
  • Requires central line

Tigecycline:

  • Dose: 100 mg IV loading, then 50 mg IV q12h
  • Glycylcycline (tetracycline derivative)
  • Broad-spectrum including VRSA
  • Black box warning: Increased mortality in clinical trials
  • Reserved for situations with no alternatives

Ceftaroline:

  • Dose: 600 mg IV q12h
  • Fifth-generation cephalosporin
  • May have activity against some VRSA strains (check susceptibilities)

Telavancin:

  • Dose: 10 mg/kg IV daily
  • Lipoglycopeptide
  • May retain activity against some vancomycin-resistant strains

Combination Therapy: 1

  • Often used for serious VRSA infections
  • Examples: Daptomycin + ceftaroline, linezolid + rifampin
  • Guided by infectious disease consultation

Key Principles: 1

  • Always obtain susceptibility testing
  • Infectious disease consultation mandatory
  • Consider combination therapy for serious infections
  • Monitor for drug toxicities closely
  • Source control essential (remove infected devices, drain abscesses)

Difference Between Ertapenem vs Meropenem/Imipenem

Ertapenem lacks anti-pseudomonal and anti-Acinetobacter activity and has a longer half-life allowing once-daily dosing, while meropenem and imipenem have broad-spectrum coverage including Pseudomonas aeruginosa and Acinetobacter, require more frequent dosing, but have lower seizure risk (meropenem) compared to imipenem.

Ertapenem: 1

Spectrum:

  • Broad gram-positive, gram-negative, and anaerobic coverage
  • NO activity against:
    • Pseudomonas aeruginosa (major limitation)
    • Acinetobacter species
    • Enterococcus species
  • Excellent ESBL coverage

Dosing:

  • 1 g IV/IM once daily (long half-life ~4 hours)
  • Convenient for outpatient parenteral antibiotic therapy (OPAT)

Indications:

  • Community-acquired intra-abdominal infections
  • Complicated UTI/pyelonephritis (non-Pseudomonal)
  • Diabetic foot infections
  • Community-acquired pneumonia
  • ESBL infections (outpatient setting)

Advantages:

  • Once-daily dosing
  • Lower seizure risk than imipenem
  • Suitable for outpatient IV therapy

Meropenem: 1

Spectrum:

  • Broad gram-positive, gram-negative, and anaerobic coverage
  • Includes activity against:
    • Pseudomonas aeruginosa
    • Acinetobacter species
    • Most Enterobacteriaceae (including ESBL)
  • Less active against Enterococcus than imipenem

Dosing:

  • 1 g IV q8h (standard)
  • 2 g IV q8h (severe infections, meningitis, Pseudomonas)
  • Shorter half-life (~1 hour) requires more frequent dosing

Indications:

  • Hospital-acquired pneumonia (including VAP)
  • Severe sepsis/septic shock
  • Febrile neutropenia
  • Complicated intra-abdominal infections (nosocomial)
  • Meningitis (excellent CSF penetration)
  • Pseudomonal infections

Advantages:

  • Lower seizure risk than imipenem (preferred in CNS infections)
  • Excellent CSF penetration
  • Broader spectrum than ertapenem

Imipenem-Cilastatin: 1

Spectrum:

  • Similar to meropenem
  • Includes activity against:
    • Pseudomonas aeruginosa
    • Acinetobacter species
    • Enterococcus (better than meropenem)
    • Most Enterobacteriaceae (including ESBL)

Dosing:

  • 500 mg IV q6h (standard)
  • 1 g IV q6-8h (severe infections)
  • Requires cilastatin (inhibits renal metabolism)

Indications:

  • Similar to meropenem
  • Slightly better Enterococcus coverage

Disadvantages:

  • Higher seizure risk than meropenem (especially with renal impairment, CNS disorders)
  • Not preferred for meningitis
  • More frequent dosing

Key Differences Summary: 1

Feature Ertapenem Meropenem Imipenem
Pseudomonas coverage NO YES YES
Acinetobacter coverage NO YES YES
Dosing frequency Once daily q8h q6h
Seizure risk Low Low Higher
CNS penetration Poor Excellent Moderate
Enterococcus coverage NO Limited Better
OPAT suitability Excellent Poor Poor

Clinical Decision-Making: 1

  • Use ertapenem for community-acquired infections without Pseudomonas risk (ESBL UTI, diabetic foot)
  • Use meropenem for hospital-acquired infections, Pseudomonas risk, or CNS infections
  • Use imipenem when Enterococcus coverage needed (rare indication)

How to Interpret Culture Results

Culture results should be interpreted by assessing: organism identification (pathogen vs contaminant vs colonizer), colony count (quantitative cultures), susceptibility patterns (MIC values and resistance mechanisms), clinical correlation (symptoms, source, timing), and prior antibiotic exposure; always correlate microbiologic findings with clinical presentation to distinguish infection from colonization.

Key Principles of Culture Interpretation: 1

1. Organism Identification:

True Pathogens (Usually Significant):

  • Staphylococcus aureus (including MRSA)
  • Streptococcus pneumoniae
  • Streptococcus pyogenes (Group A Strep)
  • Neisseria meningitidis
  • Mycobacterium tuberculosis
  • Salmonella, Shigella
  • Candida in blood cultures

Potential Contaminants (Skin Flora):

  • Coagulase-negative staphylococci (e.g., S. epidermidis)
  • Corynebacterium species (diphtheroids)
  • Bacillus species (not B. anthracis)
  • Propionibacterium acnes
  • Viridans group streptococci (in single blood culture)

Context-Dependent (Pathogen vs Colonizer):

  • Enterococcus species
  • Candida species (non-blood cultures)
  • Pseudomonas aeruginosa
  • Enterobacteriaceae (E. coli, Klebsiella)

2. Colony Count (Quantitative Cultures): 1

Urine Cultures:

  • ≥10^5 CFU/mL: Significant bacteriuria (cystitis)
  • ≥10^4 CFU/mL: May be significant in symptomatic patients, catheterized patients
  • ≥10^3 CFU/mL: Significant in suprapubic aspirate
  • <10^3 CFU/mL: Usually contamination or colonization
  • Multiple organisms: Suggests contamination (repeat culture)

Respiratory Cultures:

  • Sputum: >25 PMNs and <10 epithelial cells per low-power field (adequate specimen)
  • BAL: ≥10^4 CFU/mL suggests pneumonia
  • Endotracheal aspirate: ≥10^5 CFU/mL suggests VAP

3. Susceptibility Patterns: 1

Interpret MIC (Minimum Inhibitory Concentration):

  • Susceptible (S): Organism likely to respond to standard dosing
  • Intermediate (I): May respond to higher doses or if drug concentrates at infection site
  • Resistant (R): Unlikely to respond, avoid this antibiotic

Recognize Resistance Patterns:

  • MRSA: Resistant to all beta-lactams (use vancomycin, daptomycin, linezolid)
  • ESBL: Resistant to most cephalosporins and penicillins (use carbapenems)
  • CRE (Carbapenem-Resistant Enterobacteriaceae): Resistant to carbapenems (use ceftazidime-avibactam, meropenem-vaborbactam, colistin)
  • VRE (Vancomycin-Resistant Enterococcus): Resistant to vancomycin (use linezolid, daptomycin)
  • MDR Pseudomonas: Resistant to multiple anti-pseudomonal agents (use ceftolozane-tazobactam, ceftazidime-avibactam, colistin)

4. Clinical Correlation: 1

Distinguish Infection from Colonization:

  • Infection: Organism + clinical signs/symptoms + inflammatory markers
  • Colonization: Organism present without clinical evidence of infection
  • Examples of colonization:
    • MRSA nasal swab in asymptomatic patient
    • Candida in sputum without pneumonia
    • Bacteriuria in asymptomatic patient (except pregnancy)
    • Positive respiratory culture in COPD patient without new symptoms

Timing:

  • Cultures obtained before antibiotics: More reliable
  • Cultures obtained after antibiotics: May be falsely negative or show resistant organisms

Source:

  • Blood cultures: Almost always significant (except contaminants)
  • Sputum cultures: Often colonization (correlate with clinical pneumonia)
  • Wound cultures: May represent colonization (correlate with purulence, inflammation)
  • Urine cultures: Asymptomatic bacteriuria common (treat only if symptomatic or pregnant)

5. Special Considerations: 1

Polymicrobial Cultures:

  • Intra-abdominal infections: Expected (anaerobes + aerobes)
  • Diabetic foot infections: Expected (polymicrobial)
  • Blood cultures: Unusual, suggests contamination or endocarditis

Repeat Cultures:

  • Persistent bacteremia: Suggests endocarditis, undrained abscess, or inadequate therapy
  • Negative cultures after treatment: Confirms clearance

Fungal Cultures:

  • Candida in blood: Always treat (candidemia)
  • Candida in sputum/urine: Often colonization (treat only if symptomatic)

Anaerobic Cultures:

  • Require special transport media
  • Suspect in abscesses, aspiration pneumonia, intra-abdominal infections

Clinical Pitfall: Never treat culture results in isolation; always correlate with clinical presentation, inflammatory markers, and imaging 1

Phases of Dengue and Complications

Dengue has three phases: febrile phase (days 1-3 with high fever, myalgia, rash), critical phase (days 4-7 with plasma leakage, thrombocytopenia, hemorrhage risk), and recovery phase (days 8-10 with fluid reabsorption); complications include dengue hemorrhagic fever (DHF) with plasma leakage and bleeding, and dengue shock syndrome (DSS) with hypotension and organ failure.

Three Phases of Dengue: 1

1. Febrile Phase (Days 0-3 to 5):

Clinical Features:

  • High fever (40°C/104°F), sudden onset
  • Severe headache (retro-orbital pain)
  • Myalgia and arthralgia ("breakbone fever")
  • Nausea, vomiting
  • Maculopapular rash (appears day 3-4, "islands of white in sea of red")
  • Facial flushing
  • Mild hemorrhagic manifestations: Petechiae, positive tourniquet test, mucosal bleeding

Laboratory:

  • Leukopenia (low WBC)
  • Thrombocytopenia begins (platelets start dropping)
  • Hemoconcentration may begin

Complications:

  • Febrile seizures (children)
  • Dehydration from poor oral intake

2. Critical Phase (Days 3-7, typically days 4-5):

Clinical Features:

  • Defervescence (fever subsides) - WARNING SIGN that critical phase beginning
  • Plasma leakage (capillary permeability increases)
  • Thrombocytopenia (platelets <100,000, often <50,000)
  • Hemoconcentration (hematocrit rises ≥20% from baseline)

Warning Signs (Indicate Severe Dengue):

  • Abdominal pain or tenderness
  • Persistent vomiting
  • Clinical fluid accumulation (ascites, pleural effusion)
  • Mucosal bleeding (epistaxis, gum bleeding, hematemesis, melena)
  • Lethargy or restlessness
  • Liver enlargement (>2 cm)
  • Rapid drop in platelet count with rising hematocrit

Complications:

  • Dengue Hemorrhagic Fever (DHF): Plasma leakage + hemorrhagic manifestations
  • Dengue Shock Syndrome (DSS): Plasma leakage leading to shock
  • Severe bleeding: GI bleeding, intracranial hemorrhage (rare)
  • Organ impairment: Hepatitis, myocarditis, encephalitis, acute kidney injury
  • Severe plasma leakage: Pleural effusion, ascites, hypoalbuminemia

3. Recovery/Convalescent Phase (Days 7-10):

Clinical Features:

  • Reabsorption of extravasated fluid
  • Improvement in clinical status
  • Platelet count recovery
  • Hematocrit stabilizes or decreases
  • Convalescent rash: "Islands of white in sea of red" or desquamation
  • Bradycardia common
  • Fatigue may persist for weeks

Complications:

  • Fluid overload: From aggressive IV fluid resuscitation during critical phase (pulmonary edema, heart failure)
  • Hypervolemia: Monitor for signs during fluid reabsorption

Dengue Hemorrhagic Fever (DHF) Criteria: 1

All 4 Required:

  1. Fever or recent history of fever (2-7 days)
  2. Hemorrhagic manifestations: Positive tourniquet test, petechiae, purpura, bleeding from mucosa/GI/injection sites
  3. Thrombocytopenia: Platelets ≤100,000/mm³
  4. Plasma leakage: Hemoconcentration (hematocrit increase ≥20%), pleural effusion, ascites, hypoalbuminemia

DHF Grading:

  • Grade I: Fever + positive tourniquet test
  • Grade II: Grade I + spontaneous bleeding
  • Grade III: Circulatory failure (rapid, weak pulse, narrow pulse pressure <20 mmHg)
  • Grade IV: Profound shock (undetectable pulse and blood pressure)

Dengue Shock Syndrome (DSS): 1

  • DHF Grade III or IV
  • Hypotension or narrow pulse pressure (<20 mmHg)
  • Cold, clammy skin
  • Altered mental status
  • Oliguria
  • Requires immediate aggressive fluid resuscitation

Management Principles: 1

  • Febrile phase: Supportive care, hydration, antipyretics (acetaminophen ONLY, avoid NSAIDs/aspirin)
  • Critical phase: Close monitoring, IV fluid resuscitation (crystalloids), platelet transfusion if severe bleeding
  • Recovery phase: Monitor for fluid overload, taper IV fluids

Modified Duke Criteria for Infective Endocarditis

The Modified Duke Criteria diagnose infective endocarditis as definite (2 major criteria, 1 major + 3 minor, or 5 minor criteria) or possible (1 major + 1 minor, or 3 minor criteria); major criteria include positive blood cultures with typical organisms and evidence of endocardial involvement on echocardiography; minor criteria include predisposing conditions, fever, vascular/immunologic phenomena, and microbiologic/serologic evidence not meeting major criteria.

Modified Duke Criteria for Infective Endocarditis: 1

Definite IE (Any of the Following):

  1. 2 major criteria, OR
  2. 1 major + 3 minor criteria, OR
  3. 5 minor criteria

Possible IE:

  1. 1 major + 1 minor criteria, OR
  2. 3 minor criteria

Rejected:

  • Firm alternative diagnosis, OR
  • Resolution of syndrome with ≤4 days of antibiotics, OR
  • No pathologic evidence at surgery/autopsy after ≤4 days of antibiotics

MAJOR CRITERIA:

1. Positive Blood Cultures (Typical Organisms):

A. Typical microorganisms for IE from 2 separate blood cultures:

  • Viridans streptococci
  • Streptococcus gallolyticus (formerly S. bovis)
  • HACEK group: Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella
  • Staphylococcus aureus
  • Enterococcus (community-acquired, without primary focus)

B. Persistently positive blood cultures:

  • ≥2 positive cultures drawn >12 hours apart, OR
  • All of 3, or majority of ≥4 separate blood cultures (first and last drawn ≥1 hour apart)

C. Single positive blood culture for Coxiella burnetii or anti-phase I IgG titer >1:800

2. Evidence of Endocardial Involvement:

A. Positive echocardiogram (TEE recommended for prosthetic valves, definite IE by clinical criteria, or complicated IE):

  • Vegetation: Oscillating intracardiac mass on valve/supporting structures, in path of regurgitant jet, or on implanted material
  • Abscess: Perivalvular cavity
  • New partial dehiscence of prosthetic valve
  • New valvular regurgitation (increase or change in pre-existing murmur not sufficient)

MINOR CRITERIA:

1. Predisposing Condition:

  • Predisposing heart condition (prosthetic valve, previous IE, congenital heart disease, rheumatic heart disease, hypertrophic cardiomyopathy)
  • IV drug use

2. Fever:

  • Temperature ≥38°C (100.4°F)

3. Vascular Phenomena:

  • Major arterial emboli
  • Septic pulmonary infarcts
  • Mycotic aneurysm
  • Intracranial hemorrhage
  • Conjunctival hemorrhages
  • Janeway lesions (painless hemorrhagic macules on palms/soles)

4. Immunologic Phenomena:

  • Glomerulonephritis
  • Osler nodes (painful nodules on finger/toe pads)
  • Roth spots (retinal hemorrhages with pale centers)
  • Rheumatoid factor positive

5. Microbiologic Evidence:

  • Positive blood culture not meeting major criterion, OR
  • Serologic evidence of active infection with organism consistent with IE

Clinical Application: 1

When to Suspect IE:

  • Fever + new murmur
  • Fever + prosthetic valve
  • Fever + IV drug use
  • Bacteremia with S. aureus, Enterococcus, or viridans streptococci
  • Embolic phenomena of unknown source
  • Fever of unknown origin with predisposing cardiac condition

Diagnostic Workup:

  • 3 sets of blood cultures from different sites before antibiotics
  • Transthoracic echocardiogram (TTE) first-line
  • Transesophageal echocardiogram (TEE) if TTE negative but high clinical suspicion, prosthetic valve, or complicated IE (sensitivity 90-100% vs TTE 50-70%)

Treatment:

  • Prolonged IV antibiotics (4-6 weeks)
  • Pathogen-directed therapy
  • Surgical intervention if heart failure, uncontrolled infection, large vegetations, or recurrent emboli

Febrile Neutropenia: Definition, Classification, and ANC Calculation

Febrile neutropenia is defined as single oral temperature ≥38.3°C (101°F) or ≥38°C (100.4°F) for ≥1 hour with absolute neutrophil count (ANC) <500 cells/μL or <1000 cells/μL with expected decline to <500; neutropenia is classified as mild (ANC 1000-1500), moderate (ANC 500-1000), or severe (ANC <500); ANC is calculated as: WBC × (% neutrophils + % bands) / 100.

Definition of Febrile Neutropenia: 1

Fever:

  • Single oral temperature ≥38.3°C (101°F), OR
  • Temperature ≥38.0°C (100.4°F) sustained for ≥1 hour

Neutropenia:

  • ANC <500 cells/μL, OR
  • ANC <1000 cells/μL with expected decline to <500 cells/μL within 48 hours

Classification of Neutropenia (by ANC): 1

  • Mild Neutropenia: ANC 1000-1500 cells/μL
  • Moderate Neutropenia: ANC 500-1000 cells/μL
  • Severe Neutropenia: ANC <500 cells/μL
  • Profound Neutropenia: ANC <100 cells/μL (highest infection risk)

How to Calculate Absolute Neutrophil Count (ANC): 1

Formula:

ANC = WBC × (% Neutrophils + % Bands) / 100

Example:

  • WBC = 2000 cells/μL
  • Neutrophils (segs) = 20%
  • Bands = 5%
  • ANC = 2000 × (20 + 5) / 100 = 2000 × 0.25 = 500 cells/μL

Alternative Formula:

ANC = WBC × (% Polys + % Bands) / 100

(Polys = polymorphonuclear cells = mature neutrophils = segs)

Clinical Significance: 1

Risk of Infection by ANC:

  • ANC >1500: Normal, low infection risk
  • ANC 1000-1500: Mild risk
  • ANC 500-1000: Moderate risk
  • ANC <500: High risk (febrile neutropenia threshold)
  • ANC <100: Very high risk (profound neutropenia)

Duration of Neutropenia:

  • <7 days: Lower risk
  • ≥7 days: Higher risk of serious infection
  • >10 days: Highest risk

Common Causes of Neutropenia: 1

  • Chemotherapy (most common in oncology)
  • Bone marrow disorders: Aplastic anemia, myelodysplastic syndrome, leukemia
  • Medications: Clozapine, carbamazepine, methimazole, sulfasalazine
  • Infections: HIV, viral hepatitis, sepsis
  • Autoimmune: SLE, rheumatoid arthritis
  • Nutritional: Vitamin B12, folate deficiency

Management of Febrile Neutropenia: 1

Immediate Actions:

  • Obtain blood cultures (2 sets from different sites, including central line if present)
  • Administer empiric broad-spectrum antibiotics within 1 hour
  • Assess for source (physical exam, chest X-ray, urinalysis, other cultures as indicated)

Empiric Antibiotic Regimens:

Monotherapy (Low-Risk Patients):

  • Cefepime 2 g IV q8h, OR
  • Piperacillin-tazobactam 4.5 g IV q6h, OR
  • Meropenem 1 g IV q8h (if beta-lactam allergy or high local resistance)

Combination Therapy (High-Risk Patients):

  • Anti-pseudomonal beta-lactam (above) PLUS:
    • Vancomycin 15-20 mg/kg IV q8-12h (if suspected catheter infection, skin/soft tissue infection, pneumonia, hemodynamic instability, or high local MRSA prevalence)
    • Aminoglycoside (gentamicin, tobramycin, amikacin) if severe sepsis/shock

Add Antifungal Coverage if:

  • Persistent fever after 4-7 days of broad-spectrum antibiotics
  • Empiric antifungal: Echinocandin (caspofungin, micafungin) or liposomal amphotericin B

Risk Stratification (MASCC Score): 1

  • Low-risk (MASCC score ≥21): Consider outpatient management with oral antibiotics (ciprofloxacin + amoxicillin-clavulanate)
  • High-risk (MASCC score <21): Hospitalize, IV antibiotics

Criteria for Fever of Unknown Origin and Common Causes

Fever of unknown origin (FUO) is defined as: temperature ≥38.3°C (101°F) on multiple occasions, duration ≥3 weeks, and no diagnosis after 3 outpatient visits or 3 days of inpatient investigation; common causes include infections (tuberculosis, abscesses, endocarditis), malignancies (lymphoma, leukemia), and autoimmune diseases (Still's disease, temporal arteritis, SLE).

Classic Criteria for Fever of Unknown Origin (FUO): 1

All 3 Required:

  1. Temperature ≥38.3°C (101°F) on multiple occasions

  2. Duration ≥3 weeks

  3. No diagnosis after:

    • 3 outpatient visits, OR
    • 3 days of inpatient investigation, OR
    • 1 week of outpatient investigation (modern definition)

Subtypes of FUO: 1

1. Classic FUO:

  • Meets above criteria in immunocompetent patient

2. Nosocomial (Hospital-Acquired) FUO:

  • Hospitalized patient
  • Fever ≥38.3°C on multiple occasions
  • No infection present or incubating on admission
  • No diagnosis after 3 days despite appropriate investigation

3. Neutropenic FUO:

  • ANC <500 cells/μL
  • Fever ≥38.3°C on multiple occasions
  • No diagnosis after 3 days despite appropriate investigation (including 2 days of cultures)

4. HIV-Associated FUO:

  • HIV-positive patient
  • Fever ≥38.3°C on multiple occasions for ≥4 weeks (outpatient) or ≥3 days (inpatient)
  • No diagnosis after 3 days despite appropriate investigation

Common Causes of FUO (by Category): 1

1. Infections (20-40% of cases):

Bacterial:

  • Tuberculosis (most common infectious cause worldwide, especially extrapulmonary)
  • Abscesses: Intra-abdominal, hepatic, splenic, renal, pelvic
  • Endocarditis (especially culture-negative)
  • Osteomyelitis (vertebral)
  • Catheter-related bloodstream infections
  • Brucellosis
  • Q fever (Coxiella burnetii)
  • Typhoid fever (Salmonella typhi)
  • Lyme disease

Viral:

  • Epstein-Barr virus (EBV)
  • Cytomegalovirus (CMV)
  • HIV (acute retroviral syndrome)

Fungal:

  • Histoplasmosis
  • Coccidioidomycosis

Parasitic:

  • Malaria
  • Toxoplasmosis

2. Malignancies (20-30% of cases):

Hematologic:

  • Lymphoma (Hodgkin's and non-Hodgkin's) - most common malignant cause
  • Leukemia (acute and chronic)
  • Multiple myeloma

Solid Tumors:

  • Renal cell carcinoma
  • Hepatocellular carcinoma
  • Colon cancer
  • Pancreatic cancer
  • Atrial myxoma (cardiac tumor)

3. Autoimmune/Inflammatory Diseases (10-20% of cases):

Rheumatologic:

  • Adult-onset Still's disease (high spiking fevers, salmon-colored rash, arthritis, very high ferritin)
  • Temporal arteritis (Giant cell arteritis) - especially in patients >50 years
  • Systemic lupus erythematosus (SLE)
  • Rheumatoid arthritis
  • Polymyalgia rheumatica
  • Vasculitis (polyarteritis nodosa, Takayasu arteritis)

Inflammatory Bowel Disease:

  • Crohn's disease
  • Ulcerative colitis

Other:

  • Sarcoidosis
  • Kikuchi disease (histiocytic necrotizing lymphadenitis)

4. Miscellaneous (10-20% of cases):

Drug-Induced Fever:

  • Antibiotics (beta-lactams, sulfonamides)
  • Anticonvulsants (phenytoin, carbamazepine)
  • Allopurinol
  • Heparin

Thromboembolic:

  • Pulmonary embolism
  • Deep vein thrombosis

Endocrine:

  • Thyrotoxicosis
  • Adrenal insufficiency

Factitious Fever:

  • Self-induced (thermometer manipulation, injection of pyrogens)

5. Undiagnosed (10-30% of cases):

  • Despite extensive workup, no diagnosis found
  • Many resolve spontaneously

Diagnostic Approach to FUO: 1

Initial Evaluation:

  • Detailed history: Travel, exposures, medications, family history, occupational history
  • Comprehensive physical examination: Repeat frequently (findings may evolve)
  • Basic laboratory tests: CBC with differential, CMP, LFTs, ESR, CRP, urinalysis, blood cultures (×3), chest X-ray

Second-Line Tests (Based on Clinical Clues):

  • Imaging: CT chest/abdomen/pelvis, PET-CT (excellent for occult malignancy, infection, inflammation)
  • Serologies: HIV, EBV, CMV, ANA, RF, ANCA, ACE level (sarcoidosis)
  • Tuberculosis testing: Tuberculin skin test, IGRA, sputum AFB (if pulmonary symptoms)
  • Echocardiography: TTE or TEE (endocarditis)
  • Bone marrow biopsy: If hematologic malignancy suspected
  • Temporal artery biopsy: If age >50 and elevated ESR (giant cell arteritis)
  • Liver biopsy: If hepatomegaly or elevated LFTs

Third-Line Tests (If Above Unrevealing):

  • Lymph node biopsy: If lymphadenopathy present
  • Exploratory laparotomy: Rarely needed (if intra-abdominal pathology suspected but imaging non-diagnostic)

Key Diagnostic Clues: 1

  • Very high ferritin (>1000 ng/mL): Still's disease, hemophagocytic lymphohistiocytosis
  • Elevated ESR/CRP: Infection, malignancy, autoimmune disease
  • Anemia + high ESR: Temporal arteritis, malignancy
  • Eosinophilia: Drug reaction, parasitic infection, vasculitis
  • High LDH: Lymphoma, hemolysis
  • Positive ANA: SLE, other autoimmune diseases

HIV Screening and Confirmatory Tests

The screening test for HIV is a fourth-generation antigen/antibody immunoassay detecting HIV-1/2 antibodies and p24 antigen; if positive, confirmation is performed with HIV-1/HIV-2 antibody differentiation immunoassay, followed by HIV-1 RNA assay if differentiation is negative or indeterminate.

HIV Testing Algorithm (CDC Recommended): 1

Step 1: Screening Test

Fourth-Generation Antigen/Antibody Immunoassay (Preferred):

  • Detects HIV-1 and HIV-2 antibodies AND HIV-1 p24 antigen
  • Advantages:
    • Detects infection earlier than antibody-only tests (1-3 weeks post-infection vs 3-4 weeks)
    • p24 antigen appears before antibodies during acute infection
    • High sensitivity (>99%) and specificity (>99%)
  • Window period: 18-45 days (earlier than third-generation tests)

Alternative Screening Tests:

  • Third-generation antibody-only immunoassay: Detects HIV-1/2 antibodies only (longer window period)
  • Rapid HIV tests: Point-of-care, results in 20 minutes (lower sensitivity, requires confirmation)

If Screening Test is NEGATIVE:

  • No HIV infection (if outside window period)
  • Repeat testing if acute HIV suspected (within window period) or high-risk exposure

If Screening Test is POSITIVE:

  • Proceed to Step 2 (confirmatory testing)

Step 2: Confirmatory Test

HIV-1/HIV-2 Antibody Differentiation Immunoassay:

  • Differentiates HIV-1 from HIV-2 antibodies
  • Performed on same specimen as screening test

If Differentiation Assay is POSITIVE for HIV-1 or HIV-2:

  • HIV infection confirmed
  • Identify HIV type (HIV-1 vs HIV-2)
  • Proceed to baseline HIV care (CD4 count, viral load, resistance testing, initiate ART)

If Differentiation Assay is NEGATIVE or INDETERMINATE:

  • Proceed to Step 3

Step 3: HIV-1 RNA Assay (Nucleic Acid Test)

HIV-1 Viral Load (Quantitative RNA PCR):

  • Detects HIV-1 RNA in plasma
  • Performed if differentiation assay negative or indeterminate

If HIV-1 RNA is DETECTABLE:

  • Acute HIV-1 infection (antibodies not yet developed)
  • HIV-1 infection confirmed
  • Initiate ART immediately

If HIV-1 RNA is UNDETECTABLE:

  • False-positive screening test (no HIV infection), OR
  • HIV-2 infection (HIV-1 RNA assay does not detect HIV-2)
  • If HIV-2 suspected (epidemiologic risk), perform HIV-2 RNA assay

Special Situations: 1

Acute HIV Infection (Window Period):

  • Fourth-generation test may be positive (p24 antigen) before antibodies develop
  • If high clinical suspicion (fever, rash, lymphadenopathy, high-risk exposure), order HIV RNA even if screening test negative

HIV-2 Infection:

  • Rare in US (endemic in West Africa)
  • Fourth-generation test detects HIV-2 antibodies
  • Differentiation assay identifies HIV-2
  • HIV-1 RNA assay will be negative (order HIV-2 RNA if suspected)

Post-Exposure Prophylaxis (PEP) or Pre-Exposure Prophylaxis (PrEP):

  • Baseline HIV test before starting
  • Repeat testing at 4-6 weeks, 3 months, and 6 months post-exposure

Rapid HIV Testing:

  • Used in emergency departments, outpatient settings, community testing
  • Positive rapid test requires confirmatory testing (fourth-generation immunoassay + differentiation assay)

Summary of HIV Testing Algorithm: 1

  1. Fourth-generation antigen/antibody immunoassay (screening)

    • Negative → No HIV (if outside window period)
    • Positive → Proceed to step 2

  2. HIV-1/HIV-2 antibody differentiation immunoassay (confirmatory)

    • Positive for HIV-1 or HIV-2 → HIV confirmed
    • Negative or indeterminate → Proceed to step 3

  3. HIV-1 RNA assay (nucleic acid test)

    • Detectable → Acute HIV-1 infection confirmed
    • Undetectable → False-positive screening test (or HIV-2 if epidemiologic risk)

HIV Categorization, AIDS Definition, and CD4 Count in AIDS

HIV is categorized by CD4 count (Category 1: ≥500 cells/μL, Category 2: 200-499 cells/μL, Category 3: <200 cells/μL) and clinical stage (Stage A: asymptomatic, Stage B: symptomatic non-AIDS conditions, Stage C: AIDS-defining illnesses); AIDS is defined as HIV infection with CD4 count <200 cells/μL or CD4 percentage <14%, or presence of an AIDS-defining illness regardless of CD4 count.

HIV Classification System (CDC): 1

Based on CD4 Count and Clinical Stage:

CD4 Count Categories:

  • Category 1: CD4 ≥500 cells/μL (or ≥29%)
  • Category 2: CD4 200-499 cells/μL (or 14-28%)
  • Category 3: CD4 <200 cells/μL (or <14%) - AIDS

Clinical Stages:

  • Stage A: As

References

1
Guideline

Chronic Disease Management Programs

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

2
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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