Pneumonia — CAP, HAP, VAP

Typical bacterial (alveolar-filling, lobar) CAP

• Streptococcus pneumoniae: the single most common bacterial cause of CAP; polysaccharide capsule resists opsonization until type-specific antibody appears
• ***Haemophilus influenzae* and *Moraxella catarrhalis***: favor damaged airways (COPD, bronchiectasis, smoking); both are frequently beta-lactamase producers
• Klebsiella pneumoniae and other Enterobacterales: aspiration-prone hosts with alcohol use disorder or diabetes
• Staphylococcus aureus (including MRSA): classically post-influenza, when viral denudation of respiratory epithelium exposes adhesion sites; may be necrotizing

Atypical (interstitial, intracellular or cell wall–deficient)

• Mycoplasma pneumoniae: young, crowded settings (dorms, barracks); no cell wall, so beta-lactams fail
• Legionella pneumophila: aerosolized water — cooling towers, hot tubs, hospital plumbing; replicates within alveolar macrophages
• Chlamydia pneumoniae, C. psittaci (birds), Coxiella burnetii (parturient livestock)

• Aspiration and inoculation: Microorganisms bypass upper airway defenses (impaired gag reflex, altered consciousness, aspiration during sleep) and colonize distal airways; in VAP, biofilm formation on endotracheal tubes facilitates bacterial adherence and chronic infection
• Impaired mucociliary clearance: Loss of ciliary function (smoking, viral infection, intubation) and decreased surfactant production reduce mechanical clearance; ventilator-associated lung injury exacerbates this through positive pressure trauma and ventilator dyssynchrony
• Breakdown of alveolar-capillary barrier: Bacterial virulence factors (lipopolysaccharide, exotoxins, proteases) and host inflammatory mediators (TNF-α, IL-1, IL-6) trigger neutrophil infiltration and release of proteolytic enzymes, causing increased vascular permeability, pulmonary edema, and impaired gas exchange
• Host defense failure: Immunosuppression (age, malnutrition, chronic disease, immunosuppressive medications), complement depletion, and compromised opsonization reduce pathogen clearance and promote bacterial proliferation
• Organ dysfunction cascade: Systemic inflammation leads to SIRS/sepsis; impaired oxygenation causes V/Q mismatch and hypoxemia; metabolic acidosis and shock develop in severe cases

Community-Acquired Pneumonia (CAP)

• Acute onset: Fever (38.5–40°C), cough (productive with purulent or rusty sputum), dyspnea, and pleuritic chest pain developing over hours to days
• Constitutional symptoms: Fatigue, malaise, myalgias; atypical presentations more common in elderly (confusion, functional decline) and immunocompromised (minimal fever, subtle infiltrates)
• Physical examination: Tachypnea (RR >20), tachycardia, crackles/rales on auscultation, dullness to percussion and egophony if consolidation present; hypoxia on pulse oximetry
• Clinical variants: Atypical pneumonia (Mycoplasma, Legionella, Chlamydia) presents with prominent extrapulmonary symptoms (headache, GI symptoms, rash); aspiration pneumonia often occurs in dependent lung segments (posterior apical, superior basal)

Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP)

• Fever and respiratory deterioration: New or progressive fever, increased sputum production (purulent or blood-tinged), hypoxemia, increase in ventilator settings or failure to wean
• Subtle presentation: HAP/VAP may present insidiously without classic fever; VAP often detected through routine surveillance (increasing secretion volume/character, fever spikes)
• Clinical pearl: VAP diagnosis is challenging because any mechanically ventilated patient develops some degree of airway colonization; clinical worsening must be correlated with microbiologic data to avoid overtreatment

CAP Diagnosis

• Clinical criteria + imaging: Symptoms (cough, dyspnea, fever) plus infiltrate on chest X-ray (CXR) or CT; typical patterns include lobar consolidation (bacterial), interstitial or patchy infiltrates (atypical organisms or viral)
• Sputum culture and Gram stain: Not routinely required for outpatient CAP but useful in hospitalized patients; Gram-negative diplococci suggest Streptococcus pneumoniae, gram-negative rods suggest Enterobacteriaceae, and curved gram-negative rods suggest Legionella
• Blood cultures: Obtain in all hospitalized patients (positive in ~10–15% of CAP); ≥2 sets before antibiotics to improve yield
• Pneumonia severity assessment tools: CURB-65 (Confusion, Urea >7 mmol/L, Respiratory rate ≥30, Blood pressure SBP <90 or DBP ≤60, age ≥65) or PSI (Pneumonia Severity Index); scores guide outpatient vs. admission decisions
• Additional testing: Procalcitonin may aid in distinguishing bacterial from viral pneumonia (elevated in bacterial); respiratory viral PCR or multiplex panels increasingly used; Legionella and Streptococcus pneumoniae urinary antigens useful in severe CAP

HAP/VAP Diagnosis

• Clinical suspicion with microbiologic confirmation: Lower respiratory tract specimens (endotracheal aspirate, bronchoalveolar lavage [BAL], protected specimen brush) sent for culture; quantitative cultures help differentiate colonization from true infection
• Diagnostic criteria (VAP): Clinical criteria (fever, new/progressive infiltrate, purulent secretions) plus either quantitative BAL culture ≥104 CFU/mL or quantitative PSB culture ≥103 CFU/mL; clinical pulmonary infection score (CPIS) ≥6 suggests VAP requiring antibiotics
• Imaging: CXR may show new infiltrates, but in ventilated patients baseline changes limit sensitivity; CT reserved for complicated cases or diagnostic uncertainty

CAP Treatment — Outpatient (Non-Severe)

• First-line: Amoxicillin-clavulanate 875 mg PO BID × 5–7 days OR macrolide (azithromycin 500 mg day 1, then 250 mg daily × 4 days) for suspected Streptococcus pneumoniae and Haemophilus influenzae
• Alternative: Fluoroquinolone monotherapy (levofloxacin 750 mg daily × 5 days or moxifloxacin 400 mg daily × 5 days) covers both typical and atypical organisms; preferred if concern for atypical pathogens

CAP Treatment — Hospitalized (Non-Severe)

• First-line regimen: Ceftriaxone 1 g IV Q12H (or cefotaxime 1 g IV Q8H) PLUS azithromycin 500 mg IV daily (or fluoroquinolone if macrolide contraindicated); covers S. pneumoniae, H. influenzae, and atypical pathogens
• Duration: 5–7 days total (switch to oral step-down when clinically stable and tolerating PO)

CAP Treatment — ICU/Severe (with Risk Factors for Pseudomonas or Other MDR)

• Empiric coverage: Antipseudomonal beta-lactam (piperacillin-tazobactam 4.5 g IV Q6H OR cefepime 2 g IV Q12H OR meropenem 1 g IV Q8H) PLUS antipseudomonal fluoroquinolone (ciprofloxacin 400 mg IV Q8H) OR aminoglycoside (gentamicin/tobramycin dosing per renal function)
• Atypical coverage: Add azithromycin 500 mg IV daily or doxycycline for Legionella (especially if nosocomial source or travel history)
• De-escalation: Narrow spectrum once cultures/sensitivities available; typical step-down after 48–72 hours clinical improvement

HAP Treatment

• Early HAP (<5 days, low risk of MDR): Ceftriaxone 1 g IV Q12H or ampicillin-sulbactam 3 g IV Q6H covers S. pneumoniae, H. influenzae, E. coli, Klebsiella
• **Late HAP (≥5 days, high risk of MDR including Pseudomonas, Acinetobacter, *Staphyloc

Pleural and parenchymal

• Parapneumonic effusion: inflammatory capillary leak into the pleural space; persistent fever plus a layering effusion. Uncomplicated effusions resolve with antibiotics alone
• Empyema (emergency): bacterial invasion of the pleural space with loculation and fibrin deposition. Signaled by pleural fluid pH <7.20, glucose low, LDH markedly elevated, or frank pus/positive Gram stain — antibiotics alone will not sterilize it, so tube thoracostomy (± intrapleural fibrinolytic/DNase or VATS decortication) is required
• Lung abscess / necrotizing pneumonia: tissue destruction by anaerobes, Klebsiella, or PVL-producing S. aureus; air-fluid level on upright film, foul-smelling sputum
• Bronchopleural fistula and pneumatocele: late sequelae of necrotizing infection

Systemic

• Sepsis and septic shock (emergency): cytokine-driven vasoplegia; hypotension refractory to fluids plus lactate elevation — the Surviving Sepsis Campaign calls for cultures, early broad-spectrum antibiotics, and fluid resuscitation without delay
• ARDS (emergency): diffuse alveolar damage with bilateral infiltrates and hypoxemia not explained by cardiogenic edema; requires low-tidal-volume ventilation
• Metastatic infection: pneumococcal bacteremia seeding meninges, joints, or heart valves (Austrian syndrome — pneumonia, meningitis, endocarditis)
• SIADH with hyponatremia: classically Legionella
• Cold-agglutinin hemolytic anemia, erythema multiforme/SJS, and Guillain–Barré: Mycoplasma
• Decompensation of comorbidity: acute MI, AF, and heart failure exacerbation in the weeks after pneumonia

Treatment-related

• ***Clostridioides difficile* colitis**: flora disruption from any regimen, especially fluoroquinolones and broad beta-lactams
• Vancomycin nephrotoxicity: risk rises with concurrent piperacillin-tazobactam; the 2020 IDSA/ASHP consensus dose vancomycin to a 24-hour AUC/MIC of 400–600, not to a AUC/MIC 400-600 per the 2020 IDSA/ASHP consensus
• Fluoroquinolones: QT prolongation, tendinopathy/rupture, aortopathy, CNS effects, dysglycemia
• Macrolides: QT prolongation and CYP3A4 interactions
• Aminoglycosides: dose-dependent ototoxicity and acute tubular necrosis
• Linezolid: thrombocytopenia and serotonin syndrome with SSRIs

• Sputum color is a scripted clue: rust-colored sputum → S. pneumoniae; currant-jelly sputum in an alcohol-using patient with an upper-lobe bulging fissure → Klebsiella; foul-smelling sputum with an air-fluid level → anaerobic aspiration abscess
• Hyponatremia + diarrhea + transaminitis + high fever with relative bradycardia → Legionella. Best next test is the urinary antigen (detects serogroup 1 only), and treatment is a respiratory fluoroquinolone or azithromycin — a beta-lactam alone will fail
• Cold agglutinins, bullous myringitis, or target lesions in a college student with a chest film worse than the exam → Mycoplasma; treat with a macrolide or doxycycline, never a beta-lactam (no cell wall)
• Cavitary pneumonia days after influenza → S. aureus; if MRSA is plausible, add vancomycin (AUC-guided per the 2020 IDSA/ASHP consensus) or linezolid
• The single best next step in persistent fever despite appropriate antibiotics with a layering effusion is diagnostic thoracentesis, not antibiotic escalation — you are looking for an empyema that needs drainage
• HIV with CD4 <200, subacute dyspnea, diffuse ground-glass, and a markedly elevated LDH → Pneumocystis jirovecii; TMP-SMX plus adjunctive corticosteroids when hypoxemia is significant (PaO₂ <70 mmHg on room air or A–a gradient ≥35)
• Distractor to avoid — "healthcare-associated pneumonia": the IDSA/ATS 2019 CAP guideline abandoned the HCAP category. Do not reflexively give MRSA/Pseudomonas coverage just because a patient came from a nursing home or had recent dialysis; base it on prior respiratory isolation of the organism, recent IV antibiotics, structural lung disease, or severe illness
• Distractor to avoid — procalcitonin: it may support de-escalation, but IDSA/ATS explicitly says a low procalcitonin should not withhold empiric antibiotics in clinically suspected CAP. Likewise, routine follow-up chest imaging in a clinically improving patient is not required