Pneumonia¶

Part 5: Infectious Diseases | Chapter 131: Pneumonia · Part 5 – Infectious Diseases: Bacterial · Chapter 131

Key Clinical Points¶

Pneumonia is an infection of the pulmonary parenchyma, classified as Community-Acquired (CAP), Hospital-Acquired (HAP), or Ventilator-Associated (VAP).
Clinical progression follows four stages: edema, red hepatization, gray hepatization, and resolution.
CAP is a leading cause of death in patients >65 years old; risk factors include alcoholism, asthma, and immunocompromise.
Severity assessment tools like CURB-65 and PSI help determine the site of care (outpatient vs. inpatient).
Empirical therapy for CAP targets S. pneumoniae and atypical pathogens; MRSA/Pseudomonas coverage is reserved for specific risk factors.
Sputum Gram stain requires >25 neutrophils/HPF and <10 squamous cells/HPF to be considered valid.
Urinary antigen tests (Legionella, pneumococcus) and PCR panels are key diagnostic tools for rapid identification.
Antibiotic resistance in S. pneumoniae involves PBP remodeling, ribosomal methylation, and efflux pumps.
CA-MRSA strains often carry genes for superantigens and Panton-Valentine leukocidin.
VAP management focuses on preventing complications like aspiration via drainage, hygiene, and source control.

DEFINITION & CLASSIFICATION¶

• Definition (Harrison's 22e): infection of the pulmonary parenchyma • Classifications: ◦ Community-acquired (CAP) ◦ Hospital-acquired (HAP) ◦ Ventilator-associated (VAP) ◦ Aspiration pneumonia (accounts for 5–15% of CAP cases; lacks reliable HAP data) • Pathophysiology: ◦ Microbial proliferation in alveoli → host immune response ◦ Inflammatory triggers (e.g., viral infections) → cytokine release (IL-6, TNF) → enhanced bacterial growth ◦ Positive feedback loop: inflammation → nutrient availability → bacterial proliferation → worsened inflammation ◦ Failure of immune containment → alveolar capillary leak, hypoxemia, and respiratory failure ◦ Bacterial toxins exacerbate inflammation; impaired hypoxic vasoconstriction may cause severe hypoxemia.

Pathology¶

• Stages of Progression: ◦ Edema: Proteinaceous exudate with bacteria ◦ Red hepatization: Erythrocytes in alveolar exudate (characteristic appearance) ◦ Gray hepatization: Lysed erythrocytes, neutrophil dominance, fibrin deposition ◦ Resolution: Macrophage clearance of debris and inflammatory response • Patterns: ◦ Lobar pattern: Dominates bacterial CAP ◦ Bronchopneumonia: Common in nosocomial infections ◦ Viral/Pneumocystis: Alveolar processes despite radiographic appearance

EPIDEMIOLOGY¶

• Statistics (US): ◦ Annual CAP cases: >7 million ◦ Adult incidence: 16–23/1000 ◦ Hospitalization rates: 650/100,000 (general) vs. 2000/100,000 (elderly) ◦ Mortality: 1–5% for outpatients; 20–30% for ICU patients ◦ Readmission: 18% within 1 month • Risk Factors: ◦ Age >70 years (decreased cough reflex, antibody response) ◦ Alcoholism, asthma, immunocompromise, institutionalization ◦ Comorbidities: Dementia, COPD, heart failure, HIV • Table 131-2 (Epidemiologic Factors): ◦ Alcoholism → S. pneumoniae, oral anaerobes, Klebsiella, Acinetobacter, M. tuberculosis ◦ Structural lung disease (e.g., bronchiectasis) → P. aeruginosa, Burkholderia cepacia, S. aureus ◦ Lung abscess → CA-MRSA, oral anaerobes, endemic fungi, M. tuberculosis, NTM ◦ Travel to SW United States → Hantavirus, Coccidioides spp. ◦ Stay in hotel/cruise (prev. 2 weeks) → Legionella spp. ◦ Exposure to humans → SARS-CoV-2 ◦ Exposure to rabbits → Francisella tularensis

ETIOLOGY & PATHOPHYSIOLOGY¶

• Pathogen Categories: ◦ Typical: S. pneumoniae, H. influenzae, K. pneumoniae ◦ Atypical: M. pneumoniae, C. pneumoniae, Legionella ◦ Viral: Influenza, RSV (present in 20–30% of patients via PCR) • Polymicrobial CAP: Occurs in 10–15% of cases (typical + atypical) • Aspiration Pneumonia: Includes CAP/HAP pathogens; anaerobes relevant in necrotizing cases • Table 131-1 (Microbial Causes by Site of Care): ◦ Outpatients: S. pneumoniae, M. pneumoniae, H. influenzae, C. pneumoniae, Respiratory viruses ◦ Hospitalized (Non-ICU): S. pneumoniae, M. pneumoniae, C. pneumoniae, H. influenzae, Legionella spp., Respiratory viruses ◦ ICU: S. pneumoniae, S. aureus, Legionella spp., Gram-negative bacilli, H. influenzae, Respiratory viruses • Antibiotic Resistance: ◦ S. pneumoniae: Penicillin-binding protein changes, efflux pumps; 58.9% of penicillin-resistant are macrolide-resistant ◦ CA-MRSA: Panton-Valentine leukocidin and superantigens ◦ M. pneumoniae: Macrolide-resistant (up to 95% in China) ◦ Enterobacteriaceae: ESBL-producing strains require carbapenems

CLINICAL FEATURES¶

• Symptoms: ◦ Constitutional: Fever, chills, sweats ◦ Respiratory: Productive cough (mucoid/purulent), dyspnea, pleuritic chest pain ◦ Gastrointestinal: Nausea, vomiting, diarrhea (20% of cases) ◦ Elderly presentation: Confusion, worsening of chronic illness • Physical Exam: ◦ Severity-dependent findings ◦ Severe cases: Accessory muscle use, decreased fremitus, pleural friction rub ◦ Elderly: May lack classic signs like crackles

Clinical Diagnosis¶

• Differential Diagnosis: Bronchitis, heart failure, pulmonary embolism ◦ Chest Radiography: Identifies new infiltrates (Sensitivity 58%, Specificity 67%) ◦ CT Scan: Useful for cavitary/loculated effusion cases

DIAGNOSTIC APPROACH¶

Clinical & Radiographic Confirmation: Confirm pneumonia via clinical presentation and chest imaging.
Pathogen Identification: ◦ Sputum Gram stain/culture: Required for hospitalized patients with severe disease or risk of MRSA/Pseudomonas. → Criteria for validity: >25 neutrophils/HPF AND <10 squamous cells/HPF ◦ Blood cultures: 5–14% positive (mostly S. pneumoniae); indicated in high-risk patients (neutropenia, asplenia). ◦ Rapid tests: Influenza PCR; Urinary antigen tests (Legionella and pneumococcus). ◦ Serology: IgM titer rise for specific pathogens (e.g., Coxiella burnetii).
Biomarkers: CRP/PCT levels to correlate with bacterial infection severity.

MANAGEMENT & TREATMENT¶

Determine Severity (Table 131-3): ◦ Minor Criteria: Respiratory rate ≥ 30; PaO/FiO ≤ 250; Multilobar infiltrates; Confusion/disorientation; Uremia (BUN ≥ 20 mg/dL); Leukopenia (<4000); Thrombocytopenia (<100,000); Hypothermia (<36°C); Hypotension requiring fluids. ◦ Major Criteria: Respiratory failure requiring invasive mechanical ventilation; Septic shock requiring vasopressors.
Assess MRSA/Pseudomonas Risk (Flowchart 131-1): ◦ Nonsevere → No risk → Prior respiratory isolation → Add treatment ◦ Nonsevere → Risk → Recent hospitalization and antibiotics ± local validation → Obtain cultures ◦ Severe → No risk → Prior respiratory isolation → Add treatment ◦ Severe → Risk → Recent hospitalization and antibiotics ± local validation → Add treatment
Select Empirical Regimen (Table 131-4 & 131-5): ◦ Outpatient (No risk factors): → Amoxicillin (1 g tid) + macrolide OR doxycycline (100 mg bid) → OR Monotherapy with doxycycline (100 mg bid) → OR Monotherapy with a macrolide ◦ Inpatient Nonsevere (No risk factors): → β-lactam + macrolide OR respiratory fluoroquinolone ◦ Inpatient Nonsevere (Risk factor present): → Add coverage for MRSA/Pseudomonas only if cultures are positive ◦ Inpatient Severe (Prior respiratory isolation): → Add coverage for MRSA/Pseudomonas
HAP & VAP Management (Table 131-8): ◦ No risk for resistant Gram-negative: Piperacillin-tazobactam (4.5 g IV q6h) OR Cefepime (2 g IV q8h) OR Ceftazidime (2 g IV q8h) OR Levofloxacin (750 mg IV q24h) ◦ Risk for resistant Gram-negative: → Piperacillin-tazobactam (4.5 g IV q6h) OR Cefepime (2 g IV q8h) OR Ceftazidime (2 g IV q8h) OR Imipenem (500 mg IV q6h) OR Meropenem (1 g IV q8h) → Add Amikacin (15–20 mg/kg IV q24h), Gentamicin (5–7 mg/kg IV q24h), Tobramycin (5–7 mg/kg IV q24h), Ciprofloxacin (400 mg IV q8h), Levofloxin (750 mg IV q24h), or Colistin (loading 5 mg/kg; maintenance 2.5 mg imes [1.5 imes CrCl + 30] IV q12h) OR Polymyxin B (2.5–3.0 mg/kg per day in 2 divided doses) ◦ Risk for MRSA: → Linezolid (600 mg IV q12h) OR Adjusted-dose vancomycin (trough level, 15–20 mg/dL)
VAP Prevention Strategies (Table 131-7): ◦ Oropharyngeal colonization: Avoid prolonged antibiotics; consider oral chlorhexidine ◦ Aspiration: Short course of prophylactic antibiotics for comatose patients; short course of inhaled aminoglycosides ◦ Gastroesophageal reflux: Postpyloric enteral feeding; avoid high gastric residuals; prokinetic agents ◦ Bacterial overgrowth: Avoid agents raising gastric pH; selective decontamination of digestive tract ◦ Ventilation issues: Endotracheal intubation; rapid-sequence technique; avoid sedation; change circuits only when soiled; replace HME every 5–7 days ◦ Host defenses: Tight glycemic control; lower hemoglobin transfusion threshold.

VAP Pathogens (Table 131-6)¶

• Non-MDR (Core): S. pneumoniae, Other S. spp., H. influenzae, MSSA, Antibiotic-sensitive Enterobacteriaceae ◦ MDR: Pseudomonas aeruginosa, MRSA, Acinetobacter spp., Antibiotic-resistant Enterobacteriaceae (ESBL+, Carbapenem-resistant), Legionella pneumophila, Burkholderia cepacia, Aspergillus spp.

PROGNOSIS & COMPLICATIONS¶

• Mortality: ◦ Outpatients: 1–5% ◦ ICU patients: 20–30% • Complications: Septic shock, ARDS, empyema, pleural effusion • Readmission: 18% within 1 month • Long-term: Lung fibrosis or chronic respiratory impairment • Risk Factors for Mortality: Age >65, comorbidities (COPD, heart failure), severe sepsis ◦ Readmission Predictors: Inadequate initial treatment, persistent fever, underlying immunosuppression.

SPECIAL POPULATIONS¶

• Aspiration Pneumonia: Risk factors include dysphagia, alcoholism, and stroke ◦ Immunocompromised: Risks include Pneumocystis jirovecii, CMV, fungal infections ◦ Pediatric CAP: Common pathogens (S. aureus, RSV); requires lumbar puncture in patients <2 months ◦ Risk Factor-Pathogen Associations (Table 131-2): → Alcoholism: S. pneumoniae, Klebsiella, Acinetobacter, M. tuberculosis → Lung abscess: CA-MRSA, M. tuberculosis, NTM → Travel to SE Asia: Burkholderia pseudomallei, avian influenza → Exposure to birds: H. capsulatum, Chlamydia psittaci → Exposure to sheep/goats: Coxiella burnetii

KEY PEARLS & CLINICAL TRAPS¶

• Pearls: ◦ CURB-65 score ≥ 4 (Note: Source says >4 for ICU) → ICU admission ◦ Sputum Gram stain validity: Requires >25 neutrophils/HPF ◦ Legionella: Associated with recent travel or hospitalization • Clinical Traps: ◦ Atypical pneumonia may mimic viral infections (e.g., M. pneumoniae without fever) ◦ Overuse of broad-spectrum antibiotics increases resistance ◦ Elderly patients may present with confusion rather than classic symptoms.

Reference Tables¶

TABLE 131-2 Epidemiologic Factors Suggesting Possible Causes of Community-Acquired Pneumonia FACTOR Alcoholism¶

Harrison's 22e, p.1024

OUTPATIENTS	HOSPITALIZED PATIENTS
	NON-ICU	ICU
Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydia pneumoniae Respiratory virusesa	S. pneumoniae M. pneumoniae C. pneumoniae H. influenzae Legionella spp. Respiratory virusesa	S. pneumoniae Staphylococcus aureus Legionella spp. Gram-negative bacilli H. influenzae Respiratory virusesa

TABLE 131-2 Epidemiologic Factors Suggesting Possible Causes of Community-Acquired Pneumonia

FACTOR	POSSIBLE PATHOGEN(S)
Alcoholism	Streptococcus pneumoniae, oral anaerobes, Klebsiella pneumoniae, Acinetobacter spp., Mycobacterium tuberculosis
Structural lung disease (e.g., bronchiectasis)	P. aeruginosa, Burkholderia cepacia, Staphylococcus aureus
Lung abscess	CA-MRSA, oral anaerobes, endemic fungi, M. tuberculosis, nontuberculous mycobacteria
Travel to southwestern United States	Hantavirus, Coccidioides spp.
Stay in hotel or on cruise ship in previous 2 weeks	Legionella spp.
Exposure to infected humans	SARS-CoV-2
Exposure to rabbits	Francisella tularensis

TABLE 131-3 Criteria for Severe Community-Acquired Pneumonia Minor criteria¶

Harrison's 22e, p.1026

Minor criteria
Respiratory rate ≥30 breaths/min
PaO/FiO ratio ≤250
2 2
Multilobar infiltrates
Confusion/disorientation
Uremia (BUN level ≥20 mg/dL)
Leukopenia (WBC count <4000 cells/μL)
Thrombocytopenia (platelet count <100,000 cells/μL)
Hypothermia (core temperature <36°C)
Hypotension requiring aggressive fluid resuscitation
Major criteria
Respiratory failure requiring invasive mechanical ventilation
Septic shock requiring vasopressors

TABLE 131-4 Initial Treatment Strategies for Outpatients with Community-Acquired Pneumonia STATUS No comorbidities or…¶

Harrison's 22e, p.1027

STATUS	STANDARD REGIMEN
No comorbidities or risk factors for antibiotic resistancea	Combination therapy with amoxicillin (1 g tid) + either a macrolideb or doxycycline (100 mg bid) or
	Monotherapy with doxycycline (100 mg bid) or
	Monotherapy with a macrolideb,c

TABLE 131-5 Initial Treatment for Inpatients with or without Risk Factors for Infection with MRSA or Pseudomonas…¶

Harrison's 22e, p.1028

DISEASE SEVERITY, RISK STATUS	REGIMEN
Nonsevere
No risk factors	A β-lactama + a macrolideb or A respiratory fluoroquinolonec
Recent hospitalization, antibiotic treatment, ± LVf	Add coverage for MRSAd or P. aeruginosae only if cultures are positive
Severe
Prior respiratory isolation	Add coverage for MRSAd or P. aeruginosae

TABLE 131-6 Microbiologic Causes of Ventilator-Associated Pneumonia¶

Harrison's 22e, p.1029

NON-MDR PATHOGENS (CORE PATHOGENS)	MDR PATHOGENS
Streptococcus pneumoniae Other Streptococcus spp. Haemophilus influenzae Methicillin-sensitive Staphylococcus aureus Antibiotic-sensitive Enterobacteriaceae Escherichia coli Klebsiella pneumoniae Proteus spp. Enterobacter spp. Serratia marcescens	Pseudomonas aeruginosa Methicillin-resistant S. aureus Acinetobacter spp. Antibiotic-resistant Enterobacteriaceae ESBL-positive strains Carbapenem-resistant strains Legionella pneumophila Burkholderia cepacia Aspergillus spp.

TABLE 131-7 Pathogenic Mechanisms and Corresponding Prevention Strategies for Ventilator-Associated Pneumonia¶

Harrison's 22e, p.1030

PATHOGENIC MECHANISM	PREVENTION STRATEGY
Oropharyngeal colonization with pathogenic bacteria
Elimination of normal flora, overgrowth by pathogenic bacteria	Avoidance of prolonged antibiotic courses; consider oral chlorhexidinea
Large-volume oropharyngeal aspiration around time of intubation	Short course of prophylactic antibiotics for comatose patients; short course of prophylactic inhaled aminoglycoside antibioticsb
Gastroesophageal reflux	Postpyloric enteral feeding with orally placed feeding tubea; avoidance of high gastric residuals, prokinetic agents
Bacterial overgrowth of stomach	Avoidance of prophylactic agents that raise gastric pHa; selective decontamination of digestive tract with nonabsorbable antibioticsa
Large-volume aspiration Ventilator circuit humidification	Endotracheal intubation; rapid-sequence intubation technique; avoidance of sedation; decompression of small-bowel obstruction Change ventilator circuits only when soiled and with new patient; drain ventilator circuit condensate away from patient; replace heat moisture exchanger every 5–7 days or if soiled or malfunctioninga
Altered lower respiratory host defenses	Tight glycemic controla; lowering of hemoglobin transfusion threshold

TABLE 131-8 Empirical Antibiotic Treatment of Hospital-Acquired and Ventilator-Associated Pneumonia NO¶

Harrison's 22e, p.1032

NO RISK FACTORS FOR RESISTANT GRAM-NEGATIVE PATHOGEN	RISK FACTORS FOR RESISTANT GRAM-NEGATIVE PATHOGENa (CHOOSE ONE FROM EACH COLUMN)
Piperacillin- tazobactam (4.5 g IV q6h) Cefepime (2 g IV q8h) Levofloxacin (750 mg IV q24h)	Piperacillin-tazobactam (4.5 g IV q6h) Cefepime (2 g IV q8h) Ceftazidime (2 g IV q8h) Imipenem (500 mg IV q6h) Meropenem (1 g IV q8h) Consider newer agentsc	Amikacin (15–20 mg/kg IV q24h) Gentamicin (5–7 mg/kg IV q24h) Tobramycin (5–7 mg/kg IV q24h) Ciprofloxacin (400 mg IV q8h) Levofloxacin (750 mg IV q24h) Colistin (loading dose of 5 mg/kg IV followed by maintenance doses of 2.5 mg × [1.5 × CrCl + 30] IV q12h) Polymyxin B (2.5–3.0 mg/kg per day IV in 2 divided doses)
Risk Factors for MRSAb (Add to above)
Linezolid (600 mg IV q12h) or Adjusted-dose vancomycin (trough level, 15–20 mg/dL)