What is the best approach for managing hospital-acquired pneumonia (HAP) in any location?

Management of Hospital-Acquired Pneumonia (HAP)

Base your empiric antibiotic selection on risk stratification for multidrug-resistant (MDR) pathogens and mortality risk, using local ICU-specific antibiograms to guide therapy. 1, 2

Risk Stratification Framework

Stratify patients into low-risk versus high-risk categories before selecting antibiotics:

Low-risk patients have ALL of the following: 1, 2

• No septic shock or need for ventilatory support
• No prior IV antibiotic use within 90 days
• Hospitalization ≤5 days
• No previous MDR pathogen colonization
• Local ICU resistance rates <25% for MDR pathogens

High-risk patients have ANY of the following: 3, 1

• Septic shock or need for ventilatory support due to HAP
• Prior IV antibiotic use within 90 days
• Hospitalization >5 days
• Previous MDR colonization
• Unit where >20% of S. aureus isolates are methicillin-resistant (or MRSA prevalence unknown)
• Local ICU resistance rates >25% for MDR pathogens

Empiric Antibiotic Selection

For Low-Risk HAP (No MDR Risk Factors, No High Mortality Risk)

Use narrow-spectrum monotherapy with ONE of: 3, 1, 2

• Piperacillin-tazobactam 4.5g IV q6h
• Cefepime 2g IV q8h
• Levofloxacin 750mg IV daily
• Meropenem 1g IV q8h
• Imipenem 500mg IV q6h
• Ertapenem, ceftriaxone, cefotaxime, or moxifloxacin (alternative options)

Caveat: Third-generation cephalosporins (ceftriaxone, cefotaxime) carry higher risk of Clostridioides difficile infection compared to penicillins or quinolones. 1

For High-Risk HAP (MDR Risk Factors or High Mortality Risk)

Use combination therapy with: 3, 1, 4

Antipseudomonal beta-lactam (choose ONE):

• Piperacillin-tazobactam 4.5g IV q6h
• Cefepime 2g IV q8h
• Meropenem 1g IV q8h
• Imipenem 500mg IV q6h

PLUS a second antipseudomonal agent (choose ONE): 3, 4

• Levofloxacin 750mg IV daily
• Ciprofloxacin 400mg IV q8h
• Amikacin 15-20 mg/kg IV daily
• Gentamicin 5-7 mg/kg IV daily
• Tobramycin 5-7 mg/kg IV daily

Avoid using two beta-lactams together. 3

PLUS MRSA coverage (if MRSA risk factors present): 3, 1

• Vancomycin 15 mg/kg IV q8-12h (target trough 15-20 mg/mL; consider loading dose 25-30 mg/kg for severe illness)
• OR Linezolid 600mg IV q12h

Critical pitfall: Aminoglycosides should NEVER be used as monotherapy for HAP, even when the isolate appears susceptible. 2, 4

Microbiological Sampling

Obtain lower respiratory tract samples BEFORE initiating antibiotics to guide subsequent de-escalation. 1, 2 Options include:

• Distal quantitative samples (preferred in stable patients for improved diagnostic accuracy and reduced antibiotic exposure) 1, 2
• Proximal quantitative samples
• Qualitative cultures

Timing matters: Negative culture results are most reliable when obtained before antibiotics or within 72 hours of antibiotic changes. 1

Reassessment and De-escalation

Reassess at 48-72 hours using: 1

• Temperature trends
• White blood cell count
• Chest radiography
• Oxygenation parameters
• Hemodynamic stability

De-escalate by day 3 when culture susceptibilities return: 1, 2, 4

• Tailor therapy to culture results
• Switch from combination to monotherapy once susceptible organisms identified
• Exception: Maintain dual therapy for XDR/PDR nonfermenting gram-negatives or carbapenem-resistant Enterobacteriaceae 1

Duration of Therapy

Treat for 7-8 days in patients with: 1, 2

• Good clinical response
• No immunodeficiency
• No complications (lung abscess, empyema, cavitation, necrotizing pneumonia)

Longer courses required for: 1

• Immunocompromised patients
• Complications present
• Inadequate initial empiric therapy

Local Antibiogram Utilization

Use ICU-specific antibiograms, not hospital-wide data. 1, 2 The ICU resistance rate is the relevant factor for empiric therapy decisions. 1

All hospitals should regularly generate and disseminate local antibiograms tailored to their HAP population. 3

Special Considerations for Structural Lung Disease

If patient has bronchiectasis or cystic fibrosis, use two antipseudomonal agents due to increased risk of gram-negative infection. 3

Critical Pitfalls to Avoid

• Do not use aminoglycosides as sole antipseudomonal agent 4
• Do not assume hospital-wide antibiograms apply to ICU patients 4
• Do not use third-generation cephalosporins for empiric HAP 4
• Do not use linezolid empirically for suspected bacteremia 4
• Switch to daptomycin for MRSA coverage when vancomycin MIC >2 μg/mL 4
• Do not delay therapy while awaiting cultures 4

Mortality Considerations

Tigecycline should be avoided for HAP. Meta-analyses demonstrate increased all-cause mortality (4.0% vs 3.0% for comparators), with particularly poor outcomes in ventilator-associated pneumonia (mortality 19.1% vs 12.3%). 5 Reserve tigecycline only when alternative treatments are unsuitable. 5