What is the recommended treatment for Hospital-Acquired Pneumonia (HAP)?

Treatment of Hospital-Acquired Pneumonia (HAP)

For hospital-acquired pneumonia, stratify patients by risk factors for multidrug-resistant (MDR) pathogens and mortality, then initiate empiric antibiotics accordingly: low-risk patients without MRSA risk factors receive narrow-spectrum monotherapy with piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem, while high-risk patients require dual antipseudomonal therapy plus MRSA coverage with vancomycin or linezolid. 1, 2, 3

Risk Stratification Framework

Low-Risk HAP Criteria

• Patients qualify as low-risk when they have all of the following: no septic shock, no prior IV antibiotic use within 90 days, hospitalization ≤5 days, no previous MDR colonization, and local ICU resistance rates <25% for MDR pathogens 1
• These patients can receive narrow-spectrum monotherapy 1, 2, 3

High-Risk HAP Criteria

• Patients are high-risk if they present with septic shock and/or any of the following: prior IV antibiotic use within 90 days, prolonged hospitalization (>5 days), previous MDR colonization, or local ICU resistance rates >25% for MDR pathogens 1
• Additional mortality risk factors include need for ventilatory support due to HAP 2

MRSA Risk Factors (Separate Assessment)

• Prior IV antibiotic use within 90 days 4, 2, 3
• Hospitalization in a unit where >10-20% of S. aureus isolates are methicillin-resistant 4, 2, 3
• Unknown MRSA prevalence in the unit 2, 3

Empiric Antibiotic Regimens

Low-Risk HAP Without MRSA Risk Factors

• Use monotherapy with one of the following: 1, 2, 3
  • Piperacillin-tazobactam 4.5g IV q6h 1, 3, 5
  • Cefepime 2g IV q8h 1, 2, 3
  • Levofloxacin 750 mg IV/PO daily 1, 2, 3
  • Meropenem 1g IV q8h 1, 2, 3
  • Imipenem 500mg IV q6h 1, 2, 3
• Ertapenem, ceftriaxone, cefotaxime, or moxifloxacin are also acceptable alternatives 1
• Important caveat: Third-generation cephalosporins carry higher risk of Clostridioides difficile infection compared to penicillins or quinolones 1

Low-Risk HAP With MRSA Risk Factors

• Use the same monotherapy options listed above plus MRSA coverage 2, 3
• For MRSA coverage, add: 1, 2
  • Vancomycin 15 mg/kg IV q8-12h, or
  • Linezolid 600 mg IV/PO q12h

High-Risk HAP (With or Without MRSA Risk Factors)

• Initiate dual antipseudomonal therapy from different classes plus MRSA coverage 1, 2
• Choose two antipseudomonal agents from different classes: 1, 2
  • Antipseudomonal beta-lactams: piperacillin-tazobactam 4.5g IV q6h, cefepime 2g IV q8h, meropenem 1g IV q8h, or imipenem 500mg IV q6h
  • Fluoroquinolones: levofloxacin 750 mg IV daily or ciprofloxacin
  • Aminoglycosides (for nosocomial pneumonia specifically) 5, 6
• Plus vancomycin or linezolid for MRSA coverage 1, 2

Special Populations Requiring Dual Antipseudomonal Therapy

• Patients with structural lung disease (bronchiectasis, cystic fibrosis) require two antipseudomonal agents regardless of other risk factors 2, 3
• Patients with gram stain showing numerous gram-negative bacilli 2
• Patients with septic shock at time of HAP 4
• Patients with ARDS preceding HAP 4
• Patients on acute renal replacement therapy prior to HAP onset 4

Critical Pitfalls to Avoid

• Never use aminoglycosides as monotherapy for HAP, even when the isolate appears susceptible, as this is associated with treatment failure 3
• Never combine two β-lactams together in combination regimens, as they have overlapping mechanisms and do not provide synergy 3
• Never delay empiric antibiotics while awaiting cultures—inappropriate or delayed therapy greatly increases mortality 2, 7

Microbiological Sampling and De-escalation

Culture Collection

• Obtain lower respiratory tract samples (distal quantitative, proximal quantitative, or qualitative culture) before initiating antibiotics to guide de-escalation 1
• Distal quantitative samples in stable patients reduce antibiotic exposure and improve diagnostic accuracy 1
• Sputum cultures are positive in only 24.7% of clinical HAP cases, but when positive, predominantly grow gram-negative bacilli or S. aureus 8

Reassessment and Tailoring

• Reassess at 48-72 hours using temperature trends, white blood cell count, chest radiography, oxygenation parameters, and hemodynamic stability 1
• Tailor therapy to culture susceptibilities by day 3—this represents good practice 1, 2
• De-escalate from combination to monotherapy once cultures identify susceptible organisms, unless treating extensively drug-resistant (XDR)/pandrug-resistant (PDR) nonfermenting gram-negatives or carbapenem-resistant Enterobacteriaceae 1
• For Pseudomonas aeruginosa, use monotherapy with an antibiotic to which the isolate is susceptible for patients not in septic shock 2

Duration of Therapy

• Treat for 7-8 days in patients with good clinical response, no immunodeficiency, and no complications (lung abscess, empyema, cavitation, necrotizing pneumonia) 4, 1, 2
• Longer courses (up to 14 days) may be necessary for immunocompromised patients, those with complications, or inadequate initial empiric therapy 1, 5

Pharmacokinetic Optimization

• Consider extended infusions for β-lactams (infusing over 3-4 hours rather than 30 minutes) to optimize time-dependent killing and drug exposure 2, 3
• Dose based on pharmacokinetic/pharmacodynamic principles rather than simply following standard prescribing information, particularly in critically ill patients 3

Local Antibiogram Considerations

• All empiric regimens must be based on local antibiogram data whenever possible, as resistance patterns vary significantly between institutions 1, 2, 3
• The ICU-specific resistance rate (not hospital-wide) is the relevant factor for determining empiric coverage 1
• The threshold of >20% MRSA prevalence for empiric MRSA coverage can be adjusted based on local epidemiology 3
• Negative culture results are most reliable when obtained before antibiotics or within 72 hours of antibiotic changes 1