What is the recommended treatment for hospital-acquired pneumonia (HAP)?

Treatment of Hospital-Acquired Pneumonia

Risk-Stratified Empiric Antibiotic Therapy

For hospital-acquired pneumonia, treatment must be stratified based on mortality risk and MRSA risk factors, with low-risk patients receiving monotherapy (piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem) and high-risk patients requiring dual antipseudomonal coverage plus MRSA-active agents (vancomycin or linezolid). 1, 2

Low Mortality Risk WITHOUT MRSA Risk Factors

Use monotherapy with one of the following: 1, 2

• Piperacillin-tazobactam 4.5 g IV every 6 hours 2, 3
• Cefepime 1
• Levofloxacin 750 mg IV daily 2
• Imipenem 1
• Meropenem 1

Low Mortality Risk WITH MRSA Risk Factors

Use one antipseudomonal agent PLUS MRSA coverage: 1, 2

• Select one antipseudomonal agent from the list above 2
• PLUS vancomycin OR linezolid 1, 2, 4

High Mortality Risk OR Recent IV Antibiotics

Use two antipseudomonal agents from different classes PLUS MRSA coverage: 1, 2

• Select two agents from different classes: piperacillin-tazobactam, cefepime, ceftazidime, meropenem, imipenem, aztreonam, ciprofloxacin, levofloxacin, or aminoglycoside 2
• PLUS vancomycin OR linezolid 1, 2
• Critical caveat: Aminoglycosides should never be used as monotherapy, even when the isolate appears susceptible 2

Risk Factor Identification

MRSA Risk Factors (require MRSA coverage):

• Prior IV antibiotic use within 90 days 1, 2
• Hospitalization in a unit where >20% of S. aureus isolates are methicillin-resistant 1, 2
• Unknown MRSA prevalence in the unit 1, 2
• Prior detection of MRSA by culture 2

Mortality Risk Factors (require dual antipseudomonal coverage):

• Need for ventilatory support due to HAP 1, 2
• Septic shock 1, 2

Additional Risk Factors Requiring Dual Antipseudomonal Coverage:

• Structural lung disease (bronchiectasis, cystic fibrosis) 1, 5
• Gram stain showing numerous gram-negative bacilli 1, 2

Duration and Optimization

• Standard duration is 7 days, with adjustments based on clinical, radiologic, and laboratory improvements 1
• Consider extended infusions for beta-lactams to optimize drug exposure through pharmacokinetic/pharmacodynamic principles 1, 2, 5
• Base empiric therapy on local antibiogram data whenever possible 1, 2, 5
• Early, appropriate antibiotic therapy is critical as delays increase mortality 1, 6

De-escalation Strategy

• De-escalate therapy once culture results are available 1
• For Pseudomonas aeruginosa in patients not in septic shock, use monotherapy with an antibiotic to which the isolate is susceptible 1
• For P. aeruginosa patients remaining in septic shock when susceptibility results are known, continue combination therapy with two active agents 2, 7

Pathogen-Specific Considerations

For ESBL-Producing Gram-Negative Bacilli:

• Base therapy on antimicrobial susceptibility testing and patient-specific factors 1

For Carbapenem-Resistant Pathogens:

• Use intravenous polymyxins with adjunctive inhaled colistin for pathogens sensitive only to polymyxins 1

For Acinetobacter Species:

• Use carbapenem or ampicillin/sulbactam for susceptible isolates 1
• Use intravenous polymyxin with adjunctive inhaled colistin for isolates sensitive only to polymyxins 1

Administration Details

• Administer all agents by intravenous infusion over 30 minutes 3
• Piperacillin-tazobactam and aminoglycosides should be reconstituted, diluted, and administered separately (co-administration via Y-site can be done under certain conditions) 3

Critical Pitfalls to Avoid

• Never use aminoglycosides as monotherapy for HAP, even when the isolate appears susceptible 2
• Do not delay empiric antibiotics while awaiting cultures, as delays are associated with increased mortality 1, 6
• Monitor for nephrotoxicity in critically ill patients receiving piperacillin-tazobactam, as it is an independent risk factor for renal failure 3
• Adjust dosing in renal impairment (creatinine clearance ≤40 mL/min) 3