What is the recommended empiric antibiotic therapy for hospital-acquired pneumonia (HAP)?

Empiric Antibiotic Therapy for Hospital-Acquired Pneumonia (HAP)

For patients with hospital-acquired pneumonia, empiric antibiotic therapy should be based on risk factors for mortality and MRSA, with patients at low risk of mortality and without MRSA risk factors receiving monotherapy with piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem, while patients at high risk of mortality or with MRSA risk factors should receive combination therapy with two antipseudomonal agents plus MRSA coverage. 1

Risk Stratification for HAP Treatment

Low Risk of Mortality and No MRSA Risk Factors

• Use one of the following as monotherapy 1:
  • Piperacillin-tazobactam 4.5 g IV q6h
  • Cefepime 2 g IV q8h
  • Levofloxacin 750 mg IV daily
  • Imipenem 500 mg IV q6h
  • Meropenem 1 g IV q8h

Low Risk of Mortality but With MRSA Risk Factors

• Use one of the following antipseudomonal agents 1:
  • Piperacillin-tazobactam 4.5 g IV q6h
  • Cefepime or ceftazidime 2 g IV q8h
  • Levofloxacin 750 mg IV daily
  • Ciprofloxacin 400 mg IV q8h
  • Imipenem 500 mg IV q6h
  • Meropenem 1 g IV q8h
  • Aztreonam 2 g IV q8h (if severe penicillin allergy)
• Plus MRSA coverage with 1:
  • Vancomycin or linezolid

High Risk of Mortality or Recent IV Antibiotics

• Use two antipseudomonal agents from different classes 1:
  • Options include piperacillin-tazobactam, cefepime, ceftazidime, meropenem, imipenem, aztreonam, ciprofloxacin, levofloxacin, or an aminoglycoside
• Plus MRSA coverage with 1:
  • Vancomycin or linezolid
• Avoid using aminoglycoside as the sole antipseudomonal agent 1

Risk Factors to Consider

MRSA Risk Factors 1, 2:

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

Mortality Risk Factors 1:

• Need for ventilatory support due to HAP
• Septic shock

Risk Factors for Gram-Negative Infections 1:

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

Dosing Considerations

• Dosing should be optimized using pharmacokinetic/pharmacodynamic principles rather than simply following manufacturer's prescribing information 1
• Extended infusions may be appropriate for beta-lactams to optimize drug exposure 1
• For patients with HAP due to P. aeruginosa, definitive therapy should be based on antimicrobial susceptibility testing results 1

Important Caveats

• Empiric therapy should be based on local antibiogram data whenever possible 1, 3
• Early appropriate therapy is critical as inadequate initial coverage is associated with increased mortality, longer hospital stays, and higher healthcare costs 3, 4
• De-escalation of therapy should be performed once culture results are available to minimize antibiotic resistance 4
• For patients with HAP due to P. aeruginosa who remain in septic shock when susceptibility results are known, combination therapy with two active agents is suggested 1
• Aminoglycosides should never be used as monotherapy for HAP, even when the isolate appears susceptible 1

Special Considerations

• For patients with severe penicillin allergy, aztreonam can be used as an alternative, but should be combined with coverage for MSSA 1, 2
• Levofloxacin is indicated for nosocomial pneumonia due to methicillin-susceptible S. aureus and various gram-negative pathogens, but not for MRSA 5
• For patients with HAP due to multidrug-resistant gram-negative pathogens, newer antibiotics like ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, or cefiderocol may be considered 6