What are the recommended IV antibiotics for hospital-acquired pneumonia?

IV Antibiotics for Hospital-Acquired Pneumonia

For hospital-acquired pneumonia (HAP), the recommended IV antibiotic regimen depends on risk factors for multidrug-resistant pathogens, with piperacillin-tazobactam 4.5g IV every 6 hours plus an aminoglycoside being the first-line treatment for patients at high risk of mortality or with risk factors for resistant pathogens. 1

Risk Stratification for HAP Treatment

Patients NOT at high risk of mortality and NO risk factors for MRSA:

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

Patients NOT at high risk of mortality but WITH risk factors for MRSA:

• Monotherapy with one of the following:
  • Piperacillin-tazobactam 4.5g IV q6h
  • Cefepime or ceftazidime 2g IV q8h
  • Levofloxacin 750mg IV daily
  • Ciprofloxacin 400mg IV q8h
  • Imipenem 500mg IV q6h
  • Meropenem 1g IV q8h
  • Aztreonam 2g IV q8h 1

Patients at HIGH risk of mortality OR received IV antibiotics within 90 days:

• Combination therapy with TWO of the following (avoid using two β-lactams):

  • Piperacillin-tazobactam 4.5g IV q6h
  • Cefepime or ceftazidime 2g IV q8h
  • Levofloxacin 750mg IV daily
  • Ciprofloxacin 400mg IV q8h
  • Imipenem 500mg IV q6h
  • Meropenem 1g IV q8h
  • Amikacin 15-20mg/kg IV daily
  • Gentamicin 5-7mg/kg IV daily
  • Tobramycin 5-7mg/kg IV daily
  • Aztreonam 2g IV q8h 1

• PLUS one of the following for MRSA coverage:

  • Vancomycin 15mg/kg IV q8-12h (target trough 15-20mg/mL)
  • Linezolid 600mg IV q12h 1

Risk Factors for MRSA and Multidrug-Resistant Pathogens

• Prior IV antibiotic use within 90 days
• Hospitalization in a unit where >20% of S. aureus isolates are methicillin-resistant
• Unknown local MRSA prevalence
• High risk for mortality (need for ventilatory support or septic shock) 1

Special Considerations for Pseudomonas aeruginosa

For patients with suspected or confirmed Pseudomonas aeruginosa infection, combination therapy is recommended:

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, ceftazidime, imipenem, or meropenem) PLUS
• Aminoglycoside or antipseudomonal fluoroquinolone 1, 2

For nosocomial pneumonia caused by P. aeruginosa, the FDA-approved dosage of piperacillin-tazobactam is 4.5g IV every 6 hours plus an aminoglycoside, with treatment duration of 7-14 days 2

Duration of Therapy

• Standard duration for HAP: 7-10 days 2
• For nosocomial pneumonia: 7-14 days 2
• Consider shorter duration (≤8 days) in responding patients to minimize resistance development 3

Dosage Adjustments for Renal Impairment

For patients with renal impairment, dosage adjustment is necessary:

Creatinine clearance	HAP Dosage
>40 mL/min	4.5g IV q6h
20-40 mL/min	3.375g IV q6h
<20 mL/min	2.25g IV q6h
Hemodialysis	2.25g IV q8h (plus 0.75g after each dialysis)
CAPD	2.25g IV q8h [2]

Monitoring and Assessment

• Assess clinical response within 48-72 hours of initiating therapy
• Monitor for clinical stability criteria: temperature ≤37.8°C for 48 hours, heart rate ≤100 beats/min, respiratory rate ≤24 breaths/min, systolic BP ≥90 mmHg, and oxygen saturation ≥90% 3
• For patients on prolonged therapy, monitor hematologic tests due to potential hematological effects 2

Potential Pitfalls and Caveats

• Inadequate dosing: Standard dosing of piperacillin-tazobactam (4g/0.5g q8h) may provide insufficient concentrations in lung tissue for severe nosocomial pneumonia. Consider higher doses or combination therapy for severe infections 4
• Nephrotoxicity risk: Piperacillin-tazobactam has been associated with nephrotoxicity in critically ill patients 2
• Resistance development: Limit antibiotic exposure to minimize resistance development; use the narrowest-spectrum agent once susceptibilities are known 3
• Prolonged infusion consideration: Prolonged infusion of piperacillin-tazobactam (over 3 hours) may provide more stable plasma concentrations and better clinical outcomes compared to regular 30-minute infusions 5
• Neuromuscular excitability or seizures: Monitor patients with renal impairment or seizure disorders closely, as higher doses may increase risk 2

For multidrug-resistant Gram-negative pathogens, newer antibiotics such as ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, and cefiderocol may be considered based on susceptibility testing 6.