What are the recommended antibiotic regimens for hospital-acquired pneumonia (HAP)?

Recommended Antibiotic Regimens for Hospital-Acquired Pneumonia (HAP)

For hospital-acquired pneumonia, empiric antibiotic therapy should be stratified based on risk factors for mortality and MRSA, with high-risk patients receiving combination therapy including an antipseudomonal agent plus MRSA coverage. 1

Risk Assessment and Initial Antibiotic Selection

Empiric antibiotic therapy for HAP should be guided by:

1. Risk of mortality
2. Risk factors for MRSA
3. Prior antibiotic exposure
4. Local antibiogram data

Low-Risk Patients

(Not at high risk of mortality AND no risk factors for MRSA)

Choose ONE of the following:

• 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 1

Moderate-Risk Patients

(Not at high risk of mortality BUT with risk factors for MRSA)

Choose ONE of the following:

• 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 (for severe penicillin allergy)

PLUS MRSA coverage with:

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

High-Risk Patients

(High risk of mortality OR receipt of IV antibiotics within 90 days)

Choose TWO of the following (avoid using two β-lactams):

• 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
• Amikacin 15-20 mg/kg IV daily
• Gentamicin 5-7 mg/kg IV daily
• Tobramycin 5-7 mg/kg IV daily
• Aztreonam 2 g IV q8h (for severe penicillin allergy)

PLUS MRSA coverage with:

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

Special Considerations

Pseudomonas aeruginosa Coverage

For nosocomial pneumonia caused by P. aeruginosa, combination therapy with an antipseudomonal β-lactam plus an aminoglycoside is recommended 1. The FDA label for piperacillin-tazobactam specifically notes that for nosocomial pneumonia, it should be administered at 4.5 g every six hours plus an aminoglycoside 2.

Duration of Therapy

• Standard HAP: 7-10 days
• Nosocomial pneumonia: 7-14 days 2

Immunocompromised Patients

For immunocompromised patients (e.g., those on chemotherapy), broader coverage is recommended with piperacillin-tazobactam plus vancomycin or linezolid due to higher risk of resistant organisms 3.

Antibiotic Adjustments for Renal Impairment

For patients with renal impairment, dosage adjustments are necessary:

Creatinine Clearance	HAP (non-nosocomial)	Nosocomial Pneumonia
>40 mL/min	3.375 g q6h	4.5 g q6h
20-40 mL/min	2.25 g q6h	3.375 g q6h
<20 mL/min	2.25 g q8h	2.25 g q6h
Hemodialysis	2.25 g q12h	2.25 g q8h
CAPD	2.25 g q12h	2.25 g q8h

2

Implementation of Therapy

1. Obtain cultures before initiating antibiotics whenever possible without delaying therapy
2. Reassess therapy at 48-72 hours based on clinical response and culture results
3. De-escalate therapy when possible based on culture results
4. Monitor for adverse effects including nephrotoxicity, especially in critically ill patients 1

Common Pitfalls to Avoid

• Inadequate initial coverage: Failure to cover likely pathogens increases mortality
• Delayed therapy: Each hour of delay in appropriate antibiotic therapy increases mortality
• Overuse of broad-spectrum agents: Contributes to antimicrobial resistance
• Failure to adjust for renal function: Increases risk of toxicity
• Inadequate dosing: Subtherapeutic concentrations can lead to treatment failure and resistance 1, 4

Pharmacodynamic studies show that meropenem, imipenem, cefepime, ceftazidime (2 g every 8 hrs), and piperacillin-tazobactam have high probabilities of achieving adequate pharmacodynamic exposures for empirical treatment of nosocomial pneumonia, while ciprofloxacin monotherapy has lower target attainment rates 5.