What is the recommended empiric antibiotic therapy for new onset Hospital-Acquired Pneumonia (HAP)?

Empiric Antibiotic Therapy for New Onset Hospital-Acquired Pneumonia

For new onset HAP, prescribe an antipseudomonal beta-lactam (piperacillin-tazobactam 4.5g IV q6h, cefepime 2g IV q8h, or meropenem 1g IV q8h) as monotherapy if the patient has no MRSA risk factors and is not at high risk of mortality; add vancomycin 15mg/kg IV q8-12h or linezolid 600mg IV q12h for MRSA coverage if the patient has prior IV antibiotic use within 90 days, is in a unit where >20% of S. aureus isolates are methicillin-resistant, or has high mortality risk (ventilatory support or septic shock). 1

Risk Stratification Framework

The decision algorithm hinges on two critical assessments that must be made immediately:

MRSA Risk Assessment

Empiric MRSA coverage is indicated when ANY of the following are present: 1

• Prior intravenous antibiotic use within 90 days
• Treatment in a unit where >20% of S. aureus isolates are methicillin-resistant (or prevalence unknown)
• High mortality risk: need for ventilatory support due to HAP or septic shock

Mortality Risk Assessment

High mortality risk is defined as: 1

• Need for ventilatory support due to HAP
• Septic shock at time of presentation

Empiric Antibiotic Regimens

Low-Risk HAP (No MRSA Risk Factors, Not High Mortality Risk)

Monotherapy with ONE of the following: 1

• Piperacillin-tazobactam 4.5g IV q6h
• Cefepime 2g IV q8h
• Levofloxacin 750mg IV daily
• Imipenem 500mg IV q6h
• Meropenem 1g IV q8h

These regimens provide adequate MSSA coverage without requiring separate anti-staphylococcal agents. 1 Cefepime demonstrates optimal pharmacodynamic exposure with standard dosing, achieving >90% probability of target attainment against common HAP pathogens. 2

Moderate-Risk HAP (MRSA Risk Factors Present, But Not High Mortality Risk)

Monotherapy PLUS MRSA coverage: 1

Choose ONE antipseudomonal agent:

• 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

PLUS MRSA coverage with ONE of:

• Vancomycin 15mg/kg IV q8-12h (target trough 15-20 mg/mL; consider loading dose 25-30mg/kg IV × 1 for severe illness)
• Linezolid 600mg IV q12h

The 2016 IDSA/ATS guidelines strongly recommend vancomycin or linezolid over alternative MRSA agents based on superior evidence. 1

High-Risk HAP (High Mortality Risk OR Prior IV Antibiotics Within 90 Days)

Double antipseudomonal coverage PLUS MRSA coverage: 1, 3

Choose TWO antipseudomonal agents from DIFFERENT classes (avoid two beta-lactams):

Beta-lactam options:

• Piperacillin-tazobactam 4.5g IV q6h
• Cefepime or ceftazidime 2g IV q8h
• Imipenem 500mg IV q6h
• Meropenem 1g IV q8h
• Aztreonam 2g IV q8h

Second agent options:

• Levofloxacin 750mg IV daily
• Ciprofloxacin 400mg IV q8h
• Amikacin 15-20mg/kg IV daily
• Gentamicin 5-7mg/kg IV daily
• Tobramycin 5-7mg/kg IV daily

PLUS MRSA coverage:

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

Critical Implementation Details

Infusion Strategy

All IV antibiotics should be infused over approximately 30 minutes. 1, 4 For beta-lactams, consider extended infusions (3 hours) to optimize pharmacokinetic/pharmacodynamic parameters, particularly for late-onset or severe HAP. 3, 2 Extended infusions of cefepime 2g q8h, ceftazidime 2g q8h, and meropenem 2g q8h achieve >90% probability of optimal pharmacodynamic exposure. 2

Local Antibiogram Integration

Empiric regimens must be informed by local distribution of pathogens and their antimicrobial susceptibilities, as institutional resistance patterns vary significantly. 1, 3 Hospitals should regularly generate and disseminate local antibiograms tailored to their HAP population. 1

Treatment Duration

Standard duration is 7-8 days for uncomplicated HAP if clinical stability is achieved. 3, 5 This shorter duration applies to patients who receive initially appropriate therapy and demonstrate good clinical response. 1

Common Pitfalls and How to Avoid Them

Aminoglycoside Selection

Prefer fluoroquinolones over aminoglycosides as the second antipseudomonal agent when possible. 3 Aminoglycoside regimens were associated with lower clinical response rates with no mortality benefit in IDSA/ATS analyses. 3 If aminoglycosides are used, limit duration to 5 days when combined with a beta-lactam for P. aeruginosa. 1

Severe Penicillin Allergy

If using aztreonam due to severe penicillin allergy, add MSSA coverage (vancomycin or linezolid) because aztreonam lacks gram-positive activity. 3

De-escalation Strategy

Obtain appropriate respiratory cultures before initiating antibiotics, then de-escalate therapy once culture results return. 3 This narrows coverage and reduces selection pressure for resistance. 3 Negative lower respiratory tract cultures obtained in the absence of antibiotic changes within 72 hours can be used to stop antibiotic therapy. 1

Renal Dose Adjustment

Adjust cefepime dosing in patients with creatinine clearance ≤60 mL/min to prevent neurotoxicity. 4 Serious adverse reactions have occurred in geriatric patients with renal impairment given unadjusted doses. 4

Structural Lung Disease

If the patient has structural lung disease increasing risk of gram-negative infection (bronchiectasis or cystic fibrosis), use two antipseudomonal agents regardless of other risk factors. 1

Carbapenem-Resistant Organisms

Reserve colistin and polymyxin B only for settings with high prevalence of carbapenem-resistant organisms and local expertise in using these medications, given significant nephrotoxicity risks. 3