Treatment of Pneumonia in Hospitalized Patients
For patients who develop pneumonia while already hospitalized (hospital-acquired pneumonia), treatment depends critically on timing of onset, risk factors for multidrug-resistant organisms, and severity of illness—with early-onset cases (<5 days) without MDR risk factors treated with narrower-spectrum agents, while late-onset or high-risk patients require broad-spectrum coverage including antipseudomonal and anti-MRSA therapy. 1
Classification and Initial Assessment
The key distinction is whether this represents hospital-acquired pneumonia (HAP) developing ≥48 hours after admission versus healthcare-associated pneumonia (HCAP) in a patient with recent healthcare contact 1. For true HAP in currently hospitalized patients, stratify by:
- Timing: Early-onset (<5 days) vs late-onset (≥5 days) 1
- MDR risk factors: Prior IV antibiotics within 90 days, high local MRSA prevalence (>20%), structural lung disease, immunosuppression 1
- Severity: ICU-level care, septic shock, or need for mechanical ventilation 1
Empiric Antibiotic Regimens
Low-Risk HAP (Early-Onset, No MDR Risk Factors, Not Severely Ill)
Monotherapy with one of the following: 1
- Piperacillin-tazobactam 4.5 g IV q6h 1
- Cefepime 2 g IV q8h 1
- Levofloxacin 750 mg IV daily 1
- Imipenem 500 mg IV q6h or Meropenem 1 g IV q8h 1
These regimens provide coverage for methicillin-sensitive S. aureus (MSSA) and common gram-negative pathogens without Pseudomonas coverage 1.
Moderate-Risk HAP (MDR Risk Factors Present but Not Severely Ill)
Same monotherapy options as above, but with added consideration for MRSA coverage if: 1
- Prior IV antibiotic use within 90 days 1
- Hospitalization in unit where >20% of S. aureus isolates are methicillin-resistant 1
- Unknown local MRSA prevalence 1
If MRSA coverage needed, add: 1
- Vancomycin 15 mg/kg IV q8-12h (target trough 15-20 mg/mL; consider loading dose 25-30 mg/kg for severe illness) 1
- OR Linezolid 600 mg IV q12h 1
High-Risk HAP (Severe Illness, ICU-Level Care, or Recent Antibiotics)
Dual antipseudomonal therapy PLUS anti-MRSA coverage: 1
Choose TWO from different classes (avoid two β-lactams): 1
- Antipseudomonal β-lactam: Piperacillin-tazobactam 4.5 g IV q6h, cefepime or ceftazidime 2 g IV q8h, imipenem 500 mg IV q6h, or meropenem 1 g IV q8h 1
- Fluoroquinolone: Levofloxacin 750 mg IV daily or ciprofloxacin 400 mg IV q8h 1
- Aminoglycoside: Amikacin 15-20 mg/kg IV daily, gentamicin 5-7 mg/kg IV daily, or tobramycin 5-7 mg/kg IV daily 1
- Aztreonam 2 g IV q8h (if severe penicillin allergy) 1
PLUS anti-MRSA agent: 1
Critical Implementation Points
Obtain Cultures Before Starting Antibiotics
Collect lower respiratory tract cultures from all patients before initiating therapy, but do not delay antibiotics in critically ill patients 1. Options include:
- Bronchoscopic sampling (bronchoalveolar lavage, protected specimen brush) 1
- Non-bronchoscopic sampling (endotracheal aspirate) 1
- Both quantitative and semiquantitative cultures are acceptable 1
Local Antibiogram Guidance
All hospitals should regularly generate and disseminate local antibiograms tailored to their HAP population 1. Empiric regimens must be based on local pathogen distribution and antimicrobial susceptibilities 1. This is particularly important as resistance patterns vary significantly between institutions 2.
Duration of Therapy
7-8 days is recommended for uncomplicated HAP with good clinical response and initially appropriate therapy 1. Extend to 14-21 days if: 1
- Legionella pneumonia confirmed or suspected 1
- Staphylococcal pneumonia 1
- Gram-negative enteric bacilli pneumonia 1
Biomarkers, particularly procalcitonin, may guide shorter treatment duration 1.
De-escalation Strategy
Once culture results and clinical response are available, narrow antibiotic spectrum (de-escalation) 1. This is a critical antimicrobial stewardship principle. Negative lower respiratory tract cultures obtained without recent antibiotic changes (within 72 hours) can be used to stop antibiotic therapy 1.
Switch to Oral Therapy
Sequential IV-to-oral therapy should be considered in all patients except the most severely ill once clinical stability is achieved 1. Clinical stability criteria typically include:
- Temperature ≤37.8°C 1
- Heart rate ≤100 bpm 1
- Respiratory rate ≤24 breaths/min 1
- Systolic blood pressure ≥90 mmHg 1
- Oxygen saturation ≥90% on room air 1
Most patients do not need to remain hospitalized after switching to oral therapy 1.
Common Pitfalls and Caveats
Avoid Underdosing in Severe Illness
Use adequate doses to optimize antimicrobial efficacy, particularly in critically ill patients 1. For example, meropenem can be dosed up to 6 g daily (3 × 2 g in 3-hour infusions) for severe Pseudomonas infections 1.
Consider Structural Lung Disease
Patients with bronchiectasis or cystic fibrosis require two antipseudomonal agents due to increased risk of gram-negative infection 1.
Monitor for Nephrotoxicity
Piperacillin-tazobactam use is an independent risk factor for renal failure in critically ill patients and may delay recovery of renal function compared to other β-lactams 3. Close monitoring of renal function is essential 3.
Adjust for Renal Impairment
Dosage reduction is required for patients with creatinine clearance ≤40 mL/min and those on dialysis 3. Failure to adjust doses increases risk of neurotoxicity and seizures 3.
Recognize Aminoglycoside Limitations
When using aminoglycosides in combination with β-lactams for Pseudomonas pneumonia, consider short-duration therapy (5 days) to minimize toxicity 1. Aminoglycosides and piperacillin-tazobactam should be reconstituted and administered separately, though co-administration via Y-site is acceptable under certain conditions 3.
Don't Modify Inadequate Initial Therapy Too Late
Modifying initially inadequate therapy after microbiological results does not improve outcomes 2. This underscores the critical importance of appropriate initial empiric coverage based on risk stratification 2.