What are the latest guidelines for managing hospital-acquired pneumonia (HAP)?

Hospital-Acquired Pneumonia: Latest Guidelines

Definition and Diagnosis

Hospital-acquired pneumonia (HAP) is defined as pneumonia occurring ≥48 hours after hospitalization in non-intubated patients, and should be diagnosed based on clinical criteria including new or progressive radiographic infiltrates plus clinical signs (fever, leukocytosis, purulent secretions) rather than biomarkers alone. 1, 2

• Obtain respiratory samples (sputum or endotracheal aspirate) noninvasively before starting antibiotics to guide targeted therapy and enable subsequent de-escalation 2
• Distal quantitative samples are preferred in stable patients with suspected ventilator-associated pneumonia (VAP) to reduce unnecessary antibiotic exposure 2
• A common pitfall is over-diagnosis: approximately 35% of clinically diagnosed HAP cases lack radiological confirmation when objective criteria are applied 3

Risk Stratification for Empiric Therapy

Low-Risk HAP (Early-Onset, No MDR Risk Factors)

For patients with early-onset HAP (<5 days hospitalization) and no risk factors for multidrug-resistant (MDR) pathogens, use narrow-spectrum monotherapy. 2

Acceptable regimens include:

• Ertapenem 2
• Ceftriaxone 2
• Cefotaxime 2
• Moxifloxacin or levofloxacin 2

High-Risk HAP (Requires Broad-Spectrum Coverage)

Broad-spectrum empiric therapy targeting MRSA, Pseudomonas aeruginosa, and other gram-negative bacilli is mandatory for patients with any of the following risk factors: 1, 2

• Prior intravenous antibiotic use within 90 days 1, 2
• Hospitalization in a unit where >20% of S. aureus isolates are methicillin-resistant (MRSA) or MRSA prevalence is unknown 1
• Septic shock or need for ventilatory support due to HAP 1
• Hospitalization >5 days 2, 4
• Structural lung disease (bronchiectasis, cystic fibrosis) 1
• Prior colonization with MDR pathogens 2, 4

The 20% MRSA threshold was chosen to balance effective initial therapy against risks of excessive antibiotic use; individual units may adjust this threshold based on local epidemiology. 1

Empiric Antibiotic Regimens

For High-Risk HAP

Empiric therapy must include coverage for Pseudomonas aeruginosa and other gram-negative bacilli using an antipseudomonal beta-lactam. 1, 2

Recommended antipseudomonal beta-lactams:

• Piperacillin-tazobactam 1, 2, 3
• Cefepime 1, 2
• Meropenem 1, 2, 3
• Imipenem 1, 2

For patients with factors increasing likelihood of Pseudomonas infection (prior IV antibiotics within 90 days, structural lung disease) or high mortality risk (septic shock, ventilatory support), use combination therapy with two different antibiotic classes active against Pseudomonas. 1

Never use aminoglycosides as the sole antipseudomonal agent, even when the isolate appears susceptible. 1, 2

MRSA Coverage

When MRSA coverage is indicated, use either vancomycin or linezolid. 1

• The choice between vancomycin and linezolid should be guided by patient-specific factors including blood cell counts, concurrent serotonin-reuptake inhibitors, renal function, and cost 1
• For proven MRSA HAP/VAP, both agents are strongly recommended over other options 1

Common Pitfall: Ceftriaxone Plus Metronidazole

Ceftriaxone plus metronidazole is NOT appropriate empiric therapy for HAP because ceftriaxone lacks adequate coverage for Pseudomonas aeruginosa and other high-risk gram-negative pathogens. 5

• Metronidazole provides anaerobic coverage that is not routinely needed for HAP unless there is suspected aspiration with necrotizing pneumonia or lung abscess 5
• This regimen is a common error when clinicians mistakenly apply community-acquired pneumonia treatment principles to HAP 5

Pharmacokinetic/Pharmacodynamic Optimization

Antibiotic dosing should be determined using PK/PD data rather than standard manufacturer's prescribing information. 1

• Extended or continuous infusions of beta-lactams may be appropriate to optimize pharmacokinetics 1, 2
• Weight-based dosing should be used for certain antibiotics 1
• This approach prioritizes improving clinical outcomes through therapy optimization 1

Definitive Therapy Based on Culture Results

Pseudomonas aeruginosa

For HAP/VAP due to P. aeruginosa, base definitive therapy on antimicrobial susceptibility testing results. 1

For patients NOT in septic shock or at high risk for death (mortality risk <15%), use monotherapy with an antibiotic to which the isolate is susceptible. 1

For patients in septic shock or at high mortality risk (>25%) when susceptibility results are known, use combination therapy with two antibiotics to which the isolate is susceptible. 1

• If septic shock resolves when antimicrobial sensitivities are known, discontinue combination therapy 1
• Never use aminoglycoside monotherapy for P. aeruginosa 1

MRSA

For proven MRSA HAP/VAP, treat with either vancomycin or linezolid rather than other antibiotics. 1

MSSA

For proven methicillin-susceptible S. aureus (MSSA), oxacillin, nafcillin, or cefazolin are preferred agents. 1

ESBL-Producing Gram-Negative Bacilli

For HAP/VAP due to ESBL-producing organisms, base definitive therapy on antimicrobial susceptibility testing and patient-specific factors. 1

Highly Resistant Gram-Negative Bacilli

For VAP due to gram-negative bacilli susceptible only to aminoglycosides or polymyxins (colistin or polymyxin B), use both inhaled and systemic antibiotics rather than systemic antibiotics alone. 1

• Consider adjunctive inhaled antibiotic therapy as a treatment of last resort for patients not responding to intravenous antibiotics alone, regardless of MDR status 1

De-escalation and Duration of Therapy

The recommended duration for HAP treatment is 7-14 days, with shorter courses (7-8 days) appropriate for patients with uncomplicated HAP who received initially appropriate therapy and had a good clinical response. 1, 2

De-escalate therapy based on culture results and clinical response, typically by day 3. 2, 5

• Negative lower respiratory tract cultures obtained in the absence of an antibiotic change in the past 72 hours can be used to stop antibiotic therapy 1
• This approach balances effective treatment against risks of C. difficile infection, antimicrobial resistance, adverse drug effects, and increased cost 1

Key Algorithmic Approach

1. Obtain respiratory cultures before antibiotics 2
2. Assess risk factors for MDR pathogens (prior IV antibiotics within 90 days, >5 days hospitalization, septic shock, ventilatory support, structural lung disease, local MRSA prevalence >20%) 1, 2
3. If NO risk factors: Use narrow-spectrum monotherapy (ertapenem, ceftriaxone, levofloxacin) 2
4. If risk factors present: Use antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, meropenem, or imipenem) PLUS MRSA coverage (vancomycin or linezolid) if indicated 1, 2
5. If high mortality risk or prior IV antibiotics within 90 days: Add second antipseudomonal agent from different class 1
6. Review cultures at 48-72 hours and de-escalate 2, 5
7. Treat for 7-14 days based on clinical response 1, 2