Hospital-acquired pneumonia (HAP) is defined as pneumonia occurring ≥48 hours after admission and excluding any infection that is incubating at the time of admission.
Ventilator-associated pneumonia (VAP) is described as pneumonia occurring >48-72 hours after endotracheal intubation and within 48 hours after removal of endotracheal tube.
Early-onset HAP or VAP is the pneumonia occurring within the first 4 days of hospitalization that may be cause by antibiotic-sensitive bacteria that usually carries a better diagnosis.
Late-onset HAP or VAP is the pneumonia occurring after ≥5 days. It is likely caused by multidrug-resistant pathogens associated with increased mortality and morbidity.

Principles of Therapy

Initiation of Empiric Therapy 

  • Antibiotic therapy should be started within 4 hours after diagnosis of hospital-acquired pneumonia (HAP) has been established
  • Prompt initiation of appropriate initial antibiotic therapy can decrease mortality
  • When deciding to start empiric therapy, treatment should be microbiologically-defined rather than empiric therapy-based
  • All patients w/ HAP & ventilator-associated pneumonia (VAP) should be treated initially w/ intravenous (IV) therapy, but switch to oral therapy may be considered in some patients who are responding to therapy
  • Initial treatment of healthcare-associated pneumonia (HCAP) should be similar to that of HAP & VAP since spectrum of pathogens closely resemble late-onset HAP & VAP

Choice of Antibiotics for Empiric Therapy

  • Empiric choice of antibiotic agents should take into consideration the local microbiology, availability, cost & formulary restrictions
    • Initial empiric therapy should be adapted to local patterns of antibiotic resistance & when possible each ICU should collect this information on a regular basis
  • Empiric therapy also needs to take into consideration what therapies the patient has received within the last 2 weeks
    • If patient has received antibiotics recently for a different infection, therapy should utilize an agent from a different antibiotic class for resistance is predicted by recent antibiotic exposure
  • An antibiotic course of 5-10 days is recommended for patients w/ confirmed HAP
  • Not only should appropriate antibiotics be used, they should be used at the optimum doses & correct route of administration
  • A major risk factor for mortality & increasing length of hospital stay is the administration of inappropriate antibiotics


Empiric Therapy in Patients w/ No Risk Factors for Multidrug-resistant (MDR) Pathogens
  • Narrow-spectrum antibiotics are recommended for patients w/ low-risk & early-onset HAP/VAP
Possible Pathogens
  • Streptococcus pneumoniae
    • Local resistance patterns should be followed because the frequency of Penicillin-resistant & multidrug- resistant S pneumoniae is increasing
    • An aminopenicillin at appropriate dose remains the treatment of choice for most Penicillin-resistant S pneumoniae w/ MIC ≤2 mcg/mL
  • Other potential pathogens
    • Haemophilus influenzae, Methicillin-sensitive Staphylococcus aureus (MSSA)
    • Gram-negative bacilli (eg Escherichia coli, Klebsiella pneumoniae, Enterobacter sp, Proteus sp, Serratia marcescens)
Early-onset hospital-acquired pneumonia (HAP)
  • Patients w/ early-onset HAP without risk factors for MDR organisms will likely respond to monotherapy w/ 1 of the following agents:
    • Beta-lactam/beta-lactamase inhibitor combinations (eg Piperacillin/tazobactam)
    • Nonpseudomonal 3rd generation cephalosporins (eg Ceftriaxone, Cefotaxime, Cefepime or Cefpirome)
    • Carbapenems without antipseudomonal activity (eg Ertapenem, Imipenem, Meropenem)
    • Quinolones (eg Levofloxacin or Moxifloxacin)
  • Patients who have allergy to beta-lactam agents may be given quinolone alone or monobactam plus Clindamycin
  • If combination therapy is indicated, quinolone or 3rd generation cephalosporins plus macrolide may be given
  • If MSSA is confirmed, may consider treatment w/ Oxacillin, Nafcillin, or Cefazolin
Early-onset ventilator-associated pneumonia (VAP)
  • The following agents are recommended in patients w/ early-onset VAP without risk factors for MDR organisms:
    • Antipseudomonal 4th generation cephalosporins
      • Cefepime & Cefpirome are more resistant to some beta-lactamases
    • Carbapenems w/ antipseudomonal activity (eg Imipenem or Meropenem)
    • Antipseudomonal beta-lactam/beta-lactamase inhibitors (eg Piperacillin/tazobactam)
    • Quinolones (eg Levofloxacin)
  • If combination therapy is indicated, the following are recommended: Quinolones or aminoglycosides w/ or without glycopeptides (eg Vancomycin or Teicoplanin) or Linezolid
    • Some authorities recommend beta-lactam agent & aminoglycoside combination regimen based on improved survival rate
  • If L pneumophila is suspected, a quinolone should be included rather than an aminoglycoside
  • If MSSA is confirmed, may consider treatment w/ Oxacillin, Nafcillin, or Cefazolin
Empiric Therapy in Patients w/ Risk Factors for Multidrug-resistant (MDR) Pathogens
  • Broad-spectrum antibiotics w/ activity against MDR pathogens are recommended for patients w/ high risk & early-onset HAP/VAP
  • Those at risk for the below organisms should initially receive a combination of broad-spectrum coverage
    • This will decrease the risk of inappropriate antibiotic therapy
  • Concurrent treatment w/ 2-3 drugs should be considered in patients w/ late-onset VAP
Possible Pathogens
  • All the pathogens listed in section Empiric Therapy in Patients w/ No Risk Factors for MDR Pathogens are possible causative organisms
Multidrug-resistant (MDR) pathogens
  • Pseudomonas aeruginosa, K pneumoniae, Acinetobacter sp, & Stenotrophomonas maltophilia
  • Extended-spectrum beta-lactamase-producing (ESBL) Enterobacteriaceae
  • MRSA should be considered if MRSA risk factors (eg antibiotic therapy prior to onset of pneumonia, prolonged hospital stay) are present, presence of severe pneumonia/sepsis &/or if there is high local incidence
  • Legionella pneumophila
Late-onset Hospital-acquired Pneumonia (HAP) & Ventilator-associated Pneumonia (VAP)
  • The following agents are given as primary agents in patients w/ late-onset HAP & VAP w/ risk factors for MDR organisms:
    • Antipseudomonal carbapenems (eg Imipenem or Meropenem)
    • Antipseudomonal beta-lactam/beta-lactamase inhibitors (eg Piperacillin/tazobactam)
    • Antipseudomonal cephalosporins: 3rd & 4th generation (eg Cefepime, Ceftazidime)
      • Recommended only in patients w/ late-onset HAP
    • Antipseudomonal quinolones (eg Ciprofloxacin or Levofloxacin)
    • Aztreonam may be considered if w/ treatment failure w/ other agents
  • If combination therapy is indicated, aminoglycosides (eg Amikacin, Gentamicin or Tobramycin) may be considered as secondary agents
  • Glycopeptides (eg Vancomycin, Telavancin) or Linezolid may be added in the regimen or as a 3rd drug if patient requires coverage for possible Methicillin-resistant S aureus (MRSA) pneumonia
  • 2 antipseudomonal agents from different classes are recommended if patient is at increased risk for antibiotic resistance, w/ >10% resistance during drug sensitivity testing, or an ICU patient
Specific Pathogens

Suspected Pseudomonal Infection

  • Empiric treatment should include an antipseudomonal beta-lactam or carbapenem plus a quinolone or an aminoglycoside especially in high-risk patients
  • Monotherapy based on susceptibility test is preferred in HAP/VAP patients w/ pseudomonal infection without comorbidities rather than combination therapy 
  • Choice of specific agents if Pseudomonas sp is found should be based on the results of sensitivity testing
  • Pseudomonas sp can rapidly develop resistance to all classes of antibiotics & resistance develops in 30-50% of patients who receive monotherapy
    • Evidence is lacking to show that this does not occur when combination therapy is used but there is limited data showing patients w/ Pseudomonas sp bacteremia are less likely to die when combination therapy is used
  • Polymyxins B or E may be given as an alternative drug if patient remains unresponsive
Acinetobacter sp
  • Acinetobacter sp have native resistance to many classes of antibiotics
  • Carbapenems, Sulbactam (eg Ampicillin/sulbactam or Cefoperazone/sulbactam) & Polymyxins B or E (eg Colistin) tend to be the most consistently effective agents
    • Carbapenem-resistant clones can be a problem & therefore, optimal dosing should be used
    • IV Polymyxins (eg Colistin, Polymyxin B) are recommended for HAP/VAP patients w/ carbapenem-resistant strains; adjunctive inhaled Colistin may also be considered
  • Combination therapy of Imipenem plus Ampicillin/sulbactam or Sulbactam alone is recommended
  • Acinetobacter sp; however, Netilmicin has been shown to be effective in 50% of strains based on an Asian study
Extended-spectrum beta-lactamases (ESBL) Enterobacteriaceae
  • Carbapanems are generally a reliable choice
  • Tigecycline is effective against ESBL strains of K pneumoniae & E coli
  • Piperacillin/tazobactam has been proven to be highly active in vitro against K pneumoniae & E coli
  • Cephalosporin susceptibility is variable, therefore 3rd & 4th generation cephalosporins should not be used as monotherapy if this organism is suspected
    •  If Enterobacter sp is suspected, 3rd generation cephalosporins should be avoided because of possible emergence of resistance during treatment
  • If L pneumophila is suspected, antibiotic regimen should include a macrolide (eg Azithromycin) or quinolone (eg Ciprofloxacin or Levofloxacin) rather than an aminoglycoside
Methicillin-resistant Staphylococcus aureus (MRSA)
  • Vancomycin or Linezolid is recommended as1st-line agent for MRSA
  • Linezolid has been shown to have comparable or superior efficacy to Vancomycin in patients w/ HAP
  • Telavancin may be considered if Vancomycin & Linezolid are unavailable or w/ treatment failure but benefitsshould outweigh the risk
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