Pneumonia%20-%20hospital-acquired Treatment

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
• Empiric antibiotic therapy may be started in patients suspected of viral pneumonia if with clinical evidence of bacterial co-infection
• All patients with HAP and ventilator-associated pneumonia (VAP) should be treated initially with intravenous (IV) therapy, but switch to oral therapy may be considered in some patients who are responding to therapy

Choice of Antibiotics for Empiric Therapy

• Empiric choice of antibiotic agents should take into consideration the local microbiology, availability, cost and formulary restrictions
  • Initial empiric therapy should be adapted to local patterns of antibiotic resistance and 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 with confirmed HAP
• Not only should appropriate antibiotics be used, they should be used at the optimum doses and correct route of administration
• A major risk factor for mortality and increasing length of hospital stay is the administration of inappropriate antibiotics

• Narrow-spectrum antibiotics are recommended for patients with low-risk HAP/VAP

• Streptococcus pneumoniae
  • Local resistance patterns should be followed because the frequency of Penicillin-resistant and multidrug- resistant S pneumoniae is increasing
  • An aminopenicillin at appropriate dose remains the treatment of choice for most Penicillin-resistant S pneumoniae with 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)

• Low-risk HAP patients without risk factors for Methicillin-resistant Staphylococcus aureus (MRSA) will likely respond to monotherapy with 1 of the following agents:
  • Beta-lactam/beta-lactamase inhibitor combinations (eg Co-amoxiclav, Piperacillin/tazobactam)
  • Nonpseudomonal 3rd generation cephalosporins (eg Cefepime, Ceftazidime, Ceftriaxone, or Cefotaxime)
  • Quinolones (eg Levofloxacin or Moxifloxacin)
• May consider Doxycycline, Cefalexin or Cotrimoxazole for patients with low-severity HAP 
• May consider treatment with Ertapenem, Imipenem or Meropenem in patients with increased risk for extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacillus and with contraindications to Cefepime
• If MSSA is confirmed, may consider treatment with Oxacillin, Nafcillin, or Cefazolin

• Broad-spectrum antibiotics with activity against MDR pathogens are recommended for patients with high risk 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

• All the pathogens listed in section Empiric Therapy in Patients with No Risk Factors for MDR Pathogens are possible causative organisms

• Pseudomonas aeruginosa, K pneumoniae, Acinetobacter sp, and 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 and/or if there is high local incidence
• Legionella pneumophila

• Vancomycin or Linezolid is recommended for patients at high risk for MRSA (>10-20% MRSA isolates)
  • 2 antipseudomonal antibiotics are recommended if with >10% resistance to recommended monotherapy and for ICU patients
    • Antipseudomonal beta-lactam/beta-lactamase inhibitor (eg Piperacillin/tazobactam, Cefoperazone/sulbactam)
    • Antipseudomonal carbapenems Imipenem or Meropenem
    • Antipseudomonal 3rd- and 4th-generation cephalosporins Cefepime or Ceftazidime
    • Aztreonam: May be considered if with treatment failure with other agents
• If combination therapy is indicated, an aminoglycoside (eg Amikacin, Gentamicin or Tobramycin) or antipseudomonal quinolone (Ciprofloxacin or Levofloxacin) may be considered as secondary agents
  • Aminoglycoside therapy should be discontinued once susceptibility to beta-lactam therapy is confirmed and if with clinical improvement
  • Use of polymyxins (eg Colistin, Polymyxin B) instead of an aminoglycoside or quinolone may be considered in ICU patients with Acinetobacter etiology or if high prevalence of multidrug resistance is present; should not be used if other Gram-negative antibiotics are available
• Telavancin may be considered in patients with MRSA pneumonia when neither Linezolid nor Vancomycin can be used
• Other recently approved agents include Ceftazidime/avibactam, Ceftolozane/tazobactam, Cefiderocol, Imipenem/cilastatin/relebactam, Meropenem/vaborbactam, and Sulbactam/durlobactam

• Monotherapy may be sufficient for patients at high risk but with >90% Gram-negative antibiotic activity
• Combination therapy with 2 different classes of antibiotics is recommended for HAP patients with increased risk for Pseudomonas sp or other Gram-negative infection, patients who received IV antibiotics within the last 90 days, or those at high risk for mortality
• Recommended therapy for HAP patients at high risk for MRSA and Gram-negative pathogens but low risk for mortality:
  • Antipseudomonal beta-lactam/beta-lactamase inhibitor (eg Piperacillin/tazobactam, Cefoperazone/sulbactam, Ceftazidime/avibactam, Ceftolozane/tazobactam, Meropenem/vaborbactam)
  • Antipseudomonal carbapenems Imipenem or Meropenem
  • Antipseudomonal 3rd- and 4th-generation cephalosporins (eg Cefepime, Ceftazidime)
  • Antipseudomonal fluoroquinolone (eg Ciprofloxacin, Levofloxacin): In combination with another drug class
  • Aztreonam: May be considered if with treatment failure with other agents
• Use of an aminoglycoside (eg Amikacin, Gentamicin, Tobramycin) in combination with another drug class maybe considered in patients who received IV antibiotics within the last 90 days
• Addition of Vancomycin, Linezolid or Teicoplanin is recommended for patients at high risk for MRSA (>10-20% MRSA isolates)
  • Telavancin may be considered in patients with MRSA pneumonia when neither Linezolid nor Vancomycin can be used
  • Tedizolid may be considered in patients who are able to take oral medications
• If MSSA is confirmed, may consider treatment with Oxacillin, Nafcillin, or Cefazolin
• Other recently approved agents include Ceftazidime/avibactam, Ceftolozane/tazobactam, Cefiderocol, Imipenem/cilastatin/relebactam, and Sulbactam/durlobactam

Pseudomonal Infection

• Definitive therapy based on susceptibility tests is recommended instead of empiric therapy if positive for P aeruginosa infection
• Monotherapy based on susceptibility test is preferred in HAP/VAP patients with pseudomonal infection without comorbidities rather than combination therapy 
  • For patients with comorbidities and at high risk for mortality with known antibiotic susceptibility test result, combination of 2 antibiotics based on susceptibility test is recommended
• 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 and 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 with Pseudomonas sp bacteremia are less likely to die when combination therapy is used
• Polymyxins may be given as an alternative drug if patient remains unresponsive

• Acinetobacter sp have native resistance to many classes of antibiotics
• Carbapenems, Sulbactam (eg Ampicillin/sulbactam, Cefoperazone/sulbactam, Sulbactam/durlobactam) and Polymyxins B or E (eg Colistin) tend to be the most consistently effective agents
  • Carbapenem-resistant clones can be a problem and therefore, optimal dosing should be used
  • IV Polymyxins (eg Colistin, Polymyxin B) are recommended for HAP/VAP patients with carbapenem-resistant strains; adjunctive inhaled Colistin may also be considered
  • Sulbactam/Durlobactam, a beta-lactam-beta-lactamase inhibitor combination, is used for HAP/VAP patients with susceptible isolates of Acinetobacter baumannii-calcoaceticus complex
• 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

• Therapy based on antibiotic susceptibility testing and presence of comorbidities are recommended 
• Carbapanems are generally a reliable choice
• Piperacillin/tazobactam has been proven to be highly active in vitro against K pneumoniae and E coli
• Cephalosporin susceptibility is variable, therefore 3rd- and 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 co-infection or superinfection is suspected, antibiotic regimen should include a macrolide (eg Azithromycin) or quinolone (eg Ciprofloxacin or Levofloxacin) rather than an aminoglycoside

• Vancomycin or Linezolid is recommended as first-line agent for MRSA
• Linezolid has been shown to have comparable efficacy to Vancomycin in patients with HAP
• Telavancin may be considered if Vancomycin and Linezolid are unavailable or with treatment failure but benefits should outweigh the risk
• Tedizolid may be considered in patients who are able to take oral medications