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Evaluation
CURB65 Scoring System for Mortality Risk Assessment
The CURB65 scoring system may be used as a prognostic baseline for patients
diagnosed with hospital-acquired pneumonia.
Prognostic Features (1 point for each feature present)
- Confusion (abbreviated Mental Test score ≤8 or new disorientation)
- Increased blood urea nitrogen (≥7 mmol/L)
- Increased respiratory rate (≥30 breaths/minute)
- Decreased blood pressure (≤90/60 mmHg)
- ≥65 years old
Stratification
- 0 or 1: Low risk (<3% mortality risk)
- 2: Moderate risk (3-15% mortality risk)
- 3-5: High risk (>15% mortality risk)
Clinical improvement usually becomes apparent within the first 48-72
hours, wherein antibiotics should not be changed unless progressive
deterioration is noted.

Follow-up on Day 2 or 3 of Therapy
Follow-up includes checking cultures/sensitivities, assessing the patient’s clinical response, and assessing the purulence of sputum. Chest X-rays may have limited value in documenting improvement because results lag behind clinical parameters, especially in the elderly and in those with comorbidities. Monitor for hemodynamic changes, check organ function, oxygenation (eg partial pressure of oxygen [PaO2], fraction of inspired oxygen [FiO2]), temperature, and WBC.
Consider serial measurements of serum biomarkers (eg CRP, procalcitonin [PCT], copeptin, mid-regional pro-atrial natriuretic peptide [MR-proANP]) to assess disease severity and response to treatment. CRP and PCT can help guide de-escalation of treatment and serve as prognostic markers for prediction of morbidity and mortality.
Principles of Therapy
Initiation of Empiric Therapy
Antibiotic therapy should be started within 4 hours after the diagnosis
of hospital-acquired pneumonia 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 there is clinical evidence of bacterial
co-infection. All patients with HAP and VAP should be treated initially with IV
therapy, but a 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 the 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, but they should also 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.
Pharmacological therapy
EMPIRIC THERAPY IN PATIENTS WITH NO RISK FACTORS FOR
MULTIDRUG-RESISTANT (MDR) PATHOGENS
Narrow-spectrum antibiotics are recommended for patients with low-risk hospital-acquired
pneumonia/ventilator-associated pneumonia.
Possible Pathogens
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 a minimum inhibitory
concentration (MIC) of 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)
Hospital-acquired Pneumonia (HAP)/Ventilator-associated Pneumonia
(VAP)
Low-risk patients without risk factors for methicillin-resistant Staphylococcus
aureus will likely respond to monotherapy with one of the following agents:
- Beta-lactam/beta-lactamase inhibitor combination (eg Co-amoxiclav, Piperacillin/tazobactam)
- Non-pseudomonal third-generation cephalosporins (eg Ceftriaxone, Cefotaxime)
- Quinolones (eg Levofloxacin or Moxifloxacin)
Consider
Doxycycline, Cefalexin or Cotrimoxazole for patients with low-severity HAP. 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, consider treatment with
Oxacillin, Nafcillin, or Cefazolin. Ceftobiprole, a fifth-generation
cephalosporin that demonstrated good in vitro activity against Gram-positive and
Gram-negative bacteria, may be used especially in cases of high MRSA infection
risk.

EMPIRIC THERAPY IN PATIENTS WITH RISK FACTORS FOR MULTIDRUG-RESISTANT (MDR) PATHOGENS
Broad-spectrum antibiotics with activity against multidrug-resistant 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.
Possible Pathogens
Multidrug-resistant (MDR) Pathogens
- Pseudomonas aeruginosa, K pneumoniae, Acinetobacter sp, and Stenotrophomonas maltophilia
- ESBL Enterobacteriaceae
- MRSA should be considered if MRSA risk factors (eg antibiotic therapy prior to onset of pneumonia, prolonged hospital stay) are present, the presence of severe pneumonia/sepsis and/or if there is high local incidence
- Legionella pneumophila
Hospital-acquired Pneumonia (HAP)
Monotherapy may be sufficient for patients at high risk but with
>90% Gram-negative antibiotic activity. Combination therapy with two
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 hospital-acquired pneumonia patients at high
risk for methicillin-resistant Staphylococcus aureus 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 third- and fourth-generation cephalosporins (eg Cefepime, Ceftazidime)
- Antipseudomonal fluoroquinolone (eg Ciprofloxacin, Levofloxacin): In combination with another drug class
Aztreonam may be considered if there is treatment failure with other
agents. The use of an aminoglycoside (eg Amikacin, Gentamicin, Tobramycin) in
combination with another drug class may be 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, consider
treatment with Oxacillin, Nafcillin or Cefazolin. Other recently approved
agents include Ceftazidime/avibactam, Ceftolozane/tazobactam, Cefiderocol, Imipenem/cilastatin/relebactam
and Sulbactam/Durlobactam.
Ventilator-associated Pneumonia (VAP)
Vancomycin or Linezolid is recommended for patients at high risk for methicillin-resistant
Staphylococcus aureus (>10-20% MRSA isolates).
Two 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 third- and fourth-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. The use of polymyxins (eg Colistin, Polymyxin B)
instead of an aminoglycoside or quinolone may be considered in ICU patients with
Acinetobacter etiology or if a high prevalence of multidrug resistance
is present; these 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,
and Meropenem/vaborbactam, and Sulbactam/durlobactam.

Specific Pathogens
Pseudomonal Infection
Definitive therapy based on susceptibility tests is recommended instead of empiric therapy if positive for P Âaeruginosa infection. Monotherapy based on susceptibility test is preferred in HAP/VAP patients without comorbidities rather than combination therapy. For patients with comorbidities and at high risk for mortality with known antibiotic susceptibility test results, a combination of two antibiotics based on susceptibility tests is recommended. 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 the patient remains unresponsive.
Acinetobacter sp
Acinetobacter sp has 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. Aminoglycosides generally may not be effective against Acinetobacter sp; however, Netilmicin has been shown to be effective in 50% of strains based on an Asian study.
Extended-spectrum Beta-lactamase (ESBL) Enterobacteriaceae
Therapy based on antibiotic susceptibility testing and the presence of comorbidities are recommended. Carbapenems 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 third- and fourth-generation cephalosporins should not be used as monotherapy if this organism is suspected. If Enterobacter sp is suspected, third-generation cephalosporins should be avoided because of the possible emergence of resistance during treatment. If L pneumophila co-infection or superinfection is suspected, the 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 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.
Nonpharmacological
Supportive Therapy
Oxygen (O2) Therapy
Indications
for Continuous Oxygen Therapy
- Patient with PaO2 <8 kPa (60 mmHg)
- Hypotension with systolic blood pressure <100 mmHg
- Metabolic acidosis with bicarbonate <18 mmol/L
- Respiratory distress with a respiratory rate >24 breaths/minute
Goal
of Oxygen Therapy
The
goal of O2 therapy is to maintain PaO2 ≥8 kPa (60 mmHg)
or oxygen saturation (SaO2) ≥92%.

Other Therapies
Other therapies include adequate hydration and nutritional support.
Prevention
The
recommended preventive measures for ventilator-associated pneumonia and/or ventilator-associated
events (VAE) by the Society for Healthcare Epidemiology of America (SHEA), the
Infectious Diseases Society of America (IDSA) and the Association for
Professionals in Infection Control and Epidemiology (APIC) include the
following:
- Avoidance of intubation and use of non-invasive positive pressure ventilation (NIPPV) instead
- Reducing the use of sedatives, and assessing the patient's readiness for extubation by interruption of sedation and spontaneous awakening trials
- Physical conditioning and positioning such as early exercise and mobilization and head-of-bed elevation to 30°-45°
- Physical conditioning and positioning such as early exercise and mobilization and head-of-bed elevation to 30°-45°
- Provide early enteral rather than parenteral nutrition
- Ventilation circuit maintenance on as-needed basis only
- Instillation of saline solution before tracheal suctioning
The
recommended additional approaches by SHEA, IDSA and APIC for patients with ventilator-associated
pneumonia and/or ventilator-associated events are as follows:
- For patients requiring mechanical ventilation, selective oral decontamination with Chlorhexidine or other topical non-absorbable antibiotics may be considered to eliminate potential pathogens from the oropharyngeal tract. A selective digestive decontamination by the application of topical non-absorbable antimicrobial agents to the oropharynx and gastrointestinal tract together with IV antibiotics may also be considered in patients at low risk for antibiotic resistance.
- Endotracheal tubes with subglottic secretion drainage ports should be used for patients expected to require >48-72 hours of mechanical ventilation
- Consider early tracheostomy
- Post-pyloric feeding should be considered for patients with gastric intolerance or at high risk for aspiration in place of gastric feeding
Recommended
preventive measures for non-ventilator-hospital-acquired pneumonia (NV-HAP) by
the SHEA, IDSA and APIC include the following:
- Teeth and mouth hygiene: Regular oral care with tooth brushing
- Diagnose and manage dysphagia
- Provide early mobilization
Interventions against viral infections include:
- Screening of patients and healthcare workers for symptoms of viral infection
- All admitted patients to undergo surveillance testing
- Precautions against viral transmission should be placed for patients with suspected and confirmed respiratory viral infections
- Universal masking should be implemented when respiratory viral transmission rates are high in the hospital or community
- Assuring adequate ventilation
- Vaccination of healthcare personnel and patients
The
prevention bundle includes heterogeneous combinations of oral hygiene, bed
positioning, dysphagia diagnosis and management, mobilizing patients, nasal
hygiene, sedation restrictions, incentive spirometry, education for physicians and
nurses, and/or electronic order-set bundles. Encourage healthcare workers and
at-risk patients to receive influenza and pneumococcal vaccines.