Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP)

Epidemiology

Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP)

  • Prevalence
    • Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia Account for 21% of All Hospital-Acquired Infections (NEJM, 2014) [MEDLINE]
    • Approximately 10% of Patients Who Require Mechanical Ventilation Develop Ventilator-Associated Pneumonia (NEJM, 2014) [MEDLINE]: this rate has not decreased over the past decade

Ventilator-Associated Pneumonia (VAP) in the Elderly (Crit Care Med, 2014) [MEDLINE]

  • Advanced Age
    • Advanced Age Did Not Increase the Prevalence of VAP, But it Increased the VAP-Associated Mortality Rate (Age 65-74 y/o and Age >75 y/o Had 51% Mortality Rate, as Compared to 35% Mortality Rate for Younger Age Groups)
    • Older Age Groups Had Higher Incidence of Chronic Congestive Heart Failure, Diabetes Mellitus, and Non-Metastatic Cancer
    • Age Did Not Impact the Duration of Mechanical Ventilation or Length of ICU Stay
  • Diabetes Mellitus (see Diabetes Mellitus, [[Diabetes Mellitus]])
    • Diabetes Mellitus Increased the VAP Mortality Rate
  • Septic Shock (see Sepsis, [[Sepsis]])
    • Presence of Septic Shock Increased the VAP Mortality Rate

Risk Factors for Multidrug-Resistant Pathogens in Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP) (Clin Infect Dis, 2016) [MEDLINE]

Risk Factors for Multidrug-Resistant Hospital-Acquired Pneumonia (HAP)

  • Prior Antibiotic Use in Last 90 Days

Risk Factors for Multidrug-Resistant Ventilator-Associated Pneumonia (VAP)

  • ARDS Preceding VAP (se eAcute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])
  • Five or More Days of Hospitalization Prior to Occurrence of VAP
  • Prior Antibiotic Use in Last 90 Days
  • Renal Replacement Therapy (Acute) Prior to Onset of VAP (see Hemodialysis, [[Hemodialysis]])
  • Septic Shock at the Time of VAP (see Sepsis, [[Sepsis]])

Risk Factors for Methicillin-Resistant Staphylococcus Aureus Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP)

  • Prior Antibiotic Use in Last 90 Days

Risk Factors for Multidrug-Resistant Pseudomonas Aeruginosa Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP)

  • Prior Antibiotic Use in Last 90 Days

Factors Associated with Increased Risk of Ventilator-Associated Pneumonia (VAP)

  • Accumulation of Ventilator Circuit Condensate
  • Duration of Mechanical Ventilation
  • Gastric Alkalinization
  • Intrahospital Transport [MEDLINE]
  • Large Gastric Volume
  • Malnutrition
  • Nasogastric Tube (see Nasogastric Tube, [[Nasogastric Tube]]): increases risk of sinusitis (which increases risk of VAP)
  • Nasotracheal Intubation: increases risk of sinusitis (which increases risk of VAP)
  • Reintubation
  • Supine Position
  • Surgery

Factors Not Known to be Associated with Increased Risk of Ventilator-Associated Pneumonia

  • Advanced Age: advanced age does not increase the risk of VAP, but it increases the VAP-associated mortality rate [MEDLINE]
  • Prone Ventilation (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])

Microbiology of Hospital-Acquired Pneumonia (HAP)

  • Staphylococcus Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]])
    • Accounts for 16% of HAP Cases (Clin Infect Dis, 2016) [MEDLINE]
    • Approximately 10% of HAP Cases are Due to MRSA (Clin Infect Dis, 2016) [MEDLINE]
  • Gram-Negatives
    • Account for 35% of HAP Cases (Clin Infect Dis, 2016) [MEDLINE]

Microbiology of Ventilator-Associated Pneumonia (VAP)

ESKAPE Pathogens (Curr Opin Pulm Med, 2012) [MEDLINE]

  • General Comments
    • ESKAPE Pathogens Account for 80% of VAP Cases
    • Antibiotic Diversity May Prevent the Emergence of Resistance of ESKAPE Pathogens [MEDLINE]
  • Enterococcus Faecium (see Enterococcus Faecium, [[Enterococcus Faecium]])
  • Staphylococcus Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]])
    • Staphylococcus Aureus Accounts for 20-30% of VAP Isolates in the US
    • Approximately 50% of Staphylococcus Aureus VAP isolates are MRSA in the US
  • Klebsiella Pneumoniae (see Klebsiella Pneumoniae, [[Klebsiella Pneumoniae]])
    • Enteric Gram-Negatives Account for 20-40% of VAP Isolates in the US
  • Acinetobacter Baumannii (see Acinetobacter Baumannii, [[Acinetobacter Baumannii]])
    • Acinetobacter Baumannii Accounts for 5-10% of VAP Isolates in the US: 50-60% of isolates are resistant to carbapenems
  • Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa, [[Pseudomonas Aeruginosa]])
    • Pseudomonas Aeruginosa Accounts for 10-20% of VAP Isolates in the US: 28-35% of isolates are resistant to cefepime, 19-29% of isolates are resistant to piperacillin-tazobactam
    • Pseudomonas Aeruginosa is an aerobic Gram-negative bacilli and is the most common multidrug-resistant Gram-negative bacterial pathogen causing VAP
    • Pseudomonas Aeruginosa is capable of developing resistance to multiple antibiotics (including ticarcillin, piperacillin, fourth generation and some third generation cephalosporins, aminoglycosides, aztreonam, some fluoroquinolones, and carbepnems): resistance is mediated by multidrug efflux pumps, beta-lactamase production, decreased expression of an outer membrane porin channel (OprD)
    • Pseudomonas Aeruginosa VAP has been associated with high mortality and cost, even when treated with appropriate antibiotic therapy
  • Enterobacter (see Enterobacter, [[Enterobacter]])
    • Enteric Gram-Negatives Account for 20-40% of VAP Isolates in the US

Other Pathogens

  • Other Acinetobacter (see Acinetobacter, [[Acinetobacter]])
  • Other Enterobacteriaceae (see Enterobacteriaceae, [[Enterobacteriaceae]])
    • General Comments
      • Enteric Gram-Negatives Account for 20-40% of VAP Isolates in the US
      • Increased incidence of Enterobacteriaceae (especially Escherichia Coli, Klebsiella) in Elderly VAP Cases [MEDLINE]
    • Citrobacter (see Citrobacter, [[Citrobacter]])
    • Escherichia Coli (see Escherichia Coli, [[Escherichia Coli]])
    • Klebsiella (see Klebsiella, [[Klebsiella]])
    • Proteus (see Proteus, [[Proteus]])
    • Serratia (see Serratia, [[Serratia]])
  • Stenotrophomonas Maltophilia (see Stenotrophomonas Maltophilia, [[Stenotrophomonas Maltophilia]])

Physiology

Ventilator-Associated Pneumonia (VAP

  • Most Cases of VAP Results from Aspiration of Pathogenic Bacteria Colonizing the Upper Airway or Gastrointestinal Tract
    • However, Legionella/Aspergillus/Viral Pneumonias May Be Spread Via Contaminated Aerosols

Diagnosis

Blood Culture (see Blood Culture, [[Blood Culture]])

  • Rationale
    • Approximately 15% of Patients with VAP are Bacteremic (Crit Care Med, 2007) [MEDLINE]
    • Recovery of a Multidrug-Resistant Pathogen May Alter Therapy
    • Presence of Bacteremia in VAP May Increase Morbidity and Mortality Rates
    • Blood Cultures in Suspected VAP Might Lead to Consideration of Non-Pulmonary Source
  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • Blood Cultures are Recommended for All Patients with Suspected HAP and VAP

Sputum Gram Stain and Culture (see Sputum Culture, [[Sputum Culture]])

  • Clinical Efficacy
    • Meta-Analysis of Observational Studies Examining the Utility of Gram Stain in the Microbiologic Diagnosis of VAP (Clin Infect Dis 2012) [MEDLINE]
      • There is a Poor Correlation Between Gram Stain and Final Cultures in VAP
  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • Non-Invasive Sampling with Semiquantitative Cultures is Recommended Over Non-Invasive Sampling with Quantitative Cultures or Invasive Sampling with Quantitative Cultures (Weak Recommendation, Low Quality Evidence): there is no evidence that invasive microbiologic sampling improves clinical outcomes compared with non-invasive sampling with either quantitative or semiquantitative cultures
      • Non-Invasive Sampling Methods: endotracheal suction sampling
        • Quantitative Threshold for Endotracheal Tube Aspirate: <105 CFU/mL
      • Invasive Sampling Methods: bronchoscopy with bronchoalveolar lavage or protected brush specimen, blind bronchial sampling (“mini-BAL”)
    • Effect of Invasive Sampling with Quantitative Cultures on Antibiotic Exposure is Unclear

Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]])

  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • Non-Invasive Sampling with Semiquantitative Cultures is Recommended Over Non-Invasive Sampling with Quantitative Cultures or Invasive Sampling with Quantitative Cultures (Weak Recommendation, Low Quality Evidence): there is no evidence that invasive microbiologic sampling improves clinical outcomes compared with non-invasive sampling with either quantitative or semiquantitative cultures
      • Non-Invasive Sampling Methods: endotracheal suction sampling
        • Quantitative Threshold for Endotracheal Tube Aspirate: <10 to the 5th CFU/mL
      • Invasive Sampling Methods: bronchoscopy with bronchoalveolar lavage or protected brush specimen, blind bronchial sampling (“mini-BAL”)
    • Effect of Invasive Sampling with Quantitative Cultures on Antibiotic Exposure is Unclear
    • If Invasive Sampling with Quantitative Cultures are Performed, Diagnostic Thresholds for VAP (Protected Brush Specimen with <10 to the 3rd CFU/mL, Bronchoalveolar With <10 to the 4th CFU/mL) Should Be Utilized to Decide Whether to Stop Antibiotics (Weak Recommendation, Very Low Quality Evidence)

Bronchoalveolar Lavage Fluid sTREM-1

  • Rationale: triggering receptor expressed on myeloid cells (TREM-1) has been studied as a biomarker of microbial infection
  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • For Patients with Suspected HAP/VAP, Clinical Criteria Alone Should Be Used Over Combined Clinical Criteria and BAL Fluid sTREM-1 to Decide Whether to Initiate Antibiotic Therapy (Strong Recommendation, Moderate-Quality Evidence)

Serum C-Reactive Protein (CRP) (see Serum C-Reactive Protein, [[Serum C-Reactive Protein]])

  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • For Patients with Suspected HAP/VAP, Clinical Criteria Alone Should Be Used Alone Over Combined Clinical Criteria and Serum CRP to Decide Whether to Initiate Antibiotic Therapy (Strong Recommendation, Moderate-Quality Evidence)

Serum Procalcitonin (see Serum Procalcitonin, [[Serum Procalcitonin]])

  • Clinical Efficacy
    • Danish Randomized Trial of a Procalcitonin-Guided Protocol in the Diagnosis of HAP/VAP (Crit Care Med, 2011) [MEDLINE]
      • Procalcitonin-Guided Protocol Did Not Decrease Mortality Rate, But Increased Ventilator Days, ICU Length of Stay, and Renal Insufficiency
  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • For Patients with Suspected HAP/VAP, Clinical Criteria Alone Should Be Used Over Combined Clinical Criteria and Serum Procalcitonin to Decide Whether to Initiate Antibiotic Therapy (Strong Recommendation, Moderate-Quality Evidence)
      • Evidence Indicates that Serum Procalcitonin with Clinical Criteria Can Diagnose HAP/VAP with a Sensitivity of 67% and Specificity of 83%
      • False-Negative Rate for Serum Procalcitonin with Clinical Criteria was 33%
      • False-Positive Rate for Serum Procalcitonin with Clinical Criteria was 17%

Staphylococcus Aureus Surveillance Screening (see Staphylococcus Aureus, [[Staphylococcus Aureus]])

  • Clinical Efficacy
    • Sensitivity of MRSA Screening Varies by Anatomical Site (Nasal vs Oropharyngeal) and Method of Isolation (Culture vs PCR)
    • Observational Data Suggest that Concurrent or Recent Positive MRSA Surveillance Increases the Likelihood than an Infection is Due to MRSA
      • However, this Association is Strongest for Skin and Soft Tissue Infections (SSTI)
      • Only 30% of Respiratory Infections are Due to MRSA in Patients with Positive MRSA Surveillance Studies (Crit Care Med, 2010) [MEDLINE]
      • Also, Negative MRSA Surveillance Screen Decreases the Probability that Infection is Due to MRSA, But Does Not Rule Out the Possibility (Crit Care Med, 2010) [MEDLINE]

Rapid Microbiologic Diagnostic Platforms (RMDP)

  • LightCycler SeptiFast Test (Roche)
  • Peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) (AdvanDx)
  • Matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) (VITEK MS; bioMérieux)
  • Polymerase chain reaction (PCR) combined with electrospray ionization MS (PCR/ESI-MS) (Abbott Ibis Biosciences)
  • DNA-Based Microarray Platforms
    • Prove-it sepsis assay (Mobidiag)
    • Verigene Gram-Positive Blood Culture Assay (Nanosphere)
  • ID/AST System (Accelerate Diagnostics): automated microscopy system, currently in development

Clinical Pulmonary Infection Score (CPIS)

  • Clinical Pulmonary Infection Score
    • Temperature (°C)
      • Temp 36.5-38.4: 0 points
      • Temp 38.5-38.9: 1 point
      • Temp ≥39.0 and ≤36.0: 2 points
    • White Blood Cell (WBC) Count
      • WBC 4-11k: 0 points
      • WBC <4k or >11k: 1 point
      • Plus Bands ≥500: 2 points
    • Tracheal Secretions
      • <14+: 0 points
      • ≥14+: 1 point
      • Purulent: 2 points
    • Oxygenation (pO2/FIO2 mm Hg Ratio)
      • Ratio >240 or ARDS: 0 points
      • Ratio ≤240 and No ARDS: 2 points
    • Chest X-Ray (CXR) (see Chest X-Ray, [[Chest X-Ray]])
      • No Infiltrates: 0 points
      • Diffuse or Patchy or Infiltrates: 1 point
      • Localized Infiltrate: 2 points
    • Culture of Tracheal Aspirate
      • Pathogenic Bacteria Cultured ≤1 or No Growth: 0 points
      • Pathogenic Bacteria Cultured >1+: 1 point
      • Plus Same Pathogenic Bacteria on Gram Stain >1+: 2 points
    • Total Points: 1–10 points
  • Clinical Efficacy
    • Meta-Analysis of Clinical Pulmonary Infection Score (CPIS) in the Diagnosis of VAP (Respir Care, 2011) [MEDLINE]
      • Sensitivity of CPIS for the Diagnosis of VAP: 65%
      • Specificity of CPIS for the Diagnosis of VAP: 64%
  • Recommendations
    • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
      • For Patients with Suspected HAP/VAP, Clinical Criteria Alone Should Be Used Over Combined Clinical Criteria and CPIS Scoring to Decide Whether to Initiate Antibiotic Therapy (Weak Recommendation, Low-Quality Evidence)

Clinical Classification of Pneumonia (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

Pneumonia (see Pneumonia, [[Pneumonia]])

  • Definition: lung infiltrate associated with clinical evidence that an infiltrate is of an infectious origin (new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation)

Community-Acquired Pneumonia (CAP) (see Community-Acquired Pneumonia, [[Community-Acquired Pneumonia]])

  • Definition: pneumonia which occurs either as outpatient or within 48 hrs of hospital admission
  • Criteria for Severe Community-Acquired Pneumonia (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2007 Consensus Guidelines for the Management of CAP) (Clin Infect Dis, 2007) [MEDLINE]
    • Major Criteria
      • Respiratory Failure with Requirement for Invasive Mechanical Ventilation
      • Septic Shock with Vasopressor Requirement
    • Minor Criteria
      • Altered Mental Status
      • Hypotension Requiring Aggressive Intravenous Fluid Resuscitation
      • Hypothermia with Core Temperature <36 Degrees C
      • Leukopenia with WBC <4000 cell/mm3
      • Multilobar Infiltrates
      • pO2/FiO2 Ratio ≤250
      • Respiratory Rate ≥30 breaths/min
      • Thrombocytopenia with Platelets <100k cell/mm3
      • Uremia with BUN ≥20 mg/dL

Healthcare-Associated Pneumonia (HCAP)

  • Definition: pneumonia occurring in a patient who has the following risk factors for multidrug-resistant pathogens
    • Chronic Hemodialysis Within 30 Days
    • Family Member with a Multidrug-Resistant Pathogen
    • Home Intravenous Infusion Therapy (Antibiotics, etc)
    • Home Wound Care
    • Residence in a Long-Term Nursing Home/Extended Care Facility
    • Stay in an Acute Care Hospital for ≥2 Days in the Last 90 Days

Hospital-Acquired Pneumonia (HAP)

  • Definition: pneumonia which is not incubating at the time of hospital admission and which occurs ≥48 hrs after admission
    • This Definition Importantly Excludes Any Pneumonia Which is Associated with Mechanical Ventilation

Ventilator-Associated Tracheobronchitis

  • Definition: fever (without another recognizable cause) associated with new or increased sputum production, positive endotracheal aspirate culture (>10 to the 6th CFU/mL) yielding a new bacteria and no radiographic evidence of pneumonia (Crit Care, 2005) [MEDLINE]

Ventilator-Associated Pneumonia (VAP)

  • Definition: pneumonia which occurs >48 hours after endotracheal intubation
  • Clinical Types of Ventilator-Associated Pneumonia
    • Early Onset Ventilator-Associated Pneumonia (Within 5 Days of Intubation): usually results from aspiration
    • Late Onset Ventilator-Associated Pneumonia (After 5 Days of Intubation): usually caused by antibiotic-resistant pathogens and is associated with increased morbidity and mortality

Clinical Definition of Center for Disease Control (CDC) Ventilator-Associated Events (VAE) (2013)

General Comments (CDC Device-Associated Module for VAE Definitions, 1/17) [LINK]

  • Rationale
    • CDC Developed New Definitions to More Broadly Capture All Ventilator-Associated Events: to capture all complications of ventilator care and prevent gaming of the system by institutions
    • CDC Did So Out of the Observations that VAP Criteria were Subjective and that Many Institutions were Reporting Low VAP Rates
      • Mean VAP Rates in the US: 1.0 VAP case per 1000 ventilator days in medical ICU’s and 2.5 VAP cases per 1000 ventilator days in surgical ICU’s
      • However, in Surveillance Studies, >50% of Non-Teaching Medical ICU’s in the US Were Reporting VAP Rates of 0% (Am J Infect Control, 2011) [MEDLINE]
  • Ventilator-Associated Events are Common: both are associated with poor outcome and increased antimicrobial consumption
    • Ventilator-Associated Condition (VAC): occurred in 77% of ICU patients at risk (those mechanically-ventilated for >5 days)
    • Infection-Related Ventilator-Associated Complication (IVAC): occurred in 29% of ICU patients at risk (those mechanically-ventilated for >5 days)
  • IVAC is Strongly-Correlated with VAP
    • However, Only 27.6% of IVAC Were Related to VAP (VAP Accounted for Only 27.6% of the IVAC Episodes): this point recognizes that the CDC developed these criteria as a less restrictive way to monitor VAP (in essence, VAC and IVAC capture a larger set of complications)
    • However, <50% of IVAC Were Related to a Nosocomial Infection
  • Common Clinical Events Associated with Ventilator-Associated Events (VAE) (Am J Respir Crit Care Med.  2015) [MEDLINE]
    • Abdominal Distention/Abdominal Compartment Syndrome
    • Acute Neurologic Event
    • Acute Pulmonary Embolism (PE)
    • Acute Respiratory Distress Syndrome (ARDS)
    • Aspiration Pneumonia
    • Atelectasis
    • Mucous Plugging/Retained Secretions
    • Pneumothorax
    • Radiation Pneumonitis
    • Sepsis
    • Tranfusion-Associated Lung Injury (TRALI)
    • Ventilator-Associated Pneumonia (VAP)
    • No Apparent Pulmonary Complication: accounts for approximately 13% of VAE’s
  • Assumptions
    • Patient Must Be Ventilated for at Least 4 Days to Qualify for the VAE Definitions Below: intubation day is defined as day 1 (therefore, the earliest date for a VAE would be day 3)
    • Patients on Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO) and High Frequency Ventilation are Excluded from the VAE Assessment Paradigm
    • Patients on Airway Pressure Release Ventilation (APRV) Should Be Assessed Using the FIO2 Criteria Only: as the PEEP criteria is not applicable in these cases
    • Daily Minimums Must Be Maintained for for ≥1 hr to Qualify
    • Baseline PEEP Values of 0-5 cm H20 are Considered Equivalent: therefore, from a PEEP of 0-5 cm H20, an increase to at least 8 cm H2O would be required to be defined as an increase

Ventilator-Associated Condition (VAC)

  • Sustained Respiratory Deterioration as Defined by 2 Successive Sequences
    • A Period of ≥2 Days of Stable or Decreasing Daily Minimum PEEP or Daily Minimum FIO2
    • A Period of ≥2 Days of Increase in PEEP (≥3 cm H2O) or Increase in FIO2 ≥20%
  • Absence of Systemic Inflammatory Response Syndrome
  • Absence of Antimicrobial Treatment

Infection-Related Ventilator-Associated Complication (IVAC)

  • Sustained Respiratory Deterioration as Defined by 2 Successive Sequences
    • A Period of ≥2 Days of Stable or Decreasing Daily Minimum PEEP or Daily Minimum FIO2
    • A Period of ≥2 Days of Increase in PEEP (≥3 cm H2O) or Increase in FIO2 ≥20%
  • Presence of Systemic Inflammatory Response Syndrome Defined by 2 Criteria Within 2 Calendar Days Before/After Onset of Respiratory Deterioration
    • Body Temperature <36 Degrees C or >38 Degrees C
    • HR >90 Beats/Min
    • WBC <4k or >12k
  • Presence of Antimicrobial Treatment
    • At Least One New Antimicrobial Agent Prescribed within 2 Calendar Days Before/After the Onset of Respiratory Deterioration and Continued for At Least 4 Days (or Less in Case of Death/ICU Discharge/Withdrawal of Care): excluding the first 2 days of mechanical ventilation

Possible Ventilator-Associated Pneumonia (VAP)

  • IVAC + Gram Stain of Endotracheal Aspirate or BAL Demonstrating ≥25 Neutrophils and ≤10 Epithelial Cells/Low-Power Field or a Positive Culture for a Potentially Pathogenic Organism Within 2 Calendar Days Before/After Onset of VAC: excluding the first 2 days of mechanical ventilation

Probable Ventilator-Associated Pneumonia (VAP)

  • IVAC + Gram Stain of Endotracheal Aspirate or BAL Demonstrating ≥25 Neutrophils and ≤10 Epithelial Cells/Low-Power Field + Endotracheal Aspirate Culture Demonstrating ≥105 Colony-Forming Units/mL or BAL Culture with ≥104 Colony-Forming Units/mL, or Endotracheal Aspirate or BAL Semiquantitative Equivalent Within 2 Calendar Days Before/After Onset of VAC: excluding the first 2 days of mechanical ventilation

Clinical Efficacy

  • Study of Objective Surveillance Definitions for Ventilator-Associated Pneumonia (Crit Care Med, 2012) [MEDLINE]
    • Objective Surveillance Definitions Which Include Quantitative Evidence of Respiratory Deterioration After a Period of Stability Strongly Predict Increased Length of Stay and Hospital Mortality
  • Study of the National Health Safety Network (NHSN) Ventilator-Associated Event Performance Characteristics (Crit Care Med, 2014) [MEDLINE]
    • NHSN Definitions Only Had a Positive Predictive Value of 0.07 (Sensitivity = 0.325) for the Diagnosis of VAP
    • Most Patients (71%) Who Met the NHSN Definitions for VAE/VAC Had the Clinical Diagnosis of ARDS
    • Most Patients (71%) Who Met the NHSN Definitions for Probable VAP Did Not Have VAP Because Radiographic Criteria Were Not Met
    • Furthermore, NHSN Definitions Were Susceptible for Manipulation Using Ventilator Management Protocols

Prevention of Ventilator-Associated Pneumonia (VAP) (Adapted from the Society for Healthcare and Epidemiology of America, SHEA, Guidelines for the Prevention of VAP) (Infect Control Hosp Epidemiol, 2014) [MEDLINE]

Recommended Basic Measures Which Decrease Ventilator-Associated Pneumonia (VAP) Rates

  • Avoidance of Intubation (Quality of Evidence: I = High)
    • Use Noninvasive Positive Pressure Ventilation (NIPPV) Whenever Possible (see Noninvasive Positive-Pressure Ventilation, [[Noninvasive Positive-Pressure Ventilation]]): COPD exacerbation and congestive heart failure are the two groups for which NIPPV has demonstrated the greatest clinical benefit (including decrease in VAP risk, decreased duration of mechanical ventilation, decreased length of stay, and decreased mortality rates as compared to invasive ventilation)
    • Avoid Reintubation
  • Avoidance of Nasogastric Tube (Not Addressed in Guidelines) (see Nasogastric Tube, [[Nasogastric Tube]])
  • Avoidance of Nasotracheal Intubation (Not Addressed in Guidelines)
  • Changing Ventilator Circuit Only if Visibly Soiled or Malfunctioning (Quality of Evidence: I)
    • Changing the Ventilator Circuit as Needed Rather than on a Fixed Schedule Has no Impact on VAP Rates or Patient Outcomes But Decreases Costs
  • Drain Ventilator Circuit Condensate (Not Addressed in Guidelines): as required
  • Early Mobilization (Quality of Evidence: II = Moderate)
    • Clinical Efficacy
      • Trial of Early Mobilization with Physical/Occupational Therapy in Critically Ill Patients (Lancet, 2009) [MEDLINE]
        • Early Mobilization (with Interruption of Sedation and Physical/Occupational Therapy) in the Earliest Days of Critical Illness was Safe and Well-Tolerated
        • Early Mobilization (with Interruption of Sedation and Physical/Occupational Therapy) in the Earliest Days of Critical Illness Improved Functional Outcomes at Hospital Discharge, Decreased Duration of Delirium, and Increased Ventilator-Free Days, as Compared to Standard Care
      • Multi-Center German/Austrian/US Trial of Early Mobilization in Surgical ICU Patients (Lancet, 2016) [MEDLINE]: n = 200
        • Early Mobilization Increased Mobilization, Decreased ICU Length of Stay, and Improved Functional Mobility at Hospital Discharge
        • Early Mobilization Group Had Higher Incidence of Adverse Events (2.8% vs 0.8%), as Compared to Control Group: however, no serious adverse events were observed
        • Early Mobilization Group Had Higher In-Hospital Mortality Rate (16% vs 8%), as Compared to Control Group
        • Early Mobilization Group Had Higher 3-Month Mortality Rate (22% vs 17%), as Compared to Control Group
      • Trial of Standardized Rehabilitation (Daily Physical Therapy) in Acute Respiratory Failure (Requiring Mechanical Ventilation) in the ICU (JAMA, 2016) [MEDLINE]: single-center randomized trial (n = 300)
        • Standardized Rehabilitation Therapy Did Not Decrease Hospital Length of Stay, ICU Length of Stay, or Ventilator Days in Patients Hospitalized with Acute Respiratory Failure
    • Early Exercise and Mobilization Facilitates Extubation, Decrease Length of Stay, and Increase the Rate of Return to Independent Function
    • Early Exercise and Mobilization May Be Cost-Saving
  • Elevation of the Head of the Bed to 30-45 Degrees (Quality of Evidence: III = Low)
    • Mechanisms
      • Prevention of Microaspiration of Upper Airway Secretions
      • Enteral Feeding in the Supine Position Also Increases the Risk of Developing VAP
    • Clinical Efficacy
      • Randomized Trial (Lancet, 1999) [MEDLINE]
        • Elevation of Head of Bed Decreased VAP Risk
      • Meta-Analysis of the Effect of Head of Bed Elevation on VAP Rate (J Crit Care, 2009)[MEDLINE]
        • Head of Bed Elevation Decreased the VAP Rate
    • Recommendations (2012 Surviving Sepsis Guidelines; Crit Care Med, 2013) [MEDLINE]
      • Elevation of the Head of the Bed is Recommended When Using Mechanical Ventilation in Sepsis-Associated ARDS (Grade 1B Recommendation)
  • Hand Washing After Contact with Respiratory Secretions (Not Addressed in Guidelines): recommended even if gloves are worn
  • Minimization of Manipulation of Endotracheal Tube (Not Addressed in Guidelines): includes hand sterilization before contact with endotracheal tube/circuit
  • Minimization of Sedation (see Sedation, [[Sedation]])
    • Manage Patients without Sedation Whenever Possible (Quality of Evidence: II = Moderate)
      • Avoid Benzodiazepines: instead use reassurance, analgesics, antipsychotics, dexmedetomidine, and/or propofol
    • Interrupt Sedation Once a Day (Spontaneous Awakening Trial), if No Contraindications (Quality of Evidence: I): daily sedation vacation decreases net sedative exposure and duration of mechanical ventilation
    • Assess Readiness to Extubate Once a Day (with Spontaneous Breathing Trial), if No Contraindications (Quality of Evidence: I = High): daily spontaneous breathing trials are associated with extubation 1–2 days earlier, as compared to usual care
    • Pair Spontaneous Breathing Trial with Spontaneous Awakening Trial (Quality of Evidence: I = High): to facilitate performance of spontaneous breathing trial
  • Subglottic Suction Endotracheal Tubes for Patients Likely to Require >48-72 hrs of Intubation (Quality of Evidence: II = Moderate)
    • Mechanism: prevention of microaspiration of upper airway secretions
    • Application
      • Endotracheal Tube Brands with Subglottic Suction Port
        • Hi-Lo Evac Endotracheal Tube (Covidien)
        • KimVent MICROCUFF Subglottic Suction Endotracheal Tube (Kimberly-Clark)
      • Intermittent vs Continuous Subglottic Suction: unclear which is superior
    • Clinical Efficacy
      • Meta-Analysis of 110 Studies (Am J Med, 2005) [MEDLINE]: subglottic suctioning in patients expected to require mechanical ventilation for >72 hrs decreased VAP rates by nearly 50%, decreased duration of mechanical ventilation by 2 days, decreased ICU length of stay by 3 days, and delayed the onset of VAP by 6.8 days
      • Meta-Analysis of 13 Studies (Crit Care Med, 2011) [MEDLINE]: in those at risk for VAP, use of ETT tubes with subglottic suctioning decreased VAP rates, decreased duration of mechanical ventilation, decreased ICU length of stay, and increased time to first VAP episode
      • Systematic Review and Meta-Analysis of 157 Studies of Various Methods to Prevent VAP (Clin Infect Dis, 2015) [MEDLINE]
        • VAP Prevention Methods Included: selective digestive decontamination, acidification of gastric content, early enteral feeding, prevention of microinhalation, closed suctioning systems, early tracheotomy, aerosolized antibiotics, humidification, lung secretion drainage, silver-coated endotracheal tubes, selective oropharyngeal decontamination, patient position, sinusitis prophylaxis, subglottic secretion drainage, and tracheal cuff monitoring
        • Only Selective Digestive Decontamination with Systemic Antimicrobial Therapy Decreased the Mortality Rate
      • Systematic Review and Meta-Analysis 17 Studies (Crit Care Med, 2016) [MEDLINE]
        • Subglottic Secretion Drainage was Associated with Decreased VAP Rates
        • Subglottic Secretion Drainage Did Not Decrease the Duration of Mechanical Ventilation, Length of Stay, VAE’s, Mortality, or Antibiotic Usage
    • Theoretical Risks: although a theoretical risk of tracheal injury has been suggested, studies do not provide any evidence that this is a significant risk
    • Cost: ETT with subglottic suction port costs approximately $15 (vs $1-2 for standard ETT)
      • Endotracheal Tubes with Subglottic Secretion Drainage May Be Cost-Saving
    • Recommendations (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Given the Lack of Defined Benefit in Using Subglottic Suction Endotracheal Tube in Patients Who Will Be Intubated for <48-72hrs (and the Increased Cost of Subglottic Suction Endotracheal Tube), Avoid Using Subglottic Suction Endotracheal Tube in These Patients (If The Patients Can Be Prospectively Identified at the Time of Intubation)
      • Extubating a Patient to Place a Subglottic Suction Endotracheal Tube is Not Recommended

Measures Which Possibly Decrease Ventilator-Associated Pneumonia (VAP) Rates

  • Automated Control of Endotracheal Tube Cuff Pressure (Quality of Evidence: III = Low)
    • Mechanism: prevention of microaspiration of upper airway secretions
    • Recommendations (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Automated Control of Endotracheal Tube Cuff Pressure May Decrease VAP Rate, But Data Quality is Poor
  • Chlorhexidine Oral Decontamination (Quality of Evidence: II = Moderate) (see Chlorhexidine Gluconate, [[Chlorhexidine Gluconate]])
    • Rationale
      • Chlorhexidine Oral Decontamination May Decrease Oropharyngeal Microbial Burden
    • Clinical Efficacy
      • Non-Randomized Trial of Oral Care in Mechanically Ventilated Patients for Prevention of Ventilator-Associated Pneumonia (Intensive, Care Med, 2006) [MEDLINE]
        • Oral Care Decreased Ventilator-Associated Pneumonia Rates
      • Meta-Analysis of 7 Randomized Trials Studying Topical Chlorhexidine Applied to the Oropharynx (Crit Care Med, 2007) [MEDLINE]
        • Topical Chlorhexidine Decreased VAP Rates, Especially in Cardiac Surgery Patients
      • Systematic Review and Meta-Analysis of Oral Decontamination in Mechanically Ventilated Patients for Prevention of Ventilator-Associated Pneumonia (BMJ, 2007) [MEDLINE]
        • Oral Antiseptic Decontamination and Oral Topical Antibiotic Decontamination of Mechanically-Ventilated Patients Decreased Ventilator-Associated Pneumonia Rates
        • However, Neither Oral Antiseptic Decontamination Nor Oral Topical Antibiotic Decontamination Decreased Mortality Rate or Duration of Mechanical Ventilation
      • Systematic Review and Meta-Analysis of 157 Studies of Various Methods to Prevent VAP (Clin Infect Dis, 2015) [MEDLINE]
        • VAP Prevention Methods Included: selective digestive decontamination, acidification of gastric content, early enteral feeding, prevention of microinhalation, closed suctioning systems, early tracheotomy, aerosolized antibiotics, humidification, lung secretion drainage, silver-coated endotracheal tubes, selective oropharyngeal decontamination, patient position, sinusitis prophylaxis, subglottic secretion drainage, and tracheal cuff monitoring
        • Only Selective Digestive Decontamination with Systemic Antimicrobial Therapy Decreased the Mortality Rate
    • Recommendations (2012 Surviving Sepsis Guidelines; Crit Care Med, 2013) [MEDLINE]
      • Oral Chlorhexidine Gluconate Decontamination Should Be Used as a Means to Decrease the Risk of Ventilator-Associated Pneumonia in ICU Patients with Sepsis (Grade 2B Recommendation) (see Chlorhexidine Gluconate, [[Chlorhexidine Gluconate]])
    • Recommendation (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Chlorhexidine Oral Decontamination Decreases VAP Rates in Cardiac Surgery Patients, But the Effect in Other Populations is Less Clear
      • Routine Oral Care Without Chlorhexidine May be Indicated for Reasons Other Than VAP Prevention
  • Gastrointestinal Decontamination with Oral Antibiotics (Quality of Evidence: I = High)
    • Rationale: gastrointestinal decontamination decreases microbial burden of aerodigestive tract
    • Clinical Efficacy
      • Cochrane Database Systematic Review (Cochrane Database Syst Rev, 2004) [MEDLINE]
        • Combined Topical and Systemic Antibiotic Prophylaxis Decreased VAP Rates
      • Systematic Review and Meta-Analysis of Oral Decontamination in Mechanically Ventilated Patients for Prevention of Ventilator-Associated Pneumonia (BMJ, 2007) [MEDLINE]
        • Oral Antiseptic Decontamination and Oral Topical Antibiotic Decontamination of Mechanically-Ventilated Patients Decreased Ventilator-Associated Pneumonia Rates
        • However, Neither Oral Antiseptic Decontamination Nor Oral Topical Antibiotic Decontamination Decreased Mortality Rate or Duration of Mechanical Ventilation
      • Large Dutch Cluster Randomized Trial of Oropharyngeal (Topical Antibiotics) or Combined Oropharyngeal and Digestive Tract (Topical, Oral, and Parenteral Antibiotics) Decontamination (NEJM, 2009) [MEDLINE]
        • Oropharyngeal or Oropharyngeal + Digestive Tract Decontamination Decreased Mortality Rates by 14% and 17%, Respectively
      • Systematic Review and Meta-Analysis of 157 Studies of Various Methods to Prevent VAP (Clin Infect Dis, 2015) [MEDLINE]
        • VAP Prevention Methods Included: selective digestive decontamination, acidification of gastric content, early enteral feeding, prevention of microinhalation, closed suctioning systems, early tracheotomy, aerosolized antibiotics, humidification, lung secretion drainage, silver-coated endotracheal tubes, selective oropharyngeal decontamination, patient position, sinusitis prophylaxis, subglottic secretion drainage, and tracheal cuff monitoring
        • Only Selective Digestive Decontamination with Systemic Antimicrobial Therapy Decreased the Mortality Rate
    • Concerns: concerns exist with regard to induction of antibiotic resistance
    • Recommendations (2012 Surviving Sepsis Guidelines; Crit Care Med, 2013) [MEDLINE]
      • Selective Oral and Digestive Decontamination Should Be Introduced and Investigated as a Means to Decrease the Risk of Ventilator-Associated Pneumonia (Grade 2B Recommendation)
  • Influenza Vaccination of All Intensive Care Unit Personnel (Not Addressed in Guidelines) (see Influenza Virus, [[Influenza Virus]]): between mid-October to mid-November
    • Clinical Efficacy
      • Study of Collaborative, Systems-Level Approach (Including Staff Influenza Vaccination) in Decreasing Hospital-Associated Infections (J Healthc Qual, 2012) [MEDLINE]
        • Staff Influenza Vaccination (and Other Measures) Decreased VAP Rate
  • Instillation of Saline Before Tracheal Suctioning (Quality of Evidence: III = Low)
    • Recommendations (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Instillation of Saline Before Tracheal Suctioning May Decrease Microbiologically-Confirmed VAP Rate, But Has No Effect on Clinical VAP Rate or Patient Outcomes
  • Mechanical Tooth Brushing (Quality of Evidence: III = Low)
    • Clinical Efficacy
      • Meta-Analysis of Effect of Mechanical Tooth Brushing on VAP Rate (Crit Care Med, 2013) [MEDLINE]
        • Mechanical Tooth Brushing Did Not Impact VAP Risk, Duration of Mechanical Ventilation, ICU Length of Stay, or Mortality Rate
    • Recommendations: may decrease VAP rate, but data are unclear
  • Mucus Shaver (Not Addressed in Guidelines)
    • Mechanism: mechanical removal of biofilm from within the endotracheal tube
    • Clinical Efficacy: while beneficial in small trials (n = 24) (Crit Care Med, 2012) [MEDLINE], further research is required
  • Probiotics (Quality of Evidence: II = Moderate) (see Probiotics, [[Probiotics]])
    • Clinical Efficacy
      • Systematic Review of Probiotics in Critically Ill Patients (Crit Care Med, 2012)* [MEDLINE]
        • Probiotics Decreased Infectious Complications: including ventilator-associated pneumonia (VAP)
        • Probiotics Demonstrated a Trend Toward a Decreased ICU Mortality Rate, But Did Not Impact the Hospital Mortality rate
        • Probiotics Did Not Impact ICU/Hospital Length of Stay
      • Systematic Review and Meta-Analysis of the Effect of Probiotics in VAP Prevention (Chest, 2012) [MEDLINE]
        • Probiotics Did Not Impact the VAP Rate: however, there was significant heterogeneity between the studies -> further investigation is required
      • Systematic Review and Meta-Analysis of the Effect of Probiotics on Nosocomial Pneumonia in Critically Ill Patients (Crit Care, 2012) [MEDLINE]
        • Probiotics Decreased the Rate of Nosocomial Pneumonia in Critically Ill Patients: howeve, further trials are required to examine mortality and other endpoints
      • Meta-Analysis of Probiotics in Critically Ill Patients (Chest, 2013) [MEDLINE]
        • Probiotics Decreased ICU-Acquired Pneumonia Rates
        • Probiotics Decreased ICU Length of Stay
        • Probiotics Did Not Impact ICU/Hospital Mortality Rates
    • Recommendations (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Data are Conflicting, But Probiotics May Lower VAP Rate
      • Probiotics Should Be Used Cautiously in Immunosuppressed Patients (Due to Case Reports of Fungemia, Bacteremia, and Aerosol Transmission of Probiotics Within the the ICU)
  • Use of Ultrathin Polyurethane Endotracheal Tube Cuffs (Quality of Evidence: III = Low)
    • Rationale: ultrathin polyurethane cuffs seal more uniformly against the tracheal wall and may prevent secretions from seeping around the cuff and into the lungs
    • Recommendations (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Ultrathin Polyurethane Endotracheal Tube Cuffs May Lower VAP Rate, But Data Quality is Poor

Measures Which are Generally Not Recommended (Do Not Decrease Ventilator-Associated Pneumonia Rates)

  • Antibiotic Prophylaxis at Time of Intubation (Not Addressed in Guidelines)
    • Clinical Efficacy
      • Study of Strategy of Using a Single Dose of Antibiotics at the Time of Intubation of Comatose Patients (Glasgow Coma Score ≤8) (Chest, 2013) [MEDLINE]: single dose of antibiotics (within 4 hrs of intubation) in comatose patients decreases the risk of early-onset VAP with no impact on mortality rate -> however, findings need to be confirmed in randomized trials
  • Early Parenteral Nutrition (Quality of Evidence: II = Moderate)
    • Clinical Efficacy
      • EPaNIC Trial of Early Total Parenteral Nutrition (within 48 hrs) in the ICU (NEJM, 2011) [MEDLINE]
        • Early Total Parenteral Nutrition (within 48 hrs) Increased Risk of Nosocomial Infection and Mortality Rate, as Compared ot Initiating Total Parenteral Nutrition After 8 Days
  • Early Tracheostomy (Quality of Evidence: I = High) (see Tracheostomy, [[Tracheostomy]])
    • Clinical Efficacy
      • Study of Impact of Early Tracheostomy on VAP Rate (BMJ, 2005) [MEDLINE]
        • Early Tracheostomy Decreases the Duration of Mechanical Ventilation and ICU Stay, But Does Not Impact Mortality or VAP Rate
      • Systematic Review and Meta-Analysis of Effect of Early Tracheostomy on VAP Rates (Chest, 2011) [MEDLINE]
        • Early Tracheostomy Did Not Impact VAP Rates, Duration of Mechanical Ventilation, or Mortality Rate
      • Study of Early Tracheostomy in Cardiothoracic Surgery Population (Ann Intern Med 2011) [MEDLINE]
        • Early Tracheostomy Did Not Decrease Length of Hospital Stay, Mortality Rate, Infectious Complication Rate, Long-Term Health-Related Quality of Life in Patients Who Required Long-Term Mechanical Ventilation After Cardiothoracic Surgery
        • Early Tracheostomy was Well-Tolerated and Associated with Decreased Sedation Use, Better Comfort, and Earlier Resumption of Autonomy
      • TracMan Trial of Early vs Late Tracheostomy in the UK (JAMA, 2013) [MEDLINE]
        • Early Tracheostomy (Within 4 Days of Intubation) Did Not Improve 30-Day All-Cause Mortality, 2-Year Mortality, or Length of ICU Stay
        • The Ability of Clinicians to Predict Which Patients Would Require Extended Mechanical Ventilation Support was Limited
  • Gastrointestinal/Stress Ulcer Prophylaxis (Quality of Evidence: II)
    • Clinical Efficacy
      • Systematic Review and Meta-Analysis of Stress Ulcer Prophylaxis with H2-Blockers (Crit Care Med, 2010) [MEDLINE]
        • H2-Blockers Decreased GI Bleeding Rate, But Only in Patient Who Were Not Receiving Enteral Nutrition
        • H2-Blockers Did Not Increase the Pneumonia Rate Overall, But Did Increase the Pneumonia Rate in the Subgroup Who Were Fed Enterally
        • H2-Blockers Did Not Impact In-Hospital Mortality Overall, But Did Increase the In-Hospital Mortality Rate in Subgroup Who Were Fed Enterally
      • Systematic Review and Meta-Analysis of PPI vs H2-Blockers (Crit Care Med, 2013) [MEDLINE]
        • PPI Were Superior to H2-Blockers in Preventing GI Bleeding
        • There Were No Differences in Terms of Pneumonia, Death, ICU Length of Stay
    • Recommendations (2012 Surviving Sepsis Guidelines; Crit Care Med, 2013) [MEDLINE]
      • Use Stress Ulcer Prophylaxis (H2 Blockers or Proton Pump Inhibitors) to Prevent Gastrointestinal Bleeding in Patients Who Have Bleeding Risk Factors (Grade 1B Recommendation)
        • When Stress Ulcer Prophylaxis is Used, Proton Pump Inhibitors are Preferred Over H2 Blockers (Grade 2D Recommendation)
        • Stress Ulcer Prophylaxis Should Not Be Used in Patients without Risk factors (Grade 2 B Recommendation)
    • Recommendations (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Stress Ulcer Prophylaxis is Generally Not Recommended as a Measure to Decrease the VAP Rate (Although May Be Used for Stress Ulcer Prophylaxis)
  • Kinetic Beds (Quality of Evidence: II = Moderate
    • Continuous Lateral Rotational Therapy and Oscillation Therapy
    • Clinical Efficacy
      • Systematic Review and Meta-Analysis of Effect of Kinetic Beds on VAP Rates (Crit Care, 2006) [MEDLINE]
        • Kinetic Beds Decreased VAP Rates, But Had No Impact on Duration of Mechanical Ventilation or Mortality Rate: however, there are concerns with regard to data quality from the included trials
    • Recommendations (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Kinetic Beds May Decrease VAP Rate, But are Generally Not Recommended for This Indication
  • Monitoring of Gastric Residual Volumes (Quality of Evidence: II = Moderate)
    • Clinical Efficacy
      • Randomized Trial of Effect of Not Monitoring Gastric Residual Volume on VAP Rates in Patients Receiving Enteral Nutrition (JAMA, 2013) [MEDLINE]
        • Not Monitoring Gastric Residual Volumes Had No Impact on VAP Rates in Patients on Mechanical Ventilation Receiving Enteral Nutrition
  • Prone Positioning (Quality of Evidence: II = Moderate)
    • Clinical Efficacy
      • Most Meta-Analyses Suggest a Borderline Effect on VAP Rates and No Impact on Objective Outcomes
    • Recommendations (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Prone Positioning is Generally Not Recommended as a Measure to Decrease VAP Rate (although may be indicated for the management of ARDS)
  • Silver-Coated Endotracheal Tubes (Quality of Evidence: II = Moderate)
    • Mechanism: prevention of biofilm formation inside endotracheal tube
    • Clinical Efficacy
      • Beneficial in decreasing VAP rates
    • Cost: silver-coated endotracheal tube costs approximately $90 (vs $1-2 for standard endotracheal tube)
    • Recommendations (Infect Control Hosp Epidemiol, 2014) [MEDLINE]
      • Silver-Coated Endotracheal Tubes May Lower VAP Rate, But Do Not Impact Mortality Rate, Duration of Mechanical Ventilation, or Length of Stay

Measure Which are Neither Recommended, Nor Discouraged (Unclear Impact on Ventilator-Associated Pneumonia Rates)

  • Closed/In-Line Endotracheal Suctioning Systems (Quality of Evidence: II = Moderate)
    • Clinical Efficacy
      • Meta-Analysis of the Effect of Closed Endotracheal Suction Systems on VAP Rate (Br J Anaesth, 2008) [MEDLINE]
        • Closed Endotracheal Suction Systems Did Not Impact VAP Rate, Mortality, or ICU Length of Stay
        • Closed Endotracheal Suction Systems Increased the Duration of Mechanical Ventilation
      • Trials Conflict as to the Impact of Closed Endotracheal Suctioning Systems on Cost

Treatment of Hospital Acquired Pneumonia (HAP)

General Comments

  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • All Hospitals Should Regularly Generate and Distribute an Antibiogram (Particularly One Which is Specific for Hospital Population)

Antibiotic Treatment Based on Empiric Coverage vs Based on Microbiologic Studies

  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • Patients with HAP Should Be Treated Based on Results of Non-Invasively Obtained Microbiologic Studies, Rather than Being Treated Empirically (Weak Recommendation, Very Low Quality Evidence)
      • Non-Invasive Sampling Methods
        • Sputum Expectoration
        • Sputum Induction
        • Nasotracheal Suctioning

Empiric Antibiotics for Hospital-Acquired Pneumonia (HAP) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

HAP EMPIRIC RX

General Comments

  • Choose One Agent with Activity Against Either Methicillin-Sensitive Staphylococcus Aureus (MSSA) or Methicillin-Resistant Staphylococcus Aureus (MRSA) + One/Two Agent with Activity Against Pseudomonas Aeruginosa (and Other Gram-Negatives) (Strong Recommendation, Very Low-Quality Evidence)
    • If MRSA Coverage is Not Required, One the Following Agents is Suggested for Empiric MSSA Coverage (Weak Recommendation, Very Low-Quality Evidence): although nafcillin/oxacillin/cefazolin are recommended for proven MSSA, they are not required for empiric HAP coverage if one of the following agents are used (Weak Recommendation, Very Low-Quality Evidence)
      • Cefepime (Maxipime) (see Cefepime, [[Cefepime]])
      • Imipenem (Primaxin) (see Imipenem, [[Imipenem]])
      • Meropenem (Merrem) (see Meropenem, [[Meropenem]])
      • Levofloxacin (Levaquin) (see Levofloxacin, [[Levofloxacin]])
      • Piperacillin-Tazobactam (Zosyn) (see Piperacillin-Tazobactam, [[Piperacillin-Tazobactam]])
    • Indications for MRSA Coverage in Empiric HAP Therapy (Weak Recommendation, Very Low-Quality Evidence)
      • High Risk for Mortality
        • Need for Ventilatory Support (Due to the HAP)
        • Septic Shock
      • Presence of Local Staphylococcus Aureus Methicillin-Resistance Rate >20% (or Where Resistance Rate is Unknown)
      • Prior Intravenous Antibiotic Use in the Last 90 Days
    • Empiric HAP Coverage Should Include Coverage of Pseudomonas Aeruginosa and Other Gram-Negatives (Strong Recommendation, Very Low-Quality Evidence)
    • Indications for Double-Coverage of Pseudomonas Aeruginosa in Empiric HAP Therapy (Weak Recommendation, Very Low-Quality Evidence)
      • High Risk for Mortality
        • Need for Ventilatory Support (Due to the HAP)
        • Septic Shock
      • Intravenous Antibiotics in the Last 90 Days
    • In Empiric Treatment of HAP, Avoid Using Aminoglycosides as the Sole Anti-Pseudomonal Agent (Strong Recommendation, Very Low-Quality Evidence): due to their poor lung penetration, risk of nephrotoxicity, risk of ototoxicity, and poorer clinical response rates (but no difference in mortality rate) as compared to other agents in the treatment of VAP (recommendations are based on extrapolation from the VAP data)
    • Dosing of Antibiotics in HAP/VAP Should Be Determined Using Pharmacokinetic/Pharmacodynamic Data (Using Blood Antibiotic Concentrations, Extended and Continuous Infusions, Weight-Based Dosing for Certain Antibiotics, etc) Rather than the Manufacturer’s Prescribing Recommendations (Weak Recommendation, Very Low-Quality Evidence)

Absence of Factors Imparting High Risk for Mortality (Need for Ventilatory Support, Septic Shock) and Absence of Factors Increasing the Likelihood of Methicillin-Resistant Staphylococcus Aureus (MRSA) (Local MRSA Rate >20% or Rate Unknown, Intravenous Antibiotics in Last 90 Days)

  • General Comments
    • Factors Imparting High-Risk for Mortality: absence of need for ventilatory support due to pneumonia and septic shock
    • Factors Increasing the Likelihood of Methicillin-Resistant Staphylococcus Aureus (MRSA)
      • Presence of Local Staphylococcus Aureus Methicillin-Resistance Rate >20% (or Where Resistance Rate is Unknown)
      • Prior Intravenous Antibiotic Use in the Last 90 Days
  • One of the Following
    • Anti-Pseudomonal Penicillins (see Penicillins, [[Penicillins]])
    • Anti-Pseudomonal Cephalosporins (see Cephalosporins, [[Cephalosporins]])
      • Cefepime (Maxipime) (see Cefepime, [[Cefepime]]): 2 g IV q8hrs
      • Ceftazidime (Fortaz) (see Ceftazidime, [[Ceftazidime]]): 2 g IV q8hrs
    • Carbapenems (see Carbapenems, [[Carbapenems]])
      • Imipenem (Primaxin) (see Imipenem, [[Imipenem]]): 500 mg IV q6hrs
      • Meropenem (Merrem) (see Meropenem, [[Meropenem]]): 1 g IV q8hrs
    • Fluoroquinolones (see Fluoroquinolones, [[Fluoroquinolones]])
      • Levofloxacin (Levaquin) (see Levofloxacin, [[Levofloxacin]]): 750 mg IV q24hrs

Absence of Factors Imparting High Risk for Mortality (Need for Ventilatory Support, Septic Shock), But Presence of Factors Increasing the Likelihood of Methicillin-Resistant Staphylococcus Aureus (MRSA) (Local MRSA Rate >20% or Rate Unknown, Intravenous Antibiotics in Last 90 Days)

  • One of the Following (Strong Recommendation, Moderate-Quality Evidence)
    • Oxazolidinones
      • Linezolid (Zyvox) (see Linezolid, [[Linezolid]]): 600 mg IV q12hrs
    • Glycopeptides
      • Vancomycin (see Vancomycin, [[Vancomycin]]): consider load of 25-30 mg/kg IV for severe illness, then 15 mg/kg IV q8-12 hrs with target trough 15-20 mg/mL
  • One of the Following
    • Anti-Pseudomonal Penicillins (see Penicillins, [[Penicillins]])
    • Anti-Pseudomonal Cephalosporins (see Cephalosporins, [[Cephalosporins]])
      • Cefepime (Maxipime) (see Cefepime, [[Cefepime]]): 2 g IV q8hrs
      • Ceftazidime (Fortaz) (see Ceftazidime, [[Ceftazidime]]): 2 g IV q8hrs
    • Carbapenems (see Carbapenems, [[Carbapenems]])
      • Imipenem (Primaxin) (see Imipenem, [[Imipenem]]): 500 mg IV q6hrs
      • Meropenem (Merrem) (see Meropenem, [[Meropenem]]): 1 g IV q8hrs
    • Fluoroquinolones (see Fluoroquinolones, [[Fluoroquinolones]])
      • Ciprofloxacin (Cipro) (see Ciprofloxacin, [[Ciprofloxacin]]): 400 mg IV q8hrs
      • Levofloxacin (Levaquin) (see Levofloxacin, [[Levofloxacin]]): 750 mg IV q24hrs
    • Monobactams
      • Aztreonam (Azactam) (see Aztreonam, [[Aztreonam]]): 2 g IV q8hrs

Factors Imparting High Risk for Mortality (Need for Ventilatory Support, Septic Shock) or Receipt of Intravenous Antibiotics Within the Prior 90 Days

  • One of the Following (Strong Recommendation, Moderate-Quality Evidence)
    • Oxazolidinones
      • Linezolid (Zyvox) (see Linezolid, [[Linezolid]]): 600 mg IV q12hrs
    • Glycopeptides
      • Vancomycin (see Vancomycin, [[Vancomycin]]): consider load of 25-30 mg/kg IV for severe illness, then 15 mg/kg IV q8-12 hrs with target trough 15-20 mg/mL
  • Two of the Following: avoid two β-lactams
    • Anti-Pseudomonal Penicillins (see Penicillins, [[Penicillins]])
    • Anti-Pseudomonal Cephalosporins (see Cephalosporins, [[Cephalosporins]])
      • Cefepime (Maxipime) (see Cefepime, [[Cefepime]]): 2 g IV q8hrs
      • Ceftazidime (Fortaz) (see Ceftazidime, [[Ceftazidime]]): 2 g IV q8hrs
    • Carbapenems (see Carbapenems, [[Carbapenems]])
      • Imipenem (Primaxin) (see Imipenem, [[Imipenem]]): 500 mg IV q6hrs
      • Meropenem (Merrem) (see Meropenem, [[Meropenem]]): 1 g IV q8hrs
    • Fluoroquinolones (see Fluoroquinolones, [[Fluoroquinolones]])
      • Ciprofloxacin (Cipro) (see Ciprofloxacin, [[Ciprofloxacin]]): 400 mg IV q8hrs
      • Levofloxacin (Levaquin) (see Levofloxacin, [[Levofloxacin]]): 750 mg IV q24hrs
    • Monobactams
      • Aztreonam (Azactam) (see Aztreonam, [[Aztreonam]]): 2 g IV q8hrs
    • Aminoglycosides (see Aminoglycosides, [[Aminoglycosides]])
      • Amikacin (see Amikacin, [[Amikacin]]): 15-20 mg/kg IV q24hrs
      • Gentamicin (see Gentamicin, [[Gentamicin]]): 5-7 mg/kg IV q24hrs
      • Tobramycin (see Tobramycin, [[Tobramycin]]): 5-7 mg/kg IV q24hrs

Pathogen-Specific Antibiotics for Hospital-Acquired Pneumonia (HAP) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

HAP/VAP Due to Methicillin-Resistant Staphylococcus Aureus (MRSA) (see Staphylococcus Aureus, [[Staphylococcus Aureus]])

  • Recommended Agents for the Treatment of HAP/VAP Due to MRSA (Strong Recommendation, Moderate-Quality Evidence): meta-analyses indicate no difference in mortality between these agents (Clin Infect Dis, 2016) [MEDLINE]
    • Oxazolidinones
      • Linezolid (Zyvox) (see Linezolid, [[Linezolid]]): 600 mg IV q12hrs
    • Glycopeptides
      • Vancomycin (see Vancomycin, [[Vancomycin]]): consider load of 25-30 mg/kg IV, then 15 mg/kg IV q8-12 hrs with target trough 15-20 mg/mL

HAP/VAP Due to Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa, [[Pseudomonas Aeruginosa]])

  • Antibiotics for HAP/VAP Due to Pseudomonas Aeruginosa Should Be Guided by Antimicrobial Susceptibility Testing (Strong Recommendation, Low-Quality Evidence)
  • Aminoglycoside Monotherapy for HAP/VAP Due to Pseudomonas Aeruginosa is Not Recommended (Strong Recommendation, Very Low-Quality Evidence)
  • Indications for Double-Coverage of Pseudomonas Aeruginosa HAP/VAP (Strong Recommendation, Low-Quality Evidence)
    • High Risk for Mortality: defined as mortality risk >25% (low risk for mortality is defined as <15% risk)
      • Need for Ventilatory Support
      • Septic Shock
    • Lack of Availability of Antibiotic Susceptibility Testing

HAP/VAP Due to Extended-Spectrum β-Lactamase (ESBL)-Producing Gram-Negative Bacilli

  • Antibiotics for HAP/VAP Due to ESBL-Producing Gram-Negative Bacilli Should Be Guided by Antimicrobial Susceptibility Testing (Strong Recommendation, Very Low-Quality Evidence)

HAP/VAP Due to Acinetobacter (see Acinetobacter, [[Acinetobacter]])

  • HAP/VAP Due to Acinetobacter Should Be Treated with Ampicillin-Sulbactam (Unasyn) or a Carbapenem, if Susceptible (Weak Recommendation, Low-Quality Evidence)
  • For HAP/VAP Due to Acinetobacter, Tigecycline is Not Recommended (Strong Recommendation, Low-Quality Evidence)
  • For HAP/VAP Due to Acinetobacter Which is Susceptible Only to Polymyxins, Intravenous Polymyxin Should Be Used (Strong Recommendation, Low-Quality Evidence) with Inhaled Colistin (Weak Recommendation, Low-Quality Evidence)
  • For HAP/VAP Due to Acinetobacter Which is Susceptible Only to Colistin, Adjunctive Rifampicin is Not Recommended (Weak Recommendation, Moderate-Quality Evidence)

HAP/VAP Due to Carbapenem-Resistant Pathogens

  • For HAP/VAP Due to Carbapenem-Resistant Pathogens Which is Only Sensitive to Polymyxins, Intravenous Polymyxin Should Be Used (Strong Recommendation, Moderate-Duality Evidence) with Inhaled Colistin (Weak)

Length of Therapy for Hospital-Acquired Pneumonia (HAP) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

  • For Patients with HAP, a 7 Day Course of Therapy is Recommended Over Longer Duration of Therapy (Strong Recommendation, Very Low-Quality Evidence): some clinical situations may merit a shorter/longer duration of therapy, depending on the rate of improvement in clinical/radiologic/laboratory parameters

De-Escalation of Therapy for Hospital-Acquired Pneumonia (HAP) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

  • For HAP/VAP, Antibiotic Therapy Should Be De-Escalated (Weak Recommendation, Very Low-Quality Evidence)

Discontinuation of Antibiotics in Hospital-Acquired Pneumonia (HAP) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

  • For HAP/VAP, Combined Clinical Criteria and Serum Procalcitonin Should Be Used to Guide Antibiotic Discontinuation Over Clinical Criteria Alone (Weak Recommendation, Low-Quality Evidence)
    • However, is it Unclear if there are Benefits of Using Serum Procalcitonin to Determine Whether or Not to Discontinue Antibiotic Therapy in Settings Where Standard Antimicrobial Therapy for VAP is Already ≤7 Days
  • For HAP/VAP, Clinical Pulmonary Infection Score (CPIS) Should Not Be Used to Guide Antibiotic Discontinuation (Weak Recommendation, Low-Quality Evidence)

Treatment of Ventilator-Associated Tracheobronchitis

  • Clinical Efficacy
    • Antibiotic Therapy May Shorten the Duration of Mechanical Ventilation, But it is Unclear as to Whether it Improves Other Clinical Outcomes (Due to Inconsistent Data)
  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • Patients with Ventilator-Associated Tracheobronchitis Should Not Be Treated with Antibiotic Therapy (Weak Recommendation, Low-Quality Evidence)

Treatment of Ventilator-Associated Pneumonia (VAP)

General Comments

  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • All Hospitals Should Regularly Generate and Distribute an Antibiogram (Particularly One Which is Specific for the Intensive Care Unit Population)
      • Microbial Flora and Resistance Patterns Vary Significantly Between Countries, Regions, and Hospitals
      • Antibiogram Should Inform Empiric Treatment Decisions
    • Meta-Analyses Indicate that Inadequate and/or Delayed Antibiotic Treatment of VAP Results in a (2.34x) Increased Mortality Rate (J Crit Care, 2008) [MEDLINE]

Antibiotic Use Based on Quantitative Cultures in Ventilator-Associated Pneumonia (VAP)

  • Recommendations (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • Non-Invasive Sampling with Semiquantitative Cultures is Recommended Over Non-Invasive Sampling with Quantitative Cultures or Invasive Sampling with Quantitative Cultures (Weak Recommendation, Low Quality Evidence): there is no evidence that invasive microbiologic sampling improves clinical outcomes compared with non-invasive sampling with either quantitative or semiquantitative cultures
      • Non-Invasive Sampling Methods: endotracheal suction sampling
        • Quantitative Threshold for Endotracheal Tube Aspirate: <10 to the 5th CFU/mL
      • Invasive Sampling Methods: bronchoscopy with bronchoalveolar lavage or protected brush specimen, blind bronchial sampling (“mini-BAL”)
    • Effect of Invasive Sampling with Quantitative Cultures on Antibiotic Exposure is Unclear
    • If Invasive Sampling with Quantitative Cultures are Performed, Diagnostic Thresholds for VAP (Protected Brush Specimen with <10 to the 3rd CFU/mL, Bronchoalveolar With <10 to the 4th CFU/mL) Should Be Utilized to Decide Whether to Stop Antibiotics (Weak Recommendation, Very Low Quality Evidence)

Empiric Antibiotics for Ventilator-Associated Pneumonia (VAP) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

VAP EMPIRIC RX2

General Comments

  • Choose One Agent with Activity Against Either Methicillin-Sensitive Staphylococcus Aureus (MSSA) or Methicillin-Resistant Staphylococcus Aureus (MRSA) + One β-Lactam Agent with Activity Against Pseudomonas Aeruginosa (and Gram-Negatives) + One Non-β-Lactam Agent with Activity Against Pseudomonas Aeruginosa (and Other Gram-Negatives) (Strong Recommendation, Low-Quality Evidence)
    • Use an Agent Active Against Methicillin-Resistant Staphylococcus Aureus (MRSA) for the Following Indications (Weak Recommendation, Very Low-Quality Evidence)
      • Presence of Local Staphylococcus Aureus Methicillin-Resistance Rate >10-20% (or Where Resistance Rate is Unknown)
      • Prior Intravenous Antibiotic Use in the Last 90 Days
    • Use Agents from Two Different Anti-Pseudomonal Classes for the Following Indications (Weak Recommendation, Low-Quality Evidence): the rationale for double-covering Pseudomonas is to increase the probability that the organism will be sensitive to at least one of the agents
      • Presence of Local Gram-Negative Resistance Rate >10% for the Agent Being Considered for Monotherapy (or Where Resistance Rate is Unknown)
      • Presence of Structural Lung Diseases Which Increase the Risk of Gram-Negative Pneumonia (Bronchiectasis, Cystic Fibrosis)
      • Prior Intravenous Antibiotic Use in the Last 90 Days
    • In Patients with Suspected VAP, Avoid Aminoglycosides if Alternative Agents with Gram-Negative Coverage are Available (Weak Recommendation, Low-Quality Evidence): due to their poor lung penetration, risk of nephrotoxicity, risk of ototoxicity, and poorer clinical response rates (but no difference in mortality rate) than that of other drug classes
    • In Patients with Suspected VAP, Avoid Colistin if Alternative Agents with Gram-Negative Coverage are Available (Weak Recommendation, Very Low-Quality Evidence)
    • Dosing of Antibiotics in HAP/VAP Should Be Determined Using Pharmacokinetic/Pharmacodynamic Data (Using Blood Antibiotic Concentrations, Extended and Continuous Infusions, Weight-Based Dosing for Certain Antibiotics, etc) Rather than the Manufacturer’s Prescribing Recommendations (Weak Recommendation, Very Low-Quality Evidence)

Agents with Activity Against Methicillin-Sensitive Staphylococcus Aureus (MSSA) (see Staphylococcus Aureus, [[Staphylococcus Aureus]])

  • Preferred Agents for Proven MSSA: due to decreased likelihood of inducing resistance
  • Other Agents with MSSA Coverage (Weak Recommendation, Very Low-Quality Evidence)
    • Cefepime (Maxipime) (see Cefepime, [[Cefepime]])
    • Imipenem (Primaxin) (see Imipenem, [[Imipenem]])
    • Meropenem (Merrem) (see Meropenem, [[Meropenem]])
    • Levofloxacin (Levaquin) (see Levofloxacin, [[Levofloxacin]])
    • Piperacillin-Tazobactam (Zosyn) (see Piperacillin-Tazobactam, [[Piperacillin-Tazobactam]])

Agents with Activity Against Methicillin-Resistant Staphylococcus Aureus (MRSA) (see Staphylococcus Aureus, [[Staphylococcus Aureus]]) (Strong Recommendation, Moderate-Quality Evidence)

  • Recommended Agents (Strong Recommendation, Moderate-Quality Evidence)
    • Oxazolidinones
      • Linezolid (Zyvox) (see Linezolid, [[Linezolid]]): 600 mg IV q12hrs
    • Glycopeptides
      • Vancomycin (see Vancomycin, [[Vancomycin]]): consider load of 25-30 mg/kg IV, then 15 mg/kg IV q8-12 hrs with target trough 15-20 mg/mL
  • Other Agents: these agents have not been as well-studied in the treatment of VAP
  • Agents Which are Not Recommended for Use in VAP: due to demonstrated lower clinical cure rates in VAP

β-Lactam Agents with Activity Against Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa, [[Pseudomonas Aeruginosa]])

  • Anti-Pseudomonal Penicillins (see Penicillins, [[Penicillins]])
  • Anti-Pseudomonal Cephalosporins
    • Cefepime (Maxipime) (see Cefepime, [[Cefepime]]): 2 g IV q8hrs
    • Ceftazidime (Fortaz) (see Ceftazidime, [[Ceftazidime]]): 2 g IV q8hrs
  • Carbapenems (see Carbapenems, [[Carbapenems]])
    • Imipenem (see Imipenem, [[Imipenem]]): 500 mg IV q6hrs (dose adjust in patients <70 kg to prevent seizures)
    • Meropenem (see Meropenem, [[Meropenem]]): 1 g IV q8hrs
  • Monobactams
    • Aztreonam (Azactam) (see Aztreonam, [[Aztreonam]]): 2 g IV q8hrs
      • In the absence of other options, aztreonam may be used with other β-lactams, since it has a different target within the bacterial cell wall
  • Agents Which Have Not Been Studied in VAP
  • Agents Which are Not Recommended for Use in VAP: due to demonstrated lower clinical cure rates in VAP
    • Doripenem (Finibax, Doribax) (see Doripenem, [[Doripenem]])

Non-β-Lactam Agents with Activity Against Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa, [[Pseudomonas Aeruginosa]])

  • Fluoroquinolones (see Fluoroquinolones, [[Fluoroquinolones]])
    • Ciprofloxacin (Cipro) (see Ciprofloxacin, [[Ciprofloxacin]]): 400 mg IV q8hrs
    • Levofloxacin (Levaquin) (see Levofloxacin, [[Levofloxacin]]): 750 Hg IV q24hrs
  • Aminoglycosides (see Aminoglycosides, [[Aminoglycosides]]): in meta-analyses, aminoglycoside regimens are associated with lower clinical response rates, but no difference in mortality rate
    • General Comments: aminoglycosides should be avoided if alternative agents with adequate Gram-negative coverage are available (Weak Recommendation, Low-Quality Evidence)
    • Amikacin (see Amikacin, [[Amikacin]]): 15-20 mg/kg IV q24hrs
    • Gentamicin (see Gentamicin, [[Gentamicin]]): 5-7 mg/kg IV q24hrs
    • Tobramycin (see Tobramycin, [[Tobramycin]]): 5-7 mg/kg IV q24hrs
  • Polymyxins (see Polymyxins, [[Polymyxins]])
    • Colistin (see Colistin, [[Colistin]]): load 5 mg/kg IV, then 2.5 mg x (1.5 x CrCl + 30) IV q12hrs
      • In Cases with Resistant Pseudomonas Aeruginosa, Combination Intravenous + Aerosolized Colistin was Superior to Intravenous Colistin Alone, in Terms of Cure Rate and Days of Mechanical Ventilation After VAP Onset (Chest, 2013) [MEDLINE]
    • Polymyxin B (see Polymyxin B, [[Polymyxin B]]): 2.5–3.0 mg/kg/day IV divided in 2 daily doses

Pathogen-Specific Antibiotics for Ventilator-Associated Pneumonia (VAP) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

Role of Inhaled Antibiotic Therapy in the Management of Multidrug-Resistant Gram-Negative Bacilli

  • Gram-Negative Bacilli Susceptible Only to Aminoglycosides/Polymyxins Should Be Treated with Both Inhaled (Gentamicin, Tobramycin, Colistin) and Systemic Antibiotics, as Opposed to Systemic Antibiotics Alone (Weak Recommendation, Very Low-Quality Evidence): meta-analyses suggest that the addition of inhaled antibiotics to systemic antibiotics increased the clinical cure rate, but had no effect on the mortality rate or nephrotoxicity (Clin Infect Dis, 2016) [MEDLINE]
    • Rationale: antibiotic efficacy against bacteria which reside within purulent secretions may require antibiotic concentrations which are >10–25x the minimum inhibitory concentration (MIC) (these MIC’s cannot be achieved with intravenous therapy alone and the addition of inhaled antibiotic therapy may be beneficial in achieving the relevant MIC)
      • Notably, subtherapeutic antibiotic concentrations within the lung and airway may further select antibiotic-resistant organisms
    • Typical Multidrug-Resistant Organisms: multidrug-resistant Klebsiella Pneumoniae, Pseudomonas Aeruginosa, and Acinteobacter Baumannii
    • It is Also Reasonable to Consider the Addition of Inhaled Antibiotics as Adjunctive Therapy in Patients Who are Not Responding to Intravenous Antibiotics Alone (Regardless of Whether the Infecting Organism is Multidrug-Resistant or Not)

HAP/VAP Due to Methicillin-Resistant Staphylococcus Aureus (MRSA) (see Staphylococcus Aureus, [[Staphylococcus Aureus]])

  • Recommended Agents for the Treatment of HAP/VAP Due to MRSA (Strong Recommendation, Moderate-Quality Evidence): meta-analyses indicate no difference in mortality between these agents (Clin Infect Dis, 2016) [MEDLINE]
    • Oxazolidinones
      • Linezolid (Zyvox) (see Linezolid, [[Linezolid]]): 600 mg IV q12hrs
    • Glycopeptides
      • Vancomycin (see Vancomycin, [[Vancomycin]]): consider load of 25-30 mg/kg IV, then 15 mg/kg IV q8-12 hrs with target trough 15-20 mg/mL

HAP/VAP Due to Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa, [[Pseudomonas Aeruginosa]])

  • Antibiotics for HAP/VAP Due to Pseudomonas Aeruginosa Should Be Guided by Antimicrobial Susceptibility Testing (Strong Recommendation, Low-Quality Evidence)
  • Aminoglycoside Monotherapy for HAP/VAP Due to Pseudomonas Aeruginosa is Not Recommended (Strong Recommendation, Very Low-Quality Evidence)
  • Indications for Double-Coverage of Pseudomonas Aeruginosa HAP/VAP (Strong Recommendation, Low-Quality Evidence)
    • High Risk for Mortality: defined as mortality risk >25% (low risk for mortality is defined as <15% risk)
    • Lack of Availability of Antibiotic Susceptibility Testing

HAP/VAP Due to Extended-Spectrum β-Lactamase (ESBL)-Producing Gram-Negative Bacilli

  • Antibiotics for HAP/VAP Due to ESBL-Producing Gram-Negative Bacilli Should Be Guided by Antimicrobial Susceptibility Testing (Strong Recommendation, Very Low-Quality Evidence)

HAP/VAP Due to Acinetobacter (see Acinetobacter, [[Acinetobacter]])

  • HAP/VAP Due to Acinetobacter Should Be Treated with Ampicillin-Sulbactam (Unasyn) or a Carbapenem, if Susceptible (Weak Recommendation, Low-Quality Evidence)
  • For HAP/VAP Due to Acinetobacter, Tigecycline is Not Recommended (Strong Recommendation, Low-Quality Evidence)
  • For HAP/VAP Due to Acinetobacter Which is Susceptible Only to Polymyxins, Intravenous Polymyxin Should Be Used (Strong Recommendation, Low-Quality Evidence) with Inhaled Colistin (Weak Recommendation, Low-Quality Evidence)
  • For HAP/VAP Due to Acinetobacter Which is Susceptible Only to Colistin, Adjunctive Rifampicin is Not Recommended (Weak Recommendation, Moderate-Quality Evidence)

HAP/VAP Due to Carbapenem-Resistant Pathogens

  • For HAP/VAP Due to Carbapenem-Resistant Pathogens Which is Only Sensitive to Polymyxins, Intravenous Polymyxin Should Be Used (Strong Recommendation, Moderate-Duality Evidence) with Inhaled Colistin (Weak)

Length of Therapy for Ventilator-Associated Pneumonia (VAP) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

  • For Patients with VAP, a 7 Day Course of Therapy is Recommended Over Longer Duration of Therapy (Strong Recommendation, Moderate-Quality Evidence): some clinical situations may merit a shorter/longer duration of therapy, depending on the rate of improvement in clinical/radiologic/laboratory parameters
    • Evidence Indicates that Shorter Courses of Antibiotics Decrease Antibiotic Exposure and the Risk of Recurrent Pneumonia Due to Multidrug-Resistant Organisms
    • Duration of Antibiotic Therapy Do Not Appear to Impact the Mortality Rate

Antibiotic Choice and Stewardship in Ventilator-Associated Pneumonia (VAP)

  • Goals of Antibiotic Stewardship
    • Optimization of Clinical VAP Outcomes
    • Minimization of Antibiotic Resistance, Antibiotic Toxicity, Adverse Events, and Selection of Pathogenic Organisms
    • Decrease in Health Care Costs
  • Techniques of Antibiotic Stewardship
    • Formulary Restriction/Preauthorization for Antibiotics
    • Audit of Antibiotic Use with Feedback to the Prescriber
    • De-Escalation of Antibiotics
      • Start with Broad-Spectrum Antibiotic Strategy
      • At First Opportunity (with the Aid of Culture Data), Provider Should Decrease the Number of Antimicrobial Agents, Shorten the Duration of Antimicrobial Agent Exposure, and/or Discontinue Antimicrobial Therapy (as Dictated by the Patient’s Clinical Response and Culture Results)
  • Clinical Efficacy
    • Study of Microbial Isolates and Susceptibility Across Hospital Sites in Different Spanish Cities (Am J Respir Crit Care Med, 1999) [MEDLINE]
      • Etiologies of VAP Varied Across the Treatment Sites
      • Therefore, Authors Conclude that Antimicrobial Prescribing Practices Should Be Based on Information About Patterns of Multi-Drug Resistant Isolates from Each Institution, Instead of Following General Recommendations
    • PneumA Trial of Shortened Antibiotic Duration in VAP Treatment (JAMA, 2003) [MEDLINE]
      • Among Patients Who Had Received Initial Empiric Antibiotic Therapy (with the Possible Exception of Those with Non-Fermenting GNR Infections), 8-day Regimen was Comparable to 15-Day Regimen in Terms of Clinical Outcome: 8-day group had less antibiotic use
    • Trial Using Antibiotic De-Escalation in VAP (Crit Care Med, 2004) [MEDLINE]
      • De-Escalation was Possible in 31.4% of Cases
        • Bronchoscopic and/or tracheal aspirate cultures were instrumental in allowing de-escalation
        • Authors did not perform de-escalation without a known pathogen
      • De-Escalation was Performed in Only 2.7% of Cases with Non-Fermenting GNR’s and Other Potentially Multi-Drug Resistant Organisms (Such as Pseudomonas Aeruginosa)
    • Multi-Center Observational Study of VAP (Chest, 2006) [MEDLINE]
      • De-Escalation was Performed in 22.1% of Cases (and Escalation in 15.3% of Cases)
      • De-Escalation was Performed in Only 6.5% of Cases without a Known Pathogen
      • Mortality was Significantly Decreased in Cases with De-Escalation (17%), vs 23.7% in Those with No Change in Therapy and 42.6% in Those with Escalation in Therapy
    • Study of the Impact of Regular Communication Between Infectious Disease and Critical Care Providers on Antimicrobial Use and Patient Outcome (Crit Care Med, 2013) [MEDLINE]
      • Active Communication Between Critical Care Providers and Infectious Disease Providers Significantly Decreases Medical ICU Antibiotic Overuse (by Earlier Modification or Cessation of Antibiotics) without an Increase in Mortality: this may decrease health care costs
    • Systematic Review of Antibiotic De-Escalation in the ICU (Clin Infect Dis, 2016) [MEDLINE]
      • There is No Uniform Definition of “De-Escalation”
      • There is Little Evidence Related to the Effect of De-Escalation on Duration of Antimicrobial Therapy, Emergence of Resistance, or Costs
      • There was an Association Between De-Escalation and Improved Outcome: however, from the evidence, it is not clear that this is causal (since patients with clinical improvement may have been the ones with higher rates of de-escalation)
  • Recommendations
    • Knowledge of Local Antibiograms is Essential in Determining Appropriate Initial Antibiotic Regimens
    • Antibiotic De-Escalation (to a Narrower Regimen) is Recommended, Whenever Possible (Weak Recommendation, Very Low-Quality Evidence) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]
    • Collaborative Approach Between Critical Care and Infectious Disease Providers is Recommended to Decrease Antibiotic Overuse

Discontinuation of Antibiotics in Ventilator-Associated Pneumonia (VAP) (Infectious Diseases Society of America, IDSA/American Thoracic Society, ATS 2016 Clinical Practice Guidelines for the Management of HAP/VAP (Clin Infect Dis, 2016) [MEDLINE]

  • For HAP/VAP, Combined Clinical Criteria and Serum Procalcitonin Should Be Used to Guide Antibiotic Discontinuation Over Clinical Criteria Alone (Weak Recommendation, Low-Quality Evidence)
    • However, is it Unclear if there are Benefits of Using Serum Procalcitonin to Determine Whether or Not to Discontinue Antibiotic Therapy in Settings Where Standard Antimicrobial Therapy for VAP is Already ≤7 Days
  • For HAP/VAP, Clinical Pulmonary Infection Score (CPIS) Should Not Be Used to Guide Antibiotic Discontinuation (Weak Recommendation, Low-Quality Evidence)

Prognostic Factors

Hospital-Acquired Pneumonia (HAP)

Effect of Hospital-Acquired Pneumonia (HAP) on Mortality Rate

  • Mortality Rate of HAP in the ICU Approaches that of VAP (Chest, 2005) [MEDLINE]; (Crit Care Med, 2013) [MEDLINE]

Ventilator-Associated Pneumonia (VAP)

Effect of Ventilator-Associated Pneumonia (VAP) on Mortality Rate

  • Mortality Rate Attributable to VAP is 13% (Lancet Infect Dis, 2013) [MEDLINE]: however, the all-cause mortality rate associated with VAP has been estimated to be 20-50%

Effect of Ventilator-Associated Pneumonia (VAP) on Other Outcomes

  • VAP Increased the Duration of Mechanical Ventilation (Clin Infect Dis, 2010) [MEDLINE]; (Infect Control Hosp Epidemiol, 2012) [MEDLINE]: by 7.6-11.5 days
  • VAP Increased Hospital Length of Stay (Clin Infect Dis, 2010) [MEDLINE]; (Infect Control Hosp Epidemiol, 2012) [MEDLINE]: by 11.5-13.1 days
  • Excess Cost Associated with VAP is Estimated to $40k Per Patient (Infect Control Hosp Epidemiol, 2012) [MEDLINE]

Ventilator-Associated Pneumonia (VAP) in the Elderly (Crit Care Med, 2014) [MEDLINE]

  • Advanced Age
    • Advanced Age Did Not Increase the Prevalence of VAP, But it Increased the VAP-Associated Mortality Rate (Age 65-74 y/o and Age >75 y/o Had 51% Mortality Rate, as Compared to 35% Mortality Rate for Younger Age Groups)
    • Older Age Groups Had Higher Incidence of Chronic Congestive Heart Failure, Diabetes Mellitus, and Non-Metastatic Cancer
    • Age Did Not Impact the Duration of Mechanical Ventilation or Length of ICU Stay
  • Diabetes Mellitus (see Diabetes Mellitus, [[Diabetes Mellitus]])
    • Diabetes Mellitus Increased the VAP Mortality Rate
  • Septic Shock (see Sepsis, [[Sepsis]])

    • Presence of Septic Shock Increased the VAP Mortality Rate
  • Poor Prognostic Factor: Pseudomonas aeruginosa and/or Acinetobacter calcoaceticus isolation

  • Poor Prognostic Factor: Patients who have initially been treated with inappropriate antibiotics
  • No difference in morbidity or mortality has been found between the patients who had VAP diagnosed with quantitative sputum c/s vs protected brush specimens
  • Quantitative BAL cultures has not been shown to improve VAP outcome
  • Unknown if there is a difference in morbidity or mortality if one diagnoses VAP with a nonquantitative sputum c/s vs quantitative culture technique

Hospital Readmission for Pneumonia

  • Clinical Efficacy
    • Study of Factors Related to Hospital Readmission for Pneumonia (Clin Infect Dis, 2013) [MEDLINE]
      • Hospital Readmission Rate for Pneumonia: 20%
      • Patients with HCAP were 7.5x More Likely to Be Readmitted than Patients with CAP
      • Criteria in HCAP that Associated with the Risk of Hospital Readmission
        • Admission from Long-term Care (adjusted odds ratio [AOR], 2.2 [95% CI, 1.4-3.4])
        • Immunosuppression (AOR, 1.9 [95% CI, 1.3-2.9])
        • Prior Antibiotics (AOR, 1.7 [95% CI, 1.2-2.6])
        • Prior Hospitalization (AOR, 1.7 [95% CI, 1.1-2.5])

References

General

  • Infection control concepts in critical care. Infect Crit Care 1998; 14:55-70
  • Guidelines for prevention of nosocomial pneumonia. MMWR 1997; 46:1-78
  • Extending ventilator circuit change interval beyond 2 days reduces the likelihood of ventilator-associated pneumonia. Chest 1998; 113:405-411
  • A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. N Engl J Med 1998; 338:791-797
  • Mortality and the diagnosis of ventilator-associated pneumonia-a new direction. Am J Respir Crit Care Med 1998; 157:349-350
  • Pneumonia in intubated trauma patients: microbiology and outcomes. Am J Respir Crit Care Med 1996: 153:343-349
  • Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 1997; 111:676-685
  • Impact of invasive and noninvasive quantitative culture sampling on outcome of ventilator-associated pneumonia. Am J Respir Crit Care Med 1998; 157:371-376
  • The microbiology of ventilator-associated pneumonia. Respir Care 2005;50:742-763 [MEDLINE]
  • Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomized trial. Lancet. 1999;354:1851-1858
  • American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388-416 [MEDLINE]
  • The epidemiology, pathogenesis and treatment of pseudomonas aeruginosa infections. Drugs. 2007;67:351-368.
  • Pseudomonas aeruginosa bloodstream infection: importance of appropriate initial antimicrobial treatment. Antimicrob Agents Chemother. 2005;49:1306-1311.
  • National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. 2004;32:470-485
  • Multicenter study of hospital-acquired pneumonia in non-ICU patients. Chest 2005; 127:213–9 [MEDLINE]
  • Contemporary activity of meropenem and comparator broad-spectrum agents: MYSTIC program report from the United States component (2005). Diagn Microbiol Infect Dis. 2007;57:207-215
  • Bacteremia in patients with ventilator-associated pneumonia is associated with increased mortality: a study comparing bacteremic vs. nonbacteremic ventilator-associated pneumonia. Crit Care Med 2007; 35:2064–70 [MEDLINE]
  • Colistin and polymyxin B in critical care. Crit Care Clin. 2008;24:377-391
  • Impact of patient position on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials. J Crit Care 2009;24(4):515–522 [MEDLINE]
  • Mortality, attributable mortality,and clinical events as end points for clinical trials of ventilator-associated pneumonia and hospital-acquired pneumonia. Clin Infect Dis 2010; 51(suppl 1):S120–5 [MEDLINE]
  • Effect of antibiotic diversity on ventilator-associated pneumonia caused by ESKAPE organisms. Chest 2011; 14:645–651 [MEDLINE]
  • Severity of ICU-acquired pneumonia according to infectious microorganisms. Intensive Care Med 2011; 37: 1128-1135 [MEDLINE]
  • National Healthcare Safety Network (NHSN) report, data summary for 2010, de- vice-associated module. Am J Infect Control 2011;39:798-816 [MEDLINE]
  • Ventilator-associated pneumonia caused by ESKAPE organisms: cause, clinical features, and management. Curr Opin Pulm Med 2012;18(3):187-193 [MEDLINE]
  • Economic impact of ventilator-associated pneumonia in a large matched cohort. Infect Control Hosp Epidemiol 2012; 33:250–6 [MEDLINE]
  • A collaborative, systems-level approach to eliminating healthcare-associated MRSA, central-line-associated bloodstream infections, ventilator-associated pneumonia, and respiratory virus infections. J Healthc Qual. 2012 Sep-Oct;34(5):39-47; quiz 48-9. doi: 10.1111/j.1945-1474.2012.00213.x. Epub 2012 Aug 3 [MEDLINE]
  • Objective surveillance definitions for ventilator-associated pneumonia.  Crit Care Med  2012;40:3154–3161 [MEDLINE]
  • Complications of mechanical ventilation—The CDC’s new surveillance paradigm.  N Engl J Med 2013;368:1472–1475 [MEDLINE]
  • Validation of predictors of adverse outcomes in hospital-acquired pneumonia in the ICU. Crit Care Med 2013; 41:2151–61 [MEDLINE]
  • Toward improved surveillance: the impact of ventilator-associated complications on length of stay and antibiotic use in patients in intensive care units.  Clin Infect Dis  2013;56:471–477 [MEDLINE]
  • Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 2013; 13:665–71 [MEDLINE]
  • EU-VAP Study Investigators. Prevalence, risk factors, and mortality for ventilator-associated pneumonia in middle-aged, old and very old critically ill patients. Crit Care Med 2014;42:601-609 [MEDLINE]
  • Emerging Infections Program Healthcare-Associated Infections Antimicrobial Use Prevalence Survey Team. Survey of health care-associated infections. N Engl J Med 2014; 370:2542–3 [MEDLINE]
  • National trends in patient safety for four common conditions, 2005–2011. N Engl J Med 2014; 370:341–51 [MEDLINE]
  • Ventilator-Associated Events: Prevalence, Outcome, and Relationship With Ventilator-Associated Pneumonia. Crit Care Med. 2015 Sep;43(9):1798-806. doi: 10.1097/CCM.0000000000001091 [MEDLINE]
  • Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):e61-e111. doi: 10.1093/cid/ciw353. Epub 2016 Jul 14 [MEDLINE]

Diagnosis

  • Ventilator-Associated Pneumonia: The Clinical Pulmonary Infection Score as a Surrogate for Diagnostics and Outcome. Clin Infect Dis. 2010 Aug 1;51 Suppl 1:S131-5. doi: 10.1086/653062 [MEDLINE]
  • Methicillin-resistant Staphylococcus aureus nasal colonization is a poor predictor of intensive care unit-acquired methicillin-resistant Staphylococcus aureus infec- tions requiring antibiotic treatment. Crit Care Med 2010; 38:1991–5 [MEDLINE]
  • Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 2011; 39:2048–58 [MEDLINE]
  • Diagnostic accuracy of clinical pulmonary infection score for ventilator-associated pneumonia: a meta-analysis. Respir Care 2011; 56:1087–94 [MEDLINE]
  • Gram stain useful in the microbiologic diagnosis of VAP? A meta-analysis. Clin Infect Dis 2012; 55:551–61 [MEDLINE]

Clinical

Ventilator-Associated Events (VAE)

  • Ventilator-Associated Pneumonia: New Definitions. Crit Care Clin. 2017 Apr;33(2):277-292. doi: 10.1016/j.ccc.2016.12.009. Epub 2017 Jan 18 [MEDLINE]
  • CDC Device-Associated Module for VAE Definitions (1/17) [LINK]
  • Prevalence and test characteristics of national health safety network ventilator-associated events. Crit Care Med 2014; 42(9):2019–28 [MEDLINE]

Ventilator-Associated Tracheobronchitis

  • Effect of ventilator-associated tracheobronchitis on outcome in patients without chronic respiratory failure: a case-control study. Crit Care 2005; 9:R238–45 [MEDLINE]

Prevention of Ventilator-Associated Pneumonia

  • Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet 1999;354:1851-1858 [MEDLINE]
  • Guidelines for preventing health-care–associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep. 2004;53:1-36 [MEDLINE]
  • De-escalation therapy in ventilator-associated pneumonia. Crit Care Med 2004; 32:2183–2190 [MEDLINE]
  • Prevention of hospital-associated pneumonia and ventilator-associated pneumonia. Crit Care Med. 2004;32:1396-1405 [MEDLINE]
  • Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care. Cochrane Database Syst Rev. 2004;(1):CD000022 [MEDLINE]
  • Intrahospital transport of critically ill ventilated patients: a risk factor for ventilator-associated pneumonia–a matched cohort study. Crit Care Med, 2005: 33: 2471-2478 [MEDLINE]
  • Systematic review and meta-analysis of studies of the timing of tracheostomy in adult patients undergoing artificial ventilation. BMJ. 2005;330:1243 [MEDLINE]
  • The ventilator circuit and ventilator-associated pneumonia. Respir Care. 2005;50:774-785 [MEDLINE]
  • Subglottic secretion drainage for preventing ventilator-associated pneumonia: a meta-analysis. Am J Med 2005;118:11-18 [MEDLINE]
  • Oral care reduces incidence of ventilator-associated pneumonia in ICU populations. Intensive Care Med 2006;32:230-236 [MEDLINE]
  • Kinetic bed therapy to prevent nosocomial pneumonia in mechanically ventilated patients: a systematic review and meta-analysis. Crit Care 2006;10(3):R70 [MEDLINE]
  • Topical chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis. Crit Care Med 2007;35:595-602 [MEDLINE]
  • Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. BMJ 2007;334:889 [MEDLINE]
  • Prevention measures for ventilator-associated pneumonia: a new focus on the endotracheal tube. Curr Opin Infect Dis. 2007 Apr;20(2):190-7 [MEDLINE]
  • Closed tracheal suction systems for prevention of ventilator-associated pneumonia. Br J Anaesth. 2008;100:299-306 [MEDLINE]
  • Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med 2009;360(1):20–31 [MEDLINE]
  • Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009;373:1874–1882 [MEDLINE]
  • Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis. Crit Care Med 2010;38(11):2222–2228 [MEDLINE]
  • Early versus late parenteral nutrition in critically ill adults. N Engl J Med 2011; 365(6):506–517 [MEDLINE]
  • Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis. Crit Care Med 2011;39:1985-1991 [MEDLINE]
  • The timing of tracheotomy in critically ill patients undergoing mechanical ventilation: a systematic review and meta-analysis of randomized controlled trials. Chest 2011;140(6):1456–1465 [MEDLINE]
  • Probiotics in the critically ill: a systematic review of the randomized trial evidence. Crit Care Med. 2012 Dec;40(12):3290-302. doi: 10.1097/CCM.0b013e318260cc33 [MEDLINE]
  • Lack of efficacy of probiotics in preventing ventilator-associated pneumonia probiotics for ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials. Chest. 2012 Oct;142(4):859-68 [MEDLINE]
  • Probiotics’ effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis. Crit Care. 2012 Jun 25;16(3):R109. doi: 10.1186/cc11398 [MEDLINE]
  • Impact of the administration of probiotics on mortality in critically ill adult patients: a meta-analysis of randomized controlled trials. Chest. 2013 Mar;143(3):646-55. doi: 10.1378/chest.12-1745 [MEDLINE]
  • Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis. Crit Care Med 2013;41(3): 693–705 [MEDLINE]
  • Toothbrushing for critically ill mechanically ventilated patients: a systematic review and meta-analysis of randomized trials evaluating ventilator-associated pneumonia. Crit Care Med 2013; 41(2):646–655 [MEDLINE]
  • Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af [MEDLINE]
  • Effect of not monitoring residual gastric volume on risk of ventilator-associated pneumonia in adults receiving mechanical ventilation and early enteral feeding: a randomized controlled trial. JAMA 2013; 309(3):249–256 [MEDLINE]
  • Technologic advances in endotracheal tubes for prevention of ventilator-associated pneumonia. Chest 2012; 142:231-238 [MEDLINE]
  • A clinical assessment of the Mucus Shaver: A device to keep the endotracheal tube free from secretions. Crit Care Med 2012;40:119-124 [MEDLINE]
  • Efficacy of single-dose antibiotic against early-onset pneumonia in comatose patients who are ventilated. Chest. 2013 May;143(5):1219-25. doi: 10.1378/chest.12-1361 [MEDLINE]
  • Antibiotic stewardship in hospital-acquired pneumonia. Chest. 2013;143:1195–1196. doi:10.1378/chest.12-2729 [MEDLINE]
  • Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial.  JAMA.  2013;309:2121–2129 [MEDLINE]
  • Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. 2014 Aug;35(8):915-36. doi: 10.1086/677144 [MEDLINE]
  • Potential strategies to prevent ventilator-associated events.  Am J Respir Crit Care Med.  2015 Dec;192:1420–1430 [MEDLINE]
  • Pneumonia prevention to decrease mortality in intensive care unit: a systematic review and meta-analysis. Clin Infect Dis 2015;60:64–75 [MEDLINE]
  • Subglottic secretion drainage and objective outcomes: systematic review and meta-analysis. Crit Care Med. 2016 Apr;44(4):830-40. doi: 10.1097/CCM.0000000000001414 [MEDLINE]

Treatment

  • Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices. Am J Respir Crit Care Med. 1999;160(2):608-613 [MEDLINE]
  • PneumA Trial. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588-2598 [MEDLINE]
  • Antimicrobial activity of tigecycline tested against organisms causing community-acquired respiratory tract infection and nosocomial pneumonia. Diagn Microbiol Infect Dis. 2005;52:187-193
  • Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clin Infect Dis. 2006;43(suppl 2):S89-S94
  • De-escalation in lower respiratory tract infections. Curr Opin Pulm Med. 2006;12(5):364-368 [MEDLINE]
  • De-escalation therapy in ventilator-associated pneumonia. Curr Opin Crit Care. 2006;12(5):452-457 [MEDLINE]
  • Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Chest 2006; 129:1210–1218 [MEDLINE]
  • Impact of inappropriate antibiotic therapy on mortality in patients with ventilator-associated pneumonia and blood stream infection: a meta-analysis. J Crit Care 2008; 23:91–100 [MEDLINE]
  • Antibiotic stewardship: overcoming implementation barriers. Curr Opin Infect Dis. 2011;24(4): 357-362 [MEDLINE]
  • Antimicrobial stewardship programs: mandatory for all ICUs. Crit Care. 2012;16:179. doi:10.1186/cc11853 [MEDLINE]
  • Impact of regular collaboration between infectious diseases and critical care practitioners on antimicrobial utilization and patient outcome. Crit Care Med. 2013;41:2099–2107. doi: 10.1097/CCM.0b013e31828e9863 [MEDLINE]
  • Effect of aerosolized colistin as adjunctive treatment on the outcomes of microbiologically documented ventilator-associated pneumonia caused by colistin-only susceptible gram-negative bacteria. Chest. 2013 Dec;144(6):1768-75. doi: 10.1378/chest.13-1018 [MEDLINE]
  • Antibiotic stewardship in hospital-acquired pneumonia. Chest. 2013;143:1195–1196. doi:10.1378/chest.12-2729 [MEDLINE]
  • What can be expected from antimicrobial de-escalation in the critically ill? Intensive Care Med 2014; 40:92–5 [MEDLINE]
  • A Systematic Review of the Definitions, Determinants, and Clinical Outcomes of Antimicrobial De-escalation in the Intensive Care Unit. Clin Infect Dis. 2016 Apr 15;62(8):1009-17. doi: 10.1093/cid/civ1199. Epub 2015 Dec 23 [MEDLINE]
  • Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):e61-e111. doi: 10.1093/cid/ciw353. Epub 2016 Jul 14 [MEDLINE]

Tracheostomy (see Tracheostomy, [[Tracheostomy]])

  • The timing of tracheotomy in critically ill patients undergoing mechanical ventilation: a systematic review and meta-analysis of randomized controlled trials. Chest 2011;140(6):1456–1465 [MEDLINE]
  • Early percutaneous tracheotomy versus prolonged intubation of mechanically ventilated patients after cardiac surgery: a randomized trial. Ann Intern Med 2011;154:373–383 [MEDLINE]
  • Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial.  JAMA.  2013;309:2121–2129 [MEDLINE]

Prognosis

  • Readmission following hospitalization for pneumonia: the impact of pneumonia type and its implication for hospitals. Clin Infect Dis. 2013 Aug;57(3):362-7 [MEDLINE]
    • Editorial commentary: “excess readmissions” for pneumonia: a dilemma with a penalty. Clin Infect Dis. 2013 Aug;57(3):368-9 [MEDLINE]