This document discusses hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). It covers the definitions, risk factors, pathogenesis, microbiology, prevention, clinical features, diagnosis through imaging and respiratory sampling, and treatment considerations for HAP and VAP. Key points include that HAP develops 48 hours after admission, VAP develops 48 hours after intubation, and the most common causes are gram-negative bacteria and Staphylococcus aureus. Invasive respiratory sampling methods like bronchoscopic BAL are preferred for diagnosis but carry more risk than noninvasive methods.

1. hospital-acquired and
ventilator-associated
pneumonia in adults

2. INTRODUCTION
• HAP (or nosocomial pneumonia) is pneumonia that occurs 48 hours or more after admission
and did not appear to be incubating at the time of admission.
• VAP is a type of pneumonia that develops ≥48 hours after endotracheal intubation.
• Patients with severe HAP who require mechanical ventilation after the onset of infection do
not meet the definition of VAP. This is termed ventilated hospital-acquired pneumonia (VHAP)

3. INTRODUCTION
• Antimicrobial resistance — The United States Centers for Disease Control and Prevention (CDC)
and the European Centre for Disease Prevention and Control (ECDC) have developed standard
terminology for antimicrobial-resistant gram-negative bacilli, which are important causes of HAP
and VAP :
• ●Multidrug resistant (MDR) refers to acquired nonsusceptibility to at least one agent in three
different antimicrobial classes.
• ●Extensively drug resistant (XDR) refers to nonsusceptibility to at least one agent in all but two
antimicrobial classes.
• ●Pandrug resistant (PDR) refers to nonsusceptibility to all antimicrobial agents that can be used for
treatment.
• Awareness of local resistance patterns is critical for decisions regarding empiric therapy for HAP
and VAP . All hospitals should regularly create and disseminate a local antibiogram, ideally one
that is specific to the different units in the hospital (although small numbers of cases per unit may
preclude this) .

4. EPIDEMIOLOGY
• HAP is one of the most common and morbid hospital-acquired infections .
• Most cases of HAP occur in nonventilated patients . However, the highest risk for HAP is in
patients on mechanical ventilation (ie, VAP), in whom the entity has been best studied.

5. MDR risk factors
• Older age ,Chronic lung disease
• Depressed consciousness ,Aspiration ,Chest or upper abdominal surgery
• Agents that increase gastric pH (H2 blockers, antacids, PPI
• Previous antibiotic exposure, especially broad-spectrum Reintubation or prolonged intubation
• Mechanical ventilation for acute respiratory distress syndrome Frequent ventilator circuit changes
• Total opioid exposure
• Multiple trauma [26 Paralysis
• Number of central venous catheter placements and surgeries [
• Use of muscle relaxants or glucocorticoids
• The presence of an intracranial pressure monitor
• Malnutrition, chronic renal failure, anemia,, previous hospitalization

6. PATHOGENESIS
• The primary route of infection of the lungs is through micro aspiration of organisms that have
colonized the oropharyngeal tract (or, to a lesser extent, the gastrointestinal tract)
• Approximately 45 percent of healthy patient aspirate during sleep and an even higher
proportion of severely ill patients aspirate routinely
• the near sterility of the stomach and upper gastrointestinal tract may be disrupted by
alterations in gastric pH due to illness, medications, or enteric feedings

7. MICROBIOLOGY
• aerobic gram-negative bacilli (eg, Escherichia coli, Klebsiella
pneumoniae, Enterobacter spp, Pseudomonas aeruginosa, Acinetobacter spp) and gram-
positive cocci (eg, Staphylococcus aureus, including methicillin-resistant S.
aureus [MRSA], Streptococcus spp)
• may be due to viruses in general medical and surgical patients and both viruses and fungi in
immunocompromised patients
• Similar findings have been observed in other surveillance studies

8. MICROBIOLOGY
• CDC from 2009 to 2010, the distribution of pathogens associated was S. aureus (24.1
percent), P. aeruginosa (16.6 percent), Klebsiella species (10.1 percent) , Enterobacter species
(8.6 percent), Acinetobacter baumannii (6.6 percent), and E. coli (5.9 percent) .
• The infecting flora in patients with VAP included methicillin-susceptible S. aureus (MSSA; 9
percent), MRSA (18 percent), P. aeruginosa (18 percent), Stenotrophomonas maltophilia (7
percent), Acinetobacter spp (8 percent), and other species (9 percent).
• The infecting flora in nonventilated patients with HAP was similar, except non-
Enterobacteriaceae gram-negative bacilli (P. aeruginosa, Acinetobacter, and S. maltophilia)
were less likely. Specifically, it included MSSA (13 percent), MRSA (20 percent), P.
aeruginosa (9 percent), S. maltophilia (1 percent), Acinetobacter spp (3 percent), and other
species (18 percent).

9. Role of gastric pH
• Several studies have noted an increased incidence of HAP when the gastric pH is increased
with the use of H2 blockers, antacids, or PPIs
• Some meta-analyses have found decreased rates of pneumonia in critically ill patients
using sucralfate for stress ulcer prophylaxis compared with H2 blockers and PPIs

10. PREVENTION
• for preventing VAP in all acute care hospitals include avoiding intubation, when possible (eg,
noninvasive ventilation),
• minimizing transport while ventilated (when feasible),
• implementation of weaning protocols,
• minimizing sedation,
• maintaining and improving physical conditioning, minimizing pooling of secretions above the
endotracheal tube cuff, elevating the head of the bed, and maintaining ventilator circuits.

14. Clinical features
• the presence of a new or progressive radiographic infiltrate plus at least two of three clinical features
(fever >38ºC, leukocytosis or leukopenia, and purulent secretions) has a 69 percent sensitivity and 75
percent specificity for VAP
• Most patients with VAP present with a gradual or sudden onset of the following more than 48 hours after
intubation :
• Symptoms – dyspnea (few patients have symptoms since most are nonverbal on mechanical ventilation)
• Signs – fever, tachypnea, increased or purulent secretions, hemoptysis, rhonchi, crackles, reduced breath
sounds, bronchospasm
• Ventilator mechanics – reduced tidal volume, increased inspiratory pressures
• Laboratory findings – worsening hypoxemia, leukocytosis
• Imaging –alveolar infiltrates, air bronchograms, and silhouetting of adjacent solid organs.
• Features may also be accompanied by systemic abnormalities, such as encephalopathy or sepsis.
• Importantly, as isolated findings, none of these features are sensitive or specific for the diagnosis of VAP

15. Chest imaging
• The chest radiograph can also help determine the severity of the disease (multilobar versus
unilobar) and identify complications, such as pleural effusions or cavitation.
• Chest imaging abnormalities alone are insufficient to diagnose VAP because the findings are
nonspecific (ie, imaging is frequently abnormal even in the absence of VAP). This was
illustrated by an observational study in which only 43 percent of patients who had clinical and
radiographic evidence of VAP at the time of their death were subsequently confirmed to have
VAP by postmortem examination

16. Advanced imaging
• CT, without contrast, is not routine in patients with suspected VAP may be useful in patients
with a normal chest radiograph who have clinical symptoms of respiratory tract infection
• CT may also help identify a target lobe for sampling. Chest CT may also be appropriate in
those with a previous CT diagnosis of pneumonia to look for new or progressive changes or
the development of a pleural effusion.
• However, in mechanically ventilated patients, pulmonary infiltrates are frequently identified
and may be associated with multiple causes. Therefore, imaging determination of VAP in the
critical care setting remains nonspecific
• Lung ultrasonography may be more useful for ruling out pneumonia, although subpleural
consolidations and dynamic air bronchograms may support VAP .Bedside ultrasound can also
be employed to diagnose VAP, although whether it leads to improved outcomes over
conventional chest imaging is unknown

17. Respiratory tract sampling
• invasive sampling methods (eg, mini-bronchoalveolar lavage [BAL], bronchoscopic BAL, or protected specimen
brush [PSB]) with quantitative cultures .
• The wide variation in practice is partially explained by a lack of gold standard for the diagnosis of Vap
• Additional factors include the ability of the patient to tolerate invasive sampling, and the presence of other
indications for bronchoscopy (eg, endobronchial obstruction, bleeding, cancer, invasive pneumonia in an
immunosuppressed patient, suspicion for a second organism [eg, patients with bronchiectasis]), available
expertise, and institutional availability and cost of quantitative cultures.
• As an example, while bronchoscopy may be preferred in an immunosuppressed patient with hemoptysis,
endotracheal aspiration may be preferred in patients in whom the suspicion for VAP is low or in whom the risk
of bronchoscopy is high (eg, patients with barotrauma, high peak pressures, severe hypoxemia)

18. Invasive respiratory sampling
• Bronchoscopic BAL is our preferred method of lower respiratory tract sampling. The rationale
for this approach is that BAL, compared with PSB (and probably mini-BAL), is a larger sample
that obtains a dominant alveolar component with minimal airway contamination. When
compared with noninvasive sampling techniques (endotracheal aspirates), bronchoscopic
sampling has been shown in several studies to reduce antibiotic overuse and result in more
rapid de-escalation of antimicrobial therapy without impacting mortality or length of stay
• differential cell count can be performed on BAL fluid
• Additional advantages include the ability to inspect the airways for purulence and exclude
conditions like malignancy and hemorrhage.

19. PSB
• PSB is a brush that is contained within a protective sheath, which minimizes the likelihood
that the brush will be contaminated during bronchoscopy. The procedure involves placing
the bronchoscope tip next to the affected bronchial segmental orifice, pushing the sheath
through the bronchoscope under direct visual guidance, and then advancing the brush out of
the sheath and into the airway. Specimens are collected by brushing the airway wall,
withdrawing the brush into the sheath, and then removing the sheath from the
bronchoscope. The distal end of brush can be cut and sent for microscopic analysis and
culture.

20. • mini-BAL is performed by advancing a catheter through the endotracheal tube blindly until
resistance is met, infusing sterile saline through the catheter (typically three 50 mL aliquots)
and then aspirating using the syringe (the catheter is estimated to be located in the distal
endobronchial). We generally reserve mini-BAL for those in whom bronchoscopy is too risky
or not available. This procedure requires less expertise and training than bronchoscopy and it
is often performed by ancillary staff (eg, nurses and respiratory therapists) rather than
clinicians. Complications are rare but include hypoxemia, endobronchial perforation, and
barotrauma. While mini-BAL samples are likely to be less contaminated by the airway than
endotracheal aspirates, they are less likely to contain a deep alveolar sample

21. • Microscopic analysis – This involves semi-quantitative analysis of polymorphonuclear leukocytes and other cell
types, as well as the Gram stain. While not diagnostic of VAP per se, the microscopy results return before
cultures and can be helpful in determining a possible pathogen and alter antibiotic selection . The presence of
abundant neutrophils is consistent with VAP and the bacterial morphology may suggest a likely pathogen (eg,
Gram-negative rods). In a prospective cohort study of 39 patients who underwent BAL, VAP was correctly
excluded in all patients in whom neutrophils were fewer than 50 percent of the total nucleated cells .
• ●Quantitative cultures – Bacteria can be counted on any respiratory specimen. VAP is supported when an
established threshold of bacterial growth is exceeded . Only bacteria that are pulmonary pathogens should be
counted. As examples, Staphylococcus epidermidis and most Gram-positive bacilli (except actinomycosis and
nocardia) should not be counted.
• Typical thresholds include the following:
• •Endotracheal aspirates – ≥1,000,000 colony forming units (cfu)/mL
• •Bronchoscopic- or mini-BAL – 10,000 cfu/mL
• •PSB – 1000 cfu/mL

22. Alternative approach
• Noninvasive sampling (ie, endotracheal aspirates) with semiquantitative cultures (or less
commonly, qualitative cultures) is the alternative approach preferred
• Noninvasive respiratory sampling — Tracheobronchial aspiration (ie, endotracheal aspirate) is
performed by advancing a catheter through the endotracheal tube until resistance is met and
suction is applied (likely located in trachea or main stem bronchu
• A clinician is not necessary to perform or supervise tracheobronchial aspiration. This method
is cheap, safe, efficient, and facilitates serial sampling. However, it may be less accurate for
sampling the alveolar component of the lower respiratory tract and lead to the over
diagnosis of VAP

23. Microscopic analysis and nonquantitative culture
• Semiquantitative cultures are typically reported as showing heavy, moderate, light, or no
bacterial growth. The amount of growth suggests VAP has not been firmly established, but
most experts consider moderate or heavy growth to be positive. Compared with quantitative
cultures, semiquantitative cultures are less likely to distinguish patients whose airways are
colonized from those who have VAP . As a result, false-positive results are more likely, which
can potentially lead to over treatment of VAP. Semiquantitative cultures are generally less
labor intensive than quantitative cultures and less costly

24. • Lung biopsy is not routinely performed in patients with suspected VAP since a diagnosis of
VAP can be made in most patients using lower respiratory tract sampling and cultures. Lung
biopsy may be reserved for patients in whom infiltrates are progressive despite antibiotic
therapy or patients in whom a non-infectious etiology is suspected
• The purpose of acquiring tissue under these circumstances is to identify a pathogen that may
have been missed with previous sampling or a pathogen that is difficult to culture (eg,
fungus, herpes viruses) or to identify a noninfectious process masquerading as infection (eg,
cancer, cryptogenic organizing pneumonitis, lymphangitis, interstitial pneumonitis, vasculitis).

25. • One disadvantage of bronchoscopic sampling is that it is only performed by physicians with
expertise in the procedure and cannot be performed by ancillary staff. In addition, it is more
invasive and ventilated patients are at risk of complications including worsening hypoxemia
and barotrauma.

26. TESTS OF LIMITED VALUE
• Biomarkers including procalcitonin, C-reactive protein (CRP), and soluble triggering receptor
(sTREM-1), and the clinical pulmonary infection score (CPIS), are additional diagnostic tests
that have been investigated. However, they have little role in the evaluation of suspected VAP
• Procalcitonin may be useful in patients with confirmed VAP when making the decision to
discontinue antibiotic therapy and it may be a useful prognostic marker

27. • Cultures of pulmonary secretions (sputum, endotracheal aspirates, bronchoalveolar lavage)
are also prone to false positives and false negatives. When compared with histology,
quantitative endotracheal aspirate cultures had a pooled sensitivity of 48 percent (95% CI 38-
57 percent) and positive predictive value of 81 percent (95% CI 67-91 percent); quantitative
bronchoalveolar lavage cultures had a sensitivity of 75 percent (95% CI 58-88 percent) and
positive predictive value of 77 percent (95% CI 66-85 percent) .
• Molecular diagnostic tests for detection

28. DIFFERENTIAL DIAGNOSIS (VAP)
• Aspiration pneumonitis
• pulmonary embolism with infarction it is distinguished from VAP when imaging
• Acute respiratory distress syndrome (ARDS) is distinguished from VAP by history (ie, risk
factors for ARDS may be present)
• Pulmonary hemorrhage Definitively distinguishing pulmonary hemorrhage from VAP
requires that the cause of the hemoptysis be identified
• Pulmonary contusion is distinguished from VAP by history (ie, recent trauma)
• Infiltrative tumor is distinguished from VAP by history (ie, history of malignancy
• Drug reaction s (eg, cyclophosphamide, methotrexate)

29. treatment
• In patients with suspected VAP, most experts agree that the lower respiratory tract should be
sampled and peripheral blood cultures should be sent obtained prior to the initiation of
antibiotics or change of antibiotic therapy (in those already receiving antibiotics). Once the
respiratory specimens have been obtained, empiric antibiotic therapy should be
administered.

32. • MDR refers to acquired nonsusceptibility to at least one agent in three different antimicrobial
classes.
• ●Extensively drug resistant refers to nonsusceptibility to at least one agent in all but two
antimicrobial classes.
• ●Pandrug resistant refers to nonsusceptibility to all antimicrobial agents that can be used for
treatment.
• Awareness of local resistance patterns is critical for decisions regarding empiric therapy for
HAP and VAP

33. EMPIRIC THERAPY
• mpiric therapy for HAP and VAP should include agents with activity against Staphylococcus
aureus, Pseudomonas aeruginosa, and other gram-negative bacilli. The choice of a specific
regimen for empiric therapy should be based upon knowledge of the prevailing pathogens
and susceptibility patterns within the patient’s health care setting as well as the patient's
individual risk factors for multidrug resistance, including their prior microbiology data. A
good-quality Gram stain can also be useful for guiding the choice of initial therapy.
• Start antibiotics within 4 hours of diagnosing HAP (if antibiotics have not already been started
[e.g., for suspected sepsis])

34. Approach to therapy
• Delaying treatment and failing to give a regimen with activity against the causative pathogens are
both associated with higher mortality rates in patients with sepsis due to HAP or VAP
• broader regimens and longer treatment courses increase the risks of adverse drug
effects, Clostridioides difficile infections, and antimicrobial resistance
• An appropriate compromise is to pair early and aggressive treatment for patients with signs of
sepsis or septic shock with early and aggressive de-escalation once the causative pathogen and
susceptibilities are known or an alternative diagnosis is established.
• patients experience worse outcomes if initial antimicrobial therapy is ineffective against the
causative pathogen
• f patients have recently received antibiotics, empiric therapy should generally be with a drug from
a different class since earlier treatment may have selected for pathogens resistant to the initial
class

37. CONVERSION TO ORAL ANTIBIOTICS
• Generally, patients can be switched to oral therapy when they are hemodynamically stable,
clinically improving, and able to tolerate oral medications. If a pathogen has been identified,
the choice of antibiotic for oral therapy should be based on the organism's susceptibility
pattern. If a pathogen has not been identified, the oral antibiotic selected should have similar
antimicrobial coverage as the intravenous agent and should have good lung penetration.

38. Allergy to penicillins or cephalosporins
• If there is a history of a mild reaadminister a cephalosporin or an antipseudomonal
carbapenem using a simple graded challenge ction to penicillin
• aztreonam (2 g intravenously [IV] every eight hours) is recommended.
• with the possible exception of those allergic to ceftazidime
• Potential toxicities

39. • MRSA linezolid or vancomycin should be included
• Telavancin, tedizolid, and ceftaroline are alternatives when neither linezolid nor vancomycin can be
used
• Daptomycin cannot be used to treat pneumonia because it is inactivated by surfactant and does
not achieve adequate concentrations in the respiratory tract.
• Tigecycline (Tygacil) Ceftaroline (Zevtera) It has been approved by the FDA for community-
acquired pneumonia (CAP) but not for CAP caused by MRSA, nor for HAP or VAP.
• Ceftobiprole (Zevtera) has been approved in Europe and Canada for treatment of HAP and CAP
not VAP.
Methicillin-susceptible S. aureus empiric therapy for MRSA should be replaced with nafcillin (2 g
every four hours), oxacillin (2 g IV every four hours), or cefazolin (2 g IV every eight hours) .

41. PROGNOSIS
• espite high absolute mortality rates in hospital-acquired (or nosocomial) pneumonia patients, the mortality attributable to the
infection is difficult to gauge. Many studies have found that HAP is associated with significant increased risk of death. However, many
of these critically ill patients die from their underlying disease and not from pneumonia. While crude all-cause mortality associated
with VAP has ranged from 20 to 50 percent in different studies ,a meta-analysis of randomized trials of VAP prevention estimated the
attributable mortality at 13 percent .Another study estimated that eliminating VAP would lead to a relative decrease in 60-day
intensive care unit mortality of 3.6 percent .
• Variables associated with increased mortality include :
• Serious illness at the time of diagnosis (eg, high Acute Physiology and Chronic Health Evaluation [APACHE] score, shock, coma,
respiratory failure, acute respiratory distress syndrome [ARDS])
• Bacteremia
• Severe underlying comorbid disease
• Infection caused by an organism associated with multidrug resistance (eg, P. aeruginosa, Acinetobacter spp, and Enterobacteriaceae,
including K. pneumoniae)
• Multilobar, cavitating, or rapidly progressive infiltrates on lung imaging
• Delay in the institution of effective antimicrobial therapy