RESP: L7 Hospital Acquired Pneumonia

CAP is pneumonia in a patient not hospitalized for ≥ … days before the onset of symptoms

• Microbiology:

  • …, H. influenzae, M. pneumoniae, C. pneumoniae, Legionella, viruses

14, S. pneumoniae

Epidemiology

• HAP is the … most common nosocomial infection

  • Incidence: 5-10 cases per 1000 admissions

• Has the … mortality rate of all nosocomial infections

  • Overall HAP mortality rate: 20%

  • VAP mortality rate: 24-50%

• Associated with … hospital stay and costs

2nd, highest, longer

HAP is pneumonia developing > … hours after admission to hospital

• Early onset

  • HAP occurring within the first … hours (<… days) of hospitalization

• Late onset

  • HAP occurring after more than … hours (≥… days) of hospitalization

48, 96, 5, 96, 5

Pathophysiology

• … of oropharyngeal tract → … of oropharyngeal contents → HAP

• … spread (less common) → HAP

Colonization, Microaspiration, Hematogenous

Patient risk factors for HAP

• Advanced age (>… years)

• …

• …

• …

• … dysfunction

70, Coma, COPD, Alcoholism, CNS

Intervention risk factors for HAP

• …/narcotics (can promote microaspirations or compromises immune system)

• … and cytotoxic agents

• Surgery (especially … surgery)

• … tubes

Sedatives, Corticosteroid, cardiothoracic, Nasogastric

Other risk factors for HAP

• Colonization of respiratory and gastrointestinal tract with pathogenic microorganisms

  • Previous/current … therapy

  • Endotracheal …

  • …

  • …

  • Dental …

  • … suppression

antimicrobial, intubation, Smoking, Malnutrition, plaque, Gastric acid

Diagnosis of HAP

• Usual diagnostic criteria for HAP:

  • Abnormal findings on … radiograph PLUS

  • At least 2 of: …, …, … tracheal secretions

• Has high diagnostic …, but low … to HAP

• Features can also be found in other conditions such as … failure, pulmonary embolism, pulmonary hemorrhage, malignancy, pulmonary drug reactions

chest, fever, leukocytosis, purulent , sensitivity, specificity, heart

Clinical presentation

• Vitals:

  • …

  • Increased …

  • Increased … requirements

Fever, respiratory rate, oxygen

Clinical presentation

• Respiratory:

  • Shortness of breath, … chest pain, cough ± … production

    • Physical exam: … to percussion, … air entry and … on auscultation

    • Radiology: new pulmonary … on chest radiograph

pleuritic, sputum, dullness, decreased, crackles, infiltrates

Clinical presentation

• Other:

  • Increased …

  • …, anorexia, nausea, vomiting

  • … (hypotension, end organ dysfunction, lactic acidosis, etc) in approx 10% of cases

WBC, Confusion, Sepsis

Microbiology

• Recommended that a … respiratory (i.e. exporated sputum) and … cultures are taken for patients with suspected HAP to guide antimicrobial choice and allow for future de-escalation of therapy

• … swab for respiratory … if appropriate (e.g. during influenza season)

non-invasive, blood, Nasopharyngeal, viruses

Sputum culture

• Sensitivity and specificity of gram stain and culture of sputum ranges from …% and …%, resepctively (depends on type and quality of sample)

• In patients in whom sputum cultures are taken with no prior antimicrobial therapy, a … gram stain and culture has good negative predictive value (…%)

  • Other diagnosis should be considered

• It is hard to acquire sputum because there tend to be … in it too and it has its own bacteria

57-95, 48-87, negative, 94, saliva

Gram stain and sputum culture interpretation

• E.g.

  • 3+ polymorphs

    • Presence of polymorphonucleocytes indicates …

  • >23 epithelial cells per light power field

    • Indicates sample is contaminated with …; interpret results with caution

  • 2+ gram negative bacilli

• Culture: moderate growth of … oxytoca

• Susceptibilities to drug: pending

• Note:

  • A … does not necessarily indicate the presence of infection

  • Culture results must be put into … with patient’s clinical presentation

inflammation, saliva, Klebsiella, positive, context

Bronchoscopy

• More … method of obtaining deeper airway samples

  • Includes procedures such as bronchoalveolar lavage (BAL) and protected specimen brush (PSB)

  • Less likely to be contaminated with … secretions

  • Requires …, specialty personnel, and use of …; not used routinely

  • Reserved for patients who do not respond to usual … therapy or in whom etiology of respiratory syndrome is …

invasive, oral, intubation, sedation, empiric, unclear

Chest x-ray (CXR)

• Radiographic patterns of HAP can be variable; most likely to be … with … or multilobar consolidation

  • Radiographic signs are also …; most reliable feature pf pneumonia is the presence of an air …

• Complications of pneumonia seen on CXR include:

  • … (associated with S. aureus, gram negative organisms, and anaerobes)

  • Lung …

  • Parapneumonic pleural …

bilateral, diffuse, non-specific, bronchogram, Cavitation, abscess, effusions

Computerized tomography

• Not used routinely

• Used to better … CXR findings in patients where the diagnosis of pneumonia is not … or in patients that are not responding to usual … antimicrobial therapy

characterize, clear, empiric

Goals of therapy

• Prevent …

• Prevent … such as sepsis, prolonged hospital stay

• Cure infection

• Resolve signs/symptoms of infection

• Minimize adverse effects

mortality, complications

Considerations affecting antimicrobial choice

• … of illness

• Likely …

  • Risk factors for resistant organisms such as P. aeruginosa and MRSA

  • Early vs late onset

• Local antimicrobial … (antibiogram)

• …/… factors

• … status

• … (i.e. renal and hepatic) function

• … interactions

• Adverse effects

Severity, pathogens, susceptibilities, Pharmacokinetic, pharmacodynamic, Allergy, End-organ, Drug-drug

Severity of illness

• Several studies showing increase in mortality with increasing delay to administration of … antimicrobial therapy in patients with … shock

• Clinical features suggesting high risk of …

  • Need for … support

  • Septic shock

effective, septic, mortality, ventilatory

Risk factors for resistance

• Hospitalization for at least … days (i.e. late onset)

• Receipt of antimicrobial therapy in the previous … days

• MRSA

  • Prior detection of MRSA (on culture or screening)

  • Treatment in a unit where prevalence of MRSA amongst S. aureus isolates is > … %

• Other

  • Persons who inject drugs (PWID), hemodialysis patients, skin disease, venous catheters, other foreign bodies (i.e. pacemakers), surgical procedures, hospitalization

5, 90, 20

Risk factors for resistance — pseudomonas:

• … ventilation

• History of …

• Cystic fibrosis and bronchiectasis

Mechanical, COPD

Local susceptibilities (antibiogram)

• Empiric antimicrobial therapy should be guided by local … of pathogens as well as their antimicrobial …

• Antibiograms list the proportion of organisms, isolated in a particular ward/institution, susceptible to antimicrobials over a set time period

frequencies, susceptibilities

… is well known to be sequestered by pulmonary surfactant resulting in inactivation of drug

Daptomycin

PK/PD considerations in pneumonia

• Current knowledge of PK/PD of antimicrobials in lung tissue based on concentration of drug in epithelial lung fluid (ELF)

• Macrolides, fluoroquinolones, oxazolidinones have ELF:plasma ratios >…

• Beta-lactams, aminoglycosides, and glycopeptides have ELF:plasma ratios <…

• Clinical significance of ELF:plasma ratios not well-understood

1, 1

Empiric Therapy for Patients Not at High Risk of Mortality & No Risk Factors for Resistance (Mild Presentation):

• Initial empiric treatment

  • … or …

• For severe beta-lactam allergy

  • …

Amoxicillin-clavulanate 875 mg PO BID, Ceftriaxone 1 g IV q24h, Moxifloxacin 400 mg PO/IV q24h

Empiric Therapy for Patients with Moderate Presentation OR Risk Factors for Resistance (same treatment for patients at High Risk of Mortality— severe)

• Initial empiric

  • …

• Severe beta-lactam allergy or concern for ESBL organisms

  • …

• MRSA known/suspected

  • …

Piperacillin-tazobactam 3.375 g IV q6h, Meropenem 500 mg IV q6h, Vancomycin 15 mg/kg IV q12h

… initially thought to provide advantage over vancomycin in treating respiratory infections due to higher epithelial lining fluid …

• In meta-analyses, … difference in mortality, clinical cure or serious adverse events were found

Linezolid, concentrations, no

Double coverage of pseudomonas

• Concept of using … agents for the treatment of Pseudomonas infections stems from a 1989 study suggesting mortality benefit with use of 2 agents vs monotherapy (primarily aminoglycosides)

• Other arguments for use of combination therapy:

  • … empiric coverage

  • In vitro synergy

  • Prevent or delay emergence of resistance

• A meta-analysis observed no mortality benefit with combination therapy in Pseudomonas bacteremia

• Insufficient evidence exists to confirm whether in vitro synergy results in improved clinical outcomes or whether combination therapy prevents resistance

• Routine use of … therapy for Pseudomonas infections is not recommended

• Combination therapy can be considered in critically … patients to improve likelihood that the pathogen is covered by at least one agent

  • Once susceptibilities are known, therapy should be stepped down to …

2, Broadened, combination, ill, monotherapy

De-escalation of therapy

• Therapy should be adjusted once pathogen has been … and susceptibilities are known

• If no pathogen identified and patient is clinically improving, appropriate to de-escalate or rationalize empiric therapy to a …spectrum therapy (eg. piperacillin-tazobactam → amoxicillin- clavulanate)

identified, narrower

It is recommended that HAP is treated for … days

7

Monitoring parameters for treatment of pneumonia:

• Clinical symptoms

• Laboratory

  • Normalization of …, clearance of blood cultures if associated bacteremia

• Repeat chest radiography is generally … recommended due to … in radiographic changes

leukocytosis, not, lag

VAP

• Subset of HAP

• Pneumonia in a patient mechanically ventilated for >… hours with at least 2 of:

  • Temperature >… degrees Celsius

  • Leukocytosis or leukopenia

  • … tracheal secretions

• At least one of:

  • New or persistent … on chest radiographs

  • Isolation of same … from pleural fluid and tracheal secretions

  • Radiographic cavitation

  • Histopathological demonstration of pneumonia and positive cultures obtained from bronchoalveolar lavage

48, 38.3, Purulent, infiltrates, microorganism,

… ventilation decreases work of breathing, reverses hypoxemia, and respiratory acidosis

Mechanical

Pathophysiology

• … of endotracheal secretions around endotracheal cuff → … of endotracheal secretions → VAP

Leakage, Aspiration

Management of VAP = management of …

HAP

Aspiration pneumonia

• Seen in both community and hospital settings, however, … can put patients at higher risk for aspiration

• Aspiration: inhalation of oropharyngeal or … contents into the larynx and lower respiratory tract

• Incidence not known, however, in healthy individuals, microaspiration occurs in about 50% of individuals

• Large volume aspiration (…) is main component of aspiration pneumonia

hospitalization, gastric, macroaspiration

Risk factors for aspiration pneumonia

• Impaired …

• Decreased level of …

• Increased chance of … contents reaching lungs

• Impaired … reflex

• …

swallowing, consciousness, gastric, cough, medication

Aspiration → macroaspiration of …./oropharyngeal contents → … pneumonitis

gastric, chemical

Aspiration → macrosaspiration of … bacteria from oropharyngeal or gastric contents → … pneumonia

pathogenic, aspiration

Chemical pneumonitis is …

sterile

Both chemical pneumonitis and aspiration pneumonia can have very … clinical and radiographic presentations making it difficult to … between the two syndromes

similar, distinguish

If patient has adequate respiratory reserve, can monitor and reassess in 24 hours

• Aspiration pneumonitis will have … onset and resolution, with … and hypoxemia resolving within … hours

abrupt, fever, 24

Empiric therapy for chemical pneumonitis

• …

  • … are not indicated

Supportive, Antibiotics

Empiric therapy for aspiration pneumonia

• Empiric

  • …

• If severe

  • …

• Plus, if known or suspected MRSA

  • …

• Severe beta-lactam allergy

  • …

• Duration and de-escalation

  • … and duration

  • Duration of therapy: … days

• Additional anaerobic coverage can be added to ceftriaxone if: subacute onset, putrid sputum; or lung abscess, necrotizing pneumonia or empyema

  • …

Ceftriaxone 1 g IV q24h, Piperacillin-tazobactam 3.375 g IV q6h, Vancomycin, Moxifloxacin 400 mg PO/IV q24h, Oral stepdown, 5-7, Metronidazole 500 mg PO/IV q12h