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PHRM 111 – IID > IID 13: Therapeutics of Community Acquired Pneumonia > Flashcards

IID 13: Therapeutics of Community Acquired Pneumonia Flashcards

1
Q

What is pneumonia?

A

acute infection of pulmonary parenchyma
(ie. LRTI) accompanied by:

  • more than one symptom of acute infection
  • acute infiltrate on chest X-ray or auscultation
    findings consistent with pneumonia
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2
Q

What is CAP?

A

community-acquired pneumonia

  • in a patient not hospitalized for > 14 days before the onset of symptom
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3
Q

What is HAP?

A

hospital-acquired pneumonia

  • developing > 48 hours after admission to hospital
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4
Q

What is VAP?

A

ventilator-associated pneumonia

  • developing 48 hours post-intubation
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5
Q

Compare CAP and HAP/VAP.

A
  • multi-drug resistance higher in HAP/VAP
  • mortality higher in HAP/VAP
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6
Q

Pathophysiology

What organisms usually colonize the oropharynx?

A
  • non-virulent, non-pathogenic organisms
  • gram-positive
  • aerobic
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7
Q

Pathophysiology

What are the 3 routes that microorganisms access the LRT via?

A
  • aspiration of oropharyngeal contents (most common
  • inhalation of aerosolized particles
  • via bloodstream from extrapulmonary site of infection
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8
Q

Pathophysiology

What are the pulmonary defenses?

A
  • mechanical barriers
  • secretory
  • phagocytic
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9
Q

Epidemiology

A
  • most common cause of death from infection
  • 7-8th most common cause of death overall
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10
Q

What are the risk factors for CAP?

A
  • altered mental status – sleep, intoxication (alcohol or other CNS depressants), neurological diseases (stroke or seizure, dementia, etc)
  • impaired mechanical defenses – smoking, impaired cough/gag reflexes, endotracheal intubation, chest tubes, etc.
  • impaired cellular or humoral immunity – elderly, malnourished, HIV/AIDS, patients on chronic corticosteroids or other immunosuppressives, cancer, asplenia etc.
  • chronic debilitating diseases – chronic heart, lung, liver, or renal disease; diabetes
  • lifestyle – alcoholism, current or past smoking, underweight, living with >10 people, lots of contact with children
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11
Q

What are the symptoms of CAP?

A
  • cough (typically productive)
  • fever with chills, rigors and sweats
  • shortness of breath
  • chest pain
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12
Q

What are the signs of CAP?

A
  • fever, tachycardia, tachypnea
  • crackles/rhonchi/dullness on lung exam
  • leukocytosis, left shift, drop in PO2
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13
Q

What test is performed in all patients suspected having pneumonia?

A

chest x-ray

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14
Q

How are chest x-rays used in patients suspected of having pneumonia?

A
  • never used alone to diagnose pneumonia
  • useful to monitor for complications of pneumonia like pleural effusions, empyemas, and abscess formation
  • lag time for resolution of CXR
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15
Q

Chest X-rays

What do classic bacterial pneumonias present as?

A

unilateral or bilateral infiltrates

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16
Q

Chest X-rays

What do classic aspiration pneumonias primarily affect?

A

right lobes

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17
Q

Chest X-rays

What do ‘atypical’ infections present as?

A

a diffuse, interstitial pattern

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18
Q

Gram-Stain/Culture

A

rapid, early test to identify potential etiologic organism(s)

  • sensitivity and specificity is low at 15-100%
  • adequate specimen – seen when > 25 neutrophils and < 10 epithelial cells per LPF
  • neutrophils (or PMNS) are hallmarks of infection – without neutrophils may represent colonization only
  • if admission is required, obtain sputum gram stain & culture and blood cultures
  • patients who have been adequately treated with a course of antibiotics and are clinically improved despite ongoing positive sputum cultures should be deemed to be colonized, and bacterial eradication is not an appropriate endpoint of therapy
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19
Q

Microbiology

A
  • Streptococcus pneumoniae
  • ‘atypicals’ – Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella spp.
  • Haemophilus influenzae
  • respiratory viruses
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20
Q

Microbiology

Ambulatory Patients

A
  • S. pneumoniae
  • M. pneumoniae
  • H. influenzae
  • C. pneumoniae
  • respiratory viruses – influenza A and B, parainfluenza, RSV, rhinvirus, adenovirus
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21
Q

Microbiology

Hospital, Non-ICU

A
  • S. pneumoniae
  • M. pneumoniae
  • H. influenzae
  • Legionella spp.
  • respiratory viruses – influenza A and B, parainfluenza, RSV, rhinvirus, adenovirus
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22
Q

Microbiology

Hospital, ICU

A
  • S. pneumoniae
  • S. aureus
  • Legionella spp.
  • gram-negative bacilli
  • respiratory viruses – influenza A and B, parainfluenza, RSV, rhinvirus, adenovirus
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23
Q

Streptococcus pneumonia

A
  • gram (+), lancet-shaped diplococcus in chains
  • most common etiologic organism in CAP
  • most common cause of bacteremic pneumonia
  • highest mortality
  • abrupt onset of shaking chills, chest pain, productive ‘rust-coloured’ cough preceded by malaise, sore throat, rhinorrhea
  • penicillin-resistant strains becoming more common – higher doses of beta-lactams are adequate to treat non-CSF isolates of Streptococcus
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24
Q

Streptococcus pneumonia

What are the agents of choice for very resistant organisms?

A

vancomycin or levofloxacin

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25
Q

Non-Meningitis Streptococcus pneumonia

Oral – S, I, R

A
  • S ≤ 0.06
  • I = 0.12-1
  • R ≥ 2
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26
Q

Non-Meningitis Streptococcus pneumonia

IV – S, I, R

A
  • S ≤ 2
  • I = 4
  • R ≥ 8
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27
Q

Meningitis Streptococcus pneumonia

S, R

A
  • S ≤ 0.06
  • R ≥ 0.12
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28
Q

What is S. pneumo resistant to?

A

significant resistance to macfrolides

  • azithromycin in particular has been shown to promote DRSP due to its longer half-life which promotes tissue concentrations well below the MIC of the organism
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29
Q

What are the risk factors for resistant S. pneumoniae?

A
  • age > 65 years
  • alcoholism
  • immune-suppressive illness or medications
  • multiple medical comorbid conditions
  • exposure to a child in a day care center
  • beta-lactam therapy within the past 3 months
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30
Q

Hemophilus influenzae/Moraxella catarrhalis

A
  • gram-negative coccobacillus, encapsulated
  • most common gram-negative organism in CAP – more common in smokers, COPD, alcoholics
  • 30-50% of strains produce beta lactamase that destroys penicillins (ampicillin, amoxicillin) – no longer recommended for empiric treatment
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31
Q

Hemophilus influenzae/Moraxella catarrhalis

What antibiotics are effective?

A
  • beta lactams/beta lactamase inhibitors –amoxicillin/clavulanic acid, 2nd/3rd generation cephalosporins
  • fluoroquinolones
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32
Q

Mycoplasma pneumonia / Chlamydophila pneumonia

A
  • ‘atypical’ bacteria with no cell wall
  • transmitted by aerosolization, incubation period of 2-4 weeks
  • outbreaks in young adults with no or few comorbidities
  • prodrome of fever, chills, headache, sore throat, malaise, dry cough that’s turns mucoid
  • difficult to identify via standard culture methods, empirical treatment
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33
Q

Mycoplasma pneumonia / Chlamydophila pneumonia

What is this treated with?

A
  • macrolide
  • doxycyline
  • resp fluoroquinolone
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34
Q

Legionella pneumophilia

A
  • gram-negative bacilli (sometimes classified as atypical), water-lover, moist environments
  • transmitted by aerosolization, usually localized outbreaks
  • risks are recent travel, older age, chronic illness
  • life-threatening in immunocompromised patients
  • starts slowly, then high fever, CNS effects like H/A, obtundation, seizures, malaise, non-productive cough, hyponatremia, increased LFTS, BUN, Cr
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35
Q

Legionella pneumophilia

What is this treated with?

A
  • IV azithromycin
  • resp fluoroquinolone
36
Q

What are the risk factors for acquiring enteric gram-negative bacteria?

A
  • residence in a nursing home
  • underlying cardiopulmonary disease
  • prior isolation of ESBL
  • recent hospitalization (within 90 days)
  • recent IV antibiotics (within 90 days)
37
Q

What are the risk factors for acquiring Pseudomonas aeruginosa?

A
  • structural lung disease (bronchiectasis, CF, COPD)
  • corticosteroid therapy (prednisone, >10 mg/d)
38
Q

What are the risk factors for resistance to Pseudomonas aeruginosa?

A
  • prior isolation of PA
  • recent hospitalization (within 90 days)
  • recent IV antibiotics (within 90 days)
39
Q

What are the risk factors for resistance to methicillin-Resistant Staphylococcus aureus (MRSA)?

A
  • prior isolation of MRSA
  • recent hospitalization (within 90 days)
  • recent IV antibiotics (within 90 days)
40
Q

What are the risk factors for acquiring methicillin-Resistant Staphylococcus aureus (MRSA)?

A
  • IVDU
  • HD
  • CVC
  • skin disease
  • surgery
  • foreign material
41
Q

What are the guidelines principles for diagnosis and treatment of CAP? (4)

A
  • treatment setting (outpatient/inpatient)
  • severity (inpatient)
  • potential for the presence of resistant organisms
  • presence of comorbidities
42
Q

What are the goals of CAP therapy?

A
  • prevent mortality
  • prevent need for intubation/mechanical ventilation, ICU admission
  • reduce prolonged hospital stay
  • cure infection
  • resolve signs and symptoms of infection
  • prevent/minimize risk for future infection
  • minimize ADR from antibiotics
43
Q

What are the steps of CAP therapy?

A
  1. where to treat – outpatient or inpatient
  2. determine disease severity
  3. think about potential for resistant pathogens, and comorbidities
  4. what are the possible therapeutic alternatives for empiric treatment (outpatient/inpatient)
  5. what will you recommend for empiric treatment (inpatient)
  6. monitoring for efficacy and safety
44
Q

Steps to CAP Therapy

Step 1: How do we determine where to treat?

A

scoring systems used to determine where to treat as they predict risk for death

  • CURB65 / CRB65
  • PSI
45
Q

Steps to CAP Therapy

What is CURB65/CRB65?

A
  • C – confusion (1 pt)
  • U – blood urea nitrogen > 7 mmol/L (1 pt)
  • R – Respiratory rate ≥ 30/min (1 pt)
  • B – Blood pressure, systolic < 90 mmHg or diastolic ≤ 60mmHg (1 pt)
  • age ≥ 65 yrs (1 pt)

*no BUN needed

46
Q

Steps to CAP Therapy

What is PSI?

A

pneumonia severity index

  • score ≤ 90 send home
  • score ≥ 91 admit to hospital
47
Q

Steps to CAP Therapy

Step 2: How is disease severity determined?

A

patient meets at least one major criteria or 3 minor criteria

48
Q

Steps to CAP Therapy

Step 3: What are the strong risk factors associated with MRSA or PA or resistant gram-negative bacilli?

A
  • prior isolation (especially from RT), OR
  • recent hospitalization (in last 90 days), OR
  • exposure to parenteral abx in last 90 days
  • consider epidemiologic factors – surgery means SA, chronic lung disease means PA
49
Q

Steps to CAP Therapy

Step 3: What are some comorbidities?

A
  • chronic heart, lung, liver, or renal disease;
  • diabetes mellitus
  • alcoholism
  • malignancy
  • asplenia
  • immunocompromised
50
Q

Steps to CAP Therapy

Step 4: What are the possible therapeutic alternatives for empiric treatment (outpatient) if the patient has no risk factors or comorbidities?

A
  • amoxicillin 500-1000 mg tid
  • doxycycline 100mg bid
  • macrolide (ONLY use if PRSP < 25%)
  • duration: 5 days**

(azithromycin 500mg po day 1, then 250mg po daily x 4 days / clarithromycin 500mg po bid or 1000mg XL daily)

** = DBND suggests 3-5 days

51
Q

Steps to CAP Therapy

Step 4: What are the possible therapeutic alternatives for empiric treatment (outpatient) if the patient has comorbidities?

A
  • beta-lactam (po)* + (macrolide or doxycycline) (po)
  • respiratory quinolone (po)
  • duration: 5 days**
  • = amox-clavulanate (875/125mg BID or 500/125mg TID) or cefuroxime 500mg BID should target > 95% S.pneumoniae

resp FQ = levofloxacin 750mg po daily or
moxifloxacin 400mg po daily

** = DBND suggests 3 to 5 days

52
Q

Steps to CAP Therapy

Step 4: What are the possible therapeutic alternatives for empiric treatment (outpatient) if the patient has severe allergy to penicillin/amoxicillin?

A

cefuroxime 500 mg PO BID x 5 days

53
Q

Steps to CAP Therapy

Step 4: What are the possible therapeutic alternatives for empiric treatment (outpatient) if the patient has severe allergy to penicillin/amoxicillin/cefuroxime?

A

doxycycline 100 mg PO BID x 5 days

54
Q

What are the 4 main adverse effects of fluoroquinolone antibiotics?

A
  • tendonitis
  • peripheral neuropathy
  • prolongation of QT interval
  • blood glucose disturbances
55
Q

Steps to CAP Therapy

Step 4: What are the possible therapeutic alternatives for empiric treatment (inpatient) if the patient has non-severe disease, CRB65 = 2, with no risk factors?

A

duration: 5-7 days

  • beta-lactam (po/iv) +
  • add doxycycline (po) or macrolide (po/iv) if
    suspect atypicals, OR
  • respiratory quinolone (po/iv)
56
Q

Steps to CAP Therapy

Step 4: What are the possible therapeutic alternatives for empiric treatment (inpatient) if the patient has non-severe disease, CRB65 = 2, with risk factors?

A

duration: 5-7 days

  • same regimen as no risk factors
  • same DOT
  • take cultures for MRSA/PA
  • do not add empiric tx for MRSA/PA unless patient had a prior respiratory isolate
57
Q

What is the rationale for using IV beta lactam + macrolide for treatment)?

A
  • 3rd generation cephalosporins have broad coverage (work against SP/H glu/Morexella)
  • macrolide covers for atypicals and Legionella
58
Q

What is the rationale for using double tx for treatment?

A

studies have shown that double tx has lower mortality than beta lactams alone

59
Q

What is the rationale for using fluoroquinolone monotherapy for treatment?

A

covers for SP/GNB, atypicals, and Legionella, with studies showing similar outcomes as double therapy

60
Q

Steps to CAP Therapy

Step 4: What are the possible therapeutic alternatives for empiric treatment (inpatient) if the patient has severe disease/ICU, CRB65 = 3-4, with no risk factors?

A

duration: 5-14 days

  • beta-lactam (iv)** + FQ
  • beta-lactam (iv)** + macrolide
61
Q

Steps to CAP Therapy

Step 4: What are the possible therapeutic alternatives for empiric treatment (inpatient) if the patient has severe disease/ICU, CRB65 = 3-4, with risk factors?

A

duration: 5-14 days

  • same regimen as no risk factors
  • same DOT
  • take cultures for MRSA/PA
  • add empiric tx for MRSA/PA

MRSA:

  • add vancomycin 25-30mg/kg IV once then 15mg/kg IV q8-12h, OR
  • linezolid 600mg po/iv bid

Pseudomonas:

  • use anti-pseudomonal BL
  • piperacillin-tazobactam (4.5 g every 6 h), cefepime (2 g every 8 h), ceftazidime (2 g every 8 h), imipenem (500 mg every 6 h), meropenem (1 g every 8 h), or aztreonam (2 g every 8 h)
62
Q

What would be used to treat penicillin non-resistant Streptococcus pneumoniae?

A
  • initial therapy: amoxicillin or pen G
  • alternatives: macrolides, doxycycline, new FQ
63
Q

What would be used to treat penicillin resistant Streptococcus pneumoniae?

A
  • initial therapy: cefotaxime, ceftriaxone OR moxifloxacin
  • alternatives: vancomycin, linezolid
64
Q

What would be used to treat BL-susceptible Hemophilus influenzae?

A

amoxicillin

65
Q

What would be used to treat BL-resistant Hemophilus influenzae?

A

2nd or 3rd generation cephalosporin, amoxicillin/clavulanate, new macrolides, or new fluoroquinolones

66
Q

What would be used to treat Legionella?

A

fluoroquinolones, azithromycin

67
Q

What would be used to treat Mycoplasma or Chlamydophila pneumoniae?

A

macrolides, doxycycline, fluoroquinolones

68
Q

What would be used to treat aerobic gram-negatives?

A
  • 3rd or 4th or 5th generation cephalosporin
  • carbapenem (imipenem, ertapenem, meropenem)
69
Q

What would be used to treat Pseudomonas aeruginosa?

A

anti-pseudomonal beta-lactam + fluoroquinolone or aminoglycoside

70
Q

When do we step down to oral antibiotic therapy?

A

patient clinically improving, with ≥ 2 of following:

  • afebrile
  • HR < 90 beats/min
  • RR < 20 breaths/min
  • WBC 4-12 x 109 cells/mm3
  • able to tolerate oral
  • no factors affecting absorption
  • oral options available based on susceptibilities
71
Q

Steps to CAP Therapy

Step 6: Why might corticosteroids be used as adjunctive therapy?

A

attempt to reduce the inflammatory response
to pneumonia → morbidity of the disease

  • no benefit in non-severe CAP
  • severe CAP have shown a small mortality benefit – may use in these patients, but consider adverse events
72
Q

Describe invasive vs. non-invasive pneumococcal disease.

A
  • invasive: meningitis, bacteremia
  • non-invasive (mucosal): pneumonia, acute otitis media, sinusitis
  • non-invasive forms of disease may become invasive (ie. pneumonia when accompanied by bacteremia)
  • serotype can be associated with disease severity and invasiveness
73
Q

How effective are pneumococcal vaccines?

A

among the > 100 recognized serotypes of S. pneumoniae, invasive disease caused by 24 serotypes can be prevented by vaccination

74
Q

What are the risk factors for pneumococcal disease in immunocompetent adults?

A
  • chronic heart disease
  • chronic lung disease
  • diabetes
  • functional or anatomic asplenia
  • chronic liver disease
  • cerebrospinal fluid leaks
  • cochlear implants
  • chronic renal failure, nephrotic syndrome
75
Q

What are the risk factors for pneumococcal disease in immunocompromised adults?

A
  • HIV infection
  • cancer (solid, hematologic)
  • solid organ transplantation
  • autoimmune diseases
  • immunosuppressive therapy
  • primary immunodeficiencies
  • prednisone (ie. >20 mg/day)
76
Q

What are the external risk factors for pneumococcal disease?

A
  • socioeconomic
  • environmental
  • preceding viral respiratory infection (ie. influenza)
  • residence in an institution
77
Q

What are the behavioural risk factors for pneumococcal disease?

A
  • smoking
  • alcohol abuse
  • homelessness
  • illicit drug use
78
Q

What are the age risk factors for pneumococcal disease?

A

≥ 65 years

79
Q

Compare polysaccharide vaccines and conjugate vaccines.

A

conjugate vaccines produce a more robust response compared to polysaccharide vaccines and induce immune memory

80
Q

Describe the efficacy of PPV23.

A
  • not effective in children → not used routinely
  • 60-75% against IPD among healthy young adults
  • 50% to 80% among the elderly and in high-risk groups
  • 30% for pneumococcal pneumonia!!
  • failure to stimulate memory (T cell independent pathways)
81
Q

What are the NACI 2025 recommendations for pneumococcal vaccines in adults?

A

recommends routine administration of PCV20 or PCV21 for:

  • all adults ≥ 65 years
  • 18+ years living with risk factors
82
Q

What are the BCCDC recommendations for PPV23?

A
  • individuals ≥ 65 years of age
  • any age living in LTCF
  • individuals ≥ 2 years of age at risk of IPD
83
Q

What are the BCCDC recommendations for PCV13?

A
  • children 2-59 months of age
  • adults – HSCT, HIV
84
Q

What are the non-immunocompromising conditions resulting in risk of IPD?

A
  • chronic CSF leak
  • chronic neurologic condition that may impair clearance of oral secretions
  • cochlear implants
  • chronic heart disease
  • diabetes mellitus
  • chronic kidney disease
  • chronic liver disease
  • chronic lung disease
85
Q

What are the immunocompromising conditions resulting in risk of IPD?

A
  • sickle cell disease, congenital or acquired asplenia, or splenic dysfunction
  • congenital immunodeficiencies involving any part of the immune system
  • HIV infection
  • hematopoietic stem cell transplant (recipient)
  • immunocompromising therapy, including use of long-term corticosteroids, biologic therapy, chemotherapy, radiation therapy, and post-organ transplant therapy
  • malignant neoplasms, including leukemia and lymphoma
  • nephrotic syndrome
  • solid organ or islet transplant (candidate or recipient)

PHRM 111 – IID (20 decks)

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