IID 13: Therapeutics of Community Acquired Pneumonia Flashcards
(85 cards)
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
2
Q
What is CAP?
A
community-acquired pneumonia
- in a patient not hospitalized for > 14 days before the onset of symptom
3
Q
What is HAP?
A
hospital-acquired pneumonia
- developing > 48 hours after admission to hospital
4
Q
What is VAP?
A
ventilator-associated pneumonia
- developing 48 hours post-intubation
5
Q
Compare CAP and HAP/VAP.
A
- multi-drug resistance higher in HAP/VAP
- mortality higher in HAP/VAP
6
Q
Pathophysiology
What organisms usually colonize the oropharynx?
A
- non-virulent, non-pathogenic organisms
- gram-positive
- aerobic
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
8
Q
Pathophysiology
What are the pulmonary defenses?
A
- mechanical barriers
- secretory
- phagocytic
9
Q
Epidemiology
A
- most common cause of death from infection
- 7-8th most common cause of death overall
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
11
Q
What are the symptoms of CAP?
A
- cough (typically productive)
- fever with chills, rigors and sweats
- shortness of breath
- chest pain
12
Q
What are the signs of CAP?
A
- fever, tachycardia, tachypnea
- crackles/rhonchi/dullness on lung exam
- leukocytosis, left shift, drop in PO2
13
Q
What test is performed in all patients suspected having pneumonia?
A
chest x-ray
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
15
Q
Chest X-rays
What do classic bacterial pneumonias present as?
A
unilateral or bilateral infiltrates
16
Q
Chest X-rays
What do classic aspiration pneumonias primarily affect?
A
right lobes
17
Q
Chest X-rays
What do ‘atypical’ infections present as?
A
a diffuse, interstitial pattern
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
19
Q
Microbiology
A
- Streptococcus pneumoniae
- ‘atypicals’ – Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella spp.
- Haemophilus influenzae
- respiratory viruses
20
Q
Microbiology
Ambulatory Patients
A
- S. pneumoniae
- M. pneumoniae
- H. influenzae
- C. pneumoniae
- respiratory viruses – influenza A and B, parainfluenza, RSV, rhinvirus, adenovirus
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
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
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
24
Q
Streptococcus pneumonia
What are the agents of choice for very resistant organisms?
A
vancomycin or levofloxacin
25
Non-Meningitis Streptococcus pneumonia
Oral – S, I, R
- S ≤ 0.06
- I = 0.12-1
- R ≥ 2
26
Non-Meningitis Streptococcus pneumonia
IV – S, I, R
- S ≤ 2
- I = 4
- R ≥ 8
27
Meningitis Streptococcus pneumonia
S, R
- S ≤ 0.06
- R ≥ 0.12
28
What is S. pneumo resistant to?
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
29
What are the risk factors for resistant S. pneumoniae?
- 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
30
Hemophilus influenzae/Moraxella catarrhalis
- 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
31
Hemophilus influenzae/Moraxella catarrhalis
What antibiotics are effective?
- beta lactams/beta lactamase inhibitors – amoxicillin/clavulanic acid, 2nd/3rd generation cephalosporins
- fluoroquinolones
32
Mycoplasma pneumonia / Chlamydophila pneumonia
- '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
33
Mycoplasma pneumonia / Chlamydophila pneumonia
What is this treated with?
- macrolide
- doxycyline
- resp fluoroquinolone
34
Legionella pneumophilia
- 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
35
Legionella pneumophilia
What is this treated with?
- IV azithromycin
- resp fluoroquinolone
36
What are the risk factors for acquiring enteric gram-negative bacteria?
- residence in a nursing home
- underlying cardiopulmonary disease
- prior isolation of ESBL
- recent hospitalization (within 90 days)
- recent IV antibiotics (within 90 days)
37
What are the risk factors for acquiring Pseudomonas aeruginosa?
- structural lung disease (bronchiectasis, CF, COPD)
- corticosteroid therapy (prednisone, >10 mg/d)
38
What are the risk factors for resistance to Pseudomonas aeruginosa?
- prior isolation of PA
- recent hospitalization (within 90 days)
- recent IV antibiotics (within 90 days)
39
What are the risk factors for resistance to methicillin-Resistant Staphylococcus aureus (MRSA)?
- prior isolation of MRSA
- recent hospitalization (within 90 days)
- recent IV antibiotics (within 90 days)
40
What are the risk factors for acquiring methicillin-Resistant Staphylococcus aureus (MRSA)?
- IVDU
- HD
- CVC
- skin disease
- surgery
- foreign material
41
What are the guidelines principles for diagnosis and treatment of CAP? (4)
- treatment setting (outpatient/inpatient)
- severity (inpatient)
- potential for the presence of resistant organisms
- presence of comorbidities
42
What are the goals of CAP therapy?
- 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
What are the steps of CAP therapy?
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
Steps to CAP Therapy
Step 1: How do we determine where to treat?
scoring systems used to determine where to treat as they predict risk for death
- CURB65 / CRB65
- PSI
45
Steps to CAP Therapy
What is CURB65/CRB65?
- 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
Steps to CAP Therapy
What is PSI?
pneumonia severity index
- score ≤ 90 send home
- score ≥ 91 admit to hospital
47
Steps to CAP Therapy
Step 2: How is disease severity determined?
patient meets at least one major criteria or 3 minor criteria
48
Steps to CAP Therapy
Step 3: What are the strong risk factors associated with MRSA or PA or resistant gram-negative bacilli?
- 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
Steps to CAP Therapy
Step 3: What are some comorbidities?
- chronic heart, lung, liver, or renal disease;
- diabetes mellitus
- alcoholism
- malignancy
- asplenia
- immunocompromised
50
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?
- 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
Steps to CAP Therapy
Step 4: What are the possible therapeutic alternatives for empiric treatment (outpatient) if the patient has comorbidities?
- 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
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 500 mg PO BID x 5 days
53
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?
doxycycline 100 mg PO BID x 5 days
54
What are the 4 main adverse effects of fluoroquinolone antibiotics?
- tendonitis
- peripheral neuropathy
- prolongation of QT interval
- blood glucose disturbances
55
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?
duration: 5-7 days
- beta-lactam (po/iv) +
- add doxycycline (po) or macrolide (po/iv) if
suspect atypicals, OR
- respiratory quinolone (po/iv)
56
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?
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
What is the rationale for using IV beta lactam + macrolide for treatment)?
- 3rd generation cephalosporins have broad coverage (work against SP/H glu/Morexella)
- macrolide covers for atypicals and Legionella
58
What is the rationale for using double tx for treatment?
studies have shown that double tx has lower mortality than beta lactams alone
59
What is the rationale for using fluoroquinolone monotherapy for treatment?
covers for SP/GNB, atypicals, and Legionella, with studies showing similar outcomes as double therapy
60
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?
duration: 5-14 days
- beta-lactam (iv)** + FQ
- beta-lactam (iv)** + macrolide
61
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?
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
What would be used to treat penicillin non-resistant Streptococcus pneumoniae?
- initial therapy: amoxicillin or pen G
- alternatives: macrolides, doxycycline, new FQ
63
What would be used to treat penicillin resistant Streptococcus pneumoniae?
- initial therapy: cefotaxime, ceftriaxone OR moxifloxacin
- alternatives: vancomycin, linezolid
64
What would be used to treat BL-susceptible Hemophilus influenzae?
amoxicillin
65
What would be used to treat BL-resistant Hemophilus influenzae?
2nd or 3rd generation cephalosporin, amoxicillin/clavulanate, new macrolides, or new fluoroquinolones
66
What would be used to treat Legionella?
fluoroquinolones, azithromycin
67
What would be used to treat Mycoplasma or Chlamydophila pneumoniae?
macrolides, doxycycline, fluoroquinolones
68
What would be used to treat aerobic gram-negatives?
- 3rd or 4th or 5th generation cephalosporin
- carbapenem (imipenem, ertapenem, meropenem)
69
What would be used to treat Pseudomonas aeruginosa?
anti-pseudomonal beta-lactam + fluoroquinolone or aminoglycoside
70
When do we step down to oral antibiotic therapy?
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
Steps to CAP Therapy
Step 6: Why might corticosteroids be used as adjunctive therapy?
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
Describe invasive vs. non-invasive pneumococcal disease.
- 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
How effective are pneumococcal vaccines?
among the > 100 recognized serotypes of S. pneumoniae, invasive disease caused by 24 serotypes can be prevented by vaccination
74
What are the risk factors for pneumococcal disease in immunocompetent adults?
- 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
What are the risk factors for pneumococcal disease in immunocompromised adults?
- HIV infection
- cancer (solid, hematologic)
- solid organ transplantation
- autoimmune diseases
- immunosuppressive therapy
- primary immunodeficiencies
- prednisone (ie. >20 mg/day)
76
What are the external risk factors for pneumococcal disease?
- socioeconomic
- environmental
- preceding viral respiratory infection (ie. influenza)
- residence in an institution
77
What are the behavioural risk factors for pneumococcal disease?
- smoking
- alcohol abuse
- homelessness
- illicit drug use
78
What are the age risk factors for pneumococcal disease?
≥ 65 years
79
Compare polysaccharide vaccines and conjugate vaccines.
conjugate vaccines produce a more robust response compared to polysaccharide vaccines and induce immune memory
80
Describe the efficacy of PPV23.
- 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
What are the NACI 2025 recommendations for pneumococcal vaccines in adults?
recommends routine administration of PCV20 or PCV21 for:
- all adults ≥ 65 years
- 18+ years living with risk factors
82
What are the BCCDC recommendations for PPV23?
- individuals ≥ 65 years of age
- any age living in LTCF
- individuals ≥ 2 years of age at risk of IPD
83
What are the BCCDC recommendations for PCV13?
- children 2-59 months of age
- adults – HSCT, HIV
84
What are the non-immunocompromising conditions resulting in risk of IPD?
- 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
What are the immunocompromising conditions resulting in risk of IPD?
- 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)
