3rd yr CAP-joint Flashcards

• Mechanical barriers
• Nasal turbinates
• Glottis
• Reflexes
• Cough, sneeze
• Maintenance of oropharyngeal flora
• Saliva
• Bacterial competition

lower Airway
• Branching airways
• Mucociliary escalator
• Alveolar space defenses
• Alveolar lining fluid

Lower respiratory tract infection
• Acute infection of lung parenchyma & alveoli
• Acquisition of organisms via
• Inhalation
• Aspiration
• Bloodstream

- By Organism: Typical vs. Atypical

CAP, HAP, VAP

- By Morphology: Lobar pneumonia vs. Bronchopneumonia

pneumonia acquired outside the hospital setting (or within 48 hours of hospital
admission)

Hospital-acquired pneumonia (HAP)
pneumonia which occurs > 48 hours after admission, which was not incubating at
the time of admission

Ventilator-associated pneumonia (VAP)
pneumonia that arises > 48 hours after endotracheal intubation

Pneumonia due to “atypical” bacterial pathogens
• Chlamydophila pneumoniae
• Mycoplasma pneumoniae
• Legionella pneumophila

Atypical symptoms or imaging findings
• Zoonotic bacteria - from animals to humans
• Eg. Coxiella burnetti (aka Q fever), Chlamydia psittaci (birds)

• Bronchopneumonia-in the bronchials
• Lobar pneumonia-in part of the lung muscle
• Interstitial pneumonia-in interstitial fluid around the lungs

Aspiration of oropharyngeal or gastric contents into the lung resulting
in bacterial infection
large amount of aspirated material associated with recognizable pulmonary
sequelae (vs. microaspiration: initial step in pathogenesis of most bacterial
pneumonia)

- Chemical injury caused by aspiration of acidic gastric contents
-Resultant inflammatory response

Influenza and Pneumonia
• 8th leading cause of death in Canada
• In 2020 there were 5931 deaths from influenza and pneumonia
• 135,000 pneumonia-related ED visits in 2018
• COVID
• 3rd leading cause of death in Canada
• In 2020 there were 16, 151 deaths from COVID

Required for Diagnosis
– Constellation of suggestive clinical features
– Demonstrable infiltrate by chest radiograph
– With our without supporting microbiological data
• Routine micro and laboratory assessment of ambulatory/outpatients is
unnecessary
• Admitted patients:
! attempt to obtain blood and sputum cultures in patients with severe CAP or those
with risk factors for MRSA or P. aeruginosa

NO

attempt to obtain blood and sputum cultures

Fever, fatigue, weakness, decreased exercise tolerance, light headedness, cough, sputum production, shortness of breath, chest pain, confusion.

Asthma, COPD, cardiovascular disease, cerebrovascular disease

Causes of pneumonia
Compromise to normal physiologic barrier
- function of microvilli
- cough—rib #s, diaphragm muscle weakness
- gag—stroke
- Mechanically ventilated
- Immunosuppressed
Social Hx: smoking status, ETOH use, sick contacts, exposure to health care system

- Previous antimicrobials
- Immunosuppressants
- Anything that decreases level of consciousness
- Immunizations up to date

Febrile, BP may be up or down, tachycardic, increased RR, decreased O2 sats.

CNS-dec level of consciousness, confusion, not orientated.

CVS: Chest discomfort or pain

Resp:
! Cough
! Tactile fremitus
! Dull to percussion in area of pneumonia
! Wheeze
! Most likely localized reduced air entry (i.e., decreased air entry to LLL)
! Purulent secretions
! ABGs- hypoxemic respiratory failure
GU:
may have decreased urine output, BUN, SrCr.

WBC elevation (other acute phase reaction)
C- reactive protein

Additional diagnostic testing to detect influenza and other viruses, including SARS-CoV-2
Uses polymerase chain reaction (PCR) to detect nucleic acid sequences
Urine testing for Legionella antigen

CXR: infiltrates (new or progressive)
Bronchoscopy

a patchy infiltrate represents broncopneumonia in a pt with streptococcus pneumonia infection.

1. Prevent mortality
2. Eradicate infection/clinical cure
3. Prevent progression (e.g., resp failure, intubation)
4. Minimize complications (e.g. empyema, parapneumonic effusion)
5. Prevent relapse/readmission
6. Improve signs and symptoms that patient presented with
7. Minimize adverse effects (e.g., C. difficile infection)
8. Minimize antimicrobial resistance and practice antimicrobial
stewardship principles

Cultures:
Sputum (many neutrophils, no to few epithelial cells)
Positive blood cultures
Endotracheal aspirates
Bronchoalveolar lavage

Inherent Susceptibility
Site of infection
Gram stain
Exposure-history to
Abx

Efficacy
Safety
Bactericidal/ Bacteriostatic
Pharmacodynamics/
Pharmacokinetics
Formulations
Cost

Age/Weight
Allergy Status
Residence
Medical History
Immune Function
Organ Function
(liver/GU/GI)
Pregnant?
Source-control

1. Generate list of most likely pathogens
• Severity of illness (site of care decisions)
– outpatients, inpatients on hospital ward, intensive care unit
2. Consider local susceptibility patterns
3. Determine patient specific factors
• allergy
• organ function (e.g., creatinine clearance)
• risk factors for resistance (e.g., previous antibiotic use)
4. Select empiric therapy.

In addition to clinical judgement, we recommend that clinicians use a
validated clinical prediction rule for prognosis,
preferentially the Pneumonia Severity Index (PSI) (strong
recommendation, moderate quality of evidence) over the CURB-65
(tool based on confusion, urea level, respiratory rate, blood pressure,
and age >65) (conditional recommendation, low quality of evidence)
To determine the need for hospitalization in adults diagnosed with
CAP. (ATS/IDSA 2019

demographics, co-morbidities, physical exam/vital signs, lab/imaging.

confusion, uremia, respiratory rate, BP, age ≥ 65

Scores ≥2: hospitalization recommended
• Confusion (person, place, time)
• Uremia (BUN > 7 mmol/L)
• Respiratory rate >30 breaths/min
• Blood pressure (SBP <90, DBP < 60)
• Age > 65 years old

Number of factors Mortality Rate Recommended Site Of Care
0 0.7 % Outpatient
1 2.1 % Outpatient
2 9.2 % Inpatient ward
3 14.5 % Inpatient ICU
4 40 % Inpatient ICU
5 57 % Inpatient ICU

outpatient

if score eq or > 3 =hospital admission

direct admission to ICU

cocci(staphylococcus-clustered and steptococcus and enterococcus -pairs/chains)

bacilli

1. aerobic- (corynebact, bacillus, listeria)

2.anaerobic- clostridium actinomyces

1. lactose fermenters: e.coli, klebsiella sp , citrobacter sp.

2. non lactose fermenters: pseudomonas sp, burkholderia sp, acinetobacter sp, morganella sp, proteus sp, serratia sp, stenotrophomonas sp.

legionella, haemophilus, bordetella, camylobacter

Respiratory viruses
Streptococcus pneumoniae
Haemophilus influenzae
Mycoplasma pneumoniae
Chlamydophila pneumoniae

Respiratory viruses
S. pneumoniae
H. influenzae
M. pneumoniae
C. pneumoniae
Legionella pneumophila
Gram – bacilli
Staphylococcus aureus

Respiratory viruses
S. pneumoniae
H. influenzae
Legionella pneumophila
Gram – bacilli
S. aureu

Mortality
ITT: beta-lactam monotherapy was non-inferior to beta-lactam + macrolide or FQ
ITT & PP: beta-lactam was not non-inferior to Fluoroquinolone

amoxicillin 500-1000mg TID(renal adjust required)

-cefuroxime 500mg BID, Doxy 100mg BID or levo 750mg DAILY IF PENICILLIN ALLERGY

amoxi-clav

if no comorbidities or risk factors for MRSA or pSuedomonas aeruginosa- amoxil or doxy or macrolide if local resistance is < 25%

combo therapy with amoxi-clav or cephalosporin AND macrolide or doxy

macrolide or doxy

Comorbidities
• Chronic heart, lung, liver, or renal disease
• Diabetes mellitus
• Alcoholism
• Malignancy
• Asplenia
• Immunosuppression (drugs or diseases)

• Prior respiratory isolation of MRSA or P. aeruginosa OR
• Recent hospitalization AND receipt of parenteral antibiotics (in the last 90 d

amoxil 500-1g TID OR ampicillin 2g IV q6h

levo 750mg PO/IV daily.

cefuroxime 500mg PO BID or 750mg IV q8h

cefrotriaxone 1g IV q24h

routine coverage has not been proven to be of benefit in this setting.

consider risk factors-i.e prior resp isolation of MRSa or P-aeroginosa or recent hospitalization/ receipt of parenteral antibiotics in the last 90 days.

if strong suspicion of atypical pathogens and not on fluoroquinolone,

-azithro 500mg x3 days

-doxy 100mg BID preffered (if prolonged QTC)

cefriaxone 1 g IV q24h plus azithromycin 500mg PO /IV daily. OR Levo 750mg PO/IV daily (preffered if legionella is isolated)

consider risk factors-i.e prior resp isolation of Pseudomonas or recent hospitalization/ receipt of parenteral antibiotics in the last 90 days- give pip/tazo 4.5 g IV q6h

in the case of prior resp isolation of MRSa- Add vancomycin to standard regimen.

is recommended empiric therapy in hospitalized patients with suspicion of influenza, regardless of timing of symptom onset.

beta-lactam(clavulin) + macrolide(e.g erythro) OR respiratory fluoroquinolone.

beta lactam plus macrolide OR beta- lactam + fluoroquinolone.

Penicillin G, amoxicillin

alternatives-macrolide, cephalosporin, cefpodoxime, cefprozil,cefuroxime,ceftriaxone, cefotaxime, clindamycin,doxy, resp-fluoroquinolone

-vanco, linezoid, high-dose amoxil (3g/day with penicillin MIC <=4mcg/ml)

preferred agents chosen on the basis of susceptibility, including cefotaxime, ceftriaxone, fluoroquinolone

amoxil preferred

alternatives fluoroquinolone, doxycycline, azithromycin, clarithromycin.

preferred= 2nd or 3rd gen cephalosporin, amoxil-clav

Alternatives= alternatives fluoroquinolone, doxycycline, azithromycin, clarithromycin.

preferred= macrolide, a tetracycline

alternative= fluoroquinolone

preferred = fluoroquinolone, azithromycin

alternative= doxycycline

Penicillins (i.e., amoxicillin)
Cephalosporins (i.e., cefuroxime)
Cephalosporins (i.e., ceftriaxone)
Tetracyclines (i.e., doxycycline)
Marcolides (i.e., azithromycin)
Fluoroquinolones (i.e., levofloxacin and moxifloxacin)
Vancomycin
Piperacillin/tazobactam
Carbapenems (i.e., meropenem and imipenem

Streptococci pneumoniae, Group A, B, C and G streptococcus
Gram negatives; most enterobacteriaceae (eg. E. coli), H. influenzae, M. Catarrhalis
Does not cover Enterococci, pseudomonas, listeria, B. Fragilis or atypicals and not preferred for staphylococcus aureus infections.

PK/PD -Time above MIC
Protein binding- 85 to 95%
Vd -0.2 L/kg
Elimination - 33 to 67% excreted in urine as unchanged drug
T1/2- 8 hours
Dosing- 1 g IV daily (most indications)
Adverse effects - Allergy, rash, cytopenias, pseudocholelithiasis, seizures (beta-lactams)
Drug interactions - Do not administer with calcium containing solutions

temp <= 37.8 deg c

hrt rate <=100beats/min

respiratory rate <=24 24 breaths/min

systolic blood pressure >=90% or PO2 >=60mmHg on room air

Ability to maintain oral intake

normal mental status

Treatment Duration
-Minimum treatment duration = 5 days AND

Afebrile (T ≤ 37.8 x 48-72 h) AND
≤ 1 sign of CAP-related clinical instability
T ≥ 37.8
HR ≥ 100 beats/min
RR ≥ 24 breaths/min
SBP ≤ 90 mmHg
SaO2 ≤ 90% or PaO2 ≤ 60 mm Hg on room air
Inability to maintain oral intake
Abnormal mental status
Longer duration may be needed if initially inappropriate therapy.

Drug factors
• Pharmacokinetics (A, D, M, E)
• Pharmacodynamics (Low levels) – Drug Interactions
• Bug factors
• Resistance
• Superinfection or mixed infection
• Host factors
• Incompetent immune status due to disease, drugs
• Source control – e.g. failure to drain abscesses

• Establish diagnosis
• Patient assessment of severity, treatment disposition
• Obtain Gram stain & culture (inpatients)
• Select empiric antimicrobials targeting most likely organisms
• Understand local susceptibility patterns
• Optimize dosing (PK/PD)
• Tailor antimicrobials to narrowest spectrum once/if C&S known
• If IV agents initiated, step-down to enteral route when able
• Use the minimum effective duration possible

Hospital-acquired pneumonia (HAP)
• pneumonia which occurs > 48 hours after admission, which was not
incubating at the time of admission

Pneumonia – Classification
Hospital-acquired pneumonia (HAP)
• pneumonia which occurs > 48 hours after admission, which was not
incubating at the time of admission

critical care settings

HAP

endogenous

-oropharynx

trachea

nasal carriage

sinusitis

gastric fluids

health care workers

ventilatory circuits

nebulizers

biofilms

it occurs when colonized secretions are inhaled into the lungs through the endotracheal tube

2 of the following
-New onset fever
-Purulent sputum
-Leukocytosis or leucopenia
-Decline in oxygenation
Respiratory tract cultures to guide antibiotic choices

1. Presence of risk factors for MDRO
2. Local pathogen prevalence, particularly MRSA
3. Local antibiotic susceptibility patterns (i.e., institution-specific
antibiogram)
4. Severity of infection (i.e., requiring ICU admission)

= If prior IV antibiotic use within the preceding 90 days, patient is at
increased risk for:
!MRSA
!Pseudomonas
!Multidrug resistant organisms

Consider vancomycin if:
– Treatment in a unit where the prevalence of MRSA among S. aureus isolates
is not known or is >20%
• Consider double coverage for Pseudomonas if:
! Greater than 10% of gram-negative isolates are resistant to an agent being
considered for monotherapy
(Weak recommendation, low-quality evidence)

The following risk factors for mortality = severe illness requiring ICU
admission
-Septic shock
-Requiring invasive ventilation
As a result of pneumonia

ceftriaxone 1 g IV q 24h or amox-clav 875/125 mg BID or levo 750mg IV/po Q24h

strep pneumonia

H. influenzae

staph. aureus

enteric gram-neg bacilli(klebsiella, E. coli, Enterobacter, proteus)

staph aureus(and MRSA), Enteric gram-neg bacilli(incr resistance) klebsiella, E. coli, enterobacter, proteus.

serratia, pseudomonas, acinetobacter

Piperacillin-tazobactam* 4.5 g IV q6h
+/-
Consider vancomycin (for MRSA)
Loading dose 25–30 mg/kg × 1 for severe illness
Followed by 15 mg/kg IV q 8–12h

meropenem if IGE-Mediated penicillin allergy

Staph. aureus (and MRSA)
Enteric gram-negative bacilli (ñ resistance)
Klebsiella, E. Coli, Enterobacter, Proteus
Serratia
Pseudomonas
Acinetobacter

Piperacillin-tazobactam* 4.5 g IV q6h
+/-
Consider vancomycin (for MRSA)
Loading dose 25–30 mg/kg × 1 for severe illness
Followed by 15 mg/kg IV q 8–12h

Meropenem if IgE-mediated penicillin allergy

Cephalosporins (i.e., ceftriaxone)
Fluoroquinolones (i.e., levofloxacin and moxifloxacin)
Fluoroquinolones (i.e., ciprofloxacin)
Aminoglycosides (i.e., tobramycin)
Vancomycin
Piperacillin/tazobactam
Carbapenems (i.e., meropenem and imipenem

Antipseudomonal penicillin+ beta-lactamase inhibitor

Streptococci pneumoniae, Group A, B, C and G streptococcus, Staphylococcus aureus (MSSA),
Enterococcus Faecalis
Gram negatives; most enterobacteriaceae (eg. E. coli), pseudomonas, H. influenzae, M. Catarrhalis
B. Fragilis
Does not cover atypicals

time above MIC

30%

0.25L/kg

70 to 80% renally eliminated

1h

Pseudomonas 4.5 g IV q6h, other indications 3.375g IV q6h interval depends on renal function, prolonged infusions used to optimize PK/PD.

Platelet dysfunction, thrombocytopenia, allergy, serum sickness, cytopenias, nausea vomiting,
headache, seizures (beta-lactams), increased LFTs, SrCr (acute kidney injury)

Avoid concomitant administration with methotrexate (increased methotrexate levels)

Streptococci pneumoniae, Streptococcus spp., Staphylococcus aureus (MSSA), Enterococcus Faecalis
(imipenem)
Gram negatives; enterobacteriaceae (e.g., Acinetobacter, Citrobacter, Enterobacter), Pseudomonas, H.
influenzae, M. Catarrhalis
B. Fragilis
Does not cover atypicals

Time above MIC

2% (meropenem), 20% (imipenem)

0.25 L/kg

70 % renally eliminated
1h

500 mg IV q6h (local strategy)
Prolonged infusions may be used to optimize PK/PD
Allergy, seizure risk, thrombocytopenia, cytopenias, serum sickness, nausea vomiting diarrhea, headache, increased SrCr
Valproic acid

(not comprehensive)
Gram-negative organisms (eg. E. coli, Pseudomonas*) Gentamicin does not cover Pseudomonas
Synergy achieved in combination for gram positive organisms

PD Concentration dependent killing
Post antibiotic effect PAE (gram-negative organisms)
Protein binding 0 - 30%
Vd 0.25 L/kg
Elimination 60 to 85% renally eliminated
T1/2 1.6 to 3 hr (normal renal function)
Dosing Traditional: tobramycin 1-2 mg/kg/dose, interval is dependent on renal function
Extended interval: 5-7 mg/kg, interval is dependent on renal function
(use dosing body weight [DBW] if IBW >125% ABW

• Lower dose given
more often
• Typically q 8 h

Extended interval
(once daily dosing)
• Higher dose given less often
• Utilizes concentration
dependent killing & PAE
• ↔ effectiveness
• ↔/↓? nephrotoxicity
• ?↓ ototoxicity

Ascites
• Burns on >20% of total body surface area
• Pregnant patients
• Dialysis
• Patients with gram positive bacterial endocarditis (i.e., synergy)
• Pediatrics (<18yo)

Ototoxicity (not reversible)
• Accumulation of aminoglycoside in lymph of inner ear and damage cochlear and/or vestibular cells
• Vestibular
• First sign may be loss of balance
• Loss of equilibrium, headache, ataxia, nausea, vomiting, nystagmus, vertigo
• Auditory
• First sign may be tinnitis
• Hearing loss , initially at high frequencies and will progress to lower frequencies if treatment is not stopped
Nephrotoxicity (may be reversible)
• Accumulation in the proximal renal tubule, decreasing the kidney’s ability to concentrate urine, and
decreases glomerular filtration

• Duration > 7days
• weekly trough
• Scr/BUN ≥ 2X/week
• Audiometric testing to detect high frequency losses
• Avoid concomitant nephrotoxic and ototoxic drugs
• Ask about tinnitus, test balance

Antipseudomonal cephalosporin (ceftazidime, cefepime, ceftolozane-tazobactam)
• Piperacillin-tazobactam
• Carbapenem (imipenem or meropenem)
• Fluoroquinolone (ciprofloxacin)
• Aminoglycosides (tobramycin)

antibiotics with activity against p. aeruginosa and other gram-negative bacilli

Double Coverage?
Combination of 2 antipseudomonal therapy for critically ill patients
• Beta-lactam PLUS tobramycin OR ciprofloxacin
• Provides broad spectrum of coverage
• Minimizes potential for inappropriate initial therapy
• May be initial therapy if Pseudomonas aeruginosa suspected
• Step down to single coverage once susceptibilities known

Vancomycin is still the agent of choice for MRSA pneumonia

-Establish diagnosis
-Determine severity of illness
-Determine risk factors for multidrug resistant pathogens
-Determine when/if patient intubated

For patients with HAP and VAP we recommend a 7-day
course of antimicrobial therapy
– Strong recommendation, low quality evidence for non-VAP and
moderate for VAP

Exclusions: complicated, abscess, empyema, immunocompromised

-Initiate broad spectrum antibiotics based on most likely organisms and patient specific factors
Quick, adequate dose, adequate coverage
- De-escalate to narrowest spectrum once cultures are known
Adjust based on organ dysfunction/kinetics
- Write stop date
-Minimum/rationale duration
- IV to PO step down if criteria are met

ceftriaxone 1 g IV q24h OR amoxi-clav 875mg bid.

OR levo 750mg PO/IV q24h

pip-taz 4.5g IV q6h OR meropenem 500mg IV q6h -preffered if colonized/infected with pip-taz resistant microorganism OR IgE mediatd penicillin allergy

add

vancomycin IV