Pneumonia

Question 1

Most common organisms

causing pneumonia

Answer 1

1. Streptococcus pneumoniae (~ 65%)
2. Haemophilus influenzae (~ 10%)
3. Mycoplasma pneumoniae, Legionella sp. and Chlamydia pneumoniae (~ 20%)
4. Mycobacterium tuberculosis
5. Viruses

Question 2

other organism that cause pneumonia

Answer 2

1. Staphylococcus aureus
2. Gram negative bacilli – Burkholderia pseudomallei (meloidosis), Klebsiella pneumoniae
3. Anaerobic bacteria – Peptococcus, Peptostreptococcus a. Cause aspiration pneumonia

Question 3

Risk factor for

CAP

Answer 3

A. Host factors

1. Increasing age
2. Male sex

B. Modifiable risk factors

1. Smoking
2. Malnutrition
3. Low vitamin D level

C. Underlying lung disease

1. COPD, asthma
2. Preceding viral respiratory infection

D. Chronic medical conditions

1. Stroke
2. Diabetes
3. Renal disease
4. Dysphagia

E. Immune suppression 1. TNFα inhibitors
2. HIV infection

F. Medications

1. PPI’s
2. Inhaled steroids

G. Socioeconomic factors

1. Low-income household
2. Crowded living conditions

Question 4

Clinical presentation CAP

Answer 4

A. Usual presentation 1. Fever
2. Cough – productive 3. Shortness of breath 4. Tachypnea

Non-specific

• N/V/HA
• myalgia

B. Clinical signs and symptoms cannot reliably be used to predict the microbial etiology of community-acquired pneumonia.

C. Physical examination findings - Lungs

1. Decreased breath sounds
2. Inspiratory crackles 3. Dullness on percussion

D. Elderly and patients with co-existing illnesses may not present with usual signs and symptoms

1. May present with poor feeding, drowsiness, no fever

Question 5

Diagnosis of CAP

Answer 5

A. Clinical presentation
B. Chest X-ray
1. Changes that may indicate pneumonia – consolidation, infiltrate 2. Assess pre-existing lung disease
3. Baseline assessment – monitor response to therapy

C. White blood cell count
1. Aid in the diagnosis of infection, in general

D. Other
1. Electrolytes
2. Renal function
3. C-reactive protein (CRP) – Not specific for infection
4. Procalcitonin
- Released in response to bacterial toxins and inflammatory mediators - Aids in differential diagnosis of viral vs. bacterial infection
- Non-ICU patients
> 0.25mcg/L or ICU patients > 0.5mcg/L → can aid in decision to start antibiotic therapy

E. Microbiologic

1. Aid selection of antibiotic therapy
   a. Use drug active against organism
   b. Narrow down spectrum of drug
   c. Use lower cost drug
2. Identify unusual pathogens
3. Gram stain sputum
   a. Sputum vs. saliva
   i. < 10 epithelial cells
   ii. > 25 neutrophils
   b. Technique and operator dependent
4. Sputum culture
   a. Takes at least 48 – 72 hours to get results

Question 6

Diagnosis

5. Blood culture
   a. Bacteremia in ~ 11% of patients
   b. Infection can spread from blood to lungs, or lungs to blood
   c. Associated with higher mortality
   d. Selected hospitalized patients
   i. severe pneumonia
   ii. immunocompromised
6. Urine culture

Answer 6

Diagnosis

5. Blood culture
   a. Bacteremia in ~ 11% of patients
   b. Infection can spread from blood to lungs, or lungs to blood
   c. Associated with higher mortality
   d. Selected hospitalized patients
   i. severe pneumonia
   ii. immunocompromised
6. Urine culture

Question 7

Diagnosis

7. Urine antigen tests (hard to grow on culture)
   a. Legionella, Strep. pneumoniae
   b. Only indicates that there has been exposure to the organism and an immunologic response
8. Polymerase chain reaction (PCR) assays (blood)
   a. Selected organisms - Legionella, Mycoplasma, Strep. pneumoniae, Chlamydia and Viruses
   b. Higher sensitivity and specificity compared to urine antigen tests

Answer 7

Diagnosis

7. Urine antigen tests
   (hard to grow on culture)
   a. Legionella, Strep. pneumoniae
   b. Only indicates that there has been exposure to the organism and an immunologic response
8. Polymerase chain reaction (PCR) assays (blood)
   a. Selected organisms - Legionella, Mycoplasma, Strep. pneumoniae, Chlamydia and Viruses
   b. Higher sensitivity and specificity compared to urine antigen tests

Question 8

F. Guidelines on CAP are conflicting for recommendations on extent and importance of diagnostic work-up
1. Performing diagnostic tests should never delay the start of antibiotic therapy

Answer 8

F. Guidelines on CAP are conflicting for recommendations on extent and importance of diagnostic work-up
1. Performing diagnostic tests should never delay the start of antibiotic therapy

Question 9

Risk stratification for CAP (IN OR OUT PT tx )

Answer 9

1) pneumonia seerity index (PSI)
- Need lots of data
- Complicated
(Lvl 1-3 = low
lvl 4 = moderate
lvl 5 = high)

2) CURB-65 severity score. 
Based on 
- Confusion ( =<8 
                  score)
- Urea >7mmol/L
- Respiratory rates >= 30/min

• BP (SBP<90mmhg; DBP<= 60mmhg)
• Age >= 65yo

Group 1
= 0/1 score
= LOW mortality
= outpatient

Group 2
= 2 score 
= intermediate mortality
= Consider hospital supervised tx 
( a: Short stay inpatient
  b: Hospital supervised outpatient) 

Group 3
= >=3 score
= High mortality
= managed in hospital as severe pneumonia
= Asess for ICU admission especially if CURB-65 score = 4or5

3) social issue
a. Caregiver support at home
b. Likelihood of compliance with outpatient therapy and follow-up

Question 10

B. Other factors to consider in choosing initial empiric antibiotic therapy
1. Adverse reactions or allergies to antibiotics 2. Co-existing illnesses

Answer 10

B. Other factors to consider in choosing initial empiric antibiotic therapy
1. Adverse reactions or allergies to antibiotics 2. Co-existing illnesses

Question 11

Target organism 
outpatient 
PSI  = I or II
 OR 
CURB-65 = 0 - 1

Answer 11

strep. pneumonia

Atypical organisms

Question 12

Empiric therapy for CAP 
outpatient 
PSI  = I or II
 OR 
CURB-65 = 0 - 1

Answer 12

Erythromycin
500mg PO QDS
OR 800mg BD (EES)

OR 
Clarithromycin 
500mg PO BD
OR
Azithromycin 
500mg PO OM
OR
Doxycycline 
100mg PO BD

OR in sever case
Macrolide/Doxycycline

PLUS 
amoxicillin/clavulanate 
625mg po TDS
OR
Ampicillin/sulbactam 
750 po BD
OR
Cefuroxime 
250-500mg po BD

Question 13

Inpatient (Non-ICU) PSI = III or IV
OR
CURB-65 = 2

Target organism

Answer 13

Strep. pneumoniae Haemophilus influenzae Atypical organisms

Question 14

Inpatient (Non-ICU) PSI = III or IV
OR
CURB-65 = 2

empiric tx

Answer 14

Amo/clavu IV/PO
1.2g IV q8hr

OR

Ampi/sulbactam IV/PO
1.5g IV q6hr

OR 
ceftriaxone
1g IV q12h 
OR 
2g IV q24hr

PLUS 
Clarithromycin PO
500mg BD
OR 
Azithromycin PO 
500mg OM

OR in penicillin allergy
levofloxacin
750mg IV/PO q24hr

Question 15

Inpatient (Severe pneumonia, ICU)

PSI = V
OR
CURB-65 ≥ 3

Target organism

Answer 15

Strep. pneumoniae Atypical organisms

Burkholderia pseudomallei

Klebsiella pneumoniae

Question 16

Inpatient (Severe pneumonia, ICU)

PSI = V
OR
CURB-65 ≥ 3

empiric tx

Answer 16

Penicillin 4MU IV q6h
OR
amo/clavu 1.2g IV q6h

PLUS 
Azithromycin 
500mg IV q24h
PLUS
Ceftazidime 
2g IV q8h

OR 
Levofloxacin 
750mg IV q24hr
PLUS 
Ceftazidime
2g IV q8h

Question 17

Respiratory fluoroquinolones, anti-pneumococcal fluoroquinolones

Not recommended as first-line treatment (local practice)

Answer 17

• Concerns about development of resistance with overuse
• Concerns about inappropriate use for other respiratory infections
• Use has been associated with delays in diagnosis and treatment of pulmonary TB

Question 18

CAP Need for empiric coverage of atypical organisms

Answer 18

Legionella sp., Mycoplasma pneumoniae, Chlamydophila pneumoniae

β-lactam plus macrolide or fluoroquinolone monotherapy had better outcomes compared to β-lactam alone

Question 19

CAP Early initiation of antibiotics for hospitalized patients

Answer 19

Early initiation of antibiotics for hospitalized patients

i. Early initiation (within 8 hours) results in better outcomes
ii. Start therapy in emergency department rather than wait until patient is on ward

Question 20

duration of therapy for CAP

Answer 20

Traditionally = 7 – 14 days

ii. Rationale for shorter courses of therapy
- Decrease development of resistance
- Reduce costs
- Decrease adverse reactions

ii. New agents with long serum and tissue half-lives may be able to give shorter course (3 – 5 days)

iii. IDSA/ATS guidelines (2007)
- Treat for minimum of 5 days
- Should be afebrile for 48-72 hours and clinically stable before discontinuation of therapy

iv. Levofloxacin dosing - Recent guidelines specify 750mg once daily x 5 days

Question 21

e. Adjunctive corticosteroid therapy CAP

Answer 21

i. Rationale - Inflammatory response in lungs
ii. Only studied in patients who were hospitalized due to CAP

iii. Outcomes
- May decrease need for mechanical ventilation, length of stay and time to clinical stability
- Some evidence to show decreased mortality

Question 22

Monitoring response to therapy CAP

Answer 22

1. Goals of therapy
   a. Cure of infection
   b. Eradication of organism
2. Time course of response
   a. Should start to see improvement in signs and symptoms in 48 – 72 hours
   b. Elderly and patients with co-existing illnesses may be slower to respond

c. Should not change antibiotics within first 72 hours
- Unless patient is deteriorating or culture results available

Question 23

Monitoring parameters CAP

Answer 23

a. Efficacy i. Chest X-ray
- Changes are slow to resolve
– 4-6 weeks or longer - Repeat if patient deteriorates

WBC count
temperature 
CRP 
Cough SOB
HR

Toxicity

Question 24

conversation from IV to oral

Answer 24

1) benefits
- discharged
- cheaper

2) Criteria for switching a. Vital signs stable for 24 hours (Afebrile)
b. Able to take oral diet and oral medications
c. Others
- WBC count decreasing
- Improvement in signs and symptoms

3) Can be discharged the same day as convert to oral

Question 25

Patients who do not respond to initial therapy CAP

Answer 25

1. Incorrect diagnosis (e.g., heart failure, pulmonary embolus) 2. Correct diagnosis a. Drug-related issues i. Compliance ii. Drug interactions iii. Wrong dose iv. Wrong drug b. Pathogen-related issues i. Unusual pathogen ii. Resistant organism

Question 26

HAP definition

Answer 26

- Development of a pneumonia at least 48 hours after hospital admission - Not incubating (present) at the time of admission

Question 27

HAP Prolongs hospital stay 7 – 9 days

Answer 27

HAP Prolongs hospital stay 7 – 9 days

Question 28

Risk Factors for HAP

Answer 28

A. Patient-related factors 1. Age > 70 years 2. Coma or impaired consciousness 3. Prolonged hospitalization 4. Malnutrition 5. Cigarette smoking 6. Co-existing illnesses a. COPD b. Diabetes mellitus c. Renal failure i. Associated with impaired lung function and defenses B. Infection control-related factors 1. Transmission of bacteria from hands of healthcare workers to patients 2. Use of contaminated respiratory care equipment C. Intervention-related factors 1. Drugs a. Sedatives, narcotic analgesics b. Antibiotics c. Steroids and immunosuppressive agents 2. Nasogastric tubes 3. Intubation/mechanical ventilation (ventilator-associated pneumonia)

Question 29

HAP GRAM +ve

Answer 29

1. Streptococcus pneumoniae 2. Methicillin-sensitive Staphylococcus aureus (MSSA) 3. Methicillin-resistant Staph aureus (MRSA)

Question 30

HAP GRAM -ve

Answer 30

1. Escherichia coli 2. Haemophilus influenzae 3. Proteus species 4. Serratia marcescens 5. Enterobacter species 6. Klebsiella pneumoniae (including MDR and ESBL-producing) 7. Acinetobacter species (including MDR and ESBL-producing) 8. Pseudomonas aeruginosa (including MDR)

Question 31

HAP A. Up to 50% of cases do not identify an organism B. Cannot wait to start antibiotics until culture results are available 1. Studies show that mortality can be reduced with early initiation of appropriate empiric therapy

Answer 31

HAP A. Up to 50% of cases do not identify an organism B. Cannot wait to start antibiotics until culture results are available 1. Studies show that mortality can be reduced with early initiation of appropriate empiric therapy

Question 32

HAP categories of pt

Answer 32

1. Not at high risk of mortality and no risk factors increasing likelihood of MRSA 2. Not at high risk of mortality, but with risk factors increasing likelihood of MRSA 3. High risk of mortality or receipt of IV antibiotics in prior 90 days

Question 33

Initial empiric therapy for HAP Not at high risk of mortality and no risk factors increasing likelihood of MRSA

Answer 33

Piperacilin/tazobactam 4.5g IV q6h OR Cefepime 1-2g IV q8hr OR Levofloxaccin 750mg IV q24hr OR imipenem 500mg IV q6hr OR meropenam 1g IV q8hr

Question 34

Not at high risk of mortality, but with risk factors increasing likelihood of MRSA Initial empiric therapy for HAP

Answer 34

Piperacilin/tazobactam 4.5g IV q6h OR Cefepime 1-2g IV q8hr OR Levofloxaccin 750mg IV q24hr OR imipenem 500mg IV q6hr OR meropenam 1g IV q8hr OR Ceftazidime 1-2g IV q8hr OR ciprofloxacin 400mg IV q8-12hr OR Aztreonam 1-2g IV q8h PLUS vancomycin 15-20mg/kg IV q8-12hr (target trough = 15-20mg/L) OR linezolid 600mg IV q12h

Question 35

Initial empiric therapy for HAP High risk of mortality or receipt of IV antibiotics in prior 90 days

Answer 35

Piperacilin/tazobactam 4.5g IV q6h OR Cefepime 1-2g IV q8hr OR imipenem 500mg IV q6hr OR meropenam 1g IV q8hr OR Ceftazidime 1-2g IV q8hr PLUS ciprofloxacin 400mg IV q8-12hr OR Levofloxaccin 750mg IV q24hr OR Aztreonam 1-2g IV q8h OR Amikacin 7.5mg/kg IV q12hr OR 15mg/kg IV q24hr OR Gentamicin 1-2mg/kg IV q8h or 5-7mg/kg IV q24h PLUS vancomycin 15-20mg/kg IV q8-12hr (target trough = 15-20mg/L) OR linezolid 600mg IV q12h

Question 36

Indications for empiric MRSA coverage HAP

Answer 36

1. Prior IV antibiotic use within 90 days 2. Hospitalization in a unit where > 20% of Staph aureus isolates are methicillin-resistant 3. Where the prevalence of MRSA is not known

Question 37

Risk factors for mortality HAP

Answer 37

1. Need for ventilatory support due to the pneumonia 2. Septic shock

Question 38

Duration of therapy for HAP

Answer 38

a. Historically = 14-21 days b. Optimal duration not clearly established from clinical trials c. More recent recommendations for shorter duration (i.e., 5 – 7 days) - Patient is responding to therapy - No multidrug-resistant organism isolated d. IDSA/ATS guidelines (2016) = 7 days

Question 39

Monotherapy vs. Combination therapy | HAP

Answer 39

- Synergistic activity - Prevent development of resistance - Broader spectrum of coverage - More expensive - Increased risk of adverse effects Combination therapy recommended - High risk of mortality - Receipt of IV antibiotics in prior 90 days - Pseudomonas aeruginosa as causative organism i. Patients in septic shock or at high risk for death Monotherapy sufficient if - Gram positive organism as cause of pneumonia - Mild to moderate infection