Yuanlin Song, M.D.

Department of Pulmonary Medicine, Fudan University

Pneumonia: inflammation and consolidation of lung tissue due to an infectious agent.

Category: community acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP)

HAP divided into Ventilator Associated Pneumonia (VAP) or Non-ventilator Associated Pneumonia

Bacillus Pseudomonas Clostridium Escherichia

Spirulina Staphylococcus Streptococcus Salmonella

http://www.denniskunkel.com/

Upper- airway: (1)nasal turbinates, (2)mucocillary transport system: ciliary, mucus layer,

sIgA, mucosal pH, colonization of non-pathogenic bacteria

Lower airway: (1)glottis, cough, (2)innate immunity: macrophages, lysozymes, lactoferrin,

IgG, defensins, complement, cathelicidins, collectins (3)epithelial barrier and antimicrobial peptide (4)specific host defense: T lymphocyte

ciliary

mucus

Liquid

Submucosal gland

Goblet cell

mucus layer

mucosa

Microbial factors: virulence factors: chlamydia, maycoplasma, influenza virus, S. Pneuomiae, Mycobacteria, Pneumococccal, polypeptide pneumolysin.

Host factors: hypogammaglobulimia, CD4+ T cell reduction, underlying lung disease, medicine

Routes of pathogenesis: gross aspiration, microaspiration, aerosolization, hematogenous spread, direct spread

Pili

Flagellum

Non-pilus adhesins

Alginate/biofilm

LPS

Cell-associated factors

Quorum Sensing

ExoS, ExoU , ExoT, ExoY

Type III secretion

Intracellular factors

Proteases: LasA elastase (type II)

LasB elastase (type II) Alkaline protease (type I)

Hemolysins: Phospholipase C (type II) Rhamnolipid

Exotoxin A (Type II) Exoenzyme S Pyocyanin, Pyoverdin

Type I & II secretion

Extracellular factors

Type III secretion

Biofilm

Lobar pneumonia: congestion-red hepatization-grey hepatization-resolution

Bronchopneumonia: patchy consolidation, neutrophilic exudate centerted in bronchi(ioles), centrifugal spread

Miliary pneumonia: bloodstream spread or blood dissemination induced numerous discrete lesions (2-3mm in diameter)

Interstitial pneumonia: patchy or diffuse

Necrotizing pneumonia, lung abscess, vascular invasion, cavitation, empyma, bronchopleural fistula.

Interstitial emphysema, pneumothorax, ARDS

Organizing pneumonia, brochiolitis obliterans, pleural adhesions

Epidemiology 1. Annual cost: 9.7 billion 2. 4 million adults 3. 20%-hospitalization 4. 8-15/1000 person/per year 5. Aged patients, winter time Independent risk factors 1. Alcoholism 2. Asthma 3. Immunosuppression 4. age 5. Cigarette smoking

Diagnosing method: regular culture, IgM, molecular biology-from blood, sputum, pleural fluid, BAL

Diagnosing category: definite, probable, possible

Special pathogen detection: chlymedia, mycoplasma, tuberculosis, anaerobic pathogens

Determination of colonization, infection

Legionella pneumonia—1976 in US

C. pneumonia-1965 in Taiwan

Hantavirus-1978 in south Korea

Nipah Virus-1999 in Malaysia

Hendra virus-1994 in Australia

Metapneumovirus -2001 in Netherland

SARS-2003 in Hongkong

http://en.wikipedia.org/wiki/File:Pteropus_vampyrus2.jpg

Factors Possible agents

Occupational history

Health care works Mycobacterium tuberculosis

Veterinarians, farmer Coxiella burnetii

Cooling tower workers Legionella

Host factor

Diabetic ketoacidosis S. Pneumoniae, SA

Alcoholism SP, KP, SA, anaerobes

Factors Possible agents

Travel and environmental factors

South Asia TB, Burkholderia

China, Taiwan, Toronto SARS

Arizona

Coccidioides immitis

Air conditioning Legionella

Pneumonia in nursing home Exposure to mouse dropping

C pneumoniae Hantavirus

Ambulatory Ward ICU

SP S Pneumoniae S. P.

Mycoplasma Mixed etiology S.A

C Pneumoniae virus virus

H. Infl H. Infl Mixed etiology

Inf. Virus C Pneumoniae Aerobic G- bacilli

Penumocystis L. Pneumoniae L. spp

Definite: recovered from blood, pleural space, lung tissue; L. spp from sputum, M Tb from sputum

Probable: isolation of SA, SP, HI, MC, PA from purulent sputum; 4 folder increase of IgM; Urinary antigen positive for SP

Possible: Gram stain for SP, SA, HI; isolation without positive stain; higher titer of LP (1:1024) or MP (1:64)

Symptoms: fever, cough, chest pain, chills, shortness breath, headache, nausea, vomiting, diarrhea, myalgia, arthragia, fatigue, confusion

Physical signs: tachypnea, dullness to percussion, increased tactile and vocal fremitus, egophony, whispered pectoriloquy, crackles, pleural friction rub

Chest X-way, CT

British Thoracic Society Rules for Definition of S-CAP

Confusion

Urea > 7mmol/L RR> 30/min Blood pressure: D<60 or S<90 mmHg

ATS: definition of severe CAP Category Criteria Major: need mechanical ventilation requirement for vasopressor > 4hour Minor: Systolic blood pressure < 90 PaO2/FiO2 <250 Multilobar involvement

Respiratory failure, congestive heart failure, shock, atrial dysrhythmias, myocardial infarction, GI bleeding, renal insufficiency

Mortality around 8%. Most common reason: respiratory failure, heart disease and infections

Chest x-ray

CT

Specific imaging: air-fluid level, crescent sign

Aspegillous TB

Blood culture: before antibiotic use!! Most common isolates: SP, SA, E Coli

Sputum stain and culture: 1. Quality of sputum: >25 WBC <10 squamous cell /low power field 2. 1/3 yield positive culture in elderly patients 3. Differentiate colonization and infection pathogens 4. Presence of: M Tb, Legionella spp, H capsulatum, C immitiis, B.

deematidis 5. Specific stain: acid-fast bacilli, fungi, pneumocystis Urinary antigen detection 1. Legionella pneumophila serogroup 1 2. S. pneumoniae

SA

Candida E Coli

TB PCP NC

http://www.bestkj.com/htm/1005/36942.html

Detection of 4 fold increase of IgM against specific antigens

M. Pneumoniae, C. Pneumonia, L. spp, Chlamydia psittaci, C. burnetii, adnovirus, parainfluenza, influenza virus

Usually non-specific

Not routinely recommended

Empirical:

1. Start antibiotics 8 hours after onset

2. Regiment based on local antibiotics resistance report

3. Considering risk factors and host immune function

4. Determine treatment location

http://www.idsociety.org/badbugsnodrugs.html; last access Feb 12, 2010

Antibiotic options decline:

10 x '20 Initiative

bacterial resistance

The situation

worsens…

62.9

82.889.0 88.0

0

20

40

60

80

100

ORSA S. epidermidis S. haemolyticus Staphylococcus

spp.

Perc

en

t (%

) re

sis

tan

t

aMinistry of Health National Antimicrobial Resistance Surveillance Net.

Xiao YH, et al. Eur J Microbiol Infect Dis. 2008;27:697-708.

Hawser SP, et al. Antimicrob Agents Chemother. 2009;53:3280-4

Overall ESBL+

(n/N)

E. coli 578/1368

K. pneumoniae

189/528

K. oxytoca

22/51

Escherichia coli

9.3 7.52.6 0.7

64.9

0

60.1

28.6

0

20

40

60

80

100

Cef

otaxi

me

Cef

tazidim

e

Cef

epim

e

Cef

o/Sul

Pip

/Taz

o

Cip

roflo

xaci

n

Imip

enem

Gen

tam

icin

Perc

en

t (%

) re

sis

tan

ce

Xiao YH, et al. Eur J Microbiol Infect Dis. 2008;27:697-708.

Acinetobacter baumannii

67.760.7

23.4

43.8

61

10.4

69.2

0

20

40

60

80

100

Ceftazidime Cefepime Cefo/Sul Pip/Tazo Ciprofloxacin Imipenem Gentamicin

Perc

en

t (%

) re

sis

tan

ce

Xiao YH, et al. Eur J Microbiol Infect Dis. 2008;27:697-708.

Antibacterial Activity in Gram-Negative Non-Fermenters in China: Report of the Mohnarin From 2004-2005

RR>28/min

Systolic pressure <90 or 30 below baseline

New onset confusion/impaired consciousness

PO2<60 or SaO2% <90 (air)

Unstable comorbid illness

Mutilobar pneumonia

Pleural effusion >1cm

Macrolide: clathrimycin 0.5Bid, azithromycin (C-dependent)0.5qd

Doxycycline: 0.1 bid (T-dependent)

Quinolones: levofloxin 0.5 qd (C-dependent)

Beta-lactam: amoxicillin 1g tid (T-dependent)

Major sides effects

Duration: generally 10-14 days. Exception for L spp, 21 days

Switching from IV to oral: de-escalation therapy

1. WBC—>normal

2. Tem <37.5C two times (16 hours apart)

3. Improvement of cough and shortness of breath

Possible reasons

1. Reconsider diagnosis

2. Treating wrong pathogens?

3. Wrong drugs?

4. Mechanical reason?

5. Pyogenic source ?

6. Drug associated fever

Rate of pneumonia resolution dependents on underlying disease

COPD patients has slowed resolution

If pneumonia is caused by obstruction, long term follow up is necessary for eventual diagnosis. Keep in mind tumor

Generally 6 weeks for people<50 without underlying lung disease, 12 weeks for patients over 60 years old with COPD

Complicated pleural effusion:

1. >1cm, should be aspirated, drained if

(1)pH<7, Glucose <2.2mmol/L, (2)LDH >1000unit

(3)Gram stain (+)

2. Drain plus intrapleural lytic agent (Urine kinase)

3. Positive treatment of pleural effusion to prevent pyogenic pleural effusion

Lung abscess risk factors: impaired cough, aspiration, alcoholism, drug abuse, epilepsy, stroke, dental caries, bronchioectasis, bronchial carcinoma, lung infarction

Symptom: weight loss, night sweats, fever, productive cough, foul tasting sputum.

Treatment require prolonged duration. Surgical operation is needed if case of medical

failure

Recurrent pneumonia

1. COPD

2. Obstruction

3. Macro-aspiration

4. Immunodeficiency

5. Use of CT to detect anatomical abnormalities

Definition: pneumonia occurring 48 hours after hospital administration and not incubating at the time of admission.

5-10% of hospital discharges Most common nosocomial pneumonia, 30% 20% intubated patients, 70% ARDS patients develop HAP VAP Incident rates is associated with MV duration: 48 hours after

admission and 48 hours within extubation Crude mortality 30-70% VAP is a contributable factor to HAP mortality Post operative pneumonia: age >80, poor function, weight loss,

alcohol use are predictors. Most risky operations: abdominal aortic aneurysm repair, thoracic

surgery, emergency surgery

Additional risk factors: endotracheal intubation

Presence of nasal gastric tubes

Increased gastric pH

Steroid application

Ventilator tubes

Hands washing

Position in bed

64% gram negative bacilli: P.aeruginosa(21%), Acinetobacter spp.(6%), Enterobacter spp.(9%), K. pneumonia (8%)

S. aureus: most common cause in US: MRSA increased from 2% to 64%.

Enterobacter spp: ESBL became worldwide problem

Plasmid-mediated carbapenemase in Enterobacteriaceae.

In HAP no risk patients, Core pathogens aer: S. pneumoniae, H. Infl. S. aureus, E coli, K. spp, Proteus spp., and Serratia marcescents.

HAP risk patients: S. aureus, Legionella, spp.

Early VAP and later VAP: pathogens are different

Most common factor for HAP are later onset infection and recent antibiotic use.

Most common organisms: MRSA, acinetobacter Baumannii, stenotrophomonas maltophilia, ESBL producing enterobacteriaceae.

P. aeruginosa: steroid therapy, neutropenea, manlnutrition, MV, structural lung changes: effective antibiotics including imipenem, ciprofloxin, ceftazidime, piperacillin/tazobactam,

Acinetobacter: neurosurgery, head trauma, ARDS,aspiration S. Maltophilia: increased ICU stay, tracheostomy, treatment

with cefepime, severe trauma. MRSA: Prior antibiotic use, surgery, enteral feeding, later

onset VAP ESBL producing enterobacteriaceae: intubation, previous

antibiotic use, central venous catheterization.

New and progressive infiltration on chest

radiograph plus at least two of the following:

1. Fever >37.8 ° C

2. WBC >10,000/uL

3. Purulent sputum

Clinical diagnosis

Imaging diagnosis

Microbiology diagnosis

1. Endotracheal aspirate: >10^5cfu

2. BAL: >10^4cfu

3. PSB: >10^3cfu

CPIS 0 1 2

Airway secretion no non-purulent purulent

Chest x ray no infiltration yes

Tem（oC） 36.5and38.4 38.5and38.9 39or36

WBC（mm3） 4000and10000 <4000or>11000 <4000or>11000

PaO2/FiO2 >240orARDS 240,无ARDS

Airway aspiration 1+ or no growth >1+ >1+，favor gram stain

Bacteria culture

CPIS > 6 high sensitivity and specificity

Pugin J, et al. Am Rev Respir Dis, 1991: 143, 1121

Principle: based on local pattern of antibiotic resistance. Initial empirical treatment cover all suspected pathogens, then de-escalation to narrow band antibiotics when microbiology data is available.

Early treatment (<8 hour) could reduce mortality

Avoid inadequate and over treatment

Evidence class I: Effective infection control

Avoid intubation and re-intubation

Non-invasive ventilation

Sub-glottis aspiration

Semi-recumbent position

Start empirical therapy within 24 hours

Control blood glucose using insulin

Limit blood infusion

Oral decontamination

Oral hygiene

Ventilator tube exchange when necessary

Keep

artificial

airway

antibiotic

drainage

(pulmonary infection control window, PIC window)

Need mechanical

ventialtion

（VAP） PIC window

pulmonary infection control window

Sequential ventilation

Early extubation to avoid VAP/HAP

invasive Non-invasive

Positive pressure support