Dr. S.

YUVARAJAN,MBBS,MD(PULMONARY MEDICINE) GOLD MEDALIST Consultant Pulmonologist

The New Treatment Paradigm Selecting Appropriate Empiric Antibiotics

Community Acquired Pneumonia (CAP)

Definition

an acute infection of the pulmonary parenchyma

that is associated with clinical symptoms accompanied by the presence of an acute infiltrate

on a chest radiograph, or auscultatory findings

consistent with pneumonia, in a patient not hospitalized or residing in a long term care facility for > 14 days before onset of symptoms. 3
Bartlett. Clin Infect Dis 2000;31:347-82.

Pathophysiology
Aspiration of oropharyngeal organisms

Inhalation of infected aerosols

Hematogenous spread from extra-pulmonary sites Contiguous spread Direct inoculation

Pneumonias Classification

CAP

Community Acquired Health Care Associated

HCAP HAP
HCAP VAP
6
Nosocomial Pneumonias

Hospital Acquired

Ventilator Acquired

Pathological classification
Lobar pneumonia

Interstitial pneumonia
Bronchopneumonia Multi-lobar pneumonia Cavitary pneumonia Necrotizing pneumonia Lung Abscess

Pathophysiology
TYPICAL Organisms
Streptococcus pneumoniae
Haemophilus influenza Streptococcus pyogenes

Klebsiella pneumoniae
Moraxella catarrhalis Staph aureus

Enterobacteriaceae/Gram negative bacilli

Anaerobic organisms (aspiration) 8

Fusobacterium sp.

Prevotella sp.

Pathophysiology
ATYPICAL Organsims
Mycoplasma pneumoniae
Chlamydia pneumoniae Chlaymida sp.

Legionella sp.
Respiratory viruses Others

Pathophysiology

10

Guidelines for CAP

American Thoracic Society (ATS)

Guidelines - Management of Adults with CAP (2001)

Infectious Diseases Society of America (IDSA) Update of Practice Guidelines Management of CAP

in Immuno-competent adults (2003)

ATS and IDSA joint effort (we will follow this) IDSA/ATS Consensus Guidelines on the Management of CAP in Adults (March 2007) 11

Why Guidelines?
Evidence-based practice
Best outcome for patients Best use of resource Restricts idiosyncratic behaviour

Legal protection
Identify research needs

A tool for education

Gain public confidence
12

CAP The Two Types of Presentations

Classical
Sudden onset of CAP High fever, shaking chills Pleuritic chest pain, SOB Productive cough Rusty sputum, blood tinge Poor general condition High mortality up to 20% in patients with bacteremia S.pneumoniae causative

Atypical
Gradual & insidious onset Low grade fever Dry cough, No blood tinge Good GC Walking CAP Low mortality 1-2%; except in cases of Legionellosis Mycoplasma, Chlamydiae, Legionella, Ricketessiae, Viruses are causative

13

CAP Pathogenesis

Inhalation Aspiration

Hematogenous

14

CAP Risk Factors for Pneumonia

15

Age Obesity; Exercise is protective Smoking, PVD Asthma, COPD Immuno-suppression, HIV Institutionalization, Old age homes etc Dementia
ID Clinics 1998;12:723. Am J Med 1994;96:313

Community Acquired Pneumonia (CAP)

Epidemiology

4-5 million cases annually

~500,000 hospitalizations 20% require admission ~45,000 deaths

Fewest cases in 18-24 yr group

Probably highest incidence in <5 and >65 yrs Mortality disproportionately high in >65 yrs Over all mortality is 2-30%; Hospitalized Pt mort <1% for those not requiring hospitalization 16
Bartlett. CID 1998;26:811-38.

CAP The Pathogens Involved

40-60% - No causative agent identified 2-5% - Two are more agents identified
9% 4% 4% 5% 6% 6% 10% 56%

S.pneumoniae H.influenza Chlamydia Legionella spp S.aureus Mycoplasma Gram Neg bacilli Viruses

17

Streptococcus pneumonia
(Pneumococcus)

Most common cause of CAP

About 2/3 of CAP are due to S.pneumoniae

These are gram positive diplococci Typical symptoms (e.g. malaise, shaking chills fever, rusty sputum, pleuritic chest pain, cough) Lobar infiltrate on CXR

May be Immuno suppressed host

25% will have bacteremia serious effects
18

Strep pneumo

19

Strep pneumo
Gram positive lancet-shaped, encapsulated diplococcus Most common cause of CAP Multiple serotypes

High mortality if untreated >> Sepsis

20

S. aereus CAP Dangerous

This CAP is not common; Multi lobar Involvement

Post Influenza complication, Class IV or V

Compromised host, Co-morbidities, Elderly CA MRSA A Problem; CA MSSA also occurs Empyema and Necrosis of lung with cavitations Multiple Pyemic abscesses, Septic Arthritis

Hypoxemia, Hypoventilation, Hypotension common

Vancomycin, Linezolid are the drugs for MRSA
21

CAP Age wise Incidence

1400
1200

1000
800 # of cases 600 400 200

22

<5

5 to 17 18-24

25-44

45-64

>65

CAP Age wise Mortality

80 74.9

70
60 50 40 30 20 10 0 0 <4 0 5 to 14 0 15-24 2 25-44 5.7 45-64 >65
# of deaths

23

CAP Risk Factors for Hospitalization

Older, Unemployed, Unmarried

Recurrent common cold

Asthma, COPD; Steroid or bronchodilator use

Chronic diseases, Diabetes, CHF, Neoplasia

Amount of smoking Alcohol is NOT related to increased risk for hospitalization
24
ID Clinics 1998;12:723. Am J Med 1994;96:313

CAP Risk Factors for Mortality Age > 65 Bacteremia (for S. pneumoniae) S. aureus, MRSA , Pseudomonas

Extent of radiographic changes

Degree of immuno-suppression

Amount of alcohol consumption

25
ID Clinics 1998;12:723. Am J Med 1994;96:313

CAP Bacteriology in Hospitalized Pts

26

CAP Evaluation of a Patient

Hx. PE, CXR

No Infiltrate

Infiltrate or Clinical evidence of CAP Evaluate need for Admission Out Patient PORT & CURB 65 Medical Ward

Alternate Dx.

ICU Adm.

27

Diagnosis of Pneumonia
100 80

PERCENT

60 40 20 0 Cough Fever Dyspnea Phlegm Chest Pain

28

Diagnostics
Labs
CBC
BMP

Imaging
CXR
CT scans

Cultures
Blood
Sputum

29

Other tests

CAP Management Guidelines

Rational use of microbiology laboratory Pathogen directed antimicrobial therapy whenever possible

Prompt initiation of Antibiotic therapy

Decision to hospitalize based on prognostic criteria - PORT or CURB 65

30

Clinical Parameter Age in years For Men (Age in yrs) For Women (Age -10) NH Resident Co-morbid Illnesses Neoplasia Liver Disease CHF CVD Renal Disease (CKD)

Scoring Example 50 (50-10) 10 points 30 points 20 points 10 points 10 points 10 points

Clinical Parameter

Scoring 20 points 20 points 20 points 15 points 10 points 30 points

Clinical Findings
Altered Sensorium Respiratory Rate > 30 SBP < 90 mm Temp < 350 C or > 400 C Pulse > 125 per min Investigation Findings Arterial pH < 7.35

BUN > 30
Serum Na < 130 Hematocrit < 30% Blood Glucose > 250 Pa O2

20 points
20 points 10 points 10 points 10 points

PORT Scoring PSI

31
Pneumonia Patient Outcomes Research Team (PORT)

X Ray e/o Pleural Effusion 10 points

Classification of Severity - PORT

Class I Predictors Absent

Class II

70

Class III

71 90

Class IV

91 - 130

Class V

> 130

32

PSI: Mortality in Risk Classes

30 25
Percent

Outpatients

Hospitalised

20 15 10 5 0 I II (<71) III (71-90) IV (91-130) V (>130)

Score

33

Fine et al. New Engl J Med 1997; 336(4):243-250

CAP Management based on PSI Score

PORT Class Class I Class II PSI Score No RF 70 Mortality % 0.1 0.4 0.6 0.7 Treatment Strategy Out patient Out patient

Class III
Class IV Class V

71 - 90
91 - 130 > 130

0.9 2.8
8.5 9.3 27 31.1

Brief hospitalization
Inpatient IP - ICU

34

CURB 65 Rule Management of CAP

CURB 0 or 1 CURB 2 CURB 3 CURB 4 or 5 Home Rx Short Hosp Medical Ward ICU care

CURB 65 Confusion BUN > 30 RR > 30 BP SBP <90 DBP <60 Age > 65

35

Algorithmic Approach
Step 4 Step 1
< 50 Years

Step 2
No Co-morbidity

Step 3
Class I
No CURB

Only OP
CURB +

CAP Patient

Co-morbidity Present
50 Years

PORT 36

OP / IP/ ICU Class II-V

Who Should be Hospitalized?

Class I and II Usually do not require hospitalization

Class III
Class IV and V

May require brief hospitalization

Usually do require hospitalization

Severity of CAP with poor prognosis

RR > 30; PaO2/FiO2 < 250, or PO2 < 60 on room air Need for mechanical ventilation; Multi lobar involvement Hypotension; Need for vasopressors Oliguria; Altered mental status 37

CAP Criteria for ICU Admission

Major criteria Invasive mechanical ventilation required Septic shock with the need of vasopressors Minor criteria (least 3) Confusion/disorientation Blood urea nitrogen 20 mg% Respiratory rate 30 / min; Core temperature < 36C Severe hypotension; PaO2/FiO2 ratio 250 Multi-lobar infiltrates WBC < 4000 cells; Platelets <100,000

38

CAP Laboratory Tests

CXR PA & lateral

CBC with Differential

BUN and Creatinine FBG, PPBG Liver enzymes Serum electrolytes Gram stain of sputum Culture of sputum Pre Rx. blood cultures Oxygen saturation 39

CHEST X RAY

40

Diagnostics: CXR
Findings
Infiltrates

Pleural effusions
Abscess/Cavities Bulging fissures

Atelectasis
Air bronchograms

Other findings
PTX
Pleural thickening/Scarring Pulmonary edema

41

Lymphadenopathy/Masses

Diagnostics: CXR
Normal CXR
Immunocompromised

Dehydrated
Early infection

American Journal of Medicine Sept. 2004: 117, 305-11

2706 patients
911 patients with pneumonia and ()CXR These patients were older, increased co-morbidities

These patients had similar rates of + sputum/blood cultures

These patients had a similar mortality

42

Diagnostics: CXR
Respiratory Medicine May 2006: 100, 926-32
192 patients with pneumonia
Excellent IR for lobes involved, extent of infiltrate, pleural effusion Poor IR for pattern of infiltrate Minimal relation found between cultured pathogens and radiologic features of infiltrate on CXR

43

Diagnostics: CT scan
CT scan
Alternative diagnoses
Unresolved cases Complications suspected

Concerning CXR
Treatment failure

44

 In addition to a constellation of suggestive clinical features, a demonstrable infiltrate by chest radiograph or other imaging technique, with or without supporting microbiological data, is required for the diagnosis of pneumonia.

Patients with CAP should be investigated for specific pathogens that would significantly alter standard (empirical management decisions, when the presence of such pathogens is suspected on the basis of clinical and epidemiologic clues
45

CAP Value of Chest Radiograph

Usually needed to establish diagnosis It is a prognostic indicator

To rule out other disorders

May help in etiological diagnosis

J Chr Dis 1984;37:215-25

46

Infiltrate Patterns and Pathogens

CXR Pattern Lobar Patchy Interstitial Cavitatory Large effusion Possible Pathogens S.pneumo, Kleb, H. influ, Gram Neg Atypicals, Viral, Legionella Viral, PCP, Legionella Anerobes, Kleb, TB, S.aureus, Fungi Staph, Anaerobes, Klebsiella

47

Diagnostics: Cultures
Sputum gram stain/culture
Change antibiotic therapy

Unusual pathogens/antibiotic resistance issues

Do not change antibiotics/outcomes

Cost
Process issues

Sputum cultures?
Are sputum cultures useful in ED? Are sputum cultures useful in ICU? Do antibiotics affect yield of sputum?

48

Diagnostics: Cultures
Sputum cultures: Recommendations
Outpatient
Optional

Inpatient
Optional Recommended when result may change therapy

Recommended
ICU admission/Severe CAP

Failure of outpatient therapy

Cavitary infiltrates (suspect TB) Alcoholism

49

Severe COPD

CAP Grams Stain of Sputum

Good sputum samples is obtained only from 39% 83% show only one predominant organism Efficiency of test Sensitivity Specificity S. pneumoniae H. influenza

57 % 97 %

82 % 99 %

Positive Predictive Value

Negative Predictive Value

95 %
71 %

93 %
96 %

50

RECOMMENDATIONS
Pretreatment Gram stain and culture of expectorated sputum should be performed only with a good-quality specimen. Patients with severe CAP, as defined above, should at least have blood samples drawn for culture, urinary antigen tests for Legionella pneumophila and S. pneumoniae performed, and expectorated sputum samples collected for culture.

For intubated patients, an endotracheal aspirate sample should be obtained

51

 The yield of sputum bacterial cultures is variable and strongly influenced by the quality of the entire process.
The yield of S. pneumoniae, for example, is only 40%50% from sputum cultures from patients with bacteremic pneumococcal pneumonia.

The yield of cultures is substantially higher with endotracheal aspirates, bronchoscopic sampling, or transthoracic needle aspirates although specimens obtained after initiation of antibiotic therapy are unreliable and must be interpreted carefully .
52

Diagnostics: Cultures
Blood Cultures
Yield pathogen 5-15%

Blood cultures often do not change management

Most commonly isolated organismStrep pneumo High false positive rate

Yield of blood cultures decreased by 50% by prior antibiotic therapy

Optional Recommended
Severe CAP Immunodeficient states (asplenia, liver disease, HIV) Indications for sputum cultures

53

 Pretreatment blood cultures yielded positive results for a probable pathogen in 5%14% in large series of nonselected patients hospitalized with CAP.

The yield of blood cultures is, therefore, relatively low when management decisions are analyzed, the impact of positive blood cultures is minor.

54

 The most common blood culture isolate in all CAP studies is S. pneumoniae.

Because this bacterial organism is always considered to be then most likely pathogen, positive blood culture results have not clearly led to better outcomes or improvements in antibiotic selection .
Blood cultures are also indicated when patients have a host defect in the ability to clear bacteremia

55

Pathogens Retrieved from Blood Culture

5% S.pneumoniae Enterobacteria Staph.aureus Others

11% 16%

68%

56

C-reactive Protein and Disease Severity

1000

ns

100

CRP (mg/L)

10

0.1

2 CRB-65 score

57

Procalcitonine and Disease Severity

1000

P<0.0001

100

PCT (ng/mL)

10

0.1

0.01

0.001

2 CRB-65 score

Good correlation between PCT and Severity of Disease

58

Mortality of CAP Based on Pathogen

P. aeruginosa 61.0 %

K. pneumoniae S. aureus -

35.7 %
31.8 %

Legionella S. pneumoniae C. pneumoniae H. influenza 59

14.7 %
12.0 % 9.8 % 7.4 %

Therapy Algorithm CAP

Diagnosis

Outpatient Care

Hospital Admission

Ward

ICU

oral

i.v.

G. Hffken, J. Lorenz, W. Kern, T. Welte, T. Bauer, K. Dalhoff, E. Dietrich, S. Ewig, P. Gastmeier, B. Grabein, E. Halle, M. Kolditz, R. Marre, and H. Sitter. Guidelines of the Paul-Ehrlich-Society of Chemotherapy, the German Respiratory Diseases Society, the German Infectious Diseases Society and of the Competence Network CAPNETZ for the Management of Lower Respiratory Tract Infections and Community-acquired Pneumonia. Pneumologie 64 (3):149-154, 2010.

60

Placebo-controlled Study

61

Evans GM, Gaisford WF. Lancet 1938;14-19.

Methods

39 g/day of M.& B. 693 2(p-Aminobenzenesulphonamido)pyridine Gram stain White blood cell count Clinical data
62

Evans GM, Gaisford WF. Lancet 1938;14-19.

Mortality of CAP

p = 0,0004
63
Evans GM, Gaisford WF. Lancet 1938;14-19.

Traditional Treatment Paradigm

Conservative start with workhorse antibiotics

Reserve more potent drugs for non-responders

64

New Treatment Paradigm

Hit hard and early with appropriate antibiotic(s)

Short Rx. Duration; De-escalate where possible

65

The Therapy Conundrum

Avoid emergence of multidrug resistant microorganisms

Immediate Rx. of patients with serious sepsis

Objective 1

Objective 2

66

The Effect of the Traditional Approach

50 40 30 20 10 0

Inappropriate therapy (%)

34

45

17

CAP

HAP

HAP on CAP
Kollef, et al. Chest 1999;115:462474

67

Dont Wait for Results !

Mortality (%)
n=75 p<0.001

Switching after susceptibility results

Adequate treatment within a few hours

68

Tumbarello, et al. Antimicrob Agents Chemother 2007;51:19871994

CAP Treatment Consensus

Risk assessment approach

Early Antibiotic selection

Change treatment driven by local surveillance Hit hard and hit early As short a duration as possible

De-escalate when and where possible

69

OPAT OP Parenteral Antimicrobial Therapy

70

Antibiotics of choice for CAP

Macrolide -M

Azithromycin Clarithromycin Erythromycin

Telithromycin

Fluroquinolone-FQ

Levofloxacin
Moxifloxacin

Betalactum B

Ceftriaoxone Cefotaxime
B Inhibitor BI

Gatifloxacin
Trovafloxacin

Doxycycline

71

Sulbactam Tazobactam Piperacillin

Antibiotic

Dosage, Route, Frequency and Duration

Doxyclycline
Azithromycin

100-200 mg PO/IV BID for 7 to 10 days

500 mg OD IV 3 days + 500 mg OD PO for 7-10 days

Clarithromycin
Telithromycin

250 500 mg BID PO for 7 14 days

800 mg PO OD for 7 10 days

Levofloxacin
Gatifloxacin Moxifloxacin Gemifloxacin Amoxyclav Ceftriaxone

750 mg PO/IV OD for 5 days

400 mg PO or IV OD for 5 to 7 days 400 mg PO or IV OD for 5 to 7 days 320 mg PO OD for 5 7 days 2 g of Amoxi +125 mg of Clauv PO BID for 7 to 10 days 2 g IV BID for 3 to 5 days + PO 3G CS 1 g OD IV or IM for 7 to 14 days

72

Ertapenum

Empiric Treatment Outpatient

Healthy and no risk factors for DR S.pneumoniae 1. Macrolide or Doxycycline Presence of co-morbidities, use of antimicrobials within the previous 3 months, and regions with a high rate (>25%) of infection with Macrolide resistant S. pneumoniae 1. Respiratory FQ Levoflox, Gemiflox or Moxiflox 2. Beta-lactam (High dose Amoxicillin, AmoxicillinClavulanate is preferred; Ceftriaxone, Cefpodoxime, Cefuroxime) plus a Macrolide or Doxycycline 73

Empiric Treatment Inpatient Non ICU

1. A Respiratory Fluoroquinolone (FQ) Levo or

2. A Beta-lactam plus a Macrolide (or Doxycycline)

(Here Beta-lactam agents are 3 Generation

Cefotaxime, Ceftriaxone, Amoxiclav)

3. If Penicillin-allergic Respiratory FQ or Ertapenem is another option

74

Empiric Treatment: Inpatient in ICU

1. A Beta-lactam (Cefotaxime, Ceftriaxone, or Ampicillin-Sulbactam) plus either Azithromycin or Fluoroquinolone 2. For penicillin-allergic patients, a respiratory Fluoroquinolone and Aztreonam

75

Empiric Rx. Suspected Pseudomonas

1. Piperacillin-Tazobactam, Cefepime, Carbapenums

(Imipenem, or Meropenem) plus either Cipro or Levo

2. Above Beta-lactam + Aminoglycoside + Azithromycin 3. Above Beta-lactam + Aminoglycoside + an antipseudomonal and antipneumococcal FQ 4. If Penicillin allergic - Aztreonam for the Beta-lactam

76

Empiric Rx. CA MRSA

For Community Acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA) Vancomycin or Linezolid Neither is an optimal drug for MSSA For Methicillin Sensitive S. aureus (MSSA) B-lactam and sometimes a respiratory Fluoroquinolone, (until susceptibility results).

Specific therapy with a penicillinase-resistant

semisynthetic penicillin or Cephalosporin 77

Duration of Therapy
Minimum of 5 days Afebrile for at least 48 to 72 h No > 1 CAP-associated sign of clinical instability Longer duration of therapy If initial therapy was not active against the identified pathogen or complicated by extra pulmonary infection

78

New data The Speed of Delay ! (Class 4,5)

90 80 70 60 50 40 30 20 10 0 0.5 1 2 3 4 5 6

Survival (%)

Each hour of delay carries 7.6% reduction in survival

Delay in treatment (hours) from hypotension onset

79

Kumar, et al. Crit Care Med 2006;34:15891596

CAP Summary of Empiric Treatment

Outpatient Rx any one of the three Macrolide or Doxycycline or Fluoroquinolone Patients in General Medical Ward 3rd Generation Cephalosporin + Macrolide

Betalactum / B-I + Macrolide or B / B-I + FQ

Fluroquinolone alone Patients in ICU

3GC + Macrolide or 3GC + FQ

B/B-I + Macrolide or B/B-I + FQ 80
IDSA guidelines: Clin Infect Dis 2000;31:347-82

CAP Treatment Summary

CAP Class Site of Care OP OP OP + IP Med Ward ICU Treatment 1 AZ FQ
FQ IV

Treatment 2 CLR B+M I V - B + AZ B 3G + AZ B 3G + FQ

Treatment 3 ER / Doxy B + Doxy Aztreo + FQ Etrap + M Carbepenum Sulbac ,Tazob

Class I Class II Class III Class IV Class V

FQ + AZ B 3G + AZ

81

Strategies for Prevention of CAP

Cessation smoking Influenza Vaccine (Flu shot Oct through Feb)

It offers 90% protection and reduces mortality by 80%

Pneumococcal Vaccine (Pneumonia shot) It protects against 23 types of Pneumococci 70% of us have Pneumococci in our RT It is not 100% protective but reduces mortality

Age 19-64 with co morbidity of high for pneumonia

Above 65 all must get it even without high risk 82 Starting first dose of antibiotic with in 4 h & O2 status

Switch to Oral Therapy

Four criteria
Improvement in cough, dyspnea & clinical signs Afebrile on two occasions 8 h apart WBC decreasing towards normal Functioning GI tract with adequate oral intake

If overall clinical picture is otherwise favorable, hemodynamically stable; can switch to oral therapy while still febrile.
83

Management of Poor Responders

Consider non-infectious illnesses Consider less common pathogens Consider serologic testing

Broaden antibiotic therapy

Consider bronchoscopy

84

CAP Complications
Hypotension and septic shock

3-5% Pleural effusion; Clear fluid + pus cells

1% Empyema thoracis pus in the pleural space Lung abscess destruction of lung - CSLD Single (aspiration) anaerobes, Pseudomonas Multiple (metastatic) Staphylococcus aureus Septicemia Brain abscess, Liver Abscess Multiple Pyemic Abscesses 85

CAP So How Best to Win the War?

Early antibiotic administration within 4-6 hours Empiric antibiotic Rx. as per guidelines (IDSA / ATS) PORT PSI scoring and Classification of cases Early hospitalization in Class IV and V

Change Abx. as per pathogen & sensitivity pattern

Decrease smoking cessation - advice / counseling Arterial oxygenation assessment in the first 24 h Blood culture collection in the first 24 h prior to Abx. Pneumococcal & Influenza vaccination; Smoking X 86

NOSOCOMIAL PNEUMONIA

87

Definition of ATS/IDSA guidelines:

1)Hospital-acquired pneumonia (HAP) is pneumonia that occurs 48 hours or more after admission, which was not incubating at the time of admission. 2)Ventilator-associated pneumonia (VAP) refers to pneumonia that develops more than 48 to 72 hours after endotracheal intubation. 3)Healthcare-associated pneumonia (HCAP) includes any patient who was either hospitalized in an acute care hospital for two or more days within 90 days of the infection; or resided in a long term care facility; or received intravenous antimicrobial therapy, chemotherapy, or wound care within the 30 days prior to the current infection; or attends a hospital or hemodialysis clinic

88

Nosocomial Pneumonia
Epidemiology Common hospital-acquired infection Occurs at a rate of approximately 5-10 cases per 1000 hospital admissions Incidence increases by 6-20 fold in patients being ventilated mechanically. One study suggested that the risk for developing VAP increases 1% per day Another study suggested, highest risk occur in the first 5 days after intubation 89

Etiology
Early vs. Late VAP1
Early onset= Pneumonia develops within 96 hours (4 days) of patients admission to the ICU or intubation for mechanical ventilation
Late onset= Pneumonia develops after 96 hours (4 days) of patients admission to the ICU or intubation for mechanical ventilation Very early onset= within 48 hours after intubation2
1

CDC.gov. Guidelines for preventing health-care-associated pneumonia, 2003. DR. The microbiology of ventilator-associated pneumonia.

2 Park

90

Nosocomial pneumonia

91

Mortality and Time of Presentation of HAP

P<.001

50

P<.001

P = .504

* *

Hospital Mortality (%)

40 30 20

*
10

0
*Upper 95% confidence interval

None

Early Onset

Late Onset

Nosocomial Pneumonia

92

Ibrahim, et al. Chest. 2000;117:1434-1442.

Nosocomial Pneumonia
Hence, the importance of focusing on:
Accurate diagnosis
Appropriate treatment Preventive measures

93

Nosocomial Pneumonia
Pathogenesis

Risk factors
Etiologic agents Differential diagnosis Treatment Prevention

94

Nosocomial Pneumonia
Pathogenesis

Pathogenesis
Microaspiration may occur in up to 45% of healthy volunteers during sleep

Oropharynx of hospitalized patients is colonized with GNR in 35-75% of patients depending on the severity and type of underlying illness
Multiple factors are associated with higher risk of colonization with pathogenic bacteria and higher risk of aspiration Invasion of the lower respiratory tract by:

Aspiration of oropharyngeal/GI organisms

Inhalation of aerosols containing bacteria Hematogenous spread 96

Oropharyngeal colonization
Scannapieco et al showed a transition in the colonization of dental plaques in patients in the ICU Control=25 subjects presenting to preventive dentistry clinic Study group=34 noncardiac patients admitted to medical ICU at VA hospital (sampled within 12 hours of admission and every third day)

Scannapieco et al. Colonization of dental plaque by respiratory pathogens in medical intensive care patients

97

Colonization of oropharynx
Medical ICU (N=34) Dentistry Clinic (N=25)

Species

Plaque

Mucosa

Plaque

Mucosa

S. aureus P. aeruginosa

2 8

5 7

0 0

1 0

K. pneumoniae
S. marcescens E. aerogenes E. cloacae E. asburiae P. mirabilis E. coli C. diversus A. calcoaceticus Pasteurella spp. Total

2
3 0 1 0 1 0 1 0 0 18

5
4 0 1 0 0 1 1 1 0 24

0
0 0 0 0 0 0 0 0 1 1

0
0 1 0 1 0 0 0 0 0 3

Scannapieco et al. Colonization of dental plaque by respiratory pathogens 98 in medical intensive care patients

GI colonization
Increased gastric pH leads to bacterial overgrowth

Reflux can then lead to colonization of oropharynx

Use of antacids and H2 blockers associated with GI colonization

99

Safdar et al. The pathogenesis of ventilator-associated pneumonia: its relevance to developing effective strategies for prevention

100

Nosocomial Pneumonia
Risk Factors

Etiology- select risk factors for pathogens

Streptococcus pneumoniae Smoking, COPD, absence of antibiotic therapy Smoking, COPD, absence of antibiotic therapy Younger age, Traumatic coma, Neurosurgery COPD, steroid therapy, longer duration of MV, prior antibiotics COPD, steroid therapy, longer duration of MV, prior antibiotics Haemophilus influenzae MSSA MRSA Pseudomonas aeruginosa

Acinetobacter species

ARDS, head trauma, neurosurgery, gross aspiration, prior cephalosporin therapy

102

Park DR. The microbiology of ventilator-associated pneumonia.

Nosocomial Pneumonia
Risk Factors
Host Factors
Extremes of age, severe acute or chronic illnesses, immunosupression, coma, alcoholism, malnutrition, COPD, DM

Factors that enhance colonization of the oropharynx and stomach by pathogenic microorganisms
admission to an ICU, administration of antibiotics, chronic lung disease, endotracheal intubation, etc.

103

Nosocomial Pneumonia
Risk Factors
Conditions favoring aspiration or reflux
Supine position, depressed consciousness, endotracheal intubation, insertion of nasogastric tube

Mechanical ventilation
Impaired mucociliary function, injury of mucosa favoring bacterial binding, pooling of secretions in the subglottic area, potential exposure to contaminated respiratory equipment and contact with contaminated or colonized hands of HCWs

Factors that impede adequate pulmonary toilet

Surgical procedures that involve the head and neck, being immobilized as a result of trauma or illness, sedation etc.

104

Risk factors for MDR pathogens

1.Receipt of antibiotics within the preceding 90 days

2.Current hospitalization of 5 days

3.Admission from a healthcare-related facility (eg, long-term care facility, dialysis unit)

4.High frequency of antibiotic resistance in the community or in the specific hospital unit
5.Presence of risk factors for HCAP including: hospitalization for two days or more in the preceding 90 days; residence in an extended care facility; home infusion therapy; chronic dialysis; home wound care; and a family member with an MDR pathogen 105 6.Immunosuppressive disease and/or therapy

Risk Factors Of VAP In Patient receiving Mechanical Ventilation

Age >70 years Chronic lung disease Depressed consciousness Large volume aspiration Chest surgery Frequent ventilator circuit changes The presence of an intracranial pressure monitor or nasogastric tube H-2 blocker or antacid therapy Transport from the ICU for diagnostic or therapeutic procedures Previous antibiotic exposure, particularly to third generation cephalosporins Reintubation Hospitalization during the fall or winter season 106 ventilation for ARDS Mechanical

Nosocomial Pneumonia
Etiologic Agents
S.aureus
Enterobacteriaceae P.aeruginosa

Acinetobacter sp.
Polymicrobial Anaerobic bacteria

Legionella sp.
Aspergillus sp. Viral

107

Pathogens Associated With HAP

P = .003

40

Early-onset NP Late-onset NP
PA = P aeruginosa OSSA = Oxacillin-sensitive S aureus ORSA = Oxacillin-resistant S aureus ES = Enterobacter species SM = S marcescens

Nosocomial Pneumonia (%)

35 30 25
P = .043
P = .408

20 15 10 5 0 PA OSSA ORSA ES SM
P = .985

P = .144

Pathogen 108 Ibrahim, et al. Chest. 2000;117:1434-1442.

Nosocomial Pneumonia
Diagnosis
Not necessarily easy to accurately diagnose HAP

Criteria frequently include:

Clinical
fever ; cough with purulent sputum,

Radiographic
new or progressive infiltrates on CXR,

Laboratorial
leukocytosis or leukopenia

Microbiologic
Suggestive gram stain and positive cultures of sputum, tracheal aspirate, BAL, bronchial brushing, pleural fluid or blood

109

Quantitative cultures

Nosocomial pneumonia
Bronchoscopically Directed Techniques for diagnosis of VAP and Quantitative cultures
Bronchoscopy with BAL/bronchial brushings (10,000 to 100,000 CFU/ml and less than 1% of squamous cells) Protected specimen brush method (>10 CFU/ml) Protected BAL with a balloon tipped catheter (>5% of neutrophils or macrophages with intracellular organisms on a Wright-Giemsa stain)

110

Nosocomial Pneumonia
Differential diagnosis
ARDS
Pulmonary edema Pulmonary embolism

Atelectasis
Alveolar hemorrhage Lung contusion

111

Nosocomial Pneumonia
Duration of antimicrobial treatment
Optimal duration of treatment has not been established

Most experts recommend 14-21 days of treatment

Recent data support shorter treatment regimens (8 days)

112

Treatment of Nosocomial Pneumonia

Comparison of 8 vs.15 days of antibiotics for VAP
Prospective, randomized, double blind clinical trial 51 French ICUs 401 patients with VAP (quantitative culture results) Clinical effectiveness comparable, with the possible exception of VAP caused by non fermenting GNR

JAMA 290 No 19, November 2003

113

Treatment of Nosocomial Pneumonia

45 42 39 36 33 30 27 24 21 18 15 12 9 6 3 0

8days 15 days

Mortality

Recur Infec

P.aerug Abx Free Days

114

Nosocomial Pneumonia
Preventive Measures
Incentive spirometry
Promote early ambulation Avoid CNS depressants

Decrease duration of immunosupression

Infection control measures Educate and train personnel

115

Nosocomial Pneumonia
Preventive Measures
Avoid prolonged nasal intubation
Suction secretions Semi-recumbent position( 30-45head elevation)

Do not change ventilator circuits routinely more often than every 48 hours
Drain and discard tubing condensate Use sterile water for respiratory humidifying devices Subglottic secretions drainage

116

117 Craven, et al. Chest. 1995;108:s1-s16.

Nosocomial Pneumonia
Preventive Measures
Remove NGT when no longer needed
Avoid gastric overdistention Stress ulcer prophylaxis:
sulcrafate; antacids; H2 receptor antagonists

Acidification of enteral feedings Prophylactic antibiotics

Inhaled antibiotics Selective digestive decontamination

Chlorexidine oral rinses

118

Vaccines ( Influenza; Strep.pneumoniae)

Role of gastric pH
gastric pH by H-2 blockers or antacids HAP Sucralfate >ranitidine>antacid = 10% > 6% > 4%

macroscopic gastric bleeding (P > 0.2)

Early-onset pneumonia was not statistically different (P > 0.2).

Late-onset pneumonia(4 days ) (P = 0.022). Sucralfate >antacid >ranitidine = 5% >16% > 21%

Mortality : no statistically difference

119

Role of gastric pH(2)

Sucralfate : lower median gastric pH (P < 0.001) and less frequent gastric colonization (P = 0.015)

84% late-onset GNB pneumonia have gastric colonization with the same bacteria before pneumonia developed CONCLUSION: Stress ulcer prophylaxis with sucralfate reduces the risk for late-onset pneumonia in ventilated patients compared with antacid or ranitidine
120

Decontamination of the digestive tract

preventing oropharyngeal and gastric colonization with aerobic GNB and Candida spp, without disrupting the anaerobic flora locally administered nonabsorbable antibiotic (eg, polymyxin) and an aminoglycoside or fluoroquinolone + amphotericin B or nystatin. One RCS showed decrease in pneumonia due to GNB

121

Decontamination of the digestive tract (2)

A large prospective randomized trial of ICU in the Netherlands (pt 934) :
SDD group lower mortality both in the ICU and during hospitalization (mortality :15 vs 23% ICU, 24 vs 31 % hospital)

The preventative effects of SDD for HAP have been considerably lower in ICUs with high rates of endemic MDR pathogens
122

Patient positioning
Several studies supine position vs semirecumbent predisposed to microaspiration of gastric contents lower incidence of both clinically suspected and microbiologically confirmed HAP in semirecumbent versus supine patients No difference in mortality Suggest : place intubated patients in the semirecumbent position unless contraindicated. 123

Patient positioning
Lateral slight-Trendelenburg position achieved with the bed tilted few degrees below horizontal

The 450 semilateral horizontal position of the intubated patient

The 450 semilateral horizontal position of the intubated patient

Current Opinion in Critical Care 2011, 17:5763 Ventilator-associated pneumonia: role of 124 positioning

Subglottic drainage

Hi-Lo EVAC tube

(CASS)

125

Continuous aspiration of subglottic secretions (CASS)

126

Kollef et al. A randomized clinical trial of continuous aspiration of Subglottic secretions in cardiac surgery patients

Subglottic drainage (2)

Lessen risk of aspiration 5 studies (896 intubated pt) The use of CASS reduced the incidence of VAP by nearly half - risk ratio 0.51 (95% CI 0.37-0.71). The effect of CASS in limiting VAP was most pronounced among patients expected to require >72 hours of mechanical ventilation.

127

Via the tube

1) Ventilator circuit changes

2) Condensate
3) Silver-lined ET tubes

128

Ventilator circuit management

Craven and colleagues showed that ventilator circuit change every 24 hours compared to 48 hours increased VAP incidence Several later studies showed that circuit changes could be used safely for greater than 48 hours

Kollef et al. Mechanical ventilation with or without 7-day circuit changes

129

Ventilator circuit management

1999 study by Kollef et al.

Randomized clinical trial looking at circuit change every 7 days vs. no routine circuit change
Study group incidence=24.5%

Control group incidence=28.8%

Cost of ventilator circuit changes
$7410 control group

$330 for study group

Kollef et al. Mechanical ventilation with or without 7-day circuit changes

130

Condensate management
Heat-moisture exchanger
Theoretical advantage=prevents bacterial colonization of tubing
Studies= Mixed results Disadvantage=increases dead space and resistance to breathing

Heated wire to elevate temp of inspired air

Advantage=Decreases condensate formation Disadvantage=Blockage of ET tube by dried secretions

CDC.gov. Guidelines for preventing health-care-associated pneumonia, 2003.

131

NEBULISERS
Recommendations from theminutes of meeting in GOA 2013 (THE FUTURE OF NEBULISATION). Panel of 28 pulmonologists from all over india.

132

 Safety isues of nebulisers in home Safety isues of using nebulisers in in patients and icu Developing guidelines regarding adequate care and proper usage of nebulisers. Change of tubings and masks.

133

Silver-lined ET tube
Broad-spectrum antimicrobial activity in vitro

Reduces bacterial adhesion to devices in vitro

Blocks biofilm formation on the device in animal models

Dog model- decreased severity of lung colonization

134

135

1) Baseline
2) When VAP is clinically suspected 3) 3 days later

CPIS>6 suggests of pneumonia

136

Am J Respir Crit Care Med 2000;162:505

Noninfectious causes of fever and pulmonary infiltrates in VAP

Chemical aspiration without infection (Aspiration pneumonitis) Atelectasis Pulmonary embolism ARDS Pulmonary hemorrhage Lung contusion Infiltrative tumor Radiation pneumonitis Drug137 reaction

Diagnosis

Imaging
Gram's stain and culture Bronchoscopy

138

Gram's stain and culture

unreliable due to contamination with bacteria colonizing the oropharynx The presence of many polymorphonuclear leukocytes (and few epithelial cells) and bacteria, which are morphologically consistent with bacteria found on culture, improve the predictive power In addition, the lack of isolation of a pathogen (eg, MRSA or Pseudomonas) from a well-collected and adequate expectorated sputum sample can be used to narrow the antimicrobial regimen Blood cultures are extremely helpful when positive, but the yield is low 139

Gram's stain and culture

negative direct staining : - previous antibiotic therapy

- steroids
- presence of Pseudomonas aeruginosa 1 microbiological findings are useful mainly based on two rules: 1. the presence of intracellular bacteria 2. a positive Gram stain (or other direct tests) may be of great help in selecting the initial antibiotic regimen but not in making the diagnosis of pneumonia 2 The diagnostic technique used, bronchoscopic or tracheal aspirate with quantitative cultures, does not influence either the rate of de-escalation or of mortality 3
1. Eur J Microbiol Infect Dis 1994;13:549558 2. Chest 2001;120:95570 3. Crit Care Med 2004;32:218390

140

Bronchoscopy
Protected brush specimen (PBS) Using a threshold of >103 colony forming units (CFU)/mL
sensitivity : 64 to 100 % specificity : 60 to 100 %

Bronchoalveolar lavage (BAL) Quantitative cultures using a threshold of >104 CFU/mL

sensitivity : 72 - 100 % specificity : 69 - 100 %

At least 4 studies concluded that bronchoscopically directed techniques were not more accurate for diagnosis of VAP than clinical and X-ray criteria, combined with cultures of tracheal aspirate

141

Therefore no gold standard criteria exist

Initial Antibiotic Therapy

Inappropriate therapy is a major risk factor for excess mortality and length of stay in patients with HAP, and antibiotic resistant organisms are the pathogens most commonly associated with inappropriate therapy. In selecting empiric therapy for patients who have recently received an antibiotic use an agent from a different antibiotic class, since recent therapy increases the probability of inappropriate therapy and can predispose to resistance to that same class of 142 antibiotics.

Initial Antibiotic Therapy

Initial antibiotic therapy should be given promptly since delays in administration may add to excess mortality in VAP. Initial empiric therapy is more likely to be appropriate if a protocol for antibiotic selection is developedbut adapted to local patterns of antibiotic resistance, with each ICU collecting this information, and updating it on a regular basis.

143

144

TABLE 3. INITIAL EMPIRIC ANTIBIOTIC THERAPY FOR HAP OR VAP IN PATIENTS WITH NO KNOWN RISK FACTORS FOR MDR PATHOGENS, EARLY ONSET, AND ANY DISEASE SEVERITY Potential Pathogen
Streptococcus pneumoniae

Recommended Antibiotic*

Ceftriaxone

Haemophilus influenzae

or
Levofloxacin, moxifloxacin, or ciprofloxacin

Methicillin-sensitive Staphylococcus aureus Antibiotic-sensitive enteric gram-negative bacilli

or

Escherichia coli
Klebsiella pneumoniae Enterobacter species Proteus species

Ampicillin/sulbactam
or Ertapenem

Serratia marcescens
* See Table 5 for proper initial doses of antibiotics. The frequency of penicillin-resistant S. pneumoniae and multidrug-resistant S. pneumoniae is increasing; levofloxacin or moxifloxacin are preferred to ciprofloxacin and the role of other new quinolones, such as gatifloxacin, has not been established.

145

TABLE 4. INITIAL EMPIRIC ANTIBIOTIC THERAPY FOR HAP OR VAP IN PATIENTS WITH LATE-ONSET DISEASE OR RISK FACTORS FOR MDR PATHOGENS, AND ANY DISEASE SEVERITY

Potential Pathogen
Pathogens listed in Table 3 and MDR pathogens Pseudomonas aeruginosa Klebsiella pneumoniae (ESBL) Acinetobacter species

Combination Antibiotic Therapy*

Antipseudomonal cephalosporin (cefepime, ceftazidime) or Antipseudomonal carbepenem (imipenem or meropenem) or Lactam/-lactamase inhibitor (piperacillintazobactam) plus Antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) or Aminoglycoside (amikacin, gentamicin, or tobramycin) plus

Methicillin-resistant Staphylococcus aureus (MRSA) Legionella pneumophila

Linezolid or vancomycin

* Initial antibiotic therapy should be adjusted or streamlined on the basis of microbiologic data and clinical response to therapy. If an ESBL strain, such as K. pneumoniae, or an Acinetobacter species is suspected, a carbepenem is a reliable choice. If L. pneumophila is suspected, the combination antibiotic regimen should include a macolide (e.g., azithromycin) or a fluoroquinolone (e.g., ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside. If MRSA risk factors are present or there is a high incidence locally.

146

Optimal Antibiotic Therapy

Empiric therapy of patients with severe HAP or VAP requires the use of antibiotics at optimal doses to assure maximum efficacy. Initial therapy should be administered to all patients intravenously, with a switch to oral/enteral therapy in selected patients with a good clinical response and a functioning intestinal tract. Highly bioavailable agents, such as the quinolones and linezolid, may be easily switched to oral therapy in such patients.

Aerosolized antibiotics have not been proven to have value in the therapy of VAP.

147

Optimal Antibiotic Therapy

Combination therapy should be used if patients are likely to be infected with MDR pathogens. No data have documented the superiority of this approach to monotherapy, except to enhance the likelihood of initially appropriate empiric therapy.
If patients receive combination therapy with an aminoglycoside containing regimen, the aminoglycoside can be stopped after 5-7 days in responding patients. Monotherapy with selected agents can be used for patients with severe HAP and VAP in the absence of resistant pathogens. Patients in this risk group should initially receive combination therapy until the results of lower respiratory tract cultures are known and confirm that a single agent can be used.

148

Optimal Antibiotic Therapy

MRSA pneumonias: - prolonged intubation periods - prior use of antibiotics
Pseudomonas aeruginosa pneumonias:
linezolid

- structural pulmonary disease - 1 week of prior hospitalization - prolonged periods of intubation (>5 days) - prior exposure to antibiotics A. Baumannii VAP: - neurosurgery - ARDS - head trauma - large-volume pulmonary aspiration.

Combination piperacillin/tazobactam + ciprofloxacin, or amikacin + imipenem, meropenem or an antipseudomonal cephalosporin.

carbapenems, sulbactam, tigecycline, colistin

149

Duration of antimicrobial treatment

Optimal duration of treatment has not been established

Most experts recommend 14-21 days of treatment

Recent data support shorter treatment regimens (8 days)

150

Comparison of 8 vs.15 days of antibiotics for VAP

Prospective, randomized, double blind clinical trial 51 French ICUs 401 patients with VAP (quantitative culture results) Clinical effectiveness comparable, with the possible exception of VAP caused by non fermenting GNR

JAMA 290 No 19, November 2003

151

152

Non resolving pneumonia

Non resolving pneumonia is a clinical syndrome in which focal infiltrates begin with some clinical association of acute pulmonary infection and despite a minimum of 10 days of antibiotic therapy patients either dont improve or worsen or radiographic opacities fail to resolve within 12 week

153

Causes of non resolution

Complications Host factors Delayed radiological recovery Presence of resistant organisms Presence of unusual organisms Defects in defense Diseases mimicking pneumoni

154

Normal CXR & Pneumonic Consolidation

155

Lobar Pneumonia S.pneumoniae

156

CXR PA and Lateral Views

157

Lobar versus Segmental - Right Side

158

Lobar Pneumonia

159

Special forms of Consolidation

160

Round Pneumonic Consolidation

161

Special Forms of Pneumonia

162

Special Forms of Pneumonia

163

Complications of Pneumonia

164

Empyema

165

Mycoplasma Pneumonia

166

Mycoplasma Pneumonia

167

Chlamydia Trachomatis

168

Rare Types of Pneumonia

169