Dr. R V S N Sarma., MD., MSc., (Canada) Consultant Physician & Chest Specialist visit us at: www.drsarma.

in

The New Treatment Paradigm Selecting Appropriate Empiric Antibiotics

Pneumonias Classification

CAP

Community Acquired Health Care Associated

HCAP HAP
ICUAP VAP
3
Nosocomial Pneumonias

Hospital Acquired
ICU Acquired Ventilator Acquired

Community Acquired Pneumonia (CAP)

Definition

an acute infection of the pulmonary parenchyma

that is associated with some symptoms of acute infection, 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. 4
Bartlett. Clin Infect Dis 2000;31:347-82.

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) 5

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
6

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

CAP Pathogenesis

Inhalation Aspiration

Hematogenous

CAP Risk Factors for Pneumonia

9

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 10
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

11

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
12

CAP Special Features Pathogen wise

Typical S.pneumoniae, H.influenza, M.catarrhalis Lungs Blood tinged sputum - Pneumococcal, Klebsiella, Legionella

H.influenzae CAP has associated of pleural effusion

S.Pneumoniae commonest penicillin resistance problem S.aureus, K.pneumoniae, P.aeruginosa not in typical host S.aureus causes CAP in post-viral influenza; Serious CAP K.pneumoniae primarily in patients of chronic alcoholism

P.Aeruginosa causes CAP in pts with CSLD or CF, Nosocom

Aspiration CAP only is caused by multiple pathogens Extra pulmonary manifestations only in Atypical CAP 13

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
14

CAP Age wise Incidence

1400 1200 1000 800 # of cases 600 400 200 0
<5 5 to 17 18-24 25-44 45-64 >65

15

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

16

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
17
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

18
ID Clinics 1998;12:723. Am J Med 1994;96:313

CAP Bacteriology in Hospitalized Pts

19

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.

20

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

21

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

22
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

23

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

24

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

25

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 26

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 27

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

28

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 29

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

30

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

31

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 %

32

Pathogens Retrieved from Blood Culture

5% S.pneumoniae Enterobacteria Staph.aureus Others

11% 16%

68%

33

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 34

14.7 %
12.0 % 9.8 % 7.4 %

Traditional Treatment Paradigm

Conservative start with workhorse antibiotics

Reserve more potent drugs for non-responders

35

New Treatment Paradigm

Hit hard and early with appropriate antibiotic(s)

Short Rx. Duration; De-escalate where possible

36

The Therapy Conundrum

Avoid emergence of multidrug resistant microorganisms

Immediate Rx. of patients with serious sepsis

Objective 1

Objective 2

37

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

38

New data Dont Wait for Results !

Mortality (%)
n=75 p<0.001

Switching after susceptibility results

Adequate treatment within a few hours

39

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

40

OPAT OP Parenteral Antimicrobial Therapy

41

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

42

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

43

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 44

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

45

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

46

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

47

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 48

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

49

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

50

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 51
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

52

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 53 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.
54

Management of Poor Responders

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

Broaden antibiotic therapy

Consider bronchoscopy

55

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 56

Pneumocystis carinii (PCP)

Important cause of pneumonia in the severely

immuno-compromised, i.e. not a primary atypical

pneumonia. Classically PCP pneumonia presents with slight fever, dyspnea and non-productive cough Diagnosis usually histological (silver staining). Treatment Co-trimoxazole or Pentamidine.

57

Viruses and Pneumonia

Pneumonia in the normal host Adults or Children Influenza A and B, RSV, Adenovirus Para Influenza Pneumonia in the immuno-compromised

Measles, HSV, CMV, HHV-6, Influenza viruses

Can cause a primary viral pneumonia. Cause partial paralysis of mucociliary escalator - increased risk of secondary bacterial LRTI. S.aureus pneumonia is a known complication following influenza infection. 58

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 59

Normal CXR & Pneumonic Consolidation

60

Lobar Pneumonia S.pneumoniae

61

CXR PA and Lateral Views

62

Lobar versus Segmental - Right Side

63

Lobar Pneumonia

64

Special forms of Consolidation

65

Round Pneumonic Consolidation

66

Special Forms of Pneumonia

67

Special Forms of Pneumonia

68

Complications of Pneumonia

69

Empyema

70

Mycoplasma Pneumonia

71

Mycoplasma Pneumonia

72

Chlamydia Trachomatis

73

Rare Types of Pneumonia

74


shrothram shruthae naiva na kundalaena dhaanaena paanir na thu kankanaena vibhaathi kaayah karunaa paraanaam paropakaaraena na chandanaena
BHARTHRU HARI

Hearing science glorifies the ears, nay diamond ear-rings Giving to the needy enriches the hand, nay golden bangles To be kind and sympathetic and helping in all possible ways Enriches the beauty of our body, nay perfume or sandal paste
shrothram shruthae naiva na kundalaena dhaanaena paanir na thu kankanaena vibhaathi kaayah karunaa paraanaam paropakaaraena na chandanaena

Visit our website: www.drsarma.in our blog: http://drsarma.blogspot.com