The Big Beasts of ID - Pneumonia - Physician · The Big Beasts of ID - Pneumonia ... Pneumonia occurring ≤48 hours of hospital admission in ... Impaired gas exchange VQ mismatch

The Big Beasts of ID - Pneumonia

Charles Feldman

Professor of Pulmonology and Chief Physician

Charlotte Maxeke Johannesburg Academic Hospital

University of the Witwatersrand

0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5

No. of deaths (millions)

2.2 Other infectious

diseases

2.2 Hepatitis B

0.2 Measles

0.2 Pertussis

0.3 Meningitis

0.8 Malaria

1.3 Tuberculosis

1.8 HIV/AIDS

2.5 Diarrhoeal disease

4.3 Respiratory infections

Fauci AS et al. NEJM 200th Year Edition 2012; 366: 454-461

Leading Causes of Death from ID

Estimated 58.8 million deaths per year

15 million (25.5%) due to Infectious diseases

Number of Citations on PubMed

Complete citation list

Pneumonia 106840

Chest infections 22488

CAP 7431

HAP 1051

HCAP 220

Citations for 2012

Pneumonia 4000

Chest infections 1000

CAP 650

HAP 100

HCAP 40

PubMed last accessed 5 October 2012

The Alphabet Soup of Pneumonia

Pneumonia occurring ≤48 hours of hospital admission in

patients who do not meet the criteria for HCAP

CAP

Pneumonia occurring ≤48 hours of hospital admission in patients

with ≥1 of the following risk factors for MDR bacteria as cause of

infection:

Hospitalization for ≥ 2 days in acute-care facility within 90 days

of infection

Residence in a nursing home or long-term care facility

Antibiotic therapy, chemotherapy, or wound care within 30 days

of current infection

Haemodialysis treatment at a hospital or clinic

Home infusion therapy or home wound care

Family member with infection due to MDR bacteria

HCAP

Anand N et al. Semin Respir Crit Care Med 2009; 30: 3-9

Pneumonia occurring >48 hours after endotracheal intubation

Risk factors for MDR bacteria causing VAP

Presence of HCAP or HAP risk factors for MDR

VAP

Pneumonia occurring > 48 hours after hospital admission

Risk factors for MDR bacteria causing HAP

Antibiotic therapy within 90 days of infection

Current hospitalization of ≥5 days

High frequency of antibiotic resistance in community or

specific hospital unit

Immunosuppressive disease of therapy

Presence of HCAP risk factors for MDR

HAP


The Alphabet Soup of Pneumonia

0 5 10 15 20 25

Patient mortality

Kolief MH, et al. Chest 2005;128 3854

Micek S, et al. Antimicrob Agents Chemother 2007;51:3568

Carratala J, et al. Arch Intern Med 2007;167 1393

P=0.007

P<0.001

P<0.001 CAP

HCAP

Mortality in Patients with CAP and HCAP


0

20

40

60

80

Pa

ien

ts w

ith

PD

R p

ath

og

en

s (

%)

0

n=165

1

n=77

2

n=93

4

n=4

Number of HCAP risk factors

P > 0.01 for trend

0

20

40

60

80

0 - 2

n=185

Total score

P > 0.01 for trend

3 - 5

n=95

≥ 6

n=59

Risk of PDR Pathogens in HCAP

Park SC et al. Respiratory Medicine 2012; 106: 1131-1319

100

80

60

40

20

0

0 20 40

100-Specifity

80 100

Sensitiv

ity

New scoring

system

Current

HCAP

criteria

Park SC et al. Respiratory Medicine 2012; 106: 1131-1319

Proposed Algorithm for HCAP Therapy

Severe pneumonia

Assess severity of illness (need for mechanical ventilation, ICU admit)

AND

Presence of risk factors for MDR pathogens (recent antibiotics, recent

hospitalization, poor functional status, immune suppression)

HCAP is present: From a nursing home, recent hospitalization,

haemodialysis, home infusion therapy

No Yes

0 – 1 Risks

Treat for common CAP

pathogens (consider

oral Rx). Quinolone or

β-lactam / macrolides.

≥ 2 Risks

Consider hospital.

Treat for MDR

pathogens with

HAP therapy.

0 Risks

Treat for severe

pneumonia in hospital.

β-lactam PLUS

macrolide or quinolone.

≥ 1 Risk

Treat for MDR

pathogens with HAP

recommendations.

Use 3 drugs.

Brito V e al. Curr Opin Infect Dis 2009; 22: 316-325

Overall Reported Etiology of CAP

Herrero FS et al. Semin Respir Crit Care Med 2012; 33: 220-231

Community (%) ICU (%) Hospital (%)

Streptococcus pneumoniae

Haemophilus influenzae

Legionella spp.

Staphylococcus aureus

Gram-neg. bacteria Enterobacteriae

Virus

Chlamydophila pneumoniae

Mycoplasma pneumoniae

No pathogen identified

14-19

1-4

2

0-0.2

0-0.4

12-15

6-12

16-22

44-60

25-27

4-8

3-4

1-3

3-5

10-12

3-5

6-8

37-44

17-22

3-5

8-10

3-7

5-7

4-6

-

-

41-42

PSI I-III (%) PSI IV (%) PSI V (%)

Legionella pneumophila S. pneumoniae H. influenzae M. catarrhalis

Virus C. pneumoniae M. pneumoniae S. aureus

Gram-negative bacteria Eterbacteriaceae P. aeruginosa mixed

13 1

1

1

9

5

8

8 0.3 4

42

15 3

2

2

11

3

2 10 0.4 6

41

17

8

4

2

10

2 1 5 0.3 5

44

CAP Etiology and Pneumonia Severity

Herrero FS et al. Semin Respir Crit Care Med 2012; 33: 220-231

S. pneumoniae 26 (62)

S. pyogenes 1 (2)

S. aureus 2 (5)

M. pneumoniae 3 (7)

M. catarrhalis 1 (2)

C. burnetti 1 (2)

E. coli 1 (2)

P. aeruginosa 6 (14)

Fusobacterium sp. 1 (2)

Bacterial Co-infection in Patients with CAP Associated with H1N1 Infection

Cilloniz C et al. J Infect 2012; 65: 223-230

PCT

NE cells CRP

IL-1

IL-6

TNF TLR4

LPS

sRAGE

TREM-1

sTREM-1 PTX3

RAGE

TNF

IL-1

TNF

HMGB1

NFκB

Macrophage

Liver

7 PTX3

PAMPs C1q

PAI-1: fibrinolysis

Endothelial cells

Lichtenstern C et al. Curr Opin Infect dis 2012; 25: 328-336

Biomarkers Related to Sepsis

The Routine Use of Biomarkers

Due to the complex pathophysiology of sepsis, many biomarkers

display relevant correlation with the clinical outcome of patients

with severe sepsis and septic shock

CRP and PCT are widely introduced in clinical practice, and

provide a reasonable correlation to sepsis severity and outcome,

whereas IL-6 possesses advantage in early sepsis diagnosis

No absolute level of a parameter or a combination of parameters is

highly and consistently reliable to predict death; consideration of

time course may be more reliable

In patients with severe sepsis and septic shock, critical clinical

decision, for example relaparotomy on demand, should be based

on both biomarkers and organ dysfunctions over the course of

time

Lichtenstern C et al. Curr Opin Infect Dis 2012; 25: 328-336

Variation of Diagnostic Capacity after Adding Determination of Biological Markers

Clinical data

CRP

PCT

Clinical data + CRP

Clinical data + PCT

Clinical data + CRP + PCT

50

0.25

0.79

0.9

0.88

0.92

Threshold AUC

Torres A et al. Semin Respir Crit Care Med 2012; 33: 266-271

Utility of CRP in Diagnosis of CAP

Almirall et al

Flanders et al

Study

design

CRP

threshold Sensitivity Specificity AUC

CAP vs. controls

CAP vs. controls

33.15

40.00

83%

70%

44%

90%

0.69

0.93

Torres A et al. Semin Respir Crit Care Med 2012; 33: 266-271

Interventional Studies with PCT Controlled, prospective, randomized

ProRESP

ProCOLD

ProCAP

PARTI

ProHOSP

ProVAP

HannoverPro

I-PCT

LRTI

AECOPD

CAP

LRTI

LRTI

VAP

LRTI

LRTI

PCT

PCT

PCT

PCT

PCT

PCT

PCT

PCT

ED

ED

ED, hospital

Primary care

ED, hospital

ICU

Primary care

ED, hospital

1

1

1

53

6

7

45

1

243

226

302

458

1359

101

550

210

44

40

14

72

35

27

42

25

Study Infection Biomarker

Centres

(n)

Patients

(n)

Reduction

AB (%)

10.7 vs 4.8

7.0 vs 3.7

12.9 vs 5.7

6.8 vs 1.5

8.7 vs 5.7

9.5 vs 13*

36.7 vs 32.5 (%)

6.8 vs 5.1

AB control

vs PCT

(days)

* All free days

Kruger S et al. Expert Rev Respir Med 2012; 6: 203-214

PCT Guided Antibiotic Therapy

Adapted after Chris-Crain et al.

Suspected LRTI

Clinical parameters Procalcitonin Chest x-ray

0.1-0.25 <0.1 0.25-0.5 >0.5

AB no AB NO AB yes AB YES

Yes AB No no AB

AB overruling: clinical decision, severe comorbidities, clinical severe infection

according to score, respiratory or haemodynamic instability, ICU admission PCT control after 6-24 h in persistent severe illness

or patient without AB

Under AB: PCT control on day 3,5,7

Stop after PCT algorithm; if very high initial PCT stop at decrease of PCT >80-90% of

initial value If PCT remains high treatment failure?

AB NO AB yes AB no AB NO

Clinically relevant bacterial infection - +

Kruger S et al. Expert Rev Respir Med 2012; 6: 203-214

Infection IL-1

TNF-α

IL-6

Cortisol

Adrenal cortex

Pituitary gland

ACTH

Hypothalmus

CRH

Additional Biomarkers for CAP?

Meijvis SCA et al. J Intern Med 2012; 272: 25-35

HPA Axis

300

250

Inte

rle

ukin

-6 (

pg

/mL

)

150

100

50

0

200

P<0.001

A

50

40

Inte

rle

ukin

-8 (

pg

/mL

)

20

10

0

30

P<0.001

B

1200

1000

Mo

no

cyte

ch

em

ota

ctic p

rote

in-1

(p

g/m

L)

600

400

200

0

800

P<0.001

C

500

400

C-r

eactive

pro

tein

(m

gm

L)

200

100

0

300

P<0.015

D

Remmelts HHF et al. J Infect 2012; 65: 25-31

Cytokine Response and Cortisol Level

Cortisol Levels by Severity of CAP

3000

Cort

isol nm

ol/l

2500

2000

1500

1000

500

0 0 1 2 3,4

CRB-65 score

* * *

Kolditz M et al. BMC Infectious Diseases 2012; 12: 90

1.0

0.8

0.6

0.2

0.0

Se

nsitiv

ity

0.4

0 0.2

1 - Specificity

0.4 0.6 0.8 1.0

CRB-65 (AUC=0.76)

Cortisol (AUC-0.70)

Cortisol + CRB-65 (AUC=0.81)

1.0

0.8

0.6

0.2

0.0

0.4

0 0.2

1 - Specificity

0.4 0.6 0.8 1.0

CRB-65 (AUC=0.77)

Cortisol (AUC-0.71)

Cortisol + CRB-65 (AUC=0.81)

30-day Mortality Critical Pneumonia

Kolditz M et al. BMC Infectious Diseases 2012; 12: 90

Cortisol Levels for Predicting Severity of CAP

Heart failure - 239 (66.8%)

Cardiac arrhythmia - 79 (22.1%)

Myocardial infarction - 13 (3.6%)

Indeterminate 27 - (7.5%)

Inpatients (n = 1343)

Heart failure - 13 (65.0%)

Cardiac arrhythmia - 7 (35.0%)

Myocardial infarction - 0 (0.0%)

Indeterminate 0 - (0.00%)

Cardiac complications

385 (26.7%)

No cardiac complications

985 (74.3%) Cardiac complications

20 (2.1%)

No cardiac complications

924 (97.9%)

Outpatients (n = 944)

Cardiac Complications in Patients with CAP

Corrales-Medina VF et al. Circulation 2012; 125: 773-781

25%

20%

15%

10%

5%

0% Heart failure

279 (20.8%)

Cardiac arrhyhmia

137 (10.2%)

Myocardial infarction

43 (3.1%)

Inpatients (n = 1343) Outpatients (n = 944)

Heart failure

13.1 (1.4%)

Cardiac arrhyhmia

9 (1.0%)

Myocardial infarction

1 (0.1%)

Only event

First event

Secondary event


Cardiac Complications and Death in CAP

30%

20%

40%

50%

10%

0% I

1.2%

II

4.8%

III

18.1%

IV

37.0%

PSI risk- class

V

47.3%

p<0.01

% of CAP Patients who Developed Incident Cardiac Complications in each PSI Risk-class


6 5 4 3 2 1 0

Odds Ratios & 95% CI

Adjusted for PSI-score 1.6 (1.04-2.5) 0.03

Without adjustment for PSI-score 3.5 (2.3-5.2) <0.01

OR 95% CI p Less likely to die More likely to die


30-day Mortality risk with Cardiac Complications

Pneumonia

Impaired electrolyte and water metabolism; acute kidney injury

Endothelial dysfunction

Non-ischaemic myocardial/pericardial injury

Impaired gas exchange

VQ mismatch

Myocardial Ischaemia/infraction

Coronary vasoconstriction

Arrhythmia

Heart failure

SVR

Pulsatile ventricular afterload

Volume overload

Bacterial/viral infection of myocardium/pericardium

Sympathetic activation

Procoagulant state

Plaque instability and rupture

Hypoxaemia

Systemic inflammatory response

Arrhythmogenic drugs

Intravenous sodium administration

Corrales-Medina VF et al. Lancet 2013; 381: 496-505

Records after duplicates removed (n=505)

Additional records identified though other sources

(n=505)

Records identified through database searching

(n=2834)

Records screened by title and/or abstract

(n=2362) Records excluded

(n=2304)

Full-text articles assessed for eligibility

(n=58)

Studies included in qualitative synthesis

(n=23)

Studies included in quantitative synthesis

(meta-analysis) (n=23)

Full-text articles excluded (n=35)

Inappropriate/no comparison arm n=16),

included ICU or outpatients (n=12),

missing mortality data (n=4),

same database as studies already included (n=2),

study in progress (n=1)

Elig

ibili

ty

Incl

ud

ed

Scr

een

ing

Id

enti

fica

tio

n

Asadi L et al. Clin Infect Dis 2012; 55: 371-380

Treatment with Macrolide Regimens and Mortality

Arnold 2009

Asadi 2012

Blasi 2008

Brandenburg 2000

Bratzler 2008

Brown 2003

Dambrava 2008

Frei 2003

Frei 2006

Lin 2997

Lodise 2007

Marass 2007

McCabe 2009

Menedez 2002

Menendez 2005

Menendez 2012

Minhas 2007

Portier 2007

Querol-Ribelles 2005

Reyes-Calzada 2007

Romanelli 2002

Welte 2005

Zervos 2004

Total (95% CI)

Total events

Heterogeneity: t2= 0.12; 2 = 146.24, df = 22 (p = 0.001); I2 = 85%

Test for overall effect: Z = 2.50 (p = 0.1)

44

48

47

1

374

559

7

27

3

0

14

18

447

19

24

44

4

7

25

21

7

5

3

1738

Events Total Events Total Weight M-H,Random, 95% CI

Macrolide Nonmacrolide Risk Ratio Risk Ratio

M-H, Random, 95% CI

500

556

49

6851

22736

373

872

255

24

240

122

11050

194

598

1128

24

175

209

276

101

77

102

47071

100

273

166

3

942

1328

15

46

18

1

19

43

2702

12

27

110

3

6

15

14

7

6

5

5861

833

2647

1193

82

12542

22078

198

1581

255

26

227

541

43569

101

697

2915

31

174

250

149

103

200

110

90503

6.6%

7.0%

6.8%

0.7%

8.0%

8.1%

3.1%

5.0%

2.0%

0.4%

4.2%

5.2%

8.1%

4.1%

5.1%

6.6%

1.6%

2.4%

4.5%

4.3%

2.6%

2.1%

1.6%

100.0%

0.73 (0.52-1.03)

0.84 (0.62-1.13)

0.60 (0.44-0.82)

0.56 (0.06-5.28)

0.73 (0.65-0.82)

0.41 (0.37-0.45)

0.25 (0.10-0.60)

0.67 (0.39-1.16)

0.17 (0.05=0.56)

0.36 (0.02-7.43)

0.70 (0.36-1.36)

1.85 (1.11-3.10)

0.65 (0.59-0.72)

0.82 (0.42-1.63)

1.04 (0.60-1.78)

1.03 (0.73-1.46)

1.72 (0.43-6.98)

1.16 (0.40-3.38)

1.99 (1.08-3.68)

0.81 (0.42-1.55)

1.02 (0.37-2.80)

2.16 (0.68-6.89)

0.65 (0.16-2.64)

0.78 (0.64-0.95)

0.001 0.1 1 10

Favours macrolide

100

Favours nonmacrolide

Asadi L et al. Clin Infect Dis 2012; 55: 371-380

2.76

2.16

2.46

2.91

6.31

5.11

8.15

4.94

0 2 4 6 8

Mortality (%)

Ceftriaxone

Other ceph.

Penicillin

Quinolone

10

Monotherapy

Macrolide combination

18 500

16 000

4 500

1 800

P<0.05

P<0.0001

P<0.0001

P<0.0001

Macrolide Combination and Mortality of CAP

Wunderink R et al. Semin Respir Crit Care Med 2012; 33: 311-318 From Brown et al. Chest 2003

12

10

18

20

8

16

14

6

4

2

0

30 D

ay e

vent

rate

s (

%)

Mortality Death or hospitalization

0.2

3

6

5

14

16 Macrolides

Respiratory fluoroquinolones

Guideline-discordant antbiotics

Is it Macrolides or Guideline Concordance?

Asadi L et al. Respiratory Medicine 2012; 106: 451-458

APC

Peptidoglycan Lipoprotein Lipoarabinomannan Zymosan

Lipoteichoic acid (LTA) RSV F-protein Flagellin

Complement PAMPs

Gene transcription DNA

TLR1 TLR2 TLR5 TLR2 TLR5

TLR4

peptidolycan N001

N002

CD 14

muramyl dipeptide

PRRs

LPS

Cytokines IL-1, IL-6, TNF-α

NFkB

Rolling & adhesion Strong binding

Cell nucleus

Diapedesis

NO Vasodilatation Leuokocyte recruitment

Inflammation

APC

Complement

Antibody

Ingestion

Phagosome

Innate effector response

Exocytosis of debris

Phagolysosome

Killing and degradation

Phagocytosis

Pathogen recognition

B

TH

Adaptor immune response

TH

Tc Tc

Corticosterods & Statins

Antibodies

Intracellular killing

Cytokines

Cytoxoxic effector

TLR blockade

Macrolides


Pathogenesis of Infections

Immunomodulatory Effects of Macrolides

Vascular

epithelium

Inlammatory cells

IL-6 TNF-α IL-8

Barrier Bacteria CL¯ H2O2

Airway

epithelium

Mucin

- Pro-inflammatory cytokine production

- Reactive oxygen species generation

- Release of polymorphonuclear cells

Effect on bacteria

- Proteinsynthesis

- Biofilm formation

- Virulence factors production

Anti-secretory effect

- Ion transport

- Mucus secretion

Epthelial cell barrier

- Mucociliary function

- Tight junctions

- β-defensin


Anti-inflammatory effects

Cytokines

Cytokines

Numbers

Numbers

T-lymphocytes

Macrophages

Dendritic cells

Smooth muscle cells

β2

receptors

Mucus

secretion

Leak

Transcription

factors

(NF-κB)

Mucus glands

Endothelial cells

Inflammatory cells Structural cells of the

respiratory tract

Epithelial cells

Corticosteroids

Immunomodulatory Effects of Steroids


Adjunctive Therapy with Steroids

Data from observational studies show that adjunctive

steroid therapy in pneumonia is prescribed in roughly

half of the patients

The quality of the evidence to support this approach is

poor

Recent data from RCTs and large observational studies

were unable to show any positive impact of adjunctive

steroid therapy on mortality in patients with pneumonia

Systemic steroids were frequently found to be

associated with adverse reactions, namely

hyperglycaemia, superinfections and late clinical

failures

Povoa P et al. Curr Opin Infect Dis 2012; 25: 199-204

Excluded review articles,

commentaries, expression

studies and reports that clearly

did not evaluate statin and risk

of pneumonia (n=375)

1. Commentary (n=7)

2. Mechanistic studies (n=11)

3. Reviews (n=5)

4. Not outcome of interest (n=18)

5. Not exposure of interest (n=1)

6. Laboratory study (n=1)

7. Other (different outcomes and

exposures, no results reported,

repeat of included study) (n=25)

Articles excluded after detailed

screening to specific criteria (n=68)

Titles and abstracts retrieved from

MEDLINE and EMBASE search (n=451)

Potentially relevant articles selected for

detailed checking of full text after initial

screening of title and abstract (n=76)

8 different studies selected for inclusion in

the meta-analysis

1 additional relevant study found from

PubMed automated electronic updates

Kwok SC et al. Eur J Clin Pharmacol 2012; 68: 747-755

Risk of Pneumonia with Statin Therapy

Adjusted Risk of Pneumonia with Statin Therapy

Community-acquired pneumonia

Dublin 2009

Fleming 2010

Kwong 2009

Myles 2009

Schlienger 2007

Smeeth 2008

Van de Garde 2006

Subtotal (85% CI)

Heterogeneity: Tau2 = 0.03; Chi2 = 37.17, df = 6 (p<0.0001; F + 84%

Test for overall effect: Z = 2.25 (p=0.02)

Hospital acquired pneumonia

Le Manach 2011

Subtotal (95% CI)

Heterogeneity: Not applicable


Total (95% CI)

Heterogeneity: Tau2 = 0.08; Chi2 =37.36, df = 7 (p<0.00001); F = 81%


Test for subgroup differences: Chi2 = 0.03, df = 1 (p=0.85), F = 0%

0.5 0.7 1 1.5

Statins reduce risk

100

Statins increase risk

12.3%

12.2%

18.1%

13.5%

11.8%

15.7%

8.3%

91.9%

8.1%

8.1%

100.0%

Weight

Odds Rati0

IV, Random, 95% CI

1.26 (1.01-1.57)

0.91 (0.73-1.13)

0.97 (0.94-1.00)

0.78 (0.65-0.94)

0.71 (0.58-0.90)

0.84 (0.35-0.95)

0.49 (0.35-0.69)

0.85 (0.74-0.98)

0.88 (0.62-1.25)

0.88 (0.62-1.25)

0.85 (0.75-0.97)

Odds Rati0

IV, Random, 95% CI

Kwok SC et al. Eur J Clin Pharmacol 2012; 68: 747-755

Readmitted within 30 days

Any mechanical ventilation

Admission to ICU

Stratification method

14 253

10 545

21 326

N

(11.8)

(8.7)

(17.6)

%

All

11 494

8 939

17 678

N

(11.7)

(9.1)

(18.0)

%

N=97 969

2 759

1 606

3 648

N

(11.8)

(6.9)

(15.76)

%

N=23 285

0.61

<0.001

<0.001

P No statin Statin

Rothberg MB et al. J Gen Intern Med 2011: 27: 280-286

Statin Given in Hospital and Mortality

0.8 0.7

Unadjusted

Covariate adjusted

Propensity adjusted

Propensity, covariate adjusted

Propensity-matched sample

Unadjusted

Covariate adjusted

Intensive Care Unit Strata

Inside ICU

Non ICU

Antibiotic strata

Broad-spectrum

No broad-spectrum

Primary diagnosis strata

Pneumonia

Sepsis

Respiratory failure

Odds of mortality

0.6 0.5 0.9 0.4 1 1.1

Statin better No statin better

Model


Use of Statins on Hospital Admission

Mortality with other Cholesterol Medications

Ezetimbe

Crude

Adjusted

Fibrates

Crude

Adjusted

Resins

Crude

Adjusted

Niacin

Crude

Adjusted

Medication

0.51

0.82

0.54

0.79

1.79

0.97

0.90

1.36

0.36-0.72

0.57-1.19

0.41-0.70

0.60-1.05

1.45-2.21

0.77-1.22

0.65-1.26

0.96-1/94

0.0001

0.29

<0.0001

0.10

<0.0001

0.78

0.55

0.09

OR 95% CI p


Pneumococcal Serotypes Contained in Pneumococcal Vaccines for Adults

1, 3, 4, 5, 6A, 6B, 7F, 9V

14, 18C, 19F, 19A, and 23F

1, 2, 3, 4, 5, 6B, 7F, 8, 9N,

9V, 10A, 11A, 12S, 14,

15B, 17F, 18C, 19F, 19A,

20, 22F, 23F, and 33F

6A

2, 8, 9N, 10A,

11A, 12F, 15B,

17F, 20, 22F, and

33F

PCV13

PPSV23

Vaccine Serotypes included Serotypes unique

to formulation

Grabenstein JD. Vaccines 2012; 55: 255-258

Pneumococcal Polysaccharide Conjugate Vaccine (13-valent, absorbed)

Features indication

In adults aged ≥50 years, prevention of pneumonia (US) and

invasive disease (US, EU) caused by the 13 S. pneumoniae

serotypes covered by the vaccine

Vaccine composition

Polysaccharides from pneumococcal serotypes 1, 3, 4, 5, 6A,

7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 µg) and 6B (4.4 µg),

conjugated individually to non-toxic diphtheria CRM197 carrier

protein (≈32 µg) and absorbed on aluminium phosphate

Sanford M. Drugs 2012; 72: 1243-1255

PCV13

(n = 417)

PCV13

(n = 403)

PPSV23

(n = 414)

PCV13

(n = 108)

PPSV23

(n = 108)

PPSV23

(n = 189)

PCV13

(n = 214)

Dose 1 Dose 2

Age: 60 - 64 yrs

Age: 50 - 59 yrs

Study population

PPSV23 Naive

US

Cohort designation

PCV13/PCV13

PCV13/PPSV23

PPSV23/PPSV23

PCV13/PCV13

Paradiso PR. Vaccines 2012; 55: 259-264

Pneumococcal Conjugate Vaccine in Adults

Study population

PPSV23 exposed

(≥5 years prior)

US and Sweden

Cohort designation

Age: ≥70 yrs

Dose 1 Dose 2

PPSV23

(n = 474)

PCV13

(n = 464)

PCV13

(n = 394)

PCV13

(n = 403)

PCV13/PCV13

PPSV23/PCV13

Pneumococcal Conjugate Vaccine in Adults


0

300

350

400

450

250

200

150

100

50

Pre-dose 1 1-month post 12-months post Pre-dose 2 Post-dose 2

PCV13/PCV13

(50 – 59 years)

PCV13/PPS23

(60 – 64 years)

PCV13/PCV13

(60 – 64 years)

PSV23/PPSV23

(60 – 64 years)

OP

A

(GM

T)

Immunological Response in Adults


60

70

80

90

50

40

30

10

0

OP

A

(GM

T)

20

Pre-dose 1 Post-dose 1 Pre-dose 2 Post-dose 2

PCV13/PCV13

PPSV23/PCV13

Immunological Response in Adults


Pneumonia is a leading cause of death and

continues to have significant medical impact

The concept of HCAP and its treatment are

problematic and evolving – more important to

look at severity of the infection and presence of

risk factors for MDR pathogens than routinely

treating for them

Biomarkers may be useful to confirm bacterial

cause, assess severity and guide antibiotic use

and CRP and PCT are currently most promising

Issues Regarding Pneumonia Arising from Recent Studies

Issues Regarding Pneumonia Arising from Recent Studies

Treatment that is guideline compliant is

associated with lower mortality and

macrolide-based combination therapy may

have an advantage over fluoroquinolone

monotherapy

Issues with regard to adjunctive therapy still

await further clarification

Pneumococcal conjugate vaccine is now

licenced for use in adults and the indications

may expand in the future

Documents

The Big Beasts of ID - Pneumonia - Physician · The Big Beasts of ID - Pneumonia ... Pneumonia occurring ≤48 hours of hospital admission in ... Impaired gas exchange VQ mismatch