Tratamiento de la NAC: importancia de los factores de riesgo

1

XXV Curso de Avances en Neumología

DR. JORDI ROIGPneumologia

Enf cardiaca isquémica

Enf cerebrovascular

Infección respiratoria

Enf diarreicas

Trast perinatales

EPOC

Tuberculosis

Sarampión

Accidentes de tráfico

Cáncer de pulmón

3ª

Cáncer gástrico

SIDA

Suicidio

1990 2020

Murray CJ & Lopez AD. Lancet 1997

Mortalidad Global Prevista

4ª

Neumonía comunitaria: Mortalidad

Bodi M et al CID 2005;41:1709; Rello J et al ICM 2002;28:1030; BTS Thorax 2001;56

(suppl IV) 1-64; Fine JM et al NEJM 1997;336:243; Marik PE. J Crit Care 2000;15:85

1%5%

40%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

No Hospitalizada Hospitalizada UCI

Mort

alit

at

S.pneumoniae

S.aureus

Legionella

PA

H.influenzae

Enterobac.

Community Acquired Pneumonia:

Etiology

Angus DC et al . Am J Respir Crit Care Med 2002;166:717-723

“S.pneumoniae is

the principal

microorganism

responsible of

CAP”

“The etiologic

pattern was similar

in both ICU and

non-ICU patients”.

¿Es S. pneumoniae la causa principal de

neumonía de etiología desconocida?

Ruiz-Gonzalez A. A microbiologic study with lungaspirates in consecutive patients with CAP. Am JMed 1999.

• n= 109

• Conventional microbial work-up + in 54 cases(50%) 9 of them S. pneumoniae

• Lung aspiration in remaining 55 provided diagnosis in 36:

– S. pneumoniae 18

– H. influenzae 6

Edad 50 años

o

comorbilidad

o

anomalias en signos

vitales

calcular PSI score

http://pda.ahqr.gov/

Male age (yrs)

Female - 10

Nursing home + 10

cardiac + 10

hepatic + 20

renal + 10

CNS + 10

neoplasia + 20

HR 125/bpm + 10

RR 30/min + 20

SBP < 90 mmHg + 20

Temp. < 35 or 40 C + 15

Confusion + 20

pH < 7.35 + 30

Blood urea nitrogen 30 mg/dl + 20

Sodium < 130 mmol/l + 20

Glucose 250 mg/dl + 10

Hemotocrit < 30% + 10

PaO2 < 60 mmHg + 10

Pleural effusion + 10

Fine MJ.NEJM 1997; 336:243 Pneumonia Severity Index PSI

Definition of SCAP: PSI Score

Fine MJ et al NEJM 1997; 336:243

COPD?

Prevalencia España

En España 1.300.000 personas entre 40 y 69 años padecen una EPOC. El 78% no estaba diagnosticado.

Leves: 38.3%

Mod.: 39.7%

Graves: 22%

Sobradillo V et al. Chest. 2000 Oct;118(4):981-9.

La EPOC en la NAC que ingresa en UCI

supone mayor mortalidad (OR 1.58)

10

Rello J et al . Eur Respir J 2006; 27: 1210-6

Cillóniz C et al.

Microbial aetiology of community-acquired

pneumonia and its relation to severity.

Thorax. 2011 Jan 21. [Epub ahead of print]

AETIOLOGY PSI I-IIIn= 659(%)

PSI IVn=500(%)

PSI Vn=301(%)

TOTALn=1460(%)

p value

St. pneumoniae 276 (42) 205 (41) 132 (44) 613 (42) 0.728

H. influenzae 27 (4) 28 (6) 15 (5) 70 (5) 0.488

Atypical bacteriaLegionellaMycoplasmaChlamydiaCoxiella

163 (25)54 (8)51 (8)31 (5)27 (4)

77 (15)50 (10)12 (2)13 (3)2 (0.4)

23 (8)14 (5)2 (1)6 (2)1 (0.3)

263 (18)118 (8)65 (4)50 (3)30 (2)

<0.0010.027<0.0010.046<0.001

Virus 62 (9) 57 (11) 29 (10) 148 (10) 0.511

Mixed 84 (13) 73 (15) 51 (17) 208 (14) 0.217

Cillóniz C et al.

Microbial aetiology of community-acquired

pneumonia and its relation to severity.

Thorax. 2011 Jan 21. [Epub ahead of print]

AETIOLOGY PSI I-IIIn= 659(%)

PSI IVn=500(%)

PSI Vn=301(%)

TOTALn=1460(%)

p value

St. pneumoniae 276 (42) 205 (41) 132 (44) 613 (42) 0.728

H. influenzae 27 (4) 28 (6) 15 (5) 70 (5) 0.488

Moraxella cath.S. aureusMSSAMRSA

GNEnterobact

2 (0.3)9 (1)5 (1)4 (1)7 (1)

2 (0.4)10 (2)5 (1)5 (1)9 (2)

1 (0.3)6 (2)4 (1)2 (1)11 (4)

5 (0.3)25 (2)14 (1)11 (1)27 (2)

0.9610.6510.6970.7310.022

Pseudomonas 9 (1) 17(3) 23 (8) 49 (3) <0.001

Others 20 (3) 22 (4) 10 (3) 52 (4) 0.448

46,2

10,1 8,8 8,2 7,6

59,3

4,37,6 5,9 8,4

0

10

20

30

40

50

60

70

S.pneumoniae S.aureus L.pneumophila P.aeruginosa H.influenzae

Shock

No Shock

CAP: Etiology (CAPUCI Study)

“The etiologic pattern was similar in both shock and non-

shock patients”.

Bodí M (CAPUCI study). CID 2005

Factores que aumentan el riesgo de

infección por S.pneumoniae resistente

-Edad:>65 años o <2 años

-Beta-lactámicos en los últimos 3 meses

-Alcoholismo

-Inmunosupresión

-Comorbilidades

-Contacto con niños en guarderías

- Hospitalización reciente o actual

CAP ATS/IDSA Guidelines 2005

Risk factors for multidrug-resistant

pneumococcal pneumonia

Pneumonia Severity Index (PSI) score

Asthma

HIV infection

Previous hospital admission

Nursing home residence

Shock associated with 30-day mortality

Aspa J, Rajas O, et al. Infect Dis Clin Pract 2008.

RESISTENCIA NEUMOCOCO

• Historia de antibióticos utilizados

recientemente

– Terapia previa con beta-lactámicos,

macrólidos y quinolonas favorece

resistencia al mismo agente

• Escoger un antibiótico diferente al

indicado la última vez aunque haya

habido éxito terapéutico

Ho et al. Risk factors for acquisition of levofloxacin

resistant Streptococcus pneumoniae: a case-control

study. Clin Infect Dis 2001

• Case-control study: 27 with levo-Resist pneumococci: 10 AECB, 11 pneumonia, 6 colonized; 54 controls (levo-Sens pneumococci)

• Risks for resistance in logistic regression: nursing home residence (OR= 7.4), COPD (OR=10.3), nosocomial (OR=16.2), recent hospitalization (OR= 4.6), prior quinolones within 12 months (OR= 10.7), prior beta-lactam within 6 weeks (OR=14.7)

• 11/14 got prior quinolones (8 with levofloxacin) for COPD.

Puntos clave: resistencia y etiología

• La selección de cepas resistentes se

asocia fuertemente a tratamientos

antimicrobianos subóptimos

• Las pautas de tratamiento cortas

ayudan a reducir la aparición de

bacterias multiresistentes

Rello J & Roig J. In: Respiratory infections. Chapter 40; Hodder

Arnold Pub, London, 2006.

30,1%

21,4%

0%

5%

10%

15%

20%

25%

30%

35%

COPD Non COPD

Mo

rtal

ity

rate

(%

)

p=0.05

n=176n=252

COPD (%) Non-COPD(%)

Streptococcus

pneumoniae

52 (54.1) 68 (51.5)

P. aeruginosa 13 (13.5) 1 (0.8)

Haemophillus

influenzae

11 (11.4) 7 (5.3)

Legionella spp. 4 (4.1) 15 (11.4)

Staphylococcus aureus 3 (3.1) 12 (9.0)

Enterobacteriaceae 3 (3.1) 9 (6.8)

Microorganismos aislados en pacientes

inmunocompetentes con y sin EPOC con CAP grave

Rello J, Rodriguez A, Torres A, Roig J. ERJ 2006

Risk factors for infection with P. aeruginosa

Structural lung disease

Corticosteroid therapy (> 10 mg/d)

Use of broad-spectrum antibiotics

Malnutrition

Leukopenic immunosuppression

Previous hospital admission

Malignancy

Rapid X-ray spread

Weyers CM. Clin Chest Med 2005; Arancibia F. Arch

Intern Med 2002; Bodí M (CAPUCI, CID 2005)

Risk factors for infection with enteric gram-

negative organisms

Nursing home residence

Cardiopulmonary disease

Multiple co-morbidities

Recent antibiotic use

Previous hospital admission

Probable aspiration

Weyers CM. Clin Chest Med 2005. Arancibia F. Arch Intern

Med 2002

0%

10%

20%

30%

40%

50%

60%

Inappropriate Appropriate

COPD PATIENTS WITH SCAP:

MORTALITY RATE / EMPIRIC ATB TREATMENT

Rello J, Rodriguez A, Torres A, Roig J et al. ERJ 2006

p<0.05

RISK FACTORS OF TREATMENT FAILURE IN

CAP / MORTALITY RATE

Menéndez R et al. Thorax 2004;59:960

0%

5%

10%

15%

20%

25%

30%

Failure No Failure

p<0.001

¿Es importante la administración

precoz de antibióticos?

• Meehan TP. Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA 1997; 278: 2080-84

• Houck PM. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with CAP. Arch Intern Med; 2004; 164: 637-644

8 Horas

4 Horas

Tratamiento de la CAP grave

• Escoger apropiadamente antibiótico inicial

9,2%

15,5%

9,9%

16,5%

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

Hospital 30-days

<4 hs

> 4 hs

Houck PM et al. Arch Intern Med 2004;164:637-644

p = 0.04p = 0.03

Early recognition of LD leads to prompt

therapy and low mortality

• Symptoms > 5 days: higher mortality1 in severe cases

• Adequate Rx < 24 h ICU: 78% survival vs 54% (p=0.005)2

• Fatality rate11% in outbreaks if delayed recognition3

• Lower fatality rates (<2%) if early recognition, as reported in Australia and Murcia, Spain (n=449)3,4

1Gacouin 2002; 2Lettinga 2002; 3Navarro, Eurosurveillance Weekly 2001; 4Garcia-Fulgueiras 2003

COPD PATIENTS: ICU MORTALITY RATE

RISK FACTORS (Cox proportional regression

analysis)

Rello J, Rodriguez A, Torres A, Roig J et al. ERJ 2006

DEVELOPMENT OF SHOCK: Risk Factors

CAPUCI Study

.2 .3 .4 .5 .6 .7 .8 .9 1 2 3 4 5

OR

0.3Previous ATB

APACHE II score >20

3.4

4.4Rapid X-rays spread

Normativa SEPAR de Neumonia

Adquirida en la Comunidad:

actualización de septiembre de 2010.

R. Menéndez, A. Torres, J. Aspa, A. Capelastegui, C. Prat, F.

Rodríguez de Castro

Sociedad Española de Neumología y Cirugía Torácica;

www. separ.es

Características del antibiótico ideal

• Alta actividad contra patógenos potenciales

• Perfil farmacodinámico adecuado (buena penetración tisular)

• Perfil de seguridad bueno

• Posología fácil

• Relación coste/beneficio favorable

Efecto de los antibióticos en la

mortalidad en bacteremia por

neumococo

0

10

20

30

40

50

60

70

80

90

100

0 2 4 6 8 10 12 14 16 18 20 22

Days of illness Austrian and GoldAnn Int Med 1964

Penicillin (298)

Serum (93)

Untreated (384)

Penicillin vs Placebo RT

0

20

40

60

80

100

Mortality

All cases Very Severe

Age Group

Penicillin

None

N=200

Evans and Brim Lancet 1938; 2: 14-19

Mortalidad: neumonía por

neumococo

0

5

10

15

20

25

30

35

40

45

50

1920

1926

1932

1938

1944

1950

1956

1962

1968

1974

1980

1986

1992

1998

2004

USA data compiled from published studies and Vital Statistics Reports

% m

ort

alit

y

MO

RTALIT

Y (

%)

Antibioterapia combinada es mejor que

monoterapia en neumonía neumocócica

bacteriémica

18,2%20,0%

55,3%

23,4%

4,3%6,9%

0%

10%

20%

30%

40%

50%

60%

Waterer Martinez Baddour

Monoth.

Combo

(1) Waterer GW et al. Arch Intern Med 2001;161:1837-42

(2) Martínez JA et al. CID 2003;36:389-395

(3) Baddour LM et al. Am J Respir Crit Care Med 2004; 170:440-444

Mortality rate

Tipo de Combinación / Mortalidad

OR: 2.7

Mortensen EM et al. Crit Care 2006;10:R8 p=0.004

20-year longitudinal study of Bacteremic pneumococcal

pneumonia in Huntington, West Virginia

0

2

4

6

8

10

12

14

16

18

20

1978-1982 1983-1987 1988-1992 1993-1997

Pen alone

Pen+Mac

Mufson MA & Stanek RJ. Am J Med 1999

p<0.001

806040200

DAYS

1,0

0,8

0,6

0,4

0,2

0,0

Cu

mu

late

d S

urv

iva

l MONOTHERAPY-censured

COMBINED-censured

MONOTHERAPY

COMBINED RX

Severe LD(Capuci): Kaplan – Meier survival curve

P=0.203

(Log Rank)

HRCT in patients with dyspnea, fever of unknown origin and normal X-ray

Brown MJ. Acute lung disease in the immunocompromised host:

CT and pathologic findings. Radiology 1994

Ramila E. Bronchoscopy guided by HRCT for the diagnosis of

pulmonary infections in patients with hemathologic malignancies

and normal plain chest X-rays. Haematologica 2000

• Immunocompromise, severe emphysema

• May detect an unsuspected alveolar infiltrate or a subtle interstitial pattern

• Guide for FOB techniques ► better yield

Epidemiological features

• Travel or residence in high-risk areas for

some pathogens: rickettsiosis, fungal

infection, viral hemorrhagic pneumonia

• Occupational risk: F. tularensis, Coxiella

burnetti, Leptospira, Adenovirus

• Family illness: Mycoplasma, C. pneumoniae

• Bioterrorism setting

• Close contact (schools,…): H1N1

Acinetobacter as causative agent of SCAP

•Marik PE. The clinical features of SCAP

presenting as septic shock. Norasept II Study

Investigators. J Crit Care 2000; 15:85-90.

•Anstey NM. Community-acquired bacteremic

Acinetobacter pneumonia in tropical Australia is

caused by diverse strains of A. baumannii, with

carriage in the throat in at-risk groups. J Clin

Microbiol 2002; 40: 685-686.

•Lee K. Novel acquired metallo-β-lactamase gene,

in a class 1 integron from A. baumannii clinical

isolates from Korea. AAC 2005; 49: 4485-4491.

•Leung W. Fulminant A. baumannii CAP as a

distinct clinical syndrome. Chest 2006; 129:102-9.

S. aureus infection in healthy patients

•Gillet Y. Association between S. aureus strains

carrying gene for Panton-Valentine leukocidin and

highly lethal necrotising pneumonia in young

immunocompetent patients. Lancet 2002;359:753-

59.

•Boussaud V. Life-threatening hemoptysis in

adults with CAP due to PV leukocidin-secreting S.

aureus. Intensive Care Med 2003;29:1840-3.

•Francis J. Severe Community-onset pneumonia

in healthy adults caused by methicillin-resistant S.

aureus carrying the PV leukocidin genes. CID

2005; 40: 100-7.

221.200

Mercè Agustí

Jordi Roig

157.200

165.138

73.800 40.000

231.468

Jordi Almirall

Eugènia Carandell

Imma Hospital

Pilar Ayuso Andreu Estela

Población diana: 888.806 habitantes

Almirall J et al. New evidence of risk factors for

CAP: a population-based study. PACAP group.

Eur Respir J 2008

269/267

353/376

232/230

129/127 79/80

159/171

115/75

N: 1336/1326

OR P

DENTISTA 0.69 0.02

VACUNA NEUMOCOCO 0.54 0.003

PREVIA NAC 1.48 0.001

TABAQUISMO <150 paq/año >150 paq/año

1.01 1.46

0.006

BRONQUITIS CRÓNICA 1.81 0.006

OXÍGENO 2.42 0.01

INHALADORES 1.57 0.03 HALADORES

New evidence of risk factors for CAP: a population-based study

Almirall J et al. PACAP group. Eur Respir J 2008

OR P

CORTICOIDES INH 7.44 0.05

BETA-2 1.17 0.45

IPRATROPIO 2.30 0.002

OXIGENOTERAPIA 5.04 0.014

INHALADORES Con cámara Sin cámara

2.28 1.39

0.01

ANÁLISIS MULTIVARIANTE(tratamiento)

casos n=473; controles n=235

Prevención de la CAP

Vacunación antigripal

Vacuna antineumocócica:

Johnstone J.Effect of pneumococcal vaccination

in hospitalized adults with CAP. Arch Intern Med

2007. OR of death or ICU was 0.62

Tabaco ↑ riesgo adquisición y muerte.

Nuorti JP. Cigarette smoking and invasive

pneumococcal dis. NEJM2000

Control odontólogo riesgo de adquisición

Cambio brusco Tª ↑ riesgo

FUMADOR

ACTIVO

Pacientes

n (%)

Controles OR

ajustada

p

Nº cig

0/ dia 92 (42) 224 (76) 1.0

1-14/dia 48 (22) 39 (13) 2.3 (1.3-

4.3)

0.006

15-24/dia 41 (19) 19 (6) 3.7 (1.8-

7.8)

<0.001

> 25/dia 37 (17) 13 (4) 5.5 (2.5-

12.9)

<0.001

Nuorti JP. Cigarrette smoking and invasive pneumococcal

disease. NEJM 2000

No

FUMADOR

Pacientes

n (%)

Controles OR

ajustada

p

No

exposición

40 (59) 125 (80) 1.0

1-4h /dia 16 (24) 25 (16) 2.4 (0.9-

6.3)

0.08

> 4h /dia 12 (18) 7 (4) 3.9 (1.0-

16)

0.05

Nuorti JP. Cigarrette smoking and invasive pneumococcal

disease. NEJM 2000

Effect of nicotine on L. pneumophila growth

in alveolar macrophages0

24

control nicotine 0.1 nicotine 1 nicotine 10

24h afterinfection

48h afterinfection

Matsunaga K et al. J Immunol 2001

Estudio TORCH

6.112 pacientes EPOC y

FEV1<60%Salmeterol+fluticasona

Fluticasona

Salmeterol

Placebo

52

Calverley P et al. N Engl J Med 2007; 356: 775-789

Estudio TORCH

NEUMONÍA

Salmeterol+fluticasona 19.6%

Fluticasona 18.3%

Placebo 12.3%

(P<0.001)

53Calverley P et al. N Engl J Med 2007; 356: 775-789

Inhaled drugs as risk factors for

community-acquired pneumonia

J. Almirall, I. Bolíbar, M. Serra-Prat, E. Palomera, J. Roig, I.

Hospital, E. Carandell, M. Agustí, P. Ayuso, A. Estela, A. Torres

and the Community-Acquired Pneumonia in Catalan Countries

(PACAP)

Eur Respir J 2010; 36: 1080–1087

COPD OR p

Upper respiratory tract infection in the

past month2.25 (0.84–6.01) 0.107

Oxygen therapy 1.18 (0.19–7.39) 0.863

Inhaled steroids 3.26 (1.07–9.98) 0.038

Inhaled β-agonists 0.68 (0.23–2.02) 0.483

Inhaled anticholinergics 1.19 (0.39–3.63) 0.757

Asthma 1.00 (0.38–2.62) 0.998

Oral corticosteroids 1.30 (0.31–5.47) 0.718

Smoking history pack-yrs

0 1 0.081

1–150 4.23 (1.07–16.7) 0.039

>150 2.44 (0.83–7.21) 0.105

Influenza vaccine 0.39 (0.12–1.27) 0.118

Table 3– Association between inhaled drug treatments and the risk of CAP adjusted for

respiratory comorbidity and its severity, respiratory treatments and other non-respiratory

risk factors, by strata of patients with specific respiratory diseases

Table 3– Association between inhaled drug treatments and the risk of CAP adjusted for

respiratory comorbidity and its severity, respiratory treatments and other non-respiratory

risk factors, by strata of patients with specific respiratory diseases

Asthma alone OR p

Upper respiratory tract infection

in the past month1.46 (0.92–2.30) 0.105

Inhaled steroids 1.10 (0.40–3.00) 0.857

Inhaled β-agonists 1.24 (0.58–2.67) 0.582

Inhaled anticholinergics 8.80 (1.02–75.7) 0.048

Influenza vaccine 0.67 (0.42–1.08) 0.096

Pneumococcal vaccine at any

time of life0.35 (0.14–0.84) 0.020

N-Acetylcysteine 0.23 (0.03–1.87) 0.168

Depression 0.70 (0.40–1.21) 0.200

5,81

0,73

4,52

3,02

1,19

5,16

0

1

2

3

4

5

6

7

Biologic Adoptive

Infection

Vascular

Cancer

Sorenson TI et al N Engl J Med 1988

Dying from infection is hereditary

Sorenson et al N Engl J Med 1988

Pathogen coverage Timely initiation

Correct dose Correct route

Optimal

therapy

Increased survival

Pea F et al. Clin Infect Dis. 2006;42:1764-1771; Rello J et al. Chest.

2006;130:938

Tratamiento “OPTIMO”

Inmunomodulación?